Solithromycin

We report here on the structure-activity relationships of hybrids combining 3-descladinosyl clarithromycin with quinolones linked by extended diamine connectors. Several hybrids, exemplified by 23Bc, 23Be, 23Bf, 26Be, and 30Bc, not only restored potency against inducibly resistant pathogens but also exhibited significantly enhanced activities against constitutively resistant strains of Staphylococcus pneumoniae and Staphylococcus pyogenes, which express high-level resistance independent of clarithromycin or erythromycin induction. Additionally, the novel hybrids showed susceptibility against Gram-negative Haemophilus influenzae. Notably, hybrid 23Be demonstrated dual modes of action by inhibiting both protein synthesis and DNA replication in vitro and in vivo. Given these promising characteristics, 23Be emerges as a potential candidate for the treatment of community-acquired bacterial pneumonia.

A polemic in response to the Glenn S. Tillotson et. al., (J Antimicrob Chemother 2024; 79: 2080-2081) is given.Author discussed that estimates of CAP incidence, they do not address the associated mortality, which is estimated at 50000 deaths annually in the USA, making CAP the ninth leading cause of death.This underscores the critical need for effective management of the infection.The discussion on the evolving etiol. of CAP is particularly relevant given the emergence of multidrug-resistant organisms.While Streptococcus pneumoniae remains the predominant pathogen, the article does not explore the impact of mol. diagnostic methods, which could significantly de-escalate empirical therapies due to their rapid results.The article displays several inconsistencies and gaps in its coverage of antibiotics.The pharmacokinetic properties of omadacycline and other antibiotics approved for community-acquired bacterial pneumonia (CABP), such as half-life, tissue penetration, metabolism, and potential drug-drug interactions, are crucial topics that merit discussion, especially given their significance for patients receiving multiple drugs for conditions such as asthma or chronic obstructive pulmonary disease.The author concluded that the emergence of multidrugresistant organisms in CABP is a concern, it is important to carefully consider the spectrum of activity and approved uses of antibiotics, such as for complicated urinary tract infections as well as ventilatorassocd. and hospital-acquired pneumonia, before recommending them for off-label use.Finally, the discontinued development of solithromycin following the FDA's request for more extensive studies in 2016 is included in the discussion.Given its irrelevance to current treatment protocols, its inclusion in this article is somewhat confusing.