scholarly journals Antifungal sensitivity profile of Fusarium spp. resulting keratitits

2017 ◽  
Vol 1 (1) ◽  

Fungal keratitis is an important cause of visual impairment and blindness. Genus Fusarium is a leading cause for fungal keratitis and it has higher degree of resistance to antifungal agents. Our objectives were to identify Fusarium spp. isolated from corneal specimens (received at Dept. of Mycology - MRI from 2013-2016) up to species level and to determine antifungal susceptibility pattern of them. All Fusarium isolates (51) obtained from specimens of patients with keratitis were included in the study. Speciation was done using morphological characteristics of fungi. Antifungal sensitivity testing was done according to CLSI M 51- A guideline, against amphotericin B (10 µg), itraconazole (10 µg). and voriconazole (1 µg). Majority of the isolates were F. solani complex (n=24). Three isolates were difficult to speciate morphologically. Significant number of Fusarium isolates had inhibitory zone diameters (IZD) less than tentative zone diameter epidemiological cut off values (TZD ECVs) for both itraconazole and amphotericin B, indicating emergence of resistant strains against these drugs. Forty five isolates (97.82%) had IZD more than corresponding TZD ECV for voriconazole. All F. solani complexes had IZD less than TZD ECVs for itraconazole. Morphological identification cannot be used as the only method for speciation of Fusarium isolates. Antifungal sensitivity testing should be done for Fusarium isolates from keratitis patients as emergence of resistance strains is not uncommon against commonly used antifungal agents.

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Devarshi U. Gajjar ◽  
Anuradha K. Pal ◽  
Bharat K. Ghodadra ◽  
Abhay R. Vasavada

Purpose.Fusarium,Aspergillus, and Dematiaceous are the most common fungal species causing keratitis in tropical countries. Herein we report a prospective study on fungal keratitis caused by these three fungal species.Methodology. A prospective investigation was undertaken to evaluate eyes with presumed fungal keratitis. All the fungal isolates (n=73) obtained from keratitis infections were identified using morphological and microscopic characters. Molecular identification using sequencing of the ITS region and antifungal susceptibility tests using microdilution method were done. The final clinical outcome was evaluated in terms of the time taken for resolution of keratitis and the final visual outcome. The results were analyzed after segregating the cases into three groups, namely,Fusarium,Aspergillus, and Dematiaceous keratitis.Results. Diagnosis of fungal keratitis was established in 73 (35.9%) cases out of 208 cases. The spectra of fungi isolated wereFusariumspp. (26.6%),Aspergillusspp. (21.6%), and Dematiaceous fungi (11.6%). The sequence of the ITS region could identify theFusariumandAspergillusspecies at the species complex level, and the Dematiaceous isolates were accurately identified. Using antifungal agents such as fluconazole, natamycin, amphotericin B, and itraconazole, the minimum inhibitory concentrations (MICs) forFusariumspp. were >32 μg/mL, 4–8 μg/mL, 0.5–1 μg/mL, and >32 μg/mL, respectively. Antifungal susceptibility data showed thatCurvulariaspp. was highly resistant to all the antifungal agents. Overall, natamycin and amphotericin B were found to be the most effective antifungal agents. The comparative clinical outcomes in all cases showed that the healing response in terms of visual acuity of the Dematiaceous group was significantly good when compared with theFusariumandAspergillusgroups (P<0.05). The time required for healing in theFusariumgroup was statistically significantly less when compared with theAspergillusand Dematiaceous groups.Conclusion. This study demonstrates important differences in microscopic features of scraping material and antifungal susceptibility between the three groups. Early and accurate identification coupled with the MIC data, and thereby appropriate treatment is crucial for complete recovery.


2003 ◽  
Vol 47 (8) ◽  
pp. 2404-2412 ◽  
Author(s):  
Dominique Sanglard ◽  
Françoise Ischer ◽  
Tania Parkinson ◽  
Derek Falconer ◽  
Jacques Bille

ABSTRACT The role of sterol mutations in the resistance of Candida albicans to antifungal agents has not been thoroughly investigated. Previous work reported that clinical C. albicans strains resistant to both azole antifungals and amphotericin B were defective in ERG3, a gene encoding sterol Δ5,6-desaturase. It is also believed that a deletion of the lanosterol 14α-demethylase gene, ERG11, is possible only under aerobic conditions when ERG3 is not functional. We tested these hypotheses by creating mutants by targeted deletion of the ERG3 and ERG11 genes and subjecting those mutants to antifungal susceptibility testing and sterol analysis. The homozygous erg3/erg3 mutant created, DSY1751, was resistant to azole derivatives, as expected. This mutant was, however, slightly more susceptible to amphotericin B than the parent wild type. It was possible to generate erg11/erg11 mutants in the DSY1751 background but also, surprisingly, in the background of a wild-type isolate with functional ERG3 alleles under aerobic conditions. This mutant (DSY1769) was obtained by exposure of an ERG11/erg11 heterozygous strain in a medium containing 10 μg of amphotericin B per ml. Amphotericin B-resistant strains were obtained only from ERG11/erg11 heterozygotes at a frequency of approximately 5 × 10−5 to 7 × 10−5, which was consistent with mitotic recombination between the first disrupted erg11 allele and the other remaining functional ERG11 allele. DSY1769 was also resistant to azole derivatives. The main sterol fraction in DSY1769 contained lanosterol and eburicol. These studies showed that erg11/erg11 mutants of a C. albicans strain harboring a defective erg11 allele can be obtained in vitro in the presence of amphotericin B. Amphotericin B-resistant strains could therefore be selected by similar mechanisms during antifungal therapy.


2016 ◽  
Vol 62 (1) ◽  
pp. 65-76
Author(s):  
Gordana Mirchevska ◽  
Maja Jurhar Pavlova ◽  
Elena Trajkovska-Dokic ◽  
Zaklina Cekovska ◽  
Gordana Jankoska ◽  
...  

Candida species are opportunistic yeasts that can be a serious threat for immunocompromised and critically ill patients, and a cause for increased morbidity and mortality in hospitalized patients. The aim of this study was to determine the frequency and distribution of different Candida species in clinical specimens in patients with increased risk for fungal infections, and to determine the antifungal susceptibility profile of invasive Candida species to antifungal agents. During a two year period, clinical specimens from 120 patients divided into 4 groups were analysed at the Institute of microbiology and parasitology, Faculty of Medicine, Skopje, Republic of Macedonia. Each of these 4 groups consisted of specimens from 30 patients, with primary immune deficiency, critically ill patients treated in the intensive care units (ICU), patients with mucosal candidiasis only, and patients with cystic fibrosis. All specimens were investigated with conventional mycological methods. Identification of Candida species was performed with VITEK-2 system (bioMérieux, France). E-test strips of fluconazole, voriconazole, amphotericin B and caspofungin (AB bioMerieux, France) were used for determination of the antifungal susceptibility profile. In this study, a total of 115 isolates of Candida species were confirmed in different clinical specimens (91 isolates from mucosal surfaces and 24 isolates from blood culture). Colonisation of mucosal membranes of gastrointestinal, respiratory and/or urinary tracts was registered in 56.67% (17/30), 56.67% (17/30), 90% (27/30) and 100% (30/30) of the specimens in the first, second, third and fourth group respectively. In all four groups of patients, the following Candida species were confirmed: C. albicans - 55%, C. glabrata - 17.6%, C. parapsilosis - 7.7%, C. tropicalis - 6.6%, unidentified Candida species - 4.4%, C. dubliniensis - 3.3%, C. kefyr - 2.2%, and one isolate of C. rugosa, C. pelliculosa and C. krusei each. Positive blood culture was registered in 23.33% specimens from the first group, 43.33% in the second group, 23.08% of the third group, and in one specimen of the fourth group. The most frequent isolates from blood culture were C. tropicalis and C. krusei, followed by C. albicans, C. parapsilosis and C. tropicalis, and in the second group C. albicans and C. pelliculosa were equally distributed, followed by C. parapsilosis and C. glabrata. All invasive isolates of Candida species were susceptible to amphotericin B, voriconazole and caspofungin. Resistance to fluconazole was registered in 8.3% (2/24) of all confirmed Candida species. Dose-dependent susceptibility to fluconazole was confirmed in 46% (11/24) of the isolates. Our study confirms high prevalence of colonisation and candidemia with non-albicans Candida species. Resistance to antifungal agents was registered only in two isolates of C. krusei. An epidemiological study is necessary for surveillance of dynamics of candidemia and antifungal susceptibility profile of invasive isolates of Candida species in our patients.


2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Claudy Oliveira dos Santos ◽  
Eva Kolwijck ◽  
Henrich A. van der Lee ◽  
Marlou C. Tehupeiory-Kooreman ◽  
Abdullah M. S. Al-Hatmi ◽  
...  

ABSTRACT Fungal keratitis is a common but severe eye infection in tropical and subtropical areas of the world. In regions with a temperate climate, the frequency of infection is rising in patients with contact lenses and following trauma. Early and adequate therapy is important to prevent disease progression and loss of vision. The management of Fusarium keratitis is complex, and the optimal treatment is not well defined. We investigated the in vitro activity of chlorhexidine and seven antifungal agents against a well-characterized collection of Fusarium isolates recovered from patients with Fusarium keratitis. The fungus culture collection of the Center of Expertise in Mycology Radboudumc/CWZ was searched for Fusarium isolates that were cultured from cornea scrapings, ocular biopsy specimens, eye swabs, and contact lens fluid containers from patients with suspected keratitis. The Fusarium isolates that were cultured from patients with confirmed keratitis were all identified using conventional and molecular techniques. Antifungal susceptibility testing was performed according to the EUCAST broth microdilution reference method. The antifungal agents tested included amphotericin B, voriconazole, posaconazole, miconazole, natamycin, 5-fluorocytosine, and caspofungin. In addition, the activity of chlorhexidine was determined. The fungal culture collection contained 98 Fusarium isolates of confirmed fungal keratitis cases from 83 Dutch patients and 15 Tanzanian patients. The isolates were collected between 2007 and 2017. Fusarium oxysporum (n = 24, 24.5%) was the most frequently isolated species followed by Fusarium solani sensu stricto (n = 18, 18.4%) and Fusarium petroliphilum (n = 11, 11.2%). Amphotericin B showed the most favorable in vitro inhibition of Fusarium species followed by natamycin, voriconazole, and chlorhexidine, while 5-fluorocytosine, posaconazole, miconazole, and caspofungin showed no relevant inhibiting effect. However, chlorhexidine showed fungicidal activity against 90% of F. oxysporum strains and 100% of the F. solani strains. Our study supports the clinical efficacy of chlorhexidine and therefore warrants its further clinical evaluation for primary therapy of fungal keratitis, particularly in low and middle income countries where fungal keratitis is much more frequent and, currently, antifungal eye drops are often unavailable.


2007 ◽  
Vol 51 (5) ◽  
pp. 1818-1821 ◽  
Author(s):  
H. Seifert ◽  
U. Aurbach ◽  
D. Stefanik ◽  
O. Cornely

ABSTRACT Isavuconazole is the active component of the new azole antifungal agent BAL8557, which is entering phase III clinical development. This study was conducted to compare the in vitro activities of isavuconazole and five other antifungal agents against 296 Candida isolates that were recovered consecutively from blood cultures between 1995 and 2004 at a tertiary care university hospital. Microdilution testing was done in accordance with CLSI (formerly NCCLS) guideline M27-A2 in RPMI-1640 MOPS (morpholinepropanesulfonic acid) broth. The antifungal agents tested were amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, and isavuconazole. C. albicans was the most common species, representing 57.1% of all isolates. There was no trend found in favor of non-Candida albicans species over time. In terms of MIC50s, isavuconazole was more active (0.004 mg/liter) than amphotericin B (0.5 mg/liter), itraconazole (0.008 mg/liter), voriconazole (0.03 mg/liter), flucytosine (0.125 mg/liter), and fluconazole (8 mg/liter). For isavuconazole, MIC50s/MIC90s ranged from 000.2/0.004 mg/liter for C. albicans to 0.25/0.5 mg/liter for C. glabrata. Two percent of isolates (C. glabrata and C. krusei) were resistant to fluconazole; C. albicans strains resistant to fluconazole were not detected. There were only two isolates with MICs for isavuconazole that were >0.5 mg/liter: both were C. glabrata isolates, and the MICs were 2 and 4 mg/liter, respectively. In conclusion, isavuconazole is highly active against Candida bloodstream isolates, including fluconazole-resistant strains. It was more active than itraconazole and voriconazole against C. albicans and C. glabrata and appears to be a promising agent against systemic Candida infections.


2018 ◽  
Vol 56 (10) ◽  
Author(s):  
Hsuan-Chen Wang ◽  
Ming-I Hsieh ◽  
Pui-Ching Choi ◽  
Chi-Jung Wu

ABSTRACT This study compared the YeastOne and reference CLSI M38-A2 broth microdilution methods for antifungal susceptibility testing of Aspergillus species. The MICs of antifungal agents were determined for 100 Aspergillus isolates, including 54 Aspergillus fumigatus (24 TR34/L98H isolates), 23 A. flavus, 13 A. terreus, and 10 A. niger isolates. The overall agreement (within 2 2-fold dilutions) between the two methods was 100%, 95%, 92%, and 90% for voriconazole, posaconazole, itraconazole, and amphotericin B, respectively. The voriconazole geometric mean (GM) MICs were nearly identical for all isolates using both methods, whereas the itraconazole and posaconazole GM MICs obtained using the YeastOne method were approximately 1 dilution lower than those obtained using the reference method. In contrast, the amphotericin B GM MIC obtained using the YeastOne method was 3.3-fold higher than that observed using the reference method. For the 24 A. fumigatus TR34/L98H isolates assayed, the categorical agreement (classified according to the CLSI epidemiological cutoff values) was 100%, 87.5%, and 83.3% for itraconazole, voriconazole, and posaconazole, respectively. For four A. niger isolates, the itraconazole MICs were >8 μg/ml using the M38-A2 method due to trailing growth, whereas the corresponding itraconazole MICs obtained using the YeastOne method were all ≤0.25 μg/ml without trailing growth. These data suggest that the YeastOne method can be used as an alternative for azole susceptibility testing of Aspergillus species and for detecting the A. fumigatus TR34/L98H isolates but that this method fails to detect A. niger isolates exhibiting trailing growth with itraconazole. Additionally, for isolates with azole MICs that approach or that are at susceptibility breakpoints or with high amphotericin B MICs detected using the YeastOne method, further MIC confirmation using the reference CLSI method is needed.


2002 ◽  
Vol 15 (2) ◽  
pp. 106-113
Author(s):  
Manjunath P. Pai ◽  
Larry H. Danziger ◽  
Susan L. Pendland

Fungal infections have been increasing at an alarming rate in critically ill patients. Candida is now the fourth most common pathogen isolated from the bloodstream and is associated with significant morbidity, mortality, and economic consequences. Novel antifungals have been developed in recent years to provide alternatives to amphotericin B, which continues to be the standard therapy for most invasive fungal infections. These alternatives include lipid-based amphotericin B, ketoconazole, fluconazole, itraconazole, caspofungin, and potentially voriconazole. Optimal therapy for the various forms of candidiasis remains controversial. A standardized antifungal susceptibility testing method for Candida isolates has been developed to assist drug selection, but its clinical relevance remains to be determined. The relative susceptibility of Candida isolates can be estimated by the species. Specifically, C krusei is resistant to azoles, C glabrata may be resistant to azoles, and C lusitaniae may be resistant to amphotericin B Candida infections can affect any organ system, and the diagnosis of such infections remains difficult. The Infectious Diseases Society of America recently developed guidelines for the management of candidiasis. This review includes a brief discussion of systemically administered antifungal agents and provides a synopsis of the practice guidelines for the management of candidiasis.


2010 ◽  
Vol 54 (7) ◽  
pp. 3058-3060 ◽  
Author(s):  
Ana Alastruey-Izquierdo ◽  
Isabel Cuesta ◽  
Grit Walther ◽  
Manuel Cuenca-Estrella ◽  
Juan Luis Rodriguez-Tudela

ABSTRACT Forty-four isolates belonging to human pathogenic species of Lichtheimia were tested against nine antifungal agents by using the EUCAST methodology. No remarkable differences were found between the clinical species, although L. ramosa showed slightly higher MICs for all drugs. Amphotericin B was the most active drug. Among azole drugs, posaconazole had the best activity in vitro and voriconazole was inactive. Echinocandins showed activity for some isolates, suggesting a potential role in combination therapy.


2011 ◽  
Vol 71 (2) ◽  
pp. 126-130 ◽  
Author(s):  
Tarcieli P. Venturini ◽  
Luana Rossato ◽  
Tatiana B. Spader ◽  
Giordano R. Tronco-Alves ◽  
Maria Izabel Azevedo ◽  
...  

Author(s):  
Parvez Anwar Khan ◽  
Nazish Fatima ◽  
Haris Manzoor Khan ◽  
Midhat Ali Khan ◽  
Asim Azhar ◽  
...  

Candidiasis is recognized as a significant cause of morbidity, especially in immunocompromised individuals. An epidemiologic change in Candida species and emergence of resistance can impact the usage of antifungal agents as empirical therapy for Candidiasis in patients with or without AIDS. The present study was done to find out: i) The species of Candida isolated from H.I.V. and Non-HIV infected patients. ii) The resistance pattern of these Candida isolates to antifungal agents. A total of 160 Candida species isolates (80 isolates each from H.I.V. and Non-HIV infected patients) were characterized. Identification of yeast isolates was made by standard procedures including morphology (Staib agar, cornmeal agar, CHROMagar), germ tube test, fermentation, and assimilation of sugars and growth at 42°C. In addition, sensitivity testing was done using the broth microdilution method (M27-A2) as per the C.L.S.I. guidelines against amphotericin B, nystatin, voriconazole, fluconazole, ketoconazole, and itraconazole. In both the groups, i.e., H.I.V. and Non-HIV infected patients, Candida albicans was the most common species (61.2 % and 85 % respectively), followed by Candida guilliermondi (16.2 % and 5 %), Candida tropicalis (5 % and 3.7 %), Candida krusei (5% and 2.5 %), Candida dubliniensis 1(5 % and 1.2 %) and others. Among HIV infected patients fluconazole resistance was 16.25%, ketoconazole 13.5%, clotrimazole 12.5%, itraconazole 6.25 %. In the non-HIV infected group, fluconazole resistance was 8.75% and itraconazole 1.25%. For the appropriate treatment of Candida infections, antifungal susceptibility has become an essential tool, especially in the present scenario of increasing resistance.


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