Table 1.
Clonal types of the 17 KPC-2-positive K. pneumoniae isolates studied, MICs of fosfomycin, meropenem, colistin, and gentamicin, ratio of the concentration of each antibiotic used in time-kill studies to the MIC, and in vitro interactions of the combinations tested against these isolates
| Strain | Clonal type | MIC (μg/ml), ratio of concn testeda to MIC |
Interactionb of FOF with (growth time[s] [h]): |
|||||
|---|---|---|---|---|---|---|---|---|
| Fosfomycin | Meropenem | Colistin | Gentamicin | Meropenem | Colistin | Gentamicin | ||
| m 4096C | C | 8, 12.5 | 4, 2.5 | 0.75, 6.67 | >8, <0.61 | Ind | Ind | Ind |
| 439 CII | A2 | 8, 12.5 | 64, 0.16 | 0.38, 13.16 | ≤2, ≥2.5 | Syn (24) | Ind | Ind |
| m 4908C | D | 16, 6.25 | 64, 0.16 | 32, 0.16 | ≤2, ≥2.5 | Syn (24) | Ind | Ind |
| b 1013 | A2 | 16, 6.25 | 64, 0.16 | 0.38, 13.16 | 4, 1.25 | Syn (24) | Ind | Ind |
| P 908 | A1 | 16, 6.25 | 32, 0.31 | 12, 0.42 | ≤2, ≥2.5 | Syn (24) | Syn (24) | Ind |
| 258 | A1 | 16, 6.25 | 64, 0.16 | 8, 0.63 | ≤2, ≥2.5 | Syn (24) | Ind | Ind |
| 202 | A1 | 16, 6.25 | 32, 0.31 | 48, 0.10 | ≤2, ≥2.5 | Syn (24) | Ind | Ind |
| P 903 | A1 | 32, 3.13 | 32, 0.31 | 16, 0.31 | 4, 1.25 | Syn (6, 24) | Syn (6) | Ind |
| m 538C | A2 | 32, 3.13 | 128, 0.08 | 0.38, 13.16 | 8, 0.61 | Ind | Ind | Ind |
| m 2573A | A1 | 32, 3.13 | 8, 1.25 | 6, 0.83 | >8, <0.61 | Ind | Ind | Ind |
| m 4185C | B1 | 32, 3.13 | 32, 0.31 | 0.5, 10 | ≤2, ≥2.5 | Syn (24) | Ind | NDc |
| m 4362C | B1 | 32, 3.13 | 64, 0.16 | 0.38, 13.16 | ≤2, ≥2.5 | Syn (24) | Ind | Ind |
| m 3353 | B1 | 32, 3.13 | 32, 0.31 | 0.75, 6.67 | ≤2, ≥2.5 | Syn (24) | Ind | ND |
| m 1044C | A2 | 256, 0.39 | >256, <0.04 | 24, 0.21 | 4, 1.25 | Ind | Ind | Ind |
| 608 | A2 | 256, 0.39 | >256, <0.04 | 4, 1.25 | ≤2, ≥2.5 | Ind | Ind | Ind |
| 878 P | A2 | 256, 0.39 | 256, 0.04 | 0.5, 10 | ≤2, ≥2.5 | Ind | Ind | Ind |
| m 3473C | B2 | >256, <0.39 | 8, 1.25 | 1, 5 | >8, <0.61 | Syn (24) | Ind | Ind |
The antibiotic concentrations used in time-kill studies were as follows: fosfomycin, 100 μg/ml; meropenem, 10 μg/ml; colistin and gentamicin, 5 μg/ml. The MICs (μg/ml) for 50 and 90%, respectively, of the isolates studied (percent susceptible) were as follows: fosfomycin, 32 and 256 (76.5); meropenem, 64 and >256 (5.9); colistin, 1 and 32 (52.9); gentamicin, ≤2 and >8 (76.5).
Ind, indifference; Syn, synergy. The number (%) of isolates showing synergy/total number of isolates was as follows: meropenem, 11/17 (64.7%);colistin, 2/17 (11.8%); gentamicin, 0/15 (0%). The number (%) of isolates in which resistance to fosfomycin was prevented (the denominator is the number of fosfomycin-susceptible isolates tested) was as follows: meropenem, 9/13 (69.2%); colistin, 7/13 (53.8%); gentamicin, 9/11 (81.8%).
ND, not done.