[Sensitivity surveillance of Streptococcus pneumoniae isolates for several antibacterial agents in Gifu and Aichi prefecture (2008-2009)].

We investigated the susceptibility to antibacterials, genotype of penicillin-binding protein (PBP) genes and macrolide resistant genes, and the serotypes against 377 strains of Streptococcus pneumoniae isolated from medical facilities in Gifu and Aichi prefectures between June 2008 and April 2009. These results were compared with those against 160 strains of S. pneumoniae isolated in 2004. Referring to CLSI (M100-S17), the overall incidence of penicillin-susceptible (PSSP), penicillin-intermediate (PISP) and penicillin-resistant (PRSP) S. pneumoniae was 143 (38%), 185 (49%) and 49 (13%) strains, respectively. PISP and PRSP were isolated higher in the material of nasal cavity and throat, and PRSP was isolated higher in the area of Chuno district. The number of gPSSP with 3 normal PBP genes, gPISP with 1 or 2 normal PBP genes and gPRSP with 3 abnormal genes was 23 (6.1%), 173 (46%) and 181 (48%) strains, respectively. The isolates with no macrolide-resistant gene, only mefA, only ermB, and both mefA and ermB were 28 (7.4%), 138 (37%), 166 (44%) and 45 (12%). The prevalent pneumococcal serotypes were type 19 (92 strains; 24%), following by type 23 (60 strains; 16%) and type 6 (56 strains; 15%). The 80% of pneumococcal serotypes of PRSP were serotype 19 and 6. The MIC90 of each antibacterial was as follows; 0.1 microg/mL for imipenem, panipenem and garenoxacin, 0.2 microg/mL for moxifloxacin, 0.39 microg/mL for meropenem and tosufloxacin, 0.78 microg/ mL for amoxicillin, clavulanic acid/amoxicillin, cefditoren and cefcapene, 1.56 microg/mL for benzylpenicillin, piperacillin, cefteram and levofloxacin, 3.13 microg/mL for cefotiam, flomoxef and pazufloxacin, 6.25 microg/mL for cefdinir, 12.5 microg/mL for norfloxacin and minocycline, > 100 microg/mL for clarithromycin, and these MIC90s were about the same as those in 2004.

[Sensitivity surveillance of Pseudomonas aeruginosa isolates for several antibacterial agents in Gifu and Aichi prefecture (2008)].

We investigated the susceptibility to antibacterial agents of 334 strains of Pseudomonas aeruginosa isolated from medical facilities in Gifu and Aichi prefectures from May to September 2008. For the beta-lactams, meropenem (MEPM) and doripenem (DRPM) gave the lowest MIC50 at 0.5 microg/mL, and tazobactam/piperacillin (TAZ/PIPC) gave the highest susceptible rate of the breakpoint by Clinical and Laboratory Standards Institute (CLSI) at 93.1%. For the quinolones, ciprofloxacin (CPFX) gave the lowest MIC50 at 0.25 microg/mL, followed by pazufloxacin (PZFX) at 0.5 microg/mL, and levofloxacin (LVFX) at 1 microg/mL, and susceptible rate was 76.0% for CPFX and 73.4% for LVFX. Susceptible rates to amikacin (AMK) and tobramycin (TOB) of aminoglycocides and colistin (CL) of polypeptides were 98.2%, 97.6% and 96.4%. In 334 strains, IMP-1 MBL producing P. aeruginosa was 1 strain, and the strain showed resistance to all antibacterial agents except AMK and CL used in this study. The strains isolated from urine were lower susceptible rate in comparison with those from sputum, notably the susceptible rate to CPFX from urine was less over 30% than those from sputum. Because the results of the susceptibility test against P. aeruginosa were different in each area, it is important for us to pay attention to the susceptibility to antibacterial agents and the emergence of resistance in the clinical strains through continuous susceptibility surveillance.

[Epidemiological analysis of Streptococcus pneumoniae in Gifu prefecture and the northern district of Aichi prefecture--2009].

High pathogenicity and drug resistance of Streptococcus pneumoniae are serious problem in clinical practice. Since 1999, we have conducted epidemiologic analyses of S. pneumoniae in Chubu district. We report the results of the analysis conducted in 2009. Three hundred and eight (308) S. pneumoniae isolates with a gene coding for autolysin lyt-A, which had been isolated from patients at 21 medical institutions in Gifu prefecture and the northern part of Aichi prefecture in 2009, were enrolled in this study. The strains were classified according to their drug resistance based on the presence of the pbp mutation, and examined for the presence of the two macrolide-resistance genes, ermB and mefA. Moreover, they were serotyped using type-specific antisera. The mean age of the patients from whom these S. pneumoniae strains were isolated, was 23.4 +/- 30.1 years old, and children aged 15 years old or less accounted for 66% of all the patients. Genotype penicillin-susceptible S. pneumoniae (gPSSP), genotype penicillin-intermediate S. pneumoniae (gPISP) and genotype penicillin-resistant S. pneumoniae (gPRSP) were 22 (7.1%), 131 (42.5%) and 155 (50.3%), respectively. The strains with mefA positive and ermB negative, mefA negative and ermB positive, and mefA positive and ermB positive were 80 (26.0%), 153 (49.7%), and 47 (15.3%), respectively. The MIC90 values of tebipenem (TBPM) and faropenem were 0.06 microg/mL and 0.5 microg/mL, respectively. TBPM showed the high bactericidal activity against gPRSP. In carbapenems, panipenem and biapenem exhibited higher bactericidal activities. Quinolone-resistant S. pneumoniae (QRSP) were isolated from 10 (3.2%). QRSP dominated 5 (7.9%) and 3 (1.5%) among the elderly (over 65 years old) and children, respectively. (As for the serotype, serotypes 6, 19 and 23 were 60 (19.5%), 62 (20.1%), and 44 (14.3%), respectively. Further epidemiologic studies on S. pneumoniae might be required also in the future, including the relationship between the serotype and drug resistance.

[Epidemiological analysis of Streptococcus pneumoniae in Gifu prefecture].

Since antimicrobial resistance in Streptococcus pneumoniae become serious problem, we have conducted the epidemiological analysis of Streptococcus pneumoniae in Gifu prefecture. We have investigated the mutations of penicillin-binding protein (PBP) cording genes, the mutations of macrolide-resistant cording genes, and antimicrobial susceptibility using broth microdilution method, for 345 strains isolated from clinical specimens between May 2006 and July 2006 at 12 clinical facilities of 5 medical area. The ratio of penicillin-susceptible S. pneumoniae (gPSSP), penicillin-intermediate S. pneumoniae (gPISP), and penicillin-resistant S. pneumoniae (gPRSP), which were judged by molecular techniques, were 7.2%, 53.5%, and 39.4%, respectively. Only 1 gPSSP strain was isolated from children under three years old. There have been regional differences of the isolation rate of gPRSP between Gifu/Chuno area (55-60%) and Tono/Hida area (23-32%) in second- or third-medical facilities. The isolation rate of PBP mutation genes, pbp2x, pbp1a and pbp2b, were 92.8%, 52.5% and 53.3%, respectively. The isolation rate of macrolide-resistant cording genes, mefA only, ermB only, and both mefA and ermB, were 30%, 50% and 8%, respectively. The strains of S. pneumoniae with both mefA and ermB mutations, increased from 4% in 2002 to 8% in 2006. The antimicrobial susceptibility of S. pneumoniae to penicillin G (PCG) showed two peaks around 0.03 and 1 microg/mL, and 89% of S. pneumoniae with minimum inhibitory concentration (MIC) value 1 microg/mL was gPRSP. The MIC values of PCG against 69% strains of gPRSP distributed between 0.25 and 1 microg/mL. There have been the decreased tendency for the differences among medical facilities in penicillin resistant strains. Although cefditoren showed the most effective antimicrobial activity in oral cephems tested, there have been the strains with MIC value of over 1 microg/mL. The MIC90 of panipenem was 0.125 microg/mL, which was the best antimicrobial activity in carbapenems. The resistant rates of clarithromycin and azithromycin were 85% and 84%, respectively. The strains with the gene mutation of ermB have showed resistant to clindamycin. The MIC90 of tosufloxacin was 0.25 microg/mL, which was the best antimicrobial activity in quinolones. We have detected 4 levofloxacin highly resistant S. pneumoniae, of which MIC value was over 32 microg/mL. Also, we have encountered the episode of the spread of S. pneumoniae in one family, which was clarified by scientific approach.

[Antibiotic susceptibility of blood-borne Streptococcus pneumoniae and efficacy assessment of respiratory quinolones using Monte Carlo simulation].

We analyzed Streptococcus pneumoniae isolates from the bloodstream between April 2005 and February 2007. We analyzed isolates of 28 strains from medical facilities in Gifu prefecture to determine antibiotic susceptibility, genotype of penicillin-binding protein (PBP) genes and macrolide resistant genes. We also assessed the efficacy of respiratory quinolones using Monte Carlo simulation. Garenoxacin (GRNX) and moxifloxacin (MFLX) showed the lowest MIC90 value of 0.125 microg/mL, followed by MIC90 of imipenem (IPM) of 0.25 microg/mL and tosufloxacin (TFLX), MIC90 of meropenem (MEPM) and vancomycin (VCM) of 0.5 microg/mL. Twenty-two strains possessed at least one mutation in PBP-encoding genes pbp1a, pbp2x or pbp2b and seven strains possessed all three mutant alleles. Twenty-two strains possessed either of macrolide resistant genes ermB or mefA, and one strain possessed both. On efficacy assessment, we calculated the probability of target attainment for free-drug area under the curve (fAUC)/MIC ratio (fAUC/MIC). GRNX and MFLX showed a probability of 90% or more at fAUC/MIC of 30 and 125, each considered effective against Gram-positive bacteria and suppression of resistance development, furthermore, GRNX showed a probability of 89.7% at fAUC/MIC of 250.

[Sensitivity surveillance of streptococci isolates for several antibiotics in Gifu prefecture (2005-2007)].

We investigated the susceptibility to antibacterials of streptococci isolated from 8 medical facilities in Gifu prefecture between 2005 and 2007. Strains used in this study include 118 of Group A streptococci, 89 of Group B streptococci, and 58 of group G streptococci. For Group A streptococci, cefteram and imipenem gave the lowest MIC90 at 0.0078 microg/mL, followed by cefditoren and cefcapene at 0.0156 microg/mL and penicillin G, amoxicillin and meropenem at 0.0313 microg/mL. For Group B streptococci, cefteram, cefditoren, cefcapene and imipenem gave the lowest MIC90 at 0.0313 microg/mL, followed by penicillin G and meropenem at 0.0625 microg/mL and amoxicillin at 0.125 microg/mL. For Group G streptococci, cefteram and imipenem gave the lowest MIC90 at 0.0078 microg/mL, followed by penicillin G, cefditoren, cefcapene and meropenem at 0.0156 microg/mL and amoxicillin at 0.0313 microg/mL. With Group A and B streptococci, the susceptibility data obtained in this study were compared with those of strains between 2000 and 2001. As for group A streptococci, the MIC50 and MIC90 of beta-lactam agents were about the same as those of previous study, however the MIC90 of quinolones increased about 2.5-fold and resistant strains were found. As for Group B streptococci, the MIC50 and MIC90 of almost all of the antibacterials were about the same as those of the previous study, however the MIC90 of clarithromycin increased about 10-fold, indicating that the resistant strains are widely spread.

[Sensitivity surveillance of Haemophilus influenzae isolates for several antibiotics in Gifu Prefecture (2006)].

We investigated the susceptibility to antibacterials of 194 strains of Haemophilus influenzae isolated from medical facilities in Gifu prefecture between 2005 and 2006, and compared these results with those of 280 strains of H. influenzae isolated between 1999 and 2000. Additionally, the strains that had been separated between 2005 and 2006 were examined for beta-lactamase (BL) production, the mutation of ftsI gene coding for PBP3, the bla gene coding for TEM type of BL and the serotype. Referring to the CLSI breakpoint, H. influenzae strains were classified into the following categories: (1) beta-lactamase-negative ampicillin-susceptible (BLNAS) strains, which showed BL negative, ampicillin (ABPC) and ampicillin/sulbactam (ABPC/SBT)-MIC < or = microg/ml, (2) beta-lactamase producing ampicillin-resistant (BLPAR) strains, which showed BL producing and ABPC/SBT-MIC < or =2 microg/ml, (3) beta-lactamase-negative ampicillin-resistant (BLNAR) strains, which showed BL negative, ABPC and ABPC/SBT-MIC > or =2 microg/ml, (4) beta-lactamase-producing amoxicillin/clavulanic acid-resistant (BLPACR) strains, which showed BL producing and ABPC/SBT-MIC > or =4 microg/ml. The prevalence of each resistance class were 71.8% for BLNAS, 7.9% for BLPAR, 19.6% for BLNAR and 0.7% for BLPACR in strains isolated between 1999 and 2000. But they were 38.1% for BLNAS, 4.6% for BLPAR, 54.6% for BLNAR and 2.6% for BLPACR in strains isolated between 2005 and 2006, indicating that the percentage of BLNAS and BLPAR decreased and that of BLNAR and BLPACR increased from 1999-2000 to 2005-2006. On the basis of ftsI substitutions and having bla gene, the strains isolated between 2005 and 2006 were classified into the following distribution: 24.2% for gBLNAS, 4.1% for gBLPAR, 10.8% for gLow-BLNAR, 57.7% for gBLNAR, and 3.1% for gBLPACR-II. Ratio of BLNAR belonging to gBLNAR and gLow-BLNAR based on the ftsI substitutions and having bla gene was higher than that based on the susceptibility pattern. The MIC50 and MIC90 for those strains isolated between 2005 and 2006 were as follows; 0.0039, 0.0156 microg/ml for garenoxacin, 0.0078, 0.0156 microg/ml for tosufloxacin and ciprofloxacin, 0.0156, 0.0313 microg/ml for levofloxacin, 0.0313, 0.0625 microg/ml for norfloxacin, 0.0625, 0.25 microg/ml for piperacillin/ tazobactam, 0.0625, 0.5 microg/ml for piperacillin, 0.125, 0.25 microg/ml for ceftriaxone and cefditoren, 0.5, 1 microg/ml for cefteram, chloramphenicol and tetracycline, 0.5, 2 microg/ml for cefotaxime, 2, 8 microg/ml for ampicillin, ampicillin/sulbactam and cefdinir. In comparison with the values for the strains isolated between 1999 and 2000, the MIC50s of beta-lactam for the strains isolated between 2005 and 2006 increased over 4 times.