Achromobacter denitrificans pneumonia in a kidney transplant recipient – dose-dependent decrease of phagocytic activity as a potential mechanism for everolimus pulmonary toxicity

Mammalian target of rapamycin (mTOR) inhibitors inclusive regimens are associated with increased risk of pulmonary toxicity, but the underlying mechanism has not been elucidated so far. We present the case of a 68-year-old man, after deceased-donor kidney transplantation (KTx), maintained on de novo everolimus (EVR) based immunosuppression, who developed Achromobacter denitrificans pneumonia 3 months after KTx. There was clinical improvement with antibiotic treatment, but without a radiological resolution. An additional reduction of the EVR dose resulted only in partial resolution of radiological abnormalities. We performed a functional analysis of peripheral blood neutrophils and monocytes. The ability of phagocytosis and oxidative burst generation against A. denitrificans and Escherichia coli was significantly decreased on EVR treatment as compared to the control healthy person, and significantly improved after 3 weeks of EVR absence. Additionally, these processes were significantly affected by increasing doses of EVR in vitro in the control healthy donor in a dose-dependent manner. EVR discontinuation, with no additional antibiotic treatment, resulted in complete recovery and resolution of pulmonary infiltrates. Our findings suggest that dose-dependent impairment of neutrophil/monocyte phagocytic activity and oxidative burst generation might be a potential mechanism for EVR pulmonary toxicity.