ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2015
Pharmacodynamic Modeling of Bacillary Elimination Rates and Detection of Bacterial Lipid Bodies in Sputum to Predict and Understand Outcomes in Treatment of Pulmonary Tuberculosis.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 80 citations in OpenAlex.
- Pharmacokinetics, bactericidal activity and toxicity of short oral regimens for rifampicin-resistant tuberculosis treatment.Nature communications · 2026Trial
- A pharmacometric multistate model for predicting long-term treatment outcomes of patients with pulmonary TB.The Journal of antimicrobial chemotherapy · 2024Trial
- High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial.The Lancet. Infectious diseases · 2017Trial
- Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials.BMC medicine · 2016Trial
- Insights into the Role of Rifampicin Exposure and Clinical Baseline Covariates on the Response to Pulmonary Tuberculosis Treatment.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- Article
- Granulysin Antimicrobial Activity Promotes Dormancy in Mycobacterium tuberculosis.European journal of immunology · 2025Article
- Can lipid body-positive rates ofFrontiers in immunology · 2025Article
- Examining effective monotherapy hypothesis for TB therapy failure and resistance emergence.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2024Article
- Monitoring Live Mycobacteria in Real-Time Using a Microfluidic Acoustic-Raman Platform.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Intrabacterial lipid inclusion-associated proteins: a core machinery conserved from saprophyte Actinobacteria to the human pathogen Mycobacterium tuberculosis.FEBS open bio · 2023Article
- Revolutionizing control strategies against Mycobacterium tuberculosis infection through selected targeting of lipid metabolism.Cellular and molecular life sciences : CMLS · 2023Review
- Article
- High Intrapulmonary Rifampicin and Isoniazid Concentrations Are Associated With Rapid Sputum Bacillary Clearance in Patients With Pulmonary Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Bacterial growth dynamics and pharmacokinetic-pharmacodynamic relationships of rifampicin and bedaquiline in BALB/c mice.British journal of pharmacology · 2022Article
- Implications of drug-induced phenotypical resistance: Is isoniazid radicalizingFrontiers in antibiotics · 2022Article
- Phenotypic adaptation ofFrontiers in cellular and infection microbiology · 2022Review
- Drug resistant tuberculosis: Implications for transmission, diagnosis, and disease management.Frontiers in cellular and infection microbiology · 2022Review
- Host lipidome and tuberculosis treatment failure.The European respiratory journal · 2022Article
- Intrapulmonary Pharmacokinetics of First-line Anti-tuberculosis Drugs in Malawian Patients With Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundAntibiotic-tolerant bacterial persistence prevents treatment shortening in drug-susceptible tuberculosis, and accumulation of intracellular lipid bodies has been proposed to identify a persister phenotype of Mycobacterium tuberculosis cells. In Malawi, we modeled bacillary elimination rates (BERs) from sputum cultures and calculated the percentage of lipid body-positive acid-fast bacilli (%LB + AFB) on sputum smears. We assessed whether these putative measurements of persistence predict unfavorable outcomes (treatment failure/relapse).
methodsAdults with pulmonary tuberculosis received standard 6-month therapy. Sputum samples were collected during the first 8 weeks for serial sputum colony counting (SSCC) on agar and time-to positivity (TTP) measurement in mycobacterial growth indicator tubes. BERs were extracted from nonlinear and linear mixed-effects models, respectively, fitted to these datasets. The %LB + AFB counts were assessed by fluorescence microscopy. Patients were followed until 1 year posttreatment. Individual BERs and %LB + AFB counts were related to final outcomes.
resultsOne hundred and thirty-three patients (56% HIV coinfected) participated, and 15 unfavorable outcomes were reported. These were inversely associated with faster sterilization phase bacillary elimination from the SSCC model (odds ratio [OR], 0.39; 95% confidence interval [CI], .22-.70) and a faster BER from the TTP model (OR, 0.71; 95% CI, .55-.94). Higher %LB + AFB counts on day 21-28 were recorded in patients who suffered unfavorable final outcomes compared with those who achieved stable cure (P = .008).
conclusionsModeling BERs predicts final outcome, and high %LB + AFB counts 3-4 weeks into therapy may identify a persister bacterial phenotype. These methods deserve further evaluation as surrogate endpoints for clinical trials.
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