Therapeutic drug monitoring in cystic fibrosis and associations with pulmonary exacerbations and lung function.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy have resulted in longer life expectancies, yet pulmonary exacerbations remain a leading cause of morbidity. Intravenous antibiotics is the mainstay treatment, however achieving adequate concentrations remains challenging. The effect of therapeutic drug monitoring (TDM) of beta-lactams on exacerbations and lung function has not been studied. METHODS: Patient demographics, antibiotic regimens, forced expiratory volume 1 s (FEV1), and exacerbation history was obtained from 32 patients with cystic fibrosis admitted for exacerbations. All patients were colonized with Pseudomonas aeruginosa, received CFTR therapy for at least one year, and had 3-month interval follow ups. Plasma concentrations, FEV1, and exacerbation history was obtained before and after therapeutic drug monitoring. This included peak and trough plasma concentrations of piperacillin-tazobactam and cefepime using liquid chromatography with mass spectrometry. T-test and Mann-Whitney U test were used to compare medians/means of FEV1 and pulmonary exacerbations pre and post-TDM as well as free trough-to-minimum inhibitory concentration ratio (fCmin/MIC) ≥1 and ≥ 4. RESULTS: TDM was associated with decreased exacerbations/year from 1.91 to 1.31 (p = 0.04) and among the cohort with >/ = 2 exacerbations per year, there was a longer exacerbation free interval after TDM (196.2 vs 103.7 days, p = 0.02). The decline in FEV1% predicted after therapeutic drug monitoring to the first exacerbation was -4.9 compared to -9.7 prior (p = 0.03). CONCLUSIONS: TDM for cystic fibrosis pulmonary exacerbations results in decreased pulmonary exacerbations, longer intervals to pulmonary exacerbation, and lower decline in FEV1% predicted.

Malpositioned nephrostomy tube with associated hemorrhagic pleural effusion.

Pleural effusion of extra-vascular origin has a large differential diagnosis. Ultrasonography can be utilized alongside pleural fluid analysis to determine a pleural effusion's complexity and size, thus helping aid in both diagnostic and therapeutic management. We describe the case of a 38-year-old male with a prior medical history of neurogenic bladder and nephrolithiasis with percutaneous nephrostomy tube placed one week prior to presentation. Using ultrasonography, the nephrostomy tube was determined to be positioned within the pleural cavity with a resultant hemorrhagic pleural effusion.

CFTR modulator use in post lung transplant recipients.

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator therapy has previously been contraindicated in solid organ transplant recipients. This was due to lack of data and concern for interactions with immunosuppressive drug regimens. However, in post-lung transplant recipients, CFTR modulators may improve extrapulmonary manifestations of cystic fibrosis without impacting graft function or immunosuppressive drug levels. Herein, we present our single center experience with the use of elexacaftor/tezacaftor/ivacaftor, Trikafta, in adult post-lung transplant recipients.

A rare case of disseminated Sporothrix schenckii with bone marrow involvement in a patient with idiopathic CD4 lymphocytopenia.

Sporothrix schenckii is a pathogen with a predilection for dissemination in immunocompromised individuals, often with HIV. We report a case of disseminated sporotrichosis in an unfortunate 25 year old male (without HIV) who was originally treated for presumed pneumonia. The patient continued to worsen clinically and further work-up eventually revealed Sporothrix schenckii species with involvement of multiple organs including the skin, heart, lungs and bone marrow. Despite treatment with multiple antibacterials and antifungals, he ultimately passed away. This case illustrates the aggressive nature of this disease along with the importance of early/proper diagnosis and treatment.