Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates: II. Gram-negative bacteria

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, carbapenems, monobactams, and penicillins. Changes in CZOP susceptibility among bacteria were also evaluated with the bacterial resistance ratio calculated from the breakpoint MIC. Twenty-five species (4,154 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2001, and consisted of Moraxella (Branhamella) catarrhalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens, Citrobacter freundii, Citrobacter koseri, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Acinetobacter baumannii, Acinetobacter lwoffii, Burkholderia cepacia, Stenotrophomonas maltophilia, Bacteroides fragilis group, and Prevotella/Porphyromonas. CZOP preserved its antibacterial activity against M. (B.) catarrhalis (MIC₉₀: 4 μg/mL) and showed comparable activity to carbapenems against H. influenzae (MIC₉₀: 1 μg/mL). The antibacterial activity of CZOP against E. coli was preferable (MIC₉₀: 0.125 μg/mL) and comparable to those of cefpirome (CPR), cefepime (CFPM), and imipenem (IPM). The MIC₉₀ of CZOP against K. pneumoniae and K. oxytoca was 1 and 0.25 μg/mL, respectively. The MIC₉₀ of CZOP against E. cloacae increased during 6 years (32 to 128 μg/mL). The antibacterial activity of CZOP against E. aerogenes was preferable (MIC₉₀: 1 μg/mL). The antibacterial activities of CZOP against S. marcescens and S. liquefaciens were relatively potent (MIC₉₀: 0.5 and 0.25 μg/mL) and comparable to those of CPR, CFPM, and carumonam. CZOP preserved comparable antibacterial activity to CPR against C. freundii and C. koseri (MIC₉₀: 8 and 0.125 μg/mL). The MIC₉₀ of CZOP against P. mirabilis, P. vulgaris, and M. morganii was 0.25, 16, and 2 μg/mL, respectively. The antibacterial activity of CZOP against Providencia spp. was moderate (MIC₉₀: 64 μg/mL). The antibacterial activity of CZOP against P. aeruginosa was the most potent (MIC₉₀: 16 μg/mL) among the test agents and comparable to those CFPM, IPM, and MEPM. CZOP had low activity against Pfluorescens and P. putida (MIC₉₀: 128 μg/mL). The antibacterial activity of CZOP against A. baumannii was comparable to those of ceftazidime (CAZ), CPR and CFPM (MIC ₉₀: 32 μg/mL) and against A. lwoffii was moderate (MIC ₉₀: 64 μg/mL). Most of the test agents including CZOP had low antibacterial activity against B. cepacia, S. maltophilia, and B. fragilis group. The MIC₉₀ of CZOP against Prevotella/Porphyromonas was 64 μg/mL. Bacterial cross-resistance ratio between CZOP and other agents was low in most of the species, ranging from 0.0 to 15.1%. In non-glucose fermentative bacteria, however, the bacterial cross-resistance ratio between CZOP and CFPM, CAZ, CPR, or IPM was high, being 36.8%, 28.0%, 38.7%, or 31.1%, respectively. In conclusion, the 6-year duration study suggested that the antibacterial activity of CZOP against E. cloacae possibly decreased, but against other Gram-negative bacteria was consistent with the study results obtained until the new drug application approval.