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Systematic review of room temperature stability of key beta-lactam antibiotics for extended infusions in inpatient settings
  1. Abi Jenkins1,
  2. Conor Jamieson2,
  3. Mark Santillo3
  1. 1Pharmacy, University Hospitals Birmingham, Birmingham, UK
  2. 2NHS England, Birmingham, UK
  3. 3UK and University Hospitals Bristol and Weston NHS Trust, Plymouth Bristol, UK
  1. Correspondence to Dr Abi Jenkins, Pharmacy, University Hospitals Birmingham, Edgbaston, UK; Abigail.jenkins{at}


Background Extended infusion (EI) of beta-lactam antibiotics may offer clinical benefits aligned with improved probability of target attainment for critical pharmacokinetic/pharmacodynamic parameters that correlate with efficacy. There is much research interest in prolonged and continuous infusions (collectively, extended infusions) of beta-lactams to improve patient outcomes, particularly in critically ill patients in intensive care. While definitive clinical trial data demonstrating beneficial outcomes is awaited, there has been limited focus on the stability of the agents given by EI, which may be an equally critical parameter. EI may allow for savings in nursing time due to reduced need for drug reconstitution. We set out to examine the data for stability for EI at room temperature, consistent with the requirements of 'A Standard Protocol for Deriving and Assessment of Stability- Part 1 Aseptic Preparation (Small Molecules)’, which allows a 5% loss of active pharmaceutical ingredient (API) applicable for those territories that use the British Pharmacopoeia also for a 10% loss applicable in much of rest of the world.

Methods Searches using preferred reporting items for systematic reviews and meta-analyses (PRISMA) principles for stability data on freshly prepared beta-lactam antimicrobials for extended administration at room temperature (at or above 23°C) were conducted in November 2021 and updated in December 2022.

Results We found data to support the extension of the shelf life of 12 key beta-lactam antibiotics once reconstituted (aztreonam, amoxicillin, benzylpenicillin, flucloxacillin, piperacillin/tazobactam, cefazolin, cefmetazole, ceftaroline, ceftazidime, ceftriaxone, imipenem and meropenem) compliant with the NHS protocol, and data for five other agents (ticarcillin, cefepime, cefiderocol, cefoxitin and doripenem) which would be acceptable in regions outside the UK beyond that listed in the Summary of Product Characteristics.

This review has not been registered under PROSPERO.

  • Drug stability
  • systematic review
  • Drug Compounding

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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