Treatment strategies for nitroimidazole-refractory giardiasis: a systematic review

Rationale for review: Giardiasis is one of the most common human protozoal infections worldwide. First line therapy of giardiasis includes nitroimidazole antibiotics. However, treatment failure with nitroimidazoles is increasingly reported with up to 45% of patients not responding to initial treatment. There is no clear consensus on the approach to the management of nitroimidazole refractory giardiasis. This systematic review aims to summarize the literature on pharmacotherapy for nitroimidazole refractory giardiasis. METHODS: We conducted a systematic review of the literature to determine the optimal management strategies for nitroimidazole refractory giardiasis. We searched Pubmed/MEDLINE, Embase, and Cochrane library using the following search terms 'Giardia' AND 'treatment failure' OR 'refractory giardia' OR 'resistant giardia' with date limits of January 1, 1970 to June 30, 2021. We included all reports on humans which described clinical outcomes of individuals with treatment refractory giardiasis, including case series and case reports. A descriptive synthesis of the data was conducted with pooling of data for interventions. KEY FINDINGS: Included in this review were 5 prospective studies, 3 retrospective studies, 7 case series and 9 case reports. Across these reports, a wide heterogeneity of treatment regimens was employed, including re-treatment with an alternative nitroimidazole, combination therapy with a nitroimidazole and another agent, and monotherapy with non-nitroimidazole regimens including quinacrine, paromomycin and nitazoxanide. Retreatment with a nitroimidazole was not an effective therapy for refractory giardiasis. However, treatment with a nitroimidazole in combination with albendazole had a cure rate of 66.9%. In the included studies, quinacrine monotherapy was administered to a total of 179 patients with a clinical cure rate of 88.8%. Overall, quinacrine was fairly well tolerated. CONCLUSIONS: Reports on the treatment of nitroimidazole refractory giardiasis demonstrate a heterogeneous approach to treatment. Of these, quinacrine appeared to be highly effective though more data on its safety is needed.