Stability and compatibility study of cefepime in comparison with ceftazidime for potential administration by continuous infusion under conditions pertinent to ambulatory treatment of cystic fibrosis patients and to administration in intensive care units

Abstract

Cefepime has been examined for stability, potential liberation of degradation products and compatibility with other drugs under conditions mimicking its potential use by continuous infusion in cystic fibrosis and intensive care patients (5-12% w/v solutions; temperatures from 20 to 37 degrees C; 1 h contact at 25 degrees C with other drugs frequently co-administered by intravenous route to these types of patients). Ceftazidime was used as a comparator based on a previous normative study with this antibiotic for the same indications. Based on a limit of max. 10% degradation, cefepime can be considered stable for a maximum of 24 h at 25 degrees C, but for only approximately 14 h at 30 degrees C, and for <10 h at 37 degrees C. Cefepime released so far unidentified degradation products if maintained at >30 degrees C for >12 h as shown from a marked increase in pH and from the development of a strong red-purple colour. Incompatibilities were observed with erythromycin, propofol, midazolam, phenytoin, piritramide, theophylline, nicardipine, N-acetylcysteine and a concentrated solution of dobutamine. We conclude that: (i) cefepime cannot be used safely by continuous infusion if containers are kept for more than a few hours at 37 degrees C (as will be the case for cystic fibrosis patients if using portable pumps carried under clothes); (ii) caution must be exercised in intensive care patients if the temperature and co-administration of other drugs is not kept under tight control. The nature and safety of the cefepime degradation products need to be studied further.

Pharmacodynamics of Cefepime Alone and in Combination with Various Antimicrobials against Methicillin-Resistant Staphylococcus aureus in an In Vitro Pharmacodynamic Infection Model

“…Although not statistically significant, we observed a greater reduction in bacterial density as a function of dosing interval. This relationship has been previously shown with cefepime against gram-negative organisms (6,9,11,12,41). The observed activity of cefepime against MRSA in this study may be related to some minimal activity against penicillin-binding protein 2a and/or due to a heteroresistance profile for beta-lactams in which some initial activity may be expected against a portion of the bacterial inoculum (40).…”

“…The maximal efficacy for cephalosporins in animal infection models is observed when serum concentrations are greater than the MIC for 40 to 50% of dosing interval for S. aureus (14). Therefore, we evaluated cefepime dosing at continuous infusion versus every 8 h and every 12 h (4,6,7,9). In our models, the percent time above the MIC was 100, 100, and 84% for continuous infusion, every 8 h, and every 12 h, respectively.…”

Continuous versus Intermittent Infusions of Ceftazidime for Treating Exacerbation of Cystic Fibrosis

“…No adverse effects of the CI of ceftazidime have ever been reported in patients with CF (4,22). Ceftazidime (120 g/liter) displays 90% stability for up to 24 h at 25°C but for only 8 h at 37°C (2,30). Temperature control is therefore critical for the administration of ceftazidime via portable pumps, which should not be carried under clothing for prolonged periods (30).…”

Continuous versus intermittent infusion of temocillin, a directed spectrum penicillin for intensive care patients with nosocomial pneumonia: stability, compatibility, population pharmacokinetic studies and breakpoint selection

“…Based on the temocillin registered daily dose (4 g) and on practical experience with the preparation of b-lactam solutions for CI in IC units 13 (daily dose prepared in a volume of 48 mL), stability was tested at a concentration of 83.4 g/L in water (Milli-Q Academic Ultrapure w Water System, Millipore Corp., Bedford, MA, USA) at temperatures ranging from 20 to 378C for up to 24 h and under exposure to normal room light. To detect incompatibilities related to the infusion of temocillin with other drugs through a common infusion set, 11,13 temocillin and each other drug were mixed at those concentrations susceptible to be observed in a common infusion line (following conventional conditions of administration) and left at 258C for 1 h before being examined for physical and chemical compatibilities as described previously.…”