Potential clinical implications due to essential differences in antimicrobial susceptibility profiles of actinomycetoma causative agents of the Actinomadura, Nocardia and Streptomyces genera towards commonly used anti-actinomycetoma drugs.

BACKGROUND

Actinomycetoma is a neglected tropical disease characterized by large tumorous lesions. It is caused by actinomycetes belonging to the genera Actinomadura, Nocardia and Streptomyces. Despite the differences between these genera and species, all actinomycetoma cases are treated with the same antibiotics. It is currently not known if the actinomycetoma causative agents have similar susceptibility patterns against these antibiotics. We therefore set out to determine the MICs for the most common causative agents against commonly used antibiotics.

MATERIALS AND

METHODS

We used the standard in vitro susceptibility method from the CLSI to assess the antimicrobial susceptibility of 94 actinomycete isolates belonging to the Actinomadura, Nocardia and Streptomyces genera and associated with actinomycetoma against 12 antibiotics. The molecular basis behind the reduced susceptibility was further explored using the genomes of the isolates.

RESULTS

All isolates were highly susceptible to linezolid (100%), amikacin (98.9%) and trimethoprim/sulfamethoxazole (87.2%). For amoxicillin/clavulanate and rifampicin, species-dependent susceptibility was noted. We found that 55% of Actinomadura madurae isolates, 61.5% of Nocardia brasiliensis isolates and 100% of Streptomyces somaliensis and Streptomyces sudanensis were susceptible to amoxicillin/clavulanate. All A. madurae, Actinomadura pelletieri and N. brasiliensis isolates were resistant to rifampicin, whereas all S. somaliensis and S. sudanensis isolates were susceptible. This was most likely due to amino acid differences in the RpoB gene.

CONCLUSIONS

Clear differences in antimicrobial susceptibility patterns were noted for the different actinomycetoma causative agents, indicating that actinomycetoma treatment should be tailored to the causative agent.