Antimicrobial resistance of the enteric protozoon Giardia duodenalis – A narrative review

Abstract

IntroductionAs therapy-refractory giardiasis is an emerging health issue, this review aimed at summarizing mechanisms of reduced antimicrobial susceptibility in Giardia duodenalis and strategies to overcome this problem.MethodsA narrative review on antimicrobial resistance in G. duodenalis was based upon a selective literature research.ResultsFailed therapeutic success has been observed for all standard therapies of giardiasis comprising nitroimidazoles like metronidazole or tinidazole as first line substances but also benznidazoles like albendazole and mebendazole, the nitrofuran furazolidone, the thiazolide nitazoxanide, and the aminoglycoside paromomycin. Multicausality of the resistance phenotypes has been described, with differentiated gene expression due to epigenetic and post-translational modifications playing a considerable bigger role than mutational base exchanges in the parasite DNA. Standardized resistance testing algorithms are not available and clinical evidence for salvage therapies is scarce in spite of research efforts targeting new giardicidal drugs.ConclusionIn case of therapeutic failure of first line nitroimidazoles, salvage strategies including various options for combination therapy exist in spite of limited evidence and lacking routine diagnostic-compatible assays for antimicrobial susceptibility testing in G. duodenalis. Sufficiently powered clinical and diagnostic studies are needed to overcome both the lacking evidence regarding salvage therapy and the diagnostic neglect of antimicrobial resistance.

Genetic diversity in the metronidazole metabolism genes nitroreductases and pyruvate ferredoxin oxidoreductases in susceptible and refractory clinical samples of Giardia lamblia

“…This may as well mean that the drug resistant cells were not able to grow properly in the new environment after encystation. Loss of resistance during cell cycles may be linked to epigenetic and post-transcriptional changes than specific mutations being responsible for this temporary resistance pattern ( Loderstädt and Frickmann, 2021 ). MTZ is most likely activated through several different pathways and will therefore exhibit a pleiotropic mode of action ( Holmes et al, 2016 ).…”

Incidence, Management Experience and Characteristics of Patients with Giardiasis and Common Variable Immunodeficiency

“…Moreover, since there are few cases of refractory giardiasis, multicenter studies are required to define the best therapeutic alternatives. At the diagnostic level, it would be interesting to develop a strategy that combines the culture of the parasite with sequencing and comparative proteomics [ 55 ], which may allow moving from empirical treatment to targeted treatment in the future.…”

Evaluating the Effect of Lactobacillus casei FEGY 9973 and Curcumin on Experimental Giardiasis

“…Giardia lamblia was assumed to be a harmless bystander in the microbial gut flora until a few decades ago, but once the parasite’s pathogenicity was discovered, numerous types of medications were utilized to treat it [ 4 ]. These medications are mainly from the nitroimidazole, benzimidazole, quinacrine, paromomycin, or furazolidone families; however, due to an increase in the number of emerging resistant cases, new effective alternative treatments are needed [ 5 ]. There was an urgent need for alternate bio-therapeutic approaches, which included natural interventions such as probiotics and plant extracts, due to the continued evolution of infections resistant to normal giardiasis treatment, as well as reports of resistant G. lamblia strains [ 6 ].…”