Safety of treatment with high-dose daptomycin in 102 patients with infective endocarditis.
Daptomycin is commonly used at doses >6 mg/kg/day for various indications, including infective endocarditis (IE). A systematic assessment of skeletal muscle, renal, haematological, hepatic and pulmonary toxicity of high-dose daptomycin (HDD) in IE is lacking. A total of 102 IE patients treated with HDD were included in this non-comparative, observational, single-centre cohort study conducted from 2007 to 2014. The incidence, timing, severity and evolution of adverse events (AEs) were assessed. Patients had a median age of 61.5 years and a high prevalence of co-morbidities. Staphylococci were cultured in 87.2% of cases (62.2% meticillin-resistant). The median daptomycin dose was 8.2 mg/kg/day for a median of 20 days (range, 1-60 days). HDD was withdrawn due to AEs in 12 patients (11.8%). On-treatment death occurred in 4 cases (3.9%, none HDD-related). Muscle toxicity occurred in 15 patients in a median of 15 days after HDD starts, which was largely mild and reversible with ongoing HDD use. Mild renal toxicity was observed in 9 patients (8.8%) after a median of 12 days of HDD (RIFLE-Risk in 8, Injury in 1). A rise of peripheral blood eosinophils occurred in 16 patients (15.7%). There were three cases of eosinophilic interstitial pneumonia. Four patients (3.9%) had mild allergic or idiosyncratic reactions. No other hepatic or haematological AEs were observed. Our current experience with 102 patients suggests that HDD is safe in significantly ill IE patients with multiple co-morbidities. Muscle toxicity was clinically negligible. Most importantly, there was no significant renal toxicity. Eosinophils should be carefully monitored.
Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N., Naples, Italy; Unit of Infectious & Transplant Medicine, 'V. Monaldi' Hospital, AORN dei Colli, Naples, Italy. Electronic address: emanuele.durante@unina2.it.
Emanuele
E
Durante-Mangoni
Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N., Naples, Italy.
Roberto
R
Andini
Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N., Naples, Italy.
Antonio
A
Parrella
Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N., Naples, Italy.
Irene
I
Mattucci
Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N., Naples, Italy.
Giusi
G
Cavezza
Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N., Naples, Italy.
Alessandra
A
Senese
Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N., Naples, Italy.
Claudia
C
Trojaniello
Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N., Naples, Italy.
Roberta
R
Caprioli
Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N., Naples, Italy.
Maria Veronica
MV
Diana
Internal Medicine, Department of Cardiothoracic Sciences, University of Naples S.U.N., Naples, Italy; Unit of Infectious & Transplant Medicine, 'V. Monaldi' Hospital, AORN dei Colli, Naples, Italy.
Riccardo
R
Utili
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D017576:Daptomycin / Q000009:adverse effects* / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology*; D004696:Endocarditis / Q000188:drug therapy*; D004802:Eosinophilia / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000473:pathology; D011446:Prospective Studies; D055815:Young Adult
D000900:Anti-Bacterial Agents; D017576:Daptomycin
Daptomycin; Endocarditis; Safety