OBJECTIVES

We sought to evaluate the pharmacodynamics of β-lactam antibacterials against polymicrobial communities of clinically relevant gram-positive and gram-negative pathogens.

METHODS

Two isolates, two isolates, and three isolates with varying β-lactamase production were evaluated in static time-killing experiments. Each gram-positive isolate was exposed to a concentration array of ampicillin () or cefazolin () alone and during co-culture with an isolate that was β-lactamase-deficient, produced TEM-1, or produced KPC-3/TEM-1B. The results of the time-killing experiments were summarized using an integrated pharmacokinetic/pharmacodynamics analysis as well as mathematical modelling to fully characterize the antibacterial pharmacodynamics.

RESULTS

In the integrated analysis, the maximum killing of ampicillin (E) against both isolates was ≥ 4.11 during monoculture experiments or co-culture with β-lactamase-deficient , whereas the E was reduced to ≤ 1.54 during co-culture with β-lactamase-producing . In comparison to monoculture experiments, culturing with KPC-producing resulted in reductions of the cefazolin E from 3.25 and 3.71 down to 2.02 and 2.98, respectively. Two mathematical models were created to describe the interactions between and either or . When in co-culture with , experienced a reduction in its cefazolin K by 24.8% (23.1%RSE). Similarly, β-lactamase-producing preferentially protected the ampicillin-resistant subpopulation, reducing K by 90.1% (14%RSE).

DISCUSSION

β-lactamase-producing were capable of protecting and from exposure to β-lactam antibacterials.