Background
Materials and methods
Strains
Antimicrobial susceptibility testing
Time-kill assay
Effect of ceftazidime-avibactam against K. pneumoniae strain Y8 infection in the mouse model
Bacterial load in the blood and tissues of mice
Results
Antimicrobial susceptibility testing
Strain no. | Bacteria | β-lactamase | MIC (mg/L) | Associated β-lactamase | |||
---|---|---|---|---|---|---|---|
CAZ-AVI | CAZ | IPM | MEM | ||||
R16- Hefei |
K. pneumoniae
| KPC-2 | 8 | 128 | 64 | 64 | CTX-M-14, SHV-11, DHA-1 |
R18- Hefei |
K. pneumoniae
| KPC-2 | 4 | 128 | 8 | 16 | SHV-28, DHA-1 |
R19- Hefei |
K. pneumoniae
| KPC-2 | 4 | 128 | 16 | 16 | SHV-12, DHA-1 |
R31- Beijing |
K. pneumoniae
| KPC-2 | 8 | 128 | 64 | 256 | SHV-11, DHA-1 |
R35- Beijing |
K. pneumoniae
| KPC-2 | 8 | 128 | 128 | 256 | SHV-11, DHA-1 |
R39-Fuzhou |
K. pneumoniae
| KPC-2 | 8 | > 256 | 32 | 64 | CTX-M-14, SHV-12, DHA-1 |
R42- Fuzhou |
K. pneumoniae
| KPC-2 | 8 | > 256 | 32 | 64 | CTX-M-14, SHV-12, DHA-1 |
R44- Fuzhou |
K. pneumoniae
| KPC-2 | 8 | > 256 | 64 | 128 | CTX-M-14, SHV-12, DHA-1 |
R46- Fuzhou |
K. pneumoniae
| KPC-2 | 8 | > 256 | 64 | 64 | SHV-12, DHA-1 |
R52- Fuzhou |
K. pneumoniae
| KPC-2 | 8 | > 256 | 64 | 128 | CTX-M-14, SHV-12, DHA-1 |
R53- Fuzhou |
K. pneumoniae
| KPC-2 | 8 | > 256 | 64 | 128 | CTX-M-14, SHV-12, DHA-1 |
R59- Hangzhou |
K. pneumoniae
| KPC-2 | 8 | 32 | 8 | 16 | CTX-M-14, SHV-11, DHA-1 |
R60- Hangzhou |
K. pneumoniae
| KPC-2 | 4 | 32 | 4 | 4 | CTX-M-14, SHV-11, DHA-1 |
JSD-Shanghai |
K. pneumoniae
| KPC-2 | 8 | 128 | 128 | 512 | CTX-M-14, SHV-11, DHA-1 |
WJQ-Shanghai |
K. pneumoniae
| KPC-2 | 8 | > 256 | 128 | 256 | CTX-M-14, SHV-11, DHA-1 |
LDX-Shanghai |
K. pneumoniae
| KPC-2 | 8 | > 256 | 32 | 64 | CTX-M-55, SHV-31, DHA-1 |
PED-Shanghai |
K. pneumoniae
| OXA-232 | 2 | > 32 | 1 | 4 | CTX-M-15, SHV-1 |
Strain no. | Bacteria | β-lactamase | MIC(mg/L) single dosing | MIC(mg/L) Combined dosing | FIC value | Associated β-lactamase | ||
---|---|---|---|---|---|---|---|---|
ATM | CAZ-AVI | ATM | CAZ-AVI | ATM + CAZ-AVI | ||||
R078 Anhui |
K. pneumoniae
| NDM | 256 | 32 | 8 | 1 | 0.06 | SHV-28, DHA-1, CTX-M-15 |
R080 Hainan |
K. pneumoniae
| NDM | 128 | 4 | 32 | 0.25 | 0.31 | SHV-11, DHA-1, CTX-M-14 |
R081 Hainan |
K. pneumoniae
| NDM | 1024 | 8 | 64 | 2 | 0.31 | SHV-11, DHA-1, CTX-M-14 |
R082 Hainan |
K. pneumoniae
| NDM | 256 | 64 | 16 | 1 | 0.08 | SHV-11, DHA-1, CTX-M-15, CTX-M-14 |
R083 Hainan |
K. pneumoniae
| NDM | 128 | 64 | 32 | 0.5 | 0.26 | SHV-12, DHA-1, CTX-M-15 |
R084 Hainan |
K. pneumoniae
| NDM | 512 | 64 | 16 | 1 | 0.05 | SHV-12, DHA-1 |
R085 Hainan |
K. pneumoniae
| NDM | 1024 | 128 | 32 | 2 | 0.05 | SHV-12, DHA-1, CTX-M-15 |
R086 Hainan |
K. pneumoniae
| NDM | 128 | 64 | 16 | 0.5 | 0.13 | SHV-12, DHA-1, CTX-M-15 |
R088 Hainan |
K. pneumoniae
| NDM | 32 | 2 | 4 | 0.5 | 0.38 | SHV-11, DHA-1, CTX-M-14 |
R093 Hebei |
K. pneumoniae
| NDM | 32 | 64 | 4 | 0.5 | 0.13 | SHV1, DHA-1, CTX-M-14 |
R094 Hebei |
K. pneumoniae
| NDM | 32 | 64 | 8 | 0.25 | 0.25 | SHV-12, DHA-1, CTX-M-14 |
R095 Hebei |
K. pneumoniae
| NDM | 32 | 2 | 8 | 0.25 | 0.38 | SHV-12, DHA-1, CTX-M-15 |
R096 Henan |
K. pneumoniae
| NDM | 16 | 64 | 16 | 0.5 | 1.01 | SHV1, DHA-1, CTX-M-15 |
R097 Henan |
K. pneumoniae
| NDM | 8 | 256 | 4 | 128 | 1.00 | SHV1, DHA-1, CTX-M-14 |
R098 Henan |
K. pneumoniae
| NDM | 256 | 64 | 32 | 1 | 0.14 | DHA-1 |
R100 Shanxi |
K. pneumoniae
| NDM | 8 | 32 | 4 | 32 | 1.50 | SHV-78, DHA-1, CTX-M-14 |
R101 Shanxi |
K. pneumoniae
| NDM | 256 | 128 | 16 | 1 | 0.07 | SHV-78, DHA-1, CTX-M-14 |
R102 Shanxi |
K. pneumoniae
| NDM | 32 | 256 | 4 | 1 | 0.13 | SHV-78, DHA-1, CTX-M-14 |
R103 Shanxi |
K. pneumoniae
| NDM | 128 | 64 | 32 | 0.25 | 0.25 | SHV1, DHA-1, CTX-M-15 |
R106 Sanxi |
K. pneumoniae
| NDM | 128 | 64 | 8 | 1 | 0.08 | SHV-12, DHA-1 |
R110 Sanxi |
K. pneumoniae
| NDM | 128 | 256 | 8 | 1 | 0.07 | SHV-12, DHA-1 |
R113 Sanxi |
K. pneumoniae
| NDM | 128 | 64 | 16 | 0.5 | 0.13 | SHV-12, DHA-1 |
R122 Tianjin |
K. pneumoniae
| NDM | 32 | 1 | 4 | 0.25 | 0.38 | SHV-12, DHA-1, CTX-M-14 |
R126 Tianjin |
K. pneumoniae
| NDM | 512 | 64 | 16 | 1 | 0.05 | SHV-12, DHA-1, CTX-M-14 |
R127 Tianjin |
K. pneumoniae
| NDM | 256 | 128 | 32 | 1 | 0.13 | SHV2, DHA-1 |
R128 Zhejiang |
K. pneumoniae
| NDM | 128 | 256 | 8 | 2 | 0.07 | SHV1, DHA-1 |
R129 Zhejiang |
K. pneumoniae
| NDM | 4 | 0.5 | 0.5 | 0.125 | 0.38 | SHV-12, DHA-1, CTX-M-15 |
R136 Zhejiang |
K. pneumoniae
| NDM | 256 | 64 | 16 | 1 | 0.08 | SHV-12, DHA-1 |
R148 Tianjing |
K. pneumoniae
| KPC-2,NDM | 2048 | 8 | 256 | 2 | 0.38 | SHV-12, DHA-1, CTX-M-14 |
R153 Henan |
K. pneumoniae
| KPC-2,NDM | 2048 | 128 | 128 | 8 | 0.13 | SHV-12, DHA-1 |