Candidiasis is the most common fungal infection in the world. Candida is isolated almost invariably from cutaneous lesions, but rarely cultured from the blood or vitreous fluid. The sources of the fungus in these cases remain uncertain. Although some authors have suggested that Candida may contaminate heroin, attempts to culture Candida from heroin have been unsuccessful (11). The recreational use of illicit drugs has aroused concerns that drug abuse-mediated immune dysfunction increases host susceptibility to microbial pathogens. Opiates can also affect the immune system directly through opioid receptors on immune cells leading to reduced phagocytosis and chemotaxis. Endogenous Candida albicans endophthalmitis in injecting drug users has been extensively documented in the literature and is one of the most common ocular complications of drug use (12).
In the present study, we evaluated the prevalence of C. glabrata isolates in oral samples taken from drug addicts. The results showed that about 22% of the isolates were C. glabrata. Disruption of the mucosal defense or immune system can provide suitable conditions for opportunistic pathogens (13). In some studies, non-albicans species such as C. glabrata were the most frequently isolated Candida strains (14).
Previous studies reported C. glabrata, C. tropicalis, C. krusei, and C. parapsilosis as the main causes of mucosal fungal infections (15). Similar to our findings, a study of the oral mucosa of immunocompromised patients in 1998 reported the high prevalence of non-albicans Candida species, including C. glabrata (16).
The importance of non-albicans Candida species has become more profound due to the emergence and development of resistance to antifungal drugs in some of these species, such as C. glabrata and C. krusei, which has led to a dramatic increase in the prevalence of candidiasis. Hence, there is an urgent need for its detection and determining the frequency of resistant Candida species to help develop and implement effective control measures (17).
In our study, 61% and 44.4% of C. glabrata isolates were resistant to fluconazole and voriconazole, respectively. In 2006, researchers stated that 43% of the strains isolated from blood samples of hospitalized patients were C. glabrata. Of these isolates, 23% were voriconazole-resistant and 41% were fluconazole-resistant (18), which are less than the rates observed in our study. This difference can be attributed to the difference in the characteristics of the studied populations, the type of samples taken, the type of infections, and the presence of underlying diseases. This highlights the necessity of determining susceptibility to azoles and other antifungal agents. In some studies, C. glabrata was the least susceptible species to voriconazole. Likewise 60% of C. glabrata isolates were susceptible to fluconazole, and 92%, were inhibited by ≤ 1 µg of voriconazole per mL (19).
Similar to our findings, in a study in Spain on 21 male and female drug addicts, the prevalence of C. albicans and C. glabrata was 67% and 28.9%, respectively (6). However, the mentioned study examined only heroin addicts, while our subjects were addicted to various substances.
In the present study, the MIC90 value of voriconazole was 16 times less than that of fluconazole against these isolates. Nevertheless, there was no statistically significant difference between voriconazole- and fluconazole-resistant isolates.
It has been suggested that voriconazole breakpoints are dependent on the pharmacodynamic analysis (19), but the pharmacodynamic properties of the antifungal agents are not fully understood. In a study on the pharmacokinetic/pharmacodynamic parameters of voriconazole, an AUC24/MIC ratio of 20 at a dose of 200 mg was effective for the treatment of infections caused by C. albicans in a mouse model with MIC of 0.25 µg/mL (20).
A new formulation of antifungal drugs, combination therapy, and the development of new bioactive compounds may improve therapeutic outcomes. Regarding the use of combination therapy for the management of candidiasis, researchers demonstrated that a combination of fluconazole and Silybum marianum extract was four-fold more effective than fluconazole or the extract alone (7).
In general, determining the susceptibility of pathogenic fungi before treatment may be beneficial for improving treatment efficacy and preventing drug overuse and the subsequent drug resistance.
5.1. Conclusions
Our results demonstrated the high prevalence and high rate of drug resistance among non-albicans Candida isolates, particularly C. glabrata, among the studied population of addicts. Given the high prevalence of resistance to fluconazole and voriconazole in these subjects, there might be the need to use higher doses of the drugs for favorable therapeutic outcomes. Therefore, it is proposed to accurately diagnose infections in drug users and exploit combination therapy at low doses or seek novel antifungal agents for the treatment of drug-resistant candidiasis.
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