Clearance of carbapenemase-producing Enterobacteriaceae (CPE) carriage: a comparative study of NDM-1 and KPC CPE

ObjectivesThe aim of this study was to compare clearance rates and related characteristics of patients carrying KPC-producing carbapenemase-producing Enterobacteriaceae (CPE) with those of patients carrying NDM-1-producing CPE.MethodsFrom November 2010 to October 2016, consecutive patients whose clinical or surveillance cultures yielded CPE were prospectively identified and followed in a 2700-bed tertiary referral hospital. CPE control protocols included strict single-room isolation, contact precautions and weekly surveillance cultures. CPE clearance was defined as three or more consecutive CPE-negative cultures without relapse. We compared patients carrying NDM-1 CPE and KPC and those with and without clearance. The time to CPE clearance or discharge was assessed using the Kaplan–Meier method and NDM-1 CPE and KPC CPE groups were compared.ResultsA total of 147 patients carrying CPE, 106 with NDM-1 and 41 with KPC, were included in the study. At the time of hospital discharge, 12 of the 106 patients carrying NDM-1 CPE were clear of CPE, whereas none of the KPC CPE patients were (NDM-1, 11.3% (12/106) versus KPC, 0% (0/41), p 0.02). There was no significant association between CPE clearance and factors such as an immunocompromised condition, antibiotic usage, or species of colonizing organism. Among 40 patients who were readmitted, CPE non-clearance was significantly higher in patients carrying KPC CPE (NDM-1, 36.7% (11/30) versus KPC, 80.0% (8/10), p 0.03).ConclusionsCompared with NDM-1 CPE patients, patients carrying KPC CPE had a significantly lower probability of clearance during hospitalization. Furthermore, KPC CPE carriage persisted for a substantial period of time following patient discharge.     

Detection of Enterobacter cloacae complex strain with a blaNDM-1-harboring plasmid from an elderly resident at a long-term care facility in Okayama,Japan

Amidst the global spread of antimicrobial resistance, New Delhi metallo-β-lactamase (NDM)-type carbapenemase-producing Enterobacterales (CPE) remain uncommon in Japan, and the detection of such highly drug-resistant organisms is limited to inbound cases. There is little evidence regarding the prevalence of NDM β-lactamase gene (bla_NDM)-harboring CPE in the domestic community, especially in the provincial cities of Japan. Herein, we report the isolation of a bla_NDM-1-harboring plasmid in Enterobacter cloacae complex strain isolated from an elderly woman without a history of traveling abroad who had resided in a long-term care facility in Okayama, Japan. The multidrug-resistant bla_NDM-harboring CPE isolate was detected in a stool sample of the patient during routine screening at admission. We performed whole-genome sequencing analysis of the isolate using MiSeq (Illumina) and MinION (Oxford Nanopore Technologies) platforms. The isolate was identified as sequence type 171, which has predominantly been reported in the United States and China. The bla_NDM-1 gene was encoded on the 46,161 bp IncX3 plasmid, with sequence similarity to plasmids of similar size isolated from individuals in China. Collectively, the genomic data suggest that an imported CPE isolate may have spread among healthy individuals in the regional area of Japan.     

Extensively Drug-Resistant New Delhi Metallo-β-Lactamase–Encoding Bacteria in the Environment,Dhaka, Bangladesh, 2012

Carriage of the New Delhi metallo-β-lactamase variant 1 (NDM-1) enables drug resistance to move between communities and hospitals. In Bangladesh, we found the bla_NDM-1 gene in 62% of environmental waters and in fermentative and nonfermentative gram-negative bacteria. Escherichia coli sequence type (ST) 101 was most commonly found, reflecting a common global relationship between ST101 and NDM-1.     

Comparison of clinical outcomes of patients infected with KPC- and NDM-producing Enterobacterales: a retrospective cohort study

ObjectivesWe aimed to compare clinical outcomes of patients with Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales and those with New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales.MethodsWe performed a retrospective cohort study of all adult patients with KPC- or NDM-producing Enterobacterales isolates in a 2700-bed tertiary referral hospital in Seoul, South Korea, between 2010 and 2019. The primary outcome was 30-day mortality after first isolation of KPC- or NDM-producing Enterobacterales. The secondary outcome was the development of infection within 30 days by the colonizing isolates, among colonized patients. We performed Cox regression analysis for 30-day mortality and competing risk analysis for development of infection.ResultsA total of 859 patients were identified during the study period; 475 (55%) had KPC and 384 (45%) had NDM. Thirty-day mortality was significantly higher in the KPC group than in the NDM group (17% (81/475) vs 9% (33/384); p < 0.001). The KPC group developed infection within 30 days from the initial colonization after first isolation more frequently than the NDM group (8% (27/353) vs. 3% (10/295); p 0.02). Multivariable analysis revealed that independent risk factors for 30-day mortality were solid cancer (adjusted hazard ratio (aHR) 2.51; 95% confidence interval (CI) 1.66–3.79; p < 0.001), solid organ transplant (aHR 0.32; 95% CI 0.17–0.61; p < 0.001), a high APACHE II score (aHR 1.11; 95% CI 1.08–1.13; p < 0.001), KPC-producing Enterobacterales (aHR 1.69; 95% CI 1.02–2.79; p 0.04), previous carbapenem use within 3 months (aHR 1.86; 95% CI 1.26–2.75; p < 0.001) and site of KPC- or NDM-producing Enterobacterales infection at the time of the first culture (p < 0.001).DiscussionOur study suggests that KPC-producing Enterobacterales is significantly associated with poorer outcomes than NDM-producing Enterobacterales.     

Evaluation of Disk carbapenemase test using improved disks for rapid detection and differentiation of clinical isolates of carbapenemase-producing Enterobacterales

ObjectivesRapid detection of carbapenemase-producing Enterobacterales (CPE) is important to control spread of the resistance. We previously reported that imipenem disks prepared from injectable imipenem-cilastatin could rapidly detect KPC- and NDM-type carbapenemases. In the present study, we evaluated performance of disks of IPM and combined disks of imipenem-tazobactam and imipenem-EDTA, which were prepared from powders of imipenem and inhibitors.MethodsIsolates of Enterobacterales were recovered from specimens of patients at a tertiary care hospital in Korea during January 2017 and March 2018. Routine CPE detection was performed by the CPE surveillance personnel whereas evaluation of the Disk carbapenemase test (DCT) was performed by the other personnel without knowing the results of surveillance. The DCT was carried out by pressing disks on to colonies and rehydrating in Petri plates and observing color change.ResultsThe DCT differentiated 688 of 694 (sensitivity 99.1%) carbapenemase-producing isolates in 2.5–20 min: 630 with KPC, 51 with NDM, three with IMP, one with VIM, two with KPC and IMP, and one with NDM and OXA-181. The DCT failed to detect six OXA- 48-like enzyme-producing isolates, but the modified method using 96-well flat-bottom microplates with mineral oil cover detected all 29 OXA-48-like enzyme-producing isolates in 20–120 min. The DCT was negative for all 440 ertapenem-nonsusceptible, carbapenemase gene-negative isolates (specificity 100%).ConclusionThe procedure of DCT is simple and can differentiate isolates of Enterobacterales with KPC-, NDM-, IMP- and VIM-type carbapenemases rapidly, and the modified DCT can detect isolates with OXA-48-like enzymes rapidly.     

The prevalence of colistin resistance in Escherichia coli and Klebsiella pneumoniae isolated from food animals in China: coexistence of mcr-1 and blaNDM with low fitness cost

Increasing colistin resistance is a global concern because colistin is used as a last resort for the treatment of carbapenem-resistant Enterobacteriaceae infections. The plasmid-mediated colistin resistance gene, mcr-1 was found in distinct bacterial species isolated from humans, animals, and the environment. In this study, farms in four different agricultural provinces in China were investigated to determine the occurrence of the antimicrobial resistance and related genes. A total of 373 Escherichia coli and 54 Klebsiella pneumoniae were isolated from 510 non-duplicated samples. Of the E. coli and K. pneumoniae isolates, 72.7% and 66.7%, respectively, were susceptible to colistin. Isolates resistant to colistin comprised 46.6% of the samples isolated from Shandong, and 17.8% and 16.4% of the samples from Jilin and Henan, respectively. Twenty-six carbapenem-resistant E. coli isolates were resistant to colistin, in which both mcr-1 and bla_NDM were present. Specifically, the co-existence was found in isolates from animals and sewage. Most of the resistance genes were located on plasmids and were 40–244 kilobases. Growth curves of transconjugants carrying mcr-1, bla_NDM-1, bla_NDM-4, bla_NDM-5, and bla_NDM-9 showed a low fitness cost compared with the recipient. In conclusion, mcr-1 was widespread in E. coli and K. pneumoniae isolated from farms in China. Co-existence of mcr-1 and bla_NDM-9 was identified in different sequence types of E. coli with low fitness cost from various origins, indicating an urgent need to take measures for decreasing dissemination.     

Diversity of carbapenemases in clinical isolates of Enterobacteriaceae in Croatia—the results of a multicentre study

Since the first carbapenem-resistant Klebsiella pneumoniae strain was isolated in 2008, Enterobacteriaceae with reduced susceptibility to one or more carbapenems have emerged sporadically in different geographical regions in Croatia. These observations gave rise to a multicenter study on carbapenem resistance in Enterobacteriaceae from Croatia. Fifty-seven carbapenem-non-susceptible strains of Enterobacteriaceae were collected during 2011–2012 from four large hospital centres in Croatia. Overall, 36 strains produced VIM-1 β-lactamase, three produced NDM-1, and one produced KPC-2. A high degree of clonal relatedness was observed in Enterobacter cloacae and Citrobacter freundii strains, in contrast to K. pneumoniae strains. Bla_VIM genes were located within class1 integron which contained genes encoding resistance to aminoglycosides (aac_A4). The study found strong association between bla_VIM and qnr_B6 and between bla_NDM and qnr_A6 genes.     

Evidences for the regulation of GnRH and GTH expression by GnIH in the goldfish, Carassius auratus

Gonadotrophin-inhibitory hormone (GnIH) plays an important role in regulating of reproduction in teleosts. To clarify the mode of action of GnIH on the synthesis of gonadotropin releasing hormone (GnRH) and gonadotrophin (GtH), three GnIHR cDNAs were cloned from the goldfish brain. In situ hybridization results showed that GnIHRs were localized to the hypothalamus and pituitary. In the hypothalamus, GnIHRs were found in the NPP, NPO and NLT, whereas sGnRH neurons were reported to be located, and potentially regulated by GnIH. In the pituitary, only two GnIHRs were observed and they were localized to the PI instead of the adenohypophysis where GtH-expressing cells are localized, suggesting indirect regulation of GtH by GnIH. In vivo, intraperitoneal (i.p.) injections of synthetic goldfish GnIH-II peptide and GnIH-III peptide significantly decreased sGnRH and FSHβ mRNA levels. Only GnIH-II decreased LHβ mRNA levels significantly. In vitro, both GnIH-II and GnIH-III showed no effect on GtH synthesis, but an inhibition of GnRH-stimulated LHβ and FSHβ synthesis was observed when GnIH-III was applied to primary pituitary cells in culture. Thus, GnIH could contribute to the regulation of gonadotropin in the brain and pituitary in teleosts.     

Microcephaly with simplified gyral pattern,epilepsy and permanent neonatal diabetes syndrome (MEDS). A new patient and review of the literature

Microcephaly with simplified gyration, epilepsy and permanent neonatal diabetes syndrome (MEDS) is a recently described, autosomal recessive-inherited syndrome. We report the case of an infant presenting with lethargy at age five weeks and clinical findings of persistent hyperglycaemia and microcephaly with simplified gyration, suggestive of MEDS. The diagnosis was confirmed by the detection of a known c.233 T > C mutation in the IER3IP1 gene. Only eight cases of MEDS have been reported in the literature. We reviewed these with the aim of better delineating their clinical manifestations, which should allow earlier and more accurate diagnosis and genetic counseling.     

An Xpert screen to identify carbapenemases

To prevent the spread of carbapenemases-producing Enterobacteriaceae (CPE) active surveillance, contact isolation and cohorting infected patients should be practiced. Rectal swabs for the Xpert MDRO-assay of 32 patients were included. 71.85% were positive for targets incorporated into the MDRO-assay; whereas 28% were phenotypically not CRE and Xpert negative (9.37% had different mechanism [bla_OXA]). The assay identified 59.3%, 9.37% and 3.1% as bla_NDM, bla_NDM+VIM and bla_VIM, respectively. The assay is a screening test that identifies CPE harbouring organism within an hour and can be installed at tertiary-care facilities to screen colonized patients.