Enterococcus faecium Clade Competition in the Presence of β-Lactam Antibiotics in a Mouse GI Tract Colonization Model

Abstract

Previously, we showed that Enterococcus faecium clade B strains outcompeted health care-associated clade A1 strains in murine gastrointestinal colonization. Here, parenterally administered piperacillin-tazobactam and ceftriaxone significantly promoted colonization by clade A1 over clade B strains except that ceftriaxone, at the dose used, did not favor the least β-lactam-resistant A1 strain. The advantage that β-lactam administration gives to more highly ampicillin-resistant E. faecium over ampicillin-susceptible strains mirrors what occurs in hospitalized patients administered these antibiotics.

Keywords: E. faecium; ampicillin resistant; ceftriaxone; mouse GI colonization; piperacillin-tazobactam.

FIG 1

Mouse gastrointestinal tract (GIT) colonization by E. faecium clade A1 versus clade B strains in a mixed inoculation (1:1) competition assay; shown are the percentages (%) of total E. faecium CFU of clade A1 versus that of clade B strains in the inoculum mix and from fecal pellets recovered 2, 4, 7, and 14 days after oral inoculation. The horizontal lines indicate the means. A paired t test was used to calculate P values for the percentage of bacteria recovered in the fecal pellets versus that of the inoculum mix. The total E. faecium CFU per milliliter (inoculum) or CFU per gram (pellets) is given below the day. (A) Top left panel shows the effect of s.c. CRO administration (n = 6) after inoculation of a mix of strains TX82_A1 and Com15_B. Top right panel shows the effect of s.c. TZP administration (n = 4) after oral inoculation of mice with the same mixture. Solid red circles represent TX82_A1, and solid blue triangles represent Com15_B. (B) Top left panel shows the effect of s.c. CRO administration (n = 6) after inoculation of a mix of strains C68_A1 and Com15_B. Top right panel shows the effect of s.c. TZP administration (n = 4) after oral inoculation of mice with the same mixture. Solid red circles represent C68_A1, and solid blue triangles represent Com15_B. (C) Top left panel shows results with s.c. CRO administration (n = 6) after inoculation of a mix of strains TX16_A1 versus E980_B. Top right panel shows the effect of s.c. TZP antibiotic treatment (n = 4) after inoculation of a mix of the same strains. Solid red circles represent TX16_A1, and solid blue triangles represent E980_B.