Widening the net: a literature review of antimicrobial agents with potential suitability for outpatient parenteral antimicrobial therapy services—the importance of storage and stability

Abstract

ObjectivesOutpatient parenteral antimicrobial therapy (OPAT) services using continuous infusions (CIs) of antimicrobial agents in elastomeric devices require evidence of acceptable stability of the agent over the infusion period. A period of refrigerated storage of filled devices, followed by the CI period, is useful for OPAT services but can present a significant challenge to the stability of drugs. The aims of this study were to review fresh-filled stability data on antimicrobials which would be useful for OPAT services and to identify suitable candidates for further assessment.MethodsSearches identified papers relating to stability assessments of antimicrobials for immediate use tested above 31°C using a stability-indicating method.ResultsWe identified 18 stability studies published in 12 papers between 2015 and 2020, assessing the stability of 10 agents. Aminopenicillins like ampicillin and amoxicillin appear too unstable for CI, while benzylpenicillin may benefit from buffering to improve its stability. Cephalosporins vary in their stability and CI periods of 24 hours may not be achievable. Of the carbapenems, there are insufficient data for doripenem but meropenem has been extensively studied and is unsuitable for CI longer than 6 hours. Voriconazole may be suitable for CI but needs further investigation.ConclusionsSome drugs identified in our review are unlikely to be suitable for continuous infusion in OPAT services due to instability. Using a ‘fresh-fill’ approach, without refrigerated storage, may make some drugs useful while other agents should be considered for further assessment to Yellow Cover Document standards. The impact of buffering for penicillins should be assessed further.

Stability Studies of Antipseudomonal Beta Lactam Agents for Outpatient Therapy

“…Our investigation has found the same stability results in both devices when other parameters such as external temperature and concentration are identical, although it is known that the composition of the devices could have an impact on drug stability [ 32 ]. The last fundamental factor over drug stability is the external temperature, especially within the 20 °C to 37 °C range, since it is well-known that an increment in temperature leads to an increase in drug degradation [ 33 ]. When administered at home, the temperature is not usually under control, and high temperatures are commonly achieved, so it is an essential parameter that must be taken into account.…”

Ampicillin Stability in a Portable Elastomeric Infusion Pump: A Step Forward in Outpatient Parenteral Antimicrobial Therapy

“…All these aspects are critical to ensure drug stability as they determine therapeutic efficacy, safety, and the emergence of resistant microorganisms [ 44 ]. Numerous studies have been published recently, favoring the use of this strategy [ 1 , 10 , 22 ]; however, AMP has not been routinely included in OPAT precisely because of its limited stability after more than 24 h at room temperature, especially in countries with warmer climates [ 45 ].…”

“…To overcome stability challenges, several approaches can be addressed, such as adding stabilizers/buffering compounds to the solutions, pH adjustment, or lowering the temperature [ 21 , 22 ]. Nakamura et al evaluated the effect of five infusion solutions on the stability of 50 mg/mL AMP, namely normal saline, acetate ringer, 5% dextrose and dextrose-electrolyte with or without potassium.…”

Successful Integration of Clinical Pharmacists in an OPAT Program: A Real-Life Multidisciplinary Circuit

“…In fact, the frequency of visits by our HaH unit at patients’ homes is determined by drug stability (unless a patient requires special medical assistance), as it occurs with the scheduling of workflows at the pharmacy department. Information on antimicrobial stability in elastomeric pumps can be obtained through distinct sources: databases from elastomeric pump manufacturers (with access usually restricted to customers), the Stabilis ® database, systematic published reviews [ 94 , 95 , 96 ], official guidelines or consensus documents [ 10 , 65 ], or specific publications about a single antimicrobial or family [ 97 , 98 ]. Sometimes, a lack of stability data or short stability time are the main factors that prevent a patient from entering an OPAT program or cause the replacement of an initially prescribed antimicrobial.…”

“…The multidisciplinary circuit presented here originated from the emerging need, detected back in 2013, that antimicrobial device manipulation should be improved for the higher quality and safety of the OPAT program [ 96 , 127 ]. From the point of view of management, the pharmacy department struggled with the dedication to achieve the proper resources to improve these procedures.…”