Abstract

With the emergence of multidrug-resistant organisms in
an era when drug development faces challenges causing
pharmaceutical companies to curtail or abandon
research on anti-infective agents, the use of combined
existing antimicrobial agents may be an alternative.
This study evaluated the effects of combining amoxicillin
and chloramphenicol, to which many bacteria have
become resistant, in vitro against Gram positive and
Gram negative bacteria by agar diffusion, checkerboard
and time-kill assays. The test isolates were susceptible
to amoxicillin with minimum inhibitory concentrations
(MICs) ranging between 0.448 and 500 ?g/ml and between
1.953 and 31.25 ?g/ml for chloramphenicol. Upon
combining these agents, there was a drastic reduction in
their MICs indicating an increased antibacterial activity
that showed synergistic interaction against all the bacteria.
At the highest concentrations, the inhibition zones
ranges were 20.33–38.33±0.58 ?g/ml for amoxicillin,
27.67–37.67±0.58 ?g/ml for chloramphenicol and 31.67–
39.33±0.58 ?g/ml for the combined agents. The fractional
inhibitory concentration indices (FICIs) showed synergy
ranging from 0.129 to 0.312 while FICIs for additive
interaction were between 0.688 and 1.0. There was no
antagonistic interaction. At the 1/2MICs of the combined
antibiotics, all the tested bacteria, except for Klebsiella
pneumoniae ATCC 4352, Proteus vulgaris CSIR 0030 and
Enterococcus cloacae ATCC 13047 were eliminated before
24 h. At the MICs, all the tested bacteria were eliminated
except Enterococcus cloacae ATCC 13047 which was almost
totally eliminated. Post-antibiotic assessment after
48 h showed that all the cultures were sterile with the
exception for that of Enterococcus cloacae ATCC 13047.
The lack of antagonism between these antibacterial
agents in checkerboard and time-kill assays suggested
that combining amoxicillin with chloramphenicol can
provide an improved therapy in comparison to the use
of each antibiotic individually. The study indicates the
potential beneficial value of combining amoxicillin and
chloramphenicol in the treatment of microbial infections
in clinical settings.