Outpatient parenteral antibiotic therapy (OPAT) is associated with both patient convenience and cost savings. However, several antibiotics that may be beneficial as OPAT require multiple daily dosing in order to optimize their pharmacokinetic-pharmacodynamic profile. The use of continuous infusion (CI) may help circumvent this limitation, but there are numerous factors to consider with the use of this dosing schedule.

A recent review article explored the evidence, antimicrobial stability data, and feasibility considerations for the use of CI OPAT. Among the practice considerations are patient/caregiver acceptance, cost, and stability data.

The two most common devices utilized for CI include ambulatory electronic infusion pumps (EIPs; also called continuous ambulatory delivery devices) and elastomeric devices (EDs). Whereas EIPs are battery-powered pumps that are connected to a compounded or premixed bag or cassette, EDs utilize a positive-pressure patented membrane technology system that is independent of the effects of gravity. There are advantages and differences to both systems. In the case of EIPs, they can be used to administer large infusion volumes, have alarms that detect when the device is malfunctioning, and are associated with a lower margin of error (5%), but they are more complicated for a patient or caregiver to operate. On the other hand, EDs are easier to use but have a higher margin of error (15%) and their flow rate is dependent on fluid viscosity and temperature. Examples of EDs include AutoDose, Homepump Eclipse/C-series, Intermate, MedFlo, Easypump II, SMARTez, MEDI-FLO, Accuflo, ReadyMED, FOLfusor, and Accufuser.

Cost avoidance associated with the use of CI OPAT has been estimated to be from $2 million to $3.5 million. However, cost comparison data between the different types of devices are limited.

A major concern with the use of these devices is the stability of the sterile antimicrobial preparation. Normally, stability is studied either at room temperature (i.e., 25 ◦C) or under refrigeration (i.e., 5 ◦C). However, prolonged contact with the patient’s body may affect stability, as may the temperature of the home environment. This article is an excellent resource for pharmacist as it provides tables on stability data of antibiotics used in EIPs and EDs. For the EIPs, it lists the medication, the type of container (i.e., ethylvinyl acetate or polyvinyl chloride), the diluent (i.e., normal saline, dextrose 5% in water or sterile water for injection), drug concentration studied, and stability at 5 ◦C, 25 ◦C, and >30 ◦C. For EDs, the list is similar except that instead of type of container, the table reports on the device studied. Additionally, lactated ringers are also used as a diluent in EDs. Drug concentrations that lack stability data at 25 ◦C or higher for no less than 24 hours are highlighted in gray.

The article discusses outcome data associated the CI of penicillins, piperacillin-tazobactam, cephalosporins, and cephalosporins. Antimicrobial agents that are best suited for CI OPAT include penicillin, piperacillin/tazobactam, and vancomycin whereas ampicillin and meropenem, which are not recommended due to stability concerns.

The article describes clinical controversies associated with the use of CI including:

• In the management of staphylococcal infections where oxacillin is preferred over nafcillin due to similar efficacy but decreased rates of nephrotoxicity, rash, abnormal liver function tests, and hyperkalemia
• In the management of enterococcal endocarditis where the use of ampicillin may be limited due to the frequency of administration, short stability of the drug at room temperature, and the need to pause the CI if concomitantly administered with ceftriaxone because of concerns over physical incompatibility issues
• Use of vancomycin and the maintenance of adequate AUC:MIC (area under the curve: minimum inhibitory concentration) ratios while avoiding nephrotoxicity
• The use of meropenem, which has variable stability data at different concentrations.

The article also highlights CI OPAT experience with newer antimicrobials, such as ceftolozane/tazobactam, ceftazidime/avibactam, and ceftaroline.

This article is a must-read for any pharmacist involved in preparing OPAT for CI.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.