No abstract

Based on the results of this study, monitoring antifactor Xa levels is warranted to ensure the safety and efficacy of enoxaparin in the obese patient population (defined as a total body weight more than 150 kg or BMI higher than 40 kg/m(2)). Enoxaparin dose individualization and antifactor Xa level monitoring need further validation with clinical outcomes.

The antifactor Xa assay should be used to monitor UFH versus aPTT due to less variability in measurements, the absence of a need for calibration with new reagents/coagulometers, quicker attainment of therapeutic levels, fewer dose adjustments, and similar bleeding rates.

CI of beta-lactam antibiotics is associated with better cure rates and higher %fT > MIC when administered to critically ill patients with respiratory infections, but may be most beneficial in severely ill patients with more resistant Gram-negative bacterial infections.

No abstract

Meropenem-vaborbactam is a carbapenem and β-lactamase inhibitor combination that is newly indicated for the treatment of complicated urinary tract infections (cUTI), including adult pyelonephritis. Vaborbactam was developed due to emergence of carbapenem-resistant strains of Enterobacteriaceae. In a phase I trial, patients that received meropenem-vaborbactam 2-2 g intravenously over 3 h every 8 h, C was 58.2 ± 10.8 μg/mL for meropenem and 59.0 ± 8.4 μg/mL for vaborbactam. AUC was 186 ± 33.6 μg • h/mL for meropenem and 204 ± 34.6 μg • h/mL for vaborbactam. V = 16.3 ± 2.6 L for meropenem and 17.6 ± 2.6 L for vaborbactam. Protein binding for vaborbactam averaged 33% in humans. Plasma clearance ranged from 10.42 ± 1.85 to 14.77 ± 2.84 L/h. One phase III trial evaluated efficacy for meropenem-vaborbactam 2-2 g intravenously every 8 h versus piperacillin-tazobactam 4-0.5 g intravenously every 8 h in complicated UTI. It found non-inferiority and statistical superiority for meropenem in overall success at the end of treatment primary end point. In another phase III trial evaluating efficacy in carbapenem-resistant Enterobacteriaceae (CRE) infections, meropenem-vaborbactam 2-2 g intravenously every 8 h was associated with decreased 28-day mortality and increased clinical cure compared with a best available therapy group.

Complicated intra-abdominal infections (cIAIs) are an important cause of morbidity and mortality worldwide. They are diagnosed when the initial abdominal organ infection has spread into the peritoneal space. Successful treatment relies on adequate source control and appropriate empiric antimicrobial therapy. Inappropriate antimicrobial therapy may result in poor patient outcomes and increases in healthcare costs. Current guidelines recommend several single and combination antimicrobial regimens; however, empiric antimicrobial treatment has been complicated by the increasing rates of resistant organisms, especially the extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Additionally, the overuse of carbapenems to combat these resistant pathogens has contributed to the rise of carbapenemase-producing microorganisms, especially Klebsiella pneumoniae. This increasing resistance has prompted the development of novel antimicrobials like ceftazidime-avibactam and ceftolozane-tazobactam, whose activity extends to ESBL-producing microorganisms. Furthermore, the optimal duration of antimicrobial therapy is still unknown, and further research is necessary to find a definitive answer. This review will focus on antimicrobial therapies recommended by the current guidelines, the individual properties of these agents, appropriate duration of therapy, recent clinical trials, and place in therapy of the antimicrobial agents recently approved for the treatment of cIAIs.

To determine the efficacy of standard dose unfractionated heparin (UFH) for venous thromboembolism (VTE) prophylaxis in critically ill morbidly obese patients. Retrospective single-center observational cohort study in a single tertiary teaching hospital intensive care units (ICUs) in Multiparameter Intelligent Monitoring in Intensive Care II Clinical Database. Patients 18 years or older, admitted to the ICU, and received either UFH 5000 units subcutaneously twice daily or UFH 5000 units three times daily for VTE prophylaxis between 2001 and 2008 were included. Total 243 patients in the BMI ≥ 40 kg/m group and 2813 patients in the BMI < 40 kg/m group were identified. There was no difference in VTE incidence between the two groups. However, a strong linear association was found showing as BMI increased so did the rate of VTE incidence. Morbidly obese patients had longer hospital (17 vs. 14 days, P = 0.016) and ICU length of stay (10 vs. 8 days, P = 0.007). After controlling Padua score, logistic regression analysis revealed the odds of VTE increased by a factor of 1.026 for each one-unit increase in BMI. Additionally, having a BMI ≥ 40 kg/m was associated with a greater likelihood of VTE incidence in males (OR 3.92) but not in females. In patients treated with standard dose UFH, morbid obesity does not increase VTE risk overall. However, BMI has a strong linear relationship with VTE incidence and morbid obesity is more likely associated with greater hospital and ICU length of stay.