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Efficacy and safety of daptomycin in patients with renal impairment: a multicenter retrospective analysis.
Pharmacotherapy. 2014 Jun; 34(6):582-9.P

Abstract

STUDY OBJECTIVE

Daptomycin is a therapeutic option for patients with underlying renal insufficiency who are vulnerable to nephrotoxicity from vancomycin. We evaluated the efficacy and safety of daptomycin in patients with renal impairment.

DESIGN

Multicenter, retrospective, observational, case series analysis.

SETTING

Two academic medical centers.

PATIENTS

One hundred and sixty adults with creatinine clearance (Clcr) of 50 ml/minute or less who received daptomycin for at least 72 hours for complicated Gram-positive infections from 2008-2011.

MEASUREMENTS AND MAIN METHODS

Clinical and microbiologic outcomes were assessed at the end of daptomycin therapy. Safety evaluations were documented for all patients, and when available, creatine phosphokinase (CPK) levels were recorded. Thirty-eight (23.8%) patients were on hemodialysis, and 122 (76.3%) had a decreased baseline renal clearance not requiring hemodialysis with a median interquartile range (IQR) Clcr of 32.4 ml/minute (24.2-40.4 ml/min). The median (IQR) daptomycin dose was 6.0 mg/kg (5.8-7.8 mg/kg) administered every 24 hours in 68 patients (42.5%) and every 48 hours in 92 patients (57.5%). Daptomycin success, including cure or improvement, (Cure: signs and symptoms resolved and no additional antibiotic therapy required, or infection cleared with negative cultures reported at the end of daptomycin therapy; Improvement: partial resolution of signs and symptoms and additional antibiotic therapy necessary at the end of daptomycin therapy) was achieved in 128 of 160 (80.0%) patients at the end of therapy. Methicillin-resistant Staphylococcus aureus (MRSA) was the most common pathogen (45%) isolated. The most frequent reason for using daptomycin was due to vancomycin-associated nephrotoxicity (20%). Daptomycin therapy was discontinued in six patients (3.8%) because of elevated CPK (median time to onset, 11.5 days). Loss of daptomycin susceptibility occurred in two patients with complex endovascular infections who were on hemodialysis.

CONCLUSIONS

Daptomycin demonstrated clinical and microbiologic success rates comparable with prior studies. Discontinuation of therapy because of elevated CPK levels may have been avoided in some patients with adjustment to every 48-hour dosing for Clcr less than 30 ml/minute. The relatively early time to onset suggests the need for CPK monitoring more frequently than once/week in renally impaired patients receiving daptomycin. The treatment of bacteremia in patients with renal insufficiency warrants further study.

Authors+Show Affiliations

Department of Medical Affairs, Cubist Pharmaceuticals, Lexington, Massachusetts; College of Pharmacy, Oregon State University/Oregon Health and Science University, Portland, Oregon.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

24658897

Citation

Kullar, Ravina, et al. "Efficacy and Safety of Daptomycin in Patients With Renal Impairment: a Multicenter Retrospective Analysis." Pharmacotherapy, vol. 34, no. 6, 2014, pp. 582-9.
Kullar R, McClellan I, Geriak M, et al. Efficacy and safety of daptomycin in patients with renal impairment: a multicenter retrospective analysis. Pharmacotherapy. 2014;34(6):582-9.
Kullar, R., McClellan, I., Geriak, M., & Sakoulas, G. (2014). Efficacy and safety of daptomycin in patients with renal impairment: a multicenter retrospective analysis. Pharmacotherapy, 34(6), 582-9. https://doi.org/10.1002/phar.1413
Kullar R, et al. Efficacy and Safety of Daptomycin in Patients With Renal Impairment: a Multicenter Retrospective Analysis. Pharmacotherapy. 2014;34(6):582-9. PubMed PMID: 24658897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and safety of daptomycin in patients with renal impairment: a multicenter retrospective analysis. AU - Kullar,Ravina, AU - McClellan,Ian, AU - Geriak,Matthew, AU - Sakoulas,George, Y1 - 2014/03/21/ PY - 2014/3/25/entrez PY - 2014/3/25/pubmed PY - 2015/2/11/medline KW - MRSA infections KW - daptomycin KW - renally impaired SP - 582 EP - 9 JF - Pharmacotherapy JO - Pharmacotherapy VL - 34 IS - 6 N2 - STUDY OBJECTIVE: Daptomycin is a therapeutic option for patients with underlying renal insufficiency who are vulnerable to nephrotoxicity from vancomycin. We evaluated the efficacy and safety of daptomycin in patients with renal impairment. DESIGN: Multicenter, retrospective, observational, case series analysis. SETTING: Two academic medical centers. PATIENTS: One hundred and sixty adults with creatinine clearance (Clcr) of 50 ml/minute or less who received daptomycin for at least 72 hours for complicated Gram-positive infections from 2008-2011. MEASUREMENTS AND MAIN METHODS: Clinical and microbiologic outcomes were assessed at the end of daptomycin therapy. Safety evaluations were documented for all patients, and when available, creatine phosphokinase (CPK) levels were recorded. Thirty-eight (23.8%) patients were on hemodialysis, and 122 (76.3%) had a decreased baseline renal clearance not requiring hemodialysis with a median interquartile range (IQR) Clcr of 32.4 ml/minute (24.2-40.4 ml/min). The median (IQR) daptomycin dose was 6.0 mg/kg (5.8-7.8 mg/kg) administered every 24 hours in 68 patients (42.5%) and every 48 hours in 92 patients (57.5%). Daptomycin success, including cure or improvement, (Cure: signs and symptoms resolved and no additional antibiotic therapy required, or infection cleared with negative cultures reported at the end of daptomycin therapy; Improvement: partial resolution of signs and symptoms and additional antibiotic therapy necessary at the end of daptomycin therapy) was achieved in 128 of 160 (80.0%) patients at the end of therapy. Methicillin-resistant Staphylococcus aureus (MRSA) was the most common pathogen (45%) isolated. The most frequent reason for using daptomycin was due to vancomycin-associated nephrotoxicity (20%). Daptomycin therapy was discontinued in six patients (3.8%) because of elevated CPK (median time to onset, 11.5 days). Loss of daptomycin susceptibility occurred in two patients with complex endovascular infections who were on hemodialysis. CONCLUSIONS: Daptomycin demonstrated clinical and microbiologic success rates comparable with prior studies. Discontinuation of therapy because of elevated CPK levels may have been avoided in some patients with adjustment to every 48-hour dosing for Clcr less than 30 ml/minute. The relatively early time to onset suggests the need for CPK monitoring more frequently than once/week in renally impaired patients receiving daptomycin. The treatment of bacteremia in patients with renal insufficiency warrants further study. SN - 1875-9114 UR - https://www.unboundmedicine.com/medline/citation/24658897/Efficacy_and_safety_of_daptomycin_in_patients_with_renal_impairment:_a_multicenter_retrospective_analysis_ L2 - https://doi.org/10.1002/phar.1413 DB - PRIME DP - Unbound Medicine ER -