A new macrocyclic antibiotic, fidaxomicin (OPT-80), causes less alteration to the bowel microbiota of Clostridium difficile-infected patients than does vancomycin

Tannock, Gerald W.; Munro, Karen; Taylor, Corinda; Lawley, Blair; Young, Wayne; Byrne, Brendan; Emery, Judy; Louie, Thomas

doi:10.1099/mic.0.042010-0

Cited by 194 publications

(157 citation statements)

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“…In recent phase 3 clinical trials in patients with C. difficile infection, fidaxomicin not only was well tolerated and achieved the primary end point of clinical cure but also demonstrated a significantly lower rate of recurrence of infection compared with vancomycin (Crook et al, 2010;Louie et al, 2009b;Miller et al, 2009). Analysis of stool samples from subjects during a phase 2 doseranging study demonstrated that fidaxomicin not only lacks activity against Gram-negative bacteria but is also sparing of Gram-positive commensals (Louie et al, 2009a;Tannock et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Killing kinetics of fidaxomicin and its major metabolite, OP-1118, against Clostridium difficile

Babakhani

Gomez

Robert

et al. 2011

Journal of Medical Microbiology

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The kinetics of bacterial killing for fidaxomicin and its major metabolite, OP-1118, were investigated against Clostridium difficile strains, including two clinical strains belonging to the restriction endonuclease analysis group BI (ORG 1687 and 1698), the ATCC 43255 strain and two laboratory-derived mutant strains with decreased susceptibility to fidaxomicin (ORG 919 and 1620). Both fidaxomicin and OP-1118 demonstrated time-dependent killing of C. difficile strains. Fidaxomicin (at 4¾ MIC) reduced bacterial counts of the ATCC 43255 strain, clinical strain ORG 1687 and the two laboratory-generated mutant strains by ¢3 logs within 48 h of exposure. The other BI strain, ORG 1698, was tested at 2¾ MIC fidaxomicin with bacterial counts decreasing 1 log in 48 h. Exposure to OP-1118 (at 4¾ MIC) also resulted in a ¢3 log drop in c.f.u. counts for the ATCC 43255 strain, the clinical BI strain ORG 1687 and the mutant strain ORG 919. Higher concentrations of OP-1118 (32¾ MIC) were required for a 3 log reduction in c.f.u. counts for the other BI strain, ORG 1698. In summary, the results indicate that both fidaxomicin and its major metabolite, OP-1118, are bactericidal against C. difficile strains, including the hypervirulent restriction endonuclease analysis group BI strains, at concentrations that are many fold below the detected faecal concentrations of these compounds after oral administration of fidaxomicin.

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Section: Introductionmentioning

confidence: 99%

Killing kinetics of fidaxomicin and its major metabolite, OP-1118, against Clostridium difficile

Babakhani

Gomez

Robert

et al. 2011

Journal of Medical Microbiology

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“…By altering the normal composition of the protective colonic microbial flora, antibiotic treatments create favourable conditions for colonization and hence infection by C. difficile (Wilson & Perini, 1988;Tannock et al, 2010). However, spores require the presence of certain compounds in order to undergo germination.…”

Section: Discussionmentioning

confidence: 99%

Nisin is an effective inhibitor of Clostridium difficile vegetative cells and spore germination

Lay

Dridi

Bergeron

et al. 2016

Journal of Medical Microbiology

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Clostridium difficile is the most frequently identified enteric pathogen in patients with nosocomial antibiotic-associated diarrhoea and pseudomembranous colitis. Several clinically isolated C. difficile strains are resistant to antibiotics other than metronidazole and vancomycin. Recently, bacteriocins of lactic acid bacteria have been proposed as an alternative or complementary treatment. The aim of this study was to investigate the inhibitory effect of nisin, a bacteriocin produced by several strains of Lactococcus lactis, against clinical isolates of C. difficile. Nisin Z obtained from culture of L. lactis subsp. lactis biovar. diacetylactis was tested along with commercial nisin A. The effect of nisin A on C. difficile spores was also examined. Nisin A and Z both inhibited the growth of all C. difficile isolates, and MICs were estimated at 6.2 mg ml 21 for nisin Z and 0.8 mg ml 21 for nisin A. In addition, C. difficile spores were also susceptible to nisin A (25.6 mg ml 21 ), which reduced spore viability by 40-50 %. These results suggested that nisin and hence nisin-producing Lactococcus strains could be used to treat C. difficile-associated diarrhoea. INTRODUCTIONClostridium difficile, a Gram-positive anaerobic sporeforming bacterium, is an emerging pathogen capable of causing severe gastrointestinal illness in individuals undergoing antibiotic therapy (Kelly & LaMont, 2008;Rupnik et al., 2009;Stanley et al., 2013). Infection with C. difficile may produce a wide spectrum of outcomes that range from asymptomatic colonization to acute diarrhoea and pseudomembranous colitis, which can result in colonic perforation and death if untreated (Kelly & LaMont, 2008;Rupnik et al., 2009;Stanley et al., 2013). Whilst the vegetative form of C. difficile is responsible for producing the toxins that cause illness, the spore is the principal transmitted form (Sorg & Sonenshein, 2008). Many antibiotics have been implicated in C. difficile-associated diarrhoea, including clindamycin, ampicillin and amoxicillin, as well as the cephalosporins and fluoroquinolones (Wiström et al., 2001;Stevens et al., 2011;Slimings & Riley, 2014) Current treatment for C. difficile-associated diarrhoea is limited mainly to administration of the antibiotics metronidazole or vancomycin (Surawicz et al., 2013). Furthermore, treatment failure and recurrence of infection have also been reported in 2-38 and 8-50 % of cases, respectively (Aslam et al., 2005). Based on its in vitro activity, its efficacy by either the oral or the intravenous route and its low cost, metronidazole was commonly used for treatment of mild C. difficile infection. However, some studies reported the emergence of C. difficile isolates with a reduced susceptibility to metronidazole (Baines et al., 2008; Peláez et al., 2008). Vancomycin is considered a second-line therapy, as prolonged treatment is associated with higher risk of selecting vancomycin-resistant Enterococcus in addition to its high cost.It is clear that the health sector would benefit from efficacious alternative...

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“…Ultima nata, inserita nella farmacopea italiana nel novembre 2013, fidaxomicina [61,[72][73][74][75][76][77][78] rappresenta la molecola antibatterica oggi più avanzata e moderna. La sua farmacodinamica è caratterizzata da un'azione diretta e mirata sul C. difficile con un ridotto impianto sul resto del microbiota intestinale, che pertanto ne risulta risparmiato e protetto.…”

Section: Introduzioneunclassified

Fidaxomicin in the treatment of colitis due to Clostridium difficile: preliminary results

Cortese

Meledandri

Ballardini

et al. 2014

CMI

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5y sostenute, anche nello stesso ambito ospedaliero, da ceppi batterici differenti anche con diversa virulenza [21][22][23][24][25]; y complicanze di percorsi clinici intensivi, chirurgici, internistici spesso combinati tra loro [26][27][28][29][30][31][32]; y caratterizzate dalla necessità di intraprendere misure ospedaliere logistiche articolate come l'isolamento dei pazienti [33,34]; y causa di incremento dei costi di ricovero [35,36]. La CDI non è quasi mai un'infezione de novo, ma colpisce soggetti con patologie attive o nel decorso di procedure diagnosticooperative spesso articolate. Sono stati indi- INTRODUZIONEClostridium difficile è un bacillo Gram-positivo, anaerobio e sporigeno. La sua azione patogena si esplica nel 99% dei casi nella colite [1], che configura la Clostridium difficile Infection (CDI) [2][3][4]. Questa condizione rappresenta una vera e propria sindrome in costante e importante incremento in tutto il mondo occidentale [5][6][7][8][9]. Le CDI sono: y nella stragrande maggioranza dei casi infezioni nosocomiali di pazienti complessi nei quali aumentano morbilità e mortalità [10][11][12][13][14][15]; y causa di sindromi differenti con coefficienti di gravità diversi [16][17][18][19][20];

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A new macrocyclic antibiotic, fidaxomicin (OPT-80), causes less alteration to the bowel microbiota of Clostridium difficile-infected patients than does vancomycin

Cited by 194 publications

References 14 publications

Killing kinetics of fidaxomicin and its major metabolite, OP-1118, against Clostridium difficile

Killing kinetics of fidaxomicin and its major metabolite, OP-1118, against Clostridium difficile

Nisin is an effective inhibitor of Clostridium difficile vegetative cells and spore germination

Fidaxomicin in the treatment of colitis due to Clostridium difficile: preliminary results

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