Mutations in fusA Associated with Posttherapy Fusidic Acid Resistance in Clostridium difficile

Abstract

In silico, we identified fusA (2,067 bp) in Clostridium difficile 630. Sequencing of fusA in posttherapy fusidic acid-resistant C. difficile isolates from 12 patients with C. difficile-associated diarrhea (CDAD) identified fusA mutations, one or two nonsynonymous substitutions, or in one case a deletion of one codon associated with resistance. Five of these mutations have previously been described in fusA of fusidic acid-resistant Staphylococcus aureus, but seven were novel fusA mutations. Fusidic acid monotherapy for CDAD seemed to rapidly select conserved resistant mutants.

Antimicrobial resistance in Clostridium difficile

“…Met16 → Ile, Ser116 → Leu and Val119 → Ala mutations and the deletion of Ala375. Except the deletion of one amino acid (Ala375) that results in a moderately increased MIC (4 mg/L), the amino acid alterations in EF-G yield MICs of 64-256 mg/L [55].…”

Disruption of the Gut Microbiome: Clostridium difficile Infection and the Threat of Antibiotic Resistance

“…This has been observed with antibiotics belonging to the rifamycin class of antibiotics, in particular rifampin and rifaximin, which were previously investigated as alternative CDI therapies [ 58 ], with resistance resulting from mutations in the β subunit of bacterial RNA polymerase, rpoB [ 59 , 60 , 61 ]. Resistance has also been observed in C. difficile strains isolated from patients treated with fusidic acid [ 62 ], with mutations occurring in the fusA gene encoding a protein elongation factor [ 63 ].…”

Increased Sporulation Rate of Epidemic Clostridium difficile Type 027/NAP1

“…Antibiotic susceptibility was determined by Etest (AB Biodisk, Solna, Sweden) using IsoSensitest agar (Oxoid Ltd, Basingstoke, United Kingdom) supplemented with 5% defibrinated horse blood and 20 g/ml of ␤-NAD (Swedish Reference Group for Antibiotics [www.srga.org]). The isolation of bacterial DNA, PCR, and sequencing were performed as described previously (24) by using primers for tcdC (28). For growth experiments, overnight cultures were diluted 10 6 -fold into triplicate tubes containing peptone-yeast without cysteine or glucose that were further grown for 48 h (13,14).…”