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Importance: The Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) study is the only ongoing nationwide antibiotic resistance surveillance program specific to ocular pathogens., Objective: To report resistance rates and trends among common ocular isolates collected during the first 5 years of the ARMOR study., Design, Setting, and Participants: This antibiotic resistance surveillance study was performed at an independent central laboratory. Clinical centers across the United States were invited to submit ocular isolates of Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa. Isolates were collected from January 1, 2009, through December 31, 2013, and analyzed from January 16 to May 15, 2015., Main Outcomes and Measures: Minimum inhibitory concentrations for various antibiotic classes were determined by broth microdilution according to the guidelines of the Clinical and Laboratory Standards Institute. Minimum inhibitory concentrations were interpreted as susceptible, intermediate, or resistant based on established break points., Results: A total of 3237 ocular isolates (1169 S aureus, 992 CoNS, 330 S pneumoniae, 357 H influenzae, and 389 P aeruginosa) were collected from 72 centers. Methicillin resistance was found among 493 S aureus isolates (42.2%; 95% CI, 39.3%-45.1%) and 493 CoNS isolates (49.7%; 95% CI, 46.5%-52.9%), and methicillin-resistant (MR) isolates had a high probability of concurrent resistance to fluoroquinolones, aminoglycosides, or macrolides (P < .001). Multidrug resistance to at least 3 additional antibiotic classes was found in 428 MR S aureus isolates (86.8%) and 381 MRCoNS isolates (77.3%). All staphylococcal isolates were susceptible to vancomycin. Resistance among S pneumoniae isolates was highest for azithromycin (113 isolates [34.2%]) whereas resistance among P aeruginosa and H influenzae was low against the antibiotics tested. Staphylococcal isolates from elderly patients were more likely to be MR, as were S aureus isolates obtained from the southern United States (P < .001). Methicillin resistance among staphylococci did not increase during the 5-year study period (P ≤ .22), and small decreases in resistance to ciprofloxacin among CoNS and MRCoNS and to tobramycin among CoNS (P ≤ .03) were found., Conclusions and Relevance: Methicillin resistance was prevalent among staphylococcal isolates from ocular infections, with many strains demonstrating multidrug resistance. These findings are consistent with resistance trends reported for nonocular staphylococcal isolates. Overall ocular resistance did not increase during the 5-year study period. Continued surveillance of ocular isolates provides critical information to guide selection of topical antibacterials used for empirical management of ocular infections.

Streptococcus pneumoniae, an inhabitant of the upper respiratory mucosa, causes respiratory and invasive infections as well as conjunctivitis. Strains that lack the capsule, a main virulence factor and the target of current vaccines, are often isolated from conjunctivitis cases. Here we perform a comparative genomic analysis of 271 strains of conjunctivitis-causing S. pneumoniae from 72 postal codes in the United States. We find that the vast majority of conjunctivitis strains are members of a distinct cluster of closely related unencapsulated strains. These strains possess divergent forms of pneumococcal virulence factors (such as CbpA and neuraminidases) that are not shared with other unencapsulated nasopharyngeal S. pneumoniae. They also possess putative adhesins that have not been described in encapsulated pneumococci. These findings suggest that the unencapsulated strains capable of causing conjunctivitis utilize a pathogenesis strategy substantially different from that described for S. pneumoniae at other infection sites.

Purpose: Outbreaks of bacterial conjunctivitis have been linked to nontypeable strains of Streptococcus pneumoniae that lack a capsule, a key virulence factor for invasive infections. In contrast, isolates from sporadic, nonoutbreak cases of conjunctivitis were thought to be similar to invasive or nasopharyngeal isolates with respect to their capsular serotype and antibiotic resistance profile. This hypothesis was tested for 302 strains isolated during three prospective, multicenter clinical studies of bacterial conjunctivitis., Materials and Methods: S. pneumoniae capsular serotypes were determined by agglutination assay and confirmed by the Statens Serum Institute. The presence of the cpsAB capsule genes was determined by polymerase chain reaction (PCR). Minimum inhibitory concentrations were measured for 17 antibacterial drugs by the broth microdilution method., Results: Only 25 (8.3%) isolates reacted with the capsule-specific antisera and only one (0.3%) of these serotypes was covered by the capsule-specific PCV7 vaccine. The remaining 277 (91.7%) isolates were nontypeable, suggesting that they did not produce a capsule. PCR analysis indicated the loss of the capsule operon in 24/25 randomly selected nontypeable strains. Resistance rates were highest for azithromycin, trimethoprim, and tetracycline, while no resistance was detected for the fluoroquinolones, linezolid, and vancomycin. Antibiotic resistance rates were generally lower than those reported for invasive isolates, although some highly resistant or multidrug-resistant isolates were identified., Conclusions: The prevalence of nontypeable strains of S. pneumoniae was higher than expected, while the number of isolates responsive to the PCV7 vaccine was surprisingly low. These results highlight the need for new vaccines that can target all S. pneumoniae strains regardless of the presence or nature of a capsule. In addition, resistance to azithromycin, erythromycin, tetracycline, and trimethoprim was greater than 10%, which may be relevant when selecting empiric treatments for ocular surface infections.

Objectives: Besifloxacin is a novel fluoroquinolone that was recently approved for topical treatment of bacterial conjunctivitis. The compound was shown to be active in vitro against a broad spectrum of bacteria, including isolates resistant to other antibacterials. Here, the bactericidal activity of besifloxacin was evaluated against the most common bacterial conjunctivitis pathogens., Methods: MIC, MBC and time-kill experiments with besifloxacin and comparators were performed according to CLSI guidelines. Quinolone resistance-determining regions (QRDRs) were sequenced using standard PCR-based techniques., Results: MIC and MBC data indicated that besifloxacin was the most potent fluoroquinolone tested against Staphylococcus aureus (n = 30), Staphylococcus epidermidis (n = 15) and Streptococcus pneumoniae (n = 35), while all fluoroquinolones were highly active against Haemophilus influenzae (n = 40). Besifloxacin MBC:MIC ratios were < or = 4 for 97.5% of all isolates tested (n = 120). All fluoroquinolones tested, as well as tobramycin, were bactericidal, while azithromycin was bactericidal against S. pneumoniae and H. influenzae, but bacteriostatic against the staphylococci. Time-kill assays with all four species showed that besifloxacin caused > or = 1000-fold killing within 2 h for 11 of 12 isolates. Only one isolate treated with moxifloxacin and three ciprofloxacin-treated isolates achieved the same level of bactericidal activity under the same conditions. Unlike the comparator fluoroquinolones, besifloxacin maintained a high potency and bactericidal activity even against strains that contained multiple mutations in the genes encoding DNA gyrase and topoisomerase IV., Conclusions: Overall, besifloxacin demonstrated rapid bactericidal activity against the four major human pathogens tested here, including isolates that showed in vitro resistance to other fluoroquinolones, beta-lactams, macrolides or aminoglycosides.

Introduction: The choice of empiric therapy for bacterial conjunctivitis should be guided by an awareness of typical causative pathogen distributions. Bacterial conjunctivitis can be polybacterial, although pediatric-specific data are lacking. Methods: This was a post-hoc analysis of data in pediatric subjects (1– 17 years) from five bacterial conjunctivitis trials evaluating besifloxacin ophthalmic solution 0.6%. Results: Of the 730 pediatric subjects with culture-confirmed conjunctivitis, nearly one-fourth (23.6%) had polybacterial infections and three-fourths (76.4%) had monobacterial infections at baseline. In both polybacterial and monobacterial infections, the most prevalent organisms were Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, and Streptococcus mitis/S. mitis group. In polybacterial versus monobacterial infections, S. mitis/S. mitis group (8.7% vs 4.3%; P=0.032) and Moraxella catarrhalis (4.7% vs 0.5%; P< 0.001) were identified more frequently, whereas S. pneumoniae (14.0% vs 28.1%; P< 0.001) was identified less frequently, as the dominant infecting species. MICs for individual species were similar for tested antibiotics regardless of polybacterial or monobacterial infection, except Staphylococcus epidermidis for which fluoroquinolone MICs were ≥ 3 dilutions higher for isolates of this species sourced from polybacterial compared to monobacterial infections. Treatment with besifloxacin resulted in microbial eradication in 79.1% of polybacterial and 92.3% of monobacterial infections (P≤ 0.005 vs vehicle). Discussion: One in four pediatric bacterial conjunctivitis infections is polybacterial, highlighting the need for a broad-spectrum antibiotic when choosing empiric therapy. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: The Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) study is an ongoing nationwide surveillance program that surveys in vitro antibiotic resistance rates and trends among ocular bacterial pathogens. We report resistance rates by geographic region for isolates collected from 2009 through 2016.Methods: Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa isolates from ocular infections were collected at clinical centers across the US and categorized by geographic region based on state. Minimum inhibitory concentrations (MICs) for various antibiotics were determined at a central laboratory, and isolates were classified as susceptible or resistant based on established breakpoints. Geographic differences in methicillin resistance among staphylococci were evaluated by χ2 test with multiple comparisons, whereas geographic differences in mean percentage antibiotic resistance were evaluated by one-way analyses of variance and Tukey’s test.Results: Overall, 4829 isolates (Midwest, 1886; West, 1167; Northeast, 1143; South, 633) were evaluated. Across all regions, azithromycin resistance was high among S. aureus (49.4-67.8%), CoNS (61.0-62.8%), and S. pneumoniae (22.3-48.7%), whereas fluoroquinolone resistance ranged from 26.1% to 47.8% among S. aureus and CoNS. Across all regions, all staphylococci were susceptible to vancomycin; besifloxacin MICs were similar to those of vancomycin. Geographic differences were observed for overall mean resistance among S. aureus, S. pneumoniae, and P. aeruginosa isolates (p ≤ 0.005); no regional differences were found among CoNS and H. influenzae isolates. Methicillin resistance in particular was higher among S. aureus isolates from the South and CoNS isolates from the Midwest (p ≤ 0.006).Conclusion: This analysis of bacterial isolates from the ARMOR study demonstrated geographic variation in resistance rates among ocular isolates, with greater in vitro resistance apparent in the South and Midwest for some organisms. These data may inform clinicians in selecting appropriate treatment options for ocular infections.Funding: Bausch & Lomb, Inc. [ABSTRACT FROM AUTHOR]

Purpose: To study the efficacy of topical administration of gatifloxacin (0.3%), moxifloxacin (0.5%) ophthalmic solutions, and besifloxacin (0.6%) ophthalmic suspension as prophylaxis and treatment of pneumococcal endophthalmitis. Methods: Four groups of New Zealand white rabbits were topically treated with gatifloxacin, moxifloxacin, besifloxacin, and phosphate-buffered saline (PBS) at the following time points: 60, 45, 30, and 15 min before infection, immediately after infection, and then 6, 12, 18, and 24 h postinfection. Penicillin-resistant Streptococcus pneumoniae (PRSP; 106 colony-forming unit [CFU] in 50 μL) was injected into the aqueous humor of each eye. The clinical severity of the eyes was assessed by 2 masked observers 24 h postinfection. Aqueous and vitreous samples were collected, diluted, and plated to determine recovered CFU. Results: Fluoroquinolone-treated eyes had significantly lower clinical scores and bacteria recovered from the aqueous humor than the PBS-treated eyes. There was no difference, however, among the fluoroquinolone-treated groups. In contrast, none of the fluoroquinolones reduced the number of bacteria recovered (CFU) from the vitreous humor. Conclusions: Besifloxacin is as effective as moxifloxacin and gatifloxacin in a rabbit model for topical prophylaxis and treatment of PRSP-induced endophthalmitis. [ABSTRACT FROM AUTHOR]