As healthcare has shifted from inpatient to the medical home model, there has been an increase in the use of OPAT. One modality that has allowed for the expanded use of OPAT is the elastomeric infusion pump (EIP). While the use of outpatient EIPs offers advantages such as increased patient convenience, reduced cost, and avoidance of nosocomial infections, data are limited on the stability of antibiotics administered via this method.
A recent systematic review of original articles and conference communications listed in PubMed, Embase, Web of Science, and the Cochrane Database through January 2, 2021, was conducted to examine antibiotic stability in EIPs.
To be in this systematic review, studies had to include clearly identified EIP brands; had to test antibiotic chemical stability in the portable EIPs under controlled laboratory conditions that included time and storage conditions (i.e., maximum time and temperature at which chemical stability was successfully proved); and had to utilize a reliable quantification technique (e.g., high-performance liquid chromatography or liquid chromatography/mass spectrometry) to study the chemical stability of the antibiotic.
For an antibiotic to be deemed chemically stable in the EIP, there had to be retention of more than 90% of the baseline antibiotic concentration by the end of the study period. When available, data were also gathered about the physical stability of antibiotics in EIPs. Unacceptable physical stability included pH variability greater than 0.5, significant changes in the color of the antibiotic solution, and/or the appearance of visible particles.
The authors identified 33 papers on the stability of antibiotics in EIPs. Among the antibiotics studied that were available in the United States were amoxicillin, ampicillin, aztreonam, cefazolin, cefepime, ceftaroline fosamil, ceftazidime, ceftolazane/tazobactam, ceftriaxone, clindamycin, colistimethate sodium, ertapenem, gentamicin, imipenem/cilastatin, meropenem, meropenem/vaborbactam, nafcillin, penicillin G potassium, penicillin G sodium, piperacillin, piperacillin/tazobactam, telavancin, tobramycin, and vancomycin. Antibiotics studied that have been discontinued in the U.S. included cefmetazole, ceftazidime with arginine, doripenem, mezlocillin, and ticarcillin/clavulanic acid. Additional antibiotics studied that are not available in the U.S. included cefsulodin, colistin methane-sulfonate, flucloxacillin, and temocillin.
The investigators found that while stability was observed in 93% of the antibiotics in EIPs, only some conditions had to be met to be deemed "stable." For example, only 9% of articles defined chemical stability as the maintenance of 95% of the initial concentration. Approximately three-quarters (75.7%) of articles described the use of both chemical and physical stability testing. While chemical stability was acceptable in two articles, the authors also found evidence of physical instability. An additional six studies found unacceptable pH variations; however, the antibiotics were deemed "stable." Testing conditions varied, with only 6% of articles describing testing the drugs (i.e., penicillin G sodium, telavancin) under refrigeration. Two-fifths (42%) of studies analyzed antibiotic stability under sequential refrigeration followed by room temperature conditions.
The authors recommend that future studies of antibiotic stability in EIPs should follow the guidance provided by the National Health Service's Yellow Cover Document (YCD). The YCD describes recommended elements to assess the chemical and physical stability of sterile products. Among these elements are information on the antibiotic's excipients, the reconstitution and diluent vehicle, pH, the final antibiotic concentration, light exposure, the maximum temperature and time at which chemical stability is maintained, and the absorption of the drug to the device.
This paper serves as a useful resource for pharmacists involved in providing OPAT via EIPs. It also calls for more high-quality research to examine the chemical and physical stability of antibiotics administered by this administration method.
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