The Brief Case: IMP, the Uncommonly Common Carbapenemase.
Ontology highlight
ABSTRACT:
SUBMITTER: Lowe CF
PROVIDER: S-EPMC7098757 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
Publications
The Brief Case: IMP, the Uncommonly Common Carbapenemase.
Lowe Christopher F CF Matic Nancy N Champagne Sylvie S Romney Marc G MG Leung Victor V Ritchie Gordon G
Journal of clinical microbiology 20200325 4
Similar Datasets
Project description:BackgroundThe emergence of Enterobacteriaceae harboring IMP-4 or IMP-8 carbapenemases is rare. We report an occurrence of Enterobacteriaceae harboring IMP-4 or IMP-8 carbapenemases in a Chinese tertiary care hospital from November 2010 to December 2012.MethodsThe clinical characteristics of 30 patients were described. The genetic relationship of isolates was determined by pulsed-field gel electrophoresis (PFGE). Carbapenemases were detected by modified Hodge test (MHT) and polymerase chain reactions (PCRs). Amplicons were sequenced and blasted to determine the genotype.ResultsMost infected patients were from intensive care unit and had complex and serious underlying illnesses requiring mechanical ventilation. PFGE revealed that Klebsiella pneumoniae showed two major PFGE types. Two Klebsiella oxytoca had an indistinguishable PFGE pattern, while four Enterobacter cloacae were different strains. The sequencing studies showed Enterobacteriaceae harboring IMP-4 or IMP-8 carbapenemase in the 23 infected patients. The majority of patients had infections with the carbapenemase-producing Enterobacteriaceae (CPE) strain, most were successfully treated with a range of antibiotics and discharged.ConclusionIt is important to maintain a high index of suspicion to screen for carbapenemase-producing Enterobacteriaceae strains. Rapid identification of these strains and implementation of stringent procedures are the key to prevent major outbreaks in a hospital setting.
| S-EPMC4915421 | biostudies-literature
Project description:Two novel IMP-type metallo-β-lactamase variants, IMP-43 and IMP-44, were identified in multidrug-resistant Pseudomonas aeruginosa isolates obtained in medical settings in Japan. Analysis of their predicted amino acid sequences revealed that IMP-43 had an amino acid substitution (Val67Phe) compared with IMP-7 and that IMP-44 had two substitutions (Val67Phe and Phe87Ser) compared with IMP-11. The amino acid residue at position 67 is located at the end of a loop close to the active site, consisting of residues 60 to 66 in IMP-1, and the amino acid residue at position 87 forms a hydrophobic patch close to the active site with other amino acids. An Escherichia coli strain expressing blaIMP-43 was more resistant to doripenem and meropenem but not to imipenem than one expressing blaIMP-7. An E. coli strain expressing blaIMP-44 was more resistant to doripenem, imipenem and meropenem than one expressing blaIMP-11. IMP-43 had more efficient catalytic activities against all three carbapenems than IMP-7, indicating that the Val67Phe substitution contributed to increased catalytic activities against carbapenems. IMP-44 had more efficient catalytic activities against all carbapenems tested than IMP-11, as well as increased activities compared with IMP-43, indicating that both the Val67Phe and Phe87Ser substitutions contributed to increased catalytic activities against carbapenems.
| S-EPMC3754296 | biostudies-literature
Project description:We sequenced all nonduplicate 934 VIM/IMP carbapenemase-producing Enterobacterales (CPE) reported in Poland during 2006-2019 and found ≈40% of the isolates (n = 375) were Enterobacter spp. During the study period, incidence of those bacteria gradually grew in nearly the entire country. The major factor affecting the increase was clonal spread of several E. hormaechei lineages responsible for multiregional and interregional outbreaks (≈64% of all isolates), representing mainly the pandemic sequence type (ST) 90 or the internationally rare ST89 and ST121 clones. Three main VIM-encoding integron types efficiently disseminated across the clone variants (subclones) with various molecular platforms. Those variants were predominantly Pseudomonas aeruginosa-derived In238-like elements, present with IncHI2+HI2A, IncFII+FIA, IncFIB, or IncN3 plasmids, or chromosomal genomic islands in 30 Enterobacter STs. Another prevalent type, found in 34 STs, were In916-like elements, spreading in Europe recently with a lineage of IncA-like plasmids.
| S-EPMC10370858 | biostudies-literature
Project description:BackgroundIdentification of carbapenemase-producing Enterobacteriaceae (CPE) in faecal specimens is challenging. This fact is particularly critical because low-level carbapenem-resistant organisms such as IMP-producing CPE are most prevalent in Japan. We developed a modified selective medium more suitable for IMP-type CPE.MethodsFifteen reference CPE strains producing different types of β-lactamases were used to evaluate the commercially available CHROMagar KPC and chromID CARBA as well as the newly prepared MC-ECC medium (CHROMagar ECC supplemented with meropenem, cloxacillin, and ZnSO4) and M-ECC medium (CHROMagar ECC supplemented with meropenem and ZnSO4). A total of 1035 clinical samples were then examined to detect CPE using chromID CARBA and M-ECC medium.ResultsAll tested strains producing NDM-, KPC-, and OXA-48-carbapenemases were successfully cultured in the media employed. Although most of the IMP-positive strains did not grow in CHROMagar KPC, chromID CARBA, or MC-ECC, all tested strains grew on M-ECC. When faecal samples were applied to the media, M-ECC medium allowed the best growth of IMP-type CPE with a significantly higher sensitivity (99.3%) than that of chromID CARBA (13.9%).ConclusionsM-ECC medium was determined as the most favourable selective medium for the detection of IMP-type CPE as well as other types of CPE.
| S-EPMC5366124 | biostudies-literature
Project description:Carbapenem-resistant Enterobacteriaceae (CRE) are a pressing public health issue due to limited therapeutic options to treat such infections. CREs have been predominantly isolated from humans and environmental samples and they are rarely reported among companion animals. In this study we report on the isolation and plasmid characterization of carbapenemase (IMP-4) producing Salmonella enterica Typhimurium from a companion animal. Carbapenemase-producing S. enterica Typhimurium carrying blaIMP-4 was identified from a systemically unwell (index) cat and three additional cats at an animal shelter. All isolates were identical and belonged to ST19. Genome sequencing revealed the acquisition of a multidrug-resistant IncHI2 plasmid (pIMP4-SEM1) that encoded resistance to nine antimicrobial classes including carbapenems and carried the blaIMP-4-qacG-aacA4-catB3 cassette array. The plasmid also encoded resistance to arsenic (MIC-150 mM). Comparative analysis revealed that the plasmid pIMP4-SEM1 showed greatest similarity to two blaIMP-8 carrying IncHI2 plasmids from Enterobacter spp. isolated from humans in China. This is the first report of CRE carrying a blaIMP-4 gene causing a clinical infection in a companion animal, with presumed nosocomial spread. This study illustrates the broader community risk entailed in escalating CRE transmission within a zoonotic species such as Salmonella, and in a cycle that encompasses humans, animals and the environment.
| S-EPMC5073282 | biostudies-literature
Project description:Purpose:To investigate the occurrence and genetic characteristics of the bla IMP-26-positive plasmid from a multidrug-resistant clinical isolate, Enterobacter hormaechei L51. Methods:Species identification was determined by MALDI-TOF MS and Sanger sequencing. Antimicrobial susceptibility testing was performed by the agar dilution and broth microdilution. Whole-genome sequencing was conducted using Illumina HiSeq 4000-PE150 and PacBio Sequel platforms, and the genome was annotated by the RAST annotation server. The ANI analysis of genomes was performed using OAT. Phylogenetic reconstruction and analyses were performed using the Harvest suite based on the core-genome SNPs of 61 publicly available E. hormaechei genomes. Results:The E. hormaechei L51 genome consists of a 5,018,729 bp circular chromosome and a 343,918 bp conjugative IncHI2/2A plasmid pEHZJ1 encoding bla IMP-26 which surrounding genetic context was intI1-bla IMP-26-ltrA-qacE?1-sul1. A new sequence type (ST1103) was assigned for the isolate L51 which was resistant to cephalosporins, carbapenems, but sensitive to piperacillin-tazobactam, amikacin, tigecycline, trimethoprim-sulfamethoxazole and colistin. Phylogenetic analysis demonstrated that E. hormaechei L51 belonged to the same subspecies as the reference strain E. hormaechei SCEH020042, however 18,248 divergent SNP were identified. Resistance genes in pEHZJ1 including aac(3)-IIc, aac(6') -IIc, bla SHV-178, bla DHA-1, bla TEM-1, bla IMP-26, ereA2, catII, fosA5, qnrB4, tet(D), sul1 and dfrA19. Conclusion:In our study, we identified a conjugative IncHI2/2A plasmid carrying bla IMP-26 and bla SHV-178 in E. hormaechei ST1103, a novel multidrug-resistant strain isolated from China, and describe the underlying resistance mechanisms of the strain and detailed genetic context of mega plasmid pEHZJ1.
| S-EPMC7039083 | biostudies-literature
Project description:IMP-type carbapenemase, found in various Gram-negative bacteria, has been increasingly detected worldwide. We aimed to study the outcomes and risk factors for acquisition of IMP-type carbapenemase-producing carbapenem-resistant Enterobacteriaceae (IMP-CRE), as this has not been evaluated in detail. We conducted a matched case-case-control study of patients from whom IMP-CRE isolates were obtained. All patients who tested positive for IMP-CRE were included; they were matched with patients with carbapenem-susceptible Enterobacteriaceae (CSE) and with controls at a ratio of 1:1:2. The risk factors for acquisition for the CRE and CSE groups and mortality rates, which were calculated using multivariate logistic regression models with weighting according to the inverse probability of propensity scores, were compared. In total, 192 patients (96 patients each in the CRE and CSE groups, with 130 Enterobacter cloacae isolates and 62 Klebsiella sp. isolates) were included. The IMP-11 type was present in 43 patients, IMP-1 in 33, and IMP-60 and IMP-66 in 1 each; 31 patients with CRE (32.3%) and 34 with CSE (35.4%) developed infections. Multivariate analysis identified the following independent risk factors: gastrostomy, history of intravenous therapy or hemodialysis, and previous exposure to broad-spectrum β-lactam antibiotics, including penicillin with β-lactamase inhibitors, cephalosporins, and carbapenems. In propensity score-adjusted analysis, mortality rates for the CRE and CSE groups were similar (15.0% and 19.5%, respectively). We found that IMP-CRE may not contribute to worsened clinical outcomes, compared to CSE, and gastrostomy, previous intravenous therapy, hemodialysis, and broad-spectrum antimicrobial exposure were identified as risk factors for CRE isolation. Fluoroquinolone and aminoglycosides are potentially useful antibiotics for IMP-CRE infections.
| S-EPMC8092526 | biostudies-literature
Project description:Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) poses a significant public health challenge worldwide, but research on IMP-producing CR-hvKP and its tigecycline resistance is extremely scarce. We report herein the recovery of two IMP-4-producing, capsular serotype K2, sequence type 65 (K2-ST65), hypervirulent K. pneumoniae isolates (C1672 and C2051), which caused severe and fatal infections in ICU patients, after retrospectively screening 3,285 carbapenem-resistant K. pneumoniae isolates from 26 provinces in China. Notably, C2051 also demonstrated tigecycline nonsusceptibility, mediated by a frameshift mutation in the TetR/AcrR family transcriptional regulator. Both strains harbored blaIMP-4 and critical plasmid-borne virulence genes (rmpA/rmpA2, iucA, and iroN) and demonstrated high virulence in Galleria mellonella, indicating CR-hvKP. The blaIMP-4 gene was located on the IncU- and IncN-type plasmids, which showed high stability in C1672 and C2051 after serial passage for 5 days, with retention rates of 87% and 93.7%, respectively. No significant differences in growth rates were observed among the parental strains and the corresponding resistance plasmid-cured mutants (P = 0.5273), suggesting that strains carrying the blaIMP and virulence plasmids have the potential to exist for a long time without compromising fitness. The genetic environments of the blaIMP-4 gene in both strains were similar, and it has been inferred that the genetic regions of blaIMP-4 were inserted into different backbones. Several conjugal transfer genes, such as traO, traE, traN, and traBCD, were identified in the blaIMP-4-bearing plasmid of C2051, suggesting a higher ability for plasmid transmission. The convergence of IMP carbapenemase and tigecycline nonsusceptibility in a classic hypervirulent K. pneumoniae lineage highlights the need to enhance clinical awareness and epidemiologic surveillance. IMPORTANCE To date, research on IMP-producing CR-hvKP is extremely scarce. Only one case of urinary tract infection caused by an IMP-6-producing K1-ST23 hypervirulent K. pneumoniae isolate in Japan was recorded, with a limited description of clinical information and genomic features. None of the published studies examined the virulence of the reported strains or the stability and fitness of resistance plasmids or presented a phylogenetic analysis. This dearth of data is notable because CR-hvKP infections are increasingly identified, but critical characteristics of the emerging resistance mediated by IMP carbapenemases in CR-hvKP remain unknown. Here, we report the emergence of two IMP-4 carbapenemase-producing K2-ST65 hypervirulent K. pneumoniae isolates that caused severe and fatal infections in clinical settings in China. Notably, one of them also demonstrated tigecycline nonsusceptibility. These strains carrying blaIMP and virulence plasmids had the potential to exist for a long time without compromising their fitness, highlighting the urgent need to enhance clinical awareness and epidemiologic surveillance to prevent their dissemination.
| S-EPMC8549734 | biostudies-literature
Project description:Carbapenem-resistant Enterobacterales (CRE) are some of the most important pathogens causing infections, which can be challenging to treat. We identified four blaIMP-carrying CRE isolates and collected clinical data. The transferability and stability of the plasmid were verified by conjugation, successive passaging, and plasmid elimination assays. The IncC blaIMP-4-carrying pIMP4-ECL42 plasmid was successfully transferred into the recipient strain, and the high expression of traD may have facilitated the conjugation transfer of the plasmid. Interestingly, the plasmid showed strong stability in clinical isolates. Whole-genome sequencing was performed on all isolates. We assessed the sequence similarity of blaIMP -harboring plasmid from our institution and compared it to plasmids for which sequence data are publicly available. We found that four blaIMP-carrying CRE belonged to four different sequence types. The checkerboard technique and time-kill assays were used to investigate the best antimicrobial therapies for blaIMP-carrying CRE. The time-kill assay showed that the imipenem of 1× minimum inhibitory concentration (MIC) alone had the bactericidal or bacteriostatic effect against IMP-producing strains at 4-12 h in vitro. Moreover, the combination of tigecycline (0.5/1/2 × MIC) and imipenem (0.5/1 × MIC) showed a bactericidal effect against the blaIMP-26-carrying CRECL60 strain.IMPORTANCECarbapenem-resistant Enterobacterales (CRE) are an urgent public health threat, and infections caused by these microorganisms are often associated with high mortality and limited treatment options. This study aimed to determine the clinical features, molecular characteristics, and plasmid transmissible mechanisms of blaIMP carriage as well as to provide a potential treatment option. Here, we demonstrated that conjugated transfer of the IncC blaIMP-4-carrying plasmid promotes plasmid stability, so inhibition of conjugated transfer and enhanced plasmid loss may be potential ways to suppress the persistence of this plasmid. The imipenem alone or tigecycline-imipenem combination showed a good bactericidal effect against IMP-producing strains. In particular, our study revealed that imipenem alone or tigecycline-imipenem combination may be a potential therapeutic option for patients who are infected with IMP-producing strains. Our study supports further trials of appropriate antibiotics to determine optimal treatment and emphasizes the importance of continued monitoring of IMP-producing strains in the future.
| S-EPMC10846200 | biostudies-literature
Project description:A multispecies outbreak of IMP-6 carbapenemase-producing Enterobacterales (IMP-6-CPE) occurred at an acute care hospital in Japan. This study was conducted to understand the mechanisms of IMP-6-CPE transmission by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing and whole-genome sequencing (WGS), and identify risk factors for IMP-6-CPE acquisition in patients who underwent abdominal surgery. Between July 2013 and March 2014, 22 hospitalized patients infected or colonized with IMP-6-CPE (Escherichia coli [n = 8], Klebsiella oxytoca [n = 5], Enterobacter cloacae [n = 5], Klebsiella pneumoniae [n = 3] and Klebsiella aerogenes [n = 1]) were identified. There were diverse PFGE profiles and sequence types (STs) in most of the species except for K. oxytoca. All isolates of K. oxytoca belonged to ST29 with similar PFGE profiles, suggesting their clonal transmission. Plasmid analysis by WGS revealed that all 22 isolates but one shared a ca. 50-kb IncN plasmid backbone with blaIMP-6 suggesting interspecies gene transmission, and typing of plasmids explained epidemiological links among cases. A case-control study showed pancreatoduodenectomy, changing drains in fluoroscopy room, continuous peritoneal lavage and enteric fistula were associated with IMP-6-CPE acquisition among the patients. Plasmid analysis of isolates in an outbreak of IMP-6-CPE suggested interspecies gene transmission and helped to clarify hidden epidemiological links between cases.
| S-EPMC7057946 | biostudies-literature