ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2018
Levofloxacin Pharmacokinetics/Pharmacodynamics, Dosing, Susceptibility Breakpoints, and Artificial Intelligence in the Treatment of Multidrug-resistant Tuberculosis.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- d-Cycloserine Pharmacokinetics/Pharmacodynamics, Susceptibility, and Dosing Implications in Multidrug-resistant Tuberculosis: A Faustian Deal.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Pooled it
- Levofloxacin pharmacokinetics in saliva as measured by a mobile microvolume UV spectrophotometer among people treated for rifampicin-resistant TB in Tanzania.The Journal of antimicrobial chemotherapy · 2021Trial
- Population Pharmacokinetic Model and Limited Sampling Strategies for Personalized Dosing of Levofloxacin in Tuberculosis Patients.Antimicrobial agents and chemotherapy · 2018Trial
- Single Saliva Sample Model-Informed Precision Dosing of Levofloxacin for Multidrug-Resistant Tuberculosis.Clinical pharmacokinetics · 2026Article
- Research on a Predictive Model for Microalbuminuria in Type 2 Diabetes Based on Machine Learning and SHAP Analysis.International journal of endocrinology · 2026Article
- Artificial intelligence for tuberculosis management in Africa: opportunities, challenges, and implementation.Frontiers in public health · 2026Review
- Wild-type MIC distribution and evaluation of epidemiological cut-offs of second-line TB-drugs in susceptible and MDR-TB clinical isolates from Chennai, India.Frontiers in microbiology · 2026Article
- Harnessing the gut microbiome to combat tuberculosis: a technological and clinical review.Frontiers in cellular and infection microbiology · 2026Review
- Imipenem Pharmacokinetics/Pharmacodynamics in Preclinical Hollow Fiber Model, Dose Finding in Virtual Patients, and Clinical Evidence of Efficacy for Mycobacterium abscessus Lung Disease.The Journal of infectious diseases · 2025Article
- The effect of pregnancy on the population pharmacokinetics of levofloxacin in South Africans with rifampicin-resistant tuberculosis.Antimicrobial agents and chemotherapy · 2025Article
- Pharmacokinetics and Safety of Levofloxacin for Treatment of Rifampicin-Resistant Tuberculosis During Pregnancy and the Postpartum Period: Results from IMPAACT P1026s.Clinical pharmacokinetics · 2025Observational
- Fluoroquinolones and rifampin combination in the backdrop of heteroresistant tuberculosis.Antimicrobial agents and chemotherapy · 2025Article
- Clinical Pharmacokinetics of Antitubercular Drugs in the Overweight and Obese Population: Implications for Dosage Adjustments.Clinical pharmacokinetics · 2025Review
- Levofloxacin activity at increasing doses in a murine model of fluoroquinolone-susceptible and -resistant tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- Therapeutic drug monitoring in tuberculosis.European journal of clinical pharmacology · 2024Review
- Role of therapeutic drug monitoring in the treatment of multi-drug resistant tuberculosis.Journal of clinical tuberculosis and other mycobacterial diseases · 2024Article
- QSPR analysis of distance-based structural indices for drug compounds in tuberculosis treatment.Heliyon · 2024Article
- Levofloxacin combined with azithromycin shows greater efficacy in cervicitis treatment compared to azithromycin monotherapy.American journal of translational research · 2024Article
- Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management.Journal of pharmaceutical analysis · 2024Review
- Pharmacokinetics and Safety of Group A and B Anti-Tuberculosis Drugs Used in Treatment of Rifampicin-Resistant Tuberculosis during Pregnancy and Post-Partum: A Narrative Review.Pathogens (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Background: Levofloxacin is used for the treatment of multidrug-resistant tuberculosis; however the optimal dose is unknown. Methods: We used the hollow fiber system model of tuberculosis (HFS-TB) to identify 0-24 hour area under the concentration-time curve (AUC0-24) to minimum inhibitory concentration (MIC) ratios associated with maximal microbial kill and suppression of acquired drug resistance (ADR) of Mycobacterium tuberculosis (Mtb). Levofloxacin-resistant isolates underwent whole-genome sequencing. Ten thousands patient Monte Carlo experiments (MCEs) were used to identify doses best able to achieve the HFS-TB-derived target exposures in cavitary tuberculosis and tuberculous meningitis. Next, we used an ensemble of artificial intelligence (AI) algorithms to identify the most important predictors of sputum conversion, ADR, and death in Tanzanian patients with pulmonary multidrug-resistant tuberculosis treated with a levofloxacin-containing regimen. We also performed probit regression to identify optimal levofloxacin doses in Vietnamese tuberculous meningitis patients. Results: In the HFS-TB, the AUC0-24/MIC associated with maximal Mtb kill was 146, while that associated with suppression of resistance was 360. The most common gyrA mutations in resistant Mtb were Asp94Gly, Asp94Asn, and Asp94Tyr. The minimum dose to achieve target exposures in MCEs was 1500 mg/day. AI algorithms identified an AUC0-24/MIC of 160 as predictive of microbiologic cure, followed by levofloxacin 2-hour peak concentration and body weight. Probit regression identified an optimal dose of 25 mg/kg as associated with >90% favorable response in adults with pulmonary tuberculosis. Conclusions: The levofloxacin dose of 25 mg/kg or 1500 mg/day was adequate for replacement of high-dose moxifloxacin in treatment of multidrug-resistant tuberculosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.