bedaquiline
Mechanisms of ResistanceIn Vitro Study of Stepwise Acquisition of rv0678 and atpE Mutations Conferring Bedaquiline ResistanceBedaquiline resistance within Mycobacterium tuberculosis may arise through efflux-based (rv0678) or target-based (atpE) pathway mutations. M. tuberculosis mutant populations from each of five sequential steps in a passaging approach, using a pyrazinamide-resistant ATCC strain, were...
SusceptibilityIn Vitro Activity of Bedaquiline and Delamanid against Nontuberculous Mycobacteria, Including Macrolide-Resistant Clinical IsolatesWe evaluated the in vitro activities of the antimicrobial drugs bedaquiline and delamanid against the major pathogenic nontuberculous mycobacteria (NTM). Delamanid showed high MIC values for all NTM except Mycobacterium kansasii. However, bedaquiline showed low MIC values for the major pathogenic NTM, including...
Editor's Pick Mechanisms of Action: Physiological EffectsBedaquiline Eliminates Bactericidal Activity of β-Lactams against Mycobacterium abscessusThe β-lactams imipenem and cefoxitin are used for the treatment of Mycobacterium abscessus lung infections. Here, we show that these cell wall synthesis inhibitors trigger a lethal bacterial ATP burst by increasing oxidative phosphorylation. Cotreatment of M. abscessus with the antimycobacterial ATP...
SusceptibilityIn Vitro Activities of Bedaquiline and Delamanid against Nontuberculous Mycobacteria Isolated in Beijing, ChinaDue to the natural resistance of nontuberculous mycobacteria (NTM) against multiple antibiotics, treatment of infections caused by them is often long-course and less successful. The main objective of our study was the evaluation of in vitro susceptibility of 209 isolates consisting of different NTM species against bedaquiline and delamanid. Furthermore, reference strains of 33 rapidly growing mycobacterium (RGM) species and 19...
Experimental TherapeuticsShortening Buruli Ulcer Treatment with Combination Therapy Targeting the Respiratory Chain and Exploiting Mycobacterium ulcerans Gene DecayBuruli ulcer is treatable with antibiotics. An 8-week course of rifampin (RIF) and either streptomycin (STR) or clarithromycin (CLR) cures over 90% of patients.
Experimental TherapeuticsContribution of Pretomanid to Novel Regimens Containing Bedaquiline with either Linezolid or Moxifloxacin and Pyrazinamide in Murine Models of TuberculosisNovel regimens combining bedaquiline and pretomanid with either linezolid (BPaL regimen) or moxifloxacin and pyrazinamide (BPaMZ regimen) shorten the treatment duration needed to cure tuberculosis (TB) in BALB/c mice compared to that of the first-line regimen and have yielded promising results in initial clinical trials. However, the independent contribution of the investigational new drug pretomanid to the efficacy of BPaMZ has not...
Experimental TherapeuticsActivity of a Long-Acting Injectable Bedaquiline Formulation in a Paucibacillary Mouse Model of Latent Tuberculosis InfectionThe potent antituberculosis activity and long half-life of bedaquiline make it an attractive candidate for use in long-acting/extended-release formulations for the treatment of latent tuberculosis infection (LTBI). Our objective was to evaluate a long-acting injectable (LAI) bedaquiline formulation in a validated paucibacillary mouse model of LTBI.
Mechanisms of Action: Physiological EffectsIsoniazid Bactericidal Activity Involves Electron Transport Chain PerturbationAccumulating evidence suggests that the bactericidal activity of some antibiotics may not be directly initiated by target inhibition. The activity of isoniazid (INH), a key first-line bactericidal antituberculosis drug currently known to inhibit mycolic acid synthesis, becomes extremely poor under stress conditions, such as hypoxia and starvation.
SusceptibilityHigh Prevalence of Bedaquiline Resistance in Treatment-Naive Tuberculosis Patients and Verapamil EffectivenessIn the regions where bedaquiline (BDQ) is introduced into the regimen, analysis of MIC and screening for preexisting resistance mutations could be crucial. The high prevalence of isolates with high BDQ MICs without prior exposure to BDQ was worrisome.
Mechanisms of ResistanceClofazimine Exposure In Vitro Selects Efflux Pump Mutants and Bedaquiline ResistanceSix in vitro clofazimine-resistant spontaneous mutants obtained from a wild-type or pyrazinamide-resistant ATCC reference strain were selected to evaluate bedaquiline cross-resistance. The reverse was conducted for bedaquiline mutants.