Identification of Vancomycin Resistance in Methicillin-resistant Staphylococcus aureus in two macaque species and decolonization and long-term prevention of recolonization in Cynomolgus Macaques (Macaca fascicularis)

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a S. aureus strain with resistance to beta-lactam antibiotics, making it a global human and veterinary health concern. Specifically, immunosuppressed patients have a remarkably higher risk of clinical MRSA infections with significantly increased rates of prolonged clinical recovery, morbidity, and mortality. The current treatment of choice for MRSA is vancomycin. Importantly, we report the first known vancomycin-resistant S. aureus (VRSA) carriers in a cohort of Mauritian cynomolgus macaques (CM) imported to the Oregon National Primate Research Center (ONPRC), with a MRSA carrier rate of 76.9% (10/13 animals). All MRSA isolates also demonstrated resistance to vancomycin with prevalence of vancomycin-intermediate Staphylococcus aureus (VISA) at 30% (3/10 MRSA-positive CMs) and VRSA at 70% (7/10 MRSA-positive CMs). Additionally, we identified VRSA in a rhesus macaque (RM) housed within the same room as the VRSA-positive CMs and identified a MRSA/VISA carrier rate of 18.8% in RMs (3/16 positive for both MRSA and VISA) in unexposed recently assigned animals directly from the ONPRC RM breeding colony. Considering that the MRSA and VRSA/VISA-positive CMs future study aims included significant immunosuppression, MRSA/VRSA/VISA decolonization treatment and expanded "MRSA-free" practices were employed to maintain this status. We report the first controlled study using in-depth analyses with appropriate diagnostic serial testing to definitively show an MRSA decolonization therapy (90% success rate) and expanded barrier practice techniques to successfully prevent recolonization (100%) of a cohort of CMs MRSA-free (up to 529 days with a total of 4,806 MRSA-free NHP days).

Keywords: antibiotic resistance; cynomolgus macaques; decolonization; methicillin-resistant Staphylococcus aureus; mupirocin; occupational safety; rhesus macaques; vancomycin- resistant Staphylococcus aureus.

Figure 1

Antibiotic sensitivity results for the 10 MRSA-positive CM prior to decolonization therapy show a high rate of resistance profiles including VRSA (7/10) and VISA (3/10). The number of animals (y-axis) and each antibiotic resistance profile (x-axis) are represented by a single vertically stacked bar plot; antibiotic susceptible (green), intermediate (orange), and resistant (red).

Figure 2

Similar antibiotic sensitivity patterns as the CMs were present for the one MRSA-positive RM that was housed within the same room, including VRSA. Each antibiotic resistance profile (x-axis) is represented by a bar plot for the single MRSA-positive RM (y-axis); antibiotic susceptible (green), intermediate (orange), and resistant (red).

Figure 3

Antibiotic sensitivity results for the three MRSA-positive RMs with no history of prior exposure to CMs differed for the antibiotic sensitivity profile, with high prevalence of VISA (100%, 3/3 RMs) and no evidence of VRSA. The number of animals (y-axis) and each antibiotic resistance profile (x-axis) are represented by a single vertically stacked bar plot; antibiotic susceptible (green), intermediate (orange), and resistant (red).