title: High rate of decreasing daptomycin susceptibility during the treatment of persistent Staphylococcus aureus bacteremia.
abstract: Daptomycin is bactericidal against Staphylococcus aureus, with susceptibility defined as a minimal inhibitory concentration (MIC) < or =1 microg/ml. Higher MIC developed in a few cases during therapy. The frequency of MIC rise in persistent bacteremia is unknown. We evaluated all patients with S. aureus bacteremia (SAB) treated with daptomycin (> or =2 days) from 1 April 2004 to 30 October 2006. All patients with post-daptomycin-exposure saved isolates were studied. Daptomycin susceptibility was determined (in duplicate) on all pre- and post-daptomycin-exposure isolates by the broth (Mueller-Hinton) microdilution method. Among 74 treatment courses in 67 patients, 18 were for SAB. Ten had persistent bacteremia (median = 11 days; range = 1-21) and post-daptomycin-exposure saved isolates. The patient age was 29-84 years (median = 57.5 years). Intravascular catheter was the most common source (50%). Most patients (90%) failed therapy prior to starting daptomycin. The initial daptomycin dose was 4 mg/kg in four (40%) cases. The pre-exposure MIC was 0.125-0.5 microg/ml. The post-exposure MIC increased in four cases and was elevated in two cases (60%), to 2 microg/ml in five and 4 microg/ml in one. MIC rise was noted within 5-15 days of exposure and persisted up to 247 days after stopping daptomycin. Pulse-field gel electrophoresis (PFGE) band pattern of isolates with increased MIC revealed 1-3-band differences, implying genetic relatedness. All patients with non-susceptible isolates relapsed or failed therapy. These findings illustrate that daptomycin susceptibility often decreases during the treatment of persistent SAB. Therefore, susceptibility should be closely monitored during therapy.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, St. John Hospital & Medical Center, 22101 Moross Road, Detroit, MI 48236, USA. mamta.sharma@stjohn.org
authors.forename: M
authors.initials: M
authors.lastname: Sharma
authors.forename: K
authors.initials: K
authors.lastname: Riederer
authors.forename: P
authors.initials: P
authors.lastname: Chase
authors.forename: R
authors.initials: R
authors.lastname: Khatib
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000188:drug therapy*; D017576:Daptomycin / Q000494:pharmacology / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D017576:Daptomycin