The antimicrobial susceptibility of clinical isolates from specimens of patients in primary care clinics in 2005 was investigated by determining the minimum inhibitory concentrations of oral antibacterial agents. The numbers of test strains were 550 for Gram-positive aerobes, 700 for Gram-negative aerobes, and 150 for anaerobes. Cefcapene (CFPN), cefditoren (CDTR), and cefteram (CFTM) showed the most potent activities against Staphylococcus spp. and Streptococcus spp. among the cephems tested and moxifloxacin (MFLX) and tosufloxacin among the new quinolones. Although the new quinolones generally showed potent activities against these species, resistant strains were frequently detected in methicillin-resistant Staphylococcus aureus. In addition, 70% or more of Streptococcus pneumoniae isolates were intermediate or resistant to macrolides. Cephems showed good activities against aerobic Gram-negative bacteria except for Proteus spp. Specifically, CFPN, CDTR, and CFTM showed the most potent activity against Haemophilus influenzae among the cephems tested. The new quinolones showed potent activities against Gram-negative bacteria, especially H. influenzae and Moraxella catarrhalis, but not against Proteus mirabilis and Providencia spp. When compared with the susceptibilities of clinical isolates from tertiary care hospitals, found in other research, differences were noted, for example, there was a lower frequency of quinolone-resistant strains of methicillin-susceptible S. aureus but a higher frequency of macrolide-resistant strains of Streptococcus pyogenes. Therefore, to accurately grasp susceptibility trends, well-focused surveillance studies are necessary.

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We examined antibacterial activities of 4 kinds of macrolides (MLs), erythromycin (EM), clarithromycin (CAM), azithromycin (AZM) and rokitamycin (RKM), against 4 bacterial species of clinical strains isolated in 2004. Bacterial isolates used were 51 strains of methicillin-susceptible Staphylococcus aureus (MSSA), 20 of Streptococcus pyogenes, 68 of Streptococcus agalactiae, and 120 of Streptococcus pneumoniae. Macrolide resistance genes, ermB and mefE, in macrolide-resistant S. pyogenes and S. agalactiae, and all of pneumococci were analyzed by PCR. Antimicrobial activities against macrolide-susceptible MSSA of EM and CAM, were more potent than those of RKM. By contrast, against S. pneumoniae, RKM was more effective than EM, CAM and AZM. Against S. pyogenes and S. agalactiae, 4 antibiotics showed similar antimicrobial activities. Twelve, 1 and 2 strains of MSSA, S. pyogenes and S. agalactiae, respectively, were resistant to EM, CAM and AZM, whereas RKM was active to almost, but not quite, of them. Among 120 strains of S. pneumoniae, 76 (63.3%) were resistant to EM (MIC; ≥0.5μg/mL), and 23, 15 and 28 strains were highly resistant (MIC; >128μg/mL) to EM, CAM and AZM, respectively. By contrast, for RKM, there were far fewer resistant strains, and there was no highly resistant strain. PCR analyses of macrolide-resistant genes revealed that 1 resistant strain of S. pyogenes and 2 of S. agalactiae carried mefE and ermB, respectively. In the case of S. pneumoniae, 59, 19 and 5 strains, respectively, carried ermB, mefE and both ermB and mefE.
We also studied about bactericidal activities and postantibiotic effects (PAE) of MLs using macrolide-susceptible, and ermB-and mefE-carrying S. pneumoniae, and observed morphological alterations of the strains treated with the drugs by a scanning electron microscope. It was demonstrated that RKM had superior bactericidal activities and PAE than other 3 drugs, and potent destructive effects to all of 3 strains.

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Streptococcus pneumoniae and Haemophilus influenzae are two major pathogens for respiratory tract infections, and those infections might cause critically ill patients. We performed the analysis with Monte Carlo Simulation for 253 strains of S. pneumoniae and 309 strains of H. influenzae isolated in the Gifu prefecture in 2002 and 2003. As for the pneumococcal infection in patient with good immunological response, good clinical effect might be obtained by panipenem/betamipron (PAPM/BP) 500 mg, imipenem/cilastatin (IPM/CS) 500 mg, meropenem (MEPM) 500 mg and biapenem (BIPM) 300 mg, b.i.d., while for immunocompromised hosts or infections by penicillin-resistant Streptococcus pneumoniae (PRSP), PAPM/BP, 500 mg, b.i.d., or IPM/CS 500 mg, MEPM 500 mg, t.i.d. or BIPM 600 mg, b.i.d. would be recommended. As for the infections caused by H. influenzae, in patient with good immunological response, good clinical effect might be obtained by MEPM 500 mg, b.i.d or PAPM/BP 1000 mg, b.i.d., while for immunocompromised hosts, MEPM 500 mg, t.i.d. would be recommended. Monte Carlo Simulation would be one of the useful tools for appropriate antimicrobial chemotherapy also against respiratory infections.

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