Capability Of Enterococcus Faecalis To Shield Gram-Negative Pathogens From Aminoglycoside Exposure

Background: Enterococcus faecalis commonly produce aminoglycoside-modifying enzymes (AMEs) and are implicated in polymicrobial infections.Objectives: To determine if AME-producing E. faecalis is capable of protecting Enterobacteriaceae and Pseudomonas aeruginosa from gentamicin exposure.Methods: Two Klebsiella pneumoniae isolates, two Escherichia coli isolates, and two Pseudomonas aeruginosa isolates were investigated in monoculture time-kill experiments, and each Gram-negative organism was also evaluated during co-culture with either AME-producing or AME-deficient E. faecalis. A pharmacokinetic/pharmacodynamics analysis that utilized Log Ratio Areas and a Hill-type mathematical model was used to determine if the maximal killing or potency of gentamicin against the Gram-negative organisms was altered by the presence of the E. faecalis.Results: The maximal killing and potency of gentamicin was the same during monoculture and co-culture experiments for both K. pneumoniae isolates and one E. coli isolate (P>0.05). In contrast, the maximal killing of gentamicin was attenuated against one E. coli isolate and both P. aeruginosa isolates during co-culture with E. faecalis (P<0.05). The potency of gentamicin was variable against the three aforementioned isolates. Against the E. coli isolate, the potency of gentamicin was significantly reduced by the presence of either E. faecalis isolate (EC50 95% CI=4.23-4.43mg/L monoculture versus 3.86-4.19mg/L and 3.55-3.96mg/L during co-culture with AME-producing and AME-deficient E. faecalis, respectively). The potency of gentamicin increased or decreased for P. aeruginosa depending on which E. faecalis isolate was investigated.Conclusions: The AME-producing E. faecalis did not provide a consistent protective effect from aminoglycosides for the Gram-negative pathogens.