Non-tubercular Mycobacterial Infections Research Articles

Polycationic phosphorous dendrimer potentiates multiple antibiotics against drug-resistant mycobacterial pathogens

Mycobacterium tuberculosis (Mtb), causative agent of tuberculosis (TB) and non-tubercular mycobacterial (NTM) pathogens such as Mycobacterium abscessus are one of the most critical concerns worldwide due to increased drug-resistance resulting in increased morbidity and mortality. Therefore, focusing on developing novel therapeutics to minimize the treatment period and reducing the burden of drug-resistant Mtb and NTM infections are an urgent and pressing need. In our previous study, we identified anti-mycobacterial activity of orally bioavailable, non-cytotoxic, polycationic phosphorus dendrimer 2G0 against Mtb. In this study, we report ability of 2G0 to potentiate activity of multiple classes of antibiotics against drug-resistant mycobacterial strains. The observed synergy was confirmed using time-kill kinetics and revealed significantly potent activity of the combinations as compared to individual drugs alone. More importantly, no re-growth was observed in any tested combination. The identified combinations were further confirmed in intra-cellular killing assay as well as murine model of NTM infection, where 2G0 potentiated the activity of all tested antibiotics significantly better than individual drugs. Taken together, this nanoparticle with intrinsic antimycobacterial properties has the potential to represents an alternate drug candidate and/or a novel delivery agent for antibiotics of choice for enhancing the treatment of drug-resistant mycobacterial pathogens.

Immunobiology of tubercle bacilli and prospects of immunomodulatory drugs to tackle tuberculosis (TB) and other non-tubercular mycobacterial infections

The COVID-19 pandemic has set back progress made on antimicrobial resistance (AMR). Without urgent re-focus, we risk slowing down drug discovery and providing treatment for drug resistant Mycobacterium tuberculosis. Unique in its immune evasion, dormancy and resuscitation, the causal pathogens of tuberculosis (TB) have demonstrated resistance to antibiotics with efflux pumps and the ability to form biofilms. Repurposing drugs is a prospective avenue for finding new anti-TB drugs. There are many advantages to discovering novel targets of an existing drug, as the pharmacokinetic and pharmacodynamic properties have already been established, they are cost-efficient and can be commercially accelerated for the new development. One such group of drugs are non-steroidal anti-inflammatory drugs (NSAIDs) that are originally known for their ability to supress the host proinflammatory responses. In addition to their anti-inflammatory properties, some NSAIDs have been discovered to have antimicrobial modes of action. Of particular interest is Carprofen, identified to inhibit the efflux mechanism and disrupt biofilm formation in mycobacteria. Due to the complexities of host-pathogens interactions in the lung microbiome, inflammatory responses must carefully be controlled alongside the in vivo actions of the prospective anti-infectives. This critical review explores the potential dual role of a selection of NSAIDs, as an anti-inflammatory and anti-tubercular adjunct to reverse the tide of antimicrobial resistance in existing treatments.

Tuberculosis and Non-tubercular Mycobacterial infections of Head and Neck: A Case Series

Tuberculosis and Non-tubercular Mycobacterial infections of Head and Neck: A Case Series

Antimicrobial and Efflux Pump Inhibitory Activity of Carvotacetones from Sphaeranthus africanus Against Mycobacteria.

Carvotacetones (1–7) isolated from Sphaeranthus africanus were screened for their antimycobacterial and efflux pump (EP) inhibitory potential against the mycobacterial model strains Mycobacterium smegmatis mc2 155, Mycobacterium aurum ATCC 23366, and Mycobacterium bovis BCG ATCC 35734. The minimum inhibitory concentrations (MICs) of the carvotacetones were detected through high-throughput spot culture growth inhibition (HT-SPOTi) and microbroth dilution assays. In order to assess the potential of the compounds 1 and 6 to accumulate ethidium bromide (EtBr) in M. smegmatis and M. aurum, a microtiter plate-based fluorometric assay was used to determine efflux activity. Compounds 1 and 6 were analyzed for their modulating effects on the MIC of EtBr and the antibiotic rifampicin (RIF) against M. smegmatis. Carvotacetones 1 and 6 had potent antibacterial effects on M. aurum and M. bovis BCG (MIC ≤ 31.25 mg/L) and could successfully enhance EtBr activity against M. smegmatis. Compound 1 appeared as the most efficient agent for impairing the efflux mechanism in M. smegmatis. Both compounds 1 and 6 were highly effective against M. aurum and M. bovis BCG. In particular, compound 1 was identified as a valuable candidate for inhibiting mycobacterial efflux mechanisms and as a promising adjuvant in the therapy of tuberculosis or other non-tubercular mycobacterial infections.

Pulmonary tuberculosis: A collage of radiological portraits

For close to a hundred years, diagnostic radiology has been an invaluable ally of physicians engaged in the diagnosis and treatment of various forms of tuberculosis. Over time, its realm has benefited with quantum expansion in imaging technology and emergence of greater understanding of morphological signs, which can play a decisive role in diagnosis, in monitoring the response to treatment, in screening the close contacts of sputum smear positive pulmonary tuberculosis patients, and in guiding thoracic interventions. This photomontage unveils the classic changes of pulmonary manifestations of the disease through its primary and post-primary forms, expressions in an immunocompromised host, and presentations in multidrug-resistant tuberculosis and in nontubercular mycobacterial infection.

Breast abscess due to Mycobacterium abscessus: A rare case

Non-tubercular mycobacterial infections (NTM-Non-tubercular mycobacterial infections) are becoming increasingly common. Mycobacterium abscessus is a rare cause of human infection and is difficult to diagnose unless suspected for the same. A 31-year-old patient, diagnosed to have right breast abscess associated with axillary lyphadenopathy with fever. When pus was sent to the microbiology laboratory, after culture it was confirmed to be due to M. abscess. Definitive identification of this species of mycobacterium was possible by growth characteristics and biochemical tests. The organism was sensitive to Kanamycin, Clarithromycin, Ciprofloxacin, and Amikacin. However, complete recovery from infection was possible after prolonged treatment with clarithromycin to which the organism was sensitive.

Novel Mutation of Interferon-γ Receptor 1 Gene Presenting as Early Life Mycobacterial Bronchial Disease.

Mendelian susceptibility to mycobacterial diseases (MSMD) are a spectrum of inherited disorders characterized by localized or disseminated infections caused by atypical mycobacteria. Interferon-γ receptor 1 (IFNGR1) deficiency was the first identified genetic disorder recognized as MSMD. Mutations in the genes encoding IFNGR1 can be recessive or dominant and cause complete or partial receptor deficiency. We present the case of a 2½-year-old boy with a history of recurrent wheezing, diagnosed with endobronchial mycobacterial infection. Immunological workup revealed a homozygous nonsense mutation in the IFNGR1 gene, a novel mutation predicted in silico to cause complete IFNGR1 deficiency. This case demonstrates that (a) Interferon-γ receptor deficiency can present resembling common disorders of the lung; (b) mycobacterial infections should be suspected when parenchymal lung disease, hilar lymphadenopathy, and endobronchial disease are present; and (c) high index of suspicion for immunodeficiency should be maintained in patients with disseminated nontubercular mycobacterial infection.

Interferon- release assays in tuberculosis contacts: is there a window period?

The tuberculin skin test (TST) is the established procedure for diagnosis of latent tuberculosis infection (LTBI) among the contacts of an infectious tuberculosis (TB) case. TST may convert to positive ≤8 weeks after Mycobacterium tuberculosis infection, an interval that is usually referred to as the “window period”. A negative TST obtained <8 weeks before does not exclude infection, and a second test is recommended 1, 2. However, TST has some limitations, such as cross-reactivity with Bacille Calmette–Guerin (BCG) and with nontubercular mycobacterial infections. T-cell interferon-γ release assays (IGRA) are emerging as new screening tools for LTBI diagnosis. IGRAs incorporate specific antigens of M. tuberculosis that are absent in BCG strains and in the majority of nontubercular mycobacteria, offering enhanced specificity for detecting M. tuberculosis infection 3. In addition, their use has been approved for screening of infection in contacts 1, 4. Most TB contact studies have shown a better correlation of IGRA with the intensity of M. tuberculosis exposure than that obtained using TST, particularly in patients previously vaccinated with BCG 5. Yet, to our knowledge, no study has considered carefully the window period after M. tuberculosis exposure while simultaneously evaluating responses for TST and IGRA. The aim of this study was to find out which of the two tests converts earlier to positive in persons with recent infection after contact with an infectious TB case. We used a longitudinal prospective analysis to study 184 healthy adults, all having had recent contact with a microbiologically confirmed pulmonary TB index patient. The setting was a specialized TB clinic in Pontevedra, Spain, where the incidence of TB has historically been among the highest in Western …

Gastro-oesophageal reflux disease and non-asthma lung disease

Gastro-oesophageal reflux disease (GERD) is a common disorder in Western countries, and its relationship to airways disorders (e.g. asthma) has been well established. Lung diseases other than asthma have also been associated with GERD, but the nature and scope of this relationship has not been fully defined. Diseases that have been associated with GERD include bronchiolitis syndromes, idiopathic pulmonary fibrosis, scleroderma and nontubercular mycobacterial infection. Diagnostic evaluation centres upon proving both reflux and pulmonary aspiration, which may be accomplished in some cases by lung biopsy. However, in many cases a compatible clinical and radiographic picture coupled with proof of proximal reflux by combined oesophageal probe testing may suffice for a provisional diagnosis and allow institution of anti-reflux measures. Proton-pump inhibitors are the medications of choice for GERD; other interventions shown to reduce reflux are weight loss, elevation of the head of the bed and avoidance of recumbency after meals. However, acid suppression therapy does not address non-acid reflux that may be important in disease pathogenesis in select patients, and lifestyle modifications often fail. Laparoscopic fundoplication is the procedure of choice for medically refractory GERD with excellent short-term results with respect to respiratory symptoms associated with GERD; however, long-term studies document a significant percentage of patients requiring ongoing acid suppression therapy.

Broncolitiasis secundaria a infección activa por Mycobacterium avium

The case of a 65-years-old woman with non-productive cough persisting for one year is described. The X-ray showed lower right paratracheal calcification. The diagnosis of broncholithiasis was made by fiberoptic bronchoscopy, and Mycobacterium avium was isolated after analysis of the specimen collected by bronchial biopsy. We discuss the characteristics of the case, emphasizing the association of broncholithiasis and non-tubercular mycobacterial infection. The literature is reviewed.