Pseudomonas aeruginosa antibiotic susceptibility profiles, genomic epidemiology and resistance mechanisms: a nation-wide five-year time lapse analysisResearch in context

Summary: Background: Pseudomonas aeruginosa healthcare-associated infections are one of the top antimicrobial resistance threats world-wide. In order to analyze the current trends, we performed a Spanish nation-wide high-resolution analysis of the susceptibility profiles, the genomic epidemiology and the resistome of P. aeruginosa over a five-year time lapse. Methods: A total of 3.180 nonduplicated P. aeruginosa clinical isolates from two Spanish nation-wide surveys performed in October 2017 and 2022 were analyzed. MICs of 13 antipseudomonals were determined by ISO-EUCAST. Multidrug resistance (MDR)/extensively drug resistance (XDR)/difficult to treat resistance (DTR)/pandrug resistance (PDR) profiles were defined following established criteria. All XDR/DTR isolates were subjected to whole genome sequencing (WGS). Findings: A decrease in resistance to all tested antibiotics, including older and newer antimicrobials, was observed in 2022 vs 2017. Likewise, a major reduction of XDR (15.2% vs 5.9%) and DTR (4.2 vs 2.1%) profiles was evidenced, and even more patent among ICU isolates [XDR (26.0% vs 6.0%) and DTR (8.9% vs 2.6%)] (p < 0.001). The prevalence of Extended-spectrum β-lactamase/carbapenemase production was slightly lower in 2022 (2.1%. vs 3.1%, p = 0.064). However, there was a significant increase in the proportion of carbapenemase production among carbapenem-resistant strains (29.4% vs 18.1%, p = 0.0246). While ST175 was still the most frequent clone among XDR, a slight reduction in its prevalence was noted (35.9% vs 45.5%, p = 0.106) as opposed to ST235 which increased significantly (24.3% vs 12.3%, p = 0.0062). Interpretation: While the generalized decrease in P. aeruginosa resistance, linked to a major reduction in the prevalence of XDR strains, is encouraging, the negative counterpart is the increase in the proportion of XDR strains producing carbapenemases, associated to the significant advance of the concerning world-wide disseminated hypervirulent high-risk clone ST235. Continued high-resolution surveillance, integrating phenotypic and genomic data, is necessary for understanding resistance trends and analyzing the impact of national plans on antimicrobial resistance. Funding: MSD and the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea—NextGenerationEU

Sars-Cov-2 Infection in Patients on Long-Term Treatment with Macrolides in Spain: A National Cross-Sectional Study

The aim of this study was to know the prevalence and severity of COVID-19 in patients treated with long-term macrolides and to describe the factors associated with worse outcomes. A cross-sectional study was conducted in Primary Care setting. Patients with macrolides dispensed continuously from 1 October 2019 to 31 March 2020, were considered. Main outcome: diagnosis of coronavirus disease-19 (COVID-19). Secondary outcomes: symptoms, severity, characteristics of patients, comorbidities, concomitant treatments. A total of 3057 patients met the inclusion criteria. Median age: 73 (64–81) years; 55% were men; 62% smokers/ex-smokers; 56% obese/overweight. Overall, 95% of patients had chronic respiratory diseases and four comorbidities as a median. Prevalence of COVID-19: 4.8%. This was in accordance with official data during the first wave of the pandemic. The most common symptoms were respiratory: shortness of breath, cough, and pneumonia. Additionally, 53% percent of patients had mild/moderate symptoms, 28% required hospital admission, and 19% died with COVID-19. The percentage of patients hospitalized and deaths were 2.6 and 5.8 times higher, respectively, in the COVID-19 group (p &lt; 0.001). There was no evidence of a beneficial effect of long-term courses of macrolides in preventing SARS-CoV-2 infection or the progression to worse outcomes in old patients with underlying chronic respiratory diseases and a high burden of comorbidity