Stopping postop infection

Take-Home Message: Postoperative infections with ocular surgeries may be reduced substantially by effectively treating active ocular disease in advance before the patient enters the operating room.

By Lynda Charters; Reviewed by Terrence P. O’Brien, MD

Miami-The ocular isolates that are most likely to be recovered in the United States from infections related to ophthalmic surgeries are predominantly gram-positive bacterial organisms, especially coagulase-positive and coagulase-negative staphylococci.

These organisms are linked in upward of 95% of post-cataract infections with gram negative and fungal organisms being much less commonly implicated.

“This trend to recovery of gram-positive organisms, while not new, is continuing, and studies over the past few years have documented the preponderance,” said Terrence P. O’Brien, MD, professor of ophthalmology, University of Miami, and co-director, Ocular Microbiology Laboratory, Bascom Palmer Eye Institute, Miami.

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The most recent laboratory research has reinforced that no single antibiotic agent is universally effective for eradicating these bacteria and suggests that a combination of antibacterial agents may be more effective.

However, turning one’s attention on the host, i.e., the patient, and identifying specific risk factors may be a more effective approach for beating these culprits of infection rather than reacting to the organisms-given their ability to rapidly evolve and become resistant to prevention as well as treatment.

An alarming trend that has surfaced over the past several years is the evolving resistance seen among the ocular pathogens to commonly used antibiotics, especially fluoroquinolones, as well as other frequently prescribed antibiotics. Among the predominantly recovered gram-positive organisms, reduced susceptibility to the commonly used antibiotics is being observed, he noted.

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Another unfortunate trend compounds this problem, according to Dr. O’Brien. Fewer new drugs are being investigated by fewer companies because of the daunting costs of research and development (R&D), he observed.

“Compared with the golden age of R&D of antibiotics in the 1970s when multiple new agents were introduced every year, now the situation for drug development . . . to treat systemic as well as ocular infections is in marked contrast to that enjoyed four decades ago,” he said.

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Ophthalmic surgeons recognize the eye’s particularly precarious and vulnerable situation because of its unique structure and the easy access through which organisms can gain entry during ophthalmic surgery.

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“Because bacteria can be sequestered in a relatively closed environment, this a unique risk factor for all ophthalmic procedures, including cataract and glaucoma surgeries, LASIK, and even injections into the vitreous cavity for retinal disorders,” Dr. O’Brien said.

“Ocular surgeons must gain an understanding of those risk factors and use strategies to improve or reduce the likelihood of patients contracting infection,” he added.

These strategies include adopting universal precautions to prevent infection and special attention that is unique to the eye. One important step is to treat patients who may have chronic external ocular infections, such as blepharitis and blepharoconjunctivitis, before they undergo an ocular surgery, he noted.

“Many studies have found that these external ocular infections are the sources of the organism’s access at the time of an ocular surgery,” Dr. O’Brien said. “Pre-treatment is a recognized approach that prevents patients from going into surgery with an active external ocular disease.”

Having said this, Dr. O’Brien also noted there is controversy surrounding the use of antibiotics before, during, and following cataract surgeries regarding their effectiveness and the most optimal route of administration.

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“Topical antibiotics, which have been the mainstay of ophthalmic care, have not been shown conclusively to universally lower the risk of infection during ocular surgery,” he said. “There is a rationale for their use, but no large-scale multicenter study that definitively proves their effectiveness has been completed.”

To date, two steps have been shown to substantially reduce infections, especially during cataract surgeries:

• Topical antiseptic (povidone iodine) during patient preparation for surgery, and

• Intracameral injection of antibiotic.

While the latter was proven beneficial in a large European study, questions remained about which antibiotic was preferred for delivery and the manner in which the drug should be made and delivered. In the United States, no such commercial drugs are yet approved for intracameral use in a prophylactic fashion.

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With the goal of reducing ocular infections associated with surgery, Dr. O’Brien noted a trend away from the use of nondisposable instruments. This is the result of investigations into development of toxic anterior segment syndrome (TASS) after cataract surgery because of incomplete processing and handling of the instruments.

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In the same way, surgeons have recognized that small-gauge cannulas are hard to clean and material can be retained in the absence of proper cleaning and sterilization. Cataract surgeons are using more IOLs that are preloaded and injected, which eliminates excessive handling and lowers the risk of contamination.

“Alternatives to conventional antibiotics-such as antimicrobial peptides, antisense agents or natural killers, like hypochlorous acid present in human neutrophils-may have an increasing role in both treatment and prevention of infection”, Dr. O’Brien predicted.

These alternatives are attractive because of their novel mechanisms of action and resistance to the development of resistance, he noted.

New drug delivery systems are being considered to transport and distribute available antibiotics and thereby extend their usefulness.

“Some strategies are afoot to use drug delivery, especially nanotechnology, that may enhance the penetration and potency of the existing compounds so that higher concentrations can be achieved in the target tissues and even greater contact time to facilitate greater drug activity,” Dr. O’Brien explained.

The ARMOR Study

The ongoing Antibiotic Resistance Monitoring in Ocular MicroRganisms (ARMOR) study of bacterial resistance underscores the importance of concern about this growing resistance problem.

Dr. O’Brien commends surveillance efforts such as the ARMOR Study and other such large undertakings to maintain awareness of the evolving trends in organisms that cause ocular infections and in the antimicrobial susceptibility patterns.

“These surveillance strategies are essential for a better understanding of the enemy, as well as the rational choices of optimal agents for treatment and prevention of infection,” he said.

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The ARMOR Study has been an important tool for monitoring trends in resistance to antibiotics, especially fluoroquinolones, he noted.

The latest data collected over the previous few years have reinforced the concern about growing microbial resistance to available drugs. Resistance is growing among the commonly seen organisms to the most commonly administered ocular antibiotics.

“These data suggested that in some instances a single agent may be insufficient, but rather a combination of more than one agent may be preferred for treating an active infection or for prophylaxis,” Dr. O’Brien said.

The latest data from the ARMOR study are expected to be presented at the 2015 annual meeting of the Association for Research in Vision and Ophthalmology in Denver.

A key strategy

Dr. O’Brien emphasized the importance of heightened preoperative awareness about the patients who may be at unique risk of developing an infection by focusing attention on the hosts first, and not reacting later to the organisms.

“The latter approach over the years has shown that the bugs tend to win because they are clever and have evolved over time,” he said. “They have devised increasingly cunning strategies to evade our efforts to eliminate them. Extra endeavors exerted preoperatively aimed to protect the patient during the window of vulnerability can eliminate problems postoperatively in these altered hosts.”

Focusing on the host may help uncover newer strategies to protect patients who are uniquely at risk of infection, he said.

Terrence P. O’Brien, MD

E: tobrien@med.miami.edu

Dr. O’Brien is an ad hoc non-salaried consultant for Alcon Laboratories, Allergan, Bausch + Lomb, Santen Pharmaceuticals, Senju, and Shire.