Multicenter evaluation of the clinical outcomes of daptomycin with and without concomitant β-lactams in patients with Staphylococcus aureus bacteremia and mild to moderate renal impairment

Abstract

Patients with underlying renal disease may be vulnerable to vancomycin-mediated nephrotoxicity and Staphylococcus aureus bacteremia treatment failure. In light of recent data demonstrating the successful use of β-lactam plus daptomycin in very difficult cases of S. aureus bacteremia, we examined safety and clinical outcomes for patients who received daptomycin with or without concomitant β-lactams. We identified 106 patients who received daptomycin for S. aureus bacteremia, had mild or moderate renal insufficiency according to FDA criteria, and enrolled in the Cubicin Outcomes Registry and Experience (CORE), a multicenter registry, from 2005 to 2009. Daptomycin treatment success was 81%. Overall treatment efficacy was slightly enhanced with the addition of a β-lactam (87% versus 78%; P = 0.336), but this trend was most pronounced for bacteremia associated with endocarditis or bone/joint infection or bacteremia from an unknown source (90% versus 57%; P = 0.061). Factors associated with reduced daptomycin efficacy (by logistic regression) were an unknown source of bacteremia (odds ratio [OR] = 7.59; 95% confidence interval [CI] = 1.55 to 37.2), moderate renal impairment (OR = 9.11; 95% CI = 1.46 to 56.8), and prior vancomycin failure (OR = 11.2; 95% CI = 1.95 to 64.5). Two patients experienced an increase in creatine phosphokinase (CPK) that resolved after stopping daptomycin. No patients developed worsening renal insufficiency related to daptomycin. In conclusion, daptomycin appeared to be effective and well tolerated in patients with S. aureus bacteremia and mild to moderate renal insufficiency. Daptomycin treatment efficacy might be enhanced with β-lactam combination therapy in primary endovascular and bone/joint infections. Additional studies will be necessary to confirm these findings.

Figures

Fig 1

Daptomycin treatment success based on source of Staphylococcus aureus bacteremia, with and without β-lactam therapy. Dark gray bars represent all patients who received daptomycin either with or without a β-lactam. The light gray bars represent the subset of patients who received daptomycin with a β-lactam, and the black bars show the subset who received daptomycin without a β-lactam. When data were stratified by source of bacteremia, a statistical difference in daptomycin treatment success was not seen with the addition of a β-lactam: P = 1.00 for skin, P = 0.757 for central venous catheter, P = 0.333 for bone/joint, P = 0.470 for biomedical device, P = 1.0 for endocarditis, and P = 0.197 for unknown source.

Fig 2

Daptomycin treatment success in S. aureus bacteremia, stratified by concomitant β-lactam use and risk of failure by logistic regression. The dark gray bars represent all patients who received daptomycin either with or without a β-lactam. The light gray bars represent the subset of patients who received daptomycin with a β-lactam, and the black bars show the subset who received daptomycin without a β-lactam. When data were stratified by characteristic, no statistical difference in daptomycin treatment success was seen with the addition of a β-lactam: P = 0.334 for mild renal insufficiency (CLCR of 30 to 50 ml/min), P = 0.474 for moderate renal insufficiency (CLCR of <30 ml/min, not requiring dialysis), P = 0.361 for no previous vancomycin failure, and P = 0.823 with prior vancomycin failure.

Fig 3

Infection types showing improved daptomycin outcomes with concomitant β-lactam therapy, i.e., infective endocarditis (IE), bone or joint infection (B/J) (without a biomedical device present), or an unknown source of bacteremia. The figure shows daptomycin treatment success for S. aureus bacteremia, stratified by concomitant β-lactam use. The overall daptomycin treatment success rate in this population was 67% (22/33 patients) (dark gray bar), with success rates of 90% (9/10 patients) with the addition of a β-lactam (light gray bar) and 57% (13/23 patients) without a β-lactam (black bar) (P = 0.061).