Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant <i>Escherichia coli</i> Bacteremic Urinary Tract Infections

Sojo-Dorado, Jesús; López-Hernández, Inmaculada; Rosso-Fernández, Clara María; Morales, Isabel; Palacios‐Baena, Zaira R.; Hernández-Torres, Alícia; Lucas, Esperanza Merino de; Escolà-Vergé, Laura; Bereciartúa, Elena; García-Vázquez, Elisa; Pintado, Vicente; Boix-Palop, Lucía; Natera-Kindelán, Clara; Sorlí, Luisa; Borrell, Núria; Giner, Livia; Amador-Prous, Concha; Shaw, Evelyn; Jover-Saénz, Alfredo; Molina, José Antonio; Martínez‐Álvarez, Rosa; Dueñas, Carlos; Calvo-Montes, Jorge; Silva, Jose T.; Cárdenes, Miguel Ángel; Lecuona, María; Pomar, Virginia; Santis, Lucía Valiente de; Yagüe-Guirao, Genoveva; Lobo-Acosta, María Ángeles; Merino-Bohórquez, Vicente; Pascual, Álvaro; Rodríguez-Baño, Jesús; Almirante, Benito; Fernández, María Beatriz Carenas; Paño‐Pardo, José Ramón; Cueto, Marina de; Retamar-Gentil, Pilar; López‐Cortés, Luis Eduardo; Gutiérrez‐Gutiérrez, Belén; Docobo, Fernando; Borreguero, Irene; Cameán, Manuel; Moral-Escudero, Encarnación; Vera, Ana Pareja-Rodríguez de; Martínez-Toldos, María del Carmen; Blázquez-Abellán, Ana; Bellés, Alba Bellés; Ramírez-Hidalgo, Maria Fernanda; Mirelis, Beatriz; Calbo, Esther; Xercavins, Mariona; Gracia-Ahufinger, Irene; Cano-Yuste, Angela M.; Guío, Laura; Hernández, José L.; Pigrau-Serrallach, Carlos; Viñado-Pérez, Belen; Asensio, Mireia Puig; Ardanuy, Carmen; Pujol, Miquel; García-Rosado, Dácil; Gil-Anguita, Concepción; Siverio, Ana; Gimeno-Gascón, Adelina; Boix-Martínez, Vicente; Reus, Sergio; Agea-Durán, Iván; Fariñas, Carmen; Palop, Begoña; Vilchez, Helem H; Lepe, José Antonio Suárez; Gil-Navarro, María Victoria; Sanjuán, Rafael; Cháves, Fernando; Escudero, Rosa; Gioia, Francesca; Sánchez-Díaz, Ana Maria; Cañas-Pedrosa, Ana María; Sangil-Monroy, Nayra; Toyas-Miazza, Carla

doi:10.1001/jamanetworkopen.2021.37277

Cited by 51 publications

(41 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A recent open‐label RCT compared intravenous fosfomycin versus a β‐lactam (ceftriaxone or meropenem) for patients with BSI from urinary source due to MDR (mainly ESBL‐producing) E. coli . While clinical or microbiological failure was lower with fosfomycin than with the comparator (14.3% vs. 19.7%, respectively), the primary outcome of non‐inferiority was not met due to an increased rate of AE‐related discontinuations in the former group, mostly due to the occurrence of heart failure (which happened only in patients over 80 years and those with preexisting heart disease or renal failure) 118 . Although fosfomycin showed high efficacy, this trial exemplifies that patients to be treated with intravenous fosfomycin at doses of 4–6 g every 6–8 h should be properly selected.…”

Section: Therapeutic Options For Esbl‐e and Cre Infections In The Sot...mentioning

confidence: 95%

Extended‐spectrum β‐lactamase‐producing and carbapenem‐resistant Enterobacterales bloodstream infection after solid organ transplantation: Recent trends in epidemiology and therapeutic approaches

Pérez‐Nadales

2022

Transplant Infectious Dis

View full text Add to dashboard Cite

Background: Infections caused by multidrug-resistant gram-negative bacilli (MDR GNB), in particular extended-spectrum β-lactamase-producing (ESBL-E) and carbapenem-resistant Enterobacterales (CRE), pose a major threat in solid organ transplantation (SOT). Outcome prediction and therapy are challenging due to the scarcity of randomized clinical trials (RCTs) or well-designed observational studies focused on this population. Methods: Narrative review with a focus on the contributions provided by the ongoing multinational INCREMENT-SOT consortium (ClinicalTrials identifier NCT02852902) in the fields of epidemiology and clinical management. Results: The Spanish Society of Transplantation (SET), the Group for Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC), and the Spanish Network for Research in Infectious Diseases (REIPI) recently published their recommendations for the management of MDR GNB Elena Pérez-Nadales and Mario Fernández-Ruiz contributed equally to this work.

show abstract

Section: Therapeutic Options For Esbl‐e and Cre Infections In The Sot...mentioning

confidence: 95%

Extended‐spectrum β‐lactamase‐producing and carbapenem‐resistant Enterobacterales bloodstream infection after solid organ transplantation: Recent trends in epidemiology and therapeutic approaches

Pérez‐Nadales

2022

Transplant Infectious Dis

View full text Add to dashboard Cite

show abstract

“…Eine spanische, randomisierte, kontrollierte Multicenterstudie untersuchte, ob bei Patient*innen mit bakteriämischer Escherichia-coli -Harnwegsinfektion der Cephalosporin- und Carbapenem-Verbrauch reduziert werden können. Es wurde geprüft, ob eine Therapie mit Fosfomycin (4-mal 4 g/Tag) anstatt eines 3.-Generations-Cephalosporins (Ceftriaxon 1 g/Tag) oder – bei Cephalosporin-Resistenz – Carbapenem (Meropenem 3‑mal 1 g/Tag) eingesetzt werden kann [ 25 ]. Patient*innen mit komplizierenden Faktoren wie septischem Schock, Prostatitis, Zustand nach Nierentransplantation und verzögerter Drainage bzw.…”

Section: Gibt Es Cephalosporin- Oder Carbapenem-sparende Alternativsu...unclassified

Antibiotic Stewardship (ABS) im Kontext schwerer Infektionen

2022

View full text Add to dashboard Cite

Hintergrund Schwere Infektionen stellen aufgrund der häufigen Komplikationen und hohen Sterblichkeit eine große klinische Herausforderung dar. Ziel der Arbeit (Fragestellung) Am Beispiel der Sepsis, gramnegativer Blutstrominfektionen und COVID-19 sollen Anwendung und Bedeutung von Antibiotic Stewardship(ABS)-Strategien im Kontext schwerer Infektionen erläutert werden. Material und Methode Es erfolgen die Zusammenfassung der aktuellen Literatur und Empfehlungen mit Fokus auf klinische ABS-Implikationen bei schweren Infektionen wie Sepsis, gramnegativen Blutstrominfektionen und COVID-19. Ergebnisse Die aktualisierte Sepsis-Leitlinie schlägt ein differenziertes Vorgehen zum Beginn der Antibiotikatherapie bei Patient*innen mit Sepsis, aber ohne Schock vor. Bei unsicherer Diagnose und bei fehlendem Schock kann der Zeitraum bis zur Einleitung der Antibiotikatherapie auf 3 h ausgedehnt werden. In dieser Zeit gilt es, die Differenzialdiagnostik und ein adäquates mikrobiologisches Sampling zu komplettieren, um eine Antibiotikatherapie aufgrund belastbarer Befunde zu initiieren oder alternativ zu verwerfen. Bei unkomplizierten gramnegativen Blutstrominfektionen ist eine 7‑tägige antibiotische Therapie ausreichend. Eine regelhafte Kombinationstherapie bei Blutstrominfektionen mit Pseudomonas aeruginosa ist aufgrund der bisher vorliegenden Daten nicht erforderlich. Bakterielle Koinfektionen bei COVID-19 sind selten. Eine prophylaktische antibiotische Therapie ist daher nicht gerechtfertigt. Bakterielle Sekundärinfektionen (> 48 h nach Hospitalisierung) treten v. a. bei kritisch kranken COVID-19-Patient*innen auf. Bei pulmonalen Ko- oder Sekundärinfektion ist ein therapeutisches Vorgehen entsprechend den Pneumonie-Leitlinien geboten. Schlussfolgerungen Trotz der Schwere und Komplexität der genannten Infektionen gelten die grundlegenden Prinzipien des Antibiotic Stewardship (ABS) im Sinne einer rationalen Antiinfektivaverordnung hinsichtlich Substanz, Dosis und Dauer der Therapie.

show abstract

“…Additionally, the activity of tebipenem against selected strains within the tested collection expressing co-resistance to ciprofloxacin and trimethoprim/sulfamethoxazole was also assessed in order to ascertain the suitability of tebipenem as a potential alternative to these traditional oral options. Although there has been renewed interest in the use of fosfomycin for the treatment of bacteraemia due to MDR E. coli , 23 several studies have reported an increased likelihood of treatment failure with regard to K. pneumoniae and, consequently, caution in the use of fosfomycin for such infections. 24 , 25 …”

Section: Introductionmentioning

confidence: 99%

Determining thein vitrosusceptibility of tebipenem, an oral carbapenem, against third-generation cephalosporin-resistantEscherichia coliandKlebsiella pneumoniaeisolated from bloodstream infections

Ranasinghe

Henderson

Cottrell

et al. 2022

JAC-Antimicrobial Resistance

View full text Add to dashboard Cite

Background Antimicrobials for bloodstream infections due to ESBL- and AmpC-producing Escherichia coli and Klebsiella pneumoniae are significantly limited due to widespread antimicrobial resistance. Tebipenem, an oral carbapenem, exhibits stability against these resistance mechanisms and may prove an attractive alternative. Methods The in vitro susceptibility of tebipenem was assessed against previously whole-genome sequenced ESBL- and AmpC-producing E. coli (274 isolates) and K. pneumoniae (42 isolates) derived from bloodstream infections using broth microdilution testing. Resulting tebipenem MICs were compared with those of other carbapenems previously tested against the isolate collection. Tebipenem activity was also compared against those isolates expressing co-resistance to the common oral antibiotics ciprofloxacin and trimethoprim/sulfamethoxazole. Results The tebipenem MIC90 value was found to be 0.03 mg/L for E. coli and 0.125 mg/L for K. pneumoniae. For E. coli, the tebipenem MIC90 value was equivalent to that of meropenem, 2-fold lower than that of doripenem, and 8-fold and 4-fold lower than that of imipenem and ertapenem, respectively. For K. pneumoniae, the tebipenem MIC90 value was 2-fold higher than that of meropenem, equivalent to that of doripenem, and 4-fold and 2-fold lower than that of imipenem and ertapenem, respectively. Tebipenem MICs were also unaffected by the expression of co-resistance to ciprofloxacin and trimethoprim/sulfamethoxazole. Conclusions The in vitro activity of tebipenem was unaffected by the production of ESBL and AmpC enzymes. Tebipenem also retained its activity against those isolates expressing co-resistance to ciprofloxacin and trimethoprim/sulfamethoxazole. These findings therefore highlight tebipenem as a potential option for the treatment of invasive MDR infections.

show abstract

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

Abstract: This randomized clinical trial investigates noninferiority of fosfomycin vs ceftriaxone or meropenem in achieving clinical and microbiological cure among patients with urinary tract infections due to multidrug-resistant Escherichia coli .

Cited by 51 publications

References 23 publications

Extended‐spectrum β‐lactamase‐producing and carbapenem‐resistant Enterobacterales bloodstream infection after solid organ transplantation: Recent trends in epidemiology and therapeutic approaches

Extended‐spectrum β‐lactamase‐producing and carbapenem‐resistant Enterobacterales bloodstream infection after solid organ transplantation: Recent trends in epidemiology and therapeutic approaches

Antibiotic Stewardship (ABS) im Kontext schwerer Infektionen

Determining thein vitrosusceptibility of tebipenem, an oral carbapenem, against third-generation cephalosporin-resistantEscherichia coliandKlebsiella pneumoniaeisolated from bloodstream infections

Contact Info

Product

Resources

About