[Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2012].

The nationwide surveillance of antibacterial susceptibility to meropenem (MEPM) and other parenteral antibiotics against clinical isolates during 2012 in Japan was conducted. A total of 2985 strains including 955 strains of Gram-positive bacteria, 1782 strains of Gram-negative bacteria, and 248 strains of anaerobic bacteria obtained from 31 medical institutions were examined. The results were as follows; 1. MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA). 2. Of all species tested, there were no species, which MIC90 of MEPM was more than 4-fold higher than those in our previous studies in 2009 or 2006. Therefore, the tendency to increase in antimicrobial resistance rates was not observed. 3. MEPM resistance against Pseudomonas aeruginosa was 17.8% (56/315 strains). Compared to our previous results, it was the lowest than that in 2006 and 2009. 4. Carbapenem-resistant Klebsiella pneumoniae, and multi-drug-resistant Acinetobacter species, which emerged in worldwide, were not observed. 5. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 6.2% (59/951 strains) in enterobacteriaceae, which increased compared with that of our previous studies in 2009 or before. Whereas, the proportion of metallo-beta-lactamase strains was 1.6% (5/315 strains) in P. aeruginosa, which was stable. In conclusion, the results from this surveillance suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem for serious infections treatment at present, 17 years passed after available for commercial use in Japan.

[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.

[Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2009].

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 2655 strains including 810 strains of Gram-positive bacteria, 1635 strains of Gram-negative bacteria, and 210 strains of anaerobic bacteria obtained from 30 medical institutions during 2009 was examined. The results were as follows; (1) MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multidrug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA). (2) MEPM maintained potent and stable antibacterial activity against Pseudomonas aeruginosa. The proportion of MEPM-resistant strains to ciprofloxacin-resistant strains or imipenem-resistant strains were 53.1% and 58.0% respectively. (3) The proportion of extended-spectrum beta-lactamase (ESBL) strains was 3.1% (26 strains) in enterobacteriaceae. And the proportion of metallo-beta-lactamase strains was 2.0% (6 strains) in P. aeruginosa. (4) Of all species tested, there were no species except for Bacteroides fragilis group, which MIC90 of MEPM was more than 4-fold higher than those in our previous study. Therefore, there is almost no significant decrease in susceptibility of clinical isolates to meropenem. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem for serious infections treatment at present, 14 years passed after available for commercial use in Japan.

[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.

[Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2006].

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 876 strains of Gram-positive bacteria, 1764 strains of Gram-negative bacteria, and 198 strains of anaerobic bacteria obtained from 30 medical institutions during 2006 was measured. The results were as follows; 1. MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus. 2. As for Pseudomonas aeruginosa, all of the MEPM-resistant strains were resistant to imipenem (IPM). MEPM showed low cross-resistant rate both againt IPM-resistant P. aeruginosa (41.8%) and ciprofloxacin-resistant P. aeruginosa (33.3%). 3. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 4.3% (6 strains) in Escherichia coli, 1.1% (1 strain) in Citrobacter freundii, 21.7% (5 strains) in Citrobacter koseri, 3.1% (4 strains) in Klebsiella pneumoniae, 3.3% (3 strains) in Enterobacter cloacae, 0.8% (1 strain) in Serratia marcescens, and 4.9% (2 strains) in Providencia spp. The proportion of metallo-beta-lactamase strains was 3.1% (10 strains) in P. aeruginosa. 4. Of all species tested, there were no species, which MIC90 of MEPM was more than 4-fold higher than those in our previous study. Therefore, there is almost no significant decrease in susceptibility of clinical isolates to meropenem. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem at present, 11 years after available for commercial use.

[Surveillance on Pseudomonas aeruginosa isolated in Gifu prefecture (2004)].

We analyzed Pseudomonas aeruginosa isolates in Gifu prefecture between September and October 2004. We conducted antimicrobial susceptibility test for 266 strains isolated from 8 medical institutes and 1 clinical laboratory, based on broth microdilution method. The MIC50 and MIC90 of piperacillin, amikacin, imipenem, and ciprofloxacin were 4 and 64, 4 and 8, 1 and 16, 0.25 and 8 microg/mL, respectively. The strains isolated from urine had higher MIC level in comparison with from sputum, which was remarkable in penicillins, cephalosporins and fluoroquinolones. We isolated 7 strains of multi-drug resistant Pseudomonas aeruginosa (MDRP), in which 3 strains showed under 16 microg/mL in MIC against anti-MRSA (methicillin-resistant Staphylococcus aureus) drug arbekacin. Continuous surveillance would be needed for antimicrobial resistance on P. aeruginosa in Gifu prefecture.

[Surveillance based on molecular epidemiology for Haemophilus influenzae Isolates in Gifu Prefecture].

We analyzed Haemophilus influenzae isolates in Gifu prefecture between May 2003 and August 2003. We conducted molecular-level epidemiological studies for 313 strains using PCR to identify resistant genes in H. influenzae. Our four sets of primers are as follows: (i) p6 gene of P6 membrane protein, (ii) TEM-1 type beta-lactamase gene (bla), (iii) normal PBP 3 gene (ftsl), and (iv) mutational ftsl gene detected in beta-lactamase-nonproducing ampicillin (ABPC) resistant H. influenzae (BLNAR). H. influenzae strains were classified into 6 types based on PCR: (i) beta-lactamase-nonproducing ABPC-susceptible strains (BLNAS; n = 85) with no any resistant genes, (ii) TEM-1 type beta-lactamase-producing ABPC resistant strains (BLPAR; n = 6), (iii) beta-lactamase-nonproducing and low-level ABPC-resistant strains (Low-BLNAR; n = 77) possessing Asn-526 --> Lys-526 amino acid substitution, (iv) BLNAR strains (n = 138) possessing Asn-526 --> Lys-526 and 3 amino acids substitutions detected around the Ser-Ser-Asn conserved motif, (v) beta-lactamase-producing amoxicillin-clavulanate resistant strains (BLPACR-I; n = 3) possessing TEM-1 and Low-BLNAR resistant genes, and (vi) beta-lactamase-producing amoxicillin-clavulanate resistant strains (BLPACR-II; n = 4) possessing TEM-1 and BLNAR resistant genes. Amoxicillin (AMPC) MIC90s in Low-BLNAR was 4 microg/mL and in BLNAR was 16 microg/mL. In oral cephalosporins, cefditoren MIC90 was the most excellent with 0.5 microg/mL against BLNAR. The prevalence of H. influenzae type b isolates in Matsubara Otorhinolaryngology Clinic was 66.7%. Selection of appropriate antimicrobial agents should be performed to prevent resistant microorganisms. Also, the vaccination for H. influenzae type b would be strongly recommended in near future.

[In vitro susceptibilites to levofloxacin and various antibacterial agents of 11,475 clinical isolates obtained from 52 centers in 2002].

The susceptibilities of bacteria to fluoroquinolones (FQs), especially levofloxacin, and other antimicrobial agents were investigated using 11,475 clinical isolates collected in Japan during 2002. Methicillin susceptible staphylococci, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, the family of Enterobactericeae, Haemophilus influenzae and Acinetobacter spp. exhibited stable and high susceptibilities to FQs. The rate of FQs-resistant MRSA was 80 approximately 90%, being markedly higher than that of FQs-resistant MSSA. The FQs-resistance rate of MRCNS was also higher than that of MSCNS, however, it was lower than that of MRSA. No FQs-resistant clinical isolates of Salmonella spp. were detected in any of the surveys. Thirteen of Escherichai coli 696 isolates, 8 of Klebsiella pneumoniae 630 isolates and 33 of Proteus mirabilis 373 isolates produced extended-spectrum beta-lactamase (ESBL), furthermore 6 of 13 in E. coli, 1 of 8 in K. pneumoniae and 14 of 31 ESBL-producing isolates, and in P. mirabilis were FQs resistant. Attention should be focused in the future on the emergence of ESBL in relation to FQs resistance. The rate of FQs-resistant P. aeruginosa isolated from urinary tract infection (UTI) was 40 approximately 60%, while 15 approximately 25% of isolates from respiratory tract infection (RTI) were resistant. IMP-1 type metallo beta-lactamase producing organisms were found in 49 of P. aeruginosa 1,095 isolates, 7 of S. marcescens 586 isolates and 4 of Acinetobacter spp. 474 isolates, respectively. Glycopeptide-resistant enterococci or S. aureus was not found.

[Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2004].

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 907 strains of Gram-positive bacteria, 1790 strains of Gram-negative bacteria, and 192 strains of anaerobic bacteria obtained from 30 medical institutions during 2004 was measured. The results were as follows; 1. MIC90 of MEPM for almost all of enterobacteriaceae and Haemophilus influenzae were 4-fold to 32-fold lower than those of other carbapenems. MEPM was more active than other carbapenem antibiotics against Gram-negative bacteria, especially against enterobacteriaceae and H. influenzae. MEPM were active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus. 2. As for Pseudomonas aeruginosa, imipenem (IPM) showed high cross-resistant rate againt meropenem-resistant P. aeruginosa (87.9%). MEPM showed low cross-resistant rate both againt IPM-resistant P. aeruginosa (49.2%) and ciprofloxacin-resistant P. aeruginosa (38.0%). 3. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 3.1% (4 strains) in Escherichia coli, 8.0% (2 strains) in Citrobacter koseri, 2.5% (3 strains) in Klebsiella pneumoniae, 2.5% (2 strains) in Enterobacter cloacae, 0.9% (1 strains) in Serratia marcescens, and 2.2% (2 strains) in Proteus mirabilis. The proportion of metallo-beta-lactamase strains was 1.6% (5 strains) in P. aeruginosa. 4. Of all species tested, Peptostreptococcus spp. was the only species, which MIC90 of MEPM was more than 4-fold higher than that in our previous study using clinical isolates during 2002 (0.25 microg/ml --> 1 microg/ml). Therefore, there is almost no siginificant decrease in susceptibility of clinical isolates to meropenem. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem at present, 9 years after available for commercial use.

[Epidemiology of Streptococcus pneumoniae isolates in Gifu Prefecture].

We analyzed Streptococcus pneumoniae isolates confirmed by direct PCR in Gifu prefecture between May 2002 and August 2002. We analyzed isolates of 254 strains from 6 hospitals to determine antibiotic susceptibility, genotype of penicillin-binding protein (PBP) genes and macrolide resistant genes, and the serotypes distribution of isolates from Matsubara Otorhinolaryngology Clinic. Isolates in which abnormal PBP genes of pbp1a, pbp2x, and pbp2b were identified by PCR were classified based on PCR results as follows; (i) penicillin-susceptible (PSSP) with 3 normal PBP genes, (ii) penicillin-intermediate (PISP) with an abnormal pbp2x, (iii) PISP with an abnormal php2b, (iv) PISP with abnormal pbp2x and pbp2b, (v) PISP with abnormal pbpla and pbp2x, (vi) penicillin-resistant (PRSP) with 3 abnormal PBP genes. The overall incidence of PRSP, PISP and PSSP was 121 (49%), 109 (42%) and 24 (9%), respectively, and there was a significant difference among some hospitals (p<0.05). However, there was no significant difference among the hospitals for the incidence of abnormal macrolide-resistant genes (mefA, ermB). Panipenem showed an excellent antimicrobial activity for injectable carbapenems against PRSP, following biapenem, imipenem, and meropenem. Cefditoren (CDTR) showed an excellent antimicrobial activity for oral cephalosporins against PRSP, following cefteram and cefcapene. Interestingly, there were 2 and 3 strains on MIC of CDTR for 8 and 4 microg/mL, respectively. The prevalent pneumococcal serotypes of isolates in Matsubara Clinic were 6 (17/55), following by 40 (8/55), 9 (6/5) and 15 (5/55). The endemic strains were observed in this study using pulsed field gel electrophoresis. These findings suggest the needs to continue the surveillance of bacterial resistance not only in the nationwide but also in the distict.

[Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2002].

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 899 strains of Gram-positive bacteria, 1500 strains of Gram-negative bacteria, and 158 strains of anaerobic bacteria obtained from 28 medical institutions during 2002 was measured. The results were as follows; 1. MEPM was more active than other carbapenem antibiotics against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MIC90 of MEPM against Pseudomonas aeruginosa was the lowest of the drugs tested. MEPM showed low cross-resistant rate against both imipenem-resistant P. aeruginosa and ciprofloxacin-resistant P. aeruginosa. MEPM was active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE). 2. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 3.1% (4 strains) in Escherichia coli and 1.9% (2 strains) in Klebsiella pneumoniae. Carbapenems including MEPM were active against these ESBL strains. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem; at present, 7 years after available for commercial use.

Distribution of an antifungal drug, itraconazole, in pathological and non-pathological tissues.

An antifungal drug, itraconazole (ITZ) is effective for chromomycosis patients, but the distribution of ITZ and its metabolite, hydroxy-intraconazole (OH-ITZ) is unclear in pathological tissues. This study investigated how much ITZ and OH-ITZ accumulated in the lesional tissues of chromomycosis and non-lesional skin after oral treatment with ITZ. We determined the concentrations of ITZ and OH-ITZ in the lesional tissues of chromomycosis by Foncecaea pedrosoi and non-lesional skin after oral treatment with a total dose of 2.3g of ITZ. ITZ concentration was significantly higher in pathological skin than non-pathological skin. The ITZ concentration in the lesional tissues was higher in the central site than in the marginal site. No difference was seen in the OH-ITZ concentrations among three skin parts, the center and the margin in lesional skin, and non-lesional skin adjacent to the lesion. This study showed higher concentrations of ITZ in pathological tissues than in non-pathological tissues.

[Activities of antimicrobial agents against 8,474 clinical isolates obtained from 37 medical institutions during 2000 in Japan].

A survey was conducted to determine the antimicrobial activity of fluoroquinolones and other antimicrobial agents against 8,474 clinical isolates obtained from 37 Japanese medical institutions in 2000. A total of 25 antimicrobial agents were used, comprising 4 fluoroquinolones, 13 beta-lactams, minocycline, chloramphenicol, clarithromycin, azithromycin, gentamicin, amikacin, sulfamethoxazole-trimethoprim, and vancomycin. A high resistance rate of over 85% against fluoroquinolones was exhibited by methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium. Isolates showing resistance to fluoroquinolones among methicillin-resistant coagulase-negative Staphylococci, Enterococcus faecalis, and Pseudomonas aeruginosa from UTI accounted for 30-60%. However, many of the common pathogens were still susceptible to fluoroquinolones, such as Streptococcus pneumoniae (including penicillin-resistant isolates), Streptococcus pyogenes, methicillin-susceptible S. aureus (MSSA), methicillin-susceptible coagulase-negative Staphylococci, Moraxella catarrhalis, the Enterobacteriaceae family, and Haemophilus influenzae (including ampicillin-resistant isolates). About 85% of P. aeruginosa isolated from RTI were susceptible to fluoroquinolones. In conclusion, this survey of sensitivity to antimicrobial agents clearly indicated trend for increasing resistance to fluoroquinolones among MRSA, Enterococci, and P. aeruginosa isolated from UTI, although fluoroquinolones are still effective against other organisms and P. aeruginosa from RTI as has been demonstrated in previous studies.