Bacterial conjunctivitis

John Epling

. 2012 Feb 20;2012:0704.

Bacterial conjunctivitis

John Epling ¹

PMCID: PMC3635545 PMID: 22348418

Abstract

Introduction

Most cases of conjunctivitis in adults are probably due to viral infection, but children are more likely to develop bacterial conjunctivitis than they are viral forms. The main bacterial pathogens are Haemophilus influenzae and Streptococcus pneumoniae in adults and children, and Moraxella catarrhalis in children. Contact lens wearers may be more likely to develop gram-negative infections. Bacterial keratitis occurs in up to 30 per 100,000 contact lens wearers.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of empirical treatment in adults and children with suspected bacterial conjunctivitis? What are the effects of treatment in adults and children with bacteriologically confirmed bacterial conjunctivitis? What are the effects of treatment in adults and children with clinically confirmed gonococcal conjunctivitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 44 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: ocular decongestants, oral antibiotics, parenteral antibiotics, saline, topical antibiotics, and warm compresses.

Key Points

Conjunctivitis causes irritation, itching, foreign body sensation, and watering or discharge of the eye.

Most cases in adults are probably due to viral infection, but children are more likely to develop bacterial conjunctivitis than viral forms. The main bacterial pathogens are Staphylococcus species in adults, and Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis in children.
A bacterial cause is more likely if there is gluing of the eyelids and no itch.
Contact lens wearers may be more likely to develop gram-negative infections. Bacterial keratitis occurs in up to 30/100,000 contact lens wearers.
Gonococcal ophthalmia neonatorum can occur in up to 10% of infants exposed to gonorrhoeal exudate during delivery despite prophylaxis, and can be associated with bacteraemia and meningitis.
Otitis media can occur in 25% of children with H influenzae conjunctivitis, and meningitis can develop in 18% of people with meningococcal conjunctivitis.

Conjunctivitis resolves spontaneously within 2 to 5 days in more than half of people without treatment, but infectious complications can occur rarely.

Topical antibiotics may speed up clinical and microbiological cure of bacterial conjunctivitis, but the benefit is small.

In people with suspected, but not confirmed, bacterial conjunctivitis, empirical treatment with topical antibiotics may be beneficial. However, this benefit is marginal, so it is advisable to suggest that patients take antibiotics only if symptoms do not resolve after 1 to 2 days.
Clinical and microbiological cure rates are increased in the first week in people with culture-positive bacterial conjunctivitis, but there is no good evidence of a longer-term benefit from topical antibiotics.
Adverse effects of topical antibiotics are mild, but their effect on bacterial resistance is unknown.

Parenteral antibiotics may cure gonococcal ophthalmia neonatorum, although we don't know whether they are beneficial in children in developed countries, as we only found studies from Africa. Neonates will usually require investigation for concomitant infections and complications.

We don't know whether ocular decongestants, saline, or warm compresses are beneficial in people with suspected or confirmed bacterial or gonococcal conjunctivitis.

About this condition

Definition

Conjunctivitis is any inflammation of the conjunctiva, generally characterised by irritation, itching, foreign body sensation, and watering or discharge. Treatment is often based on clinical suspicion that the conjunctivitis is bacterial, without waiting for the results of microbiological tests. In this review, therefore, we have distinguished the effects of empirical treatment from effects of treatment in people with culture-positive bacterial conjunctivitis. Bacterial conjunctivitis in contact lens wearers is of particular concern because of the risk of bacterial keratitis — an infection of the cornea accompanying acute or subacute corneal trauma, which is more difficult to treat than conjunctivitis and can threaten vision. Conjunctivitis caused by Neisseria gonorrhoeae — referred to as ophthalmia neonatorum — is primarily a disease of neonates, caused by exposure of the neonatal conjunctivae to the cervicovaginal exudate of infected women during delivery. Diagnosis The traditional criteria differentiating bacterial from other types of conjunctivitis have been: a yellow–white mucopurulent discharge; a papillary reaction (small bumps with fibrovascular cores on the palpebral conjunctiva, appearing grossly as a fine velvety surface); and bilateral infection. One systematic review was unable to find any quality research basis for these criteria, but a follow-up study performed by the authors of the review found that glued eyes and the absence of itching were predictive of a bacterial cause. A history of recent conjunctivitis argued against a bacterial cause. If eye pain is moderate or severe and visual acuity is reduced, more serious causes need to be considered. Gonococcal ophthalmia neonatorum is diagnosed by a persistent and increasingly purulent conjunctivitis in exposed infants, beginning from 3 to 21 days after delivery.

Incidence/ Prevalence

We found no good evidence on the incidence or prevalence of bacterial conjunctivitis. Bacterial keratitis is estimated to occur in 10 to 30/100,000 contact lens wearers. Gonococcal ophthalmia neonatorum occurs at rates of 0% to 10% in infants who received antibiotic prophylaxis after delivery to mothers with gonorrhoea infection, and in 2% to 48% of exposed infants without prophylaxis.

Aetiology/ Risk factors

Conjunctivitis may be infectious (causes include bacteria and viruses) or allergic. In adults, bacterial conjunctivitis is less common than viral conjunctivitis, although estimates vary widely (viral conjunctivitis has been reported to account for 8% to 75% of acute conjunctivitis). Staphylococcus species are the most common pathogens for bacterial conjunctivitis in adults, followed by Streptococcus pneumoniae and Haemophilus influenzae. In children, bacterial conjunctivitis is more common than the viral form, and is mainly caused by H influenzae, S pneumoniae, and Moraxella catarrhalis. One prospective study (428 children from southern Israel with a clinical diagnosis of conjunctivitis) found that in 55% of the children, conjunctivitis was caused by S pneumoniae, H influenzae, or M catarrhalis. Narrative reviews suggest that the causative agents of bacterial conjunctivitis and keratitis in contact lens wearers are more frequently gram-negative bacteria (such as Pseudomonas aeruginosa), but may include all of the above agents. Acanthamoeba spp. infections can be particularly difficult to diagnose and treat, and are most common in contact lens wearers.

Diagnosis

Prognosis

Most bacterial conjunctivitis is self-limiting. One systematic review (search date 2004) found clinical cure or significant improvement with placebo within 2 to 5 days in 65% of people. Some organisms cause corneal or systemic complications, or both. Otitis media may develop in 25% of children with H influenzae conjunctivitis, and systemic meningitis may complicate primary meningococcal conjunctivitis in 18% of people. Untreated gonococcal ophthalmia neonatorum can cause corneal ulceration, perforation of the globe, and panophthalmitis. Investigations to detect concomitant infections, as well as gonococcal bacteraemia and meningitis, and admission to hospital for parenteral treatment of the eye infection, are frequently required.

Aims of intervention

To achieve rapid cure and to prevent complications of infection, with minimum adverse effects of treatment.

Outcomes

Time to cure or improvement. Clinical signs/symptoms: hyperaemia, discharge, papillae, follicles, chemosis, itching, pain, and photophobia. Most studies used a numbered scale to grade signs and symptoms. Some studies also included evaluation by investigators and participants regarding success of treatment. Culture results: These are proxy outcomes, usually expressed as the number of colonies, sometimes with reference to a threshold level. Results were often classified into categories such as eradication, reduction, persistence, and proliferation.

Methods

Clinical Evidence search and appraisal July 2011. The following databases were used to identify studies for this systematic review: Medline 1966 to August 2011, Embase 1980 to August 2011, and The Cochrane Database of Systematic Reviews, July 2011 (1966 to date of issue). An additional search within The Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language, at least single blinded, and containing >20 individuals of whom >80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. We included systematic reviews of RCTs and RCTs where harms of an included intervention were studied applying the same study design criteria for inclusion as we did for benefits. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table 1.

GRADE evaluation of interventions for bacterial conjunctivitis.

Important outcomes	Cure rates, adverse effects
Number of studies (participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of empirical treatment in adults and children with suspected bacterial conjunctivitis?
8 (2515)	Cure rates	Topical antibiotics v placebo or no immediate treatment	4	−1	−1	0	0	Low	Quality point deducted for self-report of clinical cure by parents in 1 RCT. Consistency point deducted for conflicting results
24 (at least 2754)	Cure rates	Topical antibiotics v each other	4	−2	0	0	0	Low	Quality points deducted for incomplete reporting of results and for weak methods in some RCTs
1 (80)	Cure rates	Topical v oral antibiotics	4	−2	0	−1	0	Very low	Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for small number of comparators
1 (104)	Cure rates	Different regimens of topical antibiotics v each other	4	−1	0	−1	0	Low	Quality point deducted for sparse data. Directness point deducted for small number of comparators
What are the effects of treatment in adults and children with bacteriologically confirmed bacterial conjunctivitis?
8 (1933)	Cure rates	Topical antibiotics v placebo	4	0	0	−1	0	Moderate	Directness point deducted for uncertainty about generalisability of results (to situations where treatment not initiated until culture results are known, because of the delay in treatment)
9 (at least 1584)	Cure rates	Topical antibiotics v each other	4	−1	−1	0	0	Low	Quality point deducted for incomplete reporting of results. Consistency point deducted for inconsistent results between RCTs
1 (86)	Cure rates	Different regimens of topical antibiotics v each other	4	−1	0	−1	0	Low	Quality point deducted for sparse data. Directness point deducted for small number of comparators
What are the effects of treatment in adults and children with clinically confirmed gonococcal conjunctivitis?
4 (239)	Cure rates	Parenteral antibiotics plus topical antibiotics v parenteral antibiotics alone or v parenteral antibiotics plus different topical antibiotic	4	−1	−1	−1	0	Very low	Quality point deducted for incomplete reporting of results. Consistency point deducted for conflicting results. Directness point deducted for all studies in Africa, which may affect generalisability

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Type of evidence: 4 = RCT. Consistency: similarity of results across studies. Directness: generalisability of population or outcomes. Effect size: based on relative risk or odds ratio.

Glossary

Low-quality evidence: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Moderate-quality evidence: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Very low-quality evidence: Any estimate of effect is very uncertain.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

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BMJ Clin Evid. 2012 Feb 20;2012:0704.

Empirical treatment with topical antibiotics in people with suspected bacterial conjunctivitis

Summary

CURE RATES Compared with placebo or no immediate treatment: Topical antibiotics may be more effective at improving microbiological cure rates at 2 to 7 days, but we don't know about clinical cure rates as results varied between RCTs depending on the topical antibiotic used and the analysis undertaken ( low-quality evidence ). Compared with each other: We don't know whether any one topical antibiotic is consistently more effective than the others at improving clinical or microbiological cure (low-quality evidence). Compared with oral antibiotics: We don't know whether polymyxin B sulphate–bacitracin ointment is more effective than oral cefixime at improving clinical cure or bacteriological failure rates in children aged 2 months to 6 years with suspected bacterial conjunctivitis ( very low-quality evidence ). Different regimens compared with each other: We don't know whether topical gatifloxacin applied twice daily is more effective than topical gatifloxacin applied 4 times daily at increasing clinical cure at 5 days (low-quality evidence). NOTE Topical antibiotics are associated with burning, stinging, and bad taste.

Benefits

Topical antibiotics versus placebo or no immediate treatment:

We found two systematic reviews and two additional RCTs.

The first systematic review (search date 2005, 3 RCTs, 791 people with suspected bacterial conjunctivitis) compared topical antibiotics (norfloxacin, fusidic acid, and chloramphenicol) versus placebo. The review performed a meta-analysis including RCTs of both suspected and confirmed culture-positive bacterial conjunctivitis, but did not perform separate meta-analyses for these populations; therefore, we report results of the individual RCTs here. Two RCTs identified by the review found no significant difference in clinical cure between topical antibiotics and placebo at 3 or 7 days. One RCT found that topical antibiotics significantly increased clinical cure at 5 days compared with placebo. Cure rates after 5 days were generally high in both treatment groups (see table 1 ).

Table 1.

Topical antibiotics in adults and children with suspected or confirmed bacterial conjunctivitis: results of RCTs.

Intervention	Number of participants	Age of participants	Proportion culture-positive	Microbiological cure rate	Clinical cure rate	Adverse effects
Topical antibiotics versus placebo
Suspected bacterial conjunctivitis
Norfloxacin 0.3% every 2 hours while awake, for 1 day, then 4 times daily for 5 to 6 more days	284 adults	18 years and over	With or without positive cultures	At 2 to 3 days: 65% with norfloxacin v 26% with placebo; P <0.01At 5 to 7 days (excluding coagulase-negative Staphylococcus): 74% with norfloxacin v 42% with placebo; P <0.01	At 5 days: 88% with norfloxacin v 72% with placebo; P <0.01	Minor events (including chemosis and burning): 4% with norfloxacin v 7% with placebo; significance not reported
Chloramphenicol 0.5% 1 drop every 2 hours while awake, for 1 day, then 4 times daily until 48 hours after infection has resolved	326 children	6 months to 12 years	78%	Microbiological cure at 7 days: 40% with chloramphenicol v 23% with placebo; ARI 17%, 95% CI 5.5% to 28.1% Microbiological cure or improvement at 7 days: 65% with chloramphenicol v 55% with placebo; ARI +9.6%, 95% CI –2.5% to +21.7%	At 3 days: 39% with chloramphenicol v 33% with placebo; ARI +6.2%, 95% CI –4.3% to +16.5%At 7 days: 86% with chloramphenicol v 79% with placebo; ARI +7.4%, 95% CI –0.9% to +15.6%	2% with chloramphenicol v 2% with placebo; ARI 0%, 95% CI –2.9% to +2.9%
Fusidic acid gel 10 mg/g 1 drop 4 times daily until 1 day after signs and symptoms disappear	181 adults	18 years and over	34%	At 7 days: 76% with fusidic acid v 41% with placebo; ARI 34.8%, 95% CI 9.3% to 60.4%	At 7 days: 62% with fusidic acid v 59% with placebo; ARI +2.8%, 95% CI –13.5% to +18.6%	14% with fusidic acid v 3% with placebo; ARI 10.4%, 95% CI 1.6% to 19.1%
Chloramphenicol eye drops (immediate, every 2 hours for 2 days, then 4 times daily), chloramphenicol eye drops (delayed, same regimen, prescriptions available from surgery up to 3 days after consultation at patient's/parent's discretion), no antibiotics	307 adults and children	Over 1 year, mean age 27 years	50%	Not reported	Mean symptom score (days 1–3 after consultation): 1.9 with immediate antibiotics v 2.1 with no antibiotics; P = 0.2 Mean symptom score (days 1–3 after consultation): 2.0 with delayed antibiotics v 2.1 with no antibiotics; P = 0.4	1 person in immediate-antibiotic group was admitted 11 days post-consultation for orbital cellulitis
Besifloxacin 0.6% twice a day for 3 days	202 adults and children	1 year and over	54%	At days 4/5: 87% with besifloxacin v 57% with vehicle; P <0.001 At days 6/7/8: 87% with besifloxacin v 70% with vehicle; P = 0.038	At days 4/5: 70% with besifloxacin v 38% with vehicle; P <0.001 At days 6/7/8: 74% with besifloxacin v 66% with vehicle; P = NS Individual clinical outcomes of ocular discharge (83% with besifloxacin v 54% with vehicle) and conjunctival injection (77% with besifloxacin v 47% with vehicle) also favoured besifloxacin at visit 2, but not at visit 3	No difference in adverse events in all treated eyes: 6% with besifloxacin v 11% with vehicle; all were mild to moderate severity (non-specific conjunctivitis, bacterial conjunctivitis, and installation-site pain); non-ocular adverse events similar between groups and not considered related to treatments
Confirmed bacterial conjunctivitis
Levofloxacin 0.5%	249 recruited; 117 people included in efficacy analysis	2 to 91 years	117 culture-positive and included in per-protocol cohort	At "end point", defined as the last evaluable observation (up to day 10 post-treatment): 90% with levofloxacin v 53% with placebo; P <0.001	At "end point", defined as the last evaluable observation (up to day 10 post-treatment): 77% with levofloxacin v 60% with placebo; P = 0.026	No significant difference between levofloxacin and placebo in transient burning (2.4% of 124 people); transiently decreased vision (2.4% of 124 people) with levofloxacin
Moxifloxacin	73 recruited; number included in efficacy analysis not reported; unclear whether analysis was restricted only to people with culture-positive bacterial conjunctivitis	1 to 89 years	51 culture-positive	After about 1 week of treatment: 78% with moxifloxacin v 39% with placebo; P = 0.005	After about 1 week of treatment: 93% with moxifloxacin v 63% with placebo; P = 0.009	All adverse events reported as not serious
Polymyxin B sulphate 10,000 U/g plus bacitracin 500 U/g (in ointment) 4 times daily for 7 days	66	1 month to 18 years	Cultures positive for Haemophilus influenzae or Streptococcus pneumoniae	Eradicated at 3 to 5 days: 71% with polymyxin B sulphate–bacitracin v 19% with placebo; P <0.001Eradicated at 8 to 10 days: 79% with polymyxin B sulphate–bacitracin v 31% with placebo; P <0.001	Cured at 3 to 5 days: 62% with polymyxin B sulphate–bacitracin v 28% with placebo; P <0.02At 8 to 10 days: 91% with polymyxin B sulphate–bacitracin v 72% with placebo; P >0.05; NS	Allergic reaction to topical polymyxin B sulphate–bacitracin in initial group of participants
Polymyxin B sulphate plus bacitracin in people taking systemic antibiotics: amoxicillin, trimethoprim–sulfamethoxazole, cefaclor, or penicillin (subgroup analysis of RCT described above)	18	1 month to 18 years	Cultures positive for H influenzae or S pneumoniae	72% with polymyxin B sulphate–bacitracin eradicated at 3 to 5 days, and 78% at 8 to 10 days. In people receiving systemic antibiotics, no significant difference in microbiological cure between adding polymyxin B sulphate–bacitracin and adding placebo (reported as NS; P value not reported)	83% cured at 3 to 5 days; 100% cured at 8 to 10 days. In people receiving systemic antibiotics, there was no significant difference in clinical cure between adding polymyxin B sulphate–bacitracin and adding placebo (reported as NS; P value not reported)	Allergic reaction to topical polymyxin B sulphate–bacitracin in initial group of participants
Ciprofloxacin 0.3% every 2 hours while awake on days 0 to 1, then every 4 hours while awake for 1 to 2 more days	177	Age not specified	Culture-positive	Eradicated or reduced at 3 days: 132/140 (94%) with ciprofloxacin v 22/37 (59%) with placebo; RR 1.59; P <0.001	Not reported	Adverse effects not assessed in the RCT
Ofloxacin 0.3% 6 times daily for 2 days	132	Age not specified	Culture-positive	At 2 days: 72% with ofloxacin v 35% with placebo; P <0.001	Improved at 2 days: 64% with ofloxacin v 22% with placebo; P <0.001	Adverse effects not assessed in the RCT
Besifloxacin 0.6% v vehicle only (placebo) 1 drop 3 times daily for 5 days	118 (269 in "safety" population who got drug for clinical diagnosis)	1 to 92 years	44%	At day 4: 90% with besifloxacin v 47% with vehicle; P <0.001At day 8: 88% with besifloxacin v 60% with vehicle; P <0.001	At day 4: 33% with besifloxacin v 17% with vehicle; P = NSAt day 8: 73% with besifloxacin v 43% with vehicle; P <0.001	Mild–moderate severity adverse events common (50% with besifloxacin v 53% with vehicle); 1 preseptal cellulitis in vehicle group thought unrelated to study
Besifloxacin 0.6% v vehicle only (placebo) 1 drop 3 times daily for 5 days	390 culture-positive for efficacy analysis (957 enrolled for clinical diagnosis analysed for safety)	10 months to 98 years	41%	At day 5: 92% with besifloxacin v 59% with vehicle; P <0.0001At days 8 to 9: 88% with besifloxacin v 72% with vehicle; P <0.0001	At day 5: 45% with besifloxacin v 33% with vehicle; P = 0.0084At days 8 to 9: 84% with besifloxacin v 69% with vehicle; P = 0.0011	More conjunctivitis (non-specific and bacterial) in vehicle-only group (14% with besifloxacin v 9% with placebo; P = 0.0047); more pruritus in besifloxacin group (1% with besifloxacin v 0.3% with placebo; P = 0.03) and viral conjunctivitis (0.7% with besifloxacin v 0% with placebo; P = 0.02)
Azithromycin 1% 1 drop twice daily on days 1 and 2, then once daily on days 3 to 5 v vehicle-only placebo dosed in same manner	685 enrolled, 630 completed, 279 analysed in per-protocol analysis	1 to 96 years	41%	At visit 3 (day 6 or 7): 89% with azithromycin v 66% with vehicle; P <0.001; difference 22.0%, 95% CI 12.7% to 31.4%	At visit 3: 63% with azithromycin v 50% with vehicle; P <0.03; difference 13.4%, 95% CI 1.9% to 25.0%	Similar between groups in frequency and magnitude
Topical antibiotics versus each other
Suspected bacterial conjunctivitis
Chloramphenicol 0.5% drops v tobramycin 0.3%	50	8 to 81 years	36% culture-positive for bacteria (2% positive for Candida)	Not reported	No significant difference between chloramphenicol and tobramycin in clinical scores assessed by patients or investigators (P >0.05)	0% with chloramphenicol v 8% with tobramycin had irritation; statistical analysis not reported
Ciprofloxacin 0.3% drops v tobramycin 0.3% drops; regimen unspecified (abstract reviewed, but full paper unavailable)	40	Age unspecified	Not all culture-confirmed	Eradication: 80% with ciprofloxacin v 95% with tobramycin; reported as NS	Cure: 95% with ciprofloxacin v 95% with tobramycin; reported as NS	Adverse events (burning, bitter taste, pruritus, punctate epithelial erosions: 20% with ciprofloxacin v 35% with tobramycin
Fusidic acid 1% viscous drops twice daily v rifamycin 1% drops 4 times daily	163	Adults and children	72% to 75% culture-positive	Not reported in each group separately	Cure: 87% with fusidic acid v 89% with rifamycin; P = 0.71; median: 7 days with fusidic acid v 6 days with rifamycin; P = 0.31	Burning and bad taste: 4/74 (5%) with fusidic acid v 13/77 (17%) with rifamycin; reports of allergy with rifamycin
Fusidic acid 1% viscous drops twice daily v norfloxacin 0.3% drops 4 times daily	400	Over 1 year	34% culture-positive	Not reported	Success of treatment as assessed by investigator after 7 days' treatment: 91% with fusidic acid v 93% with norfloxacin; P = 0.49	Bad taste: 6% with fusidic acid v 20% with norfloxacin; P = 0.001; stinging: 37% with fusidic acid v 50% with norfloxacin; P = 0.007
Fusidic acid 1% viscous drops twice daily v chloramphenicol 0.5% drops 4-hourly	541	Over 1 year	17% culture-positive	Not reported	Success of treatment, assessed by investigator: 96% with fusidic acid v 97% with chloramphenicol cured; P = 0.56Complete absence of symptoms: 71% with fusidic acid v 77% with chloramphenicol; P = 0.14	Bad taste: 11% with fusidic acid v 37% with chloramphenicol; P = 0.001
Fusidic acid 1% viscous drops twice daily after loading dose v chloramphenicol 0.5% drops 6 times daily after loading dose	340	Adults and children (ratio not specified)	161/340 (47%) culture-positive	Not reported	>90% cured/improved; median: 6.6 days with fusidic acid v 6.2 days with chloramphenicol; no significant difference between fusidic acid and chloramphenicol	Itching, burning, blurred vision, bad taste: 31% with fusidic acid v 16% with chloramphenicol
Fusidic acid 1% suspension in carbomer gel twice daily after loading dose v chloramphenicol 0.5% drops 5 to 6 times daily after loading dose	250	221 adults (16–89 years), 29 children (1–14 years)	Not all culture-confirmed	Not reported	Cured: 84% with fusidic acid v 81% with chloramphenicol (mean: 3.3 days with fusidic acid v 3.6 days with chloramphenicol); P = NS	Mild to moderate itching, stinging, local discomfort: 5% with fusidic acid v 14% with chloramphenicol
Fusidic acid viscous drops 1% twice daily for 5 to 7 days v chloramphenicol 1% ointment 3-hourly	505 recruited; 16 lost to follow-up	1 to 90 years	27% of 486 culture-positive for pathogenic bacteria	Not reported	83% with fusidic acid v 84% with chloramphenicol; P = NS	Smarting, irritation, stinging, red eye, blurred vision: 15% with fusidic acid v 11% with chloramphenicol; treatment discontinuation because of adverse effects greater with chloramphenicol (P <0.01)
Lomefloxacin 0.3% drops twice daily v norfloxacin 0.3% 4 times daily	145	Age not specified	27% culture-positive	No significant difference in reduction of bacterial counts between lomefloxacin and norfloxacinBy day 7 to 9, colony count score reduced by 96% with lomefloxacin v 85% with norfloxacin (P = 0.47)	No significant difference in reduction of signs and symptoms at 7 to 9 days between lomefloxacin and norfloxacinClinical scores reduced by 96% with lomefloxacin v 90% with norfloxacin (P >0.4)	12 with lomefloxacin v 14 with norfloxacin (more burning with norfloxacin)
Lomefloxacin 0.3% drops twice daily after loading dose v chloramphenicol 0.5% drops 5 times daily after loading dose	191	16 to 85 years	96/191 culture-positive	No significant difference between lomefloxacin and chloramphenicol by 3 to 5 days, 0 colonies in 79% with lomefloxacin v 80% with chloramphenicol; no significant difference in colony count scores by 3 to 5 days (P = 0.97) or at days 7 to 9 (P = 0.12)	No significant difference between lomefloxacin and chloramphenicol in the cumulative score of signs and symptoms in people with bacteriologically confirmed (at 3–5 days, P = 0.83; at 7–9 days, P = 0.18) or clinically diagnosed (3–5 days, P = 0.54; 7–9 days, P = 0.63) bacterial conjunctivitis	Good to excellent tolerance rating
Lomefloxacin 0.3% drops twice daily v gentamicin 0.3% drops 4 times daily after loading dose	66	8 to 80 years	46% culture-positive	Most positive cultures were eradicated by days 3 to 5, with no significant difference between lomefloxacin and gentamicin. By days 3 to 5, positive cultures eradicated in 21/32 with lomefloxacin v 27/32 with gentamicin (P = 0.91)	In people with culture-positive bacterial conjunctivitis, no significant difference in clinical scores at 7 to 9 days between lomefloxacin and gentamicin (reduced by 82% with lomefloxacin v 78% with gentamicin; P = 0.58) In people with clinically diagnosed bacterial conjunctivitis, clinical scores reduced by 78% with lomefloxacin v 73% with gentamicin (P = 0.58) at 7 to 9 days	Adverse events: 1 with lomefloxacin v 3 with gentamicin (more burning with gentamicin)
Lomefloxacin 0.3% twice daily v tobramycin 0.3% 4 times daily	99 recruited, 92 completed	Mean age 42 years; range 11 to 80 years	About 50%	At days 1 and 2: 48% with lomefloxacin v 55% with tobramycinAt days 7 and 8: 23% with lomefloxacin v 36% with tobramycin (reported as NS; P value not reported)	Not reported	Similar rates and duration of burning sensation after instillation in both groups
Lomefloxacin 0.3% drops v fusidic acid 1% gel twice daily after loading dose	45	Adults and children (ratio not specified)	81% culture-positive	Eradicated at days 3 to 5: 8/15 (53%) with lomefloxacin v 4/16 (25%) with fusidic acid; P = 0.075	No significant difference between lomefloxacin and fusidic acid in reduction of signs and symptoms (reported as NS, absolute results presented graphically)	Significantly more people using fusidic acid had burning (11% with lomefloxacin v 48% with fusidic acid; P = 0.009)
Tobramycin 0.3% drops, 1 to 2 drops 4 to 6 times daily v fusidic acid 1% viscous drops, 1 drop twice daily for 7 days	494 recruited; 487 treated; 8 people lost to follow-up; information provided only for subgroup with pathogenic bacteria	2 to 85 years; cohort was subdivided into 2 groups (2–9 years and over 9 years)	66% culture-positive, but 70% of culture-positive people had normal flora on quantitative microbiology	No significant difference between fusidic acid and tobramycin after 7 days' treatment (81% with fusidic acid v 88% with tobramycin; P = 0.34)	No significant difference in signs and symptoms at 7 days In children aged 2 to 9 years: 77% with fusidic acid v 83% with tobramycinIn people aged over 9 years: 76% with fusidic acid v 73% with tobramycin (reported as NS; P value not reported)	Fusidic acid 4% (tearing, burning, irritation, stinging, allergic reaction, conjunctival injection), tobramycin 2% (irritation, pain, red eye, photosensitivity, discharge; P value not reported); 2 people withdrawn from each treatment group because of adverse effects
Combination of trimethoprim (5 mg/g) and polymyxin B sulphate (10,000 U/g) v chloramphenicol (10 mg/g) as ointment 4 times daily	42	Adults and children (ratio not specified)	55% culture-positive	Eradicated: 13/16 (81%) with trimethoprim–polymyxin B sulphate v 4/9 (44%) with chloramphenicol; P value not reported	>90% reduction in signs and symptoms at day 10: 88% with trimethoprim–polymyxin B sulphate v 71% with chloramphenicol >50% reduction: 100% with trimethoprim–polymyxin B sulphate v 94% with chloramphenicol (P = NS)	3 people using trimethoprim–polymyxin B sulphate reported stinging, grittiness, conjunctival hyperaemia, or lid oedema
Combination of trimethoprim (1 mg/mL) and polymyxin B sulphate (10,000 U/mL) v chloramphenicol drops 6 times daily for 7 days	40	8 to 70 years (ratio not specified)	95% culture-positive	Not reported	No significant difference between trimethoprim–polymyxin B sulphate and chloramphenicol in reduction in signs/symptoms score at 7 days (56% with trimethoprim–polymyxin B sulphate v 57% with chloramphenicol; reported as NS; P value not reported)	Adverse effects not assessed in the RCT
Combination of trimethoprim (1 mg/mL) plus polymyxin B sulphate (10,000 U/mL) drops v chloramphenicol (5 mg/mL) 4 times daily. Multicentre trial with 2 separate comparisons (other comparison reported below)	130	Adults and children (ratio not specified)	43% culture-positive	Eradicated: 19/24 (79%) with trimethoprim–polymyxin B sulphate v 21/26 (81%) with chloramphenicol	>90% reduction in signs and symptoms at days 10 to 14: 74% with trimethoprim–polymyxin B sulphate v 54% with chloramphenicol (P = NS)>50% reduction: 95% with trimethoprim–polymyxin B sulphate v 85% with chloramphenicol (P = NS)	4 withdrawals from study because of stinging v 3 withdrawals because of allergic reaction
Combination of trimethoprim (1 mg/mL) plus polymyxin B sulphate (10,000 U/mL) drops v combination of polymyxin B sulphate (5000 U/mL) plus neomycin (1700 U/mL) plus gramicidin (25 U/mL) 4 times daily. Multicentre trial with 2 separate comparisons (other comparison reported above)	100	Adults and children (ratio not specified)	43% culture-positive	Eradicated: 15/27 (56%) with trimethoprim–polymyxin B sulphate v 18/33 (55%) with polymyxin B sulphate	>90% reduction in signs and symptoms at days 10 to 14: 80% with trimethoprim–polymyxin B sulphate v 68% with polymyxin B sulphate–neomycin–gramicidin (P >0.05); >50% reduction in signs and symptoms: 96% with trimethoprim–polymyxin B sulphate v 88% with polymyxin B sulphate–neomycin–gramicidin (P = NS)	See trimethoprim–polymyxin B sulphate group adverse events above; 1 withdrawal from polymyxin B sulphate group because of periorbital oedema
Trimethoprim–polymyxin B sulphate drops v neomycin–polymyxin B sulphate–gramicidin drops 6 times daily	48	Adults and children (ratio not specified)	46% culture-positive	Eradicated: 8/8 (100%) with trimethoprim–polymyxin B sulphate v 12/14 (86%) with neomycin–polymyxin B sulphate–gramicidin	No significant difference in symptoms and signs after 10 days' treatment between trimethoprim–polymyxin B sulphate and neomycin–polymyxin B sulphate–gramicidin (reported as NS; P value not reported; absolute results tabulated)	Adverse effects not assessed in the RCT
Combination of trimethoprim (5 mg/g) and polymyxin B sulphate (10,000 U/g) v chloramphenicol (10 mg/g) as ointment 3 or 4 times daily (4 separate RCTs of this comparison reported in this article)	448	Adults and children (ratio not specified)	32% to 72% culture-positive	Not reported	Trial 1: 73% with trimethoprim–polymyxin B sulphate v 67% with chloramphenicol cure (P >0.1)Trial 2: 65% with trimethoprim–polymyxin B sulphate v 42% with chloramphenicol cure (P = 0.1)Trial 3: 80% with trimethoprim–polymyxin B sulphate v 64% with chloramphenicol cure (P >0.1)Trial 4: 37% with trimethoprim–polymyxin B sulphate v 50% with chloramphenicol cure (P >0.1) (at 10 days)	22 with trimethoprim–polymyxin B sulphate v 12 with chloramphenicol people (stinging, swollen lids, irritation, tearing)
Moxifloxacin 0.5% 1 drop 3 times daily v trimethoprim 1%–polymyxin B sulphate 10,000 IU 1 drop 4 times daily*Note: trimethoprim–polymyxin B sulphate dose is the lowest recommended dose for the condition for adults and is lower than that used in most of the other studies of trimethoprim–polymyxin B sulphate reviewed here. Manufacturer has no recommended paediatric dose	56	1 month to 18 years	68/84 (81%) eyes	Microbiological cure rate at 48 hours was broken down by pathogen isolated and showed significant differences favouring moxifloxacin for all bacterial pathogens	Culture-positive eyes at 48 hours: clinical cure rate 81% with moxifloxacin v 44% with trimethoprim–polymyxin B sulphate; P = 0.001All eyes at 48 hours: clinical cure rate 88% with moxifloxacin v 44% with trimethoprim–polymyxin B sulphate; P = 0.001*Note: unit of analysis was not the unit of randomisation	No treatment-related adverse events; 1 episode otitis media in moxifloxacin group and 1 episode respiratory syncytial virus infection in trimethoprim–polymyxin B sulphate group
Azithromycin 1.5% 1 drop twice a day for 3 days v tobramycin 0.3% 1 drop every 2 hours for 2 days, then every 4 times a day for 5 days	150	4 to 17 years	58%	Day 3: 94% with azithromycin v 76% with tobramycin; P <0.01Day 9: 87% with azithromycin v 90% with tobramycin; P <0.01 by bootstrap estimation of means	ITT analysis: overall, day 3: "similar results" to "microbiologically validated" ITT group (below); day 9: 78% with azithromycin v 81% with tobramycin"Microbiologically validated" ITT (those with positive cultures): day 3: 48% with azithromycin v 27% with tobramycin (significant difference by bootstrap estimation of means; P <0.001); day 9: 80% with azithromycin v 82% with tobramycin	1 patient in azithromycin group had itching, burning, stinging, foreign body sensation, and blurry vision; 2 patients in tobramycin group had itching, burning, stinging, and/or stickiness
Besifloxacin 0.6% drops v moxifloxacin 0.5% drops both given 3 times a day for 5 days	1161 in ITT and safety group, 533 in culture-confirmed group (primary outcome population)	11 months to 100 years	533/1161	Modified ITT (mITT, culture-confirmed) population: day 5: 93% with besifloxacin v 91% with moxifloxacin (non-inferiority, P = 0.1238); day 8: 87% with besifloxacin v 85% with moxifloxacin (non-inferiority, P = 0.0608) ITT population: data not provided; according to authors, data showed similar non-inferiority	mITT (culture-confirmed) population: day 5: 58% with besifloxacin v 59% with moxifloxacin (non-inferiority, P = 0.6520; day 8: 85% with besifloxacin v 84% with moxifloxacin (non-inferiority, P = 0.5014) Investigator's "global assessment of clinical response", mITT population: day 5: 56.7% with besifloxacin v 57.3% with moxifloxacin; day 8: 84.9% with besifloxacin v 84.7% with moxifloxacinITT population: data not provided: according to authors, data showed similar non-inferiority	At least 1 mild–moderate ocular adverse event: 12% with besifloxacin and 14% with moxifloxacin, P = 0.2238; "eye irritation": 0.3% with besifloxacin v 1.4% with moxifloxacin, P = 0.0201; other mild–moderate adverse events: non-significant (conjunctivitis, bacterial conjunctivitis, blurred vision, eye pain), 2 serious adverse events (1 in each group) considered unrelated to treatment
Confirmed bacterial conjunctivitis
Ciprofloxacin 0.3% drops 4-hourly while awake after loading dose v tobramycin 0.3% drops 4-hourly while awake after loading dose	241	Age unspecified	Culture-confirmed	Eradication or reduction: 94% with ciprofloxacin v 92% with tobramycin (P = 0.5)	Not reported	Adverse effects not assessed in the RCT
Ciprofloxacin 0.3% drops 2-hourly for 2 days then 4 times daily for 5 more days v tobramycin drops 2-hourly for 2 days then 4 times daily for 5 more days	257 (only 141 evaluated for efficacy, but all evaluated for safety)	0 to 12 years	100% culture-positive	Eradicated: 90% with ciprofloxacin v 84% with tobramycin; P = 0.29	Cured by investigator assessment on day 7: 87% with ciprofloxacin v 90% with tobramycin (P = 0.6)	3 people in each group had adverse effects (dry eye, pruritus, lid oedema, leukoderma, hyperaemia; significance not calculated); 2 people using tobramycin withdrew as a result
Fusidic acid 1% gel v chloramphenicol 0.5% drops 4 to 6 times daily for 7 days	139 (114 with fusidic acid v 25 with chloramphenicol) (248 total, but only the 139 culture-positive patients used to calculated success rates)	Up to 15 years	100% culture-positive (56% of the total 248)	Not reported (resistance: 16% with fusidic acid v 55% with chloramphenicol; statistical analysis not provided)	85% with fusidic acid v 48% with chloramphenicol; P <0.0001	No adverse events associated with treatment reported by participants
Levofloxacin 0.5% v ofloxacin 0.3%	423 recruited; 208 people included in efficacy analysis	1 to 91 years	100%	At final visit (6–10 days after start of treatment): 89% with levofloxacin v 80% with ofloxacin; P = 0.034 At end point (defined as last observation, up to and including day 10 after start of treatment): 90% with levofloxacin v 81% with ofloxacin; P = 0.038	Cured at end point (defined as last observation, up to and including day 10 after start of treatment): 76% in each group; P >0.05	Burning: 1.45% with levofloxacin v 0.97% with ofloxacin; other adverse effects not examined
Levofloxacin 0.3% v ofloxacin 0.3%	132 (72 with culture-confirmed bacterial conjunctivitis)	18 to 65 years	100%	Not reported	Similar cure rates at end of study: 97% with levofloxacin v 94% with ofloxacin either completely or obviously improved; P value not reportedNo significant difference in number of days until improved (mean: 4.89 days with levofloxacin v 5.13 days with ofloxacin; P >0.05)	2 people using levofloxacin and 1 using ofloxacin had slight irritation
Lomefloxacin 0.3%, 1 drop 2-hourly on day 1 then twice daily for 1 week v ofloxacin 0.3% 4 times daily for 1 week	45 entered, 40 completed	Mean 30 years; range 1 to 78 years	100%	Not reported	88% with lomefloxacin v 75% with ofloxacin; P <0.08	1 person in each group reported burning sensation after instillation
Netilmicin v gentamicin, 1 to 2 drops 4 times daily for up to 10 days	209 recruited; 121 analysed, all of whom were culture-positive at baseline	Mean (± SD) 49 ± 19 years	100% of those analysed were culture-positive	Netilmicin significantly more effective than gentamicin at 5 days (P = 0.001) and 10 days (P = 0.037); absolute results presented graphically	Netilmicin significantly more effective than gentamicin at 3 days (P = 0.037), 5 days (P = 0.001), and 10 days (P = 0.001); absolute results presented graphically	2% with netilmicin v 4% with gentamicin (adverse events included redness, itching, and burning)
Trimethoprim hemisulphate 1.0 mg/mL plus polymyxin B sulphate 10,000 U/mL v gentamicin sulphate 3 mg/mL v sulfacetamide 100 mg/mL; all for 10 days	158	2 months to 22 years	100% culture-positive for H influenzae or S pneumoniae	At 2 to 7 days after treatment: 83% with trimethoprim–polymyxin B sulphate v 68% with gentamicin v 72% with sulfacetamide; P = NS	At 2 to 7 days after treatment: 84% with trimethoprim–polymyxin B sulphate v 88% with gentamicin v 89% with sulfacetamide; P = NS	Similar safety profiles
Levofloxacin 0.5% 1 drop 3 times daily v levofloxacin 0.5% 1 drop 2-hourly on days 1 and 2 then 1 drop 4-hourly on days 3 to 5 (usual dosing)	86 (119 originally enrolled, but 27 had negative bacteriological results)	18 to 70 years	72%	93% with 3-times-daily dosing v 96% in usual dosing; P = 1.00, NS	85% with 3-times-daily dosing v 92% in usual dosing; P = 0.48, NS	The RCT reported no adverse events in the studied groups
Azithromycin 1.5% 1 drop twice daily for 3 days v tobramycin 0.3% 1 drop 2-hourly for 2 days then 4 times daily for 5 days	1043 patients randomised (ITT set), 1015 in safety set (all "evaluable" participants who got medication), 521 in modified ITT set (culture-positive), and 417 in per-protocol set (no protocol deviations)	4 days to 87 years	50% (52% for azithromycin and 48% for tobramycin)	Bacterial resolution on worse eye only (or right eye if equal severity) in per-protocol set:At day 3: 85% with azithromycin v 84% with tobramycin (difference +1.4%, 95% CI –5.3% to +8.3%)At day 9: 93% with azithromycin v 95% with tobramycin (difference –1.8%, 95% CI –6.6% to +3.0%)	Clinical cure at 9 days:Per-protocol set: 88% with azithromycin v 89% with tobramycin (ARD +1.6%, 95% CI –7.5% to +4.4%)Modified ITT set: 86% with azithromycin v 86% with tobramycin (ARD +0.5%, 95% CI –6.6% to +5.8%)ITT set: 85% azithromycin v 85% tobramycin (ARD: +0.5%, 95% CI –3.8% to +4.9%)	Adverse events mild to moderate only: 3/508 (0.5%) reported effects related with azithromycin (burning, foreign body sensation) and 2 discontinued the study; 1/502 (0.1%) reported discharge with tobramycin
Topical versus oral antibiotics
Suspected bacterial conjunctivitis
Polymyxin B sulphate–bacitracin 4 times daily for 7 days v oral cefixime 8 mg/kg daily for 3 days	80 children	2 months to 6 years	70% culture-positive	Bacteriological failure at 3 days: 18% with polymyxin B sulphate–bacitracin v 38% with cefixime; P = 0.07	Not stated but difference reported as NS	Adverse effects not assessed in the RCT

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Antibiotic dosing ranges in this table may vary from the usual clinical recommendations for mild conjunctivitis. However, they are within the accepted ranges for clinician-directed treatment of conjunctivitis based on severity as recommended in major pharmacotherapeutic reference databases.ARD, absolute risk difference; ARI, absolute risk increase; ITT, intention to treat; NS, not significant; SD, standardised difference.

The second systematic review (search date not reported, 5 RCTs) compared moxifloxacin versus placebo. The review found that moxifloxacin significantly reduced the proportion of people who withdrew for any cause (3 RCTs; 46/609 [8%] with moxifloxacin v 97/606 [16%] with placebo; OR 2.37, 95% CI 1.19 to 4.70; P = 0.01) and significantly reduced treatment failure (3 RCTs; 18/609 [3%] with moxifloxacin v 61/606 [10%] with placebo; OR 4.05, 95% CI 1.28 to 12.84; P = 0.02) compared with placebo; however, the review reported that there was significant heterogeneity between studies (P less than or equal to 0.05). The review found no significant difference between groups in clinical cure (3 RCTs; 411/582 [71%] with moxifloxacin v 456/584 [78%] with placebo; OR 1.13, 95% CI 1.00 to 1.27; P = 0.05).

The first additional RCT (307 adults and children with acute bacterial conjunctivitis diagnosed clinically by general practitioners) compared three interventions: chloramphenicol drops prescribed immediately, chloramphenicol drops prescribed in a "delayed" fashion (to be used 2–3 days after diagnosis at the patient's discretion for worsening or persistent symptoms), and no antibiotics. This RCT used a symptom score ranging from 0 for normal to 6 for severe (which included red eye, eye discomfort, daytime eye discharge, sticky eye on waking, eyelid swelling, altered vision, and how unwell the person felt). The RCT found that both immediate and delayed antibiotics significantly reduced the duration of moderate symptoms compared with no antibiotics (see table 1 ). However, it found no significant difference between immediate or delayed antibiotics and no antibiotics in symptom scores after 1 to 3 days (see table 1 ).

The second additional RCT (202 adults and children with bacterial conjunctivitis) compared besifloxacin (0.6% drops) versus placebo (vehicle only). The RCT found that besifloxacin significantly increased clinical cure rate at the first follow-up visit (day 4 or 5) compared with placebo, but found no significant difference between groups at the second follow-up (days 6, 7, or 8) (see table 1 ).

Topical antibiotics versus each other:

We found one systematic review (search date 2006, 5 RCTs) and 25 additional RCTs (4 published in the same article) conducted in adults and children (see table 1 ). All but two of the RCTs found no significant difference in rates of clinical cure between different topical antibiotics. The first RCT, which had methodological flaws (see comment), compared moxifloxacin (a fourth-generation quinolone) with combination trimethoprim–polymyxin B sulphate (a common first-line antibiotic) and found that moxifloxacin significantly increased clinical and microbiological cure rates compared with trimethoprim–polymyxin B sulphate. The second RCT found that azithromycin significantly increased the rate of clinical cure compared with tobramycin at initial follow-up (day 3); however, this difference did not persist to the final follow-up (day 9). All but 4 RCTs also found no significant difference in rates of microbiological cure. The review found no significant difference between ofloxacin and moxifloxacin in treatment failure (1 RCT, 521 people; OR 1.81, 95% CI 0.38 to 4.12), and also found no significant difference between levofloxacin and moxifloxacin in treatment failure (1 RCT, 325 people; OR 1.58, 95% CI 0.18 to 19.19).

Topical versus oral antibiotics:

We found one RCT (80 children). It found no significant difference in clinical improvement or bacteriological failure rates between polymyxin B sulphate–bacitracin ointment plus oral placebo versus topical placebo plus oral cefixime (see table 1 ). However, it may have been underpowered to detect a clinically important difference between treatments.

Different regimens of topical antibiotics versus each other:

We found one RCT. The RCT (104 people with acute conjunctivitis) found no significant difference in rate of clinical cure between gatifloxacin used twice daily versus 4 times daily (cure rate by fifth day: 45/52 [87%] with twice-daily dosage v 37/52 [71%] with 4-times-daily dosage; P = 0.96).

Harms

Topical antibiotics versus placebo:

The first review gave no information on adverse effects. Two RCTs identified by the review found similar rates of adverse effects between topical antibiotics and placebo. One RCT identified by the review found that fusidic acid significantly increased adverse events compared with placebo. The first additional RCT found that one person receiving immediate antibiotics had cellulitis; it gave no further information on adverse effects (see table 1 ). The second additional RCT found no differences in what were mild to moderate ocular adverse reactions (non-specific conjunctivitis, bacterial conjunctivitis, and installation-site pain). One large population-based prospective cohort study (4.2 million people) found that topical chloramphenicol was associated with aplastic anaemia, but that the incidence was extremely low: 0.36 cases per million weeks of treatment with chloramphenicol. The incidence of aplastic anaemia was 0.04 per million weeks in people who did not take chloramphenicol. One non-systematic review reported three cases of Stevens–Johnson syndrome in people using topical sulphonamides. However, the review did not report the number of people using these drugs, making it difficult to exclude other possible causes of this condition. One non-systematic review (5 RCTs; 1978 adults and children) assessing safety found that moxifloxacin 0.5% given two to three times daily was associated with similar rates of overall adverse effects compared with vehicle ointment (4.7% with moxifloxacin v 2.6% with vehicle; no further data reported). The most common adverse effect in both groups was ocular discomfort.

Topical antibiotics versus each other:

Antibiotics (topical) in people with culture-positive non-gonococcal bacterial conjunctivitis

Summary

CURE RATES Compared with placebo: Topical antibiotics (polymyxin B sulphate–bacitracin, ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, besifloxacin, and azithromycin) seem more effective at increasing clinical and microbiological cure at 2 to 10 days ( moderate-quality evidence ). Compared with each other: We don't know whether any one topical antibiotic is consistently more effective at improving clinical or microbiological cure ( low-quality evidence ). Different regimens compared with each other: We don't know whether a three-times-daily application of levofloxacin drops is more effective than a standard dosing regimen at improving clinical or microbiological cure in people aged 18 to 70 years (low-quality evidence).

Benefits

Topical antibiotics versus placebo:

We found one systematic review (search date 2004), three subsequent RCTs, and 5 additional RCTs in people with culture-positive bacterial conjunctivitis, comparing antibiotics (polymyxin B sulphate–bacitracin, ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, besifloxacin, azithromycin) versus placebo or vehicle only (see table 1 ). The review performed a meta-analysis including RCTs of both suspected and confirmed culture-positive bacterial conjunctivitis, but did not perform separate meta-analyses for these populations; therefore, we report results of the individual RCTs here. All but one of the RCTs in people with culture-positive bacterial conjunctivitis (1933 people) found that topical antibiotics (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin, besifloxacin, azithromycin) significantly increased clinical and microbiological cure rates over 2 to 10 days compared with placebo. The RCT (18 people) that found different results from the others in people with culture-positive bacterial conjunctivitis found that a significant increase in clinical cure at 3 to 5 days with polymyxin B sulphate plus bacitracin compared with placebo was not sustained at 8 to 10 days. This RCT also found that, in a separate analysis of people already receiving systemic antibiotics for culture-positive bacterial conjunctivitis, there was no significant difference in clinical or microbiological cure at 3 to 5 days between adding polymyxin B sulphate–bacitracin and adding placebo.

Topical antibiotics versus each other:

We found no systematic review but found 9 RCTs in 10 reports (see table 1 ). Most RCTs found no significant difference between different topical antibiotics in clinical or microbiological cure rates. Two RCTs found no significant difference in cure rates between ciprofloxacin and tobramycin after 7 days; one assessed both clinical and microbiological cure rates, and the other assessed reduction or eradication of bacteria. A third RCT found that topical fusidic acid significantly increased clinical cure rate compared with chloramphenicol. The fourth and fifth RCTs comparing topical levofloxacin versus ofloxacin found inconclusive results. The fourth RCT found that topical levofloxacin for 5 days significantly increased microbiological cure rate compared with topical ofloxacin, but found no significant difference in clinical cure rate at 6 to 10 days. The fifth RCT found similar clinical improvement rates, and no significant difference in time until improvement, between levofloxacin and ofloxacin. The sixth RCT found no significant difference in symptom resolution after 7 days between lomefloxacin and ofloxacin. The seventh RCT found that topical netilmicin significantly increased clinical cure rate after both 5 and 10 days compared with topical gentamicin. The eighth RCT compared three topical antibiotics: trimethoprim–polymyxin B sulphate, gentamicin, and sulfacetamide (sulphacetamide). It found no significant difference between antibiotics in clinical or microbiological cure rates after 2 to 7 days. The ninth RCT (results reported in 2 papers) compared azithromycin versus tobramycin in a non-inferiority study and found no significant differences in microbiological or clinical cure rates at 9 days.

Different regimens of topical antibiotics versus each other:

We found one single-blinded RCT comparing levofloxacin 0.5% drops given one drop three times daily versus "standard dosing" (1 drop every 2 hours for 2 days, then 1 drop every 6 hours for 5 days) in adults. The study found no significant difference in microbiological or clinical cure rates (see table 1 ).

Harms

Topical antibiotics versus placebo:

Antibiotics (parenteral or topical) in people with suspected or confirmed gonococcal conjunctivitis

Summary

CURE RATES Parenteral plus topical antibiotic compared with parenteral antibiotic alone or parenteral plus different topical antibiotic: We don't know whether parenteral plus topical antibiotic is more effective than parenteral antibiotic alone at increasing clinical or microbiological cure rates in neonates with gonococcal conjunctivitis in Africa. We don't know whether parenteral kanamycin plus topical gentamicin is more effective than parenteral kanamycin plus topical chloramphenicol at improving cure rates in neonates with gonococcal conjunctivitis in Africa. We found no RCTs performed outside Africa ( very low-quality evidence ). NOTE There is consensus that single-dose parenteral antibiotics followed by topical antibiotics at the clinician's discretion are likely to be beneficial in people with suspected or confirmed gonococcal conjunctivitis.

Benefits

We found no systematic review but found four RCTs, three reported in one paper. All RCTs were carried out by the same research group treating gonococcal ophthalmia neonatorum in Africa. The first RCT (122 neonates with gonococcal conjunctivitis) compared three interventions: single-dose parenteral ceftriaxone 125 mg alone, single-dose parenteral kanamycin 75 mg plus topical gentamicin for 7 days, and single-dose parenteral kanamycin 75 mg plus topical tetracycline for 7 days. The RCT found no significant difference between groups in rates of persistent or recurrent gonococcal conjunctivitis over 14 days (0/61 [0%] with ceftriaxone v 2/32 [6%] with kanamycin/gentamicin v 1/29 [3%] with kanamycin/tetracycline; reported as not significant; P value not reported). The other three RCTs (117 neonates with gonococcal conjunctivitis) were all reported in one paper. The first RCT (53 neonates) compared parenteral kanamycin 75 mg plus topical gentamicin for 3 days versus parenteral kanamycin 75 mg plus saline washes for 3 days. It found that single-dose parenteral kanamycin 75 mg plus topical gentamicin significantly improved bacteriological cure rate at 30 days compared with single-dose parenteral kanamycin 75 mg alone (cure rate: 87% with kanamycin/gentamicin v 60% with kanamycin/saline washes; P = 0.03). The second RCT (38 infants) compared single-dose parenteral kanamycin 150 mg plus topical gentamicin for 3 days versus parenteral kanamycin 150 mg plus saline washes for 3 days. It found no significant difference in bacteriological cure rate between single-dose parenteral kanamycin 150 mg plus topical gentamicin for 3 days versus single-dose parenteral kanamycin 150 mg alone (cure rate: 87% with kanamycin/gentamicin v 89.5% with kanamycin/saline washes; reported as not significant; P value not reported). The third RCT (26 infants) compared parenteral kanamycin 150 mg plus topical gentamicin versus parenteral kanamycin 150 mg plus topical chloramphenicol. It stated that parenteral kanamycin 150 mg plus topical chloramphenicol resulted in cure rates of 80% — similar to those reported for parenteral kanamycin (150 mg) plus topical gentamicin (86%) — but did not directly assess the difference between groups.

Harms

The RCTs gave no information on adverse effects.

We found no RCTs.

Comment

None.

Substantive changes

No new evidence

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PERMALINK

Bacterial conjunctivitis

John Epling

Roles

Abstract

Introduction

Methods and outcomes

Results

Conclusions

Key Points

About this condition

Definition

Incidence/ Prevalence

Aetiology/ Risk factors

Diagnosis

Prognosis

Aims of intervention

Outcomes

Methods

Table 1.

Glossary

Disclaimer

References

Empirical treatment with topical antibiotics in people with suspected bacterial conjunctivitis

Summary

Benefits

Topical antibiotics versus placebo or no immediate treatment:

Table 1.

Topical antibiotics versus each other:

Topical versus oral antibiotics:

Different regimens of topical antibiotics versus each other:

Harms

Topical antibiotics versus placebo:

Topical antibiotics versus each other:

Topical versus oral antibiotics:

Different regimens of topical antibiotics versus each other:

Comment

Clinical guide:

Substantive changes

Empirical treatment with oral antibiotics in people with suspected bacterial conjunctivitis

Summary

Benefits

Harms

Comment

Substantive changes

Empirical treatment with ocular decongestants in people with suspected bacterial conjunctivitis

Summary

Benefits

Harms

Comment

Substantive changes

Empirical treatment with saline in people with suspected bacterial conjunctivitis

Summary

Benefits

Harms

Comment

Substantive changes

Empirical treatment with warm compresses in people with suspected bacterial conjunctivitis

Summary

Benefits

Harms

Comment

Substantive changes

Antibiotics (topical) in people with culture-positive non-gonococcal bacterial conjunctivitis

Summary

Benefits

Topical antibiotics versus placebo:

Topical antibiotics versus each other:

Different regimens of topical antibiotics versus each other:

Harms

Topical antibiotics versus placebo:

Topical antibiotics versus each other:

Different regimens of topical antibiotics versus each other:

Comment

Clinical guide:

Substantive changes

Ocular decongestants in people with confirmed bacterial conjunctivitis

Summary

Benefits

Harms