Nitroimidazole - albendazole combination therapy, quinacrine use, and risk factors in nitroimidazole-refractory giardiasis: a prospective multicentre observational study

Background 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. Methods We 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. Results A 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. Conclusion Second 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.