By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

SYNOPSIS: Quinacrine is highly effective in the treatment of giardiasis that is recalcitrant to initial therapy with other agents, but patients must be warned about neuropsychiatric effects.

SOURCES: Neumayr A, Schunk M, Theunissen C, et al. Efficacy and tolerability of quinacrine monotherapy and albendazole plus chloroquine combination therapy in nitroimidazole-refractory giardiasis: A TropNet study. Clin Infect Dis 2021; Jun 11:ciab513. doi: 10.1093/cid/ciab513. [Online ahead of print].

Ydsten KA, Hellgren U, Asgeirsson H. Quinacrine treatment of nitroimidazole-refractory giardiasis. J Infect Dis 2021; May 24:jiab287. doi: 10.1093/infdis/jiab287. [Online ahead of print].

In a prospective, open-label, non-randomized study at four European travel clinics belonging to the TropNet group, Neumayr and colleagues evaluated the outcomes of two different treatment regimens in patients with giardiasis who had failed one or more 5-nitroimidazole treatment courses. The patients, 57% of whom had acquired their infection in India, then were treated for five days with either quinacrine alone (100 mg three times daily) or the combination of albendazole (400 mg twice daily) plus chloroquine (155 mg twice daily). The choice of treatment was based on local availability of the drugs.

Among those for whom the data were available, monotherapy with quinacrine was associated with clinical cure in 59/72 (81%) and parasitological cure in 56/56 (100%). The combination of albendazole and chloroquine, in contrast, yielded clinical cure in 12/33 (36%) and parasitological cure in 12/25 (48%). In addition, clinical cure was achieved in all nine patients treated with quinacrine who had failed the combination therapy. Mild-to-moderate treatment-related adverse effects occurred in 45% of quinacrine and 30% of combination therapy recipients. One patient given quinacrine developed severe neuropsychiatric symptoms after his fourth day of treatment that led to a brief hospitalization and then completely resolved. One quinacrine recipient developed acute kidney injury, but this was judged to be due to dehydration resulting from diarrhea from giardiasis.

Separately, Ydsten and colleagues at the Karolinska University Hospital retrospectively examined the records of 87 patients who had failed two courses of treatment of giardiasis; 54 patients (62%) had traveled to India. Of the 87 patients, 54 (62%) had been given quinacrine (two in combination with metronidazole) in a dose of 100 mg three times daily — most for five to seven days. After treatment, six (12%) patients had symptom persistence, while parasitological efficacy was 94%. Repeat quinacrine treatment was effective in each of the three patients who had failed their initial course. After quinacrine, the second most frequent regimen administered to patients who had failed nitroimidazole therapy was albendazole plus metronidazole, which had a 57% failure rate among the 37 patients for whom follow-up samples were available. Among the quinacrine recipients, there were no serious adverse events among seven patients with a prior diagnosis of psychiatric disorder, although one patient, in addition to headache and gastrointestinal complaints, transiently felt distracted.

COMMENTARY

Literature suggests that the frequency of treatment failure of giardiasis with 5-nitroimidazoles, such as metronidazole, appears to be increasing. Furthermore, evidence points to India being a source of many infections recalcitrant to treatment with those agents.

The Centers for Disease Control and Prevention states that effective treatments for initial treatment of giardiasis include metronidazole, tinidazole, and nitazoxanide, and that others include paromomycin, quinacrine, and furazolidone.1 For treatment failures, they recommend considering combination therapy, but they do not recommend specific agents. A recent review of refractory disease points out that no randomized controlled trials addressing this problem have been performed in a quarter of a century. Based on the available information, they state that quinacrine is effective, but warn that side effects may limit its use.

Because of their design, the studies presented here cannot be considered to provide high-quality evidence. Neither was randomized, and one was retrospective. In the other, although it was prospective, treatment assignment was based on availability of the therapeutic agents. Nonetheless, the results clearly indicate that quinacrine is a highly effective agent in the treatment of giardiasis refractory to other treatments. One serious adverse event, a neuropsychiatric disturbance, occurred in 126 patients given quinacrine in the two studies, and this resolved with drug discontinuation.

That is the good news about quinacrine. The bad news is that quinacrine is available in the United States only through compounding pharmacies. 

REFERENCES

  1. Centers for Disease Control and Prevention. Parasites – Giardia. Diagnosis and treatment information for medical professionals. https://www.cdc.gov/parasites/giardia/medical-professionals.html
  2. Mørch K, Hanevik K. Giardiasis treatment: An update with a focus on refractory disease. Curr Opin Infect Dis 2020;33:355-364.