scholarly journals Carbapenem-Resistant Klebsiellapneumoniae Infections in ICU COVID-19 Patients—A Scoping Review

2021 ◽  
Vol 10 (10) ◽  
pp. 2067
Author(s):  
Wioletta Mędrzycka-Dąbrowska ◽  
Sandra Lange ◽  
Katarzyna Zorena ◽  
Sebastian Dąbrowski ◽  
Dorota Ozga ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Medical Community ◽  
Cochrane Library ◽  
Continuous Control ◽  
Exclusion Criteria ◽  
Scientific Databases ◽  
Carbapenem Resistant ◽  
Review Protocol

Introduction: The spread of multidrug-resistant pathogens is a serious problem and challenge for the whole medical community. Carbapenem-resistant Klebsiella Pneumoniae (CRKP) infections in immunocompromised patients have a severe course and may be fatal. Increasingly, these bacteria are exhibiting resistance to carbapenem antibiotics, which have been used as so-called drugs of last resort. The emergence of the new coronavirus and the pandemic that it has caused require changes to protect against the spread of the new SARS-CoV-2. These changes paradoxically may contribute to the spread of other infections. Methods: PubMed, Cochrane Library databases were searched using relevant keywords. A literature review of carbapenem-resistant Klebsiella Pneumoniae infection in patients hospitalized for COVID-19 was conducted according to PRISMA recommendations. A written review protocol was not prepared. Results: 1016 studies in scientific databases were searched. After rejecting duplicate studies, 964 results were obtained. Inclusion and exclusion criteria were then applied, and studies were qualitatively analyzed. Finally, 11 studies were included in the review. The results of infected patients were from six countries. The prevalence of CRKP in Covid-19 patients ranged from 0.35–53%. The majority of CRKP infected patients were male (85%), with a mean age of 61 years. Among isolates, the predominant genes were KPC, OXY-48, CTX-M, TEM, NDM and SHV. Conclusion: The results presented in our review indicate the necessity of paying attention to carbapenem-resistant Klebsiella Pneumoniae infections in patients with COVID-19. In order to prevent the increase of bacterial resistance, rational antibiotic therapy should be used, as well as continuous control and surveillance of hospital infections caused by multidrug-resistant organisms.

Molecular epidemiologic factors contributing to quinolone resistance in clinical multidrug-resistant Klebsiella pneumoniae isolates from Shanghai, China

2021 ◽  
Author(s):  
Yan Wang ◽  
Guoping Cai ◽  
Jinan Zhang ◽  
Xiaogang Xu ◽  
Hongzhou Lu
Keyword(s):  
Klebsiella Pneumoniae ◽  
Point Source ◽  
Bacterial Resistance ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
Quinolone Resistance ◽  
Epidemiologic Factors ◽  
Selective Pressures ◽  
Carbapenem Resistant ◽  
Epidemiologic Surveillance

Abstract BackgroundThe soaring quinolone-resistance rate of Klebsiella pneumoniae, a common pathogen in immunocompromised individuals, has seriously undermined the wide applications of antimicrobials of this class. This study aimed to investigate the emerging key contributors to quinolone-resistance in multidrug resistant K. pneumoniae (MDR-KP) isolates from a clinical setting with continuing point-source infection outbreaks in Shanghai, China. ResultsBetween January and March 2017, a total of 34 K. pneumoniae isolates, including 30 carbapenem-resistant K. pneumoniae (CRKP), were selected and characterized from a teaching hospital participating in an ongoing Bacterial Resistance Surveillance Project in Shanghai, China. Two predominant high-risk CRKP clones, ST11-wzi64 and ST15-wzi19/wzi24, caused three point-source nosocomial outbreaks in intensive care unit and/or neurosurgery department potentially by respiratory-route, promoting the co-selection and evolution of multidrug-resistant determinants. Multiple quinolone resistance-determining region (QRDR) mutations occurred in isolates of ST15 (S83F, D87A; S80I), ST11 (S83I, D87G; S80I), and ST218 (D87A; S80I). Plasmid-mediated quinolone resistance determinants, qnrS1, aac(6’)-Ib-cr, oqxAB, were detected in 32 (94.1%) isolates alone or in combination, spreading accompanied with β-lactamases (mainly, KPC-2-type carbapenemase and CTX-M-type extended-spectrum β-lactamase), 16S rRNA methylases (ArmA and RmtB), and putrescine ABC transporter permease (PotI) variants, independently of QRDR-mutations. AcrR, AcrAB transcriptional repressor, was insertion-inactivated by IS5-transposase in isolates of ST11. Thirteen ompK36 variants associated with specific ST (n=7) and wzi-allele (n=9) clustered into 10 (sub)lineages in the phylogenetic tree possibly affecting the MDR phenotype and the infection outcome of isolates. Isolates of ST11, ST15, and ST218 had frameshift disruptions in OmpK35 coupled with specific GD-insertion at position 134-135 in OmpK36, all showing distinct microevolution clusters of ompK36 genotypes. Seven quinolone-susceptible isolates kept the porin genes integral, including two each CRKPs of ST13-wzi74 (carbapenemase KPC-2 and NDM-1-coproducers) and ST65-wzi72. ConclusionsUnder selective pressures, accumulation of mutations of three types (QRDR, AcrR, OmpK36/OmpK35) and acquisition of resistance-conferring genes has been continuously contributing to quinolone-resistance in clinical MDR-KP isolates, reinforcing the importance of ongoing epidemiologic surveillance on the evolution and transmission of these isolates. Our findings provided detailed mechanistic analyses and epidemiologic implications for further infection control and antibiotic stewardship initiatives.

First description of NDM-1-, KPC-2-, VIM-2- and IMP-4-producing Klebsiella pneumoniae strains in a single Chinese teaching hospital

2014 ◽  
Vol 143 (2) ◽  
pp. 376-384 ◽  
Author(s):  
Y. LIU ◽  
L.-G. WAN ◽  
Q. DENG ◽  
X.-W. CAO ◽  
Y. YU ◽  
...  
Keyword(s):  
16S Rrna ◽  
Klebsiella Pneumoniae ◽  
Teaching Hospital ◽  
Multidrug Resistant ◽  
The Other ◽  
Quinolone Resistance ◽  
Resistance Determinants ◽  
Carbapenem Resistant ◽  
Extended Spectrum ◽  
Chinese Teaching

SUMMARYA total of 180 non-duplicate carbapenem-resistant Klebsiella pneumoniae isolates were recovered from patients hospitalized between December 2010 and January 2012 at a Chinese hospital. Eight KPC-2, four NDM-1, one VIM-2, and five KPC-2 plus IMP-4 producers were identified and all were multidrug resistant due to the presence of other resistance determinants, including extended-spectrum β-lactamases (CTX-M-15, SHV-12), 16S rRNA methylases (armA, rmtB) and plasmid-mediated quinolone-resistance determinants (qnrA, B, S, aac(6′)-Ib-cr). Nine K. pneumoniae clones (Kpn-A1/ST395, Kpn-A3/ST11, Kpn-A2/ST134, Kpn-B/ST263, Kpn-C/ST37, Kpn-D/ST39, Kpn-E/ST1151, Kpn-F/ST890, Kpn-G/ST1153) were identified. blaKPC-2 was located on transferable ~65 kb IncL/M (ST395, ST11, ST134, ST39) and ~100 kb IncA/C (ST37, ST1153, ST890) plasmids, respectively. On the other hand, blaNDM-1 was associated with a ~70 kb IncA/C plasmid (ST263). However, non-typable plasmids of ~40 kb containing blaVIM-2 were detected in the ST1151 clone. This work reports the first co-occurrence of four diverse types of carbapenemase of K. pneumoniae clones from a single hospital in China. IncA/C, IncL/M, and other successful plasmids may be important for the dissemination of carbapenemases, producing a complex epidemiological picture.

scholarly journals Epigenomics, genomics, resistome, mobilome, virulome and evolutionary phylogenomics of carbapenem-resistant Klebsiella pneumoniae clinical strains

2020 ◽  
Vol 6 (12) ◽  
Author(s):  
Katlego Kopotsa ◽  
Nontombi M. Mbelle ◽  
John Osei Sekyere
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Type I ◽  
Bacteriophage Therapy ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Plasmid Replicon ◽  
Size Number ◽  
Plasmid Size ◽  
Epidemiological Trends

Carbapenem-resistant Klebsiella pneumoniae (CRKP) remains a major clinical pathogen and public health threat with few therapeutic options. The mobilome, resistome, methylome, virulome and phylogeography of CRKP in South Africa and globally were characterized. CRKP collected in 2018 were subjected to antimicrobial susceptibility testing, screening by multiplex PCR, genotyping by repetitive element palindromic (REP)-PCR, plasmid size, number, incompatibility and mobility analyses, and PacBio’s SMRT sequencing (n=6). There were 56 multidrug-resistant CRKP, having bla OXA-48-like and bla NDM-1/7 carbapenemases on self-transmissible IncF, A/C, IncL/M and IncX3 plasmids endowed with prophages, traT, resistance islands, and type I and II restriction modification systems (RMS). Plasmids and clades detected in this study were respectively related to globally established/disseminated plasmids clades/clones, evincing transboundary horizontal and vertical dissemination. Reduced susceptibility to colistin occurred in 23 strains. Common clones included ST307, ST607, ST17, ST39 and ST3559. IncFIIk virulent plasmid replicon was present in 56 strains. Whole-genome sequencing of six strains revealed least 41 virulence genes, extensive ompK36 mutations, and four different K- and O-loci types: KL2, KL25, KL27, KL102, O1, O2, O4 and O5. Types I, II and III RMS, conferring m6A (G A TC, G A TGNNNNNNTTG, CA A NNNNNNCATC motifs) and m4C (C C WGG) modifications on chromosomes and plasmids, were found. The nature of plasmid-mediated, clonal and multi-clonal dissemination of blaOXA-48-like and blaNDM-1 mirrors epidemiological trends observed for closely related plasmids and sequence types internationally. Worryingly, the presence of both bla OXA-48 and bla NDM-1 in the same isolates was observed. Plasmid-mediated transmission of RMS, virulome and prophages influence bacterial evolution, epidemiology, pathogenicity and resistance, threatening infection treatment. The influence of RMS on antimicrobial and bacteriophage therapy needs urgent investigation.

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.

scholarly journals Fighting Antibiotic-Resistant Klebsiella pneumoniae with “Sweet” Immune Targets

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Roberto Adamo ◽  
Immaculada Margarit
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Therapeutic Approaches ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Surface Polysaccharides ◽  
Resistant Strains ◽  
Murine Monoclonal Antibodies

ABSTRACT Antibiotics and vaccines have greatly impacted human health in the last century by dramatically reducing the morbidity and mortality associated with infectious diseases. The recent challenge posed by the emergence of multidrug-resistant bacteria could possibly be addressed by novel immune prophylactic and therapeutic approaches. Among the newly threatening pathogens, Klebsiella pneumoniae is particularly worrisome in the nosocomial setting, and its surface polysaccharides are regarded as promising antigen candidates. The majority of Klebsiella carbapenem-resistant strains belong to the sequence type 158 (ST258) lineage, with two main clades expressing capsular polysaccharides CPS1 and CPS2. In a recent article, S. D. Kobayashi and colleagues (mBio 9:e00297-18, 2018, https://doi.org/10.1128/mBio.00297-18) show that CPS2-specific IgGs render ST258 clade 2 bacteria more sensitive to human serum and phagocytic killing. E. Diago-Navarro et al. (mBio 9:e00091-18, 2018, https://doi.org/10.1128/mBio.00091-18) generated two murine monoclonal antibodies recognizing distinct glycotopes of CPS2 that presented functional activity against multiple ST258 strains. These complementary studies represent a step toward the control of this dangerous pathogen.

scholarly journals Systematic literature review of the burden and outcomes of infections due to multidrug-resistant organisms in Europe: the ABOUT-MDRO project protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e030608 ◽  
Author(s):  
Blanca Anaya-Baz ◽  
Natalia Maldonado ◽  
Zaira R Palacios-Baena ◽  
Virginia Palomo ◽  
Maria Diletta Pezzani ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multidrug Resistant ◽  
Cochrane Library ◽  
Published Data ◽  
Surveillance Systems ◽  
Carbapenem Resistant ◽  
Hospitalised Patients ◽  
Multidrug Resistant Organisms ◽  
Tract Infections ◽  
Incidence Prevalence

IntroductionDespite the increasing importance of infections due to multidrug-resistant organisms (MDROs), there is a lack of comprehensive information about the burden of disease and outcomes of key infections caused by these pathogens. The aim of the ABOUT-MDRO (A systematic review on the burden and outcomes of infections due to multidrug resitant organisms) project is to provide estimations of the burden of some key infections and their outcomes caused by the target MDROs.Methods and analysisA systematic literature search will be performed using MEDLINE/PubMed, Elsevier’s SCOPUS, Cochrane library, Clinical trials and Web of Science, as well as the Surveillance Systems from Public Health Institutions and Scientific Societies for Antimicrobial Resistance and Healthcare-Associated Infections in Europe database of European surveillance systems, for data on prevalence/incidence, mortality and length of stay of target infections in hospitalised patients (including ventilator-associated pneumonia, hospital-acquired pneumonia, complicated intra-abdominal infections, complicated urinary tract infections, skin and soft tissue infections and bloodstream infections) and in specific populations (children, hospital wards, neutropenic patients) caused by cephalosporin-resistant or carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter spp., methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus spp. The information retrieved will be tabulated and pooled estimates and 95% CIs calculated of rates and outcomes, using random effects models. Relationships between rates and outcomes in randomised control trials and epidemiological studies, and data of proportions and incidence/prevalence rates will also be analysed. The information collected in this study will be useful for identifying gaps in our knowledge in terms of incidence/prevalence and clinical outcomes of infections caused by MDROs, and for informing priorities in infection control and the research and design of appropriate studies.Ethics and disseminationThis study will be based on published data so we did not require ethical approval. Formal consent is not required. The results of this review will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Data will be presented at international conferences and published in peer-reviewed journals.Registration detailsPROSPERO (https://www.crd.york.ac.uk/prospero/) (CRD42019124185).

scholarly journals A Recombinase Aided Amplification Assay for Rapid Detection of the Klebsiella pneumoniae Carbapenemase Gene and Its Characteristics in Klebsiella pneumoniae

2021 ◽  
Vol 11 ◽  
Author(s):  
Weiwei Zhang ◽  
Yanling Feng ◽  
Hanqing Zhao ◽  
Chao Yan ◽  
Junxia Feng ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Rapid Detection ◽  
Detection Method ◽  
Multidrug Resistant ◽  
Molecular Characteristics ◽  
Klebsiella Pneumoniae Carbapenemase ◽  
Carbapenem Resistant ◽  
Fecal Carriage ◽  
Carbapenemase Gene ◽  
Amplification Assay

Klebsiella pneumoniae carbapenemase genes (blaKPC) play an important role in carbapenem-resistant Enterobacteriaceae in China. A rapid detection method for blaKPC genes and investigations into the molecular characteristics of blaKPC positive Klebsiella pneumoniae were necessary. In this study, an easy and rapid recombinase aided amplification assay (RAA) for blaKPC was established. This protocol could be completed at 39°C in 15–20 min. The sensitivity of this assay was determined as 48 copies per reaction, and the specificity was 100%. The blaKPC RAA method could be used for clinical diagnosis and epidemiological investigation. Among 801 fecal samples from inpatients, 34 blaKPC positive isolates were identified from each sample, of which 23 isolates were K. pneumoniae. ST11 with blaKPC-2 was the most prevalent type. All these strains were multidrug resistant and carried various virulence genes. Fecal carriage of blaKPC positive carbapenem-resistant K.pneumoniae poses significant challenges for public health control.

scholarly journals KPC-mediated resistance to ceftazidime-avibactam and collateral effects in Klebsiella pneumoniae

2021 ◽  
Author(s):  
Jacqueline Findlay ◽  
Laurent Poirel ◽  
Mario Juhas ◽  
Patrice Nordmann
Keyword(s):  
Klebsiella Pneumoniae ◽  
Broad Spectrum ◽  
In Vitro Selection ◽  
Multidrug Resistant ◽  
Single Step ◽  
Carbapenem Resistant ◽  
Rapid Spread ◽  
Collateral Effects ◽  
Novel Drug

Carbapenem-resistant Enterobacterales, such as KPC-producing Klebsiella pneumoniae , represent a major threat to public health due to their rapid spread. Novel drug combinations such as ceftazidime-avibactam (CZA), combining a broad-spectrum cephalosporin along with a broad-spectrum ß-lactamase inhibitor, have recently been introduced and have been shown to exhibit excellent activity towards multidrug-resistant KPC-producing Enterobacterale strains. However, CZA-resistant K. pneumoniae isolates are now being increasingly reported, mostly corresponding to producers of KPC variants. In this study, we evaluated in vitro the nature of the mutations in the KPC-2 and KPC-3 ß-lactamase sequences (the most frequent KPC-type enzymes) that lead to CZA resistance, and the subsequent effects of these mutations on susceptibility to other ß-lactam antibiotics. Single-step in vitro selection assays were conducted resulting in the identification of a series of mutations in the KPC sequence which conferred the ability to those mutated enzymes to confer resistance to CZA. Hence, 16 KPC-2 variants and 10 KPC-3 variants were obtained. Production of the KPC variants in an Escherichia coli recombinant strain resulted in a concomitant increased susceptibility to broad-spectrum cephalosporins and carbapenems, with the exceptions of ceftazidime and piperacillin-tazobactam, compared to wild-type KPC enzymes. Enzymatic assays showed that all of the KPC variants identified exhibited an increased affinity toward ceftazidime and a slightly decreased sensitivity to avibactam, sustaining their impact on CZA resistance. However their respective carbapenemase activities were concurrently negatively impacted.

scholarly journals A review on bacterial resistance to carbapenems: epidemiology, detection and treatment options

2020 ◽  
Vol 6 (3) ◽  
pp. FSO438 ◽  
Author(s):  
Ann A Elshamy ◽  
Khaled M Aboshanab
Keyword(s):  
Public Health ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Mechanisms Of Resistance ◽  
Carbapenem Resistant ◽  
Public Health Threat ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenems are a class of antimicrobial agents reserved for infections caused by multidrug-resistant microorganisms. The emergence of carbapenem resistance has become a serious public health threat. This type of antimicrobial resistance is spreading at an alarming rate, resulting in major outbreaks and treatment failure of community-acquired and nosocomial infections caused by the clinically relevant carbapenem-producing Enterobacteriaceae or carbapenem-resistant Enterobacteriaceae. This review is focused on carbapenem resistance, including mechanisms of resistance, history and epidemiology, phenotypic and genotypic detection in the clinically relevant bacterial pathogens and the possible treatment options available.

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