Long term streptomycin toxicity in the treatment of Buruli Ulcer: follow-up of participants in the BURULICO drug trial

• Published in: PLoS neglected tropical diseases Vol. 8; no. 3; p. e2739
• Main Authors: Klis, Sandor, Stienstra, Ymkje, Phillips, Richard O, Abass, Kabiru Mohammed, Tuah, Wilson, van der Werf, Tjip S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.03.2014; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Audiometry; Buruli ulcer; Buruli Ulcer - drug therapy; Child; Child, Preschool; Complications and side effects; Creatinine - blood; Dosage and administration; Drug dosages; Drug therapy; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - pathology; Drugs; Family medical history; Female; Health aspects; Hearing loss; Hearing Loss - chemically induced; Hearing Loss - epidemiology; Hearing Loss - pathology; Humans; Kidney Diseases - chemically induced; Kidney Diseases - epidemiology; Kidney Diseases - pathology; Long term; Male; Medicine; Middle Aged; Mitochondrial DNA; Patient outcomes; Skin diseases; Streptomycin; Streptomycin - adverse effects; Streptomycin - therapeutic use; Studies; Surgery; Toxicity; Ulcers; Young Adult; Africa; Creatinine; Kidney Diseases; Streptomycin; Audiometry; Humans; Middle Aged; Child, Preschool; Male; Young Adult; Aged, 80 & over; Anti-Bacterial Agents; Drug-Related Side Effects & Adverse Reactions; Adolescent; Adult; Female; Aged; Buruli Ulcer; Child; Hearing Loss
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0002739

Buruli Ulcer (BU) is a tropical infectious skin disease that is currently treated with 8 weeks of intramuscular streptomycin and oral rifampicin. As prolonged streptomycin administration can cause both oto- and nephrotoxicity, we evaluated its long term toxicity by following-up former BU patients that had received either 4 or 8 weeks of streptomycin in addition to other drugs between 2006 and 2008, in the context of a randomized controlled trial. Former patients were retrieved in 2012, and oto- and nephrotoxicity were determined by audiometry and serum creatinine levels. Data were compared with baseline and week 8 measurements during the drug trial. Of the total of 151 former patients, 127 (84%) were retrieved. Ototoxicity was present in 29% of adults and 25% of children. Adults in the 8 week streptomycin group had significantly higher hearing thresholds in all frequencies at long term follow-up, and these differences were most prominent in the high frequencies. In children, no differences between the two treatment arms were found. Nephrotoxicity that had been detected in 14% of adults and in 13% of children during treatment, was present in only 2.4% of patients at long term follow-up. Prolonged streptomycin administration in the adult study subjects caused significant persistent hearing loss, especially in the high frequency range. Nephrotoxicity was also present in both adults and children but appeared to be transient. Streptomycin should be given with caution especially in patients aged 16 or older, and in individuals with concurrent risks for renal dysfunction or hearing loss.