scholarly journals 1113. Real-Time Evolution of Extensively Drug-Resistant Vibrio cholerae

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S334-S334
Author(s):  
Bhabatosh Das
Keyword(s):  
Vibrio Cholerae ◽  
Bacterial Species ◽  
Proteome Analysis ◽  
Diarrhoeal Disease ◽  
Drug Regimen ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Exogenous Dna ◽  
Extensively Drug Resistant ◽  
Resistance Traits

Abstract Background Bay of Bengal is known as the epicenter of a number of distinct waves of global transmission of cholera. Vibrio cholerae, the etiological agent of acute diarrhoeal disease cholera, has extraordinary competency to acquire exogenous DNA by horizontal gene transfer (HGT) and acclimatize them into their genome for structuring metabolic process, developing drug resistance and disease. Antimicrobial resistance (AMR) in V. cholerae is a global concern. However, little is known about the identity, source, acquisition process, and stability of the resistance traits in the genome of cholera pathogen. Methods Antibiotic susceptibility testing of V. cholerae isolated from different parts of India during 2001–2017 was performed using Discs and E-strips. Whole-genome sequencing of resistant (R), multidrug resistant (MDR), extensively drug resistant (XDR), and pandrug (PDR) resistant V. cholerae was done by next-generation DNA sequencing. Mobile genetic elements (MGEs) linked with AMR genes were tagged by allelic exchange methods. Whole-cell proteome analysis was done by iTRAQ analysis. Results Almost 99% of V. cholerae isolates (n = 438) are resistant against ≥2 antibiotics, 17.2% isolates (n = 76) are resistant against ≥10 antibiotics, and 7.5% isolates (n = 33) are resistant against ≥14 antibiotics. Highest resistance was detected against sulfamethaxozole (99.8%, n = 442). In addition, resistance to nalidixic acid (n = 429), trimethoprim (n = 421), and streptomycin (n = 409) are also very high. All the sequenced resistant isolates carrying multiple resistance genes and are linked with MGEs like integrating conjugative elements, transposons etc. Most of the resistance traits are functional and expressed even in the absence of antibiotics. Conclusion Our comprehensive analysis of 443 clinical V. cholerae isolates show that the cholera pathogen is continuously evolving to counterbalance the antimicrobial effects of antibiotics. Several MGEs linked with AMR genes and other fitness factors potentially propagate to other bacterial species through HGTs. Knowledge of the present study would be useful to understand the evolution of cholera pathogens and management of cholera by helping selection of specific drug regimen against the pathogens. Disclosures All authors: No reported disclosures.

scholarly journals Genomic plasticity associated with antimicrobial resistance inVibrio cholerae

2019 ◽  
Vol 116 (13) ◽  
pp. 6226-6231 ◽  
Author(s):  
Jyoti Verma ◽  
Satyabrata Bag ◽  
Bipasa Saha ◽  
Pawan Kumar ◽  
Tarini Shankar Ghosh ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Core Genome ◽  
Proteome Analysis ◽  
Multidrug Resistant ◽  
Exogenous Dna ◽  
Treatment Regimens ◽  
Stool Samples ◽  
Global Concern ◽  
Integrative Conjugative Elements ◽  
Resistance Traits

The Bay of Bengal is known as the epicenter for seeding several devastating cholera outbreaks across the globe.Vibrio cholerae, the etiological agent of cholera, has extraordinary competency to acquire exogenous DNA by horizontal gene transfer (HGT) and adapt them into its genome for structuring metabolic processes, developing drug resistance, and colonizing the human intestine. Antimicrobial resistance (AMR) inV. choleraehas become a global concern. However, little is known about the identity of the resistance traits, source of AMR genes, acquisition process, and stability of the genetic elements linked with resistance genes inV. cholerae. Here we present details of AMR profiles of 443V. choleraestrains isolated from the stool samples of diarrheal patients from two regions of India. We sequenced the whole genome of multidrug-resistant (MDR) and extensively drug-resistant (XDR)V. choleraeto identify AMR genes and genomic elements that harbor the resistance traits. Our genomic findings were further confirmed by proteome analysis. We also engineered the genome ofV. choleraeto monitor the importance of the autonomously replicating plasmid and core genome in the resistance profile. Our findings provided insights into the genomes of recent cholera isolates and identified several acquired traits including plasmids, transposons, integrative conjugative elements (ICEs), pathogenicity islands (PIs), prophages, and gene cassettes that confer fitness to the pathogen. The knowledge generated from this study would help in better understanding ofV. choleraeevolution and management of cholera disease by providing clinical guidance on preferred treatment regimens.

scholarly journals 1597. Ceftolozane-Tazobactam and Meropenem Synergy Testing Against Multi-Drug and Extensively-Drug Resistant Pseudomonas aeruginosa

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S794-S795
Author(s):  
Mary Francine P Chua ◽  
Syeda Sara Nida ◽  
Jerry Lawhorn ◽  
Janak Koirala
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Synergistic Effect ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Additive Effect ◽  
Teaching Hospitals ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Synergy Testing ◽  
Concentration Indices

Abstract Background Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Pseudomonas aeruginosa (PA) have limited therapeutic options for treatment. Ceftolozane/tazobactam is a newer anti-pseudomonal drug effective against resistant PA infections, however resistance against this drug has now also developed and is increasing. In this study, we explored the combination of ceftolozane/tazobactam (CT) and meropenem (MP) as a possible effective regimen against MDR and XDR PA. Methods We obtained 33 non-duplicate isolates of MDR and XDR PA grown from blood, urine and respiratory samples collected from patients admitted between 2015 and 2019 at our two affiliate teaching hospitals. MDR PA was defined as resistance to 3 or more classes of anti-pseudomonal antibiotics, and XDR PA as resistance to all but two or less classes of anti-pseudomonal antibiotics. Antimicrobial preparations of both MP and CT were made according to manufacturer instructions. Susceptibility testing was performed using the checkerboard method in accordance to CLSI guidelines (CLSI M100, 2017). The ATCC 27853 strain of PA used as control. Synergy, additive effect, indifference and antagonism were defined as FIC (fractional inhibitory concentration) indices of ≤0.5, >0.5 to <1, >1 to <4, and >4, respectively. Results Thirteen (39%) of 33 PA isolates were classified as XDR, while 20 (61%) PA isolates were MDR. All isolates were resistant to MP (MIC50 >32 ug/mL), while only 2 (6%) isolates were susceptible to CT (MIC50 64 ug/mL). A synergistic effect was seen in 9 (27.3%) of PA isolates (FIC index range 0.28 to 0.5)— 2 of which were XDR PA, and 7 were MDR PA. An additive effect was seen in 12 (36.4%), with indifference seen in 12 (36.4%) of isolates. In this study, no antagonism was seen when CT and MP were combined. Conclusion When used in combination, CT and MP can exert a synergistic effect against MDR and XDR PA. Additive effect and indifference can also be seen when both antibiotics were used. Moreover, there was no antagonism seen when both antibiotics were combined. This study shows that the use of CT and MP in combination may be an option against XDR and MDR PA infections. Disclosures All Authors: No reported disclosures

Metabolic profiles of multidrug resistant and extensively drug resistant Mycobacterium tuberculosis unveiled by metabolomics

Tuberculosis ◽  
2021 ◽  
Vol 126 ◽  
pp. 102043
Author(s):  
Amanda Mendes Rêgo ◽  
Duanne Alves da Silva ◽  
Nicole Victor Ferreira ◽  
Lucindo Cardoso de Pina ◽  
Joseph A.M. Evaristo ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Metabolic Profiles ◽  
Drug Resistant ◽  
Extensively Drug Resistant

scholarly journals Comparison of In Vitro Activity and MIC Distributions between the Novel Oxazolidinone Delpazolid and Linezolid against Multidrug-Resistant and Extensively Drug-Resistant Mycobacterium tuberculosis in China

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Zhaojing Zong ◽  
Wei Jing ◽  
Jin Shi ◽  
Shu'an Wen ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
23S Rrna ◽  
Drug Resistant ◽  
Content Type ◽  
Extensively Drug Resistant ◽  
Significant Difference ◽  
Mdr Tb

ABSTRACT Oxazolidinones are efficacious in treating mycobacterial infections, including tuberculosis (TB) caused by drug-resistant Mycobacterium tuberculosis. In this study, we compared the in vitro activities and MIC distributions of delpazolid, a novel oxazolidinone, and linezolid against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) in China. Additionally, genetic mutations in 23S rRNA, rplC, and rplD genes were analyzed to reveal potential mechanisms underlying the observed oxazolidinone resistance. A total of 240 M. tuberculosis isolates were included in this study, including 120 MDR-TB isolates and 120 XDR-TB isolates. Overall, linezolid and delpazolid MIC90 values for M. tuberculosis isolates were 0.25 mg/liter and 0.5 mg/liter, respectively. Based on visual inspection, we tentatively set epidemiological cutoff (ECOFF) values for MIC determinations for linezolid and delpazolid at 1.0 mg/liter and 2.0 mg/liter, respectively. Although no significant difference in resistance rates was observed between linezolid and delpazolid among XDR-TB isolates (P > 0.05), statistical analysis revealed a significantly greater proportion of linezolid-resistant isolates than delpazolid-resistant isolates within the MDR-TB group (P = 0.036). Seven (53.85%) of 13 linezolid-resistant isolates were found to harbor mutations within the three target genes. Additionally, 1 isolate exhibited an amino acid substitution (Arg126His) within the protein encoded by rplD that contributed to high-level resistance to linezolid (MIC of >16 mg/liter), compared to a delpazolid MIC of 0.25. In conclusion, in vitro susceptibility testing revealed that delpazolid antibacterial activity was comparable to that of linezolid. A novel mutation within rplD that endowed M. tuberculosis with linezolid, but not delpazolid, resistance was identified.

scholarly journals In Vitro Activity of the Novel Pleuromutilin Lefamulin (BC-3781) and Effect of Efflux Pump Inactivation on Multidrug-Resistant and Extensively Drug-Resistant Neisseria gonorrhoeae

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Susanne Jacobsson ◽  
Susanne Paukner ◽  
Daniel Golparian ◽  
Jörgen S. Jensen ◽  
Magnus Unemo
Keyword(s):  
Efflux Pump ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Drug Resistant ◽  
The Novel ◽  
Extensively Drug Resistant ◽  
Optimal Dosing ◽  
And Performance ◽  
Reference Strains

ABSTRACT We evaluated the activity of the novel semisynthetic pleuromutilin lefamulin, inhibiting protein synthesis and growth, and the effect of efflux pump inactivation on clinical gonococcal isolates and reference strains (n = 251), including numerous multidrug-resistant and extensively drug-resistant isolates. Lefamulin showed potent activity against all gonococcal isolates, and no significant cross-resistance to other antimicrobials was identified. Further studies of lefamulin are warranted, including in vitro selection and mechanisms of resistance, pharmacokinetics/pharmacodynamics, optimal dosing, and performance in randomized controlled trials.

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