Development of an HPLC Method for the Determination of Meropenem/Vaborbactam in Biological and Aqueous Matrixes.

A HPLC method was developed and validated to analyze meropenem and vaborbactam simultaneously in murine plasma and saline matrixes. A 60-μL volume of extracted sample was injected onto a 5-μm BDS Phenyl-Hypersil C18 reversed-phase column and analyzed with a UV detector set at 298 nm for the first 4.9 min and switched to 240 nm.

Single β-lactams versus combinations as empiric therapy for infections with : assessing the susceptibility.

While the value of combination versus monotherapy of infections with infection is a subject of debate, increasing antimicrobial resistance of this pathogen makes it difficult to select appropriate empiric regimens. We evaluated the probability that would be susceptible to β-lactams either as monotherapy or as part of a combination regimen. Contemporary non-duplicate isolates of derived from blood or the respiratory tract of patients hospitalized in the United States were investigated.

potency of antipseudomonal β-lactams against blood and respiratory isolates of collected from US hospitals.

Background: Challenges due to multidrug resistant (MDR) Gram-negative bacterial pathogens such as (PSA) are increasing globally. Suboptimal antimicrobial therapy of infections caused by PSA is associated with increased morbidity and mortality. As a result, antimicrobial susceptibility (%S) studies are pivotal to identifying trends in antimicrobial resistance that inform decisions regarding choice of antimicrobial therapy.

In vitro investigation of synergy among fosfomycin and parenteral antimicrobials against carbapenemase-producing Enterobacteriaceae.

Intravenous fosfomycin is undergoing clinical development in the United States for treatment of complicated urinary tract infections (cUTIs) and may be prescribed as a component of dual antibiotic regimens against carbapenemase-producing Enterobacteriaceae (CPE). Fosfomycin, aztreonam, cefepime, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem, piperacillin/tazobactam, and tobramycin minimum inhibitory concentrations (MICs) were determined by gradient diffusion strip (GDS) against CPE isolates (N = 49). The GDS cross method was used to assess antibiotic interactions between fosfomycin and the aforementioned parenteral antibiotics.

Prevalence of in vitro synergistic antibiotic interaction between fosfomycin and nonsusceptible antimicrobials in carbapenem-resistant Pseudomonas aeruginosa.

Purpose: We assessed the synergistic potential of fosfomycin and parenteral antibiotics among carbapenem-resistant Pseudomonas aeruginosa (CRP).

Methodology: Minimum inhibitory concentrations (MICs) were determined by broth microdilution for all antibiotics except fosfomycin, for which the gradient diffusion strip (GDS) method was used. The GDS cross method was performed to assess interactions between fosfomycin and: aztreonam, cefepime, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem, piperacillin/tazobactam and tobramycin.

Pharmacokinetics of Cefazolin and Vancomycin in Infants Undergoing Open-Heart Surgery With Cardiopulmonary Bypass.

Background: Gram-positive bacteria account for nearly three-quarters of all surgical site infections. Antibiotic prophylaxis against these bacteria with cephalosporins or, in select circumstances, with vancomycin is considered standard of care for prevention of surgical site infections. There is little evidence to describe the optimal dosing regimen for surgical site infection prophylaxis in infants undergoing cardiac surgery, and a great deal of institutional variability exists in dosing prophylactic antibiotics.

Development of an HPLC-MS/MS method for the determination of ceftolozane/tazobactam in bronchoalveolar lavage fluid.

Aim: We describe the validation of an HPLC-MS/MS method to analyze ceftolozane and tazobactam simultaneously in saline matrixes.

Materials & Methods: An Agilent 1260 HPLC interfaced to an Agilent 6470 triple-quadrupole mass spectrometer was used for quantification. A reverse-phase column running a gradient of water and acetonitrile containing 0.

Subcutaneous cefazolin to reduce surgical site infections in a porcine model.

Background: Surgical site infections (SSIs) pose a significant health and financial burden. A key aspect of appropriate prophylaxis is the administration of antibiotics intravenously (IV). However, subcutaneous administration of antibiotics is not well described in the literature.

Potency of parenteral antimicrobials including ceftolozane/tazobactam against nosocomial respiratory tract pathogens: considerations for empiric and directed therapy.

Background: Empiric therapy decisions are predicated on knowledge of both the epidemiology and antimicrobial susceptibility of the probable infecting pathogen(s). The objective of this study was to evaluate the microbial distribution and phenotypic profiles of nosocomial respiratory isolates collected from multiple US hospitals and assess the clinical utility of various monotherapy and combination regimens.

Methods: Hospitals provided consecutive non-duplicate adult inpatients Gram-negative nosocomial respiratory isolates from cultures received ≥48 h after hospital admission.

In vitro potency of amikacin and comparators against E. coli, K. pneumoniae and P. aeruginosa respiratory and blood isolates.

Background: The purpose of this study was to define the potency of amikacin and comparator agents against a collection of blood and respiratory nosocomial isolates implicated in ICU based pulmonary infections gathered from US hospitals.

Methods: Minimum inhibitory concentrations of amikacin, aztreonam, cefepime, ceftazidime, ceftolozane/tazobactam, ceftriaxone, ciprofloxacin, imipenem, meropenem, piperacillin/tazobactam and tobramycin were tested against 2460 Gram-negative isolates. Amikacin had 96 % susceptibility against the combined E.

Development of an HPLC Method for the Determination of Ceftolozane/Tazobactam in Biological and Aqueous Matrixes.

Herein, we report the development and validation of an HPLC method to analyze ceftolozane and tazobactam simultaneously in human plasma, human serum, swine serum and saline matrixes. A reversed-phase column was used with a UV detector set at 260 nm and switched to 218 nm. The mobile phase consisted of methanol and sodium phosphate buffer at a flow rate of 1.

Defining Extended Spectrum β-Lactamases: Implications of Minimum Inhibitory Concentration-Based Screening Versus Clavulanate Confirmation Testing.

Introduction: While the Clinical and Laboratory Standards Institute (CLSI) recommends against routine screening for extended spectrum β-lactamases (ESBLs), knowledge of these data can provide valuable insights regarding epidemiology and drug therapy decisions. The purpose of this study was to compare the impact of minimum inhibitory concentration (MIC)-based screening versus phenotypic confirmatory testing of ESBLs on the susceptibility profile of selected antimicrobials.

Methods: Broth microdilution MICs were determined for various antimicrobial agents against a collection contemporary clinical Escherichia coli and Klebsiella pneumoniae isolates.

Susceptibility Profile of Ceftolozane/Tazobactam and Other Parenteral Antimicrobials Against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa From US Hospitals.

Purpose: Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are frequently isolated pathogens in the hospital setting, and antimicrobial resistance among these organisms is on the rise. In an attempt to meet the challenge of gram-negative resistance, new therapies, including ceftolozane/tazobactam (C/T), were recently approved by the Food and Drug Administration, and others are in late-stage development. The purpose of this study is to describe the in vitro potency of C/T and other parenteral antimicrobials against a geographically diverse population of E coli, K pneumoniae, and P aeruginosa collected in US hospitals.

Impact of revised cefepime CLSI breakpoints on Escherichia coli and Klebsiella pneumoniae susceptibility and potential impact if applied to Pseudomonas aeruginosa.

The CLSI reduced the cefepime Enterobacteriaceae susceptibility breakpoint and introduced the susceptible-dose-dependent (S-DD) category. In this study, MICs were determined for a Gram-negative collection to assess the impact of this change. For Enterobacteriaceae, this resulted in <2% reduction in susceptibility, with 1% being S-DD.

To add or not to add polysorbate 80: impact on colistin MICs for clinical strains of Enterobacteriaceae and Pseudomonas aeruginosa and quality controls.

Colistin adherence to plastics can be diminished by adding a surfactant, i.e., polysorbate 80.

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 vivo comparison of CXA-101 (FR264205) with and without tazobactam versus piperacillin-tazobactam using human simulated exposures against phenotypically diverse gram-negative organisms.

CXA-101 is a novel antipseudomonal cephalosporin with enhanced activity against Gram-negative organisms displaying various resistance mechanisms. This study evaluates the efficacy of exposures approximating human percent free time above the MIC (%fT > MIC) of CXA-101 with or without tazobactam and piperacillin-tazobactam (TZP) against target Gram-negative organisms, including those expressing extended-spectrum β-lactamases (ESBLs). Sixteen clinical Gram-negative isolates (6 Pseudomonas aeruginosa isolates [piperacillin-tazobactam MIC range, 8 to 64 μg/ml], 4 Escherichia coli isolates (2 ESBL and 2 non-ESBL expressing), and 4 Klebsiella pneumoniae isolates (3 ESBL and 1 non-ESBL expressing) were used in an immunocompetent murine thigh infection model.

Development of an HPLC method for the determination of anidulafungin in human plasma and saline.

An ultraviolet high-performance liquid chromatography (HPLC) method was developed to analyze anidulafungin in human plasma and saline. A reversed-phase column was used with a UV detector set at 310 nm. The mobile phase consisted of methanol and ammonium phosphate buffer at a flow rate of 1 mL/min.

Correlation between vancomycin and daptomycin MIC values for methicillin-susceptible and methicillin-resistant Staphylococcus aureus by 3 testing methodologies.

We examined the potential correlation between vancomycin and daptomycin MIC for 298 Staphylococcus aureus by broth microdilution (BMD), Etest, and MicroScan(®). Etest and BMD identified a significant, albeit poor, correlation between MICs (ρ = 0.29, P < .

Tissue penetration and pharmacokinetics of tigecycline in diabetic patients with chronic wound infections described by using in vivo microdialysis.

Tissue penetration of systemic antibiotics is an important consideration for positive outcomes in diabetic patients. Herein we describe the exposure profile and penetration of tigecycline in the interstitial fluid of wound margins versus that of uninfected thigh tissue in 8 adult diabetic patients intravenously (IV) administered 100 mg and then 50 mg of tigecycline twice daily for 3 to 5 doses. Prior to administration of the first dose, 2 microdialysis catheters were inserted into the subcutaneous tissue, the first within 10 cm of the wound margin and the second in the thigh of the same extremity.

In vitro activity and pharmacodynamics of commonly used antibiotics against adult systemic isolates of Escherichia coli and Pseudomonas aeruginosa at Forty US Hospitals.

Background: Treatment of infections caused by gram-negative bacilli is increasingly challenging because of emerging resistance. Current surveillance data are informative, but may not discern differences by infection site and clinical setting, and do not incorporate pharmacodynamic (PD) characteristics when determining susceptibility.

Objectives: This study explored the differences in infection site and clinical setting and evaluated dose-optimization strategies using PD principles.

Comparison of the activity of a human simulated, high-dose, prolonged infusion of meropenem against Klebsiella pneumoniae producing the KPC carbapenemase versus that against Pseudomonas aeruginosa in an in vitro pharmacodynamic model.

We have previously demonstrated that a high-dose, prolonged-infusion meropenem regimen (2 g every 8 h [q8h]; 3-hour infusion) can achieve 40% free drug concentration above the MIC against Pseudomonas aeruginosa with MICs of View Article and Find Full Text PDF

Elevated vancomycin minimum inhibitory concentrations among methicillin-resistant Staphylococcus aureus isolated from patients with ventilator-associated pneumonia at a Connecticut hospital.

Emerging evidence suggests that vancomycin minimum inhibitory concentrations (MICs) within methicillin-resistant Staphylococcus aureus (MRSA) are increasing. The objective of this surveillance study was to determine vancomycin MIC distributions for MRSA isolates collected from the respiratory tract of patients with ventilator-associated pneumonia (VAP) at a large community hospital in Hartford, Connecticut. The frequency of heteroresistant vancomycin intermediate S.

In vivo microdialysis study of the penetration of daptomycin into soft tissues in diabetic versus healthy volunteers.

Daptomycin is approved for the treatment of complicated skin and soft tissue infections, including diabetic wounds of the lower extremities, at a dose of 4 mg/kg of body weight once daily. For such localized tissue infections, drug concentrations in the interstitial space are an important determinant of successful therapy. In the diabetic population, peripheral arterial disease may limit antibiotic penetration into the target tissue.