TABLE 1.
Frequency of spontaneous mutations among 14 strains tested at 4-, 8-, and 16-fold the baseline MIC for amikacin-fosfomycin (5:2)
| Species | Phenotypea | Strain no. | Baseline MIC (μg/ml) of each drug in the amikacin-fosfomycin (5:2) combination |
Mutation frequencyb at: |
|||
|---|---|---|---|---|---|---|---|
| Amikacin | Fosfomycin | 4× Baseline MIC | 8× Baseline MIC | 16× Baseline MIC | |||
| Acinetobacter sp. | MDR | 1986 | 4 | 1.6 | <1.65 × 10−9 | <1.65 × 10−9 | <1.65 × 10−9 |
| MDR | 8133 | 32 | 12.8 | <1.52 × 10−11 | <1.52 × 10−11 | <1.52 × 10−11 | |
| MDR | 8572 | 128 | 51.2 | <9.35 × 10−12 | <9.35 × 10−12 | <9.35 × 10−12 | |
| E. coli | Wild type | ATCC 25922 | 1 | 0.4 | <1.23 × 10−12 | <1.23 × 10−12 | <1.23 × 10−12 |
| E. cloacae | AmpC | 5686 | 8 | 3.2 | 4.25 × 10−8 | <7.69 × 10−11 | <7.69 × 10−11 |
| K. pneumoniae | KPC | 25 | 8 | 3.2 | 1.63 × 10−9 | <1.41 × 10−11 | <1.41 × 10−11 |
| ESBL | 341 | 1 | 0.4 | <1.74 × 10−12 | <1.74 × 10−12 | <1.74 × 10−12 | |
| ESBL | 1015 | 8 | 3.2 | 2.28 × 10−9 | <1.18 × 10−11 | <1.18 × 10−11 | |
| P. aeruginosa | Wild type | ATCC 27853 | 2 | 0.8 | <1.30 × 10−11 | <1.30 × 10−11 | <1.30 × 10−11 |
| Carb-R | 1113 | 8 | 3.2 | <1.27 × 10−11 | <1.27 × 10−11 | <1.27 × 10−11 | |
| Carb-R | 1185 | 8 | 3.2 | 3.47 × 10−10 | <1.36 × 10−12 | <1.36 × 10−12 | |
| S. aureus | MSSA | ATCC 29213 | 1 | 0.4 | <1.74 × 10−12 | <1.74 × 10−12 | <1.74 × 10−12 |
| MRSA | 70 | 8 | 3.2 | <8.13 × 10−12 | <8.13 × 10−12 | <8.13 × 10−12 | |
| S. pneumoniae | Pen-I | ATCC 49619 | 16 | 6.4 | <1.60 × 10−12 | <1.60 × 10−12 | <1.60 × 10−12 |
a
AmpC, AmpC type β-lactamase; Carb-R, carbapenem resistant; ESBL, extended-spectrum β-lactamase; KPC, Klebsiella pneumoniae carbapenemase; MDR, multidrug resistant; MRSA, methicillin-resistant S. aureus; MSSA, methicillin-sensitive S. aureus; Pen-I, penicillin intermediate.
b
Calculated as the number of resistant mutant colonies (CFU/ml) that grew on antibiotic-containing agar plates divided by the number of CFU/ml in the initial antibiotic-free starting inoculum (approximately 109 CFU/ml).