The Association of Molecular Characteristics, Vancomycin MIC and Clinical Outcomes in Methicillin-susceptible Staphylococcus aureus Osteoarticular Infections in Children

Background Methicillin-resistant Staphylococcus aureus, particularly those belonging to the USA300 pulsotype and bearing Panton–Valentine leucocidin (pvl), have been well described to cause severe osteoarticular infection (OAI). Vancomycin minimum inhibitory concentration (MIC) ≥ 1.5 µg/ml has been demonstrated to contribute to disease severity in MRSA bacteremia. Little data exist to describe the spectrum of outcomes in MSSA OAI in terms of molecular characteristics and vancomycin MIC. Methods OAI isolates were identified from 2011 to 2016 and subjected to vancomycin E-tests. MSSA isolates underwent PFGE, PCR for pvl, and a stepwise assay to determine accessory gene regulator (agr) group. A review of the medical record was performed. Orthopedic complications included chronic osteomyelitis, pathologic fracture, and growth arrest. Results During the study period, 167 cases of S. aureus OAI were identified; 115 were MSSA (68.9%). 29.1 and 26.1% of MSSA isolates were USA300 and pvl positive, respectively. USA300 isolates were more likely to be pvl-positive (66.7 vs. 13.6%, P < 0.001) and agr I (80% vs. 57.5%, P = 0.001). The presence of pvl was associated with agr I (P = 0.03), larger abscesses (6 vs. 2cm, P = 0.04), ICU admission (16.7 vs. 3.5%, P = 0.03) and a longer length of stay (11 vs. 6 days, P = 0.05). agr III and IV were associated with a higher rate of orthopedic complications (36.4 vs. 13.9%, P = 0.03) and surgical procedures (90.1 vs. 64.5%, P = 0.02) than other agr groups. An increase in the proportion of MSSA isolates with a vancomycin MIC ≥ 1.5 µg/ml occurred in the study period (P = 0.007, Figure 1). In MSSA, vancomycin MIC ≥ 2 µg/ml was associated with agr III (p = 0.07) and higher rates of orthopedic complications (P = 0.08) and venous thrombosis (P = 0.06, Figure 2). Conclusion MSSA accounts for 70% of S. aureus isolates causing OAI at TCH. While pvl-positive strains are associated with worse short-term outcomes, agr III and IV are associated with long-term morbidity. Vancomycin E-test MICs appear to be increasing among MSSA; vancomycin MIC ≥ 2 µg/ml are associated with agr-III and adverse clinical outcomes suggesting that this may be a surrogate for disease severity. Further work is needed to understand the contribution of these factors to invasive MSSA disease. Disclosures J. McNeil, NIAID, NIH: Grant Investigator, Grant recipient. 
S. L. Kaplan, Pfizer: Grant Investigator and Speaker at PCV13 Launch Meeting in China, Research grant and Speaker honorarium