Aim of the study was to assess predictors of discontinuation/toxicity of boosted PI-based (PI/r) dual therapy (DT). Observational, retrospective switch study in patients successfully treated with triple drugs regimen. Patients switched to PI/r based DT [darunavir (DRV/r), lopinavir (LPV/r) or atazanavir (ATV/r)] plus a second drug: [raltegravir (RAL), maraviroc (MVC) etravirine (ETR), lamivudine (3TC) or tenofovir (TDF)] between 2009 and 2014 were included. The effect of each drug as well as other clinical and virological cofactors over treatment discontinuation (TD) was assessed using survival analysis. Overall, 376 patients were included with mean follow-up of 73 weeks. The most commonly used drugs in DT were DRV/r (63.0 %) and RAL (53.7 %). TD was observed in 77 (20,4 %) patients: 38 (10,1 %) virological failure, 35 (9,3 %) toxicity/intolerance (4 deaths) and 4 (1 %) interruptions for patients decision. At Cox Model, adjusted by demographic and laboratory variables, DRV/r and ATV/r significantly reduced the likelihood of TD and longer treatment was associated with lower risk, while low CD4 count at baseline and number of previous regimens with a higher risk. Moreover, RAL and 3TC use were significantly associated with lower TD by toxicity. In our clinical practice experience, switching virologically suppressed patients to PI/r based DT showed adequate safety and efficacy, so that it may be used in selected patients with specific medical needs.

Background/Objectives: Urinary tract infections (UTIs) represent the most common infectious complication following kidney transplantation. An increasing number of UTIs are caused by multidrug-resistant organisms (MDROs). The role of intestinal MDRO colonisation in complicated urinary tract infections (cUTIs) among kidney transplant recipients is not fully understood. Methods: We conducted a retrospective, single-centre study of kidney or kidney–pancreas transplant recipients hospitalised for infectious diseases. Each hospitalisation was analysed as a separate event. Routine rectal screening targeted carbapenem-resistant Enterobacterales and vancomycin-resistant/vancomycin-variable enterococci. Results: The study included 65 hospitalisations from 52 kidney transplant recipients, with some patients contributing multiple admissions. cUTIs accounted for 63.1% of admissions, and 22.0% of cUTIs were associated with concomitant bloodstream infection (BSI). The most frequently isolated pathogens were Klebsiella pneumoniae (58.8%) and Escherichia coli (41.2%). Extended-spectrum β-lactamase (ESBL) production was detected in 50% of E. coli isolates, while carbapenemase production was identified in 60% of K. pneumoniae isolates. MDRO rectal carriage was detected in 43.1% of cases and was more frequent in cUTI than in other infections (53.7% vs. 25.0%, p = 0.024). Carbapenemase-producing K. pneumoniae (CP-KP) rectal carriage was also more frequent in cUTI (31.7% vs. 4.2%, p = 0.011), but did not remain statistically significant after adjustment for urinary stent presence (odds ratio 7.1, 95% CI 0.7–66.2; p = 0.087). Nevertheless, CP-KP rectal carriage was associated with CP-KP cUTI aetiology (PPV 75.0%; NPV 86.4%). The median length of hospital stay (LoS) was 15 days. In multivariable analysis, a longer median LoS was associated with BSI (12.2 days; 95% CI: 0.8–23.6; p = 0.037), urinary stent presence (6.8 days; 95% CI: 1.5–12.2; p = 0.014), and older age (2.3 days; 95% CI: 0.7–4.0; p = 0.007). Conclusions: Rectal CP-KP colonisation may represent a potential marker of cUTI risk, although its independent association was not confirmed after adjustment. These findings should be interpreted with caution, given the study design and sample size and require confirmation in larger prospective studies. Rectal screening may contribute to early risk stratification, whereas its role in guiding empirical therapy remains to be prospectively evaluated.

Background/Objectives: Acinetobacter baumannii is a critical opportunistic pathogen causing severe healthcare-associated infections, particularly in intensive care units. The global dissemination of carbapenem-resistant A. baumannii (CRAB) and its environmental persistence necessitate continuous genomic surveillance to monitor high-risk clones. Methods: We conducted whole-genome sequencing (WGS), core genome multi-locus sequence typing (cgMLST), and phylogenomic analyses on 26 CRAB isolates collected at the National Institute for Infectious Diseases (INMI) “Lazzaro Spallanzani” IRCCS (September 2023–September 2024). Antimicrobial resistance determinants, virulence-related genes, and capsular (KL) and lipooligosaccharide outer core (OCL) loci were characterized by interrogation of comprehensive bioinformatic pipelines. Results: All CRAB isolates displayed an extensively drug-resistant (XDR) phenotype, with a shared resistance pattern to carbapenems, aminoglycosides, fluoroquinolones, fosfomycin, and sulfonamides, while being susceptible only to colistin and cefiderocol. The carbapenemase gene bla_OXA-23 was detected in all CRAB isolates, together with clone-specific bla_OXA-51-like variants. For all isolates, the resistome profile fully matched the observed resistance phenotype. All isolates belonged to the International Clonal Lineage II (ICL II), Pasteur Sequence Type (ST) 2, and Oxford ST369, ST208, and ST455. Integration of cgMLST data with phylogenomic analyses and genome-based classification of KL and OCL loci revealed five distinct clusters, each one including nearly identical isolates, indicating both intra-hospital dissemination and possible inter-hospital transmission. Virulome profiling revealed heterogeneous repertoires of virulence-associated genes, resulting in cluster-specific patterns, while patristic analysis identified phylogenetic clusters linking the study isolates to other Italian and other European lineages. Conclusions: This study underscores the complex genomic landscape of CRAB in our setting, driven by the circulation of different ICL II clonal types, and reinforces the urgency of integrated genomic surveillance and robust antimicrobial stewardship to mitigate the spread of high-risk XDR A. baumannii clones.

Solid organ transplant recipients (SOTRs) are at high risk of severe coronavirus disease 2019 (COVID-19), therefore early treatment of mild infections is crucial to prevent increased morbidity and mortality. The effectiveness of early treatment in SOTRs has yet to be fully characterized due to the emergence of new SARS-CoV-2 variants and to COVID-19 vaccination implementation. The aim of this single-center retrospective study is to evaluate the outcomes, safety and impact on SARS-CoV-2 viral load kinetics of COVID-19 early treatment in SOTRs. The study includes 80 SOTRs with a laboratory-confirmed diagnosis of symptomatic SARS-CoV-2 infection enrolled between January and October 2022 and treated with either monoclonal antibodies or antivirals. All patients received COVID-19 vaccination and 68.8% of them showed detectable levels of anti-spike (S) antibodies. The occurrence of clinical events (hospitalization, intensive care unit admission, or death) was assessed within 30 days after treatment initiation. The quantification of SARS-CoV-2 viral load were performed at baseline and at day-7. The rate of hospitalization was 2.5% [0.3–9%] and no deaths occurred. All patients completed treatment with no serious adverse events. Median viral load decrease was 0.48 [0.26–0.69] log₂ cycle threshold (ct) values, with no significant differences between SOTRs treated with monoclonal antibodies and those treated with antivirals. Viral load decrease was significantly associated with positive anti-s serology at baseline ($\beta$ = 0.196, p = 0.01), number of days between symptom onset and treatment ($\beta$ = 0.05, p = 0.03) and the number of comorbidities ($\beta$ = −0.05, p = 0.03). We provide evidence of real-world effectiveness of early therapy in SOTRs infected with SARS-CoV-2 and demonstrate the relevant role of humoral response to vaccination in enhancing early viral load decay during treatment.

This is a retrospective observational study including all COVID-19 patients admitted at our Institute throughout three successive pandemic waves, from January 2021 to June 2023. The main in-hospital outcomes (clinical progression [CP], defined as admission to Intensive Care Unit [ICU]/death, and death within 28 days) were compared among participants unvaccinated (NV), fully vaccinated (FV), with one (FV&B1) and two (FV&B2) booster doses. Vaccinated participants were stratified into recently and waned FV/FV&B1/FV&B2, depending on the time elapsed from last dose (≤ and >120 days, respectively). There were 4488 participants: 2224 NV, 674 FV, 1207 FV&B1, and 383 FV&B2. Within 28 days, there were 604 ICU admissions, 396 deaths, and 737 CP. After adjusting for the main confounders, the risk of both in-hospital outcomes was reduced in vaccinated individuals, especially in those who received the booster dose (approximately by 36% for FV and >50% for FV&B1 and FV&B2 compared to NV). Similarly, after restricting the analysis to vaccinated participants only, we observed a risk reduction of approximately 40% for FV&B1 and 50% for FV&B2, compared to FV, regardless of the distance since the last dose. Our data confirm the vaccine’s effectiveness in preventing severe COVID-19 and support the efforts to increase the uptake of booster doses, mainly among older and frailer individuals, still at a greater risk of clinical progression.