The effect of verapamil on in vitro susceptibility of promastigote and amastigote stages of Leishmania tropica to meglumine antimoniate

Visceral leishmaniasis (VL) is the most severe form of leishmaniasis and is caused by Leishmania infantum in the Americas. Since the use of Milteforam™ was authorized to treat canine visceral leishmaniasis (CVL) in Brazil in 2017, there has also been fear of the emergence of parasites resistant to this drug and, through cross-resistance mechanisms, to meglumine antimoniate and amphotericin B. Additionally, the literature shows that acquisition of resistance is followed by increased parasite fitness, with higher rates of proliferation, infectivity and metacyclogenesis, which are determining factors for parasite virulence. In this context, this study aims to analyze the impact of treating a dog with Milteforan™ on the generation of parasites resistant to miltefosine, meglumine antimoniate, and amphotericin B. To this end, in vitro susceptibility tests were conducted against these drugs with T0 (parasites isolated from the dog before treatment with Milteforan™), T1 (after one course of treatment), and T2 (after two courses of treatment) isolates. The rates of cell proliferation, infectivity, and metacyclogenesis of the isolates were also evaluated. The results indicate a gradual increase in parasite resistance to miltefosine and amphotericin B with increasing the number of treatment courses. A trend increase in the metacyclogenesis rate of the parasites was also observed as drug resistance increased. Therefore, treatment of CVL with Milteforan™ induces resistance to miltefosine and amphotericin B as well as changes in parasite fitness, and may have an impact on animal and human public health.

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Increased Leishmania infantum resistance to miltefosine and amphotericin B after treatment of a dog with miltefosine and allopurinol

Parasites & Vectors ◽

10.1186/s13071-021-05100-x ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Gustavo Gonçalves ◽

Monique Paiva Campos ◽

Alessandra Silva Gonçalves ◽

Lia Carolina Soares Medeiros ◽

Fabiano Borges Figueiredo

Keyword(s):

Amphotericin B ◽

Leishmania Infantum ◽

Resistance Mechanisms ◽

Canine Leishmaniasis ◽

Cross Resistance ◽

In Vitro Susceptibility ◽

Meglumine Antimoniate ◽

Number Of Treatment ◽

The Impact

Abstract Background Leishmania infantum is the most important etiological agent of visceral leishmaniasis in the Americas and Mediterranean region, and the dog is the main host. Miltefosine was authorized to treat canine leishmaniasis (CanL) in Brazil in 2017, but there is a persistent fear of the emergence of parasites resistant not only to this drug but, through cross-resistance mechanisms, also to meglumine antimoniate and amphotericin B. Additionally, the literature shows that acquisition of resistance is followed by increased parasite fitness, with higher rates of proliferation, infectivity and metacyclogenesis, which are drivers of parasite virulence. In this context, the aim of this study was to analyze the impact of treating a dog with miltefosine and allopurinol on the generation of parasites resistant to miltefosine, amphotericin B and meglumine antimoniate. Methods In vitro susceptibility tests were conducted against miltefosine, amphotericin B and meglumine antimoniate with T0 (parasites isolated from a dog before treatment with miltefosine plus allopurinol), T1 (after 1 course of treatment) and T2 (after 2 courses of treatment) isolates. The rates of cell proliferation, infectivity and metacyclogenesis of the isolates were also evaluated. Results The results indicate a gradual increase in parasite resistance to miltefosine and amphotericin B with increasing the number of treatment courses. An increasing trend in the metacyclogenesis rate of the parasites was also observed as drug resistance increased. Conclusion The data indicates an increased L. infantum resistance to miltefosine and amphotericin B after the treatment of a dog with miltefosine plus allopurinol. Further studies with a larger number of L. infantum strains isolated from dogs with varied immune response profiles and undergoing different treatment regimes, are advocated. Graphical Abstract

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Faculty Opinions recommendation of Decreasing in vitro susceptibility of clinical Staphylococcus aureus isolates to vancomycin at the New York Hospital: quantitative testing redux.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13485031.14862158 ◽

2012 ◽

Author(s):

George Sakoulas

Keyword(s):

New York ◽

Staphylococcus Aureus ◽

In Vitro Susceptibility ◽

York Hospital

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Faculty Opinions recommendation of In Vitro Susceptibility Testing of Omadacycline against Nontuberculous Mycobacteria (NTM).

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.739179522.793581267 ◽

2020 ◽

Author(s):

James Cook

Keyword(s):

Susceptibility Testing ◽

Nontuberculous Mycobacteria ◽

In Vitro Susceptibility ◽

In Vitro Susceptibility Testing

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The Effect Study of Crud Water Extraction of Rosmarinus Officinalis Leaves on Growth of Leishmania tropica promastigots in in Vitro Rosmarinus Officinalis, Leishmania Tropica

Journal of Research on the Lepidoptera ◽

10.36872/lepi/v51i2/301158 ◽

2020 ◽

Vol 51 (2) ◽

pp. 1075-1085

Author(s):

MAKSOOD ADIL MAHMOUD AL – DOORI

Keyword(s):

Effect Study ◽

Rosmarinus Officinalis ◽

Water Extraction ◽

Leishmania Tropica

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In vitro susceptibility of T lymphocytes from chimpanzees (Pan troglodytes) to human herpesvirus 6 (HHV-6): a potential animal model to study the interaction between HHV-6 and human immunodeficiency virus type 1 in vivo.

Journal of Virology ◽

10.1128/jvi.64.6.2751-2758.1990 ◽

1990 ◽

Vol 64 (6) ◽

pp. 2751-2758 ◽

Cited By ~ 26

Author(s):

P Lusso ◽

P D Markham ◽

S E DeRocco ◽

R C Gallo

Keyword(s):

Human Immunodeficiency Virus ◽

Animal Model ◽

Pan Troglodytes ◽

Human Herpesvirus ◽

Human Herpesvirus 6 ◽

In Vitro Susceptibility ◽

Immunodeficiency Virus

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In-vitro susceptibility of anaerobic bacteria to gar-936, a new glycylcycline

Clinical Microbiology and Infection ◽

10.1046/j.1469-0691.2000.00034-6.x ◽

2000 ◽

Vol 6 (3) ◽

pp. 159-163 ◽

Cited By ~ 46

Author(s):

C. Edlund ◽

C. E. Nord

Keyword(s):

Anaerobic Bacteria ◽

In Vitro Susceptibility

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146. antifungal Susceptibility Patterns of candida Parapsilosis Bloodstream Isolates in the US, 2008–2018

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.456 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S203-S203

Author(s):

Brenda L Tesini ◽

Meghan Lyman ◽

Brendan R Jackson ◽

Anita Gellert ◽

William Schaffner ◽

...

Keyword(s):

Candida Species ◽

Regional Variation ◽

Antifungal Susceptibility ◽

Bloodstream Infections ◽

Emerging Infections ◽

In Vitro Susceptibility ◽

Fluconazole Resistance ◽

The Us ◽

Susceptibility Patterns

Abstract Background Multidrug resistant Candida is an increasing concern. C. parapsilosis in particular has decreased in vitro susceptibility to echinocandins. As a result, fluconazole had been favored for C. parapsilosis treatment. However, there is growing concern about increasing azole resistance among Candida species. We report on antifungal susceptibility patterns of C. parapsilosis in the US from 2008 through 2018. Methods Active, population-based surveillance for candidemia through the Centers for Disease Control and Prevention’s (CDC) Emerging Infections Program was conducted between 2008–2018, eventually encompassing 9 states (GA, MD,OR, TN, NY, CA, CO, MN, NM). Each incident isolate was sent to the CDC for species confirmation and antifungal susceptibility testing (AFST). Frequency of resistance was calculated and stratified by year and state using SAS 9.4 Results Of the 8,704 incident candidemia isolates identified, 1,471 (15%) were C. parapsilosis; the third most common species after C. albicans and C. glabrata. AFST results were available for 1,340 C. parapsilosis isolates. No resistance was detected to caspofungin (MIC50 0.25) or micafungin (MIC50 1.00) with only one (< 1%) isolate resistant to anidulafungin (MIC50 1.00). In contrast, 84 (6.3%) isolates were resistant to fluconazole and another 44 (3.3%) isolates had dose-dependent susceptibility to fluconazole (MIC50 1.00). Fluconazole resistance increased sharply from an average of 4% during 2008–2014 to a peak of 14% in 2016 with a subsequent decline to 6% in 2018 (see figure). Regional variation is also observed with fluconazole resistance ranging from 0% (CO, MN, NM) to 42% (NY) of isolates by site. Conclusion The recent marked increase in fluconazole resistance among C. parapsilosis highlights this pathogen as an emerging drug resistant pathogen of concern and the need for ongoing antifungal resistance surveillance among Candida species. Our data support the empiric use of echinocandins for C. parapsilosis bloodstream infections and underscore the need to obtain AFST prior to fluconazole treatment. Furthermore, regional variation in fluconazole resistance emphasizes the importance of understanding local Candida susceptibility patterns. Disclosures Lee Harrison, MD, GSK (Consultant)Merck (Consultant)Pfizer (Consultant)Sanofi Pasteur (Consultant)

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