학술논문
The renoprotective effect of concomitant fosfomycin in the treatment of pulmonary exacerbations in cystic fibrosis
ORIGINAL ARTICLE
ORIGINAL ARTICLE
Document Type
Report
Source
Clinical Kidney Journal. October 2019, Vol. 12 Issue 5, p652, 7 p.
Subject
Language
English
ISSN
2048-8505
Abstract
INTRODUCTION Effective antibiotic therapy is critical in CF, where pulmonary exacerbations typically caused by bacteria such as Pseudomonas aeruginosa (Psa) are associated with clinical decline and increased morbidity. Multiresistant isolates [...]
Background. Fosfomycin, effective in Cystic Fibrosis (CF), competes with aminoglycosides at renal binding sites and may therefore afford a renoprotective effect when used in combination therapy. We explored this by using markers of acute renal tubular damage [N-acetyl-[beta]-D-glucose-aminidase (NAG), alanine amino-peptidase (AAP) and [[beta].sub.2] -microglobulin]. Methods. Using a prospective randomized crossover trial design, at an acute pulmonary exacerbation, 18 adult CF patients received either 14 days of intravenous (IV) tobramycin or IV tobramycin and IV fosfomycin, both in combination with a second IV antibiotic (colomycin). Results. Urinary NAG (P = 0.003) and AAP (P = 0.03) following treatment with concomitant fosfomycin were lower than those after treatment with tobramycin and colomycin alone. Fosfomycin attenuated the total 24-h urinary protein leak (P = 0.0001). The 14-day improvements in all surrogate markers of exacerbation resolution ([FEV.sub.1]% predicted, FVC, white cell count and C-reactive protein) were similar for both treatment regimens. Conclusions. The addition of fosfomycin reduces acute renal injury caused by IV aminoglycoside therapy in CF pulmonary exacerbations. Keywords: acute tubular necrosis, cystic fibrosis, fosfomycin, pulmonary exacerbations, renoprotection
Background. Fosfomycin, effective in Cystic Fibrosis (CF), competes with aminoglycosides at renal binding sites and may therefore afford a renoprotective effect when used in combination therapy. We explored this by using markers of acute renal tubular damage [N-acetyl-[beta]-D-glucose-aminidase (NAG), alanine amino-peptidase (AAP) and [[beta].sub.2] -microglobulin]. Methods. Using a prospective randomized crossover trial design, at an acute pulmonary exacerbation, 18 adult CF patients received either 14 days of intravenous (IV) tobramycin or IV tobramycin and IV fosfomycin, both in combination with a second IV antibiotic (colomycin). Results. Urinary NAG (P = 0.003) and AAP (P = 0.03) following treatment with concomitant fosfomycin were lower than those after treatment with tobramycin and colomycin alone. Fosfomycin attenuated the total 24-h urinary protein leak (P = 0.0001). The 14-day improvements in all surrogate markers of exacerbation resolution ([FEV.sub.1]% predicted, FVC, white cell count and C-reactive protein) were similar for both treatment regimens. Conclusions. The addition of fosfomycin reduces acute renal injury caused by IV aminoglycoside therapy in CF pulmonary exacerbations. Keywords: acute tubular necrosis, cystic fibrosis, fosfomycin, pulmonary exacerbations, renoprotection