Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia

A ratio of the vancomycin area under the concentration-time curve to the MIC (AUC/MIC) of ≥ 400 has been associated with clinical success when treating Staphylococcus aureus pneumonia, and this target was recommended by recently published vancomycin therapeutic monitoring consensus guidelines for treating all serious S. aureus infections. Here, vancomycin serum trough levels and vancomycin AUC/MIC were evaluated in a "real-world" context by following a cohort of 182 patients with S. aureus bacteremia (SAB) and analyzing these parameters within the critical first 96 h of vancomycin therapy. The median vancomycin trough level at this time point was 19.5 mg/liter. There was a significant difference in vancomycin AUC/MIC when using broth microdilution (BMD) compared with Etest MIC (medians of 436.1 and 271.5, respectively; P373, derived using classification and regression tree analysis, was associated with reduced mortality (P=0.043) and remained significant in a multivariable model. This study demonstrated that we obtained vancomycin trough levels in the target therapeutic range early during the course of therapy and that obtaining a higher vancomycin AUC/MIC (in this case, >373) within 96 h was associated with reduced mortality. The MIC test method has a significant impact on vancomycin AUC/MIC estimation. Clinicians should be aware that the current target AUC/MIC of ≥400 was derived using the reference BMD method, so adjustments to this target need to be made when calculating AUC/MIC ratio using other MIC testing methods. Copyrigh

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

A new regimen for continuous infusion of vancomycin during continuous renal replacement therapy

Introduction: Continuous infusion (CI) of high-dose vancomycin is often used to treat life-threatening infections caused by less-susceptible Gram-positive bacteria. However, this approach has not been well studied in patients on continuous renal replacement therapy (CRRT). The aim of this study was to evaluate the adequacy of a new CI vancomycin regimen in septic patients undergoing CRRT. Methods: In this prospective study we measured vancomycin concentrations obtained with a new CI regimen for CRRT, which included a loading dose of 35 mg/kg given over a 4 h period followed by a daily dose of 14 mg/kg. Vancomycin concentrations were measured: at the end of the loading dose (T1); 12 h after the onset of therapy (T2); and 24 h after the onset of therapy (T3). Drug concentrations (at T2 and T3) were considered adequate if between 20 and 30 mg/L. CRRT intensity was calculated as: dialysate rate (mL/kg/h)+ultrafiltration rate (mL/kg/h). Vancomycin population pharmacokinetics were calculated using non-linear mixed-effects modelling. Results: We studied 32 patients who received median (IQR) loading and daily vancomycin doses of 2750 mg (2250-3150) and 1100 mg (975-1270), respectively. Drug concentrations were: T1, 44 mg/L (38-58); T2, 27 mg/L (24-31); and T3, 23 mg/L (19-31). Vancomycin concentrations were adequate in 22/32 patients (69%) at T2 and in 20/32 (63%) at T3. The two relevant covariates that significantly affected drug concentrations were body weight and CRRT intensity. Conclusions: This new vancomycin regimen allowed the rapid achievement of target drug concentrations in the majority of patients. CRRT intensity had an influence on vancomycin clearance

Implications of augmented renal clearance in critically ill patients

Critically ill patients can display markedly abnormal physiological parameters compared with those in ward-based or ambulatory settings. As a function of both the underlying inflammatory state and the interventions provided, these patients manifest substantial changes in their cardiovascular and renal function that are not always immediately discernable using standard diagnostic tests. Impaired renal function is well documented among such individuals; however, even patients with normal serum creatinine concentrations might display elevated glomerular filtration rates, a phenomenon we have termed augmented renal clearance (ARC). This finding has important ramifications for the accurate dosing of renally eliminated drugs, given that most pharmaceutical dosing regimens were validated outside the critical care environment. Empirical approaches to dosing are unlikely to achieve therapeutic drug concentrations in patients with ARC, placing them at risk of suboptimal drug exposure and potential treatment failure. With an increasing appreciation of this phenomenon, alternative dosing strategies will need to be investigated

Clinical implications of antibiotic pharmacokinetic principles in the critically ill

Successful antibiotic therapy in the critically ill requires sufficient drug concentrations at the site of infection that kill or suppress bacterial growth. The relationship between antibiotic exposure and achieving the above effects is referred to as pharmacokinetics/pharmacodynamics (PK/PD). The associated indices therefore provide logical targets for optimal antibiotic therapy. While dosing regimens to achieve such targets have largely been established from studies in animals and non-critically ill patients, they are often poorly validated in the ICU. Endothelial dysfunction, capillary leak, altered major organ blood flow, deranged plasma protein concentrations, extremes of body habitus, the application of extracorporeal support modalities, and a higher prevalence of intermediate susceptibility, independently, and in combination, significantly confound successful antibiotic treatment in this setting. As such, the prescription of standard doses are likely to result in sub-therapeutic concentrations, which in turn may promote treatment failure or the selection of resistant pathogens. This review article considers these issues in detail, summarizing the key changes in antibiotic PK/PD in the critically ill, and suggesting alternative dosing strategies that may improve antibiotic therapy in these challenging patients

Expression of Interest for a Phase-II LHCb Upgrade: Opportunities in flavour physics, and beyond, in the HL-LHC era

https://cds.cern.ch/record/224431