Comparison of Topical Gatifloxacin 0.3% and Ciprofloxacin 0.3% for the Treatment of Bacterial Keratitis

doi:10.1016/j.ajo.2005.08.081

American Journal of Ophthalmology

Volume 141, Issue 2, February 2006, Pages 282-286.e1

https://doi.org/10.1016/j.ajo.2005.08.081 Get rights and content

Purpose

To compare the bacteriologic and clinical efficacy of gatifloxacin and ciprofloxacin for the treatment of bacterial keratitis.

Design

Prospective, randomized clinical trial.

Methods

A total of 104 eyes of 104 patients with bacterial keratitis seen at a tertiary eye-care center were randomized to treatment with gatifloxacin 0.3% eyedrops (GAT group, 50 eyes) or ciprofloxacin 0.3% eyedrops (CIP group, 54 eyes). Patients and the treating physician were masked to the antibiotic being used. Main outcome measure studied was healing of the ulcer. Patients lost to follow-up before complete healing were excluded from further analysis.

Results

A significantly higher proportion of ulcers in the GAT group exhibited complete healing compared with those in the CIP group (39 eyes [95.1%] vs 38 [80.9%]; P = .042). Gatifloxacin demonstrated a significantly better action than ciprofloxacin against gram-positive cocci in vitro (P < .001), and the percentage of ulcers caused by these pathogens that healed in the GAT group was significantly better than in the CIP group (P = .009). Mean time taken for healing of ulcer and the efficacy against gram-negative bacteria did not significantly differ between the two groups.

Conclusions

Gatifloxacin had a significantly better action against gram-positive cocci both in vitro and in vivo when compared with ciprofloxacin. In view of these organisms being the leading cause of keratitis worldwide, gatifloxacin may be a preferred alternative to ciprofloxacin as the first-line monotherapy in bacterial keratitis.

Section snippets

Methods

This was a prospective, double-blind, randomized clinical trial conducted at the Cornea Service, Institute of Ophthalmology, Joseph Eye Hospital, Tiruchirappalli, India, between April 2004 and March 2005. The institutional review board approved the study, and informed consent was obtained from all patients.

All patients with a clinical diagnosis of bacterial keratitis seen during the study period were considered for inclusion in the study. Specific inclusion criteria were presence of an

Results

A total of 104 eyes of 104 patients were included in the study; 50 eyes were randomized to the GAT group, and 54 eyes were assigned to the CIP group. Baseline demographic and ulcer characteristics in the two groups are described in Table 2.

The microbiological profile of the isolates from culture-positive eyes and the in vitro antibiotic sensitivity pattern of these isolates are shown in Table 3. A significantly larger proportion of isolates of gram-positive cocci were sensitive to gatifloxacin

Discussion

The newer generation of fluoroquinolones are likely to play an important role in the treatment of bacterial keratitis in the future because of an increasing resistance to the second-generation fluoroquinolones that are in current use. In vitro studies on isolates from bacterial infections of the eye have shown an encouraging response to gatifloxacin, including those organisms resistant to ciprofloxacin.6, 10 However, these results have not yet been validated by clinical trials on human eyes. In

Pragya Parmar, MS, received her MS degree in Ophthalmology from JIPMER, Pondicherry, India in 1996. She is currently working as a Reader in Ophthalmology, Cornea service, Institute of Ophthalmology, Joseph Eye Hospital, Tiruchirapalli, India. Her areas of interest include microbial keratitis and refractive corneal surgery.

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Emerging ciprofloxacin resistant Pseudomonas aeruginosa
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Decision making in the management of microbial keratitis
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Fluoroquinolone therapy in multiple drug resistant staphylococcal keratitis after lamellar keratectomy in a rabbit model
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Antibiotic resistance of bacterial pathogens isolated from the conjunctiva in the Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) surveillance study (2009–2021)
2024, Diagnostic Microbiology and Infectious Disease
Antibiotic resistance in bacterial ocular infections is of significant clinical concern and may affect treatment outcomes. We report on in vitro antibiotic susceptibility rates and trends among conjunctival-sourced isolates collected in the Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) surveillance study. A total of 2214 conjunctival isolates (918 Staphylococcus aureus, 589 coagulase-negative staphylococci [CoNS], 194 Streptococcus pneumoniae, 171 Pseudomonas aeruginosa, and 342 Haemophilus influenzae) obtained between 2009–2021 were analyzed. Staphylococci were commonly resistant to azithromycin (≥54.8%) and oxacillin (≥29.3%). Resistance among S. pneumoniae isolates was notable for azithromycin (34.0%) and penicillin (28.9%), while P. aeruginosa and H. influenzae isolates were highly susceptible to most tested antibiotics. Methicillin-resistant staphylococci demonstrated greater concurrent resistance to other antibiotics than methicillin-susceptible isolates and exhibited high rates of multidrug resistance (≥74.0%). Among staphylococci, antibiotic resistance increased with patient age, and there were small decreases in resistance to several drugs over the 13-year period. These findings indicate that resistance to antibiotics routinely used in ophthalmic practice remains high among conjunctival isolates.
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.
The clinical treatment of bacterial keratitis: A review of drop instillation regimes
2022, Contact Lens and Anterior Eye
Bacterial keratitis (BK) presentations are often treated using the commercially available second-generation fluoroquinolones ciprofloxacin 0.3% and ofloxacin 0.3% as monotherapy. The guidelines available for instillation regimes are often not supported by data from clinical studies.
This review examines the peer-reviewed clinical studies and compared treatment failure rates for ciprofloxacin 0.3% and ofloxacin 0.3% for BK in relation to Day-1 drop-regimes. From the statistical analysis, this review derived evidence-based clinically applicable minimum drop-regimes for the treatment of BK on Day-1.
Lower numbers of drops of ciprofloxacin on Day-1 were significantly associated with increased treatment failure rates (p < 0.002). The derived minimum number of drops on Day for ciprofloxacin on Day-1 was 47 drops, and for ofloxacin 24 drops. The mean number of drops used in the clinical studies was significantly lower than the manufacturers’ recommended Day-1 regimes for both ciprofloxacin (p = 0.0006) and ofloxacin (p = 0.048). From Day-3 to −6 of treatment the drop rates for ciprofloxacin relative to recommended rates were higher, and for ofloxacin lower (p = 0.014).
The findings of this review were then compared with a representative sample of published guidelines and case studies to determine the validity of applying those drop-regimes in clinical practice. Although the manufacturers’ suggested minimum drop-regimes on Day-1 were significantly different (120 drops ciprofloxacin, 34 drops ofloxacin, p < 0.0001), many of the published guidelines suggested the same drop-regime for both fluoroquinolones. The suggested drop numbers on Day-1 for ciprofloxacin in these guidelines and case studies were significantly less than those used in the clinical studies (p = 0.043).
Increased treatment failure rates for ciprofloxacin are associated with lower drop numbers on Day-1. The Day-1 dosing rates for ciprofloxacin and ofloxacin should be considered separately, and the regimes suggested in published guidelines and case studies may need be re-considered in light of the findings of this review.
Commentary
2019, Annals of Emergency Medicine
Update on the Management of Infectious Keratitis
2017, Ophthalmology
Infectious keratitis is a major global cause of visual impairment and blindness, often affecting marginalized populations. Proper diagnosis of the causative organism is critical, and although culture remains the prevailing diagnostic tool, newer techniques such as in vivo confocal microscopy are helpful for diagnosing fungus and Acanthamoeba. Next-generation sequencing holds the potential for early and accurate diagnosis even for organisms that are difficult to culture by conventional methods. Topical antibiotics remain the best treatment for bacterial keratitis, and a recent review found all commonly prescribed topical antibiotics to be equally effective. However, outcomes remain poor secondary to corneal melting, scarring, and perforation. Adjuvant therapies aimed at reducing the immune response associated with keratitis include topical corticosteroids. The large, randomized, controlled Steroids for Corneal Ulcers Trial found that although steroids provided no significant improvement overall, they did seem beneficial for ulcers that were central, deep or large, non-Nocardia, or classically invasive Pseudomonas aeruginosa; for patients with low baseline vision; and when started early after the initiation of antibiotics. Fungal ulcers often have worse clinical outcomes than bacterial ulcers, with no new treatments since the 1960s when topical natamycin was introduced. The randomized controlled Mycotic Ulcer Treatment Trial (MUTT) I showed a benefit of topical natamycin over topical voriconazole for fungal ulcers, particularly among those caused by Fusarium. MUTT II showed that oral voriconazole did not improve outcomes overall, although there may have been some effect among Fusarium ulcers. Given an increase in nonserious adverse events, the authors concluded that they could not recommend oral voriconazole. Viral keratitis differs from bacterial and fungal cases in that it is often recurrent and is common in developed countries. The Herpetic Eye Disease Study (HEDS) I showed a significant benefit of topical corticosteroids and oral acyclovir for stromal keratitis. HEDS II showed that oral acyclovir decreased the recurrence of any type of herpes simplex virus keratitis by approximately half. Future strategies to reduce the morbidity associated with infectious keratitis are likely to be multidimensional, with adjuvant therapies aimed at modifying the immune response to infection holding the greatest potential to improve clinical outcomes.

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American Journal of Ophthalmology

Purpose

Design

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

References (17)

Antimicrobial activity of gatifloxacin tested against 1676 strains of ciprofloxacin resistant gram-positive cocci isolated from patient infections in North and South America

Diagn Microbiol Infect Dis

Emerging ciprofloxacin resistant Pseudomonas aeruginosa

Am J Ophthalmol

Fourth generation fluoroquinolonesnew weapons in the arsenal of ophthalmic antibiotics

Am J Ophthalmol

Gatifloxacin and moxifloxacinan in vitro susceptibility comparison to levofloxacin, ciprofloxacin and ofloxacin using bacterial keratitis isolates

Am J Ophthalmol

Decision making in the management of microbial keratitis

Ophthalmology

Fluoroquinolone therapy in multiple drug resistant staphylococcal keratitis after lamellar keratectomy in a rabbit model

Am J Ophthalmol

Clinical evaluation of ciprofloxacin 0.3% ophthalmic solution for treatment of bacterial keratitis

Am J Ophthalmol

Efficacy of ofloxacin versus cefazolin and tobramycin in the therapy of bacterial keratitisreport from the Bacterial Keratitis Study Research Group

Arch Ophthalmol

Cited by (67)

Antibiotic resistance of bacterial pathogens isolated from the conjunctiva in the Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) surveillance study (2009–2021)

Urgent unmet needs in the care of bacterial keratitis: An evidence-based synthesis

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

The clinical treatment of bacterial keratitis: A review of drop instillation regimes

Commentary

Update on the Management of Infectious Keratitis

Original articleComparison of Topical Gatifloxacin 0.3% and Ciprofloxacin 0.3% for the Treatment of Bacterial Keratitis

Purpose

Design

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Diagn Microbiol Infect Dis

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

Clinical evaluation of ciprofloxacin 0.3% ophthalmic solution for treatment of bacterial keratitis

Am J Ophthalmol

Efficacy of ofloxacin versus cefazolin and tobramycin in the therapy of bacterial keratitisreport from the Bacterial Keratitis Study Research Group

Arch Ophthalmol

Original article
Comparison of Topical Gatifloxacin 0.3% and Ciprofloxacin 0.3% for the Treatment of Bacterial Keratitis