Cataract/Anterior Segment, Comprehensive Ophthalmology, Cornea/External Disease, Ocular Pathology/Oncology
Study design
The Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) study is the only ongoing surveillance program in the U.S. assessing the resistance of ocular pathogens.
Researchers collected over 3200 ocular isolates from 72 centers across the country between 2009 to 2013 and analyzed the minimum inhibitory concentrations (MICs) of the various antibiotic classes for each.
Outcomes
Medications with the highest rates of resistance—defined as requiring a MIC greater than the susceptibility breakpoint by the Clinical and Laboratory Standards Institute (CLSI)—were oxacillin, ciprofloxacin and azithromycin. Vancomycin appears to be the drug of choice for managing ocular staphylococcus infections, as none of the CoNS, S. aureus (SA) or MRCoNs and MRSA isolates were resistant.
Next-generation fluoroquinolone drugs such as besifloxacin, moxifloxacin and gatifloxacin were effective against a variety of pathogens at lower MIC90 values than older generation fluoroquinolones. These agents should be used preferentially over ofloxacin, ciprofloxacin or levofloxacin.
More than 40% of S. aureus and CoNS isolates were methicillin resistant. Although high, the rates did not increase over the 5-year study period. Methicillin resistance was more common among staphylococcus isolates from older patients and from medical centers in the south. In addition, multidrug resistance continues to be a significant issue, as 86.8% of MRSA and 77.3% of MRCoNS isolates were resistant to 3 or more additional antibiotic classes. The authors calculated that MRSA isolates were 16–18 times more likely to be resistant to ciprofloxacin, azithromycin, or tobramycin compared with the methicillin susceptible (MS) strains. MRCoNS isolates were 4–8 times more likely to be resistant.
Of S. aureus isolates, 42.2%, 39.8% and 63.6% were resistant to oxacillin, ciprofloxacin and azithromycin, respectively. Clindamycin and tobramycin resistance was seen in less than 20%. MRSA samples were most commonly also resistant to oroquinolones, aminoglycosides or macrolides (P<0.001), whereas methicillin-susceptible S. aureus (MSSA) showed high resistance only to azithromycin.
CoNs isolates showed a similar distribution to of resistance to oxacillin, ciprofloxacin and azithromycin as the S. aureus, with 49.7%, 34.4% and 61.3%, respectively. Resistance to tobramycin and trimethoprim was seen in 19.2% to 25.8%. MRCoNs had higher rates of resistance to ciprofloxacin, azithromycin and other drugs compared to MSCoNs.
Resistance rates amongst S. pneumoniae and P. aeruginosa isolates were low, with good susceptibility to the fluoroquinolones. Ciprofloxacin had the lowest MIC90 for P. aeruginosa cultures and besifloxacin was best for S. pneumoniae samples (which showed low response to azithromycin and penicillin).
All but 1 H. influenzae isolate—which was resistant to azithromycin—were susceptible to each antibiotic tested and needed relatively low MIC90 values.
Clinical significance
These findings are consistent with reports monitoring non-ocular resistance rates. The plateau in rates of MR are promising, and may reflect improved antibiotic stewardship and judicious antibiotic use. In fact, a small decrease in resistance to ciprofloxacin was noted among CoNS and MRCoNS isolates. Until more rapid diagnostic methods are available, the authors recommend that clinicians use these results as a guide to prevent future increases in the already troubling rates of resistance.
Limitations
Limitations of this study included potential sampling bias stemming from the relative infrequency of culturing bacterial pathogens, such that the distribution of severe, resistant isolates collected is not reflective of their true prevalence. The use of the CLSI’s resistance break points to interpret MIC data may also be confounding, as these concentrations are based on oral or intravenous administration and may not translate directly into dosages for topical application. For this reason, the resistance to bacitracin was not evaluated as it is formulated as an ointment.