Flucloxacillin sodium

Introduction: Peripheral venous catheters (PVCs) are used to administer antimicrobials, but many fail prior to completion of therapy. While some antimicrobials are known to increase the PVC failure rate, risk profiles for many are unclear. Objective: To synthesize data from prospective PVC studies conducted between 2013 and 2019 to determine associations between common antimicrobials and PVC failure. Methods: A secondary analysis was undertaken of seven randomized controlled trials and two prospective cohort studies from three quaternary hospitals (two adult and one paediatric) in Australia between 2013 and 2019. The primary outcome was PVC failure due to vessel injury (occlusion, infiltration or extravasation) or irritation (pain or phlebitis). Associations between antimicrobial use and PVC failure were explored using multi-variable Cox regression. Results: In total, 5252 PVCs (4478 patients) were analysed; vessel injury and irritations occurred in 19% and 11% of all PVCs, respectively. Vessel injury was significantly associated with cefepime hydrochloride [hazard ratio (HR) 2.50; 95% confidence interval (CI) 1.44-4.34], ceftazidime pentahydrate (HR 1.91, 95% CI 1.11-3.31), flucloxacillin sodium (HR 1.84, 95% CI 1.45-2.33), lincomycin hydrochloride (HR 1.67, 95% CI 1.10-2.52) and vancomycin hydrochloride (HR 1.73, 95% CI 1.25-2.40). Irritation was significantly associated with flucloxacillin sodium (HR 2.58, 95% CI 1.96-3.40). Conclusions: This study identified several antimicrobials associated with increased PVC failure, including some that were already known to be associated and some that had not been identified previously. Research is needed urgently to determine superior modes of delivery (e.g. dilution, infusion time, device type) that may prevent PVC failure.

Background: Piperacillin/tazobactam is a broad-spectrum penicillin. Hypersensitivity reactions are less commonly reported than with other penicillins except in patients with cystic fibrosis. Objective: Detailed clinical characterization of a patient cohort referred with suspected piperacillin-tazobactam hypersensitivity. Methods: Retrospective analysis of the demographic characteristics, clinical presentation, investigation, and management of 87 patients presenting to 5 European allergy centers. Patients underwent skin prick and intradermal testing with piperacillin/tazobactam, major (penicilloyl-polylysine) and minor (sodium penilloate) determinants, amoxicillin, benzylpenicillin, flucloxacillin, co-amoxiclav, clavulanic acid, and meropenem with immediate and, where appropriate, delayed reading of tests. Skin test-negative patients underwent drug provocation to piperacillin/tazobactam and/or other penicillins. A multistep protocol was used, depending on risk assessment. Results: Forty-eight of 87 (55%) patients were diagnosed with hypersensitivity to piperacillin/tazobactam with either positive skin or drug provocation test results, of whom 10 (21%) had a diagnosis of cystic fibrosis. Twenty-six (54%) patients presented with immediate and 22 (45%) with nonimmediate hypersensitivity. Patients with cystic fibrosis predominantly presented with nonimmediate hypersensitivity (70%). Reactions were severe in 52% of immediate reactors (Brown's anaphylaxis grade 3) and moderately severe (systemic involvement) in 75% of nonimmediate reactors. The number of patients with negative skin test results tolerating reintroduction was comparable in immediate (80%) and nonimmediate (88%) hypersensitivity. One-third of patients were cross-sensitized to other penicillins. The cross-sensitization pattern raised the possibility of tazobactam allergy in 3 patients. In 21 patients selectively sensitized to piperacillin/tazobactam (12 immediate, 9 nonimmediate), tolerance to other beta-lactams was demonstrated by drug provocation testing. Conclusions: Piperacillin-tazobactam caused immediate and nonimmediate hypersensitivity with similar frequency. Most patients were selectively sensitized and tolerated other penicillins. Some patients may be allergic to the beta-lactamase inhibitor only.

Objectives: To investigate the effect of pH and buffers on the degradation rate of flucloxacillin and to determine if flucloxacillin can be stabilised using a buffered diluent for up to 14 days when stored at 2°C-8°C including a 24-hour infusion period at 32°C in two elastomeric devices (Accufuser and INfusor LV) filled to 240 mL. Testing as per the NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements. Methods: A validated stability indicating high-performance liquid chromatography method was used for assessing the stability of flucloxacillin diluted in 0.3% w/v citrate-buffered saline pH 7.0 when stored at 2°C-8°C in two ambulatory devices (Accufuser and INfusor LV). Flucloxacillin at 10 and 50 mg/mL diluted in 0.3% w/v citrate-buffered saline pH 7.0 to a final volume of 240 mL and stored at 2°C-8°C, including 24 hours at 32°C, was tested from two batches in replicate (n=3) at five time points for up to 14 days according to the requirements of the YCD. Results: Greater than 95% of the zero-time concentration of flucloxacillin at 10 and 50 mg/mL remained when stored at 2°C-8°C after 14 days including 24 hours at 32°C in both Accufuser and INfusor LV devices. Conclusions: Flucloxacillin sodium stability was improved, and complied with UK national standards, by using a diluent of 0.3% w/v citrate-buffered saline pH 7 in both Accufuser and INfusor LV ambulatory devices when filled to 240 mL. The data support assigning a shelf-life of up to 14 days (13 days stored at 2°C-8°C and 24 hours at 32°C). Flucloxacillin may now be used appropriately as a continuous 24-hour infusion in outpatient parenteral antimicrobial therapy services, providing further opportunity to avoid or shorten patient hospital stays, as well as support ideal antimicrobial stewardship principles.