Cristina Pitart

Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are increasingly reported among gay, bisexual, and other men who have sex with men (GBMSM) engaging in chemsex, yet data remain limited. This ambispective cohort study conducted at Hospital Clínic of Barcelona (2018–2024) aimed to characterize CA-MRSA infections among GBMSM living with HIV. Methods: Epidemiological, behavioral, and clinical data were collected from medical records and standardized questionnaires. MRSA isolates from clinically indicated samples were identified by mass spectrometry and underwent antimicrobial susceptibility testing. Results: Among 446 participants, 62 (14%) were diagnosed with CA-MRSA, accounting for 109 infection episodes over a median follow-up of 3.21 years (IQR 1.39–5.05). All episodes involved skin and soft-tissue infections; 17% required hospitalization, 35% surgery, and 51% received non-active empirical antibiotics. Recurrent infections occurred in 32% of participants, and detectable HIV viral load was present in 28% of episodes. High levels of polydrug use were reported. Resistance to clindamycin (33%), cotrimoxazole (23%), and mupirocin (96%) was observed. Decolonization was attempted in 65% of participants. Conclusions: CA-MRSA infections were frequent, with substantial recurrence and antimicrobial resistance. These findings highlight challenges for infection control and antimicrobial stewardship and support further evaluation of preventive and decolonization strategies in this population.

Background: Cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) are common toxicities after chimeric antigen receptor (CAR) T-cell therapy. We evaluated the incidence, timing, microbiology, and risk factors of microbiologically documented infections during the CRS and/or ICANS phase. Method: Consecutive adults receiving CAR T-cell therapy between 2020 and 2023 were retrospectively analyzed. Infections were classified by type and timing. The 60-day cumulative incidence of first infection and associated factors were assessed using Fine–Gray competing-risk models. Results: Among 152 CAR T-cell infusions, CRS and/or ICANS occurred in 117 (77.0%) episodes, and 70 (59.8%) required immunomodulatory therapy. An infectious etiology was documented in 30 (25.6%) episodes, yielding 45 documented infections (21 bacterial [46.7%], 17 viral [37.8%], and 7 fungal [15.6%]), more frequent in immunomodulatory-treated episodes (32.9% vs 14.9%; P = .033). At infection onset, median temperature, and C-reactive protein (CRP) levels were lower than at CRS/ICANS diagnosis (37.2°C vs 38.4°C; P < .001 and 3.9 vs 6.0 mg/L; P = .002). In immunomodulatory-treated episodes, median time to first infection was 15 (7–22) days from CRS and 9 (5–20) days from ICANS. The 60-day cumulative infection incidence was 60.0% with multimodal immunosuppression and 20.8% without; multimodal immunosuppression independently increased infection risk (subdistribution hazard ratio [sHR] 3.29; 95% CI 1.38–7.82; P = .007). Conclusions: The CRS/ICANS phase carries a high risk of bacterial, viral, and fungal infections, particularly under multimodal immunosuppression, while fever and CRP are unreliable indicators. Focused strategies for early detection, prevention, and prompt treatment of infections are urgently needed.

The management of febrile neutropenia (FN) in oncohematological patients is undergoing a paradigm shift driven by a deeper understanding of patients’ pathophysiological heterogeneity, the increasing speed and accuracy of microbiological diagnostics, the emergence of new antibiotics, and the incorporation of predictive artificial intelligence (AI) as a tool to support clinical decision-making. Our objective is to provide an updated and comprehensive overview of the factors influencing antibiotic treatment in FN. We propose that its management should be based on three essential pillars. First, accurate risk stratification for bacterial infection. Second, ensuring that patients receive appropriate empirical antibiotic therapy, tailoring the initial choice according to the results of surveillance cultures from oropharyngeal and/or fecal microbiota. Finally, prioritizing antibiotic choices that preserve intestinal microbiota eubiosis as much as possible. Reducing colonization and overgrowth of facultative aerobic/anaerobic flora (Enterobacteriaceae, non-fermenting Gram-negative bacilli, and Enterococcus spp.) while preserving strict anaerobic flora decreases the risk of bacterial translocation and complications such as graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or loss of CAR-T functionality. This decision model, grounded in objective criteria, aims to balance the need for effective empirical coverage with responsible antibiotic use.

Short-chain fatty acids (SCFAs) are bacterial metabolites with crucial roles in host homeostasis and immune system modulation. Given their benefits, they have been proposed as markers of a healthy microbiota. Their quantification, however, is time-consuming, expensive and requires specialized personal and equipment. Thus, their use for quality assessment of stool samples in clinical contexts is limited. In this study we explored the use of Fourier-transform infrared (FT-IR) spectroscopy as an alternative method for metabolomic quality assessment of stool samples. FT-IR identifies the chemical bonds present in SCFAs and allows clear discrimination between healthy and dysbiotic stool samples (caused by Clostridioides difficile infection) through Principal Component Analysis (PCA). Overall, FT-IR provides a rapid, cost-effective and simple method for stool samples quality assessment. Combined with the widespread availability of this technology in most hospitals, these advantages highlight its potential application for routine implementation in clinical laboratories.

Early detection of disseminating vancomycin-resistant Enterococcus faecium (VREfm) in ICU wards is crucial for outbreak identification and the implementation of prompt infection control measures. Genotypic methods like pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) are costly and time-consuming, hindering rapid response due to batch dependency. Fourier-transform infrared spectroscopy (FT-IR) offers the potential for real-time outbreak detection and reliable strain typing. We utilized FT-IR to identify clonal VREfm dissemination and compared its performance to PFGE and WGS. Between February through October 2023, an unusually high number of VREfm were recovered at a tertiary hospital in Barcelona. Isolates were examined for antimicrobial susceptibility, carriage of vanA/vanB genes and clonality was also studied using FT-IR, PFGE, and WGS. Routine FT-IR inspections revealed recurring VREfm clustering during the outbreak's initial weeks. In total, 104 isolates were recovered from 75 patients and from multiple wards. However, only one isolate was recovered from an environmental sample, suggesting the absence of environmental reservoirs. An ST80 vancomycin-resistant (vanA) E. faecium strain was the main strain responsible for the outbreak, although a few additional VREfm strains were also identified, all belonging to CC17. PFGE and cgMLST (WGS) yielded identical clustering results to FT-IR, and WGS confirmed vanA/vanB gene carriage in all VREfm isolates. Infection control measures led to a rapid decline in VREfm isolates, with no isolates detected in November. FT-IR spectroscopy offers rapid turnaround times, sensitivity, and reproducibility, comparable to standard typing methods. It proved as an effective tool for monitoring VREfm dissemination and early outbreak detection.

Staphylococcus pseudintermedius, a commensal opportunistic bacterium predominantly residing in the skin of companion animals, particularly dogs, has the potential to induce skin and soft tissue infections in pets, and zoonotic infections, including catheter-related complications. This study documents four cases of S. pseudintermedius infection or colonization in patients who had close contact with dogs or cats. Identification of the bacterial species was performed using MALDI-TOF mass spectrometry, and antibiotic susceptibility was determined using microdilution assay. DNA was sequenced using Nanopore technology followed by in silico analysis. Three isolates were multidrug resistant, including resistance to methicillin, with one belonging to the prevalent European lineage ST551, and the other two were attributed to a novel multilocus sequence type, ST2672. The remaining isolate was attributed to the novel multilocus sequence type ST2673 and was methicillin susceptible. All four isolates exhibited an array of virulence factors that contributed to colonization, damage to host immune cells, and biofilm formation. All the ST551 isolates included in the comparative analysis displayed clonality within the European continent. The importance of describing zoonotic infections associated with S. pseudintermedius resides in the scarcity of available scientific literature, further accentuated by its heightened resistance profile and potential complications, particularly in the context of catheter-related infections.

The inoculum effect, characterized by diminished antibacterial activity at high bacterial inocula, is studied in the context of beta-lactam and beta-lactamase inhibitor combinations against beta-lactamase-producing Enterobacterales. The inhibition of ESBL + OXA-48 and KPC enzymes, in combination with ceftazidime, demonstrates encouraging results. In this study, 20 Klebsiella pneumoniae isolates were tested with different inocula (1–5 × 10⁵ and 1–5 × 10⁷ cfu/ml) using broth microdilution methods. The inoculum effect was observed in meropenem against OXA-48 + CTX-M-15- and KPC-2-producing isolates but not with ceftazidime/avibactam. Notably, meropenem exhibited inoculum effect against carbapenemase-producing strains, whereas ceftazidime-avibactam remained effective. We conclude that ceftazidime-avibactam is recommended for high-inoculum infections.

Introduction. The antimicrobial resistance is a significant public health threat, particularly for healthcare-associated infections caused by carbapenem-resistant Gram-negative pathogens which are increasingly reported worldwide. The aim of this study was to provide data on the in vitro antimicrobial activity of cefiderocol and that of commercially available comparator antibiotics against a defined collection of recent clinical multi-drug resistant (MDR) microorganisms, including carbapenem resistant Gram-negative bacteria collected from different regions in Spain and Portugal. Material and methods. A total of 477 clinical isolates of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia were prospectively (n=265) and retrospectively (n=212) included (2016-2019). Susceptibility testing was performed using standard broad microdilution and results were interpreted using CLSI-2021 and EUCAST-2021 criteria. Results. Overall, cefiderocol showed a good activity against Enterobacterales isolates, being 99.5% susceptible by CLSI and 94.5% by EUCAST criteria. It also demonstrated excellent activity against P. aeruginosa and S. maltophilia isolates, all being susceptible to this compound considering CLSI breakpoints. Regarding A. baumannii (n=64), only one isolate was resistant to cefiderocol. Conclusions. Our results are in agreement with other studies performed outside Spain and Portugal highlighting its excellent activity against MDR gram-negative bacteria. Cefiderocol is a therapeutic alternative to those available for the treatment of infections caused by these MDR bacteria.

Background: We described the real‐life epidemiology and causes of infections on the different therapy phases in patients undergoing chimeric antigen receptor (CAR) T‐cells directed towards CD19+ or BCMA+ cells.Methods: All consecutive patients receiving CAR T‐cell therapy at our institution were prospectively followed‐up. We performed various comparative analyses of all patients and subgroups with and without infections.Results: Ninety‐one adults mainly received CAR T‐cell therapy for acute leukaemia (53%) and lymphoma (33%). We documented a total of 77 infections in 47 (52%) patients, 37 (48%) during the initial neutropenic phase and 40 (52%) during the non‐neutropenic phase. Infections during the neutropenic phase were mainly due to bacterial (29, 78%): catheter infections (11 [38%] cases), endogenous source (5 [17%]), and Clostridioides difficile (5 [17%]). Patients receiving corticosteroids after CAR T‐cell therapy had a higher risk of endogenous infection (100% vs. 16%; p = .006). During the non‐neutropenic phase, bacterial infections remained very frequent (24, 60%), mainly with catheter source (8, 33%). Respiratory tract infections were common (17, 43%).Conclusions: Infections after CAR T‐cell therapy were frequent. During the neutropenic phase, it is essential to prevent nosocomial infections and balance the use of antibiotics to lower endogenous bacteraemia and Clostridial infection rates.