CEFEPIME - A REVIEW OF ITS ANTIBACTERIAL ACTIVITY, PHARMACOKINETIC PROPERTIES AND THERAPEUTIC USE

Cefepime is a 'fourth' generation cephalosporin that has a broader spe ctrum of antibacterial activity than the third generation cephalospori ns and is more active in vitro against Gram-positive aerobic bacteria. The fact that cefepime is stable to hydrolysis by many of the common plasmid- and chromosomally-mediated beta-lactamases, and that it is a poor inducer of type I beta-lactamases, indicates that cefepime may be useful for treatment of infections resistant to earlier cephalosporin s. In comparative trials, cefepime 1 to 2g, usually administered intra venously twice daily, was as effective as ceftazidime 1 to 2g, usually administered 3 times daily for treatment of bacteraemia and infection s of the lower respiratory tract, urinary tract, pelvis and skin and s kin structures. Furthermore, cefepime was as effective as ceftazidime and piperacillin or mezlocillin in combination with gentamicin when ad ministered as empirical treatment for fever in patients with neutropen ia. A limited number of trials have found cefepime to be as effective as cefotaxime for the treatment of gynaecological and lower respirator y tract infections. Similarly, cefepime 2g twice daily intravenously ( alone or in combination with metronidazole) was as effective as gentam icin in combination with mezlocillin or clindamycin, respectively, for the treatment of intra-abdominal infection. Cefepime has a linear pha rmacokinetic profile, an elimination half-life of approximately 2 hour s and is primarily excreted by renal mechanisms as unchanged drug. Cef epime has a tolerability profile similar to that of other parenteral c ephalosporins; adverse events are primarily gastrointestinal in nature . A total of 1.4 and 2.9% of patients receiving cefepime less than or equal to 2 g/day and >2 g/day, respectively required treatment withdra wal as a result of any adverse event. Thus, cefepime has the advantage of an improved spectrum of antibacterial activity, and is less suscep tible to hydrolysis by some beta-lactamases, compared with third gener ation cephalosporins. Despite these advantages, cefepime has not been found to be more effective than ceftazidime and cefotaxime in clinical trials, although most trials selected patients,vith organisms sensiti ve in vitro to both comparator agents. Further trials, particularly in areas of widespread bacterial resistance, are required to confirm the positioning of cefepime for treatment of serious infection, and in pa rticular to further explore whether its potential advantages result in clinical benefits.