Antibiotics in GynecologyJOURNAL OF GYNECOLOGIC SURGERYMary Ann Liebert, Inc., Publishers

Second Generation CephalosporinsNEWTON G. OSBORNE, M.D., Ph.D.

Second generation cephalosporins are semisynthetic compounds derived from natural cephalosporins.Although antibiotics in this group are called collectively cephalosporins, only antibiotics and semisyn-

thetic compounds derived from organisms, such as Cephalosporium acremonium, are true cephalosporins.Cephamycins are structurally related antibiotics derived from species of Streptomyces.

Second generation cephalosporins have many similarities. They are active against many gram-positive andgram-negative organisms. They also have activity against several aerobic and anaerobic organisms.Cephalosporins that are effective against pelvic pathogens and that achieve therapeutic concentrations inpelvic tissues are useful for prophylaxis and treatment of pelvic infections.

There are several second generation cephalosporins that have properties necessary for the management ofcertain pelvic infections. Among these, cefoxitin, cefotetan, cefmetazole, cefamandole, cefuroxime, andceforanide are worth examining. The first three have a similar spectrum of activity, are ß-lactamase stable,and can achieve therapeutic concentrations in pelvic tissues. The others can be useful for the treatment ofcertain gynecologic infections.Pelvic infections are, as a rule, polymicrobial. Anaerobes of the Bacteroides group of organisms are

important pathogens in gynecologic infections. They act in synergy with organisms from the Enterobacteri-aceae and gram-positive cocci groups to produce pelvic cellulitis, peritonitis, or abscess. Second generationcephalosporins are active against many of these pelvic pathogens.All bacteria of the Bacteroides fragilis group possess chromosomally mediated ß-lactamases. The main

reasons for the usefulness of cefotetan, cefoxitin, and cefmetazole in the management of pelvic infections isbecause of their resistance to episomal and chromosomally mediated ß-lactamase hydrolysis, their spectrumof activity against gram-negative anaerobic organisms, gram-positive cocci, and Enterobacteriaceae, theirability to concentrate in pelvic tissues, and their low toxicity.Although cefuroxime and cefamandole are more active than cefoxitin, cefotetan, and cefmetazole against

Neisseria gonorrhoeae, cefuroxime and cefamandole are susceptible to the inoculum effect with ß-lactamase-producing gonococci. They are also unstable to the ß-lactamases of gram-negative organisms.Ceforanide has a more limited spectrum for pelvic pathogens than the other second generation cephalo-

sporins. However, due to its long half-life and because it is tolerated easier i.m. than the other cephalosporins,it may be useful for the treatment of pelvic infections in i. v. drug abusers when i.v. therapy may be difficult.Cefoxitin, cefotetan, and cefmetazole are equivalent drugs for the treatment of pelvic infections. The main

difference between them is cost. The long half-life of cefotetan allows for dosing every 12 hours. Cefmetazolecan be given every 8 hours. Cefoxitin must be given every 6 hours.

Second generation cephalosporins are excreted in the urine by glomerular filtration and by active tubularsecretion. Therefore, probenecid delays but does not diminish excretion. Antibiotic dosage must be adjustedwhen treating patients with renal failure.Although second generation cephalosporins penetrate well into peritoneal fluid and interstitial fluids of

surgical patients, they diffuse poorly into intraabdominal and pelvic abscesses.1Second generation cephalosporins tend to be potent inducers of ß-lactamase. The reason for in vivo

resistance, even when there is evidence of in vitro susceptibility, may be the sparing of sensitive organismswhen induced ß-lactamase binds the stable antibiotic and renders it ineffective without hydrolyzing it.2 Inother words, when a ß-lactamase-stable antibiotic that is a potent inducer of ß-lactam is given in combina-

State University of New York Health Science Center at Syracuse, Syracuse, New York.

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tion with another ß-lactam antibiotic, the inducer activity may proceed faster than the antibacterial effect. Theconcentration of ß-lactamase is then enough to hydrolyze the susceptible antibiotic and to bind to the stableantibiotic, rendering both of them ineffective.

REFERENCES

1. O'Keefe JP, Tally FP, Barza M, Gorback SL. Penetration of cephalothin and cefoxitin into experimental infectionswith Bacteroidesfragilis. Rev Infect Dis 1979;1:106.

2. Sanders CC, Sanders WE, Goering RV. In vitro antagonism of beta-lactam antibiotics by cefoxitin. AntimicrobAgents Chemother 1982;21:968.

Address reprint requests to:Newton G. Osborne, M.D., Ph.D.

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