September 2014




Antibiotic resistance continues to rise among ocular pathogens

by Lauren Lipuma EyeWorld Staff Writer

Staphylococcus aureus bacteria

Methicillin-resistant Staphylococcus aureus bacteria Source: SCIENCE SOURCE/Getty Images

Resistant organisms constitute a serious threat to treatment of eye infections

Data presented at the 2014

Association for Research in Vision and Ophthalmology (ARVO) meeting showed that bacteria frequently implicated in eye infections in the U.S. are becoming increasingly resistant to available antibiotics. Paralleling what has happened in systemic medicine, strains of resistant bacteria are becoming more common and the evolution of multidrug resistance is on the rise. Researchers from Bausch + Lomb (Bridgewater, N.J.) reported the results from the 2013 Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) study. Started in 2009, the study is a collaborative effort to track antibiotic resistance among ocular pathogens to both well-established antibiotics and new therapeutic agents. The ability to deliver antibiotics topically and achieve high concentrations in target tissues has buffeted ophthalmic infections against the increasing resistance patterns seen elsewhere in medicine, but resistant populations have nonetheless emerged and constitute a growing problem. There was this false perception that we didnt have to worry as much about resistance because we had this advantage of topically administered antibiotics, said Terrence P. OBrien, MD, professor of ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami. And it certainly is an advantage of drug delivery. But the fact that resistant organisms are communicating and resistant populations emerge is something to which eyecare practitioners need to pay attention.

The study

Participants in the ARMOR study collected more than 200 isolates of bacterial species common in eye infections and tested them for susceptibility to 16 antibiotics. Researchers tested isolates of gram-positive Streptococcus pneumoniae, Staphylococcus aureus, and Staphylococcus epidermidis, as well as gram-negative Pseudomonas aeruginosa and Haemophilus influenzae. Results indicated that resistance to several different classes of antibiotics increased from 2012 to 2013 among strains of Staphylococci and P. aeruginosa, species well known for rapidly developing resistance in systemic infections. Strains of both S. aureus and S. epidermidis showed increased resistance to penicillins, macrolides, and fluoroquinolones. Additionally, multidrug resistance was common in the 2 species, reaching levels as high as 81% in strains already resistant to methicillin. Resistance to ciprofloxacin and imipenem more than doubled to 14% and 21%, respectively, among Pseudomonas aeruginosa strains. Encouragingly, resistance to drugs not used in systemic medicine was minimal. Isolates showed susceptibility to the fourth-generation fluoroquinolone besifloxacin as well as the older antibiotics bacitracin and polymyxin B. What was encouraging and a pleasant surprise was that for besifloxacin, which doesnt have other systemic medical, animal husbandry, or agricultural use, the susceptibility profile remains very similar to what weve observed in the last several years, Dr. OBrien said.

How to use the data

Microbiologic surveillance is key to staying ahead of resistant pathogens, he said, and clinicians should use the data provided by this and other studies to inform decisions regarding management of ocular infections. The high rates of multidrug resistance among staphylococcal strains, as shown in the ARMOR study, should be taken into account when choosing the appropriate initial empirical antibiotic treatment, Dr. OBrien said. If you have or suspect a meth-resistant staph, you should choose an agent other than a fluoroquinolone for treatment, he said. Ophthalmologists should consider use of older agents with low resistance profiles, like bacitracin and trimethoprim-polymyxin B, to their advantage. These may be agents that have selective value even though theyre not the traditional broad-spectrum super drugs, Dr. OBrien said. He cautioned, however, that ophthalmologists must continue to closely monitor the effectiveness of these drugs, as the ability of organisms to evolve resistance mechanisms is so great. When it comes to prophylaxis, Dr. OBrien thinks alternatives to antibiotics are a more rational choice. Development of resistance to topical antibiotics given after repeated intravitreal injections prompted retina specialists to discontinue their use in favor of antiseptics, a practice Dr. OBrien thinks anterior segment specialists should adopt. I think for prevention, we realize that antibiotics may not be the most rational choice, so the use of antiseptics is probably preferred, he said. The challenge is how to prevent and eliminate the serious peril posed by microbial contamination around ophthalmic procedures.

Because antibiotic development has been relatively stagnant and most new drugs are molecular variants of existing drugs, these results highlight the need for new, innovative antimicrobial agents with novel mechanisms, said Dr. OBrien. Antimicrobial peptides are one option, as are analogs to N-chlorotaurine, an endogenous oxidant that has been shown to have antimicrobial activity and to neutralize some bacterial toxins. Pharmaceutical development should also include efforts to develop agents that inhibit and/or break down biofilms, he said. Dr. OBrien stressed the need to stay vigilant when it comes to antibiotic resistance, a problem that he sees as a serious global threat to public health. Surveillance is critical to heighten awareness of the threat that is before us, he said. We in eyecare need to pay attention to this. We in ophthalmology are not insulated or isolated from this problem. Its our problem, and our patients problem, just like it is for the rest of the medical world.

Editors note: Dr. OBrien serves as ad hoc consultant for Alcon (Fort Worth, Texas), Allergan (Irvine, Calif.), Bausch + Lomb, Santen Pharmaceutical (Osaka, Japan), and Senju Pharmaceutical (Osaka, Japan), but he has no financial interests in the agents or companies mentioned.

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