Comparative Effectiveness ofClostridium difficileTreatments

Drekonja, Dimitri; Butler, Mary; MacDonald, Roderick; Bliss, Donna Z; Filice, Gregory; Rector, Thomas S.; Wilt, Timothy J

doi:10.7326/0003-4819-155-12-201112200-00007

Cited by 103 publications

(77 citation statements)

References 36 publications

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“…The recurrence rate was previously shown to range from 7% to 17% with vancomycin and from 5% to 21% for metronidazole. 15) Monaghan et al reported previously that recurrent disease occurred in 15-35% of CDI patients. 17) Nevertheless, it remains unclear why patients are at risk of failure of the drug treatment and recurrence.…”

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confidence: 95%

“…14) A systematic review revealed that the percentage of patients initially cured with vancomycin and metronidazole ranged from 84% to 94% and from 73% to 94%, respectively. 15) Zar et al suggested that metronidazole and vancomycin were equally effective in the treatment of mild CDI, but that vancomycin was superior for treating patients with severe CDI. 16) However, these treatments are unsuccessful in some patients, and recurrence has been reported in other patients that had been treated successfully.…”

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confidence: 99%

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Factors Affecting Treatment and Recurrence of Clostridium difficile Infections

Matsumoto

Kanazawa

Shigemi

et al. 2014

Biological & Pharmaceutical Bulletin

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The antimicrobial agents vancomycin and metronidazole have been used to treat Clostridium difficile infections (CDIs). However, it remains unclear why patients are at risk of treatment failure and recurrence. Therefore, this study retrospectively examined 98 patients with CDIs who were diagnosed based on the detection of toxin-positive C. difficile to determine the risk factors affecting drug treatment responses and the recurrence of CDI. No significant difference was observed in the cure rate or dosage between the vancomycin and metronidazole groups. The 90-d mortality rate and total number of drugs associated with CDIs, including antiinfective agents used within 2 months before the detection of toxin-positive C. difficile, were significantly lower in the treatment success group than in the failure group. The total number of antiinfective agents and gastric acid-suppressive agents used during CDI therapy was also significantly lower in the success group than in the failure group. The period from the completion of CDI therapy to restarting the administration of anticancer agents and steroids was significantly longer in patients without than in patients with recurrence. These results indicate that the total number of drugs associated with CDIs should be minimized to reduce the risk of CDIs, that not only antibiotics but also gastric acid-suppressive agents should be discontinued during CDI therapy to increase therapeutic efficacy, and that the use of anticancer agents and steroids should be delayed as long as possible after patients are cured by CDI therapy to prevent recurrence.

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confidence: 95%

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confidence: 99%

Factors Affecting Treatment and Recurrence of Clostridium difficile Infections

Matsumoto

Kanazawa

Shigemi

et al. 2014

Biological & Pharmaceutical Bulletin

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“…The toxins result in an inflammatory immune response, with symptoms ranging from diarrhea to pseudomembranous colitis or sepsis (7)(8)(9)(10). CDI is recalcitrant to therapy with multiple antibiotics and has a high rate of recurrence, with 10 to 20% of patients experiencing reemergent symptoms after cessation of treatment (9,11).…”

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confidence: 99%

Regulation of Type IV Pili Contributes to Surface Behaviors of Historical and Epidemic Strains of Clostridium difficile

et al. 2016

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The intestinal pathogen Clostridium difficile is an urgent public health threat that causes antibiotic-associated diarrhea and is a leading cause of fatal nosocomial infections in the United States. C. difficile rates of recurrence and mortality have increased in recent years due to the emergence of so-called "hypervirulent" epidemic strains. A great deal of the basic biology of C. difficile has not been characterized. Recent findings that flagellar motility, toxin synthesis, and type IV pilus (TFP) formation are regulated by cyclic diguanylate (c-di-GMP) reveal the importance of this second messenger for C. difficile gene regulation. However, the function(s) of TFP in C. difficile remains largely unknown. Here, we examine TFP-dependent phenotypes and the role of c-di-GMP in controlling TFP production in the historical 630 and epidemic R20291 strains of C. difficile. We demonstrate that TFP contribute to C. difficile biofilm formation in both strains, but with a more prominent role in R20291. Moreover, we report that R20291 is capable of TFP-dependent surface motility, which has not previously been described in C. difficile. The expression and regulation of the pilA1 pilin gene differs between R20291 and 630, which may underlie the observed differences in TFP-mediated phenotypes. The differences in pilA1 expression are attributable to greater promoter-driven transcription in R20291. In addition, R20291, but not 630, upregulates c-di-GMP levels during surface-associated growth, suggesting that the bacterium senses its substratum. The differential regulation of surface behaviors in historical and epidemic C. difficile strains may contribute to the different infection outcomes presented by these strains. IMPORTANCEHow Clostridium difficile establishes and maintains colonization of the host bowel is poorly understood. Surface behaviors of C. difficile are likely relevant during infection, representing possible interactions between the bacterium and the intestinal environment. Pili mediate bacterial interactions with various surfaces and contribute to the virulence of many pathogens. We report that type IV pili (TFP) contribute to biofilm formation by C. difficile. TFP are also required for surface motility, which has not previously been demonstrated for C. difficile. Furthermore, an epidemic-associated C. difficile strain showed higher pilin gene expression and greater dependence on TFP for biofilm production and surface motility. Differences in TFP regulation and their effects on surface behaviors may contribute to increased virulence in recent epidemic strains.

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“…The mean duration of diarrhea is three to four days, with most cases re solving by day 7. 1,5 Persistent diarrhea warrants considering alternative causes. Retesting the stool is discouraged, because the organism and its associated toxins can persist long after symptoms have resolved.…”

Section: How Does the Physician Know Whether The Treatment Is Working?mentioning

confidence: 99%

“…Rifaximin, a minimally absorbed oral macrolide, given for two weeks after a course of vancomycin, has decreased the risk of recurrence in patients with repeated relapses. 5 Observational studies have suggested that fecal transplant is highly effective in reducing recurrence; 1 however, to date, there are no standardized regimens or published randomized trials evaluating this therapy.…”

Section: What Are Novel Strategies For Managing C Difficile Infection?mentioning

confidence: 99%

A woman with community-acquired Clostridium difficile infection

Kandel

Moayedi

Bunce

2012

CMAJ

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A 66-year-old woman who recently completed a course of levofloxacin to treat community-acquired pneumonia presents to her family physician with a two-day history of watery diarrhea. Her stool tests positive for Clostridium difficile toxin. She takes pantoprazole daily for symptoms of dyspepsia and is otherwise healthy. You consider the relevant components of managing her case. What are this patient's risk factors for C. dif ficile infection?The patient's history includes multiple risk factors for C. difficile infection. The most recognized modifiable risk factor for such infections is the use of antibiotic agents in the preceding three months.

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Comparative Effectiveness ofClostridium difficileTreatments

Abstract: U.S. Department of Health and Human Services.

Cited by 103 publications

References 36 publications

Factors Affecting Treatment and Recurrence of <i>Clostridium difficile</i> Infections

Factors Affecting Treatment and Recurrence of <i>Clostridium difficile</i> Infections

Regulation of Type IV Pili Contributes to Surface Behaviors of Historical and Epidemic Strains of Clostridium difficile

A woman with community-acquired Clostridium difficile infection

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