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

November 19, 2016 at 8:01 am

Antimicrob. Agents Chemother. November 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.

PDF

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

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

Population Pharmacokinetics and Dosing Regimen Optimization of Meropenem in Cerebrospinal Fluid and Plasma in Patients with Meningitis after Neurosurgery Results from the Canadian Nosocomial Infection Surveillance Program on Carbapenemase-Producing Enterobacteriaceae, 2010 to 2014


Calendar

November 2016
M T W T F S S
« Oct   Dec »
 123456
78910111213
14151617181920
21222324252627
282930  

Most Recent Posts


%d bloggers like this: