Different Epidemiology of Bloodstream Infections in COVID-19 Compared to non-COVID-19 Critically ill Patients

A Descriptive Analysis of the Eurobact II Study

Niccolò Buetti; Alexis Tabah; Ambre Loiodice; Stéphane Ruckly; Abdullah Tarik Aslan; Giorgia Montrucchio; Andrea Cortegiani; Nese Saltoglu; Bircan Kayaaslan; Firdevs Aksoy; Akova Murat; Özlem Akdoğan; Kemal Tolga Saracoglu; Cem Erdogan; Marc Leone; Ricard Ferrer; José-Artur Paiva; Yoshiro Hayashi; Mahesh Ramanan; Andrew Conway Morris; François Barbier; Jean-François Timsit

Disclosures

Crit Care. 2022;26(319)

Abstract and Introduction

Abstract

Background: The study aimed to describe the epidemiology and outcomes of hospital-acquired bloodstream infections (HABSIs) between COVID-19 and non-COVID-19 critically ill patients.

Methods: We used data from the Eurobact II study, a prospective observational multicontinental cohort study on HABSI treated in ICU. For the current analysis, we selected centers that included both COVID-19 and non-COVID-19 critically ill patients. We performed descriptive statistics between COVID-19 and non-COVID-19 in terms of patients' characteristics, source of infection and microorganism distribution. We studied the association between COVID-19 status and mortality using multivariable fragility Cox models.

Results: A total of 53 centers from 19 countries over the 5 continents were eligible. Overall, 829 patients (median age 65 years [IQR 55; 74]; male, n = 538 [64.9%]) were treated for a HABSI. Included patients comprised 252 (30.4%) COVID-19 and 577 (69.6%) non-COVID-19 patients. The time interval between hospital admission and HABSI was similar between both groups. Respiratory sources (40.1 vs. 26.0%, p < 0.0001) and primary HABSI (25.4% vs. 17.2%, p = 0.006) were more frequent in COVID-19 patients. COVID-19 patients had more often enterococcal (20.5% vs. 9%) and Acinetobacter spp. (18.8% vs. 13.6%) HABSIs. Bacteremic COVID-19 patients had an increased mortality hazard ratio (HR) versus non-COVID-19 patients (HR 1.91, 95% CI 1.49–2.45).

Conclusions: We showed that the epidemiology of HABSI differed between COVID-19 and non-COVID-19 patients. Enterococcal HABSI predominated in COVID-19 patients. COVID-19 patients with HABSI had elevated risk of mortality.

Trial Registration: ClinicalTrials.org number NCT03937245. Registered 3 May 2019.

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Crit Care. 2022;26(319) © 2022 BioMed Central, Ltd.
Copyright to this article is held by the author(s), licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original citation.

Table 1. Patients' characteristics on admission, at HABSI time and outcome
Variable	All HABSI (n = 829)	COVID-19 patient (n = 252)	Non-COVID-19 patient (n = 577)	p value
Patient characteristics on ICU admission:
Time from hospital admission to HABSI onset	15 [8; 27]	14 [9; 23]	15 [8; 29]	0.69
Time from ICU admission to HABSI	9 [4; 17]	10 [6; 16]	8 [2; 17]	0.017
Age, years	65 [55; 74]	66 [56; 74]	65 [55; 74]	0.30
Gender
Female	291 (35.1)	80 (31.7)	211 (36.6)	0.18
Male	538 (64.9)	172 (68.3)	366 (63.4)
BMI¹	26.8 [24.1; 30.4]	27.8 [24.9; 31.7]	26.3 [23.4; 29.4]	< 0.0001
Comorbidities
Respiratory	147 (17.7)	33 (13.1)	114 (19.8)	0.021
Cardio-vascular	191 (23)	57 (22.6)	134 (23.2)	0.85
Neurological	137 (16.5)	27 (10.7)	110 (19.1)	0.0029
Metabolic disorders	326 (39.3)	107 (42.5)	219 (38)	0.22
Gastro-intestinal	49 (5.9)	13 (5.2)	36 (6.2)	0.54
Immunosuppression	122 (14.7)	15 (6)	107 (18.5)	< 0.0001
Malignancy	143 (17.2)	19 (7.5)	124 (21.5)	< 0.0001
Steroids for sepsis or septic shock²	204 (25)	74 (29.7)	130 (22.9)	0.038
ICU admission origin
Emergency department	277 (33.4)	73 (29)	204 (35.4)	< 0.0001
Hospital ward/floor	327 (39.4)	111 (44)	216 (37.4)
Operating room/recovery	67 (8.1)	1 (0.4)	66 (11.4)
Other hospital	118 (14.2)	47 (18.7)	71 (12.3)
Other intermediate care unit	26 (3.1)	10 (4)	16 (2.8)
Other	14 (1.7)	10 (4)	4 (0.7)
Admission type
Medical	693 (83.6)	249 (98.8)	444 (76.9)	< 0.0001
Surgical elective	30 (3.6)	2 (0.8)	28 (4.9)
Surgical emergency	106 (12.8)	1 (0.4)	105 (18.2)
SAPS II	47 [37; 58]	42 [33; 50]	49 [38; 62]	< 0.0001
Glasgow coma scale³	14 [8; 15]	15 [13; 15]	12 [6; 15]	< 0.0001
Ventilation status
High-flow oxygen nasal cannula	76 (9.2)	35 (13.9)	41 (7.1)	< 0.0001
Invasive mechanical ventilation	510 (61.5)	147 (58.3)	363 (62.9)
Low-flow oxygen or no oxygen	153 (18.5)	32 (12.7)	121 (21)
Non-invasive mechanical ventilation or CPAP	90 (10.9)	38 (15.1)	52 (9)
Patient characteristics at HABSI diagnosis:
Adrenaline	37 (4.5)	13 (5.2)	24 (4.2)	0.52
Noradrenaline⁴	413 (49.9)	127 (50.4)	286 (49.7)	0.84
SOFA	8 [5; 11]	8 [4; 11]	8 [5; 12]	0.13
Glasgow coma scale⁵	12 [7; 15]	14 [8; 15]	10 [6; 15]	< 0.0001
Ventilation status
High-flow oxygen nasal cannula	42 (5.1)	13 (5.2)	29 (5)	0.0003
Invasive mechanical ventilation	617 (74.4)	210 (83.3)	407 (70.5)
Low-flow oxygen or no oxygen	123 (14.8)	23 (9.1)	100 (17.3)
Non-invasive mechanical ventilation or CPAP	47 (5.7)	6 (2.4)	41 (7.1)
Source control required but not achieved	80 (9.7)	20 (7.9)	60 (10.4)	0.27
Adequate empirical therapy within the first 24h⁶	343 (48.5)	96 (48.2)	247 (48.4)	0.96
Corticosteroids for sepsis or septic shock	204 (25%)	74 (29.7)	130 (22.9)	0.038
Status at day 28
Alive in the Hospital	133 (16)	25 (9.9)	108 (18.7)	< 0.0001
Alive in the ICU	206 (24.8)	55 (21.8)	151 (26.2)
Death in the Hospital	16 (1.9)	3 (1.2)	13 (2.3)
Death in the ICU	363 (43.8)	145 (57.5)	218 (37.8)
Discharged from the Hospital	111 (13.4)	24 (9.5)	87 (15.1)
28-day mortality	379 (45.7)	148 (58.7)	231 (40)	< 0.0001

HA-BSI hospital-acquired bloodstream infection, ICU intensive care unit, SAPS Simplified Acute Physiology Score, SOFA sequential organ failure assessment score, CPAP continuous positive airway pressure
Results reported as n (%) for categorical variables and median [IQR] for continuous variables. Missing Data (MD): ¹BMI: 1 MD. ²Steroids for sepsis or septic shock: 12 MD. ³Glasgow coma scale on admission: 10 MD. ⁴Noradrenalin at HA-BSI onset: 1 MD. ⁵Glasgow coma scale at HA-BSI onset: 7 MD. ⁶Adequate treatment in the first 24 h with 120 MD

Table 2. Source of infections and microorganism groups
Variable	All HABSI (n = 829)	COVID-19 patient (n = 252)	Non-COVID-19 patient (n = 577)	p value
Previous antibiotics:
Antimicrobials received within the 7 days prior HABSI	622 (75)	204 (81)	418 (72.4)	0.0092
Source of infection:
Intravascular catheter	257 (31)	74 (29.4)	183 (31.7)	0.50
Respiratory tract	251 (30.3)	101 (40.1)	150 (26)	< 0.0001
Primary HABSI	163 (19.7)	64 (25.4)	99 (17.2)	0.0060
Intra-abdominal tract	75 (9)	3 (1.2)	72 (12.5)	< 0.0001
Bones and soft tissues	43 (5.2)	5 (2)	38 (6.6)	0.0060
Urinary tract	35 (4.2)	8 (3.2)	27 (4.7)	0.32
Other (endocarditis, mediastinitis, central nervous system)	28 (3.4)	4 (1.6)	24 (4.2)	0.059
Multiple first sources of infection	23 (2.8)	7 (2.8)	16 (2.8)	0.997
Microorganism group:
Gram-positive bacteria	285 (34.4)	100 (39.7)	185 (32.1)	0.033
Resistant* Gram-positive bacteria	108 (13)	32 (12.7)	76 (13.2)	0.85
Gram-negative bacteria	505 (60.9)	151 (59.9)	354 (61.4)	0.70
DTR Gram-negative bacteria	124 (15)	49 (19.4)	75 (13)	0.017
Fungi	79 (9.5)	19 (7.5)	60 (10.4)	0.20
Anaerobic bacteria	16 (1.9)	1 (0.4)	15 (2.6)	0.050
Polymicrobial HABSI	97 (11.7)	37 (14.7)	60 (10.4)	0.078

Results reported as n (%) for categorical variables and median [IQR] for continuous variables.
HABSI hospital-acquired bloodstream infection, DTR difficult-to-treat resistance.
*For example methicillin-resistant S. aureus.

Authors and Disclosures

Niccolò Buetti^1,2*, Alexis Tabah^3–5, Ambre Loiodice⁶, Stéphane Ruckly⁶, Abdullah Tarik Aslan⁷, Giorgia Montrucchio^8,9, Andrea Cortegiani^10,11, Nese Saltoglu¹², Bircan Kayaaslan¹³, Firdevs Aksoy¹⁴, Akova Murat¹⁵, Özlem Akdoğan¹⁶, Kemal Tolga Saracoglu¹⁷, Cem Erdogan¹⁸, Marc Leone¹⁹, Ricard Ferrer²⁰, José-Artur Paiva^21,22, Yoshiro Hayashi²³, Mahesh Ramanan^24–26, Andrew Conway Morris^27–29, François Barbier^30,31 and Jean-François Timsit^2,32 and the Eurobact 2 study group

¹Infection Control Program and WHO Collaborating Centre on Patient Safety, Geneva University Hospitals and Faculty of Medicine, Rue Gabrielle-Perret-Gentil 4, 1205 Geneva, Switzerland. ²INSERM, IAME, Université Paris-Cité, 75006 Paris, France. ³Intensive Care Unit, Redcliffe Hospital, Metro North Hospital and Health Services, Brisbane, QLD, Australia. ⁴Queensland University of Technology, Brisbane, QLD, Australia. ⁵Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia. ⁶ICURESEARCH, 26 rue Garibaldi, Fontaine, France. ⁷Department of Internal Medicine, Hacettepe University, Sihhiye, Ankara, Turkey. ⁸Department of Surgical Sciences, University of Turin, Turin, Italy. ⁹Department of Anaesthesia, Critical Care and Emergency, Città Della Salute e Della Scienza Hospital, Turin, Italy. ¹⁰Department of Surgical Oncological and Oral Science (Di.Chir.On.S.), University of Palermo, Palermo, Italy. ¹¹Department of Anesthesia, Intensive Care and Emergency, Policlinico Paolo Giaccone, Palermo, Italy. ¹²Department of Infectious Diseases and Clinical Microbiology, Istanbul University-Cerrahpasa, Istanbul, Turkey. ¹³Department of Infectious Diseases and Clinical Microbiology, Ankara City Hospital, Ankara Yıldırım Beyazıt University, Ankara, Turkey. ¹⁴Department of Infectious Diseases and Clinical Microbiology, Karadeniz Technical University, Ortahisar, Turkey. ¹⁵Department of Infectious Diseases and Clinical Microbiology, Hacettepe University, Ankara, Turkey. ¹⁶Department of Infectious Diseases and Clinical Microbiology, Erol Olcok Research and Training Hospital, Hitit University, Çorum Merkez, Turkey. ¹⁷Department of Anesthesiology and Reanimation, Kartal Dr. Lütfi Kırdar City Hospital, Kartal, Turkey. ¹⁸Department of Anesthesiology and Reanimation, Medipol Mega Hospital, Bağcılar, Turkey. ¹⁹Department of Anesthesiology and Intensive Care Unit, Hospital Nord, Assistance Publique Hôpitaux Universitaires de Marseille, Aix Marseille University, Marseille, France. ²⁰Intensive Care Department. SODIR Research Group, Vall d'Hebron Institute of Research VHIR, Hospital Universitari Vall d'Hebron, Barcelona, Spain. ²¹Intensive Care Medicine Department, Centro Hospitalar Universitário São João (CHUSJ), Porto, Portugal. ²²Department of Medicine, Faculty of Medicine, University of Porto (FMUP), Porto, Portugal. ²³Department of Intensive Care Medicine, Kameda General Hospital, Kamogawa, Japan. ²⁴Caboolture and The Prince Charles Hospitals, Metro North Hospital and Health Services, Brisbane, QLD, Australia. ²⁵Critical Care Division, The George Institute for Global Health, University of New South Wales, Sydney, Australia. ²⁶School of Medicine, University of Queensland, St Lucia, Australia. ²⁷Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK. ²⁸Division of Immunology, Department of Pathology, University of Cambridge, Cambridge, UK. ²⁹JVF Intensive Care Unit, Addenbrooke's Hospital, Cambridge, UK. ³⁰Médecine Intensive Réanimation, Centre Hospitalier Régional d'Orléans, Orléans, France. ³¹Centre d'Etude des Pathologies Respiratoires (CEPR), INSERM U1100, Université de Tours, Tours, France. ³²Medical and Infectious Diseases Intensive Care Unit, AP-HP, Bichat-Claude Bernard University Hospital, 46 rue Henri Huchard, 75877 Paris Cedex, France.

*Correspondence
niccolo.buetti@gmail.com

Author contributions
NB, AT and JFT designed the study. All authors acquired the data. NB, AL, SR and JFT did the statistical analysis. NB, AL, SR, AT and JFT analyzed and interpreted the data. NB and JFT drafted the manuscript. All authors critically reviewed the manuscript and approved the final report. All authors read and approved the final manuscript.

Competing interests
The authors have disclosed that they do not have conflict of interest. Dr. Buetti received a grant from the Swiss National Science Foundation (Grant Number: P4P4PM_194449). Prof. Timsit received fees for lectures to 3M, MSD, Pfizer, and BioMérieux; he received research grants from Astellas, 3M, MSD, and Pfizer; and he participated to advisory boards of 3M, MSD, Bayer Pharma, Nabriva, and Pfizer. Dr. Barbier received consulting and lecture fees from MSD and BioMérieux. Prof. Cortegiani received fees for lectures from Gilead, MSD, Pfizer; and he participated to advisory boards of MSD, Gilead, Pfizer. Dr. Montrucchio received fees for lectures from Gilead, Pfizer, Thermofisher; and she participated to advisory boards of Gilead. Dr. Conway Morris sits on the scientific advisory board of Cambridge Infection Diagnostics. Prof. Akova received grants from Pfizer and Gilead, had lecture fees paid to the institution by Pfizer and Sanofi. Dr. Ramanan acknowledges support from the Metro North Hospital and Health Services Clinician-Researcher Fellowship. Dr. Conway Morris sits on the scientific advisory board of Cambridge Infection Diagnostics. Dr. Conway Morris is supported by a Clinician Scientist Fellowship from the Medical Research Council (MR/V006118/1). Prof. José-Artur Paiva received fees for consulting, advisory boards or lectures from MSD, Pfizer, Astra-Zeneca, Gilead, Jansen, Cepheid, AOP Orphan Pharmaceuticals.