[in Japanese]

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In vitro antifungal activities of omoconazole nitrate (OMZ), a new topical imidazole antifungal agent, were studied against 364 strains of 22 genera and 47 species of stock cultures of a wide range of medically important fungi. The test was carried out using the agar dilution method with bifonazole (BFZ) as the reference drug. OMZ exhibited a broad spectrum of antifungal activities. Most of yeasts including Malassezia, dimorphic fungi, non-pigmented hyphomycetes and dermatophytes were almost equally or more greatly susceptible to OMZ than to BFZ, although the MIC values of these drugs against Candida and probably some other fungi were influenced differently by testing media. Comparable susceptibility to OMZ were observed for fresh clinical isolates of dermatophytes and Candida albicans. OMZ was also active against Malassezia. These results have encouraged us to proceed in vivo studies using animal models of cutaneous mycoses.

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Minimum inhibitory concentrations (MICs) were determined for sultamicillin (SBTPC), and for other major oral β-lactam agents against clinically isolated strains collected from outpatients during a period from August, 1992 to February, 1993, and the following conclusions were obtained.
1. The ratio of penicillinase (PCase)-producing strains of Staphylococcus aureus was 96.0% and that of methicillin-resistant S. aureus (MRSA) was 12.0%. MIC₉₀ of SBTPC against S. aureus including MRSA was 6.25 μg/ml. No increasing tendency was observed for S. aureus resistant to SBTPC.
2. No resistant strains were found among Streptococcus pyogenes and Enterococcus faecalis against penicillins (PCs) including SBTPC. But PCs and cephems (CEPs) insensitive or resistant Streptococcus pneumoniae were observed in 22.0% among all the strains of S. pneumoniae.
3. 100% of the tested both strains of Escherichia coli and Proteus mirabilis were β-lactamase producers. 12.0% of the tested strains of Haemophilus influenzae and 16.0% of the strains of Neisseria gonorrhoeae were also β-lactamase producers. SBTPC showed strong antimicrobial activity against most of these β-lactamase producing strains.
However, in our study of β-lactamase productivity using plural substrates and test methods, it appeared that a part of strains of E. coli might produce β-lactamase of “Extended broad-spectrum”. MICs of SBTPC and CEPs against those strains were distributed rather in a high range.
4. The results of the study suggested that the resistant strains of S. pneumoniae against PCs and CEPs might be increasing year by year. Some of strains of E. coli, resistance against the 2 agents were observed. It is important to keep observing changes in resistance of such organisms in the future.
5. The antimicrobial activities of SBTPC against clinically isolated strains in this study indicated potential problems such as those mentioned above.
It is, however, also confirmed that SBTPC shows still strong antimicrobial activities against most of β-lactamase producing strains found in daily medical examinations. Taking into consideration of the strong activities of SBTPC against so-called indirect pathogenicity caused by β-lactamase producing indigenous bacteria reported lately, SBTPC may be a useful antibiotic for community aquired infections in the 1990's.

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Aiming at measuring the antimicrobial activities of arbekacin (ABK) against the strains of methicillin-resistant Staphylococcus aureus (MRSA), isolated from pediatrics patients in 1992, the minimum inhibitory concentration (MIC) of 8 antibiotics including ABK was determined and the coagulase types of those strains were also examined. The obtained results are summarized as follows.
1. Among coagulase types of a total of 78 strains, Type II, Type IV and Type VII were 84.6%, 12.8% and 2.6%, respectively. No clear difference in coagulase types were observed among their origins of isolation.
2. MIC₉₀ of ABK against 42 strains isolated from the air passage of suspected pneumoniae patients and 36 strains isolated from the blood of suspected septicemia patients were 1.56μg/ml and 3.13μg/ml, respectively, and MIC₉₀ of ABK against the 78 strains was 1.56μg/ml, which was equal to that of vancomycin (VCM).
3. Most of these strains exhibited resistance against multiple antibiotic agents including cefmetazole (CMZ), imipenem (IPM), fosfomycin (FOM) and minocycline. Strains isolated from the blood were mostly resistant to multiple agents, and most of them were especially highly resistant to CMZ and IPM. ABK, however, showed potent antimicrobial activities even to those strains. These results were similar to the results obtained several years ago.
4. Considering the fact that ABK demonstrates not only potent antimicrobial activities against MRSAs isolated from the pediatric patients, but also shows remarkable clinical effects with concomitant use with β-lactams or FOM, the prospect of ABK use in MRSA infectious diseases of children is excellent.

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In order to examine antibiotic activities of cefteram (CFTM), its minimum inhibitory concentrations (MIC's) and those of other cephem drugs were determined against clinically isolated strains received from July 1990 to June 1991 and from July 1992 to February 1993 from medical facilities throughout the country and against clinically isolated strains detected in our laboratory in samples from patients with various infectious diseases. The obtained results are summarized below.
1. No CFTM-resistant strains were found among β-streptococci, Klebsiella spp., Proteus mirabilis, Haemophilus influenzae, and Neisseria gonorrhoeae or even when found, they were present in extremely low proportions.
2. It appeared that Streptococcus pneumoniae insensitive or resistant to β-lactams, as well as cephems-resistant strains of Escherichia coli were increasing. The former included benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP) of PCG-resistant S. pneumoniae (PRSP), and the presence of the latter suggests the possibility of the existence of “Extended broad-spectrum β-lactamase” producing strains.
The MIC's of β-lactams against the above PISP or PRSP, and against cephems-resistant E. coli tended to be high, but those of CFTM were relatively low (in most cases).
3. Proportions of strains resitant to cephems, including CFTM among Citrobacter spp., Enterobacter spp., Serratia marcescens, Proteus vulgaris, Morganella morganii, and Providencia rettgeri were high, and in addition, the existence of these cephem resistant species suggests an increase in multiple drug resistant strains that show resistance to new quinolone drugs.
4. As mentioned above, CFTM is by no means a perfect drug or utility drug and its antimicrobial activities do not cover some recent isolates with multiple drug resistance. Except problems encountered with so-called “attenuated” strains of bacteria, increases in resistance can only be observed at a level of MIC₉₀'s, and as far as MIC₈₀'s are concerned, CFTM still is as active as before and may be used in the treatment of most infections we encounter in normal medical practices.

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Reaction mechanism of macrolide 2'-phosphotransferase [MPH (2')] from Escherichia coli to the 2'-modified macrolide antibiotics was analyzed by using microbioassay, nuclear magnetic resonance (NMR) spectrometric assay and mass spectrometry. It was found by microbioassay that the 2'-modified macrolide antibiotics as triacetyloleandomycin (TAO), erythromycin ethyl succinate (EME) and erythromycin estolate were inactivated with adenosine triphosphate (ATP) by MPH (2'). The NMR spectrometric assay for the analysis of the reaction with the 2'-modified macrolide antibiotics and MPH (2') was established using guanosine triphosphate, which was higher reaction rate than ATP, as a cofactor. It was clearly shown by NMR spectrometric assay and mass spectorometry that the C2'-side chain of TAO and EME was naturally released in phosphate buffer solution, and then, the C2' position was phospholylated with GTP by MPH (2').

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We studied clinical effects of ceftazidime (CAZ) alone or in combination with aspoxicillin (ASPC) against various infections in obstetric and gynecological patients.
1. Obstetric and gynecological patients (n=91) with various infectious diseases were treated with CAZ alone (1-2g×2/day, n=54) or in combination with ASPC (1-2g×2/day, n=37) administered via drip infusion.
2. CAZ alone or in combination with ASPC was efficacious in 50 out of 54 (92.6%) or 33 out of 36 (91.7%) patients, respectively. Overall, the efficacy ratios were 46/49 (93.9%) against gynecological infections, 21/25 (84.0%) against perinatal infections and 16/16 (100%) against other infections.
The bacteriological efficacy ratio was 21/21 (100%) while clinical effectiveness in cases in which cousative agents were known was observed in 20 out of 21 (95.2%) patients. In patients who had not respond to other treatments, CAZ alone, and in combination with ASPC were effective in 15 out of 16 (93.8%) and 6 out of 8 (75.0%) patients, respectively, hence the overall efficacy ratio was 21/24 (87.5%).
3. Abnormal values in clinical laboratory tests were obtained in 3 out of 91 (3.3%) patients. No other adverse side effects were observed in any of the patients.

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The validity of clinical use of cephem antibiotics for preventing the spread of methicillin-resistant Staphylococcus aureus (MRSA) was investigated using a methicillin-susceptible S. aureus (MSSA) carrying mecA gene. It became evident that drug with anti-staphylococcal activity, such as cefuzonam (CZON) or cefazolin (CEZ), has comparatively low selectivity of high-level methicillin resistant clones (methicillin MIC range from 25 to 800 μg/ml) from MSSA carrying mecA gene among cephem antibiotics tested. At concentrations over 1.56 μg/ml of both CZON and CEZ, about a 2-3 log₁₀ decrease in viable count was observed. Therefore, it seems that much satisfactory disappearance of bacterial cells can be obtained in cooperation with host defence mechanisms.

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