Studies on the antimicrobial properties of N-acylated ciprofloxacins.

Fluoroquinolone antibiotics have been a mainstay in the treatment of bacterial diseases. The most notable representative, ciprofloxacin, possesses potent antimicrobial activity; however, a rise in resistance to this agent necessitates development of novel derivatives to prolong the clinical lifespan of these antibiotics. Herein we have synthesized and analyzed the antimicrobial properties of a library of N-acylated ciprofloxacin analogues. We find that these compounds are broadly effective against Gram-positive and Gram-negative bacteria, with many proving more effective than the parental drug, and several possessing MICs ≤1.0 µg/ml against methicillin-resistant Staphylococcus aureus and Bartonella species. An analysis of spontaneous mutation frequencies reveals very low potential for resistance in MRSA compared to existing fluoroquinolones. Mode of action profiling reveals that modification of the piperazinyl nitrogen by acylation does not alter the effect of these molecules towards their bacterial target. We also present evidence that these N-acylated compounds are highly effective at killing intracellular bacteria, suggesting the suitability of these antibiotics for therapeutic treatment.

ATS Core Curriculum 2020. Adult Pulmonary Medicine.

The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine in a 3- to 4-year recurring cycle of topics. The topics of the 2020 Pulmonary Core Curriculum include pulmonary vascular disease (submassive pulmonary embolism, chronic thromboembolic pulmonary hypertension, and pulmonary hypertension) and pulmonary infections (community-acquired pneumonia, pulmonary nontuberculous mycobacteria, opportunistic infections in immunocompromised hosts, and coronavirus disease [COVID-19]).