Article Date: 2/1/2010

Methicillin-resistant <I>Staphylococcus aureus</I> in Eyecare and in the Contact Lens Practice
MRSA

Methicillin-resistant Staphylococcus aureus in Eyecare and in the Contact Lens Practice

Part 2

By Ron Melton, OD, FAAO, Randall Thomas, OD, MPH, FAAO, and Chris Snyder, OD, MS, FAAO

Gram-positive bacterial pathogens (particularly Staphylococcus aureus and epidermidis) are the most common causes of ocular infections.1 An evolving aspect of patient protection and safety centers on the increasing prevalence of infections from methicillin-resistant Staphylococcus aureus ("MRSA") and, accordingly, we addressed clinical aspects of MRSA infection and treatment in our 2009 Clinical Guide to Ophthalmic Drugs.1 This article allows us to take a broader look at MRSA as it relates to eyecare practitioners, their clinical practices and patients.

There are two general types of MRSA, primarily differentiated by genotypic and environmental features: Healthcare-Associated MRSA (HA-MRSA) and Community-Associated MRSA (CA-MRSA). HA-MRSA is contracted in a healthcare setting, such as a hospital or nursing home, and usually by people who are in poor health or are immunocompromised. HA-MRSA organism virulence and susceptibility to antibiotics is somewhat different than CA-MRSA, which is contracted in the general community, has more genetic variants, is susceptible to various antibiotics (whereas HA-MRSA tends to be multidrug resistant), spreads more easily — causing more skin disease than HA-MRSA, and can be associated with severe pneumonia in children.

We routinely read the scientific literature so our clinical practices are evidence-based and aligned with current knowledge and thinking in eye and healthcare. A recent article by Blomquist2 reviewed the medical records of documented cases of MRSA ophthalmic and adnexal infections in an urban area over a 2-year period. Blomquist reported that CA-MRSA infections were most commonly preseptal cellulitis and/or lid abscess, with the second-most common being conjunctivitis. Corneal ulcers, endophthalmitis and orbital cellulitis also were documented. Overall, his results were in agreement with those of other recent studies, which indicate the prevalence of CA-MRSA is rapidly increasing.

MRSA TREATMENT OVERVIEW

We offer a brief reminder of a reasonable treatment approach for the more common ophthalmic/adnexal MRSA infections that were reported in the Blomquist study.2 When preseptal cellulitis and/or lid abscess conditions present, trimethoprim is an excellent, broad-spectrum bacteriostatic antibiotic that is particularly effective against Gram-positive organisms such as Staphylococcus aureus and MRSA. Systemically, trimethoprim combined with sulfamethoxazole — historically marketed as Bactrim (AR Scientific) or Septra (Monarch Pharmaceuticals) — is a drug of choice when treating systemic soft tissue infections caused by MRSA pathogens.

For conjunctivitis caused by MRSA, topical trimethoprim solution is highly effective and available generically in combination with polymyxin B (originally known by the brand name Polytrim [Allergan]). Because this combination drug is particularly effective against Streptococcus pneumoniae and Haemophilus influenzae, two common pathogens in the pediatric population, this is the drug of choice for children with bacterial conjunctivitis.

With a corneal ulcer, if the lesion is clearly infectious, an excellent initial approach is to prescribe a fluoroquinolone every hour while awake and Polysporin ointment at bedtime. If there's no response or a suboptimal response, polymyxin B sulfate and trimethoprim may be used hourly, because if the ulcer is caused by a MRSA bacterium, the fluoroquinolone may be suboptimal but the trimethoprim should aid in the eradication of any resistant bacteria.

EXPOSURE TO MRSA AND OUR RESPONSIBILITIES IN PRACTICE

What is your daily exposure to MRSA? For every 100 patients you see, 25-30 will have Staphylococcus aureus colonized in their nostrils and 1 in 100 will be colonized with MRSA.3 The colonized individuals are not necessarily infected but rather are carriers, ready to transmit the organisms to others (or to perhaps infect themselves). Hand-washing is extremely important to prevent microorganism transmission and infection.

To supplement correct and frequent hand-washing, an alcohol-based hand sanitizer should be readily available in various locations throughout your office. Beyond aggressive hand-washing, using barriers to transmission, such as gloves and bandages, may help prevent and/or control the transmission of MRSA. It is critical to routinely disinfect instruments, counter tops and other high-touch areas. A commercial disinfectant or a 1:100 solution of diluted bleach (1 tablespoon bleach in 1 quart water) can be used to disinfect counter tops and other surfaces. In short, it is appropriate to have a protocol for infection control in place in any healthcare practice, with regular training and updates for all practice personnel.

You should educate patients on how to minimize transmission of infections. Advise them to practice good personal hygiene and remind them of these simple steps to help stop the spread of germs and infection:

■ Keep hands clean by using soap and water or an alcohol-based hand sanitizer
■ Don't share personal items that come into direct contact with bare skin, such as towels and razors
■ Keep high-touch surfaces clean
■ Use barrier-like clothing or a towel between skin and shared exercise/fitness equipment
■ Shower immediately after participating in exercise or sports activities that involve skin-to-skin contact.

MRSA AND THE CONTACT LENS PATIENT: COMPLIANCE AND SOLUTION PERFORMANCE

There are approximately 38 million contact lens wearers in the United States.4 Ocular exposure to CA-MRSA may be higher in contact lens wearers because many patients place worn lenses that could be contaminated on their eyes and they frequently touch their eyelids. As such, it is very important to remind them about the proper use of contact lens care products and clean hands to minimize the microbial exposure to the eye and adnexa. It is a well established fact, however, that patients commonly fail to heed proper "wear and care" guidelines. Examples of common noncompliance include:

■ Handling lenses under nonhygienic conditions
■ Not properly washing hands
■ Not properly following lens rub or no-rub cleaning protocols (we encourage all of our patients to rub their lenses upon removal each evening)
■ Using a dirty lens case
■ Not using enough solution in the lens case
■ Topping off used solution in the lens case with fresh solution

A number of studies have shown that the overall rate of noncompliance with contact lens care varied from 50% to 99%, despite many of the lens wearers believing they were compliant. Yung5 evaluated compliance levels in experienced contact lens wearers and reported all subjects showed some degree of noncompliance in the care of their contact lenses or lens care accessories, with a majority (60%) noncompliant with at least six of a total of 15 lens care procedures. Patient compliance with contact lens care depends, in part, on patients following the recommended minimum soak time. Yung5 also found that 12% of subjects did not soak their lenses for the minimum indicated disinfection time or longer.

Even with the ease-of-use that multipurpose solutions provide, eyecare practitioners can expect that most patients will not use a solution properly and consistently. All eyecare practitioners should use easy-to-understand, clinically relevant guidelines to give each contact lens patient as a take-home handout. These materials should stress meticulous hygiene, including hand-washing; adherence to prescribed lens-wearing and replacement schedules; following directions on lens care packaging for processing of the lenses upon removal, whether indicated for a lens rubbing or no-rub regimen; use of fresh solution each evening with specific avoidance of "topping off" behavior; and at least quarterly replacement of the contact lens case. (A downloadable copy of "What You Need to Know about Contact Lens Hygiene and Compliance" is available on the American Optometric Association's website.)6

The elimination of microorganisms from lens surfaces is an essential component of proper contact lens care to minimize the potential for adverse events, such as bacterial, fungal or protozoal keratitis. Because of the association between these events and inadequate hygienic practices and noncompliance with lens care regimens (such as cleaning, rinsing and disinfecting), multipurpose solutions (MPS) with high disinfection levels are desirable. A variety of today's MPS products are listed in Table 1.

Table 1. Today's MPS products and a hydrogen peroxide product.

An appropriate way to assess the performance of leading MPS products is to use well-accepted laboratory testing procedures and protocols. The U.S. Food and Drug Administration (FDA) and International Standards Organization (ISO) require evaluation of stand-alone biocidal efficacy, using a standard set of five microorganisms. The required panel of microorganisms is intended to represent the diverse microbial challenge that one might encounter:

■ Two Gram-negative bacteria (Pseudomonas aeruginosa and Serratia marcescens)
■ One Gram-positive bacterium (Staphylococcus aureus)
■ Two fungal microorganisms (the mold Fusarium solani and yeast Candida albicans)

This standardized testing uses microbial strains from the American Type Culture Collection (ATCC), applying the stand-alone primary criteria for effective disinfection, which is a reduction in the number of bacteria by a minimum of 3 logs (99.9%) and a reduction of mold and yeast by a minimum of 1 log (90%) within the recommended disinfection time.7 These criteria must be fully met for a lens care product to be approved for marketing in the United States. Stand-alone biocidal test results show that each of the MPS products pass FDA/ISO standards for log reduction and that differences in disinfection performance exist between the products (Figure 1).

Figure 1. FDA/ISO stand-alone procedure for MPS disinfecting products.

During a meeting of the Ophthalmic Devices Panel of the FDA in June 2008, recommendations were made for preclinical testing of contact lens products, including more rigorous and standardized "real-world" scenarios that more accurately replicate conditions and environments of consumers.8 (We aren't aware of any new official testing requirements that have been implemented as of the date of this publication.) Assessing biocidal effectiveness of lens care solutions against microorganisms collected from clinically worn lenses and used lens cases is one example of what is called a "real world" scenario. Microorganisms recovered from clinical circumstances are referred to as clinical isolates and represent a variety of microbial strains from the community.

Isolating and testing microorganisms from common environmental/community sources may provide both broader and deeper insights into the biocidal profiles of various lens care products than what is gained from testing against the standard ATCC challenge organisms. It is important to note that employing such test protocols against clinical isolates is not required for marketing approval. Only the required standards establish efficacy and safety of lens care products. Tests against clinical isolates, even though they use the identical protocols applied to testing of standard microorganisms, simply indicate differences in disinfection performance profiles of care products.

MRSA is not included by the standards organizations (ISO and FDA) as one of the lens care solution test panel microorganisms, yet, as we've discussed, MRSA is an increasingly prevalent organism in the community. Testing of the biocidal efficacy of today's leading multipurpose solutions (MPS) and a hydrogen peroxide disinfection solution has revealed notable differences in disinfection performance among the solutions against ocular clinical isolates of Staphylococcus aureus (Figure 2) and methicillin- resistant Staphylococcus aureus (Figure 3).9 Data points at or above the horizontal 3 log reduction line meet the stated stand-alone efficacy requirement established for the standard ATCC challenge organisms.

Figure 2. Contact lens care product performance against Staphylococcus aureus clinical isolates. N = 10 clinical isolates, tested 3 times each.

Figure 3. Contact lens care product performance against methicillin-resistant Staphylococcus aureus. N = 10 MRSA clinical isolates, tested 3 times each.

Yet another difference between how lens care products disinfect is their rate of disinfection. Recalling that 12% of patients did not soak their lenses for the minimum indicated disinfection time or longer,5 a good clinical question might be "how do MPS perform with respect to disinfection efficacy if patients don't follow the manufacturer's minimum soak time instructions?"

From the results of a study that examined the stand-alone disinfection efficacy of five different MPS products at 10, 20 and 30 minutes against various pathogens,10 we gain insights into how the disinfecting profiles may differ between leading care products in this simulated situation of noncompliant behavior for the time periods evaluated. But first, an important caveat to the reader: just like testing of MPS against clinical isolates, the rate of disinfection efficacy is not required for product marketing approval. It is important to note that the study cited here was neither intended to show nor meant to suggest that any MPS be used for less than its labeled, recommended disinfection soak time.

Two of the MPS lens care solutions (renu fresh, formerly ReNu MultiPlus [Bausch & Lomb] and AQuify [CIBA Vision]) showed significantly higher rates of disinfection at 30 minutes against Staphylococcus aureus (ATCC 6538).10 The minimum soak time for most of the leading lens care products to achieve adequate disinfection is 6 hours (minimum), with the exception of one (renu fresh, Bausch & Lomb) that requires only 4 hours (minimum) (Table 1), even against MRSA (Figure 3).

ENCOURAGING COMPLIANCE, PROTECTING PATIENTS

We've offered a brief overview of MRSA and its infection control and treatment in the eyecare practice. Gram-positive bacterial pathogens, particularly staphylococcal species, are some of the most common causes of ocular infections. The prevalence of CA-MRSA is rapidly rising. It is well known that compliance with the steps in proper contact lens care and wearing hygiene, even with the ease of use with MPS, is generally quite low. With questionable compliance, recommending a contact lens solution for your patients that provides strong disinfection (> 3 log reduction) against clinical isolates (even though not specifically required by official ISO/FDA lens care performance standards) of Staphylococcus aureus, and particularly against MRSA, may be in the best interest of your patients and your practice. CLS

Specific References

1. Melton R, Thomas R. 2009 Clinical Guide to Ophthalmic Drugs. Rev of Optom (Suppl), June 15, 2009.
2. Blomquist PH. Methicillin-resistant Staphylococcus aureus infections of the eye and orbit (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2006;104:322–345.
3. Centers for Disease Control and Prevention. Community-associated MRSA information for clinicians. Available at: cdc.gov/ncidod/dhqp/ar_MRSA_ca_clinicians.html# Last accessed November 2009.
4. American Optometric Association, press release, April 2009.
5. Yung AM, Boost MV, Cho P, Yap M. The effect of a compliance enhancement strategy (self-review) on the level of lens care compliance and contamination of contact lenses and lens care accessories. Clin Exp Optom. 2007;90:190-202.
6. American Optometric Association. What you need to know about contact lens hygiene and compliance. Available at: aoa.org/x8024.xml. Last accessed November 2009.
7. Rosenthal RA, Henry CL, Schlech BA. Contribution of regimen steps to disinfection of hydrophilic contact lenses. Cont Lens Anterior Eye. 2004;27:149–156.
8. Tu, EY. Contact lens disinfection systems: recommendations for preclinical testing and development. US Food and Drug Administration Website. 2008. Available at: fda.gov/ohrms/dockets/ac/08/transcripts/2008-4363t1-01.pdf. Last accessed November 2009.
9. David B, Callahan D, McGrath D, et al. Evaluation of multipurpose solutions for in vitro biocidal efficacy against a challenge of ocular clinical isolates including methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis strains. Poster presented during the 2009 meeting of the American Academy of Optometry, 2009.
10. Scheuer C, Zhao F, Erb T, Orsborn G. Multipurpose solutions and rates of biocidal efficacy. Eye Contact Lens. 2009;35:88-91.

General References

• Asbell PA, Sahm DF, Shaw M, Draghi DC, Brown NP. Increasing prevalence of methicillin resistance in serious ocular infections caused by Staphylococcus aureus in the United States: 2000 to 2005. J Cataract Refract Surg. 2008;34:814–818.
• Donshik PC, Ehlers WH, Anderson LD, Suchecki JK. Strategies to better engage, educate, and empower patient compliance and safe lens wear: compliance: what we know, what we do not know, and what we need to know. Eye Contact Lens. 2007;33:430-433.
• FDA/CDRH website. Premarket Notification FDA (510{k}). Guidance Document for Contact Lens Care Products. Available at: fda.gov/cdrh/ode/contlens.pdf. Last accessed November 2009.
• International Standards Organization ISO 14729. Ophthalmic Optics — Contact Lens Care products. Microbiological requirements and test methods for products and regimens for hygienic management of contact lenses, 2001.
• Lapple WJ. Multipurpose solution disinfection performance. In: Contact Lens Solutions: A Performance Review. Rev of Optom, Suppl, p3-6. May 2008.
• Centers for Disease Control and Prevention. Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA). Available at: cdc.gov/ncidod/dhqp/ar_mrsa_ca.html Last accessed November 2009.

Ron Melton, OD, FAAO
Dr. Melton has lectured nationally and internationally on ocular disease and pharmacology at more than 300 continuing medical education meetings. He sits on the editorial boards of Optometric Physician and Primary Care Optometry News and is a contributing editor to Clinical and Refractive Optometry. Dr. Melton has authored or co-authored more than 100 papers on optometry and is the co-author of the annual "Clinical Guide to Ophthalmic Drugs," published by Review of Optometry. He has acted as an investigator in more than 50 clinical research trials. Dr. Melton has been engaged as a consultant for Bausch & Lomb, ICARE, Pfizer and RPS and has been a member of advisory panels for Bausch & Lomb, Pfizer and RPS.

Chris Snyder, OD, MS, FAAO
Dr. Snyder earned a doctorate in optometry, a graduate degree and a residency certificate in contact lens practice from The Ohio State University. He served as an optometrist in the U.S. Navy and was a Professor of Optometry at the University of Alabama at Birmingham (UAB) School of Optometry for more than 24 years where he served as the Director and Chief of the Cornea and Contact Lens Service of UAB EyeCare and practiced optometry in the faculty practice. He has served as a Contributing Editor for Contact Lens Spectrum, as Co-editor of the International Contact Lens Clinic Journal and is the U.S. Regional Editor of the U.K.-based (British Contact Lens Association) indexed journal Contact Lens and Anterior Eye. Dr. Snyder is Director of Professional Relations for Bausch & Lomb U.S. Vision Care and continues an active relationship with UAB as an adjunct professor.

Randall Thomas, OD, MPH, FAAO Dr. Thomas has lectured nationally and internationally on ocular disease and pharmacology at more than 300 continuing medical education meetings. He sits on the editorial boards of Optometric Physician and Primary Care Optometry News and is a contributing editor to Clinical and Refractive Optometry. Dr. Thomas has authored or co-authored more than 100 papers on optometry and is the co-author of the annual "Clinical Guide to Ophthalmic Drugs," published by Review of Optometry. He is on the hospital staff at Northeast Medical Center, where he serves as the Ophthalmic Consultant to the Diabetes Management Committee, and actively teaches on the Cabarrus Family Medicine Residency Faculty. Dr. Thomas has been engaged as a consultant for Bausch & Lomb, ICARE, Pfizer and RPS and has been a member of advisory panels for Bausch & Lomb, Pfizer and RPS.



Contact Lens Spectrum, Issue: February 2010