We evaluated in vitro and in vivo anti-Legionella pneumophila activity of tosufloxacin (TFLX). The MIC range of TFLX was 0.002-0.0078μg mL and its MIC₅₀ and MIC₉₀0.0039μg mL. The MIC₉₀ of TFLX against clinical isolates of L. pneumophila was 16-fold higher than that of rifampicin (RFP), equal to that of sparfloxacin, gatifloxacin and clarithromycin, and 14-to 164-fold lower than those of levofloxacin, ciprofloxacin, moxifloxacin, azithromycin (AZM) and erythromycin. TFLX showed clear bactericidal activity against L. pneumophila ATCC 33152 in macrophages from guinea pigs at a concentration of 16 times MIC, but RFP and AZM did not exhibited bactericidal activity even at 64 times MIC. The doses of 1.25mg kg and 2.5mg kg of TFLX completely protected guinea pigs from death due to pneumonia caused by L. pneumophila. The 80% and 20% of animals treated with 1.25mg and 2.5mg kg of AZM, and the 20% of animals treated with 1.25mg kg of RFP died. Viable cell counts in lungs after TFLX treatment were significantly fewer than in non treated control. The area under the curve of the concentration in lungs for TFLX was equal to that for RFP and smaller than that for AZM.

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Vancomycin-resistant enterococci (VRE) are considered to be major causative bacteria of severe nosocomial infections resistant to antimicrobial agents, and the increase in VRE infections is a great concern in us social welfare. Although fewer hospital-acquired VRE infections are detected in Europe than that in the USA, the existence of vanA group genes in the veterinary field is considered a potential infection source. In Japan, VRE were isolated for the first time in Tokyo and Kyoto, therefore increase of VRE were uneasiness. However, only a few VRE were isolated from clinical materials in institutions. In our recent investigation on VRE incidence in northern Kyushu, 10 strains of VRE including two Enterococcus faecalis vanA, 3 E. faecalis vanB, 4 Enterococcus faecium vanA and 1 E. faecium vanB strain were isolated from patients at 4 institutions. Among antimicrobial agents (vancomycin, teicoplanin, rifampicin, ampicillin, and linezolid) tested for their susceptibility using agar dilution method against 21 vancomycins-weakly susceptible to highly resistant enterococci with either vanA, vanB, vanC-1, or van C-2/3 genotype, including the above 9 VRE strains, minimum inhibitory concentrations (MICs) of LZD against VRE strains were all determined to be ≤2μg/mL categorized as susceptible according to the NCCLS.

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RSV lower respiratory tract illness (RSV-LRI) is often severe in preterm infants and in those with chronic lung disease (CLD), also known as bronchopulmonary dysplasia (BPD). Palivizumab is a humanized monoclonal antibody developed to prevent serious RSV illness in such infants. In this study, palivizumab was given intramuscularly at 15mg/kg every 30 days for up to 2 doses to 31 infants born prematurely at<35 weeks of gestation who were<6 months old or infants with CLD who were<24 months old. Palivizumab serum concentrations were measured (30μg/mL is the effective concentration) and its safety and immunogenicity evaluated. Mean serum concentration 30 days after the first injection was 50.5±17.5μg/mL and 76±17.6μg/mL after the second, respectively. The number of infants with palivizumab serum concentrations exceeding 30μg/mL was 26/31 (83.9%) following the first infusion and 30/31 (96.8%) following the second. Adverse events included the respiratory system in 9 subjects (17 cases), fever in 6 subjects (9 cases), digestive system in 4 subjects (8 cases), and skin in 6 subjects (6 cases). One subject developed diarrhea and dehydration and was hospitalized. Laboratory abnormalities (1 subject each) included protein in urine, increased AST, and increased AST-EALT. None of these adverse events was judged by investigators to be related to palivizumab. One subject reportedly had mild RSV illness (nasal discharge and obstruction) but was not hospitalized. No antipalivizumab antibodies were observed in any subject. Palivizumab appears safe, is not immunogenic, and may inhibit serious RSV LRI in preterm infants and in those with CLD.

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The growing use of outpatient surgery has necessitated antibiotic agents having good tissue penetration after oral administration. We studied the skin penetration of levofloxacin, an oral fluoroquinolones, in surgical patients and conducted a clinical trial on antibiotic prophylaxis for wound infection. Levofloxacin concentrations in serum and skin were measured after single oral administration of 200mg in 15 surgical patients. Serum concentrations ranged from 0.05 to 3.46μg/mL and tissue concentrations ranged from 0.13 to 3.36μg/g between 2h and 3h after administration, confirming that levofloxacin is an effective antibiotic prophylactic for wound infection in outpatient surgery due to its sustained high skin concentration.

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We studied the penetration of pirarubicin (THP) into bladder cancer tissue and its prophylactic effect in 5-day intravesical administration against intravesical recurrence of bladder cancer after transurethral resection (TUR-BT), to clarify its effectiveness and safty.
(1) Penetration of THP into bladder cancer tissue after intravesical administration: Subjects were 32 patients with superficial bladder cancer. THP (30mg) was administered transurethrally 1 hour before TUR in 26 patients and 24 hours before in 6. Bladder cancer tissue and normal bladder mucosa were obtained from each patient by TUR. THP concentrations in bladder cancer tissue and normal bladder mucosa were measured by HPLC and compared. THP concentrations in bladder cancer tissue were significantly higher than in normal mucosa, when THP was administered 1 hour before TUR, but no significant difference was seen in THP concentrations between bladder cancer tissue and normal mucosa when THP was administered 24 hours before TUR.
(2) Prophylactic effect of intravesical administration of THP against intravesical recurrence of bladder cancer after TUR-BT: Subjects were 24 patients with superficial bladder cancer. After TUR-BT, THP (30mg) was administered transurethrally for 5 days. Mean follow-up was 8.8 months (2 to 26 months). Seven of 24 had intravesical recurrence 2 to 8 months postoperatively, so the short-term prophylactic effect was 70.8%. Adverse effects occurred in 11 (45.8%), mostly low-grade vesical irritability without stopping intravesical THP therapy. No general adverse effect such as leukocytepenia and heart damage were seen.
These results indicate that 5-day intravesical THP therapy is safe and effective for prophylaxis against intravesical recurrence of superficial bladder cancer after TUR-BT.

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Mycobacterium avium-intracellulare complex (MAC) has 3 colonial variants-SmT with smooth, transparent, irregularly shaped colonies; SmO with smooth, opaque, dome-shaped colonies; and Rg with rough, granular, irregularly shaped colonies. These colonial variants differ in virulence in experimental animals. We compared the susceptibilities of 3 colonial variants isolated from identical M. intracellulare strain to rifampicin, rifabutin, streptomycin, kanamycin, ethambutol, isoniazid, ofloxacin, ciprofloxacin and cefoxitin, using 7 M. intracellulare strains isolated from patients with MAC pulmonary infection. SmT variants were much more resistant to tested antimicrobial drugs, except for ethambutol and isoniazid, than SmO variants. Rg variant susceptibility patterns to tested drugs proved to lie between SmT and SmO variants, indicating the importance of determining the MAC strain colony form isolated from clinical specimens in determining drug susceptibility.

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