Optimization of Pyrazole Compounds as Antibiotic Adjuvants Active against Colistin- and Carbapenem-Resistant Acinetobacter baumannii

The diffusion of antibiotic-resistant, Gram-negative, opportunistic pathogens, an increasingly important global public health issue, causes a significant socioeconomic burden. Acinetobacter baumannii isolates, despite causing a lower number of infections than Enterobacterales, often show multidrug-resistant phenotypes. Carbapenem resistance is also rather common, prompting the WHO to include carbapenem-resistant A. baumannii as a "critical priority" for the discovery and development of new antibacterial agents. In a previous work, we identified several series of compounds showing either direct-acting or synergistic activity against relevant Gram-negative species, including A. baumannii. Among these, two pyrazole compounds, despite being devoid of any direct-acting activity, showed remarkable synergistic activity in the presence of a subinhibitory concentration of colistin on K. pneumoniae and A. baumannii and served as a starting point for the synthesis of new analogues. In this work, a new series of 47 pyrazole compounds was synthesized. Some compounds showed significant direct-acting antibacterial activity on Gram-positive organisms. Furthermore, an evaluation of their activity as potential antibiotic adjuvants allowed for the identification of two highly active compounds on MDR Acinetobacter baumannii, including colistin-resistant isolates. This work confirms the interest in pyrazole amides as a starting point for the optimization of synergistic antibacterial compounds active on antibiotic-resistant, Gram-negative pathogens

Local deprivation status and seasonal influenza vaccination coverage in adults ≥65 years residing in the Foggia municipality, Italy, 2009-2016

IntroductionIn Italy, vaccination against seasonal influenza has been recommended for the elderly since 1980, but coverage is still far below the WHO minimum target level of 75%. Effective interventions to improve influenza vaccination should understand which socioeconomic determinants may cause inequalities in vaccine uptake. This study aimed at assessing differences in vaccination coverage among people ≥65 years of age residing in the Foggia municipality, Italy, by socioeconomic status. MethodsA Socio-Economic-Health Deprivation Index (SEHDI) was constructed using a multivariate analysis model. Resident population, for census block, was classified in 5 deprivation groups. Differences in demographic and socioeconomic indicators, the standardized mortality ratios (SMRs), and the average vaccination coverage among deprivation groups were evaluated with the linear F-test. The association between census variables and influenza vaccination coverage, in each deprivation group, was assessed using the Pearson bivariate correlation. Results The SEHDI allowed to identify factors related to ageing, housing, household size and composition, and education. Forty percent of people residing in the Foggia municipality lived in conditions of socioeconomic and health deprivation. Belonging to families with 3 or 4 members was associated with increased coverage rates. In the most deprived group, vaccination uptake was positively associated with the dependency ratio.ConclusionsThe results of this study have shown that there is still large room for improving influenza vaccination coverage among subjects belonging to the most deprived areas. Surveillance of trends in influenza vaccine uptake by socioeconomic groups is a feasible contribution to implementing effective, tailored to the frail older persons, vaccine utilization programs