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

2007 ◽  
Vol 51 (5) ◽  
pp. 1840-1843 ◽  
Author(s):  
T. Norén ◽  
T. Åkerlund ◽  
M. Wullt ◽  
L. G. Burman ◽  
M. Unemo
Keyword(s):  
Staphylococcus Aureus ◽  
Clostridium Difficile ◽  
Fusidic Acid ◽  
In Silico ◽  
Acid Resistance ◽  
Nonsynonymous Substitutions ◽  
Resistant Mutants

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.

scholarly journals Frequent Emergence of Resistance in Clostridium difficile during Treatment of C. difficile-Associated Diarrhea with Fusidic Acid

2006 ◽  
Vol 50 (9) ◽  
pp. 3028-3032 ◽  
Author(s):  
T. Norén ◽  
M. Wullt ◽  
Thomas Åkerlund ◽  
E. Bäck ◽  
I. Odenholt ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Treatment Failure ◽  
Fusidic Acid ◽  
Negative Impact ◽  
Acid Resistance ◽  
Clinical Recurrence ◽  
Acid Therapy ◽  
Emergence Of Resistance ◽  
Culture Positive

ABSTRACT Samples from patients with Clostridium difficile-associated diarrhea (CDAD) that were randomized to fusidic acid (n = 59) or metronidazole (n = 55) therapy for 7 days were cultured for Clostridium difficile in feces on days 1, 8 to 13, and 35 to 40. Of the patients who were culture positive only before treatment, 77% (36/47) were permanently cured (no treatment failure and no clinical recurrence), compared to 54% (22/41) of those with persistence of C. difficile at one or both follow-ups (P = 0.03). A similar association between bacterial persistence and a worse outcome of therapy was seen in both treatment groups. Resistance to fusidic acid was found in 1 of 88 pretherapy isolates available, plus in at least 1 subsequent isolate from 55% (11/20) of patients who remained culture-positive after fusidic acid therapy. In 10 of these 11 patients, the resistant follow-up isolate(s) belonged to the same PCR ribotype as the susceptible day 1 isolate, confirming frequent emergence of resistance to fusidic acid during treatment. Despite this, 5 of these 11 patients were permanently cured with fusidic acid, relative to 5 of 9 patients with susceptible C. difficile at follow-up (P = 1.0). None of the 36 PCR ribotypes of C. difficile identified was associated with any particular clinical outcome or emergence of fusidic acid resistance. In conclusion, culture positivity for C. difficile was common after both fusidic acid and metronidazole therapy and was associated with treatment failure or recurrence of CDAD. Development of resistance in C. difficile was frequent in patients given fusidic acid, but it was without apparent negative impact on therapeutic efficacy in the actual CDAD episode.

scholarly journals Fusidic acid resistance in Staphylococcus aureus nasal carriage strains in nine European countries

2014 ◽  
Vol 9 (6) ◽  
pp. 737-745 ◽  
Author(s):  
Casper DJ den Heijer ◽  
Evelien ME van Bijnen ◽  
W John Paget ◽  
Ellen E Stobberingh
Keyword(s):  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Acid Resistance ◽  
Nasal Carriage ◽  
European Countries

Molecular analysis of fusidic acid resistance in Staphylococcus aureus

2003 ◽  
Vol 47 (2) ◽  
pp. 463-469 ◽  
Author(s):  
Silke Besier ◽  
Albrecht Ludwig ◽  
Volker Brade ◽  
Thomas A. Wichelhaus
Keyword(s):  
Staphylococcus Aureus ◽  
Molecular Analysis ◽  
Fusidic Acid ◽  
Acid Resistance

scholarly journals Genetic and Phenotypic Identification of Fusidic Acid-Resistant Mutants with the Small-Colony-Variant Phenotype in Staphylococcus aureus

2007 ◽  
Vol 51 (12) ◽  
pp. 4438-4446 ◽  
Author(s):  
Tobias Norström ◽  
Jonas Lannergård ◽  
Diarmaid Hughes
Keyword(s):  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Mammalian Cells ◽  
Antimicrobial Agents ◽  
Structural Domain ◽  
Small Colony ◽  
Resistant Mutants ◽  
Substitution Mutations ◽  
Domain V ◽  
Domain I

ABSTRACT Small-colony variants (SCVs) of Staphylococcus aureus are a slow-growing subpopulation whose phenotypes can include resistance to aminoglycosides, defects in electron transport, and enhanced persistence in mammalian cells. Here we show that a subset of mutants selected as SCVs by reduced susceptibility to aminoglycosides are resistant to the antibiotic fusidic acid (FA) and conversely that a subset of mutants selected for resistance to FA are SCVs. Mutation analysis reveals different genetic classes of FA-resistant SCVs. One class, FusA-SCVs, have amino acid substitution mutations in the ribosomal translocase EF-G different from those found in classic FusA mutants. Most of these mutations are located in structural domain V of EF-G, but some are in domain I or III. FusA-SCVs are auxotrophic for hemin. A second class of FA-resistant SCVs carry mutations in rplF, coding for ribosomal protein L6, and are designated as FusE mutants. FusE mutants fall into two phenotypic groups: one auxotrophic for hemin and the other auxotrophic for menadione. Accordingly, we have identified new genetic and phenotypic classes of FA-resistant mutants and clarified the genetic basis of a subset of S. aureus SCV mutants. A clinical implication of these data is that FA resistance could be selected by antimicrobial agents other than FA.

Fusidic Acid Resistance in Staphylococcus aureus Strains in an Interval of Ten Years (2001-2011)

2012 ◽  
Vol 32 (6) ◽  
pp. 1668-1672 ◽  
Author(s):  
Şebnem NERGİZ ◽  
Selahattin ATMACA ◽  
Tuncer ÖZEKİNCİ ◽  
Alicem TEKİN
Keyword(s):  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Acid Resistance

scholarly journals Compensatory Adaptation to the Loss of Biological Fitness Associated with Acquisition of Fusidic Acid Resistance in Staphylococcus aureus

2005 ◽  
Vol 49 (4) ◽  
pp. 1426-1431 ◽  
Author(s):  
Silke Besier ◽  
Albrecht Ludwig ◽  
Volker Brade ◽  
Thomas A. Wichelhaus
Keyword(s):  
Staphylococcus Aureus ◽  
Amino Acid ◽  
Fusidic Acid ◽  
Wild Type Strain ◽  
Elongation Factor ◽  
Acid Resistance ◽  
Resistant Bacteria ◽  
Wild Type ◽  
Compensatory Adaptation

ABSTRACT Recent studies have shown that individual amino acid exchanges within elongation factor G (EF-G) cause fusidic acid resistance in Staphylococcus aureus. The data from the present study illustrate that the fusidic acid resistance-mediating amino acid substitutions P406L and H457Y are associated with a marked impairment of the biological fitness of S. aureus. In particular, strains producing EF-G derivatives with these mutations showed reduced growth, decreased plasma coagulase activity, and an impaired capability to compete with the isogenic wild-type strain. Second-site mutations within EF-G, such as A67T and S416F, that have been encountered in clinical fusidic acid-resistant isolates containing the amino acid exchanges P406L and H457Y, respectively, were shown not to contribute to resistance. Furthermore, the substitution A67T had no impact on the biological fitness in vitro. The exchange S416F, however, was found to function as a fitness-compensating mutation in S. aureus carrying the substitution H457Y in EF-G. In conclusion, the data presented in this report provide evidence at the molecular level that the deleterious effects of fusidic acid resistance-mediating exchanges within EF-G of S. aureus can be reduced considerably by specific compensating mutations in this target protein. This compensatory adaptation most likely plays a significant role in the stabilization of resistant bacteria within a given population.

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