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BACKGROUND: Enterobacter cloacae, E. hormaechei and related subspecies remain the most clinically relevant among the Enterobacter cloacae complex (ECC). Carbapenemase-producing ECC strains are increasingly identified in hospital-acquired infections and usually belong to four main multilocus sequence types (MLST STs) named ST114, ST93, ST90 and ST78. Instead, ST182 has been sporadically reported among E. hormaechei strains, and recently, outbreaks of blaNDM-producing ST182 clonal strains have emerged. Herein, we aimed to investigate the presence of ST182 and explore its evolution and modes of blaNDM acquisition. METHODS: A phylogenetic analysis of 646 MLST STs identified among 4685 E. hormaechei whole-genome sequencing (WGS) assemblies deposited in public repositories was performed, as well as an in silico comparative and phylogenomic analyses for 55 WGS assemblies of ST182. blaNDM-harboring contigs were also compared to published plasmid sequences. RESULTS: ST182 E. hormaechei strains were recovered from patients on five continents during 2011-2021. They were divided into three major genomic clusters, comprising a separate clonal complex with six other STs. In 30 out of 55 ST182 WGS assemblies, blaNDM-harboring structures were identified that were similar to the plasmids predominant in Gram-negative bacteria, harboring resistance genes to multiple antibiotic classes and virulence genes. No associations between the genomic clusters and the country/continent of isolation or the presence and the plasmid types of the blaNDM-harboring contigs were observed. CONCLUSIONS: Our findings show that ST182 E. hormaechei strains have been identified in the past decade worldwide; 54.5% of them carried diverse blaNDM genetic structures, suggesting recent acquisition of the blaNDM alleles. Thus, blaNDM-harboring ST182 is an emerging multidrug-resistant and virulent lineage in ECC strains that requires close monitoring.
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OBJECTIVES: Carbapenemase-mediated carbapenem resistance in Pseudomonas aeruginosa is a relevant health problem. We detected for the first time in Spain two clinical NDM-producing P. aeruginosa (NDM-Pa) isolates in two Ukrainian patients admitted to our hospital between April and August 2022. METHODS: Antimicrobial susceptibility was studied by microdilution and MIC gradient strips (EUCAST-2022 criteria). Carbapenemase genes were detected by the Xpert Carba-R and immunochromatography assays. WGS (Illumina and Oxford-Nanopore) was also performed. RESULTS: In May 2022, we detected an NDM-Pa in a sternotomy wound in a patient. In June-2022, a second NDM-Pa along with an OXA-48-Klebsiella pneumoniae (OXA-48-Kp) isolate was detected in a mandibular abscess from an unrelated patient. Moreover, an NDM+OXA-48-K. pneumoniae (NDM+OXA-48-Kp) was also found in a rectal sample of this patient. Both patients had undergone surgery in Ukraine before their transfer to our hospital. NDM-Pa isolates were resistant to all tested antimicrobials with the exception of aztreonam (MIC = 8 mg/L), colistin (MIC =2 mg/L) and cefiderocol (MIC range = 0.75-2 mg/L). WGS confirmed that both P. aeruginosa isolates were NDM-1 producers, belonged to ST773 and shared an identical resistome. blaNDM-1 was located on a â¼117-Kb chromosomally integrated integrative conjugative element (ICE). OXA-48-Kp and NDM+OXA-48-Kp belonged to ST147 and contained blaOXA-48 on an identical â¼300-Kb IncHIB-plasmid. blaNDM-1 was located on a 51-Kb IncFIB-plasmid only found in NDM+OXA-48-Kp. CONCLUSIONS: This is the first description of NDM-Pa in Spain. We highlight the threat of further cross-border dissemination of NDM-1 through P. aeruginosa along with K. pneumoniae high-risk clones also carrying OXA-48, which draws a complex epidemiological scenario.
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Antibacterianos , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/genética , Antibacterianos/farmacología , España , Ucrania , Hospitales UniversitariosRESUMEN
The minimal inhibitory concentration (MIC) is conventionally used to define in vitro levels of susceptibility or resistance of a specific bacterial strain to an antibiotic and to predict its clinical efficacy. Along with MIC, other measures of bacteria resistance exist: the MIC determined at high bacterial inocula (MICHI) that allow the estimation of the occurrence of inoculum effect (IE) and the mutant prevention concentration, MPC. Together, MIC, MICHI and MPC represent the bacterial "resistance profile". In this paper, we provide a comprehensive analysis of such profiles of K. pneumoniae strains that differ by meropenem susceptibility, ability to produce carbapenemases and specific carbapenemase types. In addition, we have analyzed inter-relations between the MIC, MICHI and MPC for each tested K. pneumoniae strain. Low IE probability was detected with carbapenemase-non-producing K. pneumoniae, and high IE probability was detected with those that were carbapenemase-producing. MICs did not correlate with the MPCs; significant correlation was observed between the MICHIs and the MPCs, indicating that these bacteria/antibiotic characteristics display similar resistance properties of a given bacterial strain. To determine the possible resistance-related risk due to a given K. pneumoniae strain, we propose determining the MICHI. This can more or less predict the MPC value of the particular strain.
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Aztreonam/avibactam is being developed on the rationale that aztreonam evades metallo-ß-lactamases (MBLs) whilst avibactam protects aztreonam against co-produced serine ß-lactamases. This study measured the activity of aztreonam/avibactam against MBL-producing Enterobacterales referred to the UK Health Security Agency in 2015, 2017 and 2019. Minimum inhibitory concentrations (MICs) were determined by broth microdilution, and genome sequences were determined with Illumina technology. For Klebsiella and Enterobacter spp. with NDM, IMP or VIM enzymes, the MICs of aztreonam/avibactam were distributed unimodally, with >90% of isolates inhibited at 1+4 mg/L, and all inhibited at 8+4 mg/L. Over 85% of Escherichia coli with NDM carbapenemases were inhibited at 8+4 mg/L, but their MIC distribution was multi-modal with major peaks at 0.12 and 8 mg/L. Forty-eight of 50 NDM E. coli with high aztreonam/avibactam MICs (defined as ≥8 mg/L) had YRIK inserted after amino acid 333 of penicillin-binding protein (PBP)3, or had a YRIN insert plus an acquired AmpC ß-lactamase, commonly CMY-42. Ten of 15 E. coli with moderately raised aztreonam/avibactam MICs (defined as 0.5-4 mg/L) had YRIN inserts without acquired AmpC. Twenty-two of 24 E. coli isolates with normal MICs (defined as 0.03-0.25 mg/L) lacked PBP3 inserts. YRIK inserts were associated with E. coli ST405, and YRIN inserts with ST167; however, many isolates with high or moderately raised MICs were clonally diverse. No substantive MIC distribution shifts occurred across the three survey years; ST405 isolates with YRIK comprised more high-MIC organisms in 2019 compared with earlier years, but the apparent increase lacked significance (P>0.05).
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Aztreonam , Escherichia coli , Aztreonam/farmacología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas de Unión a las Penicilinas/genética , Compuestos de Azabiciclo/farmacología , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Reino Unido , Pruebas de Sensibilidad Microbiana , Combinación de Medicamentos , Ceftazidima/farmacologíaRESUMEN
Following prolonged hospitalization that included broad-spectrum antibiotic exposure, a strain of Providencia rettgeri was cultured from the blood of a patient undergoing extracorporeal membrane oxygenation treatment for hypoxic respiratory failure due to COVID-19. The strain was resistant to all antimicrobials tested including the novel siderophore cephalosporin, cefiderocol. Whole genome sequencing detected ten antimicrobial resistance genes, including the metallo-ß-lactamase bla NDM-1, the extended-spectrum ß-lactamase bla PER-1, and the rare 16S methyltransferase rmtB2.
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Antibacterianos/farmacología , COVID-19/terapia , Farmacorresistencia Bacteriana , Infecciones por Enterobacteriaceae/mortalidad , Neumonía Asociada al Ventilador/mortalidad , Providencia/efectos de los fármacos , Anciano , COVID-19/complicaciones , Infecciones por Enterobacteriaceae/sangre , Infecciones por Enterobacteriaceae/etiología , Infecciones por Enterobacteriaceae/microbiología , Oxigenación por Membrana Extracorpórea , Resultado Fatal , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Neumonía Asociada al Ventilador/etiología , Neumonía Asociada al Ventilador/microbiología , Providencia/genética , Providencia/aislamiento & purificaciónRESUMEN
New Delhi MBL (NDM) carbapenemase-producing Klebsiella pneumoniae has become one of the most concerning multidrug-resistant pathogens. The Balkan counties are considered a reservoir for the spread of such strains based on several reports documenting NDM infections after hospitalization in this region. Nevertheless, NDM-producing K. pneumoniae have been only occasionally documented from Balkans. The current study documents the first polyclonal outbreak caused by NDM-1-producing K. pneumoniae in Bulgaria. From July 2015 to April 2016, all 25 single-patient carbapenem-nonsusceptible K. pneumoniae isolates were collected. Phenotypic and molecular screening revealed that 17 produced NDM-1 carbapenemase. All NDM-1 producers harbored blaCTX-M-15, blaCMY-4, blaTEM-1, and blaOXA-2; five also harbored blaOXA-1. In all cases, blaNDM-1 was flanked upstream by ISAba125 element and downstream by bleMBL. Pulsed-field gel electrophoresis (PFGE) clustered NDM-1-positive isolates into four distinct clonal types, A to D. MLST assigned isolates of the dominant clonal type A (n = 14) to sequence type (ST) 11, while isolates of clonal types B, C, and D to ST16, ST15, and ST391, respectively. Of interest, ST11 isolates belonged to the same PFGE type as those of the recently described NDM-1 ST11 clonal outbreak in Greece. Traveling abroad or overseas hospitalization was not reported in any case, suggesting most likely intra- and interhospital dissemination. The study presents the first polyclonal outbreak of NDM-producing K. pneumoniae in the Balkans and underlines the need for larger epidemiological studies in the region to illustrate commonalities in the transmission of NDM clones and possible sources in the community.
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Brotes de Enfermedades , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/genética , Resistencia betalactámica/genética , beta-Lactamasas/genética , Antibacterianos/farmacología , Bulgaria/epidemiología , Carbapenémicos/farmacología , Células Clonales , Electroforesis en Gel de Campo Pulsado , Expresión Génica , Genotipo , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/clasificación , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Plásmidos/química , Plásmidos/metabolismoRESUMEN
We characterized NDM-1-producing Klebsiella isolates from Rio de Janeiro, Brazil. PCR was applied for resistance and virulence determinants. The genetic context of blaNDM was determined by S1 nuclease pulsed-field gel electrophoresis (PFGE) and hybridization. Genotyping was performed by PFGE and multilocus sequence typing (MLST). Most isolates carried multiple resistance genes and remained susceptible to amikacin, fosfomycin-trometamol, polymyxin B, and tigecycline. The spread of NDM-1-producing Klebsiella pneumoniae was not associated with clonal expansion and appears to be associated with Tn3000.