Ertapenem Concentrations in Obese Patients Undergoing Surgery.

Antimicrobial prophylaxis is a cornerstone to preventing surgical site infections (SSIs). Ertapenem, a carbapenem antibiotic, is commonly used for surgical prophylaxis for many different procedures, including patients undergoing colorectal and other gastrointestinal surgeries. Obesity complicates surgical intervention and increases the risk for SSIs.

Assessment of an online calculator's vancomycin dosing and exposure appropriateness in persons who inject drugs with methicillin-resistant Staphylococcus aureus bloodstream infections.

What Is Known And Objective: While the gold standard for calculating AUC involves two steady-state concentrations, online calculators can empirically estimate AUC and other pharmacokinetic (PK) parameters. In patients with potentially altered PK, such as persons who inject drugs (PWID), the reliability of these predictions is unclear. Our objectives were to characterize the PK of vancomycin in PWID with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) and to assess the impact of these PK parameters on dosing regimens when compared to regimens generated by an online calculator.

In vitro activity of ampicillin and ceftriaxone against ampicillin-susceptible Enterococcus faecium.

Objectives: To assess activity of the combination of ceftriaxone and ampicillin against clinical isolates of ampicillin-susceptible Enterococcus faecium.

Methods: Ampicillin-susceptible E. faecium (n = 29) and Enterococcus faecalis (n = 10) collected from locations in the USA and France were used for this analysis.

What's new in the treatment of multidrug-resistant gram-negative infections?

Eradicating multi-drug resistant (MDR) organisms has been a major challenge in healthcare settings worldwide. Newly approved drugs and those currently in the pipeline may have a promising solution to this issue. The purposes of this review are to describe the various resistance mechanisms of Gram-negative bacteria and to provide a summary of the current literature available on the newer agents, such as ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and other emerging agents used for the treatment of MDR Gram-negative infections.

Possible Hepatotoxicity Associated With Daptomycin: A Case Report and Literature Review.

Purpose: To report a case of isolated daptomycin-induced acute liver injury without elevations in creatine kinase (CK) levels or kidney dysfunction.

Summary: A 49-year-old female with a history of pancreatitis, lupus, diabetes, congestive heart failure, hypertension, and chronic pain syndrome presented to the emergency department with alteration in mental status and acute liver failure. The patient had been treated with daptomycin for methicillin-resistant Staphylococcus aureus (MRSA) endocarditis for 3 weeks.

Assessment of Clostridium difficile Burden in Patients Over Time With First Episode Infection Following Fidaxomicin or Vancomycin.

In patients with first episode Clostridium difficile infection treated with vancomycin or fidaxomicin, more patients receiving fidaxomicin achieved at least 2 log10 colony-forming units/g reduction in spores at the follow-up visit (P=.02). Similar to published literature, a higher proportion of patients receiving fidaxomicin demonstrated sustained clinical response.

Vancomycin Tissue Pharmacokinetics in Patients with Lower-Limb Infections via In Vivo Microdialysis.

Background: Vancomycin is a common treatment option for skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Given the increasing prevalence of MRSA, vancomycin is widely used as empirical therapy. In patients with lower-limb infections, antimicrobial penetration is often reduced because of decreased vascular perfusion.

Assessing the Surrogate Susceptibility of Oxacillin and Cefoxitin for Commonly Utilized Parenteral Agents against Methicillin-Susceptible Staphylococcus aureus: Focus on Ceftriaxone Discordance between Predictive Susceptibility and in Vivo Exposures.

Susceptibility testing with the use of surrogate agents is common among clinical microbiology laboratories. One such example is oxacillin and cefoxitin for β-lactams against methicillin-susceptible Staphylococcus aureus (MSSA). This study aimed to assess the surrogate predictive value (SPV) of oxacillin and cefoxitin for the susceptibility of commonly utilized parenteral β-lactams against MSSA as well as to evaluate the concordance between predictive susceptibility testing and the in vivo exposures for ceftriaxone.

Isolation and quantitation of Clostridium difficile in aqueous and fecal matter using two types of selective media.

We evaluated the isolation and quantitation of Clostridium difficile from aqueous and fecal samples utilizing ChromID CDIF and cycloserine, cefoxitin, and fructose-containing agar with horse blood and taurocholate media. Growth was similar between the two. ChromID CDIF provided enhanced isolation and required no ethanol pretreatment to inhibit normal flora.

Pharmacodynamic profile of commonly utilised parenteral therapies against meticillin-susceptible and meticillin-resistant Staphylococcus aureus collected from US hospitals.

Staphylococcus aureus is a well-recognised pathogen with an evolving phenotypic profile often limiting conventional β-lactam use. In vitro potency and pharmacodynamic profile of commonly utilised agents against 1238 meticillin-susceptible S. aureus (MSSA) and 1259 meticillin-resistant S.

In vitro microdialysis membrane efficiency of broad-spectrum antibiotics in combination and alone.

Purpose: Microdialysis is a valuable technique for studying the distribution of drugs into interstitial fluid, the target site for a pharmacologic effect. Due to incomplete equilibrium, retrodialysis is a method used to correct for relative recovery. The impact of two-drug combinations on probe recovery, however, remains unknown.

Humanized tissue pharmacodynamics of cefazolin against commonly isolated pathogens in skin and skin structure infections.

Objectives: The objective of this study was to assess the efficacy of humanized cefazolin tissue concentrations against methicillin-susceptible Staphylococcus aureus (MSSA) and Enterobacteriaceae in an in vitro pharmacodynamic model.

Methods: Nine clinical isolates [five MSSA (cefazolin MIC range 0.5-2.

Phase I, open-label, safety and pharmacokinetic study to assess bronchopulmonary disposition of intravenous eravacycline in healthy men and women.

This study evaluated the pulmonary disposition of eravacycline in 20 healthy adult volunteers receiving 1.0 mg of eravacycline/kg intravenously every 12 h for a total of seven doses over 4 days. Plasma samples were collected at 0, 1, 2, 4, 6, and 12 h on day 4, with each subject randomized to undergo a single bronchoalveolar lavage (BAL) at 2, 4, 6, or 12 h.

Efficacies of ceftazidime-avibactam and ceftazidime against Pseudomonas aeruginosa in a murine lung infection model.

This study aimed to determine the efficacy of human-simulated plasma exposures of 2 g ceftazidime plus 0.5 g avibactam every 8 h administered as a 2-h infusion or a ceftazidime regimen that produced a specific epithelial lining fluid (ELF) percentage of the dosing interval in which serum free drug concentrations remain above the MIC (fT>MIC) against 28 Pseudomonas aeruginosa isolates within a neutropenic murine pneumonia model and to assess the impact of host infection on pulmonary pharmacokinetics. The fT>MIC was calculated as the mean and upper end of the 95% confidence limit.

In vitro pharmacodynamics of polymyxin B and tigecycline alone and in combination against carbapenem-resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii is increasing in prevalence. Polymyxin B and tigecycline are among the most active antibiotics used against this pathogen in vitro. Past in vitro studies, however, neglected the importance of simulating exposures observed in humans to determine their antibacterial effects.

Tissue pharmacokinetics of cefazolin in patients with lower limb infections.

Cefazolin, a first-generation cephalosporin with activity against methicillin-susceptible Staphylococcus aureus and streptococci, is often used to treat lower limb infections caused by these pathogens. Antimicrobial penetration is often limited in these patients due to compromised vasculature. Therefore, we sought to evaluate the exposure profile of cefazolin in serum and tissue in patients with lower limb infections.

In vitro pharmacodynamics of human-simulated exposures of ampicillin/sulbactam, doripenem and tigecycline alone and in combination against multidrug-resistant Acinetobacter baumannii.

Objectives: Multidrug resistance is common among Acinetobacter baumannii, limiting the available options used to treat infections caused by this organism. The objective of this study was to compare monotherapy and combination therapy with ampicillin/sulbactam, doripenem and tigecycline against multidrug-resistant A. baumannii using an in vitro pharmacodynamic model.

Comparative pharmacokinetics, pharmacodynamics, and tolerability of ertapenem 1 gram/day administered as a rapid 5-minute infusion versus the standard 30-minute infusion in healthy adult volunteers.

Study Objective: To compare ertapenem pharmacokinetics, pharmacodynamics, and tolerability when administered as a rapid 5-minute infusion to the standard 30-minute infusion.

Design: Prospective, randomized, crossover pharmacokinetic study.

Setting: Clinical research center.

Pulmonary disposition of tedizolid following administration of once-daily oral 200-milligram tedizolid phosphate in healthy adult volunteers.

This study assessed the pulmonary disposition of tedizolid, an oxazolidinone, in adult volunteers receiving 200 mg of the prodrug tedizolid phosphate orally every 24 h for 3 days to steady state. Plasma samples were collected over the dosing interval, and participants were randomized to undergo bronchoalveolar lavage (BAL) at 2, 6, 12, or 24 h after the last dose. Drug concentrations in plasma, BAL fluid, and alveolar macrophages (AM) were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the urea correction method was used to calculate epithelial lining fluid (ELF) concentrations.

Efficacy of human simulated exposures of ceftaroline against phenotypically diverse Enterobacteriaceae isolates.

Ceftaroline fosamil, a new broad-spectrum cephalosporin, exhibits potent bactericidal activity against common Gram-negative pathogens, including Enterobacteriaceae, and Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae. The purpose of this study was to evaluate the efficacy of a human simulated dose of ceftaroline fosamil against clinical Enterobacteriaceae in both neutropenic and immunocompetent mouse thigh infection models. Thirty-five Enterobacteriaceae isolates with ceftaroline MICs ranging from 0.

In vitro evaluation of novel compounds against selected resistant Pseudomonas aeruginosa isolates.

We describe the activities of RX-P763, RX-P766, RX-P770, RX-P792, RX-P793, and RX-P808 against strains of resistant Pseudomonas aeruginosa. These compounds target the large subunit of the bacterial ribosome and have broad-spectrum activities against multidrug-resistant pathogens. All compounds demonstrated in vitro activity against P.

Physical compatibility of telavancin hydrochloride with select i.v. drugs during simulated Y-site administration.

Purpose: The physical compatibility of telavancin with select i.v. drugs during simulated Y-site administration was evaluated.

Optimizing antibiotic pharmacodynamics in hospital-acquired and ventilator-acquired bacterial pneumonia.

Nosocomial pneumonia carries a high morbidity and mortality and creates a large burden on health care use. As resistance to currently available antibiotics continues to increase, the role of pharmacodynamics in drug regimen optimization becomes pivotal to the clinical success of patient therapy. This article reviews the evidence behind pharmacodynamic optimization including the use of Monte Carlo simulations, changes in pharmacokinetic parameters of critically ill patients, and differing strategies to optimize drug regimens.