Using methicillin-resistant Staphylococcus aureus(MRSA) and Pseudomonas aeruginosa strains isolated from clinical material from hospitals throughout Japan in 1993, effects of arbekacin (ABK) and ceftazidime (CAZ) were investigated in in vitro culture and an in vivo model, and compared with those of vancomycin (VCM) and CAZ. The following results were obtained:
1) The MIC₈₀ values of ABK against 52 strains each of MRSA and P. aeruginosa were 1.56 and 6.25μg/ml, respectively, and the respective values for VCM were 1.56 and 1, 600μg/ml, and for CAZ were 400 and 50μg/ml.
2) The combined effects of ABK and CAZ were observed on all 11 strains each of MRSA and P. aeruginosa by the checkerboard method. In 20 strains the MIC₈₀ decreased to a level that overlapped the blood concentrations after normal doses.
3) In ABK plus CAZ resulted in a pronounced bactericidal action on combined MRSA and P. aeruginosa cultures that was stronger than either of the agents alone against either bacterial species.
4) Combination of ABK and CAZ against mixed infection by MRSA and P. aeruginosa in mice showed potentiation of bactericidal activity, reflecting the results in vitro. The findings in the present study suggest that combined therapy with ABK and CAZ can be an effective chemotherapeutic approach to control of the mixed MRSA and P. aeruginosa infections with are frequently observed clinically.

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The efficacy and safety of injectable ciprofloxacin (CPFX), a pyridonecarboxylic acid derivative, were investigated in patients with moderate to severe respiratory tract infections and complicated urinary tract infections. Patients received 100 or 200 mg twice a day intravenously for 3 to 14 days in this study. The following results were obtained:
1) Out of the 148 cases enrolled, 126 (63 each from internal medicine and urology) were evaluated for efficacy, 145 (74 from internal medicine and 71 from urology) for safety.
2) The clinical efficacy rate for respiratory tract infections was 59.0%(36/61 cases) in total, being 80.8%(21/26) for pneumonia/lung abscess and 42.9%(15/35) for chronic respiratory tract infections. In poor responders to pretreatment with antibiotics, the clinical efficacy was 60.0%(12/20). The clinical efficacy classified by daily dose was 60.9%(14/23) in the 200 mg dosing group and 57.9%(22/38) in the 400 mg dosing group, respectively. The elimination rate of causative organisms was 62.3%(33/53 strains) in total, in terms of bacteriological efficacy.
3) The overall clinical efficacy for complicated urinary tract infections (according to UTI criteria) was 55.3%(26/47 cases) in total, being 54.5%(18/33) for cystitis and 57.1%(8/14) for pyelonephritis. In poor responders to pretreatment with antibiotics, the clinical efficacy was 60.0%(24/40). Classified by daily dose, the clinical efficacy was 42.9%(9/21) in the 200 mg dosing group and 65.4%(17/26) in the 400 mg dosing group, respectively. The elimination rate of causative organisms was 80.0%(48/60 strains) in total, in terms of bacteriological efficacy.
4) Adverse reactions were noted in 17 cases (11.7%) with 23 events: 7 events of hypersensitivity symptoms, 5 of gastrointestinal symptoms, 4 of neurological symptoms, 5 of vascular pain, etc. None were serious. Abnormal clinical laboratory findings were noted in 16 cases (11.0%) with 23 events: 9 events of elevated liver enzymes, 5 of eosinophilia, etc.
These results suggest that injectable CPFX is useful for treating moderate to severe respiratory tract infections such as pneumonia and complicated urinary tract infections.

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The efficacy and safety of injectable ciprofloxacin (CPFX), a pyridonecarboxylic acid derivative, were investigated in patients with moderate to severe infections in the fields of internal medicine, urology and surgery. Patients received 100 or 200 mg twice a day intravenously for 5 to 14 days in this study. The following results were obtained:
1) Out of the 77 cases enrolled, 70 were evaluated for efficacy and 75 for safety.
2) The clinical efficacy rate was 59.1%(13/22 cases) for respiratory tract infections, 50.0%(12/24) for urinary tract infections and 61.9%(13/21) for infections in the surgery field. In poor responders to preadministered with antibiotics, the clinical efficacy was 50.0%(16/32). The clinical efficacy classified by daily dose was 52.8%(19/36) in the 200 mg dosing group and 66.7%(20/30) in the 400 mg dosing group.
3) The elimination rete of causative organisms was 70.7%(58/82 strains) in total, in terms of bacteriological efficacy, being 56.3%(9/16) for gram-positive bacteria and 74.2%(49/66) for gram-negative bacteria.
4) Adverse reactions were noted in 5 cases (6.7%) with 12 events: 1 case each of heartburn · shock, convulsions · shock, vascular pain · redness · itching · palpitation · chest distress, nausea-headache and chest pain. Abnormal laboratory findings were noted in 13 cases (17.6%) with 27 events: 9 events of elevated liver enzymes, 2 of eosinophilia.
These results suggest that injectable CPFX can be expected to show efficacy in various moderate to severe infections with a daily dose of 400 mg. Considering the 2 shock cases noted as a serious adverse reaction, however, it was concluded that further investigation should be suspended in Japan until international evaluation of injectable CPFX is achieved.

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The clinical efficacy, safety and usefulness of injectable ciprofloxacin for patients with severe and/or refractory infections were evaluated as a phase Ilb study. Patients were intravenously treated with 200 mg b. i. d., t. i. d. or 300 mg b. i. d. for 14 days at the longest. The following results were obtaind.
1. Among the 174 cases infused, 153 were evaluated for clinical efficacy, 163 for safety and 152 for usefulness.
2. In the 153 cases available for the efficacy evaluation, 72.5% were more than 60 years old, 44.9% had far-advanced infectious symptoms and findings, 74.5% had unacceptable underlying diseases and 54.9% were not evaluable due to having recently been treated with other antimicrobial agents.
3. Clinical efficacy was 70.6% in the total of 153 cases, 72.1% in 68 cases with respiratory infections, 86.0% in 50 cases with surgical infections, including 6 cases of bacterial sepsis, and 45.7% in 35 cases with complicated or severe urological infections. Dose dependent efficacy was seen in the group with respiratory infections, that is 66.7% in cases treated with a 400 mg daily dose and 75.6% in the 600 mg group. No dose dependency was recognized in the groups with surgical infections and urological infections.
4. One hundred sixty six strains, including those divided from the cases with polymicrobial infections, were determined as causative pathogens. Most were among the 18 strains of MRSA, 11 strains of Staphylococcus aureus, 18 strains of Enterococcus faecalis, 40 strains of Pseudomonas aeruginosa, 11 strains of other Non-fermentatable gram negative rods (NF-GNR) and 10 strains of anaerobes. The bacterial elimination ratio was 60.8%., the percentages were 50.0% MRSA, 45.5% other S. aureus, 38.9% E. faecalis, 40.0% P.aeruginosa, 72.7% NF-GNR and 80.0% anaerobes. Elimination of other community acquired pathogens, such as Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae and Haemophilus influenzae was 84.2%.
5. Side effects were noted 11 cases (6.6%). Six events of temporary pain at the injection site, 4 of gastrointestinal symptoms, were observed. Temporary cramping was seen in patients with bacterial meningitis. Neither severe side effects nor sequela occurred. Abnormalities in laboratory findings were noted in 17 cases, mostly slight elevation of GOT (9 events) and GPT (9 events). Others included slightly abnormal RBC, Hb, Ht, AL-P, γ-GTP, LDH, TP, BUN and S-Cr. No dose dependency was found between the 400 mg and the 600 mg group. The safety-ability, in terms of “overall safety”, was 82.8% in 163 cases evaluated.
6. From the above findings, the 600 mg daily dose of injectable ciprofloxacin is an acceptable treatment for patients with severe and/or refractory infections in the respiratory and surgical fields.

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Newly developed faropenem (FRPM) was evaluated clinically and pharmacokinetically in pediatrics as follows.
1. Efficacy
The clinical efficacy was determined in 494 cases. The efficacy rate was 91.9%(271/295) in 295 patients from whom the above causal agents were isolated and 93.0%(185/199) in 199 patients without isolation of the agent. The bacteriological eradication rate was 82.5%(250/303 strains). The MICs of FRPM for penicillin resistant Streptococcus pneumoniae (PRSP) were ≤ 0.025 to 0.2μg/ml. In all 10 cases, the clinical efficacy was more than good. The bacteriological eradication rate was 6 out of 8. The clinical efficacy rate for cases which were non-responsive to previous chemotherapy was 89.3%(50/56).
2. Safety
Side effects were observed in 6.6%(36/548) of the evaluated cases for safety. These were diarrhea, loose stool, gluteal candidiasis, urticaria and rash. There were abnormal laboratory findings in 37 cases including elevation of eosinophile, GPT, GOT, γ-GTP. None of the side effects or abnormal laboratory findings were serious.
3. Palatability of the drug
The palatability of the drug was quite good. It was evaluated as more than moderate by 99.3%(555/559) of the patients. From the above results FRPM is considered to be quite useful in pediatric infections including PRSP infections.

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To supply up-to-date information on effective chemotherapeutics for bacterial infections, we have been periodically determining the drug sensitivity of the clinically isolated bacteria. The organisms examined in this study were collected in our hospital in December, 1995. Distribution of the minimal inhibitory concentrations (MIC) of 19 antibacterial drugs against strains of 8 species isolated at a relatively high frequency was determined. Staphylococcus aureus strains were divided into two groups, methicillin-resistant strains (MRSA) and methicillin-sensitive strains (MSSA) for the analysis. Efficacy of the drugs was determined by MIC₅₀, MIC₉₀ and the breaking points of the drugs were calculated. To confirm the types, serotyping of Pseudomonas aeruginosa strains and coagulase typing of S. aureus strains were also carried out. All data obtained were compared with the data for the previous year. Increased incidence of imipenem/cilastatin (IPM/CS)-resistant strains was found in all species, especially in P. aeruginosa, Serratia and Enterococcus faecalis. Efficacy of all other drugs was more or less the same or slightly higher than in the previous year. Tobramycin (TOB) was found to be the drug of first choice for P. aeruginosa infections during this period, vancomycin (VCM) and arbekacin (ABK) were the first choice for MRSA;, minocycline (MINO), clarithromycin (CAM) and ofloxacin (OFLX) for MSSA; latamoxef (LMOX) and OFLX for Escherichia coli;, LMOX and OFLX for Klebsiella; IPM/CS and OFLX for Enterobacter; gentamicin (GM) for Serratia; ABPC, LMOX and OFLX for Proteus; and ABPC for Enterococcus.

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