Expert consensus on the management of adverse events and prescribing practices associated with the treatment of patients taking pirfenidone for idiopathic pulmonary fibrosis: a Delphi consensus study.

BACKGROUND: In patients with idiopathic pulmonary fibrosis (IPF) treated with pirfenidone (Esbriet®, Genentech USA, Inc. South San Francisco, CA.), effectively managing treatment-related adverse events (AEs) may improve adherence. Due to a lack of clinical evidence and expertise, managing these AEs can be challenging for patients and physicians alike. In the absence of evidence, consensus recommendations from physicians experienced in using pirfenidone to treat IPF are beneficial. METHODS: Using a modified Delphi process, expert recommendations were developed by a panel of physicians experienced with using pirfenidone for IPF. Over three iterations, panelists developed and refined a series of statements on the use of pirfenidone in IPF. Their agreement on each statement was ranked using a Likert scale. RESULTS: A panel of 12 physicians participated and developed a total of 286 statements on dosing and administration, special populations, drug-drug interactions, laboratory analysis, warnings and precautions, and AE management. Expert recommendations were achieved with regard to slower initial titrations and slower titrations for AEs, dosing with meal(s) or substantial meals, and adding other prescribed pharmacological agents for AEs. CONCLUSION: Until there is further clinical evidence, the resulting consensus recommendations are intended to provide direction on the practical management of IPF with pirfenidone, by encompassing a broad experience from the real world to complement data gleaned from clinical trials.

Single-center experience with use of letermovir for CMV prophylaxis or treatment in thoracic organ transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) infection is common in thoracic organ transplant recipients. Valganciclovir and ganciclovir are used for both prophylaxis and treatment of this infection, but intolerance and treatment failure are common. Letermovir has been demonstrated to reduce the risk of CMV infection when used for prophylaxis in allogeneic hematopoietic cell transplantation. However, there are no data on its efficacy in thoracic organ transplantation. METHODS: We examined the use of letermovir for either CMV prophylaxis (primary and secondary) or treatment in heart and lung transplant recipients at our institution from February 1, 2018, through December 31, 2018. RESULTS: Nine total patients received letermovir at our institution (8 lung transplant, 1 heart transplant) during the study period. Letermovir was prescribed for CMV prophylaxis in eight patients (primary prophylaxis in two patients and secondary prophylaxis in 6 patients), and for treatment of CMV DNAemia in two cases. One patient received letermovir for both secondary prophylaxis and treatment on separate occasions. Three out of 8 (37.5%) patients receiving letermovir for prophylaxis developed CMV DNAemia during prophylaxis. One patient treated for CMV disease had clinical failure with a sharp rise in serum CMV DNA PCR. The other patient treated for low-grade CMV DNAemia initially had a slight rise in CMV DNA PCR, but has since had a sustained response. No major side effects were experienced, and 2 patients reported minor side effects. CONCLUSION: Letermovir was well tolerated with only minor side effects reported; however, the rate of development of CMV DNAemia on prophylaxis was considerable. Further study of the dosing and efficacy of letermovir for CMV prophylaxis or treatment in thoracic organ transplant recipients is warranted.

Lung nodules due to Candida parapsilosis in a person with cystic fibrosis.

We present the first reported case of Candida parapsilosis pulmonary infection presenting as lung nodules. The patient is a 31-year-old man with cystic fibrosis (CF) colonised with multidrug-resistant Escherichia coli and increased frequency of pulmonary exacerbations in the preceding months. While on intravenous antibiotics for a pulmonary exacerbation, he developed bilateral pulmonary nodules. Bronchoalveolar lavage cultures grew C. parapsilosis He was initially treated with dual antifungal therapy, voriconazole and micafungin. Discontinuation of voriconazole due to transaminitis resulted in the development of new nodules, and isavuconazonium was added. Repeat imaging revealed no progression of disease. Micafungin was eventually discontinued. Monotherapy with isavuconazonium is planned for 1 year post lung transplant. In the CF population, C. parapsilosis may be an opportunistic pathogen. The case highlights that frequent CF exacerbations and antibiotic exposure increase the risk for opportunistic infections including Candida species and the implications for lung transplantation in this setting.