Ventilator-associated pneumonia related to extended-spectrum beta-lactamase producing Enterobacterales during severe acute respiratory syndrome coronavirus 2 infection: risk factors and prognosis
Authors: Razazi Keyvan , Luyt Charles-Edouard , Voiriot Guillaume , Rouzé Anahita , Garnier Marc , Ferré Alexis , Camous Laurent , Heming Nicholas , Lapidus Nathanaël , Charles-Nelson Anais , Mekontso-Dessap Armand ,   COVID-ICU Group on behalf of the REVA Network and the COVID-ICU Investigators, Mercat Alain , Asfar Pierre , Beloncle François , Demiselle Julien , Pham Tài , Pavot Arthur , Monnet Xavier , Richard Christian , Demoule Alexandre , Dres Martin , Mayaux Julien , Beurton Alexandra , Daubin Cédric , Descamps Richard , Joret Aurélie , Du Cheyron Damien , Pene Frédéric , Chiche Jean-Daniel , Jozwiak Mathieu , Jaubert Paul , Voiriot Guillaume , Fartoukh Muriel , Teulier Marion , Blayau Clarisse , L’Her Erwen , Aubron Cécile , Bodenes Laetitia , Ferriere Nicolas , Auchabie Johann , Le Meur Anthony , Pignal Sylvain , Mazzoni Thierry , Quenot Jean-Pierre , Andreu Pascal , Roudau Jean-Baptiste , Labruyère Marie , Nseir Saad , Preau Sébastien , Poissy Julien , Mathieu Daniel , Benhamida Sarah , Paulet Rémi , Roucaud Nicolas , Thyrault Martial , Daviet Florence , Hraiech Sami , Parzy Gabriel , Sylvestre Aude , Jochmans Sébastien , Bouilland Anne-Laure , Monchi Mehran , Danguy des Déserts Marc , Mathais Quentin , Rager Gwendoline , Pasquier Pierre , Reignier Jean , Seguin Amélie , Garret Charlotte , Canet Emmanuel , Dellamonica Jean , Saccheri Clément , Lombardi Romain , Kouchit Yanis , Jacquier Sophie , Mathonnet Armelle , Nay Mai-Ahn , Runge Isabelle , Martino Frédéric , Flurin Laure , Rolle Amélie , Carles Michel , Coudroy Rémi , Thille Arnaud W. , Frat Jean-Pierre , Rodriguez Maeva , Beuret Pascal , Tientcheu Audrey , Vincent Arthur , Michelin Florian , Tamion Fabienne , Carpentier Dorothée , Boyer Déborah , Girault Christophe , Gissot Valérie , Ehrmann Stéphan , Salmon Gandonniere Charlotte , Elaroussi Djlali , Delbove Agathe , Fedun Yannick , Huntzinger Julien , Lebas Eddy , Kisoka Grâce , Grégoire Céline , Marchetta Stella , Lambermont Bernard , Argaud Laurent , Baudry Thomas , Bertrand Pierre-Jean , Dargent Auguste , Guitton Christophe , Chudeau Nicolas , Landais Mickaël , Darreau Cédric , Ferré Alexis , Gros Antoine , Lacave Guillaume , Bruneel Fabrice , Neuville Mathilde , Devaquet Jérôme , Tachon Guillaume , Gallot Richard , Chelha Riad , Galbois Arnaud , Jallot Anne , Chalumeau Lemoine Ludivine , Kuteifan Khaldoun , Pointurier Valentin , Jandeaux Louise-Marie , Mootien Joy , Damoisel Charles , Sztrymf Benjamin , Schmidt Matthieu , Combes Alain , Chommeloux Juliette , Luyt Charles Edouard , Schortgen Frédérique , Rusel Leon , Jung Camille , Gobert Florent , Vimpere Damien , Lamhaut Lionel , Sauneuf Bertrand , Charrrier Liliane , Calus Julien , Desmeules Isabelle , Painvin Benoît , Tadie Jean-Marc , Castelain Vincent , Michard Baptiste , Herbrecht Jean-Etienne , Baldacini Mathieu , Weiss Nicolas , Demeret Sophie , Marois Clémence , Rohaut Benjamin , Moury Pierre-Henri , Savida Anne-Charlotte , Couadau Emmanuel , Série Mathieu , Alexandru Nica , Bruel Cédric , Fontaine Candice , Garrigou Sonia , Courtiade Mahler Juliette , Leclerc Maxime , Ramakers Michel , Garçon Pierre , Massou Nicole , Van Vong Ly , Sen Juliane , Lucas Nolwenn , Chemouni Franck , Stoclin Annabelle , Avenel Alexandre , Faure Henri , Gentilhomme Angélie , Ricome Sylvie , Abraham Paul , Monard Céline , Textoris Julien , Rimmele Thomas , Montini Florent , Lejour Gabriel , Lazard Thierry , Etienney Isabelle , Kerroumi Younes , Dupuis Claire , Bereiziat Marine , Coupez Elisabeth , Thouy François , Hofmann Clément , Donat Nicolas , Chrisment Anne , Blot Rose-Marie , Kimmoun Antoine , Jacquot Audrey , Mattei Matthieu , Levy Bruno , Ravan Ramin , Dopeux Loïc , Liteaudon Jean-Mathias , Roux Delphine , Rey Brice , Anghel Radu , Schenesse Deborah , Gevrey Vincent , Castanera Jermy , Petua Philippe , Madeux Benjamin , Hartman Otto , Piagnerelli Michael , Joosten Anne , Noel Cinderella , Biston Patrick , Noel Thibaut , Bouar Gurvan L. E. , Boukhanza Messabi , Demarest Elsa , Bajolet Marie-France , Charrier Nathanaël , Quenet Audrey , Zylberfajn Cécile , Dufour Nicolas , Mégarbane Bruno , Voicu Sébastian , Deye Nicolas , Malissin Isabelle , Legay François , Debarre Matthieu , Barbarot Nicolas , Fillatre Pierre , Delord Bertrand , Laterrade Thomas , Saghi Tahar , Pujol Wilfried , Cungi Pierre Julien , Esnault Pierre , Cardinale Mickael , Hong Tuan Ha Vivien , Fleury Grégory , Brou Marie-Ange , Zafmahazo Daniel , Tran-Van David , Avargues Patrick , Carenco Lisa , Robin Nicolas , Ouali Alexandre , Houdou Lucie , Le Terrier Christophe , Suh Noémie , Primmaz Steve , Pugin Jérome , Weiss Emmanuel , Gauss Tobias , Moyer Jean-Denis , Burtz Catherine Paugam , La Combe Béatrice , Smonig Rolland , Violleau Jade , Cailliez Pauline , Chelly Jonathan , Marchalot Antoine , Saladin Cécile , Bigot Christelle , Fayolle Pierre-Marie , Fatséas Jules , Ibrahim Amr , Resiere Dabor , Hage Rabih , Cholet Clémentine , Cantier Marie , Trouiler Pierre , Montravers Philippe , Lortat-Jacob Brice , Tanaka Sebastien , Tran Dinh Alexy , Duranteau Jacques , Harrois Anatole , Dubreuil Guillaume , Werner Marie , Godier Anne , Hamada Sophie , Zlotnik Diane , Nougue Hélène , Mekontso-Dessap Armand , Carteaux Guillaume , Razazi Keyvan , de Prost Nicolas , Mongardon Nicolas , Mongardon Nicolas , Lamraoui Meriam , Alessandri Claire , de Roux Quentin , de Roquetaillade Charles , Chousterman Benjamin G. , Mebazaa Alexandre , Gayat Etienne , Garnier Marc , Pardo Emmanuel , Satre-Buisson Lea , Gutton Christophe , Yvin Elise , Marcault Clémence , Azoulay Elie , Darmon Michael , Ait Oufella Hafid , Hariri Geofroy , Urbina Tomas , Mazerand Sandie , Heming Nicholas , Santi Francesca , Moine Pierre , Annane Djillali , Bouglé Adrien , Omar Edris , Lancelot Aymeric , Begot Emmanuelle , Plantefeve Gaétan , Contou Damien , Mentec Hervé , Pajot Olivier , Faguer Stanislas , Cointault Olivier , Lavayssiere Laurence , Nogier Marie-Béatrice , Jamme Matthieu , Pichereau Claire , Hayon Jan , Outin Hervé , Dépret François , Coutrot Maxime , Chaussard Maité , Guillemet Lucie , Gofn Pierre , Thouny Romain , Guntz Julien , Jadot Laurent , Persichini Romain , Jean-Michel Vanessa , Georges Hugues , Caulier Thomas , Pradel Gaël , Hausermann Marie-Hélène , Nguyen-Valat Thi My Hue , Boudinaud Michel , Vivier Emmanuel , Rosseli Sylvène , Bourdin Gaël , Pommier Christian , Vinclair Marc , Poignant Simon , Mons Sandrine , Bougouin Wulfran , Bruna Franklin , Maestraggi Quentin , Roth Christian , Bitker Laurent , Dhelft François , Bonnet-Chateau Justine , Filippelli Mathilde , Morichau-Beauchant Tristan , Thierry Stéphane , Le Roy Charlotte , Jouan Mélanie Saint , Goncalves Bruno , Mazeraud Aurélien , Daniel Matthieu , Sharshar Tarek , Cadoz Cyril , Gaci Rostane , Gette Sébastien , Louis Guillaune , Sacleux Sophie-Caroline , Ordan Marie-Amélie , Cravoisy Aurélie , Conrad Marie , Courte Guilhem , Gibot Sébastien , Benzidi Younès , Casella Claudia , Serpin Laurent , Setti Jean-Lou , Besse Marie-Catherine , Bourreau Anna , Pillot Jérôme , Rivera Caroline , Vinclair Camille , Robaux Marie-Aline , Achino Chloé , Delignette Marie-Charlotte , Mazard Tessa , Aubrun Frédéric , Bouchet Bruno , Frérou Aurélien , Muller Laura , Quentin Charlotte , Degoul Samuel , Stihle Xavier , Sumian Claude , Bergero Nicoletta , Lanaspre Bernard , Quintard Hervé , Maiziere Eve Marie , Egreteau Pierre-Yves , Leloup Guillaume , Berteau Florin , Cottrel Marjolaine , Bouteloup Marie , Jeannot Matthieu , Blanc Quentin , Saison Julien , Geneau Isabelle , Grenot Romaric , Ouchike Abdel , Hazera Pascal , Masse Anne-Lyse , Demiri Suela , Vezinet Corinne , Baron Elodie , Benchetrit Deborah , Monsel Antoine , Trebbia Grégoire , Schaack Emmanuelle , Lepecq Raphaël , Bobet Mathieu , Vinsonneau Christophe , Dekeyser Thibault , Delforge Quentin , Rahmani Imen , Vivet Bérengère , Paillot Jonathan , Hierle Lucie , Chaignat Claire , Valette Sarah , Her Benoït , Brunet Jennifer , Page Mathieu , Boiste Fabienne , Collin Anthony , Bavozet Florent , Garin Aude , Dlala Mohamed , Mhamdi Kais , Beilouny Bassem , Lavalard Alexandra , Perez Severine , Veber Benoit , Guitard Pierre-Gildas , Gouin Philippe , Lamacz Anna , Plouvier Fabienne , Delaborde Bertrand P. , Kherchache Aïssa , Chaalal Amina , Ricard Jean-Damien , Amouretti Marc , Freita-Ramos Santiago , Roux Damien , Constantin Jean-Michel , Assef Mona , Lecore Marine , Selves Agathe , Prevost Florian , Lamer Christian , Shi Ruiying , Knani Lyes , Floury Sébastien Pili , Vettoretti Lucie , Levy Michael , Marsac Lucile , Dauger Stéphane , Guilmin-Crépon Sophie , Winiszewski Hadrien , Piton Gael , Soumagne Thibaud , Capellier Gilles , Putegnat Jean-Baptiste , Bayle Frédérique , Perrou Maya , Thao Ghyslaine , Géri Guillaume , Charron Cyril , Repessé Xavier , Vieillard-Baron Antoine , Guilbart Mathieu , Roger Pierre-Alexandre , Hinard Sébastien , Macq Pierre-Yves , Chaulier Kevin , Goutte Sylvie , Chillet Patrick , Pitta Anaïs , Darjent Barbara , Bruneau Amandine , Lasocki Sigismond , Leger Maxime , Gergaud Soizic , Lemarie Pierre , Terzi Nicolas , Schwebel Carole , Dartevel Anaïs , Galerneau Louis-Marie , Diehl Jean-Luc , Hauw-Berlemont Caroline , Péron Nicolas , Guérot Emmanuel , Amoli Abolfazl Mohebbi , Benhamou Michel , Deyme Jean-Pierre , Andremont Olivier , Lena Diane , Cady Julien , Causeret Arnaud , De La Chapelle Arnaud , Cracco Christophe , Rouleau Stéphane , Schnell David , Foucault Camille , Lory Cécile , Chapelle Thibault , Bruckert Vincent , Garcia Julie , Sahraoui Abdlazize , Abbosh Nathalie , Bornstain Caroline , Pernet Pierre , Poirson Florent , Pasem Ahmed , Karoubi Philippe , Poupinel Virginie , Gauthier Caroline , Bouniol François , Feuchere Philippe , Bavozet Florent , Heron Anne , Carreira Serge , Emery Malo , Le Floch Anne Sophie , Giovannangeli Luana , Herzog Nicolas , Giacardi Christophe , Baudic Thibaut , Thill Chloé , Lebbah Said , Palmyre Jessica , Tubach Florence , Hajage David , Bonnet Nicolas , Ebstein Nathan , Gaudry Stéphane , Cohen Yves , Noublanche Julie , Lesieur Olivier , Sément Arnaud , Roca-Cerezo Isabel , Pascal Michel , Sma Nesrine , Colin Gwenhaël , Lacherade Jean-Claude , Bionz Gauthier , Maquigneau Natacha , Bouzat Pierre , Durand Michel , Hérault Marie-Christine , Payen Jean-Francois 
Published: April 2024

Background

Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring mechanical ventilation suffer from a high incidence of ventilator associated pneumonia (VAP), mainly related to Enterobacterales. Data regarding extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E) VAP are scarce. We aimed to investigate risk factors and outcomes of ESBL-E related VAP among critically ill coronavirus infectious disease-19 (COVID-19) patients who developed Enterobacterales related VAP.

Patients and methods

We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU) that included 4929 COVID-19 critically ill patients. For the present analysis, only patients with complete data regarding resistance status of the first episode of Enterobacterales related VAP (ESBL-E and/or carbapenem-resistant Enterobacterales, CRE) and outcome were included.

Results

We included 591 patients with Enterobacterales related VAP. The main causative species were Enterobacter sp (n = 224), E. coli (n = 111) and K. pneumoniae (n = 104). One hundred and fifteen patients (19%), developed a first ESBL-E related VAP, mostly related to Enterobacter sp (n = 40), K. pneumoniae (n = 36), and E. coli (n = 31). Eight patients (1%) developed CRE related VAP. In a multivariable analysis, African origin (North Africa or Sub-Saharan Africa) (OR 1.7 [1.07–2.71], p = 0.02), time between intubation and VAP (OR 1.06 [1.02–1.09], p = 0.002), PaO2/FiO2 ratio on the day of VAP (OR 0.997 [0.994–0.999], p = 0.04) and trimethoprim-sulfamethoxazole exposure (OR 3.77 [1.15–12.4], p = 0.03) were associated with ESBL-E related VAP. Weaning from mechanical ventilation and mortality did not significantly differ between ESBL-E and non ESBL-E VAP.

Conclusion

ESBL-related VAP in COVID-19 critically-ill patients was not infrequent. Several risk factors were identified, among which some are modifiable and deserve further investigation. There was no impact of resistance of the first Enterobacterales related episode of VAP on outcome.