Characterization of baseline polybacterial versus monobacterial infections in three randomized controlled bacterial conjunctivitis trials and microbial outcomes with besifloxacin ophthalmic suspension 0.6

Abstract

Background/purpose: To date, studies examining polymicrobial infections in ocular disease have mostly been limited to keratitis or endophthalmitis. We characterized polybacterial infections compared to monobacterial infections in prior clinical studies evaluating besifloxacin ophthalmic suspension 0.6% for the treatment of bacterial conjunctivitis and report on associated microbiological outcomes.

Methods: In this post-hoc analysis, microbiological data for subjects with conjunctivitis due to one or more than one bacterial species in three previous studies (two vehicle-, one active-controlled) of besifloxacin were extracted. Bacterial species identified at baseline were deemed causative if their colony count equaled or exceeded species-specific prespecified threshold criteria. In subjects with polybacterial infections, the fold-increase over threshold was used to rank order the contribution of individual species. Baseline pathogens and their minimum inhibitory concentrations (MICs) for common ophthalmic antibiotics were compared by infection type, as were microbial eradication rates following treatment with besifloxacin.

Results: Of 1041 subjects with culture-confirmed conjunctivitis, 17% had polybacterial and 83% had monobacterial conjunctivitis at baseline. In polybacterial compared to monobacterial infections, Haemophilus influenzae and Streptococcus pneumoniae were identified less frequently as the dominant infecting species (P = 0.042 and P<0.001, respectively), whereas Streptococcus mitis/S. mitis group was identified more frequently as dominant (P<0.001). Viral coinfection was also identified more frequently in polybacterial infections (P<0.001). Staphylococcus aureus was the most common coinfecting species in polybacterial infections and the second most common dominant species in such infections. With few exceptions, MICs for individual species were comparable regardless of infection type. Clinical microbial eradication rates with besifloxacin were high regardless of infection type (P≤0.016 vs vehicle at follow-up visits).

Conclusions: Approximately one in five subjects with bacterial conjunctivitis are infected with more than one bacterial species underscoring the need for a broad-spectrum antibiotic for such infections. Besifloxacin treatment resulted in robust eradication rates of these infections comparable to monobacterial infections.

Trial registration: NCT000622908, NCT00347932, NCT00348348.

Trial registration: ClinicalTrials.gov NCT00622908 NCT00347932 NCT00348348.

Conflict of interest statement

HD and CS are employees of Bausch Health US, LLC; Dr. H Proskin is an independent statistical consultant and reports receipt of statistical consultation fees from Bausch Health US, LLC for this work. Dr. J Blondeau has no disclosures to report for this current study. This research is associated with the marketed product Besivance® (besifloxacin ophthalmic suspension, 0.6%; Bausch & Lomb Incorporated; Rochester, NY). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Distribution of subjects.

Fig 2. Dominant, secondary, tertiary, and quaternary infecting species at baseline in polybacterial conjunctivitis infections.

Dominant bacterial species are shown in the inner ring, whereas secondary, tertiary, and quaternary infecting bacterial species are shown by rank order moving outwards by ring. Only those polybacterial infections in which the same dominant species was identified in more than 5 infections are presented. Co-dominant species are indicated with an asterisk.

Fig 3. Distribution of Minimum Inhibitory Concentrations (MICs) for besifloxacin and ciprofloxacin against gram-positive and gram-negative isolates from poly- and monobacterial conjunctivitis infections.

A. Gram-positive isolates from polybacterial infections (n = 286), B. Gram-negative isolates from polybacterial infections (n = 101), C. Gram-positive isolates from monobacterial infections (n = 537), and D. Gram-negative isolates from monobacterial infections (n = 327).

Fig 4. Microbial eradication of polybacterial and monobacterial conjunctivitis with besifloxacin and moxifloxacin.