Determination of critical concentrations of second-line anti-tuberculosis drugs with clinical and microbiological relevance.
BACKGROUND
Reliable DST against second-line anti-tuberculosis drugs (SLDs) is crucial for the management of the increasing burden of patients affected by multidrug- and extensively drug-resistant TB.


METHODS
This study utilizes 252 clinical isolates of Mycobacterium tuberculosis from five countries (Hong Kong Special Administrative Region, Korea, Latvia, Peru, Philippines) with documented treatment histories to establish clinically and microbiologically relevant critical concentrations (CCs) of six SLDs for three routine testing methods: the absolute concentration method using Löwenstein-Jensen (LJ) medium, the 1% proportion method using Middlebrook 7H10 agar medium, and the radiometric BACTEC 460 system.


RESULTS
In LJ medium, CCs of capreomycin, ethionamide, kanamycin, ofloxacin, rho-aminosalicylic acid and cycloserine (CS) were respectively 40.0, 40.0, 30.0, 3.0, 1.0 and 30.0 mg/l. In 7H10 agar medium, the respective CCs for the first five antibiotics (except CS) were 8.0, 2.0-3.0, 3.0-5.0, 1.0-1.5 and 0.5-1.0 mg/l. In BACTEC 460 broth, the respective CCs were 1.5-2.0, 1.0-1.5, 2.0-3.0, 0.5-1.0 and 0.5-1.0 mg/l. Precautions in DST interpretation was also discussed.


CONCLUSIONS
By adopting this set of CCs as a global standard to define second-line drug susceptibility and resistance, as well as precautions in result interpretation, the screening, diagnosis and management of patients with drug-resistant TB can be greatly improved.
Tuberculosis Reference Laboratory, Hong Kong SAR, China. kmkam@dh.gov.hk
K M
KM
Kam
A
A
Sloutsky
C W
CW
Yip
N
N
Bulled
K J
KJ
Seung
M
M
Zignol
M
M
Espinal
S J
SJ
Kim
D000995:Antitubercular Agents / Q000008:administration & dosage / Q000494:pharmacology*; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy / Q000382:microbiology
D000995:Antitubercular Agents