New insights into the activity of third-generation cephalosporins against pneumonia-causing bacteria

Abstract

Over 300 isolates representing all pathogens causing ≥ 4% of nosocomial or outpatient pneumonias were tested against currently used third-generation cephalosporins (cefotaxime, desacetylcefotaxime, ceftriaxone, ceftazidime, cefoperazone, and ceftizoxime) to determine differences in activity and effects of physiologic host and pharmacokinetic properties. Prevalent drug resistances were represented and tests were performed by reference methods of the National Committee for Clinical Laboratory Standards. Spectrums and potency of cefotaxime, desacetylcefotaxime, ceftriaxone, and ceftizoxime were most similar, but cefotaxime plus desacetylcefotaxime at in vivo ratios increased the cefotaxime spectrum (anaerobes and Pseudomonas) and potency. Ceftizoxime was least active because of current reduced activity against some Staphylococcus spp. and Pseudomonas aeruginosa. Ceftriaxone potency was adversely affected (≥ 4-fold decrease) by serum protein binding, thus reducing its susceptibility spectrum for pathogens with ≥ 4 μg/ml minimum inhibitory concentrations (MICs) and a 10.6% reduced spectrum overall. Ceftazidime provided poorest coverage against the significant and clinically increasing Gram-positive cocci and did not significantly inhibit aspiration pneumonia causing anaerobic strains. Ceftazidime and cefoperazone were more active against pseudomonas, but they were most labile to newer extended-spectrum β-lactamases. On empiric balance, the third-generation cephalosporins continue to provide the best therapeutic spectrum, particularly those favorably influenced by host factors (proteins and metabolism). These third-generation cephalosporin differences become more important since some agents (ceftazidime) have readily selected type-I enzyme mutants among intensive-care-unit respiratory tract pathogens at our institution. Cost containment will also influence drug choices for some third-generation cephalosporins, usually favoring the earliest introduced compounds such as cefotaxime.