Diagn Microbiol Infect Dis. 2014 Jun;79(2):222-7. doi: 10.1016/j.diagmicrobio.2013.09.016.

Multi-drug resistant oral Candida species isolated from HIV-positive patients in South Africa and Cameroon

Pedro Miguel dos Santos Abrantes a, Carole P. McArthur b, Charlene Wilma Joyce Africa a

a Oral Microbiology Group, Department of Medical Biosciences, University of the Western Cape, Cape Town, South Africa; b Department of Oral and Craniofacial Science, School of Dentistry, University of Missouri-Kansas City, Kansas City, USA

 

Abstract

Candida species are a common cause of infection in immune-compromised HIV-positive individuals, who are usually treated with the antifungal drug, fluconazole in public hospitals in Africa. However, information about the prevalence of drug resistance to fluconazole and other antifungal agents on Candida species is very limited. This study examined 128 Candida isolates from South Africa and 126 Cameroonian Candida isolates for determination of species prevalence and antifungal drug susceptibility. The isolates were characterized by growth on chromogenic and selective media and by their susceptibility to nine antifungal drugs tested using the TREK™ YeastOne9 drug panel (Thermo Scientific). Eighty three percent (82.8%) of South African isolates were C. albicans (106 isolates), 9.4% were C. glabrata (12 isolates) and 7.8% were C. dubliniensis (10 isolates). Of the Cameroonian isolates, 73.02% were C. albicans (92 isolates); 19.05% C. glabrata (24 isolates); 3.2% C. tropicalis (4 isolates); 2.4% C. krusei (3 isolates); 1.59% designated ‘other’ (2 isolates phenotypically resembling either C. kefyr, C. parapsilopsis or C. lusitaneae); and 0.79% C. dubliniensis (1 isolate). Widespread C. albicans resistance to azoles was detected phenotypically in both populations. Differences in drug resistance were seen within C. glabrata found in both populations. Echinocandin drugs were more effective on isolates obtained from the Cameroon than in South Africa. A multiple drug resistant (MDR) C. dubliniensis strain isolated from the South African samples was inhibited only by 5-flucytosine in vitro on the YO9 panel. Drug resistance among oral Candida species is common among African HIV patients in these two countries. Regional surveillance of Candida species drug susceptibility should be undertaken to ensure effective treatment for HIV-positive patients. Copyright © 2014 Elsevier Inc.

KEYWORDS: Antifungal agents; Candida; Drug resistance; TREK

PMID: 24726686

 

Supplement

One of the most common HIV-associated opportunistic infections is candidiasis, caused by Candida albicans or other Candida species. In immune suppressed subjects, these commensal organisms can cause an increase in patient morbidity and mortality due to oropharyngeal or systemic dissemination. Localized and systemic Candida infections are normally treated with fluconazole in public health facilities in Africa. It is thought that the widespread and improper use of this drug over the past decade has resulted in an increase in fluconazole-resistant isolates [1, 2].

 

Figure 1

Figure 1: Distribution of Candida species found in the oral mucosa of HIV+ patients.

Limited information exists on the prevalence and antifungal susceptibility of Candida species on the African continent, the most HIV-affected region globally and home to new and emerging drug resistant Candida species.

In this study, the species prevalence and susceptibility to nine antifungal drugs were tested in 254 Candida isolates obtained from the oral mucosa of HIV-positive South African and Cameroonian patients. Candida albicans, C. glabrata and C. dubliniensis were observed in both populations, with a greater diversity of species seen in Cameroon (Figure 1).

More than half of C. albicans isolates collected in this study were found to be resistant to all azole antifungals (fluconazole, itraconazole, posaconazole and voriconazole) on the TREK panel, an inexpensive broth microdilution method that can be used for susceptibility testing of multiple drugs [3,4] (Figure 2). Overall, the echinocandin drugs (anidulafungin, caspofungin and micafungin) were much more effective in their action against C. albicans. Regional differences in antifungal drug resistance were seen in C. glabrata isolates. Candida resistance to two drug classes was seen in both populations and a South African C. dubliniensis isolate was found to be resistant to all drugs on the TREK panel, with the exception of 5-flucytosine. These findings suggest that multiple-drug resistant Candida isolates may be present in the HIV-positive population.

Factors such as the high HIV infection rates, lack of regional surveillance of Candida prevalence and antifungal drug susceptibility, uncontrolled distribution and sale of medications, lack of patient access to medical treatment and limited resources in African laboratory and clinical settings have probably contributed to the emergence of Candida resistance to different classes of antifungal drugs. These factors need to be addressed as part of an effort to reduce the high morbidity and mortality rates seen in these populations.

 Figure 2Figure 2: Drug panel and different results seen on the TREK Sensititre plates.

a: Different drugs and concentrations of the TREK panel
b: Susceptible strain (growth only in red circled wells)
c: Azole drug resistance
d: Multiple drug resistance (only 5-Flucytosine >2µg/ml inhibits the growth of the organism)

 

This material is based upon work supported financially by the National Research Foundation (NRF) of South Africa. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the authors, and therefore, the NRF does not accept any liability in regards thereto.

 

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