scholarly journals A Global Perspective on the Convergence of Hypervirulence and Carbapenem-Resistance in Klebsiella pneumoniae

Author(s):  
Peng Lan ◽  
Yan Jiang ◽  
Jiancang Zhou ◽  
Yunsong Yu
2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S7-S7
Author(s):  
Alexander Lawandi ◽  
Gleice C Leite ◽  
Brigitte Lefebvre ◽  
Jean Longtin ◽  
Todd C Lee

Abstract Background Invasive infections with Carbapenemase Producing Enterobacterales are associated with considerable morbidity and mortality, in part due to the risk of inappropriate empiric therapy. Consequently, the rapid identification of carbapenem resistance is crucial to the management of these infections. We sought to evaluate possible reductions in turnaround time to identification of this resistance in blood cultures growing these organisms by applying rapid phenotypic test kits to growth from “hot chocolate” plates. Methods 30 blood cultures, spiked with carbapenem resistant Klebsiella pneumoniae isolates or susceptible controls, were inoculated onto chocolate agars that had pre-warmed at 37°C. These plates were incubated at 37ºC for 3.5 hours. The resulting minimal growth was then identified using MALDI-TOF and underwent rapid phenotypic testing using three commercially available products (β-lacta and β-carba, from Bio-Rad, Marnes-la-Coquette, France, and Carba-NP, from bioMérieux, Durham, NC). The time to identification of carbapenem resistance using this method was then compared to that of the conventional laboratory workup. Results The identification was 100% accurate to the species level using MALDI-TOF paired to the 3.5 hour growth on the “hot choocolate” plates. The β-lacta kit identified resistance to 3rd generation cephalosporins for all ESBL and carbapenemase producing Klebsiella pneumoniae isolates, while the β-carba and Carba-NP kits identified carbapenem resistance only in the carbapenemase producers. The sensitivity of all assays was 100% (95% CI 0.87–1.0) and the specificity of carbapenemase detection was 100% (97.5% one-sided CI 0.4–1.0). The corresponding sensitivities and specificities of direct disc diffusion for ertapenem resistance detection were 88.5% (95% CI 0.70–0.98) and 100% (95%CI 0.40–1.0) respectively. The turnaround time for the rapid kits coupled to the “hot chocolate” plates was 4.25 to 5.1 hours as compared to 16 hours for the conventional workup. Conclusion Rapid phenotypic tests performed after inoculation of “hot chocolate” plates are highly sensitive for the presence of carbapenemase production and can be incorporated into the laboratory workflow for Klebisella pneumoniae with important reductions in turnaround time. Disclosures All Authors: No reported disclosures


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S412-S413
Author(s):  
Michael R Jacobs ◽  
Caryn E Good ◽  
Ayman M Abdelhamed ◽  
Daniel D Rhoads ◽  
Kristine M Hujer ◽  
...  

Abstract Background Plazomicin is a next-generation aminoglycoside with in vitro activity against multidrug-resistant Gram-negative species, including carbapenem-resistant isolates. The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE) is a federally funded, prospective multicenter consortium of 20 hospitals from nine US healthcare systems to track carbapenem-resistant Enterobacteriaceae. Methods Minimum inhibitory concentrations (MICs) of plazomicin were determined by broth microdilution according to current CLSI guidelines against a collection of 697 carbapenem-resistant Klebsiella pneumoniae with defined carbapenem resistance mechanisms, including KPC and OXA carbapenemases. Isolates were submitted by participating CRACKLE centers. Results Carbapenemases present in study isolates included KPC-2 (n = 323), KPC-3 (n = 364), KPC-4 (n = 2), OXA-48 like (n = 7), and NDM (n = 1). Plazomicin MICs ranged from ≤0.12 to >32 mg/L, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively (figure). MICs of 689 (98.8%) isolates were ≤4 mg/L, while MICs of the remaining eight isolates were >32 mg/L. Plazomicin MICs were related to specific carbapenemases present in isolates: of eight isolates with MICs >32 mg/L, seven contained OXA-48 like and one contained KPC-3, suggesting that these isolates possess an aminoglycoside-resistance mechanism on the same plasmid as their carbapenemase gene, such as a 16S ribosomal RNA methyltransferase, against which plazomicin is not active. Conclusion Plazomicin has good in vitro potency against a collection of carbapenemase-producing K. pneumoniae, with MIC90 value of 1 mg/L and MICs of ≤4 mg/L for 98.9% of isolates. Disclosures M. R. Jacobs, Achaogen: Investigator, Research grant. Shionogi: Investigator, Research grant. L. Connolly, Achaogen, Inc.: Consultant, Consulting fee. K. M. Krause, Achaogen: Employee, Salary. S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant. D. Van Duin, achaogen: Scientific Advisor, Consulting fee. shionogi: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Astellas: Scientific Advisor, Consulting fee. Neumedicine: Scientific Advisor, Consulting fee. Roche: Scientific Advisor, Consulting fee. T2 Biosystems: Scientific Advisor, Consulting fee.


Author(s):  
Reyhan Kiş ◽  
Ebru Demiray Gündüz ◽  
Ayşe Nur Sarı ◽  
Zeynep Gülay

Objective: Carbapenem resistance has been reported with increasing frequency among members of Enterobacterales, especially in the last 10 years. Screening and detection of carbapenemase-producing isolates is important in terms of both directing the treatment and preventing its spread. In our study, it was aimed to determine the carbapenemase types and molecular epidemiological relationships of carbapenem resistant Klebsiella pneumoniae isolates, which were isolated sequentially from the samples sent to microbiology laboratory of our hospital. Method: A total of 32 carbapenem-resistant K. pneumoniae isolates of the samples sent to microbiology laboratory between July and September 2014, were included in the study. In addition to classical methods, identification of isolates at species level was made with BD Phoenix ID/AST automated system. Carbapenemase types (blaOXA-48, blaNDM, blaIMP, blaKPC, blaVIM and blaGES) of the isolates were investigated by PCR. The clonal relationship between the isolates was assessed with PFGE. Results: It was noted that 18 isolates were obtained from intensive care units, 9 from inpatient and 5 from outpatient departments. The blaOXA48 gene was found in all isolates while the other carbapenemase genes were not found. It was determined that strains were isolated from 32 patients in our hospital had 12 different PFGE pulsotypes, named as A-L. Among these, the most common ones were B (n=18) and closely related B1 pattern (n=2). The remaining isolates were represented by 11 different types. It was observed that the first isolate with B pulsotype was responsible for the spread of the outbreak from General Intensive Care Unit. Conclusion: It has been thought that the spread of carbapenem- resistant K. pneumoniae isolates in the hospital was probably occurred through the transfer of isolates from patients with gastrointestinal colonization to other patients through hospital staff. Therefore, the spread of the isolates in hospitals can be limited by detecting colonization with active surveillance programs and by applying contact isolation and effective infection control measures.


Antibiotics ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1174
Author(s):  
Pilar Lumbreras-Iglesias ◽  
M. Rosario Rodicio ◽  
Pablo Valledor ◽  
Tomás Suárez-Zarracina ◽  
Javier Fernández

The aim of this work was to analyze outer membrane porin-encoding genes (ompK35 and ompK36) in a collection of OXA-48 producing Klebsiella pneumoniae, to assess the effect of porin alterations on the susceptibility to ceftazidime/avibactam, and to describe a screening methodology for phenotypic detection of OXA-48-producing K. pneumoniae with disrupted porins. Antimicrobial susceptibility was tested by Microscan and Etest. The genomes of 81 OXA-48-producing K. pneumoniae were sequenced. MLST, detection of antimicrobial resistance genes, and analysis of ompK35 and ompK36 were performed in silico. Tridimensional structures of the OmpK36 variants were assessed. Receiver operating characteristics curves were built to visualize the performance ability of a disk diffusion assay using carbapenems and cefoxitin to detect OmpK36 functional alterations. A wide variety of OmpK36 alterations were detected in 17 OXA-48-producing K. pneumoniae isolates. All displayed a high-level meropenem resistance (MIC ≥ 8 mg/L), and some belonged to high-risk clones, such as ST15 and ST147. Alterations in ompK35 were also observed, but they did not correlate with high-level meropenem resistance. All isolates were susceptible to ceftazidime/avibactam and porin alterations did not affect the MICs of the latter combination. Cefoxitin together with ertapenem/meropenem low inhibition zone diameters (equal or lower than 16 mm) could strongly suggest alterations affecting OmpK36 in OXA-48-producing K. pneumoniae. OXA-48-producing K. pneumoniae with porin disruptions are a cause of concern; ceftazidime/avibactam showed good in vitro activity against them, so this combination could be positioned as the choice therapy to combat the infections caused by this difficult-to-treat isolates.


2018 ◽  
Author(s):  
Kelly L Wyres ◽  
Kathryn E Holt

Klebsiella pneumoniae is an opportunistic bacterial pathogen known for its high frequency and diversity of antimicrobial resistance (AMR) genes. In addition to being a significant clinical problem in its own right, K. pneumoniae is the species within which several new AMR genes were first discovered before spreading to other pathogens (e.g. carbapenem-resistance genes KPC, OXA-48 and NDM-1). Whilst K. pneumoniae’s contribution to the overall AMR crisis is impossible to quantify, current evidence suggests it has a wider ecological distribution, significantly more varied DNA composition, greater AMR gene diversity and a higher plasmid burden than other Gram negative opportunists. Hence we propose it plays a key role in disseminating AMR genes from environmental microbes to clinically important pathogens.


2019 ◽  
Vol 66 (3) ◽  
pp. 367-376
Author(s):  
Namita Jaggi ◽  
Nirupama Chatterjee ◽  
Vyoma Singh ◽  
Santosh Kumar Giri ◽  
Priyambada Dwivedi ◽  
...  

2020 ◽  
Vol 64 (12) ◽  
Author(s):  
Ana M. Rada ◽  
Elsa De La Cadena ◽  
Carlos Agudelo ◽  
Cesar Capataz ◽  
Nataly Orozco ◽  
...  

ABSTRACT Carbapenem-resistant Enterobacterales (CRE) pose a significant threat to global public health. The most important mechanism for carbapenem resistance is the production of carbapenemases. Klebsiella pneumoniae carbapenemase (KPC) represents one of the main carbapenemases worldwide. Complex mechanisms of blaKPC dissemination have been reported in Colombia, a country with a high endemicity of carbapenem resistance. Here, we characterized the dynamics of dissemination of blaKPC gene among CRE infecting and colonizing patients in three hospitals localized in a highly endemic area of Colombia (2013 and 2015). We identified the genomic characteristics of KPC-producing Enterobacterales recovered from patients infected/colonized and reconstructed the dynamics of dissemination of blaKPC-2 using both short and long read sequencing. We found that spread of blaKPC-2 among Enterobacterales in the participating hospitals was due to intra- and interspecies horizontal gene transfer (HGT) mediated by promiscuous plasmids associated with transposable elements that was originated from a multispecies outbreak of KPC-producing Enterobacterales in a neonatal intensive care unit. The plasmids were detected in isolates recovered in other units within the same hospital and nearby hospitals. The gene “epidemic” was driven by IncN-pST15-type plasmids carrying a novel Tn4401b structure and non-Tn4401 elements (NTEKPC) in Klebsiella spp., Escherichia coli, Enterobacter spp., and Citrobacter spp. Of note, mcr-9 was found to coexist with blaKPC-2 in species of the Enterobacter cloacae complex. Our findings suggest that the main mechanism for dissemination of blaKPC-2 is HGT mediated by highly transferable plasmids among species of Enterobacterales in infected/colonized patients, presenting a major challenge for public health interventions in developing countries such as Colombia.


2020 ◽  
Vol 26 (3) ◽  
pp. 549-559 ◽  
Author(s):  
Yahua Chen ◽  
Kalisvar Marimuthu ◽  
Jeanette Teo ◽  
Indumathi Venkatachalam ◽  
Benjamin Pei Zhi Cherng ◽  
...  

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