[Evaluation of the BD Phoenix ID Yeast System for the Species Identification of Clinical Yeast-Like Organisms].

Most fungi isolated from patients with deep-seated mycosis are yeast-like organisms such as Candida and Cryptococcus. As their respective susceptibilities to antifungal agents can vary depending on the species, rapid identification is important for the administration of appropriate antifungal therapy. The aim of this study was to evaluate the performance of a new automated identification panel, Phoenix Yeast ID (Becton, Dickinson Diagnostics, USA) as well as the time required for identification. The identification results of 106 isolates generated by this system were then compared with those of the API 20C AUX system (SYSMEX bioMérieux Co., Ltd. Japan). Among the 106 isolates, the identification agreement between the two yeast panels was 97/106 (91.5%). Of the 9 (8.5%) discrepant identifications, 5 identification using the Phoenix Yeast ID system and 1 identification using the API 20C AUX system agreed with the genotypic identification. Genotypic identification did not agree with the Phoenix Yeast ID or API 20C AUX findings for the remaining 3 discrepant identifications. Approximately 60% of the C. albicans, C. tropicalis, and C. parapsilosis isolates were identified within 4 hours. In total, about 90% of the 4 major Candida sp. (C. albicans, C. tropicalis and C. glabrata) were identified within 8 hours. In conclusion, the Phoenix Yeast ID findings agreed well with the API 20C AUX findings. Genotypic identification of the discrepant identifications confirmed most of the Phoenix Yeast ID panel identifications. As approximately 80% of the major Candida sp. could be identified within 8 hours using the Phoenix Yeast ID identification system, our results suggest that this system is a clinically useful addition to commercially available yeast identification panels. The Phoenix Yeast ID system showed excellent concordance with genotypic identification for the classification of organisms with discrepant API 20C AUX findings.

In vitro antimicrobial activity of ozenoxacin against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus and Streptococcus pyogenes isolated from clinical cutaneous specimens in Japan.

Ozenoxacin, a novel non-fluorinated topical quinolone, was assessed for in vitro antimicrobial activity against each 50 isolates of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and Streptococcus pyogenes according to the broth microdilution method recommended by the Clinical and Laboratory Standards Institute. The isolates used in this study were recovered from cutaneous specimens of Japanese adult and pediatric patients who visited hospitals in 2014. The MIC90s of ozenoxacin against MSSA, MRSA and S. pyogenes isolates from adult patients were ≤0.06, 4 and ≤0.06 µg/mL, respectively. The MIC90s of ozenoxacin against MSSA and S. pyogenes isolates from pediatric patients were equal to those against the adult isolates. On the other hand, the MIC90s of ozenoxacin against the pediatric MRSA isolates was 0.12 µg/mL, and was 32 times lower than that against the adult isolates. The antimicrobial activity of ozenoxacin against MSSA, MRSA and S. pyogenes was equal to or greater than those of 7 reference antimicrobial agents had been used for the treatment of skin infections. The MICs of ozenoxacin was highly correlated with those of nadifloxacin and levofloxacin in the 50 MRSA isolates (r(2) = 0.906 and 0.833, respectively). However, ozenoxacin kept the potent antimicrobial activity with the MIC ranging from 1 to 4 µg/mL even against MRSA low susceptible (MIC: >64 µg/mL) to nadifloxacin or levofloxacin. Ozenoxacin could represent the first-in-class non-fluorinated quinolone for the topical treatment of various superficial skin infections caused by MSSA, MRSA and S. pyogenes.

In vitro antimicrobial activity of benzoyl peroxide against Propionibacterium acnes assessed by a novel susceptibility testing method.

Benzoyl peroxide (BPO), a therapeutic agent for acne vulgaris, was assessed for in vitro antimicrobial activity against Propionibacterium acnes using a novel broth microdilution testing that improved BPO solubility. We searched for a suitable culture medium to measure the minimum inhibitory concentration (MIC) of BPO against P. acnes and finally found the Gifu anaerobic medium (GAM) broth supplemented with 0.1(v/v)% glycerol and 2(v/v)% Tween 80, in which BPO dissolved up to 1250 µg/mL and P. acnes grew well. The MICs and minimum bactericidal concentrations (MBCs) of BPO against 44 clinical isolates of P. acnes collected from Japanese patients with acne vulgaris were determined by our testing method using the supplemented GAM broth. The MICs of BPO were 128 or 256 µg/mL against all isolates of P. acnes regardless of susceptibility to nadifloxacin or clindamycin. The MBCs of BPO were also 128 or 256 µg/mL against the same isolates. Moreover, BPO at the MIC showed a rapid bactericidal activity against P. acnes ATCC11827 in time-kill assay. In conclusion, we could develop a novel assay for the MIC and MBC determinations of BPO against P. acnes, which is reliable and reproducible as a broth microdilution testing and the present results suggest that BPO has a potent bactericidal activity against P. acnes.

In vitro activity of sitafloxacin against atypical bacteria (2009-2014) and comparison between susceptibility of clinical isolates in 2009 and 2012.

In vitro activities of sitafloxacin (STFX) along with fluoroquinolones (levofloxacin (LVFX), moxifloxacin (MFLX), garenoxacin (GRNX)) and macrolides (azithromycin, clarithromycin) against atypical bacteria (Mycoplasma pneumoniae, Legionella pneumophila, Chlamydia trachomatis, Chlamydophila pneumoniae) recovered from clinical specimens from 2009 to 2014 at different healthcare facilities in Japan were investigated. The minimum inhibitory concentration of STFX at which 90% of isolates (MIC90) against M pneumoniae (n= 14) was 0.03µg/mL which was comparable to GRNX, 4- and 16-fold more active than MFLX and LVFX, respectively. Reduced susceptibilities of M pneumoniae (9/14 isolates) to macrolides were observed. MIC90 of STFX against L. pneumophila (n =15) was 0.004µg/mL which was 2- and 4-fold more active than GRNX/LVFX and MFLX, respectively. The minimum inhibitory concentration range of STFX against C. trachomatis (n=5) and C. pneumoniae (n=5) were from 0.015 to 0.03 and from 0.03 to 0.06µg/mL, respectively. Furthermore, differences between the activities of STFX against various clinical isolates in 2009 and those in 2012, which were already published in two articles (Jpn. J. Antibiotics 63:411- 430, 2010, 66:311-330, 2013), were also evaluated. The MIC90s of STFX against methicillin- susceptible Staphylococcus aureus (MSSA), Streptococcus spp. and Enterococcus faecalis isolated in 2012 were 4 or 8 times higher than those in 2009, however there was no difference between STFX activities against other species in 2009 and those in 2012. In conclusion, STFX showed potent activity against atypical bacteria (M pneumoniae, L. pneumophila, C. trachomatis, C. pneumoniae) and no tendency for emergence resistance to Gram- positive cocci, Gram-negative bacteria and anaerobes except MSSA, Streptococcus spp. andt. faecalis.

[In vitro activity of sitafloxacin against clinical isolates in 2012].

In vitro activity of sitafloxacin (STFX) and various oral antimicrobial agents against bacterial isolates recovered from clinical specimens between January and December 2012, at different healthcare facilities in Japan was evaluated. A total of 1,620 isolates including aerobic and anaerobic organisms were available for the susceptibility testing using the microbroth dilution methods recommended by Clinical and Laboratory Standards Institute. The minimum inhibitory concentration of STFX at which 90% of isolates (MIC90) was 0.5 microg/mL for methicillin-susceptible Staphylococcus aureus and was 2 times lower than that of garenoxacin (GRNX), 4 times lower than that of moxifloxacin (MFLX), and 16 times lower than that of levofloxacin (LVFX). STFX inhibited the growth of all the isolates of Streptococcus pneumoniae at 0.06 microg/mL or less. The MIC90 of STFX was 0.03 microg/mL and was 2 times lower than that of GRNX, 4 times lower than that of MFLX, and 32 times lower than that of LVFX. Against Streptococcus pyogenes, the MIC90 of STFX was 0.06 microg/mL and was 2 times lower than that of GRNX, 8 times lower than that of MFLX, and 32 times lower than that of LVFX. The MIC90 of STFX was 2 microg/mL for Enterococcus faecalis, and was 4 times lower than that of GRNX, 8 times lower than that of MFLX, and 32 times lower than that of LVFX. The MIC90 of STFX for Escherichia coli was 2 microg/mL, and the MIC90(s) of other 10 species of Enterobacteriaceae which were the lowest values of the quinolones tested ranged from 0.03 to 1 microg/mL. The MIC90 of STFX for Pseudomonas aeruginosa isolates recovered from urinary infections was 4 microg/mL and was 32 times lower than those of GRNX, MFLX and LVFX. The MIC90 of STFX for P. aeruginosa isolates recovered from respiratory infections was 4 microg/mL and was 8 to 16 times lower than those of GRNX, MFLX, and LVFX. STFX inhibited the growth of all the isolates of Haemophilus influenzae at 0.004 microg/mL or less, and was 4 times lower than that of GRNX, 16 times lower than that of MFLX, and 8 times lower than that of LVFX. The MIC90 of STFX was 0.015 microg/mL for Moraxella catarrhalis, and was equal to that of GRNX, 4 times lower than those of MFLX and LVFX. The MIC90(s) of STFX ranged from 0.03 to 0.25 microg/mL for all the species of anaerobic bacteria and were the lowest values of all the antimicrobial agents tested. In conclusion, the activity of STFX against Gram-positive cocci was comparable or superior to those of GRNX, MFLX and LVFX. STFX showed the most potent activity against Gram-negative bacteria and anaerobic bacteria of all the antimicrobial agents tested in this study.

[Antimicrobial susceptibility profile of Acinetobacter baumannii complex isolates in Japan].

The antimicrobial susceptibility of 93 Acinetobacter baumannii complex isolates from clinical specimens collected nationwide between May and October 2009 were measured by microdilution antimicrobial susceptibility testing based on CLSI M100-S20. Beta-lactamase genes, including classes B and D and ISAbal in meropenem nonsusceptible, including intermediate or resistant isolates, were detected using PCR. Rates of isolates nonsusceptible to meropenem were 18%, to ciprofloxacin 41% and to amikacin 14%. L7-L8: The rate of multidrug-resistant Acinetobacter (MDRA) isolates which were resistant to all 3 antimicrobial agents was 4.3%. MDRA isolates were classified into ST92 by multilocus sequence typing. No metallo-beta-lactamase producer was seen among the 17 meropenem nonsusceptible isolates. The blaoxa-51-like carbapenemase gene and ISAbal were detected in all 17 isolates. ISAba1 upstream presence of the blaOXA-51-like gene was observed in 7 of 17 isolates and the blaOXA-23 like gene in 5 of 17. Consistent with overseas reports, our results confirm the existence of MDRA isolates and isolates harboring OXA carbapenemase genes in Japan. While resistance rates were lower than reports elsewhere, it is clear that resistance trends must be carefully monitored.

[In vitro activity of sitafloxacin against clinical isolates in 2009].

In vitro activity of sitafloxacin (STFX) and various oral antimicrobial agents against bacterial isolates recovered from clinical specimens between January and December 2009, at different healthcare facilities in Japan was evaluated. A total of 1,620 isolates including aerobic and anaerobic organisms was available for the susceptibility testing using the microbroth dilution methods recommended by Clinical Laboratory Standard Institute. The minimum inhibitory concentration of STFX at which 90% of isolates (MIC90) was 0.06 microg/mL for methicillin-susceptible Staphylococcus aureus and was equal to that of garenoxacin (GRNX), 2 times lower than that of moxifloxacin (MFLX), and 8 times lower than that of levofloxacin (LVFX). STFX inhibited the growth of all the isolates of Streptococcus pneumoniae at 0.06 microg/mL or less. The MIC90s of STFX ranged from 0.03 to 0.06 microg/mL and were 1 to 2 times lower than those of GRNX, 2 to 4 times lower than those of MFLX, and 16 to 32 times lower than those of LVFX. Against Streptococcus pyogenes, the MIC90 of STFX was 0.06 microg/mL and was 2 times lower than that of GRNX, 4 times lower than that of MFLX, and 32 times lower than that of LVFX. The MIC90 of STFX was 0.25 microg/mL for Enterococcus faecalis, and was 2 times lower than those of GRNX and MFLX, and 8 times lower than that of LVFX. The MIC90 of STFX for E. coli was 2 microg/mL, and the MIC90s of other 10 species of Enterobacteriaceae which were the lowest values of the quinolones tested ranged from 0.03 to 1 microg/mL. The MIC90 of STFX for Pseudomonas aeruginosa isolates recovered from urinary infections was 8 microg/mL and was 16 times lower than those of GRNX, MFLX and LVFX. The MIC90 of STFX for P aeruginosa isolates recovered from respiratory infections was 2 microg/mL and was 32 times lower than those of GRNX and MFLX, and 16 times lower than that of LVFX. STFX inhibited the growth of all the isolates of Haemophilus influenzae at 0.004 microg/mL or less, and was 2 to 4 times lower than those of GRNX, 8 times lower than those of MFLX, and 4 times lower than those of LVFX. The MIC90 of STFX was 0.008 microg/mL for Moraxella catarrhalis, and was 2 times lower than that of GRNX, 8 times lower than those of MFLX and LVFX. The MIC90s of STFX ranged from 0.015 to 0.12 microg/mL for all the species of anaerobic bacteria and were the lowest values of all the antimicrobial agents tested. In conclusion, the activity of STFX against Gram-positive cocci was comparable or superior to those of GRNX, MFLX and LVFX. STFX showed the most potent activity against Gram-negative bacteria and anaerobic bacteria of all the antimicrobial agents tested in this study.

Antimicrobial activities of piperacillin-tazobactam against Haemophilus influenzae isolates, including beta-lactamase-negative ampicillin-resistant and beta-lactamase-positive amoxicillin-clavulanate-resistant isolates, and mutations in their quinolone resistance-determining regions.

Beta-lactamase-negative ampicillin-resistant (BLNAR) isolates of Haemophilus influenzae have been emerging in some countries, including Japan. The Clinical and Laboratory Standards Institute has only a susceptible MIC breakpoint (< or = 1 microg/ml) for piperacillin-tazobactam and a disclaimer comment that BLNAR H. influenzae should be considered resistant, which was adapted without presentation of data. In addition, fluoroquinolone-resistant H. influenzae isolates have recently been occasionally reported worldwide. To address these problems, we examined susceptibilities to beta-lactams, including piperacillin-tazobactam, and ciprofloxacin by microdilution and disk diffusion (only for piperacillin-tazobactam) methods, against a total of 400 recent H. influenzae clinical isolates, including 100 beta-lactamase-negative ampicillin-susceptible, beta-lactamase-positive ampicillin-resistant, BLNAR, and beta-lactamase-positive amoxicillin-clavulanate-resistant (BLPACR) isolates each. BLNAR and BLPACR isolates were tested by PCR using primers that amplify specific regions of the ftsI gene. We also detected mutations in quinolone resistance-determining regions (QRDRs) by direct sequencing of the PCR products of DNA fragments. Among beta-lactams, piperacillin-tazobactam exhibited potent activity against all isolates of H. influenzae, with all MICs at < or = 0.5 microg/ml (susceptible). A disk diffusion breakpoint for piperacillin-tazobactam of > or = 21 mm is proposed. We confirmed that all BLNAR and BLPACR isolates had amino acid substitutions in the ftsI gene and that the major pattern was group III-like (87.5%). One ciprofloxacin-resistant isolate (MIC, 16 microg/ml) and 31 ciprofloxacin-susceptible isolates (MICs, 0.06 to 0.5 microg/ml) had amino acid changes in their QRDRs. Piperacillin-tazobactam was the most potent beta-lactam tested against all classes of H. influenzae isolates. It is possible that fluoroquinolone-resistant H. influenzae will emerge since several clinical isolates carried mutations in their QRDRs.

[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.

[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.

[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.

[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.

[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.

[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.

Rapidly spreading CTX-M-type beta-lactamase-producing Proteus mirabilis in Japan.

In recent years, increased isolation of extended-spectrum beta-lactamase (ESBL)-producing Proteus mirabilis has been reported in Japan. We undertook an investigation to determine the prevalence of ESBL-producing P. mirabilis isolated in Japan and to characterise the genotype. Seventy-four P. mirabilis isolates recovered from specimens at 54 hospitals in Japan between March and October 2006 were included in the study. Of the 74 P. mirabilis isolates examined, 28 (37.8%) were ESBL-producers. The bla(CTX-M-2) gene was found in 27 isolates, whilst 1 isolate possessed bla(CTX-M-3). Amongst the 28 ESBL-producers, 25 (89.3%) were non-susceptible to ciprofloxacin, whilst 11 (23.9%) of 46 ESBL-non-producing isolates were non-susceptible to ciprofloxacin. Pulsed-field gel electrophoresis (PFGE) analysis of the 28 ESBL-producing isolates from 19 hospitals revealed 17 clusters. The same PFGE type was observed in two or more hospitals especially in the greater Tokyo area, suggesting possible clonal spread and the need for monitoring to determine whether emergence of a dominant clone occurs. Our results show that in Japan there is a high prevalence of CTX-M-type beta-lactamase-producing P. mirabilis. Moreover, these isolates are characterised by reduced susceptibility to fluoroquinolones.

Antimicrobial resistance in clinical isolates of Neisseria subflava from the oral cavities of a Japanese population.

A recent study indicated that Neisseria subflava, one of the commensal Neisseria species, may play an important role in the emergence of Neisseria gonorrhoeae strains with chromosomally mediated resistance to penicillin or cephalosporin by the horizontal genetic exchange of penA genes encoding the target site for penicillin or cephalosporin. The present investigation examined the antimicrobial susceptibility of 45 isolates of N. subflava from the oral cavities of Japanese men and women to various agents used for the treatment of gonococcal infections. Of the 45 isolates, 40 (88.9%) and 4 (8.8%) were intermediately resistant and resistant to penicillin, respectively, with the minimal inhibitory concentration (MIC)(50) and MIC(90) of penicillin being 0.5 mg/l and 1 mg/l, respectively. Of the 45 isolates, 13 (28.9%) and 14 (31.1%) were resistant to tetracycline and ciprofloxacin, respectively, and 3 (6.7%) showed reduced susceptibility to cefixime (although the susceptibility category was not determined). These results indicate that several isolates of N. subflava have acquired resistance or intermediate resistance to various antimicrobial agents, including penicillin, cephalosporin, tetracycline, and ciprofloxacin. The present study may thus confirm that N. subflava may be involved in the emergence of N. gonorrhoeae strains with either intermediate or total resistance to penicillin or cephalosporin by the horizontal genetic exchange of the penA gene.

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.