Tolerance to nifurtimox and benznidazole in adult patients with chronic Chagas' disease.
Journal
The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617
Informations de publication
Date de publication:
01 03 2020
01 03 2020
Historique:
received:
13
08
2019
revised:
11
10
2019
accepted:
15
10
2019
pubmed:
23
11
2019
medline:
25
6
2021
entrez:
23
11
2019
Statut:
ppublish
Résumé
Current options for Chagas' disease treatment are restricted to benznidazole and nifurtimox. To the best of our knowledge, no study has ever compared their tolerance in adults in a non-endemic country. To compare the completion rates and drug tolerance in a cohort of patients treated according to current guidelines. We analysed the medical records of all Chagas' disease patients aged 18 years or over who started antiparasitic treatment at the Geneva University Hospitals, Switzerland, from 2008 to 2016. We recorded treatment duration and all adverse events. We included 176 patients, 92 and 84 of whom received benznidazole or nifurtimox, respectively. The overall treatment completion rate was 62.5%, without a significant difference between the groups (P=0.436). Most patients (89.8%) suffered at least one adverse event. Those receiving nifurtimox had more events (6.2 versus 3.5, P<0.001). Mucocutaneous symptoms predominated in the benznidazole group, whereas digestive symptoms were most frequent with nifurtimox. Neuropsychiatric events frequently occurred in both groups, most notably in patients receiving nifurtimox. Arthralgia, dyspnoea, sensitive neuropathy and pruritus were independent predictors of treatment interruption. Currently recommended drug regimens for Chagas' disease are not well tolerated and entail frequent treatment discontinuation irrespective of the drug used. This highlights the need to improve treatment tolerance in adults with Chagas' disease with new therapeutic options.
Sections du résumé
BACKGROUND
Current options for Chagas' disease treatment are restricted to benznidazole and nifurtimox. To the best of our knowledge, no study has ever compared their tolerance in adults in a non-endemic country.
OBJECTIVES
To compare the completion rates and drug tolerance in a cohort of patients treated according to current guidelines.
PATIENTS AND METHODS
We analysed the medical records of all Chagas' disease patients aged 18 years or over who started antiparasitic treatment at the Geneva University Hospitals, Switzerland, from 2008 to 2016. We recorded treatment duration and all adverse events.
RESULTS
We included 176 patients, 92 and 84 of whom received benznidazole or nifurtimox, respectively. The overall treatment completion rate was 62.5%, without a significant difference between the groups (P=0.436). Most patients (89.8%) suffered at least one adverse event. Those receiving nifurtimox had more events (6.2 versus 3.5, P<0.001). Mucocutaneous symptoms predominated in the benznidazole group, whereas digestive symptoms were most frequent with nifurtimox. Neuropsychiatric events frequently occurred in both groups, most notably in patients receiving nifurtimox. Arthralgia, dyspnoea, sensitive neuropathy and pruritus were independent predictors of treatment interruption.
CONCLUSIONS
Currently recommended drug regimens for Chagas' disease are not well tolerated and entail frequent treatment discontinuation irrespective of the drug used. This highlights the need to improve treatment tolerance in adults with Chagas' disease with new therapeutic options.
Identifiants
pubmed: 31754690
pii: 5637337
doi: 10.1093/jac/dkz473
pmc: PMC7021088
doi:
Substances chimiques
Nitroimidazoles
0
Trypanocidal Agents
0
Nifurtimox
M84I3K7C2O
benzonidazole
YC42NRJ1ZD
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
690-696Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.
Références
Mem Inst Oswaldo Cruz. 2015 May;110(3):422-32
pubmed: 25946151
Am J Trop Med Hyg. 2012 Sep;87(3):489-90
pubmed: 22826485
PLoS One. 2017 Sep 26;12(9):e0185033
pubmed: 28949997
Lancet. 2010 Apr 17;375(9723):1388-402
pubmed: 20399979
Antimicrob Agents Chemother. 2015;59(6):3342-9
pubmed: 25824212
Lancet Infect Dis. 2018 Apr;18(4):419-430
pubmed: 29352704
J Antimicrob Chemother. 2009 Dec;64(6):1139-47
pubmed: 19819909
Am J Trop Med Hyg. 2015 Dec;93(6):1224-1230
pubmed: 26392162
Euro Surveill. 2011 Sep 15;16(37):
pubmed: 21944555
Am J Trop Med Hyg. 1998 Oct;59(4):526-9
pubmed: 9790423
Expert Rev Clin Pharmacol. 2018 Oct;11(10):943-957
pubmed: 30111183
PLoS Negl Trop Dis. 2016 Nov 7;10(11):e0005033
pubmed: 27820837
Antimicrob Agents Chemother. 2017 Mar 24;61(4):
pubmed: 28167552
Clin Infect Dis. 2010 Nov 15;51(10):e69-75
pubmed: 20932171
Lancet. 2018 Jan 6;391(10115):82-94
pubmed: 28673423
Rev Soc Bras Med Trop. 2007 Jan-Feb;40(1):1-10
pubmed: 17486245
Int J Infect Dis. 2018 Aug;73:93-101
pubmed: 29879524
Mem Inst Oswaldo Cruz. 2002 Jan;97(1):3-24
pubmed: 11992141
Antimicrob Agents Chemother. 2014;58(2):635-9
pubmed: 24247135
Antimicrob Agents Chemother. 2013 Jan;57(1):390-5
pubmed: 23114763
Am J Trop Med Hyg. 2017 Nov;97(5):1469-1476
pubmed: 29016287
Rev Soc Bras Med Trop. 1997 Mar-Apr;30(2):139-44
pubmed: 9148337
Antimicrob Agents Chemother. 2015 Nov 23;60(2):833-7
pubmed: 26596935
Clin Infect Dis. 2016 Oct 15;63(8):1056-1062
pubmed: 27432838
J Biomol Screen. 2015 Jan;20(1):22-35
pubmed: 25245987
Antimicrob Agents Chemother. 2010 Nov;54(11):4896-9
pubmed: 20823286
Rev Soc Bras Med Trop. 2017 May-Jun;50(3):296-300
pubmed: 28700045
PLoS Negl Trop Dis. 2015 Feb 13;9(2):e0003540
pubmed: 25680190
Lancet Infect Dis. 2015 Nov;15(11):1347-56
pubmed: 26231478
JAMA. 2007 Nov 14;298(18):2171-81
pubmed: 18000201
Pediatrics. 2011 Jan;127(1):e212-8
pubmed: 21173000
Rev Esp Quimioter. 2011 Sep;24(3):123-6
pubmed: 21947093
Clin Infect Dis. 2015 Apr 15;60(8):1237-40
pubmed: 25601454
Rev Inst Med Trop Sao Paulo. 1996 Jan-Feb;38(1):35-8
pubmed: 8762637
Rev Esp Quimioter. 2012 Mar;25(1):74-5
pubmed: 22488545
Acta Trop. 2010 Jul-Aug;115(1-2):55-68
pubmed: 19900395
Ann Intern Med. 2006 May 16;144(10):724-34
pubmed: 16702588