Clinical Study on Concentrations of Lomefloxacin in Pleural Fluid

A single dose of lomefloxacin, a new oral antibacterial agent with excellent antibacterial potency and spectrum and safety profile, was administered at 200 mg, the recommended dose, to 6 patients with accumulated pleural fluid in order to determine drug concentrations in the pleural fluid over time after treatment. Lomefloxacin appeared in the pleural fluid 1 hr after oral treatment in some cases. The mean concentration increased gradually from 0.49 μg/ml 2 hrs after treatment to 0.81, 1.00 and 1.16 μg/ml, respectively, 3, 4 and 6 hrs after treatment. A concentration of 0.45 μg/ml was still present 24 hrs after treatment. The AUC determined up to 24 hrs after treatment was 18.51 μg hr/ml. Concentrations reached in the pleural fluid 2 hrs after treatment, in particular those reached 3 hrs after treatment, were higher than MICs of lomefloxacin for most bacteria against which the drug has been found to be effective, and concentrations remained above MICs over a long period of time. In addition, concentrations in the pleural fluid obtained in different patients showed very little variability, although the drug was orally administered. This finding suggests that the drug\u27s absorption from the intestine and the passage through the pleura are very stable. Therefore, lomefloxacin seems to be a drug of choice for use in studies on passage of drues through various barriers

Effectiveness of Fluconazole for Pulmonary Aspergilloma and Its Concentration in Lung Tissue

Fluconazole was administered to two male patients aged 41 and 70 years with pulmonary aspergilloma, the diagnosis of which was based on "fungus balls" on chest X-ray films, isolation of Aspergillus from the sputum and positive serum precipitation antibody against Aspergillus. The patients received a 100 to 200 mg oral daily dose of fluconazole for six months. The fungus balls shrank and disappeared and Aspergillus culture and the serum antibody became negative. No recurrence has been observed during the two years since the end of treatment. To determine the mechanism by which fluconazole was effective in the treatment of pulmonary aspergilloma, drug levels in the blood and normal and affected lung tissues were determined in 14 patients who received surgery for lung resection. The patients generally received a 200 mg oral daily dose of fluconazole for four days prior to the surgery, during which samples of blood and healthy and affected lung tissues were collected for the determination of fluconazole levels by HPLC. The average fluconazole concentration was 8.2 μ/ml in the blood (14 patients), 9.4 μg/g in healthy lung tissue (10 patients) and 7.7 μg/g in lung lesions (12 patients). Although the results suggested that the drug was well distributed into the blood and lung tissue when administered at an oral dose of 200 mg, the drug levels obtained were found to be far below the growth inhibitory level of fluconazole against Aspergillus. Therefore, it may be essential for the future development of antifungal agents and for a better understanding of the pharmacological action of fluconazole to evaluate the mechanism by which the drug exerts its therapeutic effect on aspergilloma at below its growth inhibitory level

Assessment of the Period for Administration of Antibiotics for Primary Atypical Pneumonia

We assessed adequate period for administration of antibiotics for primary atypical pneumonia (PAP). The subjects were patients with PAP admitted to our hospital from January, 1986 to December, 1988. For treatment, 100 mg of minocycline (MINO) was dissolved into 100 ml of solution and infused intravenously for 1 hour twice a day. The patients were divided into two treatment periods: a 6 day-administration group (Group A), and a 9 day-administration group (Group B). Group A: 23 cases (which included 8 cases of mycoplasmal pneumonia) and Group B: 22 cases (which included 10 cases of mycoplasmal pneumonia). A comparative assessment was made between Groups A and B regarding body temperature, WBC, erythrocyte sedimentation rate, CRP and chest X-ray on the 3rd, 6th and 9th days of treatment but no significant difference was observed. Residual shadows at the discontinuance of treatment were present in 61% of Group A and in 36% of Group B but they disappeared gradually in both groups. No recurrent cases were observed in either Group A or B within 1 month after treatment was finished. As for the PAP treatment period using an intravenous drip infusion of minocycline, no significant clinical difference was observed between administration for 6 and 9 days, suggesting that the 6 days administration suffices for treatment. Even though the possible bacterial residue was unknown as no separation of mycoplasma pneumoniae was attempted, there were no recurrent cases

Serum Concentration of Flomoxef in Administration of One Hour Infusion Every Eight Hours a Day

Flomoxef (FMOX) is a new, parenteral oxacephem antibiotic with strong, broad-spectrum antimicrobial activity. To compensate for short half time of this drug, multi-divided administration of the drug was attempted, and the concentrations of FMOX in the blood were determined. The treatment by dripping intravenous infusion of FMOX thrice daily or one hour infusion every eight hours were carried out in six patients with an indwelling intravenous catheter. Four patients had pneumonia and the other two suffered from respiratory infections with lung cancer. With the patient\u27s permission, six blood samples were drawn from each patient just before and after infusions, and the concentration of FMOX was determined by bioassay. The mean serum concentration in the six patients ranged between three troughs just before infusion and three peaks just after infusion, being 1.40 μg/ml, 2.59 μg/ml and 1.84 μg/ml, and 47.32 μg/ml, 52.17 μg/ml and 50 μg/ml, respectively. These concentrations, even troughs, were higher than the MIC90 of almost all bacteria considered to be sensitive to FMOX. In fact, five out of six patients showed a good response to this treatment. No side effects were observed, except mild and transient elevation of transaminase in one case. In conclusion, we recommend the administration of FMOX thrice daily for patients with severe pulmonary infections, especially from the standpoint of its blood concentration