Emergence of trimethoprim resistance gene dfrG in Staphylococcus aureus causing human infection and colonization in sub-Saharan Africa and its import to Europe

Abstract

Objectives: Co-trimoxazole (trimethoprim/sulfamethoxazole) is clinically valuable in treating skin and soft tissue infections (SSTIs) caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA). The genetic basis of emerging trimethoprim/sulfamethoxazole resistance in S. aureus from Africa is unknown. Such knowledge is essential to anticipate its further spread. We investigated the molecular epidemiology of trimethoprim resistance in S. aureus collected in and imported from Africa.

Methods: Five hundred and ninety-eight human S. aureus isolates collected at five locations across sub-Saharan Africa [Gabon, Namibia, Nigeria (two) and Tanzania] and 47 isolates from travellers treated at six clinics in Europe because of SSTIs on return from Africa were tested for susceptibility to trimethoprim, sulfamethoxazole and trimethoprim/sulfamethoxazole, screened for genes mediating trimethoprim resistance in staphylococci [dfrA (dfrS1), dfrB, dfrG and dfrK] and assigned to spa genotypes and clonal complexes.

Results: In 313 clinical and 285 colonizing S. aureus from Africa, 54% of isolates were resistant to trimethoprim, 21% to sulfamethoxazole and 19% to trimethoprim/sulfamethoxazole. We found that 94% of trimethoprim resistance was mediated by the dfrG gene. Of the 47 S. aureus isolates from travellers with SSTIs, 27 (57%) were trimethoprim resistant and carried dfrG. Markers of trimethoprim resistance other than dfrG were rare. The presence of dfrG genes in S. aureus was neither geographically nor clonally restricted.

Conclusions: dfrG, previously perceived to be an uncommon cause of trimethoprim resistance in human S. aureus, is widespread in Africa and abundant in imported S. aureus from ill returning travellers. These findings may foreshadow the loss of trimethoprim/sulfamethoxazole for the empirical treatment of SSTIs caused by community-associated MRSA.

Keywords: communicable diseases; drug resistance; emerging; gene transfer; horizontal; infectious; methicillin-resistant Staphylococcus aureus; microbial; plasmids; public health surveillance; skin diseases; soft tissue infections; sulphonamides; tetrahydrofolate dehydrogenase; travel; trimethoprim/sulfamethoxazole combination.