Chemother. 63:1299C1300. therapy weighed against 5/171 (2.9%) of sufferers receiving daptomycin alone (= 0.38). CPK elevations of 1,000 U/liter happened in 5/49 (10.2%) sufferers receiving mixture therapy in comparison to 9/171 (5.3%) sufferers receiving daptomycin alone (= 0.32). Two of five sufferers suffering from CPK elevations of 1,000 U/liter in the mixture group acquired symptoms of myopathy. Three sufferers (6.1%) discontinued therapy because of CPK elevations with concurrent myalgias in the mixture group versus 6 sufferers (3.5%) in the daptomycin-alone group (= 0.42). CPK myalgias and amounts reversed upon discontinuation of daptomycin therapy. General musculoskeletal toxicity was numerically higher in the combination group but this total result had not been statistically significant. Further prospective research is certainly warranted in a more substantial population. Launch Daptomycin is certainly a cyclic lipopeptide antibiotic that has been a significant agent in the treating Gram-positive pathogens, including methicillin-resistant (MRSA) and vancomycin-resistant (VRE) types. It really is FDA accepted for make use of in Gram-positive epidermis and skin framework attacks (SSSI) and bacteremia, including right-sided infective endocarditis at dosages of 4 mg/kg of bodyweight and 6 mg/kg once daily, respectively (1). Myalgias, serum creatine phosphokinase (CPK) elevations, and muscles weakness were observed in preapproval scientific trials at dosages of 4 mg/kg double daily (2). Lowering the dosing period to once daily (the FDA-approved dosing period) significantly decreased the occurrence of drug-induced musculoskeletal toxicity. In postmarketing research, higher dosages of daptomycin ( 6 mg/kg) have already been associated with humble boosts in toxicity risk (3, 4). CPK monitoring is preferred once every seven days during daptomycin therapy (1). Concomitant usage of daptomycin and 3-hydroxy-3-methylglutarylCcoenzyme A (HMG-CoA) reductase inhibitors (statins) isn’t uncommon, nonetheless it holds problems for potential synergistic musculoskeletal toxicities. Risk elements for statin-induced muscles toxicity include old age group, high statin medication dosage, feminine gender, and renal disease (5). Concomitant usage of cytochrome P450 inhibitors such as amiodarone and Rabbit Polyclonal to NAB2 other myotoxic drugs such as fibric acid derivatives increases the risk of statin-induced rhabdomyolysis (6). Daptomycin product labeling recommends that consideration be given to discontinuing statin therapy while administering daptomycin due to potential for additive toxicity, primarily myopathic toxicities. Limited data exist regarding safety of coadministration of daptomycin with statin therapy (4, 7, 8, 9). The objective of our study was to report on Lidocaine hydrochloride the safety of concomitant statin and daptomycin therapy among hospitalized patients. (These data were presented in part at the 48th Annual Getting together with of the Infectious Diseases Society of America [IDSA], Vancouver, BC, Canada, October 2010. ) MATERIALS AND METHODS This study was a retrospective, multicenter study of adult patients hospitalized Lidocaine hydrochloride from 2005 to 2010 who received daptomycin with or without statin therapy. The first dose of daptomycin was used to determine inclusion into the study, with dosing based on actual body weight. The Institutional Review Board at each participating site approved the study prior to data collection. Patients 18 years of age hospitalized from January 2005 to May 2010 who received daptomycin for a minimum of 7 days with concurrent statin therapy for at least 24 h as part of routine care during hospitalization were included in the combination group. Patients receiving daptomycin for at least 7 days without statin therapy comprised the other group. CPK monitoring was left at the discretion of the treating clinician. CPKs were considered baseline from 1 month prior to the day of initiation of daptomycin therapy. Utilizing medical records and data documented on standardized case report forms collected during the complete course of therapy, we obtained detailed information on patient demographics, treatment indication, estimated creatinine clearance (CrCl), statin therapy, serum CPK concentrations, presence of myalgias or muscle complaints, and reason for daptomycin discontinuation (if applicable). Estimated renal clearance was calculated with the Cockcroft-Gault formula using actual body weight as recommended by the manufacturer (1). Primary safety outcomes were compared between the two groups (the combination daptomycin and statin group and the daptomycin-alone group) as follows: (i) incidence of serum CPK levels of 1,000 U/liter at any point during therapy; (ii) documented myalgias or related muscle pains during therapy; and (iii) number of patients requiring discontinuation of therapy or dose modification due to increased serum CPK levels with or without signs/symptoms of myopathy. Data were Lidocaine hydrochloride abstracted into a central spreadsheet database for analysis. Logistic regression models predicted the probability of significant adverse event occurrence, defined as CPK levels of 1,000 U/liter or myalgias. Categorical variables were compared with the chi-squared or Fisher’s exact test, as appropriate. Two independent-sample assessments were used to compare continuous variables. For model-building purposes, variables in the logistic regression model were based on evidence from our exploratory analysis, literature, and our research questions. All variables used were categorical for rational interpretation of beta-coefficients and odds ratios (ORs)..Forty-nine adult patients receiving statins concurrently with daptomycin were compared with 171 patients receiving daptomycin without statin therapy. combination group had symptoms of myopathy. Three patients (6.1%) discontinued therapy due to CPK elevations with concurrent myalgias Lidocaine hydrochloride in the combination group versus 6 patients (3.5%) in the daptomycin-alone group (= 0.42). CPK levels and myalgias reversed upon discontinuation of daptomycin therapy. Overall musculoskeletal toxicity was numerically higher in the combination group but this result was not statistically significant. Further prospective study is usually warranted in a larger population. INTRODUCTION Daptomycin is usually a cyclic lipopeptide antibiotic that has become an important agent in the treatment of Gram-positive pathogens, including methicillin-resistant (MRSA) and vancomycin-resistant (VRE) species. It is FDA approved for use in Gram-positive skin and skin structure infections (SSSI) and bacteremia, including right-sided infective endocarditis at doses of 4 mg/kg of body weight and 6 mg/kg once daily, respectively (1). Myalgias, serum creatine phosphokinase (CPK) elevations, and muscle weakness were noted in preapproval clinical trials at doses of 4 mg/kg twice daily (2). Decreasing the dosing interval to once daily (the FDA-approved dosing interval) significantly reduced the incidence of drug-induced musculoskeletal toxicity. In postmarketing studies, higher doses of daptomycin ( 6 mg/kg) have been associated with modest increases in toxicity risk (3, 4). CPK monitoring is recommended once every 7 days during daptomycin therapy (1). Concomitant use of daptomycin and 3-hydroxy-3-methylglutarylCcoenzyme A (HMG-CoA) reductase inhibitors (statins) is not uncommon, but it carries concerns for potential synergistic musculoskeletal toxicities. Risk factors for statin-induced muscle toxicity include older age, high statin dosage, female gender, and renal disease (5). Concomitant use of cytochrome P450 inhibitors such as amiodarone and other myotoxic drugs such as fibric acid derivatives increases the risk of statin-induced rhabdomyolysis (6). Daptomycin product labeling recommends that consideration be given to discontinuing statin therapy while administering daptomycin due to potential for additive toxicity, primarily myopathic toxicities. Limited data exist regarding safety of coadministration of daptomycin with statin therapy (4, 7, 8, 9). The Lidocaine hydrochloride objective of our study was to report on the safety of concomitant statin and daptomycin therapy among hospitalized patients. (These data were presented in part at the 48th Annual Getting together with of the Infectious Diseases Society of America [IDSA], Vancouver, BC, Canada, October 2010.) MATERIALS AND METHODS This study was a retrospective, multicenter study of adult patients hospitalized from 2005 to 2010 who received daptomycin with or without statin therapy. The first dose of daptomycin was used to determine inclusion into the study, with dosing based on actual body weight. The Institutional Review Board at each participating site approved the study prior to data collection. Patients 18 years of age hospitalized from January 2005 to May 2010 who received daptomycin for a minimum of 7 days with concurrent statin therapy for at least 24 h as part of routine care during hospitalization were included in the combination group. Patients receiving daptomycin for at least 7 days without statin therapy comprised the other group. CPK monitoring was left at the discretion of the treating clinician. CPKs were considered baseline from 1 month prior to the day of initiation of daptomycin therapy. Utilizing medical records and data documented on standardized case report forms collected during the complete course of therapy, we obtained detailed information on patient demographics, treatment indication, estimated creatinine clearance (CrCl), statin therapy, serum CPK concentrations, presence of myalgias or muscle complaints, and reason for daptomycin discontinuation (if applicable). Estimated renal clearance was calculated with the Cockcroft-Gault formula using actual body weight as recommended by the manufacturer (1). Primary safety outcomes were compared between the two groups (the combination daptomycin and statin group and the daptomycin-alone group) as.