[Three sisters of pulmonary Mycobacterium avium complex disease].

We reported three sisters of pulmonary Mycobacterium avium complex (MAC) disease. The oldest sister was complaining of bloody sputum, and cultures were positive for M. avium. By monotherapy with clarithromycin, symptom and imaging findings had shown no progression for six years. The second sister was complaining of productive cough, and cultures were positive for M. intracellulare. Her symptom and imaging findings had shown no progression for seven years without any treatment. The third sister had rheumatoid arthritis and diabetes mellitus, and cultures were positive for M. intracellulare. Although she received chemotherapy with rifampicin, clarithromycin, ethambutol, and kanamycin, symptom and imaging findings had progressed gradually. She died of respiratory failure four years later. Autopsy findings revealed no disseminated MAC disease. The results which three cases showed different isolate patterns and clinical courses suggest the importance of underlying anti-mycobacterial immunological impairment and defects of local host defense rather than virulence of infected strains as the pathogenesis of pulmonary MAC disease.

[In vitro activity of antimicrobial agents against clinical isolates of Pseudomonas aeruginosa].

Two hundred and seven clinical isolates of Pseudomonas aeruginosa were collected at Tenri Hospital between April 2003 and March 2004. We determined the minimum inhibitory concentration (MIC) of 16 antimicrobial agents, including prulifloxacin, pazufloxacin and biapenem which were recently published in Japan, against these isolates according to the guidelines of the Clinical and Laboratory Standards Institute. For the fluoroquinolones, the rank order of activity was prulifloxacin (MIC50, 0.5 microg/ml)>ciprofloxacin (1 microg/ml)> pazufloxacin (2 microg/ml)=levofloxacin (2 microg/ml)>gatifloxacin (4 microg/ml). For the carbapenems, the rank order of activity was meropenem (MIC50, 1 microg/ml)=biapenem (1 microg/ml)>imipenem (2 microg/m)>panipenem (8 microg/ml). For the cephalosporins and monobactam, the overall rank order of activity was cefozopran (MIC50, 4 microg/ml)= ceftazidime (4 microg/ml)>cefepime (8 microg/ml)=piperacillin/tazobactam (8 microg/ml)>aztreonam (16 microg/ml)= cefoperazone/sulbactam (16 microg/ml)=cefpirome (16 microg/ml). The rates of susceptibility to antimicrobial agents as per the criteria of the Japanese Society of Antimicrobial Chemotherapy were especially high for cefozopran (63%), biapenem and meropenem (61%), and pazufloxacin (53%) and ciprofloxacin (53%). These findings suggest that prulifloxacin, pazufloxacin and biapenem, which are newly introduced, are clinically effective in the treatment of infection caused with P. aeruginosa.

Evaluation of MicroScan ESBL confirmation panel for Enterobacteriaceae-producing, extended-spectrum beta-lactamases isolated in Japan.

We assessed use of the MicroScan ESBL confirmation panel (Dade Behring, Tokyo, Japan) for the detection of eight Enterobacteriaceae-producing extended-spectrum beta-lactamases (ESBL) species. Of 137 bacterial strains isolated from patients in 32 hospitals in the Kinki area of Japan, 91 produced ESBL and comprised 60 bacteria (of E. coli, K. oxytoca, and K. pneumoniae) targeted by the NCCLS ESBL test and 31 non-target bacteria such as chromosomal AmpC-producing bacteria (e.g., Serratia marcescens, Enterobacter spp.). Sensitivity and specificity of the MicroScan panel for the target bacteria were 92% and 93%, respectively; sensitivity and specificity for non-target bacteria were 52% and 100%, respectively. There were 20 ESBL-positive strains that were not inhibited by clavulanic acid in the MicroScan panel (3 of 32 ESBL-producing E. coli strains, 1 of 24 K. pneumoniae, 1 of 4 K. oxytoca, 8 of 13 E. cloacae, and 7 of 14 S. marcescens), and most of them were bacteria not targeted by the NCCLS test. In 19 of the 20 strains, the synergy effect of clavulanic acid was observed in the modified-double-disk synergy test using only the cefepime-disk. Because these strains had high MICs of > or = 16 microg/ml for cephamycins such as cefoxitin and cefmetazole, these strains might produce high levels of AmpC in addition to ESBL. The MicroScan ESBL confirmation panel showed excellent performance in detecting target, but not other bacteria. Addition of cefepime and clavulanic acid to the MicroScan panel may significantly improve detection of non-target bacteria.

[Application of the MIC breakpoints based on pharmacokinetics and pharmacodynamics parameter in the clinical laboratory].

The effectiveness of time-dependent antibiotics such as beta-lactams is related to the time above the MIC (TAM, %). We constructed a program to calculate the TAMs of beta-lactams using the pharmacokinetic parameters of the Japanese dosing regimen of a phase I study of the Japanese Society for Antimicrobial Chemotherapy (JSAC), and compared them with the MIC breakpoints published by the National Committee for Clinical Laboratory Standards (NCCLS) and JSAC. If the effective TAM was assumed to be more than 40% of the dosing interval, the pharmacokinetic/pharmacodynamic (PK/PD) breakpoints calculated by our program were in agreement with the JSAC breakpoints for pneumonia within 1 dilution MIC. When comparing with the NCCLS breakpoints for Enterobacteriaceae or Staphylococcus, the PK/PD breakpoints dosing three times per day of ampicillin (1 g, intravenous dose; i.v.), piperacillin (2 g, i.v.), cefotaxime (1 g, i.v.) and cefmetazole (1 g, i.v.) were calculated to be less than 2-fold dilution MIC, and those of amoxicillin (0.25 g, oral dose; p.o.) and cefaclor (0.5 g, p.o.) were calculated to be less than 3- to 4-fold dilution of MIC. Our program could calculate TAMs and PK/PD breakpoints by inputting the two factors of MIC and dosing interval. If this information is routinely reported to physicians from clinical laboratories, an appropriate dosing schedule could be proposed for various infectious cases.

[In vitro activity of a new semisynthetic echinocandin, micafungin, against clinical isolates of Candida species isolated in Tenri Hospital].

We have examined the antifungal activities of the available antifungal agents including micafungin (MCFG), one of the echinocandin antifungal group, against 92 yeast-like fungi isolated at our hospital during a 3-month period from November 2002 to February 2003. Determination of the antifungal susceptibility was conducted in conformity with the Standards of the Japanese Society for Medical Mycology. The MIC 80% of the antifungal agents against 4 fungi species including C. albicans (55 strains), C. tropicalis (20 strains), C. glabrata (8 strains), C. krusei (5 strains) were as follows; MCFG: 0.03-0.125 microgram/ml, amphotericin-B: 0.125-0.25 microgram/ml, 5-fluorocytosine: 0.125-16 micrograms/ml, itraconazole: 0.25-2 micrograms/ml, fluconazole: 0.5-32 micrograms/ml. The isolation rate of the drug-resistant fungi was 20% for the fluconazole (FLCZ)-resistant C. tropicalis and 33% when including the susceptible dose dependent (S-DD) class. The rate was 5% for FLCZ-resistant strains of C. albicans and 11% when including the S-DD class. However, MCFG was shown to have an excellent antifungal activity against those azole-resistant strains of Candida species. An analysis of the randomly amplified polymorphic DNA pattern (RAPD) was carried out to assess the fingerprinting of the azole-resistant strains. The results demonstrated a common pattern in 3 of the 6 strains of C. tropicalis that showed MIC of > or = 16 micrograms/ml for fluconazole, while all of the 6 strains of C. albicans demonstrated their respective patterns.