Ofloxacin Monotherapy for the Primary Treatment of Microbial Keratitis: A Double-masked, Randomized, Controlled Trial with Conventional Dual Therapy

doi:10.1016/S0161-6420(97)30009-8

Ophthalmology

Volume 104, Issue 11, November 1997, Pages 1902-1909

https://doi.org/10.1016/S0161-6420(97)30009-8 Get rights and content

Abstract

Background: Ofloxacin is a potent broad-spectrum fluoroquinolone antibiotic commercially available as a topical ophthalmic preparation. The authors compared ofloxacin (0.3%) as a single therapy with their conventional dual therapy of specially prepared, fortified gentamicin (1.5%) and cefuroxime (5.0%) drops for the treatment of suspected microbial keratitis.

Methods: The authors enrolled 122 patients with a clinical diagnosis of microbial keratitis in a prospective, randomized, controlled, double-masked study to compare the two therapies. The ofloxacin drops were decanted into identical-looking bottles to the conventional treatment and dispensed with a second bottle containing saline only. The initial and subsequent assessments noted any risk factors, the size and location of the ulcer, and any evidence of corneal and conjunctival toxicity. All ulcers were scraped for microbiologic culture, and isolated organisms were tested for sensitivity to the trial antibiotics. For statistical analysis, a “cure” was defined as complete healing of the ulcer (no epithelial defect). A ratio of the two outcome proportions and its confidence limits was used to compare the two treatment groups. Multiple regression analysis using Poisson models was used to adjust for confounding factors that may have modified the outcome ratios.

Results: There was no difference in the treatment success between the two treatments, with 67.9% of the conventional treatment group and 62.1 % of the of loxacin group being cured within 14 days (ratio, 1.09; [95% confidence interval, 0.83-1.43]; P = 0.59). However, there was significantly more toxicity encountered with the conventional treatment group (50.8% vs. 10.2%; ratio, 5.00 [95% confidence interval, 2.25-11.11 ]; P < 0.0001). Poisson regression with adjustment for confounders did not materially change the ratio proportions for either treatment success or toxicity. There was at least a 90% chance to detect a 30% difference between the groups.

Conclusions: The authors found that the treatment outcomes with ofloxacin monotherapy compared favorably with their conventional therapy and were associated with less toxicity.

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Bacterial keratitis in a tertiary hospital in São Paulo: a 21-year review of the epidemiological, laboratory, and clinical data
2023, Brazilian Journal of Infectious Diseases
Infectious keratitis is a sight-threatening condition that is usually an ocular emergency. The visual outcome depends on prompt and accurate clinical management as well as geographic and epidemiological awareness. We conducted a retrospective observational study to define the epidemiological and laboratory profile, as well as the clinical course of bacterial keratitis in a tertiary hospital in São Paulo over 21 years. Information about age, sex, predisposing factors, topical and surgical treatment, visual acuity, ulcers’ classification, bacterioscopy, culture, and antibiotic sensitivity tests were collected. This study included 160 patients. The mean age was 65.1 ± 18.4 years and risk factors were identified in 83.1 % of the patients. Empirical topical fortified cephalosporin with an aminoglycoside or fourth-generation fluoroquinolone was curative for 66.2 % of the cases. The mean treatment duration was 22.5 ± 9 days. The mean variation of visual acuity was -0.25 logMAR, p < 0.001. Culture revealed 64 % of Gram-positive bacteria. All Gram-positive bacteria were sensitive to cephalothin, vancomycin, and quinolones. All Gram-negative bacteria were sensitive to gentamicin, tobramycin, amikacin, and ciprofloxacin. These findings reinforce the importance of prompt empirical treatment of severe corneal ulcers with a fortified cephalosporin and aminoglycoside or a fourth-generation fluoroquinolone as there are equally effective. Collected data was insufficient to evaluate resistance of ocular infections over time in this population.
Urgent unmet needs in the care of bacterial keratitis: An evidence-based synthesis
2023, Ocular Surface
Bacterial corneal infections, or bacterial keratitis (BK), are ophthalmic emergencies that frequently lead to irreversible visual impairment. Though increasingly recognized as a major cause of global blindness, modern paradigms of evidence-based care in BK have remained at a diagnostic and therapeutic impasse for over half a century. Current standards of management – based on the collection of corneal cultures and the application of broad-spectrum topical antibiotics – are beset by important yet widely underrecognized limitations, including approximately 30% of all patients who will develop moderate to severe vision loss in the affected eye. Though recent advances have involved a more clearly defined role for adjunctive topical corticosteroids, and novel therapies such as corneal crosslinking, overall progress to improve patient and population-based outcomes remains incommensurate to the chronic morbidity caused by this disease. Recognizing that the care of BK is guided by the clinical axiom, “time equals vision”, this chapter offers an evidence-based synthesis for the clinical management of these infections, underscoring critical unmet needs in disease prevention, diagnosis, and treatment.
A Review of the Categorizations of Mild, Moderate, and Severe Bacterial Keratitis Ulcers and Day-1 Treatment Regimen When Using the Topical Fluoroquinolones 0.3% Ciprofloxacin and 0.3% Ofloxacin
2023, Current Therapeutic Research - Clinical and Experimental
There are published suggestions that bacterial keratitis (BK) can be classified as mild, moderate, or severe and that the day-1 antibiotic drop regimen may differ for each category using the topical second-generation fluoroquinolones 0.3% ciprofloxacin and 0.3% ofloxacin (2FQ). The classification criteria are not consistently defined and the suggested regimens are often unreferenced and so here, the evidence base for applying such regimens in clinical practice is examined.
To examine the evidence base regarding the categorization criteria used for BK and determine whether any evidence exists to support suggestions that different day-1 treatment regimen using the 2FQ may be applied based on any assigned categorization.
The literature on BK treatment was reviewed, as were the clinical studies involving the commercially available 2FQ. All statements pertaining to classification and treatment paradigms involving BK were then collated and reviewed, as were the methodologies employed in the 2FQ clinical studies.
There have been no clinical trials using the 2FQ, or indeed any other topical antibiotics, which have used different day-1 drop regimen depending on the size, depth, and location of the ulcer or for ulcers classified as mild, moderate, or severe. Thus, there is no evidence to support the suggestion that a lower number of drops on day 1 is as effective as a higher number on categorized BK ulcers.
No standardized method of categorizing BK was found, and there is no evidence to support the contention that mild, moderate, or smaller BK ulcers should be treated any differently to larger or severe ulcers on day 1. The manufacturers of 2FQ do not supply different treatment regimens for different ulcer sizes and severity categories. When using the 2FQ, all BK ulcers should be treated equally in line with the manufacturers’ recommended day-1 treatment regimen.
Safety and efficacy of fortified antibiotics and fluoroquinolones for the treatment of bacterial keratitis: A meta-analysis
2023, Journal Francais d'Ophtalmologie
To compare the safety and efficacy of fortified antibiotics and fluoroquinolones in the treatment of bacterial keratitis.
PubMed, EMBASE, Cochrane Library, CNKI, Wanfang database and VIP database were systematically searched for randomized controlled trials (RCT) of treatment of bacterial keratitis with fortified antibiotics and fluoroquinolones. Rev Man 5.3 software was used to analyze outcome index cure rate, time to cure, and adverse events in a meta-analysis.
After literature search and screening, 9 randomized controlled trials were included in this study. Compared with traditional fortified antibiotic therapy, fluoroquinolones show consistency in terms of cure rate and incidence of adverse events: cure rates (OR = 0.99, 95% CI: 0.75, 1.30) and incidence of adverse events (OR = 0.75, 95% CI: 0.48, 1.17). However, the time to cure for fluoroquinolones was shorter than that of fortified antibiotics (MD = 0.96, 95% CI: 0.50, 1.41).
The cure rate and safety of fluoroquinolones are equivalent to those of fortified antibiotics, so it seems reasonable to use fluoroquinolones as the preferred treatment for bacterial keratitis.
Comparer la sécurité et l’efficacité des antibiotiques fortifiés et des fluoroquinolones dans le traitement de la kératite bactérienne.
Des recherches systématiques ont été effectuées dans PubMed, EMBASE, la bibliothèque Cochrane, CNKI, la base de données Wanfang et la base de données VIP pour des essais contrôlés randomisés (ECR) sur le traitement de la kératite bactérienne avec des antibiotiques fortifiés et des fluoroquinolones. Le logiciel Rev Man 5.3 a été utilisé pour analyser l’indice de guérison, le temps de guérison et les événements indésirables dans une méta-analyse.
Après la recherche et le criblage de la littérature, neuf essais contrôlés randomisés ont été inclus dans cette étude. Comparativement au traitement traditionnel par antibiotiques fortifiés, les fluoroquinolones montrent une consistance en termes de taux de guérison et d’incidence des événements indésirables: taux de guérison (OR = 0,99, IC 95 % : 0,75, 1,30) et incidence des événements indésirables (OR = 0,75, IC 95 % : 0,48, 1,17). Cependant, le temps de guérison pour les fluoroquinolones était plus court que celui des antibiotiques fortifiés (MD = 0,96, IC 95 % : 0,50, 1,41).
Le taux de guérison et la sécurité des fluoroquinolones sont équivalents à ceux des antibiotiques fortifiés, il semble donc raisonnable d’utiliser les fluoroquinolones comme traitement de première ligne pour la kératite bactérienne.
Paradox of complex diversity: Challenges in the diagnosis and management of bacterial keratitis
2022, Progress in Retinal and Eye Research
Bacterial keratitis continues to be one of the leading causes of corneal blindness in the developed as well as the developing world, despite swift progress since the dawn of the “anti-biotic era”. Although, we have expeditiously developed our understanding about the different causative organisms and associated pathology leading to keratitis, extensive gaps in knowledge continue to dampen the efforts required for early and accurate diagnosis, and management in these patients, resulting in poor clinical outcomes. The ability of the causative bacteria to subdue the therapeutic challenge stems from their large genome encoding complex regulatory networks, variety of unique virulence factors, and rapid secretion of tissue damaging proteases and toxins.
In this review article, we provide an overview of the established diagnostic techniques and therapeutics for keratitis caused by various bacteria. We extensively report the recent in-roads through novel tools for accurately diagnosing mono- and poly-bacterial corneal infections. Furthermore, we outline the recent progress by our groups and others in understanding the sub-cellular genomic changes that lead to antibiotic resistance in these organisms. Finally, we discuss in detail, the novel therapies and drug delivery systems in development for the efficacious management of bacterial keratitis.
Bacterial keratitis treated by strengthened antibiotic eye drops: An 18 months review of clinical cases and antibiotic susceptibilities
2018, Annales Pharmaceutiques Francaises
Citation Excerpt :
In each study, the authors did not show a significant difference in treatment success. In one, they described a lower toxicity of fluoroquinolone compared to fortified antibiotics [13]. Nevertheless, the use of these eye drops can remain an option in the event of encountering resistance to fluoroquinolones.
To describe, in patients treated for infectious keratitis, the microorganisms identified and their antibiotic susceptibility over a period of 18 months.
Retrospective, descriptive, non-comparative study. Medical and biological data were extracted from the patients’ file treated with strengthened antibiotic eye drops at Angers University Hospital between January 2015 and June 2016. The main elements noted were the bacteria involved and their susceptibility to antibiotics. Patients’ visual acuity at the start and end of treatment was compared.
Forty-eight patients were included. Almost one bacterium was identified in 31 patients, totalling 43 pathogens of 24 different species. The most frequently found microorganisms were Gram-positive cocci (55.8%), including Staphylococcus Aureus (14.0%) and Epidermidis (14.0%). All Gram-negative bacilli amounted to 30.2% of the identified bacteria, including 9.3% of Pseudomonas aeruginosa. None of the Gram-positive cocci were resistant to vancomycin and all Gram-negative bacilli were susceptible to ceftazidime and amikacin. Following treatment with at least one of the three antibiotic eye drops produced by our pharmacy (amikacin at 50 mg/mL, ceftazidime at 50 mg/mL and vancomycin at 25 mg/mL), patients’ visual acuity was significantly improved (P = 0.043).
The study helped identify the bacterial ecology of patients admitted for infectious keratitis. Among the bacteria identified, none were found to be resistant to any of the three strengthened antibiotic eye drops produced by the hospital pharmacy. These eye drops allowed for a rapid and effective treatment of patients and the improvement of their visual acuity before even identifying the bacteria.
Décrire, les microorganismes responsables des kératites bactériennes.
Les données médicales et biologiques ont été extraites rétrospectivement des dossiers médicaux des patients traités pour kératites bactériennes par collyres antibiotiques renforcés. L’identification des germes ainsi que leur sensibilité aux antibiotiques ont été notées. Les acuités visuelles des patients avant l’instauration du traitement et à la fin de celui-ci ont été comparées.
Au total, 48 patients ont été inclus. Au moins un germe bactérien a été identifié chez 31 patients, soit 43 germes parmi 24 espèces différentes. Les cocci à Gram positif ont été les germes les plus fréquemment rencontrés (55,8 %), dont Staphyloccocus aureus (14,0 %), et Epidermidis (14,0 %). Les bacilles à Gram négatif ont représenté 30,2 % des germes identifiés, incluant Pseudomonas aeruginosa (9,3 %). Aucun cocci à Gram positif n’a été résistant à la vancomycine, tous les bacilles à Gram négatif ont été sensibles à la ceftazidime et l’amikacine. Après traitement avec au moins l’un des trois collyres antibiotiques renforcés produits par la pharmacie du CHU d’Angers (amikacine 50 mg/mL, ceftazidime 50 mg/mL ou vancomycine 25 mg/mL), l’acuité visuelle des patients a été significativement améliorée (p = 0,043).
L’écologie bactérienne des patients hospitalisés pour kératite bactérienne et nécessitant un traitement par collyre antibiotique renforcé est désormais connue. Parmi les bactéries identifiées, aucune n’a été résistante à l’un des trois collyres antibiotiques renforcés produits par la pharmacie du CHU. Ces antibiotiques ont permis une amélioration rapide et significative de l’acuité visuelle des patients.

View all citing articles on Scopus

: Presented in part at the International Conference on Ocular Infections, Jerusalem, 1995, and ARVO, Ft Lauderdale, Florida, 1996.

: Supported in part by Moorfields Eye Hospital LORS; in part by an unrestricted grant from Allergan, which paid for the statistical analysis; and in part by the RAGS Edward Lumley Travelling Fellowship (NM).

: The authors have no proprietary interest in the products used in this study.

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Ofloxacin Monotherapy for the Primary Treatment of Microbial Keratitis: A Double-masked, Randomized, Controlled Trial with Conventional Dual Therapy

Abstract

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Surv Ophthalmol

Topical fluoroquinolones: antimicrobial activity and in vitro corneal epithelial toxicity

Curr Eye Res

Strategies for the management of microbial keratitis

Br J Ophthalmol

Efficacy of ofloxacin vs cefazolin and tobramycin in the therapy for bacterial keratitis

Arch Ophthalmol

Topical ofloxacin compared with gentamicin in the treatment of external ocular infection

Br J Ophthalmol

Ofloxacin vs tobramycin for the treatment of external ocular infection

Arch Ophthalmol

Comparison of ofloxacin, gentamicin, and tobramycin concentrations in tears and in vitro MICs for 90% of test organisms

Antimicrob Agents Chemother

Ofloxacin in human serum, urine, and tear film after topical application

Cornea

Guide to sensitivity testing

Comparison of topical ciprofloxacin to conventional antibiotic therapy in the treatment of experimental Pseudomonas aeruginosa keratitis

Cornea

Ciprofloxacin versus tobramycin for the treatment of staphylococcal keratitis

Invest Ophthalmol Vis Sci

Topical ciprofloxacin versus topical fortified antibiotics in rabbit models of Staphylococcus and Pseudomonas keratitis

Cornea