Minimum inhibitory concentration of cycloserine against Mycobacterium tuberculosis using the MGIT 960 system and a proposed critical concentration. 2022

Xiao Wu, and Yuanyuan Shang, and Weicong Ren, and Wei Wang, and Yufeng Wang, and Zhongtan Xue, and Shanshan Li, and Yu Pang
Department of Bacteriology and Immunology, Beijing Key Laboratory on Drug-Resistant Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute/Beijing Chest Hospital, Capital Medical University, Beijing, People's Republic of China.

OBJECTIVE We aimed to determine the breakpoint of cycloserine (CS) susceptibility in MGIT and to describe the molecular characteristics of CS-resistant Mycobacterium tuberculosis (MTB) isolates. METHODS A total of 124 MTB isolates were recruited in our analysis. Minimum inhibitory concentration (MIC) was determined using the MGIT system. The mutations of MTB isolates within alr, ddl, ald, and cycA, potentially conferring CS resistance were analyzed by the whole-genome sequencing. RESULTS In vitro drug susceptibility testing of isolates with doubling concentrations of CS revealed that the modal MIC values was 4 mg/L for MGIT, accounting for 35.5% (44/124) of isolates tested. Seven isolates harbored mutations conferring CS resistance, consisting of five with alr mutations and two with ald mutations. On the basis of the MIC distributions of wild-type and resistotype populations, we proposed a tentative epidemiologic cut-off value of 16 mg/l. The proportion of CS resistance in extensively drug-resistant TB was significantly higher than that of multidrug-resistant TB. CONCLUSIONS In conclusion, we propose critical concentration for MGIT 960 to properly diagnose CS-resistant MTB and demonstrate that mutations in alr and ald genes are the major mechanism conferring CS resistance in clinical isolates.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009169 Mycobacterium tuberculosis A species of gram-positive, aerobic bacteria that produces TUBERCULOSIS in humans, other primates, CATTLE; DOGS; and some other animals which have contact with humans. Growth tends to be in serpentine, cordlike masses in which the bacilli show a parallel orientation. Mycobacterium tuberculosis H37Rv
D003523 Cycloserine Antibiotic substance produced by Streptomyces garyphalus. R-4-Amino-3-isoxazolidinone,Seromycin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000995 Antitubercular Agents Drugs used in the treatment of tuberculosis. They are divided into two main classes: "first-line" agents, those with the greatest efficacy and acceptable degrees of toxicity used successfully in the great majority of cases; and "second-line" drugs used in drug-resistant cases or those in which some other patient-related condition has compromised the effectiveness of primary therapy. Anti-Tuberculosis Agent,Anti-Tuberculosis Agents,Anti-Tuberculosis Drug,Anti-Tuberculosis Drugs,Antitubercular Agent,Antitubercular Drug,Tuberculostatic Agent,Tuberculostatic Agents,Antitubercular Drugs,Agent, Anti-Tuberculosis,Agent, Antitubercular,Agent, Tuberculostatic,Anti Tuberculosis Agent,Anti Tuberculosis Agents,Anti Tuberculosis Drug,Anti Tuberculosis Drugs,Drug, Anti-Tuberculosis,Drug, Antitubercular
D014388 Tuberculosis, Lymph Node Infection of the lymph nodes by tuberculosis. Tuberculous infection of the cervical lymph nodes is scrofula. Cervical Tuberculous Lymphadenitis,Lymphadenitis, Tuberculous,Mycobacterial Cervical Lymphadenitis,Scrofula,Cervical Lymphadenitis, Mycobacterial,Lymph Node Tuberculoses,Lymph Node Tuberculosis,Lymphadenitis, Cervical Tuberculous,Lymphadenitis, Mycobacterial Cervical,Scrofulas,Tuberculoses, Lymph Node,Tuberculous Lymphadenitis,Tuberculous Lymphadenitis, Cervical
D018088 Tuberculosis, Multidrug-Resistant Tuberculosis resistant to chemotherapy with two or more ANTITUBERCULAR AGENTS, including at least ISONIAZID and RIFAMPICIN. The problem of resistance is particularly troublesome in tuberculous OPPORTUNISTIC INFECTIONS associated with HIV INFECTIONS. It requires the use of second line drugs which are more toxic than the first line regimens. TB with isolates that have developed further resistance to at least three of the six classes of second line drugs is defined as EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS. Tuberculosis, Drug-Resistant,Tuberculosis, MDR,Tuberculosis, Multi-Drug Resistant,Drug-Resistant Tuberculosis,MDR Tuberculosis,Multi-Drug Resistant Tuberculosis,Multidrug-Resistant Tuberculosis,Tuberculosis, Drug Resistant,Tuberculosis, Multi Drug Resistant,Tuberculosis, Multidrug Resistant

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