Mateu Espasa

Background: Persistent candidemia is associated with increased mortality, yet prognostic markers beyond initial blood culture time to positivity (TTP) remain poorly defined. While the TTP ratio between follow-up blood cultures (FUBCs) has shown prognostic utility in persistent Staphylococcus aureus bacteremia, its role in persistent candidemia has not been established. We aimed to evaluate the impact of changes in TTP across serial blood cultures in people with candidemia persisting for ≥48 hours and to assess their association with clinical outcomes. Methods: Single-center retrospective study including adult patients with candidemia and persistently positive FUBC ≥48 hours despite active antifungal therapy. Time to positivity and TTP ratio were analyzed according to clinical, microbiological, and outcome variables. The association with 30-day mortality was assessed using multivariable logistic regression. Results: Among 544 people with candidemia, 69 with persistent candidemia were included. The median TTP ratio was 1.4 (1.1–2.3). Patients with a shorter TTP ratio (<1.4) had numerically higher 30-day mortality, 7-day mortality, and in-hospital mortality, but in no cases was this statistically significant. The duration of antifungal exposure was not correlated with TTP prolongation. Thirty-day mortality was 36.2% and was associated in the multivariate model with septic shock, while catheter-related infection was protective. Conclusions: Overall mortality was numerically higher among those with shorter prolongation of FUBC TTP, although a statistical difference was not reached. No significant TTP prolongation was observed in sequential blood cultures despite active antifungal therapy. Further studies are needed to optimize therapeutic strategies against tolerant and persistent Candida strains. Main points: In people with persistent candidemia, a lower time-to-positivity (TTP) ratio (<1.4) had numerically higher mortality but was not statistically significant, likely due to the low number of events. Thirty-day mortality was associated in the multivariate model with septic shock, while catheter-related infection was protective. Duration of antifungal treatment was not associated with TTP prolongation. Further studies are needed to optimize management of persistent Candida strains.

Introduction: The incidence of pneumococcal disease (PD) in people living with HIV (PLWH) is higher than in the general population; therefore, this study aimed to analyze its incidence, clinical characteristics and vaccination coverage in PLWH. Methods: We conducted a retrospective, single-center study between 2015 and 2024 in Hospital Clínic, Barcelona, involving HIV patients who presented with PD during the study period (any patient with a microbiologically confirmed result). A descriptive analysis of cases was carried out and compared with patients who did not present PD during the study period. Results: A total of 177 episodes of PD were identified in 148 individuals, with a cumulative incidence of 1.7% (95% CI: 1.4–2.0). The median age at PD diagnosis was 45.9 (36–53) years; 64% of patients were Spanish-born; 50% of patients were men who have sex with men (MSM); the HIV transmission mode was intravenous drug use in 28% of cases; the median CD4 nadir was 181 (58–324) cells/mm³; the median CD4 prior to PD was 429 (240–663) cells/mm³; and the median peak HIV viral load (VL) was 176,839 (20,900–502,000) copies/mL. Intravenous drug use (OR 3.43; 95% CI 2.19–5.36; p < 0.001), peak HIV VL (OR 1.11; 95% CI 1.02–1.21; p = 0.011), and CD4 nadir (OR 0.92; 95% CI 0.87–0.98; p = 0.005) were independently associated with PD, and fifty-one percent of patients had not received any vaccination prior to their PD episode. Conclusion: PD incidence was high in our study and associated with poor immunological status. Research on new strategies to improve vaccination coverage and immunogenicity in PLWH is needed.

Objective: To analyze trends in resistance to antituberculous drugs over a 31-year period (1991–2022) at a hospital in Barcelona and to identify associated epidemiological determinants. Methods: This study included culture-confirmed tuberculosis cases diagnosed between 1991 and 2022. Drug susceptibility testing was conducted with clinical data from hospital records and epidemiological data from the Barcelona Public Health Agency. The primary outcome was resistance to first-line drugs. A subset of isolates was tested for second-line drugs. Trends were compared between the periods 1991–2000 and 2001–2022, aligning with increased immigration. Factors associated with resistance were examined using multivariate regression analysis. Results: Among the 2448 patients included, tuberculosis cases peaked in the 1990s and subsequently declined, while drug resistance increased. Overall, 12.2% of isolates showed resistance to at least one drug: 8.5% were monoresistant, 2.3% multiresistant, and 1.4% polyresistant. The 2001–2022 period had a higher resistance rate (OR 1.63; 95%CI 1.28–2.09) but lower multiresistance (OR 0.40; 95%CI 0.23–0.69). Resistance among new cases doubled from 6.4% to 12.8%, while rates among previously treated cases remained stable. The predictors of resistance were foreign-born (OR 1.52; 95%CI 1.21–1.91) and previous tuberculosis treatment (OR 2.88; 95%CI 2.17–3.81). A total of 90% of isolates remained susceptible to fluoroquinolones and aminoglycosides. Conclusions: Although tuberculosis incidence has declined over the past three decades, antibiotic resistance has increased, driven by foreign-born and retreatment cases. Ongoing drug susceptibility testing, access to second-line therapies, and targeted public health interventions for high-risk populations are essential to maintain control in low-incidence settings.

Background/Objectives: Nontuberculous mycobacteria (NTM) infections are rising, particularly those by Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MAB). Treating NTM infections is challenging due to their poor response to antibiotics. This study aimed to optimize the treatment of NTM infection by selecting antibiotics with bactericidal activity for combination therapy. To do this, we used the minimum bactericidal concentration (MBC) determination approach to define bactericidal or bacteriostatic activity. We developed three main objectives: validate a new method to determine MBC based on a reincubation method, determine MBC values of 229 NTM clinical isolates using the reincubation method, and evaluate antibiotic stability in preincubated microtiter plates. Methods: First, we assessed the stability of the antibiotics included in SLOWMYCOI Sensititre™ microtiter plates. Five strains of MAC were studied comparing the minimum inhibitory concentrations (MICs) of those preincubated for seven days vs. non-incubated plates. Then, we evaluated the percentage of reproducibility of MBC values using two methods, reincubation and subculturing (standard or traditional method) in 30 MAC isolates. Finally, we validated the reincubation method and prospectively determined the MBC values of the 229 NTM clinical strains. Results: Antibiotic stability: The MIC was equivalent after 7 and 14 days for all the antibiotics, except rifampicin, for which the MIC increased by 2- to 3-fold after preincubation. Reincubation method: The percentage of reproducibility of the MBC values between the two methods was 95.2% (range 76.6% to 100%). Prospective validation: MBC/MIC ratios revealed differential bactericidal activity for most antibiotics according to the different species, being bactericidal in M. avium and Mycobacterium xenopi, and predominantly bacteriostatic in MAB. Conclusions: Preincubation of Sensititre™ microtiter plates did not alter the MIC values of the antibiotics included except for rifampicin, suggesting a loss of activity. MBC determination can be easily performed by the Reincubation method presented. MBC values provide useful additional information regarding MIC values since the MBC/MIC ratio reveals whether antibiotics have bactericidal or bacteriostatic activity according to the species, which is pivotal for selecting the most adequate antibiotic combination to ensure efficient treatment management.

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.