Metronidazole and Giardia: In vitro viability assay under microaerobic conditions indicates a multifactorial basis for metronidazole treatment failure

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F25%3A10504956" target="_blank" >RIV/00216208:11110/25:10504956 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Z9z5OPPR_A" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=Z9z5OPPR_A</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jgar.2025.09.010" target="_blank" >10.1016/j.jgar.2025.09.010</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Metronidazole and Giardia: In vitro viability assay under microaerobic conditions indicates a multifactorial basis for metronidazole treatment failure

Popis výsledku v původním jazyce

Objectives: Giardiasis, a worldwide intestinal infection caused by the protozoan parasite Giardia intestinalis , is treatable with metronidazole (MTZ). However, MTZ-refractory giardiasis is common. It remains unclear, however, whether MTZ-resistant pathogens cause treatment failure because the natural resistance of Giardia to MTZ has not yet been demonstrated. Methods: We developed a simple 24 h viability assay to assess the MTZ sensitivity of Giardia parasites in vitro under two atmospheric conditions, microaerobic and anaerobic. The results of the assay were statistically evaluated. Results: We tested 18 clinical isolates. Based on the minimum lethal concentration (MLC), hierarchical cluster analysis separated the isolates into three categories: sensitive, intermediate resistant, and resistant. The resistant cluster consisted of two isolates with an MLC of 400 mu g/mL MTZ, which exhibited natural MTZ resistance. Interestingly, this resistance was only manifested under microaerobic conditions. The effect of oxygen on the in vitro drug response was evident in the greater variability of MLC values among the other isolates. Two in vitro-resistant isolates originated from patients with MTZ-refractory giardiasis, suggesting that parasite resistance likely contributes to treatment failure. However, two additional isolates from patients with MTZ-refractory giardiasis showed in vitro susceptibility under both test conditions. This indicates that treatment failure in giardiasis likely stems from multiple factors. Conclusions: Our study highlights the critical importance of oxygen concentration during assessment of Giardia parasite resistance to MTZ. However, it also indicates that MTZ-refractory giardiasis may result from reasons other than parasite resistance.

Název v anglickém jazyce

Metronidazole and Giardia: In vitro viability assay under microaerobic conditions indicates a multifactorial basis for metronidazole treatment failure

Popis výsledku anglicky

Objectives: Giardiasis, a worldwide intestinal infection caused by the protozoan parasite Giardia intestinalis , is treatable with metronidazole (MTZ). However, MTZ-refractory giardiasis is common. It remains unclear, however, whether MTZ-resistant pathogens cause treatment failure because the natural resistance of Giardia to MTZ has not yet been demonstrated. Methods: We developed a simple 24 h viability assay to assess the MTZ sensitivity of Giardia parasites in vitro under two atmospheric conditions, microaerobic and anaerobic. The results of the assay were statistically evaluated. Results: We tested 18 clinical isolates. Based on the minimum lethal concentration (MLC), hierarchical cluster analysis separated the isolates into three categories: sensitive, intermediate resistant, and resistant. The resistant cluster consisted of two isolates with an MLC of 400 mu g/mL MTZ, which exhibited natural MTZ resistance. Interestingly, this resistance was only manifested under microaerobic conditions. The effect of oxygen on the in vitro drug response was evident in the greater variability of MLC values among the other isolates. Two in vitro-resistant isolates originated from patients with MTZ-refractory giardiasis, suggesting that parasite resistance likely contributes to treatment failure. However, two additional isolates from patients with MTZ-refractory giardiasis showed in vitro susceptibility under both test conditions. This indicates that treatment failure in giardiasis likely stems from multiple factors. Conclusions: Our study highlights the critical importance of oxygen concentration during assessment of Giardia parasite resistance to MTZ. However, it also indicates that MTZ-refractory giardiasis may result from reasons other than parasite resistance.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30303 - Infectious Diseases

Projekt

<a href="/cs/project/NU23-05-00441" target="_blank" >NU23-05-00441: Nové přístupy ke studiu selhání léčby giardiózy: využití next-gen sekvenování a digital PCR k identifikaci markerů rezistence parazita.</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Global Antimicrobial Resistance

ISSN

2213-7165

e-ISSN

2213-7173

Svazek periodika

45

Číslo periodika v rámci svazku

December

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

7

Strana od-do

157-163

Kód UT WoS článku

001604031000001

EID výsledku v databázi Scopus

2-s2.0-105019096166