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LONG CASE REPORT

RESPIRATORY DISTRESS DUE TO PNEUMONIA NEONATAL ( P23.3),


LATE ONSET SEPSIS (P36.9) AND
NEONATAL BACTERIAL MENINGITIS (G00.9)

By:
Ni Putu Mayasri Wulandari

Local Evaluation
Denpasar, January 22nd, 2018

POSTGRADUATE PEDIATRIC TRAINING PROGRAMME


DEPARTMENT OF CHILD HEALTH
FACULTY OF MEDICINE UDAYANA UNIVERSITY/
SANGLAH HOSPITAL DENPASAR
2018

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I. Identity
a. Patient identity
Name : Baby NKS
Age at case determination : 26 days
Date of birth : December 16nd, 2017
Sex : Female
Address : Indonesia
Date of admission : December 31nd, 2017
Date of case determination : Januari 12th, 2018
Medical record number : 17056105
b. Parents identity
Father Mother
Name (initial) NB NKS
Age 29 years old 27 years
Education Senior high school Senior high school
Occupation Courier Rafting staff employee

II. History taking (Subjective)


History of illness was gathered from parents and paramedics.
1. History of present illness
Chief complaint: shortness of breath
Patient was referred from A hospital with diagnosis suspect
bronchopneumonia. Shortness of breath since 2 days before admission, it
happened all days, could not improved with changing position. This symptom
makes patient crying more often and difficult to get sleep. Dyspnea
accompanied by chest indrawing. Parent did not noticed any blue coloration
of skin or mouth during this 2 days. Patient presented as less activity and
looked weak.
Patient have cough and runny nose since 3 days before admission Cough
happen almost all day and it followed by shortness of breath 1 day after the

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onset. Parent said that patient’s grandmother, who live in the same house, also
suffered from runny nose which started 1 week before.
Patient also had fever since 2 days before admission with temperature
range 38.0-38.5oC. The fever relieved after medication which mother get from
pediatrician, reached normal body temperature then rised again throughout all
day. Fever raised suddenly high and make patient often cried loudly and
difficult to be calmed down. Fever did not accompany by chills.
Parent also complained patient appeared less activity. This started 2 days
before admission. Patient look weaker. The patient seemed inactive and lazy
to breast feed. Patient only breastfeed few minuted and less often. After breast
feed patient looked not satisfied and then crying. This is observed throughout
the day.
Patient was born vigorously. The umbilical cord came off at the age of 4
days. No complaints of blood or fluid leaking from umbilical cord and redness
on the umbilical cord. There was no fluid discharged from ear. No history of
bleeding, trauma or swaying before admission. No yellowish colour on the eyes
or skin.
Patient was breast fed on demand (before get sick). Patient breast fed as
long as 15-20 minute, 8-10 times a day. The mother said after breast fed patient
looked calm and then sleep. She also could feel that her breast empty. Patient
never been given formula milk. No complaints of vomiting and seizure.
Urination approximately 8 times/day with clear yellowish color. The last
urination was 2 hours before admission. Defecation approximately 2
times/day, the color was yellow, with volume approximately 1-2 table spoon
each defecation and soft consistency. The last defecation was 4 hours before
admission.
2. History of past illness and medication.
Patient was born fullterm by section caesaria at hospital assisted by doctor and
discharged at 3 days old in a good condition. When patient was 12 days old, he
complained of cough and runny nose. Parent then brought her to private
pediatrician. The patient was given oral cough medicine. Parent noted that their

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children’s cough and shortness of breath getting worsened, then sixteen hours
before admission, the patient decided to bring their children to the A hospital.
The patient was given oxygen 2 litre/minutes. Patient then referred to B
hospital for further treatment. There is no history of seizure, vomiting and
yellowish skin color.

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3. Family medical history
The grandmother, who live in the same house with aptient, suffered from runny
nose 1 week before. There was no history of epilepsy, diabetes mellitus, or
other disease in the family.
4. Social history
a. Mother pregnancy history
Mother was 27 years old. It was her first pregnancy. Mother’s first day of
the last menstrual period was March 5th, 2017 and estimation date of
delivery was December 10st 2017. Mother visited obstetrician for antenatal
care every month. Ultrasonography examination revealed normal
pregnancy. Mother had history of fever for 5 days whilde in 7 month
pregnancy. She didn’t took any medication for it. Mother consumed
multivitamins during pregnancy given by the obstetrician routinely. There
was no history of smoking or alcohol
consumption before as well as during pregnancy.
Conclusion: mother had fever on 7 month of pregnancy.
b. Intranatal history
Patient was born through section caesaria on December 16st, 2017 at 20.00.
Patient was vigorous with unknown APGAR score, but mother said her
baby was crying loudly soon after birth delivery. Mother was told by the
doctor that her amniotic fluid was green. Mother did not experienced any
history of premature rupture of membrane, chorioamnionitis, fetal
distress, green amniotic fluid, vaginal discharge, or urinary tract infection.
Conclusion: Mother suffered from fever and has greenish amniotic fluid.

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c. Postnatal history
The patient was given umbilical cord care and vitamin K1 injection 1 mg
intramuscularly. Due to mother’s green amniotic fluid, patient was admitted to
neonatal ward and got antibiotic injection for 6 times. Patient was discharged
from hospital three days after birth in a good condition.
Conclusion: patient had been given antibiotic injection.
d. Nutritional history
Before admission patient was breastfed on demand. Breast milk production
was 90-100 ml every 3 hours. From birth until 2 days before admission,
patient less likely to breastfeed. After admission, initially patient was fasted
so nutritional routes was given parenterally. Enteral nutrition with breast
milk was started after patient was stable and gradually increased in volume
as the patient showed good tolerance.
Conclusion: The patient already reached fullfeed before admission.
e. Growth and developmental history
Patient birth weight was 2,800 gram, length 50 cm and head circumference
34 cm. At admission patient was 2,900 gram, length 51 cm and head
circumference 35 cm. Patient gained 100 gram in body weight, 4 cm in
length, and 1 cm in head circumference during 12 days.
Patient was able to suck well, he could watch nearby things moving,
reacted to bright lights, and responded to loud sounds.
Conclusion: Growth and development was appropriate.
f. Immunization history
Hepatitis B :once (0 day)
g. Basic needs history
Stimulation : Patient accompanied parents everyday, whenever they are
not at work. Mother and father talked and sang lullaby to
patient approximately an hour/day.
Parenting : Patient was the first child of the family, and was conceived
from an intended pregnancy. Patient was loved and
supported by the family.

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Caring : Patient has been given breast milk since birth without
additional formula milk. Mother did breast pump
regulary
and stored it to be given to the patient.
Conclusion : Optimal fulfillment of stimulation, parenting, and
caring.
h. Family socio-economic and environment
condition
Patient was the first child. Patient lived in a house with both parents,
his uncle, grandfather and grandmother, with an area of 200 m2 in
rural areas. House was facilitated with kitchen, private bathroom,
electricity and water. Patient live in densely populated area. Her
father work as courir and mother as a staff in rafting company.
Family income was approximately 4,000,000 IDR/month.
Conclusion: Patient with middle socioeconomic group.

III. History During Admission Until Determination as Case


On the first day of treatment in emergency unit (December 31th 2017),
patient was lethargic and had respiratory distress. From examination, patient
moderately ill, poor activity, tone, and reflexes, with temperatures ranged
between 38.0-38.50C, pulse rate 140-160 beats/minute, respiratory rate 60-70
breaths/minute, saturation 96% with O2 1 liter/minute, downes score 3, and pain
score was 2 with Neonatal Pain Assessment Tools (NPAT). There was subcostal
retractions. Lung auscultation revealed grunting and there was murmur at
intercostal space IV (ICS IV) midclavicular line (MCL) sinistra grade II/6.
Complete blood count obtained leukocytes 11.70 K/uL (neutrophils 6.50 K/uL
(55.52%), lymphocytes 4.41 K/uL (37.64%)); hemoglobin 15.67 g/dL;
hematocrit 49.02%; platelets 355.80 K/mL; IT ratio 0.51; procalcitonin 0.13
blood glucose 96 mg/dL. Blood smear revealed neutrofilia with toxic granule
and vacuolization. Antero-posterior chest x-ray showed pneumonia. Patient was
assessed with respiratory distress due to pneumonia neonatal (P23.3), suspect
late onset sepsis (P36.9), and suspect congenital heart disease due to patent

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ductus arteriosus (Q25.0) differential diagnosis tricuspid regurgitation (I07.1).
Patient was transferred to level II neonatal ward with incubator and oxygen 2
L/minutes. Respiratory distress had worsen in level II neonatal ward and oxygen
was raised to 3 L/minutes, blood gas analysis and electrolytes was performed.
Blood gas analysis revealed blood analysis from venous with pH 7.37, pCO2
56.62 mmHg, pO2 38.8 mmHg, HCO3- 31.9 mmol/L, BE 6.6 mmol/L, SaO2
70.4%, sodium 142 mmol/L; potassium 5.73 mmol/L; calcium 9.5 mg/dL;
chloride 100.7 mmol/L. Nutrition was given enteral using nasogastric tube with
total fluid of 120 ml/kg/day (with minimal breast milk 44 ml every 3 hours).
First line intravenous antibiotic was given, ampicillin 50 mg/kg/dose every 12
hours and amikacin 7.5 mg/kg/dose every 8 hours. Patient was given
paracetamol 10 mg/kg/day if body temperature more than 38ºC. Blood culture
examination was performed before antibiotics. Patient was planned to consult
to cardiologist and lumbal puncture after the patient was stable. Monitoring was
performed for vital signs, fluid balance, and symptoms.
On the second and third days of hospitalization (January 1st-2nd
2018) in level II neonatal ward, respiratory distress had worsen. Physical
examination revealed poor activity, tone and reflexes, with temperatures ranged
between 37.0 to 37.50C, pulse rate 150-160 beats/minute, respiratory rate 65-75
breaths/minute, saturation 79% with O2 3 liter/minute and pain score was 2 with
NPAT. Chest examination showed subcostal retraction and raised work of
breathing with downes score 4. Patient was assessed with respiratory distress
due to pneumonia neonatal (P23.3), suspect late onset sepsis (P36.9), and
suspect congenital heart disease due to patent ductus arteriosus (Q25.0)
differential diagnosis tricuspid regurgitation (I07.1). Patient was treated with
Continous Positive Airway Pressure (CPAP), O2 fraction of 25%, flow 8
L/minutes, and PEEP 6 cmH2O. Enteral feeding, antibiotics were continued and
was planned for septic marker evaluation on day 3rd of antibiotics. Monitoring
was performed for vital signs, fluid balance, downes score and symptoms.
On the fourth and fifth days of hospitalization (January 3rd-4th
2018) in cempaka ward, respiratory distress had slightly improved. The patient
was active, good tone and reflexes, with temperature ranged between 36,5-

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37,20C, pulse rate 130-140 beats/minute, respiratory rate 40-46 breaths/minute,
saturation 98% with CPAP support and pain score was 1 with NPAT. Chest
examination showed minimal subcostal retraction, murmur sound that heard
before diminished but patient still will undergo echocardiography to exclude
congenital heart disease. Complete blood count obtained leukocytes 12.96 K/uL
(neutrophils 3.13 K/uL (24.11%), lymphocytes 8.46 K/uL (65.25%));
hemoglobin 15.09 g/dL; hematocrit 49.24%; platelets 427.10 K /mL; IT ratio
0.07; procalcitonin 0,18 ng/dL. Patient was assessed with respiratory distress
due to pneumonia neonatal (P23.3), suspect late onset sepsis (P36.9), and
suspect congenital heart disease due to patent ductus arteriosus (Q25.0)
differential diagnosis tricuspid regurgitation (I07.1). Fluid requirement 120
ml/kg/day, enteral feeding and antibiotics were continued. Patient was
consulted to medical rehabilitation unit and was planned for chest
physiotherapy and oromotor stimulation. CPAP support was gradually reduced
to oxygen nasal. Monitoring was performed for vital signs, fluid balance, and
symptoms.
On the sixth to eighth days of hospitalization (January 5th-7th 2018)
in cempaka ward, the patient was stable, without any temperature instability,
or respiratory distress. Physical examination revealed good activity, tone and
reflexes. Sucking reflex was more stonger than before. Temperature ranged
between 36.5 to 37.00C, heart rate 125-140 beats/minute, respiratory rate 34-46
breaths /minute, saturation 99% with O2 2 liter/minute and pain score was 1
with NPAT. Patient was assessed with respiratory distress due to pneumonia
neonatal (P23.3), suspect late onset sepsis (P36.9), and suspect congenital heart
disease due to patent ductus arteriosus (Q25.0) differential diagnosis tricuspid
regurgitation (I07.1). Fluid requirement 120 ml/kg/day, try to switch to oral
feeding, physiotherapy and antibiotics were continued. Patient was planned for
lumbal puncture and echocardiography. The oxygen was reduced until patient
can breathe without any oxygen supporting device. Monitoring was performed
for vital signs, fluid balance, and symptoms.
On the ninth and tenth days of hospitalization (January 8th-9th 2018)
in cempaka ward, the patient was stable, without any temperature instability,

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or respiratory distress. Physical examination revealed good activity, tone and
reflexes. Sucking reflex was good. Temperature ranged between 36.5 to
37.00C, heart rate 125-140 beats/minute, respiratory rate 34-40 breaths /minute,
saturation 98% with room air and pain score was 1 with NPAT. Head
circumference was 35 cm. The major fontanelle was flat, no anemic, no icteric,
round pupils with diameter of 2 mm and good light reflexes. There was no sign
of lateralitation. Echocardiography showed normal echocardiography.
Cerebrospinal fluid (CSF) analysis revealed the colour was clear, no blood nor
clot, nonne positive (+), pandy positive (+), cell 44 cell/uL, mononuclear 30%,
polymorphonuclear 70%, erythrocyte 3-4/field, glucose 52, MTP 56.45 mg/dL.
Staphylococcus haemolyticus was detected in blood culture. Patient was
assessed with respiratory distress due to pneumonia neonatal (P23.3), late onset
sepsis (P36.9), and neonatal bacterial meningitis (G00.9). Patient was breathing
without any oxygen supporting device. Fluid requirement 120 ml/kg/day, oral
feeding with breast milk, physiotherapy and antibiotics were continued.
Monitoring was performed for vital signs, fluid balance, and symptoms.
On the eleventh and twelfth days of hospitalization (January 10th-
11th 2018) in cempaka ward, patient showed no temperature instability,
vomiting or lethargic. Physical examination revealed good activity, tone and
reflexes. Temperature ranged between 36.6 to 37.00C, heart rate 126-144
beats/minute, respiratory rate 32-42 breaths /minute, saturation 98% with room
air and pain score was 1 with NPAT. Head circumference was 35 cm. The major
fontanelle was flat, no anemic, no icteric, round pupils with diameter of 2 mm
and good light reflexes. There was no sign of lateralitation. Patient was assessed
with respiratory distress due to pneumonia neonatal (P23.3), late onset sepsis
(P36.9), and neonatal bacterial meningitis (G00.9). Patient was breathing
without any oxygen supporting device. Fluid requirement 120 ml/kg/day, oral
feeding with breast milk, and antibiotics were continued until day 21th. Patient
was planned to undergo evaluation CSF analysis on day 21th of antibiotics.
Monitoring was performed for vital signs, fluid balance, and symptom.

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IV. Physical examination (objective) at case determination (January 12th, 2018)
a. Present status
General condition : good activity, tone, reflex, and cry
Heart rate : 140 beats/minutes, regular
Respiration rate : 36 breaths/minutes, regular
Axilla temperature : 36,7°C
Oxygen saturation : 99% in room air
Neonatal Pain Assessment Tools (NPAT) score: 1

b. General status
Head : normocephaly (head circumference 35 cm), major fontanelle
opened and flat, diameter 4 cm, firm hair, easily separated.
Minor fontanelle was opened.
Face : no abnormality, no edema, no syndromic facies.
Eye : no sunken eyes, no palpebral edema, symmetrical of both
eyelids, conjunctivas were not pale, scleras were not icteric, both
pupils were round, and diameter were 3 mm with good light
reflexes.
Ear : no abnormality in shape, no secretion was found. Curved pinna,
soft, ready recoil.
Nose : no nasal flare, no septal deviation, no secret, no bleeding.
Throat : no palatal cleft, pharynx and tonsil were normal.
Mouth : no cyanosis on surrounding mouth and tongue, no enlargement
of tongue, no white plaque on tongue and mouth, symmetrical of
both corners of the mouth, no drooling, strong sucking reflex,
good swallowing reflex, positive rooting reflex.
Chest :
Cardiac :
Inspection : ictus cordis was not seen
Palpation : ictus cordis was palpable in the intersection of left midclavicular
line and fourth intercostals space, without thrill.
Auscultation : normal heart sounds, regular, M1>T1, P2>A2, no murmur.
Lung :
Inspection : normal chest shape, symmetrical on static and dynamic,
without retraction.
Palpation : symmetrical chest movement.
Auscultation : bronchovesicular, neither rales nor wheezing were found.
Breast : stippled areola 10 mm in diameter, pink colour
Abdominal :
Inspection : no distention, vein not apparent, no hiperemic on umbilical, no
umbilical hernia
Auscultation : normal peristaltic
Palpation : liver was just palpable, unpalpable spleen
Percusion : tympanic
Genitals : labia mayora and labia minora equally prominent.
Anus : normal anus
Limbs :
Upper : no single palmar crease, no short fingers, no cyanosis of fingers,
palm was not pale, warm on palpation, normal muscle tone,
positive palmar grasp reflex on both palms, positive Moro reflex,
no edema.
Lower : no short fingers, no cyanosis of fingers, sole was not pale, warm
on palpation, normal muscle tone, no edema.
Skin : reddish, not pale, not peeled, not icteric, no petechiae or
hematoma on the skin, no cutis marmorata.
Lymphnodes : no lymphnodes enlargement found on neck, axilla, or inguinals.

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c. Anthropometric status
At birth
Weight : 2800 gram ( 10th - 25th percentile of Lubchenco curve)
Body length : 50 cm (50th - 75th percentile of Lubchenco curve)
Head circumference : 34 cm (10th - 25th percentile of Lubchenco curve)
At case determination (January 12th, 2018)
Weight : 3150 gram
Length : 51 cm
Head circumference : 35 cm
Weight/age : 0 - (-2) SD of WHO chart (normal)
Length/age : 0 - (-2) SD of WHO chart (normal)
Weight/length : (-1) - (-2) SD of WHO chart (normal)
Head circumference/age : (-1) - (-2) SD of WHO chart ~ normal)
Weight increments : 350 gram (1th - 3th percentile of WHO chart)
Ideal weight : 3500 gram

d. Neurological examination
Tone : No hypertonia or hypotonia.
Movement : spontaneous movement of the limbs, trunk, face and neck. No
tremor or clonic movement.
Reflex examination :
Protective reflex : (+)
Glabellar reflex : (+)
Rooting reflex : (+)
Sucking reflex : (+)
Palmar grasp reflex : (+)
Plantar grasp reflex : (+)
Moro reflex : (+)

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Cranial nerve :
N I,II : Can not be evaluated.
N III, IV, VI : No palpebral retraction, no ptosis, pupil reflects
+/+ equally, normal eyes movement.
NV : Can not be evaluated.
N VII : Equal nasolabial folds, symmetric facial
movement.
N VIII : Can not be evaluated.
N IX, X : Swallowing reflect (+)
N XI, XII : Can not be evaluated.

V. Resume
Patient was a 26 days old girl, first child from married parent. Patient was referred
from A hospital with diagnosis suspect bronchopneumonia. Patient had cough and
runny nose since 3 days before admission. Shortness of breath since 2 days before
admission, dyspneu was not improved with change of the position. Dyspneu
accompanied by chest indrawing. From examination, patient moderately ill, poor
activity, tone, and reflexes, with temperatures ranged between 38.0-38.50C, pulse rate
140-160 beats/minute, respiratory rate 60-70 breaths/minute, saturation 96% with O2
1 liter/minute and pain score was 2 with NPAT. On the second days of hospitalization,
respiratory distress had worsen and patient was treated with CPAP support for 3 days
as respiratory distress improved. The first few days, there was a murmur listen on
auscultation, end then murmur was disappeared. Antero-posterior chest x-ray showed
pneumonia. First line antibiotic was administered accompanied with nutrition care
with breastmilk. Patient was undergo echocardiography and revealed normal
echocardiography. CSF analysis was performed and showed neonatal bacterial
meningitis and Staphylococcus haemolyticus was detected in blood culture. Fluid
requirement 120 ml/kg/day, oral feeding with breast milk, and antibiotics were
continued until day 21th. Patient was planned to undergo evaluation CSF analysis on
day 21th of antibiotics.

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VI. Diagnosis
Respiratory distress due to pneumonia neonatal, clinically late onset sepsis and neonatal
bacterial meningitis

VII. Problems
a. Short-term
1. Neonatal infection with a concurrent focus of infection is not rare, and a higher
rate of infectious complications. At initial presentation of neonatal infections,
systemic evaluation should be performed to identify a possible source of
infection after blood cultures are obtained. Neonatal infection with a
concurrent focus of infection, especially in case with respiratory distress
syndrome, meningitis, and NEC, efforts to limit the risk of infectious
complications and prolong hospitalization.
2. Gold standard of late onset sepsis and bacterial meningitis is blood culture and
CSF culture. This patients have been given empirical antibiotics at previous
hospital before the culture specimen collected. This may result in false
negative in blood and CSF cultures. A journal search will be carried out to
look for accuration of CSF analysis to diagnose neonatal meningitis compared
to CSF culture.
3. Meningitis bacterial is associated with high mortality and morbidity in
neonatal population, there for early prognostic outcome can be helpful On the
first day of diagnosis, all of the patient suspected with meningitis undergo CSF
analysis. A journal search will be carried out to look for use of CSF analysis
as one of the risk factors affecting prognosis in bacterial menigitis.

b. Long-term
Patients with neonatal meningitis are at risk of long term adverse effect include
hearing loss, visual impairment, hydrocephalus, motoric disorders, cognitive
dysfunction and behavioral disorders. A journal search will be conducted to
determine long term outcome in neonatal meningitis compared with healthy
neonates.

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VIII. Planning
a. Emergency management
Emergency management was not necessary due to normal physical findings and
stable hemodynamic status.
b. Laboratorium
Confirmation blood and CSF culture, septic marker evaluation on day 7th of
antibiotics and CSF analysis evaluation on day 21th of antibiotics.
c. Supportive and pharmacological therapy
Initial antibiotics used were empirical antibiotics according to guidelines at
hospital in the form of ampicillin with a dose of 50 mg/kg/dose every 6 hours and
amikacin 7.5 mg/kg/dose every 8 hours. The antibiotics will adjusted to blood
culture and CSF culture results. Duration of therapy was planned to be 21 days.
Patient also given paracetamol 10 mg/kg/dose when fever.
d. Pediatric nutritional care
1. Nutritional assessment:
Weight/age : 0-(-2) SD of WHO chart (normal)
Length/age : 0-(-2) SD of WHO chart (normal)
Weight/length : (-1)–(-2) SD of WHO chart (normal)
2. Nutritional requirement: daily fluid requirement for patient is 120
ml/kg/day. Minimal energy requirement is 120 kkal/kg/day and protein 2.5
gr/kg/day.
3. Nutritional route: oral
4. Nutritional selection: breast milk
5. Monitoring: nutritional tolerance (vomiting, diarrhea, abdominal distention),
complications, fluid balance, urine production (0.5-3 ml/kg/day), and
growth.
e. Monitoring
1. Temperature monitoring: the patient is treated in the incubator, body
temperature is maintained with a range of 36.5-37.5⁰C.
2. Monitor head circumference everyday to determine the presence of
hydrocephalus complications.

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3. Monitor fluid balance and urine production.
4. Monitoring of body weight daily with increment target of 20-40 g/day.
Monitoring of length every week with increment target of 0.8-1.4 cm/week.
Monitoring of head circumference with increment target of 0.5-0.8 cm/week.
Monitoring of growth was adjusted with WHO growth chart.
5. Monitoring of development with Denver II and CAT-CLAMS assessment
will be performed every 1 month after patient discharged.
6. Long-term monitoring was performed on the presence of residual symptoms
by performing routine neurological clinical examination, vision tests and
hearing tests before 2 months old, minimum until 2 years old.
f. Communication, information and education
1. Parents were given explanation about the disease, therapy, risk of
complication, and prognostic of patients.
2. Parents are provided with information about the plan of hearing and visual,
growth and neurodevelopment monitoring.
3. Parents were informed about immunization planning that will be given to the
patient after patient discharged from hospital include BCG, Polio, Hepatitis
B, DPT, and Hib.

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IX. FOLLOW UP
Day Subjective Objective Assesment Planning
6th day Seizure (-), Physical examination: Suspect late onset Therapy:
temperature Present status sepsis and Neonatal - Nursed in incubator
December instability General condition: activity, tonus, reflex, and bacterial meningitis - Fluid requirement 100
13rd , 2017 (-), lethargic cry were sufficient ml/kg/day  415 ml/day
(-) Vital sign: heart rate: 130-145 bpm, regular.
- Energy requirement 120
Respiratory rate: 40-45 breaths per minute,
regular. Axillary temperature: 36.8-37.2°C. kkal/kg/day ~ 480 kkal/day,
Oxygen saturation: 100%. protein requirement 2.5
NPAT scale: 1 gram/kg/day ~ 10 gram/day
- Breast milk on demand
General status - Ampicillin 50 mg/kg/dose ~
Head: normocephaly, anterior fontanelle open 215 mg every 6 hours
and flat, head circumference 38.2 cm
intravenously (day 6th)
Eyes: pale (-), icteric (-), sunken (-).
Thorax and abdoman within normal limit. - Amikacin 7.5 mg/kg/dose ~
Extremity: warm, CRT <2 second. 32 mg every 8 hours
intravenously (day 6th)
Neurological status : - Phenytoin 5 mg/kg/day ~11
Tone, movement, reflect and cranial nerve mg every 12 hours
within normal limit. intravenously
Urine production: 2.2 ml/kg/hour. Diagnostic : Confirmation for blood
and CSF culture, septic marker
evaluation on 7th day of antibiotics,
and CSF analysis on 14th day of
antibiotics.

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Monitor: vital signs, head
circumference, neurological deficits,
and fluid balance.
Screening for auditory function,
visual impairment, growth and
neurodevelopmental at outpatient
clinic.
7th day Seizure (-), Physical examination: Suspect late onset Therapy:
temperature Present status sepsis and Neonatal - Nursed in incubator
December instability General condition: activity, tonus, reflex, and bacterial meningitis - Fluid requirement 100
14rd , 2017 (-), lethargic cry were sufficient ml/kg/day  415 ml/day
(-), Vital sign: heart rate: 130-140 bpm, regular.
- Energy requirement 120
respiratory Respiratory rate: 40-45 breaths per minute,
distress (-) regular. Axillary temperature: 36.6-37.3°C. kkal/kg/day ~ 480 kkal/day,
Oxygen saturation: 100%. protein requirement 2.5
NPAT scale: 0 gram/kg/day ~ 10 gram/day
- Breast milk on demand
General status - Ampicillin 50 mg/kg/dose ~
Head: normocephaly, anterior fontanelle open 215 mg every 6 hours
and flat, head circumference 38.2 cm
intravenously (day 7th)
Eyes: pale (-), icteric (-), sunken (-).
Thorax and abdoman within normal limit. - Amikacin 7.5 mg/kg/dose ~
Extremity: warm, CRT <2 second. 32 mg every 8 hours
intravenously (day 7th)
Neurological status - Phenytoin 5 mg/kg/day ~11
Tone, movement, reflect and cranial nerve mg every 12 hours
within normal limit. intravenously
Urine production: 2 ml/kg/hour. Diagnostic : Confirmation for blood
and CSF culture, CSF analysis on
Laboratory result: 14th day of antibiotics.

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Leukocytes 8.91 K/µL (neutrophils 1.33 K/µL Monitor: vital signs, head
(14.88%), lymphocytes 5.96 K/µL (66.95%)); circumference, neurological deficits,
hemoglobin 10.85 g/dL; hematocrit 33.42%; and fluid balance.
platelets 445 K/µL; IT ratio 0.51; Screening for auditory function,
procalcitonin 0.13 ng/ml. visual impairment, growth and
neurodevelopmental at outpatient
clinic.
8th day Seizure (-), Physical examination: Clinically late onset Therapy:
temperature Present status sepsis and Neonatal - Weaning incubator ~ admitted
December instability General condition: activity, tonus, reflex, and bacterial meningitis to perinatology room level II
15rd , 2017 (-), lethargic cry were sufficient - Fluid requirement 100
(-), Vital sign: heart rate: 130-145 bpm, regular.
ml/kg/day  415 ml/day
respiratory Respiratory rate: 40-45 breaths per minute,
distress (-) regular. Axillary temperature: 36.5-37.5°C. - Energy requirement 120
Oxygen saturation: 100%. kkal/kg/day ~ 480 kkal/day,
NPAT scale: 0 protein requirement 2.5
Body weight : 4,150 gram gram/kg/day ~ 10 gram/day
Lenght : 53.3 cm - Breast milk on demand
- Ampicillin 50 mg/kg/dose ~
General status
215 mg every 6 hours
Head: normocephaly, anterior fontanelle open
and flat, head circumference 38.2 cm intravenously (day 8th)
Eyes: pale (-), icteric (-), sunken (-). - Amikacin 7.5 mg/kg/dose ~
Thorax and abdoman within normal limit. 32 mg every 8 hours
Extremity: warm, CRT <2 second. intravenously (day 8th)
- Phenytoin 5 mg/kg/day ~11
Neurological status mg every 12 hours oral
Tone, movement, reflect and cranial nerve
within normal limit. Diagnostic : CSF analysis on 14th
day of antibiotics.
Urine production: 2.8 ml/kg/hour.

9
Laboratory result: Monitor: vital signs, head
Blood culture and CSF culture no growth circumference, neurological deficits,
and fluid balance.
Screening for auditory function,
visual impairment, growth and
neurodevelopmental at outpatient
clinic.
9th day Seizure (-), Physical examination: Clinically late onset Therapy:
temperature Present status sepsis and Neonatal - Nursed in crib
December instability General condition: activity, tonus, reflex, and bacterial meningitis - Fluid requirement 100
16rd , 2017 (-), lethargic cry were sufficient ml/kg/day  415 ml/day
(-), Vital sign: heart rate: 130-145 bpm, regular.
- Energy requirement 120
respiratory Respiratory rate: 35-45 breaths per minute,
distress (-) regular. Axillary temperature: 36.5-37°C. kkal/kg/day ~ 480 kkal/day,
Oxygen saturation: 100%. protein requirement 2,5
NPAT scale: 0 gram/kg/day ~ 10 gram/day
Body weight : 4,150 gram - Breast milk on demand
Lenght : 53.3 cm - Ampicillin 50 mg/kg/dose ~
215 mg every 6 hours
General status
intravenously (day 9th)
Head: normocephaly, anterior fontanelle open
and flat, head circumference 38.2 cm - Amikacin 7.5 mg/kg/dose ~
Eyes: pale (-), icteric (-), sunken (-). 32 mg every 8 hours
Thorax and abdoman within normal limit. intravenously (day 9th)
Extremity: warm, CRT <2 second. - Phenytoin 5 mg/kg/day ~11
mg every 12 hours oral
Neurological status
Tone, movement, reflect and cranial nerve Diagnostic : CSF analysis on 14th
within normal limit. day of antibiotics.

Urine production: 3.2 ml/kg/hour.

10
Monitor: vital signs, head
circumference, neurological deficits,
and fluid balance
Screening for auditory function,
visual impairment, growth and
neurodevelopmental at outpatient
clinic.
10-12th day Seizure (-), Physical examination: Clinically late onset Therapy:
temperature Present status sepsis and Neonatal - Nursed in crib
December instability General condition: activity, tonus, reflex, and bacterial meningitis - Fluid requirement 100
17rd -19th, (-), lethargic cry were sufficient ml/kg/day  415 ml/day
2017 (-), Vital sign: heart rate: 130-145 bpm, regular.
- Energy requirement 120
respiratory Respiratory rate: 35-45 breaths per minute,
distress (-) regular. Axillary temperature: 36.5-37°C. kkal/kg/day ~ 480 kkal/day,
Oxygen saturation: 100%. protein requirement 2.5
NPAT scale: 0 gram/kg/day ~ 10 gram/day
Body weight : 4,170 gram - Breast milk on demand
Lenght : 53.5 cm - Ampicillin 50 mg/kg/dose ~
215 mg every 6 hours
General status
intravenously (day 10-12th)
Head: normocephaly, anterior fontanelle open
and flat, head circumference 38.5 cm - Amikacin 7.5 mg/kg/dose ~
Eyes: pale (-), icteric (-), sunken (-). 32 mg every 8 hours
Thorax and abdoman within normal limit. intravenously (day 10-12th)
Extremity: warm, CRT <2 second. - Phenytoin 5 mg/kg/day ~11
mg every 12 hours oral
Neurological status
Tone, movement, reflect and cranial nerve Diagnostic : CSF analysis on 14th
within normal limit. day of antibiotics.

Urine production: 3 ml/kg/hour.

11
Monitor: vital signs, head
circumference, neurological deficits,
and fluid balance
Screening for auditory function,
visual impairment, growth and
neurodevelopmental at outpatient
clinic.

12
X. PROGNOSIS
Ad vitam: Bonam
Patient has passed his critical phase and showed favourable response to therapy.
Ad functionam: dubius ad bonam
Patient was at risk of long term complication, including neurological, hearing, vision,
growth, and developmental disturbance. These complication will be evaluated further in
outpatient clinic.
Ad sanactionam: dubius ad bonam
Patient showed clinnicaly and laboratory improvement after 12th of therapy. Patient still
needs a follow-up examination to determine therapeutic final responses.

13
XI. SCHEME OF ILLNESS

Desember 31st- January 2nd 2018 January 3rd-4th 2018 January 5th-7th 2018 January 8th-9th 2018 January 10th-11th 2018
- Patient was born with risk of infection, and - respiratory distress had - the patient was stable, without - the patient was stable, without - patient showed no
got antibiotics 4 days at RS BR slightly improved.The any temperature instability, or any temperature instability, or temperature instability,
- On the first day of treatment in emergency patient was active, respiratory distress respiratory distress
vomiting or lethargic.
unit, patient was lethargic and had good tone and reflexes - No fever (ranged 36.5-37.0oC) Physical examination
respiratory distress - Head circumference was 35 revealed good activity,
- Laboratory evaluation
- Patient was transferred to level II neonatal results: leucocytes Diagnosis: cm. The major fontanelle was tone and reflexes.
ward with incubator and oxygen 2 12,96x103/µL, respiratory distress et causa flat, no anemic, no icteric, Temperature ranged
L/minutes. neutrophil 3,13x103/µL pneumonia neonatal, suspect late round pupils with diameter of 2 between 36.6 to 37.00C
- Patient was assessed with respiratory (24,11%), hemoglobin onset sepsis, and suspect mm and good light reflexes - Head circumference was
distress et causa pneumonia neonatal, 15,09 g/dL, platetets congenital heart disease et causa - CSF analysis: nonne +, pandy 35 cm. The major
suspect late onset sepsis, and suspect 316.10x103/µL; IT ratio patent ductus arteriosus +, cell 44 cell/uL, mononuclear
fontanelle was flat, no
congenital heart disease et causa patent 0.07; procalcitonin differential diagnosis tricuspid anemic, no icteric, round
ductus arteriosus differential diagnosis 30%, polymorphonuclear 70%, pupils with diameter of 2
0.18 ng/mL regurgitation
tricuspid regurgitation, and was planned to Diagnosis Therapy: glucose 52 mg/dL, MTP 56,45 mm and good light
consult to cardiologist and lumbal puncture respiratory distress et oral feeding with breast milk mg/dL reflexes. There was no
after the patient was stable. causa pneumonia increased gradually, - Blood culture: Staphylococcus sign of lateralitation
- On the second and third days of neonatal, suspect late physiotherapy and antibiotics, haemolyticus
hospitalization, respiratory distress had onset sepsis, and The oxygen was reduced until - Echocardiography: normal Diagnosis:
worsen, and Patient was treated with CPAP suspect congenital heart patient can breathe without any respiratory distress et
cardiac
- Laboratory results: leucocyte 11.70 x disease et causa patent oxygen supporting device causa pneumonia
103/µL, neutrophil 6,50 x 103/µL (55,52%), ductus arteriosus Diagnosis: neonatal, late onset
hemoglobin 15,67 g/dL, platetets 355,80 x differential diagnosis Plan: respiratory distress et causa sepsis, and neonatal
103/µL; IT ratio 0.51; procalcitonin 0.13 tricuspid regurgitation. lumbal puncture and pneumonia neonatal, late onset bacterial meningitis
ng/mL.Thorax : pneumonia echocardiography sepsis, and neonatal bacterial
Diagnosis Therapy: meningitis Therapy:
respiratory distress et causa pneumonia continued antibiotics, oral feeding with breast
neonatal, suspect late onset sepsis, and CPAP support was Therapy: milk, physiotherapy and
suspect congenital heart disease et causa gradually reduced to oral feeding with breast milk, antibiotics, no oxygen
patent ductus arteriosus differential oxygen nasal physiotherapy and antibiotics, supporting device
diagnosis tricuspid regurgitation. no oxygen supporting device
Therapy: Plan: Plan:
nursed in incubator, first line antibiotics lumbal puncture and Plan: CSF analysis on day 21th
(ampicillin and amikacin), CPAP support, echocardiography, CSF analysis on day 21th of of antibiotics
plan for lumbal puncture and consulted to medical antibiotics
echocardiography rehabilitation

21
22
XI. SCHEME OF ILLNESS

Desember 31st- January 2nd 2018 January 3rd-4th 2018 January 5th-7th 2018 January 8th-9th 2018 January 10th-11th 2018
- Patient was born with risk of infection, and - respiratory distress had - the patient was stable, without - the patient was stable, without - patient showed no
got antibiotics 4 days at RS BR slightly improved.The any temperature instability, or any temperature instability, or temperature instability,
- On the first day of treatment in emergency patient was active, respiratory distress respiratory distress
vomiting or lethargic.
unit, patient was lethargic and had good tone and reflexes - No fever (ranged 36.5-37.0oC) Physical examination
respiratory distress - Head circumference was 35 revealed good activity,
- Laboratory evaluation
- Patient was transferred to level II neonatal results: leucocytes Diagnosis: cm. The major fontanelle was tone and reflexes.
ward with incubator and oxygen 2 12,96x103/µL, respiratory distress et causa flat, no anemic, no icteric, Temperature ranged
L/minutes. neutrophil 3,13x103/µL pneumonia neonatal, suspect late round pupils with diameter of 2 between 36.6 to 37.00C
- Patient was assessed with respiratory (24,11%), hemoglobin onset sepsis, and suspect mm and good light reflexes - Head circumference was
distress et causa pneumonia neonatal, 15,09 g/dL, platetets congenital heart disease et causa - CSF analysis: nonne +, pandy 35 cm. The major
suspect late onset sepsis, and suspect 316.10x103/µL; IT ratio patent ductus arteriosus +, cell 44 cell/uL, mononuclear
fontanelle was flat, no
congenital heart disease et causa patent 0.07; procalcitonin differential diagnosis tricuspid anemic, no icteric, round
ductus arteriosus differential diagnosis 30%, polymorphonuclear 70%, pupils with diameter of 2
0.18 ng/mL regurgitation
tricuspid regurgitation, and was planned to Diagnosis Therapy: glucose 52 mg/dL, MTP 56,45 mm and good light
consult to cardiologist and lumbal puncture respiratory distress et oral feeding with breast milk mg/dL reflexes. There was no
after the patient was stable. causa pneumonia increased gradually, - Blood culture: Staphylococcus sign of lateralitation
- On the second and third days of neonatal, suspect late physiotherapy and antibiotics, haemolyticus
hospitalization, respiratory distress had onset sepsis, and The oxygen was reduced until - Echocardiography: normal Diagnosis:
worsen, and Patient was treated with CPAP suspect congenital heart patient can breathe without any respiratory distress et
cardiac
- Laboratory results: leucocyte 11.70 x disease et causa patent oxygen supporting device causa pneumonia
103/µL, neutrophil 6,50 x 103/µL (55,52%), ductus arteriosus Diagnosis: neonatal, late onset
hemoglobin 15,67 g/dL, platetets 355,80 x differential diagnosis Plan: respiratory distress et causa sepsis, and neonatal
103/µL; IT ratio 0.51; procalcitonin 0.13 tricuspid regurgitation. lumbal puncture and pneumonia neonatal, late onset bacterial meningitis
ng/mL.Thorax : pneumonia echocardiography sepsis, and neonatal bacterial
Diagnosis Therapy: meningitis Therapy:
respiratory distress et causa pneumonia continued antibiotics, oral feeding with breast
neonatal, suspect late onset sepsis, and CPAP support was Therapy: milk, physiotherapy and
suspect congenital heart disease et causa gradually reduced to oral feeding with breast milk, antibiotics, no oxygen
patent ductus arteriosus differential oxygen nasal physiotherapy and antibiotics, supporting device
diagnosis tricuspid regurgitation. no oxygen supporting device
Therapy: Plan: Plan:
nursed in incubator, first line antibiotics lumbal puncture and Plan: CSF analysis on day 21th
(ampicillin and amikacin), CPAP support, echocardiography, CSF analysis on day 21th of of antibiotics
plan for lumbal puncture and consulted to medical antibiotics
echocardiography rehabilitation

23
XII. SCHEME OF CASE ANALYSIS

Baby, M/31 days

Maternal Fetal Environment


Systemic illness and infection
Infection
Risk Factor

Poor hygiene
Premature rupture of membrane Fetal distress
Nosocomial infection

Maternal rectovaginal GBS colonization Very Low Birthweight Foreign invasive device

Chorioamnionitis or maternal fever Slum environtment

Respiration Cardiovascular Gastrointestine Hematology Growth and developmental


Problems

disturbances

LATE ONSET NEONATAL BACTERIAL


CNS
NEONATAL SEPSIS MENINGITIS
Hearing, vision and
neurological disturbances

- EEG 2nd journal


Diagnosis

Level of evidence 2b,


- Hearing and visual test grade of
Septic marker CSF analysis 1st journal
Level of evidence recommendation B
- Growth monitoring
2b, grade of
Blood culture CSF culture recommendation B - Denver test

Causal Supportive Diet


Theraphy

General management Additional therapy

Antibiotics Anticonvulsant Antipyretic Head circumference evaluation, Breast milk 24


neurological deficits, and fluid balance

3rd journal Response to initial therapy Ad vitam ad bonam


sis

Level of evidence 2b, grade


XIII. CASE ANALYSIS
The incidence of neonatal pneumonia 1-35%, 1% occurs in infants aterm and 10%
occurs in preterm infants. Neonatal pneumonia is a perinatal / postnatal pulmonary
infection (at 3 days of age), via placenta transmission. Etiology is mostly caused by
bacteria Group B Streptococcus, Staphylococcus aureus, Staphylococcus epidermidis, E
coli, Pseudomonas, Serratia marcescens dan Klebsiella.1 Criteria for diagnosis of
neonatal pneumonia based on history of chorioamnionitis in the mother, infants born with
low APGAR scores, physical examination of respiratory distress obtained several hours
after born (tachypnea, whimper, nasal lobe, chest wall retraction, cyanosis) and chest x-
rays found infiltrates in the lung. Management in the form of antibiotics refers to the most
common types of bacteria and germ-resistant patterns in each health center and is adjusted
after culture results. Oxygenation therapy according to the degree of respiratory distress
based on the Downe score, and supportive therapy in the form of temperature control,
fluid management and nutrition.2 In the case, there is a risk factor for neonatal pneumonia
that is a mother with fever (>38 ºC), green amniotic fluid and premature rupture of
membrans. Clinical symptoms with respiratory distress (downe score 3), temperature
instability, lethargy, cough and runny nose and radiological examination with the
impression of pneumonia that the patient was diagnosed with neonatal pneumonia and
received antibiotic therapy, low flow oxygen, and suportif therapy.
Neonatal sepsis is a clinical syndrome involving systemic abnormalities
accompanied by bacteremia, occurring in the first month of life. Based on the onset,
neonatal sepsis is divided into early onset sepsis and late onset sepsis (LOS). Early onset
neonatal sepsis occurs at age less than 72 hours after birth. Late onset neonatal sepsis
occurs at age above 72 hours after birth.3,4 The incidence of neonatal sepsis is 30 per
1,000 live births and only 2.7 per 1,000 live births are LOS.5,6
Neonatal sepsis is diagnosed based on criterias of clinically sepsis or proven sepsis.
Clinically sepsis is defined as the presence of at least one sign or symptom of sepsis
accompanied by at least 2 septic markers supporting sepsis, while proven sepsis is
clinically sepsis entailed with microbial growth in blood culture. Signs and symptoms of
neonatal sepsis are not specific and involving multi system; neurological (lethargy,
seizure, poor tones), cardiopulmonary (respiratory distress, tachy- or bradycardia,

23
cyanosis, poor perfusion), gastrointestinal (vomiting, abdominal distention, feeding
intolerance), hematology (ptechiae, hematemesis, melena), and metabolic (icterus and
temperature instability). Septic markers supporting neonatal sepsis are leukocytosis
(>30,000 x103 /µL), leukopenia (<4,000 x103/µL), thrombocytopenia, IT ratio >0.2,
procalcitonin >0.05 ng/mL and presence of toxic granule or vacuolization in blood smear.
Positive blood culture is the gold standard for diagnosing sepsis.5,7 The diagnosis of LOS
is more difficult to enforce because clinical symptoms are nonspecific and rapidly alter
as sepsis proceed. These infants may have unidentifiable focus. Bacteria responsible for
LOS include those acquired after birth from the maternal genital tract (vertical
transmission) as well as organisms acquired after birth from human contact or from
contaminated equipment or environment (nosocomial). In late onset sepsis, organism can
be acquired from the colonized mother, poor hand hygiene among caregivers, or foreign
invasive devices.8 The reason of delayed clinical manifestation including predilection of
central nervous system (CNS) disease, less severe systemic and cardiorespiratory
symptoms are still unclear.3 Once a neonate is suspected for sepsis, antibiotics must be
initiated soon until sepsis is resolved or not proven.5 In this case, patient was 15 days old
girl, with three clinically sign of sepsis i.e. temperature instability, lethargic and
respiratory distress that appeared above 72 hours after birth, and three positive blood
results i.e. IT ratio 0.51, procalcitonin 0.18 ng/mL presence of toxic granule and
vacuolization in blood smear. Blood cultures was taken after administration of antibiotics
at previous hospital and revealed growth with staphylococcus haemolyticus, there for this
patient diagnosed with conform/proven late onset sepsis.
Meningitis is one of the most common complications of LOS. Meningitis is an
infection of CNS in the first month of life.6 Incidence of neonatal meningitis increased in
developing countries by 0.8-6.1 per 1,000 live births, with 40-58% mortality.8 Most
organisms implicated in neonatal sepsis also cause neonatal meningitis. The types of the
organism in neonatal meningitis depend on postnatal age, location and gestational age.
On late onset infection the most common causative agents are Coagulase-negative
Stapylococcus, Stapylococcus aureus, Escherichia coli, Klebsiella sp., Enterococcus sp.,
Enterobacter sp., Pseudomonas sp., and Group B Streptococcus.4 While several
mechanisms in the development of neonatal meningitis have been described, primary

24
bloodstream infection with secondary hematogenous distribution to the CNS is the most
common. Other mechanism is by infectious foci with direct extension into the CNS and
primary CNS infection.9
The clinical manifestations of neonatal meningitis can be subtled and not specific.
Signs and symptoms of meningitis include temperature instability, lethargy, irritability,
poor tone, seizures, feeding intolerance, vomiting, respiratory distress, apnea, or cyanotic
episodes. Seizures, often focal, can be the presenting manifestation in up to 50% of the
cases. Late manifestations of meningitis include a bulging major fontanelle and coma.6,8
There are several laboratory features in meningitis, including blood culture,
complete blood count, IT-ratio, procalcitonin, blood smear and lumbar puncture (LP) to
examine cerebrospinal fluid (CSF), CSF culture, protein, glucose, and cell count. CSF
pleocytosis is variable. Normal values range from 0-20/mm5, some of which may be
polymorphonuclear cells. Gram-stained smear can be helpful in making a more rapid
definitive diagnosis and identifying the initial classification of the causative
agent. Cerebrospinal fluid glucose level must be compared with serum glucose level.
Normal CSF values are one-half to two-thirds of serum values. Typically, neonates with
meningitis have CSF glucose level <20-30 mg/dL. Cerebrospinal protein is usually
elevated (>100-150 mg/dL). Some cases of neonatal meningitis have normal CSF
parameters without bacteremia. Therefore a definite diagnosis of neonatal meningitis is a
positive CSF culture.8,9 Of all neonates with positive blood culture results, only 30%
showed positive culture CSF results. Neonates with proven meningitis, 15-38% have a
negative blood culture. Patients with meningitis often have been given empirical
antibiotics before lumbar puncture procedure. This may result in false negative in blood
and CSF cultures.6,8 In this case, sign and symptom of meningitis were temperature
instability, lethargic, irritability, and poor tone. The mechanism of infection was
suspected from primary bloodstream infection. The results of the CSF analysis showed
feature of bacterial meningitis, ie, obtained pleocytosis (cells over 20/mm3) and increased
protein. But the exact diagnosis of bacterial causes was unknown because no bacterial
growth was found in CSF and blood cultures.
This raises the question, does CSF analysis can used to diagnose meningitis
compared to CSF culture, there for we obtained a journal of “Neonatal meningitis: what

25
is the correlation among cerebrospinal fluid cultures, blood cultures, and
cerebrospinal fluid parameters?” By Garges HP et al of the American Academy of
Pediatrics 2006 (valid, important, and applicable) level of evidence 2b, and grade of
recommendation B. Journal conclusions found only 1% of meningitis patients with
positive CSF cultures. There is no single CSF parameter capable of diagnosing
meningitis, but the leukocytes in CSF >21 cells/mm5 have the best sensitivity and
specificity, at 79% and 81% respectively. In this case, the leukocytes in CSF was 537
cells/mm.5 Even the CSF culture shows negative result, the diagnosis and treatment of
neonatal meningitis still continued.
Management of patient with neonatal meningitis and LOS including the emergency,
definitive antibiotic therapy, and supportive therapy. General supportive treatment
including oxygenation support, cardiovascular support, and nutritional support through
intravenous dextrose.6 On late onset infection commonly used empirical antibiotics are
ampicillin, cefotaxime, gentamicin and vancomycin. Infants who were previously
admitted to other hospital, and have late-onset sepsis manifestation, would have empiric
therapy consists of vancomycin (cover gram~positive organisms, especially coagulase-
negative staphylococci) and gentamicin with the addition of cefotaxime when CSF
findings suggest meningitis (extended coverage of gram-negative rods). At last, for
infants aged <60 days old without history of hospital admission, the empiric therapy
consists of ampicillin and cefotaxime.6,10 Repeated lumbar puncture in 48 hours after the
beginning of antibiotic therapy is recommended to document CSF sterilization.
Persistence of infection may indicate a focus, such as obstructive ventriculitis, subdural
empyema, or multiple small vessel thrombi. Infants with repeated positive CSF cultures
after initiation of appropriate antibiotics are at risk for complications as well as a poor
outcome. In general, 3 days are required to sterilize the CSF in infants with gram-negative
meningitis, whereas in gram-positive meningitis, sterilization usually occurs within 36-
48 hours. Follow-up of CSF examination is recommended until steril CSF is documented.
Treatment should be continued until 14 days after cultures are negative or for 21 days.6
For uncomplicated meningitis, the minimum recommended treatment durations are 14
days for Group B Streptococcus, Listeria monocytogene, Streptococcus pneumonia and
21 days for Pseudomonas and gram-negative enteric bacteria such as Eschericia coli.8,11

26
In this case, patient was given first line antibiotics with Ampicillin and Amikacin. The
causative agent was unknown. After 3rd days of antibiotics, the laboratorium test showed
normal complete blood count, normal IT ratio, high procalitonin, even so there was
improvement on clinically sign. There for the antibiotics were continued.
The mortality rate of neonatal meningitis has decreased over the past 15 years to
343%, compared with 25-30% from earlier decades. There is a higher incidence (20-50%)
of neurodevelopmental sequelae in survivors, and this figure has not changed over the
years. Factors predictive of poor prognosis include preterm birth, neutropenia, seizures
persisting more than 72 hours after hospitalization, focal neurologic deficits, initial
inotropic support, delayed sterilization of the CSF, and parenchymal lesions (abscess,
thrombi, infarcts, and encephalomalacia).6 In this case, we don’t find any of those factors.
Early recognition of neonates at risk of poor prognosis would be helpful. At the first day
of diagnosis, all of the patient suspected with meningitis undergo CSF analysis and we
want to know if the CSF analysis result could be used to estimated the prognosis. To find
out the role of CSF analysis as a risk factor to affect the prognosis of neonatal meningitis,
we performed journal searching and obtained a journal entitled “Clinical Prognosis in
Neonatal Bacterial Meningitis: The Role of Cerebrospinal Fluid Protein” by Tan J.
et.al., from Plos One, 2015. Evidence based analysis from this journal showed this journal
was valid, important, and applicable, with level od evidence 3b and grade
recommendation B. Conclusion of the journal is high CSF protein concentration may
predict poor outcome in neonates with bacterial meningitis (cut-offs for predicting poor
outcome were 188 mg/dL in CSF protein concentration with sensitivity 70.8%, specificity
86.2%). In this case, protein concentration in CSF was 56,45 mg/dL then raised to
152.05 mg/dL, so that we expected this patient have good prognosis.
Residual symptoms are often found, among others, intellectual impairment, impaired
vision, hearing loss, and hydrocephalus. We performed journal searching to find out the
long term outcomes after neonatal meningitis compared with healthy neonates, and
obtained a journal entitled "Long term outcome of neonatal meningitis” by J P Stevens,
et.al., from Arch Dis Child Fetal Neonatal Ed, 2008, showed it is valid, important, and
applicable, with level of evidence 3b, and grade of recommendation B. Conclusion of the
journal is in children with neonatal meningitis, at aged 9-10 years had mean intelligence

27
quotient (IQ) significantly less than that of the hospital controls (99.4) or the GP controls
(99.6)) (p<0,001). The mABC score was significantly worse for the cases (7.08) than the
hospital (5) (p = 0.001) or GP (4) controls (p = 0.001). Some 3.6% of cases had
sensorineural hearing loss, 2.7% had persisting hydrocephalus; no controls did. Some
5.4% of cases and 1.7% of hospital controls had treatment for seizures.

28
XIV. References
A. References (Case analysis)
1. Reiterer F. Neonatal Pneumonia. London: Reiterer; 2013. Tersedia di:
http://www.intechopen.com.sci-hub.cc/books/neonatal-bacterial-infection/
neonatal-pneumonia [Diakses tanggal 16 Maret 2017].
2. RSUP Sanglah Denpasar. Panduan Praktik Klinis SMF Ilmu Kesehatan Anak –
Pneumonia; 2016.
3. Gomella TL. Sepsis. In: Gomella TL, Cunningham MD, Eyal FG, Zenk KE,
editors. Neonatology: management, procedures, on-call problems, disease, and
drugs. 7th ed. London: Appleton & Lange; 2013. p.865-74.
4. Dong Y, Speer CP. Late-onset neonatal sepsis : recent developments. Arch Dis
Child Fetal Neonatal. 2015;100:257-63.
5. Aminullah A. Sepsis pada bayi baru lahir. In: Kosim M, Yunanto A, Dewi R,
Saroso GI, Usman A, editors. Buku Ajar Neonatologi. 1st ed. Jakarta: Badan
Penerbit IDAI; 2008. p.170-87.
6. Gomella TL. Meningitis. In: Gomella TL, Cunningham MD, Eyal FG, Zenk KE,
editors. Neonatology: management, procedures, on-call problems, disease, and
drugs. 7th ed. London: Appleton & Lange; 2013. p.754-7.
7. Wu IH, Ming-HT, Mei-Yin. Incidence, clinical features, and implications on
outcomes of neonatal late-onset sepsis with concurrent infectious focus. BMC
Infectious Disease; 2017:17:465.
8. Ku LC, Boggess KA, Wolkowiez MC. Bacterial meningitis in the Infant. Clin
Perinatol; 2015:42:29-45.
9. Edwards M. Postnatal bacterial infections. In: Martin RJ, Fanaroff AA, Walsh
MC, editors. Fanaroff and Martin's neonatal-perinatal medicine : diseases of the
fetus and infant. 9th edition. Philadelphia: Saunders/Elsevier; 2011. p.793-830.
10. Weisfelt M, de Gans J, van de Beek D. Bacterial meningitis: a review of effective
pharmacotherapy. Expert Opin Pharmacother. 2007; 8:1493–504.
11. Greenberg RG, Benjamin DK Jr, Cohen-Wolkowiez M, Clark RH, Cotten M,
Smith PB. Repeat lumbar punctures in infants with meningitis in the neonatal
intensive care unit. J Perinatol. 2011; 31:425-9.

29
B. Journal (Evidence Based Practice)
1. Lihong Yang, Ying Zhang, Xuehui Yu, Man Luo. Prevalence and risk factors of
neonatal pneumonia in China: A longitudinal clinical study. Biomedical
Research;2017:28(15).
2. Wu IH, Ming-HT, Mei-Yin. Incidence, clinical features, and implications on
outcomes of neonatal late-onset sepsis with concurrent infectious focus. BMC
Infectious Disease; 2017:17:465.
3. Tan J, Kan J, Qiu G, Zhao D, Ren F, Luo Z, Zhang Y. Clinical prognosis in
neonatal bacterial meningitis: the role of cerebrospinal fluid protein. PLoS One.
2015;10(10);1-9.
4. Garges HP, Moody A, Cotten M, Smith PB, Tiffany KF, Lenfestey R, Li SL,
Fowler VG, Benjamin DK. Neonatal meningitis: what is the correlation among
cerebrospinal fluis cultures, blood cultures, and cerebrospinal fluid parameters.
Pediatrics. 2006;117:1094-100.

30
XV. Abbreviation
AABR : automated auditory brainstem responses
aEEG : amplitude integrated electroencephalography
APGAR : appearance, pulse, grimace, activity, respiration
BCG : Bacillus Calmette-Guerin
CFM : cerebral function monitor
CNS : central nervous system
CNV : continuous normal voltage
CRT : capillary refill time
CT-scan : computed tomography scan
CSF : cerebrospinal fluid
DNV : discontinuous normal voltage
DPT : Diphtheria, tetanus and pertussis
EA : electrographic seizure activity
EEG : electroencephalography
EPO : erythropoietin
GIR : glucose infusion rate
GOS : glasgow outcome scale
GP : general practitioner
Hb : hemoglobin
Hib : Haemophilus influenzae type B
IQ : intelligence quotient
IT ratio : immature to total neutrophil ratio
LOS : late onset sepsis
LP : lumbar puncture
mABC : movement assessment battery for children
MRI : magnetic resonance imaging
MTP : micro total protein
NICU : neonatal intensive care unit
NPAT : neonatal pain assessment tools

31
OAE : otto acoustic emission
SWC : sleep wake cycling
WBC : white blood cell
WHO : World Health Organization

32
Attachment 1.

33
34
EVIDENCE-BASED CRITICAL APPRAISAL

CASE
Patient was a 26 days old girl, first child from married parent. Patient was referred
from A hospital with diagnosis suspect bronchopneumonia. Patient had cough and
runny nose since 7 days before admission. Shortness of breath since 2 days before
admission, dispneu was not improved with change of the position. Dispneu
accompanied by chest indrawing. From examination, patient moderately ill, poor
activity, tone, and reflexes, with temperatures ranged between 38.0-38.50C, pulse rate
140-160 beats/minute, respiratory rate 60-70 breaths/minute, saturation 96% with O2
1 liter/minute and pain score was 2 with NPAT. On the second days of hospitalization,
respiratory distress had worsen and patient was treated with CPAP support for 3 days
as respiratory distress improved.
The first few days, there was a murmur listen on auscultation, end then murmur
was disappeared. Antero-posterior chest x-ray showed pneumonia. First line antibiotic
was administered accompanied with nutrition care with breastmilk. Patient was
undergo echocardiography and revealed normal echocardiography. CSF analysis was
performed and showed neonatal bacterial meningitis and Staphylococcus
haemolyticus was detected in blood culture. Fluid requirement 120 ml/kg/day, oral
feeding with breast milk, and antibiotics were continued until day 21th. Patient was
planned to undergo evaluation CSF analysis on day 21th of antibiotics.

DIAGNOSIS
Respiratory distress et causa pneumonia neonatal, clinically late onset sepsis and neonatal
bacterial meningitis

35
PROBLEM
1. In neonatal pneumonia, what are the associated risk of developing neonatal
pneumonia?
2. In neonates with late onset sepsis, what is the sepsis attributable mortality of neonatal
late onset sepsis with a concurrent focus of infection compare to those without focus of
infection?
3. In neonates with bacterial meningitis, does cerebrospinal fluid analysis may predict
prognosis?
4. In neonates with bacteremia-associated neurological complication, how is the outcome
or sequele if compared to those without bacteremia-associated neurological
complication?

36
PROBLEM 1

PICO
According to the problems, PICO can be described as follows:
P (Patient/Problem) : Neonatal pneumonia
I (Intervention) :
C (Comparation/Control) : Non neonatal pneumonia
O (Outcome) : Risk factors

CLINICAL QUESTION
In neonatal pneumonia, what are the associated risk of developing neonatal pneumonia?

JOURNAL SEARCHING STRATEGY


Keywords: Pneumonia AND neonates AND chinese patients AND pregnancy AND
prevalence

RESULT
“Prevalence and risk factors of neonatal pneumonia in China: A longitudinal
clinical study.”
Lihong Yang, Ying Zhang, Xuehui Yu, Man Luo.
Biomedical research. 2017:28;1-4.

ABSTRACT
Methods: In this longitudinal clinical study, we identified a total of the 953 medical
records of neonatal who were admitted at Medical college of ChiFeng University, China
between March 2010 to 2017. Parents of each neonate patient were instructed to complete
questionnaire about the symptoms associated with pneumonia. Potential risk factors were
assessed using a hospital record of all childbirths occurred between March 2010 to 2017.
Results: Medical records of 953 neonate (male: 553, female: 400) with mean (SD) age
of 2.4 (1.2) days who were admitted during March 2010 to 2017 were studied. Incidence
of pneumonia among neonates was found to be 14%. Our statistical analysis results

37
showed that weight at the time of birth (p=0.032), poor prenatal care (p=0.02), C-section
surgery and delivery (p=0.02), home delivery of baby at home (p<0.05), delivery of baby
by unexperienced peoples (p<0.05), new-born resurgence (p<0.05), fever at birth
(p<0.05), gynaecological problem during pregnancy (p<0.005), vulgar sensing fluid
(p<0.05), extended break of tissue (p<0.005), sustained labour (p=0.023) were
meaningfully related to pneumonia.
Conclusion: In China, a total of 14% of neonates had experienced pneumonia. Among
identified risk factors, the multivariate regression analysis suggested that inadequate poor
prenatal care, home delivery of baby at home, fever at birth, and gynaecological problem
during pregnancy, sustained labor period were found as noteworthy risk factors of
neonatal pneumonia among Chinese patients.

EVIDENCE-BASED CRITICAL APPRAISAL


(CAUSATION)

Is the study design valid?


1. Were there clearly defined groups of Yes, this study was retrospective study,
patients, similar in all important ways with similar clinical symptom and
other than exposure to the treatment or sign, demography, and maternal
other causes? characteristics.
.
2. Were treatments/exposures and clinical Yes, Potential risk factors were assessed
outcomes measured in the same way for using a hospital onlide database
both groups? Was the assessment of and parents, specially the mother of all
outcomes either objective or blinded to neonates whose medical records were
exposure? reviewed and asked to fill the
questionnaire which capture all
pregnancy related characteristics
including demography and maternal
characteristics

3. Was the follow-up of study patients Yes, this is a logitudinal study by


sufficiently long for the outcome to identifying medical record of neonatase
occur?

38
who were admitted during March 2010 to
2017.
4. Is it clear that the exposure preceded Yes, it is clear that the exposure preceded
the onset of the outcome? the onset of the outcome

5. Is there a dose-response gradient? No, this study was not associated with
dose response gradient
6 Is the association consistent from study Yes, previously identified risk factor
to study? which plays an important role in
development of neonatal pneumonia were
including birth weight and age of women
before and after pregnancy.
7 Does the association make biological Yes, it does. inadequate poor prenatal
sense? care, home delivery of baby at home,
fever at birth, and gynaecological
problem during pregnancy, sustained
labor period.
This study is valid

Are the results important?


1. How strong is the association between The study results showed that weight at
exposure and outcome, i.e. the estimate the time of birth (p=0.032), poor prenatal
of risk? care (p=0.02), C-section surgery and
delivery (p=0.02), home delivery of baby
at home (p<0.05), delivery of baby by
unexperienced peoples (p<0.05), new-
born resurgence (p<0.05), fever at birth
(p<0.05), gynaecological problem during
pregnancy (p<0.005), vulgar sensing fluid
(p<0.05), extended break of tissue
(p<0.005), sustained labour (p=0.023)
were meaningfully related to pneumonia
2. How precise is the estimate of risk? 95% CI for birth weight 2.5-4.5
95% CI for inadequate antenatal care
21.2-28.6
95% CI for C-section surgery and
delivery 3.3-4.6
95% CI for home delivery 30.2-36.4
95% CI for delivery by untrained
personnel 4.3-8.6

39
95% CI for neonatal rescucitation 2.0-8.6
95% CI for fever at birth 23.3-29.5
This study is important

Are the results important for my patient?


1. Is my patient so different from those No, characteristic type of subjects in this
included in the study that its results don’t study similar with our patients
apply?
2. What is my patient’s risk of the adverse This evidence is worth for our clinical
event? What is my patient’s potential practices.
benefit from therapy?
3 What are my patient’s preferences, By knowing the risk factors of
concerns and expectations from this developing neonatal pneumonia
treatment?
This study is applicable

Conclusion: Valid, Important, and Applicable.


Level of evidence 3b with grade of recommendation B.

40
PROBLEM 2

PICO
According to the problems, PICO can be described as follows:
P (Patient/Problem) : neonatus with late onset sepsis with concurrent focus of
infection
I (Intervention) :-
C (Comparation/Control) : neonatal late onset sepsis patient without concurrent focus
of infection
O (Outcome) : sepsis attributable mortality

CLINICAL QUESTION
In neonates with late onset sepsis, what is the sepsis attributable mortality of neonatal late
onset sepsis with a concurrent focus of infection compare to those without focus of
infection?

JOURNAL SEARCHING STRATEGY


Keywords: Bacteremia AND Neonates AND Catheter-related bloodstream infection
AND Late-onset sepsis AND Risk

RESULT
“Incidence, Clinical Features, and Implications on
Outcomes of Neonatal Late-Onset Sepsis with Concurrent
Infectious Focus.”
I-Hsyuan Wu, Ming-Horng Tsai, Mei-Yin Lai, Lee-Fen Hsu,
Ming-Chou Chiang, Reyin Lien, dkk.
BMC Infectious Diseases. 2017;17:465-75

ABSTRACT
Background: Neonatal bloodstream infection (BSI) is the most important cause of
morbidity and mortality in the neonatal intensive care unit (NICU). Although most

41
neonatal BSIs are primary bacteremia, some are associated with a focus of infection.
This distinction is not well characterized.
Methods: All patients with neonatal late-onset sepsis (LOS) between January 2006 and
December 2013 were enrolled. LOS was categorized as a BSI with a concurrent focus
of infection if LOS occurred before or within 24 h after the diagnosis of a specific
infectious entity, and as “primary bacteremia” if no concurrent focus of infection was
identified. Data concerning demographics, hospital course, microbiology, and
outcomes were compared via
univariate and multivariate analyses.
Results: Of 948 episodes of neonatal LOS, 781 (82.4%) were primary bacteremia,
whereas 167 (17.6%) were associated with a known focus of infection, including
meningitis (n = 51, 5.4%), ventilator-associated pneumonia (VAP) (n = 36, 3.8%),
catheter-related bloodstream infections (n = 57, 6.0%), and necrotizing enterocolitis
(NEC) (n = 21, 2.2%). The majority of NEC-associated BSIs were caused by gram-
negative bacilli (85.7%). Group B streptococcus accounted for nearly one-third of all
meningitis cases (29.4%). Although sepsis-attributable mortality was comparable
between primary bacteremia and neonatal BSIs with a focus of infection, neonatal BSIs
with meningitis, VAP, and NEC had significantly higher rates of infectious
complications. The independent risk factors of sepsis-attributable mortality were
infectious complications (Odds ratio [OR] 6.98; 95% confidence interval [CI] 3.64-
13.39, P < 0.001); history of one or more than one previous episode(s) of BSI (OR 2.40
and 7.40; 95% CI 1.21–4.74 and 3.70–14.78, P = 0.012 and <0.001, respectively); and
underlying secondary pulmonary hypertension in neonates (OR 4.77; 95% CI 1.91–
11.96, P = 0.001).
Conclusions: A considerable proportion of neonatal LOS can be associated with
known infectious foci in the NICU. The microbiologic etiology of neonatal LOS with
a concurrent focus of infection is significantly different from that of primary
bacteremia. Neonatal BSIs with concurrent meningitis, VAP, or NEC are significantly
more likely to have infectious complications. This association independently leads to
sepsis-attributable mortality.

42
EVIDENCE-BASED CRITICAL APPRAISAL
(PROGNOSTIC STUDIES)

Are the results of the study valid? (internal validity)


1. Was the defined representative sample of Yes, the subject in this study are patients
patients assembled at a common (usually with neonatal late-onset sepsis (LOS)
early) point in the course of their between January 2006 and December 2013.
All BSIs identified were “late-onset”,
disease)?
defined as a positive blood culture
occurring at >72 h of life.
1. Was patient follow-up sufficiently long Yes, For more than ten years, the NICU at
and complete ? CGMH has had an electronic database
maintained by a full-time nurse specialist
dedicated to following neonates from birth
(or admission if the neonate was transferred
from another hospital) until discharge or
death.
2. Were outcome criteria either objective or Yes. Observation was done blindly.
applied in a “blind” fashion?

2. If subgroups with different prognoses are


identified,
 Did adjustment for important Yes, adjusment were done to the groups.
prognostic factors take place?
 Was there validation in an
indeendent group of patients? Not explained in this study

The study is valid

What are the results?


1. How likely are the outcomes over time? The independent risk factors of sepsis-
How precise are the prognostic attributable mortality were infectious
estimates? complications (Odds ratio [OR] 6.98;
95% confidence interval [CI] 3.64–
13.39, P < 0.001); history of one or more
than one previous episode(s) of BSI (OR
2.40 and 7.40; 95% CI 1.21–4.74 and
3.70–14.78, P = 0.012 and <0.001,
respectively); and underlying secondary
pulmonary hypertension in neonates

43
(OR 4.77; 95% CI 1.91–11.96, P =
0.001).

Can I apply this valid, important evidence about pronosis to my patient?

1. Is my patient so different to those in Yes, patients in this study have similar


the study that the results can not characteristics with ours.
apply?

2. Will this evidence make a clinically Yes, with this evidence we can explain
important impact on my conclusions to the parents that neonatal late onset
about what to offer to tell my sepsis with concurrent meningitis, VAP,
patients? or NEC are significantly more likely to
have infectious complications.
The study is important

Conclusion: Valid, Important, and Applicable.


Level of evidence 2b with grade of recommendation B.

44
PROBLEM 3

PICO
According to the problems, PICO can be described as follows:
P (Patient/Problem) : Neonates with bacterial meningitis
I (Intervention) :-
C (Comparation/Control) :-
O (Outcome) : Risk factor

CLINICAL QUESTION
In neonates with bacterial meningitis, does cerebrospinal fluid analysis may predict
prognosis?

JOURNAL SEARCHING STRATEGY


Keywords: neonates AND bacterial meningitis AND cerebrospinal fluid AND prognosis

RESULT
“Clinical Prognosis in Neonatal Bacterial Meningitis: The Role of Cerebrospinal
Fluid Protein”
Tan J, Kan J, Qiu G, Zhao D, Ren F, Luo Z, Zhang Y.
Plos One. 2015. 10(10);1-9.

ABSTRACT
Background: Neonates are at high risk of meningitis and of resulting neurologic
complications. Early recognition of neonates at risk of poor prognosis would be helpful
in providing timely management.

45
Methods and Results: From January 2008 to June 2014, we enrolled 232 term neonates
with bacterial meningitis admitted to 3 neonatology departments in Shanghai, China. The
clinical status on the day of discharge from these hospitals or at a postnatal age of 2.5 to
3 months was evaluated using the Glasgow Outcome Scale (GOS). Patients were
classified into two outcome groups: good (167 cases, 72.0%, GOS = 5) or poor (65 cases,
28.0%, GOS = 1-4). Neonates with good outcome had less frequent apnea, drowsiness,
poor feeding, bulging fontanelle, irritability and more severe jaundice compared to
neonates with poor outcome. The good outcome group also had less pneumonia than the
poor outcome group. Besides, there were statistically significant differences in
hemoglobin, mean platelet volume, platelet distribution width, C-reaction protein,
procalcitonin, cerebrospinal fluid (CSF) glucose and CSF protein. Multivariate logistic
regression analyses suggested that poor feeding, pneumonia and CSF protein were the
predictors of poor outcome. CSF protein content was significantly higher in patients with
poor outcome. The best cut-offs for predicting poor outcome were 1,880 mg/L in CSF
protein concentration (sensitivity 70.8%, specificity 86.2%). After 2 weeks of treatment,
CSF protein remained higher in the poor outcome group.
Conclusion: High CSF protein concentration may prognosticate poor outcome in
neonates with bacterial meningitis.

Evidence-based Critical Appraisal: Causation

Is the study design valid?


1. Were there clearly defined groups of Yes, this study was retrospective study,
patients, similar in all important ways with similar clinical symptom and sign,
other than exposure to the treatment or range of age and gestation age.
other causes?
2. Were treatments/exposures and clinical Yes, exposures were measured in the
outcomes measured in the same way for same way for both groups. The
both groups? Was the assessment of examination was evaluated with
outcomes either objective or blinded to glasglow outcome scale on the day of
exposure? discharge or a postnatal age of 2,5 to 3
months

46
3. Was the follow-up of study patients No, this study using retrospective method
sufficiently long for the outcome to
occur?
4. Is it clear that the exposure preceded Yes, it is clear that the exposure preceded
the onset of the outcome? the onset of the outcome

5. Is there a dose-response gradient? No, this study was not associated with
dose response gradient
6 Is the association consistent from study Yes, poor feeding, pneumonia and CSF
to study? protein associated with poor outcome in
neonatal meningitis, it has been shown in
some follow up studies of neonatal
meningitis,.
7 Does the association make biological Yes, it does. Outcome neonatal
sense? meningitis associated with poor feeding,
pneumonia and CSF protein.
This study is valid

Are the results important?


2. How strong is the association between Predictor factors of outcome in neonatal
exposure and outcome, i.e. the estimate meningitis associated with poor feeding
of risk? OR 3.83; P=0.02, Pneumonia OR 3.37;
P=0.03; CSF protein OR 4.07; P=<0.001.

2. How precise is the estimate of risk? 95% CI for poor feeding: 1.22 to 12.05
95% CI for pneumonia : 1.15 to 9.84
95% CI for CSF protein: 2.33 to 7.11
This study is important

Are the results important for my patient?


1. Is my patient so different from those No, characteristic type of subjects in this
included in the study that its results don’t study similar with our patients
apply?
2. What is my patient’s risk of the adverse This evidence is worth for our clinical
event? What is my patient’s potential practices.
benefit from therapy?

47
3 What are my patient’s preferences, By knowing the predictor factor
concerns and expectations from this associated outcomes of neonatal
treatment? meningitis, we can explain to the
patient about the prognosis and how to
prevent it.
This study is applicable

Conclusion: Valid, Important, and Applicable.


Level of evidence 3b with grade of recommendation B.
PROBLEM 4

PICO
According to the problems, PICO can be described as follows:
P (Patient/Problem) : neonatus with bacteremia-associated neurological
complication
I (Intervention) :-
C (Comparation/Control) : neonatus without bacteremia-associated neurological
complication after bacteremia
O (Outcome) : outcomes

CLINICAL QUESTION
In neonates with bacteremia-associated neurological complication, how is the outcome or
sequele if compared to those without bacteremia-associated neurological complication?

JOURNAL SEARCHING STRATEGY


Keywords: Bacteremia AND Neonates AND neurologic complication AND outcomes

RESULT
“Neurological Complications after Neonatal Bacteremia:
The Clinical Characteristics, Risk Factors, and Outcomes”

48
Shih-Ming Chu1, Jen-Fu Hsu1, Chiang-Wen Lee, Reyin Lien,
Hsuan-Rong Huang, Ming-Chou Chiang, dkk.
PLOS one. 2014;9:1-8

ABSTRACT
Background: Neurological complications after neonatal bacteremia with or without
meningitis are important, because they can be life-threatening and may require
neurosurgical treatment. There are a large number of studies on the incidence, risk
factors, microbiology, and mortality of neonatal bacteremia or meningitis [1–8], but
there is paucity of literature regarding acute and subacute neurological morbidities
caused by neonatal bacteremia.
Study Design: This was a retrospective cohort study of neonates with bacteremia-
related neurologic complications (BNCs) in a tertiary-level neonatal intensive care unit
(NICU). A systemic chart review was performed conducted to identify clinical
characteristics and outcomes. A cohort of related conditions was constructed as the
control group. Logistic regression analysis was used to identify independent risk factors
for BNC.
Results: Of 1037 bacteremia episodes, 36 (3.5%) had BNCs. Twenty-four cases of
BNCs were related to meningitis, five were presumed meningitis, and seven occurred
after septic shock. The most common causative pathogens were Group B streptococcus
(41.7%) and E. coli (16.7%). The major BNCs consisted of seizures (28),
hydrocephalus (20), encephalomalacia (11), cerebral infarction (7), subdural empyema
(6), ventriculitis (8), and abscess (4). Eight (22.8%) neonates died and six (16.7%) were
discharged in critical condition when the family withdrew life-sustaining treatment.
Among the 22 survivors, eight had neurologic sequelae upon discharge. After
multivariate logistic regression analysis, neonates with meningitis caused by Group B
streptococcus (adjusted odds ratio [OR]: 8.90, 95% confidence interval [CI]: 2.20–
36.08; p = 0.002) and combined meningitis and septic shock (OR, 5.94; 95% CI: 1.53–
23.15; p = 0.010) were independently associated with BNCs.
Conclusions: Neonates with bacteremia-related neurologic complications are
associated with adverse outcomes or sequelae. Better strategies aimed at early detection

49
and reducing the emergence of neurologic complications and aggressive treatment of
Group B streptococcus sepsis are needed in neonates with meningitis and septic shock.

EVIDENCE-BASED CRITICAL APPRAISAL


(PROGNOSTIC STUDIES)

Are the results of the study valid? (internal validity)


1. Was the defined representative sample Yes, Bacteremia-associated neurological
of patients assembled at a common complication (BNC) was defined as any
(usually early) point in the course of newly
neurological symptoms or signs and
their disease)?
abnormalities on neuroimaging study
(Transcranial ultrasound, computed
tomography [CT] scan or magnetic
resonance imaging [MRI]) that occurred
soon after an episode of bacteremia, or
judged by a clinical
neonatologist to be directly resulted from an
episode of bacteremia.
2. Was patient follow-up sufficiently long Yes, subject were followed by ndependent
and complete ? investigators through the medical record
from onset of bacteremia until any newly
neurological complication appear.
3. Were outcome criteria either objective or Yes. Observation was done blindly. all
applied in a “blind” fashion? patient records/information was
anonymized and de-identified prior to
analysis

3. If subgroups with different prognoses are


identified,
 Did adjustment for important Yes, adjusment were done to the groups.
prognostic factors take place?
 Was there validation in an
independent group of patients? Not explained in this study

The study is valid

What are the results?

50
1. How likely are the outcomes over time? The major BNCs consisted of seizures
How precise are the prognostic (28), hydrocephalus (20),
estimates? encephalomalacia (11), cerebral
infarction (7), subdural empyema (6),
ventriculitis (8), and abscess (4). Eight
(22.8%) neonates died and six (16.7%)
were discharged in critical condition
when the family withdrew life-
sustaining treatment. Among the 22
survivors, eight had neurologic sequelae
upon discharge. After multivariate
logistic regression analysis, neonates
with meningitis caused by Group B
streptococcus (adjusted odds ratio [OR]:
8.90, 95% confidence interval [CI]:
2.20–36.08; p = 0.002) and combined
meningitis and septic shock (OR, 5.94;
95% CI: 1.53–23.15; p = 0.010) were
independently associated with BNCs
Can I apply this valid, important evidence about pronosis to my patient?

1. Is my patient so different to those in Yes, patients in this study have similar


the study that the results can not apply? characteristics with ours.

2. Will this evidence make a clinically Yes, with this evidence we can explain
important impact on my conclusions to the parents that neonates with
about what to offer to tell my patients? bacteremia-related neurologic
complications are associated with
adverse outcomes or sequelae.
The study is important

Conclusion: Valid, Important, and Applicable.


Level of evidence 2b with grade of recommendation B.

51
52

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