5-Nitroimidazole refractory giardiasis is common in Matanzas, Cuba and effectively treated by secnidazole plus high-dose mebendazole or quinacrine: a prospective observational cohort study

Abstract

Objective: To evaluate the effectiveness and tolerability of secnidazole combined with high-dose mebendazole for treatment of 5-nitroimidazole-resistant giardiasis.

Method: Adults with microscopically verified Giardia intestinalis monoinfection attending a secondary level hospital in Matanzas City, Cuba were prospectively included in a cohort. A recently introduced treatment ladder consisting of metronidazole as first-line treatment, followed by secnidazole, tinidazole, secnidazole plus mebendazole and quinacrine as second-to fifth-line treatments, respectively, was used. Adverse events and treatment success were determined by questioning and microscopy on concentrated stool samples, respectively on days 3, 5 and 7 after the end of treatment. If G. intestinalis was detected on day 3, 5 or 7, then the infection was classified as refractory and no further microscopy was performed.

Results: A total of 456 individuals were included. Metronidazole, 500 mg three times daily for 5 days, cured 248/456 (54%) patients. A single 2-g secnidazole dose as second-line treatment cured 50/208 (24%) patients. A single 2-g tinidazole dose as third-line treatment cured 43/158 (27%) patients. Three rounds of 5-nitroimidazole therapy therefore cured 341/456 (75%) patients. Secnidazole plus mebendazole (200 mg every 8 hours for 3 days) cured 100/115 (87%) of nitroimidazole refractory infections. Quinacrine cured the remaining 15 patients. All treatments were well tolerated.

Conclusions: 5-Nitroimidazole refractory giardiasis was common, indicating that an alternative first-line treatment may be needed. Retreatment of metronidazole refractory giardiasis with an alternative 5-nitroimidazole was suboptimal, indicating cross-resistance. Mebendazole plus secnidazole were well tolerated and effective for the treatment of 5-nitroimidazole refractory G. intestinalis infection in this setting.

Keywords: Giardia intestinalis; Mebendazole; Metronidazole; Quinacrine; Refractory giardiasis; Secnidazole; Tinidazole; Treatment failure.