A new colorimetric bioassay of an aminoglycoside antibiotic, netilmicin (NTL), was investigated. Discoloration of the color-indicator on the paper disc (indicator disc) is due to the presence of CO₂ produced by Bacillus subtilis. Discoloration of the indicator disc by CO₂ was studied as follows: A mixture of B. subtilis suspension, nutrient broth, 0.1 M phosphate buffer (pH 8.0) and NTL solution was transfered to a 5 ml Reacti-Vial^®. An indicator disc containing thymolphthalein (TP), methyl red (MR) and NaOH was attached to the inside of the Reacti-Vial septum. The vials were then placed in a shaking water-bath (37±1°C) for 3 h. The blue indicator disc was discolored, the degree of discoloration depending on the growth of B. subtilis in the medium. When the concentration of NTL was high and the level of CO₂ low, no change was observed. The color of the indicator disc was determined spectrophtometically after 3 h of incubation, using complementary tristimulus colorimetry, which is useful in determining pH-dependent chemical species like TP and MR. Our proposed method was found to save more than 13 h of working time when compared with the conventional bioassay method, so it is a useful and convenient method for determining NTL.

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The penetration of ofloxacin (OFLX), sparfloxacin (SPFX), fleroxacin (FLRX), tosufloxacin (TFLX) and temafloxacin (TMFX) into human cerebrospinal fluid (CSF) was examined. OFLX, SPFX and FLRX (200mg), and TFLX and TMFX (150mg) were given to urological patients who required endourological surgery and examination under spinal anesthesia.
1) CSF/serum ratios were SPFX·FLRX>OFLX·TMFX> TFLX.
2) FLRX and TMFX remained in human cerebrospinal fluid 12-24 h after oral administration.
3) We suggest that central nerve system side effects might partially dependend upon drug penetration and concentration in human cerebrospinal fluid.

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To investigate the clinical safety of S-1108, which contains pivalic acid, we measured both free carnitine, total carnitine and pivaloylcarnitine in plasma and urine, and the acyl/free carnitine ratio in the plasma of pediatric patients (4-17 yrs) with pneumonia, bronchitis, and tonsillitis. The results are as follows:
1. Mean free and Total carnitine concentrations in the plasma of pediatric patients (n=120; male, 63; female, 57) untreated with S-1108 were 42.8±9.5 and 54.5±11.8 nmol/ml, respectively.
2. After the 4 to 12 days of treatment with daily dose of 6-18 mg/kg/day, free carnitine concentrations were reduced in all cases. The degree of free carnitine reduction depended on the dose and duration of S-1108 treatment. Free carnitine levels, however, showed a tendency to increase after the cessation of administration, and returned to normal within 3-4 days to about 7 days, at the lower and higher doses, respectively. Free carnitine concentrations in plasma were moderately reduced by 20% of pretreatment values at the highest doses, 16-18 mg/kg/day, however, there seemed to be full reversibility of carnitine status within a few days after cessation of treatment.
3. The acyl/free carnitine ratio, a parameter of secondary carnitine deficiency, was less than 0.5 in almost all cases during treatment, and there was no change in the ratio before, during and after S-1108 treatment.
4. No symptoms or adverse effects associated with carnitine deficiency were observed in any of the patients.
Regarding carnitine status, S-1108 was demonstrated to be safe and well tolerated when administered at the recommended dosage schedule.

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The efficacy and safety of carumonam and G-CSF were compared with those of historical controls for prophylaxis against bacterial infection in neutropenic children with malignancy. All patients were administered antibiotics by nebuliser (amphotericin B and tobramycin) and orally (amphotericin B or fluconazole and sulfamethoxazole/trimethoprim). The incidence of febrile episodes (body temperature higher than 38°C) was significantly lower in group C patients (both carumonam- and G-CSF-treated, 32%, 1.0±1.9 days) than in group A patients (neither carumonam- nor G-CSFtreated, 82%, 5.2±3.5 days) and group B patients (only G-CSF-treated, 78%, 2.9±1.9 days). Although the duration of neutropenia (neutrophil count lower than 250/μl) was shortest in group B, there was no difference in the minimum neutrophil count in these three groups. Fewer carumonam-treated patients (group C) experienced microbiologically documented infections compared with patients treated without carumonam (groups A and B). There were no serious adverse reactions associated with Carumonam that required discontinuation of the medication. These results suggest that carumonam is both safe and effective in preventing serious bacterial infection in neutropenic patients.

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Imipenem/cilastatin sodium (IPM/CS), a newly developed carbapenem antibiotic, was administered to a total of 72 patients with hematologic disease complicated by infection. The underlying diseases included acute leukemia (33/66), malignant lymphoma (11/66) and myelodysplastic syndrome (11/66), and most patients were suffering from sepsis or suspected sepsis (45/66). Out of 66 patients in whom efficacy could be evaluated using the criteria for estimation of the clinical effect of antimicrobial drugs in treatment of infectious diseases associated with granulocytopenia by Takaku et al.(1984), responses were excellent in 29 patients, good in 13, fair in 10, and poor in 14. The overall clinical efficacy rate was 64%(42/66). Patients whose peripheral neutrophil counts were <100/μl and who were continued on IPM/CS therapy also had significant effects on their clinical response. The overall eradication rate of bacteria was 83%. Side effects were observed in 6 cases, and consisted of transient laboratory liver function test abnormalities (5 cases) and a renal function test abnormalities (1 case). Among 17 patients in whom (1→3)-β-D-glucan and CAND-TEC titers were measured, before and 7 days after IPM/CS medication, one episode showed both (1→3)-β-Dglucan and CAND-TEC titers to be markedly increased, suggesting fungal superinfection. Longterm medication with IPM/CS may cause fungal infection. Further examination is necessary to clarify this point. From the above findings, IPM/CS is considered to be a useful antibiotic for the treatment of bacterial infection accompanying hematologic diseases with neutropenia.

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