Oral Vancomyin for Primary Clostridium Difficile Infection Prophylaxis in Patients Receiving High-Risk Antibiotics

Overview

The purpose of this study is to determine if oral vancomycin used as primary Clostridium difficile prophylaxis can reduce the incidence of this infection in high-risk patients.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: None (Open Label)
  • Study Primary Completion Date: May 2017

Detailed Description

Clostridium difficile infection is a common healthcare-associated infection and one that is associated with significant morbidity as well as a risk for mortality. Current practice throughout the United States is targeted at infection prevention measures such as hand washing and isolation. Despite these measures, incidence of Clostridium difficile infections continue to rise as some institutions, including our own. Recently, a study published in Clinical Infectious Diseases found oral vancomycin for secondary prophylaxis to reduce the incidence of recurrence. No studies to date have evaluated primary prophylaxis with oral vancomycin. This will be a single center, prospective study to evaluate oral vancomycin use as primary Clostridium difficile prophylaxis. Patients treated by infectious disease physicians will be identified as "high risk" and after pager notification the ID physician will have the option to start oral vancomycin 125 mg by mouth daily if they determine it to be appropriate. Risk factors include age older than 65 years, taking gastric acid suppression medication, and receiving select broad-spectrum antibiotics. Oral vancomycin will be continued until de-escalation of antibiotics or hospital discharge and patients will be evaluated for Clostridium difficile infection development from the current hospital admission up to 4 weeks following antibiotic discontinuation.

Interventions

  • Drug: Vancomycin Oral
    • This arm will receive oral vancomycin 125 mg daily if “high risk” and determined to be appropriate by an ID physician

Arms, Groups and Cohorts

  • No Intervention: Control
    • This will be the historical arm that has not received oral vancomycin but match criteria for “high risk”
  • Experimental: Vancomycin Oral
    • This arm will receive oral vancomycin 125 mg daily if “high risk” and determined to be appropriate by an ID physician Intervention type: drug, vancomycin 125 mg daily

Clinical Trial Outcome Measures

Primary Measures

  • Clostridium Difficile Infection Occurrence
    • Time Frame: Within 4 weeks from the completion of antibiotic treatment
    • The incidence of clostridium difficile infection as detected for GDH/toxin positive or PCR if the GDH/toxin is equivocal.

Secondary Measures

  • Time to Clostridium Difficile Infection Occurence
    • Time Frame: Within 4 weeks from completion of antibiotic treatment
    • This is the time from the start of antibiotics to the diagnosis of clostridium difficile.
  • Clostridium Difficile Infection Severity
    • Time Frame: Within 4 weeks from completion of antibiotic treatment
    • Severity as defined by the IDSA/SHEA guidelines (mild to moderate, defined as white-cell count less than 15,000 cells/µL or increase in serum creatinine (SCr) by <1.5 times the baseline; severe, defined as white-cell count greater than 15,000 cells/µL or increase in SCr by >1.5 times the baseline; and fulminant, defined as the criteria above for severe with shock, hypotension, ileus, or megacolon)

Participating in This Clinical Trial

Inclusion Criteria

  • "High-risk" patients defined as: age older than 65, on gastric acid suppression, and select antibiotics – Gastric acid suppression includes proton pump inhibitors and histamine-2 receptor antagonists – Selected antibiotics include fluoroquinolone (ciprofloxacin, levofloxacin), clindamycin, a 3rd or 4th generation cephalosporin, a broad-spectrum aminopenicillin (ampicillin-sulbactam, piperacillin-tazobactam), or a carbapenem Exclusion Criteria:

  • Failure to meet all three requirements for "high risk" – Vancomycin allergy – Active clostridium difficile infection prior to inclusion – Prophylactic oral vancomycin prior to study inclusion (i.e. prolonged vancomycin taper) – Receipt of medications that also treat Clostridium difficile (metronidazole, rifaximin, fidaxomicin) – Pregnant or breastfeeding

Gender Eligibility: All

Minimum Age: 65 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • St. Luke’s Hospital, Chesterfield, Missouri
  • Provider of Information About this Clinical Study
    • Principal Investigator: Ryan Medas, PGY2 Pharmacy Internal Medicine Resident – St. Luke’s Hospital, Chesterfield, Missouri
  • Overall Official(s)
    • Ryan E Medas, PharmD, Principal Investigator, St. Luke’s Hospital

References

Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, Farley MM, Holzbauer SM, Meek JI, Phipps EC, Wilson LE, Winston LG, Cohen JA, Limbago BM, Fridkin SK, Gerding DN, McDonald LC. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015 Feb 26;372(9):825-34. doi: 10.1056/NEJMoa1408913.

O'Brien JA, Lahue BJ, Caro JJ, Davidson DM. The emerging infectious challenge of clostridium difficile-associated disease in Massachusetts hospitals: clinical and economic consequences. Infect Control Hosp Epidemiol. 2007 Nov;28(11):1219-27. doi: 10.1086/522676. Epub 2007 Oct 3.

Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC, Pepin J, Wilcox MH; Society for Healthcare Epidemiology of America; Infectious Diseases Society of America. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol. 2010 May;31(5):431-55. doi: 10.1086/651706.

Owens RC Jr, Donskey CJ, Gaynes RP, Loo VG, Muto CA. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis. 2008 Jan 15;46 Suppl 1:S19-31. doi: 10.1086/521859.

Magill SS, Edwards JR, Bamberg W, Beldavs ZG, Dumyati G, Kainer MA, Lynfield R, Maloney M, McAllister-Hollod L, Nadle J, Ray SM, Thompson DL, Wilson LE, Fridkin SK; Emerging Infections Program Healthcare-Associated Infections and Antimicrobial Use Prevalence Survey Team. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014 Mar 27;370(13):1198-208. doi: 10.1056/NEJMoa1306801. Erratum In: N Engl J Med. 2022 Jun 16;386(24):2348.

Marra F, Ng K. Controversies Around Epidemiology, Diagnosis and Treatment of Clostridium difficile Infection. Drugs. 2015 Jul;75(10):1095-118. doi: 10.1007/s40265-015-0422-x.

Van Hise NW, Bryant AM, Hennessey EK, Crannage AJ, Khoury JA, Manian FA. Efficacy of Oral Vancomycin in Preventing Recurrent Clostridium difficile Infection in Patients Treated With Systemic Antimicrobial Agents. Clin Infect Dis. 2016 Sep 1;63(5):651-3. doi: 10.1093/cid/ciw401. Epub 2016 Jun 17.

Johnson S. Editorial Commentary: Potential Risks and Rewards With Prophylaxis for Clostridium difficile Infection. Clin Infect Dis. 2016 Sep 1;63(5):654-5. doi: 10.1093/cid/ciw424. Epub 2016 Jun 28. No abstract available.

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