Novel Microdilution Method to Assess Double and Triple Antibiotic Combination Therapy In Vitro
Table 3
Double combinations of the antibiotics against the clinical isolates.
(a)
Isolate number
Antibiotics (µg/mL)
CIP + AMK
CIP + CAZ
CIP + PIP
CIP + IMP
IMP + PIP
MIC
MBC
IC
IT
MIC
MBC
IC
IT
MIC
MBC
IC
IT
MIC
MBC
IC
IT
MIC
MBC
IC
IT
PA2
0.062
0.125
1
I
0.062
0.125
1
I
0.125
0.125
0
I
0.125
0.125
0
I
2
2
0
I
PA3
0.062
0.125
1
I
0.062
0.125
1
I
0.031
0.031
2
S
0.125
0.125
0
I
16
>128
0
I
PA9
0.25
1
1
I
0.25
1
1
I
0.125
0.25
2
S
0.5
1
0
I
2
8
0
I
PA11
4
16
1
I
8
>16
2
S
>16
>16
0
I
>16
>16
0
I
>32
>32
0
I
PA14
1
8
1
I
1
8
1
I
2
8
0
I
2
8
0
I
2
>32
0
I
PA15
0.125
0.125
0
I
0.062
0.125
1
I
0.062
0.125
1
I
0.062
0.125
1
I
8
>32
−1
I
PA18
0.031
0.062
0
I
0.031
0.062
0
I
0.031
0.062
0
I
0.015
0.062
1
I
32
>32
−2
A
PA19
0.031
0.125
1
I
0.062
0.125
0
I
0.062
0.125
0
I
0.031
0.125
1
I
8
>32
−1
I
PA20
2
16
1
I
>16
>16
0
I
>16
>16
0
I
16
>16
1
I
>32
>32
0
I
PA21
0.125
0.25
0
I
0.125
0.25
0
I
0.062
0.25
1
I
0.062
0.25
1
I
64
>128
−3
A
(b)
Isolate number
Antibiotics (µg/mL)
AMK + CAZ
AMK + IMP
AMK + PIP
CAZ + IMP
CAZ + PIP
MIC
MBC
IC
IT
MIC
MBC
IC
IT
MIC
MBC
IC
IT
MIC
MBC
IC
IT
MIC
MBC
IC
IT
PA2
0.50
4
1
I
1
8
1
I
2
8
1
I
2
8
−1
I
0.25
4
2
S
PA3
2
8
0
I
2
8
0
I
1
8
1
I
32
>32
−4
A
2
16
2
S
PA9
1
4
2
S
1
8
1
I
2
32
1
I
2
8
0
I
4
8
1
I
PA11
4
16
1
I
8
16
0
I
4
16
1
I
>32
>32
0
I
32
>32
1
I
PA14
1
16
1
I
2
16
0
I
1
16
1
I
2
>32
0
I
0.5
4
3
S
PA15
1
4
2
S
4
16
1
I
1
4
2
S
2
32
1
I
4
16
0
I
PA18
0.50
2
2
S
1
8
1
I
2
8
1
I
8
8
−2
A
0.5
0.5
2
S
PA19
2
2
0
I
1
2
1
I
1
2
1
I
2
4
0
I
1
4
1
I
PA20
2
8
1
I
2
16
1
I
2
16
1
I
>32
>32
0
I
>32
>32
0
I
PA21
0.25
2
3
S
2
8
1
I
0.50
2
2
S
16
16
−2
A
2
4
1
I
(i) The IC (Interaction Code) is the change in the MIC of the most potent antibiotic in double or triple combination compared with the antibiotic alone. (ii) The IC is assigned zero value if the MIC is not changed in combination, while a value of 1 or −1 is given if the MIC value decreases or increases by one dilution, respectively, in combination. (iii) The IT (interaction type) is indifferent (I) when the IC value lies between −1 and <2, synergistic (S) if the IC value is ≥2, and antagonistic (A) if the IC value is ≤−2.