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High-dose daptomycin an option in cardiac device-related endocarditis

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – High-dose daptomycin appears to be a safe and effective therapeutic option for cardiac implantable electronic device (CIED)-related infective endocarditis due to staphylococci, clinicians from Italy report.

In a small study, they observed that daptomycin at a daily dose greater than 6 mg/kg was associated with “high microbiological responses and clinical success.” They didn’t see any serious treatment-related adverse events.

In a report online in Clinical Infectious Diseases, Dr. Riccardo Utili and colleagues from University of Naples and Monaldi Hospital note that the incidence of CIED infections has increased disproportionately more than the rate of new implants.

“The major challenges of CIED endocarditis are the rapid development of bacterial biofilms on the intravascular leads that are relatively impermeable to antimicrobial agents as well as the overall poor cardiac performance, often associated with significant medical comorbidities, of those affected,” they write.

Management involves removing the hardware and appropriate long-term antimicrobial treatment. Daptomycin, at the dose of 6 mg/kg/day, has demonstrated efficacy in staphylococcal endocarditis, but limited data exist on CIED endocarditis. It’s unknown whether higher doses could be more effective but equally safe in this setting.

Dr. Utili’s team recently treated 25 patients with CIED endocarditis due to staphylococci with daptomycin at a median daily dose of 8.3 mg/kg (range, 6.4 to 10.7 mg/kg) for a median of 20 days (range 8 to 52 days).

Overall, clinical success with complete cure was achieved in 20 patients (80%) and complete microbiological success was achieved in 23 patients (92%). Two patients (8%) failed treatment. No patient died from the infection.

The cohort was made up largely of elderly white men with large lead vegetations. The infected CIED was a pacemaker in 68% and a defibrillator in 32% of cases. All patients had staphylococcal species isolated from blood cultures and/or removed from intracardiac leads.

Pathogens were Staphylococcus epidermidis (56%), Staphylococcus aureus (28%), and other coagulase-negative staphylococci (16%). Most patients (88%) had a history of fever.

There was a high prevalence of methicillin-resistant staphylococcal isolates as well as a predominance of patients with impaired renal function. “Our clinical experience suggests that in patients with CIED endocarditis due to staphylococci, a setting where vancomycin may fail or be toxic, high-dose daptomycin may produce good clinical responses with no significant adverse events,” Dr. Utili and colleagues say.

High-dose daptomycin did not cause clinically significant adverse events or biochemical abnormalities and was well tolerated. The renal toxicity profile, they note, was “very good overall” and no significant reductions in glomerular filtration rates were observed. No patient had to discontinue treatment due to muscle toxicity.

Based on their experience, Dr. Utili and colleagues think high-dose daptomycin “deserves further consideration in CIED endocarditis,” especially if caused by methicillin-resistant staphylococcal strains and when vancomycin fails. They suggest studies looking at different doses and schedules in this patient population.


High-Dose Daptomycin for Cardiac Implantable Electronic Device–Related Infective Endocarditis

Clin Infect Dis 2011.