RESUMEN
The major cause of mortality in people with cystic fibrosis (pwCF) is progressive lung disease characterised by acute and chronic infections, the accumulation of mucus, airway inflammation, structural damage and pulmonary exacerbations. The prevalence of Pseudomonas aeruginosa rises rapidly in the teenage years, and this organism is the most common cause of chronic lung infection in adults with cystic fibrosis (CF). It is associated with an accelerated decline in lung function and premature death. New P. aeruginosa infections are treated with antibiotics to eradicate the organism, while chronic infections require long-term inhaled antibiotic therapy. The prevalence of P. aeruginosa infections has decreased in CF registries since the introduction of CF transmembrane conductance regulator modulators (CFTRm), but clinical observations suggest that chronic P. aeruginosa infections usually persist in patients receiving CFTRm. This indicates that pwCF may still need inhaled antibiotics in the CFTRm era to maintain long-term control of P. aeruginosa infections. Here, we provide an overview of the changing perceptions of P. aeruginosa infection management, including considerations on detection and treatment, the therapy burden associated with inhaled antibiotics and the potential effects of CFTRm on the lung microbiome. We conclude that updated guidance is required on the diagnosis and management of P. aeruginosa infection. In particular, we highlight a need for prospective studies to evaluate the consequences of stopping inhaled antibiotic therapy in pwCF who have chronic P. aeruginosa infection and are receiving CFTRm. This will help inform new guidelines on the use of antibiotics alongside CFTRm.
Asunto(s)
Antibacterianos , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Fibrosis Quística , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Humanos , Administración por Inhalación , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Fibrosis Quística/complicaciones , Fibrosis Quística/microbiología , Fibrosis Quística/tratamiento farmacológico , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Infecciones por Pseudomonas/tratamiento farmacológicoRESUMEN
BACKGROUND: The use of elexacaftor/tezacaftor/ivacaftor (ETI) in people with cystic fibrosis (pwCF) after solid organ transplantation is controversial because of potential drug-drug interactions (DDI) with tacrolimus. We aimed to improve insight into the safety and clinical benefits of co-administration of ETI and tacrolimus in liver or kidney transplanted adult pwCF. METHODS: In 5 pwCF, tacrolimus concentrations were monitored during 2 weeks before and 4 weeks after starting ETI treatment. Trough levels, area under the curve (AUC) and clinical effect of ETI were investigated. During the study (6 weeks in total) adverse events were monitored. RESULTS: The DDI between tacrolimus and ETI resulted in an increased exposure of tacrolimus in all subjects, the dose adjusted AUC0-24h was 1.79 (median) times higher at the end of the study. Five dose adjustments were performed in 4 subjects in order to attain tacrolimus target range. No adverse events were reported and all subjects showed clinical improvement during ETI treatment. CONCLUSION: The clinical value of ETI treatment in kidney and liver transplanted pwCF is clear. The use of ETI may increase tacrolimus levels moderately. Therefore, we recommend close monitoring of tacrolimus trough levels in patients who start ETI.
Asunto(s)
Aminofenoles , Benzodioxoles , Fibrosis Quística , Interacciones Farmacológicas , Inmunosupresores , Indoles , Trasplante de Riñón , Trasplante de Hígado , Quinolonas , Tacrolimus , Humanos , Fibrosis Quística/cirugía , Fibrosis Quística/tratamiento farmacológico , Tacrolimus/administración & dosificación , Tacrolimus/farmacocinética , Tacrolimus/efectos adversos , Masculino , Femenino , Adulto , Benzodioxoles/efectos adversos , Benzodioxoles/administración & dosificación , Benzodioxoles/uso terapéutico , Quinolonas/administración & dosificación , Quinolonas/efectos adversos , Quinolonas/farmacocinética , Trasplante de Hígado/métodos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Inmunosupresores/farmacocinética , Trasplante de Riñón/efectos adversos , Aminofenoles/administración & dosificación , Aminofenoles/efectos adversos , Aminofenoles/farmacocinética , Aminofenoles/uso terapéutico , Indoles/administración & dosificación , Indoles/efectos adversos , Indoles/farmacocinética , Pirazoles/farmacocinética , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Combinación de Medicamentos , Piridinas/administración & dosificación , Piridinas/farmacocinética , Piridinas/efectos adversos , Pirroles/administración & dosificación , Pirroles/farmacocinética , Pirroles/efectos adversos , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Quinolinas/farmacocinética , Adulto Joven , Monitoreo de Drogas/métodos , PirrolidinasRESUMEN
Abstract Background With improvements in care for people with Cystic Fibrosis (pwCF), total survival after Lung Transplantation (LTx) will be longer. Therefore, this population's up-to-date analysis of late-onset post-transplant metabolic and vascular complications will be more relevant in current clinical practice. Methods We studied 100 pwCF who underwent an LTx between 2001 and 2020 at the University Medical Centre Utrecht, the Netherlands. The median age at transplant was 31 years and 55 percent was male. We assessed survival, the prevalence of metabolic complications (diabetes, renal damage, dyslipidemia, and metabolic syndrome), and vascular complications (hypertension, heart rhythm disease, micro-, and macrovascular disease). In addition, differences in risks for developing complications based on sex and overall survival were analyzed. Results The prevalence of macrovascular disease raised to 15.9 percent 15 years post-LTx. The prevalence of diabetes increased from 63 percent at LTx to over 90 percent 15 years post-LTx and the prevalence of dyslipidemia increased from 21 percent to over 80 percent. Survival 1-, 2-, 5-, and 10 years post-transplant were 84, 80, 76, and 58 percent respectively. No significant differences were found based on sex. Conclusion This study shows that the prevalence of cardiovascular risk factors increases after LTx for CF, potentially leading to major complications. These data emphasize the necessity of regular check-ups for metabolic and vascular complications after LTx with specific attention to renal damage. Early recognition of these complications is crucial and will lead to earlier intervention, which could lead to improved prognosis after lung transplantation.