An experimental Staphylococcus aureus carriage and decolonization model in rhesus macaques (Macaca mulatta)

Our human model of nasal colonization and eradication of S. aureus is limited by safety issues. As rhesus macaques are closely related to humans and natural hosts for S. aureus, we developed an experimental decolonization and inoculation protocol in these animals. Animals were screened for nasal carriage of S. aureus and 20 carriers were selected. Decolonization was attempted using nasal mupirocin (10 animals) or mupirocin plus trimethoprim/ sulfadiazine intramuscularly (10 animals) both once daily for 5 days, and checked by followup cultures for 10 weeks. Intranasal inoculation was performed with S. aureus strain 8325–4 in culture-negative animals. 11/20 animals, of which 5 received mupirocin and 6 the combination treatment, became culture-negative for S. aureus for 10 weeks and these 11 animals were subsequently inoculated. Swabs were taken once a week for 5 weeks to test for the presence of the inoculated strain. In 3 animals, strain 8325–4 was cultured from the nose 1 week after inoculation, indicating short-term survival of this strain only, a finding similar to that previously found in our human model. These data demonstrate that rhesus macaques may constitute a relevant animal model to perform S. aureus eradication and inoculation studies with relatively limited invasive handling of the animals

Staphylococcus aureus kolonisatie, dragerschap en transmissie

In this thesis, colonization, carriage and transmission of Staphylococcus aureus (S. aureus) were studied. A novel experimental decolonization and carriage model in rhesus macaques (Macaca mulatta) was set up. We showed that we could decolonize the nose of rhesus macaques that carried S. aureus, for a period of 10 weeks or more and we were able to inoculate the noses of the rhesus macaques with human S. aureus strain 8325–4. Another study with the human inoculation model was performed and methicillin-susceptible S. aureus (MSSA) strain 5062 of bovine origin (ST398, CC398) was found capable of surviving in the human nose for at least 21 days and it successfully outcompeted a human strain 1036 (ST931, CC8). We investigated, using whole-genome sequencing (WGS), whether nosocomial acquisition of S. aureus via healthcare workers (HCWs) occurred in neonates admitted to a neonatal intensive care unit (NICU). We also studied whether transmission and the presence of specific virulence genes support the occurrence of neonatal bloodstream infections. With our data, we can confirm that HCWs might be an important reservoir and link in the transmission of MSSA to neonates and this could partly explain the occurrence of neonatal S. aureus bacteremia