In Vitro Activities of Miltefosine and Antibacterial Agents from the Macrolide, Oxazolidinone, and Pleuromutilin Classes against Pythium insidiosum and Pythium aphanidermatum

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ABSTRACT

We tested 29 isolates of Pythium insidiosum and one isolate of Pythium aphanidermatum to investigate their susceptibility to miltefosine and antibacterial drugs from the macrolide, oxazolidinone, and pleuromutilin classes. We found that miltefosine, azithromycin, clarithromycin, josamycin, linezolid, sutezolid, retapamulin, tiamulin, and valnemulin had inhibitory and cidal activity against the pathogens at concentrations ranging from 0.25 to 64 μg/ml. Our results suggest that these antimicrobials are promising candidates for future studies on pythiosis in animals and humans.

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Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis.

Thomas Dorlo, Manica Balasegaram, Jos H. Beijnen … (2012)

Miltefosine is an alkylphosphocholine drug with demonstrated activity against various parasite species and cancer cells as well as some pathogenic bacteria and fungi. For 10 years it has been licensed in India for the treatment of visceral leishmaniasis (VL), a fatal neglected parasitic disease. It is the first and still the only oral drug that can be used to treat VL and cutaneous leishmaniasis (CL). The standard 28 day miltefosine monotherapy regimen is well tolerated, except for mild gastrointestinal side effects, although its teratogenic potential severely hampers its general use in the clinic and roll-out in national elimination programmes. The pharmacokinetics of miltefosine are mainly characterized by its long residence time in the body, resulting in extensive drug accumulation during treatment and long elimination half-lives. At the moment, different combination therapy strategies encompassing miltefosine are being tested in multiple controlled clinical trials in various geographical areas of endemicity, both in South Asia and East Africa. We here review the most salient pre-clinical and clinical pharmacological aspects of miltefosine, its mechanism of action against Leishmania parasites and other pathogens, and provide a systematic overview of the efficacy and safety data from all clinical trials of miltefosine, either alone or in combination, in the treatment of VL and CL.

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Clinical and epidemiological analyses of human pythiosis in Thailand.

Theerapong Krajaejun, Boonmee Sathapatayavongs, Roongnapa Pracharktam … (2006)

Pythiosis is an emerging and life-threatening infectious disease in humans and animals that is caused by the pathogenic oomycete Pythium insidiosum. Human pythiosis is found mostly in Thailand, although disease in animals has been increasingly reported worldwide. Clinical information on human pythiosis is limited, and health care professionals are unfamiliar with the disease, leading to underdiagnosis, delayed treatment, and poor prognosis. To retrospectively study the clinical and epidemiological features of human pythiosis, we analyzed clinical data from patients with pythiosis diagnosed during the period of January 1985 through June 2003 at 9 tertiary care hospitals throughout Thailand. A total of 102 cases of human pythiosis were documented nationwide. A substantial proportion (40%) of cases occurred in the last 4 years of the 18-year study interval. Clinical presentations fell into 4 groups: cutaneous/subcutaneous cases (5% of cases), vascular cases (59%), ocular cases (33%), and disseminated cases (3%). Almost all patients with cutaneous/subcutaneous, vascular, and disseminated pythiosis (85%) had underlying thalassemia-hemoglobinopathy syndrome. Most ocular cases (84%) were associated with no underlying disease. A majority of the patients were male (71%), were aged 20-60 years (86%), and reported an agricultural occupation (75%). Regarding treatment outcomes, all patients with disseminated infection died; 78% of patients with vascular disease required limb amputation, and 40% of these patients died; and 79% of patients with ocular pythiosis required enucleation/evisceration. Here, we report, to our knowledge, the largest case study of human pythiosis. The disease has high rates of morbidity and mortality. Early diagnosis and effective treatment are urgently needed to improve clinical outcomes. Because P. insidiosum is distributed worldwide and can infect healthy individuals, an awareness of human pythiosis should be promoted in Thailand and in other countries.

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New insights into animal pathogenic oomycetes.

James V. Anderson, Brett T. Phillips, Elizabeth J. Robertson … (2007)

Many species of oomycetes cause economic and environmental damage owing to their ability to infect a range of plants and animals. Although research on plant pathogenic oomycetes has flourished in recent years, the animal pathogenic oomycetes have received less attention. This is unfortunate because several species are responsible for devastating diseases in aquaculture and natural ecosystems and proper treatments are not available or are limited. Therefore, momentum is being created to revive research into this neglected group of pathogens. Here, we discuss the latest developments in our current understanding of the biology, host-pathogen interactions and environmental and economical impact of the animal pathogenic oomycetes and review the recent advances in this emerging field.