CaspoNEB: Efficacy and Safety of Caspofungin Aerosols for the Curative Treatment of Pneumocystis Pneumonia

Part 1: safety of inhaled caspofungin

* frequency of adverse events * severity of adverse events

Part 2: proportion of patients alive and with a favorable clinical course* at the seventh day (day-7) after the first administration.

Composite outcome defined by at least one of the two following items persisting ≥24 hours in alive patients: * Relative reduction (de-escalation or withdrawal) of respiratory assistance due to clinical improvement (depending on the initial support): * extubation, or * weaning of non-invasive ventilatory support, or * weaning of nasal high-flow or low-flow oxygen therapy; (NB: all participating centers will implement uniform protocols for ventilatory assistance weaning) * Occurrence of a +50% increase in oxygenation (PaO2 / FiO2 ratio vs. the worst value observed after inclusion).

Individual components of the composite primary outcome at day-7 (d-7)

* All-cause mortality and Pneumocystis pneumonia-related mortality * Improvement of respiratory function: * Proportion of patients alive and with relative reduction (de-escalation or withdrawal) of respiratory assistance (in percentage) * Proportion of patients alive and with a +50% increase in oxygenation (PaO2 / FiO2 ratio vs. the worst value observed after inclusion) (in percentage)

Safety of nebulized caspofungin in patients with Pneumocystis pneumonia through

* Occurrence of serious and non-serious pulmonary adverse events and adverse effects at day-1 (d-1), d-2, d-3, d-4, d-5, d-6, and d-7 (with active monitoring of the nebulization procedure), and serious pulmonary adverse events and adverse effects at hospital discharge, d-28 and d-90 * Occurrence of other serious adverse events and adverse effects at day-1 (d-1), d-2, d-3, d-4, d-5, d-6, d-7, hospital discharge, d-28 and d-90 * Liver and kidney markers at day 1 (d-1), d-3, d-7, d-28 and d-90 * transaminases (in international units/liter) * glutamate transferase (in international units/liter) * alkaline phosphatase (in international units/liter) * serum creatinine (in micromol/liter) * urea (in millimol/liter) * Blood counts (same dates) * complete blood count (in giga/liter) * platelets (in giga/liter) * Serum electrolytes (same dates) * sodium (in mmol/liter) * potassium (in mmol/liter) * chloride (in mmol/liter) * bicarbonates (in mmol/liter)

Pharmacokinetics of nebulized caspofungin

in blood at 0, 2, 4, 6, 12, 24 hours, plus residual concentration at day-3 (d-3) and d-7 for the five first included patients receiving caspofungin, and in tracheo-bronchial aspirates at 4, 6, 24 h, at day-3 (d-3) and d-7 (or just before extubation if still alive at time of extubation) for the five first included patients receiving caspofungin and who are intubated. Caspofungin concentration measurements (in milligram/liter) will be centrally carried out at Tours university hospital at the end of the study only for patients who received nebulized caspofungin (intervention group), once the blind process will be lifted).

Mortality

* All-cause at hospital discharge, day-28 (d-28) and d-90 * Pneumocystis pneumonia-related at hospital discharge, day-28 (d-28) and d-90