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Burden and serotype distribution of invasive Pneumococcal disease among high-risk patients from Latin America and the Caribbean: A systematic review and meta-analysis

2026-03-05T13:00:39Z

Title: Burden and serotype distribution of invasive Pneumococcal disease among high-risk patients from Latin America and the Caribbean: A systematic review and meta-analysis Authors: Bardach, Ariel; Ruvinsky, Silvina; Ciapponi, Agustin; Alconada, Tomás; Brizuela, Martín; Voto, Carla; Roel, Macarena; Gagetti, Paula Abstract: Invasive pneumococcal diseases (IPD), caused by Streptococcus pneumoniae , entail significant morbidity and mortality, especially in high-risk populations. In Latin America and the Caribbean (LAC) data are scarce. Objective: To estimate the disease burden, serotype distribution, and healthcare resource use among high- risk children and adults with IPD in LAC. Methods: We conducted a systematic review following PRISMA guidelines and a preregistered protocol (PROSPERO CRD42025629682). We searched CENTRAL, PubMed, Embase, LILACS, EconLIT, Global Health, CINAHL, SciELO, surveillance networks, and grey literature sources (Jan 20 0 0-Dec 2024). Results: Search yielded 6227 records, 181 studies were included, representing 63,671 IPD cases from 20 LAC countries. Pneumonia accounted for 52% of IPD cases, followed by meningitis 22% and bacteremia 20%. Median incidence was 13.13 cases per 10 0,0 0 0 persons per year, global case fatality rate was 17%, in meningitis 23% and in adults ≥60 years was 35%. In 36% of patients ICU admission was required. Post- PCV introduction, vaccine serotypes declined while nonvaccine serotypes increased, particularly among children < 5 years, with variability across LAC countries. Conclusion: This review highlights the burden and patterns of IPD serotypes among high-risk populations in LAC. Optimized vaccination strategies and continuous surveillance are required. ©2025 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases

Novel Insights on the Synergistic Mechanism of Action Between the Polycationic Peptide Colistin and Cannabidiol Against Gram-Negative Bacteria

2026-03-05T13:00:25Z

Title: Novel Insights on the Synergistic Mechanism of Action Between the Polycationic Peptide Colistin and Cannabidiol Against Gram-Negative Bacteria Authors: Corleto, Melina; Garavaglia, Matias; Martínez, Melina M. B; Weschenfeller, Melanie; Urrea Montes, Santiago; Aran, Martín; Pellizza, Leonardo; Faccone, Diego; Maffia, Paulo C. Abstract: Background/Objectives: Colistin (polymyxin E) has re-emerged as a last-hope treatment against MDR Gram-negative pathogens due to the development of extensively drugresistant Gram-negative bacteria. Unfortunately, rapid global resistance towards colistin has emerged, which represents a major public health concern. In this context (CBD), a lipophilic molecule derived from Cannabis sativa, exhibits antimicrobial activity mainly against Gram-positive bacteria but is generally ineffective against Gram-negative species. However, synergistic antibacterial activity between CBD and polymyxin B has been reported. The objective of this work is to analyze the colistin–CBD synergy against clinically relevant Gram-negative isolates displaying diverse mechanisms of colistin resistance and to explore the basis of the possible mechanism of action involved in the first steps of this synergy. Methods: Microbiological assays, minimal inhibitory concentration, cell culture, synergy tests by checker board and time kill, biofilm inhibition evaluation by crystal violet and MTT, SEM (scanning electron microscopy), molecules interaction analysis by nuclear magnetic resonance (NMR). Results: The colistin–CBD combination displayed synergy in colistin resistant Gram-negative bacteria and also disrupted preformed biofilms and killed bacteria within them. Time-kill assays revealed rapid bactericidal activity and SEM showed mild surface alterations on bacterial outer membranes after sublethal colistin monotherapy. Furthermore, a series of sequential treatment assays on colistin-resistant Escherichia coli showed that simultaneous exposure to both compounds was required for activity, as introducing a washing step between treatments abolished the antibacterial effect. In order to obtain deeper insight into this mechanism, NMR analyses were performed, revealing specific molecular interactions between CBD and colistin molecules. Conclusions: These results provide evidence for the first time that both molecules engage through a specific and structurally meaningful interaction and only display synergy when acting together on colistin-resistant bacteria.

Vitamin B12 promotes cefiderocol resistance and small-colony variants in carbapenem-resistant Acinetobacter baumannii

2026-03-05T13:00:12Z

Title: Vitamin B12 promotes cefiderocol resistance and small-colony variants in carbapenem-resistant Acinetobacter baumannii Authors: Mezcord, Vyanka; Luu, Irene; Akhar, Usman; Traglia, German M; Rodriguez, Cecilia; Moheb, Samyar; Sanchez, Shayra D.; Soto, Maria T.; Cima Clave, Maria J.; Sieira, Rodrigo; Tuttobene, Marisel R; Corso, Alejandra; Tolmasky, Marcelo E.; Bonomo, Robert A; Actis, Luis A; Rao, Gauri G.; Pasteran, Fernando; Ramirez, Maria S. Abstract: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a global health threat with few effective treatment options remaining. Cefiderocol, a last-resort siderophore-cephalosporin antibiotic, exploits bacterial iron transport systems via TonB-dependent receptors (TBDRs) to gain cellular entry. However, treatment failures and the emergence of resistance highlight concerns with in vivo efficacy. In this study, we report an unanticipated cefiderocol resistance mechanism where vitamin B12, a micronutrient supplement, modulates cefiderocol susceptibility. Our work revealed that vitamin B12 (methylcobalamin) affects and interacts with TBDRs and other metabolic and adaptation processes that contribute to increased cefiderocol MIC levels and the emergence of persistence phenotypes. We demonstrate that vitamin B12 supplementation elicits strain-specific transcriptomic responses in the AB5075 and AMA17 CRAB strains, characterized by the downregulation of genes encoding siderophore-mediated iron acquisition functions, stress responses, metabolic reprogramming, and biofilmbiofilmbiogenesis. Structural modeling and molecular docking reveal overlapping binding sites for vitamin B12 and cefiderocol within TBDRs such as CirA and PirA, suggesting competitive inhibition. Additionally, vitamin B12 exposure increases cefiderocol MICs across a panel of A. baumannii clinical and reference strains, enhances survival in time-kill assays, and promotes the emergence of small-colony variants displaying persistent phenotypes. Notably, this effect is stable, dose dependent, and further enhanced in the presence of host-derived fluids. These findings describe a previously unrecognized host–pathogen–drug interaction with potential clinical implications, suggesting that vitamin B12 exposure could contribute to cefiderocol treatment failure. Our results underscore the urgent need to consider the potential contribution of vitamin supplements to antimicrobial therapy and management strategies for CRAB infections.

Genomic characterization of XDR Mycobacterium tuberculosis isolates in Argentina (2006–2015)

2026-03-05T13:00:00Z

Title: Genomic characterization of XDR Mycobacterium tuberculosis isolates in Argentina (2006–2015) Authors: Castello, Florencia; Sosa, Ezequiel Jorge; Campos, Josefina; Monteserin, Johana; Poklépovich, Tomás Javier; Palumbo, Miranda; Serral, Federico; Messano, Joaquin; García, Gabriel; Simboli, Norberto; Turjanski, Adrián G; Paul, Roxana; López, Beatriz; Matteo, Mario; Palomino, María; Marti, Marcelo A; Fernández Do Porto, Darío Augusto Abstract: Tuberculosis (TB), caused by the intracellular bacterium Mycobacterium tuberculosis complex (Mtbc), remains a significant global health challenge, with Mtbc once again being the leading infectious killer worldwide. Despite over a century of research, the disease continues to pose a major threat, with an estimated one-fourth of the global population latently infected. According to the World Health Organization (WHO), approximately 1.3 million deaths were attributed to TB in 2024 alone. The emergence of multidrug-resistant (MDR) strains, resistant to isoniazid and rifampicin, and extensively drug-resistant (XDR) strains, resistant to rifampicin (and may also be resistant to isoniazid), to at least one fluoroquinolone (levofloxacin or moxifloxacin) and to at least one other Group A drug (bedaquiline or linezolid), further complicates the situation, posing significant challenges for healthcare systems. While the WHO definition of XDR-TB has recently been updated, in this study we applied the classification in effect during the 2006–2015 period, when the isolates were collected and characterized. In Argentina, TB burden is moderate compared to other countries, with approximately 10,500 new cases and 1,000 deaths reported annually. While standard therapy is generally effective, XDR Mtb infections require prolonged and costly treatment and are often associated with a guarded prognosis. Description: Fil: Castello, Florencia. Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Fil: Sosa, Ezequiel Jorge. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Fil: Campos, Josefina. Instituto Nacional de Enfermedades Infecciosas-ANLIS Carlos Malbrán, Buenos Aires, Argentina. Fil: Monteserin, Johana. Instituto Nacional de Enfermedades Infecciosas-ANLIS Carlos Malbrán, Buenos Aires, Argentina. Fil: Poklepovich, Tomás. Instituto Nacional de Enfermedades Infecciosas-ANLIS Carlos Malbrán, Buenos Aires, Argentina. Fil: Palumbo, Miranda. Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Fil: Serral, Federico. Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina. Fil: Messano, Joaquín. Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. Fil: García, Gabriel. Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. Fil: Simboli, Norberto. Instituto Nacional de Enfermedades Infecciosas-ANLIS Carlos Malbrán, Buenos Aires, Argentina. Fil: Turjanski, Adrián. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales, IQUIBICEN, CONICET, Buenos Aires, Argentina. Fil: Paul, Roxana. Instituto Nacional de Enfermedades Infecciosas-ANLIS Carlos Malbrán, Buenos Aires, Argentina. Fil: López, Beatriz. Instituto Nacional de Enfermedades Infecciosas-ANLIS Carlos Malbrán, Buenos Aires, Argentina. Fil: Matteo, Mario. Instituto de Tisioneumonología Raúl F. Vaccarezza, Hospital de Infecciosas Dr. F. J. Muñiz, Buenos Aires, Argentina. Fil: Palomino, María. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales, IQUIBICEN, CONICET, Buenos Aires, Argentina. Fil: Martí, Macelo. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina; Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales, IQUIBICEN, CONICET, Buenos Aires, Argentina. Fil: Fernandez Do Porto, Darío Augusto. Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina; Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.