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Mycoplasma pneumoniae is one of the common pathogens of the community-acquired pneumonia in adults and children. Macrolide antibiotics are considered to be the first-choice drug for M. pneumoniae infections. However, macrolide-resistant M. pneumoniae was first detected from Japanese pediatric patients in 2000,and it has been increasing over the past decade. On the other hand, the Immunocard Mycoplasma IgM test is widely used as a rapid and easy diagnostic method for M. pneumoniae pneumonia, but false-positive or false-negative cases have been reported in adults. Therefore new methods have been developed recently. Using the LAMP assay, the results are available rapidly and accurately. We report herein on two cases of M. pneumoniae bronchopneumonia in which the LAMP assay was useful in the diagnosis and treatment.

For the purpose of nationwide surveillance of the antimicrobial susceptibility of bacterial respiratory pathogens collected from patients in Japan, the Japanese Society of Chemotherapy conducted a third year of nationwide surveillance during the period from January to April 2008. A total of 1,097 strains were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections. Susceptibility testing was evaluable with 987 strains (189 Staphylococcus aureus, 211 Streptococcus pneumoniae, 6 Streptococcus pyogenes, 187 Haemophilus influenzae, 106 Moraxella catarrhalis, 126 Klebsiella pneumoniae, and 162 Pseudomonas aeruginosa). A total of 44 antibacterial agents, including 26 β-lactams (four penicillins, three penicillins in combination with β-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), three aminoglycosides, four macrolides (including a ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standard Institute (CLSI). The incidence of methicillin-resistant S. aureus (MRSA) was as high as 59.8%, and those of penicillin-intermediate and penicillin-resistant S. pneumoniae (PISP and PRSP) were 35.5 and 11.8%, respectively. Among H. influenzae, 13.9% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant (BLNAI), 26.7% to be β-lactamase-non-producing ABPC-resistant (BLNAR), and 5.3% to be β-lactamase-producing ABPC-resistant (BLPAR) strains. A high frequency (76.5%) of β-lactamase-producing strains was suspected in Moraxella catarrhalis isolates. Four (3.2%) extended-spectrum β-lactamase-producing K. pneumoniae were found among 126 strains. Four isolates (2.5%) of P. aeruginosa were found to be metallo β-lactamase-producing strains, including three (1.9%) suspected multidrug-resistant strains showing resistance to imipenem, amikacin, and ciprofloxacin. Continual national surveillance of the antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.

Objectives: The aim of this study was to evaluate the dissemination of metallo-beta-lactamase (MBL)-encoding genes among multidrug-resistant (MDR) Pseudomonas aeruginosa isolates recovered from major hospitals in the Hiroshima region., Methods: During July to December from 2004 to 2006, a surveillance of eight major hospitals in the Hiroshima region identified 387 non-duplicate isolates resistant to imipenem (MIC >or= 16 mg/L). They were screened for resistance to amikacin (MIC >or= 64 mg/L) and ciprofloxacin (MIC >or= 4 mg/L) and MBL-encoding genes. The structure of the variable regions of the integrons was determined using PCR mapping. Clonality was assessed using PFGE and multilocus sequence typing (MLST)., Results: The frequency of MBL-positive isolates in MDR P. aeruginosa isolates significantly increased from 42.3% in 2004 to 81.4% in 2006. Most of the MBL-positive isolates produced IMP-1 followed by VIM-2. The bla(IMP-1) and bla(VIM-2) genes were present in class 1 integrons. Characterization of the variable regions of the integron showed the presence of six different gene cassette arrays in bla(IMP-1) cassettes and a single array in bla(VIM-2) cassettes. The IMP-1 producers belonged to two clonal lineages using PFGE and MLST analyses and the integron variations correlated well with the clonal complexes. Among them, strains positive for a newly identified In113-derived bla(IMP-1) gene cassette array were most widely distributed in Hiroshima., Conclusions: This study shows a dramatic increase in MBL genes, primarily bla(IMP-1), in MDR P. aeruginosa isolates in Hiroshima during these 3 years. In addition, MDR P. aeruginosa with the newly discovered In113-derived bla(IMP-1) gene cassette array appears to be clonally expanding.

To characterize the PK/PD of biapenem (BIPM) in critically ill patients under continuous venovenous hemodiafiltration (CVVHDF), we conducted a prospective, open-label study in nine adult CVVHDF patients with acute renal failure at the Critical Care Medical Center, Hiroshima Prefectural Hospital. Plasma and filtrate samples were obtained at six time points. The concentrations of BIPM in plasma and filtrate were determined by HPLC. PK parameters were analyzed using Monte Carlo simulation with MIC data. BIPM concentrations in the plasma and CVVHDF filtrate peaked at the end of infusion, and the values were similar. The drug clearance by CVVHDF and non-CVVHDF was 1.28 +/- 0.14 and 9.05 +/- 4.05 L/h, respectively. Monte Carlo simulation showed that the more administration times, there were the higher the probability. In conclusion, a dosing regimen of 300 mg BIPM q8h had a higher probability of therapeutic efficacy than q12h in patients with severe sepsis under CVVHDF.

Pseudomonas aeruginosa showing resistance to imipenem were found in 100 of 1,058 strains (9.5%) from six hospitals (a-f) in Hiroshima City, Japan. Of the 100 strains, 14 (14%) were double disk synergy test positive using sodium mercaptoacetic acid disks, and 18 (18%) were bla(IMP-1) or bla(VIM-2) allele positive by polymerase chain reaction (PCR). Among 100 imipenem-resistant strains, 32 were categorized into multi-drug resistant strains, in which 13 were positive for the metallo-beta-lactamase gene. Fifty-one strains (51%) among the 100 imipenem-resistant strains had elevated RND efflux pump activity against levofloxacin. But only 6 of 51 strains were classified as multi-drug resistant strains. The pulsed field gel electrophoresis analysis of the Spe I-digested DNA from the 100 isolates suggested not only clonal spread but spread of heterogeneous clones started to contribute to the prevalence of metallo-beta-lactamase producing P. aeruginosa strains in Japanese hospitals.

A total of 18,639 clinical isolates in 19 species collected from 77 centers during 2004 in Japan were tested for their susceptibility to fluoroquinolones (FQs) and other selected antibiotics. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae showed a high susceptible rate against FQs. The isolation rate of beta lactamase non-producing ampicillin-resistant H. influenzae was approximately three times as large as those of western countries. Most strains of Enterobacteriaceae were also susceptible to FQs. The resistance rate of Escherichia coli against FQs has however been rapidly increasing so far as we surveyed since 1994. The FQs-resistant rate in methicillin-resistant Staphylococcus aureus (MRSA) showed approximately 90% except for 36%. of sitafloxacin while FQs-resistant rate in methicillin-susceptible S. aureus (MSSA) was around 5%. The FQs-resistant rate of methicillin-resistant coagulase negative Staphylococci (MRCNS) was also higher than that of methicillin-susceptible coagulase negative Staphylococci (MSCNS), however, it was lower than that of MRSA. In Pseudomonas aeruginosa clinical isolates, 32-34% from UTI and 15-19% of from RTI was resistant to FQs. Acinetobacter spp. showed a high susceptibility to FQs. Although FQs-resistant Neisseria gonorrhoeae have not been increased in western countries, it is remarkably high in Japan. In this survey, isolates of approximately 85% was resistant to FQs.

We tested the drug susceptibility to 8 anti-pseudomonal agents of 97 strains of Pseudomonas aeruginosa isolated from urine between January 1998 and May 2004. The results were as follows. 1. Antimicrobial activity was, in order of superiority to biapenem (BIPM), meropenem (MEPM), ciprofloxacin (CPFX), imipenem (IPM), pazufloxacin (PZFX), amikacin (AMK), ceftazidime (CAZ), piperacillin (PIPC). 2. The resistance rate (intermediate+resistance) to carbapenem drugs was 10.3% for BIPM and MEPM, and 13.4% for IPM. Many of the IPM-resistant strains showed crossover resistance with BIPM and MEPM. 3. The resistance rate (intermediate+resistance) to fluoroquinolone drugs was 23.7% for CPFX and 20.6% for PZFX. 4. One strain showed simultaneous resistance to IPM = 16 microg/mL, CPFX = 4 microg/mL, and AMK = 32 microg/mL, and produced IMP-1 metallo-beta-lactamase. Susceptibility of P. aeruginosa isolated from urine developed resistance to fluoroquinolone drugs. It is important to promote appropriate use of antimicrobial agents and continue to survey emerging resistance in the clinical isolates.

To evaluate the resistance for major oral antimicrobial agents, mainly new quinolones, we carried out a drug susceptibility surveillance of 3,050 strains of 11 microbial species clinically isolated at 8 institutions such as general hospitals and examination centers in Hiroshima city. 10 antimicrobial agents were used: 3 new quinolone drugs, 5 beta-lactam drugs, minocycline and clarithromycin. Among Gram-positive bacteria, methicillin resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis showed low susceptibility to the new quinolone drugs, while methicillin susceptible Staphylococcus aureus (MSSA) and Streptococcus pneumoniae were highly sensitive to these drugs. Among Gram-negative bacteria, Pseudomonas aeruginosa showed high resistance for the new quinolone drugs, but enteric bacteria and Haemophilus influenzae did not show marked resistance, maintaining almost good sensitivity to these drugs. To reduce the appearance of resistant bacteria, appropriate antimicrobial agents should be selected. Drug susceptibility surveillance in the community will be also important in the future.

During the period of January 1992 and August 1995, 75 strains of Pseudomonas aeruginosa were isolated from sputum at the Hiroshima Prefectural Hiroshima Hospital. The antimicrobial susceptibilities and serotypes of those strains were investigated. The results are summarized as follows: 1. The analyses of antimicrobial susceptibilities revealed that meropenem (MEPM) was the most active among the carbapenems tested against those P. aeruginosa strains with MIC of < or = 6.25 micrograms/ml. All of the strains were thus found to be susceptible to MEPM, while 9 strains out of 75 (12%) were resistant to imipenem showing cross-resistance to biapenem. 2. The activities of the beta-lactams other than carbapenems were found to be the order of cefozopran > or = ceftazidime > aztreonam > piperacillin with MIC50 and MIC90 ranging of 3.13-6.25 micrograms/ml and 25- > or = 100 micrograms/ml, respectively. 3. Among aminoglycosides tested, 3 strains (4.0%) of the strains showed resistance to amikacin, however none of them were resistant to tobramycin. 4. Distribution of serotypes among the strains was; type G 22.7%, type M 21.3%, type A 16.0%, type B 13.3% and type E 8.0%. Strains of types M and E showed multiple resistance to beta-lactams except carbapenems. As documented in this study, the frequency of isolation of beta-lactam-resistant P. aeruginosa (including carbapenem-resistant) is steadily increasing. Continuous surveillance of antimicrobial susceptibility among clinically isolated P. aeruginosa seems to be necessary.

Norfloxacin (NFLX), a new quinolone antibacterial agent, was investigated for its antibacterial activity and clinical efficacy on respiratory tract infections. The results obtained are summarized as follows: 1. Antibacterial activities were evaluated against 127 strains of various bacteria isolated from clinical sources. MIC80's of this drug were: against Staphylococcus aureus and Streptococcus pyogenes 1.56 micrograms/ml; Haemophilus influenzae 0.05 microgram/ml or less; and Klebsiella sp. and Enterobacter sp. 0.10 microgram/ml. These antibacterial activities were superior to these of ampicillin and cephalexin, except against S. pyogenes. 2. Clinical responses to NFLX in a total of 32 cases with respiratory tract infections were excellent in 9 cases, good in 12, fair in 9, poor in 2, with an efficacy rate of 65.6%. Neither adverse reactions nor abnormalities of laboratory test results were observed.

Susceptibilities in various types of clinical isolates to cefmetazole (CMZ) were determined by the disk method and the serial agar dilution method for MIC measurement. CMZ showed high antibacterial activity for all Gram-positive cocci except E. faecalis, and for H. influenzae, E. coli, Klebsiella sp. and Proteus sp.. CMZ was administered on 33 patients with infections, mainly biliary tract infections, in the field of internal medicine. The clinical efficacy of the drug was 86.7% for infections of the biliary tract, 80.0% for respiratory tract infections, 100% for urinary tract infections and 76.7% for all cases. There were no adverse reaction or changes in laboratory findings caused by CMZ in any of the patients.