> A couple of cases of giardiasis have recently given us reason to suspect
> flagyl resistance. Previously most suspected resistance we could
> attribute to non-compliance or reinfection. Our problem is that quinacrine is
> getting harder and harder to get. Here in Canada, Tinidazole is not an
> option. Any other alternatives? Any suggestions?
Albendazole has some efficacy against Giardia. For a good, if dated
review, see Reynoldson, J.A., Thompson, R.C.A. and Horton, R.J. 1992.
Albendazole as a future antigardial agent. Parasitology Today 8: 412-414.
A recent search of Current Contents combining Giardia and albendazole
produced the following:
Xiao LH. Saeed K. Herd RP.
EFFICACY OF ALBENDAZOLE AND FENBENDAZOLE AGAINST GIARDIA INFECTION IN
Veterinary Parasitology. 61(1-2):165-170, 1996 Jan.
Efficacies of albendazole and fenbendazole in suppressing Giardia cyst
output of infected calves were evaluated in two clinical trials. In the
first trial, 18 naturally infected calves were allocated to an untreated
control group (n = 9) and an albendazole-treated group (n = 9). Calves in
the treated group were given 20 mg kg(-1) oral albendazole once daily for
3 days. Compared to controls, treated calves showed 98.5%, 97.6% and 90.8%
reductions in cysts per gram of feces (cpg) 1, 2 and 6 weeks respectively
after the start of treatment. In a second trial, 13 infected calves were
allocated to an untreated control group (n = 6) and a fenbendazole-treated
group (n = 7). Calves in the treated group were given 10 mg kg(-1)
fenbendazole orally twice daily for 3 days. Compared to the control group,
treatments reduced cpg counts by 100%, 98.5% and 59.5% 1, 2, and 3 weeks
respectively after the start of treatment. Both albendazole and
fenbendazole appeared to be effective in suppressing cyst excretion by
Giardia-infected calves. [References: 29]
Farbey MD. Reynoldson JA. Thompson RCA.
IN VITRO DRUG SUSCEPTIBILITY OF 29 ISOLATES OF GIARDIA DUODENALIS FROM
HUMANS AS ASSESSED BY AN ADHESION ASSAY
International Journal for Parasitology. 25(5):593-599, 1995 May.
Twelve isolates of Giardia duodenal is from Caucasian hosts in the Perth
metropolitan area, along with 16 isolates from Aborigines in the north of
Western Australia and the reference isolate P1C10 were examined for their
in vitro drug sensitivity. Dose-response curves were constructed for each
isolate for metronidazole, the most common clinically used antigiardial
agent, as well as for the benzimidazole compound albendazole. Less than a
9-fold variation was found in the susceptibility of the isolates to
albendazole, while for metronidazole there was well over a 16,000-fold
variation between the same group of isolates. In addition, it was found
that isolates of Giardia obtained from Aboriginal hosts were significantly
less sensitive to albendazole than those obtained from Caucasians. The
results of this study have important implications for the continued use of
metronidazole and the potential use of albendazole for the treatment of
giardiasis. [References: 48]
Andrews BJ. Panitescu D. Jipa GH. Vasilebugarin AC. Vasiliu RP.
CHEMOTHERAPY FOR GIARDIASIS - RANDOMIZED CLINICAL TRIAL OF BACITRACIN,
BACITRACIN ZINC, AND A COMBINATION OF BACITRACIN ZINC WITH NEOMYCIN
American Journal of Tropical Medicine & Hygiene. 52(4):318-321, 1995 Apr.
This study describes a prospective, randomized, clinical trial in patients
infected with the protozoa Giardia lamblia. Patients received a 10-day
treatment with twice a day doses of either 120,000 U (USP) of bacitracin
zinc, 120,000 U (USP) of bacitracin, 120,000 U (USP) of neomycin, or
60,000 U (USP) of bacitracin zinc and 60,000 U (USP) of neomycin. At the
first assessment (day 11), all 21 subjects (100%) treated with bacitracin
zinc had ceased to show Giardia parasites in their stools compared with 19
(95%) of 20 receiving bacitracin, 20 (90.9%) of 22 subjects receiving
neomycin, and 17 (89.5%) of 19 subjects receiving bacitracin zinc plus
neomycin. During the two-week follow up period, one (5.3%) of the 19
subjects examined who received bacitracin zinc experienced a recurrence
compared with one (6.7%) of 15 receiving bacitracin, one (5.0%) of 20
receiving neomycin, and 0 (0%) of 14 receiving the combination treatment.
Final cure rates of 94.7% for bacitracin zinc, 87.5% for bacitracin, 86.4%
for neomycin, and 87.5% for bacitracin zinc plus neomycin were obtained.
No synergistic activity was noted between bacitracin zinc and neomycin.
Side effects were generally limited to nausea, abdominal discomfort, and
diarrhea in a small number of patients. [References: 25]
Katiyar SK. Gordon VR. Mclaughlin GL. Edlind TD.
ANTIPROTOZOAL ACTIVITIES OF BENZIMIDAZOLES AND CORRELATIONS WITH
Antimicrobial Agents & Chemotherapy. 38(9):2086-2090, 1994 Sep.
Benzimidazoles have been widely used since the 1960s as anthelmintic
agents in veterinary and human medicine and as antifungal agents in
agriculture. More recently, selected benzimidazole derivatives were shown
to be active in vitro against two protozoan parasites, Trichomonas
vaginalis and Giardia lamblia, and clinical studies with AIDS patients
have suggested that microsporidia are susceptible as well. Here, eve first
present in vitro susceptibility data for T. vaginalis and G. lamblia using
an expanded set of benzimidazole derivatives. Both parasites were highly
susceptible to four derivatives, including mebendazole, flubendazole, and
fenbendazole (50% inhibitory concentrations of 0.005 to 0.16 mu g/ml).
These derivatives also had lethal activity that was time dependent: 90% of
T. vaginalis cells failed to recover following a 20-h exposure to
mebendazole at 0.17 mu g/ml. G. lamblia, but not T. vaginalis, was highly
susceptible to five additional derivatives. Next, we examined in vitro
activity of benzimidazoles against additional protozoan parasites: little
or no activity was observed against Entamoeba histolytica, Leishmania
major, and Acanthamoeba polyphaga. Since the microtubule protein
beta-tubulin has been identified as the benzimidazole target in helminths
and fungi, potential correlations between benzimidazole activity and
beta-tubulin sequence were examined. This analysis included partial
sequences (residues 108 to 259) from the organisms mentioned above, as
well as the microsporidia Encephalitozoon hellem and Encephalitozoon
cuniculi and the sporozoan Cryptosporidium parvum. beta-tubulin residues
Glu-198 and, in particular, Phe-200 are strong predictors of benzimidazole
susceptibility; both are present in Encephalitozoon spp. but absent in C.
parvum. [References: 29]
Oxberry ME. Thompson RCA. Reynoldson JA.
EVALUATION OF THE EFFECTS OF ALBENDAZOLE AND METRONIDAZOLE ON THE
ULTRASTRUCTURE OF GIARDIA DUODENALIS, TRICHOMONAS VAGINALIS AND
SPIRONUCLEUS MURIS USING TRANSMISSION ELECTRONMICROSCOPY
International Journal for Parasitology. 24(5):695-703, 1994 Aug.
The three closely related parasitic protozoa, Giardia duodenalis,
Trichomonas vaginalis and Spironucleus muris, all have very different
sensitivities to albendazole and metronidazole. Ultrastructural studies
reveal that the cytoskeletal elements of the ventral disk in G. duodenalis
are affected by albendazole, whereas the other two parasites, neither of
which possess this structure, are not affected by albendazole to the same
extent. This suggests that albendazole may be having its primary affect on
G. duodenalis by binding to cytoskeletal proteins and ultimately causing
death of the parasite. Death may be occurring as the parasite loses its
ability to adhere to the intestinal villi and obtain nutrients.
Metronidazole showed a different pattern of activity against the three
parasites. The evidence obtained from these ultrastructural studies
supports the current theory that metronidazole adversely affects protozoa
by disrupting inner cell membranes. [References: 22]
Katelaris PH. Naeem A. Farthing MJG.
ACTIVITY OF METRONIDAZOLE, AZITHROMYCIN AND THREE BENZIMIDAZOLES ON
GIARDIA LAMBLIA GROWTH AND ATTACHMENT TO A HUMAN INTESTINAL CELL LINE
Alimentary Pharmacology & Therapeutics. 8(2):187-192, 1994 Apr.
Background: Attachment of Giardia lamblia trophozoites to enterocytes is
essential for colonization of the small intestine and is considered a
prerequisite for Giardia-induced enterocyte damage. Inhibition of
attachment may therefore have therapeutic potential.
Methods: Enterocyte-like differentiated Caco-2 cells were used as a
biologically appropriate attachment surface to determine the effect of
three benzimidazole compounds (albendazole, mebendazole and
thiabendazole), azithromycin and metronidazole on Giardia attachment. The
results were compared with the ability for each drug to inhibit Giardia
growth, measured using [H-3]-thymidine uptake.
Results: The benzimidazoles inhibited Giardia attachment at much lower
concentrations than did metronidazole. However, metronidazole was a much
more potent inhibitor of growth than any of the benzimidazoles.
Azithromycin did not significantly impair Giardia attachment or growth.
The benzimidazoles decrease attachment but are less giardiacidal than
Conclusion: This model appears useful for testing potential antigiardial
compounds and investigating mechanisms of drug action. [References: 24]
Kollaritsch H. Jeschko E. Wiedermann G.
ALBENDAZOLE IS HIGHLY EFFECTIVE AGAINST CUTANEOUS LARVA MIGRANS BUT NOT
AGAINST GIARDIA INFECTION - RESULTS OF AN OPEN PILOT TRIAL IN TRAVELLERS
RETURNING FROM THE TROPICS
Transactions of the Royal Society of Tropical Medicine & Hygiene.
87(6):689, 1993 Nov-Dec.
Reprint available from:
INST SPECIF PROPHYLAXIS & TROP MED
Bell CA. Dykstra CC. Naiman NA. Cory M. Fairley TA. Tidwell RR.
STRUCTURE-ACTIVITY STUDIES OF DICATIONICALLY SUBSTITUTED
BIS-BENZIMIDAZOLES AGAINST GIARDIA LAMBLIA - CORRELATION OF ANTIGIARDIAL
ACTIVITY WITH DNA BINDING AFFINITY AND GIARDIAL TOPOISOMERASE II
Antimicrobial Agents & Chemotherapy. 37(12):2668-2673, 1993 Dec.
Nine dicationically substituted bis-benzimidazoles were examined for their
in vitro activities against Giardia lamblia WB (ATCC 30957). The potential
mechanisms of action of these compounds were evaluated by investigating
the relationship among in vitro antigiardial activity and the affinity of
the molecules for DNA and their ability to inhibit the activity of
giardial topoisomerase II. Each compound demonstrated antigiardial
activity, as measured by assessing the incorporation of
[methyl-H-3]thymidine by giardial trophozoites exposed to the test agents.
Three compounds exhibited excellent in vitro antigiardial activities, with
50% inhibitory concentrations which compared very favorably with those of
two currently used drugs, quinacrine HCl and metronidazole. Putative
mechanisms of action for these compounds were suggested by the strong
correlation observed among in vitro antigiardial activity and the affinity
of the molecules for natural and synthetic DNA and their ability to
inhibit the relaxation activity of giardial topoisomerase II. A strong
correlation between the DNA binding affinity of these compounds and their
inhibition of giardial topoisomerase II activity was also observed.
Barr SC. Bowman DD. Heller RL. Erb HN.
EFFICACY OF ALBENDAZOLE AGAINST GIARDIASIS IN DOGS
American Journal of Veterinary Research. 54(6):926-928, 1993 Jun.
Efficacy of albendazole for treating giardiasis in dogs was assessed in 3
experiments. In experiment 1, Giardia cysts were cleared from feces of 5
of 7 dogs (as determined by the zinc-sulfate concentration technique)
after the dogs received a single dose of albendazole (25 mg/kg of body
weight, PO), whereas feces of 3 of 7 dogs became clear of cysts without
treatment. In experiment 2, feces of 5 of 5 dogs became clear of cysts
after albendazole treatment (25 mg/kg, PO, q 12 h for 4 doses); feces of 1
of 5 untreated control dogs became clear. In experiment 3, feces of 18 of
20 dogs became clear of cysts after albendazole (25 mg/kg, PO, q 12 h for
4 doses) was given; none of the 20 control dogs had feces clear of cysts.
Signs of toxicosis were not observed in any dog. These results indicate
that a single dose of albendazole (25 mg/kg, PO) is not effective for
treating giardiasis in dogs. However, 4 doses of albendazole (25 mg/kg,
PO, q 12 h) are highly effective and nontoxic for treatment of giardiasis
in dogs. [References: 18]
Department of Public Health and Tropical Medicine
James Cook University
email: Richard.Speare at jcu.edu.au