TY - JOUR
T1 - Paradox between the responses of Escherichia coli K1 to ampicillin and chloramphenicol in vitro and in vivo
AU - Kim, K. S.
AU - Manocchio, M.
AU - Anthony, B. F.
PY - 1984
Y1 - 1984
N2 - We evaluated the activity of ampicillin and chloramphenicol in vitro and in vivo against an Escherichia coli K1 strain. In vitro, the strain was relatively susceptible to both antibiotics (MIC and MBC of ampicillin, 2 and 4 μg/ml; MIC and MBC of chloramphenicol, 4 and 64 μg/ml). Checkerboard determinations of MBCs of drug combinations were consistent with antibiotic antagonism. Killing curves with concentrations of antibiotics similar to in vivo levels in blood and cerebrospinal fluid of infected rats indicated antagonism within the first 4 h and an indifferent effect of the combination at 24 h. Paradoxically, the combination was significantly more effective than ampicillin or chloramphenicol alone in vivo in infant rats. This was shown by (i) more rapid bacterial clearance from the blood and cerebrospinal fluid, (ii) a decreased incidence of meningitis in bacteremic animals, and (iii) improved survival. These findings illustrate a divergence between the effects of ampicillin and chloramphenicol against E. coli in vitro and in vivo and suggest that this combination is an effective synergistic regimen in this experimental model of E. coli bacteremia and meningitis.
AB - We evaluated the activity of ampicillin and chloramphenicol in vitro and in vivo against an Escherichia coli K1 strain. In vitro, the strain was relatively susceptible to both antibiotics (MIC and MBC of ampicillin, 2 and 4 μg/ml; MIC and MBC of chloramphenicol, 4 and 64 μg/ml). Checkerboard determinations of MBCs of drug combinations were consistent with antibiotic antagonism. Killing curves with concentrations of antibiotics similar to in vivo levels in blood and cerebrospinal fluid of infected rats indicated antagonism within the first 4 h and an indifferent effect of the combination at 24 h. Paradoxically, the combination was significantly more effective than ampicillin or chloramphenicol alone in vivo in infant rats. This was shown by (i) more rapid bacterial clearance from the blood and cerebrospinal fluid, (ii) a decreased incidence of meningitis in bacteremic animals, and (iii) improved survival. These findings illustrate a divergence between the effects of ampicillin and chloramphenicol against E. coli in vitro and in vivo and suggest that this combination is an effective synergistic regimen in this experimental model of E. coli bacteremia and meningitis.
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U2 - 10.1128/AAC.26.5.689
DO - 10.1128/AAC.26.5.689
M3 - Article
C2 - 6393867
AN - SCOPUS:0021749666
SN - 0066-4804
VL - 26
SP - 689
EP - 693
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 5
ER -