The efficacy of enrofloxacin, alone or combined with metronidazole, in the therapy of canine leishmaniasis

Abstract

We evaluated the efficacy of enrofloxacin, alone or combined with metronidazole, against Leishmania infantum. The in vitro activity of this fluoroquinolone was assessed using two different methods: a direct test aimed at assessing the drug activity on the parasite, and an indirect test aimed at evaluating the drug effect on macrophage killing, lymphomonocyte activation and nitric oxide production. An in vivo test was also performed on 36 dogs with leishmaniasis, subdivided into three groups, one treated with enrofloxacin, another with enrofloxacin plus metronidazole, and a control group with meglumine antimoniate. The direct test did not show any action of enrofloxacin on the parasite, while the indirect testing showed an enhancement of macrophage killing and an increase in nitric oxide production. These findings show that enrofloxacin does not exert a direct anti-leishmanial activity in vitro. However, on the basis of the positive immunostimulation results shown in vitro and the clinical improvement, particularly of the cutaneous lesions, obtained in several dogs in the in vivo trial, the use of enrofloxacin in association with a specific anti-leishmanial drug can be proposed in the therapeutic protocol of canine leishmaniasis.

Canine leishmaniosis: in vitro efficacy of miltefosine and marbofloxacin alone or in combination with allopurinol against clinical strains of Leishmania infantum

“…Miltefosine is known to affect membrane integrity directly or indirectly and is able to exert antileishmanial action independently of cell-mediated parasiticidal mechanisms, whereas marbofloxacin acts mainly via indirect mechanisms ). Other fluoroquinolones such as enrofloxacin were not found to be directly active against L. infantum although capable of stimulating a significant macrophage killing in the cells infected by the parasite (Bianciardi et al 2004). …”

“…Moreover, toxicity and the emergence of resistance often limit their efficacy. Therefore investigations are still in progress to discover new antileishmanial drugs (Bianciardi et al 2004;Pujals et al 2008;Zhang et al 2010). Recently miltefosine has been registered for use in dogs and different studies have demonstrated its leishmanicidal effect (Mirò et al 2009).…”

Antimicrosporidial activity of (fluoro)quinolones in vitro and in vivo

“…For example, fumagillin, though active against microsporidia, was found to be somewhat toxic in humans (Molina et al 2002), but perhaps when administered at lower non-toxic doses in combination with fluoroquinolones, may show greater efficacy. In practice, the combination of enrofloxacin in combination with metronidazole was effective for treating canine leishmaniasis (Bianciardi et al 2004) and trovafloxacin, in combination with clarithromycin, pyrimethamine, or sulfa-diazine, was more effective than each compound alone for treating acute murine toxoplasmosis (Khan et al 1997). These results would therefore support continued studies to determine if fluoroquinolones can be applied for successfully treating microsporidiosis and to further characterize and identify the topoisomerase drug targets in the microsporidia.…”

Selective Action of Fluoroquinolones Against Intracellular Amastigotes of Leishmania (Viannia) Panamensis in Vitro

“…Studies on antileishmanial effects of FQs lag well behind research on African trypanosomes, but the limited available data indicate significant interspecies variation in the in vitro sensitivities of Leishmania spp. amastigotes (Croft and Hogg, 1988;Savoia et al, 1993;Bianciardi et al, 2004). Nevertheless, certain FQs have shown promising in vivo efficacies against L. donovani, L. infantum and L. major in animal models (Raether et al, 1989;Savoia et al, 1993;Zucca et al, 1996) and have been employed in combination therapy of canine leishmaniasis (Bianchini and DAmico, 2004;Bianciardi et al, 2004).…”