Cefpirome (HR 810) is a new cephalosporin with a 2, 3-cyclopentenopyridine group in the 3-position side chain. It was compared with other cephem antibiotics in protective and therapeutic effects on various experimental infections, systemic and local, in mice and rats.
HR 810 had more potent protective effect than ceftazidime (CAZ), cefoperazone (CPZ), and cefotaxime (CTX) on systemic infections induced byEscherichia coliEc-31,Staphylococcus aureusSMITH, andSerratia marcescensSm-6 in mice. Against systemic infection withPseu-domonas aeruginosaHR 810 was as effective as CAZ.
Mice with leukopenia induced by cyclophosphamide were systemically infected with methicillin-resistantS. aureus(MRSA), methicillin-susceptibleS. aureus(MSSA),Enterobacter cloacae, Acinetobacter calcoaceticus, andEnterococcus faecalis. HR 810 was superior to cefuzonam (CZON) and cefmetazole against MRSA and MSSA and was much more active than any other antibiotics tested againstE. cloacae and A. calcoaceticus. In the activity againstE. faecalis, HR 810 was inferior to ampicillin but superior to CZON.
In mice with pyelonephritis caused byE. coliEc-7, the rank order of activities was HR 810> CAZ> CTX> CPZ.
HR 810 was more effective than latamoxef, CAZ, CTX, and CPZ in improving lung infections induced byStreptococcus pneumoniaeHL 438 and Klebsiella pneumoniaeKp-51 in mice.
HR 810 was superior to CTX and CPZ and comparable to cefazolin in therapeutic effects on intrauterine infections withE. coliEc-89 andS. aureusSMITH in rats.

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The clinical utility of imipenem/cilastatin sodium (IPM/CS, Tienam®) was studied in 9 patients with respiratory tract infections from whomPseudomonas aeruginosawas isolated using transtracheal aspiration.
The patients treated were 6 males and 3 females, with ages between 42 and 78 years. The infections diagnosed were chronic bronchitis in 5 patients, diffuse panbronchiolitis in 2 and bronchopneumonia in 2.P. aeruginosaalone was isolated from 6 patients and concomitantly with other organisms from 3.
Clinical efficacy was good in 6 patients, fairly good in 1 and poor in 2. No side effects or abnormal laboratory test values were observed, except for a slight elevation of LDH in 1 patient.
From these results, it appears that IPM/CS is a clinically useful antibiotic for the treatment of respiratory tract infections caused byP. aeruginosa.

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Imipenem/cilastatin sodium (IPM/CS) was administered to 55 patients with respiratory tract infections (RTI). A clinical evaluation of IPM/CS was carried out in 51 patients, 28 with pneumonia, 4 with pulmonary abscess, 1 with pyothorax, 6 with bronchitis, 9 with bronchiectasis, 1 with diffuse panbronchiolitis and 2 with RTI with chronic obstructive pulmonary disease, and the clinical efficacy rate was 78.4%.
Causative organisms were isolated in 23 strains out of 20 patients, such asStaphylococcus aureus4 strains,Staphylococcus epidermidis1 strain,Streptococcus pneumoniae1 strain,Branhamella catarrhalis1 strain,Haemophilus influenzae2 strains,Klebsiella pneumoniae4 strains,Pseudomonas aeruginosa6 strains,Pseudomonas sp. 1 strain,Acinetobacter calcoaceticus1 strain,Acinetobactersp. 1 strain and glucose non-fermentative Gram-negative rod 1 strain. An eradication rate of 70.6% was obtained. An overall eradication rate of main causative organisms in RTI includingS. aureus, S. pneumoniae, H. influenzaeandK. pneumoniaewas 75.0%.
Clinical adverse effects were observed in 5 patients, and these were eruption in 2, itching in 1, vomiting in 1 and drug fever in 1. Abnormalities in laboratory test results were observed in 8 patients. These disappeared or returned to normal values after completion or discontinuation of IPM/CS administration.
IPM/CS appears to be a useful antibiotic for the treatment of RTI, especially severe infections

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In an open, prospective, multicenter trial the clinical efficacy of imipenem/cilastatin sodium (IPM/CS) for the treatment of 14 cases with aspiration pneumonia was investigated.
The mean age was 75.4 years old. Diseases of central nervous system were present in 11 cases, cardiovascular diseases, pulmonary diseases and diabetes mellitus in 2 cases each respectively. Seven cases were community-acquired and another seven were hospital-acquired. Six cases were moderate and 8 cases were severe.
Causative organisms were determined in 9 cases (64.3%), multiple causative organisms were isolated in 3 cases. Isolated organisms wereStaphylococcus aureus(4),Pseudomonas aeruginosa(3),Klebsiella pneumoniae(3), Escherichia coli(1),Acinetobacter calcoaceticus(1). Detection of anaerobes was not attempted.
Clinical effects of IPM/CS were excellent in 3, good in 8, fair in 2, poor in 1, the efficacy rate was thus 78.6%.
P. aeruginosawas isolated from 2 out of 3 cases in which therapy with IPM/CS failed.
Monotherapy with IPM/CS appears to be highly effective for cases of aspiration pneumonia, but the disease due to IPM-resistantP. aeruginosais an exception.

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Clinical studies of imipenem/cilastatin sodium (IPM/CS)were conducted in 40 pediatric patients. 29 out of the 40 patients were treated for infections and 11 for prophylaxis. The following results were obtained.
1. The response rate in 29 patients with infections was 79.3%. Among the 29 patients, 16 patients who presented with malignant diseases showed the response rate of 68.8%. The response rate was lower in patients with severe infections than in those with mild or moderate infections, and a lower response rate was associated with severe neutropenia. However, there were no differences in the response rates between patients who had previously been treated and those who had been untreated with other antibiotics. The response rate in 6 patients from whom causative organisms were isolated was 83.3% and that in the remaining 23 patients was 78.3%.
2. The response rate in 11 patients to whom IPM/CS was administered prophylactically was 63.6%.
3. As for side effects, a rash was observed in 1 patient and hematuria in another, and the abnormal laboratory test results observed were elevations of GOT and GPT in 1 patient. However, they were not clinically significant.
From the above results, it appears that IPM/CS may be used as a drug of the first choice for the treatment of patients with severe infections in which the causative organisms are unknown, and for the prophylaxis of infection in patients with neutropenia.

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Cefpiramide (CPM) 2 g was preoperatively administered to 29 patients by intravenous drip infusion for 20 minutes. Concentrations of CPM in bone marrow blood, peripheral blood, and bone tissue were determined at 30, 60,120,180,240 and 360 minutes after CPM administration.
Mean concentrations of CPM in peripheral blood, bone marrow blood were peaked at 60 minutes after injection, those in bone tissues (cortex, cancellous bone) peaked at 30 minutes after injection. The mean ratio of the CPM concentration in bone marrow blood to peripheral blood was 105.5%, that in cortex (/g) to peripheral blood (/ml) was 17.7%, and that in can-cellous bone (/g) to peripheral blood was 18.2%. These concentrations were maintained above MI₈₀for 6 hours.
From the above results, CPM appears useful for the prevention of infections in orthopaedicoperation (skeletal surgery).

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We determined MIC values of cefpiramide (CPM) against clinical isolates from 100 patients who were subjected to total hysterectomy between April 1986 and March 1988.
We also investigated the concentrations of CPM in uterine tissue and assessed the clinical efficacy of postoperative prophylaxis.
1. Against bacteria isolated from clinical materials the MIC₈₀values of CPM were as fol-lows:Staphylococcus epidermidis1.56μEg/ml, Enterococcus faecalis25μg/ml, andEscherichia coli6.25μg/ml.
2. Peak concentrations of CPM in various tissues and tissue/serum ratios of AUC were as. follows: cervix uteri 35μg/g (39.5%), perimetrium 43μg/g (44.9%), endometrium 39μg/g (51.6%), myometrium 28μg/g (26.8%), oviduct 67μg/g (41.9%), and ovary 27μg/g (45.8%).
In all tissues examined CPM concentrations were above 4μg/g after 600 minutes.
3. Serum half-lives were T 1/2 (α) =13.2 minutes and T 1/2 (β) =260.2 minutes.
4. The efficacy rate in postoperative prophylaxis was 97.9%.
5. No serious side effects were observed.

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A 3 arm prospective randomized trial was designed to compare the effectiveness of aztreonam (AZT) +clindamycin (CLDM), amikacin (AMK) +AZT and CLDM+AMK as antibiotic therapy for fever in patients with hematological disorders. Between July 1987 and June 1988, one hundred and sixty of the 199 febrile episodes entered in this study were evaluated for response. Underlying diseases were hematological malignancies in 88.8 % of the subjects, and there was no statistically significant differences in incidences of the diseases among the 3 groups.
Efficacy rates were 64.2% in the AZT+CLDM group, 52.8% in the AMK+AZT group and 35.2% in the CLDM+AMK group. Efficacy rates in those with neutrophil counts was less than 500/μl before starting the antibiotics were 53.3%, 43.8% and 25.0%, respectively, in the 3 groups. The combination of AZT+CLDM was found to be the most effective even in the treatment of infections associated with febrile neutropenic patients.

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Aztreonam (AZT) was administered to 73 cases and its usefulness and safety were evalu-ated upon reviewal of the transfer of the drug into maternal blood, umbilical cord blood and amniotic fluid. The result obtained are summarized as follows.
1. AZT was intravenously administered by single injection to obtain actual data. Based on the data, theoretical changes of drug concentrations in serum in mother were reviewed according to the lapse of time. Drug concentration in maternal blood showed its peak im-mediately after administration and gradually decreased thereafter. Umbilical cord blood con-centration showed a lower peak, which was reached with a slight delay to the T_maxfor maternal blood concentration, then decreased. The decrease, however, was more moderate than the decrease in maternal blood concentration and, according to the theoretical values, umbilical cord blood concentration was higher than maternal blood concentration at 2.23 or 2.24 hours. after administration. AZT concentrations in amniotic fluid slowly increased after administra-tion and were higher than umbilical cord blood concentrations at 1.68, 1.73 hours after adminis-tration, higher than maternal blood concentrations at 1.82, 1.85 hours after administration, and they reached their peak somewhat later. Subsequently, high concentrations of AZT in amniotic fluid were maintained for a long time. The result suggests that AZT is useful for prophylaxis and treatment of amniotic fluid infections.
2. Theoretical values were analyzed by applying two-compartment model and three-com-partment model to the actually-measured values, and each parameter was compared. T 1/2 of AZT concentrations in maternal blood and in umbilical cord were 1.29 hours, 1.29 hours, 2.14 hours, 2.00 hours; C_max187.09μg/ml, 184.15μg/ml, 30.63μg/ml, 30.66μg/ml and AUC 153.25 g·Ehr/ml, 153.40μg·Ehr/ml, 123.19μg·Ehr/ml, 123.09μg·Ehr/ml respectively showing approximat·eE values. Cmax values of ATZ in amniotic fluid were 47.08μg/ml, 47.74μg/ml; AUC 948.03 g·Ehr/ml, 1,028.70μg·Ehr/ml also showing approximate values. However, volume of distributio·nE of umbilical cord blood and amniotic fluid showed a difference according to compartment model.
3. It was considered from the above results that application of only two-compartment open model would make analysis possible when only T 1/2, C_maxand AUC values must be measured for mother-to-fetal transfer of a drug.
4. No subjective and objective side effects nor abnormal laboratory values were observed in any of these cases tboth mothers and fetuses).

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Cefteram pivoxil (CFTM-PI), a new ester type cephem antibiotic, was administered at a daily dose of 600 mg to 81 patients with respiratory infections. They included 4 cases of laryngopharyngitis, 5 cases of tonsillitis, 26 cases of acute bronchitis, 13 cases of pneumonia, 10 cases of chronic bronchitis, 1 case of diffuse panbronchiolitis, 14 cases of infected bronchiectasis and 8 cases of infected other chronic respiratory diseases. Clinical effects were excellent in 18 cases, good in 50 cases, fair in 7 cases, and poor in 6 cases, thus, the efficacy rate was 84.0%. Nausea was observed in 2 cases, and diarrhea, vertigo, or fever was observed in 1 case each. The elevation of GOT and GPT values were found in 4 cases and a slight elevation of total bilirubin value was found in 1 case. These adverse reactions, however, were slight in their grades. CFTM-PI appears to be a useful oral cephem antibiotic in the treatment of respiratory infections.

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Susceptibilities of Escherichia coli, Salmonella and Staphylococcus aureus isolated from chickens, pigs and cattle to ofloxacin (OFLX) and commonly used antimicrobial agents were investigated.
1. E. coli (28 isolates) demonstrated the highest level of susceptibility to OFLX (MIC 0.10-0.39 μg/ml for all the isolates) among all the test drugs. Commonly used antimicrobial agents to which these isolates responded with relatively high susceptibilities (MIC₅₀ 0.78-6.25μg/ml) included oxolinic acid (OXA), ampicillin (ABPC), kanamycin (KM) and chloramphenicol (CP) with their MIC₅₀ values in the increasing order as above. Drugs to which these isolates responded with moderate to weak susceptibilities (MIC₅₀ 25-> 800 μg/ml) were doxycycline (DOXY), streptomycin (SM), spectinomycin (SPCM) and sulfadimethoxine (SDMX) in the increasing order of MIC₅₀. E. coli isolates with resistances to all the test drugs other than OFLX and OXA amounted to 7.1-57.1% of the isolates examined and 20 isolates (71.4%) in total.
2. Susceptibilities to OFLX and 4 existing pyridonecarboxylic acid derivatives of E. coli (48 samples) isolated recently from diarrheal pigs were compared. When evaluated in terms of MIC₅₀, the values of OFLX and norfloxacin were both 0.10μg/ml. The values increased by differences of 0.39-3.13μg/ml in an order of OXA, pipemidic acid and nalidixic acid.
3. Salmonella (28 isolates) demonstrated the highest level of susceptibility to OFLX (MIC 0.20-0.39μg/ml for all the isolates) among all the test drugs. The drugs to which these isolates responded with relatively high to moderate susceptibilities (MIC₅₀ 0.78-12.5μg/ml) included ABPC, OXA, DOXY, KM, CP and SM with their MIC₅₀ values increasing in this order. The drugs to which the isolates responded with low susceptibilities (MIC₅₀ above 100μg/ml) were SPCM and SDMX. Of all the 28 Salmonella isolates tested, 7.1-32.1% were resistant to all the test drugs other than OFLX and OXA. These resistant isolates amounted to a total of 12 isolates (42.9%).
4. S. aureus (28 isolates) were highly susceptible to OFLX (MIC₅₀ and MIC₉₀ were both 0.78μg/ml). Commonly used antimicrobial agents to which the isolates responded with high to relatively high susceptibilities (MIC₅₀ 0.10-6.25μg/ml) were, in the increasing order of MIC₅₀: DOXY, ABPC, tylosin, tiamulin, KM, OXA and CP. Drugs with moderate to low bacterial susceptibilities (MIC50 12.5-100μg/ml) were SM, SDMX and SPCM. Isolates resistant to all the test drugs except OFLX and SDMX amounted to 3.6-50% of the 28 isolates examined and they totalled 20 isolates (71.4%).
5. In conclusion, the 3 bacterial species included many isolates that were resistant to the commonly used antimicrobial agents tested. All the isolates, however, were highly susceptible to OFLX and none of the isolates showed resistance to this drug.

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We studied the clinical efficacy of ofloxacin (OFLX) in the treatment of 13 cases of Mycoplasma pneumoniae pneumonia.
OFLX was given to each patient orally at 200 mg/dose, 3 doses daily. One case was excluded because of a side effect i.e., nausea. In 12 evaluable cases, the clinical efficacy rate was 100% i.e., excellent in 7, good in 5.
OFLX is one of the useful drugs in the treatment of M. pneumoniae pneumonia.

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CREDE'S method was evaluated using of ofloxacin (OFLX) and gentamicin (GM) to show the clinical significance of chemoprophylaxis against ophthalmia neonatorum occuring through vertical infection. The obtained results are summarized as follows.
1. OFLX and GM were separately instilled using CREDE'S original method to 260 cases selected from all the cases of delivery encounterd in this hospital during a period of 6 months from 1987 to 1988. Both groups had similar backgrounds.
2. OFLX and GM were effective in 123 of 129 cases and in 116 of 131 cases, respectivery. No side effects were found.
3. OFLX to which recent isolates of Staphylococci and Escherichia coli from obstetric clinics were sensitive was more effective for the prevention than GM to which many isolates were tolerant. These findings indirectly proved the clinical significance of CREDE'S method.
4. Cases showing ineffectiveness of the prophylaxis may have been due to nosocomial infections.

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Clinical studies on ceftibuten (CETB, 7432-S) were carried out in the field of obstetrics and gynecology.
A total of 6 patients comprising 1 case of endometritis, 3 of bartholin's abscess, 1 of adnexitis and 1 of vulvar abscess was given 200-300 mg of CETB divided into 2 or 3 equal oral doses daily for 5 days.
The clinical efficacy rate was 83 percent.
Neither adverse reactions nor abnormal laboratory values were observed in any of the cases.
From the results, it was concluded that CETB was an useful antibiotic in the field of obstetrics and gynecology.

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The prophylactic and therapeutic effects of the oral administration of amphotericin B (AMPH) to patients with deep mycosis associated with hematologic diseases were evaluated in an investigation including determinations of serum concentrations of the antibiotic.
Prophylactic effects were examined in 111 subjects, and the efficacy rates averaged 83.8 % at daily doses from 1,200 to 4,800 mg. The efficacy was significantly higher at a dose of 2,400 mg/day than at a dose of 1,200 mg/day (P <0.05).
The efficacy rate tended to be higher when the length of administration period was 1 month or more. The percentage of the number of days of fever by neutrophil count was significantly less at a daily dose of 2,400 mg than at 1,200 mg in patients with neutrophil count of 1,000 cells/mm³ or less (P<0.001). The safety was evaluated in 131 subjects, and adverse effects were found in only 2 cases of nausea for an incidence rate of 1.5 %.
Therapeutic effects were studied in 12 cases, and efficacy rates averaged 58.3 % at daily doses from 2,400 to 7,200 mg. Adverse effects consisted of 1 case of diarrhea among 15 subjects who were evaluated for the safety for an incidence rate of 6.7 %.
The serum concentrations of the antibiotic were examined in 60 of the prophylactic and therapeutic subjects. Average concentrations of AMPH at 4 hours after the first daily dose of 1,200, 2,400 and 4,800 mg were 0.040, 0.053 and 0.078μg/ml, respectively. Concentrations gradually increased thereafter and reached averages of 0.089, 0.090 and 0.132μg/ml, respectively, for the 3 dose levels on the 7th day.
These results indicated that there were no serious adverse effects and serum concentrations were above the Candida MIC values at daily prophylactic and therapeutic doses of 1,200 to 7,200 mg of AMPH. Based on these findings, this drug can be expected to show prophylactic and therapeutic effects with safety in cases of deep mycosis.

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Assessment has been made, using MIC values and coagulase types, of 214 strains of Staphylococcus aureus isolated from the lesions of inpatients at the First Surgical Department, Hiroshima University, from 1983 to 1988. The obtained results are summarized below:
1. Frequency of MRSA among all the strains of S. aureus during a period from 1983 to 1987 was higher than 50%.
2. Highly methicillin-resistant strains (MIC of methicillin>100μg/ml) emerged in 1984 and thereafter, showed a trend of increase through 1987.
3. The highly methicillin-resistant strains are of coagulase II type strain and they are considered to be inhospital epidemic strains.
4. Both ofloxacin and minocycline (MINO) showed good activities against highly methicillin-resistant strains, but many resistant strains were resistant to il-lactam and aminoglycoside agents.
Based on the above basic assessment, chemotherapies mainly using MINO were performed on cases of MRSA infections experienced at the First Surgical Department, Hiroshima University in a period from July, 1987, to November, 1988, and the following results were obtained.
1. Drugs used were: single MINO in 2 cases; MINO+imipenemicilastatin (IPM/CS) in 4 cases; MINO+IPM/CS-F-tobramycin in 1 case; MINO+cefmetazole (CMZ) in 1 cases; and MINO+fosfomycin+CMZ (changed to MINO+Amikacin) in 1 case, a total of 9 cases. Clinical result showed remarkable effectiveness of these therapies in 3 cases with some degrees of effectiveness in 6 cases, thus the therapies were all effective or better.
2. No particular abnormality was observed in subjective or objective symptoms or clinical laboratory tests, judged from values obtained before and after administration of MINO.
The above results agreed with well those of the basic assessment, suggesting the possibility that the chemotherapies mainly using MINO would exhibit effectiveness on MRSA infections.

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Asymptomatic bacteriospermia was studied as an entity and its treatment was investigated in 65 subjects who clinically needed their semen tested. The obtained results are summarized as follows.
1. The rate of detection of bacteria in semen was 89.2%, and the rates of detection of aerobic and anaerobic bacteria were 55.4% and 70.8%, respectively. Forty Gram-positive strains were identified among the aerobic bacteria ; rates of detection for Staphylococcus epidermidis and Enterococcus faecalis were high, and 6 strains (9.2%) of Streptococcus agalactiaewere also present. The rate of detection of Gram-negative bacteria was low; only 3 strains were identified. Among the anaerobic bacteria 90 Gram-positive strains were identified; the rate of detection of Peptostreptococcus (58 strains) was high, and only 11 strains of Gram-negative bacteria were present.
2. Among cefaclor (CCL), cephalexin, lomefloxacin, latamoxef and flomoxef (FMOX) FMOX was, in general, superior to the other drugs in terms of antibacterial activities against those strains isolated from semen.
3. Bacterial changes were observed in the semen specimens from 11 subjects who were subjected to oral administration of CCL (1,500 mg/days). After the treatment, 25 strains of bacteria disappeared but 7 strains remained among 32 strains that were present before treatment, and 23 strains appeared due to superinfection.

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Since 1981, in cooperation with research institutions across the nation, IKEMOTOe, t al. have been collecting clinical isolates from patients with respiratory tract infections and conducting an annual retrospective survey of patients' background factors and of isolated strains and their sensitivities to various antibacterial agents and antibiotics.
In the period from October, 1987 to September, 1988, 17 institutions participated in the survey and a total of 706 strains which were demonstrated to be causative organisms were isolated from 562 patients with respiratory tract infections. Strains were mostly isolated from the sputum. The taxonomic breakdown of these strains was: Staphylococcus aureus (69 strains), Streptococcus pneumoniae (120), Haemophilus influenzae (170), Mucoid-producing P.seudomonas aeruginosa (42), Non-mucoid-producing P.aeruginosa (87), Escherichia coli (11), Klebsiella pneumoniae (35), Brahamella catarrharis (72), etc. Of these strains, 629 were used to determine MICs of various antibacterial agents and antibiotics for susceptibility analyses. Relationships between patient backgrounds and diagnoses and between infections diseases and causative organisms were also investigated.
Most of the major causative organisms, such as H. influenzae and P. aeruginosa, showed no substantial changes from previous years, with regard to their sensitivities to antibiotic agent, but S. aureus, particularly methicillin/cephem-resistant strains of S. aureus (MCRSA) showed some what lower sensitivity to β-lactams and, as in recent years, to ofloxacin, a new quinolone drug, as well.
Regarding background factors of patients, the age distribution was heavily concentrated in age brackets of 50 years and older, thus patients in these age group accounted for 75.2% of all the patients, which was comparable to 73.5% in 1985 and 77.9% in 1986. Among infections encountered, bacterial pneumonia was most frequent at 28.3%, followed by chronic bronchitis (27.2%) and bronchiectasis (16.0%). Bacterial pneumonia was actually the most frequent, throughout the entire age groups accounting for 34.3% of patients up to 29 years, 26.6% in the group of 30-69 years and 30.7% in patients aged 70 years and older. Chronic bronchitis was next most frequent and accounted for 20.0%, 26.4% and 30.7% among the three age groups, respectively.
Breaking down clinical isolates by diagnosis, H. influenzae, S. pneumoniae and P. aeruginosa were isolated frequently from most of the infectious diseases. Among 331 strains isolated as causative organisms at during symptomatic periods of infection in bronchiectasis, chronic bronchitis and diffuse panbronchiolitis, H. influenzae, P. aeruginosa and S. pneumoniae were frequent, accounting for 29.6%, 23.9% and 16.6% of all the isolates, respectively. In bacterial pneumonia, S. aureus was frequently detected in addition to the above species. Chronologically, the frequency of H. in fl has been declining year by year, while the frequency of S. pneumoniae has been steadily increasing. Among Gram-negative bacteria, B. catarrhalis is gradually gaining ground thus demanding our attention.
Regarding the bacteria isolated before the first administration of antibacterial agents or antibiotics and the classification of the isolates by the duration of treatment, H. influenzae and S.pneumoniae were most frequent, accounting for 29.8% and 18.6%, respectively, but the incidence of both declined gradually in accordance with the duration of treatment. Conversely, the frequency of P. aeruginosa increased from 15.2% prior to administration to 39.0% on day 15 of treatment.
This retrospective survey will be continued, taking into account new antibacterial and antibiotic agents that will be developed in the years to come.

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Norfloxacin (NFLX, AM-715), a new quinolone antibiotic agent, was evaluated clinically and bacteriologically for its efficacy and safety in pediatrics by a study group organized with pediatricians from all over the country. A summary of the results of the evaluation is as follows.
1. Incidence of NFLX-resistant strains (MIC over 12.5-Eg/ml) isolated from children with various infections was 1.6% (8/512). One resistant strain was observed among 45 isolates of Staphylococcus aureus, and none among 30 isolates of Pseudomonas aeruginosa.
2. After single oral administration of 1.5-2.9, 3.0-4.8 and 5.1-6.1 mg/kg NFLX in tablet form at fasting, mean peak values of serum concentration of 0.37, 0.56, 0.92μg/ml, T 1/2 of 2.5, 2.6, 2.6 hours and urinary recovery rates in 8 hours at 25.3, 25.3, 27.1% were observed, respectively.
3. Clinical effects were studied chiefly in intestinal and urinary tract infections. Among 317 patients from whom pathogens had been isolated, responses to the treatment were excellent in 187, good in 79, fair in 9, poor in 7, and unknown in 35 cases. The overall efficacy rate was 94.3% (266/282) and the efficacy rate for excellent responses was 70.3% (187/266). Among all the 406 patients treated, including those with undetermined pathogens, responses were excellent in 233, good in 106, fair in 11, poor in 11, and unknown in 45 cases. The overall efficacy rate was 93.9% (339/361).
4. Clinica l effects of NFLX classified by diseases with identified pathogens were 81.8% (9/11) for acute pneumonia, 80.8% (21/26) for other respiratory infections, 95.8% (23/24) for bacillary dysentery, 98.6% (70/71) for Campylobacter enteritis, 100% (24/24) for Salmonella enteritis, 100% (6/6) for other acute enteritis and 98.1% (104/106) for urinary tract infections. Including other infections as high as 94.3% (266/282) of efficacy rate was obtained in total. There was no significant difference in NFLX efficacies between unidentified and identified pathogens. Thus, the total clinical efficacy rate was 93.9% (339/361).
5. The total eradication rate of 325 pathogens evaluable was 84.3%, with identical eradication rates for Gram-positive cocci (GPC)(43/51) and for Gram-negative rods (GNR)(231/274).
6. The optimal daily dose of NFLX seemed to be in a range between 6.0 and 12.0 mg/kg, and the optimal duration of treatment to be 7 days for children over 5 years old.
7. The clinical efficacy in treating P. aeruginosa infections in 12 patients w as 100% (11/11) and the eradication rate was 83.3% (10/12).
8. In 59 non-responsive cases to other antimicrobials (treated over 3 days), efficacy rate was 88.9% with 58.3% of the excellent responder rate. Particularly in 13 cases treated with penicillin of cephems the overall efficacy rate was 90.9%, and the eradication rate was 93.6%.
Except 1 strain of Streptococcus pneumoniae in 10 strains of GPC and 2 strains of P. aeruginosa in 37 strains of GNR, all bacteria were eradicated.
9. Adverse reactions were found in 6 (1.5%) cases of 406 patients. The reactions were all mild and could continue the administration of the drug. The joint injuries were not found in all cases nevertheless our careful observation to the joint. Laboratory examinations revealed transient and mild eosinophillia in 8 cases of 309 patients studied. And no changed was observed in serum Cathepsin D, ASPRO-GP, Al-P, urinary mucopolysaccharide titers and electrophoretic isozyme patterns of Al-P which suggest arthropathy, during the course of NFLX therapy.

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