bWe describe here in vitro activity for the combination of azithromycin or terbinafine and benzalkonium, cetrimide, cetylpyridinium, mupirocin, triclosan, or potassium permanganate. With the exception of potassium permanganate, the remaining antimicrobial drugs were active and had an MIC 90 between 2 and 32 g⁄ml. The greatest synergism was observed for the combination of terbinafine and cetrimide (71.4%). In vivo experimental evaluations will clarify the potential of these drugs for the topical treatment of lesions caused by Pythium insidiosum.
Pythium insidiosum is the main oomycete pathogen associated with severe diseases in humans and animals, particularly horses and dogs. In humans, clinical presentations include ocular, cutaneous⁄subcutaneous, vascular, and disseminated pythiosis. While underlying diseases, such as thalassemia and hemoglobinopathy syndrome, have been observed in cutaneous, vascular, and disseminated forms of disease, ocular pythiosis can affect otherwise healthy individuals. Moreover, no underlying diseases have been observed with animal pythiosis, for which most cases are associated with pyogranulomatous disease in subcutaneous tissue or in a gastrointestinal form (1, 2).Treating pythiosis remains a challenge because this microorganism produces hyaline hyphae similar to those of true fungi but is unable to synthesize ergosterol, which is the direct or indirect main target of most antifungal drugs. Consequently, there are no definitive treatment protocols for this disease, and despite some contradictory results, P. insidiosum can be considered intrinsically resistant to most antifungal drugs (2-4). The most commonly used effective clinical management of pythiosis is aggressive surgical resection, such as amputation, and surgical debridement of skin lesions. Unfortunately, surgical interventions are not always possible, and a high rate of recurrence has been observed. Additionally, immunotherapy cure rates can reach approximately 55% and 80% in humans and horses, respectively (2, 3, 5). Independent of the use of single or combination therapies, the best cure rates are associated with rapid diagnosis and early treatment (1, 2). Regardless of the therapy of choice, little attention has been given to the specific topical treatment of pythiosis lesions.Considering the high tissue concentrations achieved by azithromycin and terbinafine and the above context, this study aimed to assess the in vitro activity for combinations of azithromycin or terbinafine (systemic therapeutic options) and benzalkonium, cetrimide, cetylpyridinium, mupirocin, triclosan, or potassium permanganate (topical therapeutic options).We evaluated the susceptibility of 20 isolates of P. insidiosum from equine pythiosis cases and the reference strain ATCC 58637. Clinical isolates were previously identified by a nested PCR assay (6). The drugs (final concentrations tested in the wells) azithromycin (0.06 to 32 g⁄ml), benzalkonium chloride (0.25 to 32 g⁄ml), alkyltrimethylammonium bromide (cetrimide) (0.5 to 32 g⁄ml), cetylpyrid...
