Publications 2024

Treatment of positive catheter tip culture without bloodstream infections in

critically ill patients. A case-cohort study from the OUTCOMEREA network.

Buetti N(1)(2), Zahar JR(3)(4), Adda M(5), Ruckly S(3)(6), Bruel C(7), Schwebel

C(8), Darmon M(9), Adrie C(10), Cohen Y(11), Siami S(12), Laurent V(13),

Souweine B(5), Timsit JF(3)(6)(14); OUTCOMEREA Network.

PURPOSE: This study aimed to evaluate the impact on subsequent infections and

mortality of an adequate antimicrobial therapy within 48 h after catheter

removal in intensive care unit (ICU) patients with positive catheter tip

culture.

METHODS: We performed a retrospective analysis of prospectively collected data

from 29 centers of the OUTCOMEREA network. We developed a propensity score (PS)

for adequate antimicrobial treatment, based on expert opinion of 45 attending

physicians. We conducted a 1:1 case-cohort study matched on the PS score of

being adequately treated. A PS-matched subdistribution hazard model was used for

detecting subsequent infections and a PS-matched Cox model was used to evaluate

the impact of antibiotic therapy on mortality.

RESULTS: We included 427 patients with a catheter tip culture positive with

potentially pathogenic microorganisms. We matched 150 patients with an adequate

antimicrobial therapy with 150 controls. In the matched population, 30 (10%)

subsequent infections were observed and 62 patients died within 30 days. Using

subdistribution hazard models, the daily risk to develop subsequent infection up

to Day-30 was similar between treated and non-treated groups (subdistribution

hazard ratio [sHR] 1.08, 95% confidence interval [CI] 0.62-1.89, p = 0.78).

Using Cox proportional hazard models, the 30-day mortality risk was similar

between treated and non-treated groups (HR 0.89, 95% CI 0.45-1.74, p = 0.73).

CONCLUSIONS: Antimicrobial therapy was not associated with decreased risk of

subsequent infection or death in short-term catheter tip colonization in

critically ill patients. Antibiotics may be unnecessary for positive catheter

tip cultures.

DOI: 10.1007/s00134-024-07498-1

PMID: 38913096

Presentation, management, and outcomes of older compared to younger adults with

hospital-acquired bloodstream infections in the intensive care unit: a

multicenter cohort study.

Margalit I(1)(2), Yahav D(3)(4), Hoffman T(3)(4), Tabah A(5)(6)(7), Ruckly

S(8)(9), Barbier F(10), Singer P(4)(11), Timsit JF(8)(12), Prendki

V(#)(13)(14)(15), Buetti N(#)(8)(15); EUROBACT-2 Study Group, the European

Society of Intensive Care Medicine (ESICM), the European Society of Clinical

Microbiology and Infectious Diseases (ESCMID) Study Groups for Infections in

Critically Ill Patients (ESGCIP) and Infections in the Elderly (ESGIE), and the

OUTCOMEREA Network.

PURPOSE: Older adults admitted to the intensive care unit (ICU) usually have

fair baseline functional capacity, yet their age and frailty may compromise

their management. We compared the characteristics and management of older

(≥ 75 years) versus younger adults hospitalized in ICU with hospital-acquired

bloodstream infection (HA-BSI).

METHODS: Nested cohort study within the EUROBACT-2 database, a multinational

prospective cohort study including adults (≥ 18 years) hospitalized in the ICU

during 2019-2021. We compared older versus younger adults in terms of infection

characteristics (clinical signs and symptoms, source, and microbiological data),

management (imaging, source control, antimicrobial therapy), and outcomes

(28-day mortality and hospital discharge).

RESULTS: Among 2111 individuals hospitalized in 219 ICUs with HA-BSI, 563 (27%)

were ≥ 75 years old. Compared to younger patients, these individuals had higher

comorbidity score and lower functional capacity; presented more often with a

pulmonary, urinary, or unknown HA-BSI source; and had lower heart rate, blood

pressure and temperature at presentation. Pathogens and resistance rates were

similar in both groups. Differences in management included mainly lower rates of

effective source control achievement among aged individuals. Older adults also

had significantly higher day-28 mortality (50% versus 34%, p < 0.001), and lower

rates of discharge from hospital (12% versus 20%, p < 0.001) by this time.

CONCLUSIONS: Older adults with HA-BSI hospitalized in ICU have different

baseline characteristics and source of infection compared to younger patients.

Management of older adults differs mainly by lower probability to achieve source

control. This should be targeted to improve outcomes among older ICU patients.

DOI: 10.1007/s15010-024-02304-y

PMID: 38869773

Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a

post-hoc analysis of the EUROBACT-2 international cohort study.

Wozniak H(1)(2), Tabah A(3)(4)(5)(6), Barbier F(7), Ruckly S(8)(9), Loiodice

A(9), Akova M(10), Leone M(11), Conway Morris A(12)(13)(14), Bassetti M(15),

Arvaniti K(16), Ferrer R(17), de Bus L(18)(19), Paiva JA(20)(21), Bracht H(22),

Mikstacki A(23)(24), Alsisi A(25)(26), Valeanu L(27), Prazak J(28), Timsit

JF(29)(30), Buetti N(29)(31); EUROBACT-2 Study Group, ESICM, ESCMID ESGCIP and

the OUTCOMEREA Network.

BACKGROUND: Hospital-acquired bloodstream infections are common in the intensive

care unit (ICU) and have a high mortality rate. Patients with cirrhosis are

especially susceptible to infections, yet there is a knowledge gap in the

epidemiological distinctions in hospital-acquired bloodstream infections between

cirrhotic and non-cirrhotic patients in the ICU. It has been suggested that

cirrhotic patients, present a trend towards more gram-positive infections, and

especially enterococcal infections. This study aims to describe epidemiological

differences in hospital-acquired bloodstream infections between cirrhotic and

non-cirrhotic patients hospitalized in the ICU regarding infection sources,

microorganisms and mortality.

METHODS: Using prospective Eurobact-2 international cohort study data, we

compared hospital-acquired bloodstream infections sources and microorganisms in

cirrhotic and non-cirrhotic patients. The association between Enterococcus

faecium and cirrhosis was studied using a multivariable mixed logistic

regression. The association between cirrhosis and mortality was assessed by a

multivariable frailty Cox model.

RESULTS: Among the 1059 hospital-acquired bloodstream infections patients

included from 101 centers, 160 had cirrhosis. Hospital-acquired bloodstream

infection source in cirrhotic patients was primarily abdominal (35.6%), while it

was pulmonary (18.9%) for non-cirrhotic (p < 0.01). Gram-positive

hospital-acquired bloodstream infections accounted for 42.3% in cirrhotic

patients compared to 33.2% in non-cirrhotic patients (p = 0.02).

Hospital-acquired bloodstream infections in cirrhotic patients were most

frequently caused by Klebsiella spp (16.5%), coagulase-negative Staphylococci

(13.7%) and E. faecium (11.5%). E. faecium bacteremia was more frequent in

cirrhotic patients (11.5% versus 4.5%, p < 0.01). After adjusting for possible

confounding factors, cirrhosis was associated with higher E. faecium

hospital-acquired bloodstream infections risk (Odds ratio 2.5, 95% CI 1.3-4.5,

p < 0.01). Cirrhotic patients had increased mortality compared to non-cirrhotic

patients (Hazard Ratio 1.3, 95% CI 1.01-1.7, p = 0.045).

CONCLUSIONS: Critically ill cirrhotic patients with hospital-acquired

bloodstream infections exhibit distinct epidemiology, with more Gram-positive

infections and particularly Enterococcus faecium.

DOI: 10.1186/s13613-024-01299-x

PMCID: PMC11065852

PMID: 38698291

The role of centre and country factors on process and outcome indicators in

critically ill patients with hospital-acquired bloodstream infections.

Buetti N(1)(2), Tabah A(3)(4)(5)(6), Setti N(7), Ruckly S(7)(8), Barbier

F(9)(10), Akova M(11), Aslan AT(12)(13), Leone M(14), Bassetti M(15), Morris

AC(16)(17)(18), Arvaniti K(19), Paiva JA(20)(21)(22), Ferrer R(23), Qiu H(24),

Montrucchio G(25)(26), Cortegiani A(27)(28), Kayaaslan B(29), De Bus L(30)(31),

De Waele JJ(30)(31), Timsit JF(7)(32); EUROBACT-2 Study Group, the European

Society of Intensive Care Medicine (ESICM), the European Society of Clinical

Microbiology, the Infectious Diseases (ESCMID) Study Group for Infections in

Critically Ill Patients (ESGCIP), and the OUTCOMEREA Network.

PURPOSE: The primary objective of this study was to evaluate the associations between centre/country-based factors and two important process and outcome indicators in patients with hospital-acquired bloodstream infections (HABSI). METHODS: We used data on HABSI from the prospective EUROBACT-2 study to evaluate the associations between centre/country factors on a process or an outcome indicator: adequacy of antimicrobial therapy within the first 24 h or 28-day mortality, respectively. Mixed logistical models with clustering by centre identified factors associated with both indicators. RESULTS: Two thousand two hundred nine patients from two hundred one intensive care units (ICUs) were included in forty-seven countries. Overall, 51% (n = 1128) of patients received an adequate antimicrobial therapy and the 28-day mortality was 38% (n = 839). The availability of therapeutic drug monitoring (TDM) for aminoglycosides everyday [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.03-2.14] or within a few hours (OR 1.79, 95% CI 1.34-2.38), surveillance cultures for multidrug-resistant organism carriage performed weekly (OR 1.45, 95% CI 1.09-1.93), and increasing Human Development Index (HDI) values were associated with adequate antimicrobial therapy. The presence of intermediate care beds (OR 0.63, 95% CI 0.47-0.84), TDM for aminoglycoside available everyday (OR 0.66, 95% CI 0.44-1.00) or within a few hours (OR 0.51, 95% CI 0.37-0.70), 24/7 consultation of clinical pharmacists (OR 0.67, 95% CI 0.47-0.95), percentage of vancomycin-resistant enterococci (VRE) between 10% and 25% in the ICU (OR 1.67, 95% CI 1.00-2.80), and decreasing HDI values were associated with 28-day mortality. CONCLUSION: Centre/country factors should be targeted for future interventions to improve management strategies and outcome of HABSI in ICU patients.

DOI: 10.1007/s00134-024-07348-0

PMCID: PMC11164726

PMID: 38498170 [Indexed for MEDLINE]

Single-drug versus combination antimicrobial therapy in critically ill patients

with hospital-acquired pneumonia and ventilator-associated pneumonia due to

Gram-negative pathogens: a multicenter retrospective cohort study.

Barbier F(1)(2), Dupuis C(3), Buetti N(4)(5), Schwebel C(6), Azoulay É(7),

Argaud L(8), Cohen Y(9), Hong Tuan Ha V(10), Gainnier M(11), Siami S(12), Forel

JM(13), Adrie C(14), de Montmollin É(15), Reignier J(16), Ruckly S(17), Zahar

JR(5)(18), Timsit JF(5)(15); OutcomeRéa Study Group.

KEY MESSAGES: In this study including 391 critically ill patients with

nosocomial pneumonia due to Gram-negative pathogens, combination therapy was not

associated with a reduced hazard of death at Day 28 or a greater likelihood of

clinical cure at Day 14. No over-risk of AKI was observed in patients receiving

combination therapy.

BACKGROUND: The benefits and harms of combination antimicrobial therapy remain

controversial in critically ill patients with hospital-acquired pneumonia (HAP),

ventilated HAP (vHAP) or ventilator-associated pneumonia (VAP) involving

Gram-negative bacteria.

METHODS: We included all patients in the prospective multicenter OutcomeRea

database with a first HAP, vHAP or VAP due to a single Gram-negative bacterium

and treated with initial adequate single-drug or combination therapy. The

primary endpoint was Day-28 all-cause mortality. Secondary endpoints were

clinical cure rate at Day 14 and a composite outcome of death or

treatment-emergent acute kidney injury (AKI) at Day 7. The average effects of

combination therapy on the study endpoints were investigated through inverse

probability of treatment-weighted regression and multivariable regression

models. Subgroups analyses were performed according to the resistance phenotype

of the causative pathogens (multidrug-resistant or not), the pivotal

(carbapenems or others) and companion (aminoglycosides/polymyxins or others)

drug classes, the duration of combination therapy (< 3 or ≥ 3 days), the SOFA

score value at pneumonia onset (< 7 or ≥ 7 points), and in patients with

pneumonia due to non-fermenting Gram-negative bacteria, pneumonia-related

bloodstream infection, or septic shock.

RESULTS: Among the 391 included patients, 151 (38.6%) received single-drug

therapy and 240 (61.4%) received combination therapy. VAP (overall, 67.3%), vHAP

(16.4%) and HAP (16.4%) were equally distributed in the two groups. All-cause

mortality rates at Day 28 (overall, 31.2%), clinical cure rate at Day 14 (43.7%)

and the rate of death or AKI at Day 7 (41.2%) did not significantly differ

between the groups. In inverse probability of treatment-weighted analyses,

combination therapy was not independently associated with the likelihood of

all-cause death at Day 28 (adjusted odd ratio [aOR], 1.14; 95% confidence

interval [CI] 0.73-1.77; P = 0.56), clinical cure at Day 14 (aOR, 0.79; 95% CI

0.53-1.20; P = 0.27) or death or AKI at Day 7 (aOR, 1.07; 95% CI 0.71-1.63;

P = 0.73). Multivariable regression models and subgroup analyses provided