Fluconazole Resistance among Oral Candida Isolates from People Living with HIV/AIDS in a Nigerian Tertiary Hospital (original) (raw)

Fluconazole resistant opportunistic oro-pharyngeal Candida and non-Candida yeast-like isolates from HIV infected patients attending ARV clinics in Lagos, Nigeria

African health sciences, 2008

BACKGROUND Oro-Pharyngeal Candidiasis (OPC) continues to be considered the most common opportunistic fungal disease in HIV/AIDS patients globally. Azole antifungal agent has become important in the treatment of mucosal candidiasis in HIV patients. Presently, antifungal drug resistance is fast becoming a major problem particularly with the immune depleted population. OBJECTIVES This study was designed to investigate the: existence of OPC, species distribution fluconazole susceptibility profile of yeast cells isolated from oral specimens of HIV/AIDS patients from Lagos Nigeria, between Oct. 2004 and June, 2005. METHODOLOGY The venous blood samples were screened for HIV antibodies using the Cappillus HIV I and II test kit (Trinity Biotech Plc UK), and Genie II HIV I and II EIA kit (Bio-Rad France). The positive results were subsequently confirmed at the laboratory attached to each of the clinics, using the Nigerian Federal Ministry of Health approved algorithm. The samples from 213 (10...

Fluconazole-resistant Candida species in the oral flora of fluconazole-exposed HIV-positive patients

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 1998

The purpose of this study was to examine the effect of preceding fluconazole treatment on the oral mycologic flora and on the sensitivity of oral Candida albicans isolates to fluconazole. Saline oral rinses were collected from 89 HIV-positive patients, of whom 48 had been exposed to fluconazole and 41 were fluconazole-naive. The rinses were cultured on Sabouraud's and Pagano Levin agars, and yeasts were identified by standard methods. Fluconazole sensitivity of C. albicans isolates was measured by disk diffusion assay. C albicans was isolated from 69% of patients who had received fluconazole and from 93% of the patients who were fluconazole-naive (p < 0.05). Nine other species of yeasts were also isolated, most commonly C. glabrata. Five patients previously exposed to fluconazole harbored fluconazole-resistant C. albicans, whereas no resistance was detected among the patients who were fluconazole-naive (p < 0.01). Sixteen of the patients who were fluconazole-exposed carried yeasts other than C albicans, compared with only five patients in the fluconazole-naive group (p < 0.01). All of the fluconazole-resistant strains were isolated from patients with low CD4 counts (less than 100 cells/ml) and after lengthy fluconazole exposures. Nevertheless, patients in Charlotte, N.C., who had a greater mean fluconazole exposure time (10.25 _+ 1.41 months) than patients in Glasgow, UK, (0.65 _+ 0.18 months; p < 0.005), did not develop significantly more in vitro resistance or species diversity. This study indicates that longterm fluconazole treatment can have significant effects on the yeast flora of the mouth, particularly in a patient with a CD4 count of less than 100 cells/ml. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:558-64)

Patterns of Fluconazole Susceptibility in Isolates from Human Immunodeficiency Virus-Infected Patients with Oropharyngeal Candidiasis Due to Candida albicans

Clinical Infectious Diseases, 1997

We evaluated 119 episodes of oropharyngeal candidiasis due to C. albicans to study the patterns of fluconazole susceptibility of the isolates and the characteristics of the patients and to confirm the correlation between fluconazole susceptibility of isolates and therapeutic outcome. Sixty-one isolates were considered susceptible to fluconazole (MICs, 0.5 Ag/mL), 33 were intermediate (MICs, 1.0-8.0 ,ug/mL), and 25 were resistant (MICs, 16.0 aug/mL). Patients infected with resistant strains had significantly lower CD4+ cell counts and a less recent AIDS diagnosis than patients infected with intermediate or susceptible strains. Previous fluconazole therapy and prophylaxis were significantly more frequent for patients infected with resistant and intermediate strains (P < .001). Decreased susceptibility to ketoconazole and itraconazole was observed in resistant and intermediate strains. Fluconazole treatment was ineffective for patients infected with resistant isolates; however, high doses of ketoconazole or itraconazole were successful for nine (81%) of them. Different patterns of fluconazole susceptibility among C. albicans strains are correlated with patients' characteristics and with therapeutic outcomes. Oropharyngeal candidiasis is the commonest opportunistic infection in patients infected with HIV, occurring in up to 90% of them. Candida albicans is the species most frequently isolated from patients with AIDS who have oral thrush [1], and antifungal therapy without microbiological confirmation is appropriate. Treatment with azole derivatives is effective for both oral thrush and esophageal candidiasis [2-4]. Fluconazole is an orally active, triazole antifungal agent that is less toxic, is better tolerated, and has greater in vivo activity against C. albicans than ketoconazole, and it is absorbed more reliably [5]. Fluconazole is associated with significantly greater rates of endoscopic and clinical cure than is ketoconazole for HIV-infected patients with oral or esophageal candidiasis [2, 3]. However, oropharyngeal or esophageal, candidiasis recurs

Infection Due to Fluconazole-Resistant Candida in Patients with AIDS: Prevalence and Microbiology

Clinical Infectious Diseases, 1997

A cross-sectional study was conducted to assess the prevalence and microbiology of oral infection due to fluconazole-resistant Candida in patients with AIDS. Oral swab specimens for fungal cultures were obtained from 100 consecutive outpatients with CD4 lymphocyte counts of <200/mm 3 . At least one fungal organism demonstrating in vitro resistance to fluconazole (minimum inhibitory concentration, ,ug/mL) was isolated from 26 (41%) of 64 patients for whom cultures were positive. When fluconazole-resistant C. albicans was isolated, in vitro resistance correlated with clinical thrush. None of 10 patients from whom only non-albicans species of Candida were isolated had active thrush. The patients from whom fluconazole-resistant Candida albicans was isolated had lower CD4 cell counts (median, 9/mm3), a greater number of treated episodes of thrush (median, 4.5), and a greater median duration of prior fluconazole treatment (231 days) than did patients from whom fluconazole-susceptible C. albicans was isolated (median CD4 cell count, 58/mm3 [P = .004]; median number of treated episodes of thrush, 2.0 [P = .001]; and median duration of prior fluconazole treatment, 10 days [P = .01]; respectively). In a multivariate analysis, the number of episodes and duration of fluconazole therapy were independent predictors of resistance.

Detection and Significance of Fluconazole Resistance in Oropharyngeal Candidiasis in Human Immunodeficiency Virus-Infected Patients

Journal of Infectious Diseases, 1996

The epidemiology and clinical significance of fluconazole resistance were assessed in a cohort of advanced human immunodeficiency virus (HIV)-infected patients with recurrent oropharyngeal candidiasis. Fifty patients were prospectively evaluated using a novel method of detecting fluconazole resistance with chromogenic media containing fluconazole; results were confirmed with macrobroth testing. Resistant yeasts, defined as MICs~8 pg/mL, were detected in 16 (32%) of 50 patients: 7 (14%) had resistant Candida albicans, 7 (14%) had resistant non-C. albicans yeast, and 2 (4%) had mixed resistant yeasts. MICs were~32 in 11 of 16 isolates. Previous fluconazole use and severe immunosuppression were risk factors for resistance. However,S of 26 patients had resistant isolates with no prior fluconazole use, and all were severely immunosuppressed. Despite the high prevalence of resistance, 48 patients clinically responded to fluconazole. Fluconazole-resistant C. albicans and non -C. albicans yeast infections are common in patients with advanced immunodeficiency, but clinical efficacy of fluconazole remains high.

Fluconazole susceptibility and strain variation of Candida albicans isolates from HIV-infected patients with oropharyngeal candidosis [published erratum appears in J Antimicrob Chemother 1998 Sep;42(3):413]

Journal of Antimicrobial Chemotherapy, 1998

Over a 16 month period we conducted a prospective study in a cohort of 45 HIV-positive patients to detect the development of resistance to fluconazole and to analyse the epidemiology of oropharyngeal candidosis (OPC). Each episode was treated with fluconazole 100 mg/day po for 10 days. All yeast isolates were tested for their in-vitro susceptibility to fluconazole. Multiple strains of Candida albicans simultaneously isolated from a given patient were typed by electrophoretic karyotyping. Overall, 106 episodes of OPC were diagnosed among the 45 patients: 18/45 patients (40%) had only one episode, 11/45 (24%) had two episodes, and the remaining 16/45 (36%) had three or more episodes (range 3-7). Cure (complete resolution of signs and symptoms and negative post-treatment cultures) and improvement (complete resolution of signs and symptoms but positive post-treatment cultures) were observed in 30/106 (28%) and 69/106 (65%) episodes of OPC, respectively. Failure (absence of improvement or exacerbation of signs and symptoms) was observed in seven episodes (7%) from four patients. In two of these four patients a significant and progressive increase in fluconazole MICs was observed: from 0.25 to 16 mg/L in one patient, and from ≤0.125 to 32 mg/L in the second one. Tests on multiple colonies from individual isolation plates showed that it was not unusual to obtain different fluconazole MICs, indicating that, in order to avoid misleading results, one should perform in-vitro susceptibility testing by using a multiple colony inoculum rather than an inoculum made from a single colony. A total of 213 strains of C. albicans isolated from seven patients who suffered from four or more episodes of OPC through the course of the study were typed by electrophoretic karyotyping. Five individuals (71%) were infected with yeasts with only one DNA type, while the other two patients showed the presence of two or three different DNA types. The simultaneous presence of multiple types was found only in one of the seven subjects. Our data confirm the efficacy of fluconazole 100 mg/day for the treatment of OPC in HIV patients. Isolation of fluconazoleresistant strains of C. albicans with this regimen is rare. The vast majority of HIV patients are infected with a unique strain of C. albicans throughout each episode of infection. A minority of patients, however, can harbour strains of C. albicans with variable patterns of fluconazole susceptibility simultaneously.

Fluconazole and voriconazole susceptibility in oral colonization isolates of Candida spp. in HIV patients

Investigación Clínica, 2019

The identification of Candida species and their antifungal susceptibility is important for the treatment of infected patients. The aim was to determine the susceptibility to fluconazole and voriconazole in isolates from oral colonization of Candida spp. in HIV patients. From the 135 patients studied, 33.3% were females and 66.7% males, with a mean age of 36.6 years and 83.7% of them were under treatment. The identification of the specie was performed by the API20CAUX ® test and the antifungal susceptibility was determined by the disc diffusion test. Strains of C. parapsilosis and C. krusei were used as quality controls. The Candida species identificated were: C. parapsilosis complex 52%, C. albicans complex 36% and C. famata 12%. 60% of the isolates were susceptible to fluconazole and 40% were dose-dependent. All were susceptible to voriconazole. In this study, none of the patients had oropharyngeal candidiasis however, 18.5% had Candida spp. colonization, this percentage being below other studies in HIV carriers. We found a high proportion of nonalbicans species but no difference in the CD4+ counts between patients.

Oral Candida isolates among HIV-infected subjects in Nigeria

Journal of Microbiology, Immunology and Infection, 2011

Background: Nigeria is a West African country of more than 150 million persons with the second highest case of HIV/AIDS infected patients in the world. The species spectrum of oral yeast colonization and the susceptibility to a wide range of antifungal agents is poorly understood in Nigeria especially in the south east, south south, and the northern axis. This study evaluates the species spectrum of oral colonization by Candida species in HIV-infected patients in Nigeria and the in vitro susceptibility pattern of the Candida isolates to a broad range of antifungal agents. Methods: Two hundred oropharyngeal swabs from HIV-infected patients and 100 age-matched healthy controls were screened for yeast isolates using standard procedures and confirmed by the analytical profile index 20C along with other biochemical tests. In vitro susceptibility testing of the yeast isolates to antifungals were performed using the broth microdilution method protocol recommended by the Clinical Laboratory Scientific Institute. Results: Of 200 patients screened, 120 (60%) were colonized by yeasts. C albicans was the dominating species in both groups with 54 (45%) isolated from HIV subjects. The non-albicans Candida species accounted for 55% with C tropicalis 22 (18.3%) showing the highest frequency. We observed that 11.7% of all yeasts isolates were resistant to fluconazole, 8.3% to flucytosine, 7.5% to itraconazole, and 1.7% to voriconazole. All isolates were susceptible to amphotericin B and most of them demonstrated very low voriconazole minimal inhibitory concentrations. Apart from C albicans, C tropicalis and C parapsilosis isolates were also recovered from apparently healthy control subjects. Conclusion: Although C albicans continues to be the dominant Candida species in oral Candida carriage of HIV-infected patients in Nigeria, the nonalbicans Candida species are increasing. Furthermore, the finding of resistant isolates in our study emphasizes the need for antifungal

Mechanisms of resistance to fluconazole in Candida albicans clinical isolates from Iranian HIV-infected patients with oropharyngeal candidiasis

Objectives. — The opportunistic pathogen Candida albicans is the major agent of oropharyngeal candidiasis (OPC) in HIV/AIDS patients. The increased use of fluconazole can lead to the emergence of azole-resistant strains and treatment failures in PLWH (people living with HIV) receiving long- term therapy for OPC. The purpose of this study was to evaluate CDR1, CDR2, MDR1, and ERG11 gene expression in C. albicans clinically isolated from HIV-infected patients in Iran.Patients and Methods. — In this study, we evaluated the molecular mechanisms of azole resistance in 20 fluconazole-resistant C. albicans isolates obtained from Iranian HIV-infected patients with oropharyngeal candidiasis by Real-Time polymerase chain reaction.Results. — The overexpression of drug efflux pump CDR1 gene was found to be the major resistance mechanism observed in these isolates. The overexpression of the CDR1 gene correlated strongly with increasing resistance to fluconazole (P < 0.05). Additionally, an increased level of mRNA in ERG11 was not observed in any of the tested isolates.Conclusions. — Our findings suggested that the CDR1 gene expression to fluconazole resistance in C. albicans is greater than other known genes.