Antifungal activity of micafungin against Candida and Aspergillus spp. isolated from pediatric patients in Japan.

The in vitro antifungal activities of micafungin in comparison to caspofungin, fluconazole, itraconazole, voriconazole, and amphotericin B were evaluated against 93 Candida and 23 Aspergillus isolates recovered from pediatric patients with fungal infections. MICs were determined by the CLSI M27-A2 and M38-A for Candida and Aspergillus species, respectively. Micafungin showed potent activity against Candida albicans, Candida tropicalis, and Candida glabrata with a MIC range of <= 0.002 to 0.015mug/ml. In contrast, micafungin demonstrated higher MIC levels against Candida parapsilosis with a MIC range of 0.12 to 2 mug/ml. Micafungin showed potent antifungal activity against Aspergillus species tested with a MIC range of 0.004 to 0.015 mug/ml. Overall, micafungin had excellent in vitro antifungal activities against Candida and Aspergillus species recovered from pediatric patients with fungal infections.

[In-vitro activity of panipenem against clinical isolates in 2006].

The antimicrobial activity of various antibiotics against clinical bacterial isolates recovered from patients with infectious diseases at the medical facilities in the Kanto region between March and September 2006 was evaluated. A total of 1030 clinical isolates were available for susceptibility tests: 420 aerobic Gram-positive organisms, 520 aerobic Gram-negative organisms, 30 anaerobic Gram-positive organisms and 60 anaerobic Gram-negative pathogens. Antimicrobial susceptibility data for Streptococcus pneumoniae and Haemophilus influenzae isolates from pediatric and adult patients were analyzed separately. Panipenem (PAPM), imipenem (IPM), meropenem (MEPM), biapenem (BIPM), doripenem (DRPM), cefozopran (CZOP), cefepime (CFPM), and sulbactam/cefoperazone (SBT/CPZ) were used as test antibiotics. PAPM, IPM and DRPM exhibited excellent in vitro antibacterial activities against methicillin-susceptible Staphylococcus, with all isolates exhibiting a MIC of < or =0.06 microg/mL. Against Streptococcus including penicillin-resistant S. pneumoniae, PAPM demonstrated the strongest antibacterial activity among the carbapenems with a MIC range of < or =0.06 to 0.12 microg/mL. Against Enterobacteriaceae, MEPM showed the strongest antibacterial activity, and PAPM had comparable activity to IPM. Against the extended-spectrum beta-lactamase producing Escherichia coli, Klebsiella species and Proteus species, the MICs for the cephems were high, however, those for the carbepenems were low. Against H. influenzae, PAPM had comparable activity to IPM. With respect to anaerobes, each of the carbapenems tested demonstrated almost the same strong antibacterial activity. In conclusion, 13 years has passed since PAPM was launched in 1993, PAPM still maintains potent antibacterial activity and is considered an effective antimicrobial agent for various types of infectious diseases.

In vitro antimicrobial activity of telavancin against methicillin-resistant Staphylococcus aureus clinical isolates from Japan (2006).

In vitro antimicrobial activity of telavancin, a rapidly bactericidal lipoglycopeptide, was evaluated against 1500 strains of MRSA recently isolated in Japan. Telavancin had potent activity, with MIC values that ranged from 0.12 microg/ml to 0.5 microg/ml and a MIC90 value of 0.5 microg/ml. The MIC90s of vancomycin and linezolid were 1.0microg/ml and 2 microg/ml, respectively. No vancomycin intermediate resistant or vancomycin-resistant MRSAs were detected in this surveillance study.

[Antibacterial activity of tosufloxacin against major organisms detected from patients with respiratory infections].

We determined the susceptibility of bacteria which were isolated from the patients with respiratory infections between January and October 2005, to tosufloxacin and other fluoroquinolones. A total of 900 isolate including 300 Streptococcus pneumoniae, 100 Streptococcus pyogenes, 100 Moraxella catarrhalis, 200 Haemophilus influenzae, 100 Klebsiella pneumoniae and 100 Pseudomonas aeruginosa were tested. Tosufloxacin, gatifloxacin, levofloxacin, moxifloxacin, ciprofloxacin and prulifloxacin were used as the test antimicrobials. Tosufloxacin, gatifloxacin and moxifloxacin were potent antibiotics tested for the antibacterial activity against Streptococcus including penicillin-resistant S. pneumoniae; the MIC90 were 0.12-0.5/ micromL. Fluoroquinolones exerted the potent antibacterial activity against M. catarrhalis and H. influenzae; the MIC90 of fluoroquinolones tested were < or =0.06 microg/mL. Tosufloxacin, ciprofloxacin and prulifloxacin showed to be more active against K. pneumoniae and P. aeruginosa, but parts of some strains were resistant. These results indicate that tosufloxacin has the potent antibacterial activity against major organisms detected from patients with respiratory infections. Since it was approved in 1990, tosufloxacin was considered to be useful as a therapeutic antimicrobial for the treatment of respiratory infections.

[Antibacterial activity of nadifloxacin against Staphylococcus and Propionibacterium isolated from patients with dermatological infections].

Nadifloxacin (NDFX) is a fluoroquinolone antibiotic developed by Otsuka Pharmaceutical Co., Ltd. and is used as a topical drug for the treatment of infections in the field of dermatology. We investigated the susceptibility of a total of 575 strains (two kinds of Staphylococcus species and Propionibacterium species which were isolated from patients with dermatological infections for 3 periods, i.e., 1996, 2000 and 2005) to NDFX and other reference antibiotics. The minimum inhibitory concentration of the four antibiotics, NDFX, levofloxacin (LVFX), clindamycin (CLDM) and gentamicin (GM), against the test strains were determined by the agar dilution methods, in according with the Japan Society of Chemotherapy. The antibacterial activity of NDFX against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis and P. acnes was the most potent of all the antibiotics tested, and there were no test organisms which became resistant to NDFX with period. The MIC90 values of NDFX for the four test organisms isolated in 2005 were 0.05 microg/mL; MSSA, 1.56 microg/mL; MRSA, 0.78 microg/mL; S. epidermidis and 0.20 microg/mL; P. acnes, respectively. On the other hand, there were LVFX-, CLDM- and GM-resistant MRSA. The MIC50 values of CLDM and GM for MRSA were >100 and 25 microg/mL, respectively. The MIC50 value of GM for P acnes was 12.5 microg/mL, but NDFX was potently active against these organisms as compared with these two antibiotics and the MIC50 values of NDFX were 0.05 microg/mL for MRSA and 0.20 microg/mL for P. acnes. These results suggest that NDFX is even at present useful as an antibiotic for the treatment of infections in the field of dermatology though it is more than 12 years since the approval to manufacture and sell the drug was obtained in 1993.

Antibacterial activity of tosufloxacin against major organisms detected from patients with respiratory or otorhinological infections: comparison with the results obtained from organisms isolated about 10 years ago.

The minimum inhibitory concentrations (MICs) of tosufloxacin and other fluoroquinolone antimicrobials for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis, isolated, between January 2003 and July 2004, from patients suspected of having respiratory or otorhinological infections were determined. The results were compared with those for these organisms isolated in 1994, plus some H. influenzae strains isolated in 1998. Tosufloxacin was the most potent of all the antibiotics tested for antibacterial activity against S. pneumoniae (including penicillin-intermediate S. pneumoniae and penicillin-resistant S. pneumoniae). The MIC50 and MIC90 values did not differ from those obtained for the strains isolated in 1994. Fluoroquinolones exerted the most potent antibacterial activity against M. (B.) catarrhalis; the MICs for most of the strains were < or = 0.06 microg/ml; fluoroquinolones inhibited the growth of all the strains at 0.25 microg/ml or less. Fluoroquinolones showed the most potent antibacterial activity against H. influenzae strains isolated between 2003 and 2004, and in 1994, but, for one H. influenzae strain isolated, between 2003 and 2004, the MICs of fluoroquinolones were high. Some strains of S. pneumoniae and H. influenzae were resistant to fluoroquinolones. Genetic analysis showed that all of these strains had mutations in the quinolone resistance-determining region, but there were no differences according to the years of isolation. These results indicate that tosufloxacin has potent antibacterial activity against major organisms isolated from patients with respiratory or otorhinological infections; further, the results of the present study did not differ from those obtained about 10 years ago.

[Antibacterial activity of ceftriaxone against various clinical strains isolated in 2004].

The susceptibility of clinical strains isolated from patients with infection to ceftriaxone (CTRX) and injectable beta-lactam antibiotics was determined in Japanese medical institutions in 2004. The in vitro antibacterial activity of the above antibiotics against clinical strains isolated in 2004 was compared with that against part of the clinical strains isolated about ten years ago (1994 - 1996). The antibacterial activity of CTRX against Streptococcus including penicillin-intermediate and penicillin-resistant Streptocuccus pneumoniae was potent and there were no large differences between clinical strains isolated in 1994 - 1996 and those in 2004 in the antibacterial activity of CTRX. CTRX inhibited the growth of all the strains of Haemophilus influenzae including beta-lactamase-negative, ampicillin-resistant (BLNAR) strains at 0.5 microg/mL or less and showed the potent antibacterial activity against these strains. In addition, since there are no large differences between strains isolated in the past and those isolated in 2004 in the antibacterial activity, CTRX is considered to be a useful antibiotic in the treatment of BLNAR infections which are increased by the causative organism of infections especially in the field of pediatrics in recent years. CTRX showed the excellent antibacterial activity against Escherichia coli and Klebsiella pneumoniae but one of the 50 strains of E. coli tested was highly resistant. The antibacterial activity of CTRX against Neisseria gonorrhoeae was the most potent in all the antibiotics tested. These results indicate that CTRX shows excellent antimicrobial activity against fresh strains isolated from patients with infections. CTRX is thus useful as a therapeutic antimicrobial for the treating a variety of infections.

[Antimicrobial susceptibility surveillance of recent isolates from ophthalmological infections to gatifloxacin and other antimicrobial drugs].

The antimicrobial susceptibility of 240 isolates from the ophthalmological infections during July 2003 to March 2004 was determined to gatifloxacin (GFLX), levofloxacin, lomefloxacin and cefmenoxime applicable for ophthalmological infections. The in vitro activities of these drugs against the fresh isolates were compared. The quinolones including GFLX were potently active against Gram-positive bacteria, except for MRSA, a major causative pathogens for ophthalmological infection. When MIC ranges, MIC50 and MIC90 of three quinolones were compared, it was considered that the activity of GFLX was the most active of them. GFLX showed to be more active against opportunistic pathogens including Pseudomonas aeruginosa than other antimicrobial agents, and GFLX was especially potent against Streptococcus pneumoniae and Enterococcus faecalis. In conclusion, GFLX exhibits a potently active against fresh isolates from ophthalmological infections, and has an effective potential in the treatment of ophthalmological infections with the drug to administer eye drops.

[Antimicrobial susceptibility surveillance of Streptococcus pneumoniae and Haemophilus influenzae isolates to cefteram and other antimicrobial drugs during January 2003 to July 2004].

The antimicrobial susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates during January 2003 to July 2004 was determined to seven various antimicrobial drugs including cefteram (CFTM). The in vitro activities of these drugs against the fresh isolates were compared. The oral cephalosporins including CFTM were potently active against penicillin susceptible S. pneumoniae. The activity of CFTM and cefditoren was the most active among four oral cephalosporins. The susceptibilities of penicillin intermediate S. pneumoniae and penicillin resistant S. pneumoniae to antimicrobial agents were decreased. The MIC of CFTM was not beyond 4 microg/mL for any isolate of S. pneumoniae. The activity of CFTM was very high to beta-lactamase-negative and ampicillin-susceptible H. influenzae isolates. These MIC against all isolates were 0.03 microg/mL or less. The MIC of CFTM was not beyond 1 microg/mL for any isolate of beta-lactamase-positive H. influenzae or beta-lactamase-negative-ampicillin resistant H. influenzae. In conclusion, CFTM exhibits a potent activity against fresh isolates of S. pneumoniae and H. influenzae, and has a potential of effectiveness in the infections.

[Effect of delay of blood cultures on positive detection by automated blood culture system].

The effect of entry delayed blood culture bottles until the start of incubation for mechanical detection of organism were compared using 2 major blood culture systems; BACTEC 9240 system and BacT/ALERT 3D system. Total of 13 bacterial strains; 5 gram-positive cocci, 7 gram-negative bacilli and Candida parapsilosis which were isolated mainly from blood cultures were used as the test strains. BACTEC 92F, 93F and BacT/ALERT FA, FN bottles were used as the blood culture bottles. All the bottles inoculated with the test strains were incubated and evaluated immediately after standing at room temperature for 24, 42, 48, 54 or 72 hours, using the respective automated blood culture systems. All the bottles were subcultured. The effect of entry delay the blood culture bottles for the mechanical detection was observed in many gram-negative organisms in BACTEC 9240 system. The blood cultures were evaluated not to be positive in 4 of the 10 samples on delaying for 24 hours or in any of the samples on delaying for 42 hours in the BACTEC 92F bottles inoculated with Escherichia coli. In Serratia marcescens, the blood cultures were evaluated not to be positive in 5 of the 10 samples on delaying for 24 hours or in any of the samples on delaying for 42 hours in the BACTEC 92F bottles. In Klebsiella pneumoniae, the blood cultures were evaluated not to be positive in 9 of the 10 samples on delaying for 42 hours. In Enterococcus faecalis, Pseudomonas aeruginosa and Proteus mirabilis, the blood cultures were evaluated not to be positive in 5-6 of the 10 samples on delaying for 42 hours. On the other hand, the blood cultures were evaluated to be positive in most of the samples of Acinetobacter calcoaceticus (except 3 of the 10 samples which were evaluated not to be positive) on delaying for 42 hours in BacT/ALERT 3 D system. The samples except part of Streptococcus spp. were detected by subculture in both the bottles. These results indicate that the delayed time of blood culture bottles before inoculation with the test bacterial samples affects the positive detection of blood cultures markedly in the blood culture system. Therefore, the immediate incubation was considered to be necessary.

[Susceptibility of major pathogens of acute pharyngitis and tonsillitis to levofloxacin and other oral antimicrobial drugs].

A total of 2865 strains of the causative organisms isolated from the patients with acute pharyngitis and tonsillitis at the primary medical institutions were used in this study. The MICs of levofloxacin (LVFX) and other oral antimicrobial drugs were determined and evaluated by the NCCLS guideline. LVFX, cefditoren (CDTR) and cefcapene (CFPN) were potently active against 773 isolates of Hemophilus influenzae, the MIC50S of LVFX being < or = 0.06 microgram/mL and also the same as the MIC90S of LVFX. LVFX was the most active against 496 isolates of Enterobacteriaceae. The MIC50S of LVFX were < or = 0.06 microgram/mL and were lower than those of CDTR, cefdinir (CFDN) and cefpodoxime (CPDX) (MIC50S: 0.5 microgram/mL). The MIC90S of these cephems were markedly higher than the respective MIC50S, whereas MIC50 of LVFX was 0.12 microgram/mL, only twice the MIC50. Against the majority of Streptococcus pyogenes (555 isolates) and Streptococcus spp. (495 isolates), CDTR, CFDN, CPDX and CFPN were highly active (MICs: < or = 0.06 microgram/mL), and clarithromycin (CAM) and azithromycin (AZM) were also active against these organisms (MICs: 0.12 to 0.25 microgram/mL). Against S. pneumoniae (92 isolates), CDTR and CFDN were active (MIC50S: 0.12 and 0.25 microgram/mL, respectively). However, the MIC90S of these drugs were 4-8 times the MIC50S. Against Moraxella (Branhamella) catarrhalis (454 isolates), LVFX was potently active, the MIC90 of LVFX being < or = 0.06 microgram/mL and MIC90S of the other cephems being 0.5 microgram/mL or more. When the susceptibility of these strains to LVFX was evaluated by the NCCLS guideline, about 3% of other Streptococcus spp. were resistant to the drug but no test strains resistant to LVFX were detected in H. influenzae, S. pyogenes or Enterobacteriaceae. On the other hand, the percentages of strains susceptible to the cephems tested were 60-90%, which were quite different according to kinds of drugs and species used. Furthermore, the strains of S. pneumoniae resistant to CFDN and CPDX, and those to CAM and AZM were 21-25% and 50% or more, respectively, whereas no LVFX-resistant strains were detected. The major pathogens isolated from patients with pharyngitis and tonsillitis in the primary institutions were highly susceptible to LVFX. These results suggest that LVFX is a useful drug which is potently active against the strains resistant to oral cephem and macrolide antibiotics.

[Evaluation of rapid identification method for Mycobacterium tuberculosis complex using the immunochromatographic slide test kit].

Capilia TB, a lateral flow immunochromatographic slide test kit for directly identifying Mycobacterium tuberculosis complex (MTC), was evaluated by using culture-positive specimens from Mycobacteria Growth Indicator Tubes (MGIT). Sputum specimens from patients suspected of having tuberculosis were treated with NALC-NaOH and cultivated in MGIT960. Liquid specimens were collected from the positive tubes and directly inoculated with Capilia TB. Liquid specimens were also directly tested with AccuProbe. Of the organisms isolated from the 100 MGIT positive tubes, M. tuberculosis complex was identified in 49 (49%) tubes with Capilia TB and not identified in 51 (51%) with Capilia TB. Mycobacterium avium-intracellulare complex (MAC) was identified in 46 (46%) with AccuProbe MAC and other acid-fast bacteria were identified in 5 (5%) by DNA-DNA hybridization method. There were one tube in which M. tuberculosis complex was detected with Capilia TB and M. tuberculosis complex was not detected with AccuProbe MTC, but no tubes in which M. tuberculosis complex was detected with AccuProbe MTC and M. tuberculosis complex was not detected with Capilia TB. Capilia TB is excellent in sensitivity and specificity and very suitable for rapid diagnosis of tuberculosis and is considered to contribute to public health intervention measures taken for the tuberculosis control in Japan.

[Antibacterial activity of gatifloxacin against various fresh clinical isolates in 2002].

Antibacterial activities of gatifloxacin (GFLX) and other antibacterial drugs against various fresh clinical strains (800 isolates) isolated from specimens of patients in 2002 were compared. GFLX was more active than levofloxacin and ciprofloxacin against Gram-positive bacteria such as methicillin susceptible Staphylococcus aureus and Streptococcus pneumoniae. For these isolates, clarithromycin and azithromycin were less active (MIC90; > 16- > 64 micrograms/mL), GFLX was more active than cefdinir. For Escherichia coli, Klebsiella pneumoniae, Acinetobacter species, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis, three quinolones including GFLX were potently active (MIC90; < or = 0.06-0.5 microgram/mL). Pseudomonas aeruginosa isolated from urinary tract infections were resistant to three quinolones including GFLX (MIC90; 32-64 micrograms/mL), however P. aeruginosa isolated from respiratory and otolaryngological infections were more susceptible (MIC90; 0.5-2 micrograms/mL). Quinolones were less active against Neisseria gonorrhoeae as compared with the cephem antibiotics tested, but GFLX was the most active against N. gonorrhoeae among the quinolones tested. In this study, we investigated activity of GFLX against fresh clinical strains isolated early in 2002, GFLX is widely and potently active against S. aureus, S. pneumoniae and various Gram-negative bacteria.