Abstract
Background Fecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridium difficile infection (CDI). However, in 12% of patients treated with FMT, CDI recurs within one month. Zinc deficiency predicts increased diarrheal frequency in malnourished children, but little is known about its association with FMT outcome. We hypothesized that zinc levels were an independent predictor of CDI recurrence after FMT. Methods We performed a retrospective cohort study of 80 patients (mean age, 66; 59 women) receiving FMT for CDI from 9/2013–9/2016 at a tertiary care center. Zinc levels were measured within 90 days before FMT. The primary outcome was CDI recurrence within 90 days after FMT. We controlled for risk factors for FMT failure using Cox regression. We also analyzed the effect of zinc supplementation in individuals with deficiency. Results Forty-nine subjects had a normal zinc level, and 31 had a low level (<0.66 µg/mL). CDI recurred in 3/49 (6%) patients with normal zinc and 5/31 (16%) patients with low zinc (HR = 11.327, 95% CI = 2.162–59.336, p=0.004). Among low zinc subjects, 2 of 25 (8%) that received zinc supplements and 3 of 6 (50%) that did not receive zinc supplements had recurrence of CDI (HR = 0.102, 95% CI = 0.015–0.704, p=0.021). Conclusion Zinc deficiency was associated with increased CDI recurrence after FMT. Among zinc-deficient patients, supplementation was associated with reduced recurrence. Further study is needed to determine whether zinc deficiency represents a pathophysiologic mechanism and target for therapy.
Highlights
Clostridium difficile infection (CDI) is a leading cause of healthcare-associated illness. e incidence of CDI in hospitalized adults in the US nearly doubled from 2001 to 2010, increasing from 4.5/1,000 to 8.2/1,000 [1]
Measurement of serum zinc was included in the routine clinical evaluation of patients with recurrent CDI as many of these patients had a history of chronic diarrhea, inflammatory bowel disease (IBD), and/or elderly age, all risk factors for zinc deficiency [12]. is study was approved by the University of Virginia Institutional Review Board, and all data were collected via examination of electronic medical records
A total of 127 patients were treated with Fecal microbiota transplant (FMT) for CDI at our institution between September 2013 and September 2016; 95 patients had zinc levels measured within 90 days pre-FMT, and 80 met study criteria (Table 1). e population mean age was 66 and included 59 (74%) women and 21 (26%) men
Summary
Clostridium difficile infection (CDI) is a leading cause of healthcare-associated illness. e incidence of CDI in hospitalized adults in the US nearly doubled from 2001 to 2010, increasing from 4.5/1,000 to 8.2/1,000 [1]. Initial CDI classically occurs following use of antibiotics and results from the inadvertent eradication of gut microbes less resilient than spore-forming C. difficile [3]. As many of these microbes and their metabolites serve to suppress C. difficile, their removal from the microbiome facilitates the disproportionate and deleterious expansion of toxinforming C. difficile strains, leading to CDI [3]. Fecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridium difficile infection (CDI). In 12% of patients treated with FMT, CDI recurs within one month. We hypothesized that zinc levels were an independent predictor of CDI recurrence after FMT. Zinc deficiency was associated with increased CDI recurrence after FMT. Further study is needed to determine whether zinc deficiency represents a pathophysiologic mechanism and target for therapy
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