Affiliation:
1. State Key Laboratory of Microbial Technology, Shandong University, Jinan, Shandong Province, China
Abstract
ABSTRACT
The bactericidal pharmacodynamics of antibiotics against
Escherichia coli
were analyzed by a concentration-killing curve (CKC) approach, and the novel parameters median bactericidal concentration (BC
50
) and bactericidal intensity (
r
) for bactericidal potency were proposed. By using the agar plate method, about 500
E. coli
cells were inoculated onto Luria-Bertani plates containing a series of antibiotic concentrations, and after 24 h of incubation at 37°C, all the viable colonies were enumerated. This resulted in a sigmoidal CKC that could be perfectly fitted (
R
2
> 0.9) with the function
N
=
N
0
/[1 + e
r
(
x
− BC
50
)
], where
N
is number of colonies surviving on each plate with an
x
series of concentrations of an antibiotic, and
N
0
represents the meaningful inoculum size. Construction of the CKC method was based on the bactericidal effect of each antibiotic against the bacterial strain versus the concentration in two dimensions and may be a more valid, accurate, and reproducible method for estimating the bactericidal effect than the endpoint minimum bactericidal concentration (MBC) method. Mathematically, the CKC approach was point symmetrical toward its inflexion (BC
50
,
N
0
/2); thus, 2BC
50
could replace MBC. The parameter BC
1
can be defined as BC
50
+ [ln(
N
0
− 1)/
r
], which is the drug concentration at which only one colony survived and which is the least critical value of MBC in the CKC. The variate
r
, which determined the tangent slope on inflexion when
N
0
was limited, could estimate the bactericidal intensity of an antibiotic. This verified that the CKC approach may be useful in studies with other classes of antibiotics and has considerable value as a tool for the accurate and proper administration of antibiotics.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
23 articles.
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