Comparison of the Drug-Drug Interaction Potential of Daptomycin in Combination with Rifampin in Healthy Adult Volunteers.

We evaluated the effects of rifampin coadministration and MDR1 single nucleotide polymorphisms on the disposition of daptomycin in twelve healthy adults. There were no significant changes from baseline in the clearance (0.53 versus 0.55 liters/h, P = 1.00), volume of distribution (7.0 versus 7.2 liter, P = 0.62), or half-life (9.7 versus 9.6 h, P = 0.89) of daptomycin after exposure to rifampin. The tested MDR1 polymorphisms were not associated with significant differences in daptomycin disposition.

Patient Variables Associated with Nafcillin Plasma Concentrations and Toxicity.

PRIMARY OBJECTIVE: To retrospectively review nafcillin plasma concentrations (CNAF ) and determine nafcillin clearance (CLNAF ) in a diverse sample of patients treated with nafcillin administered as a continuous infusion. SECONDARY OBJECTIVE: To identify clinical variables associated with CLNAF and nafcillin-related adverse drug reactions (ADRs). METHODS: Retrospective chart review of patients receiving nafcillin via continuous infusion at University of Utah Health Care from 2006 to 2013 who had at least one steady-state CNAF measured. CLNAF was determined by dividing the nafcillin rate of infusion by CNAF . Adverse drug reactions (ADRs) were defined using the National Institutes of Health, Division of Microbiology and Infectious Diseases criteria and scored for probability of association with nafcillin by using Naranjo criteria. Multivariate models were constructed to identify independent variables associated with CLNAF and ADRs. MAIN RESULTS: Seventy-six CNAF from 54 patients were included. Median CLNAF was 13.9 L/hour (range ≤ 4.2 to 36.9 L/hr). Congestive heart failure (p=0.007), hyperbilirubinemia (p<0.0001), and serum creatinine (p<0.0001) were associated with reduced CLNAF , and Hispanic race (p=0.002) was associated with increased CLNAF by multivariate analysis. Twenty patients (37.0%) experienced an ADR. CNAF were significantly higher between patients that experienced an ADR and those that did not (66.0 vs 25.5 mg/L, p<0.001). Individual ADRs associated with CNAF included hepatotoxicity (62.8 vs 27.0 mg/L, p=0.001), nausea/vomiting (80.0 vs 28.5 mg/L, p=0.01), and diarrhea (66.5 vs 26.5 mg/L, p<0.001). Multivariate analysis identified CNAF as being independently associated with ADRs. A putative toxicity relationship between CNAF and predicted probability of ADR was established. CONCLUSIONS: Several patient variables were associated with impaired CLNAF , and elevated CNAF were associated with ADRs. Additional studies assessing the utility of nafcillin therapeutic drug monitoring to minimize toxicity are warranted.

Crowdsourced Data Indicate Widespread Multidrug Resistance in Skin Flora of Healthy Young Adults.

In a laboratory exercise for undergraduate biology majors, students plated bacteria from swabs of their facial skin under conditions that selected for coagulase-negative Staphylococcus; added disks containing the antibiotics penicillin, oxacillin, tetracycline, and erythromycin; and measured zones of inhibition. Students also recorded demographic and lifestyle variables and merged this information with similar data collected from 9,000 other students who had contributed to the database from 2003 to 2011. Minimum inhibitory concentration (MIC) testing performed at the Harborview Medical Center Microbiology Laboratory (Seattle, WA) indicated a high degree of accuracy for student-generated data; species identification with a matrix-assisted laser desorption ionization (MALDI) Biotyper revealed that over 88% of the cells analyzed by students were S. epidermidis or S. capitus. The overall frequency of resistant cells was high, ranging from 13.2% of sampled bacteria resistant to oxacillin to 61.7% resistant to penicillin. Stepwise logistic regressions suggested that recent antibiotic use was strongly associated with resistance to three of the four antibiotics tested (p = 0.0003 for penicillin, p << 0.0001 for erythromycin and tetracycline), and that age, gender, use of acne medication, use of antibacterial soaps, or makeup use were associated with resistance to at least one of the four antibiotics. Furthermore, drug resistance to one antibiotic was closely linked to resistance to the other three antibiotics in every case (all p values << 0.0001), suggesting the involvement of multidrug-resistant strains. The data reported here suggest that citizen science could not only provide an important educational experience for undergraduates, but potentially play a role in efforts to expand antibiotic resistance (ABR) surveillance.

Random effects models and multistage estimation procedures for statistical population reconstruction of small game populations.

Recently, statistical population models using age-at-harvest data have seen increasing use for monitoring of harvested wildlife populations. Even more recently, detailed evaluation of model performance for long-lived, large game animals indicated that the use of random effects to incorporate unmeasured environmental variation, as well as second-stage Horvitz-Thompson-type estimators of abundance, provided more reliable estimates of total abundance than previous models. We adapt this new modeling framework to small game, age-at-harvest models with only young-of-the-year and adult age classes. Our Monte Carlo simulation results indicate superior model performance for the new modeling framework, evidenced by lower bias and proper confidence interval coverage. We apply this method to male wild turkey harvest in the East Ozarks turkey productivity region, Missouri, USA, where statistical population reconstruction indicates a relatively stationary population for 1996-2010.