Abc en Nac

Antibiotics for community acquired pneumonia in children
(Review)
Kabra SK, Lodha R, Pandey RM
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2009, Issue 4
http://www.thecochranelibrary.com
Antibiotics for community acquired pneumonia in children (Review)

Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Analysis 1.1. Comparison 1 Azithromycin versus erythromycin, Outcome 1 Mean age (months). . . . . . . . 34
Analysis 1.2. Comparison 1 Azithromycin versus erythromycin, Outcome 2 Male sex. . . . . . . . . . . . 35
Analysis 1.3. Comparison 1 Azithromycin versus erythromycin, Outcome 3 Wheezing present. . . . . . . . . 35
Analysis 1.4. Comparison 1 Azithromycin versus erythromycin, Outcome 4 Cure rate. . . . . . . . . . . . 36
Analysis 1.5. Comparison 1 Azithromycin versus erythromycin, Outcome 5 Failure rate. . . . . . . . . . . 36
Analysis 1.6. Comparison 1 Azithromycin versus erythromycin, Outcome 6 Side effects. . . . . . . . . . . 37
Analysis 1.7. Comparison 1 Azithromycin versus erythromycin, Outcome 7 Organisms identified by serology or
nasopharyngeal cultures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Analysis 2.1. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 1 Age less than one year. . . . . . . 38
Analysis 2.2. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 2 Male sex. . . . . . . . . . . . 38
Analysis 2.3. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 3 Numbers received antibiotics in previous one
week. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Analysis 2.4. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 4 Failure rate. . . . . . . . . . . 39
Analysis 2.5. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 5 Cure rate. . . . . . . . . . . . 40
Analysis 2.6. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 6 Lost to follow up. . . . . . . . . 40
Analysis 2.7. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 7 Death rates. . . . . . . . . . . 41
Analysis 2.8. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 8 Organisms isolated on blood culture. . 41
Analysis 2.9. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 9 H. influenzae on blood culture. . . . 42
Analysis 2.10. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 10 S. pneumoniae on blood culture. . . 42
Analysis 3.1. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 1 Adverse events. . . . 43
Analysis 3.2. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 2 Death. . . . . . . 43
Analysis 3.3. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 3 Change of antibiotics. . 44
Analysis 3.4. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 4 Readmission before 30 days. 44
Analysis 3.5. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 5 Absconded. . . . . 45
Analysis 3.6. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 6 Hospitalization rate. . 45
Analysis 3.7. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 7 Age (months). . . . . 46
Analysis 3.8. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 8 Culture positive. . . . 46
Analysis 3.9. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 9 Male sex. . . . . . 47
Analysis 3.10. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 10 Received antibiotics in
previous one week. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Analysis 3.11. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 11 Lost to follow up. . 48
Analysis 4.1. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 1 Poor or no response. . . . . 48
Analysis 4.2. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 2 Cure rate. . . . . . . . 49
Analysis 4.3. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 3 Complications. . . . . . . 49
Analysis 4.4. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 4 Age (months). . . . . . . 50
Analysis 4.5. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 5 Weight. . . . . . . . . 50
Analysis 4.6. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 6 Male sex. . . . . . . . . 51
Analysis 4.7. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 7 Wheeze present. . . . . . 51
Antibiotics for community acquired pneumonia in children (Review) i
Analysis 4.8. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 8 Cure rate. . . . . . . . 52
Analysis 4.9. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 9 Side effects. . . . . . . . 52
Analysis 5.1. Comparison 5 Benzathin penicillin versus procaine penicillin, Outcome 1 Cure rate. . . . . . . . 53
Analysis 5.2. Comparison 5 Benzathin penicillin versus procaine penicillin, Outcome 2 Failure rate. . . . . . . 53
Analysis 5.3. Comparison 5 Benzathin penicillin versus procaine penicillin, Outcome 3 Male Sex. . . . . . . . 54
Analysis 5.4. Comparison 5 Benzathin penicillin versus procaine penicillin, Outcome 4 Age between two to six years. 54
Analysis 5.5. Comparison 5 Benzathin penicillin versus procaine penicillin, Outcome 5 Age between 7 to 12 years. . 55
Analysis 5.6. Comparison 5 Benzathin penicillin versus procaine penicillin, Outcome 6 Lost to follow up. . . . . 55
Analysis 6.1. Comparison 6 Amoxycillin versus penicillin, Outcome 1 Nasopharyngeal aspirates for S. pneumoniae. . 56
Analysis 6.2. Comparison 6 Amoxycillin versus penicillin, Outcome 2 Age less than one year. . . . . . . . . 56
Analysis 6.3. Comparison 6 Amoxycillin versus penicillin, Outcome 3 Male sex. . . . . . . . . . . . . . 57
Analysis 6.4. Comparison 6 Amoxycillin versus penicillin, Outcome 4 Weight below 2 Z score (indicating severe
malnutrition). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Analysis 6.5. Comparison 6 Amoxycillin versus penicillin, Outcome 5 Breast fed. . . . . . . . . . . . . . 58
Analysis 6.6. Comparison 6 Amoxycillin versus penicillin, Outcome 6 Received antibiotics in last one week. . . . 58
Analysis 6.7. Comparison 6 Amoxycillin versus penicillin, Outcome 7 Failure rate at 48 hours. . . . . . . . . 59
Analysis 6.8. Comparison 6 Amoxycillin versus penicillin, Outcome 8 Failure rate on day five. . . . . . . . . 59
Analysis 6.9. Comparison 6 Amoxycillin versus penicillin, Outcome 9 Failure rate on day 14. . . . . . . . . 60
Analysis 6.10. Comparison 6 Amoxycillin versus penicillin, Outcome 10 Death rates. . . . . . . . . . . . 60
Analysis 6.11. Comparison 6 Amoxycillin versus penicillin, Outcome 11 Nasopharyngeal H. influenzae. . . . . . 61
Analysis 6.12. Comparison 6 Amoxycillin versus penicillin, Outcome 12 Respiratory syncytial virus (RSV) in nasopharyngeal
swabs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Analysis 7.1. Comparison 7 Cefpodoxime versus co-amoxyclavulanic acid, Outcome 1 Cure rate (response rate) at end of
treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Analysis 7.2. Comparison 7 Cefpodoxime versus co-amoxyclavulanic acid, Outcome 2 Mean age (months). . . . 62
Analysis 7.3. Comparison 7 Cefpodoxime versus co-amoxyclavulanic acid, Outcome 3 Adverse effects. . . . . . 63
Analysis 7.4. Comparison 7 Cefpodoxime versus co-amoxyclavulanic acid, Outcome 4 Age in years. . . . . . . 63
Analysis 7.5. Comparison 7 Cefpodoxime versus co-amoxyclavulanic acid, Outcome 5 Follow up. . . . . . . . 64
Analysis 8.1. Comparison 8 Ampicillin alone versus penicillin with chloramphenicol, Outcome 1 Cure rates. . . . 64
Analysis 8.2. Comparison 8 Ampicillin alone versus penicillin with chloramphenicol, Outcome 2 Age (months). . . 65
Analysis 8.3. Comparison 8 Ampicillin alone versus penicillin with chloramphenicol, Outcome 3 Male sex. . . . . 65
Analysis 8.4. Comparison 8 Ampicillin alone versus penicillin with chloramphenicol, Outcome 4 Duration of hospital
stay. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
Analysis 8.5. Comparison 8 Ampicillin alone versus penicillin with chloramphenicol, Outcome 5 Grade 2 to 4
malnutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
Analysis 9.1. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 1 Age less than one year. . . . . 67
Analysis 9.2. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 2 Age one to five years. . . . . 67
Analysis 9.3. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 3 Age 5 to 12 years. . . . . . . 68
Analysis 9.4. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 4 Duration of illness in days. . . 68
Analysis 9.5. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 5 Male sex. . . . . . . . . . 69
Analysis 9.6. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 6 Cure rate. . . . . . . . . 69
Analysis 9.7. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 7 Hospitalization rate. . . . . . 70
Analysis 9.8. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 8 Well at end of follow up. . . . 70
Analysis 9.9. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 9 Death. . . . . . . . . . 71
Analysis 9.10. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 10 Treatment failure. . . . . . 71
Analysis 10.1. Comparison 10 Co-trimoxzole versus procaine penicillin and ampicillin, Outcome 1 Mean age in months. 72
Analysis 10.2. Comparison 10 Co-trimoxzole versus procaine penicillin and ampicillin, Outcome 2 Age less than one
year. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72
Analysis 10.3. Comparison 10 Co-trimoxzole versus procaine penicillin and ampicillin, Outcome 3 Male sex. . . . 73
Analysis 10.4. Comparison 10 Co-trimoxzole versus procaine penicillin and ampicillin, Outcome 4 Cure rate. . . . 73
Analysis 10.5. Comparison 10 Co-trimoxzole versus procaine penicillin and ampicillin, Outcome 5 Hospitalization rate. 74
Analysis 10.6. Comparison 10 Co-trimoxzole versus procaine penicillin and ampicillin, Outcome 6 Death rate. . . 74
Analysis 11.1. Comparison 11 Azithromycin versus amoxycilin, Outcome 1 Age in months. . . . . . . . . . 75
Antibiotics for community acquired pneumonia in children (Review) ii
Analysis 11.2. Comparison 11 Azithromycin versus amoxycilin, Outcome 2 Duration of illness. . . . . . . . . 75
Analysis 11.3. Comparison 11 Azithromycin versus amoxycilin, Outcome 3 Wheezing present. . . . . . . . . 76
Analysis 11.4. Comparison 11 Azithromycin versus amoxycilin, Outcome 4 Cure rate clinical. . . . . . . . . 76
Analysis 11.5. Comparison 11 Azithromycin versus amoxycilin, Outcome 5 Cure rate radiological. . . . . . . 77
Analysis 11.6. Comparison 11 Azithromycin versus amoxycilin, Outcome 6 Fever day seven. . . . . . . . . . 77
Analysis 12.1. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 1 Age less than one year. . . . . . . 78
Analysis 12.2. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 2 Male sex. . . . . . . . . . . 78
Analysis 12.3. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 3 Mean Z score for weight. . . . . . 79
Analysis 12.4. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 4 Received antibiotics in previous one week. 79
Analysis 12.5. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 5 Non-severe pneumonia. . . . . . 80
Analysis 12.6. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 6 Severe pneumonia. . . . . . . . 80
Analysis 12.7. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 7 Failure rate. . . . . . . . . . 81
Analysis 12.8. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 8 Failure rate non-severe pneumonia clinical
diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Analysis 12.9. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 9 Failure rate severe pneumonia clinical
diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
Analysis 12.10. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 10 Failure rate radiological positive
pneumonia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
Analysis 12.11. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 11 Failure rate radiological negative for
pneumonia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Analysis 12.12. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 12 Death rate. . . . . . . . . . 83
Analysis 12.13. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 13 Lost to follow up. . . . . . . 84
Analysis 12.14. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 14 Wheeze positive. . . . . . . . 84
Analysis 12.15. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 15 Cure rate. . . . . . . . . . 85
Analysis 12.16. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 16 Change of antibiotics. . . . . . 85
Analysis 13.1. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 1 Age in months. . . . . . . 86
Analysis 13.2. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 2 Male sex. . . . . . . . . 86
Analysis 13.3. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 3 Weight for age. . . . . . . 87
Analysis 13.4. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 4 Wheezing positive. . . . . . 87
Analysis 13.5. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 5 Cure rate. . . . . . . . . 88
Analysis 13.6. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 6 Failure rate. . . . . . . . 88
Analysis 13.7. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 7 Excluded. . . . . . . . . 89
Analysis 13.8. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 8 Relapse rate. . . . . . . . 89
Analysis 13.9. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 9 Need for change in antibiotics. . 90
Analysis 13.10. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 10 Death rate. . . . . . . . 90
Analysis 13.11. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 11 Organisms isolated on blood culture
or lung puncture. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Analysis 14.1. Comparison 14 Co-trimoxazole versus co-amoxyclavulanic acid, Outcome 1 Children below one year of
age. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Analysis 14.2. Comparison 14 Co-trimoxazole versus co-amoxyclavulanic acid, Outcome 2 Male sex. . . . . . . 92
Analysis 14.3. Comparison 14 Co-trimoxazole versus co-amoxyclavulanic acid, Outcome 3 Failure rate. . . . . . 92
Analysis 15.1. Comparison 15 Amoxycillin versus cefpodoxime, Outcome 1 Age in months. . . . . . . . . . 93
Analysis 15.2. Comparison 15 Amoxycillin versus cefpodoxime, Outcome 2 Male sex. . . . . . . . . . . . 93
Analysis 15.3. Comparison 15 Amoxycillin versus cefpodoxime, Outcome 3 Response/cure rate. . . . . . . . 94
Analysis 16.1. Comparison 16 Amoxycillin versus chloramphenicol, Outcome 1 Age (mean/median). . . . . . . 94
Analysis 16.2. Comparison 16 Amoxycillin versus chloramphenicol, Outcome 2 Male sex. . . . . . . . . . 95
Analysis 16.3. Comparison 16 Amoxycillin versus chloramphenicol, Outcome 3 Cure rate. . . . . . . . . . 95
Analysis 16.4. Comparison 16 Amoxycillin versus chloramphenicol, Outcome 4 Failure rates. . . . . . . . . 96
Analysis 17.1. Comparison 17 Amoxycillin versus procaine penicillin, Outcome 1 Median age. . . . . . . . . 96
Analysis 17.2. Comparison 17 Amoxycillin versus procaine penicillin, Outcome 2 Failure rate. . . . . . . . . 97
Analysis 18.1. Comparison 18 Co-trimoxazole versus single dose procaine penicillin followed by oral ampicillin, Outcome
1 Mean age (months). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Antibiotics for community acquired pneumonia in children (Review) iii

2 Male sex. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
3 Cure rate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
4 Hospitalization rate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
5 Death rate. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Analysis 19.1. Comparison 19 Azithromycin versus co-amoxyclavulanic acid, Outcome 1 Cure rate. . . . . . . 100
Analysis 19.2. Comparison 19 Azithromycin versus co-amoxyclavulanic acid, Outcome 2 Failure rate. . . . . . 100
Analysis 19.3. Comparison 19 Azithromycin versus co-amoxyclavulanic acid, Outcome 3 Improved. . . . . . . 101
Analysis 19.4. Comparison 19 Azithromycin versus co-amoxyclavulanic acid, Outcome 4 Side effects. . . . . . 101
Analysis 19.5. Comparison 19 Azithromycin versus co-amoxyclavulanic acid, Outcome 5 Organisms isolated. . . . 102
Analysis 19.6. Comparison 19 Azithromycin versus co-amoxyclavulanic acid, Outcome 6 Mycoplasma serology positive. 102
Analysis 20.1. Comparison 20 Chloramphenicol versus chloramphenicol plus penicillin, Outcome 1 Need for change of
antibiotics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103
Analysis 20.2. Comparison 20 Chloramphenicol versus chloramphenicol plus penicillin, Outcome 2 Death rates. . 103
Analysis 20.3. Comparison 20 Chloramphenicol versus chloramphenicol plus penicillin, Outcome 3 Lost to follow up. 104
Analysis 21.1. Comparison 21 Chloramphenicol plus penicillin versus ceftrioxone, Outcome 1 Cure rates. . . . . 104
Analysis 22.1. Comparison 22 Clarithromycin versus erythromycin, Outcome 1 Age below five years. . . . . . . 105
Analysis 22.2. Comparison 22 Clarithromycin versus erythromycin, Outcome 2 Cure rates. . . . . . . . . . 105
Analysis 22.3. Comparison 22 Clarithromycin versus erythromycin, Outcome 3 Clinical success rate. . . . . . . 106
Analysis 22.4. Comparison 22 Clarithromycin versus erythromycin, Outcome 4 Failure rates. . . . . . . . . 106
Analysis 22.5. Comparison 22 Clarithromycin versus erythromycin, Outcome 5 Relapse rates. . . . . . . . . 107
Analysis 22.6. Comparison 22 Clarithromycin versus erythromycin, Outcome 6 Radiologic resolution. . . . . . 107
Analysis 22.7. Comparison 22 Clarithromycin versus erythromycin, Outcome 7 Radiologic success. . . . . . . 108
Analysis 22.8. Comparison 22 Clarithromycin versus erythromycin, Outcome 8 Radiologic failure. . . . . . . 108
Analysis 22.9. Comparison 22 Clarithromycin versus erythromycin, Outcome 9 Adverse events. . . . . . . . 109
Analysis 22.10. Comparison 22 Clarithromycin versus erythromycin, Outcome 10 Bacteriologic response. . . . . 109
APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111
Antibiotics for community acquired pneumonia in children (Review) iv

[Intervention Review]
Antibiotics for community acquired pneumonia in children
Sushil K Kabra1 , Rakesh Lodha2 , R M Pandey3

1 Pediatric Pulmonology Division, Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, India. 2 Department
of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, India. 3 Department of Biostatistics, All India Institute of Medical
Sciences, Ansari Nagar, India
Contact address: Sushil K Kabra, Pediatric Pulmonology Division, Department of Pediatrics, All India Institute of Medical Sciences,
Ansari Nagar, New Delhi, 110029, India. skkabra@rediffmail.com. (Editorial group: Cochrane Acute Respiratory Infections Group.)
Cochrane Database of Systematic Reviews, Issue 4, 2009 (Status in this issue: Unchanged)
DOI: 10.1002/14651858.CD004874.pub2
This version first published online: 19 July 2006 in Issue 3, 2006.
Last assessed as up-to-date: 7 May 2006. (Help document - Dates and Statuses explained)
This record should be cited as: Kabra SK, Lodha R, Pandey RM. Antibiotics for community acquired pneumonia in children.
Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004874. DOI: 10.1002/14651858.CD004874.pub2.
ABSTRACT
Background
Pneumonia is the leading cause of mortality in children. In developing countries, pneumonia is usually caused by bacterial pathogens.
The early administration of empirical antibiotics improves the patients’ clinical outcomes. There are currently no systematic reviews of
clinical trials on this subject.
Objectives
To identify effective antibiotic drug therapy for community acquired pneumonia (CAP) in children by comparing various antibiotics.
Search strategy
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2005, issue 4) which contains
the Acute Respiratory Infections Groups specialized register, MEDLINE (OVID) (1966 to January 2006) and EMBASE (WebSPIRS)
(1990 to September 2005).
Selection criteria
Randomized controlled trials (RCTs) in children of either sex, which compared at least two antibiotics for CAP in hospital or ambulatory
settings.
Data collection and analysis
Data from full articles of selected studies were independently extracted by two authors.
Main results
The review of these studies suggests that for treatment of pneumonia, co-trimoxazole is inferior in efficacy to both amoxycillin (failure
rates odds ratio (OR) 1.33; 95% CI 1.05 to 1.67) and procaine penicillin (cure rates OR 2.64; 95% CI 1.57 to 4.45). Penicillin in
conjunction with gentamycin was better than chloramphenicol alone (re-hospitalization rates OR 1.61; 95% CI 1.02 to 2.55). Co-
amoxyclavulanic acid was better than amoxycillin alone (cure rates OR 10.44; 95% CI 2.85 to 38.21). There was no differences between
injectable penicillin and oral amoxycillin (failure rates OR 1.03; 95% CI 0.81 to 1.31); azithromycin and erythromycin (cure rates
OR 1.17; 95% CI 0.70 to 1.95); cefpodoxime and amoxycillin (cure rates OR 0.69; 95% CI 0.18 to 2.60); or azithromycin and co-
amoxyclavulanic acid (cure rates OR 1.02; 95% CI 0.54 to 1.95, failure rates OR 1.42; 95% CI 0.43 to 4.66).
Antibiotics for community acquired pneumonia in children (Review) 1
Authors’ conclusions
There were many studies each investigating multiple antibiotics with different methodologies. For treatment of ambulatory patients
with CAP, amoxycillin was better than co-trimoxazole; there was no difference between azithromycin and erythromycin, or between
cefpodoxime and co-amoxyclavulanic acid. For hospitalized patients, procaine penicillin was better than co-trimoxazole; and the
combination of penicillin and gentamycin was better than chloramphenicol alone. Injectable penicillin and oral amoxycillin had similar
failure rates. For the rest of the antibiotics there were only single studies available. There is a need for more studies with large patient
populations and similar methodologies in order to compare newer antibiotics.
PLAIN LANGUAGE SUMMARY
We compared different antibiotics for community acquired pneumonia in children below 18 years of age in both hospital and
ambulatory settings
Pneumonia is the leading cause of mortality in children under five years of age. Most community acquired pneumonia in developing
countries is caused by bacteria. This systematic review found 20 randomized controlled trials comparing antibiotics, most by single
studies only. We found that: for ambulatory treatment of pneumonia, amoxycillin or procaine penicillin are more effective than co-
trimoxazole; for treatment of hospitalized children with pneumonia, a combination of penicillin and gentamycin is more effective than
chloramphenicol alone; for hospitalized treatment of pneumonia, oral amoxycillin gives a similar result to injectable penicillin.
BACKGROUND
formed routinely in most cases. The yield from blood cultures is
5% to 15% for bacterial pathogens, and cannot be relied upon (
Mac Cracken 2000).
Description of the condition
Pneumonia is the leading cause of mortality and a common cause
of morbidity especially in children under five years of age. In de-
veloping countries, pneumonia kills three million children every
year (Kirkwood 1995; WHO 1999). It is responsible for 19% of
all deaths in children under five years of age and for 8.2% of all
Description of the intervention
disabilities and premature mortality as measured by disability ad- Administration of appropriate antibiotics at an early stage of pneu-
justed life years (DALYs) (Kabra 1999). The etiology of pneumo- monia improves the outcome of the illness, particularly when the
nia in this group is bacterial in most cases (Berman 1990). A review causative agent is bacterial. To meet the public health goal of re-
of 14 studies involving 1096 lung aspirates taken from hospital- ducing the child mortality due to pneumonia, empirical antibiotic
ized children prior to administration of antibiotics reported bac- administration is relied upon in most instances. This is necessary
terial pathogens in 62% (Berman 1990). In 27% of patients the in view of the inability of most commonly available laboratory
common bacterial pathogens identified were Streptococcus pneumo- tests to identify causative pathogens. The World Health Organiza-
niae (S. pneumoniae) and Haemophilus influenzae (H. influenzae) tion (WHO) has suggested diagnosis and assessment of the sever-
(Berman 1990). In infants under three months of age, common ity of pneumonia on the basis of clinical features (WHOYISG
pathogens include S. pneumoniae, H. influenzae, gram-negative 1999) and suggests administration of co-trimoxazole for most
bacilli, and Staphylococcus (WHOYISG 1999). The causative or- cases. The commonly used antibiotics for CAP include co-trimox-
ganisms are different in developed countries and include more viral azole, amoxycillin, oral cephalosporins and macrolide drugs. De-
and atypical organisms (Gendrel 1997; Ishiwada 1993; Numazaki spite evidence of rising bacterial resistance to co-trimoxazole (IBIS
2004; Wubbel 1999). It is very difficult to identify the causative 1999; Timothy 1993), studies conducted in the same time period
organism in most cases of pneumonia. The common methods showed good clinical efficacy of oral co-trimoxazole for non-se-
used for identification of the etiologic agents include blood cul- vere pneumonia (Rasmussen 1997; Straus 1998). However, one
ture, lung puncture, nasopharyngeal aspiration, immune assays study reported a doubling of clinical failure rates for co-trimoxa-
of blood and urine tests. Lung puncture is an invasive procedure zole treatment when compared to treatment with amoxicillin in
associated with significant morbidity and hence cannot be per- severe and radiologically confirmed pneumonia (Straus 1998).
Why it is important to do this review The clinically relevant outcome measures were:
Amoxycillin has been recommended as a suitable alternative be- • treatment failure rate;
cause of its proven efficacy against S. pneumoniae and H. influen- • relapse rate;
zae. With emerging evidence that atypical organisms (Chlamydia • hospitalization rate (in outpatient studies only);
and Mycoplasma species (spp)) may be playing important roles • length of stay in hospital.
in the development of CAP (Chaudhary 1998; Normann 1998),
macrolide antibiotics may become first line empirical treatment
Complications
for CAP. In view of the difficulty in isolating causative agents it
is important to identify the most effective treatment of CAP. At These included:
present there are no systematic reviews of clinical trials on this • need for change in antibiotics;
subject. • additional interventions used;
• mortality rate.
Clinical cure
OBJECTIVES
Defined as:
To identify effective antibiotic drug therapies for CAP in children
by comparing various antibiotics. • symptomatic and clinical recovery by the end of treat-
ment.
METHODS Treatment failure

Defined as:
• development of chest in-drawing;

Criteria for considering studies for this review • convulsions;
• drowsiness or inability to drink at any time;
Types of studies • respiratory rate above the age-specific cut-off point on
completion of treatment, or oxygen saturation of less
Randomized controlled trials (RCTs) comparing antibiotics for
than 90% (measured by pulse oximetry) after comple-
CAP in children. Only studies using the case definition of pneu-
tion of the treatment;
monia (as given by the WHO) or radiologically confirmed pneu-
• Loss to follow up or withdrawal from the study at any
monia were considered in this review.
time after recruitment was taken as failure in the anal-
ysis.
Types of participants
Children under 18 years of age with CAP treated in a hospital or on Relapse
an ambulatory basis. Studies describing pneumonia post-hospital-
Defined as:
ization in immunocompromised patients (for example following
surgical procedures) were not included in this review. • recurrence of signs of pneumonia or severe disease
within 14 days after completion of treatment.
Types of interventions
Any intervention with antibiotics (administered by intravenous
route, intramuscular route, or orally) compared with another an- Search methods for identification of studies
tibiotic.
Electronic searches
Types of outcome measures
We searched the Cochrane Central Register of Controlled Trials
(CENTRAL) (The Cochrane Library, 2005, issue 4) which con-
Primary outcomes
tains the Acute Respiratory Infections Groups specialized register,
• clinical cure MEDLINE (OVID) (1966 to January 2006) and EMBASE (Web-
SPIRS) (1990 to September 2005). There were no language or
publication restrictions. We combined the MEDLINE search with
Secondary outcomes
the highly sensitive search strategy for identifying controlled trials,

as designed by Dickersin et al (Dickersin 1994). See Appendix 1 Assessment of risk of bias in included studies
for the EMBASE search strategy. The quality of the studies was assessed using empirically derived
MEDLINE (OVID) items. We used the previously validated Jadad five point scale to
1 exp PNEUMONIA/ assess: randomization (zero to two points); double-blinding (zero
2 pneumonia to two points); and withdrawals and dropouts (zero to one point) (
3 or/1-2 Jadad 1996). Concealment of allocation was described as adequate,
4 exp Anti-Bacterial Agents/ inadequate or unclear (Schulz 1995). Sponsorship of studies was
5 antibiotic$ coded as either from a pharmaceutical company, other source, or
6 or/4-5 not mentioned (Cho 1996). Two authors (SKK and RL) assessed
7 exp CHILD/ quality and inter rater agreement was measured by the intra-class
8 exp INFANT/ correlation (Bartko 1994).
9 (children or infant$ or pediatric or paediatric)
10 or/7-9
Assessment of heterogeneity
11 3 and 6 and 10
In cases of heterogeneity between the studies efforts were made
to explore the causes. For example, they could be due to factors
Searching other resources such as resistance to study antibiotics. Fixed-effect or random-
We also searched bibliographies of selected articles to identify any effects models were used, as appropriate. A sensitivity analysis was
further trials not extracted by the search methods. performed to check the importance of each study in order to see
the effect of inclusion and exclusion criteria. Both the effect size
and summary measures with 95% confidence intervals (CI) were
computed. We did multiple analyses, firstly on studies comparing
Data collection and analysis the same antibiotics.
Assessment of reporting biases

Selection of studies
Before combining the study results we checked for publication bias
Two review authors (SKK and RL) selected potentially relevant
by using a funnel plot. For each of the outcome variables (cure rate,
studies based on their title and abstract. The complete texts of
failure rate, relapse rate, rate of hospitalization, the complications
these studies were retrieved electronically or by contacting the trial
need for change in antibiotics and mortality rate) a two-by-two
authors. The studies were independently reviewed for inclusion
table was used for each study and Breslow’s test of homogeneity
by the two review authors. Differences as to which studies should
was performed to determine variation in study results.
be included were resolved by discussion.
We also attempted to do indirect comparisons of various drugs
when studies on direct comparisons were not available. For ex-
Data extraction and management ample, we compared antibiotics A and C when a comparison of
After identification of relevant studies, the papers were masked antibiotics A and B was available and likewise a separate compar-
by obscuring the authors’ names and institutions, the location of ison between antibiotics B and C. This type of comparison was
the study, reference lists and any other potential identifiers and done only if the inclusion and exclusion criteria of these studies,
given a serial number by a person who was not involved in the the dose and duration of the common intervention (antibiotic B),
review. Data extraction was independently carried out by two au- baseline characteristics and the outcomes assessed were similar (
thors (SKK and RL). After data extraction was completed the data Bucher 1997).
was checked by a third author (RP). Data were extracted using a
structured form to define the patient’s status (inpatient or outpa-
tient); the intervention (antibiotic) and its control; the name of
the antibiotic; the route of administration; the dose and duration RESULTS
of the intervention; the age and sex distribution of patients and
associated clinical manifestations.
Data were collected on the primary outcome, cure rate; and sec- Description of studies
ondary outcomes: failure rate, relapse rate, rate of hospitalization
See: Characteristics of included studies; Characteristics of excluded
and complications: need for change in antibiotics, need for addi-
studies.
tional interventions and mortality. Additional data on potential
confounders such as underlying disease, prior antibiotic therapy
and nutritional status were also recorded when available. Results of the search

The article titles were screened by two authors (SKK and RL). • Cefpodoxime with co-amoxyclavulanic acid (Klein
Thirty-six studies were short listed as potential RCTs to be in- 1995), involving 348 children aged 3 months to 11.5
cluded and we attempted to collect the full text articles of these years.
studies. Full text articles were obtained for 35 studies. These were • Azithromycin with amoxycillin (Kogan 2003), involv-
blinded by a third person who was not involved in the review. ing 47 children aged 1 month to 14 years.
Data were independently extracted by two authors (SKK and RL) • Amoxycillin with co-amoxyclavulanic acid (Jibril
using a pre-designed data extraction form. The data extracted were 1989), involving 100 children aged 2 months to 12
matched completely except for one study (Harris 1998); differ- years.
ences were resolved by consensus. • Chloramphenicol in addition to penicillin with ceftri-
axone (Cetinkaya 2004), involving 97 children aged be-
tween 2 to 24 months admitted to hospital with severe
Included studies pneumonia.
The included (20) studies made the following comparisons. • Clarithromycin with erythromycin (Block 1995), in-
volving 260 children between 3 to 12 years of age with
• Azithromycin with erythromycin (Harris 1998; Kogan radiographically diagnosed pneumonia treated on an
2003; Roord 1996; Wubbel 1999), involving 457 chil- ambulatory basis.
dren aged 2 months to 16 years.
• Co-trimoxazole with amoxycillin (CATCHUP 2002; Excluded studies
Straus 1998), involving 2066 children aged 2 months A total of 16 studies were excluded:
to 59 months.
• Co-trimoxazole with procaine penicillin (Keeley 1990; • four studies were carried out in adult patients (Bonvehi
Sidal 1994), involving 723 children aged 3 months to 2003; Fogarty 2002; Higuera 1996; van Zyl 2002);
12 years. • three studies included children with severe infections
• Chloramphenicol with penicillin and gentamycin to- or sepsis (Haffejee 1984; Mouallem 1976; Vuori-
gether (Duke 2002), involving 1116 children aged 1 Holopaine 2000);
month to 5 years. • one did not provide separate data for children (Sanchez
• Amoxycillin with co-amoxyclavulanic acid (Jibril 1998);
1989), involving 100 children aged 2 to 12 years. • two studies were not RCTs (Agostoni 1988; Paupe
• Single dose benzathine penicillin with procaine peni- 1992);
cillin (Camargos 1997; Sidal 1994), involving 176 chil- • three studies only compared the duration of antibi-
dren between 2 and 12 years of age in one study (Sidal otic use (Ahmad-Hasali 2005; Petola 2001; Ruhrmann
1994) and 105 children aged between 3 months to 14 1982);
years in the other similar study (Camargos 1997). • one studied only sequential antibiotic use (Al-Eiden
• Amoxycillin with procaine penicillin (Tsarouhas 1998), 1999);
involving 170 children aged 6 months to 18 years. • one compared azithromycin with symptomatic treat-
• Ampicillin with chloramphenicol and penicillin ( ment for recurrent respiratory tract infection only (
Deivanayagam 1996), involving 115 children aged five Esposito 2005); and
months to four years. • full text articles could not be obtained for one study (
• Co-trimoxazole with single dose procaine penicillin fol- Aurangzeb 2003).
lowed by oral ampicillin (Campbell 1988), involving
134 children aged below five years.
• Penicillin with amoxycillin (Addo-Yobo 2004), involv- Risk of bias in included studies
ing 1702 children aged 3 months to 59 months.
Using Jadad’s five point scale:
• Co-trimoxazole with chloramphenicol (Mulholland
1995), involving 111 children aged under five years. • four studies had a score of five;
• Azithromycin with co-amoxyclavulanic acid (Harris • one study had a score of four;
1998; Wubbel 1999), involving 283 children aged un- • eight studies had a score of three; and
der five years. • seven studies had a score of two (Table 1).

Table 1. Quality assessment using Jadad’s score
Study Randomization (0-2) Double blinding (0-2 Withdrawals (0-1) Total
Duke et al 2 0 1 3
Jibril et al 1 0 1 2
Camargos et al 2 0 1 3
Keeley et al 2 0 1 3
Campbell et al 2 0 1 3
Kogan et al 1 0 1 2
Addo-yobo et al 2 0 1 3
Roord et al 1 0 1 2
Klein et al 1 0 1 2
Shann et al 2 0 0 2
Straus et al 2 2 1 5
Mulholland et al 2 2 0 4
Harris et al 2 2 1 5
CATCHUP study group 2 2 1 5
Sidal et al 2 0 1 3
Deivanayagam et al 2 0 1 3
Tsarouhaset al 2 0 1 3
Cetinkaya et al 2 2 1 5
Block et al 2 0 0 2
Wubbel et al 2 0 0 2
performed to detect the impact of individual studies in each of

There were only four comparisons that were investigated in more these four comparisons. The results did not change significantly.
than one study (azithromycin with erythromycin; co-trimoxazole Significant heterogeneity was observed for four variables (Table
with amoxycillin; co-trimoxazole with procaine penicillin; and sin- 1: variable 3, Table 9: variable 6, Table 12: variable 1 and Table
gle dose benzathine penicillin with procaine penicillin). As per the 16: variable 1). The random-effects model was applied to analyze
funnel plot, the results were in the same direction in all the studies these data.
included for combining the study results. A sensitivity analysis was
Other potential sources of bias H. influenzae in 79 children (52 in the co-trimoxazole group and
The source of funding was not mentioned in six studies (Cetinkaya 27 in the amoxycillin group) and S. pneumoniae in 49 children
2004; Deivanayagam 1996; Jibril 1989; Klein 1995; Sidal 1994; (36 in the co-trimoxazole group and 13 in the amoxycillin group).
Tsarouhas 1998). Five studies were funded by pharmaceutical The distribution was similar in the two groups.
companies (Block 1995; Duke 2002; Harris 1998; Roord 1996; Azithromycin with co-amoxyclavulanic acid: two studies (Harris
Wubbel 1999). Eight studies (Addo-Yobo 2004; Camargos 1997; 1998; Wubbel 1999) involving 283 children below five years of
Campbell 1988; Keeley 1990; Mulholland 1995; Shann 1985; age. One study (Harris 1998) scored five points on the Jadad scale
Sidal 1994; Straus 1998) were supported by the WHO, Medical while the other study (Wubbel 1999) scored two points. The cure
Research Council or universities. One study (CATCHUP 2002) rates (available for one study) (OR 1.02; 95% CI 0.54 to 1.95),
was supported by the WHO in addition to pharmaceutical com- failure rates (available for both studies) (OR 1.21; 95% CI 0.43
panies. Information on clearance by Ethics Committees or/ Insti- to 3.43) and improvement rates (OR 0.85; 95% CI 0.43 to 1.71)
tutional Review Boards was available for all except three studies ( were similar in the two groups. There were fewer side effects re-
Jibril 1989; Keeley 1990; Sidal 1994). ported in the with azithromycin group (OR 0.17; 95% CI 0.09 to
0.32). The organisms isolated were S. pneumoniae in 28 children,
H. influenzae in one, Mycoplasma pneumoniae (M. pneumoniae) in
Effects of interventions
36 and Chlamydia pneumoniae (C. pneumoniae) in 20. The sepa-
Studies compared the efficacy of multiple antibiotics. rate data for isolation of organisms in the two groups was available
in one study only (Harris 1998) only. The organisms isolated in
Studies comparing ambulatory treatment of this study (Harris 1998) were S. pneumoniae in one patient in the
pneumonia azithromycin group and H. influenzae in one patient in the same
azithromycin group. Investigations for mycoplasma were positive
Azithromycin with erythromycin: four studies (Harris 1998;
in 21 out of the 129 children (16%) tested in the azithromycin
Kogan 2003; Roord 1996; Wubbel 1999) including 623 children.
group and 9 out of the 66 children (14%) tested in the co-amoxy-
One study (Harris 1998) scored five points on Jadad’s scale and
clavulanic acid group. Investigations for C. pneumoniae were posi-
three studies (Kogan 2003; Roord 1996; Wubbel 1999) scored two
tive in 13 out of the 129 children (10%) tested in the azithromycin
points. The trials were not blinded. Information on the presence of
group and 4 out of the 66 children (6%) tested in the co-amoxy-
wheezing was available in two studies (Harris 1998; Kogan 2003):
clavulanic acid group.
104 out of 318 (33%) children had wheezing in the azithromycin
Co-trimoxazole with procaine penicillin: two studies (Keeley
group, while 62 out of 161 (39%) in the erythromycin group
1990; Sidal 1994) enrolled 723 children between 3 months to 12
experienced wheezing. The failure rates in the azithromycin and
years of age. Both studies scored three points on the Jadad scale.
erythromycin groups were 6 out of 236 (2.5%) and 7 out of 156
The cure rate was significantly better in the procaine penicillin
(4.4%) respectively (OR 0.6; 95% CI 0.19 to 1.93). There were no
group (OR 2.64; 95% CI 1.57 to 4.45). Rate of hospitalization
significant side effects in either group. Three studies reported data
was available in only one study and these data also favored procaine
on etiologic organisms separately for each of the two treatment
penicillin (OR 2.52; 95% CI 0.88 to 7.25). There was only one
groups (Harris 1998; Kogan 2003; Roord 1996). There were 234
death.
organisms identified in the azithromycin group and 135 in the
Cefpodoxime with co-amoxyclavulanic acid: one multicenter
erythromycin group (Roord 1996). The distribution of different
study (Klein 1995) enrolled 348 children between 3 months and
organisms was similar in the two groups. There were 24 organisms
11.5 years of age. The study scored two points on the Jadad scale.
identified in the fourth study (Wubbel 1999) with 59 participants
The age distribution in the two groups was comparable. The re-
tested.
sponse rate at the end of 10 days of treatment was comparable in
Co-trimoxazole with amoxycillin: two multicenter studies (
the two groups (OR 0.69; 95% CI 0.18 to 2.6). Organisms were
CATCHUP 2002; Straus 1998) involving 2054 children (1132 in
isolated in 59 cases. These organisms were H. influenzae in 28 par-
the co-trimoxazole group and 922 in the amoxycillin group) be-
ticipants (47.5%), S. pneumoniae in 14 (23%), M. catarrhalis in
tween 2 months and 59 months of age. The diagnosis of pneumo-
7 (11.9%) and H. parainfluenzae in 4 (6.8). There was no signifi-
nia was based on clinical evidence. Both the studies were double-
cant difference in the bacteriologic efficacy of either group (100%
blinded and scored five points on the Jadad scale. The failure rate
versus 96.4%).
was significantly higher in the co-trimoxazole group compared to
Amoxycillin with procaine penicillin: one study involving 170
the amoxycillin group (OR 1.33; 95% CI 1.05 to 1.671). The
children aged 6 months to 18 years (Tsarouhas 1998). The study
cure rate was available only for one study (CATCHUP 2002) and
scored three points on the Jadad scale. The age distribution in the
it was not different in either treatment group (OR 0.82; 95% CI
two groups was comparable. The failure rates were similar in the
0.63 to 1.08). Loss to follow up was comparable in the two groups
two groups (OR 0.75; 95% CI 0.17 to 3.25).
(OR 1.02; 95% CI 0.56 to 1.86). There were only two deaths in
Amoxycillin with co-amoxyclavulanic acid: one study involving
both the groups. The organisms isolated from blood cultures were

100 children between 2 and 12 years of age. It was an open- vored the penicillin-gentamycin combination over chlorampheni-
label study on children suffering from clinically diagnosed bacterial col (OR 1.6; 95% CI 1.02 to 2.55). Bacterial pathogens were iden-
pneumonia (Jibril 1989). The study scored two points on the tified in 144 children (67 in children receiving chloramphenicol
Jadad scale. Age and sex distribution, presence of wheeze and mean and 77 in the other group). Isolation rates or sensitivity of the
weight in the two groups were comparable. Cure rate was better organism and failure rates did not differ between the two groups.
with co-amoxyclavulanic acid (OR 10.44; 95% CI 2.85 to 38.21). Single dose benzathine penicillin with procaine penicillin: two
Azithromycin with amoxycillin: one study involving 47 children studies, one which included 176 children between 2 to 12 years
aged between 1 month and 14 years with classical pneumonia ( of age with chest X-ray films showing lobar consolidation or infil-
Kogan 2003). Children treated with azithromycin were older than tration (presumed streptococcal infection) (Camargos 1997) and
those treated with amoxycillin. The study scored two on the Jadad one study of 105 children between 3 months to 14 years of age (
scale. All children recovered at the end of treatment in both the Sidal 1994). Both studies scored three points on the Jadad scale.
groups. There were 19 organisms isolated out of the 47 children Cure rates were not significantly different between the two groups
tested (10 in the azithromycin group and 9 in the amoxycillin (OR 0.53; 95% CI 0.27 to 1.01). Failure rates were lower in the
group). The isolation rates were similar in the two groups. Organ- procaine penicillin group (OR 3.31; 95% CI 1.45 to 7.55). Bac-
isms included M. pneumoniae (in five and three children for the terial pathogens were identified in only one study. The isolation
azithromycin and amoxycillin groups, respectively), S. pneumo- rate for S. pneumoniae was 6 out of 90 blood cultures performed
niae (in four and three respectively) and others (in one and three, (four patients in the benzathine group and two in the procaine
respectively). penicillin group). The clinical outcome did not differ in relation
Co-trimoxazole with single dose procaine penicillin followed to the organism identified.
by oral ampicillin for five days: one study was included that had Injectable penicillin with amoxycillin: one multicenter study
enrolled 134 children below five years of age with severe pneu- involving 1702 children between 3 months and 59 months of age,
monia as defined by WHO criteria (Campbell 1988). The study suffering from severe pneumonia (diagnosed on the basis of WHO
scored three points on the Jadad scale. The cure rates (OR 1.15; criteria) (Addo-Yobo 2004). The study scored three points on the
95% CI 0.36 to 3.61), hospitalization rates (OR 1.57; 95% CI Jadad scale. Age, sex, severe malnutrition, breast feeding and the
0.25 to 9.72) and death rates were similar for the two groups. number of children who had received antibiotics in the last week
Clarithromycin with erythromycin: one single-blind multicen- were similar in both the groups. The failure rates measured at 48
ter study (Block 1995) involving 260 children between 3 to 12 hours, 5 days and 14 days were similar in both groups. There were
years of age with radiographically diagnosed pneumonia (Block seven deaths in the group receiving penicillin
1995). The study scored 2 points on the Jadad scale. The following Ampicillin with chloramphenicol plus penicillin: one trial in-
parameters were similar between the two groups: cure rates (OR volving 115 children between 5 months and 4 years of age (
1.61; 95% CI 0.84 to 3.08), clinical success rate (OR 1.92; 95% Deivanayagam 1996). The study scored three points on the Jadad
CI 0.45 to 8.23), failure rate (OR 0.52; 95% CI 0.12 to 2.23), re- scale. Age and sex distribution and proportion of children with
lapse rate (OR 0.17; 95% CI 0.02 to 1.45) and adverse events (OR severe malnutrition were comparable in the two groups. The cure
1.07; 95% CI 0.6 to 1.90). Resolution of pneumonia (diagnosed rates (OR 0.48; 95% CI 0.15 to 1.51) and duration of hospital-
radiologically) was more frequent in the clarithromycin group as ization were similar in the two groups (weighted mean difference
compared to the erythromycin group (OR 2.51; 95% CI 1.02 to (WMD) 0.1; 95% CI -1.13 to 0.93).
6.16). However, there were no differences in improvement rates Co-trimoxazole with chloramphenicol: one double-blind study
(OR 3.55; 95% CI 0.7 to 18.04) or decline rates (OR 0.34; 95% involving 111 malnourished children under five years of age (
CI 0.06 to 1.80), both of which were established with radiological Mulholland 1995). The study scored four points on the Jadad
evidence. scale. The age and sex distribution, nutritional status, children
with wheezing and numbers excluded were similar in the two
Studies comparing hospitalized treatment of groups. Cure rates (OR 1.06; 95% CI 0.47 to 2.40), failure rates
pneumonia (OR 1.03; 95% CI 0.45 to 2.33), number of patients requiring
a change in antibiotics (OR 1.42; 95% CI 0.46 to 4.40), relapse
Chloramphenicol with penicillin and gentamycin: one multi-
rates (OR 1.02; 95% CI 0.24 to 4.30) and death rates (OR 2.21;
center study including 1116 children aged between 1 month and
95% CI 0.63 to 7.83) were similar in the two groups.
5 years. This was an open RCT in children with severe pneumo-
Chloramphenicol plus penicillin with ceftriaxone: one double-
nia that was carried out in Papua New Guinea (Duke 2002). The
blind study involving 97 children between 2 to 24 months of
study scored three points on the Jadad scale. There was no sig-
age diagnosed with severe CAP with probable bacterial etiology (
nificant difference between the two groups in positive cultures,
Cetinkaya 2004). The study scored five points on the Jadad scale.
children who received antibiotics and loss to follow up. Need for
Ages in the two groups were comparable (details not available).
change in antibiotics, death rates and adverse events were similar
Cure rates in the two groups were similar (OR 1.36; 95% CI 0.47
in the two groups. However, re-admission rates before 30 days fa-

to 3.93).
Identification of etiological agents: out of 20 studies reviewed,
attempts were made to isolate or /demonstrate the etiological or-
ganisms in 10 studies. The method used for identification of bac-
teria was a blood culture in all studies. Some studies also used sero-
logical tests. For this review results of a throat swab for bacterial
isolation were ignored. Bacterial pathogens could be identified in
blood cultures or serology in 324 (8%) out of 4009 patients tested.
Out of the bacterial pathogens identified, 169 (52%) patients had
S. pneumoniae, 102 (32%) had H. influenzae, 11 (3%) had Staphy-
lococcus aureus (S. aureus) and 42 (13%) had other pathogens in-
cluding the gram negative bacilli M. catarrhalis and Staphylococcus
albus (S. albus) (Table 2). Information regarding the sensitivity pat-
tern of bacterial isolates was available in two studies (Mulholland
1995; Roord 1996). This information was only available for the
antibiotics studied. In the first study (Mulholland 1995) all 10
isolates of S. pneumoniae were susceptible to co-trimoxazole and
nine of these were also susceptible to chloramphenicol. All three
Salmonella spp. isolates were susceptible to co-trimoxazole and
chloramphenicol. A single isolate of H. influenzae was resistant
to co-trimoxazole. In the second study (Roord 1996) all 20 iso-
lates were sensitive to azithromycin while three organisms were
resistant to erythromycin. Nasopharyngeal aspirates were tested
for respiratory syncytial virus (RSV) in three studies (Addo-Yobo
2004; Mulholland 1995; Wubbel 1999) involving 1713 children.
RSV was identified in 394 children (23%). Identification of atyp-
ical organisms was attempted in four studies (Block 1995; Harris
1998; Kogan 2003; Wubbel 1999). Out of the 885 patients tested
for M. pneumoniae, 213 (24%) were tested positive. In patients
aged under five years 57 out of 388 (15%) tested positive to my-
coplasma. Tests for Chlamydia spp. were positive in 151 out of 825
(18%) patients. In children under five years there were positive
test results for Chlamydia spp. in 41 out of 388 (11%).
Table 2. Bacterial isolation
Study/total tested S. Pneumoniae H. Influenzae Staphylococcus Others
Duke et al/1116 4 10 10 36
Camargos et al/90 6 0 0 0
Kogan et al/47 7 0 0 4
Roord et al/95 11 19 1 13
Klein et al/348 14 28 0 17
Harris et al/351 5 2 0 0

Table 2. Bacterial isolation (Continued)
Mulholland et al/ 111 10 2 0 8
Straus et al/595 79 49 0 0
Block et al/ 122 2 2 0 0
Wubbel et al/ 129 35 0 0 0
Total/4009 169(4.2) 104 (2.6) 11(0.3%) 42(1.2)
Out of total bacteria 169/324 (52) 104/324(32) 11/ 324 (3.3) 42/ 324 (13)
penicillin and gentamycin was better than chloramphenicol alone,

Indirect comparison: we attempted to compare various antibi-
as the hospitalization rates and re-admission at 30 days were higher
otics (A and C) when comparisons of antibiotics A and B were
with chloramphenicol. For the other comparisons no significant
also available and B and C were available. We utilised this process
differences were observed.
to compare co-trimoxazole with co-amoxyclavulanic acid, amoxy-
cillin with chloramphenicol, amoxycillin with cefpodoxime and
amoxycillin with chloramphenicol. Baseline data of age and sex Overall completeness and applicability of
was not comparable in the first three comparisons and, there- evidence
fore, no valid comparison could be carried out. In the compar-
ison of amoxycillin with chloramphenicol (CATCHUP 2002; The WHO recommends treatment of non-severe pneumonia with
Mulholland 1995; Straus 1998), sex distribution was not compa- co-trimoxazole as a first line empirical antimicrobial treatment in
rable although age distribution was. Cure rates were better in the countries with an infant mortality higher than 40 per 1000 live
amoxycillin group compared to the chloramphenicol group (OR births (WHO 1991). This review suggests that amoxycillin or pro-
4.26; 95% CI 2.57 to 7.08) and failure rates were lower in the caine penicillin is more effective than co-trimoxazole. This find-
amoxycillin group (OR 0.64; 95% CI 0.41 to 1.00). ing has implications regarding the need to change the guidelines
to recommend amoxycillin or procaine penicillin instead of co-
trimoxazole for the empirical treatment of non-severe pneumonia.
It should be noted that amoxycillin is more expensive than co-tri-
moxazole for five days of treatment for a child weighing between
DISCUSSION 5 to 10 kg, in India (US $0.6 versus $0.3). Two recent studies (
Agarwal 2004; MASCOT Group 2002) reported similar cure rates
Summary of main results with amoxycillin given for three or five days. The cost of amoxy-
The aim of this review was to find out the most effective antibiotic cillin would be reduced to some extent if the treatment duration
for first-line empirical treatment. There was a limited number of amoxycillin is lowered to three days. Procaine penicillin is given
of RCTs fulfilling the inclusion criteria. Most of the antibiotic by intramuscular route and the patient needs to attend a health-
comparisons were available in single studies only. care facility daily for injections. In addition to this, the patient
This review suggests that failure rates were more common with may be exposed to side effects because of intramuscular injections.
co-trimoxazole than amoxycillin. Cure rates were better with pro- The WHO recommends admission to hospital and treatment with
caine penicillin than co-trimoxazole. A treatment combination of penicillin for severe pneumonia and with chloramphenicol for
very severe pneumonia (WHO 1999). In this review we could not atypical organisms are tetracycline and macrolides. In this review
separately identify children with severe and very severe pneumo- the studies that attempted to identify atypical organisms showed
nia. However, studies comparing injectable penicillins with oral equal cure rates between erythromycin and azithromycin. Two
amoxycillin in the treatment of severe pneumonia in hospitalized studies (Harris 1998; Wubbel 1999) comparing azithromycin with
patients suggest similar failure rates at 48 hours, 5 days and 14 co-amoxyclavulanic acid in children under five years of age also
days. These results are based on a single multicenter study involv- showed equal cure and failure rates. In these studies the incidence
ing 1702 children (Addo-Yobo 2004). The other relevant compar- of atypical organisms in children under 5 years of age was 15%
isons were between benzathine penicillin and procaine penicillin, and 11% for Mycoplasma spp. and Chlamydia, respectively. The
and a combination of penicillin and gentamycin with chloram- cure rates in children receiving co-amoxyclavulanic acid were com-
phenicol. The results of benzathine and procaine penicillin were parable to those receiving azithromycin. From this observation it
similar. Penicillin in combination with gentamycin was better than can be inferred that either the diagnostic tests used for atypical
chloramphenicol and, therefore, may be a better alternative for organisms in these studies may not indicate invasive infections or
treatment. the study was not adequately powered to detect small differences.
Cure and failure rates of CAP depend not only on the choice of Another important issue is the etiological role of atypical organ-
antibiotics but also on the etiology of the pneumonia, the sen- isms (Chlamydia and Mycoplasma spp.) in CAP (Chaudhary 1998;
sitivity pattern of the bacterial pathogen, the severity of disease Normann 1998; Pandey 2005). This review identified atypical or-
and any antibiotic usage in the recent past. While information on ganisms in four studies (Block 1995; Harris 1998; Kogan 2003;
resistance patterns was not included in the studies evaluated in the Wubbel 1999). Out of 885 children tested for M. pneumoniae, 213
review this is likely to be of major importance for the future - in (23%) tested positive. The positivity for Mycoplasma in children
terms of both clinical practice and research. under 5 years age was 15% (57/388). Chlamydia spp. was positive
In the management of CAP isolation of bacterial pathogens for in 151 out of the 825 children (18%). In children under 5 years of
making a decision about the choice of antibiotics is not feasi- age, the positive tests for Chlamydia spp. occurred in 41 out of 388
ble in most circumstances. Even if bacterial pathogens are iso- (11%). The most effective antibiotics against atypical organisms
lated, the child will need to be treated with empirical antibiotics are tetracycline and macrolides. In this review, the studies that at-
until the result of the culture is available. In this review iden- tempted to identify atypical organisms showed equal cure rates be-
tification of bacterial pathogens was attempted in ten studies ( tween erythromycin and azithromycin. Two studies (Harris 1998;
Block 1995; Camargos 1997; Duke 2002; Harris 1998; Klein Wubbel 1999) comparing azithromycin with co-amoxyclavulanic
1995; Kogan 2003; Mulholland 1995; Roord 1996; Straus 1998; acid in children under five years of age also showed equal cure and
Wubbel 1999). Pathogens could be isolated in only 8% of the failure rates. In these studies, the incidence of atypical organisms
study participants. S. pneumoniae and H. influenzae constituted in children under 5 years of age was 15% and 11% for Mycoplasma
84% of all the bacterial isolates. Therefore, the empirical antibiotic spp. and Chlamydia respectively. The cure rates in children receiv-
therapy for CAP should be effective against these two pathogens. ing co-amoxyclavulanic acid were comparable to those receiving
RSV could be isolated in 24% of the patients, suggesting that a azithromycin. From this observation it can be inferred that either
sizeable proportion of patients may have a viral etiology of CAP. the diagnostic tests used for atypical organisms in these studies
These patients may not need antibiotics. A child with viral pneu- may not indicate invasive infections, or the study was not ade-
monia can be identified from rapid diagnostic tests like nasopha- quately powered to detect small differences.
ryngeal aspirates (Maitreyi 2000), and can avoid administration Exposure to antibiotics in the recent past may adversely affect the
of antibiotics. However, the possibility of mixed infection (bacte- outcome of bacterial pneumonia as the chances of infection with
rial agents with viruses) has been observed in 10 to 40% of cases a resistant organism increases (Chenoweth 2000). In this review,
(Kabra 2003). At present, it is policy to treat all children with information on past antibiotic use was available in three studies (
pneumonia with antibiotics due to a lack of tests that can reliably Addo-Yobo 2004; Duke 2002; Straus 1998). The distribution of
rule out bacterial pneumonia. patients who had received antibiotics in the recent past was similar
Another important issue is the etiological role of atypical organ- in the two treatment groups. However, subgroup analysis was not
isms (Chlamydia and Mycoplasma spp.) in CAP (Chaudhary 1998; available in these studies. In a study comparing co-trimoxazole
Normann 1998; Pandey 2005). This review identified atypical or- and amoxicillin the number of patients who had received antibi-
ganisms in four studies (Block 1995; Harris 1998; Kogan 2003; otics in the recent past was higher in the amoxycillin group (34%
Wubbel 1999). Out of 885 children tested for M. pneumoniae, compared with 25.6% in the co-trimoxazole group) (Straus 1998).
213 (23%) tested positive. The positivity for Mycoplasma in chil- The failure rates were higher in the co-trimoxazole group (19%
dren under 5 years age was 15% (57/388). Chlamydia spp. testing compared with 16% in the amoxicillin group) (OR 1.33; 95%
was positive in 151 out of the 825 children (18%). In children CI 1.05 to 1.67). The cure rates were better in the amoxycillin
under 5 years of age, positive tests for Chlamydia spp. occurred compared to the co-trimoxazole group (81% in the co-trimoxazole
in 41 out of 388 (11%). The most effective antibiotics against group and 84% in the amoxycillin group) (OR 0.82; 95% CI 0.63

to 1.08) even though the proportion of children who had received For hospitalized patients, procaine penicillin is better than co-tri-
antibiotics in the past week was higher in the amoxycillin group. moxazole and the combination of penicillin and gentamycin is bet-
This may indirectly indicate the superior efficacy of amoxycillin ter than chloramphenicol alone. The data available for the follow-
over co-trimoxazole in the treatment of pneumonia; evident even ing comparisons were reported in single studies only: co-amoxy-
in those children who have recently received antibiotics. clavulanic acid with amoxycillin, azithromycin with amoxycillin,
Malnutrition may affect the treatment outcome of pneumonia. co-trimoxazole with chloramphenicol, amoxycillin with procaine
There was only one study in malnourished children (Mulholland penicillin, co-trimoxazole with single dose procaine penicillin fol-
1995) which compared co-trimoxazole and chloramphenicol. The lowed by oral ampicillin, co-trimoxazole with chloramphenicol
study did not show any significant difference in cure rates, failure and chloramphenicol in combination with penicillin with ceftri-
rates or a need for change in antibiotics. This suggests the antibi- axone. More RCTs are required for a review of these antibiotics in
otics have similar outcomes in malnourished children. order to make more accurate recommendations for their prescrip-
There are limitations on reviewing antibiotic usage in CAP. Com- tion.
parisons are often performed among groups of children for whom
identification of etiological agents is lacking. This means that if the Implications for research
distribution of viral cases is not uniform the conclusion regarding
There are many new antimicrobials available for the management
efficacy of antibiotics can be debatable. Several individual factors,
of non-severe and severe CAP. There is a need for more studies, us-
such as malnutrition, can deeply modify the evolution of CAP and
ing similar methodologies and large numbers of patients, to com-
the response to antibiotic therapy. In the present review only one
pare amoxycillin with co-amoxyclavulanic acid, macrolides with
study addressed this problem; it is highly probable that this issue
amoxycillin and amoxycillin with oral cephalosporins. A compar-
can influence the correct evaluation of the data. No data regarding
ison of co-trimoxazole with a three day course of oral amoxycillin
antibiotic resistance were reported in the majority of the studies.
will be of significant relevance to public health in low income
It is well known that in some cases the level of resistance to com-
countries.
monly used antibiotics can have great influence on the response
to therapy. The role of atypical bacteria in the determination of
CAP in children living in low income countries is not established,
probably because the methods for identifying these pathogens are
too complicated or too expensive, or both. These data are needed ACKNOWLEDGEMENTS
to more accurately define the best antibiotic therapy. We acknowledge help provided by the All India Institute of Medi-
cal Sciences, New Delhi, in providing access to the Internet. We ac-
knowledge the help provided by Elizabeth Dooley, Review Group
Co-ordinator and Ruth Foxlee, Trials Search Co-ordinator of the
Cochrane Acute Respiratory Infections Group for doing the EM-
AUTHORS’ CONCLUSIONS BASE search and getting full text articles of studies. We also ac-
knowledge the help provided by Dr Anurag Bajpai in masking
the study articles. We acknowledge the help provided by Dr GA
Implications for practice Prasad, Dr M Kunnimalaiyaan and Dr Sandhya Sanghi in retriev-
For treatment of ambulatory patients with CAP, amoxycillin is bet- ing some of the full text articles. Finally, we wish to thank the fol-
ter than co-trimoxazole. There is no apparent difference between lowing people for commenting on the draft review: Amy Zelmer,
azithromycin and erythromycin, azithromycin and co-amoxy- Nicola Principi, Feyzullah Cetinkaya, Mark Jones and Leonard
clavulanic acid or cefpodoxime and co-amoxyclavulanic acid. Leibovici.

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Harris 1998 {published data only} Tsarouhas 1998 {published data only}
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Indicates the major publication for the study

CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Addo-Yobo 2004
Methods RCT comparing amoxycillin and penicillin
Participants Children 3 to 59 months with severe pneumonia
Interventions Daily IM penicillin 200,000 IU/kg or PO amoxycillin 45 mg/kg/day
Outcomes Failure rate at 48 hours, 5 days and 14 days and death rate
Notes Exclusion criteria: asthma, audible wheeze, non-severe pneumonia, very severe disease, clinical HIV,
persistent vomiting, penicillin allergy
Risk of bias
Item Authors’ judgement Description
Allocation concealment? Unclear D - Not used
Block 1995
Methods RCT comparing clarithromycin with erythromycin in children with pneumonia
Participants Children between 3 to 16 years of age with radiographically diagnosed pneumonia
Interventions PO clarithromycin (15 mg/kg/day) for 10 days or erythromycin 40 mg/kg/day for 10 days
Outcomes Cure rates, resolution of signs and symptoms, improvement, improved but non-resolution of signs and
symptoms, failure or worsening
Notes Exclusion: hypersensitivity to macrolides, severe renal or hepatic diseases, active tuberculosis, severe in-
fections requiring intravenous antibiotics
Risk of bias
Allocation concealment? Unclear B - Unclear

Camargos 1997
Methods RCT comparing benzathine penicillin and procaine penicillin
Participants Children 2 years to 12 years with non severe pneumonia
Interventions Single dose of benzathine penicillin (600,000 U for patients below 20 kg weight and 1,200,000 U for
those above 20 kg), procaine penicillin 300,000 IU/kg/day IM for 7 days
Outcomes Cure rate, failure rate, lost to follow up
Notes Exclusion criteria: severe disease, atelectasis, post measles pneumonia, sickle cell cardiomyopathy, immun-
odeficiency, allergic to penicillin, hospitalization in previous 2 weeks
Risk of bias
Campbell 1988
Methods RCT comparing co-trimoxazole for 5 days and procaine penicillin single dose with ampicillin for 5 days
Participants Children 1 month to 4 years of age with non-severe pneumonia
Interventions Daily cotrimoxazole PO for 5 days or single dose procaine penicillin with daily PO ampicillin
Outcomes Cure rate, hospitalization rate and death rate
Notes Exclusion criteria: very severe disease, refusal of consent, unable to take tablets
Risk of bias
CATCHUP 2002
Methods RCT comparing amoxycillin and co-trimoxazole in non severe pneumonia
Participants Children 2 to 59 months with non-severe pneumonia
Interventions PO amoxycillin 25 mg/kg/day for 5 days or co-trimoxazole 20/4 mg/kg/day for 5 days

CATCHUP 2002 (Continued)
Outcomes Cure rate, failure rate, change of antibiotics
Notes Blinded, exclusion criteria: severe pneumonia, very severe disease, chronic illness, past history of 2 or more
episodes of wheeze, acute bronchial asthma, antibiotics in past 48 hours
Risk of bias
Allocation concealment? Yes A - Adequate
Cetinkaya 2004
Methods RCT comparing chloramphenicol in combination with penicillin with ceftriaxone
Participants Children aged 6 months to 16 years with clinical or radiological evidence of pneumonia
Interventions IV chloramphenicol 15 mg/kg every 6 hours plus penicillin 25,000 IU/kg every 4 hours for 10 days and
ceftriaxone 50 mg/kg every 12 hours
Outcomes Clinical recovery
Notes Blinded, children clinically diagnosed with bacterial pneumonia were enrolled
Risk of bias
Deivanayagam 1996
Methods RCT comparing ampicillin in combination with penicillin with chloramphenicol for pneumonia diag-
nosed by clinical/radiological evidence
Participants Children 5 months to 4 years with pneumonia admitted to hospital
Interventions IM/ IV ampicillin (100 mg/kg/day) for 48 hours than PO, IV penicillin (100000 IU/kg/day) plus chlo-
ramphenicol (100 mg/kg/day)
Outcomes Cure rate, failure rate

Deivanayagam 1996 (Continued)
Notes Not blinded. Exclusion criteria: acute bronchiolitis, allergy to penicillin, antibiotics in past two days, other
drugs by treating physician receiving anti-tuberculosis drugs
Risk of bias
Duke 2002
Methods RCT comparing chloramphenicol with combination of penicillin and gentamicin in children with severe
pneumonia
Participants Children aged 1 to 59 months age, with severe pneumonia
Interventions IM chloramphenicol (25 mg/ kg 6 hourly for at least 5 days) versus penicillin (50 mg/ kg 6 hourly ) and
gentamicin (7.5 mg/ kg/d single dose) for at least 5 days
Outcomes Adverse outcome (death, change in antibiotics, absconded, readmission within 30 days), rate of hospital-
ization, duration of hospital stay
Notes Not blinded

Exclusion criteria: wheezing, bronchiolitis, meningitis, tuberculosis, CHD, renal failure, jaundice, received
study antibiotics for more than 48 hours in last 1 week
Risk of bias
Harris 1998
Methods RCT comparing azithromycin, co-amoxyclavulanic acid and erythromycin in pneumonia
Participants Children aged 6 months to 16 years with clinical or radiological evidence of pneumonia
Interventions PO azithromycin (10 mg/kg/day 1 followed by 5 mg/kg/day for 4 days) or amoxycillin clavulanic acid
(40 mg/kg/day) for 10 days or erythromycin (40 mg/kg/day) for 10 days
Outcomes Cure rate (day 15 to 19), improvement rate, failure rate

Harris 1998 (Continued)
Notes Exclusion criteria: known hypersensitivity, intolerance to drugs, pregnancy, lactation, need for parental
antibiotics, severe pneumonia, antibiotics in past 72 hours, chronic steroid therapy, on carbamazepine,
ergotamine, terfenadine, loratadine
Risk of bias
Jibril 1989
Methods RCT comparing amoxycillin and co-amoxyclavulanic acid with amoxicillin alone in bacterial pneumonia
(non-severe)
Participants Children aged 2 years to 12 years age, with non-severe pneumonia
Interventions Amoxicillin and co-amoxyclavulanic acid (250 + 62.5 mg or 500 + 125 mg tds) with amoxicillin (250 mg
or 500 mg tds) for 10 days
Outcomes Poor or no response; cure rate
Notes Exclusion criteria: renal/ hepatic impairment; hypersensitivity to penicillin/cephalosporin
Risk of bias
Keeley 1990
Methods RCT comparing co-trimoxazole and procaine penicillin
Participants Children aged 3 months to 12 years with non severe pneumonia
Interventions Co-trimoxazole per oral for 5 days. Procaine penicillin IM daily for 5 days
Outcomes Cure rate, treatment failure, hospitalization, well at final follow up and death rate
Notes Exclusion criteria: children with chest indrawing, unable to feed and requiring immediate referral
Risk of bias

Keeley 1990 (Continued)
Klein 1995
Methods RCT comparing cefpodoxime and co-amoxyclavulanic acid in LRTI
Participants Children aged 3 months to 11.5 years
Interventions Cefpodoxime 5 to 12 mg/kg/day PO for 10 days or co-amoxyclavulanic acid 6 to 13 mg/kg/day for 10

days
Outcomes Response rate
Notes Exclusion criteria: nosocomial infection, antibiotics in past 48 hours, allergy to beta lactum, sus-
pected/confirmed TB congenital anomalies
Risk of bias
Allocation concealment? Unclear B - Unclear
Kogan 2003
Methods RCT comparing azithromycin and amoxycillin
Participants Children aged 1 month to 14 years with non severe pneumonia
Interventions Azithromycin (10 mg/kg/day) PO for 3 days or amoxycillin PO 75 mg/kg/day for 7 days
Outcomes Clinical and radiological cure rates fever on day 3 and day 7, chest x-ray on day 14
Notes Exclusion criteria: chronic pathology, preterm, received antibiotics in past 5 days
Risk of bias

Mulholland 1995
Methods RCT comparing chloramphenicol and co-trimoxazole in malnourished children with clinical or radiolog-
ical pneumonia
Participants Children below 5 years of age with malnutrition and clinical or radiological evidence of pneumonia
Interventions Cefpodoxime 5 to 12 mg/kg/day PO for 10 days or co-amoxyclavulanic acid 6 to 13 mg/kg/day for 10

days
Outcomes Cure rate, relapse rate, failure rate and exclusion, death rate
Notes Blinded
Exclusion criteria: already receiving antibiotics, clinical or radiological signs of TB, severe pneumonia
Risk of bias
Roord 1996
Methods RCT comparing azithromycin and erythromycin in non severe pneumonia (acute LRTI)
Participants Children aged 2 months to 16 years with non severe pneumonia (acute LRTI)
Interventions Azithromycin 10 mg/kg/day for 3 days or erythromycin 40 mg/kg/day for 10 days
Outcomes Cure rate, failure rate at day 10 to 14, improvement at day 10, and between days 25 to 30
Notes Exclusion criteria: not able to take oral medications, known hypersensitivity to azithromycin or ery-
thromycin, cystic fibrosis, immunodeficiency, need for oxygen, nosocomial pneumonia, leucocyte count
less than 3 to 105, bacteraemia, receiving alternative treatment
Risk of bias

Shann 1985
Methods RCT comparing chloramphenicol and chloramphenicol in combination with penicillin in severe pneu-
monia
Participants Children
Interventions IM chloramphenicol daily until switched over to oral, or IM chloramphenicol with benzyl penicillin until
switched over to oral
Outcomes Discharge from hospital and good improvement of symptoms
Notes Not blinded
Risk of bias
Sidal 1994
Methods RCT comparing co-trimoxazole and penicillin in non-severe pneumonia (including moderate pneumonia)
Participants Children aged 3 months to 14 years with non severe pneumonia (including moderate pneumonia)
Interventions PO cotrimoxazole (40 mg/kg/day) for 10 days or IM procaine penicillin (50,000 IU/kg/day) for 10 days
Outcomes Cure rate at day 5 and day 10, evident improvement at day 5 and day 10, failure rate
Notes Exclusion criteria: severe chest in-drawing, inability to eat or drink, moderate to severe malnutrition,
antibiotics in last 2 weeks, wheezing
Risk of bias
Straus 1998
Methods RCT comparing co-trimoxazole and amoxycillin in non severe pneumonia
Participants Children aged 2 months to 59 months with non severe pneumonia
Interventions PO cotrimoxazole 20 mg/kg/day for 5 days or amoxycillin 45 mg/kg/day for 5 days

Straus 1998 (Continued)
Outcomes Failure rate, determined by clinical and radiological evidence
Notes Blinded. Exclusion criteria: very severe pneumonia, antibiotics in past 48 hours, hospitalization in past 7
days, hypoxaemia
Risk of bias
Tsarouhas 1998
Methods RCT comparing procaine penicillin and amoxycillin for radiographically diagnosed pneumonia
Participants Children aged 6 months to 18 years with pneumonia
Interventions PO amoxycillin (50 mg/kg/day) or procaine penicillin IM (50,000 IU/ kg/day)
Outcomes Hospitalization rate, failure rate, temperature more than 38.5, ill appearance, increased respiratory rate
Notes Unblinded
Exclusion criteria: chronic illness, asthma, sickle cell disease, cystic fibrosis, allergy to amoxycillin, or
penicillin, antibiotics in past 1 week, wheezing, concurrent febrile illness
Risk of bias
Wubbel 1999
Methods RCT comparing azithromycin and erythromycin in children over 5 years of age with pneumonia; and
comparing azithromycin with co-amoxyclavulanic acid in children under 5 years of age
Participants Children aged between 6 months a 16 years with pneumonia
Interventions PO azithromycin (10mg/kg on day one followed by 5 mg/kg/day for next 4 days) or co-amoxyclavulanic
acid 40 mg/kg/day for 10 days in children under 5 years of age; and erythromycin 40 mg/kg/day for 10
days in children over 5 years
Outcomes Clinically diagnosed cure rates, failure rates and improvement

Wubbel 1999 (Continued)
Notes Unblinded. Exclusion criteria: hypersensitivity to study drugs, nosocomial pneumonia, hospitalization,
antibiotics in last 7 days
Risk of bias
PO = orally
IM = intramuscular
TDS = three times a day
LRTI = lower respiratory tract infection
CPZ = carbamazepine
Characteristics of excluded studies [ordered by study ID]
Agostoni 1988 Compares minocycline and amoxycillin in 23 children between 3 to 11.5 years with pneumonia. Not an
RCT
Ahmad-Hasali 2005 An RCT. Compared intravenous ampicillin with a combination of ampicillin and gentamycin in hospitalized
children with pneumonia, aged between 2 months and 5 years. Outcome variables included duration of
intravenous antibiotics and time taken for clinical improvement. Study does not include cure rates, failure
rates, relapse rates. These are outcome variables of interest for the review
Al-Eiden 1999 Describes results of sequential antibiotic therapy (SAT) in 89 patients with severe lower respiratory tract
infection. The sequential antibiotic use was the feature for exclusion
Aurangzeb 2003 Compares clinical response to amoxycillin, cefuroxime and clarithromycin in the treatment of community
acquired pneumonia in children admitted in hospital between 3 to 72 months. The full text article could
not be procured from authors
Bonvehi 2003 Compared clarithromycin and co-amoxyclavulanic acid in adult patients with CAP due to penicillin-
resistant and/or macrolide-resistant Streptococcus pneumoniae. The study was excluded because of its adult
study population
Esposito 2005 Compared azithromycin in addition to symptomatic treatment with symptomatic treatment alone in chil-
dren with recurrent respiratory tract infections. The study did not compare two or more antibiotics for
pneumonia

(Continued)
Fogarty 2002 Compared cefditoren with co-amoxyclavulanic acid in the management of community acquired pneumonia
in adult patients. The study had an adult population
Haffejee 1984 A single-blind therapeutic trial, using cefotaxime or a benzyl-penicillin-gentamycin combination in 68 hos-
pitalized pediatric patients with 72 episodes of severe infection (septicemia, pneumonia, neonatal menin-
gitis and others). No separate data was available for pneumonia
Higuera 1996 Compared oral cefuroxime axetil and oral co-amoxyclavulanic acid in the treatment of community-acquired
pneumonia in adult patients The study was in adult patients
Mouallem 1976 Compared cephradine and cephalexin for the treatment of bacterial infections in 162 children between four
months and eleven years of age. There was no separate data for pneumonia
Paupe 1992 Compares cefetamet (two doses) with cefaclor. The doses of antibiotics were inconsistent
Petola 2001 Describes results of treatment with a short (4-day) duration of antibiotics
Ruhrmann 1982 Randomized controlled study. Compared erythromycin with amoxycillin in treatment of 120 children
with community acquired pneumonia. Measured outcomes were duration of clinical symptoms, etiology
of pneumonia and side effects of antibiotics. The study does not provide cure rates, failure rates, death rates
or relapse rates
Sanchez 1998 Randomized controlled trial involving 409 patients admitted to internal medicine department. Compared
ceftriaxone, cefuroxime and amoxycillin-clavulanic acid. Study does not provide separate data for children
van Zyl 2002 Randomized controlled trial, compared cefditoren with cepfodoxime in community acquired pneumonia
in adult patients. The study had an adult study population
Vuori-Holopaine 2000 Compares procaine penicillin and cefuroxime in children between 3 months and 15 years of age with
suspected sepsis. There was no separate data for pneumonia available

DATA AND ANALYSES
Comparison 1. Azithromycin versus erythromycin
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
1 Mean age (months) 3 369 Mean Difference (IV, Fixed, 95% CI) -4.48 [-18.54, 9.57]
2 Male sex 3 564 Odds Ratio (M-H, Fixed, 95% CI) 0.83 [0.58, 1.17]
3 Wheezing present 2 479 Odds Ratio (M-H, Random, 95% CI) 1.23 [0.31, 4.87]
4 Cure rate 3 363 Odds Ratio (M-H, Fixed, 95% CI) 1.17 [0.70, 1.95]
5 Failure rate 3 392 Odds Ratio (M-H, Fixed, 95% CI) 0.56 [0.16, 1.89]
6 Side effects 2 153 Odds Ratio (M-H, Fixed, 95% CI) 1.00 [0.46, 2.18]
7 Organisms identified by serology 3 368 Odds Ratio (M-H, Fixed, 95% CI) 0.89 [0.58, 1.38]
or nasopharyngeal cultures
Comparison 2. Co-trimoxazole versus amoxycillin
No. of No. of
1 Age less than one year 2 2054 Odds Ratio (M-H, Fixed, 95% CI) 0.90 [0.75, 1.07]
3 Numbers received antibiotics in 1 595 Odds Ratio (M-H, Fixed, 95% CI) 0.67 [0.46, 0.97]
previous one week
6 Lost to follow up 2 2054 Odds Ratio (M-H, Fixed, 95% CI) 1.02 [0.56, 1.86]
7 Death rates 2 2054 Odds Ratio (M-H, Fixed, 95% CI) 2.13 [0.22, 20.44]
8 Organisms isolated on blood 1 595 Odds Ratio (M-H, Fixed, 95% CI) 1.11 [0.73, 1.70]
culture
9 H. influenzae on blood culture 1 595 Odds Ratio (M-H, Fixed, 95% CI) 0.95 [0.57, 1.56]
10 S. pneumoniae on blood 1 595 Odds Ratio (M-H, Fixed, 95% CI) 1.41 [0.73, 2.72]
culture
Comparison 3. Chloramphenicol versus penicillin plus gentamicin
No. of No. of
1 Adverse events 1 1116 Odds Ratio (M-H, Fixed, 95% CI) 1.26 [0.96, 1.66]
2 Death 1 1116 Odds Ratio (M-H, Fixed, 95% CI) 1.25 [0.76, 2.07]
3 Change of antibiotics 1 1116 Odds Ratio (M-H, Fixed, 95% CI) 0.80 [0.54, 1.18]
4 Readmission before 30 days 1 1116 Odds Ratio (M-H, Fixed, 95% CI) 1.61 [1.02, 2.55]
5 Absconded 1 1116 Odds Ratio (M-H, Fixed, 95% CI) 1.31 [0.83, 2.09]
6 Hospitalization rate 1 1116 Odds Ratio (M-H, Fixed, 95% CI) 1.61 [1.02, 2.55]
7 Age (months) 1 1116 Mean Difference (IV, Fixed, 95% CI) Not estimable
8 Culture positive 1 1116 Odds Ratio (M-H, Fixed, 95% CI) 0.85 [0.60, 1.21]
10 Received antibiotics in previous 1 1116 Odds Ratio (M-H, Fixed, 95% CI) 0.96 [0.75, 1.22]
one week
Comparison 4. Co-amoxyclavulanic acid versus amoxycillin
No. of No. of
1 Poor or no response 1 100 Odds Ratio (M-H, Fixed, 95% CI) 0.08 [0.01, 0.67]
3 Complications 1 100 Odds Ratio (M-H, Fixed, 95% CI) 5.21 [0.24, 111.24]
4 Age (months) 1 100 Mean Difference (IV, Fixed, 95% CI) 4.80 [-8.09, 17.69]
5 Weight 1 100 Mean Difference (IV, Fixed, 95% CI) 1.10 [-1.06, 3.26]
7 Wheeze present 1 100 Odds Ratio (M-H, Fixed, 95% CI) 0.58 [0.18, 1.92]
Comparison 5. Benzathin penicillin versus procaine penicillin
No. of No. of
3 Male Sex 2 281 Odds Ratio (M-H, Fixed, 95% CI) 1.09 [0.67, 1.76]
4 Age between two to six years 2 301 Odds Ratio (M-H, Fixed, 95% CI) 1.14 [0.72, 1.79]
5 Age between 7 to 12 years 2 301 Odds Ratio (M-H, Fixed, 95% CI) 0.52 [0.31, 0.86]
Comparison 6. Amoxycillin versus penicillin
No. of No. of
1 Nasopharyngeal aspirates for S. 1 1486 Odds Ratio (M-H, Fixed, 95% CI) 0.90 [0.72, 1.13]
pneumoniae
4 Weight below 2 Z score 1 1686 Odds Ratio (M-H, Fixed, 95% CI) 0.92 [0.70, 1.19]
(indicating severe malnutrition)
5 Breast fed 1 1702 Odds Ratio (M-H, Fixed, 95% CI) 1.12 [0.92, 1.37]
6 Received antibiotics in last one 1 1702 Odds Ratio (M-H, Fixed, 95% CI) 0.89 [0.64, 1.24]
week
7 Failure rate at 48 hours 1 1702 Odds Ratio (M-H, Fixed, 95% CI) 1.03 [0.81, 1.31]
8 Failure rate on day five 1 1702 Odds Ratio (M-H, Fixed, 95% CI) 0.97 [0.77, 1.22]
9 Failure rate on day 14 1 1702 Odds Ratio (M-H, Fixed, 95% CI) 1.04 [0.84, 1.29]
11 Nasopharyngeal H. influenzae 1 1482 Odds Ratio (M-H, Fixed, 95% CI) 1.00 [0.78, 1.29]
12 Respiratory syncytial virus 1 1528 Odds Ratio (M-H, Fixed, 95% CI) 1.05 [0.83, 1.32]
(RSV) in nasopharyngeal swabs
Comparison 7. Cefpodoxime versus co-amoxyclavulanic acid
No. of No. of
1 Cure rate (response rate) at end 1 278 Odds Ratio (M-H, Fixed, 95% CI) 0.69 [0.18, 2.60]
of treatment
2 Mean age (months) 1 348 Mean Difference (IV, Fixed, 95% CI) Not estimable
3 Adverse effects 1 278 Odds Ratio (M-H, Fixed, 95% CI) 0.46 [0.16, 1.35]
4 Age in years 1 348 Mean Difference (IV, Fixed, 95% CI) Not estimable
5 Follow up 1 278 Odds Ratio (M-H, Fixed, 95% CI) 0.37 [0.11, 1.31]
Comparison 8. Ampicillin alone versus penicillin with chloramphenicol
No. of No. of
1 Cure rates 1 101 Odds Ratio (M-H, Fixed, 95% CI) 0.48 [0.15, 1.51]
2 Age (months) 1 101 Mean Difference (IV, Fixed, 95% CI) -1.69 [-5.54, 2.16]
4 Duration of hospital stay 1 101 Mean Difference (IV, Fixed, 95% CI) -0.10 [-1.13, 0.93]
5 Grade 2 to 4 malnutrition 1 101 Odds Ratio (M-H, Fixed, 95% CI) 0.88 [0.41, 1.93]

Comparison 9. Co-trimoxazole versus procaine penicillin
No. of No. of
2 Age one to five years 1 614 Odds Ratio (M-H, Fixed, 95% CI) 0.84 [0.61, 1.16]
3 Age 5 to 12 years 2 723 Odds Ratio (M-H, Fixed, 95% CI) 0.79 [0.45, 1.38]
4 Duration of illness in days 2 723 Mean Difference (IV, Fixed, 95% CI) -0.15 [-0.49, 0.20]
6 Cure rate 2 723 Odds Ratio (M-H, Random, 95% CI) 1.58 [0.26, 9.69]
8 Well at end of follow up 1 614 Odds Ratio (M-H, Fixed, 95% CI) 0.90 [0.51, 1.57]
9 Death 1 614 Odds Ratio (M-H, Fixed, 95% CI) 3.09 [0.13, 76.13]
10 Treatment failure 1 614 Odds Ratio (M-H, Fixed, 95% CI) 1.72 [0.41, 7.27]
Comparison 10. Co-trimoxzole versus procaine penicillin and ampicillin
No. of No. of
1 Mean age in months 1 134 Mean Difference (IV, Fixed, 95% CI) Not estimable
6 Death rate 1 134 Odds Ratio (M-H, Fixed, 95% CI) 0.2 [0.01, 4.25]
Comparison 11. Azithromycin versus amoxycilin
No. of No. of
1 Age in months 1 76 Mean Difference (IV, Fixed, 95% CI) 58.10 [35.59, 80.61]
2 Duration of illness 1 47 Mean Difference (IV, Fixed, 95% CI) -0.10 [-1.50, 1.30]
3 Wheezing present 1 47 Odds Ratio (M-H, Fixed, 95% CI) 2.02 [0.59, 6.96]
4 Cure rate clinical 1 47 Odds Ratio (M-H, Fixed, 95% CI) Not estimable
5 Cure rate radiological 1 47 Odds Ratio (M-H, Fixed, 95% CI) Not estimable
6 Fever day seven 1 47 Odds Ratio (M-H, Fixed, 95% CI) 1.37 [0.41, 4.61]

Comparison 12. Co-trimoxazole versus amoxycillin
No. of No. of
1 Age less than one year 2 2074 Odds Ratio (M-H, Random, 95% CI) 0.92 [0.62, 1.37]
3 Mean Z score for weight 2 2066 Mean Difference (IV, Fixed, 95% CI) -0.06 [-0.27, 0.15]
4 Received antibiotics in previous 1 595 Odds Ratio (M-H, Fixed, 95% CI) 0.67 [0.46, 0.97]
one week
5 Non-severe pneumonia 1 595 Odds Ratio (M-H, Fixed, 95% CI) 0.97 [0.69, 1.37]
6 Severe pneumonia 1 595 Odds Ratio (M-H, Fixed, 95% CI) 1.03 [0.73, 1.45]
8 Failure rate non-severe 1 291 Odds Ratio (M-H, Fixed, 95% CI) 1.03 [0.49, 2.15]
pneumonia clinical diagnosis
9 Failure rate severe pneumonia 1 302 Odds Ratio (M-H, Fixed, 95% CI) 1.71 [0.94, 3.11]
clinical diagnosis
10 Failure rate radiological positive 1 153 Odds Ratio (M-H, Fixed, 95% CI) 2.14 [0.96, 4.78]
pneumonia
11 Failure rate radiological 1 424 Odds Ratio (M-H, Fixed, 95% CI) 1.72 [0.96, 3.09]
negative for pneumonia
14 Wheeze positive 1 1471 Odds Ratio (M-H, Fixed, 95% CI) 0.76 [0.49, 1.19]
16 Change of antibiotics 1 1459 Odds Ratio (M-H, Fixed, 95% CI) 1.26 [0.95, 1.69]
Comparison 13. Co-trimoxazole versus chloramphenicol
No. of No. of
1 Age in months 1 111 Mean Difference (IV, Fixed, 95% CI) 1.90 [-0.64, 4.44]
3 Weight for age 1 111 Mean Difference (IV, Fixed, 95% CI) Not estimable
4 Wheezing positive 1 111 Odds Ratio (M-H, Fixed, 95% CI) 0.67 [0.11, 4.15]
7 Excluded 1 111 Odds Ratio (M-H, Fixed, 95% CI) 0.94 [0.42, 2.12]
8 Relapse rate 1 111 Odds Ratio (M-H, Fixed, 95% CI) 1.02 [0.24, 4.30]
9 Need for change in antibiotics 1 111 Odds Ratio (M-H, Fixed, 95% CI) 1.42 [0.46, 4.40]
11 Organisms isolated on blood 1 111 Odds Ratio (M-H, Fixed, 95% CI) 1.25 [0.47, 3.30]
culture or lung puncture

Comparison 14. Co-trimoxazole versus co-amoxyclavulanic acid
No. of No. of
1 Children below one year of age 2 1232 Odds Ratio (M-H, Fixed, 95% CI) 117.45 [16.28,
847.47]
Comparison 15. Amoxycillin versus cefpodoxime
No. of No. of
1 Age in months 1 284 Mean Difference (IV, Fixed, 95% CI) Not estimable
3 Response/cure rate 1 238 Odds Ratio (M-H, Fixed, 95% CI) 0.20 [0.08, 0.53]
Comparison 16. Amoxycillin versus chloramphenicol
No. of No. of
1 Age (mean/median) 2 1032 Mean Difference (IV, Random, 95% CI) -6.60 [-10.52, -2.68]
4 Failure rates 2 1065 Odds Ratio (M-H, Fixed, 95% CI) 0.64 [0.41, 1.00]
Comparison 17. Amoxycillin versus procaine penicillin
No. of No. of
1 Median age 1 170 Mean Difference (IV, Fixed, 95% CI) 0.30 [-0.52, 1.12]

Comparison 18. Co-trimoxazole versus single dose procaine penicillin followed by oral ampicillin
No. of No. of
1 Mean age (months) 1 134 Mean Difference (IV, Fixed, 95% CI) Not estimable
Comparison 19. Azithromycin versus co-amoxyclavulanic acid
No. of No. of
3 Improved 1 188 Odds Ratio (M-H, Fixed, 95% CI) 0.85 [0.43, 1.71]
5 Organisms isolated 1 188 Odds Ratio (M-H, Fixed, 95% CI) 1.27 [0.24, 6.74]
6 Mycoplasma serology positive 1 192 Odds Ratio (M-H, Fixed, 95% CI) 1.19 [0.64, 2.22]
Comparison 20. Chloramphenicol versus chloramphenicol plus penicillin
No. of No. of
1 Need for change of antibiotics 1 748 Odds Ratio (M-H, Fixed, 95% CI) 0.49 [0.12, 1.97]
Comparison 21. Chloramphenicol plus penicillin versus ceftrioxone
No. of No. of

Comparison 22. Clarithromycin versus erythromycin
No. of No. of
1 Age below five years 1 260 Odds Ratio (M-H, Fixed, 95% CI) 0.93 [0.56, 1.55]
3 Clinical success rate 1 234 Odds Ratio (M-H, Fixed, 95% CI) 1.92 [0.45, 8.23]
4 Failure rates 1 234 Odds Ratio (M-H, Fixed, 95% CI) 0.52 [0.12, 2.23]
5 Relapse rates 1 226 Odds Ratio (M-H, Fixed, 95% CI) 0.17 [0.02, 1.45]
6 Radiologic resolution 1 209 Odds Ratio (M-H, Fixed, 95% CI) 2.51 [1.02, 6.16]
7 Radiologic success 1 209 Odds Ratio (M-H, Fixed, 95% CI) 3.55 [0.70, 18.04]
8 Radiologic failure 1 209 Odds Ratio (M-H, Fixed, 95% CI) 0.34 [0.06, 1.80]
9 Adverse events 1 260 Odds Ratio (M-H, Fixed, 95% CI) 1.07 [0.60, 1.90]
10 Bacteriologic response 1 45 Odds Ratio (M-H, Fixed, 95% CI) 1.0 [0.15, 6.67]
Analysis 1.1. Comparison 1 Azithromycin versus erythromycin, Outcome 1 Mean age (months).
Review: Antibiotics for community acquired pneumonia in children
Comparison: 1 Azithromycin versus erythromycin
Outcome: 1 Mean age (months)
Study or subgroup Treatment Control Mean Difference Mean Difference

N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Harris 1998 156 0 (0) 69 0 (0) 0.0 [ 0.0, 0.0 ]
Kogan 2003 33 62.6 (53.6) 26 56.2 (52.8) 6.40 [ -20.92, 33.72 ]
Roord 1996 45 58.8 (37.2) 40 67.2 (39.6) -8.40 [ -24.79, 7.99 ]
Total (95% CI) 234 135 -4.48 [ -18.54, 9.57 ]

Heterogeneity: Chi2 = 0.83, df = 1 (P = 0.36); I2 =0.0%
Test for overall effect: Z = 0.62 (P = 0.53)
-10 -5 0 5 10
Favours treatment Favours control

Analysis 1.2. Comparison 1 Azithromycin versus erythromycin, Outcome 2 Male sex.
Outcome: 2 Male sex
Study or subgroup Treatment Control Odds Ratio Weight Odds Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Harris 1998 153/285 83/135 76.1 % 0.73 [ 0.48, 1.10 ]
Kogan 2003 17/33 14/26 11.1 % 0.91 [ 0.33, 2.55 ]
Roord 1996 28/45 22/40 12.8 % 1.35 [ 0.57, 3.21 ]
Total (95% CI) 363 201 100.0 % 0.83 [ 0.58, 1.17 ]

Total events: 198 (Treatment), 119 (Control)
0.1 0.2 0.5 1 2 5 10

Analysis 1.3. Comparison 1 Azithromycin versus erythromycin, Outcome 3 Wheezing present.
Outcome: 3 Wheezing present

n/N n/N M-H,Random,95% CI M-H,Random,95% CI
Harris 1998 82/285 51/135 56.2 % 0.67 [ 0.43, 1.03 ]
Kogan 2003 22/33 11/26 43.8 % 2.73 [ 0.94, 7.89 ]
Total (95% CI) 318 161 100.0 % 1.23 [ 0.31, 4.87 ]

Heterogeneity: Tau2 = 0.82; Chi2 = 5.81, df = 1 (P = 0.02); I2 =83%
0.1 0.2 0.5 1 2 5 10


Analysis 1.4. Comparison 1 Azithromycin versus erythromycin, Outcome 4 Cure rate.
Outcome: 4 Cure rate

Harris 1998 115/152 52/67 65.5 % 0.90 [ 0.45, 1.78 ]
Kogan 2003 33/33 21/26 1.3 % 17.14 [ 0.90, 325.93 ]
Roord 1996 31/45 27/40 33.2 % 1.07 [ 0.43, 2.66 ]
Total (95% CI) 230 133 100.0 % 1.17 [ 0.70, 1.95 ]

Heterogeneity: Chi2 = 3.80, df = 2 (P = 0.15); I2 =47%
0.1 0.2 0.5 1 2 5 10

Analysis 1.5. Comparison 1 Azithromycin versus erythromycin, Outcome 5 Failure rate.
Outcome: 5 Failure rate

Harris 1998 4/152 1/67 19.8 % 1.78 [ 0.20, 16.27 ]
Roord 1996 1/45 4/40 60.8 % 0.20 [ 0.02, 1.91 ]
Wubbel 1999 0/39 1/49 19.3 % 0.41 [ 0.02, 10.33 ]
Total (95% CI) 236 156 100.0 % 0.56 [ 0.16, 1.89 ]

0.1 0.2 0.5 1 2 5 10


Analysis 1.6. Comparison 1 Azithromycin versus erythromycin, Outcome 6 Side effects.
Outcome: 6 Side effects

Roord 1996 12/45 6/40 36.8 % 2.06 [ 0.69, 6.13 ]
Wubbel 1999 5/39 8/29 63.2 % 0.39 [ 0.11, 1.34 ]
Total (95% CI) 84 69 100.0 % 1.00 [ 0.46, 2.18 ]

0.1 0.2 0.5 1 2 5 10

Analysis 1.7. Comparison 1 Azithromycin versus erythromycin, Outcome 7 Organisms identified by

serology or nasopharyngeal cultures.
Outcome: 7 Organisms identified by serology or nasopharyngeal cultures

Harris 1998 103/156 43/69 47.5 % 1.18 [ 0.65, 2.12 ]
Kogan 2003 14/33 20/26 30.2 % 0.22 [ 0.07, 0.69 ]
Roord 1996 24/44 20/40 22.3 % 1.20 [ 0.51, 2.83 ]
Total (95% CI) 233 135 100.0 % 0.89 [ 0.58, 1.38 ]

0.1 0.2 0.5 1 2 5 10


Analysis 2.1. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 1 Age less than one year.
Comparison: 2 Co-trimoxazole versus amoxycillin
Outcome: 1 Age less than one year

CATCHUP 2002 360/725 372/734 71.8 % 0.96 [ 0.78, 1.18 ]
Straus 1998 227/398 127/197 28.2 % 0.73 [ 0.51, 1.04 ]
Total (95% CI) 1123 931 100.0 % 0.90 [ 0.75, 1.07 ]

0.1 0.2 0.5 1 2 5 10

Analysis 2.2. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 2 Male sex.
Outcome: 2 Male sex

CATCHUP 2002 362/741 435/730 76.2 % 0.65 [ 0.53, 0.80 ]
Straus 1998 246/398 137/197 23.8 % 0.71 [ 0.49, 1.02 ]
Total (95% CI) 1139 927 100.0 % 0.66 [ 0.55, 0.79 ]

Test for overall effect: Z = 4.49 (P < 0.00001)
0.1 0.2 0.5 1 2 5 10


Analysis 2.3. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 3 Numbers received antibiotics in
previous one week.
Outcome: 3 Numbers received antibiotics in previous one week

Straus 1998 102/398 67/197 100.0 % 0.67 [ 0.46, 0.97 ]
Total (95% CI) 398 197 100.0 % 0.67 [ 0.46, 0.97 ]

Heterogeneity: not applicable
0.1 0.2 0.5 1 2 5 10

Analysis 2.4. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 4 Failure rate.

CATCHUP 2002 139/734 117/725 75.6 % 1.21 [ 0.93, 1.59 ]
Straus 1998 92/398 30/197 24.4 % 1.67 [ 1.06, 2.63 ]
Total (95% CI) 1132 922 100.0 % 1.33 [ 1.05, 1.67 ]

0.1 0.2 0.5 1 2 5 10


Analysis 2.5. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 5 Cure rate.

CATCHUP 2002 595/734 608/725 100.0 % 0.82 [ 0.63, 1.08 ]
Total (95% CI) 734 725 100.0 % 0.82 [ 0.63, 1.08 ]

0.1 0.2 0.5 1 2 5 10

Analysis 2.6. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 6 Lost to follow up.
Outcome: 6 Lost to follow up

CATCHUP 2002 14/734 16/725 75.3 % 0.86 [ 0.42, 1.78 ]
Straus 1998 12/398 4/197 24.7 % 1.50 [ 0.48, 4.71 ]
Total (95% CI) 1132 922 100.0 % 1.02 [ 0.56, 1.86 ]

0.1 0.2 0.5 1 2 5 10


Analysis 2.7. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 7 Death rates.
Outcome: 7 Death rates

CATCHUP 2002 1/734 0/725 43.0 % 2.97 [ 0.12, 72.96 ]
Straus 1998 1/398 0/197 57.0 % 1.49 [ 0.06, 36.76 ]
Total (95% CI) 1132 922 100.0 % 2.13 [ 0.22, 20.44 ]

0.1 0.2 0.5 1 2 5 10

Analysis 2.8. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 8 Organisms isolated on blood
culture.
Outcome: 8 Organisms isolated on blood culture

Straus 1998 88/398 40/197 100.0 % 1.11 [ 0.73, 1.70 ]
Total (95% CI) 398 197 100.0 % 1.11 [ 0.73, 1.70 ]

0.1 0.2 0.5 1 2 5 10


Analysis 2.9. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 9 H. influenzae on blood culture.
Outcome: 9 H. influenzae on blood culture

Straus 1998 52/398 27/197 100.0 % 0.95 [ 0.57, 1.56 ]
Total (95% CI) 398 197 100.0 % 0.95 [ 0.57, 1.56 ]

0.1 0.2 0.5 1 2 5 10

Analysis 2.10. Comparison 2 Co-trimoxazole versus amoxycillin, Outcome 10 S. pneumoniae on blood

culture.
Outcome: 10 S. pneumoniae on blood culture

Straus 1998 36/398 13/197 100.0 % 1.41 [ 0.73, 2.72 ]
Total (95% CI) 398 197 100.0 % 1.41 [ 0.73, 2.72 ]

0.1 0.2 0.5 1 2 5 10


Analysis 3.1. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 1 Adverse events.
Comparison: 3 Chloramphenicol versus penicillin plus gentamicin
Outcome: 1 Adverse events

Duke 2002 147/559 123/557 100.0 % 1.26 [ 0.96, 1.66 ]
Total (95% CI) 559 557 100.0 % 1.26 [ 0.96, 1.66 ]

0.1 0.2 0.5 1 2 5 10

Analysis 3.2. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 2 Death.
Outcome: 2 Death

Duke 2002 36/559 29/557 100.0 % 1.25 [ 0.76, 2.07 ]
Total (95% CI) 559 557 100.0 % 1.25 [ 0.76, 2.07 ]

0.1 0.2 0.5 1 2 5 10


Analysis 3.3. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 3 Change of
antibiotics.
Outcome: 3 Change of antibiotics

Duke 2002 49/559 60/557 100.0 % 0.80 [ 0.54, 1.18 ]
Total (95% CI) 559 557 100.0 % 0.80 [ 0.54, 1.18 ]

0.1 0.2 0.5 1 2 5 10

Analysis 3.4. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 4 Readmission
before 30 days.
Outcome: 4 Readmission before 30 days

Duke 2002 50/559 32/557 100.0 % 1.61 [ 1.02, 2.55 ]
Total (95% CI) 559 557 100.0 % 1.61 [ 1.02, 2.55 ]

0.1 0.2 0.5 1 2 5 10


Analysis 3.5. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 5 Absconded.
Outcome: 5 Absconded

Duke 2002 44/559 34/557 100.0 % 1.31 [ 0.83, 2.09 ]
Total (95% CI) 559 557 100.0 % 1.31 [ 0.83, 2.09 ]

0.1 0.2 0.5 1 2 5 10

Analysis 3.6. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 6 Hospitalization
rate.
Outcome: 6 Hospitalization rate

Duke 2002 50/559 32/557 100.0 % 1.61 [ 1.02, 2.55 ]
Total (95% CI) 559 557 100.0 % 1.61 [ 1.02, 2.55 ]

0.1 0.2 0.5 1 2 5 10


Analysis 3.7. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 7 Age (months).
Outcome: 7 Age (months)

Duke 2002 559 6.1 (0) 557 5.9 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 559 557 0.0 [ 0.0, 0.0 ]

-10 -5 0 5 10
Analysis 3.8. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 8 Culture positive.
Outcome: 8 Culture positive

Duke 2002 67/559 77/557 100.0 % 0.85 [ 0.60, 1.21 ]
Total (95% CI) 559 557 100.0 % 0.85 [ 0.60, 1.21 ]

0.1 0.2 0.5 1 2 5 10


Analysis 3.9. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 9 Male sex.
Outcome: 9 Male sex

Duke 2002 324/559 340/557 100.0 % 0.88 [ 0.69, 1.12 ]
Total (95% CI) 559 557 100.0 % 0.88 [ 0.69, 1.12 ]

0.1 0.2 0.5 1 2 5 10

Analysis 3.10. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 10 Received
antibiotics in previous one week.
Outcome: 10 Received antibiotics in previous one week

Duke 2002 212/559 217/557 100.0 % 0.96 [ 0.75, 1.22 ]
Total (95% CI) 559 557 100.0 % 0.96 [ 0.75, 1.22 ]

0.1 0.2 0.5 1 2 5 10


Analysis 3.11. Comparison 3 Chloramphenicol versus penicillin plus gentamicin, Outcome 11 Lost to follow
up.

Duke 2002 44/559 34/557 100.0 % 1.31 [ 0.83, 2.09 ]
Total (95% CI) 559 557 100.0 % 1.31 [ 0.83, 2.09 ]

0.1 0.2 0.5 1 2 5 10

Analysis 4.1. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 1 Poor or no response.
Comparison: 4 Co-amoxyclavulanic acid versus amoxycillin
Outcome: 1 Poor or no response

Jibril 1989 1/50 10/50 100.0 % 0.08 [ 0.01, 0.67 ]
Total (95% CI) 50 50 100.0 % 0.08 [ 0.01, 0.67 ]

0.1 0.2 0.5 1 2 5 10


Analysis 4.2. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 2 Cure rate.

Jibril 1989 47/50 30/50 100.0 % 10.44 [ 2.85, 38.21 ]
Total (95% CI) 50 50 100.0 % 10.44 [ 2.85, 38.21 ]

0.1 0.2 0.5 1 2 5 10

Analysis 4.3. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 3 Complications.
Outcome: 3 Complications

Jibril 1989 2/50 0/50 100.0 % 5.21 [ 0.24, 111.24 ]
Total (95% CI) 50 50 100.0 % 5.21 [ 0.24, 111.24 ]

0.1 0.2 0.5 1 2 5 10


Analysis 4.4. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 4 Age (months).
Study or subgroup Treatment Control Mean Difference Weight Mean Difference

Jibril 1989 50 63.6 (32.28) 50 58.8 (33.48) 100.0 % 4.80 [ -8.09, 17.69 ]
Total (95% CI) 50 50 100.0 % 4.80 [ -8.09, 17.69 ]

-10 -5 0 5 10
Analysis 4.5. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 5 Weight.
Outcome: 5 Weight

Jibril 1989 50 16 (5.71) 50 14.9 (5.28) 100.0 % 1.10 [ -1.06, 3.26 ]
Total (95% CI) 50 50 100.0 % 1.10 [ -1.06, 3.26 ]

-10 -5 0 5 10

Analysis 4.6. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 6 Male sex.
Outcome: 6 Male sex

Jibril 1989 35/50 32/50 100.0 % 1.31 [ 0.57, 3.03 ]
Total (95% CI) 50 50 100.0 % 1.31 [ 0.57, 3.03 ]

0.1 0.2 0.5 1 2 5 10

Analysis 4.7. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 7 Wheeze present.
Outcome: 7 Wheeze present

Jibril 1989 5/50 8/50 100.0 % 0.58 [ 0.18, 1.92 ]
Total (95% CI) 50 50 100.0 % 0.58 [ 0.18, 1.92 ]

0.1 0.2 0.5 1 2 5 10


Analysis 4.8. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 8 Cure rate.

Jibril 1989 47/50 30/50 100.0 % 10.44 [ 2.85, 38.21 ]
Total (95% CI) 50 50 100.0 % 10.44 [ 2.85, 38.21 ]

0.1 0.2 0.5 1 2 5 10

Analysis 4.9. Comparison 4 Co-amoxyclavulanic acid versus amoxycillin, Outcome 9 Side effects.

Jibril 1989 2/50 0/50 100.0 % 5.21 [ 0.24, 111.24 ]
Total (95% CI) 50 50 100.0 % 5.21 [ 0.24, 111.24 ]

0.1 0.2 0.5 1 2 5 10


Analysis 5.1. Comparison 5 Benzathin penicillin versus procaine penicillin, Outcome 1 Cure rate.
Comparison: 5 Benzathin penicillin versus procaine penicillin

Camargos 1997 84/93 78/83 31.5 % 0.60 [ 0.19, 1.86 ]
Sidal 1994 16/42 35/63 68.5 % 0.49 [ 0.22, 1.09 ]
Total (95% CI) 135 146 100.0 % 0.53 [ 0.27, 1.01 ]

0.1 0.2 0.5 1 2 5 10

Analysis 5.2. Comparison 5 Benzathin penicillin versus procaine penicillin, Outcome 2 Failure rate.

Camargos 1997 7/93 4/83 59.4 % 1.61 [ 0.45, 5.70 ]
Sidal 1994 14/42 5/63 40.6 % 5.80 [ 1.90, 17.71 ]
Total (95% CI) 135 146 100.0 % 3.31 [ 1.45, 7.55 ]

0.1 0.2 0.5 1 2 5 10


Analysis 5.3. Comparison 5 Benzathin penicillin versus procaine penicillin, Outcome 3 Male Sex.
Outcome: 3 Male Sex

Camargos 1997 56/93 47/83 62.8 % 1.16 [ 0.64, 2.11 ]
Sidal 1994 27/42 41/63 37.2 % 0.97 [ 0.43, 2.19 ]
Total (95% CI) 135 146 100.0 % 1.09 [ 0.67, 1.76 ]

0.1 0.2 0.5 1 2 5 10

Analysis 5.4. Comparison 5 Benzathin penicillin versus procaine penicillin, Outcome 4 Age between two to
six years.
Outcome: 4 Age between two to six years

Camargos 1997 58/93 42/83 47.8 % 1.62 [ 0.89, 2.95 ]
Sidal 1994 24/62 30/63 52.2 % 0.69 [ 0.34, 1.41 ]
Total (95% CI) 155 146 100.0 % 1.14 [ 0.72, 1.79 ]

0.1 0.2 0.5 1 2 5 10


Analysis 5.5. Comparison 5 Benzathin penicillin versus procaine penicillin, Outcome 5 Age between 7 to 12
years.
Outcome: 5 Age between 7 to 12 years

Camargos 1997 35/93 41/83 64.4 % 0.62 [ 0.34, 1.13 ]
Sidal 1994 7/62 17/63 35.6 % 0.34 [ 0.13, 0.90 ]
Total (95% CI) 155 146 100.0 % 0.52 [ 0.31, 0.86 ]

0.1 0.2 0.5 1 2 5 10

Analysis 5.6. Comparison 5 Benzathin penicillin versus procaine penicillin, Outcome 6 Lost to follow up.

Camargos 1997 2/93 1/83 100.0 % 1.80 [ 0.16, 20.25 ]
Total (95% CI) 93 83 100.0 % 1.80 [ 0.16, 20.25 ]

0.1 0.2 0.5 1 2 5 10


Analysis 6.1. Comparison 6 Amoxycillin versus penicillin, Outcome 1 Nasopharyngeal aspirates for S.
pneumoniae.
Comparison: 6 Amoxycillin versus penicillin
Outcome: 1 Nasopharyngeal aspirates for S. pneumoniae

Addo-Yobo 2004 201/743 217/743 100.0 % 0.90 [ 0.72, 1.13 ]
Total (95% CI) 743 743 100.0 % 0.90 [ 0.72, 1.13 ]

0.1 0.2 0.5 1 2 5 10

Analysis 6.2. Comparison 6 Amoxycillin versus penicillin, Outcome 2 Age less than one year.

Addo-Yobo 2004 532/857 513/845 100.0 % 1.06 [ 0.87, 1.29 ]
Total (95% CI) 857 845 100.0 % 1.06 [ 0.87, 1.29 ]

0.1 0.2 0.5 1 2 5 10


Analysis 6.3. Comparison 6 Amoxycillin versus penicillin, Outcome 3 Male sex.
Outcome: 3 Male sex

Addo-Yobo 2004 537/857 520/845 100.0 % 1.05 [ 0.86, 1.28 ]
Total (95% CI) 857 845 100.0 % 1.05 [ 0.86, 1.28 ]

0.1 0.2 0.5 1 2 5 10

Analysis 6.4. Comparison 6 Amoxycillin versus penicillin, Outcome 4 Weight below 2 Z score (indicating
severe malnutrition).
Outcome: 4 Weight below 2 Z score (indicating severe malnutrition)

Addo-Yobo 2004 124/845 133/841 100.0 % 0.92 [ 0.70, 1.19 ]
Total (95% CI) 845 841 100.0 % 0.92 [ 0.70, 1.19 ]

0.1 0.2 0.5 1 2 5 10


Analysis 6.5. Comparison 6 Amoxycillin versus penicillin, Outcome 5 Breast fed.
Outcome: 5 Breast fed

Addo-Yobo 2004 561/857 531/845 100.0 % 1.12 [ 0.92, 1.37 ]
Total (95% CI) 857 845 100.0 % 1.12 [ 0.92, 1.37 ]

0.1 0.2 0.5 1 2 5 10

Analysis 6.6. Comparison 6 Amoxycillin versus penicillin, Outcome 6 Received antibiotics in last one week.
Outcome: 6 Received antibiotics in last one week

Addo-Yobo 2004 75/857 82/845 100.0 % 0.89 [ 0.64, 1.24 ]
Total (95% CI) 857 845 100.0 % 0.89 [ 0.64, 1.24 ]

0.1 0.2 0.5 1 2 5 10


Analysis 6.7. Comparison 6 Amoxycillin versus penicillin, Outcome 7 Failure rate at 48 hours.
Outcome: 7 Failure rate at 48 hours

Addo-Yobo 2004 167/857 161/845 100.0 % 1.03 [ 0.81, 1.31 ]
Total (95% CI) 857 845 100.0 % 1.03 [ 0.81, 1.31 ]

0.1 0.2 0.5 1 2 5 10

Analysis 6.8. Comparison 6 Amoxycillin versus penicillin, Outcome 8 Failure rate on day five.
Outcome: 8 Failure rate on day five

Addo-Yobo 2004 185/857 187/845 100.0 % 0.97 [ 0.77, 1.22 ]
Total (95% CI) 857 845 100.0 % 0.97 [ 0.77, 1.22 ]

0.1 0.2 0.5 1 2 5 10


Analysis 6.9. Comparison 6 Amoxycillin versus penicillin, Outcome 9 Failure rate on day 14.
Outcome: 9 Failure rate on day 14

Addo-Yobo 2004 231/857 221/845 100.0 % 1.04 [ 0.84, 1.29 ]
Total (95% CI) 857 845 100.0 % 1.04 [ 0.84, 1.29 ]

0.1 0.2 0.5 1 2 5 10

Analysis 6.10. Comparison 6 Amoxycillin versus penicillin, Outcome 10 Death rates.

Addo-Yobo 2004 0/845 7/857 100.0 % 0.07 [ 0.00, 1.18 ]
Total (95% CI) 845 857 100.0 % 0.07 [ 0.00, 1.18 ]

0.1 0.2 0.5 1 2 5 10


Analysis 6.11. Comparison 6 Amoxycillin versus penicillin, Outcome 11 Nasopharyngeal H. influenzae.
Outcome: 11 Nasopharyngeal H. influenzae

Addo-Yobo 2004 146/743 145/739 100.0 % 1.00 [ 0.78, 1.29 ]
Total (95% CI) 743 739 100.0 % 1.00 [ 0.78, 1.29 ]

0.1 0.2 0.5 1 2 5 10

Analysis 6.12. Comparison 6 Amoxycillin versus penicillin, Outcome 12 Respiratory syncytial virus (RSV) in
nasopharyngeal swabs.
Outcome: 12 Respiratory syncytial virus (RSV) in nasopharyngeal swabs

Addo-Yobo 2004 192/769 183/759 100.0 % 1.05 [ 0.83, 1.32 ]
Total (95% CI) 769 759 100.0 % 1.05 [ 0.83, 1.32 ]

0.1 0.2 0.5 1 2 5 10


Analysis 7.1. Comparison 7 Cefpodoxime versus co-amoxyclavulanic acid, Outcome 1 Cure rate (response
rate) at end of treatment.
Comparison: 7 Cefpodoxime versus co-amoxyclavulanic acid
Outcome: 1 Cure rate (response rate) at end of treatment

Klein 1995 179/188 87/90 100.0 % 0.69 [ 0.18, 2.60 ]
Total (95% CI) 188 90 100.0 % 0.69 [ 0.18, 2.60 ]

0.1 0.2 0.5 1 2 5 10

Analysis 7.2. Comparison 7 Cefpodoxime versus co-amoxyclavulanic acid, Outcome 2 Mean age (months).

Klein 1995 234 31.32 (0) 114 37.2 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 234 114 0.0 [ 0.0, 0.0 ]

-10 -5 0 5 10

Analysis 7.3. Comparison 7 Cefpodoxime versus co-amoxyclavulanic acid, Outcome 3 Adverse effects.
Outcome: 3 Adverse effects

Klein 1995 7/188 7/90 100.0 % 0.46 [ 0.16, 1.35 ]
Total (95% CI) 188 90 100.0 % 0.46 [ 0.16, 1.35 ]

0.1 0.2 0.5 1 2 5 10

Analysis 7.4. Comparison 7 Cefpodoxime versus co-amoxyclavulanic acid, Outcome 4 Age in years.
Outcome: 4 Age in years

Klein 1995 234 1.8 (0) 114 3.1 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 234 114 0.0 [ 0.0, 0.0 ]

-10 -5 0 5 10

Analysis 7.5. Comparison 7 Cefpodoxime versus co-amoxyclavulanic acid, Outcome 5 Follow up.
Outcome: 5 Follow up

Klein 1995 172/188 87/90 100.0 % 0.37 [ 0.11, 1.31 ]
Total (95% CI) 188 90 100.0 % 0.37 [ 0.11, 1.31 ]

0.1 0.2 0.5 1 2 5 10

Analysis 8.1. Comparison 8 Ampicillin alone versus penicillin with chloramphenicol, Outcome 1 Cure rates.
Comparison: 8 Ampicillin alone versus penicillin with chloramphenicol
Outcome: 1 Cure rates

Deivanayagam 1996 42/52 44/49 100.0 % 0.48 [ 0.15, 1.51 ]
Total (95% CI) 52 49 100.0 % 0.48 [ 0.15, 1.51 ]

0.1 0.2 0.5 1 2 5 10


Analysis 8.2. Comparison 8 Ampicillin alone versus penicillin with chloramphenicol, Outcome 2 Age
(months).

Deivanayagam 1996 52 14.2 (9.16) 49 15.89 (10.47) 100.0 % -1.69 [ -5.54, 2.16 ]
Total (95% CI) 52 49 100.0 % -1.69 [ -5.54, 2.16 ]

-10 -5 0 5 10
Analysis 8.3. Comparison 8 Ampicillin alone versus penicillin with chloramphenicol, Outcome 3 Male sex.
Outcome: 3 Male sex

Deivanayagam 1996 26/52 26/49 100.0 % 0.88 [ 0.41, 1.93 ]
Total (95% CI) 52 49 100.0 % 0.88 [ 0.41, 1.93 ]

0.1 0.2 0.5 1 2 5 10


Analysis 8.4. Comparison 8 Ampicillin alone versus penicillin with chloramphenicol, Outcome 4 Duration of
hospital stay.
Outcome: 4 Duration of hospital stay

Deivanayagam 1996 52 6.19 (2.78) 49 6.29 (2.5) 100.0 % -0.10 [ -1.13, 0.93 ]
Total (95% CI) 52 49 100.0 % -0.10 [ -1.13, 0.93 ]

-10 -5 0 5 10
Analysis 8.5. Comparison 8 Ampicillin alone versus penicillin with chloramphenicol, Outcome 5 Grade 2 to
4 malnutrition.
Outcome: 5 Grade 2 to 4 malnutrition

Deivanayagam 1996 26/52 26/49 100.0 % 0.88 [ 0.41, 1.93 ]
Total (95% CI) 52 49 100.0 % 0.88 [ 0.41, 1.93 ]

0.1 0.2 0.5 1 2 5 10


Analysis 9.1. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 1 Age less than one year.
Comparison: 9 Co-trimoxazole versus procaine penicillin

Keeley 1990 148/303 134/311 88.5 % 1.26 [ 0.92, 1.73 ]
Sidal 1994 16/46 16/63 11.5 % 1.57 [ 0.68, 3.60 ]
Total (95% CI) 349 374 100.0 % 1.30 [ 0.96, 1.74 ]

0.1 0.2 0.5 1 2 5 10

Analysis 9.2. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 2 Age one to five years.
Outcome: 2 Age one to five years

Keeley 1990 142/303 159/311 100.0 % 0.84 [ 0.61, 1.16 ]
Total (95% CI) 303 311 100.0 % 0.84 [ 0.61, 1.16 ]

0.1 0.2 0.5 1 2 5 10


Analysis 9.3. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 3 Age 5 to 12 years.
Outcome: 3 Age 5 to 12 years

Keeley 1990 12/303 19/311 63.6 % 0.63 [ 0.30, 1.33 ]
Sidal 1994 13/46 17/63 36.4 % 1.07 [ 0.46, 2.49 ]
Total (95% CI) 349 374 100.0 % 0.79 [ 0.45, 1.38 ]

0.1 0.2 0.5 1 2 5 10

Analysis 9.4. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 4 Duration of illness in
days.
Outcome: 4 Duration of illness in days

Keeley 1990 303 3.4 (2) 311 3.6 (2.4) 96.6 % -0.20 [ -0.55, 0.15 ]
Sidal 1994 46 6.84 (3.92) 63 5.47 (6) 3.4 % 1.37 [ -0.50, 3.24 ]
Total (95% CI) 349 374 100.0 % -0.15 [ -0.49, 0.20 ]

-10 -5 0 5 10

Analysis 9.5. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 5 Male sex.
Outcome: 5 Male sex

Keeley 1990 153/303 163/311 100.0 % 0.93 [ 0.67, 1.27 ]
Total (95% CI) 303 311 100.0 % 0.93 [ 0.67, 1.27 ]

0.1 0.2 0.5 1 2 5 10

Analysis 9.6. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 6 Cure rate.

Keeley 1990 288/303 261/311 54.6 % 3.68 [ 2.02, 6.71 ]
Sidal 1994 40/46 58/63 45.4 % 0.57 [ 0.16, 2.01 ]
Total (95% CI) 349 374 100.0 % 1.58 [ 0.26, 9.69 ]

0.1 0.2 0.5 1 2 5 10


Analysis 9.7. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 7 Hospitalization rate.

Keeley 1990 12/303 5/311 100.0 % 2.52 [ 0.88, 7.25 ]
Total (95% CI) 303 311 100.0 % 2.52 [ 0.88, 7.25 ]

0.1 0.2 0.5 1 2 5 10

Analysis 9.8. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 8 Well at end of follow up.
Outcome: 8 Well at end of follow up

Keeley 1990 275/303 285/311 100.0 % 0.90 [ 0.51, 1.57 ]
Total (95% CI) 303 311 100.0 % 0.90 [ 0.51, 1.57 ]

0.1 0.2 0.5 1 2 5 10


Analysis 9.9. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 9 Death.
Outcome: 9 Death

Keeley 1990 1/303 0/311 100.0 % 3.09 [ 0.13, 76.13 ]
Total (95% CI) 303 311 100.0 % 3.09 [ 0.13, 76.13 ]

0.1 0.2 0.5 1 2 5 10

Analysis 9.10. Comparison 9 Co-trimoxazole versus procaine penicillin, Outcome 10 Treatment failure.
Outcome: 10 Treatment failure

Keeley 1990 5/303 3/311 100.0 % 1.72 [ 0.41, 7.27 ]
Total (95% CI) 303 311 100.0 % 1.72 [ 0.41, 7.27 ]

0.1 0.2 0.5 1 2 5 10


Analysis 10.1. Comparison 10 Co-trimoxzole versus procaine penicillin and ampicillin, Outcome 1 Mean age
in months.
Comparison: 10 Co-trimoxzole versus procaine penicillin and ampicillin
Outcome: 1 Mean age in months

Campbell 1988 66 22 (0) 68 21.8 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 66 68 0.0 [ 0.0, 0.0 ]

-10 -5 0 5 10
Analysis 10.2. Comparison 10 Co-trimoxzole versus procaine penicillin and ampicillin, Outcome 2 Age less
than one year.

Campbell 1988 20/66 24/68 100.0 % 0.80 [ 0.39, 1.64 ]
Total (95% CI) 66 68 100.0 % 0.80 [ 0.39, 1.64 ]

0.1 0.2 0.5 1 2 5 10


Analysis 10.3. Comparison 10 Co-trimoxzole versus procaine penicillin and ampicillin, Outcome 3 Male sex.
Outcome: 3 Male sex

Campbell 1988 41/66 38/68 100.0 % 1.29 [ 0.65, 2.58 ]
Total (95% CI) 66 68 100.0 % 1.29 [ 0.65, 2.58 ]

0.1 0.2 0.5 1 2 5 10

Analysis 10.4. Comparison 10 Co-trimoxzole versus procaine penicillin and ampicillin, Outcome 4 Cure
rate.

Campbell 1988 60/66 61/68 100.0 % 1.15 [ 0.36, 3.61 ]
Total (95% CI) 66 68 100.0 % 1.15 [ 0.36, 3.61 ]

0.1 0.2 0.5 1 2 5 10


Analysis 10.5. Comparison 10 Co-trimoxzole versus procaine penicillin and ampicillin, Outcome 5
Hospitalization rate.

Campbell 1988 3/66 2/68 100.0 % 1.57 [ 0.25, 9.72 ]
Total (95% CI) 66 68 100.0 % 1.57 [ 0.25, 9.72 ]

0.1 0.2 0.5 1 2 5 10

Analysis 10.6. Comparison 10 Co-trimoxzole versus procaine penicillin and ampicillin, Outcome 6 Death
rate.
Outcome: 6 Death rate

Campbell 1988 0/66 2/68 100.0 % 0.20 [ 0.01, 4.25 ]
Total (95% CI) 66 68 100.0 % 0.20 [ 0.01, 4.25 ]

0.1 0.2 0.5 1 2 5 10


Analysis 11.1. Comparison 11 Azithromycin versus amoxycilin, Outcome 1 Age in months.
Comparison: 11 Azithromycin versus amoxycilin
Outcome: 1 Age in months

Kogan 2003 23 64.1 (44) 53 6 (50.3) 100.0 % 58.10 [ 35.59, 80.61 ]
Total (95% CI) 23 53 100.0 % 58.10 [ 35.59, 80.61 ]

-10 -5 0 5 10
Analysis 11.2. Comparison 11 Azithromycin versus amoxycilin, Outcome 2 Duration of illness.
Outcome: 2 Duration of illness

Kogan 2003 23 3.6 (2.3) 24 3.7 (2.6) 100.0 % -0.10 [ -1.50, 1.30 ]
Total (95% CI) 23 24 100.0 % -0.10 [ -1.50, 1.30 ]

-10 -5 0 5 10

Analysis 11.3. Comparison 11 Azithromycin versus amoxycilin, Outcome 3 Wheezing present.
Outcome: 3 Wheezing present

Kogan 2003 17/23 14/24 100.0 % 2.02 [ 0.59, 6.96 ]
Total (95% CI) 23 24 100.0 % 2.02 [ 0.59, 6.96 ]

0.1 0.2 0.5 1 2 5 10

Analysis 11.4. Comparison 11 Azithromycin versus amoxycilin, Outcome 4 Cure rate clinical.
Outcome: 4 Cure rate clinical
Study or subgroup Treatment Control Odds Ratio Odds Ratio

Kogan 2003 23/23 24/24 0.0 [ 0.0, 0.0 ]
Total (95% CI) 23 24 0.0 [ 0.0, 0.0 ]

0.1 0.2 0.5 1 2 5 10


Analysis 11.5. Comparison 11 Azithromycin versus amoxycilin, Outcome 5 Cure rate radiological.
Outcome: 5 Cure rate radiological
Study or subgroup Treatment Control Odds Ratio Odds Ratio

Kogan 2003 23/23 24/24 0.0 [ 0.0, 0.0 ]
Total (95% CI) 23 24 0.0 [ 0.0, 0.0 ]

0.1 0.2 0.5 1 2 5 10

Analysis 11.6. Comparison 11 Azithromycin versus amoxycilin, Outcome 6 Fever day seven.
Outcome: 6 Fever day seven

Kogan 2003 16/23 15/24 100.0 % 1.37 [ 0.41, 4.61 ]
Total (95% CI) 23 24 100.0 % 1.37 [ 0.41, 4.61 ]

0.1 0.2 0.5 1 2 5 10


Analysis 12.1. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 1 Age less than one year.

CATCHUP 2002 372/734 360/745 56.5 % 1.10 [ 0.90, 1.35 ]
Straus 1998 227/398 127/197 43.5 % 0.73 [ 0.51, 1.04 ]
Total (95% CI) 1132 942 100.0 % 0.92 [ 0.62, 1.37 ]

0.1 0.2 0.5 1 2 5 10

Analysis 12.2. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 2 Male sex.
Outcome: 2 Male sex

CATCHUP 2002 362/734 435/730 76.0 % 0.66 [ 0.54, 0.81 ]
Straus 1998 246/398 137/197 24.0 % 0.71 [ 0.49, 1.02 ]
Total (95% CI) 1132 927 100.0 % 0.67 [ 0.56, 0.80 ]

0.1 0.2 0.5 1 2 5 10


Analysis 12.3. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 3 Mean Z score for weight.
Outcome: 3 Mean Z score for weight

CATCHUP 2002 741 -0.94 (0) 730 -1.11 (0) 0.0 [ 0.0, 0.0 ]
Straus 1998 398 -0.45 (1.28) 197 -0.39 (1.21) -0.06 [ -0.27, 0.15 ]
Total (95% CI) 1139 927 -0.06 [ -0.27, 0.15 ]

-10 -5 0 5 10
Analysis 12.4. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 4 Received antibiotics in

previous one week.
Outcome: 4 Received antibiotics in previous one week

Straus 1998 102/398 67/197 100.0 % 0.67 [ 0.46, 0.97 ]
Total (95% CI) 398 197 100.0 % 0.67 [ 0.46, 0.97 ]

0.1 0.2 0.5 1 2 5 10


Analysis 12.5. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 5 Non-severe pneumonia.
Outcome: 5 Non-severe pneumonia

Straus 1998 195/398 98/197 100.0 % 0.97 [ 0.69, 1.37 ]
Total (95% CI) 398 197 100.0 % 0.97 [ 0.69, 1.37 ]

0.1 0.2 0.5 1 2 5 10

Analysis 12.6. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 6 Severe pneumonia.
Outcome: 6 Severe pneumonia

Straus 1998 203/398 99/197 100.0 % 1.03 [ 0.73, 1.45 ]
Total (95% CI) 398 197 100.0 % 1.03 [ 0.73, 1.45 ]

0.1 0.2 0.5 1 2 5 10


Analysis 12.7. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 7 Failure rate.

CATCHUP 2002 139/734 117/725 100.0 % 1.21 [ 0.93, 1.59 ]
Total (95% CI) 734 725 100.0 % 1.21 [ 0.93, 1.59 ]

0.1 0.2 0.5 1 2 5 10

Analysis 12.8. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 8 Failure rate non-severe
pneumonia clinical diagnosis.
Outcome: 8 Failure rate non-severe pneumonia clinical diagnosis

Straus 1998 25/195 12/96 100.0 % 1.03 [ 0.49, 2.15 ]
Total (95% CI) 195 96 100.0 % 1.03 [ 0.49, 2.15 ]

0.1 0.2 0.5 1 2 5 10


Analysis 12.9. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 9 Failure rate severe
pneumonia clinical diagnosis.
Outcome: 9 Failure rate severe pneumonia clinical diagnosis

Straus 1998 56/203 18/99 100.0 % 1.71 [ 0.94, 3.11 ]
Total (95% CI) 203 99 100.0 % 1.71 [ 0.94, 3.11 ]

0.1 0.2 0.5 1 2 5 10

Analysis 12.10. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 10 Failure rate radiological
positive pneumonia.
Outcome: 10 Failure rate radiological positive pneumonia

Straus 1998 35/102 10/51 100.0 % 2.14 [ 0.96, 4.78 ]
Total (95% CI) 102 51 100.0 % 2.14 [ 0.96, 4.78 ]

0.1 0.2 0.5 1 2 5 10


Analysis 12.11. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 11 Failure rate radiological
negative for pneumonia.
Outcome: 11 Failure rate radiological negative for pneumonia

Straus 1998 54/283 17/141 100.0 % 1.72 [ 0.96, 3.09 ]
Total (95% CI) 283 141 100.0 % 1.72 [ 0.96, 3.09 ]

0.1 0.2 0.5 1 2 5 10

Analysis 12.12. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 12 Death rate.

CATCHUP 2002 1/734 0/725 42.8 % 2.97 [ 0.12, 72.96 ]
Straus 1998 1/398 0/193 57.2 % 1.46 [ 0.06, 36.01 ]
Total (95% CI) 1132 918 100.0 % 2.11 [ 0.22, 20.24 ]

0.1 0.2 0.5 1 2 5 10


Analysis 12.13. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 13 Lost to follow up.

CATCHUP 2002 14/734 16/725 75.3 % 0.86 [ 0.42, 1.78 ]
Straus 1998 12/398 4/197 24.7 % 1.50 [ 0.48, 4.71 ]
Total (95% CI) 1132 922 100.0 % 1.02 [ 0.56, 1.86 ]

0.1 0.2 0.5 1 2 5 10

Analysis 12.14. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 14 Wheeze positive.
Outcome: 14 Wheeze positive

CATCHUP 2002 37/741 47/730 100.0 % 0.76 [ 0.49, 1.19 ]
Total (95% CI) 741 730 100.0 % 0.76 [ 0.49, 1.19 ]

0.1 0.2 0.5 1 2 5 10


Analysis 12.15. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 15 Cure rate.

CATCHUP 2002 595/734 608/725 100.0 % 0.82 [ 0.63, 1.08 ]
Total (95% CI) 734 725 100.0 % 0.82 [ 0.63, 1.08 ]

0.1 0.2 0.5 1 2 5 10

Analysis 12.16. Comparison 12 Co-trimoxazole versus amoxycillin, Outcome 16 Change of antibiotics.
Outcome: 16 Change of antibiotics

CATCHUP 2002 121/734 98/725 100.0 % 1.26 [ 0.95, 1.69 ]
Total (95% CI) 734 725 100.0 % 1.26 [ 0.95, 1.69 ]

0.1 0.2 0.5 1 2 5 10


Analysis 13.1. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 1 Age in months.
Comparison: 13 Co-trimoxazole versus chloramphenicol

Mulholland 1995 56 18.5 (7.21) 55 16.6 (6.4) 100.0 % 1.90 [ -0.64, 4.44 ]
Total (95% CI) 56 55 100.0 % 1.90 [ -0.64, 4.44 ]

-10 -5 0 5 10
Analysis 13.2. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 2 Male sex.
Outcome: 2 Male sex

Mulholland 1995 22/55 24/56 100.0 % 0.89 [ 0.42, 1.89 ]
Total (95% CI) 55 56 100.0 % 0.89 [ 0.42, 1.89 ]

0.1 0.2 0.5 1 2 5 10


Analysis 13.3. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 3 Weight for age.
Outcome: 3 Weight for age

Mulholland 1995 55 60.2 (8.3) 56 60.2 (8.4) 100.0 % 0.0 [ -3.11, 3.11 ]
Total (95% CI) 55 56 100.0 % 0.0 [ -3.11, 3.11 ]

-10 -5 0 5 10
Analysis 13.4. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 4 Wheezing positive.
Outcome: 4 Wheezing positive

Mulholland 1995 2/55 3/56 100.0 % 0.67 [ 0.11, 4.15 ]
Total (95% CI) 55 56 100.0 % 0.67 [ 0.11, 4.15 ]

0.1 0.2 0.5 1 2 5 10


Analysis 13.5. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 5 Cure rate.

Mulholland 1995 39/55 39/56 100.0 % 1.06 [ 0.47, 2.40 ]
Total (95% CI) 55 56 100.0 % 1.06 [ 0.47, 2.40 ]

0.1 0.2 0.5 1 2 5 10

Analysis 13.6. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 6 Failure rate.

Mulholland 1995 16/55 16/56 100.0 % 1.03 [ 0.45, 2.33 ]
Total (95% CI) 55 56 100.0 % 1.03 [ 0.45, 2.33 ]

0.1 0.2 0.5 1 2 5 10


Analysis 13.7. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 7 Excluded.
Outcome: 7 Excluded

Mulholland 1995 16/55 17/56 100.0 % 0.94 [ 0.42, 2.12 ]
Total (95% CI) 55 56 100.0 % 0.94 [ 0.42, 2.12 ]

0.1 0.2 0.5 1 2 5 10

Analysis 13.8. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 8 Relapse rate.
Outcome: 8 Relapse rate

Mulholland 1995 4/55 4/56 100.0 % 1.02 [ 0.24, 4.30 ]
Total (95% CI) 55 56 100.0 % 1.02 [ 0.24, 4.30 ]

0.1 0.2 0.5 1 2 5 10


Analysis 13.9. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 9 Need for change in
antibiotics.
Outcome: 9 Need for change in antibiotics

Mulholland 1995 8/55 6/56 100.0 % 1.42 [ 0.46, 4.40 ]
Total (95% CI) 55 56 100.0 % 1.42 [ 0.46, 4.40 ]

0.1 0.2 0.5 1 2 5 10

Analysis 13.10. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 10 Death rate.

Mulholland 1995 8/55 4/56 100.0 % 2.21 [ 0.63, 7.83 ]
Total (95% CI) 55 56 100.0 % 2.21 [ 0.63, 7.83 ]

0.1 0.2 0.5 1 2 5 10


Analysis 13.11. Comparison 13 Co-trimoxazole versus chloramphenicol, Outcome 11 Organisms isolated
on blood culture or lung puncture.
Outcome: 11 Organisms isolated on blood culture or lung puncture

Mulholland 1995 11/56 9/55 100.0 % 1.25 [ 0.47, 3.30 ]
Total (95% CI) 56 55 100.0 % 1.25 [ 0.47, 3.30 ]

0.1 0.2 0.5 1 2 5 10

Analysis 14.1. Comparison 14 Co-trimoxazole versus co-amoxyclavulanic acid, Outcome 1 Children below
one year of age.
Comparison: 14 Co-trimoxazole versus co-amoxyclavulanic acid
Outcome: 1 Children below one year of age

CATCHUP 2002 372/734 0/50 54.8 % 103.79 [ 6.38, 1688.47 ]
Straus 1998 227/398 0/50 45.2 % 133.98 [ 8.21, 2186.87 ]
Total (95% CI) 1132 100 100.0 % 117.45 [ 16.28, 847.47 ]

0.1 0.2 0.5 1 2 5 10


Analysis 14.2. Comparison 14 Co-trimoxazole versus co-amoxyclavulanic acid, Outcome 2 Male sex.
Outcome: 2 Male sex

CATCHUP 2002 362/734 35/50 58.3 % 0.42 [ 0.22, 0.78 ]
Straus 1998 246/398 35/50 41.7 % 0.69 [ 0.37, 1.31 ]
Total (95% CI) 1132 100 100.0 % 0.53 [ 0.34, 0.83 ]

0.1 0.2 0.5 1 2 5 10

Analysis 14.3. Comparison 14 Co-trimoxazole versus co-amoxyclavulanic acid, Outcome 3 Failure rate.

CATCHUP 2002 139/734 1/50 52.6 % 11.45 [ 1.57, 83.61 ]
Straus 1998 92/398 1/50 47.4 % 14.73 [ 2.01, 108.15 ]
Total (95% CI) 1132 100 100.0 % 13.00 [ 3.18, 53.13 ]

0.1 0.2 0.5 1 2 5 10


Analysis 15.1. Comparison 15 Amoxycillin versus cefpodoxime, Outcome 1 Age in months.
Comparison: 15 Amoxycillin versus cefpodoxime

Jibril 1989 50 58.8 (0) 234 21.6 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 50 234 0.0 [ 0.0, 0.0 ]

-10 -5 0 5 10
Analysis 15.2. Comparison 15 Amoxycillin versus cefpodoxime, Outcome 2 Male sex.
Outcome: 2 Male sex

Jibril 1989 18/50 0/1 100.0 % 1.71 [ 0.07, 44.09 ]
Total (95% CI) 50 1 100.0 % 1.71 [ 0.07, 44.09 ]

0.1 0.2 0.5 1 2 5 10


Analysis 15.3. Comparison 15 Amoxycillin versus cefpodoxime, Outcome 3 Response/cure rate.
Outcome: 3 Response/cure rate

Jibril 1989 40/50 179/188 100.0 % 0.20 [ 0.08, 0.53 ]
Total (95% CI) 50 188 100.0 % 0.20 [ 0.08, 0.53 ]

0.1 0.2 0.5 1 2 5 10

Analysis 16.1. Comparison 16 Amoxycillin versus chloramphenicol, Outcome 1 Age (mean/median).
Comparison: 16 Amoxycillin versus chloramphenicol
Outcome: 1 Age (mean/median)

N Mean(SD) N Mean(SD) IV,Random,95% CI IV,Random,95% CI
CATCHUP 2002 725 12 (2.54) 55 16.6 (6.4) 50.1 % -4.60 [ -6.30, -2.90 ]
Mulholland 1995 197 8 (2.54) 55 16.6 (6.4) 49.9 % -8.60 [ -10.33, -6.87 ]
Total (95% CI) 922 110 100.0 % -6.60 [ -10.52, -2.68 ]

-10 -5 0 5 10

Analysis 16.2. Comparison 16 Amoxycillin versus chloramphenicol, Outcome 2 Male sex.
Outcome: 2 Male sex

CATCHUP 2002 435/725 24/55 61.0 % 1.94 [ 1.11, 3.37 ]
Straus 1998 137/197 24/55 39.0 % 2.95 [ 1.60, 5.45 ]
Total (95% CI) 922 110 100.0 % 2.33 [ 1.55, 3.52 ]

0.1 0.2 0.5 1 2 5 10

Analysis 16.3. Comparison 16 Amoxycillin versus chloramphenicol, Outcome 3 Cure rate.

CATCHUP 2002 608/725 39/71 100.0 % 4.26 [ 2.57, 7.08 ]
Total (95% CI) 725 71 100.0 % 4.26 [ 2.57, 7.08 ]

0.1 0.2 0.5 1 2 5 10


Analysis 16.4. Comparison 16 Amoxycillin versus chloramphenicol, Outcome 4 Failure rates.
Outcome: 4 Failure rates

CATCHUP 2002 117/725 16/71 55.0 % 0.66 [ 0.37, 1.19 ]
Straus 1998 30/198 16/71 45.0 % 0.61 [ 0.31, 1.21 ]
Total (95% CI) 923 142 100.0 % 0.64 [ 0.41, 1.00 ]

0.1 0.2 0.5 1 2 5 10

Analysis 17.1. Comparison 17 Amoxycillin versus procaine penicillin, Outcome 1 Median age.
Comparison: 17 Amoxycillin versus procaine penicillin
Outcome: 1 Median age

Tsarouhas 1998 77 2.9 (2.8) 93 2.6 (2.6) 100.0 % 0.30 [ -0.52, 1.12 ]
Total (95% CI) 77 93 100.0 % 0.30 [ -0.52, 1.12 ]

-10 -5 0 5 10

Analysis 17.2. Comparison 17 Amoxycillin versus procaine penicillin, Outcome 2 Failure rate.
Comparison: 17 Amoxycillin versus procaine penicillin

Tsarouhas 1998 3/68 5/86 100.0 % 0.75 [ 0.17, 3.25 ]
Total (95% CI) 68 86 100.0 % 0.75 [ 0.17, 3.25 ]

0.1 0.2 0.5 1 2 5 10

Analysis 18.1. Comparison 18 Co-trimoxazole versus single dose procaine penicillin followed by oral
ampicillin, Outcome 1 Mean age (months).
Comparison: 18 Co-trimoxazole versus single dose procaine penicillin followed by oral ampicillin

Campbell 1988 66 22 (0) 68 21.8 (0) 0.0 [ 0.0, 0.0 ]
Total (95% CI) 66 68 0.0 [ 0.0, 0.0 ]

-10 -5 0 5 10

ampicillin, Outcome 2 Male sex.
Outcome: 2 Male sex

Campbell 1988 41/66 38/68 100.0 % 1.29 [ 0.65, 2.58 ]
Total (95% CI) 66 68 100.0 % 1.29 [ 0.65, 2.58 ]

0.1 0.2 0.5 1 2 5 10

ampicillin, Outcome 3 Cure rate.

Campbell 1988 60/66 61/68 100.0 % 1.15 [ 0.36, 3.61 ]
Total (95% CI) 66 68 100.0 % 1.15 [ 0.36, 3.61 ]

0.1 0.2 0.5 1 2 5 10


ampicillin, Outcome 4 Hospitalization rate.

Campbell 1988 3/66 2/68 100.0 % 1.57 [ 0.25, 9.72 ]
Total (95% CI) 66 68 100.0 % 1.57 [ 0.25, 9.72 ]

0.1 0.2 0.5 1 2 5 10

ampicillin, Outcome 5 Death rate.

Campbell 1988 0/66 2/68 100.0 % 0.20 [ 0.01, 4.25 ]
Total (95% CI) 66 68 100.0 % 0.20 [ 0.01, 4.25 ]

0.1 0.2 0.5 1 2 5 10


Analysis 19.1. Comparison 19 Azithromycin versus co-amoxyclavulanic acid, Outcome 1 Cure rate.
Comparison: 19 Azithromycin versus co-amoxyclavulanic acid

Harris 1998 84/125 42/63 100.0 % 1.02 [ 0.54, 1.95 ]
Total (95% CI) 125 63 100.0 % 1.02 [ 0.54, 1.95 ]

0.1 0.2 0.5 1 2 5 10

Analysis 19.2. Comparison 19 Azithromycin versus co-amoxyclavulanic acid, Outcome 2 Failure rate.
Study or subgroup Tretament Control Odds Ratio Weight Odds Ratio

Harris 1998 11/125 4/63 73.7 % 1.42 [ 0.43, 4.66 ]
Wubbel 1999 1/39 2/49 26.3 % 0.62 [ 0.05, 7.08 ]
Total (95% CI) 164 112 100.0 % 1.21 [ 0.43, 3.43 ]

Total events: 12 (Tretament), 6 (Control)
0.1 0.2 0.5 1 2 5 10


Analysis 19.3. Comparison 19 Azithromycin versus co-amoxyclavulanic acid, Outcome 3 Improved.
Outcome: 3 Improved

Harris 1998 30/125 17/63 100.0 % 0.85 [ 0.43, 1.71 ]
Total (95% CI) 125 63 100.0 % 0.85 [ 0.43, 1.71 ]

0.1 0.2 0.5 1 2 5 10

Analysis 19.4. Comparison 19 Azithromycin versus co-amoxyclavulanic acid, Outcome 4 Side effects.

Harris 1998 14/125 19/63 46.8 % 0.29 [ 0.13, 0.63 ]
Wubbel 1999 5/39 33/49 53.2 % 0.07 [ 0.02, 0.22 ]
Total (95% CI) 164 112 100.0 % 0.17 [ 0.09, 0.32 ]

0.1 0.2 0.5 1 2 5 10


Analysis 19.5. Comparison 19 Azithromycin versus co-amoxyclavulanic acid, Outcome 5 Organisms
isolated.
Outcome: 5 Organisms isolated

Harris 1998 5/125 2/63 100.0 % 1.27 [ 0.24, 6.74 ]
Total (95% CI) 125 63 100.0 % 1.27 [ 0.24, 6.74 ]

0.1 0.2 0.5 1 2 5 10

Analysis 19.6. Comparison 19 Azithromycin versus co-amoxyclavulanic acid, Outcome 6 Mycoplasma

serology positive.
Outcome: 6 Mycoplasma serology positive

Harris 1998 85/129 39/63 100.0 % 1.19 [ 0.64, 2.22 ]
Total (95% CI) 129 63 100.0 % 1.19 [ 0.64, 2.22 ]

0.1 0.2 0.5 1 2 5 10


Analysis 20.1. Comparison 20 Chloramphenicol versus chloramphenicol plus penicillin, Outcome 1 Need
for change of antibiotics.
Comparison: 20 Chloramphenicol versus chloramphenicol plus penicillin
Outcome: 1 Need for change of antibiotics

Shann 1985 3/377 6/371 100.0 % 0.49 [ 0.12, 1.97 ]
Total (95% CI) 377 371 100.0 % 0.49 [ 0.12, 1.97 ]

0.1 0.2 0.5 1 2 5 10

Analysis 20.2. Comparison 20 Chloramphenicol versus chloramphenicol plus penicillin, Outcome 2 Death
rates.

Shann 1985 48/377 62/371 100.0 % 0.73 [ 0.48, 1.09 ]
Total (95% CI) 377 371 100.0 % 0.73 [ 0.48, 1.09 ]

0.1 0.2 0.5 1 2 5 10


Analysis 20.3. Comparison 20 Chloramphenicol versus chloramphenicol plus penicillin, Outcome 3 Lost to
follow up.

Shann 1985 105/377 96/371 100.0 % 1.11 [ 0.80, 1.53 ]
Total (95% CI) 377 371 100.0 % 1.11 [ 0.80, 1.53 ]

0.1 0.2 0.5 1 2 5 10

Analysis 21.1. Comparison 21 Chloramphenicol plus penicillin versus ceftrioxone, Outcome 1 Cure rates.
Comparison: 21 Chloramphenicol plus penicillin versus ceftrioxone

Cetinkaya 2004 39/46 41/51 100.0 % 1.36 [ 0.47, 3.93 ]
Total (95% CI) 46 51 100.0 % 1.36 [ 0.47, 3.93 ]

0.1 0.2 0.5 1 2 5 10


Analysis 22.1. Comparison 22 Clarithromycin versus erythromycin, Outcome 1 Age below five years.
Comparison: 22 Clarithromycin versus erythromycin
Outcome: 1 Age below five years

Block 1995 45/133 45/127 100.0 % 0.93 [ 0.56, 1.55 ]
Total (95% CI) 133 127 100.0 % 0.93 [ 0.56, 1.55 ]

0.1 0.2 0.5 1 2 5 10

Analysis 22.2. Comparison 22 Clarithromycin versus erythromycin, Outcome 2 Cure rates.

Block 1995 104/124 84/110 100.0 % 1.61 [ 0.84, 3.08 ]
Total (95% CI) 124 110 100.0 % 1.61 [ 0.84, 3.08 ]

0.1 0.2 0.5 1 2 5 10


Analysis 22.3. Comparison 22 Clarithromycin versus erythromycin, Outcome 3 Clinical success rate.
Outcome: 3 Clinical success rate

Block 1995 121/124 105/110 100.0 % 1.92 [ 0.45, 8.23 ]
Total (95% CI) 124 110 100.0 % 1.92 [ 0.45, 8.23 ]

0.1 0.2 0.5 1 2 5 10

Analysis 22.4. Comparison 22 Clarithromycin versus erythromycin, Outcome 4 Failure rates.
Outcome: 4 Failure rates

Block 1995 3/124 5/110 100.0 % 0.52 [ 0.12, 2.23 ]
Total (95% CI) 124 110 100.0 % 0.52 [ 0.12, 2.23 ]

0.1 0.2 0.5 1 2 5 10


Analysis 22.5. Comparison 22 Clarithromycin versus erythromycin, Outcome 5 Relapse rates.
Outcome: 5 Relapse rates

Block 1995 1/121 5/105 100.0 % 0.17 [ 0.02, 1.45 ]
Total (95% CI) 121 105 100.0 % 0.17 [ 0.02, 1.45 ]

0.1 0.2 0.5 1 2 5 10

Analysis 22.6. Comparison 22 Clarithromycin versus erythromycin, Outcome 6 Radiologic resolution.
Outcome: 6 Radiologic resolution

Block 1995 103/111 82/98 100.0 % 2.51 [ 1.02, 6.16 ]
Total (95% CI) 111 98 100.0 % 2.51 [ 1.02, 6.16 ]

0.1 0.2 0.5 1 2 5 10


Analysis 22.7. Comparison 22 Clarithromycin versus erythromycin, Outcome 7 Radiologic success.
Outcome: 7 Radiologic success

Block 1995 109/111 92/98 100.0 % 3.55 [ 0.70, 18.04 ]
Total (95% CI) 111 98 100.0 % 3.55 [ 0.70, 18.04 ]

0.1 0.2 0.5 1 2 5 10

Analysis 22.8. Comparison 22 Clarithromycin versus erythromycin, Outcome 8 Radiologic failure.
Outcome: 8 Radiologic failure

Block 1995 2/111 5/98 100.0 % 0.34 [ 0.06, 1.80 ]
Total (95% CI) 111 98 100.0 % 0.34 [ 0.06, 1.80 ]

0.1 0.2 0.5 1 2 5 10


Analysis 22.9. Comparison 22 Clarithromycin versus erythromycin, Outcome 9 Adverse events.
Outcome: 9 Adverse events

Block 1995 32/133 29/127 100.0 % 1.07 [ 0.60, 1.90 ]
Total (95% CI) 133 127 100.0 % 1.07 [ 0.60, 1.90 ]

0.1 0.2 0.5 1 2 5 10

Analysis 22.10. Comparison 22 Clarithromycin versus erythromycin, Outcome 10 Bacteriologic response.
Outcome: 10 Bacteriologic response

Block 1995 24/27 16/18 100.0 % 1.00 [ 0.15, 6.67 ]
Total (95% CI) 27 18 100.0 % 1.00 [ 0.15, 6.67 ]

0.1 0.2 0.5 1 2 5 10


APPENDICES
Appendix 1. EMBASE search strategy
EMBASE (WebSPIRS)
#1 explode ’pneumonia-’ / all subheadings in DEM,DER,DRM,DRR
#2 (pneumonia in ti) or (pneumonia in ab)
#3 #1 or #2
#4 ’antibiotic-agent’ / all subheadings in DEM,DER,DRM,DRR
#5 (antibiotic* in ti) or (antibiotic* in ab)
#6 #4 or #5
#7 ’child-’ / all subheadings in DEM,DER,DRM,DRR
#8 (child in ti) or (child in ab)
#9 (children in ti) or (children in ab)
#10 ’infant-’ / all subheadings in DEM,DER,DRM,DRR
#11 (infant* in ti) or (infant* in ab)
#12 #7 or #8 or #9 or #10 or #11
#13 #3 and #6 and #12
#14 explode ’randomized-controlled-trial’ / all subheadings
#15 explode ’controlled-study’ / all subheadings
#16 explode ’single-blind-procedure’ / all subheadings
#17 explode ’double-blind-procedure’ / all subheadings
#18 explode ’crossover-procedure’ / all subheadings
#19 explode ’phase-3-clinical-trial’ / all subheadings
#20 (randomi?ed controlled trial in ti) or (randomi?ed controlled trial in ab)
#21 ((random* or placebo* or double-blind*)in ti) or ((random* or placebo* or double-blind*)in ab)
#22 (controlled clinical trial* in ti) or (controlled clinical trial* in ab)
#23 #14 or #15 or #16 or #17 or 318 or #19 or #290 or #21 or #22
#24 (nonhuman in der) not ((human in der) and (nonhuman in der))
#25 #23 not #24
#26 #13 and #25
WHAT’S NEW
Last assessed as up-to-date: 7 May 2006.
8 August 2008 Amended Converted to new review format.
HISTORY
Protocol first published: Issue 3, 2004
Review first published: Issue 3, 2006

CONTRIBUTIONS OF AUTHORS
Dr Sushil K Kabra and Dr Rakesh Lodha jointly prepared and edited the review.
Dr RM Pandey contributed to the sections on data extraction, data analysis, quality assessment and statistical methods; in addition to
editing the review.
DECLARATIONS OF INTEREST
None known
SOURCES OF SUPPORT
Internal sources
• All India Institute of Medical Sciences, New Delhi, India.
External sources
• No sources of support supplied
INDEX TERMS
Medical Subject Headings (MeSH)

Anti-Bacterial Agents [∗ therapeutic use]; Community-Acquired Infections [drug therapy]; Drug Therapy, Combination; Pneumonia,
Bacterial [∗ drug therapy]; Randomized Controlled Trials as Topic
MeSH check words

Child; Humans


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Antibiotics for community acquired pneumonia in children

Kabra SK, Lodha R, Pandey RM

Antibiotics for community acquired pneumonia in children (Review)

Antibiotics for community acquired pneumonia in children (Review) iii

Antibiotics for community acquired pneumonia in children (Review) iv

Antibiotics for community acquired pneumonia in children

Sushil K Kabra1 , Rakesh Lodha2 , R M Pandey3

PLAIN LANGUAGE SUMMARY

METHODS Treatment failure

• development of chest in-drawing;

Antibiotics for community acquired pneumonia in children (Review) 3

Assessment of reporting biases

Antibiotics for community acquired pneumonia in children (Review) 4

Antibiotics for community acquired pneumonia in children (Review) 5

Study Randomization (0-2) Double blinding (0-2 Withdrawals (0-1) Total

CATCHUP study group 2 2 1 5

performed to detect the impact of individual studies in each of

Antibiotics for community acquired pneumonia in children (Review) 7

Antibiotics for community acquired pneumonia in children (Review) 8

Table 2. Bacterial isolation

Study/total tested S. Pneumoniae H. Influenzae Staphylococcus Others

Antibiotics for community acquired pneumonia in children (Review) 9

Mulholland et al/ 111 10 2 0 8

Block et al/ 122 2 2 0 0

Wubbel et al/ 129 35 0 0 0

Total/4009 169(4.2) 104 (2.6) 11(0.3%) 42(1.2)

penicillin and gentamycin was better than chloramphenicol alone,

Antibiotics for community acquired pneumonia in children (Review) 11

Antibiotics for community acquired pneumonia in children (Review) 12

Higuera 1996 {published data only} Berman 1990

Antibiotics for community acquired pneumonia in children (Review) 15

Characteristics of included studies [ordered by study ID]

Methods RCT comparing amoxycillin and penicillin

Participants Children 3 to 59 months with severe pneumonia

Interventions Daily IM penicillin 200,000 IU/kg or PO amoxycillin 45 mg/kg/day

Item Authors’ judgement Description

Allocation concealment? Unclear D - Not used

Methods RCT comparing clarithromycin with erythromycin in children with pneumonia

Participants Children between 3 to 16 years of age with radiographically diagnosed pneumonia

Item Authors’ judgement Description

Allocation concealment? Unclear B - Unclear

Antibiotics for community acquired pneumonia in children (Review) 16

Methods RCT comparing benzathine penicillin and procaine penicillin

Participants Children 2 years to 12 years with non severe pneumonia

Outcomes Cure rate, failure rate, lost to follow up

Item Authors’ judgement Description

Allocation concealment? Unclear D - Not used

Participants Children 1 month to 4 years of age with non-severe pneumonia

Outcomes Cure rate, hospitalization rate and death rate

Item Authors’ judgement Description

Allocation concealment? Unclear D - Not used

Methods RCT comparing amoxycillin and co-trimoxazole in non severe pneumonia

Participants Children 2 to 59 months with non-severe pneumonia

Antibiotics for community acquired pneumonia in children (Review) 17

Outcomes Cure rate, failure rate, change of antibiotics

Item Authors’ judgement Description

Allocation concealment? Yes A - Adequate

Methods RCT comparing chloramphenicol in combination with penicillin with ceftriaxone

Outcomes Clinical recovery

Item Authors’ judgement Description

Allocation concealment? Yes A - Adequate

Participants Children 5 months to 4 years with pneumonia admitted to hospital

Outcomes Cure rate, failure rate