Multiplex polymerase chain reaction (mPCR) enables recovery of viruses from airways of patients with community-acquired pneumonia (CAP), although their clinical impact remains uncertain. Among consecutive adult patients who had undergone a mPCR within 72 hours following their admission to one intensive care unit (ICU), we retrospectively included those with a final diagnosis of CAP. Four etiology groups were clustered: bacterial, viral, mixed (viral-bacterial) and no etiology. A composite criterion of complicated course (hospital death or mechanical ventilation > 7 days) was used. A subgroup analysis compared patients with bacterial and viral-bacterial CAP matched on the bacterial pathogens. Among 174 patients (132 men [76 %], age 63 [53–75] years, SAPSII 38 [27;55], median PSI score 106 [78;130]), bacterial, viral, mixed and no etiology groups gathered 46 (26 %), 53 (31 %), 45 (26 %) and 30 (17 %) patients, respectively. Virus-infected patients displayed a high creatine kinase serum level, a low platelet count, and a trend toward more frequent alveolar-interstitial infiltrates. A complicated course was more frequent in the mixed group (31/45, 69 %), as compared to bacterial (18/46, 39 %), viral (15/53, 28 %) and no etiology (12/30, 40 %) groups (p < 0.01). In multivariate analysis, the mixed (viral-bacterial) infection was independently associated with complicated course (reference: bacterial pneumonia; OR, 3.58; CI 95 %, 1.16–11; p = 0.03). The subgroup analysis of bacteria-matched patients confirmed these findings. Viral-bacterial coinfection during severe CAP in adults is associated with an impaired presentation and a complicated course.

Anti-synthetase (AS) and dermato-pulmonary associated with anti-MDA-5 antibodies (aMDA-5) syndromes are near one of the other autoimmune inflammatory myopathies potentially responsible for severe acute interstitial lung disease. We undertook a 13-year retrospective multicenter study in 35 French ICUs in order to describe the clinical presentation and the outcome of patients admitted to the ICU for acute respiratory failure (ARF) revealing AS or aMDA-5 syndromes. From 2005 to 2017, 47 patients (23 males; median age 60 [1st–3rd quartiles 52–69] years, no comorbidity 85%) were admitted to the ICU for ARF revealing AS (n = 28, 60%) or aMDA-5 (n = 19, 40%) syndromes. Muscular, articular and cutaneous manifestations occurred in 11 patients (23%), 14 (30%) and 20 (43%) patients, respectively. Seventeen of them (36%) had no extra-pulmonary manifestations. C-reactive protein was increased (139 [40–208] mg/L), whereas procalcitonine was not (0.30 [0.12–0.56] ng/mL). Proportion of patients with creatine kinase ≥ 2N was 20% (n = 9/47). Forty-two patients (89%) had ARDS, which was severe in 86%, with a rate of 17% (n = 8/47) of extra-corporeal membrane oxygenation requirement. Proportion of patients who received corticosteroids, cyclophosphamide, rituximab, intravenous immunoglobulins and plasma exchange were 100%, 72%, 15%, 21% and 17%, respectively. ICU and hospital mortality rates were 45% (n = 21/47) and 51% (n = 24/47), respectively. Patients with aMDA-5 dermato-pulmonary syndrome had a higher hospital mortality than those with AS syndrome (n = 16/19, 84% vs. n = 8/28, 29%; p = 0.001). Intensivists should consider inflammatory myopathies as a cause of ARF of unknown origin. Extra-pulmonary manifestations are commonly lacking. Mortality is high, especially in aMDA-5 dermato-pulmonary syndrome.

Life-threatening “breakthrough” cases of critical COVID-19 are attributed to poor or waning antibody (Ab) response to SARS-CoV-2 vaccines in individuals already at risk. Preexisting auto-Abs neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; their contribution to hypoxemic breakthrough cases in vaccinated people is unknown. We studied a cohort of 48 individuals (aged 20 to 86 years) who received two doses of a messenger RNA (mRNA) vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Ab levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal Ab response to the vaccine. Among them, 10 (24%) had auto-Abs neutralizing type I IFNs (aged 43 to 86 years). Eight of these 10 patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, whereas two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized type I IFNs at 10 ng/ml and three at 100 pg/ml only. Seven patients neutralized SARS-CoV-2 D614G and Delta efficiently, whereas one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only type I IFNs at 100 pg/ml neutralized both D614G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating Abs capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a notable proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.

Infectious complications are a major cause of morbidity and mortality after heart transplantation (HT). However, the epidemiology and outcomes of these infections in the recent population of adult heart transplant recipients have not been investigated. We conducted a single-center retrospective study on infectious complications occurring within 180 days following HT on consecutive heart transplant recipients, from January 2011 to June 2015 at Bichat University Hospital in Paris, France. Risk factors for non-viral infections occurring within 8, 30 and 180 days after HT were investigated using competing risk analysis. Overall, 113 patients were included. Fifty-eight (51%) HTs were high-priority allocations. Twenty-eight (25%) patients had an extracorporeal membrane oxygenation (ECMO) support at the time of transplantation. Ninety-two (81%) patients developed at least one infection within 180 days after HT. Bacterial and fungal infections (n = 181 episodes) occurred in 80 (71%) patients. The most common bacterial and fungal infections were pneumonia (n = 95/181 episodes, 52%), followed by skin and soft tissue infections (n = 26/181, 14%). Multi-drug-resistant bacteria were responsible for infections in 21 (19%) patients. Viral infections were diagnosed in 44 (34%) patients, mostly Cytomegalovirus infection (n = 39, 34%). In multivariate subdistribution hazard model, prior cardiac surgery (subdistribution hazard ratio sHR = 2.7 [95% CI 1.5–4.6] p < 0.01) and epinephrine or norepinephrine at the time of HT (sHR = 2.3 [95% CI 1.1–5.2] p = 0.04) were significantly associated with non-viral infections within 8 days after HT. Prior cardiac surgery (sHR = 2.5 [95% CI 1.4–4.4] p < 0.01), recipient age over 60 years (sHR = 2.0 [95% CI 1.2–3.3] p < 0.01) and ECMO following HT (sHR = 1.7 [95% CI 1.0–2.8] p = 0.04) were significantly associated with non-viral infection within 30 days after HT, as well as within 180 days after HT. This study confirmed the high rate of infections following HT. Recipient age, prior cardiac surgery and ECMO following HT were independent risk factors for early and late bacterial and fungal infections.

Oxacillin and cloxacillin are the most frequently used penicillins for the treatment of severe methicillin-susceptible Staphylococcus aureus infections in intensive care units (ICUs), especially endocarditis. International recommendations do not suggest any adaptation of the dosage in case of renal impairment. We wanted to assess the risk factors for overdosing in ICU and the related observed side effects. All patients with a therapeutic drug monitoring of oxa- or cloxacillin between 2008 and 2014 were included. The target range of trough concentration for total antibiotic activity was considered to be 20–50 mg/L. Data concerning the infection, the given treatment, the renal function, and the attributed side effects of overdosing were collected. A logistic regression model was used to compute the measured trough concentrations. Sixty-two patients were included in this study. We found a median trough plasma concentration of 134.3 mg/L (IQR 65.3–201 mg/L). Ten patients (16.1%) reached the target concentration; all other patients (83.9%) were overdosed. Eleven patients (17.7%) experienced neurological side effects attributed to a high antibiotic concentration, i.e. persistent coma and delirium. When adjusted on the dosage used, the risk of overdosing was significantly associated with a creatinine clearance <10 mL/min (with or without hemodialysis). With the suggested dose of 12 g/day for cloxacillin treatment in case of endocarditis and severe infections occurring in ICU, 83.9% of patients are largely overdosed. Considering the observed side effects, doses should be accurately monitored and reduced, particularly when renal replacement therapy is needed.

Objectives: In severe COVID-19 pneumonia, the appropriate timing and dosing of corticosteroids (CS) is not known. Patient subgroups for which CS could be more beneficial also need appraisal. The aim of this study was to assess the effect of early CS in COVID-19 pneumonia patients admitted to the ICU on the occurrence of 60-day mortality, ICU-acquired-bloodstream infections(ICU-BSI), and hospital-acquired pneumonia and ventilator-associated pneumonia(HAP-VAP). Methods: We included patients with COVID-19 pneumonia admitted to 11 ICUs belonging to the French OutcomeRea^TM network from January to May 2020. We used survival models with ponderation with inverse probability of treatment weighting (IPTW). Results: The study population comprised 303 patients having a median age of 61.6 (53–70) years of whom 78.8% were male and 58.6% had at least one comorbidity. The median SAPS II was 33 (25–44). Invasive mechanical ventilation was required in 34.8% of the patients. Sixty-six (21.8%) patients were in the Early-C subgroup. Overall, 60-day mortality was 29.4%. The risks of 60-day mortality (_IPTWHR = 0.86;95% CI 0.54 to 1.35, p = 0.51), ICU-BSI and HAP-VAP were similar in the two groups. Importantly, early CS treatment was associated with a lower mortality rate in patients aged 60 years or more (_IPTWHR, 0.53;95% CI, 0.3–0.93; p = 0.03). In contrast, CS was associated with an increased risk of death in patients younger than 60 years without inflammation on admission (_IPTWHR = 5.01;95% CI, 1.05, 23.88; p = 0.04). Conclusion: For patients with COVID-19 pneumonia, early CS treatment was not associated with patient survival. Interestingly, inflammation and age can significantly influence the effect of CS.