SynthesisClinical infectious diseases : an official publication of the Infectious Diseases Society of America2018
d-Cycloserine Pharmacokinetics/Pharmacodynamics, Susceptibility, and Dosing Implications in Multidrug-resistant Tuberculosis: A Faustian Deal.
Synthesis 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 54 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.American journal of respiratory and critical care medicine · 2019Guideline
- Pharmacokinetics and safety comparison of cycloserine capsules and their generic counterpart: a randomized, open-label, two-period, two-sequence, single-dose crossover bioequivalence study in healthy Chinese subjects.Frontiers in pharmacology · 2026Trial
- Substrate recognition and transport mechanism of the human proton-coupled amino-acid transporter 1 (SLC36A1).Nature communications · 2026Article
- Cerebrospinal Fluid Concentrations of Bedaquiline, Pretomanid, and Linezolid During Curative Treatment of Fluoroquinolone-Resistant Pre-Extensively Drug-Resistant Tuberculous Meningitis.Open forum infectious diseases · 2026Article
- Analysis of Adverse Drug Reactions of Clofazimine Reported in the FDA Adverse Event Reporting System from 2004 to 2025 Q1.Infectious diseases and therapy · 2025Article
- Evaluation of cycloserine dose regimens in an Indian cohort with multidrug-resistant tuberculosis: a population pharmacokinetic analysis.Antimicrobial agents and chemotherapy · 2025Article
- Tuberculosis in Pregnant Women After COVID-19: Features of Prevention, Diagnosis, and Treatment (Narrative Review).Journal of clinical medicine · 2025Review
- Harnessing Actinobacteria secondary metabolites for tuberculosis drug discovery: Historical trends, current status and future outlooks.Natural products and bioprospecting · 2025Review
- Pharmacokinetic-Pharmacodynamic (PK-PD) Analysis of Second-Line Anti-Tubercular Drugs in Indian Children with Multi-Drug Resistance.Indian journal of pediatrics · 2025Article
- Cycloserine resistance among drug-resistant tuberculosis cases in Taiwan.Microbiology spectrum · 2025Article
- An Update on the Clinical Management of HIV and Tuberculosis Co-Infection in Pregnancy: TB Preventative Therapy, Long-Acting ARVs, and Bedaquiline-Based Regimens.Current HIV/AIDS reports · 2025Review
- Synergistic behavioral and neuroplastic effects of psilocybin-NMDAR modulator administration.Translational psychiatry · 2025Article
- Development of a Spectrophotometric Assay for the Cysteine Desulfurase fromAntibiotics (Basel, Switzerland) · 2025Article
- The risk of developing depression in tuberculosis survivors: a nationwide cohort study in South Korea.Frontiers in psychiatry · 2025Article
- The microevolutionary trajectory of endemic multidrug-resistant tuberculosis strains in Portugal toward increased drug resistance levels and its clinical significance.Frontiers in microbiology · 2025Article
- Cycloserine-Induced Psychosis: A Case Report.Cureus · 2025Article
- 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
- Protocol for the selection ofMethodsX · 2024Article
- Omadacycline pharmacokinetics/pharmacodynamics and efficacy against multidrug-resistantAntimicrobial agents and chemotherapy · 2024Article
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 9 countries.
Funding
Abstract
Background: d-cycloserine is used to treat multidrug-resistant tuberculosis. Its efficacy, contribution in combination therapy, and best clinical dose are unclear, also data on the d-cycloserine minimum inhibitory concentration (MIC) distributions is scant. Methods: We performed a systematic search to identify pharmacokinetic and pharmacodynamic studies performed with d-cycloserine. We then performed a combined exposure-effect and dose fractionation study of d-cycloserine in the hollow fiber system model of tuberculosis (HFS-TB). In parallel, we identified d-cycloserine MICs in 415 clinical Mycobacterium tuberculosis (Mtb) isolates from patients. We utilized these results, including intracavitary concentrations, to identify the clinical dose that would be able to achieve or exceed target exposures in 10000 patients using Monte Carlo experiments (MCEs). Results: There were no published d-cycloserine pharmacokinetics/pharmacodynamics studies identified. Therefore, we performed new HFS-TB experiments. Cyloserine killed 6.3 log10 colony-forming units (CFU)/mL extracellular bacilli over 28 days. Efficacy was driven by the percentage of time concentration persisted above MIC (%TMIC), with 1.0 log10 CFU/mL kill achieved by %TMIC = 30% (target exposure). The tentative epidemiological cutoff value with the Sensititre MYCOTB assay was 64 mg/L. In MCEs, 750 mg twice daily achieved target exposure in lung cavities of 92% of patients whereas 500 mg twice daily achieved target exposure in 85% of patients with meningitis. The proposed MCE-derived clinical susceptibility breakpoint at the proposed doses was 64 mg/L. Conclusions: Cycloserine is cidal against Mtb. The susceptibility breakpoint is 64 mg/L. However, the doses likely to achieve the cidality in patients are high, and could be neurotoxic.
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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.