Table 2.
Summary of Antimicrobial Resistance Genes and Chromosomal Mutations in 14 Enterobacterales Cefiderocol Nonwild Type Isolates
| Organism | FDC MIC (mg/L) | ST | Source | mCIM result | β-lactamase genes | Acquired resistance genes | Mutations in genes previously associated with cefiderocol resistance | Chromosomal mutations leading to amino acid changes |
|---|---|---|---|---|---|---|---|---|
| K. pneumoniae | 32 | 258 | Skin and soft tissue | Negative | blaCTX-M-2, blaOXA-2, blaSHV-11 | aac, ant, aph, dfrA12, cat1, sul1, sul2, chrA | BaeS (A103S, P376A) | OmpK36 (E232R, F207Y, T222L, L59V, L229A, F198Y, N304E, A217S, D223G, G189T), OmpK37 (I70M, I128M, N230G, M233Q, R239K, E244D, N274S, V277I), PmrB (R256G), GyrA (F83I), GyrB (E466D), ParC (S80I, T57S), AcrR (R173G, F197I, P161R, F172S, L195V, K201M, G164A), CycA (S263A), GlpT (G206A), UhpT (E350Q) |
| K. pneumoniae | 32 | 258 | Stool | Positive | blaKPC-2, blaOXA-9, blaSHV-40, blaTEM-1 | aac, aad, aph, cat1, dfrA12, oqxA/B, sul1, chrA | BaeS (A103S, P376A) | OmpK36 (E232R, F207Y, T222L, L59V, L229A, F198Y, N304E, A217S, D223G, G189T), OmpK37 (I70M, I128M, N230G, M233Q, R239K, E244D, N274S, V277I), PmrB (R256G), GyrA (F83I), GyrB (E466D), ParC (S80I, T57S), AcrR (R173G, F197I, P161R, F172S, L195V, K201M, G164A), CycA (S263A), GlpT (G206A), UhpT (E350Q), BamB (A176T) |
| K. pneumoniae | 16 | 258 | Urine | Positive | blaKPC-3, blaSHV-12, blaTEM-1 | aac, cat1, dfrA14, mphA, qnRS7, oqxA/B, chrA | BaeS (A103S, P376A) | OmpK36 (D223G, G189Y, E232R, T222L, L59V, L229A, F198Y, N304E, F207Y, A217S), OmpK37 (I70M, I128M, N230G, M233Q, R239K, E244D, N274S, V277I), PmrB (R256G), GyrA (F83I), ParC (S80I, T57S), AcrR (R173G, F197I, P161R, F172S, L195V, K201M, G164A), CycA (S263A), GlpT (G206A), UhpT (E350Q), BamB (A176T) |
| K. pneumoniae | 4 | 231 | Blood | Positive | blaCMY-59, blaCTX-M-15, blaNDM-1, blaOXA-181, blaSHV-1, blaTEM-1 | rmtF, aac, aad, aph, arb, brp(MBL), catB, dfrA12, ermB, mphA, qnrB1, sul1, sul2, sugE, chrA | BaeS (A419V), YicM (I262V, T299M) | OmpK36 (E232R, L59V, A217S, D223G, N304E, F207Y, N218H), OmpK37 (I70M, I128M, N230G, M233Q, R239K, E244D, N274S, V277I), GyrA (F83I), ParC (S80I, T57S), AcrR (R173G, F197I, P161R, F172S, L195V, K201M, G164A), CycA (S263A), GlpT (G206A), UhpT (E350Q), BamB (A176T) |
| K. pneumoniae | 4 | 231 | Urine | Positive | blaCMY-59, blaCTX-M-15, blaNDM-1, blaOXA-181, blaSHV-1, blaTEM-1 | rmtF, aac, aad, aph, arb, brp(MBL), catB, dfrA12, ermD, mphA, qnrB1, sul2, sugE | BaeS (A419V), YicM (I262V, T299M) | OmpK36 (E232R, L59V, A217S, D223G, N304E, F207Y, N218H), OmpK37 (I70M, I128M, N230G, M233Q, R239K, E244D, N274S, V277I), GyrA (F83I), ParC (S80I, T57S), AcrR (R173G, F197I, P161R, F172S, L195V, K201M, G164A), CycA (S263A), GlpT (G206A), UhpT (E350Q), BamB (A176T) |
| K. pneumoniae | 4 | 307 | Respiratory | Positive | blaCTX-M-15, blaOXA-1, blaSHV-28, blaTEM-1 | aac, aph, catB3, dfrA14, tetA, qnrB1, sul2 | BaeS (F3L, A103T, D106N, S192N) | OmpK37 (I70M, I128M, N230G, M233Q, R239K, E244D, N274S, V277I), GyrA (F83I), ParC (S80I, T57S), AcrR (R173G, F197I, P161R, F172S, L195V, K201M, G164A), CycA (S263A), GlpT (G206A), UhpT (E350Q), BamB (A176T) |
| K. pneumoniae | 4 | 258 | Stool | Positive | blaSHV-11, blaTEM-1, blaOXA-9, blaKPC-2 | aac, aad, aph, dfrA12, cat1, sul1, oqxA/B, chrA | BaeS (A103S, P376A) | OmpK36 (E232R, F207Y, T222L, L59V, L229A, F198Y, N304E, A217S, D223G, G189T), OmpK37 (I70M, I128M, N230G, M233Q, R239K, E244D, N274S, V277I), PmrB (R256G), GyrA (F83I), GyrB (E466D), ParC (S80I, T57S), AcrR (R173G, F197I, P161R, F172S, L195V, K201M, G164A), CycA (S263A), GlpT (G206A), UhpT (E350Q), BamB (A176T) |
| Enterobacter hormaechei | 64 | 1296 | Blood | Negative | blaTEM-1, blaACT-70 | dfrA12, oqxA/B, sul1, sul2, romA | ParC (S57T), ParE (I355T), CycA (263A), GlpT (G206A, Q444E), UhpT (E350Q), SetB (I307V), 5’ OmpC truncation | |
| Enterobacter asburiae | 16 | 24 | Urine | Negative | bla ACT-1 | mcr-10, oqxA/B | GyrA (S83T), ParC (S57T), ParE (I355T), CycA (263A), GlpT (Q444E), UhpT (E350Q), SetB (I307V), OmpC Δ AA 30–75 | |
| E. asburiae | 8 | 1056 | Stool | Negative | bla MIR-8 | oqxA/B, romA | ParC (S57T), ParE (I355T), CycA (263A), GlpT (G206A, Q444E), UhpT (E350Q), SetB (I307V) | |
| E. asburiae | 4 | 807 | Intra-abdominal | Negative | bla ACT-4 | mcr-10, oqxA/B, romA | ParC (S57T), ParE (I355T), CycA (263A), GlpT (Q444E), UhpT (E350Q), SetB (I307V), OmpC Δ AA 35–75 | |
| E. asburiae | 4 | Novel | Urine | Negative | blaACT-4, blaRomA | oqxA/B | GyrA (S83T), ParC (S57T), ParE (I355T), CycA (263A), GlpT (Q444E), UhpT (E350Q), SetB (I307V) | |
| Enterobacter kobei | 4 | 125 | Urine | Negative | bla ACT-28 | mcr-10, oqxA/B, romA | ParC (S57T), ParE (I355T), CycA (263A), GlpT (Q444E), UhpT (E350Q), SetB (I307V) | |
| Citrobacter freundii | 8 | Novel | Intra-abdominal | Negative | bla CMY-59 | qnrB38 | OmpC 5′ truncation, GyrA (S83T), ParC (S57T), SoxR (R4K, T38S), cycA (S263A), GlpT (G206A, E448K), UhpT (E350Q) |
FDC, cefiderocol; mCIM, modified carbapenem inactivation method; ST, sequence type.