A novel pathway of arbekacin (ABK) acetylation was found in four ABK-resistant clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), as well as one strain of MRSA that had acquired resistance to ABK in vitro, one strain of ABK-resistant strain of MRSA including the bifunctional AAC (6')-APH (2''), and an ABK-susceptible strain of MRSA. Analysis of the ABK metabolites in suspension cultures of ABK-resistant MRSA by ¹H, ¹³C-nuclear magnetic resonance, high-resolution mass spectrometry and Fourier transform infrared spectrometry detected the (S)-4-amino-2-hydroxybutyryl (AHB) group in ABK, while only unmetabolized ABK was detected in suspension culture of the ABK-susceptible MRSA. The cell lysate of the ABK-resistant MRSA exhibited only acetylation without phosphorylation. This acetylation activity was attributed to a 28 kDa enzyme detected in all the ABK-resistant but not in ABK-susceptible MRSA by gel permeation chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the bacterial cell lysate. This enzyme has AAC (4'') actiyity. The N-terminal amino acid sequence of this enzyme had proteins which showed a strong similarity (> 90 identity over 30 amino acid) to the ABK modifying enzyme AAC (6')-APH (2''). These results suggest that this enzyme is a mutant and/or degradation protein of AAC (6')-APH (2'').

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Analogs of furanonaphthoquinone (FNQ) from the inner bark of Tecoma ipe Mart had MICs ranging from 1.56 to 25μg/ml against gram-positive bacteria. FNQ showed significantly lower MICs against methicillin-resistant Staphylococcus aureus than methicillin-susceptible species. FNQ inhibited Helicobacter pylori, which inhabits the human stomach, with an MIC of 0.1 μg/ml. Twenty-eight strains of fungi, including pathogenic species, were sensitive to FNQ, with MIC values similar to those of amphotericin B. FNQ showed activity against Aspergillus fumigatus in mice infected with the microbe. FNQ may be useful as a chemotherapeutic agent against methicillin-resistant S. aureus, H. pylori and pathogenic fungi.

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The antimicrobial activities of arbekacin (ABK) or flomoxef (FMOX) at sub-and above-MICs against clinical strain of methicillin-resistant Staphylococcus aureus (MRSA) during the postantibiotic phase PA-phase induced by FMOX or ABK were examined. Antimicrobial activities were determined growth suppression (postantibiotic sub-MIC effect: PA SME) at sub-MICs, and bactericidal activity at sub- and above-MICs. During the PA-phase induced by FMOX, growth suppression and bactericidal activity of ABK were enhanced at sub and above-MICs, compared with the non PA-phase. On the other hand, during the PA-phase induced by ABK, but bactericidal activity were declined at above-MICs compared with non PA-phase. These suggest that not only enhancement of growth suppression and bactericidal activity at sub-MICs, but decline of bactericidal activity at above-MICs during PA-phase were factors of combination effect of ABK and FMOX against MRSA.

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The antimicrobial susceptibility of 71 clinical isolates of Streptococcus pneumoniae obtained between December 1995 and December 1996 were determined. A total of 21 isolates (29.6%) demonstrated intermediate resistance (MIC, 0.1 to 1.0 μg/ml: PISP) and 10 (14.1%) high resistance (MIC, ≥2.0 μg/ml: PRSP) to penicillin. Penicillin resistant strains (PISP, PRSP) were more likely to have been recovered from otorhinolaryngology patients and children under 6 years old. The serotypes of the resistant strains were almost 19 (74.2%) and 23 (9.7%) type. The clinical effectiveness of the initial treatment against pneumococcal infections was 74.4%. However, 10 cases did not exhibit successful results with the initial treatment, 2 of which were bacteremia and meningitis due to PISP. These results suggest that follow-up studies and the establishment of a treatment for severe resistant pneumococcal infections, such as bacteremia and meningitis, are necessary.

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Objective: To clarify the clinical characteristics of prolonged lower respiratory tract infections in children younger than 6 years of age.
Subjects and methods: Retrospective survey of the patients admitted to our hospital from 1994 to 1997.
Results: Of 748 patients diagnosed as having acute pneumonia or bronchitis, 259 (35%) also suffered from acute otitis media. We examined the causative bacteria of the acute otitis media in those 259 patients, as well as, in another 114 inpatients suffering from acute otitis media only. Sixty percent of the isolated bacteria from the middle ear discharge proved to be Streptococcus pneumoniae, and 83 % of the detected S. pneumoniae were penicillin insensitive or resistant.
Conclusion: Frequent complications of acute otitis media due to penicillin insensitive or resistant S. pneumoniae may aggravate and prolong lower respiratory tract infections in small children.

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The efficacy and safety of panipenem betamipron (PAPM BP) were investigated in 173 patients with severe infections complicated with hematopoietic disorders. The results obtained are summarized below.
1) Out of 137 patients who were evaluated, the responses were excellent in 35 patients, good in 51, fair in 7 and poor in 44, with an efficacy rate of 62.8%.
2) The efficacy rate in patients previously treated with other antibiotics was 41.5%, whereas, the rate for those who were initially treated by PAPM BP was 71.9%.
3) The efficacy rate in patients whose neutrophil counts before the therapy were less than 100/mm³ was 52.5% whereas, the rate in patients whose neutrophil counts after the therapy were less than 100 mm³ was 50.0%.
4) Out of the 173 patients, adverse effects were observed in 19 patients (11.0%), including 3 with nausea, vomiting or appetite loss, and 2 with skin eruption. Abnormal laboratory tests were observed mainly in liver functions, but were reversible.
These results indicate that PAPM BP is an effective and safe antibiotic for the treatment of severe infections in patients with hematopoietic disorders.

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A clinico-epidemiological study of Clostridium difficile-associated diarrhea (CDAD) complicatin malignancies was performed. A total of 61 episodes of CDAD were identified during the period between January 1993 and December 1997 at the 316-bed Chiba Cancer Center Hospital. Forty-four episodes (72.1%) of CDAD had occurred in a single ward (E4-ward) and, interestingly, all but one CDAD in E 4-ward developed in patients with hematological neoplasm even though there were always 10 to 13 inpatients with lung cancer in the same ward. Of 45 cases of hematological neoplasms, 37 (82.2%) had received cancer chemotherapy and 10 were treated with antineoplastic drugs alone before the onset of CDAD. Furthermore, anthracyclines and vinca alkaloids, which often induce colonic stasis, were given exclusively to the patients with hematological neoplasm. The combination of nosocomial infection, frequent usage of antimicrobial agents and cancer chemotherapy most likely accounts for the sustained outbreak of CDAD among the patients with hematological neoplasm in E 4-ward of the Chiba Cancer Center Hospital.

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