clinical care

MRSA and The Eye

Learn who's at risk for this dangerous infection and how to treat and prevent it.

BRUCE E. ONOFREY, O.D., R.Ph., F.A.A.O., Albuquerque, NM

Methicillin-resistant staphylococcus aureus (MRSA) ocular disease is, unfortunately, on the rise. In fact, a study that evaluated the nationwide prevalence of MRSA ocular infections from January 2000 through December 2005 (the most recent ocular data) revealed that MRSA eye infections increased from 30% in 2000 to 42% in 2005.¹ Further, these isolates were multi-drug resistant, and most importantly, resistant to all fluoroquinolones.

MRSA ocular disease is comprised of preseptal cellulitis and/or lid disease; conjunctivitis; corneal ulcers; endophthalmitis; orbital cellulitis; blebitis; blepharoconjuctivitis; dacryocyctitis and keratitis^2,3 Ocular infections that occur in the postoperative period are the most devastating, as they include post-LASIK keratitis, post-cataract endophthalmitis and post-filter blebitis.² Research has shown that contact lens wear is a risk factor for the development of bacterial keratitis, and overnight contact lens use can increase the incidence of bacterial keratitis by 10 to 15 times.⁴

MRSA dacryocystitis.

Because MRSA ocular disease can lead to blindness and even death (the pathogen can enter the blood stream), it's essential we, as eyecare practitioners, understand what it is, who's at risk and how to effectively treat and prevent it.

What is MRSA

S. aureus is one of the most common gram-positive bacteria in our environment. In addition to being a significant cause of ocular disease, it's also responsible for infectious conditions, such as cellulitis, impetigo, bacteremia, endocarditis, wound infections and pneumonia.^5,6

S. aureus that is resistant to the synthetic penicillins (methicillin, oxacillin, naficillin, cloxacillin, dicloxacillin and amoxicillin [+] clavulanate and the cephalosporins) is known as MRSA.

Penicillin was highly effective in killing S. aureus until 1944, when a report revealed resistance.⁶ The bacteria had produced the enzyme penicillinase (beta-lactamase). This enzyme attacks the B-lactam ring — a critical element of the penicillin molecule — enabling S. aureus, and other penicillinase-producing bacteria, such as Bacillus anthracis, to inactivate the antimicrobial effect of penicillin.⁶ Four years later, resistance was so pervasive, that it seriously limited the therapeutic value of the early penicillins (i.e. penicillin G and penicillin V).⁶

Methicillin — the first semi-synthetic penicillin — rapidly became the "gold standard" for treating penicillin-resistant S. aureus in 1960.² The drug was B-lactamase resistant, making it effective against infections created by penicillinase-producing bacteria. Methicillin acted as a cell wall inhibitor to penicillin-resistant S. aureus. This mechanism is dependent on the ability of the drug to bind to and competitively inhibit the transpeptidase enzymes (collectively known as "penicillin-binding proteins [PBPs]) that are used to cross-link the peptide D-alanylalanine.⁷ Methicillin and the other B-lactamase-resistant drugs that soon followed (i.e. oxacillin, nafcillin, cloxacillin, dicloxacillin, amoxicillin [+], clavulanate and the cephalosporins) are structural analogs of this peptide and were, therefore, able to inhibit these enzymes.

Unfortunately, strains of MRSA were first detected in 1961.² The penicillin-resistant S. aureus produced altered PBS. Because the drugs could no longer bind to transpeptidase, the bacteria became resistant to the aforementioned B-lactamase-resistant drugs. The first documented U.S. outbreak of nosocomial MRSA was in 1968 at Boston City Hospital in Boston.⁸ (Currently, nosocomial strains are present in approximately 50% of hospital Staph. isolates in the United States.²) Healthcare professionals classified MRSA as nosocomial if the infected patient was hospitalized at least 48 hours prior to culturing, in the previous six months or developed the infection after exposure to medical waste.⁸

By the 1970s, MRSA began to appear in non-hospital settings.² Beginning in the mid-1990s, the U.S. media began reporting on socomial MRSA, or community-acquired MRSA (CA), infections, particularly in children.² Because CA-MRSA often looks like an insect bite or pimple, clinicians commonly mistook and continue to mistake the infection for these anomalies.

A 50 year-old presented to my practice with culture-positive MRSA orbital cellulitis.

One recent study revealed that CA-MRSA has become the most frequent cause of skin and soft tissue infections presenting to U.S. emergency rooms.³ In fact, new strains of S. aureus that have unique combinations of virulence factors and resistance traits have been linked with both high mortality and morbidity in the community.⁹ Of particular note: Outbreaks of epidemic furunculosis and cases of severe invasive pulmonary infections in young, otherwise healthy people.⁹

Further, a study that evaluated the presence of MRSA between 2000 and 2004 in a hospital revealed that of the 3,640 patients culture positive for the pathogen, 70% had CA-MRSA.² No evidence exists that exposure to contaminated water sources (river, seawater or pool water) produced an increased risk of CA-MRSA vs. HA-MRSA.¹⁰ The fact is, that certain risk factors, discussed below, led to CA-MRSA.

The CA-MRSA strains' resistance is limited to penicillin therapy.⁶ In general, the nosocomial strains have tended to exhibit multi-drug resistance. This includes not only the synthetic penicillins, but also the cephalosporins (i.e. cephalexin, cephazolin and cephradine); macrolides (erythromycin, azithromycin and clindamycin); some aminoglycosides (i.e. gentamycin and tobramycin) and all the fluoroquinolones.

As with MRSA ocular disease, MRSA-related illness in general is on the rise. For instance, one study revealed that from 1999 through 2005 (the most recent), estimated MRSA-related hospital stays more than doubled from 127,036 to 278,203.¹¹ Further, the largest increase in MRSA-related hospital stays involved infections outside the lungs or blood. And, these almost tripled from 65,361 to 185,415.¹¹

Who's at risk

S. aureus thrives on human skin and mucous membranes (it commonly resides in the nose), grows rapidly under aerobic or anaerobic conditions and is primarily transmitted through direct person-to-person contact. Airborne spread is extremely rare.⁵

Hospital-based infections are more commonly associated with prior antibiotic usage, health problems, such as chronic conditions (i.e. heart disease) or any condition that affects immunity (i.e. pneumonia) and recent hospitalization.¹² Risk factors that contribute to the propagation of CA-MRSA include a history of a roommate with prior skin infections, such as impetigo, and/or family member or friend who works in a healthcare setting.

Researchers have estimated that 30% to 50% of individuals colonize this organism, and up to 20% are chronic carriers.⁶ Colonization becomes an issue in two circumstances.

1. When the carrier experiences a skin trauma, such as a surgical incision, abrasion or cut. This gives the bacteria an opportunity to enter the body and cause infection. As a result of this circumstance, you should identify and treat any carrier who's about to undergo ophthalmic surgery. You can identify carriers by obtaining nasal swabs. You can then test isolates for the presence of MRSA strains.

2. When the carrier comes in contact with an individual who's had a skin trauma, particularly someone who has reduced immunity. This can include the elderly, those who have HIV, etc.

Hospital workers, due to increased exposure to S. aureus, tend to carry MRSA in greater numbers than the general population.¹³ In fact, an investigation following the 1968 MRSA outbreak in Boston City Hospital revealed that the major spread of the disease resulted from hospital caregivers' hands.⁸ Others at risk for colonization: family members of carriers, children in nurseries and neonatal intensive care units and those who reside in long-term care facilities, such as nursing homes and prisons.¹³ These environments contain individuals with pre-existing conditions that lead to the risk of colonization in close proximity (in some cases crowding) as well as the potential for the spread from care-givers that don't practice good hygiene.

Other MRSA risk factors: cancer, hepatitis C, IV drug abuse, diabetes, male gender, black race (possibly because they have high rates of chronic illness); and low socioeconomic status.

Treatment

We, as clinicians, commonly treat ocular and periocular infections empirically (without culture). That being said, lack of clinical response to broad-spectrum antibiotic therapy within the expected time frame should always lead you to collect cultures for the identification of the pathogen and, therefore, the determination of the antibiotic sensitivity. I've found that S. aureus grows well on Blood Agar plates. Once the colony reveals itself, you can test it to determine whether it's coagulase positive. Sensitivity testing will assist you in choosing an appropriate antibiotic regimen.

So, what drug should you use to eradicate MRSA ocular diseases? One study, which compared the clinical features and antibiotic susceptibility of ocular MRSA and methicillin-sensitive S. aureus (MSSA) revealed that 14.8% of MRSA isolates were sensitive to ciprofloxacin and erythromycin; 63.6% were sensitive to bacitracin; 93.2% were sensitive to tetracycline; 97.7% to sulfisoxazole and 100% to vancomycin.¹⁴

Topical vancomycin can be prepared in a concentration that ranges from 25 to 50mg/ml. A caveat: S. aureus infections resistant to vancomycin are beginning to emerge, so only prescribe the drug for MRSA infections and for infections, in which other antibiotics fail.¹¹

Also, a study known as Ocular TRUST (Tracking Resistance in United States Today) revealed that the only effective treatment against MRSA was trimethoprim.⁷ Ocular TRUST annually evaluates in vitro antimicrobial susceptibility of S. aureus, Streptococcus pneumoniae and Haemophilus influenzae to ciprofolaxacin, gatifloxacin, levofloxacin, moxifloxacin, penicillin, azithromycin, tobramycin, trimethoprim and polymixin B in national samples of ocular isolates.

Prevention

When a patient presents with any type of ocular infection, you must protect yourself and your other patients from possible spread of infection. This is particularly important now, considering the current magnitude of CA-MRSA. You should adhere to these preventative measures:

1. Always cover any traumas to the skin with a clean, dry bandage, until the trauma has fully healed.

2. Always wash your hands in between patients. Hand washing is the single-most important factor in the prevention of MRSA spread, as it removes transient microorganisms from the hands.² Chlorhexidine gluconate offers low toxicity and broad antimicrobial spectrum. ² Not only should you wash your hands in between patient encounters, but also immediately after contact with different anatomic sites on the same patient. An example would be after touching the pre-auricular area for evidence of lymphadenopathy and continuing with the rest of the exam. Also, wash after contact with inanimate objects within the immediate vicinity of patients.² Finally, wash prior to eating and before leaving work.

3. Wear gloves. Always wear gloves when you expect contact with body fluids i.e. (blood, tears), open wounds or sores, and replace these gloves with every new patient encounter.

4. Use a mask. This prevents the nasal passage of MRSA.²

5. Properly disinfect equipment, instruments and work surfaces. Use an appropriate Environmental Protection Agency (EPA)-approved disinfectant after every exam. The Centers for Disease Control recommends you clean surfaces of exam rooms with a commercial disinfectant or a 1:100 solution of diluted bleach (one tablespoon bleach in one quart of water.)¹⁵ Further, have your staff members wear gloves while cleaning the work area and handling potentially contaminated instruments to prevent pathogen spread. Finally, make sure you and your staff properly dispose of any contaminated waste to prevent the infection spread to cleaning and maintenance personnel.

• Establish contact isolation measures for patients whom you know are either S. aureus carriers or have a MRSA infection.² For instance, you may want to dedicate one exam lane for these patients to isolate them.²

Finally, several strategies exist that may have value in the prevention of postoperative MRSA. (See "Post-op MRSA Prevention Strategies," above.)¹⁶

Since MRSA ocular disease is on the rise, we, as eyecare practitioners, must be more vigilant than ever in identifying it, effectively treating it and limiting its spread. Our involvement not only means the difference between sight and blindness for many of these patients, but life and death as well. OM

1. Asbell PA, Sahm DF, Shaw M, et al. Increasing prevalence in serious ocular infections caused by Staphylococcus aureus in the United States: 2000 to 2005. J Cataract Refract Surg. 2008 May;34(5):814-8.

2. Blomquist PH. Methicillin-resistant Staphylococcus aureus infections of the eye and orbit (An American Ophthalmological Society Thesis). Trans Am Ophthalmol Soc. 2006;104:322-45.

3. Klevins RM, Morrison MA, Nadle J, et al. Invasive methicillin resistant Staphylococcus aureus infections in the United States. JAMA. 2007 Oct 17;298(15):1763-71.

4. Cheng KH. Leung SL, Hoekman HW, et al. Incidence of contact-lens associated microbial keratitis and its related morbidity. Lancet 1999 Jul 17;354(9174):181-5.

5. Bradley SF, Terpenning MS, Ramsey MA, et al. Methicillin-resistant Staphylococcus aureus: colonization and infection in a long-term care facility. Ann Intern Med. 1991 Sep 15;115(6):417-22.

6. Gladwin M, Trattler B. Staphylococcus. In: Gladwin M, ed. Clinical Microbiology. 3rd ed. Miami, FL: Medmaster; 2004: 22-30

7. Mitcher LA. Chemotherapeutic agents: antibiotics and antimicrobial agents. In: Lemke TL. ed. Medicinal Chemistry. 6th ed. Philadelphia, PA: Lippincott WW, 2007:1028-1081.

8. Asbell PA Colby KA Deng S, et al. Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates. Am J Ophthalmol. 2008 Jun;145(6):951-58.

9. Barrett FF, McGehee RF Jr, Finland M. Methicillin-resistant Staphylococcus aureus at Boston City Hospital. Bacteriologic and epidemiologic observations. N Engl J Med. 1968 Aug 29;279(9):441-8.

10. Zetola N, Francis JS, Nuermberger EL, Bishai WR. Community-acquired methicillin staphylococcus aureus: an emerging threat. Lancet Infect Dis. 2005 May;5(5):275-86.

11. Tolba O, Loughrey A, Goldsmith CE, et al. Survival of epidemic strains of healthcare (HA-MRSA) and community-associated (CA-MRSA) methicillin-resistant Staphylococcus aureus (MRSA) in river-, sea- and swimming pool water. Int J. Hyg Environ Health. 2008 Jul;211(3-4):398-402.

12. Klein E., Smith DL, Laxminarayan R. Hospitalizations and deaths caused by methicillin-resistant staphylococcus aureus, United States, 1999-2005. Emerg Infect Dis. 2007 Dec;13(12):1840-6.

13. Campbell KM, Vaughn AF, Russell KL, et al. Risk factors for community-associated methicillin-resistant Staphylococcus aureus infections in an outbreak of disease among military trainees in San Diego, California, in 2002. J. Clin. Microbiol. 2004 Sep;42(9):4050-3.

14. Freidlin J, Acharya N, Lietman TM, et al. Spectrum of eye disease caused by methicillin-resistant staphylococcus aureus. Am J Ophthalmol. 2007 Aug;144(2):313-5.

15. Methicillin Resistant Staphyloccocus Aureus (MRSA): Information for clinicians. http://emergency.cdc.gov/disasters/disease/pdf/mrsainfoclinicians.pdf Accessed December 20, 2008.

16. Olson RJ. Reducing the risk of postoperative endophthalmitis. Surv Ophthalmol. 2004 Mar;49 Suppl 2:S55-61.

Dr. Onofrey practices at Lovelace Medical Center and has served as the Chief of Optometry and Vice-chair of Eye Services since 2002. Faculty appointments include adjunct status at the University of California-Berkeley-College of Optometry, Pacific University and the University of Houston. In addition, he is the current editor of "Clinical Optometric Pharmacology and Therapeutics" and the author of "The Ocular Therapeutics Handbook-A Clinical Manual." E-mail him at Eyedoc3@aol.com.