Real-World Impact of the Accelerate PhenoTest BC Kit on Patients With Bloodstream Infections in the Improving Outcomes and Antimicrobial Stewardship Study: A Quasiexperimental Multicenter Study.

Background: Bloodstream infections (BSIs) are a leading cause of morbidity and mortality. The Improving Outcomes and Antimicrobial Stewardship study seeks to evaluate the impact of the Accelerate PhenoTest BC Kit (AXDX) on antimicrobial use and clinical outcomes in BSIs.

Methods: This multicenter, quasiexperimental study compared clinical and antimicrobial stewardship metrics, prior to and after implementation of AXDX, to evaluate the impact this technology has on patients with BSIs.

Improving outcomes and antibiotic stewardship (IOAS) for patients with Gram-positive bloodstream infections through use of rapid testing: a quasi-experimental multicentre study of the Accelerate PhenoTest™ BC Kit.

Background: Data from the Improving Outcomes and Antibiotic Stewardship for Patients with Bloodstream Infections: Accelerate PhenoTest™ BC Kit (AXDX) Registry Study were analysed to determine the impact of rapid organism identification and antimicrobial susceptibility testing (AST) for Gram-positive bacteraemia.

Patients And Methods: This multicentre, quasi-experimental study evaluated clinical and antimicrobial stewardship metrics following the implementation of AXDX. Data from hospitalized patients with bacteraemia were compared between groups, one that underwent testing on AXDX (post-AXDX) and one that underwent traditional identification and AST (pre-AXDX).

Performance of ceftriaxone susceptibility testing on the Accelerate Pheno® system of ESBL-producing isolates.

The correlation of ceftriaxone nonsusceptibility and ESBL production was evaluated in 40 characterized isolates. Performance of ceftriaxone susceptibility testing on the Accelerate Pheno was evaluated and compared with reference broth microdilution in triplicate. The CLSI ESBL confirmatory test was also evaluated.

Impact of antimicrobial therapy on the gut microbiome.

The gut microbiome is now considered an organ unto itself and plays an important role in health maintenance and recovery from critical illness. The commensal organisms responsible for the framework of the gut microbiome are valuable in protection against disease and various physiological tasks. Critical illness and the associated interventions have a detrimental impact on the microbiome.

Analyses of a Ceftazidime-Avibactam-Resistant Isolate Carrying Reveals a Heterogenous Population and Reversible Genotype.

A -carrying isolate developed ceftazidime-avibactam resistance during treatment with this agent. The initial and follow-up isolates exhibited ceftazidime-avibactam MICs of 4 and 64 µg/ml, respectively. Overexpression of AcrAB-TolC and porin alterations were detected in both isolates, but no other resistance mechanism was observed.

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.

Supporting the ceftaroline fosamil/avibactam Enterobacteriaceae breakpoint determination using humanised in vivo exposures in a thigh model.

Previous in vivo studies using a human-simulated regimen of ceftaroline/avibactam 600/600mg every 8h (q8h) showed activity against extended-spectrum β-lactamase-, AmpC- and KPC-producing Enterobacteriaceae with minimum inhibitory concentrations (MICs) ≤ 1 μg/mL. Here we sought to determine the efficacy of this human-simulated regimen against organisms with MICs ≥ 1 μg/mL to help determine a breakpoint value that would reliability predict efficacy in humans. In total, 31 isolates (1 Escherichia coli, 9 Klebsiella pneumoniae, 9 Enterobacter cloacae, 1 Citrobacter koseri, 2 Serratia marcescens, 1 Klebsiella oxytoca and 8 Pseudomonas aeruginosa) with ceftaroline/avibactam MICs of 1 to 16 μg/mL were tested in a murine immunocompromised thigh infection model; 15 isolates were also tested in an immunocompetent model.

In vitro pharmacodynamics of human simulated exposures of ceftaroline and daptomycin against MRSA, hVISA, and VISA with and without prior vancomycin exposure.

The effects of prior vancomycin exposure on ceftaroline and daptomycin therapy against methicillin-resistant Staphylococcus aureus (MRSA) have not been widely studied. Humanized free-drug exposures of vancomycin at 1 g every 12 h (q12h), ceftaroline at 600 mg q12h, and daptomycin at 10 mg/kg of body weight q24h were simulated in a 96-h in vitro pharmacodynamic model against three MRSA isolates, including one heteroresistant vancomycin-intermediate S. aureus (hVISA) isolate and one VISA isolate.

In vivo efficacy of humanized ceftaroline fosamil-avibactam exposures in a polymicrobial infection model.

Although Gram-positive cocci are the most common pathogens in diabetic foot infections, these infections often are polymicrobial. The objective of this study was to assess the efficacy of a simulated human dose of 600 mg ceftaroline fosamil-600 mg avibactam every 8 h as a 1-h infusion in a polymicrobial in vivo murine model. Seven isolates were used (3 methicillin-resistant Staphylococcus aureus [MRSA] isolates, 1 methicillin-susceptible S.

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.

Pharmacokinetics of doripenem in infected patients treated within and outside the intensive care unit.

Background: Doripenem often is used in the intensive care unit (ICU) to treat serious infections. However, pharmacokinetics in this population often are altered by various physiologic changes. Current pharmacokinetic data in critically ill patients receiving doripenem are limited.

Pharmacokinetics of intravenous linezolid in moderately to morbidly obese adults.

The pharmacokinetics of linezolid was assessed in 20 adult volunteers with body mass indices (BMI) of 30 to 54.9 kg/m(2) receiving 5 intravenous doses of 600 mg every 12 h. Pharmacokinetic analyses were conducted using compartmental and noncompartmental methods.

Efficacy of ceftaroline fosamil in a staphylococcal murine pneumonia model.

Ceftaroline fosamil is a cephalosporin with activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The objective of this study was to characterize the dose-response relationship of ceftaroline fosamil against S. aureus in an immunocompromised murine pneumonia model, as well as to evaluate the efficacy of the humanized regimen of 600 mg intravenously (i.