Person: Munita, Jose M.
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Munita
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Jose M.
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Publication Clinical characteristics, microbiology and outcomes of a cohort of patients treated with ceftolozane/tazobactam in acute care inpatient facilities, Houston, Texas, USA(2023) Tran, Truc; Cabrera, Nicolo; Gonzales, Anne; Carlson, Travis; Alnezary, Faris; Miller, William; Sakurai, Aki; Dinh, An; Rydell, Kirsten; Rios, Rafael; Diaz, Lorena; Hanson, Blake; Munita, Jose M.; Pedroza, Claudia; Shelburne, Samuel; Aitken, Samuel; Garey, Kevin; Dillon, Ryan; Puzniak, Laura; Arias, CesarBackground: Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR Pseudomonas aeruginosa. This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts. Thus, we sought to evaluate the utilization of ceftolozane/tazobactam at multiple tertiary hospitals in Houston, TX, USA. Methods: We conducted a multicentre retrospective study of patients receiving at least 48 h of ceftolozane/tazobactam therapy from January 2016 through to September 2019 at two hospital systems in Houston. Demographic, clinical and microbiological data were collected, including the infecting bacterial isolate, when available. The primary outcome was composite clinical success at hospital discharge. Secondary outcomes included in-hospital mortality and clinical disposition at 14 and 30 days post ceftolozane/tazobactam initiation. Multivariable logistic regression analysis was used to identify predictors of the primary outcome and mortality. Recovered isolates were tested for susceptibility to ceftolozane/tazobactam and underwent WGS. Results: A total of 263 patients were enrolled, and composite clinical success was achieved in 185 patients (70.3%). Severity of illness was the most consistent predictor of clinical success. Combination therapy with ceftolozane/tazobactam and another Gram-negative-active agent was associated with reduced odds of clinical success (OR 0.32, 95% CI 0.16-0.63). Resistance to ceftolozane/tazobactam was noted in 15.4% of isolates available for WGS; mutations in ampC and ftsI were common but did not cluster with a particular ST. Conclusions: Clinical success rate among this patient cohort treated with ceftolozane/tazobactam was similar compared with previous experiences. Ceftolozane/tazobactam remains an alternative agent for treatment of susceptible isolates of P. aeruginosa.Publication Multispecies emergence of dual blaKPC/NDM carbapenemase-producing Enterobacterales recovered from invasive infections in Chile(2025) Quesille, Ana; Solar, Camila; Martínez, Jose; Rivas Jiménez, Lina María; Quiroz, Valeria; González, Ana; Riquelme, Roberto; Ugalde, Juan; Peters, Anne; Ortega, Oscar; Araos Bralic, Rafael Ignacio; García, Patricia; Lebreton, Francois; Munita, Jose M.; Diaz, LorenaCarbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) represent a significant global threat. The emergence of dual CP-CRE is particularly alarming, as they can potentially compromise the efficacy of newer antibiotics, further decreasing therapeutic alternatives. Herein, we report the emergence of multiple species of CP-CRE recovered from invasive infections in Chile that simultaneously harbor blaKPC and blaNDM and provide an in-depth genomic characterization of these worrisome pathogens. We collected carbapenem-resistant Enterobacterales (CRE) isolates from invasive infections over a 4-year period, across 11 healthcare centers in Chile. Bacterial species and the presence of carbapenemase genes were confirmed using MALDI-TOF and PCR assays, respectively. Antimicrobial susceptibility testing was conducted through disk diffusion and broth microdilution methods. Dual CP-CRE isolates were subjected to short- and long-read whole genome sequencing to perform a detailed genomic characterization of the isolates and of the mobile genetic elements harboring the enzymes. From a total of 1,335 CRE isolates, we observed an increase in the prevalence of CP-CRE, from 11% in 2019 to 38% in 2022. A total of 11 dual CP-CRE isolates were recovered, all of them harboring blaKPC and blaNDM. Species corresponded to Escherichia coli (n = 6), Klebsiella pneumoniae (n = 2), Klebsiella oxytoca (n = 2), and Citrobacter freundii (n = 1). Dual CP-CRE isolates exhibited resistance to all tested β-lactams except for cefiderocol. The blaKPC and blaNDM encoding genes were located on independent plasmids. Platforms harboring blaKPC were diverse and included IncN, IncF, and IncFIB plasmids. In contrast, blaNDM-7 was only found on fairly conserved IncX3 plasmids. We report that a rapid increase of CP-CRE in Chile, alongside with the emergence of multiple bacterial species of CP-CRE co-harboring blaKPC-2/3 and blaNDM-7, underscores a critical public health challenge. Our data suggest that the dissemination of blaNDM-7 was predominantly facilitated by IncX3 plasmids, whereas the spread of blaKPC involved multiple plasmid backbones. Active surveillance and genomic monitoring are critical to inform public policy and curtail the spread of these highly resistant pathogens.Publication Geographic divergence of methicillin-resistant Staphylococcus aureus ST5-SCCmecI in the aftermath of a major earthquake and tsunami: impact of a plasmid harboring heavy metal resistance genes(2025) Martínez, Jose; Alcalde, Manuel; Jara, Estefanía; Reyes, Jinnethe; Carvajal, Lina; Rincon, Sandra; Ríos, Rafael; Diaz, Lorena; Quesille, Ana; Riquelme, Roberto; Rivas Jiménez, Lina María; Moustafa, Ahmed; Hanson, Blake; Undurraga, Eduardo; Olivares, Jorge; García, Patricia; Araos Bralic, Rafael Ignacio; Planet, Paul; Arias, César; Munita, Jose M.El Staphylococcus aureus resistente a la meticilina (SARM) es una importante amenaza para la salud pública. La propagación global del SARM se caracteriza por sucesivas oleadas de clones epidémicos que dominan regiones geográficas específicas. Se cree que la adquisición de genes que codifican la resistencia a metales pesados (GMMP) es una característica clave en la divergencia geográfica del SARM. Sin embargo, la relación causa-efecto entre la presencia de GMMP y la divergencia de los clones de SARM aún no se ha dilucidado. En este estudio, evaluamos el papel que los GMMP pudieron haber desempeñado en la divergencia evolutiva del linaje ST5-SCC mec I del SARM en Latinoamérica. Realizamos una caracterización genómica de 113 aislamientos clínicos de SARM de seis centros de salud latinoamericanos, incluyendo 53 aislamientos recolectados en dos ciudades de Chile (Santiago y Concepción). Encontramos un plásmido (pSCL4752) que alberga genes de resistencia al arsénico, cadmio y mercurio en el 65% ( n = 71) de los aislados ST5-SCC mec I. También observamos una divergencia geográfica asociada a la presencia de pSCL4752 en aislados chilenos, con una mayor frecuencia en aislados de Concepción (88%) en comparación con Santiago (29%). Curiosamente, un análisis de reloj molecular reveló que esta divergencia se produjo tras el terremoto y tsunami de magnitud 8,8 Mw que azotó la zona de Concepción en 2010. Además, nuestros resultados demuestran que la presencia de pSCL4752 puede ser beneficiosa o perjudicial para los aislados ST5-SCC mec I, dependiendo de la disponibilidad ambiental de estos metales pesados. Nuestros resultados sugieren que la divergencia del linaje ST5-SCC mec I MRSA en América Latina podría haber sido fomentada por desastres ambientales e influenciada por la presencia/ausencia de HMRG albergados en un plásmido. IMPORTANCIA El Staphylococcus aureus resistente a la meticilina (MRSA) es una de las principales causas de infecciones potencialmente mortales en todo el mundo y una creciente preocupación para la salud pública. El aumento de bacterias resistentes a los antibióticos, como el MRSA, a menudo está vinculado a adaptaciones genéticas que mejoran su supervivencia. Nuestra investigación arroja luz sobre cómo los cambios ambientales, como los desencadenados por un desastre natural, pueden influir en la evolución y la propagación geográfica de un linaje de MRSA altamente resistente en América Latina. Identificamos un plásmido que porta genes de resistencia al arsénico, cadmio y mercurio, el cual se asoció con la divergencia geográfica del ST5-SCC mec.Se ha identificado un linaje de SARM con diferencias notables en su prevalencia entre las regiones afectadas por un gran terremoto y tsunami. Al vincular los eventos ambientales con la evolución del patógeno, nuestro estudio destaca el papel de las presiones ecológicas en la propagación del SARM. Estos hallazgos subrayan la necesidad de integrar el monitoreo ambiental en las estrategias de salud pública para comprender mejor el desafío global de la resistencia a los antimicrobianos.