Low-dose caspofungin is a safe and effective treatment option for invasive fungal infections after cardiac surgery

Objectives: Invasive fungal infections (IFI) remain a main cause of death after heart surgery, in spite of the advances in pharmacological therapy. Caspofungin is an echinocandin with high efficacy against IFI in surgical and intensive care patients. However, the recommended dosis of caspofungin can lead to hepatic failure in patients with impaired hepatic function. Our aim was to assess the effectiveness and safety of a reduced dosage of caspofungin in patients at the ICU with a higher risk of hepatic failure after major cardiac surgery.

Methods: 134 consecutive patients presenting with suspicion of IFI after heart surgery and treated with low dose caspofungin (loading dose 50mg/d; maintenance 35mg/d) were retrospectively studied. Demographics, surgical procedure, type of infection, responsible pathogen, outcome, and adverse events were analyzed.

Results: 134 patients (96 males, 38 females; mean age 66±14 y) were studied; Procedure: CABG: 17.9%; HTX: 16.4%; VAD: 11.2%; valve surgery: 25.4%; others: 29.1%. Type of infection: catheter-related infection: 11.2%, positive blood culture 0.7%, pulmonary infection 69.4%, positive smears 3.0%, others 7.5% and no proven evidence for fungal infection 8.2%. 41 patients (30.6%) suffered from diabetes mellitus, and 12 patients (9%) from active malignomas. The fungal infection was the primary infection only in 36% of the patients. Only 15.7% of the patients stayed without bacterial co-infection during the antifungal therapy. Duration of treatment was 10.2±6.6d. Outcomes: 62.9% of the patients showed clinical improvement, in 18.7% of the patients healing without residues could be achieved. Side effects were reported in 4.5% of the cases, but did not necessitate a change of treatment. 33.6% of the patients died within 30 days after the diagnosis of IFI.

Conclusions: Low-dose caspofungin proved safe and effective in our collective of patients and may be an alternative to other antifungals, and to the recommended dose of caspofungin in high risk patients with impaired hepatic function. Prospective trials are mandatory to evaluate the possible application of low dosed caspofungin in the treatment and prophylaxis of Candida and Aspergillum infections at the ICU.