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Neisseria gonorrhoeae is one of the most important pathogens causing sexually transmitted infection, and strains that are resistant to several antimicrobials are increasing. To investigate the trends of antimicrobial susceptibility among N. gonorrhoeae strains isolated from male patients with urethritis, a Japanese surveillance committee conducted the first nationwide surveillance. The urethral discharge was collected from male patients with urethritis at 51 medical facilities from April 2009 to October 2010. Of the 156 specimens, 83 N. gonorrhoeae strains were tested for susceptibility to 18 antimicrobial agents. The prevalence of β-lactamase-producing strains and chromosomally mediated resistant strains were 7.2 % and 16.5 %, respectively. None of the strains was resistant to ceftriaxone, but the minimum inhibitory concentration (MIC) of ceftriaxone for 7 strains (8.4 %) was 0.125 μg/ml. One strain was resistant to cefixime (MIC 0.5 μg/ml). The MICs of fluoroquinolones, such as ciprofloxacin, levofloxacin, and tosufloxacin, showed a bimodal distribution. The MIC of sitafloxacin was lower than those of the three fluoroquinolones listed here, and it was found that the antimicrobial activity of sitafloxacin was stronger than that of the fluoroquinolones. The MIC of azithromycin in 2 strains was 2 μg/ml, but no high-level resistance to macrolides was detected. [ABSTRACT FROM AUTHOR]

We previously conducted nationwide surveillance of Streptococcus pneumoniae in 2000-2001 (period 1) and 2004 (period 2) and reported the findings. Subsequent surveillance surveys conducted in 2007 (period 3) and 2010 (period 4) are now reported. Bacterial strains were clinically isolated from children with meningitis, sepsis, and respiratory tract infections at 27 hospitals participating in the Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease. Twenty-one drugs were investigated for 283 isolated strains in period 3, and 24 drugs were investigated for 459 strains in period 4. In period 3, 43.8 % of strains were penicillin-susceptible S. pneumoniae (PSSP), 52.3 % were penicillin-intermediate S. pneumoniae (PISP), and 3.9 % were penicillin-resistant S. pneumoniae (PRSP). In period 4, the percentages were PSSP 23.1 %, PISP 49.9 %, and PRSP 27.0 %. The resistance rates were 56.2 % and 76.9 %, respectively. Drug sensitivity was best with panipenem, at a minimum inhibitory concentration (MIC) ≤0.063 μg/ml in period 3, and with tebipenem (MIC ≤ 0.063 μg/ml) in period 4. Patients' background factors related to increased bacterial resistance were investigated, and significant differences were found depending on whether a child had siblings ( P = 0.0056) or was a daycare center attendee ( P = 0.0195) in period 3, and age category ( P = 0.0256) in period 4. No factors were common to both periods 3 and 4. Pneumococcus is a major causative organism of pediatric infectious disease, and we plan to continue conducting surveillance and providing information in the future. [ABSTRACT FROM AUTHOR]

The Japanese surveillance committee conducted the first nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for female acute uncomplicated cystitis at 43 hospitals throughout Japan from April 2009 to November 2010. In this study, the causative bacteria ( Escherichia coli and Staphylococcus saprophyticus) and their susceptibility to various antimicrobial agents were investigated by isolation and culturing of bacteria from urine samples. In total, 387 strains were isolated from 461 patients, including E. coli ( n = 301, 77.8 %), S. saprophyticus ( n = 20, 5.2 %), Klebsiella pneumoniae ( n = 13, 3.4 %), and Enterococcus faecalis ( n = 11, 2.8 %). S. saprophyticus was significantly more common in premenopausal women ( P = 0.00095). The minimum inhibitory concentrations of 19 antibacterial agents used for these strains were determined according to the Clinical and Laboratory Standards Institute manual. At least 87 % of E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, and 100 % of S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant E. coli strains and extended-spectrum β-lactamase (ESBL)-producing E. coli strains were 13.3 % and 4.7 %, respectively. It is important to confirm the susceptibility of causative bacteria for optimal antimicrobial therapy, and empiric antimicrobial agents should be selected by considering patient characteristics and other factors. However, the number of isolates of fluoroquinolone-resistant or ESBL-producing strains in gram-negative bacilli may be increasing in patients with urinary tract infections (UTIs) in Japan. Therefore, these data present important information for the proper treatment of UTIs and will serve as a useful reference for future surveillance studies. [ABSTRACT FROM AUTHOR]

The Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease conducted national surveillance for Haemophilus influenzae in 2007 (phase 3) and 2010 (phase 4), following the previous surveillance conducted from 2000 to 2001 (phase 1) and in 2004 (phase 2). We examined the antimicrobial susceptibility for H. influenzae derived from clinical specimens of pediatric patients collected nationwide from 27 institutions during phases 3 (386 strains) and 4 (484 strains). The frequency of β-lactamase-nonproducing ampicillin (ABPC)-resistant (BLNAR) strains, which rapidly increased from 11.4 % in phase 1 to 43.4 % in phase 2, has gradually decreased from 38.3 % in phase 3 to 37.8 % in phase 4. In contrast, On the other hand, the frequency of β-lactamase-producing strains, which continuously decreased from 8.3 % in phase 1 to 4.4 % in phase 3, has increased to 8.7 % in phase 4. Prevalence of β-lactamase-producing clavulanic acid/amoxicillin-resistant (BLPACR) strains, especially, has increased from 1.6 % in phase 3 to 4.8 % in phase 4. The oral antimicrobial agents with the lowest MIC were levofloxacin in both phases, and tosufloxacin in phase 4 (≤0.063 μg/ml), whereas for intravenous use the corresponding agent was tazobactam/piperacillin in both phases (0.125 μg/ml). There was no increase in the MIC of most β-lactams between phase 3 and phase 4. In relationship to sex, age, presence of siblings, attendance at a daycare center, siblings' attendance at a daycare center, and prior administration of antimicrobial agents within 1 month, the frequency of β-lactamase-nonproducing ABPC-intermediately resistant (BLNAI) strains + BLNAR strains was high ( P = 0.005) in cases with prior administration of antimicrobial agents in phase 3. [ABSTRACT FROM AUTHOR]

Arbekacin (ABK) is an aminoglycoside and widely used in Japan for treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). Although, ABK has concentration-dependent antibacterial activity, the peak serum concentration ( C) of ABK has not yet been fully investigated as an indicator of the efficacy of ABK. The present study was conducted in patients admitted to hospitals affiliated with the ABK Dose Finding Study Group, between October 2008 and June 2011, who had pneumonia or sepsis, the cause of which was identified or suspected to be MRSA. The initial target C was set at 15-20 μg/mL and therapeutic drug monitoring was conducted. Then the relationship between serum concentration and efficacy/safety of ABK was prospectively examined to obtain sufficient clinical efficacy. In total, 89 patients from 11 clinical sites in Japan were enrolled and 29 of these patients were subjected to efficacy analysis. The mean initial dose and C were 306.9 mg/day and 16.2 μg/mL, respectively. The efficacy rate was 95 % (19/20 patients) at 5-6 mg/kg or higher, 87.5 % (7/8) for sepsis and 90.5 % (19/21) for pneumonia, and the overall efficacy rate was 89.7 % (26/29). There was no increase in the incidence of adverse events. In conclusion, we recommend the initial dose of ABK at 5-6 mg/kg or higher and the dosage regimen should be adjusted to achieve C at 10-15 μg/mL or higher in the treatment of patients with pneumonia or sepsis caused by MRSA. This strategy would surely achieve low incidence of adverse events while obtaining high clinical efficacy. [ABSTRACT FROM AUTHOR]

To investigate the trends of antimicrobial resistance in pathogens isolated from surgical site infections (SSI), a Japanese surveillance committee conducted the first nationwide survey. Seven main organisms were collected from SSI at 27 medical centers in 2010 and were shipped to a central laboratory for antimicrobial susceptibility testing. A total of 702 isolates from 586 patients with SSI were included. Staphylococcus aureus (20.4 %) and Enterococcus faecalis (19.5 %) were the most common isolates, followed by Pseudomonas aeruginosa (15.4 %) and Bacteroides fragilis group (15.4 %). Methicillin-resistant S. aureus among S. aureus was 72.0 %. Vancomycin MIC 2 μg/ml strains accounted for 9.7 %. In Escherichia coli, 11 of 95 strains produced extended-spectrum β-lactamase ( Klebsiella pneumoniae, 0/53 strains). Of E. coli strains, 8.4 % were resistant to ceftazidime (CAZ) and 26.3 % to ciprofloxacin (CPFX). No P. aeruginosa strains produced metallo-β-lactamase. In P. aeruginosa, the resistance rates were 7.4 % to tazobactam/piperacillin (TAZ/PIPC), 10.2 % to imipenem (IPM), 2.8 % to meropenem, cefepime, and CPFX, and 0 % to gentamicin. In the B. fragilis group, the rates were 28.6 % to clindamycin, 5.7 % to cefmetazole, 2.9 % to TAZ/PIPC and IPM, and 0 % to metronidazole ( Bacteroides thetaiotaomicron; 59.1, 36.4, 0, 0, 0 %). MIC of P. aeruginosa isolated 15 days or later after surgery rose in TAZ/PIPC, CAZ, IPM, and CPFX. In patients with American Society of Anesthesiologists (ASA) score ≥3, the resistance rates of P. aeruginosa to TAZ/PIPC and CAZ were higher than in patients with ASA ≤2. The data obtained in this study revealed the trend of the spread of resistance among common species that cause SSI. Timing of isolation from surgery and the patient's physical status affected the selection of resistant organisms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Bacterial meningitis is a serious problem in pediatric clinics and, therefore, needs urgent and empirical chemotherapy. We investigated 1,116 cases of empirical chemotherapy of patients aged older than 4 months from 1997 through 2008 by sending questionnaires. A single antibiotic treatment was carried out in less than 30% of the cases throughout the years, whereas the combination of two antibiotics had been practiced in more than 70% of the cases. The main antibiotics used were cephalosporins, carbapenems, and ampicillin. Combinatory use of ampicillin and cephalosporin was carried out in 74.7-82.7% of cases in 1997-2000, but sharply declined thereafter to 0-13.8% in 2004-2008. However, the combination of carbapenem and cephalosporin compensated for the decline, increasing from 3.8-6.6% in 1998-1999 to 79.5-89.9% in 2005-2008. The breakdown in the use of cephalosporins, carbapenems, and ampicillin in two-drug combinatory therapy was as follows. (i) Use of cefotaxime was 61.8-75.3% in 1997-2001, but decreased to nearly 50%, equivalent to the level of ceftriaxone use in 2003-2008. (ii) Use of ampicillin dropped from 74.7-92.3% in 1997-2000 to 4.6% in 2008, and this decreased level was compensated for by the use of carbapenems. Overall, combinatory chemotherapy of the third-generation cephalosporins and carbapenems seems to be practical. The discussion in this report includes the difference between Japan and the United States in the prevalence of the causative agents and the use of antibiotics. These studies provide information on trends in the treatment of children's meningitis in Japan and will be useful for the design of future empirical chemotherapy. [ABSTRACT FROM AUTHOR]

Limited use of linezolid for treating methicillin-resistant Staphylococcus aureus (MRSA) infection was approved in Japan in 2006. We report here the status of linezolid-resistant MRSAs in Japan. Eleven linezolid-resistant clinical isolates from 11 patients at six hospitals were collected from 2006 through 2008. The minimal inhibitory concentration (MIC) of linezolid in these strains varied from 8 to 64 μg/ml. All strains had at least one G2576T mutation in the chromosomal gene(s) encoding domain V of the 23S ribosomal RNA (rRNA). Chromosomal DNA encoding five copies of the domain V region was analyzed by polymerase chain reaction (PCR). Strains with the linezolid MICs of 64, 32, 16, and 8 μg/ml had the G2576T mutation(s) in four, three (or four), two, and one copy of the 23S rRNA genes, respectively. These results suggest that the level of linezolid resistance seems to be roughly correlated with the number of mutations in the genes encoding 23S rRNA. DNA samples from all 11 strains were subjected to pulsed-field gel electrophoresis and were classified into seven independent clones having >92% identity. Among the 11 patients, five had been treated with linezolid and the remainder, in two hospitals, had no history of prior linezolid use. The results suggested possible nosocomial infections by linezolid-resistant MRSA. [ABSTRACT FROM AUTHOR]

This study was conducted by the Japanese Society of Chemotherapy and is the first nationwide study on bacterial pathogens isolated from patients with urinary tract infections at 28 hospitals throughout Japan between January 2008 and June 2008. A total of 688 bacterial strains were isolated from adult patients with urinary tract infections. The strains investigated in this study are as follows: Enterococcus faecalis ( n = 140), Escherichia coli ( n = 255), Klebsiella pneumoniae ( n = 93), Proteus mirabilis ( n = 42), Serratia marcescens ( n = 44), and Pseudomonas aeruginosa ( n = 114). The minimum inhibitory concentrations of 39 antibacterial agents used for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. All Enterococcus faecalis strains were susceptible to ampicillin and vancomycin. Although a majority of the E. faecalis strains were susceptible to linezolid, 11 strains (7.8%) were found to be intermediately resistant. The proportions of fluoroquinolone-resistant Enterococcus faecalis, Escherichia coli, Proteus mirabilis, and S. marcescens strains were 35.7%, 29.3%, 18.3%, and 15.2%, respectively. The proportions of E. coli, P. mirabilis, K. pneumoniae, and S. marcescens strains producing extended-spectrum β-lactamase were 5.1%, 11.9%, 0%, and 0%, respectively. The proportions of Pseudomonas aeruginosa strains resistant to carbapenems, aminoglycosides, and fluoroquinolones were 9.2%, 4.4%, and 34.8%, respectively, and among them, 2 strains (1.8%) were found to be multidrug resistant. These data present important information for the proper treatment of urinary tract infections and will serve as a useful reference for periodic surveillance studies in the future. [ABSTRACT FROM AUTHOR]

In 2008 we isolated methicillin-resistant Staphylococcus aureus (MRSA) from an 11-month-old Japanese girl who lived in Saitama, Japan, and suffered from cellulitis of the lower thigh and sepsis. The MRSA (strain NN47) belonged to multilocus sequence type (ST) 8 and exhibited spa363 (t024), agr1, staphylococcal cassette chromosome mec (SCC mec) type IVa, and coagulase type III. It was positive for Panton–Valentine leukocidin (PVL) and the arginine catabolic mobile element (ACME). Pulsed-field gel electrophoresis (PFGE) demonstrated that the MRSA was the USA300 clone, which is the predominant community-acquired MRSA (CA-MRSA) in the US. Strain NN47 was divergent, in terms of the spa type and patterns of PFGE and plasmids, from the USA300-0114 type strain or USA300 strain NN36, previously isolated from a visitor (Indian girl) from the US. Strain NN47 was resistant to erythromycin, in addition to β-lactam agents (e.g., oxacillin). These data demonstrate the first emergence of the USA300 clone in Japanese children who have never been abroad and have had no contact with foreigners (and therefore, the first USA300 spread in Japan), and also emergence of multiple divergent strains of the USA300 clone in Japan. Because the USA300 clone is highly transmissible and virulent, surveillance of the USA300 clone is needed. [ABSTRACT FROM AUTHOR]

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), which often produces Panton-Valentine leucocidin (PVL), has emerged worldwide as a life-threatening pathogen. Herein, we describe molecular characteristics of MRSA isolated from abdominal cellulitis in a 7-year-old Japanese boy. This MRSA was PVL-positive and belonged to the Taiwanese multiple drug-resistant CA-MRSA clone with the genotype of ST59, staphylococcal cassette chromosome mec (SCC mec) VII (SCC mecV, according to recent reclassification), agr1a (a novel agr1 subtype), and SaPI (which carried seb1, a newly designated variant seb gene). This study demonstrates the first isolation of the Taiwanese PVL-positive ST59 MRSA clone in Japan. The data also demonstrate novel subtypes in agr1 and seb and suggest that a combination of agr1a, seb1, and PVL could contribute to cellulitis (and its recurrence). Recently, a variety of PVL-positive MRSA clones are accumulating in Japan. [ABSTRACT FROM AUTHOR]

Abstract  We evaluated the β-lactamase-producing ability and resistance to 20 antibacterial agents of 448 clinically isolated strains of Haemophilus influenzae accumulated from October 2000 to July 2001 (phase 1) and of 376 different strains accumulated from January to June 2004 (phase 2), from institutions that participated in a nationwide Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease. Between phase 1 and phase 2 the proportion of β-lactamase-negative ampicillin (ABPC)-susceptible (BLNAS) strains declined from 62.9% to 34.3%; the proportions of β-lactamase-positive ABPC-resistant (BLPAR) strains were 8.3% and 6.4% in phases 1 and 2, but the proportion of β-lactamase-negative ABPC-resistant (BLNAR) strains increased from 28.8% in phase 1 to 59.3% in phase 2. Comparison of the MIC90 values of the antibacterial agents for H. influenzae in phase 1 and phase 2 showed that cefcapene, cefpodoxime, ceftriaxone, panipenem, and clarithromycin kept the same level, while cefdinir, faropenem, and rokitamycin showed 2-fold to 8-fold decreases. With the exception of the above antibiotics, all of the other antibacterial agents tested showed 2-fold to 4-fold increases. The MIC90 values of the β-lactam drugs for BLNAR were 2-fold to 32-fold higher than the values for BLNAS. The proportion of BLNAR H. influenzae strains rose dramatically over the 3 years between phases 1 and 2. In relation to age, prior administration of antibacterial agents, and attendance at a day nursery as background factors, no significant differences between BLNAS and BLNAR were detected in phase 1. In the phase 2 survey, the proportion of BLNAR strains showed significant differences between children under 3 years and those aged 3 years or more, and there were also significant differences according to whether antibacterial agents, especially β-lactams, had been administered previously. No significant difference was found in resistant bacteria according to whether or not a child had attended a day nursery. [ABSTRACT FROM AUTHOR]

Abstract  We evaluated the resistance to 20 different antibacterial agents of 362 clinically isolated strains of Streptococcus pneumoniae accumulated from October 2000 to July 2001 (phase 1) and of 332 different strains accumulated from January to June 2004 (phase 2), from institutions throughout Japan that participated in the surveys carried out by the Drug-Resistant Pathogen Surveillance Group in Pediatric Infectious Disease. In phase 1, the proportions of penicillin-sensitive S. pneumoniae (PSSP), penicillin-insensitive S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP) were 35.4%, 34.8%, and 29.8%, respectively, and the proportions were almost the same in phase 2: 33.1%, 37.0%, and 29.8%, respectively. Comparison of the MIC90 values of the antibacterial agents for PRSP in phase 1 and phase 2 revealed that these values for cefditoren, cefpodoxime, cefdinir, faropenem, ceftriaxone, cefotaxime, meropenem, and vancomycin increased by twofold to fourfold during the 3 years between phase 1 and phase 2. However the MIC90 of rokitamycin increased more than fourfold. The proportion of S. pneumoniae that were PISP + PRSP remained almost constant over the 3 years between phase 1 and phase 2. The background factors of patient age, previous administration of antibacterial agents, and attendance at a day nursery were examined; we found that in phase 1, the proportion of PISP + PRSP was significantly higher than that of PSSP in patients under 4 years old who had previously received antibacterial agents, but no significant differences were found in any of these background factors in the phase 2 survey. No significant difference was found in the proportions of penicillin-resistant bacteria according to whether or not the child had attended a day nursery. [ABSTRACT FROM AUTHOR]

Abstract  It was reported that some methicillin-resistant Staphylococcus aureus (MRSA) show resistance to vancomycin (VCM) and β-lactam antibiotics; thus, they are termed β-lactam antibiotic-induced VCM-resistant MRSA (BIVR). The VCM resistance of MRSA is induced by the administration of β-lactam antibiotics, but this phenomenon can be difficult to detect in the clinical laboratory. We detected the BIVR strain in a 64-year-old man who had had a ventilator tube inserted directly into the windpipe during long-term VCM therapy. The patient was diagnosed with MRSA pneumonia and septicemia on July 5, 2007, and sulbactam/ampicillin (SBT/ABPC) was administered for 5 days. However, the fever recurred, and administration of VCM was resumed for 7 days from July 19. Fever developed again, and VCM was administered again for 14 days from September 30. BIVR and VCM-low-sensitive MRSA were isolated from blood on October 18 and 22, although the VCM trough concentration was 10.2 µg/ml. On October 27, we changed to a combination of fosfomycin (FOM) and arbekacin (ABK), and thereafter the fever quickly decreased and the clinical symptoms abated. We isolated five MRSA strains from the blood of the patient, three strains of VCM-sensitive MRSA, one strain of BIVR, and one strain of a VCM-low-sensitive MRSA. The DNA band patterns determined by pulsed-field gel electrophoresis were completely identical except for the VCM-low-sensitive MRSA, which was missing one band. Furthermore, the VCM-low-sensitive MRSA became sensitive to β-lactam antibiotics. Our results indicate the possibility that long-term VCM therapy is one of the factors that allow BIVR or VCM-low-sensitive MRSA to emerge, and this allows VCM therapy for MRSA to fail. [ABSTRACT FROM AUTHOR]

Abstract  For the purpose of a nationwide surveillance of the antimicrobial susceptibility of bacterial respiratory pathogens in patients in Japan, the Japanese Society of Chemotherapy conducted their second year survey, during the period from January to August, 2007. A total of 1178 strains were collected from clinical specimens obtained from adult patients with well-diagnosed respiratory tract infections. Susceptibility testing was evaluable for 1108 strains (226 Staphylococcus aureus, 257 Streptococcus pneumoniae, 6 Streptococcus pyogenes, 206 Haemophilus influenzae, 120 Moraxella catarrhalis, 122 Klebsiella pneumoniae, and 171 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 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 Standards Institute (CLSI). The incidence of methicillinresistant Staphylococcus aureus (MRSA) was high, at 59.7%, and the incidences of penicillin-intermediateresistant and -resistant Streptococcus pneumoniae (PISP and PRSP) were 30.4% and 5.1%, respectively. Among Haemophilus influenzae strains, 19.9% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately-resistant (BLNAI), 29.1% to be β-lactamasenon-producing ABPC-resistant (BLNAR), and 6.7% to be β-lactamase-producing ABPC-resistant (BLPAR) strains. Extended-spectrum β-lactamase-producing Klebsiella pneumoniae was not isolated. Two isolates (1.2%) of Pseudomonas aeruginosa were found to be metallo-β-lactamase-producing strains, including one (0.6%) suspected multidrug-resistant strain showing resistance to imipenem, amikacin, and ciprofloxacin. These data will be a useful reference for future periodic surveillance studies and for investigations to control resistant infections as well. Continued surveillance is required to prevent the further spread of these antimicrobial resistances. [ABSTRACT FROM AUTHOR]

Abstract  The Japanese Society of Chemotherapy (JSC) conducted the first nationwide surveillance of bacterial respiratory pathogens during the period from January to August 2006. With the cooperation of 32 medical institutions throughout Japan, a total of 924 strains belonging to seven clinically relevant bacterial species were collected from adult patients with well-diagnosed respiratory tract infections (RTIs). Antimicrobial susceptibility testing of the 887 evaluable strains (205 Staphylococcus aureus, 200 Streptococcus pneumoniae, 9 Streptococcus pyogenes, 165 Haemophilus influenzae, 91 Moraxella catarrhalis, 74 Klebsiella pneumoniae, and 143 Pseudomonas aeruginosa) to 42 antibacterial agents was conducted at the Central Laboratory of the Research Center for Anti-infective Drugs of the Kitasato Institute, according to recommendations issued by the Clinical and Laboratory Standards Institute (CLSI). The antibacterial agents employed were 25 β-lactams, three aminoglycosides, four macrolides (including one azalide and one ketolide), one lincosamide, one tetracycline, two glycopeptides, five fluoroquinolones, and one oxazolidinone. The incidence of methicillin-resistant S. aureus (MRSA) was 63.4%, and the incidences of penicillin-intermediately resistant S. pneumoniae (PISP) and penicillin-resistant S. pneumoniae (PRSP) were 35.0% and 4.0%, respectively. Among H. influenzae, 21.2% of the strains were found to be β-lactamase-nonproducing ampicillin (ABPC)-intermediately resistant (BLNAI), 29.1% to be β-lactamase-nonproducing ABPC-resistant (BLNAR), and 4.8% to be β-lactamaseproducing ABPC-resistant (BLPAR) strains. The incidence of extended-spectrum β-lactamase-producing K. pneumoniae was 2.7% (2 of 74 strains). Three (2.1%) of the 143 P. aeruginosa strains were found to be metallo-β-lactamaseproducing, including 1 (0.7%) multidrug-resistant strain. Through the nationwide surveillance, we obtained fundamental antimicrobial susceptibility data of clinically relevant bacterial pathogens in adult RTI to various antibacterial agents. These data will be a useful reference for future periodic surveillance studies, as well as for investigations to control antimicrobial-resistant pathogens. [ABSTRACT FROM AUTHOR]

Abstract  Some methicillin-resistant Staphylococcus aureus (MRSA) strains in which combinations of vancomycin (VCM) and β-lactam antibiotics show antagonism have recently emerged, and these strains are called β-lactaminduced VCM-resistant MRSA (BIVR). We examined whether various antibiotics exhibited an antagonistic effect with VCM when used against Mu3 and Fu10 (representative BIVR strains), using a simple agar disc method. Chloramphenicol, tetracyclines, macrolides, and lincosamides showed an antagonistic effect with VCM. We attempted to elucidate the antagonistic mechanism of a combination of VCM and minocycline (MINO) in BIVR strains. We determined the rates of autolysis, autolytic activities, and the change in morphology of Mu3 treated with a combination of VCM and MINO. We observed that Mu3 grown in a combination of VCM and MINO showed increasing rates of autolysis, and lower minimal bacteriolytic enzyme dose (MBD) values compared with Mu3 grown in VCM alone, but no cell wall thickening was observed. Taken together, these results suggest that cell wall thickening may not be essential in the increased resistance of BIVR strains. Our present data therefore suggest that these combination therapies of VCM with tetracyclines should be adopted with great care in order to prevent VCM treatment failure. [ABSTRACT FROM AUTHOR]

Abstract  HMRZ-86 was designed as a new chromogenic cephalosporin to detect extended-spectrum β-lactamases (ESBLs) and similar evolved β-lactamases, such as metallo-β-lactamases, derepressed AmpC, and extended oxacillinase. We report here our investigation of the kinetic parameters of several types of β-lactamases to show the enzymatic characteristics of HMRZ-86. The Michaelis constant (K m values of HMRZ-86 for ESBLs were twice to three and half times as high as those of nitrocefin, and the maximum velocity (Vmax) was one-fifth that of nitrocefin. The K m and Vmax of HMRZ-86 for AmpC were both smaller than those of nitrocefin. The kinetic parameters of HMRZ-86 for metallo β-lactamase (MBL) were very variable, depending on the type of buffer solution used and the concentration of zinc ions. For MBL, the K m values of HMRZ-86 were higher than those of nitrocefin, but the Vmax values were almost the same as those of nitrocefin. Although the chemical structure of HMRZ-86 is similar to that of nitrocefin, we think the enzymatic reactivities of the two entities for β-lactamases are very different. [ABSTRACT FROM AUTHOR]

Abstract  Human-origin intravenous immunoglobulin (IVIG) collected from healthy individuals was tested for its neutralizing activity against the hemolysin, toxic shock syndrome toxin-1 (TSST-1), and enterotoxins, produced by laboratory strains of methicillin-resistant Staphylococcus aureus (MRSA). The hemolytic activity of the culture supernatant against sheep red blood cells was reduced from 100% to 5.5% relative hemolysis in the presence of 0.156 mg protein/ml of IVIG. The maximum dilution endpoint of the culture supernatant for TSST-1-mediated latex aggregation was 32-fold. This level of TSST-1 activity was reduced to eightfold dilution by 0.78 mg protein/ml of IVIG, and the latex aggregation activity of undiluted TSST-1 in the culture supernatant was inhibited by 1.56 mg protein/ml of IVIG. Similarly, the enterotoxin A-mediated latex aggregation titer appeared to be a 320-fold dilution. This toxin activity was reduced to an 80-fold dilution and below a tenfold dilution by 0.049 through 0.78 and 1.56 mg protein/ml, respectively, of IVIG. These results show that IVIG has powerful neutralizing activity against hemolysin, TSST-1, and enterotoxin A. Therefore, IVIG may be useful for passive immunization therapy in patients suffering from diseases caused by MRSA exotoxins. [ABSTRACT FROM AUTHOR]

Abstract  Methicillin-resistant Staphylococcus aureus (MRSA) has been defined as S. aureus having the mecA gene or showing a minimum inhibitory concentration (MIC) of oxacillin higher than 4 mg/l. However, some clinical isolates are mecA-positive and oxacillin-susceptible. Therefore, we surveyed the occurrence of S. aureus having the mecA gene and an MIC of oxacillin of less than 2 mg/l (oxacillin-susceptible MRSA; OS-MRSA) in a total of 480 strains of S. aureus collected from 11 hospitals in different location in Japan isolated from 2003 through 2005. We found 6 strains matching the criteria for OS-MRSA. All 6 strains were staphylococcal cassette chromosome (SCC) mec-positive, without exception, and 4 strains showed the SCCmec type III-variant, which is unique in Japan. These OS-MRSAs were least resistant to oxacillin among the MRSAs tested and they were within the susceptible range to seven other β-lactam antibiotics tested. Thus, OS-MRSA may become a high-resistant MRSA upon the treatment of patients with β-lactam antibiotics. To characterize whether these OS-MRSAs were hospital-acquired or community-acquired MRSAs, we tested for the presence of the genes encoding toxins. Genes encoding hemolysin, exfoliative toxin, enterotoxin, toxic shock syndrome toxin-1, and Panton-Valentine leukocidin were found in 6, 4, 0, 0, and 0 strains, respectively. These results revealed that OS-MRSAs could be classified as a new type of MRSA that exhibits properties distinguishable from either hospital- or community-acquired MRSA. Coagulase typing of the OS-MRSAs supported the above conclusion. In this study, the occurrence of OS-MRSA at a certain frequency was noted; precautions are called for in the classification of oxacillin-resistant S. aureus and in the treatment of OS-MRSA infection. [ABSTRACT FROM AUTHOR]

We report here an outbreak of β-lactam-induced vancomycin-resistant methicillin-resistant Staphylococcus aureus (MRSA; BIVR) at one of the Cancer-Institute-affiliated hospitals in Tokyo. We examined a total of 500 strains (100 per year) of clinically isolated MRSA from 1998 to 2002. The detection rates of BIVR in the years 1998, 1999, 2000, 2001, and 2002 were 10%, 9%, 49%, 15%, and 19%, respectively. To investigate the cause of the high incidence of BIVR detection in the year 2000, we carried out pulsed-field gel electrophoresis (PFGE) of the SmaI-digested chromosomal DNA of BIVR and MRSA. The results showed that 96% of the BIVR strains isolated in 2000 were classified as an identical DNA type “A”, while only 47% of the MRSA strains were classified as this type. We concluded, based on these results, that this hospital had a nosocomial infection of BIVR in the year 2000. An important message given by this study would be that nosocomial BIVR infection could occur in any hospital where MRSA infection is treated with vancomycin and β-lactam antibiotics. [ABSTRACT FROM AUTHOR]

We have previously shown that hydroxy-imino-aminothiazol at the 7-position was important to the antimethicillin-resistant Staphylococcus aureus (MRSA) activity of isocephems. In this study, in order to optimize the linkage style at the C-3 position and cephem backbones, 9 compounds were prepared by combining 3 cephem backbones with 3 different linkage styles at the C-3 position. The compounds had thiopyridinum- N-carbamoylmethyl fixed as the C-3 side chain and hydroxy-imino-aminothiazol at the C-7 position on the cephem backbones. The cephem backbones tested were cephem, isocephem, and 2-oxaisocephem. The linkage styles at the C-3 position were methylene, vinyl, and propylene linkages. Clinically isolated strains of MRSA were used to determine the MICs of the 9 compounds with different combinations of cephem backbones and linkage styles at the C-3 position. The compounds with vinyl linkage styles were more active against MRSA than the compounds with other linkage styles at the C-3 position, and among the cephem backbones with vinyl linkages, the cephem backbone exhibited the strongest anti-MRSA activity. MICs for cephem (1-S-V), isocephem (2-S-V), and 2-oxaisocephem (2-O-V) compounds were 1.56, 6.25, and 12.5 μg/mL, respectively, and the 1-S-V compound had the highest affinity to penicillin-binding protein 2′ among the 3 compounds with the vinyl-style linkage. Thus, the combination of cephem and a vinyl linkage at the C-3 position was shown to be optimal for anti-MRSA activity. [ABSTRACT FROM AUTHOR]

Abstract  We report a 54-year-old male patient with an infection caused by linezolid-resistant methicillin-resistant Staphylococcus aureus (MRSA), isolated after long-term, repeated use of linezolid. Five MRSA strains isolated from our patient were preserved and submitted to bacteriological analysis. All five of these strains were found to have identical genotypes by pulsed-field gel electrophoresis. Two strains isolated in the early hospital period were sensitive to linezolid, while three isolated in the late hospital period were resistant. These three strains that had acquired resistance to linezolid were found to have a G2576T point mutation in the 23SrRNA domain V. Linezolid-resistant MRSA is rare, but may occur with the long-term, repeated administration of linezolid. [ABSTRACT FROM AUTHOR]

Abstract We could not detect hetero-vancomycin-intermediate resistant Staphylococcus aureus (hetero-VISA), according to the definition of hetero-VISA, from the clinical isolates of 140 methicillin-resistant S. aureus (MRSA) strains. However, 15 ß-lactam antibiotic-induced vancomycin-resistant MRSA (BIVR) strains were detected from the same strains. We screened 1882 MRSA clinical isolates obtained in 2002 from 21 institutes throughout Japan. The detection rate of blood-isolated BIVR was 12.6% (19/151), and that of nonblood-isolated BIVR was 4.9% (85/1731; P < 0.001; ?2 test). Uridine-diphosphate-N-acetylmuramyl-L-alanyl-D-isoglutamyl-L-lysine, used as the peptidoglycan material of S. aureus, showed the same results as ß-lactam antibiotics in BIVR. [ABSTRACT FROM AUTHOR]