Stability of antibiotics for intraperitoneal administration in extraneal 7.5% icodextrin peritoneal dialysis bags (stab study)

Background and objectives: Patients with peritoneal dialysis (PD)-associated peritonitis may be advised to store PD-bags with pre-mixed antibiotics at home, although there is a paucity of antibiotic stability studies in the commonly used icodextrin solutions. The purpose of this study was to assess the stability of various antibiotics in PD-bags when stored at different temperatures over a 14-day period

Use of the Hollow-Fiber Infection Model to Measure the Effect of Combination Therapy of Septic Shock Exposures of Meropenem and Ciprofloxacin against Intermediate and Resistant Pseudomonas aeruginosa Clinical Isolates

Meropenem-ciprofloxacin combination therapy was compared to the respective monotherapy in a Hollow-Fiber Infection Model against two Pseudomonas aeruginosa isolates. Following initial kill of ; 5-logs by each monotherapy, rapid regrowth occurred within 24 h, reaching 108 - 1010 CFU/mL at 120 h. In contrast, combination therapy achieved . 5-log kill within 6 h and suppressed bacterial regrowth throughout. The results suggest that meropenem-ciprofloxacin combination may provide significantly enhanced bacterial killing and resistance suppression against P. aeruginosa

Pharmacodynamic Evaluation of a Single Dose versus a 24-Hour Course of Multiple Doses of Cefazolin for Surgical Prophylaxis

The optimal perioperative duration for the administration of cefazolin and other prophylactic antibiotics remains unclear. This study aimed to describe the pharmacodynamics of cefazolin for a single 2 g dose versus a 24 h course of a 2 g single dose plus a 1 g eight-hourly regimen against methicillin-susceptible Staphylococcus aureus. Static concentration time–kill assay and a dynamic in vitro hollow-fibre infection model simulating humanised plasma and interstitial fluid exposures of cefazolin were used to characterise the pharmacodynamics of prophylactic cefazolin regimens against methicillin-sensitive Staphylococcus aureus clinical isolates. The initial inoculum was 1 × 105 CFU/mL to mimic a high skin flora inoculum. The static time–kill study showed that increasing the cefazolin concentration above 1 mg/L (the MIC) did not increase the rate or the extent of bacterial killing. In the dynamic hollow-fibre model, both dosing regimens achieved similar bacterial killing (~3-log CFU/mL within 24 h). A single 2 g dose may be adequate when low bacterial burdens (~104 CFU/mL) are anticipated in an immunocompetent patient with normal pharmacokinetics

Ceftolozane–tazobactam in an elastomeric infusion device for ambulatory care: an in vitro stability study

Objectives: Published in vitro stability data for ceftolozane-tazobactam supports intermittent short duration infusions. This method of delivery is not feasible for many outpatient antimicrobial therapy services that provide only one or two visits per day. This study aimed to assess time, temperature and concentration-dependent stability of ceftolozane-tazobactam in an elastomeric infusion device for continuous infusion across clinically relevant ranges encountered in outpatient antimicrobial therapy. Methods: Ceftolozane-tazobactam was prepared to achieve initial concentrations representing total daily doses for â € renal', â € standard' and â € high' dose schedules in elastomeric infusion devices with a volume of 240 mL. Infusion devices incubated at room and body temperature were serially sampled over 48 hours. Refrigerated infusion devices were sampled over 10 days. Concentrations of ceftolozane and tazobactam were separately quantified using a validated ultra-high performance liquid chromatography-photodiode array method. Results: The greatest loss of ceftolozane occurred at 37°C, however, stability remained above 90% at 24 hours. Tazobactam was more stable than ceftolozane under these conditions. There was minimal loss at 4°C for either component over 7 days. Conclusions: Ceftolozane-tazobactam is suitable for ambulatory care delivered as a continuous infusion via an elastomeric infusion device

A UHPLC–MS/MS method for the simultaneous determination of piperacillin and tazobactam in plasma (total and unbound), urine and renal replacement therapy effluent

Piperacillin-tazobactam is a beta-lactam/beta-lactamase combination antibiotic used in patients with moderate to severe infection. Dosing of piperacillin-tazobactam requires an understanding of this patient group to maximise the effectiveness of this antibiotic and limit a further emergence of resistant pathogens. This is the first method that measures piperacillin and tazobactam simultaneously, across this range of clinically-relevant biological matrices. The calibration line was linear across the concentration range of 0.5–500 μg/mL for piperacillin and 0.625–62.5 μg/mL for tazobactam. All validation testing for matrix effects, precision and accuracy, specificity and stability were within 15%. A calibration equivalence study was performed to investigate the suitability of applying calibration curves prepared in an alternative matrix, with a mean bias of −10.8% identified for the application of a calibration line prepared for tazobactam in plasma only. Bias for all other calibration lines prepared in alternate matrices was within the 5% acceptance criteria. The method was successfully applied to a pharmacokinetic study of a critically ill patient receiving renal replacement therapy, with the results included

Pharmacodynamic evaluation of plasma and epithelial lining fluid exposures of amikacin against in a dynamic hollow-fibre infection model

Given that aminoglycosides, such as amikacin, may be used for multi-drug resistant infections, optimization of therapy is paramount for improved treatment outcomes. This study aims to investigate the pharmacodynamics of different simulated intravenous amikacin doses on susceptible to inform ventilator-associated pneumonia and sepsis treatment choices.A hollow-fibre infection model with two isolates (MIC 2 and 8 mg/L) with an initial inoculum ∼10 colony-forming unit/mL was used to test different amikacin dosing regimens. Three regimens (15, 25 and 50 mg/kg) simulating a blood exposure and a 30 mg/kg regimen simulating the epithelial lining fluid (ELF) for potential respiratory tract infection were tested. Data were described using a semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Whole genome sequencing was used to identify mutations associated with resistance emergence.While bacterial density was reduced by >6-logs within the first 12 h in simulated blood exposures, following this initial bacterial kill, there was amplification of a resistant sub-population with ribosomal mutations that were likely mediating amikacin resistance. No appreciable bacterial killing occurred with subsequent doses. There was less