Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC 24 ) target of Ն400 mg · h/liter. Many patients with trough concentrations in this range have AUC 24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC 24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P ϭ 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P ϭ 0.002). AUCguided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure.

Pharmacodynamic dosing using extended-infusion piperacillintazobactam demonstrated favorable outcomes, including mortality, when compared with nonextended-infusion, similar-spectrum [H9252]-lactams in the treatment of patients with documented gram-negative infections. Prospective, randomized trials are needed to further corroborate these findings.

Available data support the use of maraviroc, the first CCR5 antagonist to receive FDA marketing approval, as part of an optimized antiretroviral regimen in treatment-experienced patients infected with CCR5-tropic HIV.

Apixaban in patients with impaired renal function is supported by limited data. Landmark clinical trials evaluating apixaban in patients with atrial fibrillation and/or acute venous thromboembolism excluded patients with creatinine clearance (CrCl) <25 mL/min. This multicenter, retrospective chart review was conducted to evaluate the safety and effectiveness of apixaban compared with warfarin in patients with CrCl <25 mL/min. Included patients were newly initiated on apixaban or warfarin for at least 45 days with a CrCl <25 mL/min. Patients were evaluated for thrombosis and bleeding outcomes 6 months following initiation of anticoagulation. The primary outcome was the time to first bleeding or thrombosis event. A total of 128 patients met inclusion criteria in the apixaban group and 733 patients in the warfarin group. Time to first bleeding or thrombosis event was significantly different between the apixaban and warfarin groups. Cox proportional hazards model was conducted to control for potential confounding factors for the primary outcome. After controlling for atrial fibrillation and coronary artery bypass grafting, risk of thrombotic and bleeding events was lower in the apixaban group (hazard ratio, 0.47; 95% confidence interval, 0.25-0.92). There was not a statistical difference between time to thrombosis (83 days vs 54 days, P = .648), rate of thrombosis (5.5% vs 10.3%, P = .08), time to bleeding (46 days vs 54 days, P = .886), or rate of bleeding (5.5% vs 10.9%, P = .06). The severity of bleeding and thrombotic events was not different between groups. Apixaban may serve as a reasonable alternative compared with warfarin in patients with severe renal dysfunction.

Infection is common in the critically ill and often results due to the severity of the patient's illness. Recent data suggest 51% of intensive care unit (ICU) patients are infected, and 71% receive antimicrobial therapy. Bacterial infection is the primary concern, although some fungal infections are opportunistic. Infection more than doubles the ICU mortality rate, and the costs associated with infection may be as high as 40% of total ICU expenditures. There are many contemporary antimicrobial resistance concerns that the critical care clinician must consider in managing the pharmacotherapy of infection. Methicillin resistance in Staphylococcus aureus, vancomycin resistance in Enterococci, beta-lactamase resistance in Enterobacteriaceae, multidrug resistance in Pseudomonas aeruginosa and Acinetobacter species, fluoroquinolone resistance in Escherichia coli, and fungal resistance are among the most common issues ICU clinician's must face in managing infection. Critical illness causes changes in pharmacokinetics that influence drug and dosing considerations. Absorption, distribution, metabolism, and excretion may all be affected by the various disease states that define critical illness. Several specific diseases are discussed, including ventilator-associated pneumonia, various fungal infections, gastrointestinal infections due to Clostridium difficile, urinary tract infections, and bloodstream infections. Within each disease section, discussion includes causes and prevention strategies, microbiology, evidence-based guidelines, and important caveats.