scholarly journals Increasing frequency of OXA-48-producing Enterobacterales worldwide and activity of ceftazidime/avibactam, meropenem/vaborbactam and comparators against these isolates

2021 ◽  
Author(s):  
Mariana Castanheira ◽  
Timothy B Doyle ◽  
Timothy D Collingsworth ◽  
Helio S Sader ◽  
Rodrigo E Mendes
Keyword(s):  
Klebsiella Pneumoniae ◽  
In Silico ◽  
Deleterious Mutation ◽  
Treatment Options ◽  
Resistance Mechanisms ◽  
Broth Microdilution ◽  
Nonsense Mutations ◽  
Mlst Analysis ◽  
Carbapenem Resistant ◽  
Genes Encoding

Abstract Objectives To investigate the increase in the rates of OXA-48-like-producing isolates during 3 years of global surveillance. Methods Among 55?>162 Enterobacterales isolates, 354 carbapenem-resistant isolates carried genes encoding OXA-48-like enzymes. Isolates were susceptibility tested for ceftazidime/avibactam and comparators by broth microdilution methods. Analysis of β-lactam resistance mechanisms and MLST was performed in silico using WGS data. Results OXA-48-like-producing isolates increased from 0.5% (94/18 656) in 2016 to 0.9% (169/18?>808) in 2018. OXA-48 was the most common variant; isolates primarily were Klebsiella pneumoniae (318/354 isolates) from Europe and adjacent countries. MLST analysis revealed a diversity of STs, but K. pneumoniae belonging to ST395, ST23 and ST11 were observed most frequently. Thirty-nine isolates harboured MBLs and were resistant to most agents tested. The presence of blaCTX-M-15 (258 isolates), OmpK35 nonsense mutations (232) and OmpK36 alterations (316) was common among OXA-48 producers. Ceftazidime, cefepime and aztreonam susceptibility rates, when applying CLSI breakpoints, were 12%–15% lower for isolates carrying ESBLs alone and with either or both OmpK35 stop codons and OmpK36 alterations. Meropenem and, remarkably, meropenem/vaborbactam were affected by specific OmpK36 alterations when a deleterious mutation also was observed in OmpK35. These mechanisms caused a decrease of 12%–42% in the susceptibility rates for meropenem and meropenem/vaborbactam. Ceftazidime/avibactam susceptibility rates were >98.9%, regardless of the presence of additional β-lactam resistance mechanisms. Conclusions Guidelines for the treatment of infections caused by OXA-48-producing isolates are scarce and, as the dissemination of these isolates continues, studies are needed to help physicians understand treatment options for these infections.

scholarly journals Molecular Epidemiology and Characterization of Carbapenem-Resistant Klebsiella pneumoniae Isolated from Urine at a Teaching Hospital in Taiwan

2021 ◽  
Vol 9 (2) ◽  
pp. 271
Author(s):  
Yuarn-Jang Lee ◽  
Chih-Hung Huang ◽  
Noor Andryan Ilsan ◽  
I-Hui Lee ◽  
Tzu-Wen Huang
Keyword(s):  
Klebsiella Pneumoniae ◽  
Teaching Hospital ◽  
Efflux Pump ◽  
Resistance Mechanisms ◽  
Pcr Analysis ◽  
Carbapenem Resistant ◽  
High Prevalence ◽  
Antimicrobial Susceptibility Tests ◽  
Susceptibility Tests ◽  
Tract Infections

Urinary tract infections (UTIs) are common in clinics and hospitals and are associated with a high economic burden. Enterobacterium Klebsiella pneumoniae is a prevalent agent causing UTIs. A high prevalence of carbapenem-resistant K. pneumoniae (CRKP) has emerged recently and is continuing to increase. Seventeen urinary CRKP isolates collected at a teaching hospital in Taiwan from December 2016 to September 2017 were analyzed to elucidate their drug resistance mechanisms. Two-thirds of the isolates were obtained from outpatients. Antimicrobial susceptibility tests demonstrated multidrug resistance in all the isolates. Multilocus sequence typing analysis showed high diversity among the isolates. PCR analysis demonstrated the presence of carbapenemases in three isolates. All isolates carried at least one other extended-spectrum β-lactamase, including TEM, DHA, and CTX-M. Fifteen isolates contained mutations in one of the outer membrane porins that were assessed. The expression levels of the acrB and/or oqxB efflux pump genes, as determined by qRT-PCR, were upregulated in 11 isolates. Six isolates might have utilized other efflux pumps or antimicrobial resistance mechanisms. These analyses demonstrated a highly diverse population and the presence of complex resistance mechanisms in urinary isolates of K. pneumoniae.

scholarly journals Enterobacteriaceae isolates carrying the New Delhi metallo-β-lactamase gene in Yemen

2014 ◽  
Vol 63 (10) ◽  
pp. 1316-1323 ◽  
Author(s):  
Alima Gharout-Sait ◽  
Samer-Ahmed Alsharapy ◽  
Lucien Brasme ◽  
Abdelaziz Touati ◽  
Rachida Kermas ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Susceptibility Testing ◽  
Enterobacter Cloacae ◽  
New Delhi ◽  
Carbapenem Resistant ◽  
Genes Encoding ◽  
Phenotypic Tests ◽  
Lactamase Gene ◽  
Sequence Types

Ten carbapenem-resistant Enterobacteriaceae (eight Klebsiella pneumoniae isolates and two Enterobacter cloacae) isolates from Yemen were investigated using in vitro antimicrobial susceptibility testing, phenotypic carbapenemase detection, multilocus sequence typing (MLST) and replicon typing. Carbapenemase, extended-spectrum β-lactamase (ESBL) and plasmid-mediated quinolone resistance determinant genes were identified using PCR and sequencing. All of the 10 carbapenem-resistant Enterobacteriaceae were resistant to β-lactams, tobramycin, ciprofloxacin and cotrimoxazole. Imipenem, doripenem and meropenem MICs ranged from 2 to >32 mg l−1 and ertapenem MICs ranged from 6 to >32 mg l−1. All of the K. pneumoniae isolates showed ESBL activity in phenotypic tests. Genes encoding bla NDM were detected in all strains. All K. pneumoniae strains produced CTX-M-15 ESBL and SHV β-lactamases. TEM-1 β-lactamase was detected in seven isolates. Nine isolates were qnr positive including QnrB1, QnrA1 and QnrS1, and six isolates produced AAC-6′-Ib-cr. MLST identified five different sequence types (STs): ST1399, ST147, ST29, ST405 and ST340. Replicon typing showed the presence of IncFII1K plasmids in four transformants. To the best of our knowledge, this is the first report of NDM-1-producing Enterobacteriaceae isolates in Yemen.

scholarly journals Spread of ST348 Klebsiella pneumoniae Producing NDM-1 in a Peruvian Hospital

2020 ◽  
Vol 8 (9) ◽  
pp. 1392 ◽  
Author(s):  
Maria J. Pons ◽  
Marta Marí-Almirall ◽  
Barbara Ymaña ◽  
Jeel Moya-Salazar ◽  
Laura Muñoz ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Molecular Data ◽  
Resistance Mechanisms ◽  
Conjugative Plasmid ◽  
New Delhi ◽  
Carbapenem Resistant ◽  
Gradient Diffusion ◽  
Adults And Children ◽  
First Time ◽  
Esbl Producers

The aim of this study was to characterize carbapenem-resistant Klebsiella pneumoniae (CR-Kp) isolates recovered from adults and children with severe bacteremia in a Peruvian Hospital in June 2018. Antimicrobial susceptibility was determined by disc/gradient diffusion and broth microdilution when necessary. Antibiotic resistance mechanisms were evaluated by PCR and DNA sequencing. Clonal relatedness was assessed using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Plasmid typing was performed with a PCR-based method. Thirty CR-Kp isolates were recovered in June 2018. All isolates were non-susceptible to all β-lactams, ciprofloxacin, gentamicin and trimethoprim-sulfamethoxazole, while mostly remaining susceptible to colistin, tigecycline, levofloxacin and amikacin. All isolates carried the blaNDM-1 gene and were extended spectrum β-lactamase (ESBL) producers. PFGE showed four different pulsotypes although all isolates but two belonged to the ST348 sequence type, previously reported in Portugal. blaNDM-1 was located in an IncFIB-M conjugative plasmid. To our knowledge, this is the first report of an New Delhi metallo-β-lactamase (NDM)-producing K. pneumoniae recovered from both children and adults in Lima, Peru, as well as the first time that the outbreak strain ST348 is reported in Peru and is associated with NDM. Studies providing epidemiological and molecular data on CR-Kp in Peru are essential to monitor their dissemination and prevent further spread.

scholarly journals Draft Genome Sequence of Carbapenem-Resistant Klebsiella pneumoniae XPY20 Collected from a Bloodstream Infection Patient

2018 ◽  
Vol 6 (21) ◽  
Author(s):  
Qiong Chen ◽  
Jia-wei Zhou ◽  
Sheng-hai Wu ◽  
Xiao-hua Meng ◽  
Dao-jun Yu ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Draft Genome ◽  
Bloodstream Infections ◽  
Mortality Rates ◽  
Resistance Mechanisms ◽  
Severe Problem ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Infection Patient ◽  
Generation Sequencing

ABSTRACT Bloodstream infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) strains have been a severe problem with high clinical costs and high mortality rates. The bla KPC-2-producing CRKP strain XPY20 was collected from the blood of a patient. The genome characteristics and antimicrobial resistance mechanisms were determined using next-generation sequencing.

scholarly journals Co-existence of virulence factors and antibiotic resistance in new Klebsiella pneumoniae clones emerging in south of Italy

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Teresa Fasciana ◽  
Bernardina Gentile ◽  
Maria Aquilina ◽  
Andrea Ciammaruconi ◽  
Chiara Mascarella ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Virulence Factors ◽  
In Silico ◽  
Geographical Area ◽  
In Silico Analysis ◽  
University Hospital ◽  
Uptake System ◽  
Genes Encoding ◽  
Silico Analysis

Abstract Background Endemic presence of Klebsiella pneumoniae resistant to carbapenem in Italy has been due principally to the clonal expansion of CC258 isolates; however, recent studies suggest an ongoing epidemiological change in this geographical area. Methods 50 K. pneumoniae strains, 25 carbapenem-resistant (CR-Kp) and 25 susceptible (CS-Kp), collected from march 2014 to march 2016 at the Laboratory of Bacteriology of the Paolo Giaccone Polyclinic University hospital of Palermo, Italy, were characterized for antibiotic susceptibility and fully sequenced by next generation sequencing (NGS) for the in silico analysis of resistome, virulome, multi-locus sequence typing (MLST) and core single nucleotide polymorphism (SNP) genotypes Results MLST in silico analysis of CR-Kp showed that 52% of isolates belonged to CC258, followed by ST395 (12%), ST307 (12%), ST392 (8%), ST348 (8%), ST405 (4%) and ST101 (4%). In the CS-Kp group, the most represented isolate was ST405 (20%), followed by ST392 and ST15 (12%), ST395, ST307 and ST1727 (8%). The in silico β-lactamase analysis of the CR-Kp group showed that the most detected gene was blaSHV (100%), followed by blaTEM (92%), blaKPC (88%), blaOXA (88%) and blaCTX-M (32%). The virulome analysis detected mrk operon in all studied isolates, and wzi-2 was found in three CR-Kp isolates (12%). Furthermore, the distribution of virulence genes encoding for the yersiniabactin system, its receptor fyuA and the aerobactin system did not show significant distribution differences between CR-Kp and CS-Kp, whereas the Klebsiella ferrous iron uptake system (kfuA, kfuB and kfuC genes), the two-component system kvgAS and the microcin E495 were significantly (p < 0.05) prevalent in the CS-Kp group compared to the CR-Kp group. Core SNP genotyping, correlating with the MLST data, allowed greater strain tracking and discrimination than MLST analysis. Conclusions Our data support the idea that an epidemiological change is ongoing in the Palermo area (Sicily, Italy). In addition, our analysis revealed the co-existence of antibiotic resistance and virulence factors in CR-Kp isolates; this characteristic should be considered for future genomic surveillance studies.

scholarly journals Investigation of carbapenemase and mcr-1 genes in carbapenem-resistant Klebsiella pneumoniae isolates

2019 ◽  
Vol 13 (06) ◽  
pp. 504-509 ◽  
Author(s):  
Çiğdem Arabacı ◽  
Tuba Dal ◽  
Tuğcan Başyiğit ◽  
Neslihan Genişel ◽  
Rıza Durmaz
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Bacterial Infections ◽  
Resistance Mechanisms ◽  
Control Measures ◽  
Epidemiological Methods ◽  
Infection Control Measures ◽  
Microdilution Method ◽  
Carbapenem Resistant ◽  
Susceptibility Tests

Introduction: Carbapenem-resistant Klebsiella pneumoniae are a major problem. We aimed to investigate carbapenemase-encoding genes and transferable mcr-1 genes among 57 carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from hospitalized patients. Methodology: Antibiotic susceptibility tests were performed by Phoenix (BD). Results for ertapenem and colistin were confirmed by gradient diffusion and microdilution methods. Carbapenemase and mcr-1 genes were investigated by Polymerase Chain Reaction (PCR). Results: Thirty-two (56.14%) isolates were from intensive care units (ICU). Antibiotic resistance rates by Phoenix: 52.63% for amikacin; 73.69% trimethoprim sulfamethoxazole; 91.23% cefepime; 82.46% tigecycline; 59.65% colistin. Carbapenemases positivity: 82.45% (47) for blaOXA-48, 40.35% (23) blaOXA-55, 3.50% (2) blaOXA-51, 1.75% (1) blaOXA-23, 1.75% (1) blaOXA-24, 1.75% (1) blaIMP. blaOXA-58, blaKPC, blaNDM-1, and blaVIM were not detected. Twenty (35.08%) isolates had both blaOXA-48 and blaOXA-55. Three isolates were mcr-1 (+) and blaOXA-48 (+). One mcr-1 (+) isolates was blaOXA-51 (+). One colistin sensitive isolate determined by Phoenix, was found colistin resistant by microdilution. Conclusion: OXA-48 and OXA-55 co-harboring isolates and mcr-1 gene (+) isolates were spreading. Automated colistin susceptibility results should be confirmed by microdilution method. Resistance mechanisms in Enterobacteriaceae should be determined and the isolates should be monitored by molecular epidemiological methods. Effective infection control measures will contribute to reduce risk of antibiotic resistant bacterial infections and dissemination of antibiotic resistance.

scholarly journals Aerobactin Seems To Be a Promising Marker Compared With Unstable RmpA2 for the Identification of Hypervirulent Carbapenem-Resistant Klebsiella pneumoniae: In Silico and In Vitro Evidence

2021 ◽  
Vol 11 ◽  
Author(s):  
Chaitra Shankar ◽  
Soumya Basu ◽  
Binesh Lal ◽  
Sathiya Shanmugam ◽  
Karthick Vasudevan ◽  
...  
Keyword(s):  
High Risk ◽  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
In Silico ◽  
Fitness Cost ◽  
Virulence Plasmid ◽  
Virulence Determinants ◽  
Carbapenem Resistant ◽  
Antimicrobial Resistance Genes

BackgroundThe incidence of hypervirulent (hv) carbapenem-resistant (CR) Klebsiella pneumoniae (Kp) is increasing globally among various clones and is also responsible for nosocomial infections. The CR-hvKp is formed by the uptake of a virulence plasmid by endemic high-risk clones or by the uptake of plasmids carrying antimicrobial resistance genes by the virulent clones. Here, we describe CR-hvKp from India belonging to high-risk clones that have acquired a virulence plasmid and are phenotypically unidentified due to lack of hypermucoviscosity.MethodsTwenty-seven CRKp isolates were identified to possess rmpA2 by whole-genome sequencing; and resistance and virulence determinants were characterized. By in silico protein modeling (and validation), protein backbone stability analysis, and coarse dynamics study, the fitness of RmpA, RmpA2, and aerobactin-associated proteins-IucA and IutA, were determined to establish a reliable marker for clinical identification of CR-hvKp.ResultsThe CR-hvKp belonged to multidrug-resistant (MDR) high-risk clones such as CG11, CG43, ST15, and ST231 and carried OXA-232 as the predominant carbapenemase followed by NDM. The virulence plasmid belonged to IncHI1B replicon type and carried frameshifted and truncated rmpA and rmpA2. This resulted in a lack of hypermucoviscous phenotype. However, functional aerobactin was expressed in all high-risk clones. In silico analysis portrayed that IucA and IutA were more stable than classical RmpA. Furthermore, IucA and IutA had lower conformational fluctuations in the functional domains than the non-functional RmpA2, which increases the fitness cost of the latter for its maintenance and expression among CR-hvKp. Hence, RmpA and RmpA2 are likely to be lost among CR-hvKp owing to the increased fitness cost while coding for essential antimicrobial resistance and virulence factors.ConclusionIncreasing incidence of convergence of AMR and virulence is observed among K. pneumoniae globally, which warrants the need for reliable markers for identifying CR-hvKp. The presence of non-functional RmpA2 among high-risk clones highlights the significance of molecular identification of CR-hvKp. The negative string test due to non-functional RmpA2 among CR-hvKp isolates challenges phenotypic screening and faster identification of this pathotype. This can potentially be counteracted by projecting aerobactin as a stable, constitutively expressed, and functional marker for rapidly evolving CR-hvKp.

scholarly journals Molecular Epidemiology of Carbapenem-Resistant Klebsiella pneumoniae Infections in Southwest China

2020 ◽  
Author(s):  
Xiaopin Hu ◽  
Guohang Yuan ◽  
Yaoyao Wu ◽  
Weijia Liu ◽  
Xiangyan Zhang ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Southwest China ◽  
Antibiotic Use ◽  
Resistance Mechanisms ◽  
Control Measures ◽  
Invasive Procedures ◽  
Carbapenem Resistant ◽  
Tertiary Hospitals ◽  
Resistance Rates ◽  
Epidemiological Characteristics

Abstract Background: We determined epidemiological characteristics and resistance mechanisms of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains found in Southwest China and assessed disease burden to provide evidence-based strategies for control and treatment of CRKP infection. Methods: A total of 159 strains of CRKP were isolated from sputa, blood, urine, ascites and wound secretions from three tertiary hospitals in Southwest China between August 1st, 2018 and December 31st, 2019. The sensitivity of each strain to 12 antibiotic agents was determined by micro-broth dilution. Identification of carbapenemase genes and multi-locus sequence typing (MLST) were performed using polymerase chain reaction (PCR). The disease burdens of patients with CRKP were assessed based on invasive procedures, antibiotic use, laboratory tests and clinical outcomes. Results: Of 159 CRKP strains analyzed, 50.9% were isolated from sputum samples. The percentage of patients who underwent invasive procedures before positive cultures for CRKP were detected was 96.3%. The mortality of blood infection was highest (66.6%) among patients with CRKP infection. All strains were insensitive to carbapenems. The resistance rates to levofloxacin and amikacin were 85.5% and 81.8%, respectively. All CRKP strains produced carbapenemases, with a majority of isolates (81.1%) producing KPC-2. The MICs of strains harbouring both KPC-2 and NDM-1 were higher than those of strains with only KPC-2 or NDM-1. ST11 is the most popular clonotype found in Southwest China. Conclusions: CRKP strains in Southwest China are characterized by strong drug resistance and associated with poor clinical prognoses. It is therefore urgent to both strengthen control measures and improve prevention awareness.

scholarly journals Characterization of a blaNDM-1-Bearing IncHI5-Like Plasmid From Klebsiella pneumoniae of Infant Origin

2021 ◽  
Vol 11 ◽  
Author(s):  
Ziyi Liu ◽  
Ruifei Chen ◽  
Poshi Xu ◽  
Zhiqiang Wang ◽  
Ruichao Li
Keyword(s):  
Klebsiella Pneumoniae ◽  
Genomic Analysis ◽  
Comparative Genomic ◽  
Genetic Composition ◽  
Carbapenem Resistant ◽  
Antimicrobial Resistance Genes ◽  
Genes Encoding ◽  
History Of ◽  
Core Genes

The spread of plasmid-mediated carbapenem-resistant clinical isolates is a serious threat to global health. In this study, an emerging NDM-encoding IncHI5-like plasmid from Klebsiella pneumoniae of infant patient origin was characterized, and the plasmid was compared to the available IncHI5-like plasmids to better understand the genetic composition and evolution of this emerging plasmid. Clinical isolate C39 was identified as K. pneumoniae and belonged to the ST37 and KL15 serotype. Whole genome sequencing (WGS) and analysis revealed that it harbored two plasmids, one of which was a large IncHI5-like plasmid pC39-334kb encoding a wide variety of antimicrobial resistance genes clustered in a single multidrug resistance (MDR) region. The blaNDM-1 gene was located on a ΔISAba125-blaNDM-1-bleMBL-trpF-dsbC structure. Comparative genomic analysis showed that it shared a similar backbone with four IncHI5-like plasmids and the IncHI5 plasmid pNDM-1-EC12, and these six plasmids differed from typical IncHI5 plasmids. The replication genes of IncHI5-like plasmids shared 97.06% (repHI5B) and 97.99% (repFIB-like) nucleotide identity with those of IncHI5 plasmids. Given that pNDM-1-EC12 and all IncHI5-like plasmids are closely related genetically, the occurrence of IncHI5-like plasmid is likely associated with the mutation of the replication genes of pNDM-1-EC12-like IncHI5 plasmids. All available IncHI5-like plasmids harbored 262 core genes encoding replication and maintenance functions and carried distinct MDR regions. Furthermore, 80% of them (4/5) were found in K. pneumoniae from Chinese nosocomial settings. To conclude, this study expands our knowledge of the evolution history of IncHI5-like plasmids, and more attention should be paid to track the evolution pathway of them among clinical, animal, and environmental settings.

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