JAC Advance Access originally published online on February 11, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 651-658
© 2003 The British Society for Antimicrobial Chemotherapy
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
Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, UCL 73.70 avenue E. Mounier 73, B-1200 Brussels, Belgium
Received 25 July 2002; returned 19 October 2002; revised 24 November 2002; accepted 24 December 2002
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°C; 1 h contact at 25°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°C, but for only 
14 h at 30°C, and for <10 h at 37°C. Cefepime released so far unidentified degradation products if maintained at >30°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°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.
Keywords: stability, continuous infusion, degradation, compatibility
* Corresponding author. Tel: +32-2-762-2136; Fax: +32-2-764-7373; E-mail: tulkens{at}facm.ucl.ac.be
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