Drug efflux systems produce multidrug resistance by exporting antibiotics from the cells. It is well established that drug efflux systems encoded by bacteria can confer clinically relevant resistance to antibiotics. Genomic analysis has resulted in the identification of many genes proposed to code for drug efflux systems. Bacterial genome sequences have allowed us to identify the drug-resistance gene libraries of bacteria. On the other hand, recent discoveries support the notion that at least some drug efflux systems have specific physiological substrates, because these efflux systems have been shown to have roles in bacterial virulence. Because drug efflux systems have roles in bacterial multidrug resistance and virulence, we propose that these systems have greater clinical relevance than is usually attributed to them.

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We compared the efficacy and safety of cefteram pivoxil (CFTM-PI) fine granules at the maximum approved dosager and the frequency of adverse events comparied to a group of other oral cephems (CE group). Among children under 15 years of age who visited designated medical facilities from September 2005 to March 2006 and were diagnosed with laryngeal pharyngitis, tonsillitis, acute bronchitis, or pneumonia, 259 in the CFTM-PI fine granules group (median age: 4.2 years) and 108 in the CE group (45 administered cefcapene pivoxil, 49 cefditoren pivoxil, and 14 other agents)(median age: 3.5 years). CFTM-PI fine granules were administered at 18 mg/kg/day in 3 divided doses for, in principle, 5 days (or 7 days for pneumonia), and efficacy was evaluated by day 5 or day 7 for pneumonia. For the CE group, although the duration of administration was not predetermined, dosage was determined based on the approved dosage and dosage regimen. Adverse events were assessed at the end of administration.
Duration of administration of CFTM-PI fine granules was 5.96±1.76 days and CE groups 6.27±1.94 days. In the CFTM-PI granules group, 223 cases were subjected to efficacy analysis; clinical efficacy was evaluated after 4.21±1.18 days, resulting in efficacy of 962%(128/133) for pharyngitis, 97.4%(38/39) for acute bronchitis, 97.4%(37/38) for tonsillitis, 97.4%(37/38) for tonsillstis, 100%(13/13) for pneumonia, and 96.9%(216/223) overall. Clinical efficacy for each major detected bacterium was 100%(28/28) for Streptococcus pneumoniae, 98.8%(85/86) for Streptococcus pyogenes, 95.0%(57/60) for Haemophilus influenzae, and 100%(24/24) for Moraxella (Branhamella) catarrhalis. Out of 28 strains of S. pneumoniae, 6 of PISP and 7 of PRSP were found, whereas 9 of BLNAR were found among 60 strains of H. influenzae. Organoleptic evaluation showed that 70.7%(183/259) of patients felt the drug was “easy to take”. Adverse events observed in all cases gastrointestinal symptoms and the incidence in CFTM-PI fine granules group was 5.4%(14/259) and in CE group 13.0%(14/108). For children under 3 years of age, the incidence of adverse reactions was 262% in the CE group and 9.4% in the CFTM-PI fine granules group, the latter being significantly lower than that in the CE group (p=0.0129).
These findings suggest that a high dosage of CFTM-PI fine granules produces a sufficient therapeutic effect in children with respiratory tract infections and can be expected to be effective for treating infectious diseases caused by resistant bacteria.

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The multiple-dose pazufloxacin mesilate (PZFX) pharmacokinetics have not been reported in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). We intravenously administered a 300 mg dose of PZFX after each HD session in four ESRD patients who required treatment for renal cyst infection, drawing plasma samples to evaluate pharmacokinetic profiles. Cmax after the first dose was 10.47±2.19μg/mL (mean±SD) and AUC (from zero to infinity) was 421±175μg·h/mL PZFX elimination from plasma was markedly delayed compared to that insubjects with normal renal function. After the third dose, the plasma concentration at 2 hours after completing infusion was 11.12±2.30μg/mL, lower than expected despite impaired total body clearance. Plasma PZFX concentration was markedly decreased by HD and the degrees of removal was calculated at 58.7±7.7% from before HD to just after HD and 45.2±5.9% to 1 hour after completion of HD. Adverse events related to plasma concentration were not reported during treatment. Efficient PZFX removal by regular HD helps to keep excessive plasma concentrations from accumulating and confirms the rationale for administering PZFX after each HD session.

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We analyzed the concentration of pazufloxacin mesilate (PZFX) in the blood and evaluated its clinical effects. In seven patients (mean age: 71 years) with community-acquired pneumonia admitted and treated with PZFX. They experienced a total of eight episodes and their mean creatinine clearance was estimated at 64.7±35.4 mL/min.
An intravenous drip-infusion of 500 mg of PZFX alone during a period of 30 minutes was administered every 12 hours. Blood sampling for therapeutic drug monitoring were conducted on treatment day 3. On day 3 of PZFX administration, data on fever, symptoms, and white blood cell count were obtained to evaluate clinical effects.
Assessment of the eight episodes showed T1/2β to be 2.87±1.02 hr, Cmax 30.39±12.18μg/mL, and AUC 67.89±27.87 hr·μg/mL. PZFX treatment was clinically effective in seven episodes (87.5%). Fever disappeared in less than three days in four cases and less than five days in three cases.
Cmax and AUC in this study were 1.7 to 3.1 times greater than reported in the phase I clinical study and studies conducted on the elderly.
Statistical data is thus required reflecting individual disposition to appropriately use an antimicrobial with due consideration for its pharmacokinetics/pharmacodynamics because the disposition of an antimicrobial containing PZFX differs with the patient.

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Patients with malignant tumors may develop cerebral nerve disorders due to the invasion of tumor cells, infection, and side effects of medication. We report 2 cases in which peripheral facial paralysis developed after completion of chemotherapy for malignant lymphoma. The histological type in both of the 2 cases was diffuse large B cell lymphoma, and the clinical stage was IA. One patient underwent R- CHO (rituximab, cyclophosphamide, and adriamycin) and the other R-CHOP (rituximab, cyclophosphamide, adriamycin, and prednisolone), respectively. Both developed facial paralysis on the right side, one 66 days and the other 31 days after chemotherapy was completed. Although the symptom disappeared after dexamethasone administration of in one patient, drooping mouth on the right side remained in the other despite administration of valacyclovir hydrochloride and prednisolone. The major cause of peripheral facial paralysis was herpes simplex zoster virus (HSV), and concomitant therapy with adrenocortical steroid and antiviral drug is considered effective. When paralysis develops after chemotherapy with an anticancer drug, it is necessary to keep tumor cells from invading the central nervous system, to check for infection caused by HSV, and to start treatment as early as possible because the time from the paralysis development to the start of treatment may adversely affect prognosis.

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We report a case in which teicoplanin (TEIC) was administered to a man aged 79 years who had infectious endocarditis caused by Corynebacterium jeikeium 100 days after aortic valve replacement after drug sensitivity was verified. The blood trough concentration was measured and analyzed with TEIC analysis software and the administered dose adjusted as needed. Although loading was done 3 times at the beginning, reloading was necessary on 4 days after drug was administered because drug concentration in blood takes time. The trough reached the target value of 17μg/mL, but CRP was elevated and fever developed. Reloading was repeated changing the target, leading to a final adjustment of 23-24 μg/mL. Vegitation disappeared after 6 months of administration, and no adverse events were seen. Compared to cases of autologous infection, those with infective endocarditis after prosthetic valve replacement often result in a poor prognosis, this case was an example in which TEIC was administrated effectively with TDM.

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