Ranganathan U D, Smith-Jeffcoat S E, Balaji S, Devika K, Nair D, Devaleenal Daniel B, Srinivasan R, Baskaran M, RaviKumar D, Sangamithirai D, Radhika G, Mangalambal G, Lavanya J, Maheswaran K, Kumar S, Sridhar R, Tripathy S, Swaminathan S, Eisenach K D, Cegielski J P
Departments of Microbiology, Immunology and Clinical Research, Indian Council for Medical Research-National Institute of Research for Tuberculosis, Chennai, India.
Division of Global HIV and TB, U.S. Centers for Disease Control and Prevention, Atlanta, GA, USA.
JAC Antimicrob Resist. 2025 May 22;7(3):dlaf072. doi: 10.1093/jacamr/dlaf072. eCollection 2025 Jun.
To evaluate the effect of high-dose isoniazid in patients with isoniazid-resistant TB by its bactericidal activity after 1 or more weeks of treatment.
Using the rapid direct method of phenotypic drug susceptibility testing, we screened persons with positive sputum microscopy results and genotypic drug resistance for isoniazid resistance. Those with no growth at a critical concentration of 2.0 mg/L were invited to participate in a trial of high-dose isoniazid monotherapy lasting 6 days. After 3 days of no treatment, patients received isoniazid 15 mg/kg and were followed with serial quantitative sputum cultures from Days 0 to 6.
We enrolled 15 patients after a median of 2 weeks standard first-line treatment. Their median bacillary count on Day 0 was 4.9 log cfu/mL on solid agar, and the time to detection (TTD) was 200 h in liquid medium. Neither metric showed meaningful change in bacillary burden over 6 days, declining by a non-significant 0.08 log cfu/mL/d on solid media and slowing TTD by 23 h. These effects did not differ by degree of isoniazid resistance or specific ( gene mutations.
The utility of high-dose isoniazid against low-level isoniazid resistance beyond the first 2 weeks of chemotherapy should be reconsidered.
通过治疗1周或更长时间后的杀菌活性，评估大剂量异烟肼对耐异烟肼结核病患者的疗效。
采用快速直接表型药敏试验方法，我们对痰涂片镜检结果阳性且对异烟肼具有基因型耐药性的患者进行筛查，以确定其对异烟肼的耐药情况。那些在2.0mg/L临界浓度下无生长的患者被邀请参加为期6天的大剂量异烟肼单药治疗试验。在3天未治疗后，患者接受15mg/kg异烟肼治疗，并在第0天至第6天进行系列定量痰培养随访。
在经过中位时间为2周的标准一线治疗后，我们纳入了15名患者。他们在第0天在固体琼脂上的中位菌量为4.9 log cfu/mL，在液体培养基中的检测时间（TTD）为200小时。在6天内，这两个指标均未显示出细菌负荷的有意义变化，在固体培养基上细菌负荷以无统计学意义的0.08 log cfu/mL/天下降，TTD减慢23小时。这些效应在异烟肼耐药程度或特定基因突变方面无差异。
应重新考虑大剂量异烟肼在化疗2周后对低水平异烟肼耐药的作用。
