Hepatic gas gangrene caused by Clostridium novyi.

We report the case of a patient with advanced gastric cancer and multiple liver metastases, who presented with bacteremia and hepatic gas gangrene caused by Clostridium novyi (C. novyi). The gas gangrene caused abscesses to form within metastatic lesions. This case highlights the antitumor effects of C. novyi in human.

[A multicenter study of the antimicrobial susceptibility of Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis from community acquired infections in Saitama, Japan].

We examined regional surveillance of antimicrobial susceptibility of community acquired bacterial pathogens from patients in Saitama, Japan. The fourth-year survey was conducted in three of the period 2007-2010 (period I, 2007-2008; period II, 2008-2009; period III, 2009-2010). Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Japanese Society of Chemotherapy using maximum 13 antibacterial agents. Susceptibility testing was evaluable with 789 strains (227 Streptococcus pneumoniae, 148 Streptococcus pyogenes, 220 Haemophilus influenzae, and 194 Moraxella catarrhalis). Ratio of penicillin-susceptible S. pneumoniae (PSSP, MIC of benzylpenicillin ≤ 0.06 µg/mL) was 43.5% (period I), 43.5% (period II) and 55.8% (period III), and those of erythromycin-sensitive and azithromycin-sensitive S. pyogenes were 100% and 65.5% (period I), 47.9% and 47.9% (period II), 29.4%, and 29.4% (period III) , respectively. Among H. influenzae, ß-lactamase-nonproducing ampicillin-resistant isolates were 34.9% (period I), 25.8% (period II), and 17.1% (period III); however, ß-lactamase-nonproducing ampicillin-intermediately resistant isolates were 19.8% (period I), 26.9% (period II), and 29.3% (period III). Regarding M. catarrhalis, macrolides showed potent activities, with MIC90s of ≤ 0.25-0.5 µg/mL, and fluoroquinolones showed strong activities, with MIC90s ≤0.03-0.125 µg/mL. The result of this survey indicated that the trends observed were similar to the results of previous nationwide surveillance.

[Trend of susceptibility testing of clinical isolates of Candida species from aseptic samples in hospitals in Saitama prefecture].

We investigated the susceptibility of Candida species from clinical aseptic samples, including blood, at some hospitals in Saitama prefecture. Candida spp. detected from aseptic samples in the 6 institutes in Saitama prefecture from November 2007 to July 2011 were studied. The number of isolates was 85, which are 43 (50.6%) of Candida albicans, 24 (28.2%) of Candida parapsilosis, 5 (5.9%) of Candida glabrata, 5 (5.9%) of Candida tropicalis, 4 (4.7%) of Candida guilliermondii, 2 (2.4%) of Candida fermentati, 1 (1.2%) of Candida famata and Candida lusitaniae, respectively. All isolates were susceptible to amphotericin B. However, resistant isolates against micafungin were 3 in 5 of C. glabrata. We analyzed susceptibility of Candida spp. in Saitama prefecture in the article, and our study might be useful for the fungal therapy in the region.

Prediction of the pathogens that are the cause of pneumonia by the battlefield hypothesis.

Commensal organisms are frequent causes of pneumonia. However, the detection of these organisms in the airway does not mean that they are the causative pathogens; they may exist merely as colonizers. In up to 50% cases of pneumonia, the causative pathogens remain unidentified, thereby hampering targeting therapies. In speculating on the role of a commensal organism in pneumonia, we devised the battlefield hypothesis. In the "pneumonia battlefield," the organism-to-human cell number ratio may be an index for the pathogenic role of the organism. Using real-time PCR reactions for sputum samples, we tested whether the hypothesis predicts the results of bacteriological clinical tests for 4 representative commensal organisms: Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas spp., and Moraxella catarrhalis. The cutoff value for the organism-to-human cell number ratio, above which the pathogenic role of the organism was suspected, was set up for each organism using 224 sputum samples. The validity of the cutoff value was then tested in a prospective study that included 153 samples; the samples were classified into 3 groups, and each group contained 93%, 7%, and 0% of the samples from pneumonia, in which the pathogenic role of Streptococcus pneumoniae was suggested by the clinical tests. The results for Haemophilus influenzae, Pseudomonas spp., and Moraxella catarrhalis were 100%, 0%, and 0%, respectively. The battlefield hypothesis enabled legitimate interpretation of the PCR results and predicted pneumonia in which the pathogenic role of the organism was suggested by the clinical test. The PCR reactions based on the battlefield hypothesis may help to promote targeted therapies for pneumonia. The prospective observatory study described in the current report had been registered to the University Hospital Medical Information Network (UMIN) registry before its initiation, where the UMIN is a registry approved by the International Committee of Medical Journal Editors (ICMJE). The UMIN registry number was UMIN000001118: A prospective study for the investigation of the validity of cutoff values established for the HIRA-TAN system (April 9, 2008).

[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.

[In vitro susceptibilities to levofloxacin and various antibacterial agents of 12,919 clinical isolates obtained from 72 centers in 2007].

We have reported in this journal in vitro susceptibilities of clinical isolates to antibiotics every year since 1992. In this paper, we report the results of an analysis of in vitro susceptibilities of 12,919 clinical isolates from 72 centers in Japan to selected antibiotics in 2007 compared with the results from previous years. The common respiratory pathogens, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae maintained a high susceptibility to fluoroquinolones (FQs). The resistance of S. pyogenes to macrolides has been increasing every year and this was especially clear this year. Most strains of Enterobacteriaceae except for Escherichia coli showed a high susceptibility to FQs. Almost 30% of E. coli strains were resistant to FQs and the resistance increased further this year. FQs resistance of methicillin-resistant Staphylococcus aureus (MRSA) was approximately 95% with the exception of 45% for sitafloxacin (STFX). FQs resistance of methicillin-susceptible S. aureus (MSSA) was low at about 10%. FQs resistance of methicillin-resistant coagulase negative Staphylococci (MRCNS) was higher than that of methicillin-susceptible coagulase negative Staphylococci (MSCNS), but it was lower than that of MRSA. However, FQs resistance of MSCNS was higher than that of MSSA. FQs resistance of Enterococcus faecalis was 22.5% to 29.6%, while that of Enterococcusfaecium was more than 85% except for STFX (58.3%). In clinical isolates of Pseudomonas aeruginosa derived from urinary tract infections, FQs resistance was 21-27%, which was higher than that of P. aeruginosa from respiratory tract infections at 13-21%, which was the same trend as in past years. Multidrug resistant strains accounted for 5.6% in the urinary tract and 1.8% in the respiratory tract. Acinetobacter spp. showed high susceptibility to FQs. The carbapenem resistant strains, which present a problem at present, accounted for 2.7%. Neisseria gonorrhoeae showed high resistance of 86-88% to FQs. The results of the present survey indicated that although methicillin-resistant Staphylococci, Enterococci, E. coli, P. aeruginosa, and N. gonorrhoeae showed resistance tendencies, and other species maintained high susceptibility rates more than 90% against FQs, which have been used clinically for over 15 years.

[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.

[The combination effects of antibacterial agents against clinical isolated multiple-drug resistant Pseudomonas aeruginosa].

The effectiveness of antibacterial agents against 70 strains of clinically isolated multiple-drug resistant Pseudomonas aeruginosa (MDRP) was measured by the micro dilution method. Fifty of all strains (71%) produced metallo-beta-lactamase and the IMP-1 gene was detected by polymerase chain reaction (PCR). The MIC90 (the minimum inhibitory concentration of an antibiotic necessary to inhibit the growth of 90% of bacterial strains) values of biapenem (BIPM), meropenem (MEPM), tazobactam/piperacillin (TAZ/PIPC), sulbactam/ cefoperazone (SBT/CPZ), cefepime (CFPM), ciprofloxacin (CPFX), pazufloxacin (PZFX), amikacin (AMK) and aztreonam (AZT) were found to be 265, 512, 256, 512, 512, 64, 128, 128 and 128 microg/mL, respectively. The in vitro combination effects of antibacterial agents were examined against 62 strains of MDRP and the synergy or additive effects were evaluated by fractional inhibitory concentration (FIC) index calculated by the checkerboard method. The combination of AMK and AZT showed synergy effects on 15/59 (25.4%) strains of MDRP. The synergy and additive effects on the MDRP strains were also found by the other antibacterial agents combination such as TAZ/PIPC and AMK, CFPM and AMK, and SBT/CPZ and AZT. These results suggested the necessity of further investigation of clinical usefulness.

In vitro activity of beta-lactams, macrolides, telithromycin, and fluoroquinolones against clinical isolates of Streptococcus pneumoniae: correlation between drug resistance and genetic characteristics.

The in vitro activity of antimicrobial agents against Streptococcus pneumoniae was determined using 16 strains of penicillin-susceptible S. pneumoniae (PSSP) and 26 strains of penicillin intermediately resistant S. pneumoniae (PISP) + penicillin-resistant S. pneumoniae (PRSP) in Japan. The minimum inhibitory concentrations (MICs) of potent antibiotics, including eight beta-lactams (benzylpenicillin, ampicillin, cefotiam, cefepime, cefditoren, faropenem, panipenem, and biapenem), three macrolides (erythromycin, clarithromycin, and azithromycin), telithromycin, and three fluoroquinolones (ciprofloxacin, levofloxacin, and gatifloxacin), were determined. Twenty-three strains exhibited genetic variations at pbp1a + pbp2x + pbp2b, which are genetic-PRSP (g-PRSP). g-PISP strains accounted for 62.5% (10/16) of the PSSP strains. The existence of an abnormal pbp gene conferred not only penicillin resistance but resistance to cephems; however, panipenem and biapenem had potent in vitro efficacy against alterations. Regarding the macrolide resistance mechanisms (mefA or ermB): 16 isolates had only mefA, 18 isolates had ermB, and 2 isolates had both mefA and ermB. There was no correlation between the existence of an abnormal pbp gene and the existence of the mefA gene or the ermB gene.

[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.

[Examination about utility of a Streptococcus pneumoniae capsular antigen swiftness search kit urine in a pneumonia patient].

We investigated the usefullness of Binax NOW urine antigen test, an immunochromatographic assay that binds any soluble Streptococcus pneumoniae antigen (C polysaccharide) for the diagnosis of penumoniae form September 2003 to March 2005. We used 372 samples form the patinets with pneumoniae diagnosed for blood or sputum cultuter or gram-stained sputum smear. Out of 24 culture positive specimens, Binax NOW urine antigen test, showed positive in 18 (75%) specimens. The sensitivity of sputum and blood culture was 71.7% and 83.3%, respectively. Binax NOW urine antigen test was seemed false positives in 55 samples, false negatives in 6 samples. The specificity of Binax NOW urine antigen test was evaluated 84.1%. Overall agreement among tests was 83.6%. When compared to culture, false negative urine antigen may be the result of colonizing S. pneumoniae in sputum or pneumonia caused by an agent other than S. pneumoniae. CRP values for cases were both urine antigen and culture were positive ranged from 40 mg/dl to 10 mg/dl while urine antigen and culture negative cases were predominantly less than 10 mg/dl. Positive blood and pleural fluid culture cases were consistently associated with strongly positive urine antigen tests. Non-agreement between urine antigen, culture, and microscopy may be the result of specimen quality, labile nature of S. pneumoniae and antimicrobial therapy.

[Epidemiological study of Arbekacin-resistant, methicillin resistant Staphylococcus aureus in Saitama Medical School Hospital].

Arbekacin-resistant, methicillin-resistant Staphylococcus aureus was frequently isolated in Saitama Medical School Hospital during 1996 and 1998. The minimum inhibitory concentration for ABK was 8 micrograms/ml in 14 strains, 16 micrograms/ml in 6 strains, and 32 micrograms/ml in 2 strains. The maximum isolation rate of these resistant strains in one month was 8%. Use of ABK in the hospital did not increase during the same period. The infection control team (ICT) of the hospital recognized the increase of resistant strains and started intervention for the hospital staff. The ICT instructed the staff of each ward to follow standard precautions for the prevention of nosocomial infections and the risk of ABK-resistant MRSA was explained repeatedly. Thereafter, the isolation rate decreased to 3%. An epidemiological study was done using 22 strains of ABK-resistant MRSA that were isolated in this period. The strains originated from different patients and from 10 different wards, which were designated as wards A to J. Eight strains were isolated from surgical ward A, followed by the other wards (ward B: 3, C: 2, D: 2, E: 2, F: 1, G: 1, H: 1, I: 1, J: 1). The specimens from which ABK-resistant MRSA were isolated were as follows,: sputum: 4, wound: 4, decubitus ulcer: 4, urine: 2, pus: 2, blood :1, central venous catheter: 1, drainage tube: 1, tracheal aspirate: 1, skin: 1, stool: 1. Several investigations were done using these strains. Sensitivity tests for ABK, VCM, MINO, LVFX, FOM, IPM were performed by the standard method of the Japan Society for Chemotherapy. Coagulase types were determined. Production of toxic shock syndrome toxin-1 (TSST-1), enterotoxin, and beta-lactamase was assayed. Pulse-field gel electrophoresis (PFGE) using Sma I was also done and differences were compared. Seven of the 8 strains from ward A showed the same drug sensitivity profile and biological phenotype. Two of the 3 strains from ward B and 2 strains from ward C were also identical by these methods. Six of the 8 strains from ward A were also identical by PFGE. These 6 isolates showed the same drug sensitivity pattern, same coagulase type, and same production of TSST-1 and enterotoxin. Two other strains from ward B, one strain from ward F, and one from ward I also showed the same PFGE pattern, drug sensitivity profile, and toxin profile as the 6 strains from ward A. Our data show that the same strains were transmitted around the hospital during the study period, although serious nosocomial infections due to ABK-resistant MRSA were avoided. Thus, intervention by the ICT in each ward was effective. ABK-resistant MRSA should be recognized as an important hospital pathogen and should be surveyed consistently.

[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.

[Study of resistance mechanism on cefotaxime resistant Proteus mirabilis isolated from clinical specimens and its clinical background].

Over a 6-year period (1997 to 2002), 56 strains of Proteus mirabilis (12% of the total number of P. mirabilis isolates obtained) resistant to ampicillin, piperacillin, cefazolin and cefoperazone by routine antimicrobial testing method, were isolated in Saitama Medical School Hospital. Of the 56 strains resistant to 4 beta-lactams, 12 strains were studied and were found to produce extended-spectrum beta-lactamases, identified as CTX-M-10 group and Toho-1 group in 8 and 2 strains, respectively. Susceptibility testing showed that 12 strains were resistant to cefotaxime, and cepodoxime, and ceftriaxon but susceptible to ceftazidime. Moreover, all of the beta-lactamases were inhibited by clavulanic acid. Of the 12 strains, one strain showed resistance to cephamycins such as cefoxitin, cefmetazole and cefotetan. Four of the twelve patients had infections caused by ESBL producing P. mirabilis, and eight patients were colonized, as confirmed by clinical and laboratory findings. The infections were urinary tract infections (two episodes), pneumonia (one episode), and sepsis (one episode). These patients had a favorable response to antibiotic therapy including cephalosporin. From these findings, CTX-M-type beta-lactamase producing P. mirabilis strains were confirmed from clinical specimens in our hospital.

[Comparison of a rapid antigen test and cultures for diagnosis of meningitis in children].

Fourteen pediatric patients diagnosed as bacterial meningitis between August 1997 and April 2002 were enrolled in this study. Both rapid antigen detection test, Slidex Meningite 5 Kit (Biomerieux) and culture were performed using cerebrospinal fluids (CSF). H. influenzae was isolated from 11 samples and was the most frequently isolated bacteria, followed by S. pneumoniae from 4 samples and enteric bacteriae from 2 samples. Five out of six samples with positive result by culture were also positive by the rapid antigen test. Gram-negative rod was identified in smear specimens of CSF from all these 5 samples. Significance of the rapid antigen test should be recognized under drug resistance of those bacteriae are increasing.