Antibiotic Therapy for MBL-Enterobacteriaceae Bacteremias: A Multicenter Target Trial Emulation

Tuesday, February 25, 2025

8:55am – 9:55am Eastern Time

Location: Connections Central Theater 1

Ivan A. Huespe, MD (he/him/his)

Hospital Italiano de Buenos Aires

Disclosure(s): No relevant financial relationship(s) to disclose.
MC

Maximiliano Gabriel Castro, n/a

MD
Hospital J B Iturraspe de Santa Fé

Disclosure information not submitted.
MB

Melina Beloso, N/A

MD
Hospital J B Iturraspe de Santa Fé

Disclosure information not submitted.
DA

Debora Avila Poletti, N/A

MD
Hospital Italiano de Buenos Aires

Disclosure information not submitted.
VS

Vanina Stanek, N/A

MD
Hospital Italiano de Buenos Aires

Disclosure information not submitted.
MS

Marisa Sanchez, N/A

MD
Hospital Italiano de Buenos Aires

Disclosure information not submitted.
EC

Eleonora Cunto, N/A

MD
Hospital de Infecciosas Francisco Javier Muñiz

Disclosure information not submitted.
MA

Mauro Arias, N/A

MD
Hospital Italiano de Rosario

Disclosure information not submitted.
ML

Marina Lagostena, n/a

MD
Hospital Italiano de Rosario

Disclosure information not submitted.
PN

Paola Novelli Poisson, N/A

MD
Hospital Médico Policial Churruca Visca

Disclosure information not submitted.
MB

Maria Virginia Boutet, N/A

MD
Hospital Médico Policial Churruca Visca

Disclosure information not submitted.
MB

Mayra Alejandra Brañez Merida, N/A

MD
Sanatorio Franchin

Disclosure information not submitted.
SA

Sebastian Gabriel Arias, N/A

MD
Hospital de Alta Complejidad del Bicentenario Esteban Echeverria

Disclosure information not submitted.
RC

Ricardo Cabrera, N/A

MD
Hospital Interzonal General de Agudos ''Profesor Dr. Luis Güemes''

Disclosure information not submitted.
VT

Valentina Tissera, N/A

MD
Hospital Municipal Central de San Isidro “Dr. Melchor Ángel Posse”

Disclosure information not submitted.
JS

Juan Camilo Salcedo, N/A

MD
Hospital Alemán

Disclosure information not submitted.
PE

Pedro Ivan Escobar, N/A

MD
Hospital Interdistrital Evita de Formosa

Disclosure information not submitted.
RA

Rodrigo Almanza, n/a

MD
Hospital Universitario Austral

Disclosure information not submitted.
EH

Emilio Felipe Huaier, N/A

MD
Hospital Italiano de Buenos Aires

Disclosure information not submitted.
MV

Mariana Vaena, MD

MD
hospital italiano de buenos aires

Disclosure information not submitted.

Disclosure(s):

Ivan A. Huespe, MD: No relevant financial relationship(s) to disclose.

Introduction: Cefiderocol is the only FDA-approved treatment for MetalloBeta Lactamase (MBL) bacteria, but is unavailable in many low and middle-income countries. Ceftazidime-avibactam plus Aztreonam (CAZAVI+ATM) emerges as a potential solution, though clinical evidence is limited. We aim to evaluate the efficacy and security of CAZAVI+ATM versus other active antibiotics (OAA) in treating MBL-type carbapenemase-producing Enterobacteriaceae (MBL-CPE) bacteremia.

Methods: This target trial emulation included observational data from adults with MBL-CPE bacteremia in 15 Argentine hospitals from July 2019 to June 2024. Inclusion time (T0) was MBL-CPE identification. Patients were categorized into two groups based on treatment received within 24 hours of MBL-CPE bacteremia identification: 1) CAZAVI+ATM or 2) OAA. To address selection bias, propensity score inverse probability weighting was performed. Follow-up lasted 30 days after inclusion. The primary outcome was mortality and clinical failure (bacteremia relapse, antibiotic treatment restart, suppurative complications) within 14 days, assessed using an intention-to-treat approach.

Results: We included 206 patients with MBL-type CPE bacteremia (mean age 58.2 years [SD 17.7], 62% male) of whom 55% were in ICU. The most frequent primary infection sites were respiratory (27%) and urinary tract (25.5%). Klebsiella pneumoniae was the most common species (85.9%), with NDM-producing strings representing 31%.
Overall, 61 (27%) patients received CAZAVI+ATM and 145 (73%) received OAA. The adjusted OR for 14-days mortality was 0.38 (CI95% 0.19,0.72; p< 0.01) for the CAZAVI+ATM group and 0.74 (CI95% 0.47,1.16; p=0.1) for 30-days mortality. Regarding 14-day clinical failure, the adjusted OR in the CAZAVI+ATM group was 0.4 (CI95% 0.2,0.76; p< 0.01).
No difference between groups was observed in the occurrence of Clostridium difficile, neutropenia, leukopenia, renal failure, hepatic failure, or skin rash.

Conclusions: This multicenter study is the largest cohort of patients with MBL-type EPC bacteremia evaluating the efficacy of CAZAVI+ATM. We observed that this combination reduces 14-days mortality and clinical failure compared to OAA. However, no significant difference in 30-days mortality was found, potentially due to a lack of power.