The sensitivity of methicillin-resistant Staphylococcus aureus (MRSA) isolated in our hospital during the period from November 1988 through April 1989 to various antibacterial agents was examined. Isolates were obtained from blood (4 isolates), sputum (40), bile (1), ascites (1) and urine (4).
All isolated MRSA were resistant to cefazolin, cefmetazole, cefuzonam, flomoxef, and tobramycin. More than 80% of the isolates were resistant to fosfomycin and amikacin. 60% were resistant to ofloxacin (OFLX). 46% were sensitive to minocycline. 50% or more of the isolates were sensitive to gentamicin (GM), dibekacin (DKB) and astromicin (ASTM). 88% were sensitive to netilmicin. All the isolates were sensitive to vancomycin and arbekacin. The incidence of OFLX-resistant isolates was increased compared with the results of the previous study.
Most of the isolates were coagulase type II. GM, ASTM and DKB were less active against type IV isolates, but they had sufficient antibacterial activity against the type II isolates.

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Minimum inhibitory concentrations (MIC) of norfioxacin (NFLX) to 133 strains of methicillinresistantStaphylococcus aureus (MRSA) isolated from clinical patients were investigated and compared with those of minocycline (MINO), erythromycin (EM), amoxicillin (AMPC), cefaclor (CCL) and fosfomycin (FOM).MIC₉₀ of these drugs were 3.13 μg/ml with NFLX, 0.39 μg/ml with MINO, >100 μg/ml with EM, 50 pg/ml with AMPC, >100 pg/ml with CCL and >100 pg/ml with FOM.
MIC distribution patterns with 2 peaks were recognized with EM and FOM.
Of 55 strains resistant to all of EM, AMPC, CCL and FOM, 50 and 54 strains were well susceptible to NFLX and MINO, respectively.
The present investigation demonstrated relatively potent antibiotic effect of NFLX against MRSA. Considering the safety of NFLX to children which have been confirmed and reported separately, it can be concluded that NFLX is a useful oral antimicrobial drug in the treatment of children with MRSA infections.

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First of all, vancomycin (VCM) showed good antimicrobial activity against Staphylococcus aureus including methicillin-sensitive and -resistant strains. MIC₉₀of VCM was 1.56 μg/ml.
Effects of different 2-drug combinations among cefamandole (CMD), flomoxef (FMOX) and imipenem (IPM), and activity of VCM alone were examined in vitro against 5 clinical isolates of methicillin-sensitive S. aureus (MSSA) and 22 isolates of methicillin-resistant S. aureus (MRSA).In a checkerboard study, synergism was observed against 4 strains of the 5 MSSA and all 22 strains of the MRSA with IPM and CMD, FMOX and IPM, and FMOX and CMD combinations.Mean MICs of these combinations were as low as one-fourth to one-tenth as those of individual drugs.

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Clinical evaluation, safety and kinetics in serum of sulbactam/cefoperazone (SBT/CPZ) in patients with lower respiratory tract infections have been studied in a multicenter trial participated by 28 institutions in Kyushu area during a period of 13 months from March 1987 to March 1988.
1. Mean peak serum levels of SBT and CPZ in 35 patients up to 4 hours after intravenous infusion of 2g of SBT/CPZ were 38.2±17.3 μg/ml for SBT and 104.3 ± 31.4 μg/ml for CPZ. Serum half-lives of SBT and CPZ were 0.76 hour and 1.53 hours, respectively. These results were in similar ranges to those reported elsewhere for SBT/CPZ.
2. Serum half-lives of SBT and CPZ after intravenous infusion of 2g of SBT/CPZ were not significantly prolonged in patients with moderate liver or kidney dysfunctions.
3. Clinical efficacy rates of SBT/CPZ in 217 patients were 93.1% (81/87) for pneumonia, 93.3% (14/15) for lung abscess, 78.9% (15/19) for acute exacerbation of chronic bronchitis, 57.1% (4/7) for diffuse panbronchiolitis, 72.4% (21/29), 74.4% (32/43) and 100% (9/9) for infections concurrent to bronchiectasis, chronic respiratory disease and pulmonary emphysema, respectively. Those were 50% (1/2) for bronchitis associated with lung cancer and 66.7% (4/6) for empyema. The overall efficacy rate was 83.4% (181/217).
4. Clinical efficacy rate of SBT/CPZ for pneumonia in patients with underlying diseases such as lung cancer, pulmonary tuberculosis and pneumoconiosis, etc, was 85.3% (29/34) and was not significantly different from the efficacy rate of 98.1% (52/53) in patients without these underlying diseases.
5. Of 30 patients who failed to respond of previous antibiotic treatments, 21 were effectively treated by SBT/CPZ.
6. Bacteriological eradication rates against Pseudomonas aeruginosa, Haemophilus influenzae and Streptococcus pneumoniae were 42.9% (9/21), 87.5% (14/16) and 100% (5/5), respectively. The overall eradication rate in all cases including polymicrobial infections was 72.8% (67/92).
7. The high levels of peak serum concentration of CPZ, and the difference between serum levels of SBT and of CPZ seemed to contribute to the high clinical efficacy.
8. Adverse reactions occured in 2.8% (6/217) of the patients, and consisted primarily of rash and diarrhea. Laboratory abnormalities were observed in 8 patients during the study. These were elevations of S-GOT and S-GPT, and eosinophilia.
9. SBT/CPZ is a very useful drug in the treatment of lower respiratory tract infections as it has become available just in time when increase in resistant organisms to β-lactams is notable.

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Because Campylobacter jejuni is most frequently identified as a causative organism of bacterial enteritis in pediatrics, a study was done to evaluate the clinical efficacy against Campylobacter enteritis and the safety of a macrolide antibiotic, rokitamycin (RKM).In case of acute enteritis, RKM was used in a form of dry syrup at a dose level of approximately30mg (in potency) /kg body weight and its efficacy and safety were compared to those of fosfomycin (FOM) dry syrup which is currently in use at a dose level of60mg (in potency) /kg.Both drugs were administered, as a rule, in3divided daily dose (RKM before meal and FOM after meal) for 5consecutive days.Comparisons of the drugs were made using a well-controlled method. Obtained results are summarized as follows.
1.No significant differences in background factors of the2drug groups were apparent, hence it was deemed that no obstacles existed in making comparative studies of the2groups with regard to their efficacies and safeties.
2.Overall efficacy rate against Campylobacter enteritis was100%in the RKM group with a rate of excellent efficacy of91.3%and the former was94.4%in the FOM group with the latter of72.2%.Though the RKM group apparently showed higher rates by5.6%and19.1%, respectively, for overall and excellent efficacies, they were not statistically significant as both drugs showed good efficacies.When acute cases of enteritis other than those caused by Campylobacter were included in the analysis, overall efficacy rates and rates of excellent efficacy were, respectively, 97.6%and85.7%for the RKM group and88.6%and68.2%for the FOM group, thus RKM showed higher efficacy rates by9.0%and17.5%, respectively.These differences were deemed statistically significant using the U-test.
3.Numbers of days required for most of the major symptoms to subside were3days or less for the group for which RKM was used against Campylobacter enteritis.Similar results were observed for the FOM group also.In cases of acute enteritis due to other causes than Campylobacter, slower recoveries were observed for both the RKM and the FOM groups than in Campylobacter enteritis cases, with the latter group slower than the former.In cases of puruloid stool, the recovery in the RKM group was significantly faster by U-test than the FOM group, and a similar trend was observed overall.
4.Bacteriologically, the eradication rate of Campylobacter in the RKM group was very good at91.3%with the FOM group showing a rate of78.9%.Though the RKM group showed an eradication rate12.4%higher than the FOM group, no statistical significance was found. When other causative organisms were included in addition to C.jejuni, the eradication rate in the RKM group was86.7%whereas in the FOM group was76.9%.Though the former was higher by9.8%, no significant difference existed.
5.Numbers of days required for the eradication of C.jejuni was somewhat shorter in theRKM group than in the FOM group, but again, no significant difference was found.Eradication of Salmonella spp.required somewhat shorter length of time in the RKM group than in the FOM group, but again without significance.The RKM group showed significant delay upon the U-test) compared to the FOM group in eradicating enteropathogenic Escherichia coli (EPEC), but no significance was found overall.
6.No side effect was observed in either group.In laboratory tests, 1case of eosinophilia was observed in each of the2groups, and slight simultaneous increases in GOT and GPT values were observed in1case in the RKM group.No significant differences, however, were recognized between the2groups with regard to either side effects or laboratory test results. Incidentally, no refusal of administration of either drug preparation was noted.

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Rokitamycin, a newly developed macrolide antibiotic was orally administered to 7 healthy male volunteers (22-25 years) for 7 consecutive days to study changes in bacterial flora and concentrations of the drug in feces, and to observe adverse reactions and laboratory test parameters. A dose of 200 mg (2 tablets: 100 mg/tablet) was given 3 times daily before meals and the fecal studies were done on the 5 days before administration (adm.) [b.a.], at the time of administration (0), and the 3rd, 5th, 7th (the final day of treatment) days during adm. [u.a.] and the 3rd, 5th 10th, 20th, 30th days after adm. [a.a.]. The results obtained are summarized as follows.
1. Obvious changes in mean populations of total aerobes and enterobacteriaceae were not found. In changes of each bacteria of enterobacteriaceae, Escherichia coli was not observed in cases from initial day of treatment to the 3rd day a.a. Cases from which Citrobacter sp. was isolated tended to increase after 3 days u.a. and gradually decrease after 3 days a.a. Among Gram-negative bacilli, cases where isolation of Pseudomonas sp. was observed increased temporarily on the 3rd u.a., Gram-positive cocci did not show particular patterns of changes. No changes in mean count of total anaerobes were observed during the course of the experiment.Among individual anaerobes, numbers of Lactobacillus and peptococcaceae decreased slightly from the 3rd day u.a. and returned on the 5th day a.a.
2. Clostridium difficile D-1 toxin was detected in feces at amounts approximately 500 ng/g in 2 cases each on 20th and 30th day a.a., with 1 incidence occuring in the same person on the 2 separate days.
3. The drug was detected in all 7 cases on the 3rd, 5th and 7th days u.a., and in 1 cases each on the 5th and the 30th day a.a. The mean peak level was 315.5 μg/g on the 7th day u.a. The reason for the detection of the drug in feces in 1 case on the 30th day a.a. at a value of 5.90 μg/g was not clear.
4. Adverse reactions and abnormal laboratory test results due to this drug were not observed in any cases.

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Analysis was made to determine concentrations of cefmetazole (CMZ) in maternal serum, and intrauterine tissues of myometrium, placenta, fetal membrane, amniotic fluid and fetal lung after one shot intravenous infusion of 100 mg of CMZ to rabbits with 25th day-pregnancy, and the following results were obtained.
1. Concentrations of CMZ in maternal serum, myometrium and placenta reached their maximum levels in 30 minutes after administration, then decreased rapidly.
2. The concentration of CMZ in the fetal membrane reached its maximum level in 30 to 60 minutes after the administration, then it decreased to a nearly constant level.
3. The concentration of CMZ in the amniotic fluid showed its maximum level in 30 minutes after administration, then decreased, but somewhat increased again thereafter.
4. The concentration of CMZ in the fetal lung was elevated gradually after administra tion, then decreased after reaching its maximum level at 90 minutes, after administration to a nearly constant level. It was deemed, however, that higher concentrations would be necessary to achieve therapeutic effects because attained concentrations were lower than those in other tissues.

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The relationship between indigenous bacterial floras in the lower genitals and the utero - cervical region is of importance due to a barrier-like role against ascending infections through the mechanism of the localized protection at a boundary of the uterocervical region.
Therefore, bacterial flora in the uterocervical and uterine regions was studied in cases for which gynecological operations were performed (n=77).
1. Ratios of incidences of the detection of bacteria on the uterocervical and in the uterine regions were 50/77 (64.9%) and 6/77 (7.8%), respectively. When different age groups are compared, the detection ratio from the uterocervical region was high among patients in the 40 s, and all the cases in which bacteria were detected from the uterine region were in the 40 s.
2. Gram-positive bacteria were detected at a high ratio, and anaerobic bacteria were noted in the uterocervical region, and ratios of detection of Staphylococcus epidermidis, Lactobacillus sp. and Propionibacterium acnes were high. Six strains of Gram-positive bacteria and 1 strain of Candida sp. were noted in the uterine region.
3. When cefmetazole (CMZ) was administered for the prevention of the infections after these panhysterectomy cases examined here, no postoperative infectious diseases nor adverse reactions were noted.

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The usefulness of cefteram pivoxil (CFTM-PI) was evaluated in 99 cases with respiratory tract infections: 32 cases with acute bronchitis, 51 cases with infectious exacerbations of chronic respiratory diseases and 16 cases with pneumonia.
1. The clinical efficacies included marked improvement in 27 cases, improvement in 51 cases, moderate improvement in 9 cases, no change in 10 cases and deterioration in 2 cases. The improvement rate was 78.8%.
2. Overall effects were excellent in 12 cases, good in 9 cases and fair in 5 cases. There was no case in which efficacy was not observed and the efficacy rate was 80.8%.
3. Bacteriological effects were classified according to the causative organisms. Eradication rate was 80.8% (21 of 26 strains), indicating an excellent antibacterial action of CFTM-PI. In particular, MICs of cefteram were below 0.05 μg/ml against all 10 strains of Haemophilus influenzae regardless of β-lactamase production even with an inoculum of 10⁸ or 10⁶ cells/ml.
4. Side effects rarely occured and included a slight gastrointestinal irritation in 4 of 99 cases (4%). Two cases which had abnormal elevations of GOT and GPT had abnormal values prior to administration of CFTM-PI. The elevations were slight and it was possible to continue administration. The GOT and GPT values were improved after the end of administration.
The above results indicate the usefulness of CFTM-PI in acute respiratory infections and infectious exacerbation of chronic respiratory diseases.

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Adsorption, metabolism and excretion (ADME) of cefuroxime axetil (CXM-AX) 500 mg given orally at 30 minutes after meals to male volunteers who had undergone gastrectomy was compared with that of healthy volunteers.
1. The transition of the drug's serum concentrations was observed as follows: T_max was somewhat shorter and T 1/2 longer in the gastrectomized volunteer group than in the healthy volunteer group.
2. Total urinary recovery rates of cefuroxime (CXM) were not significantly different between the 2 groups, averaging 53.6% for the gastrectomized volunteer group and averaging 54.5% for the healthy volunteer group.
3. Total urinary recovery rates of CXM-Δ² were not significantly different between the 2 groups either, averaging 1.7% for the gastrectomized volunteer group and 1.3% for the healthy volunteer group.
4. The above results suggest that ADME of CXM-AX in the gastrectomized volunteers is not fundamentally different from that of the healthy volunteers. The absorption, however, may be reduced when peristalsis of the intestinal tract is accelerated as a result of gastrectomy.

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We studied the pharmacokinetics of aztreonam (AZT) in 6 patients with renal insufficiencies during nonhemodialysis and hemodialysis.
After intravenous injection of 1g AZT, it was found that serum AZT concentrations during, hemodialysis were different from those during nonhemodialysis and serum half-lives (T1/2β) were 3.44 hours and 16.97 hours, respectively. AZT clearance changed from 0.762L/hr during hemodialysis to 3.360L/hr during nonhemodialysis.
These findings suggest that hemodialysis patients should receive the standard dose of AZT as a loading dose, followed by one-half the loading dose per day and receive a supplemental dose equal to half their usual maintenance dose after each dialysis session.

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We studied clinical effects and safety of ceftibuten (7432-S, CETB), a new oral cephem antibiotic, against chronic complicated urinary tract infections in 9 cases and bacterial prostatitis in 10 cases.
CETB was administered at a daily dose of 400-600 mg devided into twice or 3 times for a duration of 1-4 weeks. The overall clinical effect was 83.3% according to the criteria of UTI Commitees (excellent: 4 cases, moderate: 1, poor: 1) in evaluated 6 cases, and the efficacy rate was 77.8% in the bacterial prostatitis cases according to physicians' evaluation (good: 7cases, fair: 2, unknown: 1).
There was 1 case of nausea, vomiting and lightly diarrhea on the third day after treatment but those tendencies all disappeared after stopping administration.
So, we concluded that CETB was a useful agent for chronic complicated UTI and bacterial prostatitis with a daily dose level of 400-600 mg except in severe cases.

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A nationwide survey of susceptibilites of Staphylococcus aureus, Escherichia coli, Klebsiellasp. and Proteus mirabilis initiated in 1980 was continued in 1986.
This report documents differences in susceptibilities of clinical isolates of the above microorganisms to ampicillin (ABPC), cefazolin (CEZ), cefmetazole (CMZ) and gentamicin (GM) among general hospitals throughout Japan.
Clinical isolates of each species of microorganisms which were collected in 24 hospitals made up each study group and were collected at the Kosei General Hospital, Tokyo, from April 1980 to March 1986.
We compared the variability in the resistant rates (MIC>25 μg/ml) and MICs of each antibiotic for 50% and 80% of the isolates among the hospitals. MICs were determined by the serial 2 fold agar plate dilution method, standardized by the Japan Society of Chemotherapy, with an inoculum of approximately 10⁶ CFU/ml or 10⁸ CFU/ml. Susceptibility patterns of S.aureus to ABPC, CEZ and GM, of E. coil to ABPC, of Klebsiella sp. to CEZ and GM and of P. mirabilis to ABPC, CEZ and GM varied from hospital to hospital. On the other hand, the differences in the susceptibility patterns among the 6 districts of Japan were not obvious, because the differences were affected by different susceptibility patterns of each hospital located in each district.

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