Ceftizoxime: collaborative multiphased in-vitro evaluation including tentative interpretive standards for disc susceptibility tests, -lactamase stability, and inhibition

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Abstract
Ceftizoxime is a 7-aminothiazolyl α-methoxyimino cephalosporin, a new ‘third-generation’ cephalosporin. A collaborative study was undertaken to document its in vitro activity, β-lactamase inhibition, and resistance to β-lactamase hydrolysis. Over 6000 consecutive clinical isolates were tested against ceftizoxime, cefotaxime and moxalactam. Against Pseudomonas aeruginosa , cefotaxime was twice as active as ceftizoxime. Both β-methoxyimino aminothiazolyl- containing drugs were more active than moxalactam against most Enterbacteriaceae. A representative sample of 511 clinical isolates was tested against eight β-lactams and two aminoglycosides. Ceftizoxime was similar to cefotaxime. Ceftizoxime was as active as cefoxitin against 48 anaerobic bacteria. Certizoxime was resistant to hydrolysis by all tested β-lactamases and was capable of inhibiting Type I β-lactamase. Disc diffusion tests with ceftizoxime and cefotaxime discs were evaluated. Cefotaxime discs may be used to predict ceftizoxime susceptibility, but ceftizoxime discs can not be used to predict cefotaxime susceptibility of non-enteric Gram-negative bacilli. Tentative interpretive zone standards for 30 μg ceftizoxime disc tests are: ≤ 10 mm = MIC ≥ 64 mg/l, 11–19 mm = MIC 16–32mg/l and ≥ 20 mm = MIC ≤8 mg/l. If Ps. aeruginosa isolates are to be considered resistant to ceftizoxime in spite of their ‘intermediate’ MICs, zone standards for 30 μg ceftizoxime discs should be ≤ 15 mm for resistant and ≥ 20 mm for susceptible.

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