Ceftazidime, a pseudomonas-active cephalosporin: in-vitro antimicrobial activity evaluation including recommendations for disc diffusion susceptibility tests

Abstract

The in-vitro qualities of ceftazidime, as compared to other beta-lactams and three other antimicrobials (amikacin, gentamicin and chloramphenicol), were evaluated in a multilaboratory, multiphasic study in the United States. A total of 12,986 recent clinical isolates were tested by reference dilution methods in six medical centres over 45-60 days. Ceftazidime was superior to the comparison cephalosporin (cefamandole) and comparable in spectrum and activity to gentamicin against Enterobacteriaceae. Of 8038 enteric bacilli tested, over 98% had CTAZ MICs < or = 8 mg/l with a mode of < or = 0.12 mg/l. Only Citrobacter freundii and Enterobacter aerogenes had ceftazidime MIC(90S) in the resistant range ( > or =32 mg/l). Staphylococcus aureus strains were less susceptible to ceftazidime (mode MIC 8 mg/l) compared to cefamandole or gentamicin. Ceftazidime was more effective than cefamandole or gentamicin against the beta-haemolytic streptococci and the pneumococcus. More than 90% of Pseudomonas aeruginosa, most other Pseudomonas spp. and Acinetobacter spp. were inhibited by ceftazidime at concentrations of 8 mg/l. In other comparative studies ceftazidime was found remarkably similar in spectrum to cefotaxime, cefoperazone and moxalactam against the Enterobacteriaceae, staphylococci and Streptococcus spp. Enterobacter cloacae was the only enteric species having ceftazidime MIC90 >8 mg/l. Only cefsulodin (mode MIC 2 mg/l) and cefoperazone (mode MIC 4 mg/l) shared the ceftazidime activity against Ps. aeruginosa. Ceftazidime MIC(50S) for Neisseria gonorrhoeae and Haemophilus influenzae (including beta-lactamase producers) were 0.03-0.06 and 0.015 mg/l, respectively. Ceftazidime was found to be bactericidal against most strains at or one doubling dilution above the MIC, and was relatively unaffected by increasing inoculum concentration (some strain variations). It perfused readily into bacterial cells and was effective against the majority of strains resistant to currently available cephalosporins and aminoglycosides. beta-lactamases of Types I-V and Bacillus cereus failed to significantly hydrolyse ceftazidime. Ceftazidime inhibited only Type I Ent. cloacae beta-lactamase hydrolysis. Disc diffusion tests favour the use of a 30 microg ceftazidime disc for the methods described by the National Committee Clinical Laboratory Standards (NCCLS). Quality control data are presented. Tentative 30 microg disc interpretive criteria, based on susceptible MICs of < or =8 mg/l(> 17 mm) and resistant > or =32 mg/l ( < or =13 mm), resulted in < 1% (false resistance or false susceptible) interpretive error rates. Staph. aureus was the species most commonly found to have strains with indeterminate ceftazidime zones or MICs. We found ceftazidime to possess one of the widest clinically usable antimicrobial spectrum by in-vitro testing of any beta-lactam tested and to be most comparable to broad-spectrum aminoglycosides such as amikacin, gentamicin and tobramycin.