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Bedaquiline, clofazimine and linezolid are pertinent drugs for drug-resistant tuberculosis. Drug-resistant mutants provide insight into important resistance acquisition mechanisms. Methods for in vitro Mycobacterium tuberculosis mutant generation are poorly described. Induction (serial passaging) and spontaneous (adapted Luria-Delbrück assay) approaches using M. tuberculosis ATCC reference strains (one fully-susceptible, four unique mono-resistant) were performed. Mutant MIC values were confirmed (MGIT960) and resultant RAVs compared between approaches and to a catalog of previously published RAVs. Mutant MIC values showed a 3-4-fold (induced) and a 1-4-fold (spontaneous) increase compared to baseline. The pyrazinamide-resistant strain had higher baseline MIC values and acquired resistance (≥4-fold) in fewer passages than other strains (induction approach) for bedaquiline. Previously described and novel RAVs in atpE (8 vs. 1) and rv0678 (4 vs. 12) genes were identified in bedaquiline- and clofazimine-resistant mutants. No rv1979c and rv2535c RAVs were identified. Previously described RAVs were identified in rplC and rrl genes for linezolid-resistant mutants. Both approaches successfully led to in vitro mutants with novel RAVs being described in atpE and rv0678 genes. It was observed that pre-existing resistance may influence mutant phenotypic and genotypic characteristics and warrants further attention., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A comprehensive literature search was conducted to obtain previously published resistance associated mutations for bedaquiline, clofazimine and linezolid for Mycobacterium tuberculosis . Where possible, mutation frequencies for these three drugs were also identified. This catalog of previously published mutations could serve as a reference for comparing mutations associated with either in vitro or clinical resistant mutants. The usage of these data was seen in our study relating to approaches for resistance mutant creation (in vitro approaches for generation of Mycobacterium tuberculosis mutants resistant to bedaquiline, clofazimine or linezolid and identification of associated genetic variants (Ismail et al., 2018 in press). Previously published mutations for clofazimine were described in the rv0678 and rv1979c genes, for bedaquiline in atpE , rv0678 and rv2535c ( pepQ ) genes and for linezolid in the rplC and rrl genes.

Chlamydia trachomatis serovars are divided into three serogroups, namely serogroup B, serogroup I (Intermediate) and serogroup C, and subsequently into 19 different serovars. Worldwide, serogroup B is the most prevalent followed by serogroup I. Clear differences have been observed in the duration of infection and growth kinetics between serovars from different serogroups in murine and cell culture models. Reasons for these observed differences are bacterial and host related, and are not well understood. The aim of this study was to determine the differences in immunoglobulin (Ig) G responses between the three serogroups in a group of patients infected with different serovars. Serovars were assessed from 235 C. trachomatispositive patients and quantitative IgG responses were determined. Analyses of variance were used to compare the IgG responses between the three serogroups. Of the serovars, 46% were B group (with serovar E the most prevalent: 35.3%), 39.6% were I group and 14.3% were C group. A highly significant difference in serologic response was shown when comparing the mean IgG concentrations (AU/mL) of patients having serovars in the most prevalent serogroup compared to the other serogroups: B = 135, C = 46 and I = 60 (B vs. C and B vs. I, P < 0.001). In conclusion, the most prevalent serovars generate the highest serologic responses., (Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.)

Setting: Adult medical wards of a central hospital in Blantyre, Malawi., Objective: To measure the prevalence and outcome of mycobacteraemia in febrile hospitalised adults, and to determine what proportion could be identified using routine methods; to assess clinical indicators of mycobacteraemia, and the usefulness of a diagnostic trial of anti-tuberculosis treatment., Design: We prospectively examined adults admitted with fever or a history of fever. All had blood cultured for bacteria and mycobacteria, chest X-ray and sputum smears., Findings: Mycobacterium tuberculosis was the commonest cause of blood stream infection (BSI), affecting 57 of 344 patients (17%). In 44 (77%) patients with mycobacteraemia, TB was identified using routine investigations; it was not suspected in six (11%). Strong clinical indicators of mycobacteraemia were anaemia, HIV seropositivity, cough, chronic fever and a clinical diagnosis of AIDS on the day of admission. Of nine patients selected for a therapeutic trial of tuberculosis (TB) treatment, six had mycobacteraemia, of whom five died during the trial. Mortality on short-course chemotherapy, on the TB ward after 1 month was similar whether patients had mycobacteremia (21%) or not (32%)., Conclusion: TB can be identified with routine methods in most patients with mycobacteraemia. If treated, mycobacteraemia has as good an early outcome as TB without mycobacteraemia. Strengthening of basic facilities is likely to improve detection and treatment of mycobacterial disease.