Extended stability of antimicrobial agents in administration devices

Jenkins, Abi; Hills, Tim; Santillo, Mark; Gilchrist, Mark

doi:10.1093/jac/dkw556

Cited by 20 publications

(22 citation statements)

References 8 publications

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“…Using methods that are consistent with recent recommendations,2 elastomeric infusion devices for ambulatory care containing a total daily dose of ceftolozane–tazobactam in 240 mL remain stable for 24 hours at 21°C and 37°C. There were no appreciable concentration-related effects on drug stability.…”

Section: Discussionmentioning

confidence: 83%

“…Published in vitro stability data for ceftolozane–tazobactam supports intermittent short duration infusions at a standard dose of 1.5 g three times a day 1. Thrice daily visits are not practical for many outpatient parenteral antimicrobial therapy (OPAT) services and measures to facilitate once daily visits, such as continuous 24-hours infusions are preferred 2. A recent case report demonstrated the clinical utility and likely stability of ceftolozane–tazobactam administered as a continuous infusion by elastomeric infusion device 3.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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ObjectivesPublished 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.MethodsCeftolozane–tazobactam was prepared to achieve initial concentrations representing total daily doses for ‘renal’, ‘standard’ and ‘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.ResultsThe 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.ConclusionsCeftolozane-tazobactam is suitable for ambulatory care delivered as a continuous infusion via an elastomeric infusion device.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

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“…Unreliable data regarding stability of such antibiotics may have serious consequences since clinicians may use these results to promote continuous infusion over a prolonged period. This issue raises the need for clinicians to seek pharmaceutical expertise in order to assess the level of proof of the analytical methods used to provide data having clinical impact [33].…”

Section: Discussionmentioning

confidence: 99%

Overcoming stability challenges during continuous intravenous administration of high-dose amoxicillin using portable elastomeric pumps

et al. 2019

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While treatment of serious infectious diseases may require high-dose amoxicillin, continuous infusion may be limited by lack of knowledge regarding the chemical stability of the drug. Therefore, we have performed a comprehensive study so as to determine the chemical stability of high-dose amoxicillin solutions conducive to safe and effective continuous intravenous administration using portable elastomeric pumps. First, amoxicillin solubility in water was assessed within the range of 25 to 300 mg/mL. Then, amoxicillin solutions were prepared at different concentrations (25, 50, 125, 250 mg/mL) and stored in different conditions (5±2°C, 25±1°C, 30±1°C and 37±1°C) to investigate the influence of concentration and temperature on the chemical stability of amoxicillin. Finally, its stability was assessed under optimized conditions using a fully validated HPLC-UV stability-indicating method. Degradation products of amoxicillin were investigated by accurate mass determination using high-resolution mass spectrometry. Amoxicillin displayed limited water solubility requiring reconstitution at concentrations below or equal to 150 mg/mL. Amoxicillin degradation were time, temperature as well as concentration-dependent, resulting in short-term stability, in particular at high concentrations. Four degradation products of amoxicillin have been identified. Among them, amoxicilloic acid and diketopiperazine amoxicillin are at risk of allergic reaction and may accumulate in the patient. Optimized conditions allowing for continuous infusion of high-dose amoxicillin has been determined: amoxicillin should be reconstituted at 25 mg/mL and stored up to 12 hours at room temperature (22 ± 4°C) or up to 24 hours between 4 and 8°C.

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“…Room temperature studies are generally standardised at 20–25°C 1 8. Stability data are lacking for many antibiotics in solution above room temperature 9. In warmer climates, the solution temperature may exceed 25°C for over 75% of the 24 hours run-out period, occasionally reaching temperatures of up to 38°C 10.…”

Section: Introductionmentioning

confidence: 99%

“…A recent systematic review published in 2017 found that there were no published studies that complied completely with UK national standards specific to OPAT 9. The UK standards are detailed and describe the minimum data required from a study to be applicable for use in this setting.…”

Section: Introductionmentioning

confidence: 99%

Systematic review of stability data pertaining to selected antibiotics used for extended infusions in outpatient parenteral antimicrobial therapy (OPAT) at standard room temperature and in warmer climates

et al. 2019

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AimTo determine if there are sufficient stability data to confirm appropriate prescribing of antibiotics commonly used in outpatient parenteral antimicrobial therapy (OPAT) in warmer climates.Data sourcesFour databases were systematically searched using the terms ‘beta-lactams’, or ‘antibiotics’, or ‘anti-bacterial agents’ and ‘drug stability’ or drug storage’ for studies specific to drug stability published between 1966 and February 2018.Study selectionThe search strategy initially identified 2879 potential articles. After title and abstract review, the full-texts of 137 potential articles were assessed, with 46 articles matching the inclusion and exclusion criteria included in this review.ResultsA large volume of stability data is available for the selected drugs. Stability data at temperatures higher than 25°C were available for several of the medications, however few drugs demonstrated stability in warmer climates of 34°C or higher. Only buffered benzylpenicillin, cefoxitin and buffered flucloxacillin were found to have stability data supporting OPAT in warmer climates. Sequential data, profiling the drug for an extended period in solution under refrigeration prior to the run-out period at the higher temperatures, are also lacking.LimitationsThis study was limited by including only peer reviewed articles. There may be further grey literature supporting the stability of some of the drugs mentioned.ConclusionThere are insufficient stability data of antibiotic use in warmer climates. Studies to verify the stability and appropriate use of many antibiotics used in OPAT at standard room temperature and in warmer climates are urgently required. Several drugs in current use in the OPAT settings are lacking stability data.ImplicationsFurther research in this field is needed to develop structured evidence-based guidelines. Results of this review should be further compared with observed patient outcomes in current clinical practice.

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Extended stability of antimicrobial agents in administration devices

Abstract: This review found no published studies that comply with UK national standards for stability testing. We recommend further research and publication of antimicrobial stability data to support OPAT within the antimicrobial stewardship agenda.

Cited by 20 publications

References 8 publications

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

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

Overcoming stability challenges during continuous intravenous administration of high-dose amoxicillin using portable elastomeric pumps

Systematic review of stability data pertaining to selected antibiotics used for extended infusions in outpatient parenteral antimicrobial therapy (OPAT) at standard room temperature and in warmer climates

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