Patients with persisting or relapsing S. aureus bacteremia/endocarditis or poor clinical response should have repeat blood cultures.  If a blood culture is positive for S. aureus, minimum inhibitory concentration (MIC) susceptibility testing of the isolate should be performed using a standardized procedure, and diagnostic eva luation of the patient should be performed to rule out sequestered foci of infection.  Appropriate surgical intervention (e.g., debridement, removal of prosthetic devices, valve replacement surgery) and/or consideration of a change in antibacterial regimen may be required.

Failure of treatment due to persisting or relapsing S. aureus bacteremia/endocarditis may be due to reduced daptomycin susceptibility (as evidenced by increasing MIC of the S. aureus isolate) [see Clinical Trials (14.2) ].

There are limited data available from the cSSSI clinical trials regarding clinical efficacy of daptomycin treatment in patients with CrCL <50 mL/min; only 31/534 (6%) patients treated with daptomycin in the intent-to-treat (ITT) population had a baseline CrCL <50 mL/min.  Table 2 shows the number of patients by CrCL and treatment group who were clinical successes in the cSSSI trials.

In a subgroup analysis of the ITT population in the S. aureus bacteremia/endocarditis trial, clinical success rates, as determined by a treatment-blinded Adjudication Committee [see Clinical Trials (14.2) ], in the daptomycin-treated patients were lower in patients with baseline CrCL <50 mL/min (Table 3).  A decrease of the magnitude shown in Table 3 was not observed in comparator-treated patients.

Consider these data when selecting antibacterial therapy for use in patients with baseline moderate to severe renal impairment.

Table 2.  Clinical Success Rates by Treatment Group and Renal Function in the Daptomycin cSSSI Clinical Trials (Population: ITT) CrCL  Success Rate
n/N (%)
Daptomycin
4 mg/kg q24h Comparator
50-70 mL/min  25/38 (66%) 30/48 (63%)
30-<50 mL/min  7/15 (47%) 20/35 (57%)
Table 3.  Adjudication Committee Success Rates at TOC Stratified by Baseline Creatinine Clearance in the S. aureus Bacteremia/Endocarditis Trial (Population: ITT) Baseline CrCL  Success Rate
n/N (%)
Daptomycin Comparator
Bacteremia Right-Sided
Infective Endocardtis Bacteremia Right-Sided
Infective Endocardtis
>80 mL/min  30/50 (60%) 7/14 (50%) 19/42 (45%) 5/11 (46%)
50-80 mL/min  12/26 (46%) 1/4 (25%) 13/31 (42%) 1/2 (50%)
30-50 mL/min  2/14 (14%) 0/1 (0%) 7/17 (41%) 1/1 (100%)

Clinically relevant plasma concentrations of daptomycin have been observed to cause a significant concentration-dependent false prolongation of prothrombin time (PT) and elevation of International Normalized Ratio (INR) when certain recombinant thromboplastin reagents are utilized for the assay [see Drug-Laboratory Interactions (7.2) ].

The use of antibacterials may promote the overgrowth of non-susceptible microorganisms.  If superinfection occurs during therapy, appropriate measures should be taken.

Prescribing CUBICIN in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

The following adverse reactions are described, or described in greate