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Fidaxomicin inhibits spore production in Clostridium difficile.
Clin Infect Dis. 2012 Aug; 55 Suppl 2:S162-9.CI

Abstract

Fidaxomicin (FDX) is a novel antimicrobial agent with narrow-spectrum and potent bactericidal activity against Clostridium difficile. In recent clinical trials, FDX was superior to vancomycin in preventing recurrences of C. difficile infection. A possible mechanism of reducing recurrence may be through an inhibitory effect on sporulation. The effect of FDX and its major metabolite, OP-1118, on C. difficile growth and sporulation kinetics was compared with that of vancomycin, metronidazole, and rifaximin. Drugs at subminimum inhibitory concentrations (sub-MICs) were added to cells at an early stationary phase of growth; this was followed by collection of cells at various intervals for quantitation of total viable cell and heat-resistant spore counts on taurocholate-containing media. The effect of the drugs at 2-2.5× MIC on the expression of sporulation genes in C. difficile was also compared using quantitative reverse-transcriptase polymerase chain reaction. Both FDX and OP-1118 (1/4× MIC) inhibited sporulation when added to early-stationary-phase cells in C. difficile strains, including the epidemic NAP1/BI/027 strain. In contrast, vancomycin, metronidazole, and rifaximin (at similar sub-MICs) did not inhibit sporulation. The number of spores following treatment with comparator drugs increased to the same level as the no-drug control treatment. Expression of mother cell-specific (spoIIID) and forespore-specific (spoIIR) sporulation genes also was inhibited by FDX and OP-1118 but not significantly by vancomycin. Both FDX and OP-1118 (unlike vancomycin, rifaximin, and metronidazole) effectively inhibited sporulation by C. difficile. The inhibitory effect of FDX on C. difficile sporulation may contribute to its superior performance in sustaining clinical response and reducing recurrences and may also be beneficial in decreasing shedding and transmission of this pathogen.

Authors+Show Affiliations

Optimer Pharmaceuticals, Inc., San Diego, California, USA. fbabakhani@optimerpharma.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22752866

Citation

Babakhani, Farah, et al. "Fidaxomicin Inhibits Spore Production in Clostridium Difficile." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 55 Suppl 2, 2012, pp. S162-9.
Babakhani F, Bouillaut L, Gomez A, et al. Fidaxomicin inhibits spore production in Clostridium difficile. Clin Infect Dis. 2012;55 Suppl 2:S162-9.
Babakhani, F., Bouillaut, L., Gomez, A., Sears, P., Nguyen, L., & Sonenshein, A. L. (2012). Fidaxomicin inhibits spore production in Clostridium difficile. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 55 Suppl 2, S162-9. https://doi.org/10.1093/cid/cis453
Babakhani F, et al. Fidaxomicin Inhibits Spore Production in Clostridium Difficile. Clin Infect Dis. 2012;55 Suppl 2:S162-9. PubMed PMID: 22752866.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fidaxomicin inhibits spore production in Clostridium difficile. AU - Babakhani,Farah, AU - Bouillaut,Laurent, AU - Gomez,Abraham, AU - Sears,Pamela, AU - Nguyen,Ly, AU - Sonenshein,Abraham L, PY - 2012/7/4/entrez PY - 2012/7/7/pubmed PY - 2012/11/9/medline SP - S162 EP - 9 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin. Infect. Dis. VL - 55 Suppl 2 N2 - Fidaxomicin (FDX) is a novel antimicrobial agent with narrow-spectrum and potent bactericidal activity against Clostridium difficile. In recent clinical trials, FDX was superior to vancomycin in preventing recurrences of C. difficile infection. A possible mechanism of reducing recurrence may be through an inhibitory effect on sporulation. The effect of FDX and its major metabolite, OP-1118, on C. difficile growth and sporulation kinetics was compared with that of vancomycin, metronidazole, and rifaximin. Drugs at subminimum inhibitory concentrations (sub-MICs) were added to cells at an early stationary phase of growth; this was followed by collection of cells at various intervals for quantitation of total viable cell and heat-resistant spore counts on taurocholate-containing media. The effect of the drugs at 2-2.5× MIC on the expression of sporulation genes in C. difficile was also compared using quantitative reverse-transcriptase polymerase chain reaction. Both FDX and OP-1118 (1/4× MIC) inhibited sporulation when added to early-stationary-phase cells in C. difficile strains, including the epidemic NAP1/BI/027 strain. In contrast, vancomycin, metronidazole, and rifaximin (at similar sub-MICs) did not inhibit sporulation. The number of spores following treatment with comparator drugs increased to the same level as the no-drug control treatment. Expression of mother cell-specific (spoIIID) and forespore-specific (spoIIR) sporulation genes also was inhibited by FDX and OP-1118 but not significantly by vancomycin. Both FDX and OP-1118 (unlike vancomycin, rifaximin, and metronidazole) effectively inhibited sporulation by C. difficile. The inhibitory effect of FDX on C. difficile sporulation may contribute to its superior performance in sustaining clinical response and reducing recurrences and may also be beneficial in decreasing shedding and transmission of this pathogen. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/22752866/Fidaxomicin_inhibits_spore_production_in_Clostridium_difficile_ L2 - https://academic.oup.com/cid/article-lookup/doi/10.1093/cid/cis453 DB - PRIME DP - Unbound Medicine ER -