We determined the susceptibility of 56 strains of Helicobacter pylori, freshly isolated from the gastrointestinal mucosa of patients with peptic ulcer, to different types of antibacterial drugs. All the strains tested were susceptible to amoxicillin and clavulanic acid/amoxicillin with MIC values of 0.20μg/ml or less, indicating no resistance to these drugs. The antibacterial activity of fropenem was significantly more potent than that of the 8 other drugs tested. The MICs of fropenem were≤0.025μg/ml for 55 of the 56 strains and 0.05μg/ml for the remaining strain. The MICs of the 5 macrolide derivatives were 0.05-0.39μg/ml. However, the MIC₉₀ values of four drugs (erythromycin, azithromycin, roxithromycin and rokitamycin) except clarithromycin were 50μg/ml or more, which indicates that some strains were resistant to these four drugs. The MICs of levofloxacin for all of the test strains except for one were distributed between 0.10 and 6.25μg/ml. The 56 strains of H. pylori were allocated to 2 groups; Group 1 consisted of 27 strains isolated before antibiotic treatment for the eradication of the bacteria and Group 2 consisting of the remaining 29 strains isolated during or after the treatment. When both groups were compared for drug susceptibility, the number of strains resistant to these antibacterial drugs was significantly larger in Group 2 than in Group 1. These results suggest that eradicative therapy with antibacterial drugs in peptic ulcer patients infected with H. pylori may induce resistance to the antibacterial drugs used. Therefore, special attention should be paid to the prevention of the emergence of this type of resistance.

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The influence of the new quinolones on the active oxygen generation, chemotaxis and phagocytosis of polymorphonuclear leukocytes (PMNs) was examined. Four new quinolones, ofloxacin (OFLX), levofloxacin (LVFX), sparfloxacin (SPFX) and prulifloxacin (PUFX) were used. PMNs were prepared from peripheral blood and incubated for 0, 10, 20 and 30 minutes at 37°C with the new quinolones at various concentrations (0.625, 2.5 or 10μg/ml). Active oxygen generation of PMNs was measured by the chemiluminescence method with phorbol myristate acetate. Chemotaxis of PMNs was assessed by the Boyden chamber method, using formyl-methionylleucyl-phenylalanine as the chemotactic factor. Phagocytosis of PMNs was expressed as the number of Escherichia coli phagocysed by PMNs. The active oxygen generation of PMNs was significantly enhanced in the presence of 0.625, 2.5 and 10μg/ml of all new quinolones after 30 minutes incubation. Similarly, after 30 minutes incubation significant stimulation of chemotaxis of PMNs occurred at 10μg/ml of all new quinolones, and signiticant stimulation of phagocytosis of PMNs was seen at 10μg/ml of OFLX, LVFX and PUFX. The penetration of new quinolones into PMNs was measured with the bioassay method using E. coli Kp strains. The intracellular/extracellular concentraion ratio at 10μg/ml of new quinolones after 30 minutes incubation was the highest for SPFX at 14.6, with values of 13.3 for PUFX, 9.52 for LVFX and 8.29 for OFLX. The relationship between the concentrations of intracellular new quinolone and PMN functions was also examined. The correlation coefficient between the concentrations of intracellular quinolone and PMN functions was 0.657 to 0.805 for phagocytosis, 0.629 to 0.784 for active oxygen generation, and 0.539 to 0.761 for chemotaxis. These results suggest that new quinolones influence active oxygen generation, chemotaxis and phagocytosis of PMNs and that this influence correlated with the concentrations of intracellular quinolone.

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The adherence to the human larynx carcinoma cell line, HEp-2 cells, of serovars of biovars of Haemophilus influenzae, and the bactericidal effect of oral cephems on H. influenzae adhering to HEp-2 cells was investigated.
1) The biotypes of 144 strains of H. influenzae isolated from 1993 to 1995 were in the order biovar II (43%), III (24%), and I (19%). There was no difference in their susceptibilities to cefixime (CFIX), cefpodoxime (CPDX) and cefditoren (CDTR) among the biotypes.
2) The ability of nontypable H. influenzae to adhere to HEp-2 cells was significantly greater than that of serovar b strains (12-100% versus 0.5-3.3%). Invasion of the bacteria into the cells was observed at a frequency of 0.00003 to 0.015% in nontypable strains, but was not observed in serovar b strains.
3) The bactericidal activity of these cephems against the adherent bacteria, as well as the floating bacteria was strong until 6 h. But from then until 24 h. the activity against the adherent bacteria was lower than that against the floating bacteria. These cephems had only slight bactericidal activity against the invasive bacteria.
These observations suggest that nontypable H. influenzae strains have a tendency to adhere easily to epithelial cells and to invade the cells, and therefore may cause chronic respiratory tract diseases.

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To supply up-to-date information on effective chemotherapeutics for bacterial infections, we have been periodically surveying the drug sensitivity of the clinically isolated bacteria. The organisms examined in this study were collected in our hospital in November, 1994. Distribution of the minimal inhibitory concentrations (MIC) of 19 antibacterial drugs against the strains of eight species isolated at the relatively high incidence was determined. Staphylococcus aureus strains were divided into two groups, methicillin-resistant strains (MRSA) and methicillin-sensitive strains (MSSA) for the analysis. Serotyping of Pseudomonas aeruginosa strains and coagulase typing of Staphylococcus aureus strains were also carried out. Imipenem/cilastatin (IPM/CS) and tobramycin (TOB) were found to be the drugs of first for P. aeruginosa infections during this period, vancomycin (VCM) and arbekacin (ABK) were the firest choice for MRSA; ampicillin (ABPC), cefazolin (CEZ), clarithromycin (CAM) and ofloxacin (OFLX) for MSSA; latamoxef (LMOX) and OFLX for Escherichia coli; CEZ, cefmetazole (CMZ) and OFLX for Klebsiella; IPM/CS and OFLX for Enterobacter; IPM/CS for Serratia; ABPC, LMOX and OFLX for Proteus; and ABPC and IPM/CS for Enterococcus. Serotypes of the isolated P. aeruginosa strains were found to differ in their sources, and types E, G, B, A, F, I and M were frequent in that order. Most of the MRSA strains were found to belong to coagulase type II, but the coagulase types of the MSSA strains were heterogenous.

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During the period October 1993 to September 1995, we examined 191 strains of Staphylococcus aureus isolates from skin and skin structure infections and 153 strains from eczematous lesions of atopic dermatitis. Minimal inhibitory concentrations, inhibiting 90% of S. aureus isolates, for rifampicin, vancomycin, fusidic acid, and tosufloxacin were superior to those of other agents. In all, 32.5% of S. aureus isolates from skin infections were methicillin-resistant. As to coagulase typing, type III was most frequent and the ratio of type IV strains was lower than previously reported rates. The rates of β-lactamase producers among S. aureus isolates from skin infections and atopic dermatitis were 85.7% and 81.7%, respectively.

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The therapeutic effects of oral cephem antibiotics on experimental acute otitis media caused by Streptococcus pneumoniae were evaluated in guinea pigs. In the otitis media caused by penicillin susceptible S. pneumoniae (PSSP), cefteram pivoxil (CFTM-PI) and cefpodoxime proxetil (CPDX-PR) significantly reduced viable cell counts in the middle ear at a dose of 10mg/kg twice daily for 2 days (p<0.01 compared with control). The therapeutic effects of CFTM-PI and CPDX-PR were superior to those of cefdinir (CFDN), cefditoren pivoxil (CDTR-PI) and cefaclor (CCL). These therapeutic effects were reflected in both in vitro activities and pharmacokinetic properties of the drugs. In the otitis media caused by penicillin intermediate S. pneumoniae (PISP), CFTM-PI showed no effect on viable cell counts in the middle ear at a dose of 10mg/kg twice daily for 2 days, but the higher dose (50mg/kg) did produce a therapeutic effect (p<0.01). The therapeutic effects of CFTM-PI and CPDX-PR at a dose of 50mg/kg twice daily for 2 days were superior to those of other drugs (p<0.01). CFTM-PI was also effective at a dose of 20 mg/kg twice daily for 5 days (p<0.01). In conclusion, the therapeutic effects of CFTM-PI and CPDX-PR on otitis media caused by PSSP or PISP in guinea pigs were superior to those of CFDN, CDTR-PR and CCL, and an increased dose and prolonged treatment period were required to cure the otitis media caused by PISP.

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The clinical efficacy of combination therapy with amikacin (AMK), imipenem/cilastatin sodium (IPM/CS) and recombinant human granulocyte colony-stimulating factor (G-CSF) was evaluated in 32 neutropenic patients with hematological diseases. Clinical effectiveness was observed in 24 cases (including 3 cases of sepsis), an efficacy rate of 75.0%. The efficacy rate was 90% in the 10 patients with neutrophil counts less than 100/μl at the time of therapeutic evaluation. It was 81.1%(9/11) in patients whose neutrophil counts increased 20% or more during treatment and 66.7%(8/12) in patients whose neutrophil counts increased less than 20%; the difference in efficacy rates was not statistically significant. A clinical efficacy rate of 75.9% was observed in 29 neutropenic patients chosen according to the same criteria as those of the present study from among patients who were treated with AMK plus IPM/CS in a previous study (the historical controls). When the results in the historical control group were compared with those in the G-CSF group, there was no significant difference in efficacy rate, profile of body temperature or duration of fever. The results suggest that combination therapy with AMK and IPM/CS is very effective in treating infections in neutropenic patients, with or without G-CSF.

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Clindamycin was administered to a 78 year-old man with Chlamydia pneumoniae pneumonia, to specifically targetting to anaerobes, and he responded very well. Clindamycin showed a high penetration into human cells and strong in vitro activity against C. pneumoniae at a MIC value of 1μg/ml. According to our experience and these data, clindamycin was considered to an effective agent in the treatment of chlamydial pneumonia.

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