The use of TNF-α antagonists in tuberculosis to control severe paradoxical reaction or immune reconstitution inflammatory syndrome: a case series and literature review.

Paradoxical reaction (PR) and immune reconstitution inflammatory syndrome (IRIS) are common complications of tuberculosis treatment. Corticosteroids are first-line treatment for severe PR or IRIS, particularly neurological. We report four cases of severe PR or IRIS during tuberculosis treatment who required TNF-α antagonists, and identified 20 additional cases through literature review. They were 14 women and 10 men, with a median age of 36 years (interquartile range, 28-52). Twelve were immunocompromised before tuberculosis: untreated HIV infection (n=6), or immunosuppressive treatment (TNF-α antagonists, n=5; tacrolimus, n=1). Tuberculosis was mostly neuromeningeal (n=15), pulmonary (n=10), lymph node (n=6), and miliary (n=6), multi-susceptible in 23 cases. PR or IRIS started after a median time of 6 weeks (IQR, 4-9) following anti-tuberculosis treatment start, and consisted primarily of tuberculomas (n=11), cerebral vasculitis (n=8), and lymphadenitis (n=6). First-line treatment of PR or IRIS was high-dose corticosteroids in 23 cases. TNF-α antagonists were used as salvage treatment in all cases, with infliximab (n=17), thalidomide (n=6), and adalimumab (n=3). All patients improved, but 6 had neurological sequelae, and 4 had TNF-α antagonist-related severe adverse events. TNF-α antagonists are safe and effective as salvage or corticosteroid-sparing therapeutic for severe PR or IRIS during tuberculosis treatment.

Prevalence and characteristics of persistent symptoms after non-severe COVID-19: a prospective cohort study.

We performed a prospective cohort study of 311 outpatients with non-severe COVID-19 (187 women, median age 39 years). Of the 214 (68.8%) who completed the 6-week follow-up questionnaire, 115 (53.7%) had recovered. Others mostly reported dyspnea (n = 86, 40.2%), weight loss (n = 83, 38.8%), sleep disorders (n = 68, 31.8%), and anxiety (n = 56, 26.2%). Of those who developed ageusia and anosmia, these symptoms were still present at week 6 in, respectively, 11/111 (9.9%) and 19/114 (16.7%). Chest CT scan and lung function tests found no explanation in the most disabled patients (n = 23). This study confirms the high prevalence of persistent symptoms after non-severe COVID-19.

Pleural penetration of amoxicillin and metronidazole during pleural infection: An ambispective cohort study.

OBJECTIVES: The pharmacokinetics of antibiotics in pleural fluid during pleural infections has been poorly described. This study aimed to explore amoxicillin and metronidazole diffusion into the pleural space. METHODS: This was an ambispective, single-centre study that included patients with complicated parapneumonic effusion or pleural empyema managed with repeated therapeutic thoracentesis as first-line treatment between 2014 and 2022. Pleural steady-state or trough concentrations of amoxicillin and metronidazole were measured, with a lower limit of quantification of 5 mg/L. RESULTS: Seventy paired blood and pleural samples were analysed from 40 patients. The median (interquartile range) patient age was 55 years (45-67 years) and 88% were male. The median patient weight was 65.8 kg (57.3-82 kg) and median plasma albumin concentration was 29.7 g/L (23.7-33.9 g/L). Median creatinine clearance was 106 mL/min (95-117 mL/min). Median amoxicillin pleural concentrations in patients treated with oral, bolus and continuous intravenous administrations (6 g/day) were, respectively, 5.2 (<5-6.4), 9.4 (8-13.1) and 10.8 (7.1-13.1) mg/L. Pleural concentrations were <5 mg/L in 5/11 samples (45%) with oral treatment and 6/59 (10%) with intravenous treatment. Median metronidazole pleural concentrations were 18.4 (15.7-22.8) mg/L, with all patients being treated orally (1.5 g/day). CONCLUSIONS: Oral metronidazole (1.5 g/day) and intravenous amoxicillin (6 g/day) achieved therapeutic targets in pleural fluid in most cases, but oral amoxicillin did not.