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Are bacteria getting smarter?

The premium surgeon has to be prepared to combat total bacterial resistance.

Issue: July 10, 2017

ByMitchell A. Jackson, MD

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For many of us premium surgeons, golf season has finally arrived, especially in regions such as the Midwest for me. On Memorial Day weekend, I embarked on my first rounds of the year after taking a fairly long sabbatical from lumbar fusion surgery 4 years ago and a broken fibula last September. The most frustrating part of that weekend was how horrible I played when at one time I was a 6 handicap golfer, but I was thankful to be playing again without injury nevertheless.

As premium surgeons, we rarely experience that hopeless feeling of never wanting to touch a golf club again when perfect uncomplicated cataract surgery results in an unexpected intraocular infection in the immediate postoperative period for no apparent reason or known risk factors. The typical endophthalmitis pathogens of increasing prevalence are coagulase-negative staphylococci (CoNS) and methicillin-resistant Staphylococcus aureus (MRSA). Endophthalmitis rates vary from 0.028% to 0.3%, with the accepted U.S. rate approaching one in 1,000 to one in 1,500. Typical high-risk patients for developing MRSA infections after cataract surgery are prison inmates, military recruits, HIV-positive or other immunosuppressed patients (for example, diabetic patients), homeless persons, intravenous drug abusers, tattoo recipients, health care professionals (especially hospital-based), those with a known MRSA history, and those residing in nursing homes.

Resistance

Unfortunately, bacteria are getting smarter with a wide array of mechanisms to develop resistance to antibiotics no matter the method of delivery to the eye. Alteration and protection of antibiotic targets via genetic mutation and/or post-translational modification; direct modification or inactivation of antibiotics via hydrolysis and/or addition of a chemical group; prevention of access to drug targets via reduction in membrane permeability and/or active cell efflux; spontaneous mutation due to environmental stresses; horizontal gene transfer via transformation, transduction and/or conjugation; and the inappropriate use of systemic antibiotics in internal medicine, veterinary medicine and agriculture all contribute to the increasing resistance of bacteria, especially MRSA, in intraocular surgery.

Surveillance studies such as SENTRY, SMART, TRUST and ARMOR were implemented by the WHO, CDC and FDA to help combat threats from resistant pathogens. Ocular TRUST evaluated in vitro susceptibility to S. aureus, Streptococcus pneumoniae and Haemophilus influenzae in 2005 to 2006, with trimethoprim showing fairly high activity against the bad guy MRSA. Fast-forwarding to the ARMOR data from 2009 to 2013, methicillin resistance approached 43% and 50% for S. aureus and CoNS isolates, respectively. Resistance to three or more additional antibiotic classes was also realized, with 86.8% among MRSA and 77.3% among methicillin-resistant CoNS. In vitro data showed besifloxacin to be the most potent fluoroquinolone tested, especially against ciprofloxacin-resistant MRSA isolates, approaching MIC90 values similar to that of vancomycin.

Prophylaxis

So what regimen should ideally be used as prophylaxis against intraocular infection at the time of cataract surgery? No single topical antibiotic will truly cover every organism, but antibiotic prophylaxis should concentrate on broad-spectrum coverage. It is important to identify patients at higher risk for ocular MRSA infection, such as increasing age past 60 years old, prosthesis in fellow eye, immunodeficiency and/or untreated blepharitis. The go-to primary approach where no controversy exists is povidone-iodine 10% skin prep and 5% conjunctival cul-de-sac application at the time of cataract surgery. Topical antibiotic therapy with agents that have been effective at least in vitro (ARMOR data) are used widespread, but there has never been a placebo-controlled prospective study despite retrospective studies showing efficacy.

Intracameral antibiotic prophylaxis has been successful as published in 2006 in the European Society of Cataract and Refractive Surgeons study, in which there was a fivefold reduction in endophthalmitis with intracameral cefuroxime compared with antibiotic drops. The Kaiser study published in 2013 showed only one case of endophthalmitis in 2,038 patients without topical antibiotics and only intracameral cefuroxime, moxifloxacin or vancomycin used. The Swedish national study published in 2013 showed only a 0.029% incidence of endophthalmitis in 464,996 cataract operations. Recently, the American Society of Cataract and Refractive Surgery sent out an alert that intracameral vancomycin can increase the risk of hemorrhagic occlusive retinal vasculitis. Intracameral antibiotics are convincing, but legitimate questions remain because there are no head-to-head comparisons to find the optimal drug, and in the United States, only off-label or compounded antibiotics are available with or without steroid. Intravitreal compounded antibiotics with or without steroid are also readily available but can sometimes give the appearance of endophthalmitis in the immediate postoperative period if a referring doctor did not know they were used at the time of surgery. Iontophoresis and intracanalicular punctal plugs as possible delivery systems for antibiotic and/or steroid therapy loom in the near future as well.

In the end, premium cataract surgeons need to be smarter than the bacteria and overcome resistance to current antibiotic therapy — no different from my return to golf trying to sink that putt or drain a hole-in-one that stops my resistance to never wanting to play again.

• References:
• Asbell PA, et al. J Cataract Refract Surg. 2008;doi:10.1016/j.jcrs.2008.01.016.
• Asbell PA, et al. JAMA Ophthalmol. 2015;doi:10.1001/jamaophthalmol.2015.3888.
• Barry P, et al. J Cataract Refract Surg. 2006;doi:10.1016/j.jcrs.2006.02.021.
• Blair JM, et al. Nat Rev Microbiol. 2015;doi:10.1038/nrmicro3380.
• Cao H, et al. PLoS One. 2013;doi:10.1371/journal.pone.0071731.
• Culyba MJ, et al. Biochemistry. 2015;doi:10.1021/acs.biochem.5b00109.
• Friling E, et al. J Cataract Refract Surg. 2013;doi:10.1016/j.jcrs.2012.10.037.
• Gentile RC, et al. Ophthalmology. 2014;doi:10.1016/j.ophtha.2014.02.001.
• Packer M, et al. J Cataract Refract Surg. 2011;doi:10.1016/j.jcrs.2011.06.018.
• Schimel AM, et al. Am J Ophthalmol. 2013;doi:10.1016/j.ajo.2013.01.027.
• Shorstein NH, et al. J Cataract Refract Surg. 2013;doi:10.1016/j.jcrs.2012.07.031.
• Speaker MG, et al. Ophthalmology. 1991;doi:10.1016/S0161-6420(91)32239-5.
• Vazirani J, et al. Curr Opin Ophthalmol. 2013;doi:10.1097/ICU.0b013e32835a93be.

• For more information:
• Mitchell A. Jackson, MD, can be reached at Jacksoneye, 300 N. Milwaukee Ave., Suite L, Lake Villa, IL 60046; email: mjlaserdoc@msn.com.

Disclosure: Jackson reports he is a consultant for Bausch + Lomb.