Dennis Nurjadi1, Adesola O Olalekan2, Franziska Layer3, Adebayo O Shittu4, Abraham Alabi5, Beniam Ghebremedhin6, Frieder Schaumburg7, Jonas Hofmann-Eifler8, Perry J J Van Genderen9, Eric Caumes10, Ralf Fleck11, Frank P Mockenhaupt12, Mathias Herrmann13, Winfried V Kern14, Salim Abdulla15, Martin P Grobusch16, Peter G Kremsner17, Christiane Wolz18, Philipp Zanger19. 1. Deutsches Zentrum für Infektionsforschung (DZIF), Institut für Tropenmedizin, Universitätsklinikum, Wilhelmstraße 27, 72074 Tübingen, Germany Deutsches Zentrum für Infektionsforschung (DZIF), Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum, Elfriede-Aulhorn-Straße 6, 72076 Tübingen, Germany. 2. Deutsches Zentrum für Infektionsforschung (DZIF), Institut für Tropenmedizin, Universitätsklinikum, Wilhelmstraße 27, 72074 Tübingen, Germany Department of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, PO Box 4000, Ogbomoso, Nigeria. 3. Nationales Referenzzentrum für Staphylokokken und Enterokokken, Robert Koch Institut, Burgstraße 37, 38855 Wernigerode, Germany. 4. Department of Microbiology, Obafemi Awolowo University, Ile-Ife 22005, Nigeria. 5. Centre de Recherches Médicales de Lambaréné (CERMEL), B.P. 118, Lambaréné, Gabon. 6. Institut für Medizinische Mikrobiologie, Universitätsklinikum, Leipziger Straße 44, 39120 Magdeburg, Germany/Department Humanmedizin, Universität Witten/Herdecke, Alfred-Herrhausen-Straße 50, 58448 Witten, Germany/Helios Clinic, Heusnerstraße 40, 42283 Wuppertal, Germany. 7. Institut für Medizinische Mikrobiologie, Universitätsklinikum Münster, Domagkstraße 10, 48149 Münster, Germany. 8. Bagamoyo Research and Training Center, Ifakara Health Institute, PO Box 74, Bagamoyo, Tanzania Universitätsklinikum Freiburg, Abteilung Infektiologie, Hugstetter Straße 55, 79106 Freiburg, Germany. 9. Instituut voor Tropische Ziekten, Havenziekenhuis, Haringvliet 72, 3011 TG Rotterdam, The Netherlands. 10. Service de Maladies Infectieuses et Tropicales, groupe hospitalier Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, 75651 Paris cedex 13, France/Sorbonne Universités, UPMC Univ Paris 06, F-75005, Paris, France. 11. Tropenklinik, Paul-Lechler-Krankenhaus, 72076 Tübingen, Germany. 12. Institut für Tropenmedizin und Internationale Gesundheit, Charité-Universitätsmedizin Berlin, Spandauer Damm 130, 14050 Berlin, Germany. 13. Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum des Saarlandes, Kirrberger Straße, 66421 Homburg/Saar, Germany. 14. Universitätsklinikum Freiburg, Abteilung Infektiologie, Hugstetter Straße 55, 79106 Freiburg, Germany. 15. Bagamoyo Research and Training Center, Ifakara Health Institute, PO Box 74, Bagamoyo, Tanzania. 16. Centre de Recherches Médicales de Lambaréné (CERMEL), B.P. 118, Lambaréné, Gabon Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 Amsterdam, The Netherlands. 17. Deutsches Zentrum für Infektionsforschung (DZIF), Institut für Tropenmedizin, Universitätsklinikum, Wilhelmstraße 27, 72074 Tübingen, Germany Centre de Recherches Médicales de Lambaréné (CERMEL), B.P. 118, Lambaréné, Gabon. 18. Deutsches Zentrum für Infektionsforschung (DZIF), Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum, Elfriede-Aulhorn-Straße 6, 72076 Tübingen, Germany. 19. Deutsches Zentrum für Infektionsforschung (DZIF), Institut für Tropenmedizin, Universitätsklinikum, Wilhelmstraße 27, 72074 Tübingen, Germany philipp.zanger@uni-heidelberg.de.
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.
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 humanS. 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 humanS. 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.
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