[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.

Clinical utility and characteristics of nine anti-HCV antibody screening reagents used in Japan.

Nine anti-HCV antibody screening reagents currently used in Japan were investigated for diagnostic utility. The results using sera from 500 subjects and two series of anti-HCV seroconversion panels were compared. The positive detection rates of the 9 screening tests in 500 specimens ranged from 9.6% to 12.2% and the agreements between combinations ranged from 97.0-99.4%. In the 7 two-step assays, which employ recombinant antigen solid phase and anti-human antibody detection, i.e. excluding Quick Chaser and PA, agreement ranged from 97.6-99.4%. No relationship was seen between similarities of the antigen used and agreements between the 7 reagents. For the 72 specimens that showed positive with at least one screening reagent, agreements between the 9 reagents and the confirmatory tests (RIBA III) were compared. In specimens that showed positive with multiple reagents, the positive rate of RIBA III was high, thus the possibility of the existence of the anti-HCV antibody was high. In specimens that showed positive in only a single screening reagent, the RIBA III did not test positive, suggesting that the incidence of false positives may be high. The accuracy of each screening reagent was compared to RIBA III as an accuracy standard. It was found that ARCHITECT was the best in accuracy. The distance from mean to cut-off in the anti-HCV antibody negative specimens reflected the incidence of false positives in each reagent. The anti-HCV antibody seroconversion sensitivities in the initial stage of HCV infection were also compared. The earlier detection was seen with Centaur, ELISA and ARCHITECT. Each anti-HCV antibody screening reagent in use has unique features, and it is suggested that caution be used when diagnosing HCV infection on the basis of the results of a single antibody test.

[Nationwide susceptibility surveillance of ciprofloxacin and various parenteral antimicrobials against bacteria isolated from patients with severe infections--third ciproxan injection special survey (2005)].

We conducted 3 nationwide surveillance studies between 2001 and 2005 at 39 participating institutions throughout Japan according to the special survey plan to investigate susceptibility to ciprofloxacin (CPFX) and various parenteral antimicrobials using clinical isolates from patients with severe infection during the reexamination period of parenteral CPFX. Results of the first special survey (2001) were already reported in this journal. The current third special survey (2005) was conducted at 34 participating institutions throughout Japan to determine susceptibility to CPFX and 22 various parenteral antimicrobials with the use of the microdilution method with respect to 1696 strains isolated and identified from various clinical specimens between January and June 2005. The results of CPFX in this survey were compared with those in the first and second special surveys. The minimum inhibitory concentration of CPFX at which 90% of isolates were susceptible (MIC90) ranged from < or =0.063 to 2 microg/mL for methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, Haemophilus influenzae, Klebsiella spp., Citrobacter freundii, Enterobacter spp., Proteus spp., Serratia marcescens, and Acinetobacter baumannii, revealing no marked change from results of the first and second surveys. However, the CPFX-susceptibility rate of Escherichia coli decreased in the second and third surveys compared to that in the first survey. For Morganella morganii and Pseudomonas aeruginosa, the MIC90 of CPFX tended to increase with time. The CPFX-susceptibility rates calculated from the pneumonia breakpoint were 85.2% for P. aeruginosa and 67.9% for Stenotrophomonas maltophilia. With the exception of these 2 species, major causative organisms of respiratory tract infection had susceptibility rates as high as 90% or more for CPFX, which were similar to results of the first and second special surveys. These susceptibility rates for CPFX were similar to the rates for cefozopran and imipenem. These values generally indicated favorable CPFX susceptibility testing results of major bacteria and the potent antimicrobial activity of CPFX particularly against Gram-negative bacteria. Further surveillance is required regarding the trend in susceptibility of E. coli, M. morganii, and P. aeruginosa, which tended to become less susceptible with time.

Antimicrobial susceptibility of respiratory tract pathogens in Japan during PROTEKT years 1-5 (1999-2004).

Susceptibility to a range of antimicrobial agents was determined among isolates of Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae collected in 12 centers throughout Japan during years 1-5 (the respiratory seasons of 1999-2004) of the longitudinal Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin study. The most frequent source of isolates of S. pneumoniae was from patients with community-acquired pneumonia (CAP) (25.3%). Reduced susceptibility to penicillin or erythromycin resistance was common among S. pneumoniae isolates (30.9-44.5% and 77.2-81.9%, respectively). The macrolide MIC(50) for S. pneumoniae was >or=128 microg/ml (azithromycin and erythromycin) and >or=64 microg/ml (clarithromycin). The erm(B) genotype accounted for the most erythromycin-resistant isolates in each study year. H. influenzae isolates were most commonly derived from patients with CAP (26.2%). The proportion of H. influenzae isolates that were beta-lactamase positive ranged between 4.3% and 9.7%. The prevalence of beta-lactamase-negative ampicillin-resistant isolates increased from 0.4% to 2.6% between years 1 and 4 then to 19.7% in year 5. S. pyogenes isolates were highly susceptible to most antimicrobial agents except macrolides and tetracycline. Telithromycin was highly active against all three pathogens examined throughout the study.

[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.

Antimicrobial susceptibility of respiratory tract pathogens in Japan during PROTEKT years 1-3 (1999-2002).

Data are presented on antimicrobial resistance among isolates of Streptococcus pneumoniae, Streptoco-ccus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis collected in Japan during years 1-3 (1999-2002) of the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin (PROTEKT) surveillance study. In addition to the standard panel of PROTEKT antimicrobial agents, eight other agents often used in Japan also were tested against these isolates. The majority (30%-55%) of S. pneumoniae and H. influenzae isolates were collected from patients with community-acquired pneumonia, whereas most (>70%) S. pyogenes isolates came from patients with tonsillitis/pharyngitis. Penicillin and macrolide resistance were high among isolates of S. pneumoniae, averaging 30.9%-44.5% and 77.2%-79.9%, respectively, across all centers over the 3 study years; the highest occurrences were reported among pediatric patients aged 0-2 years. The erm(B) genotype accounted for >50% of all erythromycin-resistant isolates each study year. S. pyogenes isolates were highly susceptible to most antimicrobial agents except the macrolides and tetracycline. beta-Lactamase production among H. influenzae isolates range was 8.5%-9.7% per annum. A total of 9 beta-lactamase-negative, ampicillin-resistant isolates were collected during the study. Almost all (>95%) M. catarrhalis isolates were beta-lactamase positive each year. Telithromycin was highly active against all pathogens examined in this study during all 3 years.

PROTEKT 1999-2000: a multicentre study of the antimicrobial susceptibility of respiratory tract pathogens in Japan.

DESIGN: A six-centre study in Japan during the winter of 1999-2000 assessed the in vitro activity of >20 antimicrobial agents against the common respiratory pathogens Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis. The minimum inhibitory concentrations (MIC) of each antimicrobial was determined against these isolates using National Committee for Clinical Laboratory Standards (NCCLS) methodology. RESULTS: Among S. pneumoniae isolates, 44.5% were penicillin resistant. The macrolide resistance rate was 77.9% with 90.5% of penicillin-resistant strains also being macrolide resistant. Resistance mechanisms in macrolide-resistant isolates were identified as mef(A) or erm(B) in 42.5% and 52.5%, respectively. Of the fluoroquinolone-resistant isolates (1.3%), most were also penicillin and macrolide resistant. All strains were inhibited by telithromycin at

[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.

[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.

[Nationwide sensitivity surveillance of ciprofloxacin and various parenteral antibiotics against bacteria isolated from patients with severe infections--the first Ciproxan IV special investigation in 2001].

The parenteral injection of ciprofloxacin (CPFX), a fluoroquinolone antimicrobial drug, was approved in September 2000 and a re-examination period of 6 years was set at that time. As a special investigation to apply for re-examination of this drug, it has been planned to conduct 3 nationwide surveillances during the re-examination period by collecting clinically isolated bacteria from patients with severe infections, to whom the drug was mainly indicated, and examining drug susceptibilities of the bacteria to various parenteral antimicrobial drugs including CPFX. This time, we determined the minimum inhibitory concentrations (MICs) of various parenteral antimicrobial drugs including CPFX against 1,220 strains isolated from patients with severe infections by the micro-liquid dilution method and compared susceptibilities of various clinically isolated bacteria to CPFX with those to other antimicrobial drugs. Gram-positive bacteria were less susceptible to CPFX than to carbapenems except 2 bacterial species, Enterococcus faecium and Enterococcus avium but susceptibilities of methicillin-susceptible Staphylococcus aureus (MSSA), Staphylococcus epidermidis and Enterococcus faecalis to CPFX were comparable to those to cefozopran. Susceptibility of Streptococcus pneumoniae to CPFX did not differ among ampicillin (ABPC)-susceptible Streptococcus pneumoniae (MIC of ABPC: < 0.25 microgram/ml), ABPC-intermediate S. pneumoniae (MIC of ABPC: 0.25-2 micrograms/ml) and ABPC-resistant S. pneumoniae (MIC of ABPC: > or = 4 micrograms/ml) MIC90 of CPFX: 1 microgram/ml) and a decrease in the antimicrobial activity seen among cephem and carbapenem antimicrobial drugs against penicillin-intermediate strains was not noted with CPFX. Gram-negative bacteria were susceptible to CPFX similarly to carbapenems and the MIC90 values of CPFX were in the range from < or = 0.063 to 2 micrograms/ml against strains except Stenotrophomonas maltophilia and Burkholderia cepacia. Pseudomonas aeruginosa was most susceptible to CPFX among the antibacterial drugs examined and the MIC90 was 2 micrograms/ml. CPFX also showed the lowest MIC90 value (0.5 microgram/ml) against beta-lactam-resistant P. aeruginosa among the drugs examined. When extended-spectrum beta-lactamase (ESBL) production and class B beta-lactamase production were examined in 439 strains of Enterobacteriaceae and 168 strains of glucose non-fermentative bacteria out of the Gram-negative bacteria collected this time, 3 strains (0.49%) producing ESBL and 7 strains (1.15%) producing class B beta-lactamase were found. The MIC range of CPFX to these 10 strains was between < or = 0.063 to 8 micrograms/ml and 5 strains among those showed susceptibilities (MIC of CPFX: 1 microgram/ml) based on the NCCLS breakpoint. CPFX also showed a satisfactory result concerning susceptibilities of major causal bacteria based on the report of the committee of Japan Society of Chemotherapy on the standard method for determination of susceptibility to antimicrobial agents, the breakpoint of pneumonia. Furthermore, susceptibilities of various bacteria isolated clinically from patients with severe infections this time did not differ much from the result of the nationwide surveillance which we conducted in 1997. Thus, it was concluded that the antimicrobial activity of CPFX was maintained in the post-marketing surveillance for its parenteral preparation.

[Community-acquired pneumonia--from medical technologist].

The main causative microorganisms of Community-acquired pneumonia are Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. Especially the causative microorganisms affecting whole body basic disease, persons of advanced age, and alcoholic patients are Moraxella catarrhalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida spp., Cryptococcus spp., Aspergillus spp., Pneumocystis carinii and anaerobic bacteria. Other microorganisms involved in epidemic disease, action condition (travel around hot springs etc.) and pet breeding environments are Mycoplasma pneumoniae, Legionella pnumophila, Chlamydia spp., respiratory syncytial virus, influenza virus, and adeno virus. We suggest methods of advancing the microscopic and microbiological examination and report, and quickly obtaining clinical information and extracting the clinical specimen. We also describe the inspection method for a case "Legionella pneumonia" that was discussed during this symposium.

[Reviews for Gram stain].

The Gram stain is a rapid examination method providing useful information for diagnosis and treatment of infection. However, a molecular biology inspection and rapid immunological method have been developed, and gram stains have been disregarded recently. Therefore, I explain the usefulness of gram staining for rapid diagnosis, rapid treatment, and the economy. Moreover, I will explain gram stain method "Bartholomew & Mittwer(B&M)" which replaces the Hucker method.

[Study on the detection methods of Helicobacter pylori from clinical specimens].

We have attempted the detection of Helicobacter pylori using biopsy specimen (tunica mucosa vestibulum ventriculi, tunica mucosa corpus ventriculi) and of Helicobacter pylori Specific Antigen (HpSA) from feces of patients with stomach-duodenum disease. During 1991-2000, 753 patients had biopsy test for Gram-stained smear, culture, rapid urease test (RUT), and HpSA by ELISA. As a result, Gram stained smear positive were 609 (44.6%) in 1,357 specimens, culture positive were 984 (72.5%) in 1,357 specimens, and RUT positive were 445 (59.4%) in 749 specimens in method with stomach specimens. 85 (94.4%) in 90 specimens with method of HpSA were positive, and we defined that indirect detection method using feces was most significance compared with other invasive direct method using endoscopy. In addition, antimicrobial susceptibility tests were examined with 5 agents for 349 strains of H. pylori, the MICs of amoxicillin were <0.01-0.19 microgram/ml (MIC80: 0.02 microgram/ml), and clarithromicin were <0.01-50 microgram/ml (MIC80: 0.04 microgram/ml). Amoxicillin resistant strain was not observed.