Macrolide Antibiotics

Macrolide are inhibitors of protein synthesis. Three members of this class are widely used in clinical medicine. These are erythromycin, clarithromycin and azithromycin. Although their spectrum overlaps, each of these is a unique compound in the context of application. They also have differing pharmacological properties. Target site mutation, efflux, and inactivation can lead to macrolide resistance. Macrolides have important drug interactions. The main areas of macrolide therapeutics are respiratory tract infections, certain gastrointestinal infections, skin & skin structure infections, sexually transmitted infections, non-tubercular mycobacterial infections and, of late, azithromycin has been used in coronavirus disease although the evidence base for this is lacking. One compound in this class called spiramycin can prevent transmission of Toxoplasma infection from mother to baby. Macrolides can lead to serious adverse effects which include gastrointestinal side effects, thrombophlebitis, ototoxicity, toxic effects on liver and heart, and neurotoxicity. A related group of compounds are ketolides such as telithromycin. Telithromycin has been associated with a constellation of adverse effects which are together known as ketek effects. © 2022 Elsevier Inc. All rights reserved

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.

BCG vaccination induced protection from COVID-19.

There are worldwide urgency, efforts, and uncertainties for the discovery of a vaccine against SARS CoV2. If successful, it will take its own time till useful for the humans. Till the specific vaccine is available, there are evidences for repurposing existing other vaccines. It is observed that countries having a routine BCG vaccination programme, have shown to have lower incidence of COVID-19, suggesting some protective mechanisms of BCG against COVID-19 in such countries. In countries like India despite vast population density and other adversities, and growing numbers of COVID19 infections, the mortality rate and severity of COVID has been low in comparison to some TB non-endemic countries (like Europe and USA). In addition, there are evidences that BCG vaccination offers partial protection and survival in low-income countries where tuberculosis is prevalent. The nonspecific effects (NSEs) of immune responses induced by BCG vaccination protect against other infections seem to be due to its immunological memory eliciting lymphocytes response and trained immunity. The protective effect on other viral infection in humans are believed to be mediated by heterologous lymphocyte activation and the initiation of innate immune memory may be applicable to SARS CoV2. The BCG vaccination at birth does not have a protective effect beyond childhood against COVID-19. In adults, there might be other factors dampening the virulence and pathogenicity of COVID-19. In the TB endemic countries like India, with high population density, similar to BCG vaccination, the environmental Mycobacteria might be imparting some immune-protection from severity and deaths of COVID-19.