Relationship between COVID-19 and ICU-acquired colonization and infection related to multidrug-resistant bacteria: a prospective multicenter before-after study.

PURPOSE: Patients presenting the most severe form of coronavirus disease 2019 (COVID-19) pneumonia, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have a prolonged intensive care unit (ICU) stay and are exposed to broad-spectrum antibiotics, but the impact of COVID-19 on antimicrobial resistance is unknown. METHODS: Observational prospective before-after study in 7 ICUs in France. All consecutive patients with an ICU stay > 48 h and a confirmed SARS-CoV-2 infection were included prospectively and followed for 28 days. Patients underwent systematic screening for colonization with multidrug-resistant (MDR) bacteria upon admission and every week subsequently. COVID-19 patients were compared to a recent prospective cohort of control patients from the same ICUs. The primary objective was to investigate the association of COVID-19 with the cumulative incidence of a composite outcome including ICU-acquired colonization and/or infection related to MDR bacteria (ICU-MDR-col and ICU-MDR-inf, respectively). RESULTS: From February 27th, 2020 to June 2nd, 2021, 367 COVID-19 patients were included, and compared to 680 controls. After adjustment for prespecified baseline confounders, the cumulative incidence of ICU-MDR-col and/or ICU-MDR-inf was not significantly different between groups (adjusted sub-hazard ratio [sHR] 1.39, 95% confidence interval [CI] 0.91-2.09). When considering both outcomes separately, COVID-19 patients had a higher incidence of ICU-MDR-inf than controls (adjusted sHR 2.50, 95% CI 1.90-3.28), but the incidence of ICU-MDR-col was not significantly different between groups (adjusted sHR 1.27, 95% CI 0.85-1.88). CONCLUSION: COVID-19 patients had an increased incidence of ICU-MDR-inf compared to controls, but the difference was not significant when considering a composite outcome including ICU-MDR-col and/or ICU-MDR-inf.

Critically ill severe hypothyroidism: a retrospective multicenter cohort study.

BACKGROUND: Severe hypothyroidism (SH) is a rare but life-threatening endocrine emergency. Only a few data are available on its management and outcomes of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management, and in-ICU and 6-month survival rates of these patients. METHODS: We conducted a retrospective, multicenter study over 18 years in 32 French ICUs. The local medical records of patients from each participating ICU were screened using the International Classification of Disease 10th revision. Inclusion criteria were the presence of biological hypothyroidism associated with at least one cardinal sign among alteration of consciousness, hypothermia and circulatory failure, and at least one SH-related organ failure. RESULTS: Eighty-two patients were included in the study. Thyroiditis and thyroidectomy represented the main SH etiologies (29% and 19%, respectively), while hypothyroidism was unknown in 44 patients (54%) before ICU admission. The most frequent SH triggers were levothyroxine discontinuation (28%), sepsis (15%), and amiodarone-related hypothyroidism (11%). Clinical presentations included hypothermia (66%), hemodynamic failure (57%), and coma (52%). In-ICU and 6-month mortality rates were 26% and 39%, respectively. Multivariable analyses retained age > 70 years [odds ratio OR 6.01 (1.75-24.1)] Sequential Organ-Failure Assessment score cardiovascular component ≥ 2 [OR 11.1 (2.47-84.2)] and ventilation component ≥ 2 [OR 4.52 (1.27-18.6)] as being independently associated with in-ICU mortality. CONCLUSIONS: SH is a rare life-threatening emergency with various clinical presentations. Hemodynamic and respiratory failures are strongly associated with worse outcomes. The very high mortality prompts early diagnosis and rapid levothyroxine administration with close cardiac and hemodynamic monitoring.

Relationship between immunosuppression and intensive care unit-acquired colonization and infection related to multidrug-resistant bacteria: a prospective multicenter cohort study.

PURPOSE: The impact of immunosuppression on intensive care unit (ICU)-acquired colonization and infection related to multidrug-resistant (MDR) bacteria (ICU-MDR-col and ICU-MDR-inf, respectively) is unknown. METHODS: We carried out an observational prospective cohort study in 8 ICUs in France (all with single-bed rooms and similar organizational characteristics). All consecutive patients with an ICU stay > 48 h were included, regardless of immune status, and followed for 28 days. Patients underwent systematic screening for colonization with MDR bacteria upon admission and every week subsequently. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, solid-organ transplant, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic. The primary endpoint was the incidence rate of a composite outcome including ICU-MDR-col and/or ICU-MDR-inf. RESULTS: 750 patients (65.9% males, median age 65 years) were included, among whom 264 (35.2%) were immunocompromised. Reasons for ICU admission, severity scores and exposure to invasive devices and antibiotics during ICU stay were comparable between groups. After adjustment for center and pre-specified baseline confounders, immunocompromised patients had a lower incidence rate of ICU-MDR-col and/or ICU-MDR-inf (adjusted incidence ratio 0.68, 95% CI 0.52-0.91). When considered separately, the difference was significant for ICU-MDR-col, but not for ICU-MDR-inf. The distribution of MDR bacteria was comparable between groups, with a majority of Enterobacteriacae resistant to third-generation cephalosporins (~ 74%). CONCLUSION: Immunocompromised patients had a significantly lower incidence rate of a composite outcome including ICU-MDR-col and/or ICU-MDR-inf. This finding points to the role of contact precautions and isolation measures, and could have important implications on antibiotic stewardship in this population.

Central venous-to-arterial PCO2 difference as a marker to identify fluid responsiveness in septic shock.

Defining the hemodynamic response to volume therapy is integral to managing critically ill patients with acute circulatory failure, especially in the absence of cardiac index (CI) measurement. This study aimed at investigating whether changes in central venous-to-arterial CO2 difference (Δ-ΔPCO2) and central venous oxygen saturation (ΔScvO2) induced by volume expansion (VE) are reliable parameters to define fluid responsiveness in sedated and mechanically ventilated septic patients. We prospectively studied 49 critically ill septic patients in whom VE was indicated because of circulatory failure and clinical indices. CI, ΔPCO2, ScvO2, and oxygen consumption (VO2) were measured before and after VE. Responders were defined as patients with a > 10% increase in CI (transpulmonary thermodilution) after VE. We calculated areas under the receiver operating characteristic curves (AUCs) for Δ-ΔPCO2, ΔScvO2, and changes in CI (ΔCI) after VE in the whole population and in the subgroup of patients with an increase in VO2 (ΔVO2) ≤ 10% after VE (oxygen-supply independency). Twenty-five patients were fluid responders. In the whole population, Δ-ΔPCO2 and ΔScvO2 were significantly correlated with ΔCI after VE (r = - 0.30, p = 0.03 and r = 0.42, p = 0.003, respectively). The AUCs for Δ-ΔPCO2 and ΔScvO2 to define fluid responsiveness (increase in CI > 10% after VE) were 0.76 (p < 0.001) and 0.68 (p = 0.02), respectively. In patients with ΔVO2 ≤ 10% (n = 36) after VE, the correlation between ΔScvO2 and ΔCI was 0.62 (p < 0.001), and between Δ-ΔPCO2 and ΔCI was - 0.47 (p = 0.004). The AUCs for Δ-ΔPCO2 and ΔScvO2 were 0.83 (p < 0.001) and 0.73 (p = 0.006), respectively. In these patients, Δ-ΔPCO2 ≤ -37.5% after VE allowed the categorization between responders and non-responders with a positive predictive value of 100% and a negative predictive value of 60%. In sedated and mechanically ventilated septic patients with no signs of tissue hypoxia (oxygen-supply independency), Δ-ΔPCO2 is a reliable parameter to define fluid responsiveness.

Combination Therapy with Aminoglycoside in Bacteremiasdue to ESBL-Producing Enterobacteriaceae in ICU.

OBJECTIVES: Evaluation of the efficacy of empirical aminoglycoside in critically ill patients with bloodstream infections caused by extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-E BSI). METHODS: Patients treated between 2011 and 2018 for ESBL-E BSI in the ICU of six French hospitals were included in a retrospective observational cohort study. The primary endpoint was mortality on day 30. RESULTS: Among 307 patients, 169 (55%) were treated with empirical aminoglycoside. Death rate was 40% (43% with vs. 39% without aminoglycoside, p = 0.55). Factors independently associated with death were age ≥70 years (OR: 2.67; 95% CI: 1.09-6.54, p = 0.03), history of transplantation (OR 5.2; 95% CI: 1.4-19.35, p = 0.01), hospital acquired infection (OR 8.67; 95% CI: 1.74-43.08, p = 0.008), vasoactive drugs >48 h after BSI onset (OR 3.61; 95% CI: 1.62-8.02, p = 0.001), occurrence of acute respiratory distress syndrome (OR 2.42; 95% CI: 1.14-5.16, p = 0.02), or acute renal failure (OR 2.49; 95% CI: 1.14-5.47, p = 0.02). Antibiotherapy appropriateness was more frequent in the aminoglycoside group (91.7% vs. 77%, p = 0.001). Rate of renal impairment was similar in both groups (21% vs. 24%, p = 0.59). CONCLUSIONS: In intensive care unit (ICU) patients with ESBL-E BSI, empirical treatment with aminoglycoside was frequent. It demonstrated no impact on mortality, despite increasing treatment appropriateness.

Invasive Tracheobronchial Aspergillosis in Critically Ill Patients with Severe Influenza. A Clinical Trial.

Rationale: Invasive tracheobronchial aspergillosis (ITBA) is an uncommon but severe clinical form of invasive pulmonary aspergillosis in which the fungal infection is entirely or predominantly confined to the tracheobronchial tree.Objectives: To analyze the diagnostic and prognostic differences between tracheobronchial aspergillosis and pulmonary aspergillosis without tracheobronchial lesions among patients admitted to the ICU with severe influenza.Methods: This retrospective, observational study included critically ill patients with influenza associated with pulmonary aspergillosis from three hospital ICUs between 2010 and 2019. Patient characteristics and clinical and mycologic data at admission and during ICU stay were collected in a database to evaluate variables in the two groups.Measurements and Main Results: Thirty-five patients admitted to the ICU with severe influenza and pulmonary aspergillosis were included. Ten patients were included in the group with ITBA (n = 10 of 35; 28.6%), and 25 patients were included in the group without ITBA. The group with ITBA comprised more patients with active smoking, diabetes mellitus, and higher severity scores (Simplified Acute Physiology Score II). Ninety-day mortality rates in the groups with and without ITBA were 90% and 44%, respectively (P = 0.02). Moreover, significantly higher serum 1,3-ß-d-glucan and galactomannan and BAL fluid galactomannan concentrations were observed in the group with ITBA compared with the group without ITBA (P < 0.0001, P = 0.003, and P = 0.008, respectively).Conclusions: ITBA was associated with higher severity scores, mortality, and serum and BAL fluid galactomannan and 1,3-ß-d-glucan concentrations than invasive pulmonary aspergillosis without tracheobronchial lesions. ITBA should be systematically researched by bronchoscopic examination in ICU patients with concomitant pulmonary aspergillosis and influenza.Clinical trial registered with www.clinicaltrials.gov (NCT04077697).

Delayed but successful response to noninvasive ventilation in COPD patients with acute hypercapnic respiratory failure.

BACKGROUND: We evaluated a new noninvasive ventilation (NIV) protocol that allows the pursuit of NIV in the case of persistent severe respiratory acidosis despite a first NIV challenge in COPD patients with acute hypercapnic respiratory failure (AHRF). PATIENTS AND METHODS: A prospective observational multicentric pilot study was conducted in three tertiary hospitals over a 12-month study period. A total of 155 consecutive COPD patients who were admitted for AHRF and treated by NIV were enrolled. Delayed response to NIV was defined as a significant clinical improvement in the first 48 h following NIV initiation despite a persistent severe respiratory acidosis (pH <7.30) after the first 2 h of NIV trial. RESULTS: NIV failed in only 10 patients (6.5%). Delayed responders to NIV (n=83, 53%) exhibited similar nutritional status, comorbidities, functional status, frailty score, dyspnea score, and severity score at admission, compared with early responders (n=62, 40%). Only age (66 vs 70 years in early responders; P=0.03) and encephalopathy score (3 [2-4] vs 3 [2-4] in early responders; P=0.015) were different among the responders. Inhospital mortality did not differ between responders to NIV (n=10, 12% for delayed responders vs n=10, 16% for early responders, P=0.49). A second episode of AHRF occurred in 20 responders (14%), equally distributed among early and delayed responders to NIV (n=9, 14.5% in early responders vs n=11, 13% in delayed responders; P=0.83), with a poor survival rate (n=1, 5%). CONCLUSION: Most of the COPD patients with AHRF have a successful outcome when NIV is pursued despite a persistent severe respiratory acidosis after the first NIV trial. The outcome of delayed responders is similar to the one of the early responders. On the contrary, the second episode of AHRF during the hospital stay carries a poor prognosis.

Impact of combination therapy and early de-escalation on outcome of ventilator-associated pneumonia caused by Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas aeruginosa is a common cause of ventilator-associated pneumonia (VAP). Guidelines recommend dual coverage of P. aeruginosa, but the beneficial effect of combination therapy is controversial. We described antibiotic prescriptions and evaluated the clinical impact of initial combination antibiotic therapy and de-escalation strategy in patients with VAP caused by P. aeruginosa. METHODS: Between 1994 and 2014, all 100 patients with VAP caused by P. aeruginosa in our intensive care unit (ICU) were included in a retrospective cohort study to evaluate the prognostic impact of initial combination antibiotic therapy. RESULTS: Eighty-five patients received initial combination antibiotic therapy and 15 monotherapy. Nine patients received inadequate initial antibiotic therapy. De-escalation was performed in 42 patients. Thirty-nine patients died in the ICU. Factors independently associated with death were SAPS II score [SAPS II ≥40 versus <40: hazard ratio (HR) 2.49, 95% confidence interval (CI) 1.08-5.70, p = 0.03] and septic shock (HR = 4.80, 95% CI = 1.90-12.16, p < 0.01) at onset of VAP. Initial combination antibiotic therapy (HR = 1.97, 95% CI = 0.56-6.93, p = 0.29) and early de-escalation (HR = 0.59, 95% CI = 0.27-1.31, p = 0.19) had no impact on mortality. In multivariate analysis, the risk for inappropriate initial antibiotic therapy was higher in cases with multi-drug resistant P. aeruginosa [odd ratio (OR) = 7.11, 95% CI = 1.42-35.51, p = 0.02], but lower in cases with initial combination antibiotic therapy (OR = 0.12, 95% CI = 0.02-0.63, p = 0.01). CONCLUSION: In our cohort, combination therapy increased the likelihood of appropriate therapy but did not seem to impact on mortality.

Should highly active antiretroviral therapy be prescribed in critically ill HIV-infected patients during the ICU stay? A retrospective cohort study.

BACKGROUND: The impact of highly active antiretroviral therapy (HAART) in HIV-infected patients admitted to the intensive care unit (ICU) remains controversial. We evaluate impact of HAART prescription in HIV-infected patients admitted to the ICU of Tourcoing Hospital from January 2000 to December 2009. RESULTS: There were 91 admissions concerning 85 HIV-infected patients. Reasons for ICU admission were an AIDS-related diagnosis in 46 cases (51%). Fifty two patients (57%) were on HAART at the time of ICU admission, leading to 21 immunovirologic successes (23%). During the ICU stay, HAART was continued in 29 patients (32%), and started in 3 patients (3%). Only one patient experienced an adverse event related to HAART. Mortality rate in ICU and 6 months after ICU admission were respectively 19% and 27%. Kaplan-Meier estimates of the cumulative unajusted survival probability over 6 months were higher in patients treated with HAART during the ICU stay (Log rank: p = 0.04). No benefit of HAART in ICU was seen in the adjusted survival proportion at 6 months or during ICU stay. Prescription of HAART during ICU was associated with a trend to lower incidence of new AIDS-related events at 6 months (respectively 17% and 34% with and without HAART, p = 0.07), and with higher incidence of antiretroviral resistance after ICU stay (respectively 25% and 7% with and without HAART, p = 0.02). CONCLUSIONS: Our results suggest a lower death rate over 6 months in critically ill HIV-infected patients taking HAART during ICU stay. The optimal time to prescribe HAART in critically ill patients needs to be better defined.

Vascular graft infections in the intensive care unit: clinical spectrum and prognostic factors.

OBJECTIVES: To report clinical characteristics and prognosis of vascular graft infections in Intensive Care Unit (ICU). METHODS: Thirty seven patients consecutively admitted in ICU for suspected or definite vascular graft infection between January 2006 and June 2009 were included. RESULTS: Staphylococcus species (n = 18) and enterobacteriae (n = 16) were the most frequent causative organisms. Twenty six patients (70%) needed mechanical ventilation. Further surgical procedures were performed in 7 patients (19%). In case of definite infection, mortality in ICU was 33%. In non survivors, shock (92% vs 42%, p = 0.01), age > 70 years (73% vs 27%, p = 0.04), POSSUM score > 45 (73% vs 27%, p = 0.04) and extra-anatomic bypass (45% vs 14%, p = 0.05) were more frequent, intra-operative volume of red cells transfusion (6 ± 3 vs 3 ± 2 units, p = 0.006) and of fresh frozen plasma (2.8 ± 2.8 vs 0.7 ± 1.2 units, p = 0.02), and SAPS II score (58 ± 26 vs 38 ± 17, p = 0.03) were higher. Proportion of adequate initial antibiotic therapy was similar in survivors and non survivors (91% vs 100%, p = 0.4). Proportion of patients treated with an aminoglycoside tended to be higher in survivors (59% vs 27%, p = 0.07). By multivariate analysis, only shock was associated with death in ICU (AOR: 16.3; 95% CI: 1.7-152.1; p = 0.01). CONCLUSIONS: Vascular graft infection carries high morbidity and mortality rates in ICU. Extra-anatomic bypass might be associated with higher mortality. Early aminoglycoside prescription might be protective.

[The fungal risk in cystic fibrosis: a pilot study]. / Le risque fongique dans la mucoviscidose : étude pilote.

Prevalence of Aspergillus fumigatus, as well as other species, and factors associated with risk induced by fungal colonization are poorly defined in cystic fibrosis (CF). We set up a national prospective study to document this risk. As a pilot study, the fungal risk was determined for 21 CF adult patients in a multidisciplinary way: using clinical parameters, notifying treatment, determining fungal presence in sputum and documenting ABPA status. 16 (76%) patients presented with fungal presence in sputum. Aspergillus fumigatus and Candida albicans were the predominant species, but less common mould species such as Scedosporium apiospermum, or Exophiala dermatitidis were also recovered. Factors significantly associated with fungal presence were pancreatic insufficiency, malnutrition, bacterial colonization, and corticosteroids. Candida albicans was correlated with more severe Shwachman Score, Pseudomonas aeruginosa colonization, and intravenous antibiotics use. Moulds species were significantly associated with inhaled corticosteroids. In conclusion, fungal presence in CF appears frequent and various, significantly associated with clinical data, such as inhaled corticosteroids and A. fumigatus. These results confirm the interest of the national prospective French study focused on 300 CF patients, in order to establish if patients could benefit from antifungal treatments or preventive measures.