In this retrospective review, 358 microorganisms were analyzed by a single-center institution over a 6-year study period. A wide variety of Gram-positive and Gram-negative organisms were collected including CoNS, S. marcescens, K. oxytoca, and E. coli, as well as more common bacterial pathogens such as S. aureus, S. pneumoniae, H. influenzae, and P. aeruginosa. In this study the number of Gram-negative organisms (49.2%) was nearly equal to the number of Gram-positive organisms (50.8%). While other single-center studies have found a much higher proportion of Gram-positive organisms in collected samples [1,23,, 7, 18, 22–24], this study exhibited a nearly equivalent Gram-positive to Gram-negative ratio. This difference is likely due to the clinical microbiology laboratory protocols that did not require susceptibility testing of CoNS until mid-2015 from eye sources due to the likelihood of these isolates being contaminants. Specifically, there were an additional 152 CoNS isolates, the majority isolated from conjunctival swabs, which did not undergo susceptibility testing. If these isolates had undergone susceptibility testing, the distribution between Gram-positive and Gram-negative bacteria would change considerably (65.5 and 34.5% respectively) and be more in line with previously published studies.
This study also showed an uneven distribution of ocular isolates among age groups. Gram-positive organisms were most common in the elderly, while Gram-negative organisms, except H. influenzae, were most common in the middle age ranges. H. influenzae isolates had a bimodal distribution, being more common in the youngest and oldest age groups. Additionally MRSA was statistically more likely (p < 0.05) to be found in the two oldest age groups (40–64 years and >65 years) when compared to the younger age groups suggesting a higher possibility of MRSA infection with increasing age. While the link between age and risk of infection remains unclear, it may be due to the underdeveloped immune system common in infants and children as well as the depressed immune function observed in the elderly, making the risk of microbial infection in these groups higher .
Several drugs are used to treat ocular infections, each with a different mechanism of action. Despite this, many of the pathogens observed in this study are adapting in ways that lead to increased resistance to several classes of antibiotics. Fluoroquinolones, which are a class of drugs often used as first-line treatment for ocular infections, have generally been successful, especially as newer generations have been introduced [1, 22]. However, just like other antimicrobial classes, the systemic use of these fluoroquinolones as first-line broad-spectrum antibiotics tends to lead to increases in resistance due to selective pressure [4, 15, 16, 19]. In this study, 50 and 80% of MRSA isolates showed resistance to levofloxacin and ciprofloxacin respectively, while 3.53 and 7.41% of MSSA isolates showed resistance to levofloxacin and ciprofloxacin, respectively.
Multi-drug resistance (MDR) was observed in many of the MRSA isolates collected in this study (n = 12; 42.9%). When compared to MSSA isolates, MRSA isolates have shown statistically significant increases in MDR when compared to MSSA isolates, making them resilient pathogens. However, even with this increased resistance, S. aureus isolates have shown limited to no resistance to vancomycin, daptomycin or linezolid, making these treatments reliably effective in bacterial populations that have already shown high resistance to fluoroquinolones, aminoglycosides, and macrolides.
Fluctuating trends in the prevalence of MRSA strains have been reported. Some studies have presented increasing trends in MRSA over extended periods of time [23, 24], while others, including those presented by the CDC, state a decline in MRSA prevalence [26,27,28]. This study shows a non-statistically significant, decreasing trend over the 6-year study period suggesting that MRSA prevalence has not fluctuated drastically over the last several years. While it is unclear why MRSA prevalence has remained relatively stable in our review, it may result from successful infection control strategies in both hospitals and surrounding communities, or perhaps the cyclical replacement of dominant, infective MRSA strains by MSSA strains over time .
In contrast to MRSA, resistance among S. pneumoniae and P. aeruginosa isolates was low against the antimicrobials tested while resistance among H. influenzae isolates was evident primarily against ampicillin and TMP/SMZ. Overall these three organisms did not show alarming resistance to the antimicrobials tested and are consistent with other antimicrobial surveillance studies that have been conducted recently [1, 7, 13, 19].
Several factors are important in the development of antimicrobial resistance in ocular isolates. Overuse of antibiotics is one of the main causes . Other causes include use of an antibiotic when it is not warranted, as in the case of a viral infection, or improper use, such as stopping a course of antibiotics early or using them prophylactically . Since most ocular infections are often resolved through topical application rather than through systemic use, the inherent pharmacokinetic differences between the two must be taken into account when evaluating antimicrobial resistance [29, 30]. Given the high risk of permanent vision loss with eye infection, such as corneal ulcers and endopthalmitis, topical antibiotics tend to be at higher concentrations and are often used as prophylaxis despite limited evidence on their efficacy. The role that topical antibiotics play in antimicrobial resistance is still ambiguous due to the lack of research in this specific area as well as the lack of standardized ocular tissue-specific breakpoints. With the lack of these breakpoints to qualify resistance, CLSI breakpoints have been agreed upon by many researchers as useful indicators of resistance in topical antibiotics and even with the differences mentioned, similar resistance trends are observed in both topical and systemic antibiotic use [31, 32]. Additionally, since systemic antibiotics are still used to treat chronic ocular infections, in such usage, CLSI breakpoints are appropriate. In fact, systemic use of antibiotics may be the key cause of resistance in all isolates, regardless of the source of infection [33, 34]. However, the uncertainty of the role of topical antibiotics is still apparent and therefore requires further attention in order to fully delineate their role.
Limitations of this study include the retrospective nature of this study, which predetermined our sample size, ultimately limiting our analysis of all possible antimicrobial resistance trends. Because there was no standardized protocol for collection of isolates, inevitably there was a large variation in the culturing procedure among physicians. This lack of uniformity may have affected organism recovery in culture. Additionally, the antimicrobial panel underwent small fluctuations from year to year leading to slightly inconsistent susceptibility testing and excluded testing on more recently introduced fluoroquinolones, such as gatifloxacin.