Dataset Information

Carbapenem Resistance in Acinetobacter baumannii and Other Acinetobacter spp. Causing Neonatal Sepsis: Focus on NDM-1 and Its Linkage to ISAba125.

ABSTRACT: Carbapenem-resistant determinants and their surrounding genetic structure were studied in Acinetobacter spp. from neonatal sepsis cases collected over 7 years at a tertiary care hospital. Acinetobacter spp. (n = 68) were identified by ARDRA followed by susceptibility tests. Oxacillinases, metallo-?-lactamases (MBLs), extended-spectrum ?-lactamases and AmpCs, were detected phenotypically and/or by PCR followed by DNA sequencing. Transconjugants possessing the bla NDM-1(New Delhi metallo-?-lactamase) underwent further analysis for plasmids, integrons and associated genes. Genetic environment of the carbapenemases were studied by PCR mapping and DNA sequencing. Multivariate logistic regression was used to identify risk factors for sepsis caused by NDM-1-harboring organisms. A. baumannii (72%) was the predominant species followed by A. calcoaceticus (10%), A. lwoffii (6%), A. nosocomialis (3%), A. junni (3%), A. variabilis (3%), A. haemolyticus (2%), and 14TU (2%). Fifty six percent of the isolates were meropenem-resistant. Oxacillinases present were OXA-23-like, OXA-58-like and OXA-51-like, predominately in A. baumannii. NDM-1 was the dominant MBL (22%) across different Acinetobacter spp. Isolates harboring NDM-1 also possessed bla (VIM-2, PER-1, VEB-2, CTX-M-15), armA, aac(6')Ib, aac(6')Ib-cr genes. bla NDM-1was organized in a composite transposon between two copies of ISAba125 in the isolates irrespective of the species. Further, OXA-23-like gene and OXA-58-like genes were linked with ISAba1 and ISAba3 respectively. Isolates were clonally diverse. Integrons were variable in sequence but not associated with carbapenem resistance. Most commonly found genes in the 5' and 3'conserved segment were aminoglycoside resistance genes (aadB, aadA2, aac4'), non-enzymatic chloramphenicol resistance gene (cmlA1g) and ADP-ribosylation genes (arr2, arr3). Outborn neonates had a significantly higher incidence of sepsis due to NDM-1 harboring isolates than their inborn counterparts. This study demonstrates the significance of both A. baumannii and other species of Acinetobacter in cases of neonatal sepsis over an extended period. Oxacillinases and bla NDM-1 are the major contributors to carbapenem resistance. The dissemination of the bla NDM-1 is likely linked to Tn125 in diverse clones of the isolates.

SUBMITTER: Chatterjee S

PROVIDER: S-EPMC4976090 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Carbapenem Resistance in Acinetobacter baumannii and Other Acinetobacter spp. Causing Neonatal Sepsis: Focus on NDM-1 and Its Linkage to ISAba125.

Chatterjee Somdatta S Datta Saswati S Roy Subhasree S Ramanan Lavanya L Saha Anindya A Viswanathan Rajlakshmi R Som Tapas T Basu Sulagna S

Frontiers in microbiology 20160808

Carbapenem-resistant determinants and their surrounding genetic structure were studied in Acinetobacter spp. from neonatal sepsis cases collected over 7 years at a tertiary care hospital. Acinetobacter spp. (n = 68) were identified by ARDRA followed by susceptibility tests. Oxacillinases, metallo-β-lactamases (MBLs), extended-spectrum β-lactamases and AmpCs, were detected phenotypically and/or by PCR followed by DNA sequencing. Transconjugants possessing the bla NDM-1(New Delhi metallo-β-lactama ...[more]

PMID: 27551277

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Project description:BACKGROUND:Carbapenems are β-lactam antibiotics which are used to treat severe infections caused by multidrug resistant Enterobacteriacea. The recent emergence and rapid spread of Enterobacteriaceae resistant to carbapenems is a global concern. We undertook a systematic review of the antibiotic susceptibility and genotypic characteristics of carbapenem-resistant Enterobacteriaceae in Chinese neonates. METHODS:Systematic literature reviews were conducted (PubMed/Medline, Embase, Wanfang medical online databases, China National Knowledge Infrastructure (CNKI) database) regarding sepsis caused by carbapenem-resistant Enterobacteriaceae in Chinese neonates aged 0-30 days. RESULTS:17 studies were identified. Eleven patients in the six studies reported the source of infection. Ten patients (10/11, 90.9%) were hospital-acquired infections. Genotypic data were available for 21 isolates in 11 studies (20 K. pneumoniae, 1 E. coli). NDM-1 was the most frequently reported carbapenem-resistant genotype (81.0%, 17/21). Carbapenem-resistant Klebsiella pneumoniae and Escherichia coli were resistant to many antibiotic classes with the exception of colistin and fosfomycin. Sequence type 105 (ST105) was the most commonly reported K. pneumoniae ST type (30.8%; 4/13), which was from the same hospital in Western China. ST17 and ST20 were the second and third most common K. pneumoniae ST type, 23.1% (3/13) and 15.4% (2/13) respectively. The three strains of ST17 are all from the same hospital in central China. The two strains of ST20, although not from the same hospital, belong to the eastern part of China. CONCLUSIONS:Klebsiella pneumoniae with the NDM-1 genotype was the leading cause of neonatal carbapenem resistant sepsis in China. Hospital acquired infection is the main source of carbapenem resistant sepsis. There is currently no licenced antibiotic regimen available to treat such an infection in China. Improved surveillance, controlling nosocomial infection and the rational use of antibiotics are the key factors to prevent and reduce its spread.

Project description:Carbapenem-resistant Acinetobacter baumannii (CRAB), which belonged to global clones 1 (GC1) or 2 (GC2), has been widely reported and become a global threat. However, non-GC1 and non-GC2 CRAB strains are not well-studied, especially for those with rare phenotype. Here, one pyomelanin-producing CRAB strain (A. baumannii DETAB-R21) was isolated from oral swab in the ICU. Antimicrobial susceptibility testing showed it was resistant to carbapenems, ceftazidime, levofloxacin, and ciprofloxacin. DETAB-R21 was ST164Pas and ST1418Oxf with KL47 and OCL5, respectively. Whole-genome sequencing (WGS) analysis revealed chromosome contained three copies of blaOXA-23 on three 4,805-bp Tn2006 composite transposons with various novel 9-bp target site duplications (TSD). A Tn125-like structure, including blaNDM-1, a novel 4,343 bp composite transposon encoding blaCARB-16, and three prophage regions were also identified. Importantly, hmgA was interrupted by a Tn2006 and contributed to pyomelanin production and further confirmed by hmgA overexpression. Furthermore, A. baumannii irradiated with UV light, DETAB-R21 showed a higher relatively survival rate compared to a control strain that did not produce pyomelanin. No effects of pyomelanin were observed on disinfectants susceptibility, growth, or virulence. In conclusion, pyomelanin-producing CRAB carrying the blaNDM-1 and blaOXA-23 genes embedded in the bacterial chromosome is of grave concern for health care settings, highlighting the need for effective measures to prevent further dissemination. IMPORTANCE Pyomelanin production is a quite rare phenotype in A. baumannii. Moreover, the mechanisms leading to the pyomelanin production was still unclear. Here, we for the first time, confirmed the mechanism of pyomelanin production, and further investigated the impact of pyomelanin on disinfectants susceptibility, growth, virulence, and UV irradiation. More importantly, many mobile genetic elements (MGEs), including three copies of Tn2006 composite transposons, one copy of blaNDM-1 on the Tn125-like structure and three prophage regions, were identified in the chromosome, demonstrated strong plasticity of A. baumannii genome. Our study provides important insights into the new rare ST164Pas A. baumannii strain with high level carbapenem resistance, which is of great threat for patients. These findings will provide important insights into the resistance gene transfer via transposition events and further spread in the clinic.

Project description:Treatment of neonatal sepsis has become a challenge with the emergence of carbapenemase-producing bacteria. This study documents the trend of carbapenem susceptibility in Enterobacteriaceae that caused septicaemia in neonates over a five year period (2007-2011) and the molecular characterisation of Enterobacteriaceae resistant to carbapenems and cephalosporins. Hundred and five Enterobacteriaceae including Escherichia coli (n = 27), Klebsiella pneumoniae (n = 68) and Enterobacter spp. (n = 10) were isolated from blood of septicaemic neonates followed by antibiotic susceptibility tests, determination of MIC values, phenotypic and genotypic detection of β-lactamases. Carbapenem was the most active antimicrobial tested after tigecycline. CTX-M type was the most prevalent ESBL throughout the period (82%). New Delhi Metallo-β-lactamase-1 (NDM-1), which is a recent addition to the carbapenemase list, was the only carbapenemase identified in our setting. Fourteen percent of the isolates possessed blaNDM-1. Carbapenem non-susceptibility was first observed in 2007 and it was due to loss of Omp F/Ompk36 in combination with the presence of ESBLs/AmpCs. NDM-1 first emerged in E. coli during 2008; later in 2010, the resistance was detected in K. pneumoniae and E. cloacae isolates. NDM-1-producing isolates were resistant to other broad-spectrum antibiotics and possessed ESBLs, AmpCs, 16S-rRNA methylases, AAC(6')-Ib-cr, bleomycin resistant gene and class 1 integron. Pulsed field gel electrophoresis of the NDM-1-producing isolates indicated that the isolates were clonally diverse. The study also showed that there was a significantly higher incidence of sepsis caused by NDM-1-harbouring isolates in the male sex, in neonates with low birth weight and neonates born at an extramural centre. However, sepsis with NDM-1-harbouring isolates did not result in a higher mortality rate. The study is the first to review the carbapenem resistance patterns in neonatal sepsis over an extended period of time. The study highlights the persistence of ESBLs (CTX-Ms) and the emergence of NDM-1 in Enterobacteriaceae in the unit.

Project description:BackgroundWith an increase in the use of colistin methansulfonate (CMS) to treat carbapenem-resistant Acinetobacter baumannii infections, colistin resistance is emerging.MethodsPatients with infection or colonization due to colistin-resistant A. baumannii were identified at a hospital system in Pennsylvania. Clinical data were collected from electronic medical records. Susceptibility testing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were performed. To investigate the mechanism of colistin resistance, lipid A was subjected to matrix-assisted laser desorption/ionization mass spectrometry.ResultsTwenty patients with colistin-resistant A. baumannii were identified. Ventilator-associated pneumonia was the most common type of infection. Nineteen patients had received intravenous and/or inhaled CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection prior to identification of colistin-resistant isolates. The 30-day all-cause mortality rate was 30%. The treatment regimen for colistin-resistant A. baumannii infection associated with the lowest mortality rate was a combination of CMS, a carbapenem, and ampicillin-sulbactam. The colistin-susceptible and -resistant isolates from the same patients were highly related by PFGE, but isolates from different patients were not, suggesting evolution of resistance during CMS therapy. By MLST, all isolates belonged to the international clone II, the lineage that is epidemic worldwide. Phosphoethanolamine modification of lipid A was present in all colistin-resistant A. baumannii isolates.ConclusionsColistin-resistant A. baumannii occurred almost exclusively among patients who had received CMS for treatment of carbapenem-resistant, colistin-susceptible A. baumannii infection. Lipid A modification by the addition of phosphoethanolamine accounted for colistin resistance. Susceptibility testing for colistin should be considered for A. baumannii identified from CMS-experienced patients.

Dataset Information

Carbapenem Resistance in Acinetobacter baumannii and Other Acinetobacter spp. Causing Neonatal Sepsis: Focus on NDM-1 and Its Linkage to ISAba125.

Publications

Carbapenem Resistance in Acinetobacter baumannii and Other Acinetobacter spp. Causing Neonatal Sepsis: Focus on NDM-1 and Its Linkage to ISAba125.

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