Best alternative to vancomycin for serious methicillin-resistant Staphylococcus aureus infections: let's just say it.

To the Editor—The recently published articles by Patel et al [1], Kullar et al [2], and Lubin et al [3] persuasively bolster the growing consensus opinion that the goldstandard antimicrobial agent for treatment of serious infections involving methicillinresistant Staphylococcus aureus (MRSA), vancomycin, has become tarnished. Undeniably, these works add to what clearly has become fact: 1) the prevalence of MRSA infections, both inpatient and outpatient, has greatly increased to the point of dominance (inpatient infections); 2) serious infections with MRSA are associated with significantly higher morbidity, mortality, lengths of hospital stay, and total costs, especially when inadequately treated; 3) the rising minimal inhibitory concentration (MIC) of vancomycin against MRSA greatly hinders this drug from achieving the agreed-on required pharmacodynamic parameter (eg, ratio of the area under the concentration–time urve to MIC [AUC/ MIC] $400) necessary for adequate bactericidal activity; 4) automated susceptibility testing methods do not accurately reflect the higher MICs produced with standardized methods such as microbroth dilution and E test; and 5) targeting higher serum trough vancomycin levels (15–20 mg/L) to attain an AUC/ MIC $400, as recently recommended in a summary report [4], carries with it a higher probability of drug-induced nephrotoxicity. In light of this information, it is suggested that alternative anti-MRSA agents be considered in treating known or suspected serous MRSA infections, particularly bacteremia. Unfortunately, for the practicing clinician, neither these articles, nor the recently published clinical practice guidelines by the Infectious Diseases Society of America (IDSA) for the treatment of MRSA infections in adults and children [5], offer an opinion as to what actually is, or likely would be, the best alternative anti-MRSA agent. Acknowledging the absence of evidence from any head-to-head clinical trials among the relatively new antimicrobial agents with approved MRSA treatment indications (eg, quinupristin– dalfopristin, linezolid, daptomycin, tigecycline, telavancin, and ceftaroline), the most we may say is that based on the predetermined primary clinical efficacy endpoint of resolution of signs and symptoms, such that no further antimicrobial therapy was required at the testof-cure visit, for the treatment of acute bacterial skin and skin-structure infections (ABSSSI, formerly termed complicated skin and skin-structure infections [cSSSI]) involving Gram-positive microorganisms, including MRSA, each of these agents was noninferior to vancomycin. However, a post hoc analysis of treatment duration among patients achieving clinical success with intravenous therapy alone in the phase 3 trials (cSSSI) involving daptomycin revealed that 63% of patients given daptomycin required only 4–7 days of therapy compared with 33% of patients in the comparator arm that included vancomycin (P , .0001) [6]. Although the 3 days of comparative analysis now required in ABSSSI trials