Noted pharmacologist outlines treatment options

Methicillin-resistant Staphylococcus aureus (MRSA) is a rapidly emerging concern for physicians and hospitals. How to deal with it and what new treatment options may soon become available were covered by B. Joseph Guglielmo, PharmD, at the Pediatric Orthopaedic Society of North America 2008 specialty day meeting.

“I have three messages,” said Dr. Guglielmo. “First, the rate of MRSA is increasing. Second, following certain practices will reduce the perioperative risk of MRSA in your patient population, and third, a fairly strong pipeline of gram-positive drugs is being developed and may be introduced by the end of the year.”

MRSA is a real problem
The rate of hospital admissions associated with MRSA infection has doubled in the last 6 years. According to Dr. Guglielmo, community-acquired and hospital-acquired MRSA are crossing back and forth, making it more complicated to identify the point of origination. Also, the one strain of MRSA that is entirely community-based has certain unusual virulence factors that enable it to penetrate unbroken skin.

Attempting decolonization using the antibiotic mupirocin has been shown to be ineffective. One small study that examined the efficacy of mupirocin found that decolonization rates were similar to those with a placebo. Perhaps more importantly, MRSA seems to readily develop mupirocin resistance. A larger trial of 302 isolates at a single facility found that 13.2 percent were mupirocin-resistant, despite a low level of mupirocin use there.

To control MRSA in surgical cases, Dr. Guglielmo recommended limiting the course of postoperative antibiotics to less than 24 hours. He pointed to several studies that found an association between increased risk of MRSA and longer postoperative antibiotic treatments.

“If you continue an antibiotic long enough, it is essentially fertilizer for MRSA,” he said.

Vancomycin
Surgeons also need to pay attention to methicillin-resistant S. epidermidis (MRSE).

“Although MRSA continues to increase, Staph-epi (which loves hardware) has continued at about a rate of 50 percent to 60 percent methicillin-resistant for decades. Because MRSE, methicillin-sensitive S. aureus (MSSA), and MRSA are the most common perioperative pathogens, what should be the prophylactic of choice?” he asked.

Dr. Guglielmo suggested that vancomycin should be considered the drug of choice for patients at risk of MRSA. He explained that vancomycin is 100 percent effective for every type of Staphylococcus commonly encountered and has a long half-life so it shouldn’t need to be readministered intraoperatively during an extended procedure. Adverse events associated with the use of vancomycin include possible development of so-called red man syndrome, and hypotension associated with histamine release, which can complicate the dynamics of getting the patient ready for the surgical procedure. Although the U.S. Centers for Disease Control and Prevention recommends against using vancomycin perioperatively, Dr. Guglielmo pointed out that the recommendation dates back to 1995, and that things are changing rapidly.

Other options
Dr. Guglielmo reviewed some existing and forthcoming treatment options for combating MRSA (Table 1) and discussed a new drug currently in the approval process.

Peter Pollack is a staff writer for AAOS Now. He can be reached at ppollack@aaos.org

References

1. Harbarth S, Dharan S, Liassine N, Herrault P, Auckenthaler R, Pittet D: Randomized, placebo-controlled, double-blind trial to evaluate the efficacy of mupirocin for eradicating carriage of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 1999;43:1412-1416.
2. Jones JC, Rogers TJ, Brookmeyer P, et al: Mupirocin resistance in patients colonized with methicillin-resistant Staphylococcus aureus in a surgical intensive care unit. Clin Infect Dis 2007;45:541-547.
3. Raad I, Darouiche R, Vazquez J, et al: Efficacy and safety of weekly dalbavancin therapy for catheter-related bloodstream infection caused by gram-positive pathogens. Clin Infect Dis 2005;40:374-380.