251. High prevalence of the cefazolin inoculum effect in methicillin-susceptible Staphylococcus aureus causing bloodstream infections in a hospital network in Houston, TX

Abstract Background Anti-staphylococcal β-lactams, such as anti-staphylococcal penicillins (AsPen) or cefazolin are the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections. However, cefazolin has seen increasing use due to its better tolerance, lower cost, ease of administration and possibly better outcomes when compared to AsPen. Nevertheless, its efficacy may be compromised by the cefazolin inoculum effect (CzIE), defined as an increase in the minimum inhibitory concentration (MIC) of cefazolin to ≥16mg/L when a high inoculum (5x107 CFU/ml) is present. Previous studies have suggested that the prevalence of the CzIE varies geographically, with high prevalence in some Latin American countries. Prospective data evaluating the presence of the CzIE in deep-seated MSSA infections across the United States are lacking. Methods We performed a prospective observational study of MSSA bacteremia in a network of 13 hospitals in Houston, TX. Patients ≥ 18 years old, with a positive blood culture with MSSA, with at least one follow-up blood culture confirming clearance of the bacteremia, who received cefazolin or nafcillin as definitive therapy (72 hours or longer after culture results known) and whose original isolate was available for evaluation of the CzIE, were included. Patients with polymicrobial BSI, or those who received another antibiotic with activity against MSSA in the definitive therapy period were excluded. Cefazolin MICs were determined by broth microdilution at standard and high inoculum. Results We report the results of 50 patients enrolled from February 15, 2020-April 30, 2020. The baseline characteristics of each group are outlined in Table 1. A total of 37/50 (74%) received cefazolin as definitive therapy, and complicated bacteremia was seen in 27/50 (54%). A total of 16/50 (32%) of the MSSA isolates exhibited the CzIE. Two patients in our cohort died: both of whose isolates exhibited the CzIE and received cefazolin as definitive therapy. Conclusion We report a high prevalence of the CzIE in MSSA BSIs in a major US urban hospital network. Further evaluation of the clinical implications of the CzIE is urgently needed. Disclosures William R. Miller, MD, Entasis Therapeutics (Scientific Research Study Investigator)Merck (Grant/Research Support)Shionogi (Advisor or Review Panel member) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator) MeMed (Scientific Research Study Investigator) Merck (Grant/Research Support)