The rate of treatment completion was significantly higher with short-course regimens, compared with the isoniazid regimen. Although the overall risk of hepatotoxicity in patients receiving pyrazinamide and rifampin daily for the treatment of latent tuberculosis infection was higher, liver functions returned to normal after the medications were discontinued.

Introduction CYP2D6 protein activity can be inferred from the ratio of N-desmethyl-tamoxifen (NDMT) to endoxifen (E). CYP2D6 polymorphisms are common and can affect CYP2D6 protein activity and E level. Some retrospective studies indicate that E < 16 nM may relate to worse outcome. Materials and methods A target NDMT/E ratio was defined as associated with an E level of 15 nM in the 161 patient Test cohort of tamoxifen-treated patients, dichotomizing them into ‘Normal’ (NM) and ‘Slow’ (SM) CYP2D6 metabolizer groups. This ratio was then tested on a validation cohort of 52 patients. Patients were phenotyped based on the standard method (ultrarapid/extensive, intermediate or poor metabolizers; UM/EM, IM, PM) or a simplified system based on whether any variant allele (V) vs wildtype (wt) was present (wt/wt, wt/V, V/V). Comprehensive CYP2D6 genotyping was undertaken on germline DNA. Results A target NDMT/E ratio of 35 correlated with the 15 nM E level, dichotomizing patients into NM (<35; N = 117) and SM (>35; N = 44) groups. The ratio was independently validated by a validation cohort. The simplified system was better in predicting patients without slow metabolism, with specificity and sensitivity of 96% and 44% respectively, compared with the standard method - sensitivity 81% and specificity 83%. Conclusions The simplified classification system based on whether any variant was present better identified patients who were truly not CYP2D6 slow metabolizers more accurately than the current system. However, as CYP2D6 genotype is not the only determinant of endoxifen level, we recommend that direct measurement of endoxifen should also be considered.

Introduction After the FDA gave emergency approval for the use of therapeutic plasma exchange in treatment for SARS‐Coronoavirus‐2, we analyzed its efficacy in patients who had failed all other known therapies. Methods This was a prospective observational study of 42 patients with SARS‐Coronoavirus‐2 who had failed conventional therapy and were treated with therapeutic plasma exchange. Pre‐ and postexchange clinical and laboratory parameters were monitored. The patients were then also compared with a group of 147 patients with SARS‐Coronoavirus‐2 who were referred for stage 3 acute renal failure and dialysis from SARS‐Coronoavirus‐2. Results After therapeutic plasma exchange, there were significant improvements in some clinical parameters but mortality remained high; although better than the renal failure group (43.9% vs. 50.7%, p = 0.004). Conclusion SARS‐CoV‐2 patients who failed all other therapies had significant mortality with therapeutic plasma exchange; however, their survival was better than SARS‐CoV‐2 patients with stage 3 acute renal failure.

Purpose This study aims to compare the performance of alternative weight-based vancomycin dosing strategies to traditional dosing in obese patients using area under the curve (AUC) monitoring. Methods This retrospective study compared target attainment of an AUC between 400–600mcg*H/mL using alternative vancomycin dosing strategies. All patients received allometrically dosed vancomycin, with patient-specific AUCs calculated using 2 post-infusion steady-state vancomycin serum concentrations using the trapezoidal rule. Predicted AUCs were calculated using the following: 15 mg/kg total body weight (TBW), 15 mg/kg corrected body weight (CBW), and 12.5 mg/kg TBW. Predicted AUCs from the traditional 15 mg/kg TBW dosing were then compared to alternative dosing strategies using the predicted AUCs from 12.5 mg/kg TBW, 15 mg/kg CBW, and the actual AUCs calculated using allometrically scaled vancomycin dosing. The primary outcome was attainment of initial AUC within the target range of 400–600mcg*H/mL for each dosing method. Results Eighty-four patients were included. When AUCs were compared to traditional 15 mg/kg dosing strategy, the CBW, 12.5 mg/kg, and allometric dosing strategies were significantly more likely to result in initial attainment of an AUC within a target range of 400–600 mcg*H/mL (P = 0.0003, 0.0135, and 0.0088, respectively). No significant differences were seen between each of the alternative dosing methods (P = 0.73). Conclusion The 3 alternative vancomycin dosing strategies examined were all significantly more likely to achieve an initial AUC within the target range compared to traditional vancomycin dosing in obese patients. Clinicians should strongly consider one of these alternative dosing strategies for obese patients as opposed to traditional vancomycin dosing.

Background: Optimal treatment of methicillin-resistant Staphylococcus aureus bacteremias (MRSABs) with vancomycin minimum inhibitory concentrations (MICs) high within the susceptible range is of concern due to the high rate of mortality and increased prevalence. Objective: The purpose of this study is to evaluate vancomycin treatment failures in patients with MRSAB stratified by vancomycin MIC. Methods: In this retrospective chart review, patients ≥19 years of age with MRSAB between July 2010 and December 2016 were included if they received intravenous vancomycin for ≥72 hours. Vancomycin treatment failures were compared between patients with vancomycin MICs of ≤1 mg/L and 2 mg/L. Vancomycin treatment failure was defined as microbiological failure at 7 days. Inpatient mortality, 30-day readmission, vancomycin-associated nephrotoxicity, and early bacteremia clearance at 48 to 96 hours were assessed as secondary endpoints. Results: Fifty-eight patients were included in the vancomycin MIC ≤1 mg/L group and 22 patients in the vancomycin MIC 2 mg/L group. No significant difference was found in vancomycin treatment failures at 7 days between groups (88% vs 91%, respectively; P = .850). At 96 hours, there was no significant difference in vancomycin treatment failures between groups (72% vs 90%, respectively; P = .127). No significant difference was found in mortality ( P > .99) or 30-day readmission ( P > .99). Conclusions: In this study, vancomycin treatment failures were not more prevalent in patients with vancomycin MIC of 2 mg/L at 7 days. Regardless of MIC, antibiotics should be switched to an alternative agent at 7 days for persistent bacteremia.