Original article/Article original
In vitro anti-yeast activity of chloramphenicol: A preliminary reportActivité anti-levure in vitro du chloramphénicol : rapport préliminaire

https://doi.org/10.1016/j.mycmed.2014.10.019Get rights and content

Summary

Chloramphenicol is a bacteriostatic antimicrobial agent but its antifungal activity is not known. The present study aimed to investigate the activity of chloramphenicol against 30 representative yeasts. The antimicrobial assay of chloramphenicol (50 mg/mL; 100 mg/mL and 200 mg/mL) was determined by the disc diffusion method using Mueller-Hinton agar against 30 representative yeast strains. Zone of inhibition was read after 48–72 h incubation at 37 °C and results were compared with some standard antifungal agents. Most of the tested yeasts (73.3%) showed inhibition zones (5 up to 35 mm) to chloramphenicol impregnated discs (200 mg/mL). Three out of the four tested Candida albicans as well as Candida famata, Candida glabrata, Candida haemolonei and Cryptococcus neoformans showed no inhibition zones to chloramphenicol (200 mg/mL). Caspofungin acetate (50 mg/mL) inhibited 83.3% of the strains; ketoconazole (200 mg/mL) 70% and metronidazole 10%. Chloramphenicol discs: 50 and 100 mg/mL showed less activity (6.7% and 36.7%, respectively) compared to the 200 mg discs; whereas chloramphenicol (BBL; 3 μg/mL) inhibited 13.3% of the strains. The anti-yeast activities of chloramphenicol were comparable to other known antifungal compounds. Moreover, it is cheap, has fewer side effects and its inclusions in selective fungal media such as Mycosel have to be questioned.

Résumé

Le chloramphénicol est un agent antimicrobien bactériostatique mais son activité antifongique n’est pas connue. La présente étude visait à étudier l’activité de chloramphénicol contre 30 levures représentatives. L’activité antimicrobienne du chloramphénicol (50 mg/mL ; 100 mg/mL et 200 mg/mL) a été déterminée par la méthode de diffusion sur disque en utilisant la gélose de Mueller-Hinton contre 30 souches de levures représentatives. La zone d’inhibition a été lue après incubation à 37 °C pendant 48–72 h, les résultats ont été comparés avec ceux des agents antifongiques classiques. La plupart des levures testées (73,3 %) ont présenté des zones d’inhibition (5 à 35 mm) avec des disques imprégnés de chloramphénicol (200 mg/mL). Trois des quatre Candida albicans testés ainsi que Candida famata, Candida glabrata, Candida haemolonei et Cryptococcus neoformans n’ont montré aucune zone d’inhibition au chloramphénicol (200 mg/mL). L’acétate de caspofungine (50 mg/mL) inhibe 83,3 % des souches ; le kétoconazole (200 mg/mL) 70 % et le metronidazole : 10 %. Les disques de chloramphénicol : 50 et 100 mg/mL ont montré une activité moindre (6,7 % et 36,7 %, respectivement) par rapport aux disques de 200 mg ; tandis que le chloramphénicol (BBL, 3 pg/mL) inhibe 13,3 % des souches. Les activités anti-levures du chloramphénicol étaient comparables à d’autres composés antifongiques connus. En outre, il n’est pas cher, a moins d’effets secondaires et son incorporation dans les milieux fongiques sélectifs, tels que Mycosel doit être remise en question.

Introduction

Chloramphenicol was first discovered by David Gottlieb (1911–1982) who isolated it from the actinomycete Streptomyces venezuelae. Chloramphenicol was then launched to the clinical practice as bacteriostatic antimicrobial in 1949, with the trademark Chloromycetin [6]. It was the first antibiotic to be manufactured synthetically on a large scale and has been regarded as a broad-spectrum antibiotic. Chloramphenicol and in conjunction with tetracyclines were both considered low-cost and easy to produce. Moreover, it is often regarded as the antibiotic of choice in the developing world. Although this antibiotic is a well-known bacteriostatic effective against a wide variety of gram-positive and gram-negative bacteria, including most anaerobic organisms [1], [2], [5], [6] but nothing is known of its antifungal activities.

Chloramphenicol, which is 2,2-dichloro-N-[1,3-dihydroxy-1-(4-nitrophenyl) propan-2-yl] acetamide, is available as 250 mg capsules or as a liquid (125 mg/5 mL). In some countries, it is sold as chloramphenicol palmitate ester (CPE) or chloramphenicol succinate sodium (CSS). Chloramphenicol acts by inhibiting protein synthesis via binding to a receptor site on the 50S subunit of the bacterial ribosome consequently inhibiting peptidyl transferase. This inhibition accordingly blocks off amino acid transfer to the growing peptide chains, ultimately leading to inhibition of protein formation [1], [6], [10], [11].

Because of its capacity to cause fatal aplastic anemia in humans, chloramphenicol is prohibited in food animals in the U.S. and many countries but it is sometimes used topically for eye infections. Nevertheless, the global problem of advancing bacterial resistance to newer drugs and the continuing use of chloramphenicol antibiotic worldwide has renewed interest vis-à-vis its usefulness, metabolism and toxicology [4], [9], [18]. In low-income countries, chloramphenicol is still widely used because it is inexpensive and readily available. The mechanism of toxicity of chloramphenicol is not completely understood but high serum concentrations were found toxic from experimental treatment assays [9]. The most serious unpleasant effect associated with chloramphenicol treatment is the bone marrow toxicity, which may occur in two distinct forms: bone marrow suppression, which is a direct toxic effect of the drug and is usually reversible, and aplastic anemia, which is idiosyncratic (rare, unpredictable, and unrelated to dose) and generally fatal [16]. The administration of chloramphenicol to mice induced anaemia with reticulocytopenia, in combination with leucopenia, in the immediate post-dosing period; no evidence was seen at 21 days post-dosing of peripheral blood pancytopenia or a hypocellular/acellular bone marrow, which were both characteristic features of aplastic anaemia in man [14], [21].

Apart from a single report made by scientists in New Zealand who found that chloramphenicol is effective in curing chytrids disease in amphibians [20], no data is available regarding the use of chloramphenicol as antifungal. This study aimed to investigate the effect of chloramphenicol on representative yeast as an anti-yeast antifungal agent.

Section snippets

Chloramphenicol and other antifungal agents

Chloramphenicol was obtained from BioGer as powder (Cloranfenicol, 1 g) intended for injectable use. Chloramphenicol was dissolved in 5 mL sterile distilled water. Filter paper discs (5 mm) were impregnated with the chloramphenicol solution (100 mg/mL and 200 mg/mL) and dried at room temperature.

Known antifungal agents namely: caspofungin (50 mg/mL, MERCK & CO., Inc., USA); ketoconazol (200 mg/mL; Janssen-Cilag, Australia) and metronidazol (200 mg/mL, BBL) were included in the study as positive

Results

The results of the anti-yeast activity of chloramphenicol in comparison to other antifungal agents is shown in Table 1.

Most of the tested yeasts (73.3%) showed inhibition zones (ranging from 5 up to 35 mm) to chloramphenicol impregnated discs (200 mg/mL). Three out of the four tested Candida albicans as well as Candida famata, Candida glabrata, Candida haemolonei and Cryptococcus neoformans showed no inhibition zones to chloramphenicol (200 mg/mL) and were considered resistant to this agent at

Discussion

The present study is the first to explore chloramphenicol as antifungal. It is evident from the results that chloramphenicol showed high anti-yeast activity against the majority of the tested yeasts. Activities of chloramphenicol in comparison to other agents in terms of inhibited yeasts are of interest (Figs. 1 and 2). Chloramphenicol is a relatively cheap product, has fewer side effects and has its known antibacterial activities. [6] Moreover, its anti-yeast activities were comparable to

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

Acknowledgments

The authors thank the authority of Aseer Central Hospital and College of Medicine, King Khalid University the technical staff for facilitating the performance and analysis of this study. The research was funded by the Deanship of Scientific Research, King Khalid University (project number: 1433H/308).

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