scholarly journals Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing

mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Andre Mu ◽  
Jason C. Kwong ◽  
Nicole S. Isles ◽  
Anders Gonçalves da Silva ◽  
Mark B. Schultz ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Metagenomic Sequencing ◽  
Drug Resistant ◽  
Content Type ◽  
Drug Resistant Bacteria ◽  
Study Results ◽  
Culture Independent ◽  
Outbreak Investigations ◽  
Rich Data

ABSTRACT Culture-independent methods that target genome fragments have shown promise in identifying certain pathogens, but the holy grail of comprehensive pathogen genome detection from microbiologically complex samples for subsequent forensic analyses remains a challenge. In the context of an investigation of a nosocomial outbreak, we used shotgun metagenomic sequencing of a human fecal sample and a neural network algorithm based on tetranucleotide frequency profiling to reconstruct microbial genomes and tested the same approach using rectal swabs from a second patient. The approach rapidly and readily detected the genome of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in the patient fecal specimen and in the rectal swab sample, achieving a level of strain resolution that was sufficient for confident transmission inference during a highly clonal outbreak. The analysis also detected previously unrecognized colonization of the patient by vancomycin-resistant Enterococcus faecium, another multidrug-resistant bacterium. IMPORTANCE The study results reported here perfectly demonstrate the power and promise of clinical metagenomics to recover genome sequences of important drug-resistant bacteria and to rapidly provide rich data that inform outbreak investigations and treatment decisions, independently of the need to culture the organisms.

scholarly journals Genome reconstruction and characterisation of extensively drug-resistant bacterial pathogens through direct metagenomic sequencing of human faeces

2017 ◽  
Author(s):  
Andre Mu ◽  
Jason C. Kwong ◽  
Nicole S. Isles ◽  
Anders Gonçalves da Silva ◽  
Mark B. Schultz ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Sample ◽  
Microbial Pathogens ◽  
Resistant Bacteria ◽  
Metagenomic Sequencing ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Culture Independent ◽  
High Level

AbstractWhole-genome sequencing of microbial pathogens is revolutionising modern approaches to outbreaks of infectious diseases and is reliant upon organism culture. Culture-independent methods have shown promise in identifying pathogens, but high level reconstruction of microbial genomes from microbiologically complex samples for more in-depth analyses remains a challenge. Here, using metagenomic sequencing of a human faecal sample and analysis by tetranucleotide frequency profiling projected onto emergent self-organising maps, we were able to reconstruct the underlying populations of two extensively-drug resistant pathogens, Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae and vancomycin-resistant Enterococcus faecium. From these genomes, we were able to ascertain molecular typing results, such as MLST, and identify highly discriminatory mutations in the metagenome to distinguish closely related strains. These proof-of-principle results demonstrate the utility of clinical sample metagenomics to recover sequences of important drug-resistant bacteria and application of the approach in outbreak investigations, independent of the need to culture the organisms.

scholarly journals Complete Genome Sequence of a Novel Multidrug-Resistant Klebsiella pneumoniae Phage, vB_Kpn_IME260

2017 ◽  
Vol 5 (19) ◽  
Author(s):  
Shaozhen Xing ◽  
Xiangchun Pan ◽  
Qiang Sun ◽  
Guangqian Pei ◽  
Xiaoping An ◽  
...  
Keyword(s):  
Public Health ◽  
Klebsiella Pneumoniae ◽  
Phage Therapy ◽  
Bacterial Pathogen ◽  
Genomic Data ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Drug Resistant Bacteria

ABSTRACT Klebsiella pneumoniae is the most common clinically important opportunistic bacterial pathogen and its infection is often iatrogenic. Its drug resistance poses a grave threat to public health. The genomic data reported here comprise an important resource for research on phage therapy in the control of drug-resistant bacteria.

scholarly journals Agreement Assessment of Tigecycline Susceptibilities Determined by the Disk Diffusion and Broth Microdilution Methods among Commonly Encountered Resistant Bacterial Isolates: Results from the TigecyclineIn VitroSurveillance in Taiwan (TIST) Study, 2008 to 2010

2011 ◽  
Vol 56 (3) ◽  
pp. 1414-1417 ◽  
Author(s):  
Jien-Wei Liu ◽  
Wen-Chien Ko ◽  
Cheng-Hua Huang ◽  
Chun-Hsing Liao ◽  
Chin-Te Lu ◽  
...  
Keyword(s):  
Susceptibility Testing ◽  
Total Error ◽  
Error Rates ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Broth Microdilution ◽  
Content Type ◽  
E Coli ◽  
Drug Resistant Bacteria

ABSTRACTThe TigecyclineIn VitroSurveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor thein vitroactivity of tigecycline against commonly encountered drug-resistant bacteria. This study compared thein vitroactivity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistantStaphylococcus aureus(MRSA;n= 759), vancomycin-resistantEnterococcus faecium(VRE;n= 191), extended-spectrum β-lactamase (ESBL)-producingEscherichia coli(n= 602), ESBL-producingKlebsiella pneumoniae(n= 736), andAcinetobacter baumannii(n= 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC90values of tigecycline against MRSA, VRE, ESBL-producingE. coli, ESBL-producingK. pneumoniae, andA. baumanniiwere 0.5, 0.125, 0.5, 2, and 8 μg/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producingK. pneumoniaeand 33.8% forA. baumannii. Using the EUCAST criteria, the total error rate was also high (54.6%) forA. baumanniiisolates. The total error rates between these two methods were <5% for MRSA, VRE, and ESBL-producingE. coli. For routine susceptibility testing of ESBL-producingK. pneumoniaeandA. baumanniiagainst tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods.

Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Treatment Options ◽  
Strong Association ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

scholarly journals Isolation of Multidrug Resistant Bacteria from Aspirates of Cancer Patients

2019 ◽  
Vol 35 (1) ◽  
pp. 61-66
Author(s):  
Sunjukta Ahsan ◽  
Rayhan Mahmud ◽  
Kajal Ahsan ◽  
Shamima Begum
Keyword(s):  
Cancer Patients ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Multidrug Resistant Bacteria ◽  
Esbl Producer ◽  
Drug Resistant Bacteria ◽  
Treatment Facilities ◽  
Isolated Species

Infections due to Gram-negative bacteria are common affairs in cancer patients during aggressive therapy. The present study characterizedmulti-drug resistant bacteria (MDR) isolated from cancer aspirates collected from patients admitted to the National Cancer Hospital in Dhaka, Bangladesh. A total of 210 aspirate samples were collected from cancer patients. Out of 210 samples Acinetobacter spp.led the list of isolates (8.89%, n=45). Of these species, 50% exhibited resistance to Amoxycillin and Nitrofurantoin, each, 25% exhibited resistant to Cefotaxime, Azithromycin, Ciprofloxacin, Clindamycin, and Sulfamethoxazole. A total of 33.33% of the Bordetella spp.which accounted 6.67%of the total isolates exhibited resistance to Cefotaxime. All oftheLegionellapneumophila,comprising 4.4%of the isolated species, wereresistant to Cefotaxime, Azithromycin, and Clindamycin.In contrast, 50% were resistant to Cefotaxime, Azithromycin, and Ceftriaxone. Of the Escherichia coli(4.4%, n=45) isolated,50% exhibited resistance to Cefotaxime, Clindamycin, Ceftriaxone, Amoxycillinand Sulfamethoxazole.The only isolate of Klebsiella sp. was demonstrated to be an ESBL producer. The isolation of multidrug resistant bacteria from cancer patients is of particular concern in Bangladesh where cancer and drug resistance are both common phenomena but treatment facilities are poor. To our knowledge this is the first report of the isolation of drug resistant bacteria from cancer patients from Dhaka city. Bangladesh J Microbiol, Volume 35 Number 1 June 2018, pp 61-66

scholarly journals A Tailspike with Exopolysaccharide Depolymerase Activity from a New Providencia stuartii Phage Makes Multidrug-Resistant Bacteria Susceptible to Serum-Mediated Killing

2020 ◽  
Vol 86 (13) ◽  
Author(s):  
Hugo Oliveira ◽  
Graça Pinto ◽  
Bruna Mendes ◽  
Oscar Dias ◽  
Hanne Hendrix ◽  
...  
Keyword(s):  
Immune System ◽  
Prolonged Exposure ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Specific Substrate ◽  
Drug Resistant ◽  
Nosocomial Pathogen ◽  
Content Type ◽  
Serum Killing ◽  
Providencia Stuartii

ABSTRACT Providencia stuartii is emerging as a significant drug-resistant nosocomial pathogen, which encourages the search for alternative therapies. Here, we have isolated Providencia stuartii phage Stuart, a novel podovirus infecting multidrug-resistant hospital isolates of this bacterium. Phage Stuart is a proposed member of a new Autographivirinae subfamily genus, with a 41,218-bp genome, direct 345-bp repeats at virion DNA ends, and limited sequence similarity of proteins to proteins in databases. Twelve out of the 52 predicted Stuart proteins are virion components. We found one to be a tailspike with depolymerase activity. The tailspike could form a highly thermostable oligomeric β-structure migrating close to the expected trimer in a nondenaturing gel. It appeared to be essential for the infection of three out of four P. stuartii hosts infected by phage Stuart. Moreover, it degraded the exopolysaccharide of relevant phage Stuart hosts, making the bacteria susceptible to serum killing. Prolonged exposure of a sensitive host to the tailspike did not cause the emergence of bacteria resistant to the phage or to serum killing, opposite to the prolonged exposure to the phage. This indicates that phage tail-associated depolymerases are attractive antivirulence agents that could complement the immune system in the fight with P. stuartii. IMPORTANCE The pace at which multidrug-resistant strains emerge has been alarming. P. stuartii is an infrequent but relevant drug-resistant nosocomial pathogen causing local to systemic life-threatening infections. We propose an alternative approach to fight this bacterium based on the properties of phage tailspikes with depolymerase activity that degrade the surface bacterial polymers, making the bacteria susceptible to the immune system. Unlike antibiotics, phage tailspikes have narrow and specific substrate spectra, and by acting as antivirulent but not bactericidal agents they do not cause the selection of resistant bacteria.

scholarly journals Trends in the Susceptibility of Clinically Important Resistant Bacteria to Tigecycline: Results from the TigecyclineIn VitroSurveillance in Taiwan Study, 2006 to 2010

2011 ◽  
Vol 56 (3) ◽  
pp. 1452-1457 ◽  
Author(s):  
Yen-Hsu Chen ◽  
Po-Liang Lu ◽  
Cheng-Hua Huang ◽  
Chun-Hsing Liao ◽  
Chin-Te Lu ◽  
...  
Keyword(s):  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
E Coli ◽  
Drug Resistant Bacteria ◽  
Vancomycin Resistant ◽  
Susceptibility Rate ◽  
Important Drug

ABSTRACTThe TigecyclineIn VitroSurveillance in Taiwan (TIST) study, a nationwide, prospective surveillance during 2006 to 2010, collected a total of 7,793 clinical isolates, including methicillin-resistantStaphylococcus aureus(MRSA) (n= 1,834), penicillin-resistantStreptococcus pneumoniae(PRSP) (n= 423), vancomycin-resistant enterococci (VRE) (n= 219), extended-spectrum β-lactamase (ESBL)-producingEscherichia coli(n= 1,141), ESBL-producingKlebsiella pneumoniae(n= 1,330),Acinetobacter baumannii(n= 1,645), andStenotrophomonas maltophilia(n= 903), from different specimens from 20 different hospitals in Taiwan. MICs of tigecycline were determined following the criteria of the U.S. Food and Drug Administration (FDA) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST-2011). Among drug-resistant Gram-positive pathogens, all of the PRSP isolates were susceptible to tigecycline (MIC90, 0.03 μg/ml), and only one MRSA isolate (MIC90, 0.5 μg/ml) and three VRE isolates (MIC90, 0.125 μg/ml) were nonsusceptible to tigecycline. Among the Gram-negative bacteria, the tigecycline susceptibility rates were 99.65% for ESBL-producingE. coli(MIC90, 0.5 μg/ml) and 96.32% for ESBL-producingK. pneumoniae(MIC90, 2 μg/ml) when interpreted by FDA criteria but were 98.7% and 85.8%, respectively, when interpreted by EUCAST-2011 criteria. The susceptibility rate forA. baumannii(MIC90, 4 μg/ml) decreased from 80.9% in 2006 to 55.3% in 2009 but increased to 73.4% in 2010. A bimodal MIC distribution was found among carbapenem-susceptibleA. baumanniiisolates, and a unimodal MIC distribution was found among carbapenem-nonsusceptibleA. baumanniiisolates. In Taiwan, tigecycline continues to have excellentin vitroactivity against several major clinically important drug-resistant bacteria, with the exception ofA. baumannii.

scholarly journals Synergistic antibacterial effects of colistin in combination with aminoglycoside, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin on multidrug resistant Klebsiella pneumoniae isolates

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244673
Author(s):  
Julalak C. Ontong ◽  
Nwabor F. Ozioma ◽  
Supayang P. Voravuthikunchai ◽  
Sarunyou Chusri
Keyword(s):  
Antibacterial Activity ◽  
Klebsiella Pneumoniae ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Antibacterial Effects ◽  
Drug Resistant Bacteria ◽  
Multidrug Resistant Pathogens ◽  
Conventional Antibiotics ◽  
Global Health Problem

Multidrug resistant Enterobacterales have become a serious global health problem, with extended hospital stay and increased mortality. Antibiotic monotherapy has been reported ineffective against most drug resistant bacteria including Klebsiella pneumoniae, thus encouraging the use of multidrug therapies as an alternative antibacterial strategy. The present works assessed the antibacterial activity of colistin against K. pneumoniae isolates. Resistant isolates were tested against 16 conventional antibiotics alone and in combination with colistin. The results revealed that all colistin resistant isolates demonstrated multidrug resistance against the tested antibiotics except amikacin. At sub-inhibitory concentrations, combinations of colistin with amikacin, or fosfomycin showed synergism against 72.72% (8 of 11 isolates). Colistin with either of gentamicin, meropenem, cefoperazone, cefotaxime, ceftazidime, moxifloxacin, minocycline, or piperacillin exhibited synergism against 81.82% (9 of 11 isolates). Combinations of colistin with either of tobramycin or ciprofloxacin showed synergism against 45.45% (5 in 11 isolates), while combinations of colistin with imipenem or ceftolozane and tazobactam displayed 36.36% (4 of 11 isolates) and 63.64% (7 of 11 isolates) synergism. In addition, combinations of colistin with levofloxacin was synergistic against 90.91% (10 of 11 isolates). The results revealed that combinations of colistin with other antibiotics could effectively inhibit colistin resistant isolates of K. pneumoniae, and thus could be further explore for the treatment of multidrug resistant pathogens.

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