Back to Search
Start Over
The pyrazinamide susceptibility breakpoint above which combination therapy fails
- Source :
- Journal of Antimicrobial Chemotherapy
- Publication Year :
- 2014
- Publisher :
- Oxford University Press (OUP), 2014.
-
Abstract
- Objectives To identify the pyrazinamide MIC above which standard combination therapy fails. Methods MICs of pyrazinamide were determined for Mycobacterium tuberculosis isolates, cultured from 58 patients in a previous randomized clinical trial in Cape Town, South Africa. The MICs were determined using BACTEC MGIT 960 for isolates that were collected before standard treatment with isoniazid, rifampicin, pyrazinamide and ethambutol commenced. Weekly sputum collections were subsequently made for 8 weeks in order to culture M. tuberculosis in Middlebrook broth medium. Classification and regression tree (CART) analysis was utilized to identify the pyrazinamide MIC predictive of sputum culture results at the end of pyrazinamide therapy. The machine learning-derived susceptibility breakpoints were then confirmed using standard association statistics that took into account confounders of 2 month sputum conversion. Results The pyrazinamide MIC range was 12.5 to >100 mg/L for the isolates prior to therapy. The epidemiological 95% cut-off value was >100 mg/L. The 2 month sputum conversion rate in liquid cultures was 26% by stringent criteria and 48% by less stringent criteria. CART analysis identified an MIC breakpoint of 50 mg/L, above which patients had poor sputum conversion rates. The relative risk of poor sputum conversion was 1.5 (95% CI: 1.2–1.8) for an MIC >50 mg/L compared with an MIC ≤50 mg/L. Conclusions We propose a pyrazinamide susceptibility breakpoint of 50 mg/L for clinical decision making and for development of rapid susceptibility assays. This breakpoint is identical to that identified using computer-aided simulations of hollow fibre system output.
- Subjects :
- Adult
Male
Microbiology (medical)
Oncology
medicine.medical_specialty
MICs
Adolescent
genetic structures
Combination therapy
Antitubercular Agents
Microbial Sensitivity Tests
Pharmacology
drug susceptibility
South Africa
Young Adult
03 medical and health sciences
0302 clinical medicine
Internal medicine
anti-tuberculosis drugs
Drug Resistance, Bacterial
medicine
Humans
Combined Modality Therapy
Pharmacology (medical)
030212 general & internal medicine
Tuberculosis, Pulmonary
Ethambutol
Original Research
0303 health sciences
sputum culture
030306 microbiology
business.industry
Breakpoint
Sputum
Mycobacterium tuberculosis
Drug susceptibility
Middle Aged
Pyrazinamide
3. Good health
Treatment Outcome
Infectious Diseases
Drug Therapy, Combination
Female
Sputum Cytology Screening
business
pharmacokinetics
medicine.drug
Subjects
Details
- ISSN :
- 14602091 and 03057453
- Volume :
- 69
- Database :
- OpenAIRE
- Journal :
- Journal of Antimicrobial Chemotherapy
- Accession number :
- edsair.doi.dedup.....b66e5662bb074584f479ca5b1ab29499