Cefazolin and Ertapenem, a Synergistic Combination Used To Clear Persistent Staphylococcus aureus Bacteremia

October 23, 2016 at 6:22 pm

Antimicrob. Agents Chemother. November 1, 2016 V.60 N.11 P.6609-6618

George Sakoulas, Joshua Olson, Juwon Yim, Niedita B. Singh, Monika Kumaraswamy, Diana T. Quach, Michael J. Rybak, Joseph Pogliano, and Victor Nizet

aUniversity of California San Diego School of Medicine, La Jolla, California, USA

bSharp Healthcare System, San Diego, California, USA

cEugene Appelbaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA

dDepartment of Biological Sciences, University of California San Diego, La Jolla, California, USA

eSkaggs School of Pharmacy, University of California San Diego, La Jolla, California, USA

Ertapenem and cefazolin were used in combination to successfully clear refractory methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia.

In addition, recent work has demonstrated activity of combination therapy with beta-lactams from different classes against methicillin-resistant S. aureus (MRSA).

The ertapenem-plus-cefazolin combination was evaluated for synergy in vitro and in vivo in a murine skin infection model using an index MSSA bloodstream isolate from a patient in whom persistent bacteremia was cleared with this combination and against a cadre of well-described research strains and clinical strains of MSSA and MRSA.

Against the index MSSA bloodstream isolate, ertapenem and cefazolin showed synergy using both checkerboard (fractional inhibitory concentration [FIC] index = 0.375) and time-kill assays.

Using a disk diffusion ertapenem potentiation assay, the MSSA isolate showed a cefazolin disk zone increased from 34 to 40 mm. In vitro pharmacokinetic/pharmacodynamic modeling at clinically relevant drug concentrations demonstrated bactericidal activity (>3 log10-CFU/ml reduction) of the combination but bacteriostatic activity of ether drug alone at 48 h.

A disk diffusion potentiation assay showed that ertapenem increased the cefazolin zone of inhibition by >3 mm for 34/35 (97%) MSSA and 10/15 (67%) MRSA strains.

A murine skin infection model of MSSA showed enhanced activity of cefazolin plus ertapenem compared to monotherapy with these agents. After successful use in clearance of MSSA bacteremia, the combination of ertapenem and cefazolin showed synergy against MSSA in vitro and in vivo.

This combination may warrant consideration for future clinical study in MSSA bacteremia.

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http://aac.asm.org/content/60/11/6609.full.pdf+html

Entry filed under: Antimicrobianos, Bacterias, Bacteriemias, Metodos diagnosticos, Resistencia bacteriana, Sepsis, Update. Tags: .

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