In July, 1996, a massive outbreak of hemorrhagic enterocolitis involving more than 5,000 people was caused by enterohemorragic Escherichia coli (EHEC) O157: H7 occurred mainly among elementary school children of Sakai City, Japan.
The antibacterial activities in vitro against EHEC from stool specimens were determined. Norfloxacin showed the highest antibacterial activity, and fosfomycin, kanamycin, ampicillin, cefaclor were considered as effective drugs. But doxycycline showed lower antibacterial activities compared to other examined drugs, and it appears necessary to take antibiotic resistance of Escherichia coli into consideration when a treatment regimen is determined.
As a result of the oral administration of fosfomycin to 95 patients of hemorrhagic enterocolitis and carrier, no patients developed complications with hemolytic uremic syndrome (HUS). However, a study of 17 patients with HUS demonstrated the fact that most of them were subjected to intravenous administration of fosfomycin. It may be needed to consider oral administration route of effective antibiotics in the treatment of enterocolitis in order to maintain high concentrations of a drug in the intestine.

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Evaluation of efficacy and safety of cefluprenam (code number: E1077, abbreviation: CFLP), a newly developed injectable cephem antibiotics was conducted on adult patients with various infections, and followed by the study group organized from 39 institutions in pediatric field, as the drug showed no toxicity problems in suckling animals.
Informed consents from legal representatives were obtained prior to the study.
1. Clinical efficacy
Two-hundred eighty one cases were included for analysis of clinical efficacy after 40 cases of exclusion or drop-out were subtracted from a total of 321 cases. However, the cumulative number of cases evaluable for analysis was considered to be 289, because 8 cases that had 2 different diseases at the same time were counted in each category of disease.
In the cases in which causative organisms were identified (group A), 148 of 154 cases were rated as good or excellent, with an efficacy rate of 96.1 %.
As for clinical efficacies by disease, efficacy rates were 6/6 for purulent meningitis, 4/5 for sepsis, 95.7% (62/65) for pneumonia, 100.0% (29/29) for urinary tract infections, and 94.1% (16/17) for skin and soft tissue infections. The rate of excellent responses among excellent and good responses was 73.6% (109/148), showing a higher value than any of recent injectable β-lactams. On 32 cases with S. pneumoniae infection, the efficacy rate of CFLP was 100.0%. In the cases where causative organisms were not identified (group B), 128 of 135 cases were rated as good or excellent, with an efficacy rate of 94.8%. In the all cases including both the group A and the group B, the efficacy rate was 95.2% (276/289) and the rate of excellent responses among excellent and good response was 70.7% (195/276). Against severe infections, CFLP exhibited excellent clinical efficacy, showing an efficacy rate of 8/8 for meningitis, 3/5 for sepsis and 100.0% (22/22) for severe pneumonia.
As for bacteriological responses, eradication rates were 95.2% (177/186) in total. Against Gram-positive cocci, the eradication rate was 92.7% (76/82), with eradication rates of 94.3% (33/35) for Staphylococcus aureus, and 93.3% (28/30) for Streptococcus pneumoniae. Against Gramnegative rods, the eradication rate was 97.1% (101/104), and eradication rates were 100.0% (22/22) for Escherichia coli, 97.5% (39/40) for Haemophilus influenzae and 100.0% (19/19) for Molaxella catarrhalis.
In cases in which more than 3 days of treatment with previous chemotherapy resulted in no response, the efficacy rate of CFLP was 94.2% (98/104), rated excellent in 68 cases and good in 30 cases. In these cases, the eradication rate was 98.1% (52/53).
2. Pharmacokinetics
CFLP was intravenously administered to 12 subjects at doses of 20 to 40 mg (potency)/kg. In 9 subjects aged more than 12 months, maximum serum levels (C^max), T1/2β and AUC of CFLP were 155.3±9.8μg/ml, 1.43±0.18 hours and 111.7±15.0μg·hr/ml, respectively, when a dose of 20mg (potency)/kg was used. In 2 subjects aged not more than 12 months, the mean C_max, T 1/2β and AUC were 153μg/ml, 1.6 hour and 81μgEhr/ml, respectively, at a dose of 20 mg(potency)/kg. The mean C^max, T 1/2β and AUC were 332μg/ml, 0.93 hours and 157.3μgEhr/ml, respectively, in 1 subject at a dose of 40 mg (potency)/kg.
In 10 subjects dosed 20 mg (potency)/kg, urinary levels were 2413±512, 1471±524, and 470±115μg/ml in 0-2, 2-4, and 4-6 hours after dosing, respectively, showing a cumulative urinary exeretion rate of 61.4±6.3%. In 1 subject dosed 40 mg (potency)/kg, urinary levels were 5700 and 4770μg/ml in 0-2 and 2-4 hours after dosing, respectively, showing a cumulative urinary excretion rate of 42.1%.

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We evaluated the clinical efficacy of imipenem/cilastatin sodium (IPM/CS- a carbapenem antibiotic) against orthopedic infections, and the drug levels of the bone tissues were determined. The clinical efficacies for 6 patients in the infection group were good in 3 cases, and fair in the other 3; giving an efficacy rate of 50%. Bacteriologically, 8 strains were isolated from patients with the infection and an eradication rate of 87.5% was obtained upon the treatment. In 39 patients that were given the drug prophylactically, no postoperative infections occurred. Mean IPM levels in the bone and the bone marrow at 1 hour after administration in 5 patients of the prophylactic group were 17.3 μg/ml and 5.9 μg/g, respectively. The ratio of concentrations the bone to those in the bone marrow was 34.6%. The results of this study suggest that IPM/CS reaches to the bone tissue providing sufficient concentrations and that the drug is efficacious for the prophylaxis and the treatment of orthopedic infections.

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An intramuscular preparation of imipenem/cilastatin (IPM/CS, 500 mg/500 mg) was administered to 59 patients with complicated urinary tract infections (UTI; cystitis and pyelonephritis) to evaluate its efficacy and safety. The obtained results are summarized as follows: In patients with cystitis, evaluations based on daily frequencies of administration were also performed.
1) According to the treating doctors, the drug showed an overall efficacy rate of 80% (45/56 patients). The efficacy rate was 89% in patients with cystitis treated by a u. i. d. regimen. Among patients treated by a b. i. d. regimen, the efficacy rate was 67% for cystitis cases and 84% for pyelonephritis cases.
2) When clinical efficacy was assessed according to the criteria for UTI drug efficacy evaluation, the drug was markedly effective in 14 patients, effective in 23, and ineffective in 11 patients, for an efficacy rate of 77% (37/48 patients).
3) The microbiological eradication rate was 88% (59/67 strains). The rate was 95% (20/21 strains) for Gram-positive bacteria and 85% (39/46 strains) for Gram-negative bacteria. The efficacy for Enterobacter faecalis and Pseudomonas aeruginosa was 100% and 73%, respectively.
4) As side effects, pain at the injection site was reported by one patient and abnormal June 1997 laboratory test values were observed in 2 patients. All of these reactions were mild and resolved shortly after the completion of treatment.
Based on these findings, it is concluded that this intramuscular preparation of IPM/CS is effective for treating complicated urinary tract infections

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The purpose of our investigation was to monitor current trends in the susceptibility patterns of clinical bacterial isolates to roxithromycin (RXM). We measured the MICs of macrolide antibiotics, such as RXM, erythromycin (EM), clarithromycin (CAM), rokitamycin (RKM) and midecamycin (MDM), and other classes of antibacterial compounds against various clinical isolates at seven institutions between October and December in 1994 and 1995. RXM had excellent antibacterial activities for S. pyogenes, S. agalactiae, M.(B.) catarrhalis and methicillin sensitive S. aureus. Against methicillin sensitive S. epidermidis, RXM activity was fairly good but about 20% of the strains had MIC≥128 μg/ml. The activity against S. pneumoniae was not so potent and similar to activities of EM, CAM, MDM, and clindamycin. The vast majority of methicillin resistant S. aureus and S. epidermidis were also resistant to macrolide antibiotics and other classes of compounds tested.
In conclusion, RXM is an unique macrolide antibiotic by retaining potent activity against S. pyogenes, S. agalactiae, S. aureus except MRSA, M (B.) catarrhalis and M. pneumoniae.

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