Table 1.
Changes in susceptibility (MICs, mg/L) to various antimicrobials among isolates recovered from cefiderocol serial passage experiments
| Strain | Time to isolate emergence (days) | FDC | CAZ/AVI | CAZ | MIN | TMP/SMX | FDC stability: no. of drug-free passes | Variants | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 2 | 3 | 4 | gene | nucleic acid | amino acid | |||||||
| W357-Parent | — | 0.03125 | 4 | 128 | 4 | 0.5/9.5 | 0.03125 | 0.0625 | 0.03125 | — | — | — |
| W357-2-10 | 15 | 32 | ≥256 | 256 | 2 | 0.125/2.375 | 8 | 4.0–8.0 | 4.0–8.0 | smeT | c.−49_−48insTTGT | (promoter) |
| W358-Parent | — | 0.125 | 64 | ≥256 | 0.5 | 0.125/2.375 | 0.0625 | 0.0625 | 0.03125 | — | — | — |
| W358-1-25 | 21 | 32 | ≥256 | ≥256 | 0.5 | 0.25/4.75 | 16 | 16 | 8.0–16.0 | smlt1148 |
c.2413A > C |
p.Thr805Pro |
| tesB | c.−33T>C | (promoter) | ||||||||||
| panD | c.258_260delCAT | p.Ile87del | ||||||||||
| smlt3318 | c.383T>A | p.Leu128Gln | ||||||||||
| cysK1 | c.−59G>A | (promoter) | ||||||||||
| cirA | c.112_122dupTCCCGTTCCGC | p.Arg42fs | ||||||||||
| W358-2-2 | 12 | 8 | ≥256 | ≥256 | 0.5 | 0.125/2.375 | 1.0–2.0 | 1 | 1 | smf-1 | c.394A > G | p.Thr132Ala |
| W358-2-15 | 18 | 16 | ≥256 | ≥256 | 0.5 | 0.25/4.75 | 0.0625 | 0.0625 | 0.0625 | tolQ | c.647C > A | p.Pro216Gln |
| W364-Parent | — | 0.03125 | 48 | 64–128 | 1 | 1/19 | 0.03125 | 0.03125 | 0.03125 | — | — | — |
| W364-8 | 16 | 8 | ≥256 | 256 | 1 | 0.25/4.75 | 8 | 2.0–4.0 | 2 | tonB | c.376_384dupGCTCCGCCG | p.Ala126_Pro128dup |
FDC, cefiderocol; CAZ, ceftazidime; CAZ/AVI, ceftazidime/avibactam; MIN, minocycline; TMP/SMX, trimethoprim/sulfamethoxazole.
Cefiderocol MICs were repeated after passage from the freezer onto drug-free medium for up to four passes. Variants list the gene name, followed by the DNA variant and when relevant the amino acid changes.