A 72-year-old woman with a history of spinal cord injury and resultant quadriplegia from a motor vehicle accident many years earlier presents to the emergency department with fevers, abdominal pain, and increased urinary frequency. She has a neurogenic bladder for which intermittent straight catheterization is performed at home. Over the past 2 years, she has been admitted to the hospital several times for recurrent urinary tract infections (UTIs), for which she has received intravenous antibiotic therapy. Her most recent admission, 3 months ago, was complicated by a diagnosis of nonsevere Clostridioides difficile infection, which was treated with fidaxomicin.

In the emergency department, she is febrile (temperature, 38.4°C) and her condition is hemodynamically stable. Examination reveals a tired-appearing woman with suprapubic tenderness and dry mucous membranes. She reports no diarrhea, nausea, or vomiting. Laboratory studies show a neutrophilic-predominant leukocytosis and mildly elevated creatinine level, and a straight-catheter urinalysis is consistent with infection. Urine culture is pending. As the admitting general medicine provider, you review her previous microbial data and note that cultures have never grown a multidrug-resistant organism. You decide to initiate intravenous ceftriaxone for treatment of her UTI, but you must also consider whether oral vancomycin should be administered prophylactically to reduce her risk of recurrent C. difficile infection.

Treatment Options

Which one of the following approaches would you take for this patient? Base your choice on the published literature, your own experience, published guidelines, and other information sources.

1. Recommend prophylactic oral vancomycin.
2. Do not recommend prophylactic oral vancomycin.

To aid in your decision making, we asked two experts in the field to summarize the evidence in favor of approaches assigned by the editors. Given your knowledge of the patient and the points made by the experts, which approach would you choose?

1. Option 1: Recommend Prophylactic Oral Vancomycin
2. Option 2: Do Not Recommend Prophylactic Oral Vancomycin.

Do Not Recommend Prophylactic Oral Vancomycin

Andrew M. Skinner, M.D., Erik R. Dubberke, M.D., M.S.P.H.

C. difficile is the most common cause of health care–associated infections in the United States, and clinicians and hospitals continually seek strategies to prevent it.⁶ One such strategy has been the use of oral vancomycin as secondary prophylaxis when patients receive systemic antibiotics.⁵ Oral vancomycin is effective at treating C. difficile infection, but owing to a paucity of evidence surrounding the use of oral vancomycin as secondary prophylaxis, the 2017 Infectious Diseases Society of America and Society for Healthcare Epidemiology of America (IDSA–SHEA) clinical practice guidelines for C. difficile infection provide no definitive recommendations.⁶ Concerns regarding oral vancomycin as secondary prophylaxis are the disruptive effect of oral vancomycin on the gut microbiome, which may increase the risk of future C. difficile infection, and the lack of high-quality data supporting the approach.

Oral vancomycin is highly disruptive to the gut microbiome.^7,8 Oral vancomycin causes greater depletion of the microbiome Firmicute population than third-generation cephalosporins.⁸ Firmicutes have been hypothesized to play a critical role in prevention of C. difficile infection.^6,7 A study in humans has shown that oral vancomycin, when administered with other antibiotics, causes disruption to the gut microbiome beyond that caused by the other antibiotics, which further contributes to delayed microbiome recovery and greater shedding of antibiotic-resistant organisms after antibiotics are discontinued.⁷ This additional disruption to the gut microbiome may actually increase the risk of C. difficile infection once oral vancomycin prophylaxis is discontinued and may explain the high incidence of recurrence when oral vancomycin is used to treat C. difficile infection. As such, careful monitoring of patients after discontinuation of secondary prophylaxis with oral vancomycin is essential to understand its true risk–benefit profile.

In addition, there are currently no robust randomized, controlled trial data to support the use of oral vancomycin as secondary prophylaxis.⁶ Existing literature on this treatment is fraught with biases.⁶ Many but not all studies suggest that secondary prophylaxis with oral vancomycin may reduce the risk of C. difficile infection during therapy. However, these studies frequently fail to adequately follow patients beyond discontinuation of oral vancomycin. Without such data, the studies lack a critical time frame during which patients would be at increased risk for C. difficile infection.⁶

Important features to keep in mind when considering the risk–benefit balance of secondary prophylaxis with oral vancomycin in the vignette include the patient’s 2-year history of recurrent UTIs but only one episode of C. difficile infection and the fact that the patient completed fidaxomicin treatment for that episode 3 months earlier. Microbiome recovery starts soon after antibiotics are stopped. Considering that the patient completed treatment with fidaxomicin, an agent that is more sparing of the gut microbiome than oral vancomycin, 3 months ago,⁹ her risk of C. difficile infection with this course of ceftriaxone should be no higher than it would be if she had never had C. difficile infection previously. We believe that the risk of additional microbiome disruption caused by prophylaxis and the risk of C. difficile infection after discontinuation of the regimen outweigh the potential benefit of preventing infection during treatment for the UTI.

Prevention of C. difficile infection remains a critical issue. Oral vancomycin is highly disruptive to the gut microbiome, more so than cephalosporins alone, which theoretically makes the risk of C. difficile infection once vancomycin is stopped higher than if it had never been administered.^7,8 Even tapering vancomycin may not provide benefit to prevent C. difficile infection after secondary prophylaxis with oral vancomycin.⁹ Given these factors, while we wait for results from randomized, well-controlled trials (e.g., ClinicalTrials.gov number, NCT03462459. opens in new tab), we would recommend against the use of oral vancomycin as secondary prophylaxis for this patient.

Recommend Prophylactic Oral Vancomycin

Jessica Allegretti, M.D., M.P.H.

Recurrent C. difficile infection occurs in about 20% of patients after an initial episode and can be a very challenging condition to treat. Preventive strategies are needed in high-risk patients in whom a recurrent episode could lead to serious complications. In the recently updated American College of Gastroenterology guidelines,¹ oral vancomycin was conditionally recommended as prophylaxis for C. difficile infection during subsequent systemic antibiotic courses in patients with a history of C. difficile infection who are at high risk for recurrence. Given the risk factors noted in the vignette, this woman would benefit from oral vancomycin prophylaxis.

The data to support this recommendation include several retrospective cohort studies in which oral vancomycin prophylaxis was used concurrently with systemic antibiotics to reduce the risk of relapse in patients with a history of C. difficile infection.² The largest of these studies evaluated 557 patients who had received systemic antibiotics within 30 days after diagnosis of a primary or recurrent episode of C. difficile infection.³ Various doses of oral vancomycin prophylaxis were provided to 227 patients for a mean duration of 7 days. In this study, oral vancomycin prophylaxis was found to be effective at preventing another C. difficile infection in patients with a history of recurrent infection (number needed to treat to prevent one infection, 7; P<0.001).³ Another retrospective study showed decreased recurrence of C. difficile infection in the oral vancomycin prophylaxis group as compared with the control group in patients who had had one previous episode.⁴ Finally, a meta-analysis of nine studies examining oral vancomycin prophylaxis for primary or secondary prevention showed that overall recurrence of C. difficile infection was less likely in patients who received oral vancomycin prophylaxis than in controls (odds ratio, 0.24; 95% confidence interval [CI], 0.13 to 0.48).⁵ The small sample sizes, varied doses and durations of oral vancomycin prophylaxis, and retrospective design are major limitations to these studies; however, given the overall safety profile of oral vancomycin, the benefits of prophylaxis can, in the right patient, outweigh the risks. Oral vancomycin prophylaxis should be considered in high-risk patients who have been recently treated for C. difficile infection and need subsequent treatment with systemic antibiotics. These high-risk patients include those 65 years of age or older, those with significant immunocompromise, and those hospitalized for severe C. difficile infection within the previous 3 months.

With regard to the patient in the vignette, I would proceed with oral vancomycin prophylaxis given her risk factors. She is a 72-year-old woman with a history of spinal cord injury and resultant neurogenic bladder who has presented with a recurrent UTI. She is likely to continue to need systemic antibiotics, given the need for intermittent straight catheterization and has several risk factors for recurrent C. difficile infection, including her age and her recent C. difficile infection diagnosis. Taken together, I believe the benefits for this patient outweigh the risks, and I would proceed with oral vancomycin prophylaxis.