Fourth generation cephalosporins in the antimicrobial chemotherapy of surgical infections

Surgical infections include a variety of entities such as secondary periton itis, intra-abdominal abscesses, obstetric and gynecological infections as well as bone-joint and soft-tissue infections. By definition the term "surg ical infection" implies that surgery itself plays the major role in therapy , while antimicrobial chemotherapy is only supplementary. Broad-spectrum em pirical regimens employed include the combination of a 1(st) or 2(nd) gener ation cephalosporin plus clindamycin or metronidazole +/- aminoglycoside (d epending on the severity of the condition). Cefepime and cefpirome are new 4(th) generation parenteral cephalosporins with a spectrum of activity whic h makes them suitable for the treatment of infections caused by a wide vari ety of bacteria. They are active against both Gram-positive and Gram-negati ve organisms, including Staphylococcus aureus and Pseudomonas aeruginosa wi th activity comparable to or greater than that of cefotaxime or ceftazidime respectively. Cefepime in particular is also Very active against strains o f Enterobacter and Pseudomonas spp resistant to these two agents. In compar ison with 3(rd) generation cephalosporins, cefepime appears to be less like ly to induce resistance, due to a lower rate of hydrolysis by beta-lactamas es, a low affinity for these enzymes and more rapid permeation into the cel l. Despite the fact that a 4(th) generation cephalosporin is well-suited fo r the treatment of polymicrobial infections, the following should be kept i n mind: (I) MRSA strains and Bacteroides fragilis group are not included in their spectrum of activity. (II) Cefpirome is the only cephalosporin with in vitro activity against Enterococci. (III) Severe surgical infections of nosocomial origin, and particularly in settings where Enterobacter spp pred ominate, represent the major indication for empirical use of a 4(th) genera tion cephalosporin in combination with a nitroimidazole.