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1. Pseudomonas aeruginosa antibiotic susceptibility profiles, genomic epidemiology and resistance mechanisms: a nation-wide five-year time lapse analysis

Author

Galán-Sánchez, Fátima, Gracia-Ahufinger, Irene, Martínez-Martínez, Luis, Liébana-Martos, Carmen, Roldán, Carolina, Sánchez-Calvo, Juan Manuel, Clavijo, Encarnación, Mora-Navas, Laura, Aznar, Javier, Lepe, José Antonio, Rodríguez-Villodres, Ángel, Recacha, Esther, Casas-Círia, Francisco Javier, Martínez-Rubio, Carmen, Sempere-Alcocer, Marco Antonio, Martín-Hita, Lina, Seral, Cristina, López-Calleja, Ana Isabel, Aspiroz, Carmen, Monforte, Marisa, Iglesia-Martínez, Pedro de la, Jimenez-Guerra, Gemma, Riera-Pérez, Elena, Collado, Carmen, Gallegos, Carmen, Mulet, Xavier, Fernández-Muñoz, Almudena, Sastre-Femenía, Miquel Àngel, Gomis-Font, María Antonia, Zamorano, Laura, Oliver, Antonio, Siller-Ruiz, María, Calvo, Jorge, Quesada, Dolores, Wang, Jun Hao, Pitart, Cristina, Marco, Francesc, Prim, Nuria, Horcajada, Juan Pablo, Padilla, Eduardo, Del Barrio-Tofiño, Ester, Viñado-Pérez, Belen, Larrosa, Nieves, Tubau, Fe, Capilla, Silvia, Casabella, Antonio, Pérez-Moreno, Mar Olga, Padilla, Emma, Ballestero, Mónica, Rivera, Alba, Navarro, Ferrán, Gómez-Bertomeu, Fréderic, Pardo-Granell, Sergio, Picó-Plana, Ester, Guerrero, Dolores, Sarvisé-Buil, Carolina, Belles-Belles, Alba, Fernández-Esgueva, Marta, Ortega-Lafont, María del Pilar, García, Inmaculada, Arenal-Andrés, Noelia, Hernando-Real, Susana, Ibáñez, Rosario, Martínez, Jesús, Becerra, Federico, Aldea-Mansilla, Carmen, Alaoui-Sosse, Asmaa, González, José Carlos, Guzman-Puche, Julia, Blázquez-Andrada, Miguel Ángel, Martínez-Ramírez, Nora Mariela, Beteta, Alicia, Gomila-Sard, Bárbara, Almaraz, Salvador Giner, Garduño, Eugenio, Juiz-González, Pedro Miguel, Arca-Suárez, Jorge, Alba, Javier, Alonso, Pilar, Rodríguez, Ana Isabel, Paz-Vidal, María Isabel, García-Campello, Marta, Camacho, Pablo, Pallarés, María de los Ángeles, Pérez del Molino, María Luisa, Coira, Amparo, Barbeito, Gema, Rincón, Anniris, Vasallo-Vidal, Francisco José, Alonso-Acero, Laura, Iglesias-Llorente, Laura, Bordes-Benites, Ana, Florén-Zabala, Laura, Azcona, José Manuel, Alonso, Carla Andrea, Sáenz, Yolanda, Lamata-Subero, Marta, Molina, David, González-Torralba, Ana, Villa, Jennifer, Viedma, Esther, Cercenado, Emilia, Alarcón, Teresa, Vargas, Paula, Díez, María, Cantón, Rafael, Ruiz, Patricia, Sánchez-Romero, María Isabel, Pérez-García, Felipe, Yagüe-Guirao, Genoveva, Oteiza, Amaia Concepción, Leiva, José, Portillo, María Eugenia, Canut-Blasco, Andrés, Vidal, Matxalen, Alonso, Iker, Zuriarrain, Maider, Barrios-Andrés, José Luis, Sastre-Femenia, Miquel Àngel, Taltavull, Biel, López-Causapé, Carla, and Oteo-Iglesias, Jesús

Published
2023
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2. Correction: Kirkegaard-Biosca et al. Cefiderocol for the Treatment of Infections by VIM-Type-Producing Gram-Negative Bacteria. Antibiotics 2024, 13 , 874.

Author

Kirkegaard-Biosca, Cristina, del Barrio-Tofiño, Ester, Villamarín, Miguel, Larrosa, Nieves, Campany, David, González-López, Juan José, Ferrer, Ricard, Viñado, Belén, Doménech, Laura, Sellarès-Nadal, Julia, Escolà-Vergé, Laura, Fernández-Hidalgo, Nuria, and Los-Arcos, Ibai

Subjects
HEMATOPOIETIC stem cell transplantation, CHRONIC obstructive pulmonary disease, URINARY tract infections, SURGICAL stents, EXTRACORPOREAL membrane oxygenation
Abstract

The correction notice for the article "Cefiderocol for the Treatment of Infections by VIM-Type-Producing Gram-Negative Bacteria" in the journal Antibiotics highlights an error in Table 2, specifically regarding patient outcomes. The corrected version of Table 2 is provided, with adjustments made to patient 23 and 24's mortality status at day 30. The authors assure that these corrections do not impact the scientific conclusions of the study, and the original publication has been updated accordingly. [Extracted from the article]

Published
2025
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3. Ciprofloxacin for the Treatment of Infections Caused by Carbapenemase-Producing Gram-Negative Bacteria †.

Author

Rubiñan, Pablo, Viñado, Belén, Fernández-Hidalgo, Nuria, Larrosa, Nieves, Sempere, Abiu, Campany, David, Rodríguez-Pardo, Dolors, González-López, Juan José, Nuvials, Xavier, del Barrio-Tofiño, Ester, Escolà-Vergé, Laura, and Los-Arcos, Ibai

Subjects
SOFT tissue infections, URINARY tract infections, INTRA-abdominal infections, SEPTIC shock, GRAM-negative bacteria
Abstract

Background: There is no experience with ciprofloxacin for the treatment of carbapenemase-producing Gram-negative bacteria (CP-GNB) infections. Methods: This is a retrospective single-centre study where we describe the clinical evolution of all consecutive adult patients who received ciprofloxacin monotherapy for the treatment of CP-GNB infections. Primary outcomes were clinical failure (defined as death, lack of clinical improvement or a switch to another drug) at day 14 and 30-day all-cause mortality. Results: Nineteen patients were included. Fifteen (79%) were men, the median age was 74 years (IQR 66–79) and the median Charlson comorbidity index was five (IQR 3–6.5). The most frequent infections were: nine complicated urinary tract infections, three soft tissue infections and three intra-abdominal infections. Twenty CP-GNBs were isolated (one patient had a coinfection): nine VIM-type-producing Enterobacterales, nine OXA-48-type-producing Enterobacterales and two VIM-type-producing Pseudomonas aeruginosa. Six (32%) patients had positive blood cultures, and one presented with septic shock. The median duration of ciprofloxacin treatment was 14 days (IQR 10–15). One patient presented with clinical failure at day 14. There was no 30-day mortality. Two patients exhibited microbiological recurrence at day 90. There were no reported adverse effects. Conclusions: Monotherapy with ciprofloxacin may be an alternative treatment for selected, clinically stable patients with ciprofloxacin-susceptible CP-GNB infections. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Cefiderocol for the Treatment of Infections by VIM-Type-Producing Gram-Negative Bacteria.

Author

Kirkegaard-Biosca, Cristina, del Barrio-Tofiño, Ester, Villamarín, Miguel, Larrosa, Nieves, Campany, David, González-López, Juan José, Ferrer, Ricard, Viñado, Belén, Doménech, Laura, Sellarès-Nadal, Julia, Escolà-Vergé, Laura, Fernández-Hidalgo, Nuria, and Los-Arcos, Ibai

Subjects
SOFT tissue infections, RESPIRATORY infections, GRAM-negative bacteria, MORTALITY, MEDICAL drainage
Abstract

VIM-type-producing Gram-negative bacteria (GNB) infections are difficult to treat. This is a retrospective single-center study of 34 patients who received cefiderocol for the treatment of VIM-type-producing GNB infections, including 25 Pseudomonas spp., 7 Enterobacterales, and 5 Achromobacter sp. Primary outcomes were clinical failure (defined as death, lack of clinical improvement, or a switch to another drug) at day 14 and 30-day all-cause mortality. The median age was 59 years (IQR 53.7–73.4), and the median Charlson comorbidity index was 3.5 (IQR 2–5). The main infections were respiratory tract infections (n = 9, 27%) and skin and soft tissue infections (n = 9, 27%). Eight patients exhibited bacteremia. In 9/17 patients with a drainable focus, drainage was performed. The median cefiderocol treatment duration was 13 days (IQR 8–24). Five patients (15%) experienced clinical failure on day 14, and the thirty-day mortality rate was 9/34 (27%); two cases occurred because of an uncontrolled infection source, and one was due to a new infection caused by the same bacteria. The other six deaths were unrelated to the index infection. Five patients experienced microbiological recurrence within three months. Susceptibility testing revealed the development of cefiderocol resistance in 1/7 cases with persistent or recurrent positive cultures. Cefiderocol, even in monotherapy, could be considered for the treatment of VIM-type-producing GNB infections. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection

Author

Wheatley, Rachel, Diaz Caballero, Julio, Kapel, Natalia, de Winter, Fien H. R., Jangir, Pramod, Quinn, Angus, del Barrio-Tofiño, Ester, López-Causapé, Carla, Hedge, Jessica, Torrens, Gabriel, Van der Schalk, Thomas, Xavier, Basil Britto, Fernández-Cuenca, Felipe, Arenzana, Angel, Recanatini, Claudia, Timbermont, Leen, Sifakis, Frangiscos, Ruzin, Alexey, Ali, Omar, Lammens, Christine, Goossens, Herman, Kluytmans, Jan, Kumar-Singh, Samir, Oliver, Antonio, Malhotra-Kumar, Surbhi, and MacLean, Craig

Published
2021
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6. Pseudomonas aeruginosa antibiotic susceptibility profiles, genomic epidemiology and resistance mechanisms: a nation-wide five-year time lapse analysis

Author

Sastre-Femenia, Miquel Àngel, primary, Fernández-Muñoz, Almudena, additional, Gomis-Font, María Antonia, additional, Taltavull, Biel, additional, López-Causapé, Carla, additional, Arca-Suárez, Jorge, additional, Martínez-Martínez, Luis, additional, Cantón, Rafael, additional, Larrosa, Nieves, additional, Oteo-Iglesias, Jesús, additional, Zamorano, Laura, additional, Oliver, Antonio, additional, Galán-Sánchez, Fátima, additional, Gracia-Ahufinger, Irene, additional, Liébana-Martos, Carmen, additional, Roldán, Carolina, additional, Sánchez-Calvo, Juan Manuel, additional, Clavijo, Encarnación, additional, Mora-Navas, Laura, additional, Aznar, Javier, additional, Lepe, José Antonio, additional, Rodríguez-Villodres, Ángel, additional, Recacha, Esther, additional, Casas-Círia, Francisco Javier, additional, Martínez-Rubio, Carmen, additional, Sempere-Alcocer, Marco Antonio, additional, Martín-Hita, Lina, additional, Seral, Cristina, additional, López-Calleja, Ana Isabel, additional, Aspiroz, Carmen, additional, Monforte, Marisa, additional, Iglesia-Martínez, Pedro de la, additional, Jimenez-Guerra, Gemma, additional, Riera-Pérez, Elena, additional, Collado, Carmen, additional, Gallegos, Carmen, additional, Mulet, Xavier, additional, Sastre-Femenía, Miquel Àngel, additional, Siller-Ruiz, María, additional, Calvo, Jorge, additional, Quesada, Dolores, additional, Wang, Jun Hao, additional, Pitart, Cristina, additional, Marco, Francesc, additional, Prim, Nuria, additional, Horcajada, Juan Pablo, additional, Padilla, Eduardo, additional, Del Barrio-Tofiño, Ester, additional, Viñado-Pérez, Belen, additional, Tubau, Fe, additional, Capilla, Silvia, additional, Casabella, Antonio, additional, Pérez-Moreno, Mar Olga, additional, Padilla, Emma, additional, Ballestero, Mónica, additional, Rivera, Alba, additional, Navarro, Ferrán, additional, Gómez-Bertomeu, Fréderic, additional, Pardo-Granell, Sergio, additional, Picó-Plana, Ester, additional, Guerrero, Dolores, additional, Sarvisé-Buil, Carolina, additional, Belles-Belles, Alba, additional, Fernández-Esgueva, Marta, additional, Ortega-Lafont, María del Pilar, additional, García, Inmaculada, additional, Arenal-Andrés, Noelia, additional, Hernando-Real, Susana, additional, Ibáñez, Rosario, additional, Martínez, Jesús, additional, Becerra, Federico, additional, Aldea-Mansilla, Carmen, additional, Alaoui-Sosse, Asmaa, additional, González, José Carlos, additional, Guzman-Puche, Julia, additional, Blázquez-Andrada, Miguel Ángel, additional, Martínez-Ramírez, Nora Mariela, additional, Beteta, Alicia, additional, Gomila-Sard, Bárbara, additional, Almaraz, Salvador Giner, additional, Garduño, Eugenio, additional, Juiz-González, Pedro Miguel, additional, Alba, Javier, additional, Alonso, Pilar, additional, Rodríguez, Ana Isabel, additional, Paz-Vidal, María Isabel, additional, García-Campello, Marta, additional, Camacho, Pablo, additional, Pallarés, María de los Ángeles, additional, Pérez del Molino, María Luisa, additional, Coira, Amparo, additional, Barbeito, Gema, additional, Rincón, Anniris, additional, Vasallo-Vidal, Francisco José, additional, Alonso-Acero, Laura, additional, Iglesias-Llorente, Laura, additional, Bordes-Benites, Ana, additional, Florén-Zabala, Laura, additional, Azcona, José Manuel, additional, Alonso, Carla Andrea, additional, Sáenz, Yolanda, additional, Lamata-Subero, Marta, additional, Molina, David, additional, González-Torralba, Ana, additional, Villa, Jennifer, additional, Viedma, Esther, additional, Cercenado, Emilia, additional, Alarcón, Teresa, additional, Vargas, Paula, additional, Díez, María, additional, Ruiz, Patricia, additional, Sánchez-Romero, María Isabel, additional, Pérez-García, Felipe, additional, Yagüe-Guirao, Genoveva, additional, Oteiza, Amaia Concepción, additional, Leiva, José, additional, Portillo, María Eugenia, additional, Canut-Blasco, Andrés, additional, Vidal, Matxalen, additional, Alonso, Iker, additional, Zuriarrain, Maider, additional, and Barrios-Andrés, José Luis, additional

Published
2023
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7. Carbapenem Combinations for Infections Caused by Carbapenemase-Producing Pseudomonas aeruginosa: Experimental In Vitro and In Vivo Analysis

Author

Herrera-Espejo, Soraya, primary, Del Barrio-Tofiño, Ester, additional, Cebrero-Cangueiro, Tania, additional, López-Causapé, Carla, additional, Álvarez-Marín, Rocío, additional, Cisneros, José Miguel, additional, Pachón, Jerónimo, additional, Oliver, Antonio, additional, and Pachón-Ibáñez, María Eugenia, additional

Published
2022
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8. Carbapenem Combinations for Infections Caused by Carbapenemase-Producing Pseudomonas aeruginosa: Experimental In Vitro and In Vivo Analysis

Author

Universidad de Sevilla. Departamento de Medicina, CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III, Proyectos de Investigacion en Salud, Servicio Andaluz de Salud, Junta de Andalucia, Red Española de Investigación en Enfermedades Infecciosas (REIPI), Ministerio de Economía, Industria y Competitividad, Herrera Espejo, Soraya, Del Barrio-Tofiño, Ester, Cebrero Cangueiro, Tania, López Causapé, Carla, Álvarez Marín, Rocío, Cisneros, José Miguel, Pachón Díaz, Jerónimo, Oliver, Antonio, Pachón Ibáñez, María Eugenia, Universidad de Sevilla. Departamento de Medicina, CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III, Proyectos de Investigacion en Salud, Servicio Andaluz de Salud, Junta de Andalucia, Red Española de Investigación en Enfermedades Infecciosas (REIPI), Ministerio de Economía, Industria y Competitividad, Herrera Espejo, Soraya, Del Barrio-Tofiño, Ester, Cebrero Cangueiro, Tania, López Causapé, Carla, Álvarez Marín, Rocío, Cisneros, José Miguel, Pachón Díaz, Jerónimo, Oliver, Antonio, and Pachón Ibáñez, María Eugenia

Abstract

In the context of difficult-to-treat carbapenem-resistant Pseudomonas aeruginosa infections, we evaluated imipenem, meropenem, and doripenem combinations against eleven carbapenemase-producing P. aeruginosa isolates. According to the widespread global distribution of high-risk clones and carbapenemases, four representative isolates were selected: ST175 (OXA-2/VIM-20), ST175 (VIM-2), ST235 (GES-5), and ST111 (IMP-33), for efficacy studies using a sepsis murine model. Minimum inhibitory concentration (mg/L) ranges were 64–256 for imipenem and 16–128 for meropenem and doripenem. In vitro, imipenem plus meropenem was synergistic against 72% of isolates and doripenem plus meropenem or imipenem against 55% and 45%, respectively. All combinations were synergistic against the ST175, ST235, and ST155 clones. In vivo, meropenem diminished the spleen and blood bacterial concentrations of four and three isolates, respectively, with better efficacy than imipenem or doripenem. The combinations did not show efficacy compared with the more active monotherapies, except for imipenem plus meropenem, which reduced the ST235 bacterial spleen concentration. Mortality decreased with imipenem plus meropenem or doripenem for the ST175 isolate. Results suggest that carbapenem combinations are not an alternative for severe infections by carbapenemase-producing P. aeruginosa. Meropenem monotherapy showed in vivo efficacy despite its high MIC, probably because its dosage allowed a sufficient antimicrobial exposure at the infection sites.

Published
2022

9. A Genomic Snapshot of the SARS-CoV-2 Pandemic in the Balearic Islands

Author

López-Causapé, Carla, primary, Fraile-Ribot, Pablo A., additional, Jiménez-Serrano, Santiago, additional, Cabot, Gabriel, additional, del Barrio-Tofiño, Ester, additional, Prado, M. Carmen, additional, Linares, Juana María, additional, López, Aranzazu, additional, Hurtado, Adoración, additional, Riera, Elena, additional, Serra, Antoni, additional, Roselló, Eva, additional, Carbó, Lluis, additional, Fernández-Baca, M. Victoria, additional, Gallegos, Carmen, additional, Saurina, Juan, additional, Arteaga, Emilio, additional, Salom, M. Magdalena, additional, Salvá, Antonia, additional, Nicolau, Antoni, additional, González-Candelas, Fernando, additional, Comas, Iñaki, additional, and Oliver, Antonio, additional

Published
2022
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11. Emergence of Resistance to Novel Cephalosporin–β-Lactamase Inhibitor Combinations through the Modification of the Pseudomonas aeruginosa MexCD-OprJ Efflux Pump

Author

Gomis-Font, María A., primary, Pitart, Cristina, additional, del Barrio-Tofiño, Ester, additional, Zboromyrska, Yuliya, additional, Cortes-Lara, Sara, additional, Mulet, Xavier, additional, Marco, Francesc, additional, Vila, Jordi, additional, López-Causapé, Carla, additional, and Oliver, Antonio, additional

Published
2021
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12. Association between Pseudomonas aeruginosa O-antigen serotypes, resistance profiles and high-risk clones: results from a Spanish nationwide survey

Author

Del Barrio-Tofiño, Ester, Sánchez-Diener, Irina, Zamorano, Laura, Cortes-Lara, Sara, López-Causapé, Carla, Cabot, Gabriel, Bou, Germán, Martínez-Martínez, Luis, Oliver, Antonio, on behalf of the GEMARA-SEIMC/REIPI Pseudomonas study group, Castillo-García, Francisco Javier, and Seral, Cristina

Abstract

Objectives: To evaluate the correlation of O-antigen serotypes with resistance profiles and high-risk clones in a Spanish nationwide survey. Methods: Up to 30 consecutive healthcare-associated Pseudomonas aeruginosa isolates were collected during October 2017 from each of 51 hospitals (covering all Spanish regions) with a total of 1445 isolates studied. MICs of 13 antipseudomonal agents and MDR/XDR profiles had been previously determined, as well as whole-genome sequences of 185 representative XDR isolates. O-antigen serotypes (O1–O16) were determined by agglutination using serotype-specific antisera (BioRad). The Pseudomonas aeruginosa serotyper (PAst) program was used for in silico serotyping. Results: The most frequent serotypes were O6 (17.8%), O1 (15.4%) and O11 (13.3%). In contrast, the most frequent serotype among XDR isolates (17.3%) was O4 (34.1%), distantly followed by O11 (15.9%). Within serotypes, XDR phenotypes were more frequent for O12 (60.0%) and O4 (57.3%). The most frequent clone among the XDR isolates was ST175 (40.9%), followed by CC235 (10.7%), ST308 (5.2%) and CC111 (3.6%). Up to 81.6%of XDR ST175 isolates typed O4, whereas 18.4% were non-typeable. O4 genotype was detected in all sequenced (n=55) ST175 isolates. On the other hand, CC235 and ST308 were associated with O11, whereas CC111 was linked to serotype O12. Conclusions: O4 serotype is linked to the MDR/XDR profile of widespread ST175 (typically only susceptible to colistin, amikacin and the novel combinations ceftolozane/tazobactam and ceftazidime/avibactam) and therefore, after local validation, its detection in the microbiology laboratory might be useful for guiding semi-empirical antipseudomonal therapies and infection control measures in Spanish hospitals.

Published
2020

13. Pseudomonas aeruginosa Susceptibility in Spain: Antimicrobial Activity and Resistance Suppression Evaluation by PK/PD Analysis

Author

Farmacia y ciencias de los alimentos, Farmazia eta elikagaien zientziak, Valero Telleria, Ana, Rodríguez Gascón, Alicia, Isla Ruiz, Arantxazu, Barrasa González, Helena, Del Barrio Tofiño, Ester, Oliver, Antonio, Canut Blasco, Andrés, Solinís Aspiazu, María Ángeles, Farmacia y ciencias de los alimentos, Farmazia eta elikagaien zientziak, Valero Telleria, Ana, Rodríguez Gascón, Alicia, Isla Ruiz, Arantxazu, Barrasa González, Helena, Del Barrio Tofiño, Ester, Oliver, Antonio, Canut Blasco, Andrés, and Solinís Aspiazu, María Ángeles

Abstract

Pseudomonas aeruginosa remains one of the major causes of healthcare-associated infection in Europe; in 2019, 12.5% of invasive isolates of P. aeruginosa in Spain presented combined resistance to ≥3 antimicrobial groups. The Spanish nationwide survey on P. aeruginosa antimicrobial resistance mechanisms and molecular epidemiology was published in 2019. Based on the information from this survey, the objective of this work was to analyze the overall antimicrobial activity of the antipseudomonal antibiotics considering pharmacokinetic/pharmacodynamic (PK/PD) analysis. The role of PK/PD to prevent or minimize resistance emergence was also evaluated. A 10,000-subject Monte Carlo simulation was executed to calculate the probability of target attainment (PTA) and the cumulative fraction of response (CFR) considering the minimum inhibitory concentration (MIC) distribution of bacteria isolated in ICU or medical wards, and distinguishing between sample types (respiratory and non-respiratory). Ceftazidime/avibactam followed by ceftolozane/tazobactam and colistin, categorized as the Reserve by the Access, Watch, Reserve (AWaRe) classification of the World Health Organization, were the most active antimicrobials, with differences depending on the admission service, sample type, and dose regimen. Discrepancies between EUCAST-susceptibility breakpoints for P. aeruginosa and those estimated by PK/PD analysis were detected. Only standard doses of ceftazidime/avibactam and ceftolozane/tazobactam provided drug concentrations associated with resistance suppression.

Published
2021

14. Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection

Author

Epi Infectieziekten Team 1, Infection & Immunity, JC onderzoeksprogramma Infectious Diseases, Wheatley, Rachel, Diaz Caballero, Julio, Kapel, Natalia, de Winter, Fien H R, Jangir, Pramod, Quinn, Angus, Del Barrio-Tofiño, Ester, López-Causapé, Carla, Hedge, Jessica, Torrens, Gabriel, Van der Schalk, Thomas, Xavier, Basil Britto, Fernández-Cuenca, Felipe, Arenzana, Angel, Recanatini, Claudia, Timbermont, Leen, Sifakis, Frangiscos, Ruzin, Alexey, Ali, Omar, Lammens, Christine, Goossens, Herman, Kluytmans, Jan, Kumar-Singh, Samir, Oliver, Antonio, Malhotra-Kumar, Surbhi, MacLean, Craig, Epi Infectieziekten Team 1, Infection & Immunity, JC onderzoeksprogramma Infectious Diseases, Wheatley, Rachel, Diaz Caballero, Julio, Kapel, Natalia, de Winter, Fien H R, Jangir, Pramod, Quinn, Angus, Del Barrio-Tofiño, Ester, López-Causapé, Carla, Hedge, Jessica, Torrens, Gabriel, Van der Schalk, Thomas, Xavier, Basil Britto, Fernández-Cuenca, Felipe, Arenzana, Angel, Recanatini, Claudia, Timbermont, Leen, Sifakis, Frangiscos, Ruzin, Alexey, Ali, Omar, Lammens, Christine, Goossens, Herman, Kluytmans, Jan, Kumar-Singh, Samir, Oliver, Antonio, Malhotra-Kumar, Surbhi, and MacLean, Craig

Published
2021

16. Erratum for del Barrio-Tofiño et al., “Genomics and Susceptibility Profiles of Extensively Drug-Resistant Pseudomonas aeruginosa Isolates from Spain”

Author

del Barrio-Tofiño, Ester, primary, López-Causapé, Carla, additional, Cabot, Gabriel, additional, Rivera, Alba, additional, Benito, Natividad, additional, Segura, Concepción, additional, Montero, María Milagro, additional, Sorlí, Luisa, additional, Tubau, Fe, additional, Gómez-Zorrilla, Silvia, additional, Tormo, Nuria, additional, Durá-Navarro, Raquel, additional, Viedma, Esther, additional, Resino-Foz, Elena, additional, Fernández-Martínez, Marta, additional, González-Rico, Claudia, additional, Alejo-Cancho, Izaskun, additional, Martínez, Jose Antonio, additional, Labayru-Echverria, Cristina, additional, Dueñas, Carlos, additional, Ayestarán, Ignacio, additional, Zamorano, Laura, additional, Martinez-Martinez, Luis, additional, Horcajada, Juan Pablo, additional, and Oliver, Antonio, additional

Published
2018
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17. Genomics and Susceptibility Profiles of Extensively Drug-Resistant Pseudomonas aeruginosa Isolates from Spain

Author

del Barrio-Tofiño, Ester, primary, López-Causapé, Carla, additional, Cabot, Gabriel, additional, Rivera, Alba, additional, Benito, Natividad, additional, Segura, Concepción, additional, Montero, María Milagro, additional, Sorlí, Luisa, additional, Tubau, Fe, additional, Gómez-Zorrilla, Silvia, additional, Tormo, Nuria, additional, Durá-Navarro, Raquel, additional, Viedma, Esther, additional, Resino-Foz, Elena, additional, Fernández-Martínez, Marta, additional, González-Rico, Claudia, additional, Alejo-Cancho, Izaskun, additional, Martínez, Jose Antonio, additional, Labayru-Echverria, Cristina, additional, Dueñas, Carlos, additional, Ayestarán, Ignacio, additional, Zamorano, Laura, additional, Martinez-Martinez, Luis, additional, Horcajada, Juan Pablo, additional, and Oliver, Antonio, additional

Published
2017
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19. Spanish nationwide survey on Pseudomonas aeruginosa antimicrobial resistance mechanisms and epidemiology

Author

del Barrio-Tofiño, Ester, Zamorano, Laura, Cortes-Lara, Sara, López-Causapé, Carla, Sánchez-Diener, Irina, Cabot, Gabriel, Bou, Germán, Martínez-Martínez, Luis, Oliver, Antonio, Galán, Fátima, Gracia, Irene, Rodríguez, Manuel Antonio, Martín, Lina, Sánchez, Juan Manuel, Viñuela, Laura, García, Mª Victoria, Lepe, José Antonio, Aznar, Javier, López-Hernández, Inma, Seral, Cristina, Javier Castillo-García, Francisco, López-Calleja, Ana Isabel, Aspiroz, Carmen, de la Iglesia, Pedro, Ramón, Susana, Riera, Elena, Cruz Pérez, María, Gallegos, Carmen, Calvo, Jorge, Dolores Quesada, María, Marco, Francesc, Hoyos, Yannick, Pablo Horcajada, Juan, Larrosa, Nieves, González, Juan José, Tubau, Fe, Capilla, Silvia, Pérez-Moreno, Mar Olga, Centelles, Mª José, Padilla, Emma, Rivera, Alba, Mirelis, Beatriz, Elisa Rodríguez-Tarazona, Raquel, Arenal-Andrés, Noelia, del Pilar Ortega, María, Megías, Gregoria, García, Inmaculada, Colmenarejo, Cristina, González, José Carlos, Martínez, Nora Mariela, Gomila, Bárbara, Giner, Salvador, Tormo, Nuria, Garduño, Eugenio, Agulla, José Andrés, Seoane, Alejandro, Pita, Julia, Vidal, Isabel Paz, Guzmán, David Mauricio, García, Marta, Pérez del Molino, María Luisa, Barbeito, Gema, Artiles, Fernando, Azcona-Gutiérrez, José Manuel, Sáenz, Yolanda, Antonio Oteo, José, González, Ana, Villa, Jennifer, Chaves, Fernando, Cercenado, Emilia, Alarcón, Teresa, Zurita, Nelly Daniela, Merino, Irene, Morosini, María Isabel, Cantón, Rafael, Isabel Sánchez, María, Moreno, Laura, Yagüe, Genoveva, Leiva, José, Luis Barrios, José, Canut, Andrés, and Oteo, Jesús

Subjects
0301 basic medicine, Microbiology (medical), Genotype, Avibactam, 030106 microbiology, Ceftazidime, Microbial Sensitivity Tests, Drug resistance, Biology, Polymerase Chain Reaction, Tazobactam, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Drug Resistance, Bacterial, medicine, Humans, Pseudomonas Infections, Pharmacology (medical), 030212 general & internal medicine, Phylogeny, Pharmacology, Cross Infection, Molecular Epidemiology, Molecular epidemiology, Hospitals, Anti-Bacterial Agents, Electrophoresis, Gel, Pulsed-Field, 3. Good health, Infectious Diseases, chemistry, Spain, Pseudomonas aeruginosa, Colistin, Multilocus sequence typing, Ceftolozane, Multilocus Sequence Typing, medicine.drug
Abstract

Objectives To undertake a Spanish nationwide survey on Pseudomonas aeruginosa molecular epidemiology and antimicrobial resistance. Methods Up to 30 consecutive healthcare-associated P. aeruginosa isolates collected in 2017 from each of 51 hospitals were studied. MICs of 13 antipseudomonal agents were determined by broth microdilution. Horizontally acquired β-lactamases were detected by phenotypic methods and PCR. Clonal epidemiology was evaluated through PFGE and MLST; at least one XDR isolate from each clone and hospital (n = 185) was sequenced. Results The most active antipseudomonals against the 1445 isolates studied were colistin and ceftolozane/tazobactam (both 94.6% susceptible, MIC50/90 = 1/2 mg/L) followed by ceftazidime/avibactam (94.2% susceptible, MIC50/90 = 2/8 mg/L). Up to 252 (17.3%) of the isolates were XDR. Carbapenemases/ESBLs were detected in 3.1% of the isolates, including VIM, IMP, GES, PER and OXA enzymes. The most frequent clone among the XDR isolates was ST175 (40.9%), followed by CC235 (10.7%), ST308 (5.2%) and CC111 (4.0%). Carbapenemase production varied geographically and involved diverse clones, including 16.5% of ST175 XDR isolates. Additionally, 56% of the sequenced XDR isolates showed horizontally acquired aminoglycoside-modifying enzymes, which correlated with tobramycin resistance. Two XDR isolates produced QnrVC1, but fluoroquinolone resistance was mostly caused by QRDR mutations. Beyond frequent mutations (>60%) in OprD and AmpC regulators, four isolates showed AmpC mutations associated with resistance to ceftolozane/tazobactam and ceftazidime/avibactam. Conclusions ST175 is the most frequent XDR high-risk clone in Spanish hospitals, but this nationwide survey also indicates a complex scenario in which major differences in local epidemiology, including carbapenemase production, need to be acknowledged in order to guide antimicrobial therapy.

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20. Emergence of Resistance to Novel Cephalosporin–β-Lactamase Inhibitor Combinations through the Modification of the Pseudomonas aeruginosaMexCD-OprJ Efflux Pump

Author

Gomis-Font, María A., Pitart, Cristina, del Barrio-Tofiño, Ester, Zboromyrska, Yuliya, Cortes-Lara, Sara, Mulet, Xavier, Marco, Francesc, Vila, Jordi, López-Causapé, Carla, and Oliver, Antonio

Abstract

A ceftolozane-tazobactam- and ceftazime-avibactam-resistant Pseudomonas aeruginosaisolate was recovered after treatment (including azithromycin, meropenem, and ceftolozane-tazobactam) from a patient that had developed ventilator-associated pneumonia after COVID-19 infection. Whole-genome sequencing revealed that the strain, belonging to ST274, had acquired a nonsense mutation leading to truncated carbapenem porin OprD (W277X), a 7-bp deletion (nt213Δ7) in NfxB (negative regulator of the efflux pump MexCD-OprJ), and two missense mutations (Q178R and S133G) located within the first large periplasmic loop of MexD.

Published
2021
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21. Activity of Imipenem-Relebactam against a Large Collection of Pseudomonas aeruginosaClinical Isolates and Isogenic β-Lactam-Resistant Mutants

Author

Fraile-Ribot, Pablo A., Zamorano, Laura, Orellana, Rocío, del Barrio-Tofiño, Ester, Sánchez-Diener, Irina, Cortes-Lara, Sara, López-Causapé, Carla, Cabot, Gabriel, Bou, Germán, Martínez-Martínez, Luis, and Oliver, Antonio

Abstract

Imipenem and imipenem-relebactam MICs were determined for 1,445 Pseudomonas aeruginosaclinical isolates and a large panel of isogenic mutants showing the most relevant mutation-driven β-lactam resistance mechanisms. Imipenem-relebactam showed the highest susceptibility rate (97.3%), followed by colistin and ceftolozane-tazobactam (both 94.6%).

Published
2019
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22. Erratum for del Barrio-Tofiño et al., “Genomics and Susceptibility Profiles of Extensively Drug-Resistant Pseudomonas aeruginosaIsolates from Spain”

Author

del Barrio-Tofiño, Ester, López-Causapé, Carla, Cabot, Gabriel, Rivera, Alba, Benito, Natividad, Segura, Concepción, Montero, María Milagro, Sorlí, Luisa, Tubau, Fe, Gómez-Zorrilla, Silvia, Tormo, Nuria, Durá-Navarro, Raquel, Viedma, Esther, Resino-Foz, Elena, Fernández-Martínez, Marta, González-Rico, Claudia, Alejo-Cancho, Izaskun, Martínez, Jose Antonio, Labayru-Echverria, Cristina, Dueñas, Carlos, Ayestarán, Ignacio, Zamorano, Laura, Martinez-Martinez, Luis, Horcajada, Juan Pablo, and Oliver, Antonio

Published
2017
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23. Genomics and Susceptibility Profiles of Extensively Drug-Resistant Pseudomonas aeruginosaIsolates from Spain

Author

del Barrio-Tofiño, Ester, López-Causapé, Carla, Cabot, Gabriel, Rivera, Alba, Benito, Natividad, Segura, Concepción, Montero, María Milagro, Sorlí, Luisa, Tubau, Fe, Gómez-Zorrilla, Silvia, Tormo, Nuria, Durá-Navarro, Raquel, Viedma, Esther, Resino-Foz, Elena, Fernández-Martínez, Marta, González-Rico, Claudia, Alejo-Cancho, Izaskun, Martínez, Jose Antonio, Labayru-Echverria, Cristina, Dueñas, Carlos, Ayestarán, Ignacio, Zamorano, Laura, Martinez-Martinez, Luis, Horcajada, Juan Pablo, and Oliver, Antonio

Abstract

ABSTRACTThis study assessed the molecular epidemiology, resistance mechanisms, and susceptibility profiles of a collection of 150 extensively drug-resistant (XDR) Pseudomonas aeruginosaclinical isolates obtained from a 2015 Spanish multicenter study, with a particular focus on resistome analysis in relation to ceftolozane-tazobactam susceptibility. Broth microdilution MICs revealed that nearly all (>95%) of the isolates were nonsusceptible to piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, imipenem, meropenem, and ciprofloxacin. Most of them were also resistant to tobramycin (77%), whereas nonsusceptibility rates were lower for ceftolozane-tazobactam (31%), amikacin (7%), and colistin (2%). Pulsed-field gel electrophoresis–multilocus sequence typing (PFGE-MLST) analysis revealed that nearly all of the isolates belonged to previously described high-risk clones. Sequence type 175 (ST175) was detected in all 9 participating hospitals and accounted for 68% (n= 101) of the XDR isolates, distantly followed by ST244 (n= 16), ST253 (n= 12), ST235 (n= 8), and ST111 (n= 2), which were detected only in 1 to 2 hospitals. Through phenotypic and molecular methods, the presence of horizontally acquired carbapenemases was detected in 21% of the isolates, mostly VIM (17%) and GES enzymes (4%). At least two representative isolates from each clone and hospital (n= 44) were fully sequenced on an Illumina MiSeq. Classical mutational mechanisms, such as those leading to the overexpression of the β-lactamase AmpC or efflux pumps, OprD inactivation, and/or quinolone resistance-determining regions (QRDR) mutations, were confirmed in most isolates and correlated well with the resistance phenotypes in the absence of horizontally acquired determinants. Ceftolozane-tazobactam resistance was not detected in carbapenemase-negative isolates, in agreement with sequencing data showing the absence of ampCmutations. The unique set of mutations responsible for the XDR phenotype of ST175 clone documented 7 years earlier were found to be conserved, denoting the long-term persistence of this specific XDR lineage in Spanish hospitals. Finally, other potentially relevant mutations were evidenced, including those in penicillin-binding protein 3 (PBP3), which is involved in β-lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.

Published
2017
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24. In VivoEmergence of Resistance to Novel Cephalosporin–β-Lactamase Inhibitor Combinations through the Duplication of Amino Acid D149 from OXA-2 β-Lactamase (OXA-539) in Sequence Type 235 Pseudomonas aeruginosa

Author

Fraile-Ribot, Pablo A., Mulet, Xavier, Cabot, Gabriel, del Barrio-Tofiño, Ester, Juan, Carlos, Pérez, José L., and Oliver, Antonio

Abstract

ABSTRACTResistance development to novel cephalosporin–β-lactamase inhibitor combinations during ceftazidime treatment of a surgical infection by Pseudomonas aeruginosawas investigated. Both initial (97C2) and final (98G1) isolates belonged to the high-risk clone sequence type (ST) 235 and were resistant to carbapenems (oprD), fluoroquinolones (GyrA-T83I, ParC-S87L), and aminoglycosides (aacA7/aacA8/aadA6). 98G1 also showed resistance to ceftazidime, ceftazidime-avibactam, and ceftolozane-tazobactam. Sequencing identified blaOXA-2in 97C2, but 98G1 contained a 3-bp insertion leading to the duplication of the key residue D149 (designated OXA-539). Evaluation of PAO1 transformants producing cloned OXA-2 or OXA-539 confirmed that D149 duplication was the cause of resistance. Active surveillance of the emergence of resistance to these new valuable agents is warranted.

Published
2017
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26. Activity of Imipenem-Relebactam against a Large Collection of Pseudomonas aeruginosa Clinical Isolates and Isogenic β-Lactam-Resistant Mutants.

Author

Fraile-Ribot PA, Zamorano L, Orellana R, Del Barrio-Tofiño E, Sánchez-Diener I, Cortes-Lara S, López-Causapé C, Cabot G, Bou G, Martínez-Martínez L, and Oliver A

Subjects
Humans, Mutation, Pseudomonas Infections microbiology, Pseudomonas aeruginosa enzymology, Pseudomonas aeruginosa genetics, beta-Lactam Resistance, beta-Lactamases genetics, Anti-Bacterial Agents pharmacology, Azabicyclo Compounds pharmacology, Colistin pharmacology, Imipenem pharmacology, Pseudomonas Infections drug therapy, Pseudomonas aeruginosa drug effects
Abstract

Imipenem and imipenem-relebactam MICs were determined for 1,445 Pseudomonas aeruginosa clinical isolates and a large panel of isogenic mutants showing the most relevant mutation-driven β-lactam resistance mechanisms. Imipenem-relebactam showed the highest susceptibility rate (97.3%), followed by colistin and ceftolozane-tazobactam (both 94.6%). Imipenem-relebactam MICs remained ≤2 μg/ml in all 16 isogenic PAO1 mutants and in 8 pairs of extensively drug-resistant clinical strains that had developed resistance to ceftolozane-tazobactam and ceftazidime-avibactam due to mutations in OXA-10 or AmpC., (Copyright © 2020 American Society for Microbiology.)

Published
2020
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27. Erratum for del Barrio-Tofiño et al., "Genomics and Susceptibility Profiles of Extensively Drug-Resistant Pseudomonas aeruginosa Isolates from Spain".

Author

Del Barrio-Tofiño E, López-Causapé C, Cabot G, Rivera A, Benito N, Segura C, Montero MM, Sorlí L, Tubau F, Gómez-Zorrilla S, Tormo N, Durá-Navarro R, Viedma E, Resino-Foz E, Fernández-Martínez M, González-Rico C, Alejo-Cancho I, Martínez JA, Labayru-Echverria C, Dueñas C, Ayestarán I, Zamorano L, Martinez-Martinez L, Horcajada JP, and Oliver A

Published
2017
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