Lung abscess following ventilator-associated pneumonia during COVID-19: a retrospective multicenter cohort study.

BACKGROUND: Patients undergoing mechanical ventilation (MV) for COVID-19 exhibit an increased risk of ventilator-associated pneumonia (VAP). The occurrence of lung abscesses following VAP in these patients has been poorly studied. We aimed to describe the incidence, characteristics, risk factors and prognosis of lung abscesses complicating VAP after COVID-19. METHODS: We conducted an observational, retrospective study in three French intensive care units. Patients admitted for acute respiratory failure with a confirmed SARS-CoV-2 PCR and requiring MV for more than 48 h were included. RESULTS: Among the 507 patients included, 326 (64%) had a documented VAP. Of these, 23 (7%) developed a lung abscess. Enterobacterales (15/23, 65%) were the main documentation, followed by non-fermenting Gram-negative bacilli (10/23, 43%) and Gram-positive cocci (8/23, 35%). Lung abscesses were mainly plurimicrobial (15/23, 65%). In multivariate analysis, a plurimicrobial 1st VAP episode (OR (95% CI) 2.93 (1.16-7.51); p = 0.02) and the use of hydrocortisone (OR (95% CI) 4.86 (1.95-12.1); p = 0.001) were associated with lung abscess development. Intensive care unit (ICU) mortality of patients with lung abscesses reached 52%, but was not significantly higher than for patients with VAP but no lung abscess. Patients with lung abscesses had reduced ventilator-free days at day 60, a longer duration of MV and ICU stay than patients with VAP but no lung abscess (respectively, 0 (0-3) vs. 16 (0-42) days; p < 0.001, 49 (32-73) vs. 25 (11-41) days; p < 0.001, 52 (36-77) vs. 28 (16-47) days; p < 0.001). CONCLUSIONS: Lung abscessing pneumonia is not uncommon among COVID-19 patients developing VAP. A plurimicrobial first VAP episode and the use of hydrocortisone are independently associated with this complication. In COVID-19 patients with persistent VAP, a chest CT scan investigating the evolution toward lung abscess should be considered.

Cessation of oral anticoagulants in antiphospholipid syndrome.

Objective To study the outcome of patients with antiphospholipid syndrome (APS) after oral anticoagulant treatment cessation. Methods We performed a retrospective study of patients with APS experiencing cessation of oral anticoagulant and enrolled in a French multicentre observational cohort between January 2014 and January 2016. The main outcome was the occurrence of recurrent thrombotic event after oral anticoagulation cessation. Results Forty four APS patients interrupted oral anticoagulation. The median age was 43 (27-56) years. The median duration of anticoagulation was 21 (9-118) months. Main causes of oral anticoagulant treatment cessation were switch from vitamin K antagonists to aspirin in 15 patients, prolonged disappearance of antiphospholipid antibodies in ten, bleeding complications in nine and a poor therapeutic adherence in six. Eleven (25%) patients developed a recurrent thrombotic event after oral anticoagulation cessation, including three catastrophic APS and one death due to lower limb ischemia. Antihypertensive treatment required at time of oral anticoagulants cessation seems to be an important factor associated with recurrent thrombosis after oral anticoagulant cessation (15.2% in patients with no relapse versus 45.5% in patients with recurrent thrombosis, p = 0.038). Oral anticoagulant treatment was re-started in 18 (40.9%) patients. Conclusion The risk of a new thrombotic event in APS patients who stopped their anticoagulation is high, even in those who showed a long lasting disappearance of antiphospholipid antibodies. Except for the presence of treated hypertension, this study did not find a particular clinical or biological phenotype for APS patients who relapsed after anticoagulation cessation. Any stopping of anticoagulant in such patients should be done with caution.

Community-acquired pneumonia and positive urinary antigen tests: Factors associated with targeted antibiotic therapy.

BACKGROUND: The use of rapid microbiological tests is supported by antimicrobial stewardship policies. Targeted antibiotic therapy (TAT) for community-acquired pneumonia (CAP) with positive urinary antigen test (UAT) has been associated with a favorable impact on outcome. We aimed to determine the factors associated with TAT prescription. PATIENTS AND METHODS: We conducted a retrospective multicenter study including all patients presenting with CAP and positive UAT for Streptococcus pneumoniae or Legionella pneumophila from January 2010 to December 2013. Patients presenting with aspiration pneumonia, coinfection, and neutropenia were excluded. CAP severity was assessed using the Pneumonia Severity Index (PSI). TAT was defined as the administration of amoxicillin for pneumococcal infection and either macrolides or fluoroquinolones (inactive against S. pneumoniae) for Legionella infection. RESULTS: A total of 861 patients were included, including 687 pneumococcal infections and 174 legionellosis from eight facilities and 37 medical departments. TAT was prescribed to 273 patients (32%). Four factors were found independently associated with a lower rate of TAT: a PSI score≥4 (OR 0.37), Hospital A (OR 0.41), hospitalization in the intensive care unit (OR 0.44), and cardiac comorbidities (OR 0.60). Four other factors were associated with a high rate of TAT: positive blood culture for S. pneumoniae (OR 2.32), Hospitals B (OR 2.34), E (OR 2.68), and H (OR 9.32). CONCLUSION: TAT in CAP with positive UAT was related to the hospitals as well as to patient characteristics.

Impact of an assisted reassessment of antibiotic therapies on the quality of prescriptions in an intensive care unit.

OBJECTIVES: The study's objective was to assess the impact of a professional multifaceted intervention designed to improve the quality of inpatient empirical therapeutic antibiotic courses at the time of their reassessment, i.e. 24 to 96 hours after treatment initiation. DESIGN: We conducted a 5-month prospective pre- and post-intervention study in a medical Intensive Care Unit (ICU) in a teaching hospital, using time-series analysis. The intervention was a multifaceted professional intervention combining systematic 3-weekly visits of an infectious diseases specialist to discuss all antibiotic therapies, interactive teaching courses, and daily contact with a microbiologist. RESULTS: Eighty-one antibiotic prescriptions were assessed, 37 before and 44 after the intervention. The prevalence of adequate antibiotic prescriptions was high and not statistically different before and after the intervention (73% vs. 80%, P=0.31), both for sudden change (P=0.67) and linear trend (P=0.055), using interrupted time-series analysis. The intervention triggered a more frequent reassessment of the diagnosis between day 2 and day 4 (11% vs. 32%, P=0.02) and slightly improved the adaptation of antibiotic therapies to positive microbiology (25% before vs. 50% after, P=0.18). CONCLUSIONS: Our multifaceted intervention may have improved the quality of antibiotic therapies around day 3 of prescription, but the difference did not reach statistical significance, possibly because of a ceiling effect.

[Urinary pneumococcal or Legionella antigen detection tests and low-spectrum antibiotic therapy for community-acquired pneumonia]. / Antigènuries pneumocoque ou Legionella et antibiothérapie à spectre restreint au cours des pneumonies aiguës communautaires.

UNLABELLED: We performed urinary antigen tests for pneumococcus and Legionella for patients with community-acquired pneumonia (CAP), to prescribe a documented antibiotic therapy. We report the efficiency of low-spectrum antibiotic treatment, illustrating the inappropriateness of bacteriological respiratory sampling. PATIENTS AND METHODS: Patients with CAP were enrolled from three different units; the pneumonia severity index was used to assess the disease. Respiratory samples were also listed. Low-spectrum antibiotic therapy was amoxicillin for pneumococcal infection, and macrolides or non-anti-pneumococcal fluoroquinolone for legionellosis. RESULTS: Six hundred and seventy-five CAP were diagnosed during the study period,, 150 with positive urinary antigen tests (23%), among which 108 pneumococcal infections (73%), 40 legionellosis (26%), and two mixed infections. The pneumonia severity index was 106+/-38. Amoxicillin was prescribed in 108 cases, fluoroquinolone in 24 cases, macrolide in 18 cases. The outcome was favourable for 138 patients (92%). Eighty three respiratory samples allowed identification of a bacterium for 58 patients (39%), among which 24 strains were not in the antibiotic spectrum: Haemophilus influenzae and Pseudmomonas aeruginosa in six cases, Staphylococcus aureus in five cases, Klebsiella pneumoniae in two cases, and another Gram negative bacillus in five cases. These strains were resistant in vitro to the prescribed treatment in 19/24 cases (79%). One out of 12 patients who died had a respiratory sample positive for Enterobacter spp strain resistant to the ongoing antibiotic treatment. CONCLUSION: The low-spectrum antibiotic therapy based on urinary antigen tests is efficient, and demonstrates respiratory tract colonisation with bacteriological strains usually considered as pathogenic.

Enhanced T-cell apoptosis in human septic shock is associated with alteration of the costimulatory pathway.

T-cell apoptosis during septic shock (SS) has been associated with deleterious outcome, but the mechanisms of apoptosis are not well understood. As T-cells are not infected in bacterial infection, our hypothesis was that deleterious interactions between lymphocytes and monocytes could be involved. This is a cross-sectional study of 27 patients presenting with community-acquired SS, 23 infected patients without SS and 18 controls. Cytofluorometric techniques were used to study apoptosis, the costimulatory pathway and cytokine synthesis. Apoptosis was increased in SS compared to infected patients without SS and controls: the median values were 18, 2 and 3%, respectively, for CD4(+) T-cells (P < 0.001), and 12, 5 and 2%, respectively, for CD8(+) T-cells (P < 0.001). Patients with SS exhibited significant CD152 over-expression on T-cells, while CD86 expression was decreased on monocytes (P = 0.004). The synthesis of interleukin-2 was decreased in patients with SS compared to the other groups, while secretions of interferon-gamma and TNF-alpha were not altered. Ten surviving patients with SS showed a trend towards the normalisation of these parameters on day 7. In SS, T-cell apoptosis is related, at least in part, to the alteration of the costimulatory pathway, which, in turn, leads to significant modification of the cytokine network.

[Acute airway obstruction during chemotherapy-induced agranulocytosis with fever]. / Moules bronchiques au cours d'une agranulocytose fébrile post-chimiothérapie.

Acute airway obstruction caused by mucoid impaction can cause sometimes life-threatening respiratory distress. Bronchial plugging is usually observed in subjects with chronic diseases such as asthma, allergic bronchopulmonary aspergillosis, or cystic fibrosis. In children, it can be related to heart failure. Acute airway obstruction in a patient without a chronic respiratory disease is exceptional. We report the case of a patient who developed bronchial plugs obstructing the bronchi during a period of agranulocytosis induced by chemotherapy. The patient experienced acute respiratory distress with asphyxia. The plugs were composed of fibrin and required several fibroscopic procedures for clearance. To our knowledge, this is the first case report of acute airway obstruction by plugging during a period of agranulocytosis.

[Lemierre's syndrome: a report of six cases]. / Syndrome de Lemierre : à propos de 6 cas.

OBJECTIVE: Lemierre's syndrome is a rare but severe condition combining pyrexia, cervical pain and pulmonary signs following a pharyngeal infection, usually tonsillitis. This infectious disease is still present in our country despite wide use of antibiotic therapy in pharyngeal infections. METHODS: In a retrospective study conducted between 1995 and 2000 in two departments (infectious diseases and critical care unit) of Nice university hospital (Nice, France), we collected and analysed six cases of Lemierre's syndrome. RESULTS: We describe a serie of 6 cases, all of them female patients of mean age 27. We enrolled healthy patients whose initial symptom was tonsillitis. Most of these patients showed signs of severe sepsis and one died of septic shock. All the others recovered with treatment. The mean time between tonsillitis and first sign of sepsis was seven days. In four cases, patients received a beta- lactam antimicrobial agent with metronidazole. In two cases, patients were treated with amoxicillin-clavulanate. All patients were investigated for the presence of internal jugular vein thrombosis and were treated by anticoagulants when research was positive. CONCLUSIONS: A strong presumptive diagnosis can be made on the basis of clinical presentation, secondarily confirmed by para-clinical data. The prognosis depends on the speed and quality of management. We therefore wished to raise awareness of this condition among our colleagues by reporting our personal experience.

Consensual treatment of plasmodium falciparum malaria does not lead to adequate quinine blood concentrations.

Since 1996, we have a common protocol in the Infectious Diseases Department and the Intensive Care Unit for the administration of quinine in case of Plasmodium falciparum malaria. Patients were classified as uncomplicated form of malaria (UFM) or severe form of malaria (SFM) according to WHO criteria, adding parasitemia >5% as a criteria of SFM. Treatment of SFM should consist of a 4 h infusion of 16 mg/kg quinine-base loading dose, followed by 8 mg/kg every 8 h. Patients with UFM receive quinine-base, 8 mg/kg every 8 h. A therapeutic index of 10-15 mg/l was considered adequate. Hypoglycemia and cardiotoxicity were the two main adverse effects of quinine to be investigated. In order to verify that these modalities for quinine administration are associated with adequate quinine blood concentrations, we have reviewed the pharmacological data and the occurrence of adverse effects. Between April 1996 and December 2000, 95 patients were hospitalised: 25 with SFM and 70 with UFM: 78/95 patients (82%) received adequate treatment and 26/95 (28%) of the patients presented an overdosage of quinine. Six severe adverse effects were observed, even in case of adequate quinine administration. Consensual treatment of malaria does not confer adequate quinine blood concentrations, and toxic effects are still common.

[Systematic infection consultation in the intensive care unit. Impact of short-term antibiotic use]. / Consultation systématique d'infectiologie en réanimation médicale. Impact à court terme sur la consommation antibiotique.

OBJECTIVES: Multiresistant bacteria are regularly isolated in nosocomial infections occurring in intensive care units due to wide use of antibiotics. We evaluated the impact of systematic infectiology consultations on the quality of antibiotic prescriptions in an intensive care unit. PATIENTS AND METHODS: Infectiology consultations (3 per week) were initiated mid February 1999. The infectiologist gave oral advice to be implemented (or not) by the intensive care unit according to ongoing therapeutic options. The hospital pharmacy recorded antibiotic use for March and April 1999 for comparison with use recorded in 1998 for a similar period. We retrospectively reviewed the files of patients hospitalized during these periods and who had received antibiotics to determine the modalities of antibiotic use. The 4 antibiotics used for the longest period for each patient were recorded. RESULTS: Thirty-one patients in 1999 and 30 in 1998 were given antibiotics. The SAPS score was similar for the two groups. Mean duration of antibiotic treatment was lower during the March-April 1999 period than during the corresponding period in 1998: 13 +/- 9 days/patient versus 23 +/- 21 days/patient respectively, p = 0.037. In 1998, there were 596 antibiotic-days and in 1999 there were 455 (-24%). The cost of antibiotic therapy in 1998 was 70,342 FrF compared with 56,804 FrF in 1999 (-19%). CONCLUSION: Infectiology consultation, in association with the opinion of the intensive care physician, is a simple way to limit antibiotic use.

Influence of alveolar ventilation changes on calculated gastric intramucosal pH and gastric-arterial PCO2 difference.

OBJECTIVE: To evaluate the influence of changes in alveolar ventilation on the following tonometry-derived variables: gastric intramucosal CO2 tension (PtCO2), gastric arterial CO2 tension difference (PgapCO2), gastric intramucosal pH (pHi) and arterial pH-pHi difference (pHgap). DESIGN: Clinical prospective study. SETTING: A medical intensive care unit in a university hospital. PATIENTS: Ten critically ill, mechanically ventilated patients requiring hemodynamic monitoring with pulmonary artery catheter. INTERVENTIONS: Gastric tonometer placement. A progressive increase in tidal volume (V(T)) from 7 to 10 ml/ kg followed by an abrupt return to baseline V(T) level. MEASUREMENTS AND MAIN RESULTS: Tonometer saline PtCO2 and hemodynamic data were collected hourly at various V(T) levels: H0 and H0' (baseline V(T) = 7 ml/kg), H1 (V(T) = 8 ml/kg), H2 (V(T) = 9 ml/kg), H3 (V(T) = 10 ml/kg), H4 (baseline V(T)). During the "hyperventilation phase" (H0-H3), pHi (p<0.01) and pHgap (p<0.05) increased but PgapCO2 remained unchanged. Cardiac output (CO) was not affected by ventilatory change. During the "hypoventilation phase" (H3-H4), pHi fell from 7.27+/-0.11 to 7.23+/-0.09 (p<0.01) and PgapCO2 decreased from 16+/-5 mm Hg to 13+/-4 mm Hg (p<0.05). V(T) reduction was associated with a significant cardiac output elevation (p<0.05). CONCLUSIONS: PaCO2 and PtCO2 are similarly influenced by the changes in alveolar ventilation. Unlike pHi, the PgapCO2 is not affected by ventilation variations unless CO changes are associated.