TABLE 1.

Mutations in fusA associated with posttherapy fusidic acid-resistant Clostridium difficilea

Patient no.IsolatebDaycRibotypeMIC (mg/liter)Mutation(s) in fusAdAmino acid alteration in FusAd,e
126:11220.38
26:28-1322>256GAC→AACD432→N
26:335-4022>256ATG→ATA, CAC→AACM16→I, H455→N
249:1119c0.25
49:28-1319c0.25
49:335-4019c>256TCA→TTA, GCA→GTAS116→L, A374→V
351:11250.25
51:28-1325>256TCT→CCTS449→P
35-40
457:1121a0.38
8-13
57:335-4021a>256TCA→TTA, GCA→GTAS116→L, A374→V
562:1170.25
62:28-13430.25
62:335-40434Deletion of CAGDeletion of A375
663:1121b0.25
63:28-1321b64ACT→ATTT434→I
35-40
772:11160.25
72:28-1316>256TCA→TTA, GCA→GTAS116→L, A374→V
35-40
873:11120.50
73:28-1312>256ATA→AGAI459→R
35-40
9100:11570.38
100:28-1357>256GTA→GCAV119→A
35-40
10107:1129b0.19
8-13
107:335-4029b>256ATA→AGAI459→R
11248:11170.125
8-13
248:335-4017>256CAC→CGCH455→R
12f58:1116>256CAC→CAAH455→Q
58:28-1316>256CAC→CAAH455→Q
35-40
  • a The day of sampling, PCR-ribotype, fusidic acid MIC, fusA mutation(s), and resulting amino acid alteration(s) in FusA (EF-G) of all 27 sequenced isolates from 12 patients are described.

  • b —, negative culture for C. difficile.

  • c Day 1 was before initiation of the 7-day treatment with fusidic acid, and days 8 to 13 and days 35 to 40 were posttreatment follow-ups.

  • d Mutations (underlined in boldface letters) compared to the sequence of the corresponding C. difficile wild-type fusA, i.e., fusA of the fusidic acid-susceptible C. difficile isolate cultured from each patient before initiation of treatment.

  • e Corresponding amino acid alterations. Their locations were defined according to the FusA sequence of C. difficile strain 630 (accessible at http://www.sanger.ac.uk/Projects/C_difficile/).

  • f Patient treated with metronidazole in our prior trial of treatment for CDAD (25). However, this patient had been given fusidic acid 2 weeks before inclusion in that study. As the day 1 isolate was fusidic acid resistant, the substitution shown refers to comparison with the sequence of C. difficile strain 630.