The antimicrobial activity of meropenem (MEPM) and reference drugs were determinedfor recently isolated bacteria from pediatric (1, 017 strains of 21 species and 2 genera) and adult patients (714 strains of 13 species) in Japan. The following findings were obtained.
1. The antibacterial activities of MEPM against most of the clinical isolates frompediatric patients except methicillin-reisistant Staphylococcus aureus and Enterococcus faecium were superior or equivalent to those of reference β-lactams.
2. The susceptibility of clinical isolates from pediatric patients (758 strains of 13 species) to MEPM was equivalent to that of isolates from adult patients (714 strains of 13 species).
3. MEPM showed potent antimicrobial activity against major pathogens in bacterial meningitis such as Haemophilus influenzae, Streptococcus pneumoniae, Escherichia coli, Streptococcus agalactiae, Listeria monocytogenes and Neisseria meningitidis with the MICs ranging from 0.008 to 1 μg/mL.
4.β-Lactamase-negative ampicillin-resistant H. influenzae (BLNAR) and penicillin-resistant S. pneumoniae (PRSP) were susceptible to MEPM, of which the MICs ranged from 0.06 to 1μg/mL.
These results suggest that MEPM is useful in the pediatric field as with adults for various bacterial infections. In addition, based on the antimicrobial activity against important pathogens including BLNAR and PRSP, MEPM should be a promising drug for bacterial meningitis.

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We determined the MIC₅₀ and MIC₉₀ of four carbapenem antibiotics, i. e., imipenem (IPM), panipenem (PAPM), meropenem (MEPM), and biapenem (BIPM), for 125 strains of Pseudomonas aeruginosa isolated from clinical specimens between April 1999 and March 2002. The MIC₅₀ and MIC₉₀ values obtained were: 1 μ g/mL and 16μg/mL, respectively, for IPM, 4, ug/mL and 16 gemL, respectively, for PAPM, 0.5μg/mL and 8μg/mL, respectively for MEPM, and 0.5 Etig/mL and 8μg/mL, respectively, for BIPM. The results indicated that the antibiotic efficacy of BIPM and MEPM was superior to that of IPM and PAPM. The acute bactericidal action of the carbapenem antibiotics was markedly enhanced by the addition of fresh human serum to a final concentration of 50%, but the bactericidal effect of the cephem derivative ceftazidime (CAZ) was not significantly affected by fresh human serum. Neutrophils obtained from healthy adults were exposed to P. aeruginosa strain MSC-399 that had been incubated in the culture medium containing each of the four carbapenem antibiotics at 1/4 the MIC. The chemiluminescence index (CL index) of the neutrophils exposed to BIPM was 1.91, and significantly higher than that of the cells exposed to IPM, PAPM, or MEPM and the control cells (p<0.05). The results suggest that added to bacterial culture medium BIPM is the most potent of the carbapenems in stimulating the phagocytotic and bactericidal activity of neutrophils exposed to P. aeruginosa.

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The activity of amphotericin B (AMPH-B), flucytosine (5-FC), fluconazole (FLCZ), miconazole (MCZ), itraconazole (ITCZ) and micafungin (MCFG) was studied alone and in combination against 44 clinical isolates of yeast. The combination effect was determined between MCZ and 5 other agents. Among antifungal agents, amphotericin B showed the highest activity, because AMPH-B was confirmed no low activities for Candida species, although 5 other agents were resistant to different strains. FLCZ and MCZ showed the most synergistic and additive effects in all combination of Candida species (97.5%), followed by 5-FC and MCZ (94.2%), ITCZ and MCZ (92.5%), MCFG and MCZ (90%). AMPH-B and MCZ were not synergistic, additive was 50%, and antagonism was 17.5%. The highest activity of antifungal agents against Cryptococcus neoformans was ITCZ, followed by AMPH-B, MCZ, 5-FC, and FCZ, but MCFG was confirmed no activities. Synergistic and additive effects were found in all combination, especially 5-FC and MCZ, FLCZ and MCZ, and MCFG and MCZ were accepted synergistic against all 4 strains. MCZ showed good effects in combination with other antifungal agents, and the usefulness of combination therapies by MCZ are suggested in the clinical fields.

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We evaluated the antimicrobial susceptibilities of 178 strains of Neisseria gonorrhoeae isolated from male urethritis at our hospital from January 1998 to December 2002. Minimal inhibitory concentrations (MICs) for isolated strains were determined about 5 antimicrobials, penicillin G (PCG), cefpodoxime proxetil (CPDX-PR), cefotaxime (CTX), minocycline (MINO), tosufloxacin (TFLX). The population of PCG- and MINO-resistant N. gonorrhoeae did not change in this period. The population of CPDX-PRresistant N. gonorrhoeae has become more than 10% since 2000. The population of TFLX-resistant N. gonorrhoeae was increased year by year and has become more than 50% in 2002. Because fluoroquinolones were used as first-line therapy for gonococcal infection in Japan, rapid increase of fluoroquinolonesresistant N. gonorrhoeae was occurring. If we frequently treat with oral cephem antimicrobial agents for gonococcal infection, it is suggested that oral cephem-resistant N. gonorrhoeae will be increase.

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