Potent Activity of Ertapenem Plus Cefazolin Within Staphylococcal Biofilms: A Contributing Factor in the Treatment of Methicillin-Susceptible Staphylococcus aureus Endocarditis. (23rd March 2022)

• Record Type: Journal Article
• Authors: Gilbertie, Jessica; Ulloa, Erlinda R; Daiker, Jennifer C; Nguyen, Khanh; Smelter, Dan; Rose, Warren; Geriak, Matthew; Schnabel, Lauren V; Nizet, Victor; Sakoulas, George
• Is Part Of: Open forum infectious diseases. Volume 9:Number 5(2022)
• Publication Date: 2022-03-23
• Subjects: cefazolin -- ertapenem -- endocarditis -- Staphylococcus aureus; Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofac159
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: Besides antistaphylococcal beta-lactams and source control, there are limited validated antimicrobial salvage options in patients with prolonged methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, including infective endocarditis (IE). Methods: MSSA IE cases treated with ertapenem (ETP) plus cefazolin (CZ) were compared with matched IE cases treated with standard beta-lactam monotherapy. The bactericidal activity of ETP plus CZ was also compared with nafcillin (NAF), CZ, and ETP alone using an in vitro MSSA biofilm model. Results: The median duration of bacteremia experienced by patients (n = 12) while on CZ or NAF was 4 days (range 1–16 days) compared with 1 day (range 1–3 days) for patients (n = 5) treated with ETP + CZ ( P = .01, Mann-Whitney U test). Cefazolin and NAF alone or in combination did not achieve biofilm eradication at clinically relevant concentrations. However, the addition of ETP to CZ led to bactericidal eradication within biofilms at standard dosing. Conclusions: Ertapenem reduces CZ concentrations required to eradicate MSSA biofilms to those achievable in vivo by standard dosing, translating into shorter bacteremia duration in patients with MSSA endocarditis. Larger studies are needed to investigate ETP plus CZ therapy in the treatment of biofilm-related MSSA infections such as endocarditis. Abstract : Ertapenem reduces cefazolin concentrations required to eradicate methicillin-susceptible Staphylococcus aureus (MSSA) biofilms to those achievable in vivo by standard dosing, translating into shorter bacteremia duration in patients with MSSA endocarditis.