Shashikant Srivastava

ORCID: 0000-0002-8786-8851
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About
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Research Areas
  • Tuberculosis Research and Epidemiology
  • Mycobacterium research and diagnosis
  • Antibiotics Pharmacokinetics and Efficacy
  • Antibiotic Resistance in Bacteria
  • Quinazolinone synthesis and applications
  • Cancer therapeutics and mechanisms
  • Pneumonia and Respiratory Infections
  • Infectious Diseases and Tuberculosis
  • Pneumocystis jirovecii pneumonia detection and treatment
  • Infectious Diseases and Mycology
  • Diagnosis and treatment of tuberculosis
  • Helicobacter pylori-related gastroenterology studies
  • Drug Transport and Resistance Mechanisms
  • Drug-Induced Hepatotoxicity and Protection
  • Antimicrobial Resistance in Staphylococcus
  • Liver Disease and Transplantation
  • HIV/AIDS drug development and treatment
  • Pharmacogenetics and Drug Metabolism
  • Veterinary medicine and infectious diseases
  • Phenothiazines and Benzothiazines Synthesis and Activities
  • Pharmacovigilance and Adverse Drug Reactions
  • Epilepsy research and treatment
  • Pharmaceutical studies and practices
  • Gastric Cancer Management and Outcomes
  • Biosimilars and Bioanalytical Methods

The University of Texas at Tyler
2021-2025

The University of Texas Health Science Center at Tyler
2020-2025

St.John's Medical College Hospital
2024

Baylor University Medical Center
2015-2023

Texas Tech University
2019-2023

The University of Texas Southwestern Medical Center
2010-2022

Southwestern Medical Center
2008-2022

Texas Tech University Health Sciences Center
2019-2022

North Eastern Hill University
2020

Conference Board
2020

(See the editorial commentary by Dartois, on pages 1827–9.) Background. It is believed that nonadherence proximate cause of multidrug-resistant tuberculosis (MDR-tuberculosis) emergence. The level associated with emergence MDR-tuberculosis unknown. Performance a randomized controlled trial in which some patients are to would be unethical; therefore, other study designs should utilized. Methods. We performed hollow fiber studies for both bactericidal and sterilizing effect, inoculum spiked...

10.1093/infdis/jir658 article EN The Journal of Infectious Diseases 2011-10-21

We hypothesize that low-level efflux pump expression is the first step in development of high-level drug resistance mycobacteria. performed 28-day azithromycin dose-effect and dose-scheduling studies our hollow-fiber model disseminated Mycobacterium avium-M. intracellulare complex. Both microbial kill emergence were most closely linked to within-macrophage area under concentration-time curve (AUC)/MIC ratio. Quantitative PCR revealed subtherapeutic exposures over 3 days led a 56-fold...

10.1128/aac.05546-11 article EN Antimicrobial Agents and Chemotherapy 2012-07-03

Acquired resistance is an important driver of multidrug-resistant tuberculosis (TB), even with good treatment adherence. However, exactly what initiates the and how it arises remain poorly understood.To identify relationship between drug concentrations susceptibility readouts (minimum inhibitory [MICs]) in TB cavity.We recruited patients medically incurable who were undergoing therapeutic lung resection while on a cocktail second-line anti-TB drugs. On day surgery, antibiotic measured blood...

10.1164/rccm.201711-2333oc article EN American Journal of Respiratory and Critical Care Medicine 2018-06-07

Background. Ethambutol is used for the treatment of tuberculosis in cases where there isoniazid resistance. We examined emergence drug resistance to ethambutol monotherapy pharmacokinetic-pharmacodynamic studies a hollow-fiber system.

10.1086/651377 article EN The Journal of Infectious Diseases 2010-03-08

Background. The role of drug concentrations in clinical outcomes children with tuberculosis is unclear. Target for dose optimization are unknown. Methods. Plasma measured Indian were modeled using compartmental pharmacokinetic analyses. followed until end therapy to ascertain failure or death. An ensemble artificial intelligence algorithms, including random forests, was used identify predictors outcome from among 30 clinical, laboratory, and variables. Results. Among the 143 known outcomes,...

10.1093/cid/ciw471 article EN cc-by-nc-nd Clinical Infectious Diseases 2016-10-14

ABSTRACT Linezolid has an excellent sterilizing effect in tuberculosis patients but high adverse event rates. The dose that would maximize efficacy and minimize toxicity is unknown. We performed linezolid dose-effect dose-scheduling studies the hollow fiber system model of (HFS-TB) for effect. HFS-TB units were treated with several doses to mimic human-like intrapulmonary pharmacokinetics repetitively sampled drug concentration, total bacterial burden, linezolid-resistant subpopulations, RNA...

10.1128/aac.00751-17 article EN cc-by Antimicrobial Agents and Chemotherapy 2017-06-06

Levofloxacin is used for the treatment of multidrug-resistant tuberculosis; however optimal dose unknown.We hollow fiber system model tuberculosis (HFS-TB) to identify 0-24 hour area under concentration-time curve (AUC0-24) minimum inhibitory concentration (MIC) ratios associated with maximal microbial kill and suppression acquired drug resistance (ADR) Mycobacterium (Mtb). Levofloxacin-resistant isolates underwent whole-genome sequencing. Ten thousands patient Monte Carlo experiments (MCEs)...

10.1093/cid/ciy611 article EN Clinical Infectious Diseases 2018-07-27

BACKGROUND: Optimal drug dosing is important to ensure adequate response treatment, prevent development of resistance and reduce toxicity. The aim these clinical standards provide guidance on 'best practice´ for management TB drugs.METHODS: A panel 57 global experts in the fields microbiology, pharmacology care were identified; 51 participated a Delphi process. 5-point Likert scale was used score draft standards. final document represents broad consensus approved by all participants.RESULTS:...

10.5588/ijtld.22.0188 article EN cc-by The International Journal of Tuberculosis and Lung Disease 2022-06-01

Ceftazidime-avibactam is highly efficacious against extensive- and multidrug-resistant strains of Mycobacterium tuberculosis .

10.1126/sciadv.1701102 article EN cc-by-nc Science Advances 2017-08-04

ABSTRACT Mycobacterium abscessus causes chronic pulmonary infections that are extremely difficult to cure. The currently recommended combination therapy is associated with high failure rates and relapse. Tigecycline has been explored in salvage regimens, a response rate of 43% those who received at least month therapy. We performed dose-response study hollow-fiber system model M. infection which we recapitulated tigecycline human concentration-time profiles 8 different doses for 21 days....

10.1128/aac.03112-15 article EN Antimicrobial Agents and Chemotherapy 2016-03-01

Adverse effects (AE) to TB treatment cause morbidity, mortality and interruption. The aim of these clinical standards is encourage best practise for the diagnosis management AE.

10.5588/ijtld.23.0078 article EN cc-by The International Journal of Tuberculosis and Lung Disease 2023-06-24

In a hollow-fiber model, we mimicked the drug exposures achieved in lungs of humans treated with standard amikacin, clarithromycin, and cefoxitin combination therapy for Mycobacterium abscessus infection. At optimal dosing, kill rate -0.09 (95% confidence interval, -0.04 to 0.03) log10 CFU per ml/day was over first 14 days, after which there regrowth due acquired resistance. Thus, regimen quickly failed. A new is needed.

10.1128/aac.00990-16 article EN Antimicrobial Agents and Chemotherapy 2016-07-26

Bacterial genomic mutations in Staphylococcus aureus (S. aureus) have been detected isolated resistant clinical strains, yet their mechanistic effect on the development of antimicrobial resistance remains unclear. The resistance-associated regulatory systems acquire adaptive under stress conditions that may lead to a gain function and contribute phenotype. Here, we investigate single-point mutation (T331I) VraS histidine kinase, part VraSR two-component system S. aureus. senses responds...

10.1101/2025.01.06.631495 preprint EN bioRxiv (Cold Spring Harbor Laboratory) 2025-01-06

ABSTRACT The impact of heteroresistance on tuberculosis (TB) treatment outcomes is unclear, as the role different rifampin and isoniazid exposures developing resistance mutations. Hollow fiber system model TB (HFS-TB) units were inoculated with drug-susceptible Mycobacterium ( Mtb ) treated exposure identified in a clinical trial leading to failure acquired drug resistance. Systems sampled for concentration measurements, estimation total drug-resistant , small molecule overlapping reads...

10.1128/aac.01084-24 article EN cc-by Antimicrobial Agents and Chemotherapy 2025-01-16

ABSTRACT Aligned with the World Health Organization’s Road Map, there is an unmet need for research to improve treatment of Buruli ulcer caused by Mycobacterium ulcerans . The repurposing drugs could speed up new regimen development treat ulcer. Using a virulent reporter strain M. intrinsic bioluminescence (MuAL), we compared minimum inhibitory concentration (MIC) moxifloxacin, bedaquiline, telacebec, tebipenem, omadacycline, and epetraborole standard-of-care drugs—rifampin clarithromycin....

10.1128/aac.00029-25 article EN cc-by Antimicrobial Agents and Chemotherapy 2025-03-26

Ethambutol, together with a macrolide, is the backbone for treatment of disseminated Mycobacterium avium disease. However, at standard dose 15 mg/kg body weight/day, ethambutol efficacy limited. In addition, susceptibility breakpoints have consistently failed to predict clinical outcome. We performed dose-effect studies extracellular M. as well bacilli within human macrophages. The maximal kill rate (E(max)) against was 5.54 log(10) CFU/ml, compared 0.67 CFU/ml intracellular avium, after 7...

10.1128/aac.01355-09 article EN Antimicrobial Agents and Chemotherapy 2010-03-16
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