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 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, penicillins, and carbapenems. Changes in the bacterial sensitivity for CZOP were also evaluated with the resistance ratio calculated with breakpoint MIC. Sixteen species(1,913 strains)of Gram-positive bacte-ria were isolated from the clinical materials annually collected from 1996 to 2000, and consisted of methicillin- susceptible Staphylococcus aureus(MSSA; n=178), methicillin-resistant S. aureus(MRSA; n=199), methicil-lin-susceptible Staphylococcus epidermidis (MSSE; n=98), methicillin-resistant S. epidermidis(MRSE; n=164), Staphylococcus haemolyticus(n=72), Staphylococcus saprophyticus(n=28), Enterococcus faecalis(n=206), Enterococcus faecium(n=91), Enterococcus avium(n=72), Streptococcus pyogenes(n=133), Streptococcus agalactiae(n=138), penicillin-susceptible Streptococcus pneumoniae (PSSP; n=133), penicillin-intermediate resistant S. pneumoniae(PISP; n=100), penicillin-resistant S. pneumoniae(PRSP; n=29), Streptococcus milleri group(n=135) and Peptostreptococcus spp.(n=137).
CZOP possessed comparable antibacterial activities against MSSA and MSSE to other cephems, and was also effective on MRSE but not on MRSA. An antibacterial activity of CZOP against S. saprophyticus was comparable to or higher than other cephems. CZOP, however, did not indicate an antibacterial activity against S. haemolyticus, just like other cephems. An antibacterial activity of CZOP against E. faecalis was comparable to cefpirome(CPR) and higher than other cephems. No antibacterial activity of CZOP against E. faecium and E. avium was observed, just like other drugs. An antibacterial activity of CZOP against S. pyogenes was as potent as that of cefotiam(CTM), cefepime(CFPM) and CPR, and that against S. agalactiae was also preferable. CZOPand other cephems also had a preferable antibacterial activity against S. milleri group that was most sensitive to benzylpenicillin. An antibacterial activity of CZOP against Peptostreptococcus spp. was preferable but weaker than that of cefazolin, CTM and cefmetazole. The resistance ratio estimated with breakpoint MIC of CZOP was 96.5% in MRSA, 9396.5% in MRSA, 93.1% in PRSP, 60.0% in PISP, 40.3% in S. haemolyticus, 22.3% in E. faecalis, and 15.9% in MRSE. Those resistance ratios were similar to those for CFPM, but E. faecalis showed 90.8% resistance for CFPM. The difference in the resistance ratio of E. faecalis demonstrated that CZOP successfully maintained its antibacterial activity against this species.
In conclusion, no remarkable annual change in the antibacterial activities of CZOP against the Grampositive bacteria was observed. The sensitivities of PIS and PRSP to CZOP, however, was suggested to be decreasing.

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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, penicillins, monobactams, and carbapenems. Changes in CZOP susceptibility for the bacteria were also evaluated with the bacterial resistance ratio calculated with the breakpoint MIC. Twenty-five species (3,362 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2000, and consisted of Moraxella (Branhamella) catarrhalis (n=136), Haemophilus influenzae (n=289), Escherichia coli (n=276), Klebsiella pneumoniae (n=192), Klebsiella oxytoca (n=157), Enterobacter cloacae (n=189), Enterobacter aerogenes (n=93), Serratia marcescens (n=172), Serratia liquefaciens (n=24), Citrobacter freundii (n=177), Citrobacter koseri (n=70), Proteus mirabilis (n=113), Proteus vulgaris (n=89), Morganella morganii (n=116), Providencia spp.(n=41), Pseudomonas aeruginosa (n=290), Pseudomonas fluorescens (n=56), Pseudomonas putida (n=63), Acinetobacter baumannii (n=146), Acinetobacter lwoffii (n=34), Burkholderia cepacia (n=101), Stenotrophomonas maltophilia (n=169), Bacteroides fragilis group (n=196), and Prevotella/Porphyromonas (n=173).
An antibacterial activity of CZOP against E. coli, K. pneumoniae, K. oxytoca, and S. marcescens was potent and consistent with or more preferable than the study results obtained until the new drug application approval. MIC₉₀ of CZOP against M.(B.) catarrhalis, C. koseri, and P aeruginosa was not considerably changed and consistent with the study results obtained until the new drug application approval.
MIC₉₀ of CZOP against E. cloacae, E. aerogenes, and P. mirabilis increased year by year. The increase in MIC₉₀ of CZOP against E. aerogenes and P. mirabilis, however, was not considered to be an obvious decline in susceptibility. In contract, the susceptibility of E. cloacae to CZOP was suspected to be decreasing because this species showed 20.6% resistance to CZOP. MIC₉₀ of CZOP against C. freundii was variably changed or not one-sidedly, but was higher than the values obtained until the new drug application approval. Additionally, MIC₉₀ of CZOP against H. infiuenzae was stable during 5 years except being higher in 1999, and, as a whole, was a little higher than the values obtained until the new drug application approval.
An antibacterial activity of CZOP against P. fluorescens, P. putida, B. cepacia, S. maltophilia, B. fragilis group, and Prevotella/Porphyromonas was weak like the other cephems. Changes in MIC₉₀ of CZOP against the other bacteria were 2 tubes or more through 5-year study period, but did not tend towards a unilateral direction as meaning a decline in susceptibility.

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The in vitro combination effect of tazobactam/piperacillin (TAZ/PIPC) with aminoglycosides (amikacin (AMK) and isepamicin (ISP)) were investigated by the checkerboard dilution method against PIPC-resistant and TAZ/PIPC-susceptible Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli and Methicillin-sensitive Staphylococcus aureus (MSSA). The following results were obtained.
1. The combination of TAZ/PIPC with AMK showed synergistic effect for 66.7% of P. aeruginosa and 9.1% of K. pneumoniae and additive effect for 76.9% of E. coli and 74.1% of MSSA. The antagonistic effect of TAZ/PIPC with AMK was not demonstrated for all tested strains.
2. The combination of TAZ/PIPC with ISP showed synergistic effect for 61.9% of P. aeruginosa and 22.7% of K. pneumoniae and additive effect for 84.6% of E. coli and 66.7% of MSSA. The antagonistic effect of TAZ/PIPC with ISP was not demonstrated for all tested strains.
In conclusion, these results suggest that the combination therapies of TAZ/PIPC with aminoglycosides are useful for the clinical treatment of sepsis caused by above four species.

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The bactericidal activity of biapenem, a new carbapenem, against various efflux-mutants of Pseudomonas aeruginosa was compared with those of imipenem, panipenem, meropenem and ceftazidime. The bactericidal activity of biapenem against P aeruginosa KG5001, a strain deficient in MexAB-OprM, MexCD-OprJ and MexXY-OprM, was very strong compared with those of imipenem and meropenem. In terms of bactericidal activities, biapenem and imipenem had similar activities against P. aeruginosa KG5003, a strain overexpressing MexAB-OprM, as against P. aeruginosa KG5001, however meropenem and ceftazidime had weaker activities against KG5003 than KG5001. The bactericidal activity against P. aeruginosa KG5007, a strain overexpressing MexCD-OprJ, was observed only by biapenem.
The bactericidal activity of biapenem was strong and not influenced by all of these three efflux systems.

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Complication by secondary infection is observed in not only bacterial pleurisy but also other pleurisy, and the appropriate administration of antibacterial agents is necessary. It is very important to secure a smooth penetration of systemically administered antibacterial agents to pleural effusion in infection therapy. In this study, we investigated the pharmacokinetics of a carbapenem antibiotic, meropenem (MEPM), in blood and pleural effusion in patients with an accumulation of pleural effusion caused by pleurisy, who underwent placement of an indwelling thoracic drain and received intravenous drip administration of MEPM for pneumonia or other respira- tory tract infection. The blood pharmacokinetic parameters of MEPM after an intravenous drip administration of 0.5 g MEPM in six patients were: area under the blood concentration-time curve (AUC^∞), 37.9±6.2 (hr^.mg/L); volume of distribution (Vd), 27.3±4.4 (L); total clearance (CL_total), 13.4±1.8 (L/hr); elimination half life (t_1/2), 0.50±0.08 (hr^-1); and elimination rate constant (k_el), 1.42±0.22 (hr). The pharmacokinetic parameters in pleural effusion were: AUC^∞, 35.7±7.1 (hr^. mg/L); mean retention time (MRT), 5.00±3.25 (hr); variance of retention time (VRT), 29.9±44.6 (hr²); kel, 0.34±0.27 (hr^-1); and t_1/2, 3.14±2.36 (hr). The penetration rate calculated from the ratio of pleural concentration to blood concentration in each patient was 46.5±26.1%, showing good penetra- tion comparable or superior to those of other antibacterial agents previously reported. From these results, it was suggested that MEPM was rapidly penetrated to the pleural effusion and was retained for a more prolonged time in the pleural effusion than in the blood of patients with accumulated pleural effusion, and it suggested the useful- ness of MEPM in antibacterial therapy for patients with pleurisy causing accumulation of pleural effusion.

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[in Japanese]

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