Effect of Concomitant 3-Hydroxy-3-Methyl-Glutaryl-CoA Reductase Inhibitor Therapy on Creatine Phosphokinase Levels and Mortality Among Patients Receiving Daptomycin: Retrospective Cohort Study.

IntroductionThe prescribing information for daptomycin recommends discontinuing statin therapy during receipt of daptomycin. The literature supporting this recommendation is sparse. The objectives of this study were to examine the impact of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors (statins) on creatine phosphokinase (CPK) elevations and mortality among patients receiving daptomycin therapy.MethodsA retrospective cohort study was performed among daptomycin recipients in the Upstate New York Veterans' Healthcare Administration from September 15, 2003 to July 1, 2013. Inclusion criteria were: (1) daptomycin for ≥48 h, (2) availability of baseline CPK value and (3) >1 CPK level measurement taken while on therapy. The following were extracted from medical records: demographics, comorbidities, laboratory data, medication history (daptomycin, statins and concomitant drugs known to increase CPK), Acute Physiology and Chronic Health Evaluation (APACHE)-II score and vital status at 30 days. The exposure of interest was use of statins. The primary outcome was CPK elevation defined as a CPK value ≥3 times the upper limit of normal (ULN) if baseline CPK was normal, and ≥5 times ULN if baseline CPK was elevated. The secondary outcome was death within 30 days of commencing daptomycin.ResultsA total of 233 patients were included in this analysis. Among these patients, 53 received concomitant statin therapy. Most baseline clinical characteristics were similar between statin recipients and non-recipients. Five (2.1%) patients experienced a CPK elevation; 3/53 (5.7%) were statin recipients and 2/180 (1.1%) received daptomycin alone (p = 0.08). All patients with CPK elevations had normal baseline CPK values. No effect modification was observed by use of other concomitant medications known to increase CPK values. Death was observed more frequently among statin non-recipients (17.2%) than recipients (9.4%).ConclusionsAmong patients receiving daptomycin, no significant difference was observed in frequency of CPK elevation between statin recipients and non-recipients

Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter

In an effort to maximize outcomes, recent expert guidelines recommend more-intensive vancomycin dosing schedules to maintain vancomycin troughs between 15 and 20 mg/liter.The widespread use of these more-intensive regimens has been associated with an increase in vancomycin-induced nephrotoxicity reports.The purpose of this systematic literature review is to determine the nephrotoxicity potential of maintaining higher troughs in clinical practice.All studies pertaining to vancomycin-induced nephrotoxicity between 1996 and April 2012 were identified from PubMed, Embase, Cochrane Controlled Trial Registry, and Medline databases and analyzed according to Cochrane guidelines.Of the initial 240 studies identified, 38 were reviewed, and 15 studies met the inclusion criteria.Overall, higher troughs ( >15 mg/liter) were associated with increased odds of nephrotoxicity (odds ratio [OR], 2.67; 95% confidence interval [CI], 1.95 to 3.65) relative to lower troughs of >15 mg/liter.The relationship between a trough of >15 mg/liter and nephrotoxicity persisted when the analysis was restricted to studies that examined only initial trough concentrations (OR, 3.12; 95% CI, 1.81 to 5.37).The relationship between troughs of >15 mg/liter and nephrotoxicity persisted after adjustment for covariates known to independently increase the risk of a nephrotoxicity event.An incremental increase in nephrotoxicity was also observed with longer durations of vancomycin administration.Vancomycin-induced nephrotoxicity was reversible in the majority of cases, with short-term dialysis required only in 3% of nephrotoxic episodes.The collective literature indicates that an exposure-nephrotoxicity relationship for vancomycin exists.The probability of a nephrotoxic event increased as a function of the trough concentration and duration of therapy

Individualization of piperacillin dosing for critically ill patients: Dosing software to optimize antimicrobial therapy

Piperacillin-tazobactam is frequently used for empirical and targeted therapy of infections in critically ill patients. Considerable pharmacokinetic (PK) variability is observed in critically ill patients. By estimating an individual's PK, dosage optimization Bayesian estimation techniques can be used to calculate the appropriate piperacillin regimen to achieve desired drug exposure targets. The aim of this study was to establish a population PK model for piperacillin in critically ill patients and then analyze the performance of the model in the dose optimization software program BestDose. Linear, with estimated creatinine clearance and weight as covariates, Michaelis-Menten (MM) and parallel linear/MM structural models were fitted to the data from 146 critically ill patients with nosocomial infection. Piperacillin concentrations measured in the first dosing interval, from each of 8 additional individuals, combined with the population model were embedded into the dose optimization software. The impact of the number of observations was assessed. Precision was assessed by (i) the predicted piperacillin dosage and by (ii) linear regression of the observed-versus-predicted piperacillin concentrations from the second 24 h of treatment. We found that a linear clearance model with creatinine clearance and weight as covariates for drug clearance and volume of distribution, respectively, best described the observed data. When there were at least two observed piperacillin concentrations, the dose optimization software predicted a mean piperacillin dosage of 4.02 g in the 8 patients administered piperacillin doses of 4.00 g. Linear regression of the observed-versus-predicted piperacillin concentrations for 8 individuals after 24 h of piperacillin dosing demonstrated an r2 of > 0.89. In conclusion, for most critically ill patients, individualized piperacillin regimens delivering a target serum piperacillin concentration is achievable. Further validation of the dosage optimization software in a clinical trial is required. Copyrigh

Current status and best practices of shared governance in US pharmacy programs

© 2020, American Association of Colleges of Pharmacy. All rights reserved. Objective. To characterize shared governance in US schools and colleges of pharmacy and recom-mend best practices to promote faculty engagement and satisfaction. Findings. The literature review revealed only one study on governance in a pharmacy school and some data from an AACP Faculty Survey. Of the 926 faculty members who responded to the survey, the majority were satisfied or very satisfied with faculty governance (64%) and the level of input into faculty governance (63%) at their school. Faculty members in administrative positions and those at public institutions were more satisfied with governance. The forum resulted in the development of five themes: establish a clear vision of governance in all areas; ensure that faculty members are aware of their roles and responsibilities within the governance structure; ensure faculty members are able to join committees of interest; recognize and reward faculty contributions to governance; and involve all full-time faculty members in governance, regardless of their tenure status. Summary. Establishing shared governance within a school or college of pharmacy impacts overall faculty satisfaction and potentially faculty retention

Reply to "vancomycin-induced nephrotoxicity"

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Epidemiology and outcomes of community-onset methicillin-susceptible Staphylococcus aureus bacteraemia in a university hospital in Singapore

10.1186/1471-2334-8-14BMC infectious diseases81

Positive follow-up blood cultures identify high mortality risk among patients with Gram-negative bacteraemia

Objectives: The role of follow-up blood cultures (FUBCs) in the management of Gram-negative bacteraemia (GNB) is poorly understood. We aimed to determine the utility of FUBCs in identifying patients with increased mortality risk. Methods: An observational study with a prospectively enrolled cohort of adult inpatients with GNB was conducted at Duke University Health System from 2002 to 2015. FUBCs were defined as blood cultures performed from 24 hours to 7 days from initial positive blood culture. Results: Among 1702 patients with GNB, 1164 (68%) had FUBCs performed. When performed, FUBCs were positive in 20% (228/1113) of cases. FUBC acquisition was associated with lower all-cause in-hospital mortality (108/538, 20%, vs. 176/1164, 15%; p 0.01) and attributable in-hospital mortality (78/538, 15%, vs. 98/1164, 8%; p < 0.0001). Propensity score–weighted Cox proportional hazards models revealed that obtaining FUBCs was associated with reductions in all-cause (hazard ratio (HR) 0.629; 95% confidence interval (CI), 0.511–0.772; p < 0.0001) and attributable mortality (HR 0.628; 95% CI, 0.480–0.820; p 0.0007). Positive FUBCs were associated with increased all-cause mortality (49/228, 21%, vs. 110/885, 11%; p 0.0005) and attributable mortality (27/228, 12%, vs. 61/885, 7%; p 0.01) relative to negative FUBCs. Propensity score–weighted Cox proportional hazards models revealed that positive FUBCs were associated with increased all-cause (HR 2.099; 95% CI, 1.567–2.811; p < 0.0001) and attributable mortality (HR 1.800; 95% CI, 1.245–2.603; p 0.002). In a calibration analysis, a scoring system accurately identified patients at high risk of positive FUBCs. Conclusions: Rates of positive FUBCs were high and identified patients at increased risk for mortality. Clinical variables can identify patients at high risk for positive FUBCs. FUBCs should be considered in the management of GNB

The usefulness of arbekacin compared to vancomycin

The bacteriological efficacy response (improved, arbekacin vs. vancomycin; 71.2% vs. 79.5%) and clinical efficacy response (improved, arbekacin vs. vancomycin; 65.3% vs. 76.1%) were not statistically different between the two groups. The complication rate was significantly higher in the vancomycin group (32.9%) compared to the arbekacin group (15.1%) (p = 0.019). Arbekacin was not inferior to vancomycin, and it could be a good alternative drug for vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) treatment

Staphylococcus aureus Bacteraemia in a Tropical Setting: Patient Outcome and Impact of Antibiotic Resistance

Background: Most information on invasive Staphylococcus aureus infections comes from temperate countries. There are considerable knowledge gaps in epidemiology, treatment, drug resistance and outcome of invasive S. aureus infection in the tropics. Methods: A prospective, observational study of S. aureus bacteraemia was conducted in a 1000-bed regional hospital in northeast Thailand over 1 year. Detailed clinical data were collected and final outcomes determined at 12 weeks, and correlated with antimicrobial susceptibility profiles of infecting isolates. Principal Findings: Ninety-eight patients with S. aureus bacteraemia were recruited. The range of clinical manifestations was similar to that reported from temperate countries. The prevalence of endocarditis was 14%. The disease burden was highest at both extremes of age, whilst mortality increased with age. The all-cause mortality rate was 52%, with a mortality attributable to S. aureus of 44%. Methicillin-resistant S. aureus (MRSA) was responsible for 28% of infections, all of which were healthcare-associated. Mortality rates for MRSA and methicillin-susceptible S. aureus (MSSA) were 67% (18/27) and 46% (33/71), respectively (p = 0.11). MRSA isolates were multidrug resistant. Only vancomycin or fusidic acid would be suitable as empirical treatment options for suspected MRSA infection. Conclusions: S. aureus is a significant pathogen in northeast Thailand, with comparable clinical manifestations and a similar endocarditis prevalence but higher mortality than industrialised countries. S. aureus bacteraemia is frequently associated with exposure to healthcare settings with MRSA causing a considerable burden of disease. Further studies are required to define setting-specific strategies to reduce mortality from S. aureus bacteraemia, prevent MRSA transmission, and to define the burden of S. aureus disease and emergence of drug resistance throughout the developing world. © 2009 Nickerson et al