Clinical Rationale for Treatment of Endocarditis Caused by Methicillin-Susceptible Staphylococcus aureus Developing Nonsusceptibility to Daptomycin

Abstract

A recent case report by Sakoulas et al. demonstrated acquired daptomycin (lipopeptide) resistance in an immunecompetent adult patient with native valve endocarditis due to methicillin-susceptible Staphylococcus aureus (MSSA) (8). Daptomycin resistance developed following exposure to levofloxacin and vancomycin prior to daptomycin treatment. The observation that vancomycin exposure may induce resistance mechanisms in staphylococcal species is consistent with another recent report in which vancomycin exposure was accompanied by decreased expression of agr, resulting in resistance to platelet microbicidal proteins (6). It is believed that daptomycin’s mechanism of action involves functional disruption of the bacterial plasma membrane (1, 4, 7). However, what is most striking about the article is the impression that the patient was not managed optimally. Nafcillin/ cloxacillin (with/without an aminoglycoside) would be widely accepted as the drug of choice to treat MSSA native valve endocarditis; comparative studies have confirmed cloxacillin/ nafcillin to have superior efficacy to vancomycin in patients with MSSA bacteremia (2, 5). Despite confirmation that the offending organism was methicillin sensitive, the patient was first managed on levofloxacin and then switched to vancomycin. Following a poor response to vancomycin, the patient was placed on nafcillin for a very brief period (3 days only), before switching to daptomycin monotherapy. The clinical rationale applied is not explained in the methods section nor taken up in the discussion. Resistance to daptomycin was documented after 6 to 7 days of treatment. Only after 17 days of antibiotic treatment did the patient receive a prolonged course of nafcillin and gentamicin. Unfortunately, the patient’s mitral valve was destroyed by the time infection was brought under control and he underwent successful valve replacement, which remains a suboptimal outcome. It would be interesting to know why first vancomycin and then daptomycin were regarded as the drugs of choice to treat a patient with MSSA bacteremia. According to the clinical trial (3) of daptomycin versus standard therapy of S. aureus bacteremia and right-sided endocarditis referred to in the report by Sakoulas et al., success rates favored daptomycin over vancomycin among patients with methicillin-resistant S. aureus but were higher for MSSA infection treated with an antistaphylococcal penicillin (nafcillin, oxacillin, or flucloxacillin) compared to daptomycin. Despite the fact that one of the authors is affiliated with the company producing daptomycin, no conflict of interest was declared. We believe it is essential that every publication should include a conflict of interest statement. This article demonstrates the importance of ensuring transparency in order to protect the best interests of our patients.