scholarly journals Plasmids as donors of Insertion Sequence elements mediating colistin resistance in Klebsiella pneumoniae

2021 ◽  
Author(s):  
Stephen Mark Edward Fordham ◽  
Anna Mantzouratou ◽  
Elizabeth Anne Sheridan
Keyword(s):  
Klebsiella Pneumoniae ◽  
Odds Ratio ◽  
Clinical Settings ◽  
Drug Resistant ◽  
Colistin Resistance ◽  
Is Element ◽  
Is Elements ◽  
Extensively Drug Resistant ◽  
Carbapenemase Gene ◽  
Significant Difference

Colistin is a last resort antibiotic for the treatment of carbapenemase producing Klebsiella pneumoniae (CRKP) and other extensively drug resistant (XDR) gram-negative bacterial isolates. In line with rising colistin use worldwide, colistin resistant Klebsiella pneumoniae (K. pneumoniae) isolates have emerged. Insertion sequences (IS) integrating into the mgrB gene represents a significant mechanism mediating the emergence of colistin resistance in clinical settings. The disruption of mgrB by ISs has been widely reported worldwide. Evidence suggests plasmids encode mobilizable IS elements which preferentially integrate into the mgrB gene in K. pneumoniae causing gene inactivation and colistin resistance. Recognised IS elements targeting mgrB include ISL3 (ISKpn25), IS5 (ISKpn26), ISKpn14 and IS903B-like elements. K. pneumoniae represents the single largest species carrying plasmids encoding each IS element. The nucleotide reference sequence for ISKpn25, ISKpn26, ISKpn14 and IS903B were downloaded from IS finder. The BLATSn tool from NCBI was used to retrieve sequences producing significant alignment. For IS presence among species, 1000 BLASTn hits were downloaded and filtered for plasmids. Additionally, the top 120 BLASTn non-duplicate circularised plasmid contig hits for each IS element were typed for incompatibility (Inc) group and carbapenemase gene presence. Metadata pertaining to each sample was retrieved, including isolate source information to aid the understanding of the clinical threat posed by IS elements. IS903B was found in 28 unique Inc groups, while ISKpn25 was largely carried by IncFIB(pQil) plasmids. ISKpn26 and ISKpn14 were most often found associated with IncFII(pHN7A8) plasmids. Of the 34 unique countries which contained any of the IS elements, ISKpn25 was identified from 26. India, USA, and Italy were the isolation origin country for 16.6%, 13.3%, and 9.2%, respectively of the ISKpn25 insertions identified in plasmids. In contrast, ISKpn26, ISKpn14, and IS903B insertion sequences were identified from 89.3%, 44.9% and 23.9% plasmid samples from China. The stratification of carbapenemase genes presence and isolation source between ISKpn25, ISKpn26, ISKpn14 and IS903B bearing plasmids was markedly different. A significant difference between IS elements and the distribution of carbapenemase genes (χ2(3, N = 480) = 155.12, p = <.001) was detected. In addition, a significant difference between IS elements and source isolation distribution (χ2(3, N = 382) = 46.97, p = <.001) was also observed. Post hoc analysis revealed IS903B has a significantly different (p = <.001) carbapenemase and source isolation distribution relative to ISKpn26, ISKpn14 or ISKpn25. The odds ratio revealed plasmids carrying ISKpn25, ISKpn14, and ISKpn26 IS elements are 12.18, 27.0, and 44.43 times more likely to carry carbapenemase genes relative to plasmids carrying the IS element IS903B. Moreover, the odds ratio reveled ISKpn26, ISKpn25, and ISKpn14 were 6.10, 28.82, and 31.47 times more likely to be sourced from a clinical environmental setting than the environment relative to IS903B IS harboring plasmids. ISKpn25 present on IncFIB(pQil) sourced from clinical settings is established across multiple countries, while ISKpn26, ISKpn14, and IS903B appear most often in China. High carbapenemase presence in tandem with IS elements may help promote an extensively drug resistant profile in K. pneumoniae. IS element mobilisation into the mgrB gene has been linked to colistin treatment therapy, while carbapenemase gene presence has been associated with the epidemic success of K. pneumoniae in clinical settings. Plasmids which harbour both carbapenemases and IS elements may engender an extensively drug resistant phenotype during colistin therapy in hospitals.

scholarly journals 603. Identification of a Carbapenemase-Producing, Extensively Drug-Resistant Klebsiella pneumoniae Isolate Carrying a blaNDM-1-Bearing, Hypervirulent Plasmid, United States 2017

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S282-S283
Author(s):  
Richard A Stanton ◽  
Gillian A McAllister ◽  
Amelia Bhatnagar ◽  
Maria Karlsson ◽  
Allison C Brown ◽  
...  
Keyword(s):  
United States ◽  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Critical Role ◽  
Illumina Miseq ◽  
The United States ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Drug Classes ◽  
Carbapenemase Gene

Abstract Background The recent discovery of carbapenemase-producing hypervirulent Klebsiella pneumoniae (CP-HvKP) has signaled the convergence of multidrug resistance and pathogenicity, with the potential for increased mortality. While previous studies of CP-HvKP isolates revealed that most carried carbapenemase genes and hypervirulence elements on separate plasmids, a 2018 report from China confirmed that both could be harbored on a single, hybrid carbapenemase-hypervirulent plasmid. As part of a project sequencing isolates carrying multiple carbapenemase genes identified through CDC’s Antibiotic Resistance Laboratory Network (AR Lab Network), we discovered a blaNDM-1-bearing hypervirulent plasmid found in a KPC- and NDM-positive K. pneumoniae from the United States. Methods Antimicrobial susceptibility testing (AST) was performed by reference broth microdilution against 23 agents. Whole-genome sequencing (WGS) was performed on Illumina MiSeq and PacBio RS II platforms. Results AST results indicated the isolate was extensively drug-resistant, as it was non-susceptible to at least one agent in all but two drug classes; it was susceptible to only tigecycline and tetracycline. Analysis of WGS data showed the isolate was ST11, the same sequence type that caused a fatal outbreak of CP-HvKP in China in 2016. The genome included two plasmids. The smaller one (129kbp) carried seven antibiotic resistance (AR) genes, including the carbapenemase gene blaKPC-2. The larger plasmid (354kbp) harbored 11 AR genes, including the metallo-β-lactamase gene blaNDM-1, as well as virulence factors iucABCD/iutA, peg-344, rmpA, and rmpA2, which comprise four of the five genes previously identified as predictors of hypervirulence in K. pneumoniae. Conclusion This is the first report of a hybrid carbapenemase-hypervirulent plasmid in the United States. The presence of both blaNDM-1 and hypervirulence elements on the same plasmid suggests that the CP-Hv pathotype could spread rapidly through horizontal transfer. This discovery demonstrates the critical role of genomic characterization of emerging resistance and virulence phenotypes by the AR Lab Network as part of US containment efforts. Disclosures All authors: No reported disclosures.

scholarly journals First Report of an Extensively Drug-Resistant ST23 Klebsiella pneumoniae of Capsular Serotype K1 Co-Producing CTX-M-15, OXA-48 and ArmA in Spain

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 157
Author(s):  
Marta Hernández ◽  
Luis López-Urrutia ◽  
David Abad ◽  
Mónica De Frutos Serna ◽  
Alain Ocampo-Sosa ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Whole Genome ◽  
Drug Resistant ◽  
Genomic Context ◽  
Antibiotic Resistant ◽  
Resistant Genes ◽  
Extensively Drug Resistant ◽  
Oxford Nanopore ◽  
Carbapenemase Gene ◽  
16S Rrna Methylase

An extensively drug-resistant (XDR) Klebsiella pneumoniae isolate MS3802 from a tracheostomy exudate was whole-genome sequenced using MiSeq and Oxford Nanopore MinION platforms in order to identify the antimicrobial resistance and virulence determinates and their genomic context. Isolate MS3802 belonged to the clone ST23 and presented a capsular serotype K1, associated with hypervirulent K. pneumoniae (hvKp) isolates. The isolate harboured a chromosomally encoded blaCTX-M-15 gene and contained a large IncHI1B hybrid virulence/resistance plasmid carrying another copy of the blaCTX-M-15 and the virulence factors iucABCD-iutA, iroBCDN, rmpA and rmpA2. The carbapenemase gene blaOXA-48 was found in a Tn1999-like transposon and the 16S rRNA methylase armA gen located in the vicinity of other antibiotic-resistant genes on an IncM2 plasmid. This study represents, to the best of our knowledge, the first description of a blaCTX-M-15-, blaOXA-48- and armA-harbouring K. pneumoniae of ST23 and capsular serotype K1 in Spain. Our report emphasizes the importance of implementing new surveillance strategies to monitor the risk of emergence and spread of such XDR and hypervirulent K. pneumoniae isolates.

scholarly journals Genomic insights into multi-drug and extensively drug resistant Klebsiella pneumoniae from India

2020 ◽  
Vol 101 ◽  
pp. 12-13
Author(s):  
C. Shankar ◽  
P. Mathur ◽  
J.J. Jacob ◽  
C. Rodrigues ◽  
K. Walia ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Drug Resistant ◽  
Extensively Drug Resistant

scholarly journals Wastewaters, with or without Hospital Contribution, Harbour MDR, Carbapenemase-Producing, but Not Hypervirulent Klebsiella pneumoniae

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 361
Author(s):  
Adela Teban-Man ◽  
Anca Farkas ◽  
Andreea Baricz ◽  
Adriana Hegedus ◽  
Edina Szekeres ◽  
...  
Keyword(s):  
Principal Component Analysis ◽  
Klebsiella Pneumoniae ◽  
Wastewater Treatment Plants ◽  
Principal Component ◽  
Drug Resistant ◽  
Beta Lactams ◽  
Carbapenemase Gene ◽  
Antibiotic Susceptibility Patterns ◽  
Sequence Types ◽  
Susceptibility Patterns

Carbapenemase-producing Klebsiella pneumoniae (CPKP) isolated from influent (I) and effluent (E) of two wastewater treatment plants, with (S1) or without (S2) hospital contribution, were investigated. The strains belonged to the Kp1 phylogroup, their highest frequency being observed in S1, followed by S2. The phenotypic and genotypic hypervirulence tests were negative for all the strains tested. At least one carbapenemase gene (CRG), belonging to the blaKPC, blaOXA-48, blaNDM and blaVIM families, was observed in 63% of CPKP, and more than half co-harboured two to four CRGs, in different combinations. Only five CRG variants were observed, regardless of wastewater type: blaKPC-2, blaNDM-1, blaNDM-6, blaVIM-2, and blaOXA-48. Sequence types ST258, ST101 and ST744 were common for both S1 and S2, while ST147, ST525 and ST2502 were found only in S1 and ST418 only in S2. The strains tested were multi-drug resistant (MDR), all being resistant to beta-lactams, cephalosporins, carbapenems, monobactams and fluoroquinolones, followed by various resistance profiles to aminoglycosides, trimethoprim-sulphamethoxazole, tigecycline, chloramphenicol and tetracycline. After principal component analysis, the isolates in S1 and S2 groups did not cluster independently, confirming that the antibiotic susceptibility patterns and gene-type profiles were both similar in the K. pneumoniae investigated, regardless of hospital contribution to the wastewater type.

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

scholarly journals Extensively Drug-Resistant Hypervirulent Klebsiella pneumoniae From a Series of Neonatal Sepsis in a Tertiary Care Hospital, India

2021 ◽  
Vol 8 ◽  
Author(s):  
Tuhina Banerjee ◽  
Jayalaxmi Wangkheimayum ◽  
Swati Sharma ◽  
Ashok Kumar ◽  
Amitabha Bhattacharjee
Keyword(s):  
Klebsiella Pneumoniae ◽  
Neonatal Sepsis ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Plasmid Profile ◽  
Care Hospital ◽  
Drug Resistant ◽  
Maternal Complications ◽  
Extensively Drug Resistant ◽  
Recent Emergence

The recent emergence of multidrug-resistant (MDR) Klebsiella pneumoniae with hypervirulent traits causing severe infections and considerable mortality is a global cause for concern. The challenges posed by these hypermucoviscous strains of K. pneumoniae with regard to their optimal treatment, management, and control policies are yet to be answered. We studied a series of extensively drug-resistant (XDR) and hypervirulent K. pneumoniae ST5235 isolates with resistance to carbapenems and polymyxins causing neonatal sepsis in a tertiary care hospital in India. A total of 9 K. pneumoniae isolates from 9 cases of neonatal sepsis were studied with respect to their clinical relevance, antimicrobial susceptibility profile, presence of extended spectrum β lactamase (ESBL) production, and responsible genes, carbapenemases (classes A, B, and D), and aminoglycoside-resistant genes. Hypervirulence genes encoding hypermucoid nature, iron uptake, and siderophores were detected by multiplex PCR. The plasmid profile was studied by replicon typing. Isolates were typed by multilocus sequence typing (MLST) and enterobacterial repetitive intergenic consensus (ERIC) PCR to study the sequence types (STs) and clonal relation, respectively. The neonates in the studied cases had history of pre-maturity or low birth weight with maternal complications. All the cases were empirically treated with piperacillin–tazobactam and amikacin followed by imipenem/meropenem and vancomycin and polymyxin B as a last resort. However, all the neonates finally succumbed to the condition (100%). The studied isolates were XDR including resistance to polymyxins harboring multiple ESBL genes and carbapenemase genes (blaNDM and blaOXA−48). Hypervirulence genes were present in various combinations with rmpA/A2 genes present in all the isolates. IncFI plasmids were detected in these isolates. All belonged to ST5235. In ERIC PCR, 6 different clusters were seen. The study highlighted the emergence and burden of XDR hypervirulent isolates of K. pneumoniae causing neonatal sepsis in a tertiary care hospital.

Infrequent isolation of extensively drug-resistant (XDR) Klebsiella pneumoniae resistant to colistin in Spain

2018 ◽  
Vol 51 (3) ◽  
pp. 531-533 ◽  
Author(s):  
Marta Hernández ◽  
Narciso M. Quijada ◽  
Luis López-Urrutia Lorente ◽  
Mónica de Frutos ◽  
David Rodríguez-Lázaro ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Drug Resistant ◽  
Extensively Drug Resistant

Detection of extensively drug-resistant and hypervirulent Klebsiella pneumoniae ST15, ST147, ST377 and ST442 in Iran

2021 ◽  
Author(s):  
Sara Davoudabadi ◽  
Hossein Goudarzi ◽  
Mehdi Goudarzi ◽  
Abdollah Ardebili ◽  
Ebrahim Faghihloo ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Pcr Amplification ◽  
Multidrug Resistant ◽  
Diffusion Method ◽  
Drug Resistant ◽  
Carbapenem Resistant ◽  
Extensively Drug Resistant ◽  
String Test ◽  
Pcr Method ◽  
Extensively Drug Resistance

Abstract In this study, we focused on the emergence of extensively drug-resistant (XDR), pandrug-resistant (PDR), and hypervirulent Klebsiella pneumoniae (hvKP) in Iran. During 2018 to 2020 a total of 52 K. pneumoniae isolates were collected from different clinical specimens. The hvKP isolates were identified by PCR amplification of virulence and capsular serotype-specific genes. Hypermucoviscous K. pneumoniae (hmKP) were identified by string test. Carbapenem-resistant hvKP (CR-hvKP), multidrug-resistant hvKP (MDR-hvKP), extensively drug-resistant hvKP (XDR-hvKP), and pandrug-resistant hvKP (PDR-hvKP) were determined by disc diffusion method, Carba-NP test and PCR method. XDR-hvKP isolates were typed by multilocus sequence typing (MLST). Among all K. pneumoniae isolates 14 (26.9%) were identified as hvKP and 78.6% (11/14) of them were hmKP however, none of the classic K. pneumoniae (cKP) isolates were hmKP. The predominant capsular serotype of hvKP was K2 (42.85%) followed by K1 (35.71%). The prevalence of MDR-hvKP, XDR-hvKP and PDR-hvKP isolates were 6 (42.9%), 5 (35.7%) and 1 (7.1%), respectively. ESBL production was found in 85.7% of hvKP isolates and most of them carried bla TEM gene (78.6%) and 6 isolates (42.9%) were CR-hvKP. Among hvKP isolates, 1 (7.1%), 2 (14.3%), 3 (21.4%), 8 (28.6%), and 11 (78.6%) carried bla NDM-6, bla OXA-48, bla CTX-M, bla SHV, and bla TEM genes, respectively. According to MLST analysis, 2, 1, 1, and 1 XDR-hvKP isolates belonged to ST15, ST377, ST442, and ST147, respectively. The occurrence of such isolates is deeply concerning due to the combination of hypervirulence and extensively drug-resistance or pandrug-resistance.

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