Mycobacterium tuberculosis Uganda II is more susceptible to rifampicin and isoniazid compared to Beijing and Delhi/CAS families

Abstract

BackgroundMycobacterium tuberculosis Uganda family is the predominant cause of tuberculosis in Uganda. Reasons for this are not clear but are likely to be due to the rampant person-to-person transmission or delayed susceptibility of the organism to drugs during treatment, which may lead to continuous shedding of infectious bacilli, among others. The objective of this study was to determine in vitro, the susceptibility patterns of M. tuberculosis Uganda family compared with Beijing and Delhi/CAS, other M. tuberculosis sub-lineages that also circulate in Uganda but are not as prevalent. The comparisons were made after 10 days of exposure of the strains to Rifampicin and Isoniazid, the most important first-line anti-tuberculosis drugs.MethodsMinimum inhibitory concentrations (MICs) for three Isoniazid- and Rifampicin-susceptible M. tuberculosis strains (Uganda II, Beijing and Delhi/CAS families) were determined by micro-dilution plate assay. Killing curves for each strain were deduced from colony forming units after exposure to Isoniazid and Rifampicin on days 0, 2, 4, 6, 8, and 10 under aerobic and oxygen-depleted conditions. Data were analyzed with GraphPad Prism 5 software.ResultsThe MIC for Isoniazid was 0.05 μg/ml for M. tuberculosis Uganda II, and 0.03 μg/ml for M. tuberculosis Beijing and Delhi/CAS. Rifampicin MIC was 1 μg/ml for M. tuberculosis Uganda II, and 0.12 μg/ml for Beijing and Delhi/CAS. At low Rifampicin (0.03–2.5 μg/ml) and Isoniazid (0.12–5 μg/ml) concentrations under aerobic conditions, there was no significant difference in susceptibility patterns between M. tuberculosis Uganda II and Beijing or Delhi/CAS. However, at high Rifampicin (5 μg/ml) and Isoniazid (1.25 μg/ml) concentrations under oxygen-depleted conditions, M. tuberculosis Uganda II was more susceptible to the drugs compared with Beijing or Delhi/CAS families.ConclusionThe predominance of M. tuberculosis Uganda II family as the main causative agent of tuberculosis in Uganda is not attributed to its susceptibility behavior to Isoniazid and Rifampicin. Probably, its predominance is due to differences in the immune defenses in the general population against the strains, given that Beijing and Delhi/CAS families may have been introduced more recently. Further research beyond susceptibility to anti-tuberculosis drugs is required to fully explore tuberculosis strain predominance in Uganda.

High-Dose Oral and Intravenous Rifampicin for the Treatment of Tuberculous Meningitis in Predominantly Human Immunodeficiency Virus (HIV)-Positive Ugandan Adults: A Phase II Open-Label Randomized Controlled Trial

“…Geometric mean CSF concentrations were ~6-fold higher with IV-20 at 1.74 mg/L (95% CI, 1.20–2.53) and 8-fold higher with PO-35 at 2.17 mg/L (95% CI, 1.64–2.86; P < .001 for each). A CSF concentration > 1 mg/L, the rifampicin minimal inhibitory concentration (MIC) for the predominant M. tuberculosis strain in Uganda [ 29 ], occurred in 11% (2/18) with standard-of-care treatment, 93% (14/15) with IV-20, and 95% (18/19) with PO-35 ( P < .001). PK results are further described in Table 2 and Figure 2 .…”

“…As in many TBM trials, microbiological confirmation was only made in half the participants. Because a minority of TBM patients are culture positive, and the complexity of performing rifampicin MIC, the MIC was derived from population estimates within the same TB laboratory [ 29 , 38 ]. This phase II study was adequately powered for quantification of PK parameters, but due to limited sample size, no conclusions about clinical outcomes can be drawn.…”

Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year’s review

“…Data extraction and review were performed on 20,508 isolate entries of TB patients for DST. The NTRL is a Biosafety Level (BSL) 3 Laboratory that is fully furnished to manipulate TB cultures and specimens [ 12 ].…”

Evaluation of the antimicrobial activity of Cinnamomum zeylanicum essential oil and trans-Cinnamaldehyde against resistant Mycobacterium tuberculosis

“…Other authors reported an MIC of 0.06 μg/mL for INH and RIF against M. tuberculosis H37Rv strain (CAMACHO-CORONA et al, 2008). Similarly, low MICs of 0.05 μg/mL for INH and 0.03 μg/mL for RIF have been reported (KASULE et al, 2016).…”