Costellopeacock9925

In India and China, indigenous drug manufacturers market arbitrarily combined parenteral β-lactam and β-lactamase inhibitors (BL-BLI). In these fixed dose combinations, sulbactam or tazobactam is indiscriminately combined with parenteral cephalosporins, keeping BLI doses in the similar ratios as in the approved BL-BLIs. Such combinations have been introduced into clinical practice without undertaking mandatory drug development studies involving PK/PD, safety and efficacy assessments. Such unorthodox combinations compromise clinical outcomes and also potentially contribute to resistance development. Copyright © 2020 American Society for Microbiology.A strain of extensively drug resistant (XDR) Salmonella Typhi has caused a large ongoing outbreak in Pakistan since 2016. In Ontario, Canada, ten cases of mainly bloodstream infections (n=9) were identified in patients who traveled to Pakistan. Whole genome sequencing showed that Canadian cases were genetically related to the outbreak strain. The appearance of XDR typhoid cases in Ontario prompted provincial wide alert to physicians to recommend carbapenems or azithromycin in suspected typhoid cases with travel history to Pakistan. © Crown copyright 2020.ObjectivesTo obtain the optimal dosage regimen in patients receiving ECMO, we developed a population pharmacokinetics model for cefpirome and performed pharmacodynamic analyses.MethodsThis prospective study included 15 patients treated with cefpirome during ECMO. Blood samples were collected during ECMO (ECMO-ON) and after ECMO (ECMO-OFF) at pre-dose and 0.5-1, 2-3, 4-6, 8-10, and 12 h after cefpirome administration. The population pharmacokinetic model was developed using nonlinear mixed effects modeling and stepwise covariate modeling. Monte Carlo simulation was used to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) according to the MIC distribution.ResultsCefpirome pharmacokinetics were best described by a two-compartment model. Covariate analysis indicated that serum creatinine concentration (SCr) was negatively correlated with clearance, and the presence of ECMO increased clearance and the central volume of distribution. The simulations showed that patients with low SCr during ECMO-ON had lower PTA than patients with high SCr during ECMO-OFF; so, a higher dosage of cefpirome was required. Cefpirome of 2-g every 8 h for intravenous bolus injection or 2-g every 12 h for extended infusion over 4 h was recommended with normal kidney function receiving ECMO.ConclusionsWe established a population pharmacokinetic model for cefpirome in patients with ECMO, and appropriate cefpirome dosage regimens were recommended. The impact of ECMO could be due to the change in patient status on consideration of the small population and uncertainty in covariate relationships. Dose optimization of cefpirome may improve treatment success and survival in patients receiving ECMO. Copyright © 2020 American Society for Microbiology.BACKGROUND Dalbavancin offers a possible treatment option for infectious peritonitis associated with peritoneal dialysis (PD) due to its gram-positive bacteria coverage and pharmacokinetic properties. We aimed to evaluate the clinical pharmacokinetics (PK) and pharmacodynamics of dalbavancin patients receiving PD. METHODS Prospective, randomized, open-label, cross-over PK study of adult patients with ESRD who were receiving PD. Sampling occurred prior to single 30 minute dalbavancin 1500 mg infusion and hour 1, 2, 3, 4, 6, day 7, and 14 post administration. Concentration-time data were analyzed via non-compartmental analysis. Pharmacodynamic parameters were evaluated against common infectious peritonitis causing pathogens. RESULTS Ten patients were enrolled. Patients were a median of 55 years old, 78.2 kg, 50% female, and 70% Caucasian. The terminal plasma half-life of dalbavancin was 181.4 ± 35.5 hours. Day 0 -14 dalbavancin mean AUC was 40,573.2 ± 9,800.3 mg•hr/L. Terminal phase half-life of dalbavancin within the peritoneal fluid was 4.309 x 108 ± 1.140 x 109 hours. Day 0 -14 dalbavancin mean peritoneal fluid AUC was 2,125.0 ± 1,794.3mg•hr/L. Target plasma AUC/MIC was attained with the intravenous dose in all 10 patients for all Staphylococcus and Streptococcus species at recommended MIC breakpoints. The intraperitoneal arm of the study was stopped early, because the first 3 patients experienced moderate to severe pain and bloating within 1 hour following the administration of dalbavancin. CONCLUSIONS Dalbavancin 1500 mg intravenously can be utilized without dose adjustment in peritoneal dialysis patients and will likely achieve necessary peritoneal fluid concentrations to treat peritonitis caused by typical gram-positive pathogens. Copyright © 2020 American Society for Microbiology.Background Scabies is a frequent cutaneous infection caused by the mite Sarcoptes scabiei in a large number of mammals including humans. check details As the resistance of S. scabiei against several chemical acaricides has been previously documented, the establishment of alternative and effective control molecules is required.Objectives In this study, the potential acaricidal activity of beauvericin was assessed against different life stages of S. scabiei var. suis and, in comparison with dimpylate and ivermectin, two commercially available molecules used for the treatment of S. scabiei infection in animals and/or humans.Methods The toxicity of beauvericin against cultured human fibroblast skin cells was evaluated using an MTT proliferation assay. In our in vitro model, developmental stages of S. scabiei have been placed in Petri dishes filled with Columbia agar supplemented with pig serum and different concentrations of the drugs.Results Cell sensitivity assays demonstrated low toxicity of beauvericin against primary human fibroblast skin cells. At 0.5 and 5 mM, beauvericin showed higher activity against adults and eggs of S. scabiei when compared to dimpylate and ivermectin.Conclusion These results revealed that the use of beauvericin is promising and might be considered for the treatment of S. scabiei infection. Copyright © 2020 American Society for Microbiology.