[in Japanese]

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In this study, fleroxacin (FLRX), a new quinolone derivative, was orally given at 300mg once daily for 14 days to 102 patients with non-catheterized complicated urinary tract infections in order to determine the optimal treatment duration. We investigated its efficacy at day 5-7 and day 14, according to the criteria proposed by the Japanese UTI Committee, and also to the recurrence rate after the withdrawal.
The results were as follows:
1. Overall clinical efficacy rates were 86% at day 5-7 and 84% at day 14. Both incidence of bacterial replacement in bacteriuria and normalization in pyuria were increasedat day 14 as compared with those at day 5-7.
2. Bacteriological eradication rates were 91% at day 5-7 and 89% at day 14.
3. Clinical efficacy rates from physicians' evaluation were 86% at day 5-7 and 88% at day 14.
4. Incidence of side effects was 9.1%, and most of the cases were gastrointestinal symptoms which appeared within 4 days. Slight and transitory changes in laboratory findingswere noted in 2.3% of evaluable cases.
5. With the occurrence of pyuria and bacteriuria as markers, the “no recurrence” rates were 63% at 1 week, 54% at 2 weeks, 61% at 3 weeks, 81% at 4-6 weeks after the withdrawal, andthe “recurrence” rates were 4%, 4%, 6% and 5%, respectively. Remaining cases were judged as “reserved assessment”. Generally, aggravation of bacteriuria was found but the aggravation of pyuria was observed in only few cases.
6. According to breakdown of cases with bacteriuria only, cure rate was 67% and recurrence rate was 33%. Re-infections were observed much more frequently than relapse based on the identification of infecting organisms.
These results suggest that sufficient bacteriological eradication and clinical efficacy could be obtained by 14-day treatment of FLRX in non-catheterized complicated urinary tract infections. The efficacy of the treatment became evident around day 7. In approximately 30% of the cases in which eradication of the initial causative organisms was observed at day 14 reappearance of bacteriuria (≥10³CFU/ml) occurred after withdrawal of the antibiotic, but cases with pyuria were few, and the incidence of true recurrence was generally low. Onset of side effect after 5-day was not seen, hence FLRX seemed to be a safe agent.

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Effects of sulbactam/cefoperazone (SBT/CPZ) on the hostparasite relationship were studied using an established mouse macrophage cell line.Since SBT inactivates some types of β-lactamase strongly, a combination of SBT with CPZ show smarked antibacterial activities against the bacteria producing β-lactamases.In addition, sub-MIC levels of SBT/CPZ made Escherichia coli more susceptible to bactericidal activity of macrophage.
This study provides evidence that SBT/CPZ works in partnership with host defense mechanism against bacterial infections in clinical situations.

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Between March 1988 and June 1990, we gave cefepime to 5 subjects after surgery and studied the pharmacokinetics of the drug. In the same period, we treated 23 patients with surgical infections with the same drug and evaluated its clinical efficacy. In the pharmacokinetic study, 1 g was given intravenously to each individual over a 30 minutes period. The peak levels in the plasma, 59.9-118, ug/ml, were obtained at around the end of this time. The peak levels in the bile, 7.1-28.2 ug/ml, were reached at 1-5 hours after administration, depending on the patient. At hours 5 and 6, the range of plasma concentration was 3.7-12.3 jig/mi. In the 22 patients with surgical infections, clinical efficacy of the drug was excellent in 12, good in 5, fair in 1, and poor in 4, with an overall efficacy rate of 77%. The bacteriological response was evaluated in the 16 patients for whom the species of the probable causative organisms were identified. Those bacteria were eradicated in 10 patients, decreased in 3, and were persisted in 3, with an eradication rate of 63%. Against 5 strains of Escherichia coli isolated, the highest MIC was 0.05μg/ml, and against 2 strains of Pseudomonas aeruginosa isolated, the MIC was 1.56μg/ml, so this drug should be highly effective toward these species. Three strains of Staphylococcus aureus were isolated, one of which was resistant to methicillin. It was not eradicated.

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Cefpirome (HR 810, CPR), a new cephem antibiotic, was investigated for its experimental and clinical studies in pediatrics. The results obtained are summarized as follows.
1. Plasma and urinary levels of CPR were determined in 2 children (age 5 and 7 years) after the one shot intravenous injection of the drug at 20 mg/kg. Average plasma levels of the drug were44.7μg/ml, 28.5μg/ml, 10.5μg/ml, 4.6μg/ml and 1.5μg/ml at 1/2 hour, 1 hour, 2 hours, 4 hours and 6 hours, respectively, and the average half life was 1.57 hours. Average urinary levels of the drug were 1,785μg/ml, 545μg/ml and 198μg/ml at 0-2 hours, 2-4 hours, 4-6 hours, respectively and the average urinary elimination rate was 52.0%. The results were nearly equivalent to those in adults except for urinary elimination rate which tended to be slightly lower than that in adults.
2. Cerebrospinal fluid levels in 3 cases of purulent meningitis treated with CPR were investigated. Cerebrospinal fluid levels in a case of Neisseria meningitidis were 11.5-23.1μg/ml at 1 hour and 0.94μg/ml at 5 hours after intravenous injection of 44.4mg/kg, 4 times a day. Cerebrospinal fluid levels in a case of Streptococcus pneumoniae were 1.01-4.23μg/l at 1 hour after intravenous injection of 49.0mg/kg, 6 times a day, and in the other case with Streptococcus pneumoniae, the levels were 16.8-37.1μg/ml at 1 hour, 11.3 and 3.60μg/ml at 3 and 4 hours after intravenous injection 52.2 mg/kg, 6 times a day. These results are not inferior to those with cefotaxime or ceftriaxone. These levels appear to be higher than MIC₉₀ values against Escherichia coli,Streptococcus agalactiae, S. pneumoniae or Haemophilus influenzae which are the major pathogens of these diseases.
3.CPR was given to 62 patients and clinical emcacy, bacteriological response and adversereactions were evaluated.
Evaluated cases for clinical emcacy included 3 cases of purulent meningitis, 1case of acute purulent otitis media, 2 cases of acute purulent tonsillitis, 1 case of acute bronchitis, 49 cases of acute pneumoniae, 1 case of scarlet fever, 1 case of acuteosteomyelitis, 1 case of acuteenterocolitis, and 2cases of acute UTI, totalling 61 cases.
Clinical emcacies were excellent in 38 cases, good in 22 cases and fair in 1 case with an emcacy rete of 98.4%(excellent+good).Organisms presumed to be pathogens included 1 strain of staphylococcus arueus, 4 strains of Strreptococcus pyogenes, 1 strain of S.agalactiae, 10strains of S. pneumoniae, 1 strain of N.meningitidis, 1 strain of E.coli, 1 strain of Serratia liguefaciens and 18 strains of H.influenzae,S. liguefaciens persisted and 1 strain of H. influenzae decreased, and the others were eradicated with an eradication rate of 94.7% overall.These results may bespecific to this study due to the distribution of the pathogens.It was concluded, however, that CPR had good antibacterial activity for primary pathogens in pediatric infections.
Adverse reactions occurred in 2 patients.One case was diarrhea, and another case was diarrhea and eruption. These adverse reactions, however, were not severe and did not require the withdrawal of the drug, and diarrhea stopped without the use of an antidiarrheal.Abnormal changes in laboratory test values included 3 cases of elevated GOT 1 case of elevated GPT, 5 cases of thrombocytosis, 1 case of eosinophilia, 1 case of elevated GOT and thrombocytosis, 1 case of elevated GOT and GPT and eosinophilia, 1 case of elevated GOT, GPT and thrombocytosis, and 1 case of eosinophilia and decreased platelets. All of these were mild and in 11 cases for which retests were perfomed showed normal values except a few cases. Types and frequencies of these abnomlal values are not appreciably different compared with cases involved other cephem antibiotics.

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Isolated bacteria from respiratory infectious diseases were collected in cooperation with institutions located throughout Japan, since 1981, and IKEMOTO et al. have been examining sensitivities of the isolates to various antibacterial agents and antibiotics, relationships between the isolates and the backgrounds of the patients and so forth each year1-7). We report here the research results for the year 1988.
In 18 institutions around the entire Japan from October 1988 to September 1989, 554 strains of bacteria were isolated mainly from the sputa of 439 patients with respiratory infectious diseases and assumed to be the etiologic bacteria. MICs of various antibacterial agents and antibiotics against 68 strains of Staphylococcus aureus, 102 strains of Streptococcus pneumoniae, 120 strains of Haemophilus influenzae, 86 strains of Pseudomonas aeruginosa, 65 strains of Branhamella catarrhalis, 18 strains of Klebsiella pneumoniae and so forth, were determined, and the drug sensitivities of these strains were examined except for the strains which died during transportation.
The drug sensitivities of the main strains were almost the same as those determined last year for each drug. However, S. aureus strains for which MICs of methicillin were higher than 12.5μg/ml (methicillin-resistant S.aureus) accounted for 38.2%, and the frequency of drug resistant bacteria increased over last year's 18.2%.
Also, we examined changes in the backgrounds of patients, the infbctious diseases, and the etiologic bacteria and so forth.
As to patient backgrounds, there were many infbctious diseases found in a high age bracket, and the patients over age 60 accounted for 57.2% of the diseases.
In the distribution by disease, bacterial pneumonia and chronic bronchitis accounted for greatest numbers of cases 32.1% and 31.4%, respectively, followed by bronchiectasis and bronchial asthma.
As for frequencies of etiologic bacteria by disease, S.aureus (22.5%) and S. pneumoniae (15.4%) in pneumonia, S. pneumoniae (25.7%) and H. influenzae (24.1%) in chronic bronchitis, H. influenzae (32.5%) and P. aeruginosa (23.8%) in bronchiectasis, and H. influenzae (31.4%), S. pneumoniae and B. catarrhalis (20.0%) in bronchial asthma were the most ffequent.
Regarding effbcts of administration of antibiotics and isolates obtained on each day after infbction, those bacteria which were isolated before antibiotic administration and which decreased after administration included S. pneumoniae, H. influenzae, and B. catarrhalis. Frequencies of S. aureus and P. aeruginosa, however, increased after antibiotic administration. Also, when dosing continued for more than 15 days, the frequency of P. aeruginosa increased rapidly.

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