Retrospective ANalysis of multi-drug resistant Gram-nEgative bacteRia on veno-venous extracorporeal membrane oxygenation. The multicenter RANGER STUDY

Abstract

Background: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a rapidly expanding life-support technique worldwide. The most common indications are severe hypoxemia and/or hypercapnia, unresponsive to conventional treatments, primarily in cases of acute respiratory distress syndrome. Concerning potential contraindications, there is no mention of microbiological history, especially related to multi-drug resistant (MDR) bacteria isolated before V-V ECMO placement. Our study aims to investigate: (i) the prevalence and incidence of MDR Gram-negative (GN) bacteria in a cohort of V-V ECMOs; (ii) the risk of 1-year mortality, especially in the case of predetected MDR GN bacteria; and (iii) the impact of annual hospital V-V ECMO volume on the probability of acquiring MDR GN bacteria.

Methods: All consecutive adults admitted to the Intensive Care Units of 5 Italian university-affiliated hospitals and requiring V-V ECMO were screened. Exclusion criteria were age < 18 years, pregnancy, veno-arterial or mixed ECMO-configuration, incomplete records, survival < 24 h after V-V ECMO. A standard protocol of microbiological surveillance was applied and MDR profiles were identified using in vitro susceptibility tests. Cox-proportional hazards models were applied for investigating mortality.

Results: Two hundred and seventy-nine V-V ECMO patients (72% male) were enrolled. The overall MDR GN bacteria percentage was 50%: 21% (n.59) detected before and 29% (n.80) after V-V ECMO placement. The overall 1-year mortality was 42%, with a higher risk observed in predetected patients (aHR 2.14 [1.33-3.47], p value 0.002), while not in 'V-V ECMO-acquired MDR GN bacteria' group (aHR 1.51 [0.94-2.42], p value 0.090), as compared to 'non-MDR GN bacteria' group (reference). Same findings were found considering only infections. A larger annual hospital V-V ECMO volume was associated with a lower probability of acquiring MDR GN bacteria during V-V ECMO course (aOR 0.91 [0.86-0.97], p value 0.002).

Conclusions: 21% of MDR GN bacteria were detected before; while 29% after V-V ECMO connection. A history of MDR GN bacteria, isolated before V-V ECMO, was an independent risk factor for mortality. The annual hospital V-V ECMO volume affected the probability of acquiring MDR GN bacteria. Trial Registration ClinicalTrial.gov Registration Number NCTNCT06199141, date 12.26.2023.

Keywords: ECMO; ESBL; Extended-spectrum beta-lactamase; Extracorporeal membrane oxygenation; MDR; MDRO; Multi-drug resistant.

Fig. 1

MDR GN bacteria. A In predetected patients. B. In ‘V-V ECMO-acquired MDR GN bacteria’ group. Data are presented as absolute frequency (% of the patients belonging to predetected MDR GN bacteria (n. 59, 100%) or as % of patients belonging to ‘V-V ECMO acquired MDR GN bacteria ‘group (n. 80, 100%). ^*: including Enterobacter sp., Escherichia Coli; ^**: including Serratia marcescens, Enterobacter sp. and Escherichia Coli. Abbreviations; MDR: multidrug resistant; GN: Gram-negative; N: number; ESBL: extended spectrum beta-lactamase; AmpC: AmpC β-lactamase-producing; DTR: difficult-to-treat resistance; sp.: species

Fig. 2

A1-year survival curves. Kaplan Meier survival curve at 1 year. The unadjusted and adjusted (covariates: age, SOFA score at V-V ECMO connection, interfacility transport, annual hospital V-V ECMO volume) HRs were calculated according to the univariable and multivariable Cox-proportional hazards models described in additional-Tables 2 and 4, respectively. Data are presented as HR, aHR and [95% CI]. Abbreviations: ECMO: extracorporeal membrane oxygenation; MDR: multidrug resistant; GN: Gram-negative; HR: hazard ratio; aHR: adjusted hazard ratio; CI: confidential interval; V-V: veno-venous

Fig. 3

Adjusted odds of V-V ECMO-acquired MDR GN bacteria according to annual hospital V-V ECMO volume. Adjusted odds of MDR GN bacteria acquisition among patients receiving V-V ECMO support, when volume is modeled continuously. Hospital V-V ECMO volume is defined as the specific number of patients treated with V-V ECMO per year in each hospital . The adjusted odds of MDR GN bacteria acquisition are presented according to the results described in additional-Table 5. Abbreviations: ECMO: extracorporeal membrane oxygenation; MDR: multidrug resistant; GN: Gram-negative; OR: odds ratio; CI: confidential interval; IMV: invasive mechanical ventilation; V-V: veno-venous