scholarly journals Treatment Options for Colistin Resistant Klebsiella pneumoniae: Present and Future

2019 ◽  
Vol 8 (7) ◽  
pp. 934 ◽  
Author(s):  
Petrosillo ◽  
Taglietti ◽  
Granata
Keyword(s):  
Monoclonal Antibodies ◽  
Side Effects ◽  
Mortality Rate ◽  
Klebsiella Pneumoniae ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Limited Range ◽  
Therapeutic Strategies ◽  
Colistin Resistance ◽  
Carbapenem Resistant

Multidrug-resistant (MDR) Klebsiella pneumoniae represents an increasing threat to human health, causing difficult-to-treat infections with a high mortality rate. Since colistin is one of the few treatment options for carbapenem-resistant K. pneumoniae infections, colistin resistance represents a challenge due to the limited range of potentially available effective antimicrobials, including tigecycline, gentamicin, fosfomycin and ceftazidime/avibactam. Moreover, the choice of these antimicrobials depends on their pharmacokinetics/pharmacodynamics properties, the site of infection and the susceptibility profile of the isolated strain, and is sometimes hampered by side effects. This review describes the features of colistin resistance in K. pneumoniae and the characteristics of the currently available antimicrobials for colistin-resistant MDR K. pneumoniae, as well as the characteristics of novel antimicrobial options, such as the soon-to-be commercially available plazomicin and cefiderocol. Finally, we consider the future use of innovative therapeutic strategies in development, including bacteriophages therapy and monoclonal antibodies.

scholarly journals Mobile Plasmid Mediated Transition From Colistin-Sensitive to Resistant Phenotype in Klebsiella pneumoniae

2021 ◽  
Vol 12 ◽  
Author(s):  
Baoyue Zhang ◽  
Bing Yu ◽  
Wei Zhou ◽  
Yue Wang ◽  
Ziyong Sun ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Sequencing Analysis ◽  
Direct Repeats ◽  
Colistin Resistance ◽  
Health Crisis ◽  
Carbapenem Resistant ◽  
Resistant Phenotype ◽  
New Challenges

Multidrug-resistant bacteria, including carbapenem-resistant Klebsiella pneumoniae (CRKP), are becoming an increasing health crisis worldwide. For CRKP, colistin is regarded as “the last treatment option.” In this study, we isolated a clinical CRKP strain named as K. pneumoniae R10-341. Phenotyping analysis showed that this strain could transit from a colistin-sensitive to a resistant phenotype by inserting an IS4 family ISKpn72 element into the colistin-resistance associated mgrB gene. To investigate the mechanism of this transition, we performed genome sequencing analysis of the colistin-sensitive parental strain and found that 12 copies of ISKpn72 containing direct repeats (DR) are located on the chromosome and 1 copy without DR is located on a multidrug-resistant plasmid pR10-341_2. Both types of ISKpn72 could be inserted into the mgrB gene to cause colistin-resistance, though the plasmid-derived ISKpn72 without DR was in higher efficiency. Importantly, we demonstrated that colistin-sensitive K. pneumoniae strain transferred with the ISKpn72 element also obtained the ability to switch from colistin-sensitive to colistin-resistant phenotype. Furthermore, we confirmed that the ISKpn72-containing pR10-341_2 plasmid was able to conjugate, suggesting that the ability of causing colistin-resistant transition is transferable through common conjugation. Our results point to new challenges for both colistin-resistance detection and CRKP treatment.

scholarly journals Tracking Nosocomial Klebsiella pneumoniae Infections and Outbreaks by Whole-Genome Analysis: Small-Scale Italian Scenario within a Single Hospital

2015 ◽  
Vol 53 (9) ◽  
pp. 2861-2868 ◽  
Author(s):  
Raffaella Onori ◽  
Stefano Gaiarsa ◽  
Francesco Comandatore ◽  
Stefano Pongolini ◽  
Sylvain Brisse ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Small Scale ◽  
Phylogenomic Analysis ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Single Clone

Multidrug-resistant (MDR)Klebsiella pneumoniaeis one of the most important causes of nosocomial infections worldwide. After the spread of strains resistant to beta-lactams at the end of the previous century, the diffusion of isolates resistant to carbapenems and colistin is now reducing treatment options and the containment of infections. Carbapenem-resistantK. pneumoniaestrains have spread rapidly among Italian hospitals, with four subclades of pandemic clonal group 258 (CG258). Here we show that a single Italian hospital has been invaded by three of these subclades within 27 months, thus replicating on a small scale the “Italian scenario.” We identified a single clone responsible for an epidemic outbreak involving seven patients, and we reconstructed its star-like pattern of diffusion within the intensive care unit. This epidemiological picture was obtained through phylogenomic analysis of 16 carbapenem-resistantK. pneumoniaeisolates collected in the hospital during a 27-month period, which were added to a database of 319 genomes representing the available global diversity ofK. pneumoniaestrains. Phenotypic and molecular assays did not reveal virulence or resistance determinants specific for the outbreak isolates. Other factors, rather than selective advantages, might have caused the outbreak. Finally, analyses allowed us to identify a major subclade of CG258 composed of strains bearing the yersiniabactin virulence factor. Our work demonstrates how the use of combined phenotypic, molecular, and whole-genome sequencing techniques can help to identify quickly and to characterize accurately the spread of MDR pathogens.

scholarly journals Emergence of mobilized colistin resistance-1 in multidrug-resistant Klebsiella pneumoniae and Escherichia coli isolates from the Henan province in China: a multicentre study

2021 ◽  
Author(s):  
Yi Li ◽  
Wenjuan Yan ◽  
Qi Zhang ◽  
Nan Jing ◽  
Youhua Yuan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Ethylenediaminetetraacetic Acid ◽  
Multidrug Resistant ◽  
Resistance Rate ◽  
Henan Province ◽  
Close Monitoring ◽  
Colistin Resistance ◽  
E Coli ◽  
Carbapenem Resistant

Abstract Background The increased clinical use of polymyxin led to the emergence of polymyxin-resistant strains, especially those carrying plasmid-borne mobilized colistin resistance (mcr) gene variants. In this study, we aimed to evaluate the prevalence and characteristics of polymyxin-resistant Klebsiella pneumoniae and Escherichia coli isolates from the Henan province, China. Methods A total of 16 polymyxin-resistant isolates among 2301 E. coli and K. pneumoniae isolates collected in 6 local hospitals in the Henan province were studied. The isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the minimum inhibitory concentrations (MICs) were determined using the microbroth dilution technique. Polymyxin-resistant isolates were further analysed for mcr-1 and carbapenemase-mediated resistance using the modified carbapenem inactivation method, the ethylenediaminetetraacetic acid-modified carbapenem inactivation method, and polymerase chain reaction. Pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST) were performed to disclose the phylogenetic relationships of the polymyxin-resistant isolates. The clinical characteristics of patients infected with the polymyxin-resistant isolates were also retrospectively analysed. Results 5/1499 (0.3%) and 11/802 (1.4%) E. coli and K. pneumoniae isolates, respectively, were polymyxin-resistant. The MICs of polymyxin were in the range of 4–64 µg/mL and all of the 16 polymyxin-resistant isolates were susceptible to tigecycline. Additionally, four of the five E. coli polymyxin-resistant isolates were mcr-1 positive; one of them was also carbapenem-resistant, carrying blaNDM−5. Conversely, only 1/11 K. pneumoniae isolates was mcr-1 positive, while 9 polymyxin-resistant isolates were also carbapenem-resistant (PRCRKP), carrying blaKPC−2 but not mcr-1. MLST results showed that the five E. coli isolates belonged to four sequence types (STs), including ST2, ST132, ST632, and ST983, while all PRCRKP isolates belonged to ST11. However, all 16 isolates showed different PFGE types using a genetic similarity of ≥ 95%. Furthermore, 33.3% (5/15) of the patients carrying polymyxin-resistant K. pneumoniae isolates showed a history of polymyxin use, and 10/15 (66.7%) patients displayed good clinical outcomes. Conclusion The polymyxin resistance rate of K. pneumoniae was slightly higher than that of E. coli in the Henan province; however, mcr-1 was only detected in one K. pneumoniae isolate. Thus, close monitoring is needed to prevent and control the spread of PRCRKP.

scholarly journals Evidence of widespread endemic populations of highly multidrug-resistant Klebsiella pneumoniae seen concurrently through the lens of two hospital intensive care units in Vietnam

2021 ◽  
Author(s):  
My H. Pham ◽  
Hoi Thi Le ◽  
Mathew A. Beale ◽  
Fahad A. Khokhar ◽  
Hoa Thi Nguyen ◽  
...  
Keyword(s):  
Intensive Care ◽  
Klebsiella Pneumoniae ◽  
Resistance Genes ◽  
Phylogenetic Analyses ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Healthcare Settings ◽  
Carbapenem Resistant ◽  
Antimicrobial Resistance Genes ◽  
Extended Spectrum Beta Lactamases

Background: Extended spectrum beta-lactamases-producing (ESBL-P) and/or carbapenem-resistant (CR) Klebsiella pneumoniae have severely restricted available treatment options in healthcare settings in Vietnam. Understanding the diversity and transmission mechanisms of ESBL- and carbapenemase- encoding K. pneumoniae is important in both hospital and community settings for patient management. Methods: We conducted a 6-month prospective cohort study of 69 Intensive care unit (ICU) patients from two hospitals in Hanoi, Vietnam. Longitudinally collected samples from patients and the ICU environment were cultured on selective media, and 357 K. pneumoniae colonies were whole genome sequenced. We performed phylogenetic analyses, and correlated phenotypic antimicrobial susceptibility testing with genotypic features of K. pneumoniae isolates. We constructed transmission networks of patient samples, relating ICU admission times and locations with genetic similarity of infecting K. pneumoniae. Findings: Despite being geographically and clinically separated, the two hospitals shared closely related strains carrying the same array of antimicrobial resistance genes. Many patients carried the same resistant K. pneumoniae clone from admission to discharge. 45.9% of total isolates carried both ESBL- and carbapenemase- encoding genes, with high minimum inhibitory concentrations. We found a novel co-occurrence of blaKPC-2 and blaNDM 1 in 46. 6% of samples from the globally successful ST15 lineage. Interpretation: These results highlight the high prevalence of ESBL-positive carbapenem-resistant K. pneumoniae in Vietnamese ICUs. Through studying K. pneumoniae ST15 in detail, we illustrated how important resistance genes are coalescing in stains carried broadly by patients entering the two hospitals directly or through referral.

scholarly journals A Bibliometric Meta-Analysis of Colistin Resistance in Klebsiella pneumoniae

Diseases ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 44
Author(s):  
Ozioma Forstinus Nwabor ◽  
Pawarisa Terbtothakun ◽  
Supayang P. Voravuthikunchai ◽  
Sarunyou Chusri
Keyword(s):  
Klebsiella Pneumoniae ◽  
Research Collaboration ◽  
Research Output ◽  
Meta Analysis ◽  
Research Articles ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
The Usa ◽  
Carbapenem Resistant Enterobacteriaceae ◽  
Linkage Strength

Colistin is a last resort antibiotic medication for the treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae. In recent years, various mechanisms have been reported to mediate colistin resistance in K. pneumoniae. This study reports a bibliometric analysis of published articles retrieved from the Scopus database relating to colistin resistance in K. pneumoniae. The research trends in colistin resistance and mechanisms of resistance were considered. A total of 1819 research articles published between 1995 and 2019 were retrieved, and the results indicated that 50.19% of the documents were published within 2017–2019. The USA had the highest participation with 340 (14.31%) articles and 14087 (17.61%) citations. Classification based on the WHO global epidemiological regions showed that the European Region contributed 42% of the articles while the American Region contributed 21%. The result further indicated that 45 countries had published at least 10 documents with strong international collaborations amounting to 272 links and a total linkage strength of 735. A total of 2282 keywords were retrieved; however, 57 keywords had ≥15 occurrences with 764 links and a total linkage strength of 2388. Furthermore, mcr-1, colistin resistance, NDM, mgrB, ceftazidime-avibactam, MDR, combination therapy, and carbapenem-resistant Enterobacteriaceae were the trending keywords. Concerning funders, the USA National Institute of Health funded 9.1% of the total research articles, topping the list. The analysis indicated poor research output, collaboration, and funding from Africa and South-East Asia and demands for improvement in international research collaboration.

scholarly journals Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae Mediated by Chromosomal Integration of Plasmid DNA

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Astrid V. Cienfuegos-Gallet ◽  
Liang Chen ◽  
Barry N. Kreiswirth ◽  
J. Natalia Jiménez
Keyword(s):  
Klebsiella Pneumoniae ◽  
Plasmid Dna ◽  
Clonal Expansion ◽  
Genetic Alterations ◽  
Sequence Type ◽  
Chromosomal Integration ◽  
Colistin Resistance ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Single Locus Variant

ABSTRACT Here we describe the spread of colistin resistance in clinical isolates of carbapenem-resistant Klebsiella pneumoniae in Medellín, Colombia. Among 32 isolates collected between 2012 and 2014, 24 showed genetic alterations in mgrB. Nineteen isolates belonged to sequence type 512 (ST512) (or its single locus variant [SLV]) and harbored an 8.1-kb hsdMSR insertion corresponding to ISKpn25, indicating a clonal expansion of the resistant strain. The insertion region showed 100% identity to several plasmids, suggesting that the colistin resistance is mediated by chromosomal integration of plasmid DNA.

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 Genomic evolution and local epidemiology of Klebsiella pneumoniae from a major hospital in Beijing, China, over a 15 year period: dissemination of known and novel high-risk clones

2021 ◽  
Author(s):  
Mattia Palmieri ◽  
Kelly L. Wyres ◽  
Caroline Mirande ◽  
Zhao Qiang ◽  
Ye Liyan ◽  
...  
Keyword(s):  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Type Species ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Virulence Plasmid ◽  
Content Type ◽  
Origin And Evolution ◽  
Link Type ◽  
Beijing China

Klebsiella pneumoniae is a frequent cause of nosocomial and severe community-acquired infections. Multidrug-resistant (MDR) and hypervirulent (hv) strains represent major threats, and tracking their emergence, evolution and the emerging convergence of MDR and hv traits is of major importance. We employed whole-genome sequencing (WGS) to study the evolution and epidemiology of a large longitudinal collection of clinical K. pneumoniae isolates from the H301 hospital in Beijing, China. Overall, the population was highly diverse, although some clones were predominant. Strains belonging to clonal group (CG) 258 were dominant, and represented the majority of carbapenemase-producers. While CG258 strains showed high diversity, one clone, ST11-KL47, represented the majority of isolates, and was highly associated with the KPC-2 carbapenemase and several virulence factors, including a virulence plasmid. The second dominant clone was CG23, which is the major hv clone globally. While it is usually susceptible to multiple antibiotics, we found some isolates harbouring MDR plasmids encoding for ESBLs and carbapenemases. We also reported the local emergence of a recently described high-risk clone, ST383. Conversely to strains belonging to CG258, which are usually associated to KPC-2, ST383 strains seem to readily acquire carbapenemases of different types. Moreover, we found several ST383 strains carrying the hypervirulence plasmid. Overall, we detected about 5 % of simultaneous carriage of AMR genes (ESBLs or carbapenemases) and hypervirulence genes. Tracking the emergence and evolution of such strains, causing severe infections with limited treatment options, is fundamental in order to understand their origin and evolution and to limit their spread. This article contains data hosted by Microreact.

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