PharmD Case :MRSA Endocarditis

JM is a 46-year-old man with a history of actively abusing cocaine intravenously who presented with methicillin-resistant Staphylococcus aureus (MRSA) endocarditis (vegetation on tricuspid valve per TEE). After 7 days of IV vancomycin therapy (with troughs in the 15 to 20 mcg/mL range), JM’s blood cultures remain positive for MRSA, and the microbiology laboratory reports a vancomycin minimum inhibitory concentration (MIC) of 2 mcg/mL. What treatment options are available for this patient?

Vancomycin has been the mainstay of therapy for MRSA bacteremia and endocarditis. Vancomycin is recommended for the treatment of MRSA endocarditis by both the Infectious Diseases Society of America (IDSA) guidelines for the treatment of MRSA infections and the American Heart Association Infective Endocarditis guidelines.1,2 The IDSA guideline also recommends daptomycin as an alternative to vancomycin on the basis of a randomized controlled trial where daptomycin was noninferior to low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin in the treatment of S aureus bacteremia and endocarditis.1,3

The Clinical and Laboratory Standards Institute (CLSI) decreased the vancomycin MIC breakpoint for S aureus from ≤4 mcg/mL to ≤2 mcg/mL in 2006. However, data from several studies have noted an association between vancomycin MICs >1 mcg/mL and vancomycin treatment failure.4-6 The association between higher vancomycin MICs and clinical failures has even been noted in patients with methicillin-susceptible S aureus who received treatment with beta-lactam therapy.7 The IDSA MRSA treatment guidelines state that “if the patient has not had a clinical or microbiologic response to vancomycin despite adequate debridement and removal of other foci of infection, an alternative to vancomycin is recommended regardless of MIC.”1 Although there is controversy regarding the utility of vancomycin when the MIC is >1 mcg/mL, in a case such as this one, regardless of MIC an alternative treatment is indicated given JM’s treatment failure evidenced by persistently positive blood cultures.

There is a scarcity of robust data available to guide treatment choices at this point. Daptomycin is FDA approved for S aureus bacteremia and right-sided endocarditis. Other agents that can be used for MRSA when the MIC for vancomycin is >2 mcg/ mL include ceftaroline, linezolid, quinupristin/ dalfopristin, tigecycline, and telavancin; however, none of these agents are FDA approved for these indications, and consideration must be given to the site of infection and patient-specific factors.
In the case of vancomycin failure, it is important to obtain an MIC for daptomycin before initiating therapy, as daptomycin resistance has been seen in MRSA isolates with elevated vancomycin MICs.8 In this case, the daptomycin MIC was reported as 0.5 mcg/mL, and the patient was successfully treated with a 6-week course of daptomycin. This case highlights the importance of the relationship between pharmacy and the microbiology laboratory to utilize available information such as MIC data to guide treatment choices.

1. Liu C, Bayer A, Cosgrove S, et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:1-38.
2. Baddour L, Wilson W, Bayer A, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications. Circulation. 2005;111:e394-e433.
3. Fowler VG, Boucher HW, Corey GR, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureusN Engl J Med. 2006;355:653-665.
4. Lodise TP, Graves J, Evans A, et al. Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin. Antimicrob Agents Chemother. 2008;52:3315-3320.
5. Soriano A, Marco F, Martinez JA, et al. Influence of vancomycin minimum inhibitory concentration on the treatment of methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis. 2008;46:193-200.
6. Sakoulas G, Moise-Broder PA, Schentag J, et al. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcal aureus bacteremia. J Clin Microbiol. 2004;42:2398-2402.
7. Holmes N, Turnidge J, Munckhof W, et al. Antibiotic choice may not explain poor outcomes in patients with high vancomycin MIC Staphylococcus aureus bacteremia. J Infect Dis. 2011;204:340-347.
8. Patel JB, Jevitt LA, Hageman J, McDonald LC, Tenover FC. An association between reduced susceptibility to daptomycin and reduced susceptibility to vancomycin in Staphylococcus aureusClin Infect Dis. 2006;42:1652-1653.