Publications 2023

Mortality, incidence, and microbiological documentation of ventilated acquired

pneumonia (VAP) in critically ill patients with COVID-19 or influenza.

Laurichesse G(1), Schwebel C(2), Buetti N(3)(4), Neuville M(5), Siami S(6),

Cohen Y(7), Laurent V(8), Mourvillier B(9), Reignier J(10), Goldgran-Toledano

D(11), Ruckly S(3), de Montmollin E(3)(12), Souweine B(13)(14), Timsit

JF(3)(12), Dupuis C(15)(16); OUTCOME R. E. A. network.

Key message: In a prospective cohort, The risk of VAP is higher with Covid than with influenzae in mechanically ventilated patients. Risk of death of VAP patients in both groups are comparable.

BACKGROUND: Data on ventilator associated pneumonia (VAP) in COVID-19 and

influenza patients admitted to intensive care units (ICU) are scarce. This study

aimed to estimate day-60 mortality related to VAP in ICU patients ventilated for

at least 48 h, either for COVID-19 or for influenza, and to describe the

epidemiological characteristics in each group of VAP.

DESIGN: Multicentre retrospective observational study.

SETTING: Eleven ICUs of the French OutcomeRea™ network.

PATIENTS: Patients treated with invasive mechanical ventilation (IMV) for at

least 48 h for either COVID-19 or for flu.

RESULTS: Of the 585 patients included, 503 had COVID-19 and 82 had influenza

between January 2008 and June 2021. A total of 232 patients, 209 (41.6%) with

COVID-19 and 23 (28%) with influenza, developed 375 VAP episodes. Among the

COVID-19 and flu patients, VAP incidences for the first VAP episode were,

respectively, 99.2 and 56.4 per 1000 IMV days (p < 0.01), and incidences for all

VAP episodes were 32.8 and 17.8 per 1000 IMV days (p < 0.01). Microorganisms of

VAP were Gram-positive cocci in 29.6% and 23.5% of episodes of VAP (p < 0.01),

respectively, including Staphylococcus aureus in 19.9% and 11.8% (p = 0.25), and

Gram-negative bacilli in 84.2% and 79.4% (p = 0.47). In the overall cohort, VAP

was associated with an increased risk of day-60 mortality (aHR = 1.77 [1.36;

2.30], p < 0.01), and COVID-19 had a higher mortality risk than influenza

(aHR = 2.22 [CI 95%, 1.34; 3.66], p < 0.01). VAP was associated with increased

day-60 mortality among COVID-19 patients (aHR = 1.75 [CI 95%, 1.32; 2.33],

p < 0.01), but not among influenza patients (aHR = 1.75 [CI 95%, 0.48; 6.33],

p = 0.35).

CONCLUSION: The incidence of VAP was higher in patients ventilated for at least

48 h for COVID-19 than for influenza. In both groups, Gram-negative bacilli were

the most frequently detected microorganisms. In patients ventilated for either

COVID-19 or influenza VAP and COVID-19 were associated with a higher risk of

mortality.

DOI: 10.1186/s13613-023-01207-9

PMCID: PMC10616026

PMID: 37902869

Conflict of interest statement: J.F.T. is a member of scientific advisory boards

of Merck, Shionogi, Paratek, Gilead, Pfizer, Becton–Dickinson, and Aspen not

related to the submitted work. J.F.T. has given lectures at symposia for Merck,

Shionogi, Gilead, Pfizer, and Becton–Dickinson not related to the submitted

work. The other authors have no conflicts of interest to declare.

Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP) in patients with

acute exacerbation of COPD: From the French OUTCOMEREA cohort.

Galerneau LM(1)(2), Bailly S(3), Terzi N(4)(3), Ruckly S(5), Garrouste-Orgeas

M(6), Oziel J(7), Hong Tuan Ha V(8), Gainnier M(9), Siami S(10), Dupuis C(11),

Forel JM(12), Dartevel A(4), Dessajan J(13), Adrie C(14), Goldgran-Toledano

D(15), Laurent V(16), Argaud L(17), Reignier J(18), Pepin JL(3), Darmon M(19),

Timsit JF(13); OUTCOME R. E. A. network.

KEY MESSAGE:

Non invasive ventilation is extensively used in COPD patients with exacerbation in ICU and associated with an important risk of nosocomial pneumonia with poor outcome.

BACKGROUND: Non-ventilator-associated ICU-acquired pneumonia (NV-ICU-AP), a

nosocomial pneumonia that is not related to invasive mechanical ventilation

(IMV), has been less studied than ventilator-associated pneumonia, and never in

the context of patients in an ICU for severe acute exacerbation of chronic

obstructive pulmonary disease (AECOPD), a common cause of ICU admission. This

study aimed to determine the factors associated with NV-ICU-AP occurrence and

assess the association between NV-ICU-AP and the outcomes of these patients.

METHODS: Data were extracted from the French ICU database, OutcomeRea™. Using

survival analyses with competing risk management, we sought the factors

associated with the occurrence of NV-ICU-AP. Then we assessed the association

between NV-ICU-AP and mortality, intubation rates, and length of stay in the

ICU.

RESULTS: Of the 844 COPD exacerbations managed in ICUs without immediate IMV,

NV-ICU-AP occurred in 42 patients (5%) with an incidence density of 10.8 per

1,000 patient-days. In multivariate analysis, prescription of antibiotics at ICU

admission (sHR, 0.45 [0.23; 0.86], p = 0.02) and no decrease in consciousness

(sHR, 0.35 [0.16; 0.76]; p < 0.01) were associated with a lower risk of

NV-ICU-AP. After adjusting for confounders, NV-ICU-AP was associated with

increased 28-day mortality (HR = 3.03 [1.36; 6.73]; p < 0.01), an increased risk

of intubation (csHR, 5.00 [2.54; 9.85]; p < 0.01) and with a 10-day increase in

ICU length of stay (p < 0.01).

CONCLUSION: We found that NV-ICU-AP incidence reached 10.8/1000 patient-days and

was associated with increased risks of intubation, 28-day mortality, and longer

stay for patients admitted with AECOPD.

DOI: 10.1186/s13054-023-04631-2

PMCID: PMC10508006

PMID: 37726796 [Indexed for MEDLINE]

Conflict of interest statement: LMG is supported by Pfizer for attending

meetings and/or travel. NT is supported by Pfizer for attending meetings and/or

travel and non-financial supports from Gilead outside this work. The other

authors declare that they have no competing interests.

Epidemiology and risk factors of 28-day mortality of hospital-acquired

bloodstream infection in Turkish intensive care units: a prospective

observational cohort study.

Aslan AT(1)(2), Tabah A(2)(3)(4), Köylü B(1), Kalem AK(5), Aksoy F(6), Erol

Ç(7), Karaali R(8), Tunay B(9), Guzeldağ S(10), Batirel A(11), Dindar EK(12),

Akdoğan Ö(13), Bilir Y(14), Ersöz G(15), Öztürk B(16), Selçuk M(17), Yilmaz

M(18), Akyol A(19), Akbaş T(20), Sungurtekin H(21), Timuroğlu A(22), Gürbüz

Y(23), Çolak O(24), Bayindir Y(25), Eroğlu A(26), Ferlicolak L(27), Çeşme U(28),

Dağ O(29), Buetti N(30)(31), Barbier F(32), Ruckly S(33), Staiquly Q(33), Timsit

JF(34), Akova M(35).

KEY MESSAGE:

A subgroup analysis of the EUROBACT2 study in Turkey (Eurobact2 is leaded by prof A Tabah on behalf of the OUTCOMEREA study group). The risk of XDR and DTR bacteria is worrisome.

OBJECTIVES: To uncover clinical epidemiology, microbiological characteristics

and outcome determinants of hospital-acquired bloodstream infections (HA-BSIs)

in Turkish ICU patients.

METHODS: The EUROBACT II was a prospective observational multicontinental cohort

study. We performed a subanalysis of patients from 24 Turkish ICUs included in

this study. Risk factors for mortality were identified using multivariable Cox

frailty models.

RESULTS: Of 547 patients, 58.7% were male with a median [IQR] age of 68 [55-78].

Most frequent sources of HA-BSIs were intravascular catheter [182, (33.3%)] and

lower respiratory tract [175, (32.0%)]. Among isolated pathogens (n = 599),

67.1% were Gram-negative, 21.5% Gram-positive and 11.2% due to fungi. Carbapenem

resistance was present in 90.4% of Acinetobacter spp., 53.1% of Klebsiella spp.

and 48.8% of Pseudomonas spp. In monobacterial Gram-negative HA-BSIs (n = 329),

SOFA score (aHR 1.20, 95% CI 1.14-1.27), carbapenem resistance (aHR 2.46, 95% CI

1.58-3.84), previous myocardial infarction (aHR 1.86, 95% CI 1.12-3.08),

COVID-19 admission diagnosis (aHR 2.95, 95% CI 1.25-6.95) and not achieving

source control (aHR 2.02, 95% CI 1.15-3.54) were associated with mortality.

However, availability of clinical pharmacists (aHR 0.23, 95% CI 0.06-0.90) and

source control (aHR 0.46, 95% CI 0.28-0.77) were associated with survival. In

monobacterial Gram-positive HA-BSIs (n = 93), SOFA score (aHR 1.29, 95% CI

1.17-1.43) and age (aHR 1.05, 95% CI 1.03-1.08) were associated with mortality,

whereas source control (aHR 0.41, 95% CI 0.20-0.87) was associated with

survival.

CONCLUSIONS: Considering high antimicrobial resistance rate, importance of

source control and availability of clinical pharmacists, a multifaceted

management programme should be adopted in Turkish ICUs.

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DOI: 10.1093/jac/dkad167

PMCID: PMC10376926

PMID: 37264485 [Indexed for MEDLINE]

Corticosteroids for severe acute exacerbations of chronic obstructive pulmonary

disease in intensive care: From the French OUTCOMEREA cohort.

Galerneau LM(1)(2), Bailly S(2), Terzi N(1)(2), Ruckly S(3), Garrouste-Orgeas

M(4), Cohen Y(5), Hong Tuan Ha V(6), Gainnier M(7), Siami S(8), Dupuis C(9),

Darmon M(10), Azoulay E(10), Forel JM(11), Sigaud F(1), Adrie C(12),

Goldgran-Toledano D(13), Ferré A(14), de Montmollin E(15)(16), Argaud L(17),

Reignier J(18), Pepin JL(2), Timsit JF(15)(16); OUTCOMEREA network.

KEY MESSAGES

Systemic corticosteroid therapy appeared to improve outcome of severe exacerbation of COPD especially in the patients with the less severe COPD.

INTRODUCTION: Acute exacerbation of chronic obstructive pulmonary disease (COPD)

is a frequent cause of intensive care unit (ICU) admission. However, data are

scarce and conflicting regarding the impact of systemic corticosteroid treatment

in critically ill patients with acute exacerbation of COPD. The aim of the study

was to assess the impact of systemic corticosteroids on the occurrence of death

or need for continuous invasive mechanical ventilation at day 28 after ICU

admission.

METHODS: In the OutcomeReaTM prospective French national ICU database, we

assessed the impact of corticosteroids at admission (daily dose ≥ 0.5 mg/kg of

prednisone or equivalent during the first 24 hours ICU stay) on a composite

outcome (death or invasive mechanical ventilation) using an inverse probability

treatment weighting.

RESULTS: Between January 1, 1997 and December 31, 2018, 391 out of 1,247

patients with acute exacerbations of COPDs received corticosteroids at ICU

admission. Corticosteroids improved the main composite endpoint (OR = 0.70

[0.49; 0.99], p = 0.044. However, for the subgroup of most severe COPD patients,

this did not occur (OR = 1.12 [0.53; 2.36], p = 0. 770). There was no

significant impact of corticosteroids on rates of non-invasive ventilation

failure, length of ICU or hospital stay, mortality or on the duration of

mechanical ventilation. Patients on corticosteroids had the same prevalence of

nosocomial infections as those without corticosteroids, but more glycaemic

disorders.

CONCLUSION: Using systemic corticosteroids for acute exacerbation of COPD at ICU

admission had a positive effect on a composite outcome defined by death or need

for invasive mechanical ventilation at day 28.

under the terms of the Creative Commons Attribution License, which permits

unrestricted use, distribution, and reproduction in any medium, provided the

original author and source are credited.

DOI: 10.1371/journal.pone.0284591

PMCID: PMC10115304

PMID: 37075003 [Indexed for MEDLINE]

Conflict of interest statement: NT is supported by Pfizer for attending meetings

and/or travel. This does not alter our adherence to PLOS ONE policies on sharing

data and materials. The other authors declare that they have no competing

interests.

Clinical features, etiologies, and outcomes in adult patients with

meningoencephalitis requiring intensive care (EURECA): an international

prospective multicenter cohort study.

Sonneville R(1)(2)(3), de Montmollin E(4)(5), Contou D(6), Ferrer R(7), Gurjar

M(8), Klouche K(9), Sarton B(10), Demeret S(11), Bailly P(12), da Silva D(13),

Escudier E(14), Le Guennec L(15), Chabanne R(16), Argaud L(17), Ben Hadj Salem

O(18), Thyrault M(19), Frerou A(20), Louis G(21), De Pascale G(22), Horn J(23),

Helbok R(24)(25), Geri G(26), Bruneel F(27), Martin-Loeches I(28), Taccone

FS(29), De Waele JJ(30), Ruckly S(31), Staiquly Q(31), Citerio G(32)(33), Timsit

JF(4)(5); EURECA Investigator Study Group.

KEYMESSAGE:

Eureca is leaded by Prof Romain Sonneville on behalf of the Outcomerea study group. The prospective cohort of ICU patients describes epidemiology of meningoencephalitis in ICU (n=591). Poor outcome at 3 month is observed in half of the cases. Bacterial meningitis represents 42% of the cases. Early antibacterial and antiviral therapy is assoiated with an improved outcome.

PURPOSE: We aimed to characterize the outcomes of patients with severe

meningoencephalitis requiring intensive care.

METHODS: We conducted a prospective multicenter international cohort study

(2017-2020) in 68 centers across 7 countries. Eligible patients were adults

admitted to the intensive care unit (ICU) with meningoencephalitis, defined by

an acute onset of encephalopathy (Glasgow coma scale (GCS) score [Formula: see

text] 13), a cerebrospinal fluid pleocytosis [Formula: see text] 5 cells/mm3,

and at least two of the following criteria: fever, seizures, focal neurological

deficit, abnormal neuroimaging, and/or electroencephalogram. The primary

endpoint was poor functional outcome at 3 months, defined by a score of three to

six on the modified Rankin scale. Multivariable analyses stratified on centers

investigated ICU admission variables associated with the primary endpoint.

RESULTS: Among 599 patients enrolled, 589 (98.3%) completed the 3-month

follow-up and were included. Overall, 591 etiologies were identified in those

patients which were categorized into five groups: acute bacterial meningitis

(n = 247, 41.9%); infectious encephalitis of viral, subacute bacterial, or

fungal/parasitic origin (n = 140, 23.7%); autoimmune encephalitis (n = 38,

6.4%); neoplastic/toxic encephalitis (n = 11, 1.9%); and encephalitis of unknown

origin (n = 155, 26.2%). Overall, 298 patients (50.5%, 95% CI 46.6-54.6%) had a

poor functional outcome, including 152 deaths (25.8%). Variables independently

associated with a poor functional outcome were age > 60 years (OR 1.75, 95% CI

1.22-2.51), immunodepression (OR 1.98, 95% CI 1.27-3.08), time between hospital

and ICU admission > 1 day (OR 2.02, 95% CI 1.44-2.99), a motor component on the

GCS [Formula: see text] 3 (OR 2.23, 95% CI 1.49-3.45), hemiparesis/hemiplegia

(OR 2.48, 95% CI 1.47-4.18), respiratory failure (OR 1.76, 95% CI 1.05-2.94),

and cardiovascular failure (OR 1.72, 95% CI 1.07-2.75). In contrast,

administration of a third-generation cephalosporin (OR 0.54, 95% CI 0.37-0.78)

and acyclovir (OR 0.55, 95% CI 0.38-0.80) on ICU admission were protective.

CONCLUSION: Meningoencephalitis is a severe neurologic syndrome associated with

high mortality and disability rates at 3 months. Actionable factors for which

improvement could be made include time from hospital to ICU admission, early

antimicrobial therapy, and detection of respiratory and cardiovascular

complications at admission.

DOI: 10.1007/s00134-023-07032-9

PMID: 37022378 [Indexed for MEDLINE]

Outcomes in critically Ill HIV-infected patients between 1997 and 2020: analysis

of the OUTCOMEREA multicenter cohort.

Gaillet A(1)(2), Azoulay E(3), de Montmollin E(4)(5), Garrouste-Orgeas M(6),

Cohen Y(7), Dupuis C(8)(9), Schwebel C(10), Reignier J(11), Siami S(12), Argaud

L(13), Adrie C(14), Mourvillier B(15), Ruckly S(4), Forel JM(16), Timsit

JF(17)(18).

PURPOSE: Despite antiviral therapy (ART), 800,000 deaths still occur yearly and

globally due to HIV infection. In parallel with the good virological control and

the aging of this population, multiple comorbidities [HIV-associated-non-AIDS

(HANA) conditions] may now be observed.

METHODS: HIV adult patients hospitalized in intensive care unit (ICU) from all

the French region from university and non-university hospital who participate to

the OutcomeRea™ database on a voluntary basis over a 24-year period.

RESULTS: Of the 24,298 stays registered, 630 (2.6%) were a first ICU stay for

HIV patients. Over time, the mean age and number of comorbidities (diabetes,

renal and respiratory history, solid neoplasia) of patients increased. The

proportion of HIV diagnosed on ICU admission decreased significantly, while the

median duration of HIV disease as well as the percentage of ART-treated patients

increased. The distribution of main reasons for admission remained stable over

time (acute respiratory distress > shock > coma). We observed a significant drop

in the rate of active opportunistic infection on admission, while the rate of

active hemopathy (newly diagnosed or relapsed within the last 6 months prior to

admission to ICU) qualifying for AIDS increased-nonsignificantly-with a

significant increase in the anticancer chemotherapy administration in ICU.

Admissions for HANA or non-HIV reasons were stable over time. In multivariate

analysis, predictors of 60-day mortality were advanced age, chronic liver

disease, past chemotherapy, sepsis-related organ failure assessment score > 4 at

admission, hospitalization duration before ICU admission > 24 h, AIDS status,

but not the period of admission.

CONCLUSION: Whereas the profile of ICU-admitted HIV patients has evolved over

time (HIV better controlled but more associated comorbidities), mortality risk

factors remain stable, including AIDS status.

DOI: 10.1186/s13054-023-04325-9

PMCID: PMC10012467

PMID: 36915207 [Indexed for MEDLINE]

Conflict of interest statement: EA: Related to paper: none; Apart from the

paper: fees for lectures from Gilead, Pfizer, Baxter and Alexion. His research

group has been supported by Ablynx, Fisher & Payckle, Jazz Pharma, and MSD. CS:

Related to paper: none; Apart from the paper: fees for speaking

(Sanofi)—financial support for CME (Pfizer, MSD). JFT: Related to paper: none;

Apart from the paper: advisory boards: Pfizer, Gilead, Merck, BD France,

Shionogi. His research group has been supported by Merck, Thermofischer, Pfizer.

Incidence and risk factors of prolonged grief in relatives of patients with

terminal cancer in French palliative care units: The Fami-Life multicenter

cohort study.

Garrouste-Orgeas M(1)(2)(3), Marché V(4), Pujol N(5), Michel D(2), Evin A(6),

Fossez-Diaz V(7), Perruchio S(8), Vanbésien A(9), Verlaine C(10), Copel L(11),

Kaczmarek W(12), Birkui de Francqueville L(13), Michonneau-Gandon V(14), de

Larivière E(15), Poupardin C(16), Touzet L(17), Guastella V(18), Mathias C(19),

Mhalla A(20), Bouquet G(21), Richard B(22), Gracia D(23), Bienfait F(24),

Verliac V(25), Ranchou G(26), Kirsch S(27), Flahault C(28), Loiodice A(29),

Bailly S(30), Ruckly S(29), Timsit JF(1)(31).

OBJECTIVES: Psychological consequences of grief among relatives are

insufficiently known. We reported incidence of prolonged grief among relatives

of deceased patients with cancer.

METHODS: Prospective cohort study of 611 relatives of 531 patients with cancer

hospitalized for more than 72 hours and who died in 26 palliative care units was

conducted. The primary outcome was prolonged grief in relatives 6 months after

patient death, measured with the Inventory Complicated Grief (ICG > 25, range

0-76, a higher score indicates more severe symptoms) score. Secondary outcomes

in relatives 6 months after patient death were anxiety and depression symptoms

based on Hospital Anxiety and Depression Scale (HADS) score (range 0 [best]-42

[worst]), higher scores indicate more severe symptoms, minimally important

difference 2.5. Post-traumatic stress disorder symptoms were defined by an

Impact Event Scale-Revised score >22 (range 0-88, a higher score indicates more

severe symptoms).

RESULTS: Among 611 included relatives, 608 (99.5%) completed the trial. At

6 months, significant ICG scores were reported by 32.7% relatives (199/608, 95%

CI, 29.0-36.4). The median (interquartile range ICG score) was 20.0 (11.5-29.0).

The incidence of HADS symptoms was 87.5% (95% CI, 84.8-90.2%) at Days 3-5 and

68.7% (95% CI, 65.0-72.4) 6 months after patient's death, with a median

(interquartile range) difference of -4 (-10 to 0) between these 2 time points.

Improvement in HADS anxiety and depression scores were reported by 62.5%

(362/579) relatives.

SIGNIFICANCE OF RESULTS: These findings support the importance of screening

relatives having risk factors of developing prolonged grief in the palliative

unit and 6 months after patient's death.

DOI: 10.1017/S1478951523000111

PMID: 36878669

Ventilator-Associated Pneumonia in COVID-19 Patients Admitted in Intensive Care

Units: Relapse, Therapeutic Failure and Attributable Mortality-A Multicentric

Observational Study from the OutcomeRea Network.

Wicky PH(1), Dupuis C(2)(3), Cerf C(4), Siami S(5), Cohen Y(6), Laurent V(7),

Mourvillier B(8), Reignier J(9), Goldgran-Toledano D(10), Schwebel C(11), Ruckly

S(2), de Montmollin E(1)(2), Buetti N(2)(12), Timsit JF(1)(2).

KEY MESSAGES

The risk of VAP after sars Cov2 ARF is very high with a high risk of relapse.

The high relapse rate could be due to PK abnormalities, highly resistant bacteria or both.

Introduction: Ventilator-associated pneumonia (VAP) incidence is high among

critically ill COVID-19 patients. Its attributable mortality remains

underestimated, especially for unresolved episodes. Indeed, the impact of

therapeutic failures and the determinants that potentially affect mortality are

poorly evaluated. We assessed the prognosis of VAP in severe COVID-19 cases and

the impact of relapse, superinfection, and treatment failure on 60-day

mortality. Methods: We evaluated the incidence of VAP in a multicenter

prospective cohort that included adult patients with severe COVID-19, who

required mechanical ventilation for ≥48 h between March 2020 and June 2021. We

investigated the risk factors for 30-day and 60-day mortality, and the factors

associated with relapse, superinfection, and treatment failure. Results: Among

1424 patients admitted to eleven centers, 540 were invasively ventilated for 48

h or more, and 231 had VAP episodes, which were caused by Enterobacterales

(49.8%), P. aeruginosa (24.8%), and S. aureus (22%). The VAP incidence rate was

45.6/1000 ventilator days, and the cumulative incidence at Day 30 was 60%. VAP

increased the duration of mechanical ventilation without modifying the crude

60-day death rate (47.6% vs. 44.7% without VAP) and resulted in a 36% increase

in death hazard. Late-onset pneumonia represented 179 episodes (78.2%) and was

responsible for a 56% increase in death hazard. The cumulative incidence rates

of relapse and superinfection were 45% and 39.5%, respectively, but did not

impact death hazard. Superinfection was more frequently related to ECMO and

first episode of VAP caused by non-fermenting bacteria. The risk factors for

treatment failure were an absence of highly susceptible microorganisms and

vasopressor need at VAP onset. Conclusions: The incidence of VAP, mainly

late-onset episodes, is high in COVID-19 patients and associated with an

increased risk of death, similar to that observed in other mechanically

ventilated patients. The high rate of VAP due to difficult-to-treat

microorganisms, pharmacokinetic alterations induced by renal replacement

therapy, shock, and ECMO likely explains the high cumulative risk of relapse,

superinfection, and treatment failure.

DOI: 10.3390/jcm12041298

PMCID: PMC9961155

PMID: 36835834

Conflict of interest statement: JFT was on a scientific advisory board for

Merck, Shionogi, Paratek, Gilead, Pfizer, Becton-Dickinson, and Aspen, although

not related to the submitted work. JFT had given lectures at Merck, Shionogi,

Gilead, Pfizer, and Becton-Dickinson symposia, although not related to the

submitted work. The other authors have no conflicts of interest to declare.

Management of Acute Exacerbations of Chronic Obstructive Pulmonary Disease in

the ICU: An Observational Study From the OUTCOMEREA Database, 1997-2018.

Galerneau LM(1)(2), Bailly S(2), Terzi N(1)(2), Ruckly S(3), Garrouste-Orgeas

M(4), Cohen Y(5), Hong Tuan Ha V(6), Gainnier M(7), Siami S(8), Dupuis C(9),

Darmon M(10), Forel JM(11), Rigault G(1), Adrie C(12), Goldgran-Toledano D(13),

Laurent V(14), de Montmollin E(15)(16), Argaud L(17), Reignier J(18), Pepin

JL(2), Timsit JF(15)(16); OUTCOMEREA Network.

KEY MESSAGES

The prognosis of AECOPD improves with time and with increased use of non invasive ventilation. The article describes trend of care with time of AECOPD patients in the ICU.

OBJECTIVES: Our aim was to describe changes in the management of acute

exacerbations of chronic obstructive pulmonary disease (AECOPD) by ICUs and

patient outcomes.

DESIGN: We extracted data from the OutcomeRea database concerning patients

admitted for AECOPD between 1997 and 2018. We analyzed trends in the use of

ventilatory support, corticosteroid therapy, antibiotic therapy, and patient

survival.

SETTING: ICUs at 32 French sites.

PATIENTS: One thousand eight hundred sixteen patients in the database had a

diagnosis of AECOPD.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Over time, there was a reduction in the

prescription of corticosteroids and antibiotics. In a time-series analysis,

these changes in practice were not linked with ICU mortality. The proportion of

patients treated with invasive mechanical ventilation (IMV) also gradually

declined (from 51% between 1997 and 2002 to 35% between 2013 and 2018) with an

association between decrease in IMV use and reduction in ICU mortality in a time

series analysis. Rates of noninvasive ventilation (NIV) failure decreased with

an increase in NIV use to support weaning from IMV. There was a reduction in the

median ICU length of stay (from 8 d in 1997-2002 to 4 d in 2013-2018) and in the

median total duration of hospitalization (from 23 d in 1997-2002 to 14 d in

2013-2018). We observed an improvement in prognosis, with decreases in overall

hospital mortality (from 24% between 1997 and 2002 to 15% between 2013 and

2018), ICU mortality (from 14% between 1997 and 2002 to 10% between 2013 and

2018), and 90-day mortality (from 41% between 1997 and 2002 to 22% between 2013

and 2018).

CONCLUSIONS: The length of stay and mortality of patients with AECOPD admitted

to ICUs has decreased over the last 20 years, with a wider use of NIV and a

reduction in antibiotic and corticosteroid prescriptions.

DOI: 10.1097/CCM.0000000000005807

PMID: 36790209 [Indexed for MEDLINE]

Conflict of interest statement: Dr. Terzi received funding from Pfizer for

attending meetings and/or travel. Dr. Hong Tuan Ha disclosed work for hire. The

remaining authors have disclosed that they do not have any potential conflicts

of interest.

Epidemiology and outcomes of hospital-acquired bloodstream infections in

intensive care unit patients: the EUROBACT-2 international cohort study.

Tabah A(1)(2)(3)(4), Buetti N(5)(6), Staiquly Q(7), Ruckly S(6)(7), Akova M(8),

Aslan AT(9), Leone M(10), Conway Morris A(11)(12)(13), Bassetti M(14), Arvaniti

K(15), Lipman J(16)(17)(18), Ferrer R(19), Qiu H(20), Paiva JA(21)(22)(23),

Povoa P(24)(25)(26), De Bus L(27), De Waele J(28)(29), Zand F(30), Gurjar M(31),

Alsisi A(32)(33), Abidi K(34), Bracht H(35), Hayashi Y(36), Jeon K(37), Elhadi

M(38), Barbier F(39), Timsit JF(40)(41); EUROBACT-2 Study Group, ESICM, ESCMID

ESGCIP and the OUTCOMEREA Network.

KEY MESSAGES:

Eurobact2 is a large multicenter international study on HA-BSI hospitalized in ICU.

The article describes epidemiological data and the dramatic rate of bacterial resistance wordwide associated with this disease.

PURPOSE: In the critically ill, hospital-acquired bloodstream infections

(HA-BSI) are associated with significant mortality. Granular data are required

for optimizing management, and developing guidelines and clinical trials.

METHODS: We carried out a prospective international cohort study of adult

patients (≥ 18 years of age) with HA-BSI treated in intensive care units (ICUs)

between June 2019 and February 2021.

RESULTS: 2600 patients from 333 ICUs in 52 countries were included. 78% HA-BSI

were ICU-acquired. Median Sequential Organ Failure Assessment (SOFA) score was 8

[IQR 5; 11] at HA-BSI diagnosis. Most frequent sources of infection included

pneumonia (26.7%) and intravascular catheters (26.4%). Most frequent pathogens

were Gram-negative bacteria (59.0%), predominantly Klebsiella spp. (27.9%),

Acinetobacter spp. (20.3%), Escherichia coli (15.8%), and Pseudomonas spp.

(14.3%). Carbapenem resistance was present in 37.8%, 84.6%, 7.4%, and 33.2%,

respectively. Difficult-to-treat resistance (DTR) was present in 23.5% and

pan-drug resistance in 1.5%. Antimicrobial therapy was deemed adequate within

24 h for 51.5%. Antimicrobial resistance was associated with longer delays to

adequate antimicrobial therapy. Source control was needed in 52.5% but not

achieved in 18.2%. Mortality was 37.1%, and only 16.1% had been discharged

alive from hospital by day-28.

CONCLUSIONS: HA-BSI was frequently caused by Gram-negative, carbapenem-resistant

and DTR pathogens. Antimicrobial resistance led to delays in adequate

antimicrobial therapy. Mortality was high, and at day-28 only a minority of the

patients were discharged alive from the hospital. Prevention of antimicrobial

resistance and focusing on adequate antimicrobial therapy and source control are

important to optimize patient management and outcomes.

DOI: 10.1007/s00134-022-06944-2

PMCID: PMC9916499

PMID: 36764959 [Indexed for MEDLINE]

Conflict of interest statement: AT has nothing to disclose, NB has nothing to

disclose, QS has nothing to disclose, SR has nothing to disclose, MA reports

honoraria paid to his university for educational activities by Pfizer, Sanofi,

MSD and Astra Zeneca, ATA has nothing to disclose, ML reported consulting and

lecture fees from Amomed Pharma, Aspen, LFB and Gilead, ACM has received payment

for speaking on behalf of Boston Scientific and sits on the Scientific Advisory

Board of Cambridge Infection Diagnostics, a start-up seeking to develop novel

diagnostics for infectious diseases, MB received advisory board, speaker

activities from Angelini, Bayer, Biomerieux, Cidara, Gilead, Menarini, MSD,

Pfizer, Roche, Shionogi, study grants from: Angelini, Shionogi, Cidara, Gilead,

Pfizer, and MSD, KA has nothing to disclose, JL has received lecture fees and

honoraria from MSD, RF reports Payment for lectures, speakers bureaus or

advisory boards from Grifols, MSD, Pfizer, Gilead, Shionogi, Thermofisher, Hill

Rom, AOP Health, BD, HQ has nothing to disclose, JAP reports consulting,

advisory boards or lectures fees and honoraria for MSD, Pfizer, Astra-Zeneca,

Gilead, Jansen, Cepheid, AOP Orphan Pharmaceuticals, PP reported advisory boards

participation for Gilead, Technophage and Sanofi, lectures fees from MSD, Gilead

and Pfizer, and research grant from Abionic, LDB has nothing to disclose, JdW

has consulted for Pfizer, MSD (honoraria paid to institution), FZ has nothing to

disclose, MG has nothing to disclose, AA has nothing to disclose, KA has nothing

to disclose, HB has nothing to disclose, YH has nothing to disclose, KJ has

nothing to disclose, ME has nothing to disclose, FB reported consulting and

lecture fees, conference invitation from MSD and lecture fees from BioMérieux,

J-FT reported advisory boards participation for Merck, Gilead,

Beckton-Dickinson, Pfizer, Shinogi, Medimune, Paratek, research grants from

Merck, Pfizer, Thermofischer.