カンジダ ケツリュウ カンセンショウ ノ カンジャ ニ オケル ケツエキ カラ ブンリサレタ カンジダゾク キンカブ ノ キンシュ ブンプ ト コウシンキンヤク カンジュセイ オヨビ フルコナゾール タイセイ ト タンキ ヨゴ ニ カンレンスル リンショウ インシ ノ カイセキ

京都大学0048新制・課程博士博士(医学)甲第10784号医博第2768号新制||医||870(附属図書館)UT51-2004-G631京都大学大学院医学研究科内科系専攻(主査)教授 宮地 良樹, 教授 光山 正雄, 教授 一山 智学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Emergence and spread of B2-ST131-O25b, B2-ST131-O16 and D-ST405 clonal groups among extended-spectrum-β-lactamase-producing Escherichia coli in Japan.

[Objectives ]The increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli has been associated with the emergence of the CTX-M-producing sequence type 131 (ST131) pandemic clonal group, a member of the O25b serogroup and the B2 phylogenetic group. To assess the clonal spread of ESBL-producing E. coli in Japan, a regional surveillance programme was conducted. [Methods] A total of 581 ESBL-producing clinical specimen E. coli isolates were collected between 2001 and 2010. Clonal groups, including ST131, D-ST405, D-ST393 and D-ST69, were determined using the PCR O type, phylogenetic grouping by triplex PCR, allele-specific PCR and multilocus sequence typing (MLST). A subset of clonal groups underwent PFGE. [Results]Among clonal strains, 215 isolates (37%) were identified as belonging to the ST131 group, 185 as B2-ST131-O25b (32%), 26 as B2-ST131-O16 (4%), 3 as B1-ST131-O25b (0.5%) and 1 as B2-ST131-O-non-typeable (0.1%). Forty-one isolates (7%) were identified as belonging to the D-ST405 clonal group, seven (1%) as D-ST69 and two (0.3%) as D-ST393. The B2-ST131-O16 clonal group was characterized by CTX-M-14 and a significantly lower ciprofloxacin resistance rate than the B2-ST131-O25b clonal group. The B2-ST131-O16 and B2-ST131-O25b clonal groups each made up a single PFGE cluster, with 65% similarity. The rate of ESBL-producing E. coli increased over the years (0.2% in 2001 to 9.7% in 2010) and corresponded to increases in the numbers of the B2-ST131-O25b, B2-ST131-O16 and D-ST405 clonal groups. [Conclusions] The B2-ST131-O25b, B2-ST131-O16 and D-ST405 clonal groups have contributed to the spread of ESBL-producing E. coli in Japan

Risk factors and outcomes of Stenotrophomonas maltophilia bacteraemia: a comparison with bacteraemia caused by Pseudomonas aeruginosa and Acinetobacter species.

Stenotrophomonas maltophilia (SM) is an important nosocomial pathogen that exhibits intrinsic resistance to various antimicrobial agents. However, the risk factors for SM bacteraemia have not been sufficiently evaluated. From January 2005 to September 2012, we retrospectively compared the clinical backgrounds and outcomes of SM bacteraemic patients (SM group) with those of bacteraemic patients due to Pseudomonas aeruginosa (PA group) or Acinetobacter species (AC group). DNA genotyping of the SM isolates using the Diversilab system was performed to investigate the genetic relationships among the isolates. The SM, PA, and AC groups included 54, 167, and 69 patients, respectively. Nine of 17 patients in the SM group receiving trimethoprim-sulfamethoxazole prophylaxis developed SM bacteraemia. Independent risk factors for SM bacteraemia were the use of carbapenems and antipseudomonal cephalosporins and SM isolation within 30 days prior to the onset of bacteraemia. Earlier SM isolation was observed in 32 of 48 patients (66.7%) with SM bacteraemia who underwent clinical microbiological examinations. Of these 32 patients, 15 patients (46.9%) had the same focus of bacteraemia as was found in the previous isolation site. The 30-day all-cause mortality rate among the SM group (33.3%) was higher than that of the PA group (21.5%, p = 0.080) and the AC group (17.3%, p = 0.041). The independent factor that was associated with 30-day mortality was the SOFA score. DNA genotyping of SM isolates and epidemiological data suggested that no outbreak had occurred. SM bacteraemia was associated with high mortality and should be considered in patients with recent use of broad-spectrum antibiotics or in patients with recent isolation of the organism

Clinical and microbiologic characteristics of cefotaxime-non-susceptible Enterobacteriaceae bacteremia: a case control study

Abstract Background Cefotaxime plays an important role in the treatment of patients with bacteremia due to Enterobacteriaceae , although cefotaxime resistance is reported to be increasing in association with extended-spectrum \u3b2-lactamase (ESBL) and AmpC \u3b2-lactamase (AmpC). Methods We conducted a case-control study in a Japanese university hospital between 2011 and 2012. We assessed the risk factors and clinical outcomes of bacteremia due to cefotaxime-non-susceptible Enterobacteriaceae (CTXNS-En) and analyzed the resistance mechanisms. Results Of 316 patients with Enterobacteriaceae bacteremia, 37 patients with bacteremia caused by CTXNS-En were matched to 74 patients who had bacteremia caused by cefotaxime-susceptible Enterobacteriaceae (CTXS-En). The most common CTXNS-En was Escherichia coli (43%), followed by Enterobacter spp. (24%) and Klebsiella spp. (22%). Independent risk factors for CTXNS-En bacteremia included previous infection or colonization of CTXNS-En, cardiac disease, the presence of intravascular catheter and prior surgery within 30\ua0days. Patients with CTXNS-En bacteremia were less likely to receive appropriate empirical therapy and to achieve a complete response at 72\ua0h than patients with CTXS-En bacteremia. Mortality was comparable between CTXNS-En and CTXS-En patients (5 vs. 3%). CTXNS-En isolates exhibited multidrug resistance but remained highly susceptible to amikacin and meropenem. CTX-M-type ESBLs accounted for 76% of the \u3b2-lactamase genes responsible for CTXNS E. coli and Klebsiella spp. isolates, followed by plasmid-mediated AmpC (12%). Chromosomal AmpC was responsible for 89% of CTXNS Enterobacter spp. isolates. Conclusions CTXNS-En isolates harboring ESBL and AmpC caused delays in appropriate therapy among bacteremic patients. Risk factors and antibiograms may improve the selection of appropriate therapy for CTXNS-En bacteremia. Prevalent mechanisms of resistance in CTXNS-En were ESBL and chromosomal AmpC

First outbreak of methicillin-resistant Staphylococcus aureus USA300 harboring the Panton-Valentine leukocidin genes among Japanese health care workers and hospitalized patients.

This report describes the first outbreak of methicillin-resistant Staphylococcus aureus USA300 in a general hospital ward in Japan, involving 6 health care workers and 4 patients. This report emphasizes the need for health care personnel to be alert that methicillin-resistant Staphylococcus aureus harboring Panton-Valentine leukocidin gene poses a threat for both nosocomial and occupational infection

Multicenter retrospective study of cefmetazole and flomoxef for treatment of extended-spectrum-β-lactamase-producing Escherichia coli bacteremia.

The efficacy of cefmetazole and flomoxef (CF) for the treatment of patients with extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) bacteremia (ESBL-CF group) was compared with that of carbapenem treatment for ESBL-EC patients (ESBL-carbapenem group) and with that of CF treatment in patients with non-ESBL-EC bacteremia (non-ESBL-CF group). Adult patients treated for E. coli bacteremia in four hospitals were retrospectively evaluated. The 30-day mortality rates in patients belonging to the ESBL-CF, ESBL-carbapenem, and non-ESBL-CF groups were compared as 2 (empirical and definitive therapy) cohorts. The adjusted hazard ratios (aHRs) for mortality were calculated using Cox regression models with weighting according to the inverse probability of propensity scores for receiving CF or carbapenem treatment. The empirical-therapy cohort included 104 patients (ESBL-CF, 26; ESBL-carbapenem, 45; non-ESBL-CF, 33), and the definitive-therapy cohort included 133 patients (ESBL-CF, 59; ESBL-carbapenem, 54; non-ESBL-CF, 20). The crude 30-day mortality rates for patients in the ESBL-CF, ESBL-carbapenem, and non-ESBL-CF groups were, respectively, 7.7%, 8.9%, and 3.0% in the empirical-therapy cohort and 5.1%, 9.3%, and 5.0% in the definitve-therapy cohort. In patients without hematological malignancy and neutropenia, CF treatment for ESBL-EC patients was not associated with mortality compared with carbapenem treatment (empirical-therapy cohort: aHR, 0.87; 95% confidence interval [CI], 0.11 to 6.52; definitive therapy cohort: aHR, 1.04; CI, 0.24 to 4.49). CF therapy may represent an effective alternative to carbapenem treatment for patients with ESBL-EC bacteremia for empirical and definitive therapy in adult patients who do not have hematological malignancy and neutropenia

Prevalence of plasmid-mediated AmpC β-lactamase-producing Escherichia coli and spread of the ST131 clone among extended-spectrum β-lactamase-producing E. coli in Japan.

In 2010, a total of 1327 clinical Escherichia coli isolates from five hospitals in the Kyoto and Shiga regions of Japan were analysed by PCR. The prevalences of plasmid-mediated AmpC β-lactamase (pAmpC)-producers, extended-spectrum β-lactamase (ESBL)-producers and co-producers of pAmpC and ESBL were 1.7%, 9.7% and 0.3%, respectively. Less than one-half of the pAmpC-producers were reported to be resistant to third-generation cephalosporins, cephamycins and β-lactam/β-lactam inhibitors using the old 2009 Clinical and Laboratory Standards Institute (CLSI) breakpoints. CMY-2 was the most prevalent pAmpC type (95%), and CTX-M-14 (38%), CTX-M-15 (26%) and CTX-M-27 (19%) were the most prevalent ESBL types. The worldwide O25b-ST131-B2 clone accounted for 11% of pAmpC-producers and 41% of ESBL-producers. The O25b-ST131-B2 clone was characterised by a CTX-M-27- or CTX-M-15-type ESBL and ciprofloxacin-non-susceptibility with quadruple mutations in the quinolone resistance-determining regions (S83L and D87N in GyrA and S80I and E84V in ParC). A significant proportion of pAmpC-producers and the O25b-ST131-B2 clone were found in Japan by a recent regional surveillance programme