Comparative incidence and excess risk of acute kidney injury in hospitalised patients receiving vancomycin and piperacillin/tazobactam in combination or as monotherapy.

Combination therapy with vancomycin and piperacillin/tazobactam (TZP) has been associated with increased risk of acute kidney injury (AKI) compared with monotherapy with either agent. This retrospective, matched cohort study was conducted to assess the comparative incidence of AKI due to combination therapy in patients receiving vancomycin and TZP in combination or as monotherapy. Patients aged ≥18 years admitted to Albany Medical Center (Albany, NY) between September 2013 and August 2014 who had received therapy for at least two consecutive days were included.

Pilot Study of a Bayesian Approach To Estimate Vancomycin Exposure in Obese Patients with Limited Pharmacokinetic Sampling.

This study evaluated the predictive performance of a Bayesian PK estimation method (ADAPT V) to estimate the 24-h vancomycin area under the curve (AUC) with limited pharmacokinetic (PK) sampling in adult obese patients receiving vancomycin for suspected or confirmed Gram-positive infections. This was an Albany Medical Center Institutional Review Board-approved prospective evaluation of 12 patients. Patients had a median (95% confidence interval) age of 61 years (39 to 71 years), a median creatinine clearance of 86 ml/min (75 to 120 ml/min), and a median body mass index of 45 kg/m (40 to 52 kg/m).

Assessment of Time to Clinical Response in Patients with Sepsis Treated Before and After Implementation of a Matrix-Assisted Laser Desorption Ionization Time-of-Flight Blood Culture Identification Algorithm.

OBJECTIVE To evaluate time to clinical response before and after implementation of rapid blood culture identification technologies. DESIGN Before-and-after trial. SETTING Large, tertiary, urban, academic health-sciences center.

Optimizing the initial amikacin dosage in adults.

We report on the pharmacokinetics (PK) and pharmacodynamics (PD) of high-dose (>15 mg/kg of body weight per day) amikacin. A mean (standard deviation [SD]) maximum drug concentration in the serum (Cmax) and 24-h area under the concentration-time curve (AUC24) of 101 (49.4) mg/liter and 600 (387) mg · h/liter, respectively, were observed (n = 73) with 28.

Vancomycin-associated renal dysfunction: where are we now?

Vancomycin has been in clinical use for over 60 years, during which time renal toxicity has been well documented. Multiple risk factors and outcomes are associated with vancomycin-related nephrotoxicity. Risk factors include vancomycin exposure (trough levels 15 mg/L or higher, larger area under the curve, duration of therapy), host susceptibility to vancomycin (increased body weight, preexisting renal dysfunction, critical illness), and concurrent nephrotoxin therapy.

MenHibrix: a new combination meningococcal vaccine for infants and toddlers.

Objective: To review the immunogenicity and safety of the Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (Hib-MenCY-TT) for infants and toddlers.

Data Sources: Studies conducted in humans and limited to publication in English were identified through a MEDLINE (January 2000 to September 2013) search using the terms Hib-MenCY-TT, MenHibrix, and Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine. Clinical trial registries, Web sites, and reference citations from publications identified were reviewed for additional sources.

Vancomycin dosing in children and young adults: back to the drawing board.

Study Objective: To compare the likelihood of alternative vancomycin dosing strategies based on weight, height, or body surface area (BSA) in achieving isometric vancomycin area under the serum concentration-time curve (AUC) values across the body size distribution of children and young adults.

Design: Maximum a posteriori probability Bayesian (MAP-Bayesian) pharmacokinetic analysis using retrospectively collected medical record data.

Setting: Children's hospital.

Vancomycin dosing and monitoring 2 years after the guidelines.

Administration of vancomycin continues to be common despite perceived concerns of increased MICs, treatment failures and toxicity. In 2009, a consensus guideline was published in an effort to optimize dosing and monitoring of this useful agent. It was unique in targeting a specific antibiotic rather than a disease state or organism.

Vancomycin: we can't get there from here.

Background: We sought to characterize the pharmacodynamic profile of the more intensive vancomycin dosing regimens currently used in response to the recent vancomycin guidelines.

Methods: A series of Monte Carlo simulations was performed for vancomycin regimens ranging from .5 g intravenous (IV) Q12H to 2 g IV Q12H.

Therapeutic monitoring of vancomycin in adults summary of consensus recommendations from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists.

Vancomycin is a commonly used antibiotic due to its effectiveness in treating serious gram-positive infections caused by methicillin-resistant Staphylococcus aureus. As commercial drug assays and a multitude of pharmacokinetic data from a variety of patient populations are widely available, therapeutic monitoring of serum vancomycin concentrations is frequently performed by clinicians, with the expectation that targeting the concentrations within a relatively narrow range can minimize toxicity yet still achieve therapeutic success. Much debate exists, however, over the value of routine therapeutic monitoring of vancomycin levels because of conflicting evidence regarding the ability of serum concentrations to predict effectiveness or prevent toxicity.

Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients.

Background: Data suggest that higher doses of vancomycin can increase the risk of nephrotoxicity. No study has been undertaken to determine the pharmacodynamic index (ie, the area under the curve [AUC] or the trough value) that best describes the relationship between vancomycin exposure and onset of nephrotoxicity.

Methods: A retrospective study was conducted among patients who received vancomycin for a suspected or proven gram-positive infection during the period from 1 January 2005 through 31 December 2006 at Albany Medical Center Hospital.

Vancomycin therapeutic guidelines: a summary of consensus recommendations from the infectious diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists.

Practice guidelines for therapeutic monitoring of vancomycin treatment for Staphylococcus aureus infection in adult patients were reviewed by an expert panel of the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. A literature review of existing evidence regarding vancomycin dosing and monitoring of serum concentrations, in addition to patient outcomes combined with expert opinion regarding the drug's pharmacokinetic, pharmacodynamic, and safety record, resulted in new recommendations for targeting and adjustment of vancomycin therapy.

Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity.

Recent guidelines recommend vancomycin trough concentrations between 15 and 20 mg/liter. In response, some clinicians increased vancomycin dosing to >or=4 g/day. Scant data are available regarding toxicities associated with higher vancomycin doses.

Effects of gatifloxacin and levofloxacin on rates of hypoglycemia and hyperglycemia among elderly hospitalized patients.

Study Objectives: To compare rates of hypoglycemia and hyperglycemia among elderly hospitalized patients with normal blood glucose concentrations at baseline who were receiving either gatifloxacin or levofloxacin, and to determine if appropriateness of their doses, according to their package inserts, was associated with hypoglycemia or hyperglycemia.

Design: Retrospective cohort study.

Setting: Integrated Veterans Administration (VA) health care system.

Predictors of 30-day mortality among patients with Pseudomonas aeruginosa bloodstream infections: impact of delayed appropriate antibiotic selection.

Although a growing number of studies have found a relationship between delayed appropriate antibiotic therapy and mortality, few have attempted to quantify the temporal association between delayed appropriate antibiotic therapy and mortality. This study was designed to measure the elapsed time associated with an increased risk of 30-day mortality among patients with Pseudomonas aeruginosa bacteremia. The retrospective cohort study was conducted among immunocompetent, adult patients with P.

Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy.

Background: Piperacillin-tazobactam is frequently used to treat Pseudomonas aeruginosa infections in critically ill patients. In an effort to improve clinical outcomes, an extended-infusion dosing scheme for piperacillin-tazobactam therapy was devised using a Monte Carlo simulation and was adopted into clinical practice at Albany Medical Center (Albany, New York). This study evaluates the clinical implications of extended infusion of piperacillin-tazobactam therapy for critically ill patients with P.

Clinical prediction tool to identify patients with Pseudomonas aeruginosa respiratory tract infections at greatest risk for multidrug resistance.

Despite the increasing prevalence of multiple-drug-resistant (MDR) Pseudomonas aeruginosa, the factors predictive of MDR have not been extensively explored. We sought to examine factors predictive of MDR among patients with P. aeruginosa respiratory tract infections and to develop a tool to estimate the probability of MDR among such high-risk patients.

Application of antimicrobial pharmacodynamic concepts into clinical practice: focus on beta-lactam antibiotics: insights from the Society of Infectious Diseases Pharmacists.

In recent years there have been tremendous strides in understanding the relationship between the pharmacodynamics of beta-lactams and microbiologic response. For beta-lactams, in vitro and animal studies suggest that the amount of time in which free or non-protein-bound antimicrobial concentration exceeds the minimum inhibitory concentration (MIC) of the organism (fT>MIC) is the best predictor of bacterial killing and microbiologic response. Using population pharmacokinetic modeling and Monte Carlo simulation, it is possible to integrate pharmacokinetics, a pharmacodynamic target, and microbiologic surveillance data to generate empiric beta-lactam dosing strategies that maximize the likelihood of achieving fT>MIC associated with near maximal bactericidal effect against the range of pathogens encountered in clinical practice.

The spread of Klebsiella pneumoniae carbapenemase-producing K. pneumoniae to upstate New York.

Klebsiella pneumoniae carbapenemases (KPCs) have previously been identified in distinct geographic locations. We report the spread of KPC-2 to upstate New York. Our intention is to alert clinicians to problems encountered in identifying KPC-containing isolates.

Progressive esophagitis caused by Candida albicans with reduced susceptibility to caspofungin.

Candida esophagitis, a defining illness of acquired immunodeficiency syndrome (AIDS), requires systemic antifungal therapy. Candida albicans can become resistant to commonly administered azole antifungal agents. An attractive alternative is caspofungin, an echinocandin antifungal that has generally displayed predictable activity against C.

Pharmacodynamic evaluation of extending the administration time of meropenem using a Monte Carlo simulation.

A Monte Carlo simulation demonstrated that 1 g of meropenem (MEM) every 8 h (q8h) (3-h infusion) has a higher target attainment rate against Pseudomonas aeruginosa than either 500 mg of MEM q8h (3-h infusion) or 0.5 g of imipenem-cilastatin (I-C) q6h (1-h infusion). For other pathogens, 500 mg of MEM q8h was equivalent or superior to I-C.

Pharmacodynamic profiling of piperacillin in the presence of tazobactam in patients through the use of population pharmacokinetic models and Monte Carlo simulation.

The primary objectives of this analysis were to determine which pharmacokinetic model most accurately describes the elimination pathways for piperacillin in the presence of tazobactam through population pharmacokinetic modeling and to characterize its pharmacodynamic profile. Once the optimal pharmacokinetic model was identified, Monte Carlo simulation of 10,000 subjects with ADAPT II was performed to estimate the probability of attaining a target free-piperacillin concentration greater than the MIC for 50% of the dosing interval for 3.375 g every 6 h or every 4 h given as a 0.