Nitroimidazole - albendazole combination therapy, quinacrine use, and risk factors in nitroimidazole-refractory giardiasis: a prospective multicentre observational study
摘要
Nitroimidazole-refractory giardiasis is an increasing problem. We present data on efficacy of a treatment ladder and on clinical characteristics and assemblage types in nitroimidazole-refractory giardiasis.
MethodsWe conducted a prospective clinical observational study of adult patients with giardiasis at four centres in Norway and England during 2009 – 2024. Patients with nitroimidazole-refractory giardiasis were treated with albendazole plus a 5-nitroimidazole followed by quinacrine (mepacrine) if failure. Treatment efficacy was defined as negative stool microscopy and/or PCR four to six weeks after treatment. For analyses of assemblage types and risk factors for treatment failure, patients from a previously published Swiss treatment study were additionally included. Assemblage typing of Giardia isolates was performed collectively in the same laboratory by real-time PCR targeting the glutamate dehydrogenase gene (gdh). Predictors identified by univariate analyses were analysed by multivariate logistic regression for association with nitroimidazole failure.
ResultsA total of 120 patients were prospectively included; 59 of these had nitroimidazole refractory giardiasis and were treated according to the treatment ladder. In addition, 20 patients from the Swiss cohort were included for assemblage and risk factor analyses. A repeated course of nitroimidazole cured only 24% (5/21). Metronidazole or tinidazole in combination with albendazole cured 76% (35/46). Quinacrine was effective in 100% (15/15). Assemblage B was more common in travellers from India and Africa, but only acquisition of infection in India (aOR 11.9; 95%CI 2.94, 47.6) and more recent year of diagnosis (aOR 1.18, 95% CI 1.03, 1.35) were associated with nitroimidazole failure in multivariate analysis.
ConclusionSecond line treatment with nitroimidazole in combination with albendazole, and third line treatment with quinacrine, are effective options in nitroimidazole-refractory giardiasis. Nitroimidazole failure seems to be highly associated with infection acquired in India, but not with assemblage A or B. Further studies of resistance mechanisms are needed.