In vitro susceptibility to antimonials and amphotericin B of Leishmania infantum strains isolated from dogs in a region lacking drug selection pressure

2012 ◽  
Vol 187 (3-4) ◽  
pp. 386-393 ◽  
Author(s):  
K. Aït-Oudhia ◽  
E. Gazanion ◽  
D. Sereno ◽  
B. Oury ◽  
J.P. Dedet ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Leishmania Infantum ◽  
Selection Pressure ◽  
Drug Selection ◽  
In Vitro Susceptibility

scholarly journals Treatment of canine visceral leishmaniasis with Milteforan™ induces Leishmania infantum resistance to miltefosine and amphotericin B

2021 ◽  
Author(s):  
Gustavo Gonçalves ◽  
Monique Paiva Campos ◽  
Alessandra Silva Gonçalves ◽  
Lia Carolina Soares Medeiros ◽  
Fabiano Borges Figueiredo
Keyword(s):  
Visceral Leishmaniasis ◽  
Amphotericin B ◽  
Leishmania Infantum ◽  
Cross Resistance ◽  
Canine Visceral Leishmaniasis ◽  
In Vitro Susceptibility ◽  
Meglumine Antimoniate ◽  
Parasite Fitness ◽  
The Impact

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.

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

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

Stable Phenotypic Resistance of CandidaSpecies to Amphotericin B Conferred by Preexposure to Subinhibitory Levels of Azoles

1998 ◽  
Vol 36 (9) ◽  
pp. 2690-2695 ◽  
Author(s):  
Jose A. Vazquez ◽  
Maria T. Arganoza ◽  
Dina Boikov ◽  
Stephanie Yoon ◽  
Jack D. Sobel ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Clinical Setting ◽  
Fungicidal Activity ◽  
No Reduction ◽  
Growth Conditions ◽  
In Vitro Assays ◽  
In Vitro Susceptibility ◽  
Phenotypic Resistance ◽  
Time Period

The fungicidal activity of amphotericin B (AmB) was quantitated for several Candida species. Candida albicans andC. tropicalis were consistently susceptible to AmB, with less than 1% survivors after 6 h of exposure to AmB. C. parapsilosis and variants of C. lusitaniae andC. guilliermondii were the most resistant, demonstrating 50 to 90% survivors in this time period and as high as 1% survival after a 24-h exposure time. All Candida species were killed (<1% survivors) after 24 h of exposure to AmB. In contrast, overnight exposure to either fluconazole or itraconazole resulted in pronounced increases in resistance to subsequent exposures to AmB. Most dramatically, C. albicans was able to grow in AmB cultures after azole preexposure. Several other Candida species did not grow in AmB but showed little or no reduction in viability after up to 24 h in AmB. Depending on the growth conditions,Candida cells preexposed to azoles may retain AmB resistance for days after the azoles have been removed. If this in vitro antagonism applies to the clinical setting, treatment of patients with certain antifungal combinations may not be beneficial. The ability of some Candida isolates to survive transient exposures to AmB was not reflected in the in vitro susceptibility changes as measured by standard MIC assays. This finding should be considered in studies attempting to correlate patient outcome with in vitro susceptibilities of clinical fungal isolates. Patients who fail to respond to AmB may be infected with isolates that are classified as susceptible by standard in vitro assays but that may be resistant to transient antifungal exposures which may be more relevant in the clinical setting.

In vitro susceptibility of clinically important zygomycetes to combinations of amphotericin B and suramin

2009 ◽  
Vol 19 (4) ◽  
pp. 241-247
Author(s):  
L. Galgóczy ◽  
L. Ördögh ◽  
M. Virágh ◽  
T. Papp ◽  
Cs. Vágvölgyi
Keyword(s):  
Amphotericin B ◽  
In Vitro Susceptibility

Voriconazole: A New Triazole Antifungal Agent

2003 ◽  
Vol 37 (3) ◽  
pp. 420-432 ◽  
Author(s):  
Margaret M Pearson ◽  
P David Rogers ◽  
John D Cleary ◽  
Stanley W Chapman
Keyword(s):  
Amphotericin B ◽  
Antifungal Agent ◽  
Fungal Pathogens ◽  
Antimicrobial Agents ◽  
Case Reports ◽  
Empirical Therapy ◽  
Immunocompromised Patients ◽  
In Vitro Susceptibility ◽  
Medline Search

OBJECTIVE: To review the pharmacology, in vitro susceptibility, pharmacokinetics, clinical efficacy, and adverse effects of voriconazole, a triazole antifungal agent. DATA SOURCES: A MEDLINE search, restricted to English language, was conducted from 1990 to June 2002. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2001 and manufacturer information available through the Food and Drug Administration's Web site. DATA EXTRACTION: All published and unpublished trials and abstracts citing voriconazole were selected. DATA SYNTHESIS: Voriconazole has shown in vitro activity against many yeasts and a variety of mold and dermatophyte isolates. Voriconazole can be administered either orally or parenterally. It exhibits good oral bioavailability, wide tissue distribution including distribution into the central nervous system, and hepatic metabolism. Drug interactions occur through inhibition of the CYP2C9, CYP2C19, and CYP3A4 isoenzymes, resulting in alterations in kinetic parameters of either voriconazole or the interacting agent. Efficacy has been illustrated in open, noncomparative studies of aspergillosis in immunocompromised patients. Human case reports describe successful treatment of rare fungal pathogens. The most commonly reported adverse events include visual disturbances and elevations in liver function tests. CONCLUSIONS: Voriconazole is at least as effective as amphotericin B in the treatment of acute invasive aspergillosis in immunocompromised patients. It has similar efficacy as fluconazole in treatment of esophageal candidiasis. Voriconazole did not achieve statistical non-inferiority to liposomal amphotericin B for empirical therapy in patients with neutropenia and persistent fever, diminishing enthusiasm for use in this indication until additional trials are completed. Based on case reports and in vitro efficacy, voriconazole may prove to be a clinically useful agent in the treatment of other fungal disease.

scholarly journals Molecular Studies Reveal Frequent Misidentification of Aspergillus fumigatus by Morphotyping

2006 ◽  
Vol 5 (10) ◽  
pp. 1705-1712 ◽  
Author(s):  
S. Arunmozhi Balajee ◽  
David Nickle ◽  
Janos Varga ◽  
Kieren A. Marr
Keyword(s):  
Aspergillus Fumigatus ◽  
Amphotericin B ◽  
Distinct Species ◽  
Enzyme Polymorphism ◽  
Antifungal Drugs ◽  
Clinical Isolates ◽  
Polymorphism Analysis ◽  
In Vitro Susceptibility ◽  
Epidemiological Surveys

ABSTRACT Aspergillus fumigatus has been understood to be the most common cause of invasive aspergillosis (IA) in all epidemiological surveys. However, recent studies have uncovered a large degree of genetic heterogeneity between isolates morphologically identified as A. fumigatus, leading to the description of a new species, Aspergillus lentulus. Here, we examined the genetic diversity of clinical isolates identified as A. fumigatus using restriction enzyme polymorphism analysis and sequence-based identification. Analysis of 50 clinical isolates from geographically diverse locations recorded the presence of at least three distinct species: A. lentulus, Aspergillus udagawae, and A. fumigatus. In vitro, A. lentulus isolates demonstrated decreased susceptibility to antifungal drugs currently used for IA, including amphotericin B, voriconazole, and caspofungin; A. udagawae isolates demonstrated decreased in vitro susceptibility to amphotericin B. Results of the present study demonstrate that current phenotypic methods to identify fungi do not differentiate between genetically distinct species in the A. fumigatus group. Differential antifungal susceptibilities of these species may account for some of the reported poor outcomes of therapy in clinical studies.

scholarly journals In Vitro Activities of Free and Lipid Formulations of Amphotericin B and Nystatin against Clinical Isolates of Coccidioides immitis at Various Saprobic Stages

2002 ◽  
Vol 46 (5) ◽  
pp. 1583-1585 ◽  
Author(s):  
Gloria M. González ◽  
Rolando Tijerina ◽  
Deanna A. Sutton ◽  
John R. Graybill ◽  
Michael G. Rinaldi
Keyword(s):  
Amphotericin B ◽  
Clinical Laboratory ◽  
National Committee ◽  
Growth Stages ◽  
Coccidioides Immitis ◽  
In Vitro Susceptibility ◽  
Broth Macrodilution ◽  
Lipid Formulations ◽  
Different Growth Stages

ABSTRACT We investigated the susceptibilities of hyphal, mixed hyphal, ungerminated arthroconidial, and germinated arthroconidial populations of Coccidioides immitis to lipid formulations of amphotericin B and nystatin and their conventional preparations, utilizing the National Committee for Clinical Laboratory Standards M38-P broth macrodilution method. The differences in effects of the three different growth stages of the saprobic phase of C. immitis on the MIC/minimum lethal concentration (MLC) ratio were not statistically significant for any of the antifungal agents tested. These results suggest that either inocula could be used for in vitro susceptibility studies with C. immitis.

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