852. The Cefazolin Inoculum Effect and Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children: Does It Matter?

Abstract

BackgroundSelect methicillin-susceptible Staphylococcus aureus (MSSA) strains may produce β-lactamases with an affinity for first-generation cephalosporins (1GC). In the setting of a high inoculum, these β-lactamases may promote clinically meaningful cleavage of 1GCs, potentially resulting in antibiotic failure, a phenomenon known as the cefazolin inoculum effect (CIE). Acute hematogenous osteoarticular infections (AHOAIs, including osteomyelitis and septic arthritis) are the most common manifestation of invasive S. aureus infection in children. We evaluated the prevalence and potential impact of CIE among MSSA AHOAI isolates at two children’s hospitals.MethodsMSSA AHOAI isolates were obtained through surveillance studies at Texas Children’s and St. Louis Children’s Hospitals from January 2011 to December 2018. Isolates were tested for CIE via a macrobroth dilution assay with an inoculum of 107 CFU/mL; CIE was defined as a cefazolin MIC ≥16 µg/mL. Isolates were characterized by accessary gene regulator group (agr). The subsequent development of chronic osteomyelitis (CO) was regarded as a clinically important outcome.ResultsA total of 287 cases were included and the median patient age was 8.6 years. 14.3% of isolates exhibited CIE; CIE prevalence was similar across study sites. 74.6% of patients received a 1GC as definitive therapy. CIE isolates were more often resistant to clindamycin, belonged to agr III and associated with CO (Figure 1); a numerically higher rate of CO was observed with CIE isolates regardless of definitive antibiotic choice (Figure 2). In multivariable analyses, bone abscesses, agr III, positive blood cultures, multiple surgeries, and delayed source control but not CIE were independently associated with CO (Figure 3); similar results were seen if analyses were restricted to only those receiving 1GC.ConclusionCIE is exhibited by 14.3% of MSSA AHOAI isolates in children. CIE is associated with agr III and clindamycin-resistant strains. agr III strains are independently associated with CO; thus negative outcomes reported with CIE may more accurately reflect strain-dependent virulence factors rather than true antibiotic failure. Further studies are necessary to better understand the clinical significance of these findings. Disclosures All Authors: No reported Disclosures.