Fluconazole resistance

Top documents about Fluconazole resistance:

Fluconazole resistance in <em>Candida</em> species: a current perspective

Fluconazole resistance in <em>Candida</em> species: a current perspective

One study analyzed gene copy number in clinical isolates of C. albicans and determined that aneuploid chromosomes were seven times more common in fluconazole-resistant isolates as compared to fluconazole susceptible. They also reported specifically isochromosome formation of chromo- some 5 (chr5) to be associated with fluconazole resistance in C. albicans. Increases or reductions in resistance could be tied, respectively, with gain or loss of this chr5 isochro- mosome, as duplication of this segment accords additional copies of ERG11, its transcriptional regulator UPC2, as well as efflux pump regulator, TAC1. 87

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Emergence of Fluconazole Resistance in a Candida parapsilosis Strain That Caused Infections in a Neonatal Intensive Care Unit

Emergence of Fluconazole Resistance in a Candida parapsilosis Strain That Caused Infections in a Neonatal Intensive Care Unit

Candida parapsilosis is an increasing cause of bloodstream infections (BSIs) in neonatal intensive care units (NICUs). It has been a persistent problem in the NICU of Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland, since 1987. Fluconazole prophylaxis has been used to control the problem. The number of new infections has, however, increased markedly since September 2000. We assessed fluconazole consumption and occurrence of all Candida species in the NICU from 1991 to 2002. C. parapsilosis bloodstream isolates obtained in the NICU from 1990 to 2002 (n ⴝ 26) were genotyped and their fluconazole susceptibility was defined. A low rate of C. parapsilosis BSIs was correlated with high rates of consumption of fluconazole. No emergence of Candida species with primary resistance to fluconazole was detected. However, genotyping with a complex DNA fingerprinting probe revealed that a single strain of C. parapsilosis with decreasing susceptibility to fluconazole was responsible for cross-infections that caused BSIs in the NICU over a 12-year period. The emergence of fluconazole resistance in that strain was observed after more than 10 years of fluconazole prophylaxis.

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Clonal and Spontaneous Origins of Fluconazole Resistance in Candida albicans

Clonal and Spontaneous Origins of Fluconazole Resistance in Candida albicans

The genotypes and susceptibilities to fluconazole of 78 strains of the human pathogenic yeast Candida albicans were compared. The strains comprised two sets of samples from Durham, N.C.: one from patients infected with the human immunodeficiency virus (HIV) and the other from healthy volunteers. For each strain, the MIC of fluconazole was determined by the standard National Committee for Clinical Laboratory Standards protocol. Genotypes were determined by PCR fingerprinting with five separate primers. The analysis revealed little evidence for genotypic clustering according to HIV status or body site. However, a small group of fluconazole-resistant strains isolated from patients infected with HIV formed a distinct cluster. In addition, two fluconazole-resistant strains were isolated from individuals who never took fluconazole, one from a patient infected with HIV and the other from a healthy person. The results suggest both clonal and spontaneous origins of fluconazole resistance in C. albicans.

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MDR1 overexpression combined with ERG11 mutations induce high level fluconazole resistance in Candida tropicalis clinical isolates

MDR1 overexpression combined with ERG11 mutations induce high level fluconazole resistance in Candida tropicalis clinical isolates

In addition to the targeted mutations and overexpression of the enzyme Erg11p, we found that overexpression of the efflux pumps Mdr1p and Cdr1p, encoded by the MDR1 and CDR1 genes, are involved in C. tropicalis azole resist- ance [22]. Consistent with this finding, pan-azole resistant C. tropicalis isolate, which overexpresses the MDR1 gene and contains the Y132F and S154F amino acid substitu- tions in Erg11p, has reportedly been isolated from a patient with acute lymphoblastic leukemia [8]. In the present study, we found that fluconazole-resistant isolates had significantly higher expression levels of the MDR1 gene than control isolates. Furthermore, high-level fluconazole- resistant isolates had higher levels of MDR1 expression than low-level fluconazole-resistant isolates. Most importantly, among the 12 fluconazole-resistant isolates, MDR1 expres- sion levels were highest in the three pan-azole-resistant isolates. Hence, we conclude that overexpression of the MDR1 gene is associated with high-level fluconazole resistance in C. tropicalis clinical isolates. Additionally, these results indicate that the combination of MDR1 gene overexpression and the amino acid substitutions

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Hospital Specificity, Region Specificity, and Fluconazole Resistance of Candida albicans Bloodstream Isolates

Hospital Specificity, Region Specificity, and Fluconazole Resistance of Candida albicans Bloodstream Isolates

In a survey of bloodstream infection (BSI) isolates across the continental United States, 162 Candida albicans isolates were fingerprinted with the species-specific probe Ca3 and the patterns were analyzed for relatedness with a computer-assisted system. The results demonstrate that particular BSI strains are more highly con- centrated in particular geographic locales and that established BSI strains are endemic in some, but not all, hospitals in the study and undergo microevolution in hospital settings. The results, however, indicate no close genetic relationship among fluconazole-resistant BSI isolates in the collection, either from the same geographic locale or the same hospital. This study represents the first of three fingerprinting studies designed to analyze the origin, genetic relatedness, and drug resistance of Candida isolates responsible for BSI.

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Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis

Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis

Cryptococcal meningitis (CM) is a common and severe opportunis- tic infection primarily affecting patients with advanced HIV/AIDS caused by the basidiomycete yeasts Cryptococcus neoformans (Cn) or less frequently Cryptococcus gattii (1). CM mortality is particu- larly high in resource-limited settings where mortality can exceed 50% even with antifungal treatment (2, 3). CM is invariably fatal without treatment (4). Recent estimates place the annual death toll from CM approaching 200,000 deaths per year, predominantly in sub-Saharan Africa (5). The gold standard of treatment for CM in HIV-infected patients is a 2-week induction regimen of ampho- tericin B deoxycholate (AmB) combined with flucytosine (5FC), followed by a consolidation and then maintenance phase with oral fluconazole (FLC) (6). In many countries, however, and particularly those in sub-Saharan Africa, FLC is the only available antifungal; therefore, FLC monotherapy is used for induction, consolidation, and long-term maintenance regimes (7). Even with relatively high BACKGROUND. Cryptococcal meningitis (CM) causes an estimated 180,000 deaths annually, predominantly in sub-Saharan

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Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis

Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis

Cryptococcal meningitis (CM) is a common and severe opportunis- tic infection primarily affecting patients with advanced HIV/AIDS caused by the basidiomycete yeasts Cryptococcus neoformans (Cn) or less frequently Cryptococcus gattii (1). CM mortality is particu- larly high in resource-limited settings where mortality can exceed 50% even with antifungal treatment (2, 3). CM is invariably fatal without treatment (4). Recent estimates place the annual death toll from CM approaching 200,000 deaths per year, predominantly in sub-Saharan Africa (5). The gold standard of treatment for CM in HIV-infected patients is a 2-week induction regimen of ampho- tericin B deoxycholate (AmB) combined with flucytosine (5FC), followed by a consolidation and then maintenance phase with oral fluconazole (FLC) (6). In many countries, however, and particularly those in sub-Saharan Africa, FLC is the only available antifungal; therefore, FLC monotherapy is used for induction, consolidation, and long-term maintenance regimes (7). Even with relatively high BACKGROUND. Cryptococcal meningitis (CM) causes an estimated 180,000 deaths annually, predominantly in sub-Saharan

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A Study on Speciation and Antifungal Susceptibility Pattern of Candida Isolates from HIV Patients with Oropharyngeal Candidiasis and Correlation with Cd4 Count.

A Study on Speciation and Antifungal Susceptibility Pattern of Candida Isolates from HIV Patients with Oropharyngeal Candidiasis and Correlation with Cd4 Count.

In the present study, the antifungal susceptibility pattern determined by Microbroth dilution method shows that about 18 (11.8% ) isolates were resistant to Fluconazole and 23 (15.1%) were resistant to itraconazole.All the isolates were susceptible to amphotericin(100%).(Table-13) This was similar to the study done by Usha et al 2009 where 11.5% of the isolates were fluconazole resistant. CA Enwuru et al 2008 showed that fluconazole resistance was observed in 9.5% of the Candida isolates where the resistant rates were found to be slightly lower than the current study .The study conducted by Hamza et al 2008, reveals that 5% and 8.4% of the Candida isolates were resistant to fluconazole and itraconazole respectively. Carolina et al 2006 reported 8.1% of the isolates were fluconazole resistant and about 8.1% were resistant to itraconazole and no resistance to amphotericin B. Many studies done by Bailey et al 1994, Chavanet et al 1994 have estimated the incidence of clinical fluconazole resistance to be from 6 to 36%.

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Replacement of Candida albicans with C  dubliniensis in Human Immunodeficiency Virus Infected Patients with Oropharyngeal Candidiasis Treated with Fluconazole

Replacement of Candida albicans with C dubliniensis in Human Immunodeficiency Virus Infected Patients with Oropharyngeal Candidiasis Treated with Fluconazole

Candida dubliniensis is an opportunistic yeast that has been increasingly implicated in oropharyngeal candidiasis (OPC) in human immunodeficiency virus (HIV)-infected patients but may be underreported due to its similarity with Candida albicans. Although most C. dubliniensis isolates are susceptible to fluconazole, the inducibility of azole resistance in vitro has been reported. Thus, the use of fluconazole prophylaxis in the treatment of these patients may have contributed to the increasing rates of isolation of C. dubliniensis. In this study, yeast strains were collected from the oral cavities of HIV-infected patients enrolled in a longitudinal study of OPC. Patients received fluconazole for the suppression or treatment of OPC, and isolates collected at both study entry and end of study were chosen for analysis. Samples were plated on CHROMagar Candida medium for initial isolation and further identified by Southern blot analysis with the species-specific probes Ca3 (for C. albicans) and Cd25 (for C. dubliniensis). Fluconazole MICs were determined by using NCCLS methods. At study entry, susceptible C. albicans isolates were recovered from oral samples in 42 patients who were followed longitudinally (1 to 36 months). C. albicans strains from 12 of these patients developed flucon- azole resistance (fluconazole MIC, > 64 ␮ g/ml). C. dubliniensis was not detected at end of study in any of these patients. Of the remaining 30 patients, eight (27%) demonstrated a replacement of C. albicans by C. dubliniensis when a comparison of isolates obtained at baseline and those from the last culture was done. For the 22 of these 30 patients in whom no switch in species was detected, the fluconazole MICs for initial and end-of-study C. albicans isolates ranged from 0.125 to 2.0 ␮ g/ml. For the eight patients in whom a switch to C. dubliniensis was detected, the fluconazole MICs for C. dubliniensis isolates at end of study ranged from 0.25 to 64 ␮ g/ml: the fluconazole MICs for isolates from six patients were 0.25 to 2.0 ␮ g/ml and those for the other two were 32 and 64 ␮ g/ml, respectively. In conclusion, a considerable number of patients initially infected with C. albicans strains that failed to develop fluconazole resistance demonstrated a switch to C. dubliniensis. C. dubliniensis in this setting may be underestimated due to lack of identification and may occur due to the impact of fluconazole on the ecology of oral yeast species.

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The trend of susceptibilities to amphotericin B and fluconazole of Candida species from 1999 to 2002 in Taiwan

The trend of susceptibilities to amphotericin B and fluconazole of Candida species from 1999 to 2002 in Taiwan

1993 [1,2]. In the United States, yeast infections rank as the fourth most common cause of nosocomial blood- stream infection [3,4]. Furthermore, candidemia contrib- ute considerable mortality (31% to 38%), extend the length of hospital stay [5,6], and increase social cost due to lost productivity and disabling complications [7]. Con- sequently, the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) was initiated in 1999 for epi- demiological study of yeast infections in Taiwan [8,9] Candida species have various degrees of susceptibility to common antifungal agents. Candida lusitaniae is less sus- ceptible to amphotericin B [10] while Candida krusei and Candida glabrata are less susceptible to fluconazole than other Candida species [11-14]. The extent of fluconazole resistance of C. glabrata isolates causing candidemia has been reported throughout the United States [15]. Further- more, C. glabrata exhibits variable cross-resistance to the other triazoles, such as voriconazole and posaconazole [13,16-18] and amphotericin B became the next choice. The aim of this study is to investigate the trend of suscep- tibility to amphotericin B and fluconazole of Candida spe- cies in Taiwan from 1999 to 2002. Especially, we would like to determine if there is an emerging co-resistance to amphotericin B and fluconazole of Candida species, spe- cifically, of C. glabrata, in Taiwan.

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A study on biofilm production and antifungal drug resistance among Candida species from vulvovaginal and bloodstream infections

A study on biofilm production and antifungal drug resistance among Candida species from vulvovaginal and bloodstream infections

(16.8%) isolates showed biofilm production with resistance to both fluconazole and voriconazole; only one out of 102 isolates showed fluconazole resistance, and among blood samples, 13 of 74 (17.5%) isolates showed biofilm produc- tion with resistance to fluconazole and voriconazole and six out of 74 (8.1%) isolates showed biofilm production with resistance to fluconazole alone. We observed a higher degree of resistance to fluconazole in biofilm producers as compared to that in non-producers, which has been seen in NAC and reported in other studies. 5,20,25 The limitation of this

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Simple method for detecting fluconazole resistant yeasts with chromogenic agar

Simple method for detecting fluconazole resistant yeasts with chromogenic agar

Fluconazole resistance is becoming an important clinical concern (3, 4, 7, 8, 11, 13–20). Decreased fluconazole suscep- tibility has been noted especially in human immunodeficiency virus (HIV)-infected patients with recurrent oropharyngeal candidiasis and in patients infected with yeasts other than Candida albicans (4, 16, 20–22). The National Committee for Clinical Laboratory Standards’ (NCCLS) proposed standard has made yeast susceptibility testing more reproducible and may correlate with clinical outcome (5, 9). However, the stan- dard broth macrodilution technique is not easily applied for screening and is not used routinely in clinical microbiology laboratories (1).

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Multidrug Resistant Candida auris Misidentified as Candida haemulonii: Characterization by Matrix Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and DNA Sequencing and Its Antifungal Susceptibility Profile Variability by Vitek 2, CL

Multidrug Resistant Candida auris Misidentified as Candida haemulonii: Characterization by Matrix Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and DNA Sequencing and Its Antifungal Susceptibility Profile Variability by Vitek 2, CLSI Broth Microdilution, and Etest Method

care general hospitals and a pediatric center in north and south India, representing 8.6% to 30% of cases of candidemia (7, 8). The actual prevalence of C. auris in varied clinical settings in India is unexplored, as the majority of centers do not perform molecular or MALDI-TOF MS-based identification. In this work, a large number of C. auris isolates were tested for antifungal susceptibility with three methods which showed uniform fluconazole resistance and an alarming percentage of isolates (37%) exhibiting elevated caspofungin MICs by CLSI-BMD. Taken together, 10% of isolates showed highly elevated MICs to 4 antifungals drugs (AMB, FLU, CAS, VRC) by the CLSI-BMD method. Notably, 34% of isolates had coexisting elevated MICs for two commonly used azoles, i.e., FLU and VRC (MICs of ⱖ 2 ␮ g/ml), and 10% of the isolates had elevated coexisting MICs (ⱖ1 ␮g/ml) to two additional azoles, i.e., POS and ISA. Considering the frequent prevalence of MDR strains of C. auris in the intensive care units and other wards of 5 different hospitals in the present series, the accurate identification and an- tifungal susceptibility testing of this yeast is pertinent for guiding therapy and determining the prognosis in such settings. Also, ac- curate identification of the cryptic species C. auris is important in assessing the epidemiology and pathogenicity of the disease TABLE 1 In vitro antifungal susceptibility profile of C. auris, C. haemulonii, and C. duobushaemulonii strains by the CLSI M27-A3 broth

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Trends in Antifungal Use and Epidemiology of Nosocomial Yeast Infections in a University Hospital

Trends in Antifungal Use and Epidemiology of Nosocomial Yeast Infections in a University Hospital

Other investigators have noted similar increases in the fre- quency of infections caused by C. glabrata in conjunction with azole use (1, 22, 24, 26). In a study by Nguyen et al., C. glabrata was the most common species other than C. albicans causing bloodstream infections (22). In addition, C. glabrata fungemia was associated with a high complication rate (e.g., endocardi- tis, osteomyelitis, hepatosplenic abscess) (22). Abi-Said et al. found that bloodstream infections caused by C. glabrata and C. krusei were more likely to occur in patients who had received fluconazole during hospitalization, whereas infections caused by C. albicans and C. tropicalis were more likely among patients who had not received that agent (1). In contrast, other inves- tigators have noted that rates of infections caused by yeast species which are less susceptible to fluconazole, such as C. krusei, and Saccharomyces spp., usually increased before this drug was introduced or occurred as part of an outbreak (2, 5, 13, 17, 23, 39).

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Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among Candida glabrata Clinical Strains Associated with In Vivo Persistence

Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among Candida glabrata Clinical Strains Associated with In Vivo Persistence

fluconazole treatment, as observed in the mouse model, creates optimal conditions for the emergence of stress-induced mutations conferring azole resistance. The lack of significant HR to echino- candins may be related to the rapid fungicidal effect of glucan- synthase inhibition, which does not allow time for stress-induced genetic instability. It should be noted, however, that of the 52 clinical C. glabrata strains in this study, only 8 were recovered from patients treated with an azole during the preceding year (see Table S1 in the supplemental material). Hence, other types of environmental stress were probably involved in the generation of FLC HR strains. ABC transporters have broad substrate specificity,

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Correlation of anti fungal susceptibility with clinical outcomes in patients with cryptococcal meningitis

Correlation of anti fungal susceptibility with clinical outcomes in patients with cryptococcal meningitis

Anti-fungal susceptibilities were determined using the broth micro-dilution method according to the CLSI M27-A3 methodology [7]. The anti-fungal agents tested were fluconazole (Pfizer, New York, NY, USA), voricona- zole (Pfizer), and amphotericin B deoxycholate (Sigma). Stock solutions were prepared in dimethyl sulfoxide (voriconazole and amphotericin B) or water (flucona- zole), and were further diluted in RPMI 1640 medium (Sigma) buffered to a pH level of 7 with 0.165 M 3-( N - morpholino) propanesulfonic acid buffer (Sigma). Ali- quots of each agent (0.1 ml) at 2× concentrations were dispensed into 96-well micro-dilution trays. Inocula con- taining 0.5 × 10 3 to 2.5 × 10 3 cells/ml were then added to each well and the trays were incubated at 35°C. The final anti-fungal concentrations ranged from 0.06 to 8 μg/ml for voriconazole and amphotericin B, and from 0.25 to 64 μg/ml for fluconazole.

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Fluconazole for empiric antifungal therapy in cancer patients with fever and neutropenia

Fluconazole for empiric antifungal therapy in cancer patients with fever and neutropenia

therapy for patients being treated with broad-spectrum antibiotics who have prolonged fever and neutropenia has been demonstrated to be efficacious, and it has become the standard of practice [5-7]. Newer antifungal agents have used for empiric antifungal therapy included liposomal amphotericin B [8] and caspofungin [9]. Fluconazole is active against the major fungal pathogens (except for mould) in neutropenic cancer patients although conventional amphotericin B is commonly used as a first-line agent for documented infections. Clinical tri- als have shown that fluconazole is an equally effective but less toxic alternative to amphotericin B for empiric anti- fungal therapy in cancer patients with prolonged fever and neutropenia [10-13]. These trials also evaluated clin- ical response to empiric antifungal therapy and found no significant difference in treatment failure with the rates of 25%–44% in fluconazole group compared to 33%–54% in patients on amphotericin B [10,11,13]. The relation- ships between treatment failure from empiric antifungal therapy and patient characteristics have been explored in a trial [11], although economic outcomes were not reported.

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Anti-Candida Effects of Clotrimazole and Fluconazole Against Isolated C. Albicans From Patinetso Candidiasis Admitted in Medical Mycology Lab of Special Clinic of Kermanshah University of Medical Sciences, 2014

Anti-Candida Effects of Clotrimazole and Fluconazole Against Isolated C. Albicans From Patinetso Candidiasis Admitted in Medical Mycology Lab of Special Clinic of Kermanshah University of Medical Sciences, 2014

First, all the used glass and metal supplies were made sterile by an oven (temperature of 120 degree of centigrade) for an hour and all steps of the process were done beside the flame and under clean conditions. After providing anti-biotic solutions, mixing the antibiotic and medium was done before entering the plate in Erlenmeyer and then 10 milliliter of the mixture of drug and medium was poured inside each plate. The medium containing drugs was put in refrigerator for 24 hours. Then, the inoculation of fungus was done in the medium. To study the antifungal effects of each concentration of both Fluconazole and Clotrimazole antibiotics, the blank of each fungus was prepared. Providing the suspension of inoculation to medium

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Evolution of Fluconazole Resistant Candida albicans Strains by Drug Induced Mating Competence and Parasexual Recombination

Evolution of Fluconazole Resistant Candida albicans Strains by Drug Induced Mating Competence and Parasexual Recombination

As explained in the introduction, tetraploid cells are not stable and can lose chromosomes to become aneuploid and eventually revert to the diploid state. We reasoned that upon further propagation in the presence of fluconazole, the mating products would evolve increased drug resistance by reassorting their combined chromosome sets in an advantageous way. Therefore, we selected one mating product from each cross (those listed in Table 3 and shown in Fig. 3) to test this hypothesis (see below). We first analyzed the ploidy of the selected original mating products and their parental strains by flow cytometry. The starting strains that were heterozygous for the various resistance mutations exhibited the same 2C and 4C peaks as the reference strain SC5314, from which they were derived and therefore were diploid as expected (Fig. S3). In contrast, an altered ploidy was observed for some of the fluconazole-induced MTL-homozygous strains (Fig. 4A). While SCERG11R32hom1B, SCTAC1R32hom2A, and SCTAC1R32hom2B appeared diploid, SCMRR1R32hom2A and SCUPC2R12hom1A had a slightly higher than 4N DNA content, and SCERG11R32hom1A, SCMRR1R32hom1A, and SCUPC2R12hom1B ap- parently contained a subpopulation of cells with various ploidies. Most of the mating products displayed a shift of the peaks that was compatible with the expected tetraploidy (Fig. 4B). However, mating product ME1 appeared to be diploid, whereas mating product UT1 was hypertetraploid, and TU1 showed pop- ulation heterogeneity, indicating that the mating products were not stable and had undergone genomic changes during the following cell divisions before they were TABLE 3 Mating products used for passaging experiments

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A Study on the Prevalence of Oropharyngeal Candidiasis in the Immunocompromised Individuals and their Antifungal Susceptibility Pattern in Tirunelveli Medical College Hospital.

A Study on the Prevalence of Oropharyngeal Candidiasis in the Immunocompromised Individuals and their Antifungal Susceptibility Pattern in Tirunelveli Medical College Hospital.

Systemic antifungal chemotherapy can be associated with toxicity, cost, and emergence of resistance. An alternative approach is to give pre-emptive antifungal therapy, which consists of limiting antifungal therapy only to those patients at risk for serious candidal infections and who also exhibit evidence of significant colonization with candida spp. at two or more sites. This strategy has been proposed in the setting of cancer chemotherapy 160 and surgery.

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