Early discontinuation of combination antibiotic therapy in severe community-acquired pneumonia: a retrospective cohort study.

BACKGROUND: Severe community-acquired pneumonia (SCAP) is commonly treated with an empiric combination therapy, including a macrolide, or a quinolone and a ß-lactam. However, the risk of Legionella pneumonia may lead to a prolonged combination therapy even after negative urinary antigen tests (UAT). METHODS: We conducted a retrospective cohort study in a French intensive care unit (ICU) over 6 years and included all the patients admitted with documented SCAP. All patients received an empirical combination therapy with a ß-lactam plus a macrolide or quinolone, and a Legionella UAT was performed. Macrolide or quinolone were discontinued when the UAT was confirmed negative. We examined the clinical and epidemiological features of SCAP and analysed the independent factors associated with ICU mortality. RESULTS: Among the 856 patients with documented SCAP, 26 patients had atypical pneumonia: 18 Legionella pneumophila (LP) serogroup 1, 3 Mycoplasma pneumonia (MP), and 5 Chlamydia psittaci (CP). UAT diagnosed 16 (89%) Legionella pneumonia and PCR confirmed the diagnosis for the other atypical pneumonia. No atypical pneumonia was found by culture only. Type of pathogen was not associated with a higher ICU mortality in the multivariate analysis. CONCLUSION: Legionella pneumophila UAT proved to be highly effective in detecting the majority of cases, with only a negligible percentage of patients being missed, but is not sufficient to diagnose atypical pneumonia, and culture did not provide any supplementary information. These results suggest that the discontinuation of macrolides or quinolones may be a safe option when Legionella UAT is negative in countries with a low incidence of Legionella pneumonia.

Acquired agitation in acute respiratory distress syndrome with COVID-19 compared to influenza patients: a propensity score matching observational study.

BACKGROUND: A growing body of evidence reports that agitation and encephalopathy are frequent in critically ill Covid-19 patients. We aimed to assess agitation's incidence and risk factors in critically ill ARDS patients with Covid-19. For that purpose, we compared SARS-CoV-2 acute respiratory distress syndrome (ARDS) patients with a population of influenza ARDS patients, given that the influenza virus is also known for its neurotropism and ability to induce encephalopathy. METHODS: We included all the patients with laboratory-confirmed Covid-19 infection and ARDS admitted to our medical intensive care unit (ICU) between March 10th, 2020 and April 16th, 2021, and all the patients with laboratory-confirmed influenza infection and ARDS admitted to our ICU between April 10th, 2006 and February 8th, 2020. Clinical and biological data were prospectively collected and retrospectively analyzed. We also recorded previously known factors associated with agitation (ICU length of stay, length of invasive ventilation, SOFA score and SAPS II at admission, sedative and opioids consumption, time to defecation). Agitation was defined as a day with Richmond Agitation Sedation Scale greater than 0 after exclusion of other causes of delirium and pain. We compared the prevalence of agitation among Covid-19 patients during their ICU stay and in those with influenza patients. RESULTS: We included 241 patients (median age 62 years [53-70], 158 males (65.5%)), including 146 patients with Covid-19 and 95 patients with Influenza. One hundred eleven (46.1%) patients had agitation during their ICU stay. Patients with Covid-19 had significantly more agitation than patients with influenza (respectively 80 patients (54.8%) and 31 patients (32.6%), p < 0.01). After matching with a propensity score, Covid-19 patients remained more agitated than influenza patients (49 (51.6% vs 32 (33.7%), p = 0.006). Agitation remained independently associated with mortality after adjustment for other factors (HR = 1.85, 95% CI 1.37-2.49, p < 0.001). CONCLUSION: Agitation in ARDS Covid-19 patients was more frequent than in ARDS influenza patients and was not associated with common risk factors, such as severity of illness or sedation. Systemic hyperinflammation might be responsible for these neurological manifestations, but there is no specific management to our knowledge.

Impact of Arterial CO2 Retention in Patients With Moderate or Severe ARDS.

BACKGROUND: Lung-protective ventilation (reduced tidal volume and limited plateau pressure) may lead to CO2 retention. Data about the impact of hypercapnia in patients with ARDS are scarce and conflicting. METHODS: We performed a non-interventional cohort study with subjects with ARDS admitted from 2006 to 2021 and with PaO2 /FIO2 ≤ 150 mm Hg. We examined the association between severe hypercapnia (PaCO2 ≥ 50 mm Hg) on the first 5 days after the diagnosis of ARDS and death in ICU for 930 subjects. All the subjects received lung-protective ventilation. RESULTS: Severe hypercapnia was noted in 552 subjects (59%) on the first day of ARDS (day 1); 323/930 (34.7%) died in the ICU. Severe hypercapnia on day 1 was associated with mortality in the unadjusted (odds ratio 1.54, 95% CI 1.16-1.63; P = .003) and adjusted (odds ratio 1.47, 95% CI 1.08-2.43; P = .004) models. In the Bayesian analysis, the posterior probability that severe hypercapnia was associated with ICU death was > 90% in 4 different priors, including a septic prior for this association. Sustained severe hypercapnia on day 5, defined as severe hypercapnia present from day 1 to day 5, was noted in 93 subjects (12%). After propensity score matching, severe hypercapnia on day 5 remained associated with ICU mortality (odds ratio 1.73, 95% CI 1.02-2.97; P = .047). CONCLUSIONS: Severe hypercapnia was associated with mortality in subjects with ARDS who received lung-protective ventilation. Our results deserve further evaluation of the strategies and treatments that aim to control CO2 retention.

Bacterial and fungal infections: a frequent and deadly complication among critically ill acute liver failure patients.

BACKGROUND: Acute liver failure (ALF) is a rare but life-threatening condition mostly requiring intensive care unit (ICU) admission. ALF induces immune disorders and may promote infection acquisition. However, the clinical spectrum and impact on patients' prognosis remain poorly explored. METHODS: We conducted a retrospective single-centre study on patients admitted for ALF to the ICU of a referral University Hospital from 2000 to 2021. Baseline characteristics and outcomes according to the presence of infection until day 28 were analysed. Risk factors for infection were determined using logistic regression. The impact of infection on 28-day survival was assessed using the proportional hazard Cox model. RESULTS: Of the 194 patients enrolled, 79 (40.7%) underwent infection: community-acquired, hospital-acquired before ICU and ICU-acquired before/without and after transplant in 26, 23, 23 and 14 patients, respectively. Most infections were pneumonia (41.4%) and bloodstream infection (38.8%). Of a total of 130 microorganisms identified, 55 were Gram-negative bacilli (42.3%), 48 Gram-positive cocci (36.9%) and 21 were fungi (16.2%). Obesity (OR 3.77 [95% CI 1.18-14.40]; p = .03) and initial mechanical ventilation (OR 2.26 [95% CI 1.25-4.12]; p = .007) were independent factors associated with overall infection. SAPSII > 37 (OR 3.67 [95% CI 1.82-7.76], p < .001) and paracetamol aetiology (OR 2.10 [95% CI 1.06-4.22], p = .03) were independently associated with infection at admission to ICU. On the opposite, paracetamol aetiology was associated with lower risk of ICU-acquired infection (OR 0.37 [95% CI 0.16-0.81], p = .02). Patients with any type of infection had lower day 28 survival rates (57% versus 73%; HR 1.65 [1.01-2.68], p = .04). The presence of infection at ICU admission (p = .04), but not ICU-acquired infection, was associated with decreased survival. CONCLUSIONS: The prevalence of infection is high in ALF patients which is associated with a higher risk of death. Further studies assessing the use of early antimicrobial therapy are needed.

Moderate-to-severe ARDS: COVID-19 patients compared to influenza patients for ventilator parameters and mortality.

Background: This study aimed to compare ventilatory parameters recorded in the first days of acute respiratory distress syndrome (ARDS) and mortality at day 60 between coronavirus disease 2019 (COVID-19) and influenza ARDS patients with arterial oxygen tension (P aO2 )/inspiratory oxygen fraction (F IO2 ) ≤150 mmHg. Methods: We compared 244 COVID-19 ARDS patients with 106 influenza ARDS patients. Driving pressure, respiratory system compliance (C rs), ventilator ratio, corrected minute ventilation (V'Ecorr) and surrogate of mechanical power (index=(4×driving pressure)+respiratory rate) were calculated from day 1 to day 5 of ARDS. A propensity score analysis and a principal component analysis (PCA) were performed. Results: On day 1 of ARDS, COVID-19 patients had significantly higher P aO2 /F IO2 (median (interquartile range) 97 (79-129.2) versus 83 (62.2-114) mmHg; p=0.001), and lower driving pressure (13.0 (11.0-16.0) versus 14.0 (12.0-16.7) cmH2O; p=0.01), ventilatory ratio (2.08 (1.73-2.49 versus 2.52 (1.97-3.03); p<0.001), V'Ecorr (12.7 (10.2-14.9) versus 14.9 (11.6-18.6) L·min-1; p<0.001) and index (80 (70-89) versus 84 (75-94); p=0.004). PCA demonstrated an important overlap of ventilatory parameters recorded on day 1 between the two groups. From day 1 to day 5, repeated values of P aO2 /F IO2 , arterial carbon dioxide tension, ventilatory ratio and V'Ecorr differed significantly between influenza and COVID-19 patients in the unmatched and matched populations. Mortality at day 60 did not differ significantly after matching (29% versus 21.7%; p=0.43). Conclusions: Ventilation was more impaired in influenza than in COVID-19 ARDS patients on the first day of ARDS with an important overlap of values. However, mortality at day 60 did not differ significantly in the matched population.