COMPARATIVE ACTIVITY OF 12 BETA-LACTAM DRUGS TESTED AGAINST PENICILLIN-RESISTANT STREPTOCOCCUS-PNEUMONIAE FROM 5 MEDICAL-CENTERS - EFFECTS OF SERUM-PROTEIN AND CAPSULAR MATERIAL ON POTENCY AND SPECTRUM AS MEASURED BY REFERENCE TESTS

A total of 152 strains of Streptococcus pneumoniae from diverse geogra phic areas in the United States and with different levels of penicilli n resistance were tested against five broad-spectrum cephalosporins, a mpicillin, piperacillin, ticarcillin, and three beta-lactamase inhibit or combinations. Also, the effect of human serum proteins on the activ ity of selected ''third-generation'' cephalosporins was examined. The overall rank order of activity among the cephalosporins against penici llin-susceptible strains was: ceftriaxone (MIC(90), 0.03 mu g/mL) > ce fotaxime > ceftizoxime = cefuroxime > ceftazidime (MIC(90), 0.5 mu g/m L). Only cefotaxime and ceftriaxone exhibited significant activity aga inst penicillin-intermediate or -resistant isolates. Ampicillin, piper acillin, and penicillin were generally eight- to 16-fold more potent t han ticarcillin and no increase in the effectiveness of these agents w as observed with the addition of the beta-lactamase inhibitors (clavul anate, sulbactam, tazobactam). Ceftriaxone potency was significantly d ecreased (greater than or equal to four-fold) by the modest addition o f 25% pooled human serum proteins and this change modified the rank or der of potency against nonpenicillin-susceptible pneumococci to favor cefotaxime (41% resistant versus 71% for ceftriaxone; MICS at greater than or equal to 2 mu g/mL). Induced high-level capsular production ha d no measurable effect on the MIC results of tested agents. These resu lts confirm the continued activity advantages of cefotaxime and ceftri axone against various populations of pneumococci compared to other alt ernative beta-lactams. The predictive value, however, of the utilized breakpoint concentrations of the cephalosporins, remains in question f or pneumococcal infections other than those in the central nervous sys tem at unaltered, ''usual'' dosing. (C) 1996 Elsevier Science Inc.