Clonal distribution of multidrug-carbapenem-resistant Klebsiella pneumoniae in a Riyadh-based hospital: incidence of New Delhi metallo-beta-lactamase (NDM) carrying ST-152 clone

Carbapenem resistance has been encountered globally with poor outcome of infected patients. NDM-1 (New Delhi metallo-beta-lactamase) gene containing organisms have emerged and are now spreading in all continents. This is the first report of Iraqi patients referred to Lebanon from whom carbapenem resistant Enterobacteriaceae were recovered. The genes involved in carbapenem resistance were bla-OXA-48 and the novel NDM-1. This report highlights the alarming introduction of such resistance among Enterobacteriaecae to this country.

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A pentaplex real-time PCR assay for rapid identification of major beta-lactamase genes KPC, NDM, CTX, CMY, and OXA-48 directly from bacteria in blood

Journal of Medical Microbiology ◽

10.1099/jmm.0.001465 ◽

2021 ◽

Vol 70 (12) ◽

Author(s):

Taalin R. Hoj ◽

Bradley McNeely ◽

Kylie Webber ◽

Evelyn Welling ◽

William G. Pitt ◽

...

Keyword(s):

Antibiotic Resistance ◽

Klebsiella Pneumoniae ◽

Real Time ◽

Real Time Pcr ◽

Type Species ◽

New Delhi ◽

Beta Lactamase ◽

Content Type ◽

Link Type ◽

Carbapenem Resistant

Introduction. Antibiotic resistance, particularly in cases of sepsis, has emerged as a growing global public health concern and economic burden. Current methods of blood culture and antimicrobial susceptibility testing of agents involved in sepsis can take as long as 3–5 days. It is vital to rapidly identify which antimicrobials can be used to effectively treat sepsis cases on an individual basis. Here, we present a pentaplex, real-time PCR-based assay that can quickly identify the most common beta-lactamase genes ( Klebsiella pneumoniae carbapenemase (KPC); New Delhi metallo-beta-lactamase (NDM); cefotaximase-Munich (CTX-M); cephamycin AmpC beta-lactamases (CMY); and Oxacillinase-48 (OXA-48)) from pathogens derived directly from the blood of patients presenting with bacterial septicemia. Aim. To develop an assay which can rapidly identify the most common beta-lactamase genes in Carbapenem-resistant Enterobacteriaceae bacteria (CREs) from the United States. Hypothesis/Gap Statement. Septicemia caused by carbapenem-resistant bacteria has a death rate of 40–60 %. Rapid diagnosis of antibiotic susceptibility directly from bacteria in blood by identification of beta-lactamase genes will greatly improve survival rates. In this work, we develop an assay capable of concurrently identifying the five most common beta-lactamase and carbapenemase genes. Methodology. Primers and probes were created which can identify all subtypes of Klebsiella pneumoniae carbapenemase (KPC); New Delhi metallo-beta-lactamase (NDM); cefotaximase-Munich (CTX); cephamycin AmpC beta-lactamase (CMY); and oxacillinase-48 (OXA-48). The assay was validated using 13 isolates containing various PCR targets from the Centre for Disease Control Antimicrobial Resistance Isolate Bank Enterobacterales Carbapenemase Diversity Panel. Blood obtained from volunteers was spiked with CREs and bacteria were separated, lysed, and subjected to analysis via the pentaplex assay. Results. This pentaplex assay successfully identified beta-lactamase genes derived from bacteria separated from blood at concentrations of 4–8 c.f.u. ml−1. Conclusion. This assay will improve patient outcomes by supplying physicians with critical drug resistance information within 2 h of septicemia onset, allowing them to prescribe effective antimicrobials corresponding to the resistance gene(s) present in the pathogen. In addition, information supplied by this assay will lessen the inappropriate use of broad-spectrum antimicrobials and prevent the evolution of further antibiotic resistance.

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Notes from the Field: Hospital Outbreak of Carbapenem- Resistant Klebsiella pneumoniae Producing New Delhi Metallo-Beta-Lactamase—Denver, Colorado, 2012

JAMA ◽

10.1001/jama.2013.2135 ◽

2013 ◽

Vol 309 (15) ◽

pp. 1582 ◽

Cited By ~ 1

Keyword(s):

Klebsiella Pneumoniae ◽

New Delhi ◽

Beta Lactamase ◽

Field Hospital ◽

Hospital Outbreak ◽

Carbapenem Resistant

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Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae Strains Containing New Delhi Metallo-Beta-Lactamase Isolated from Two Patients in Vietnam: Table 1

Journal of Clinical Microbiology ◽

10.1128/jcm.02322-12 ◽

2012 ◽

Vol 51 (1) ◽

pp. 373-374 ◽

Cited By ~ 18

Author(s):

Tran Huy Hoang ◽

Heiman Wertheim ◽

Nguyen Binh Minh ◽

Tran Nhu Duong ◽

Dang Duc Anh ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

New Delhi ◽

Beta Lactamase ◽

Carbapenem Resistant

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Facile accelerated specific therapeutic (FAST) platform develops antisense therapies to counter multidrug-resistant bacteria

Communications Biology ◽

10.1038/s42003-021-01856-1 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Kristen A. Eller ◽

Thomas R. Aunins ◽

Colleen M. Courtney ◽

Jocelyn K. Campos ◽

Peter B. Otoupal ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Mammalian Cells ◽

Multidrug Resistant ◽

Clinical Isolates ◽

Resistant Bacteria ◽

New Delhi ◽

Beta Lactamase ◽

Extended Spectrum Beta Lactamase ◽

Carbapenem Resistant ◽

New Treatments

AbstractMultidrug-resistant (MDR) bacteria pose a grave concern to global health, which is perpetuated by a lack of new treatments and countermeasure platforms to combat outbreaks or antibiotic resistance. To address this, we have developed a Facile Accelerated Specific Therapeutic (FAST) platform that can develop effective peptide nucleic acid (PNA) therapies against MDR bacteria within a week. Our FAST platform uses a bioinformatics toolbox to design sequence-specific PNAs targeting non-traditional pathways/genes of bacteria, then performs in-situ synthesis, validation, and efficacy testing of selected PNAs. As a proof of concept, these PNAs were tested against five MDR clinical isolates: carbapenem-resistant Escherichia coli, extended-spectrum beta-lactamase Klebsiella pneumoniae, New Delhi Metallo-beta-lactamase-1 carrying Klebsiella pneumoniae, and MDR Salmonella enterica. PNAs showed significant growth inhibition for 82% of treatments, with nearly 18% of treatments leading to greater than 97% decrease. Further, these PNAs are capable of potentiating antibiotic activity in the clinical isolates despite presence of cognate resistance genes. Finally, the FAST platform offers a novel delivery approach to overcome limited transport of PNAs into mammalian cells by repurposing the bacterial Type III secretion system in conjunction with a kill switch that is effective at eliminating 99.6% of an intracellular Salmonella infection in human epithelial cells.

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Prolonged outbreak of New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE), Tuscany, Italy, 2018 to 2019

Eurosurveillance ◽

10.2807/1560-7917.es.2020.25.6.2000085 ◽

2020 ◽

Vol 25 (6) ◽

Cited By ~ 7

Author(s):

Lara Tavoschi ◽

Silvia Forni ◽

Andrea Porretta ◽

Lorenzo Righi ◽

Filippo Pieralli ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Bloodstream Infections ◽

New Delhi ◽

Beta Lactamase ◽

North West ◽

The North ◽

Carbapenem Resistant

In Tuscany, Italy, New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE) have increased since November 2018. Between November 2018 and October 2019, 1,645 samples were NDM-CRE-positive: 1,270 (77.2%) cases of intestinal carriage, 129 (7.8%) bloodstream infections and 246 (14.9%) infections/colonisations at other sites. Klebsiella pneumoniae were prevalent (1,495; 90.9%), with ST147/NDM-1 the dominant clone. Delayed outbreak identification and response resulted in sustained NDM-CRE transmission in the North-West area of Tuscany, but successfully contained spread within the region.

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Carbapenem-Resistant Enterobacteriaceae Rectal Screening during an Outbreak of New Delhi Metallo-β-Lactamase–Producing Klebsiella pneumoniae at an Acute Care Hospital

Infection Control and Hospital Epidemiology ◽

10.1086/675597 ◽

2014 ◽

Vol 35 (4) ◽

pp. 434-436 ◽

Cited By ~ 14

Author(s):

Larissa M. Pisney ◽

M. A. Barron ◽

E. Kassner ◽

D. Havens ◽

N. E. Madinger

Keyword(s):

Klebsiella Pneumoniae ◽

Acute Care ◽

Teaching Hospital ◽

Tertiary Care ◽

Acute Care Hospital ◽

University Teaching ◽

New Delhi ◽

Care Hospital ◽

Carbapenem Resistant ◽

Carbapenem Resistant Enterobacteriaceae

We describe the results of carbapenem-resistant Enterobacteriaceae (CRE) screening as part of an outbreak investigation of New Delhi metallo-β-lactamase–producing CRE at a tertiary care university teaching hospital. The manual method for CRE screening was useful for detecting patients with asymptomatic CRE carriage but was time-consuming and costly.

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

Journal of Medical Microbiology ◽

10.1099/jmm.0.073767-0 ◽

2014 ◽

Vol 63 (10) ◽

pp. 1316-1323 ◽

Cited By ~ 24

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.

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Colonisation with extended spectrum beta-lactamase-producing and carbapenem-resistant Enterobacterales in children admitted to a paediatric referral hospital in South Africa

PLoS ONE ◽

10.1371/journal.pone.0241776 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0241776

Author(s):

Babatunde O. Ogunbosi ◽

Clinton Moodley ◽

Preneshni Naicker ◽

James Nuttall ◽

Colleen Bamford ◽

...

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Sub Saharan Africa ◽

Infection Prevention And Control ◽

Invasive Infection ◽

Beta Lactamase ◽

Cross Sectional ◽

Extended Spectrum Beta Lactamase ◽

Carbapenem Resistant ◽

Extended Spectrum

Introduction There are few studies describing colonisation with extended spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and carbapenem-resistant Enterobacterales (CRE) among children in sub-Saharan Africa. Colonisation often precedes infection and multi-drug-resistant Enterobacterales are important causes of invasive infection. Methods In this prospective cross-sectional study, conducted between April and June 2017, 200 children in a tertiary academic hospital were screened by rectal swab for EBSL-PE and CRE. The resistance-conferring genes were identified using polymerase chain reaction technology. Risk factors for colonisation were also evaluated. Results Overall, 48% (96/200) of the children were colonised with at least one ESBL-PE, 8.3% (8/96) of these with 2 ESBL-PE, and one other child was colonised with a CRE (0.5% (1/200)). Common colonising ESBL-PE were Klebsiella pneumoniae (62.5%, 65/104) and Escherichia coli (34.6%, 36/104). The most frequent ESBL-conferring gene was blaCTX-M in 95% (76/80) of the isolates. No resistance- conferring gene was identified in the CRE isolate (Enterobacter cloacae). Most of the Klebsiella pneumoniae isolates were susceptible to piperacillin/tazobactam (86.2%) and amikacin (63.9%). Similarly, 94.4% and 97.2% of the Escherichia coli isolates were susceptible to piperacillin/tazobactam and amikacin, respectively. Hospitalisation for more than 7 days before study enrolment was associated with ESBL-PE colonisation. Conclusion Approximately half of the hospitalised children in this study were colonised with ESBL-PE. This highlights the need for improved infection prevention and control practices to limit the dissemination of these microorganisms.

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