Key messages
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Timely diagnosis and treatment are very important when bacterial keratitis (bacterial infection of the cornea, the clear front part of the eye) is suspected.
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Bacterial keratitis treated with vancomycin + ceftazidime combination therapy, moxifloxacin therapy alone, and cefazolin + tobramycin combination therapy may result in the shortest time to healing, while ciprofloxacin therapy alone may result in the longest time to healing. The three treatments least likely to cause harms, such as irritation or corneal perforation (hole in the cornea), were vancomycin + ceftazidime combination therapy, cefazolin + gentamicin combination therapy, and chlorhexidine + cefazolin combination therapy.
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Further research is needed to improve our confidence in the evidence.
What is bacterial keratitis?
The cornea is the clear front window of the eye that is needed for vision and defense of the eye. Bacterial keratitis is an infection of the cornea caused by bacteria. It can cause pain, redness, blurred vision, and, if not treated promptly, can result in harm to vision, blindness, and even loss of the eye. Treatment usually involves antibiotic eye drops to fight the infection, with some cases requiring sight- or eye-saving surgery such as corneal transplant.
What did we want to find out?
We wanted to find the best topical antibiotic therapy for treating bacterial keratitis. We defined 'best' therapy as the one that could result in complete corneal healing in the shortest amount of time; we also considered reduction in size of corneal ulcer (open sore in the outer part of the cornea), vision after treatment, and risk of unwanted effects.
What did we do?
We searched for studies that compared different types of antibiotic eye drops or placebo (dummy treatment, such as eye drops containing a mixture of salt and water). We wanted to know which antibiotic eye drops are most effective in curing the infection and have the fewest unwanted effects. We compared and summarized the results of the studies and rated our confidence in the evidence based on factors such as study methods and sizes.
What did we find?
We included 23 studies involving a total of 2692 people. The studies varied greatly in the type of antibiotics used and the outcomes they measured. We grouped antibiotics by medication class and combinations to make 10 broad groups. Vancomycin + ceftazidime combination therapy, moxifloxacin therapy alone, and cefazolin + tobramycin combination therapy showed the shortest time to healing. Ciprofloxacin therapy alone showed the longest time to healing. Vancomycin + ceftazidime combination therapy, cefazolin + gentamicin combination therapy, and chlorhexidine + cefazolin combination therapy were least likely to cause harms.
What are the limitations of the evidence?
We have little confidence in the evidence overall. While there was variety in the treatments studied and populations included, this was mostly reflective of clinical practice and the current uncertainty about the best treatment. There were also many differences across studies in study designs, infection severity, and ways of measuring outcomes. The effects shown in our review are likely to change with the addition of new evidence.
How up-to-date is this evidence?
The evidence is current to August 2024.
Pročitajte cijeli sažetak
Infectious keratitis, commonly known as corneal infection, is a major cause of blindness, affecting approximately six million people globally and resulting in around two million cases of monocular blindness annually. The incidence varies widely worldwide, with higher rates in low- and middle-income countries due to various risk factors, including agricultural injuries and other accidental trauma, limited access to health care, and low levels of health literacy. Bacterial keratitis (BK) is the most prevalent form in higher-income regions, contributing to significant morbidity and healthcare burden. If not diagnosed and treated promptly, BK can damage the cornea and result in corneal scarring, visual impairment and/or blindness. Broad-spectrum topical antibiotics remain the primary treatment, with regional microbiological profiles and antimicrobial resistance patterns influencing therapeutic choices. However, in view of the substantial heterogeneity in clinical practice, the optimal choice of topical antibiotics for BK remains uncertain. Addressing this unanswered question may help inform current practice and improve the clinical outcomes of BK.
Ciljevi
To compare the benefits and harms of topical antibiotics for treating BK and to rank interventions by performing a systematic review and network meta-analysis (NMA).
Metode pretraživanja
We searched CENTRAL, MEDLINE, Embase, two other databases, and two trials registries together with reference checking and contact with study authors (where necessary). The latest search date was 8 August 2024. There were no restrictions on language or year of publication.
Kriteriji odabira
We included randomized controlled trials (RCTs) in which different types of topical antibiotics (e.g. ciprofloxacin, moxifloxacin, vancomycin, etc.) and/or placebo were compared in participants with BK (diagnosed clinically or microbiologically, or both).
Prikupljanje podataka i obrada
We used standard Cochrane methodology. Our outcomes were mean days to healing, mean size of epithelial defect, mean size of infiltrate, mean corrected and uncorrected distance visual acuity, and adverse effects. We assessed risk of bias using the RoB 2 tool and the certainty of evidence using the CINeMA framework for the primary NMA results of our critical outcome.
Glavni rezultati
We included 23 parallel-group RCTs that enrolled 2692 participants diagnosed with BK. The studies were conducted in Australia, Canada, India, Iran, Israel, Japan, the Philippines, Serbia, Thailand, the UK, and the USA. The majority of participants were of working age, with a mean age ranging from 26 to 66 years, and 58% were male. We classified six types of interventions: fluoroquinolone monotherapy, cephalosporin monotherapy, penicillin monotherapy, dual therapy, triple therapy, and other monotherapy (povidone-iodine, honey, placebo), yielding 10 pair-wise comparisons. We judged 12 studies (54.5%) to be at high risk of bias and 10 studies (45.5%) to raise some concerns for bias.
Based on the critical outcome (mean days to healing) analyzed by surface under the cumulative ranking curve (SUCRA), vancomycin + ceftazidime (SUCRA of 83.8), moxifloxacin (SUCRA of 83.1), and cefazolin + tobramycin (SUCRA of 71.3) were shown to be the most effective treatments for BK. When compared with ciprofloxacin monotherapy (the comparison group), the following showed evidence of faster healing time (by more than two to seven days): moxifloxacin (mean difference [MD] −6.81, 95% confidence interval [CI] −13.83 to 0.20; moderate-certainty evidence), vancomycin + ceftazidime (MD −6.18, 95% CI −10.24 to −2.12; low-certainty evidence), cefazolin + tobramycin (MD −5.57, 95% CI −12.87 to 1.74; moderate-certainty evidence), gatifloxacin (MD −3.84, 95% CI −9.12 to 1.43; low-certainty evidence), cefazolin + gentamicin (MD −2.58, 95% CI −6.45 to 1.30; low-certainty evidence), and honey (MD −2.44, 95% CI −4.42 to −0.46; low-certainty evidence). Conversely, lomefloxacin (MD −0.94, 95% CI −3.88 to 2.00; moderate-certainty evidence) and ofloxacin (MD −0.70, 95% CI −0.90 to −0.50; high-certainty evidence) showed similar healing time to ciprofloxacin with less than one-day difference. Compared with vancomycin + ceftazidime, ofloxacin (MD 5.48, 95% CI 1.41 to 9.55; low-certainty evidence), lomefloxacin (MD 5.24, 95% CI 1.50 to 8.98; low-certainty evidence), and cefazolin + gentamicin (MD 3.60, 95% CI 2.38 to 4.82; low-certainty evidence) showed evidence of longer time to heal (by three to six days).
Of the important outcomes, including mean size of epithelial defect, mean size of infiltrate, mean corrected and uncorrected distance visual acuity, and adverse effects, only the odds of non-serious harms/non-severe harms (ranging from ocular discomfort, hyperemia, toxicity, conjunctivitis, and superficial punctate keratitis to the need for therapeutic keratoplasty) had sufficient data for analysis. The three interventions least likely to cause harm were vancomycin + ceftazidime (SUCRA of 93.1), cefazolin + gentamicin (SUCRA of 82.5), and chlorhexidine + cefazolin (SUCRA of 77.0). Regarding the odds of any non-serious or non-severe harm, vancomycin + ceftazidime was associated with fewer harms than ciprofloxacin (odds ratio [OR] 0.07, 95% CI 0.01 to 0.92), gatifloxacin (OR 0.05, 95% CI 0.00 to 0.90), and cefazolin + tobramycin (OR 0.05, 95% CI 0.00 to 0.75), whereas cefuroxime + gentamicin was found to cause more harms than ofloxacin (OR 16.13, 95% CI 1.88 to 138.47), moxifloxacin (OR 20.31, 95% CI 1.15 to 358.25), cefazolin + gentamicin (OR 96.41, 95% CI 2.52 to 3692.25), and cefazolin + chlorhexidine (OR 0.01, 95% CI 0.00 to 0.71). We did not assess the certainty of evidence for harms.
Zaključak autora
In our NMA, mostly moderate- to very low-certainty evidence suggests that vancomycin + ceftazidime combination therapy, moxifloxacin monotherapy, and cefazolin + tobramycin combination therapy may be the most effective treatments for BK in terms of corneal healing time, whereas ciprofloxacin monotherapy is the least effective. Given that most evidence was not of high certainty, the results of this NMA should be interpreted with caution, and future research could potentially alter these findings.
Funding
RQ receives grant support from the National Eye Institute (UG1EY020522). DSJT acknowledges support from the Medical Research Council/Fight for Sight Clinical Research Fellowship (MR/T001674/1) and the Birmingham Health Partners Fellowship. CH receives grant support from Glaucoma UK (183772), National Institute for Health Research Clinical Lectureship (CL-2020-18-009). The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR, NHS, or the UK Department of Health and Social Care.
Registration
Protocol available via doi: 10.1002/14651858.CD015350
