scholarly journals Homology analysis between clinically isolated extraintestinal and enteral Klebsiella pneumoniae among Neonates

2020 ◽  
Author(s):  
Chun-mei Chen ◽  
Min Wang ◽  
Xian-ping Li ◽  
Peng-ling Li ◽  
Jing-jing Tian ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Gi Tract ◽  
Homology Analysis ◽  
Gastrointestinal Colonization ◽  
Sequence Types

Abstract Background: Klebsiella pneumoniae is a leading cause of hospital-associated (HA) infections . It has been reported that gastrointestinal colonization (GI) is likely to be a common and significant reservoir for the transmission and infections of K. pneumoniae in both adults and neonates. However, the homologous relationship between clinically isolated extraintestinal and enteral K. pneumoniae in neonates hasn’t been characterized yet. Results: 43 isolates from 21 neonatal patients were collected in this study. The proportion of carbapenem resistance was 62.8%. There were 12 patients (12/21, 57.4%) whose antibiotic resistance phenotypes, genotypes, and ST types (STs) were concordant. Six sequence types were detected using MLST, with ST37 and ST54 being the dominant types. The results of MLST were consist with the results of PFGE. Conclusions: These data showed that there might be a close homologous relationship between EXKP and EKP in neonates，indicating that the K. pneumoniae from the GI tract is possibly to be a significant reservoir for causing extraintestinal infections.

scholarly journals Homology analysis between clinically isolated extraintestinal and enteral Klebsiella pneumoniae among Neonates

2020 ◽  
Author(s):  
Chun-mei Chen ◽  
Min Wang ◽  
Xian-ping Li ◽  
Peng-ling Li ◽  
Jing-jing Tian ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Gi Tract ◽  
Homology Analysis ◽  
Gastrointestinal Colonization ◽  
Sequence Types

Abstract Background: Klebsiella pneumoniae is a leading cause of hospital-associated (HA) infections. It has been reported in many studies that gastrointestinal colonization (GI) is likely to be a common and significant reservoir for the transmission and infections of K. pneumoniae in both adults and neonates. But the homologous relationship between clinically isolated extraintestinal and enteral K. pneumoniae in neonates hasn’t been characterized yet.Results: 43 isolates from 21 neonatal patients were collected in this study. The proportion of carbapenem resistance was 62.8%. There were 12 patients (12/21, 57.4%) whose antibiotic resistance phenotypes, genotypes and ST types (STs) were concordant. Six sequence types were detected using MLST, with ST37 and ST54 being the dominant types. Conclusions: These data showed that there might be a close homologous relationship between EXKP and EKP in neonates，indicating that the K. pneumoniae from the GI tract is possibly to be a significant reservoir for causing extraintestinal infections.

scholarly journals Homology analysis between clinically isolated extraintestinal and enteral Klebsiella pneumoniae among Neonates

2020 ◽  
Author(s):  
Chun-mei Chen ◽  
Min Wang ◽  
Xian-ping Li ◽  
Peng-ling Li ◽  
Jing-jing Tian ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Gi Tract ◽  
Homology Analysis ◽  
Gastrointestinal Colonization ◽  
Sequence Types

Abstract Background: Klebsiella pneumoniae is a leading cause of hospital-associated (HA) infections. It has been reported that gastrointestinal colonization (GI) is likely to be a common and significant reservoir for the transmission and infections of K. pneumoniae in both adults and neonates. However, the homologous relationship between clinically isolated extraintestinal and enteral K. pneumoniae in neonates hasn’t been characterized yet.Results: 43 isolates from 21 neonatal patients were collected in this study. The proportion of carbapenem resistance was 62.8%. There were 12 patients (12/21, 57.4%) whose antibiotic resistance phenotypes, genotypes, and ST types (STs) were concordant. Six sequence types were detected using MLST, with ST37 and ST54 being the dominant types. The results of MLST were consist with the results of PFGE.Conclusions: These data showed that there might be a close homologous relationship between extraintestinal K. pneumoniae (EXKP) and enteral K. pneumoniae (EKP) in neonates，indicating that the K. pneumoniae from the GI tract is possibly to be a significant reservoir for causing extraintestinal infections.

scholarly journals Prevalence of pathogenic Klebsiella pneumoniae based on PCR capsular typing harbouring carbapenemases encoding genes in Uganda tertiary hospitals

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Kenneth Ssekatawa ◽  
Denis K. Byarugaba ◽  
Jesca L. Nakavuma ◽  
Charles D. Kato ◽  
Francis Ejobi ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Virulence Factors ◽  
Carbapenem Resistance ◽  
Clinical Isolates ◽  
Genotypic Resistance ◽  
Pathogenic Potential ◽  
Phenotypic Resistance ◽  
Tertiary Hospitals ◽  
Encoding Genes

Abstract Background Klebsiella pneumoniae is an opportunistic pathogen that has been implicated as one of commonest cause of hospital and community acquired infections. The K. pneumoniae infections have considerably contributed to morbidity and mortality in patients with protracted ailments. The capacity of K. pneumoniae to cause diseases depends on the presence of an array virulence factors. Coexistence and expression of virulence factors and genetic determinants of antibiotic resistance complicates treatment outcomes. Thus, emergence of pathogenic MDR K. pneumoniae poses a great threat to the healthcare system. However, the carriage of antibiotic resistance among pathogenic K. pneumoniae is yet to be investigated in Uganda. We sought to investigate the carbapenem resistance profiles and pathogenic potential based on capsular serotypes of K. pneumoniae clinical isolates. Methods This was a cross sectional study involving use of archived Klebsiella pneumoniae isolates collected between January and December, 2019 at four tertiary hospitals in Uganda. All isolates were subject to antimicrobial susceptibility assays to determine phenotypic antibiotic resistance, pentaplex PCR to detect carbapenemases encoding genes and heptaplex PCR to identify capsular serotypes K1, K2, K3, K5, K20, K54 and K57. Results The study found an overall phenotypic carbapenem resistance of 23.3% (53/227) and significantly higher genotypic resistance prevalence of 43.1% (98/227). Over all, the most prevalent gene was blaOXA-48-like (36.4%), followed by blaIMP-type (19.4%), blaVIM-type (17.1%), blaKPC-type (14.0%) and blaNDM-type (13.2%). blaVIM-type and blaOXA-48-like conferred phenotypic resistance in all isolates and 38.3% of isolates that harbored them respectively. Capsular multiplex PCR revealed that 46.7% (106/227) isolates were pathogenic and the predominantly prevalent pathotype was K5 (18.5%) followed by K20 (15.1%), K3 (7.1%), K2 (3.1%) and K1 (2.2%). Of the 106 capsular serotypes, 37 expressed phenotypic resistance; thus, 37 of the 53 carbapenem resistant K. pneumoniae were pathogenic. Conclusion The high prevalence of virulent and antibiotic resistant K. pneumoniae among clinical isolates obtained from the four tertiary hospital as revealed by this study pose a great threat to healthcare. Our findings underline the epidemiological and public health risks and implications of this pathogen.

scholarly journals In vitro Bactericidal Activities of Combination Antibiotic Therapies Against Carbapenem-Resistant Klebsiella pneumoniae With Different Carbapenemases and Sequence Types

2021 ◽  
Vol 12 ◽  
Author(s):  
Jocelyn Qi-Min Teo ◽  
Nazira Fauzi ◽  
Jayden Jun-Yuan Ho ◽  
Si Hui Tan ◽  
Shannon Jing-Yi Lee ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Bactericidal Activity ◽  
Carbapenem Resistance ◽  
Polymyxin B ◽  
Apparent Difference ◽  
Initial Inoculum ◽  
Carbapenem Resistant ◽  
Limited Effectiveness ◽  
Sequence Types

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is becoming increasingly problematic due to the limited effectiveness of new antimicrobials or other factors such as treatment cost. Thus, combination therapy remains a suitable treatment option. We aimed to evaluate the in vitro bactericidal activity of various antibiotic combinations against CRKP with different carbapenemase genotypes and sequence types (STs). Thirty-seven CRKP with various STs and carbapenemases were exposed to 11 antibiotic combinations (polymyxin B or tigecycline in combination with β-lactams including aztreonam, cefepime, piperacillin/tazobactam, doripenem, meropenem, and polymyxin B with tigecycline) in static time-kill studies (TKS) using clinically achievable concentrations. Out of the 407 isolate-combination pairs, only 146 (35.8%) were bactericidal (≥3 log10CFU/mL decrease from initial inoculum). Polymyxin B in combination with doripenem, meropenem, or cefepime was the most active, each demonstrating bactericidal activity in 27, 24, and 24 out of 37 isolates, respectively. Tigecycline in combination with β-lactams was rarely bactericidal. Aside from the lower frequency of bactericidal activity in the dual-carbapenemase producers, there was no apparent difference in combination activity among the strains with other carbapenemase types. In addition, bactericidal combinations were varied even in strains with similar STs, carbapenemases, and other genomic characteristics. Our findings demonstrate that the bactericidal activity of antibiotic combinations is highly strain-specific likely owing to the complex interplay of carbapenem-resistance mechanisms, i.e., carbapenemase genotype alone cannot predict in vitro bactericidal activity. The availability of WGS information can help rationalize the activity of certain combinations. Further studies should explore the use of genomic markers with phenotypic information to predict combination activity.

scholarly journals Prevalence of Pathogenic Klebsiella Pneumoniae based on PCR Capsular Typing Harbouring Carbapenemases Encoding Genes in Ugandan Tertiary Hospitals

2020 ◽  
Author(s):  
Kenneth Ssekatawa ◽  
Denis K. Byarugaba ◽  
Jesca L. Nakavuma ◽  
Charles D. Kato ◽  
Francis Ejobi ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Clinical Isolates ◽  
Genotypic Resistance ◽  
Cross Sectional ◽  
Pathogenic Potential ◽  
Phenotypic Resistance ◽  
Tertiary Hospitals ◽  
Encoding Genes

Abstract Background: Klebsiella pneumoniae is an opportunistic pathogen that has been implicated as one of commonest cause of hospital and community acquired infections. The K. pneumoniae infections have considerably contributed to morbidity and mortality in patients with protracted ailments. The capacity of K. pneumonia to cause diseases depends on presence of an array virulent factors. Coexistence and expression of virulent factors and genetic determinants of antibiotic resistance complicates treatment outcomes. Thus, emergence of pathogenic MDR K. pneumoniae poses a great threat to the healthcare system. However, the carriage of antibiotic resistance among pathogenic K. pneumoniae is yet to be investigated in Uganda. We sought to investigate the carbapenem resistance profiles and pathogenic potential based on capsular serotypes of K. pneumoniae clinical isolates. Methods: This was a cross sectional study involving use of archived Klebsiella pneumoniae isolates collected between January and December, 2019 at four tertiary hospitals in Uganda. All isolates were subject to antimicrobial susceptibility assays to determine phenotypic antibiotic resistance, pentaplex PCR to detect carbapenemases encoding genes and heptaplex PCR to identify capsular serotypes K1, K2, K3, K5, K20, K54 and K57.Results: The study found an overall phenotypic carbapenem resistance of 23.3% (53/227) and significantly higher genotypic resistance prevalence of 43.1% (98/227). Over all, the most prevalent gene was blaOXA-48-like (36.4%), followed by blaIMP-type (19.4%), blaVIM-type (17.1), blaKP-type (14.0%) and blaNDM-type (13.2%). blaVIM-type and blaOXA-48-like conferred phenotypic resistance in all isolates and 38.3% isolates that harbored them respectively. Capsular multiplex PCR revealed that 46.7% (106/227) isolates were pathogenic and the predominantly prevalent pathotype was K5 (18.5%) followed by K20 (14.1%), K3 (7.1%), K2 (3.1%) and K1 (2.2%). Of the 106 capsular serotypes, 37 expressed phenotypic resistance; thus, 37 of the 53 carbapenem resistant K. pneumoniae were pathogenic.Conclusion: The high prevalence of virulent and antibiotic resistant K. pneumoniae among clinical isolates obtained from the four tertiary hospital as revealed by this study pose a great threat to healthcare. Our findings underline the epidemiological and public health risks and implications of this pathogen.

scholarly journals A Serendipitous Mutation Reveals the Severe Virulence Defect of a Klebsiella pneumoniae fepB Mutant

mSphere ◽  
2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Michelle Palacios ◽  
Christopher A. Broberg ◽  
Kimberly A. Walker ◽  
Virginia L. Miller
Keyword(s):  
Antibiotic Resistance ◽  
Urinary Tract ◽  
Klebsiella Pneumoniae ◽  
Drug Targets ◽  
Carbapenem Resistance ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Tract Infections ◽  
Hospital Acquired ◽  
Rapid Emergence

ABSTRACT In addition to having a reputation as the causative agent of several types of hospital-acquired infections, Klebsiella pneumoniae has gained widespread attention as a pathogen with a propensity for acquiring antibiotic resistance. It is capable of causing a range of infections, including urinary tract infections, pneumonia, and sepsis. Because of the rapid emergence of carbapenem resistance among Klebsiella strains, there is a dire need for a better understanding of virulence mechanisms and identification of new drug targets. Here, we identify the periplasmic transporter FepB as one such potential target. Klebsiella pneumoniae is considered a significant public health threat because of the emergence of multidrug-resistant strains and the challenge associated with treating life-threatening infections. Capsule, siderophores, and adhesins have been implicated as virulence determinants of K. pneumoniae, yet we lack a clear understanding of how this pathogen causes disease. In a previous screen for virulence genes, we identified a potential new virulence locus and constructed a mutant (smr) with this locus deleted. In this study, we characterize the smr mutant and show that this mutation renders K. pneumoniae avirulent in a pneumonia model of infection. The smr mutant was expected to have a deletion of three genes, but subsequent genome sequencing indicated that a much larger deletion had occurred. Further analysis of the deleted region indicated that the virulence defect of the smr mutant could be attributed to the loss of FepB, a periplasmic protein required for import of the siderophore enterobactin. Interestingly, a ΔfepB mutant was more attenuated than a mutant unable to synthesize enterobactin, suggesting that additional processes are affected. As FepB is highly conserved among the members of the family Enterobacteriaceae, therapeutic targeting of FepB may be useful for the treatment of Klebsiella and other bacterial infections. IMPORTANCE In addition to having a reputation as the causative agent of several types of hospital-acquired infections, Klebsiella pneumoniae has gained widespread attention as a pathogen with a propensity for acquiring antibiotic resistance. It is capable of causing a range of infections, including urinary tract infections, pneumonia, and sepsis. Because of the rapid emergence of carbapenem resistance among Klebsiella strains, there is a dire need for a better understanding of virulence mechanisms and identification of new drug targets. Here, we identify the periplasmic transporter FepB as one such potential target.

scholarly journals Major discrepancy between factual antibiotic resistance and consumption in South of France: analysis of 539,037 bacterial strains

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ousmane Oumou Diallo ◽  
Sophie Alexandra Baron ◽  
Gregory Dubourg ◽  
Hervé Chaudet ◽  
Philippe Halfon ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Resistance Rate ◽  
High Rate ◽  
Surveillance Systems ◽  
Bacterial Strains ◽  
Large Area ◽  
Real Rate ◽  
Oxacillin Resistance

Abstract The burden of antibiotic resistance is currently estimated by mathematical modeling, without real count of resistance to key antibiotics. Here we report the real rate of resistance to key antibiotics in bacteria isolated from humans during a 5 years period in a large area in southeast in France. We conducted a retrospective study on antibiotic susceptibility of 539,107 clinical strains isolated from hospital and private laboratories in south of France area from January 2014 to January 2019. The resistance rate to key antibiotics as well as the proportion of bacteria classified as Difficult-to-Treat (DTR) were determined and compared with the Mann–Whitney U test, the χ2 test or the Fisher’s exact test. Among 539,037 isolates, we did not observe any significant increase or decrease in resistance to key antibiotics for 5 years, (oxacillin resistance in Staphylococcus aureus, carbapenem resistance in enterobacteria and Pseudomonas aeruginosa and 3rd generation cephalosporin resistance in Escherichia coli and Klebsiella pneumoniae). However, we observed a significant decrease in imipenem resistance for Acinetobacter baumannii from 2014 to 2018 (24.19–12.27%; p = 0.005) and a significant increase of ceftriaxone resistance in Klebsiella pneumoniae (9.9–24.03%; p = 0.001) and Enterobacter cloacae (24.05–42.05%; p = 0.004). Of these 539,037 isolates, 1604 (0.3%) had a DTR phenotype. Over a 5-year period, we did not observe a burden of AR in our region despite a high rate of antibiotic consumption in our country. These results highlight the need for implementation of real-time AR surveillance systems which use factual data.

scholarly journals Major discrepancy between factual antibiotic resistance and consumption in South of France: analysis of 539,037 bacterial strains

2020 ◽  
Author(s):  
Ousmane Oumou Diallo ◽  
Sophie Alexandra Baron ◽  
Gregory Dubourg ◽  
Hervé Chaudet ◽  
Philippe Halfon ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Resistance Rate ◽  
High Rate ◽  
Surveillance Systems ◽  
Bacterial Strains ◽  
Large Area ◽  
Real Rate ◽  
Oxacillin Resistance

AbstractIntroductionThe burden of antibiotic resistance is currently estimated by mathematical modeling, without real count of resistance to key antibiotics. Here we report the real rate of resistance to key antibiotics in bacteria isolated from humans during a 5 years period in a large area in southeast in France.MethodsWe conducted a retrospective study on antibiotic susceptibility of 539,107 clinical strains isolated from hospital and private laboratories in south of France area from January 2014 to January 2019. The resistance rate to key antibiotics as well as the proportion of bacteria classified as Difficult-to-Treat (DTR) were determined and compared with the Mann-Whitney U test, the χ2 test or the Fisher’s exact test.ResultsAmong 539,037 isolates, we did not observe any significant increase or decrease in resistance to key antibiotics for 5 years, (oxacillin resistance in Staphylococcus aureus, carbapenem resistance in enterobacteria and Pseudomonas aeruginosa and 3rd generation cephalosporin resistance in Escherichia coli and Klebsiella pneumoniae). However, we observed a significant decrease in imipenem resistance for Acinetobacter baumannii from 2014 to 2018 (24.19% to 12.27%; p=0.005) and a significant increase of ceftriaxone resistance in Klebsiella pneumoniae (9.9% to 24,03%; p=0.001) and Enterobacter cloacae (24,05% to 42,05%; p=0.004). Of these 539,037 isolates, 1,604 (0.3%) had a DTR phenotype.ConclusionOver a 5-year period, we did not observe a burden of AR in our region despite a high rate of antibiotic consumption in our country. These results highlight the need for implementation of real-time AR surveillance systems which use factual data.

scholarly journals Plasmid Dissemination and Selection of a Multidrug-Resistant Klebsiella pneumoniae Strain during Transplant-Associated Antibiotic Therapy

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Sean Conlan ◽  
Anna F. Lau ◽  
Clay Deming ◽  
Christine D. Spalding ◽  
ShihQueen Lee-Lin ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Klebsiella Pneumoniae ◽  
Antibiotic Therapy ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Cell Transplant ◽  
Citrobacter Freundii ◽  
Content Type ◽  
Selection Of

ABSTRACT Antibiotics, which are used both to prevent and to treat infections, are a mainstay therapy for lifesaving procedures such as transplantation. For this reason, and many others, increased antibiotic resistance among human-associated pathogens, such as the carbapenem-resistant Enterobacteriaceae species, is of grave concern. In this study, we report on a hematopoietic stem cell transplant recipient in whom cultures detected the emergence of carbapenem resistance and spread across five strains of bacteria that persisted for over a year. Carbapenem resistance in Citrobacter freundii, Enterobacter cloacae, Klebsiella aerogenes, and Klebsiella pneumoniae was linked to a pair of plasmids, each carrying the Klebsiella pneumoniae carbapenemase gene (blaKPC). Surveillance cultures identified a carbapenem-susceptible strain of Citrobacter freundii that may have become resistant through horizontal gene transfer of these plasmids. Selection of a multidrug-resistant Klebsiella pneumoniae strain was also detected following combination antibiotic therapy. Here we report a plasmid carrying the blaKPC gene with broad host range that poses the additional threat of spreading to endogenous members of the human gut microbiome. IMPORTANCE Antibiotic-resistant bacteria are a serious threat to medically fragile patient populations. The spread of antibiotic resistance through plasmid-mediated mechanisms is of grave concern as it can lead to the conversion of endogenous patient-associated strains to difficult-to-treat pathogens.

scholarly journals Hybrid Resistance and Virulence Plasmids in “High-Risk” Clones of Klebsiella pneumoniae, Including Those Carrying blaNDM-5

2019 ◽  
Vol 7 (9) ◽  
pp. 326 ◽  
Author(s):  
Jane Turton ◽  
Frances Davies ◽  
Jack Turton ◽  
Claire Perry ◽  
Zoë Payne ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
High Risk ◽  
Klebsiella Pneumoniae ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Virulence Plasmid ◽  
Virulence Plasmids ◽  
Long Read ◽  
Multiple Resistance Genes ◽  
Sequence Types

Virulence plasmids are associated with hypervirulent types of Klebsiella pneumoniae, which generally do not carry antibiotic resistance genes. In contrast, nosocomial isolates are often associated with resistance, but rarely with virulence plasmids. Here, we describe virulence plasmids in nosocomial isolates of “high-risk” clones of sequence types (STs) 15, 48, 101, 147 and 383 carrying carbapenemase genes. The whole genome sequences were determined by long-read nanopore sequencing. The 12 isolates all contained hybrid plasmids containing both resistance and virulence genes. All carried rmpA/rmpA2 and the aerobactin cluster, with the virulence plasmids of two of three representatives of ST383 carrying blaNDM-5 and seventeen other resistance genes. Representatives of ST48 and ST15 had virulence plasmid-associated genes distributed between two plasmids, both containing antibiotic resistance genes. Representatives of ST101 were remarkable in all sharing virulence plasmids in which iucC and terAWXYZ were missing and iucB and iucD truncated. The combination of resistance and virulence in plasmids of high-risk clones is extremely worrying. Virulence plasmids were often notably consistent within a lineage, even in the absence of epidemiological links, suggesting they are not moving between types. However, there was a common segment containing multiple resistance genes in virulence plasmids of representatives of both STs 48 and 383.

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