Are there any studies comparing the use of moxifloxacin eye drops to ciprofloxacin eye drops during surgical procedures of the eye? If so what are the recommendations?

Comment by InpharmD Researcher

There are limited clinical data comparing moxifloxacin and ciprofloxacin ophthalmic solutions for ophthalmic surgical antimicrobial prophylaxis. In general, moxifloxacin 0.5% solution has been observed to have improved penetration into the cornea and aqueous humor compared to ciprofloxacin 0.3% solution. One retrospective study observed significantly reduced rates of endophthalmitis with fourth-generation ophthalmic fluoroquinolones (moxifloxacin and gatifloxacin) compared to third-generation (ciprofloxacin and ofloxacin), but the clinical significance of these findings is largely unknown. Current guidelines recommend the use of either neomycin-polymyxin B-gramicidin or fourth-generation topical fluoroquinolones given as 1 drop every 5-15 minutes for 5 doses for ophthalmic surgical antimicrobial prophylaxis.

  

PubMed: moxifloxacin ciprofloxacin eye drops surgery= 19 results; moxifloxacin ciprofloxacin eye drops surgical= 13 results

Background

For ophthalmic surgical antimicrobial prophylaxis, guidelines from the American Society of Health-System Pharmacists (ASHP), Infectious Diseases Society of America (IDSA), Surgical Infection Society (SIS), and Society for Healthcare Epidemiology of America (SHEA) recommend agents including topical neomycin-polymyxin B-gramicidin or fourth-generation topical fluoroquinolones (gatifloxacin or moxifloxacin) given as 1 drop every 5-15 min for 5 doses (Strength of Evidence B). [1]

A 2017 pharmacokinetic study aimed to quantify the penetration of ophthalmic fluoroquinolone antibiotics into the cornea and aqueous humor of cadaver eyes. A total of 60 enucleated eyes ineligible for corneal transplantation were divided into three groups and immersed in commercial solutions of 0.3% ciprofloxacin and 0.5% moxifloxacin for 10 minutes. The geometric mean concentration ratio for moxifloxacin/ciprofloxacin in the cornea was 4.16 (95% confidence interval [CI] 2.82 to 6.06; p <0.05), indicating moxifloxacin led to significantly more penetration in the cornea compared to ciprofloxacin. Similarly, the geometric mean concentration rate for moxifloxacin/ciprofloxacin in the aqueous humor was 4.68 (95% CI 3.21 to 6.79; p <0.05), indicating moxifloxacin led to significantly more penetration in the aqueous humor compared to ciprofloxacin. The amount of drug that penetrated the anterior chamber after a 10-minute immersion was determined to be below the safe limit of endothelial toxicity for each preparation. Overall, penetration of moxifloxacin into the cornea and anterior chamber appears to be superior compared to ciprofloxacin. Clinical extrapolation of these results is limited because this study is conducted in cadaver eyes. [2]

Similarly, a 2005 pharmacokinetic study in the abstract format determined the concentrations of 0.5% moxifloxacin (n= 15), 0.3% ciprofloxacin (n= 12), 0.3% gatifloxacin (n= 14), 0.3% ofloxacin (n= 13), and 0.5% levofloxacin (n= 12) ophthalmic solutions in conjunctival tissue following a single dose of study medication 20 minutes after instillation. After applying assigned eye drops, all study participants underwent screening and baseline slitlamp examination followed by preparation for biopsy from 1 eye per subject. Two palpebral conjunctival biopsies, one each from the temporal and nasal regions of the inferior cul-de-sac, were collected for laboratory analysis. Following a single dose of antibiotic eye drops, the conjunctival levels of moxifloxacin were statistically significantly higher than those of the other 4 fluoroquinolones (18 mcg/g vs. ciprofloxacin 2.65; p<0.001), corresponding to a 6.8-fold higher concentration than ciprofloxacin. However, a 2006 commentary to Wagner et al. noted that higher conjunctival concentration itself may not translate into better clinical efficacy of topical antibiotics (e.g., use during surgical procedures) but rather may indicate an increased risk of toxicity or less tolerability. [3], [4]

References:

[1] Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Surg Infect (Larchmt). 2013;14(1):73-156. doi:10.1089/sur.2013.9999
[2] Silva GCM, Jabor VAP, Bonato PS, Martinez EZ, Faria-E-Sousa SJ. Penetration of 0.3% ciprofloxacin, 0.3% ofloxacin, and 0.5% moxifloxacin into the cornea and aqueous humor of enucleated human eyes. Braz J Med Biol Res. 2017;50(7):e5901. Published 2017 Jul 3. doi:10.1590/1414-431X20175901
[3] Wagner RS, Abelson MB, Shapiro A, Torkildsen G. Evaluation of moxifloxacin, ciprofloxacin, gatifloxacin, ofloxacin, and levofloxacin concentrations in human conjunctival tissue. Arch Ophthalmol. 2005;123(9):1282-1283. doi:10.1001/archopht.123.9.1282
[4] Fiscella RG, Jensen MK. Evaluation of the penetration of fluoroquinolones in human conjunctival tissue. Arch Ophthalmol. 2006;124(12):1796-1797. doi:10.1001/archopht.124.12.1796-b
Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

Are there any studies comparing the use of moxifloxacin eye drops to ciprofloxacin eye drops during surgical procedures of the eye? If so what are the recommendations?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-2 for your response.

 

Penetration of Topically Applied Gatifloxacin 0.3%, Moxifloxacin 0.5%, and Ciprofloxacin 0.3% into the Aqueous Humor

Design

Prospective, double-masked, clinical study

N= 52

Objective

To investigate the aqueous penetration of 3 commercially available ophthalmic antibiotics

Study Groups

Gatifloxacin 0.3% (n= 16)

Moxifloxacin 0.5% (n= 14)

Ciprofloxacin 0.5% (n= 22)

Inclusion Criteria

Healthy, ≥ 21 years of age, scheduled to undergo standard cataract surgery, female patients of childbearing potential must have had a regular menstrual cycle before study entry

Exclusion Criteria

Any intraocular inflammation, any ocular medication or drops 48 hours before or during the study period, known sensitivity to any of the ingredients in the study medications or any quinolone compound, abnormal eyelid function, only one eye, use of a systemic antibiotic during the study period, corneal ulceration, keratitis, conjunctivitis, or a history of herpetic keratitis, pregnant or nursing

Methods

Patients were instructed to use randomly assigned antibiotic drops (gatifloxacin 0.3%, moxifloxacin 0.5%, or ciprofloxacin 0.3%) 4 times a day for 3 days before surgery. On the day of surgery, patients were given their assigned antibiotic every 15 minutes for 3 doses, 1 hour before their procedure.

Duration

Intervention: 3 days

Outcome Measures

Fluoroquinolone concentrations, determined by reverse-phase high-pressure liquid chromatography assay technique with ultraviolet detection at a wavelength of 275 nm

Baseline Characteristics

  

Gatifloxacin 0.3% (n= 16)

Moxifloxacin 0.5% (n= 14)

 Ciprofloxacin 0.5% (n= 22)

Age, years

 64 71 74

Female, n

 10 9 12

Results

Endpoint

Gatifloxacin 0.3% (n= 16)

Moxifloxacin 0.5% (n= 14)

Ciprofloxacin 0.5% (n= 22)

Mean aqueous concentrations, mcg/mL (range)

p-value vs. ciprofloxacin

p-value vs. gatifloxacin

0.63 ± 0.30 (0.23 to 1.18)

< 0.005

Reference

1.31 ± 0.46 (0.68 to 2.92)

< 0.001

< 0.05

0.15 ± 0.11 (0.09 to 0.58)

Reference

N/A

Nine ciprofloxacin samples that had levels below the sensitivity of the assay were arbitrarily given a ciprofloxacin level of 0.09 mcg/mL (lowest detectable level) for statistical calculations.

Adverse Events

Not disclosed

Study Author Conclusions

Both moxifloxacin and gatifloxacin penetrated the aqueous humor at significantly higher levels than ciprofloxacin. Moxifloxacin penetrated into the aqueous humor at significantly higher levels than gatifloxacin. The anterior chamber levels of moxifloxacin and gatifloxacin may be due to the difference in antibiotic concentration.

InpharmD Researcher Critique

This study did not evaluate efficacy or safety and was limited to assessing drug concentrations in the aqueous humor.



References:

Solomon R, Donnenfeld ED, Perry HD, et al. Penetration of topically applied gatifloxacin 0.3%, moxifloxacin 0.5%, and ciprofloxacin 0.3% into the aqueous humor. Ophthalmology. 2005;112(3):466-469. doi:10.1016/j.ophtha.2004.09.029

 

Third- and fourth-generation fluoroquinolones: Retrospective comparison of endophthalmitis after cataract surgery performed over 10 years

Design

Retrospective cross-sectional study

N= 40

Objective

To determine differences in endophthalmitis rates with prophylactic use of third- versus fourth-generation fluoroquinolones in cataract surgery

Study Groups

 Endophthalmitis patients (n= 40)

Inclusion Criteria

Underwent phacoemulsification and had endophthalmitis

Exclusion Criteria

Not explicitly stated

Methods

The study examined patients who had phacoemulsification at a university eye center over 10 years. A nosocomial infectious reporting database was used to report endophthalmitis occurrences according to fluoroquinolone ophthalmic antibiotic received preoperatively for cataract surgery. Analyses were based on the use of a third-generation (ofloxacin 0.3% and ciprofloxacin 0.3%) or fourth-generation (moxifloxacin 0.5% or gatifloxacin 0.3%) fluoroquinolone ophthalmic antibiotic.

Duration

Data evaluation: 1997 to 2007

Outcome Measures

Occurrence of endophthalmitis after cataract surgery

Baseline Characteristics

  

Endophthalmitis patients (n= 40)

 

  

Median age, years (range)

 71 (29 to 91)    

Female, n

 21    

Generation of fluoroquinolone used, n

Third-generation

Fourth-generation


16,710

12,566

    

Results

Endpoint

 Third-generation fluoroquinolone (n= 16,710)

Fourth-generation fluoroquinolone (n= 12,566)

p-value

Developed endophthalmitis, n

33 (0.197%)

 7 (0.056%) 0.0011

Adverse Events

Not disclosed

Study Author Conclusions

The differences in the pharmacokinetic and pharmacodynamic properties of quinolone antibiotics may affect endophthalmitis incidence after cataract surgery. The significant difference in endophthalmitis rates between gatifloxacin and moxifloxacin requires further study.

InpharmD Researcher Critique

This study may be limited by human error and data reporting within a retrospective design. Limited conclusions regarding comparative efficacy and safety between ciprofloxacin and moxifloxacin ophthalmic solutions can be determined from this study.



References:

Jensen MK, Fiscella RG, Moshirfar M, Mooney B. Third- and fourth-generation fluoroquinolones: retrospective comparison of endophthalmitis after cataract surgery performed over 10 years. J Cataract Refract Surg. 2008;34(9):1460-1467. doi:10.1016/j.jcrs.2008.05.045