Abstract

The new aminothiazoyl-cephalosporin, ceftriaxone (Ro 13-9904), was found to have excellent inhibitory activity against the Enterobacteriaceae (minimum inhibitory concentration needed to inhibit 50% of isolates (MIC 50 ⩽ 0.004–0.5 μg/ml), Haemophilus influenzae (MIC 50 ⩽ 0.004 μg/ml), Neisseria species (MIC 50 ⩽ 0.001 μg/ml), pneumococci (MIC 50 0.25 μg/ml), Staphylococcus aureus (MIC 50 2.0 μg/ml), and Streptococcus pyogenes (MIC 50 0.015 μg/ml). Ceftriaxone was less effective against Acinetobacter species, Pseudomonas aeruginosa , and other Pseudomonas species (MIC 50 8.0–16 μg/ml). Methicillin-resistant S. aureus and enterococci were not significantly inhibited by ceftriaxone. Ceftriaxone was very resistant to β-lactamase hydrolysis, although the type IV cephalosporinase minimally destroyed the compound at 16.4–19.9% of the rates for cephaloridine. Type I cephalosporinases were inhibited by ceftriaxone and related enzyme-stable cephalosporins. Based on analysis of disk-MIC regression statistics, tentative recommendations for the disk test of the National Committee for Clinical Laboratory Standards are 21 mm or more = susceptible, 14–20 mm = moderately susceptible, and 13 mm or less = resistant. These criteria produce interpretive accuracy of more than 92%, with very rare major errors. Ceftriaxone was comparable to cefotaxime in spectrum and activity, thus allowing the use of the “spectrum-class” concept (for example, cefotaxime tests in vitro to predict ceftriaxone susceptibility, and vice versa).

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