Performance of a broth microdilution assay for routine minimum inhibitory concentration determination of 14 anti-tuberculous drugs against the complex based on the EUCAST reference protocol.

This comparative study aimed at qualifying a broth microdilution (BMD) assay for phenotypic drug susceptibility testing (pDST) of complex (MTBC) strains for implementation in a routine DST workflow. The assay was developed based on the EUCAST (European Committee on Antimicrobial Susceptibility Testing) reference protocol for determination of the minimum inhibitory concentration (MIC) of 14 anti-tuberculous drugs (isoniazid [INH], rifampicin [RIF], ethambutol [EMB], amikacin [AMI], moxifloxacin [MFX], levofloxacin [LFX], bedaquiline [BDQ], clofazimine [CFZ], delamanid [DLM], pretomanid [PA], para-aminosalicylic acid [PAS], linezolid [LZD], ethionamide [ETH], and cycloserine [CS]). Forty MTBC strains with various drug resistance profiles were tested to determine the agreement between MIC results and genotypic drug susceptibility testing (gDST) results derived from whole-genome sequencing (WGS).

Increased risk of adverse drug reactions by higher linezolid dose per weight in multidrug-resistant tuberculosis.

Objectives: Linezolid treatment has a high risk of toxicity and adverse drug reactions (ADR) are frequent. Few studies have investigated risk factors of major ADRs separately, therefore, we aimed to evaluate major ADRs including peripheral neuropathy in relation to risk factors and drug concentration levels of linezolid in a high-resource setting for multidrug-resistant tuberculosis (MDR-TB).

Methods: We conducted a retrospective cohort study including participants treated with a linezolid-containing MDR-TB regimen in Sweden 1992-2018.

Loss-of-function mutations in do not confer delamanid, ethionamide, isoniazid, or pretomanid resistance in .

Results from clinical strains and knockouts of the H37Rv and CDC1551 laboratory strains demonstrated that () is not a resistance-conferring gene for isoniazid, ethionamide, delamanid, or pretomanid in . This difference in the susceptibility to NAD-adduct-forming drugs compared with other mycobacteria may be driven by differences in the absolute intrabacterial NADH concentration.

activity of new combinations of β-lactam and β-lactamase inhibitors against the complex.

As meropenem-clavulanic acid is recommended for the treatment of drug-resistant tuberculosis, the repurposing of new carbapenem combinations may provide new treatment options, including oral alternatives. Therefore, we studied the activities of meropenem-vaborbactam, meropenem-clavulanic acid, and tebipenem-clavulanic acid. One hundred nine complex (MTBC) clinical isolates were tested, of which 69 were pan-susceptible and the remaining pyrazinamide- or multidrug-resistant.

The Relative Positioning of Genotyping and Phenotyping for Tuberculosis Resistance Screening in Two EU National Reference Laboratories in 2023.

The routine use of whole genome sequencing (WGS) as a reference typing technique for epidemiology combined with the catalogued and extensive knowledge base of resistance-associated mutations means an initial susceptibility prediction can be derived from all cultured isolates in our laboratories based on WGS data alone. Preliminary work has confirmed, in our low-burden settings, these predictions are for first-line drugs, reproducible, robust with an accuracy similar to phenotypic drug susceptibility testing (pDST) and in many cases able to also predict the level of resistance (MIC). Routine screening for drug resistance by WGS results in approximately 80% of the isolates received being predicted as fully susceptible to the first-line drugs.