OPT-80 Eliminates
 Clostridium difficile
 and Is Sparing of
 Bacteroides
 Species during Treatment of
 C. difficile
 Infection

Louie, Thomas; Emery, Judy; Krulicki, Walter; Byrne, Brendan; Mah, Manuel W.

doi:10.1128/aac.01443-07

Cited by 176 publications

(134 citation statements)

References 10 publications

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“…Such an alternate strategy requires the utilization of narrow-spectrum antimicrobials. Indeed, the fact that the novel macrocycle OPT-80 eliminates C. difficile without impacting on members of the Bacteroides species (Bacteroides fragilis group) was regarded as noteworthy in a recent study (34). Culture-based techniques confirmed the narrow-spectrum nature of thuricin CD, in that it was not effective against a number of commercially important probiotic strains.…”

Section: Discussionmentioning

confidence: 88%

Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon

Rea

Dobson

O'Sullivan

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

329

263

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Vancomycin, metronidazole, and the bacteriocin lacticin 3147 are active against a wide range of bacterial species, including Clostridium difficile. We demonstrate that, in a human distal colon model, the addition of each of the three antimicrobials resulted in a significant decrease in numbers of C. difficile. However, their therapeutic use in the gastrointestinal tract may be compromised by their broad spectrum of activity, which would be expected to significantly impact on other members of the human gut microbiota. We used highthroughput pyrosequencing to compare the effect of each antimicrobial on the composition of the microbiota. All three treatments resulted in a decrease in the proportion of sequences assigned to the phyla Firmicutes and Bacteroidetes, with a corresponding increase in those assigned to members of the Proteobacteria. One possible means of avoiding such "collateral damage" would involve the application of a narrow-spectrum antimicrobial with specific anti-C. difficile activity. We tested this hypothesis using thuricin CD, a narrowspectrum bacteriocin produced by Bacillus thuringiensis, which is active against C. difficile. The results demonstrated that this bacteriocin was equally effective at killing C. difficile in the distal colon model but had no significant impact on the composition of the microbiota. This offers the possibility of developing a targeted approach to eliminating C. difficile in the colon, without collateral damage.gut microbiota | pyrosequencing | bacteriocin | antibiotic | thuricin

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Section: Discussionmentioning

confidence: 88%

Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon

Rea

Dobson

O'Sullivan

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

329

263

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“…33,34 It should be noted that rifaximin is not a widely accepted treatment modality and that there are concerns regarding the development of resistance to the medication. 40,41 Another antibiotic that holds promise for the treatment of RCDI is fidaxomicin (OPT-80). Studies using fidaxomicin as a treatment agent have shown equivalence to vancomycin in the treatment of primary CDI but with less alteration of the normal gut flora.…”

Section: Antibiotic Regimensmentioning

confidence: 99%

Management and Prevention of Recurrent Clostridium Difficile Infection in Patients After Total Joint Arthroplasty

Stein

Greenough

Mears

2012

Geriatr Orthop Surg Rehabil

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Clostridium difficile infection (CDI) is the most common infectious cause of nosocomial diarrhea in elderly patients, accounting for 15% to 25% of all cases of antibiotic-induced diarrhea in those patients. Virulent forms of this organism have developed, increasing the associated morbidity, mortality, and complication rates. The average patient undergoing total joint arthroplasty is at particular risk of CDI because of advanced age, the use of prophylactic antibiotic coverage in the perioperative period, multiple comorbid conditions, and length of hospital stay. In addition, patients who have had one CDI are at risk of another; the rate of recurrent CDI (RCDI) is 15% to 30%. To review the available information on RCDI, we conducted an extensive literature search, focusing on its epidemiology and the management strategies for its treatment and prevention. We found the management of RCDI is a controversial topic, with as yet no consensus regarding specific treatment guidelines. Several experienced clinicians have published suggested treatment algorithms, but they are based on anecdotal experience. With regard to the prevention of RCDI, the literature is scarce, and currently, the only effective strategies remain judicious use of perioperative antibiotics and appropriate implementation of infection control procedures. There are several vaccination medications that are currently being studied but are not yet ready for clinical use. We agree with the approach to management of RCDI that has been proposed in several articles, that is, on confirmation of a first recurrence of CDI by a stool toxin assay and clinical symptoms, a 14-day course of metronidazole or vancomycin; for a second recurrence, a tapered-pulsed course of vancomycin; and, for 3 or more recurrences, a repeat course of the tapered-pulsed vancomycin and adjunctive Saccharomyces boulardii or cholestyramine.

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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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OPT-80 Eliminates Clostridium difficile and Is Sparing of Bacteroides Species during Treatment of C. difficile Infection

Cited by 176 publications

References 10 publications

Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon

Effect of broad- and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon

Management and Prevention of Recurrent Clostridium Difficile Infection in Patients After Total Joint Arthroplasty

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

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