Comparative activity of twelve beta-lactam drugs tested against penicillin-resistant Streptococcus pneumoniae from five 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 geographic areas in the United States and with different levels of penicillin resistance were tested against five broad-spectrum cephalosporins, ampicillin, piperacillin, ticarcillin, and three beta-lactamase inhibitor combinations. Also, the effect of human serum proteins on the activity of selected "third-generation" cephalosporins was examined. The overall rank order of activity among the cephalosporins against penicillin-susceptible strains was: ceftriaxone (MIC90, 0.03 microgram/mL) > cefotaxime > ceftizoxime = cefuroxime > ceftazidime (MIC90, 0.5 microgram/mL). Only cefotaxime and ceftriaxone exhibited significant activity against penicillin-intermediate or -resistant isolates. Ampicillin, piperacillin, and penicillin were generally eight- to 16-fold more potent than ticarcillin and no increase in the effectiveness of these agents was observed with the addition of the beta-lactamase inhibitors (clavulanate, sulbactam, tazobactam). Ceftriaxone potency was significantly decreased (> or = four-fold) by the modest addition of 25% pooled human serum proteins and this change modified the rank order of potency against nonpenicillin-susceptible pneumococci to favor cefotaxime (41% resistant versus 71% for ceftriaxone; MICs at > or = 2 micrograms/mL). Induced high-level capsular production had no measurable effect on the MIC results of tested agents. These results confirm the continued activity advantages of cefotaxime and ceftriaxone against various populations of pneumococci compared to other alternative beta-lactams. The predictive value, however, of the utilized breakpoint concentrations of the cephalosporins, remains in question for pneumococcal infections other than those in the central nervous system and at unaltered, "usual" dosing.
Johnson
D M
DM
University of Iowa College of Medicine, Iowa City 52242, USA.
Doern
G V
GV
Haugen
T A
TA
Hindler
J
J
Washington
J A
JA
Jones
R N
RN
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D015337:Multicenter Studies as Topic; D010403:Penicillin Resistance; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D014481:United States; D047090:beta-Lactams / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D047090:beta-Lactams