Background
Methods
Bacteria, media and antibiotics
OXACILLIN (OXA) PRODUCTS | BATCH | MANUFACTURER | DISTRIBUTOR | PERFORMED TESTS |
---|---|---|---|---|
OXA-BMS (innovator)
| EL059 EG187 EF109 EF372 ED259 | Bristol-Myers Squibb de Mexico. | Bristol-Myers Squibb | MA, MIC&MBC, NMTIM |
OXA-BLA
| A 4602 B 4603 | Vitrofarma SA, Bogota, Colombia | Laboratorios Blaskov | MA, MIC&MBC, NMTIM |
OXA-CAR
| 309V1104 378V0705 | Farmacologica SA, Bogota, Colombia | Carlon Ltda | MA, MIC&MBC, NMTIM |
OXA-COL
| 0010202 05103 | Farmacologica SA, Bogota, Colombia | Colpharma Ltda | MA, MIC&MBC, NMTIM |
OXA-EXP*
| OX 010462 | Farmacologica SA Bogota, Colombia | Laboratorios Expopharma | MA, NMTIM |
OXA-MEM
| 110291 050239 090281 | Vitrofarma SA, Bogota, Colombia | Memphis Products | MA, MIC&MBC, NMTIM |
OXA-OPH
| 080267 060249 | Vitrofarma SA, Bogota, Colombia | Laboratorios Farmaceuticos Ophalac | MA, MIC&MBC, NMTIM |
OXA-PEN*
| 20275 30417 | Farmacologica SA, Bogota, Colombia | Pentacoop SA | MA, MIC&MBC, NMTIM |
OXA-QIM
| 6400702 | Vitrofarma SA, Bogota, Colombia | Quimicol | MIC&MBC, NMTIM |
OXA-SCA
| OX-010462 | Farmacologica SA, Bogota, Colombia | Farmionni Scalpi S.A. | MA, NMTIM |
OXA-SER
| OX-010508 | Farmacologica SA Bogota, Colombia | Serpharma SA | MIC&MBC, NMTIM |
OXA-VIT
| 120198 090281 110291 | Vitrofarma SA, Bogota, Colombia | Vitalis | MA, MIC&MBC, NMTIM |
Microbiological assay
In vitro activity
Neutropenic mouse thigh infection model
Statistical analysis of in vivo data
Results
Microbiological assay
In vitro activity
OXACILLIN (OXA) PRODUCTS |
S. aureusATCC 29213 |
S. aureusGRP-0057 | ||||
---|---|---|---|---|---|---|
MIC (mg/L) | MBC (mg/L) | MBC/MIC Ratio | MIC (mg/L) | MBC (mg/L) | MBC/MIC Ratio | |
OXA-BMS (innovator)
| 0.22 | 0.40 | 1.78 | 0.16 | 0.25 | 1.59 |
OXA-BLA
| 0.50 | 0.50 | 1.00 | 0.18 | 0.50 | 2.83 |
OXA-CAR
| 0.50 | 1.00 | 2.00 | 0.50 | 0.50 | 1.00 |
OXA-COL
| 0.50 | 0.71 | 1.41 | 0.18 | 0.35 | 2.00 |
OXA-MEM
| 0.13 | 0.13 | 1.00 | 0.13 | 0.13 | 1.00 |
OXA-OPH
| 0.25 | 0.71 | 2.83 | 0.18 | 0.25 | 1.41 |
OXA-PEN
| 0.25 | 0.35 | 1.41 | 0.18 | 0.21 | 1.19 |
OXA-QIM
| 0.50 | 1.00 | 2.00 | 0.18 | 0.25 | 1.41 |
OXA-SER
| 0.25 | 0.50 | 2.00 | 0.25 | 0.50 | 2.00 |
OXA-VIT
| 0.13 | 0.13 | 1.00 | 0.13 | 0.13 | 1.00 |
Exact P (KW*)
| 0.2115 | 0.2110 | 0.2611 | 0.3650 | 0.1339 | 0.2751 |
Neutropenic mouse thigh infection model
EXPERIMENT | Bacterial Load at 0 h (log10CFU/g) | Bacterial Load at 24 h (log10CFU/g) | Net Growth G (log10CFU/g) | ||
---|---|---|---|---|---|
Mean | SD | Mean | SD | ||
1 | 3.96 | 0.035 | 7.86 | 0.011 | 3.90 |
2 | 4.09 | 0.106 | 7.48 | 0.269 | 3.39 |
3 | 3.85 | 0.007 | 7.29 | 0.347 | 3.44 |
4 | 4.66 | 0.070 | 7.57 | 0.004 | 2.91 |
Mean ± SEM
|
4.14 ± 0.180
|
7.55 ± 0.119
|
3.41 ± 0.202
|
OXACILLIN (OXA) PRODUCTS | Emax(log10CFU/g) | SEM | N | SEM | ED50(mg/kg) | SEM | BD (mg/kg) | SEM | 1 LKD (mg/kg) | SEM | Adj. R2
| Sy|x
| P (CFA) |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
OXA-BMS (innovator)
| 5.42 | 0.08 | 1.73 | 0.13 | 45.19 | 2.32 | 62.24 | 3.07 | 108.36 | 7.32 | 0.99 | 0.23 | NA |
OXA-BLA
| 3.38 | 0.10 | 3.29 | 0.79 | 19.38 | 2.65 |
>750.00
| - |
>750.00
| - | 0.98 | 0.21 | <0.0001 |
OXA-CAR
| 3.69 | 0.10 | 1.81 | 0.20 | 25.44 | 2.20 | 97.61 | 16.13 |
>750.00
| - | 0.99 | 0.17 | <0.0001 |
OXA-COL
| 3.14 | 0.12 | 1.93 | 0.36 | 35.41 | 3.71 | 132.29 | 33.04 |
>750.00
| - | 0.98 | 0.20 | <0.0001 |
OXA-MEM
| 3.51 | 0.12 | 2.09 | 0.32 | 23.07 | 2.65 |
>750.00
| - |
>750.00
| - | 0.96 | 0.32 | <0.0001 |
OXA-OPH
| 3.11 | 0.15 | NS | - | NS | - |
>750.00
| - |
>750.00
| - | 0.96 | 0.31 | <0.0001*
|
OXA-QIM
| 2.22 | 0.10 | 2.72 | 0.60 | 25.00 | 3.95 |
>750.00
| - |
>750.00
| - | 0.96 | 0.20 | <0.0001 |
OXA-SCA
| 3.66 | 0.17 | 2.03 | 0.46 | 19.31 | 3.02 |
>750.00
| - |
>750.00
| - | 0.95 | 0.31 | <0.0001 |
OXA-SER† | - | - | - | - | - | - | - | - | - | - | - | - | NA |
OXA-VIT
| 3.01 | 0.12 | 1.55 | 0.26 | 18.51 | 2.50 |
>750.00
| - |
>750.00
| - | 0.97 | 0.20 | <0.0001 |
OXACILLIN (OXA) PRODUCTS | N | SEM | ED50(mg/kg) | SEM | BD (mg/kg) | SEM | 1LKD (mg/kg) | SEM |
---|---|---|---|---|---|---|---|---|
Experiment 1
| ||||||||
OXA-BMS (innovator) | 1.73 | 0.30 | 45.13 | 5.47 | 77.73 | 0.20 | 104.79 | 24.18 |
OXA-OPH | 0.47 | 0.09 | 95.15 | 35.54 |
>750.00
| - |
>750.00
| - |
OXA-MEM | 0.56 | 0.10 | 76.42 | 24.90 | 409.36 | 182.35 |
>750.00
| - |
OXA-SCA | 0.56 | 0.10 | 72.66 | 23.71 | 390.13 | 172.68 |
>750.00
| - |
OXA-VIT | 0.45 | 0.10 | 205.11 | 84.98 | 750.00* | 373.73 |
>750.00
| - |
Experiment 2
| ||||||||
OXA-BMS (innovator) | 1.73 | 0.18 | 45.13 | 3.33 | 60.71 | 4.33 | 96.48 | 12.24 |
OXA-CAR | 0.64 | 0.07 | 90.52 | 16.50 | 202.51 | 39.36 | 230.84 | 230.84 |
Experiment 3
| ||||||||
OXA-BMS (innovator) | 1.73 | 0.29 | 45.13 | 5.39 | 62.17 | 7.07 | 97.35 | 20.07 |
OXA-MEM | 0.63 | 0.12 | 127.53 | 38.29 | 307.47 | 101.82 |
>750.00
| - |
OXA-OPH | 0.55 | 0.10 | 128.00 | 42.18 | 526.98 | 225.98 |
>750.00
| - |
OXA-BLA | 0.59 | 0.11 | 101.00 | 31.58 | 259.22 | 88.45 |
>750.00
| - |
Experiment 4
| ||||||||
OXA-BMS (innovator) | 1.73 | 0.21 | 45.13 | 3.96 | 49.23 | 3.83 | 88.41 | 17.53 |
OXA-QUIM | 0.40 | 0.08 | 750.00 | 321.55 | 750.00* | 287.80 | 750.00* | 327.88 |
OXA-COL | 0.58 | 0.09 | 221.34 | 54.59 | 287.58 | 70.52 | 750.00* | 356.95 |