Professional Documents
Culture Documents
● PURPOSE: To report the efficacy of povidone–iodine as patient, the faster their conjunctivitis resolved (R ⴝ
a treatment for conjunctivitis in pediatric patients. 0.13, P ⴝ .013).
● DESIGN: Double-masked, controlled, prospective clin- ● CONCLUSIONS: Povidone–iodine 1.25% ophthalmic
ical trial. solution was as effective as neomycin–polymyxin B-
● METHODS: In an ophthalmology clinic in a general gramicidin for treating bacterial conjunctivitis, somewhat
hospital in Manila, Philippines, 459 children (mean [SD] more effective against chlamydia, and as ineffective
age 6.6 [6.6] years; range, 7 months–21 years) with against viral conjunctivitis. Povidone–iodine ophthalmic
acute conjunctivitis were studied. Infected eyes were solution should be strongly considered as treatment for
cultured for bacteria and underwent immunofluorescent bacterial and chlamydial conjunctivitis, especially in de-
testing for Chlamydia trachomatis. Viral conjunctivitis veloping countries where topical antibiotics are often
was diagnosed if bacterial cultures were negative and unavailable or costly. (Am J Ophthalmol 2002;134:
diagnostic criteria were met. Subjects were alternated to 681– 688. © 2002 by Elsevier Science Inc. All rights
receive povidone–iodine 1.25% or neomycin–polymyxin- reserved.)
B-gramicidin ophthalmic solution, one drop 4 times daily
A
in the affected eye. Ocular inflammation was evaluated CUTE CONJUNCTIVITIS IS ONE OF THE MOST COM-
daily by the family or patient and weekly by an ophthal- mon eye conditions seen by medical and pediatric
mologist. The main outcome measures were days until practitioners. Without treatment, the infection
cured and proportion cured after 1 and 2 weeks of may improve spontaneously or, infrequently, worsen to
treatment. cause keratitis, corneal ulceration, scarring, and possible
● RESULTS: Despite adequate statistical power (power blindness. These serious complications occur more fre-
>80% for a 1-day difference and P < .05), there was no quently in the setting of vitamin A deficiency, malnutri-
significant difference between treatment groups regarding tion, and shortage of appropriate topical antibiotics—a
the number of days to cure or proportion cured at 1 or 2 scenario all too common in many developing countries,
weeks whether caused by bacteria or virus (P ⴝ .133– resulting in thousands of children becoming blind annual-
.824 for the four comparisons). After 1 week of treat- ly.1 Of the 1.5 million blind children in the world most are
ment, povidone–iodine cured marginally more chlamydial in developing countries, where corneal opacification is the
infections than the antibiotic (P ⴝ .057). By 2 weeks, leading preventable cause of blindness.2
fewer chlamydial infections were cured than those of Low cost, effectiveness, and lack of microbial resistance
viral or bacterial etiology (P ⴝ .0001). The younger the make povidone–iodine an appealing drug to treat ocular
infections, especially in developing countries. Even in
developed countries, increasing bacterial resistance to
Accepted for publication June 28, 2002. conjunctivitis treatment, as reported in the United States
From the Jules Stein Eye Institute (S.J.I., L.A., M.D.S., N.G.B.), may also make povidone–iodine attractive.3 Povidone–
Departments of Ophthalmology and Pediatrics, Harbor/UCLA Medical
Center, UCLA School of Medicine, Los Angeles, California, and iodine interacts strongly with the double bonds of satu-
Torrance, California; and the Department of Ophthalmology (M.V., rated fatty acids in the bacterial cell wall and cell organelle
L.C., M.A.L., P.C.), Philippine General Hospital, University of the membranes and also oxidizes amino acid and nucleotides.
Philippines, Manila, Philippines.
This study was supported by the Thrasher Research Fund of Salt Lake It causes pore formation and solid–liquid interfaces at the
City and Research to Prevent Blindness Senior Scientific Investigator lipid membrane level of cell walls to lose cytosol material.4
Award (S.J.I.), New York, New York. Povidone–iodine ophthalmic solution has been previ-
Inquiries to Sherwin J. Isenberg, MD, Department of Ophthalmology,
Harbor/UCLA Medical Center, 1000 W. Carson St, Torrance, CA ously shown by our group to be an effective preventative
90509; fax: (310) 837-4078; e-mail: isenberg@ucla.edu germicidal agent. It was effective and safe when used
Second Quartile
Organism Medication Mean (SD) Minimum (Median) Maximum
SD ⫽ standard deviation.
Second Quartile
Organism Medication Mean (SD) Minimum (Median) Maximum
SD ⫽ standard deviation.
rior to no treatment.18 With this evidence, we believed tance to antibiotic treatment of pediatric conjunctivitis in
that the inclusion of a placebo treatment arm in our study the United States.
was not justified and might have been unethical.21 In our study, neomycin-polymyxin-B-gramicidin oph-
Lohr and associates22 found trimethoprim–polymyxin, thalmic solution was chosen as the control drug because it
gentamycin, and sodium sulfacetamide to be equally effec- is customarily used in the Philippines for infectious con-
tive in treating bacterial conjunctivitis. A Norwegian junctivitis. The drug also is frequently used to treat
study of 340 children and adults with acute conjunctivitis conjunctivitis in industrialized as well as other underde-
found that cure was achieved in approximately 6.5 days veloped countries. In a recent Bangladeshi study, neomy-
whether fusidic acid or chloramphenicol eyedrops was cin alone was found effective against 68% of all bacterial
given.23 In 1997, Gross and associates24 found that approx- isolates.25 Gibson26 reported the combination of neomy-
imately 90% of 147 patients, whether treated with cipro- cin-polymyxin-B-gramicidin more effective than chloram-
floxin or tobramycin eyedrops, were cured by day 7. phenicol in a double-masked randomized trial. The
Despite the success of antibacterial treatment, Block and combination was as effective as fusidic acid in another
associates3 recently raised concern over increasing resis- trial.27 This eyedrop is considered effective against organ-
isms responsible for at least 92% of the bacterial infections procedure with 5% povidone–iodine solution, as well as
in our series (Table 2).28,29 It is, however, considered cefazolin, vancomycin, and ciprofloxin.
ineffective against chlamydia or viruses. In 1998, Abel and Abel33 reported the treatment of 36
Among bacteria, we found the most common causative children and adults with presumed adenoviral keratocon-
bacterial species in Manila was Haemophilus species fol- junctivitis. Twenty-one patients had received previous
lowed by Moraxella species (Table 2). Immunization treatment with topical corticosteroids with or without
against Haemophilus in Manila is not required by the antibiotics. Thirty patients were then treated only with
government and is therefore only utilized in the minority 10% povidone–iodine eyelid scrubs. Six patients received
of children whose parents are willing to pay directly. The 5% povidone–iodine solution 3 times a day for 2 days.
next two were Staphylococcus aureus and Streptococcus Follow-up communication was made by telephone unless
pneumonia. Cultural differences in hygiene may explain they had not improved. There were no controls, random-
this order of frequency of bacterial species, as well the ization, or masking. Thirty-four patients had improved by
prominence of viral infections in this study. In the United the second day of treatment.
States, bacteria cause approximately 80% of acute con- Our project is the first controlled and masked study to
junctivitis cases in children.17 In our study, however, evaluate the efficacy of povidone–iodine to treat an ocular
almost 60% of the cases were attributed to viruses. In the infection. As most external eye infections begin with acute
Philippines, it is common to have multiple family members conjunctivitis, we began our treatment investigation with
present simultaneously or sequentially with viral conjunc- this disorder. The 1.25% concentration of povidone–
tivitis, presumably due to easy spread of the virus among iodine was chosen for this study based on our experience in
them. We believe this is less common in the United States. the postoperative use of povidone–iodine.9 In that study,
Valenton and associates13 suggested that the high preva- we began with the use of a 2.5% concentration, but
lence of viral conjunctivitis in their 1993 Manila study decreased it to 1.25% when a few subjects complained of
might have occurred because patients were less disturbed mild stinging when the eyedrop was used several times a
by bacterial conjunctivitis and frequently did not seek day. The drug is still highly germicidal when used at the
medical attention. lower concentration. Subsequent patients in the postoper-
All the previously mentioned investigations of povi- ative study and in this investigation tolerated the 1.25%
done–iodine studied prophylaxis of infection. We are not concentration well.
aware of previous controlled studies dealing with the use of We found the number of days needed for cure, whether
povidone–iodine to treat ongoing infections. In 1985, evaluated by the ophthalmologist or the patient, to be the
Schuhman and Vidic30 treated 40 patients with conjunc- same for either medication for bacterial and viral infec-
tivitis or keratoconjunctivitis with a 3-mg/100 ml solution tions. Thus, povidone–iodine was as effective as the
of povidone–iodine instilled 3 to 12 times a day either antibiotic against bacterial conjunctivitis. Bacteria gener-
alone or in conjunction with betamethasone eyedrops. ally adhere to the surfaces of infected tissue in biofilms
There were no controls, masking, or randomization. A within a glycocalyx matrix.34 Povidone–iodine can reach
“marked improvement” was found in 28 patients by day 3 the biofilm and has been shown to cause the outer layers of
and 35 patients were cured by day 6. Two patients the biomass to slough and be killed.35 It not only destroys
complained of ocular discomfort after instillation of the a wide range of bacteria, but also inactivates and inhibits
eyedrop. In 1995, Duffey31 successfully treated one patient the release of bacterial exotoxins.36 The superficial loca-
who developed a Serratia marcescens keratitis after radial tion of bacteria may provide susceptibility to the effects of
keratotomy with 5% povidone–iodine ophthalmic solution povidone–iodine.
along with tobramycin and ciprofloxin. Aras and associ- In this study, povidone–iodine was found as ineffective
ates32 successfully treated a single culture-negative eye as the antibiotic against viral conjunctivitis. Viruses begin
infection that followed a laser in situ keratomileusis replication by attaching to and penetrating a host cell.