Risk Factors Associated With Complications and Mortality in Patients With Clostridium difficile Infection

Morrison, Rosemary; Hall, Natalie S.; Said, Mina; Rice, Tamar; Groff, Harold L.; Brodine, Stephanie K.; Slymen, Donald J.; Lederman, Edith

doi:10.1093/cid/cir668

Cited by 83 publications

(59 citation statements)

References 17 publications

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“…Continued use of non-C. difficile antimicrobial treatment following CDAD diagnosis, Charlson comorbidity index score, and age were independently associated with development of complicated CDAD. Age Ͼ65 years has been related to all unfavorable outcomes and an increased risk of recurrent CDAD (37,38,39). Older patients have a greater number of comorbid conditions, and they often live in long-term facilities or have experienced previous prolonged hospitalizations, which facilitates C. difficile acquisition (27).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have examined the prognostic significance of gastric acid suppression in CDAD. Some have reported an association of PPI use with increased severity of CDAD and mortality (39), and others with an increased risk of recurrence (47,48). In contrast, Henrich et al (38) found no association between gastric acid suppression and severe CDAD.…”

Section: Discussionmentioning

confidence: 99%

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Epidemiology of Clostridium difficile Infection and Risk Factors for Unfavorable Clinical Outcomes: Results of a Hospital-Based Study in Barcelona, Spain

et al. 2013

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Epidemiology of Clostridium difficile Infection and Risk Factors for Unfavorable Clinical Outcomes: Results of a Hospital-Based Study in Barcelona, Spain

et al. 2013

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“…In contrast, the majority of studies report that the infection occurs more frequently in older people, but diabetes mellitus was not specifically addressed. 19 The reason for this difference in age is unknown but it might relate to an earlier and longer exposure to antibiotics. Abdominal pain but not fever was more significantly associated with hospital-acquired C. difficile infection in patients with T2DM.…”

Section: Discussionmentioning

confidence: 99%

Hospital-acquired Clostridium difficile infection among patients with type 2 diabetes mellitus in acute medical wards

Hassan

Rahman²,

Huda³

et al. 2013

J R Coll Physicians Edinb

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Background:Clostridum difficile (C. difficile) infection is increasingly seen among hospitalised patients with type 2 diabetes mellitus but its rate and associated risk factors are not known. We aimed to determine the rate and characteristics of hospital-acquired C. difficile infection in subjects with type 2 diabetes mellitus admitted into acute medical wards. Methods: Our prospective cross-sectional study involved 159 patients with established type 2 diabetes mellitus admitted into acute medical wards who developed a hospital-acquired C. difficile infection. Stools were tested for C. difficile toxins using a toxin A/B kit and a toxin A kit. Clinical features, laboratory findings, types of antibiotics, and use of a proton pump inhibitor were examined for their association with the infection. Results: Thirteen subjects were positive for toxin A and one for toxin B. Using univariable analysis, we found that patients with type 2 diabetes mellitus and hospitalacquired C. difficile infection were younger (mean 53.8 years, p=0.02), had diarrhoea and abdominal pain (p=0.001) but no fever. Sepsis (p=0.02) and use of a proton pump inhibitor (p=0.01) were more commonly implicated as the cause of the infection. Of the various types of antibiotics prescribed, carbapenem (28.6% vs 4.1%, p=0.01) and metronidazole (42.9% vs 19.3%, p=0.04) were significantly associated with hospitalacquired C. difficile infection. Conclusions: Patients with type 2 diabetes mellitus admitted into acute medical wards and who developed hospital-acquired C. difficile infection have distinct characteristics.

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“…Initial clinical cure (defined as no diarrhea for 2 consecutive days after completion of standard-of-care antibiotic therapy administered for ≤16 days) was an exploratory end point. Secondary analyses included the rate of recurrent C. difficile infection in the subgroup of participants in the modified intention-to-treat population who had an initial clinical cure, as well as in prespecified subgroups of participants with risk factors for recurrent C. difficile infection or for adverse outcomes related to C. difficile infection: an age of 65 years or older, 20,21 a history of C. difficile infection, 3,4 compromised immunity, 22,23 clinically severe C. difficile infection (defined as a Zar score ≥2; scores range from 1 to 8, with higher scores indicating more severe infection), 24 and infection with a strain associated with poor outcomes (strain 027, 20,25-27 078, 28 or 244 29,30 ). A secondary end point was the rate of sustained cure (i.e., initial clinical cure of the baseline episode of C. difficile infection and no recurrent infection through 12 weeks), also known as global cure or sustained clinical response.…”

Section: Prespecified End Pointsmentioning

confidence: 99%

Bezlotoxumab for Prevention of RecurrentClostridium difficileInfection

et al. 2017

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BACKGROUNDClostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODSWe conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTSIn both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea.: CONCLUSIONSAmong participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. 306T h e ne w e ngl a nd jou r na l o f m e dicine I n high-income countries, Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. 1,2 After completing initial antibiotic therapy, up to 35% of patients have recurrent C. difficile infection, 3,4 which is more difficult to treat and is associated with more hospitalizations, more severe outcomes, and higher costs than the first infection and a 50 to 60% chance of repeat recurrent infections. 5,6 Currently, no therapy has been approved to prevent recurrent C. difficile infection.Passive or active immunization against C. difficile toxins A and B is protective in animals that are challenged with toxigenic C. difficile, 7-9 which underscores the key importance of the toxins in causing the symptoms of C. difficile infection. The relative biologic importance of toxins A and B in C. difficile infection is controversial, but it may be host species-dependent. 10-12 Neutralization of both toxins appears to be necessary for maximal protection in rodents, but neutralization of toxin...

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Risk Factors Associated With Complications and Mortality in Patients With Clostridium difficile Infection

Abstract: Data published elsewhere have suggested that acid suppression therapy is a risk factor for CDI acquisition and relapse. These findings suggest an additional role in increased severity of disease, including mortality, and merit further study.

Cited by 83 publications

References 17 publications

Epidemiology of Clostridium difficile Infection and Risk Factors for Unfavorable Clinical Outcomes: Results of a Hospital-Based Study in Barcelona, Spain

Epidemiology of Clostridium difficile Infection and Risk Factors for Unfavorable Clinical Outcomes: Results of a Hospital-Based Study in Barcelona, Spain

Hospital-acquired Clostridium difficile infection among patients with type 2 diabetes mellitus in acute medical wards

Bezlotoxumab for Prevention of RecurrentClostridium difficileInfection

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