Vancomycin plus a beta-lactam for MRSA - what a weird idea!

MRSA is a killer but luckily we are seeing less of it in hospitals than we used to. Treatment of MRSA has been turned on its head with the advent of antibiotics like daptomycin and linezolid. But my guess is that we still turn to vancomycin in many situations, including MRSA bloodstream infections.

Counterintuitively, adding an antistaphylococcal beta-lactam (eg, flucloxacillin or nafcillin) to vancomycin is synergistic in both in vitro and animal models. Could this add to vancomycin's effectiveness in patients?

A pilot study ("CAMERA"), published in CID, showed that the mean duration of MRSA bacteremia was 3.0 days in patients assigned to vancomycin monotherapy and 1.94 days in those given vancomycin plus flucloxacillin.

These findings can be found here:

Combination of Vancomycin and β-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial.
Davis JS, Sud A, O'Sullivan MVN, Robinson JO, Ferguson PE, Foo H, van Hal SJ, Ralph AP, Howden BP, Binks PM, Kirby A, Tong SYC; Combination Antibiotics for MEthicillin Resistant Staphylococcus aureus (CAMERA) study group
Clin Infect Dis. 2016 Jan 15;62(2):173-180. 
PMID: 
26349552

Not surprisingly, with results like these, the investigators (led by Josh Davis and Steve Tong) have pursued a more definitive trial. Funding has been attained and recruitment commenced.

The full protocol for "CAMERA-2" is available free at:

https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-016-1295-3

This time the primary endpoint is a composite including mortality plus microbiologic persistence, failure and relapse. Clearly we need to wait for results before this type of combination therapy can be recommended outside a trial situation.

Talking of MRSA trials in a similar vein, an RCT comparing daptomycin/ceftaroline combination therapy with daptomycin alone would be nice!


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