Fecal carriage and molecular epidemiologic characteristics of carbapenemase-producing Enterobacterales in primary care hospital in a Japanese city.

BACKGROUND: The worldwide spread of organisms with antimicrobial resistance is of concern, especially the trend of significantly increasing carbapenemase-producing Enterobacterales (CPE). In this study, we investigated the annual trend of intestinal CPE carriage rates in inpatients and healthy adults in a primary care hospital in Tenri, Japan. METHODS: We collected 551 samples of feces from inpatients in our institution and 936 samples from healthy people living in Tenri city from December 2012 to April 2015. All samples were cultured on MacConkey agar plates containing 4 µg/mL ceftazidime for screening test. The colonies grown on the screening medium were detected for carbapenemase genes (blaIMP-1, blaIMP-2, blaVIM, blaKPC, blaGES, blaNDM, and blaOXA-48 groups) by multiplex PCR, and CPE were identified by MALDI-TOF MS. Plasmid replicon typing and pulsed-field gel electrophoresis (PFGE) were performed on PCR-positive strains. RESULTS: The CPE carriage rate was 1.6% (9/551) in the inpatient group and 0% (0/936) in the healthy adults group. The numbers of strains positive for the carbapenemase gene were 4 for Enterobacter cloacae, 2 for Klebsiella pneumoniae, 1 for Citrobacter freundii, 1 for Raoultella ornithinolytica and 1 for Escherichia coli. In all CPE strains, the carbapenemase gene was blaIMP-6 and the plasmid replicon type was IncN. The 4 E. cloacae strains showed a similar pattern in PFGE. CONCLUSION: In the same city in Japan, CPE intestinal carriers were detected only in the inpatient group in this study but not in a healthy adults, suggesting that the spread of asymptomatic CPE carriers was confined to inpatients.

Molecular epidemiology of carbapenemase-producing Enterobacteriaceae in a primary care hospital in Japan, 2010-2013.

Recently, carbapenemase-producing Enterobacteriaceae (CPE) have been spreading worldwide and have become a threat in healthcare systems. We investigated the isolation frequency and molecular epidemiological characteristics of CPE isolated from clinical samples collected at a primary care hospital over the four years of 2010-2013 in Japan. CPE were detected in 17 (0.34%) of 4875 isolates by the broth microdilution method, sodium mercaptoacetate inhibition test, and modified Hodge test using meropenem disks. The frequency of CPE isolates was 0.09% in 2010, 0.17% in 2011, 0.16% in 2012 and 0.82% in 2013. Isolates positive for carbapenemase included Klebsiella pneumoniae (0.92%), Escherichia coli (0.12%), Enterobacter cloacae (0.80%), Klebsiella oxytoca (0.55%), Enterobacter aerogenes (0.81%) and Proteus mirabilis (0.08%). Antimicrobial susceptibility testing showed low MICs for piperacillin-tazobactam, amikacin, ciprofloxacin and levofloxacin, and only one multidrug-resistant strain. The carbapenemase genotype of all strains was IMP-6, and 94% of the strains were simultaneous CTX-M-2 producers. Two K. pneumoniae and 3 E. coli isolates showed the same pulsed-field gel electrophoresis group. Multilocus sequence typing detected no international high-risk clone types. Plasmid replicon typing detected IncN from all CPE strains, and IncF and IncFIB were simultaneously detected in 24% and 18%, respectively. All patients with detected CPE were inpatients, and many were elderly long-term hospitalized patients or had a history of prior vancomycin or levofloxacin antibiotic administration. The rapid spread of CPE is a concern in Japan. Preventive measures must be implemented against the spread of CPE after considering the epidemiological trend of CPE detection, antibiograms, and risk factors.

Analysis of molecular epidemiologic characteristics of extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli colonizing feces in hospital patients and community dwellers in a Japanese city.

Infectious diseases caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli are prevalent because of nosocomial infection. In addition, colonization of ESBL-producing E. coli in the intestinal tract of community dwellers due to the contamination of meat or environmental water is assumed to be one of the sources, but the causes have not been clarified. To analyze these factors, we investigated the difference in clonal groups using a combination of phylogenetic groups and multilocus sequence typing of ESBL-producing E. coli, which were obtained from the feces of an inpatient group in our hospital and a community-dwelling group living in a Japanese city. The carriage rate of ESBL-producing E. coli in the inpatient group was 12.5% (32/257), similar to that of 8.5% (42/496) in the community dwellers (P = 0.082). Of the ESBL clonal groups detected from the community dwellers, 52% (22/42) were clonal groups, including D-ST1485, D-ST70, D-ST2847, B2-ST550, B2-ST3510, A-ST93, A-ST580, A-ST716 and B1-ST2787, that have not been detected from human pathogens, meat, companion animals and environmental water, whereas all clonal groups detected from the inpatients were those that had already been reported. The rate of fluoroquinolone-resistant ESBL clonal groups colonizing the intestinal tract of the inpatient group rose as the number of hospital days increased. These results indicated that different factors were related to colonization of ESBL-producing E. coli in the feces of the inpatient group and the community-dwelling group.

Effects of campaign for postpartum vaccination on seronegative rate against rubella among Japanese women.

BACKGROUND: Japan experienced two rubella outbreaks in the past decade (2004 and 2012-2013), resulting in 10 and 20 infants with congenital rubella syndrome (CRS), respectively. This study was performed to determine whether the seronegative rate was lower in multiparous women than in primiparous women in Japan. METHODS: Hemagglutination inhibition (HI) test results during pregnancy were analyzed retrospectively in 11048 primiparous and 9315 multiparous women who gave birth at six hospitals in northern Japan in the 5-year study period (January 2008 through December 2012). Women with HI titer <  1:8 were defined as susceptible to rubella. RESULTS: The seronegative rate was significantly lower in multiparous than primiparous women aged 30 - 31 years (2.3% [22/967] vs. 4.5% [66/1454], P  =  0.0036), 36 - 37 years (3.4% [55/1601] vs. 5.7% [79/1389], P  =  0.0030), and overall women (3.8% [350/9315] aged 34.7  ±  5.2 vs. 5.4% [597/11048] for 33.2  ±  5.9, P  <  0.001). The susceptible fraction size did not differ largely according to hospital, ranging from 3.5% to 6.3%. Those for each year did not change markedly; 4.5% [150/3369], 5.2% [221/4268], 4.4% [195/4412], 4.6% [186/4056], and 4.6% [195/4258] for 2008, 2009, 2010, 2011, and 2012, respectively. Those for teenagers were consistently high: 22.7% [5/22], 20.7% [6/29], 20.6% [7/34], 13.0% [3/23], and 23.5% [4/17] for 2008, 2009, 2010, 2011, and 2012, respectively. CONCLUSIONS: The seronegative rate was significantly lower in multiparous than primiparous women. However, Japanese rubella vaccination programs were insufficient to eliminate CRS.

Effect of insulin glargine on endogenous insulin secretion and beta-cell function in Japanese type 2 diabetic patients using oral antidiabetic drugs.

The aim of the present study was to evaluate the effect of insulin glargine (Gla) (as part of basal-supported oral therapy) on endogenous insulin secretion and beta-cell function in type 2 diabetic patients. In 33 insulin-naive patients showing poor glycemic control on treatment with sulfonylurea (SU)-based OADs without DPP4 inhibitors, once-daily injection of Gla was added without changing OADs, and the dose of Gla was titrated to attain a fasting plasma glucose (FPG) <110 mg/dL over 24 weeks. Morning meal tests were done at baseline, 12 weeks and 24 weeks. FPG and 2-hour plasma glucose (2HPG) and serum C-peptide (FCPR and 2HCPR) were measured 3 times, while serum intact proinsulin (FPI and 2HPI) was measured at baseline and 24 weeks. Levels of FPG, FCPR, 2HPG, and HbA1c were significantly reduced from baseline at 24 weeks (176±52 to 117±27 mg/dL, p<0.01; 2.0±0.9 to 1.6±1.0 ng/mL, p<0.01; 257±53 to 202±27 mg/dL, p<0.01; and 8.4±0.9 to 7.3±0.6%, p<0.01, Mean±SD), but 2HCPR was unchanged. The patients were divided into two groups depending on whether FPG at 24 weeks was <110 mg/dL or not: attained group (n=15) and not attained group (n=18). The dose of Gla did not differ between the two groups, but the 2HPI/2HCPR ratio at 24 weeks showed a significant decrease from baseline in the attained group. Supplementation with Gla improved glycemic control and maintained intrinsic basal insulin secretion, without changing 2-hour postprandial secretion. Achieving good glycemic control with an FPG<110 mg/dL by adding Gla decreased the 2HPI/2HCPR ratio at 24 weeks.

Efficacy and safety of switching from basal insulin to once-daily insulin degludec/insulin aspart in Japanese patients with inadequately controlled type 2 diabetes: A 4-week, randomized, open-label, treat-to-target study.

AIMS/INTRODUCTION: A prospective, 4-week, single-center, randomized, open-label, parallel-group, treat-to-target study was carried out to develop an algorithm for safe and effective switching from basal insulin to once-daily insulin degludec/insulin aspart (IDegAsp) in patients with inadequately controlled type 2 diabetes. MATERIALS AND METHODS: Patients were randomly assigned to continue their current basal insulin therapy (n = 10) or to switch to IDegAsp on a 1:1 unit basis (n = 10). The insulin dose could be titrated once weekly, targeting a self-measured blood glucose of 80-100 mg/dL before breakfast. A mixed meal test was carried out at baseline and after 4 weeks. RESULTS: After 4 weeks, the mean daily dose of insulin was similarly increased by 60% in both groups, and there was a significant decrease of mean plasma glucose and glucose area under the glucose concentration vs time curve for 2 h in the meal test. The mean estimated treatment difference (IDegAsp group - basal insulin group) of the mean plasma glucose level was -28 mg/dL (95% confidence interval -47 to -8, P = 0.008) after 4 weeks and that of the area under the glucose concentration vs time curve for 2 h was -2,800 mg/min/dL (95% confidence interval -5,300 to -350, P = 0.028), confirming the superiority of IDegAsp to basal insulin. In the IDegAsp group, the 2-h postprandial plasma glucose level was significantly decreased to the fasting plasma glucose range. There were no confirmed hypoglycemic episodes in either group during the 4-week study period. CONCLUSIONS: After switching from basal insulin, the IDegAsp dose can be uptitrated by 60% based on fasting plasma glucose data. However, monitoring of postprandial glucose should be considered before further uptitration of IDegAsp.