Version May 2024
INTRODUCTION — Clostridioides difficile is an important cause of antibiotic-associated diarrhea and one of the most common health care-associated pathogens [1]. Its clinical manifestations range from asymptomatic colonization or mild diarrhea to fulminant disease characterized by ileus, toxic megacolon, hypotension, or shock. C. difficile infection is less common in children than adults, but the incidence of C. difficile infection in children is increasing [2-5].
The treatment of and outcomes associated with C. difficile infection in children will be discussed here. The pathogenesis, epidemiology, clinical features, diagnosis, and prevention of C. difficile in children and C. difficile in adults are discussed separately:
●(See "Clostridioides difficile infection in children: Microbiology, pathogenesis, and epidemiology".)
●(See "Clostridioides difficile infection in children: Clinical features and diagnosis".)
●(See "Clostridioides difficile infection: Prevention and control".)
●(See "Clostridioides difficile infection in adults: Epidemiology, microbiology, and pathophysiology".)
●(See "Clostridioides difficile infection in adults: Clinical manifestations and diagnosis".)
●(See "Clostridioides difficile infection in adults: Treatment and prevention".)
There is limited high-quality evidence to guide the management of C. difficile infection in children. Most treatment recommendations are extrapolated from studies performed in adults. The treatment guidelines presented below are largely compatible with the recommendations of the American Academy of Pediatrics Committee on Infectious Diseases (2021) [6], the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America (2017) [7], and the American College of Gastroenterology (2021) [8].
GENERAL MEASURES
Discontinuation of inciting antibiotics — Discontinuation of the inciting antibiotic, when possible, is important in the management of C. difficile infection [6,7,9]. The use of concomitant antibiotics (ie, antibiotics other than those used to treat C. difficile) during treatment for C. difficile infection has been shown to prolong the duration of symptoms and increase the risk of recurrence in adults [10]. In children, the use of concomitant antibiotics has been associated with recurrent disease [11]. If an ongoing infection requires continued antibiotic treatment, we suggest modifying therapy to achieve the narrowest spectrum and shortest duration possible. (See "Clostridioides difficile infection in children: Microbiology, pathogenesis, and epidemiology", section on 'Antibiotic exposure'.)
Supportive care — Supportive care for children with diarrhea from C. difficile includes correction of fluid losses and electrolyte imbalances [9,12]. (See "Clinical assessment of hypovolemia (dehydration) in children" and "Treatment of hypovolemia (dehydration) in children in resource-abundant settings".)
Antimotility drugs (eg, loperamide) and opioids are discouraged due to concerns they may delay clearance of toxins and predispose to complications such as ileus or toxic megacolon, although this association has not been observed in clinical studies [13].
Indications for hospitalization — Children with fulminant disease (table 1) should be hospitalized. Hospitalization may be warranted for children with dehydration, electrolyte abnormalities, moderate to marked toxicity, or severe disease (table 1). Recommendations for the prevention of C. difficile infection in hospital settings are discussed separately. (See "Clostridioides difficile infection: Prevention and control", section on 'Prevention strategies'.)
Consultation with specialists in infectious diseases, gastrointestinal disease, and/or surgery may be warranted for children with severe or fulminant disease.
Indications for antimicrobial therapy — We initiate antimicrobial therapy in children with symptomatic C. difficile infection (table 2) [6,7]. The antimicrobial regimen depends upon the severity of disease (table 1). (See 'Mild or moderate disease' below and 'Severe disease' below and 'Fulminant disease' below.)
Empiric antimicrobial therapy, pending results of C. difficile testing, is not routinely recommended but may be warranted if there is a delay in laboratory confirmation or for severe or fulminant disease (table 2) [7,14].
Antimicrobial therapy is not indicated in children with asymptomatic colonization with C. difficile [6,7]. In a randomized trial of asymptomatic adults colonized with C. difficile, treatment with metronidazole had no effect on colonization status. Treatment with vancomycin, while temporarily effective in eradicating detectable colonization, was associated with increased rates of carriage two months after therapy [15].
ANTIMICROBIAL THERAPY FOR INITIAL EPISODE
Mild or moderate disease — The majority of children with C. difficile infection have mild to moderate disease (table 1). Inciting antibiotics should be discontinued if possible and supportive measures provided as indicated. (See 'General measures' above.)
For the initial episode of C. difficile infection in children and adolescents with mild or moderate disease (table 1), we suggest treatment with oral vancomycin, metronidazole, or fidaxomicin (table 3) [6,7,16]. Although most published guidelines only include vancomycin or metronidazole for mild to moderate nonrecurrent C. difficile infection in children, the US Food and Drug Administration approved the use of fidaxomicin for C. difficile infection in children in 2020.
The regimens are as follows:
●Vancomycin 40 mg/kg per day orally in four divided doses (maximum 125 mg/dose) for 10 days, or
●Metronidazole 30 mg/kg per day orally in four divided doses (maximum 500 mg/dose) for 10 days, or
●Fidaxomicin is dosed according to body weight as follows:
•4 to <7 kg (oral suspension) – 80 mg orally twice daily for 10 days
•7 to <9 kg (oral suspension) – 120 mg orally twice daily for 10 days
•9 to <12.5 kg (oral suspension) – 160 mg orally twice daily for 10 days
•≥12.5 kg (oral suspension or tablets) – 200 mg orally twice daily for 10 days
Prospective studies comparing metronidazole and vancomycin for the treatment of C. difficile infection in children are lacking. Accumulated experience suggests that children with C. difficile infection have good outcomes, including similar rates of recurrence, with either oral metronidazole or vancomycin [7,17-19]. In a meta-analysis of seven retrospective observational studies (pooled total of 433 cases), cure rates were higher with vancomycin; however, this was not statistically significant (odds ratio 0.63, 95% CI 0.36-1.10) [20].
Randomized trials including adult patients have found vancomycin to be superior to metronidazole [7,21,22]. In a 2017 meta-analysis of four randomized trials including 872 adult patients with nonsevere C. difficile infection [21-24], vancomycin was slightly more effective than metronidazole at achieving symptomatic cure without recurrence (79 versus 72 percent, risk ratio 0.90, 95% CI 0.84-0.97) [25].
Fidaxomicin and vancomycin for the treatment of C. difficile infection in children (initial or recurrent) were compared in a randomized trial in 142 children [26]. Clinical response rates at 12 days were similar (77.6 versus 70.5 percent, adjusted difference 7.5 percent [95% CI -7.4 to 23.9]). However, the rate of recurrence in the 30 days after completion of therapy was lower with fidaxomicin (11.8 versus 29.0 percent; adjusted difference -15.8 [95% CI -34.5 to 0.5]). In pooled analysis of four randomized control trials comparing fidaxomicin and vancomycin (standard dose) in adults, fidaxomicin increased sustained response of C. difficile infection after completion of therapy [27].
Other considerations when choosing between these drugs are provided below:
●Vancomycin – Vancomycin use is limited by its greater cost and concerns for promoting the intestinal carriage of vancomycin-resistant enterococci (VRE). However, the risk of subsequent intestinal colonization with VRE appears to be similar with vancomycin and metronidazole [28].
Vancomycin achieves very high fecal concentrations when administered orally because it is not absorbed. It maintains high concentrations throughout the duration of treatment [15]. The oral formulation of vancomycin is more expensive than metronidazole; thus, some hospitals use the generic intravenous (IV) formulation for oral administration [7].
●Metronidazole – Metronidazole is not labeled for the treatment of C. difficile infection in children. It is less expensive than vancomycin [7]. The risk of intestinal colonization with VRE appears to be similar with metronidazole and vancomycin [28].
Metronidazole is rapidly absorbed when administered orally; effective fecal concentrations are achieved through biliary excretion and secretion across inflamed intestinal mucosa. Fecal concentrations peak early in illness and decline as symptoms improve [29]. Metronidazole is undetectable in the stool of asymptomatic carriers [15]. C. difficile strains with decreased susceptibility to metronidazole are rare [30-32]. The use of metronidazole is limited by its metallic taste and side effects, primarily nausea and peripheral neuropathy (associated with prolonged administration or cumulative exposure).
●Fidaxomicin – Fidaxomicin is a macrolide antibiotic that has little gastrointestinal absorption [33,34]. It appears to be safe and effective in children, but data are limited [26]. Fidaxomicin is orally administered with minimal systemic absorption and highly active against C. difficile in vitro. It is also a "narrow spectrum" agent with more limited activity against enteric commensal bacteria than either metronidazole or vancomycin. Use is limited by higher cost [27]. In the United States, fidaxomicin is available for the treatment of C. difficile-associated diarrhea in people ≥6 months of age [34].
Severe disease — For the initial episode of C. difficile infection in children and adolescents with severe disease (table 1), we suggest treatment with oral vancomycin rather than other agents (table 3):
●Vancomycin 40 mg/kg per day orally in four divided doses (maximum 125 mg/dose)
The standard duration of treatment for C. difficile infection is 10 days, though the course should be tailored to clinical response.
We prefer vancomycin to metronidazole for severe disease because of the increased risk of treatment failure with metronidazole in randomized and observational studies of adult patients [21,35-38].
We prefer vancomycin to fidaxomicin for severe disease in children because we have greater clinical experience with vancomycin in children. However, for patients ≥18 years of age, expert groups suggest either fidaxomicin or vancomycin [8,27]. (See "Clostridioides difficile infection in adults: Treatment and prevention", section on 'Severe disease'.)
Fulminant disease
●Fulminant disease in children who can tolerate oral therapy – For the initial episode of C. difficile infection in children and adolescents with fulminant disease (table 1) who can tolerate oral therapy, we suggest treatment with the combination of IV metronidazole and oral vancomycin (table 3):
•Metronidazole 30 mg/kg per day in three divided doses (maximum 500 mg/dose) for 10 days, plus:
•Vancomycin 40 mg/kg per day by mouth in four divided doses (maximum 500 mg/dose until clinical improvement and then, if applicable, decrease the maximum dose to 125 mg to complete 10 days)
Although the standard duration of treatment for C. difficile infection is 10 days, the course should be tailored to clinical response.
We obtain serum vancomycin levels in children with fulminant disease who are receiving high-dose vancomycin (maximum 500 mg/dose) because systemic absorption can occur in patients with severe colitis [39].
Using an increased maximum dose of vancomycin for children with fulminant disease is suggested in the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America clinical practice guidelines for C. difficile infection in adults and children [7]. However, there are limited data to support the efficacy of this approach.
●Fulminant disease in children who cannot tolerate oral therapy – For the initial episode of C. difficile infection in children and adolescents with fulminant disease (table 1) who cannot tolerate oral therapy (eg, ileus, toxic megacolon), we suggest treatment with the combination of IV metronidazole and rectal vancomycin (table 3). Biliary and intestinal excretion of parenteral metronidazole achieve therapeutic concentrations of metronidazole in the stool [29]. Rectal vancomycin is added because monotherapy with IV metronidazole is less effective than oral metronidazole or oral vancomycin [40].
We use the following regimen:
•Metronidazole 30 mg/kg per day in three divided doses (maximum 500 mg/dose) for 10 days, plus:
•Vancomycin 10 mg/kg per dose in normal saline (maximum dose 500 mg in 100 mL normal saline) administered by retention enema four times per day for 10 days; the volume of solution varies with age [7]:
-1 through 4 years – 50 mL
-5 through 11 years – 75 mL
-≥12 years – 100 mL
Although the standard duration of treatment for C. difficile infection is 10 days, the course should be tailored to clinical response.
The optimal dose and volume for rectal vancomycin has not been established for children or adults; the dose used in published case series varies widely [41]. Dose and volume adjustments may be required depending upon individual circumstances, extent of colonic disease, and patient weight. Caution is required because perforation is possible with rectal installation of vancomycin.
We obtain serum vancomycin levels in children with fulminant disease who are receiving vancomycin via retention enema because systemic absorption can occur in patients with severe colitis [39].
SURGICAL THERAPY FOR FULMINANT DISEASE — Surgery (ie, subtotal colectomy, diversion ileostomy) may be required as a life-saving measure for severely ill children with toxic megacolon, colonic perforation, acute abdomen, or septic shock. The indications for surgery in children with fulminant disease from C. difficile infection are not well established. Subtotal or total colectomy is most often performed, although colon-sparing surgical techniques have been described [42,43].
RESPONSE TO TREATMENT — The response to treatment of C. difficile infection is assessed clinically. In patients with mild to moderate disease, symptoms generally improve within 48 to 72 hours after initiation of antibiotic therapy, but diarrhea may not fully resolve for four to five days [12,44]. Responses may be slower with metronidazole or with infection from the NAP1/BI/027 strain [45,46].
Follow-up testing for C. difficile is not recommended because patients can remain colonized with toxin-producing strains after recovery [6].
Patients remain vulnerable to recurrence of C. difficile infection for up to eight weeks (or longer) following treatment [47]. A recurrence of gastrointestinal symptoms requires evaluation. (See 'Management of recurrence' below.)
MANAGEMENT OF TREATMENT FAILURE — Treatment failure is defined as progression of disease or failure to improve after several days of therapy [12]. A minority of children with C. difficile infection fail to respond to treatment [18,48,49].
Among children with C. difficile infection and ongoing symptoms despite treatment, a proportion will have underlying gastrointestinal disorders [18]. Ongoing symptoms can also be caused by coinfection with an additional enteric pathogen. Children with progression of disease or failure to improve after three to four days of antibiotic therapy should be evaluated (or reevaluated) for other causes of diarrhea. The possibility of an underlying predisposing condition must also be considered. (See "Clostridioides difficile infection in children: Clinical features and diagnosis", section on 'Differential diagnosis' and "Clostridioides difficile infection in children: Microbiology, pathogenesis, and epidemiology", section on 'Predisposing conditions'.)
The optimal management of refractory C. difficile infection in children is not established. If another etiology cannot be identified, we suggest discontinuing the inciting antibiotic (if this has not already occurred) and switching to vancomycin or fidaxomicin in patients that fail to respond to treatment with metronidazole. For children who fail initial treatment with vancomycin or fidaxomicin, we evaluate for other causes of diarrhea.
MANAGEMENT OF RECURRENCE — Recurrent C. difficile infection is a return of symptoms with a positive assay result after a period of symptom resolution that occurs within eight weeks of the initial episode (typically within one to three weeks) [7,50,51]. (See "Clostridioides difficile infection in children: Clinical features and diagnosis", section on 'Recurrent infection'.)
First recurrence — The signs and symptoms of recurrence are similar to those in the initial episode. Investigation for other causes of diarrhea may be warranted because a return of diarrhea is not always due to a recurrence of C. difficile infection. Since persistence of C. difficile is common after effective treatment, a positive C. difficile test may represent colonization.
For children with a first recurrence, a second course of treatment with the same antibiotic (either vancomycin, metronidazole, or fidaxomicin) is suggested (table 3) [6,7]. (See "Clostridioides difficile infection in children: Clinical features and diagnosis", section on 'Differential diagnosis'.)
Subsequent recurrences — The optimal management of multiple recurrence of C. difficile infection is not established and clinical practice varies [52]. Metronidazole is not recommended for the treatment of a second (or subsequent) recurrence or for prolonged therapy due to the risk of neurotoxicity [6].
Among the available options for treatment of subsequent recurrences of C. difficile infection in children, we suggest either oral vancomycin given in a pulsed-tapered fashion or fidaxomicin (table 3). Both of these options appear to be safe and effective, but data in children are limited.
●Pulse-tapered vancomycin – We use the following regimen for pulse-tapered vancomycin [7,53-55]:
•10 mg/kg (maximum 125 mg/dose) four times daily for 10 to 14 days, followed by
•10 mg/kg (maximum 125 mg/dose) twice daily for 7 days, followed by
•10 mg/kg (maximum 125 mg/dose) once daily for 7 days, followed by
•10 mg/kg (maximum 125 mg/dose) every other day for 7 days, followed by
•10 mg/kg (maximum 125 mg/dose) every 3 days for 2 to 8 weeks
In an observational study, taper regimens that were completed with every-three-days dosing were associated with higher cure rates than regimens that ended with every-other-day dosing (81 versus 61 percent) [55].
Pulse-tapered vancomycin has been successful in clinical trials in adult patients, including a small randomized trial [54,56], and has been used in adults and children with multiple recurrences of C. difficile infection [7,52,55]. For patients with subsequent recurrence, previous treatment with pulse-tapered vancomycin also may be associated with a decreased risk of failure of fecal microbiota transplantation (FMT) [57].
●Fidaxomicin – Fidaxomicin is dosed according to body weight as follows:
•4 to <7 kg (oral suspension) – 80 mg orally twice daily for 10 days
•7 to <9 kg (oral suspension) – 120 mg orally twice daily for 10 days
•9 to <12.5 kg (oral suspension) – 160 mg orally twice daily for 10 days
•≥12.5 kg (oral suspension or tablets) – 200 mg orally twice daily for 10 days
●Adjunctive bezlotoxumab – For patients ≥1 year of age with subsequent recurrence within six months of the previous episode and risk factors for recurrent C. difficile infection (eg, immunocompromised host), adjunctive treatment with a single dose of bezlotoxumab 10 mg/kg intravenously during administration of standard-of-care antibiotics (eg, vancomycin, fidaxomicin) may prevent subsequent recurrences [27]. Bezlotoxumab is given as a 60-minute intravenous infusion at any time before completing antibacterial treatment. It should be given with caution in patients with heart failure. (See "Clostridioides difficile infection in adults: Treatment and prevention", section on 'Recurrent episode'.)
We use bezlotoxumab for patients who are ≥18 years and have immunocompromising conditions or require frequent antibiotics. In younger patients, it is not approved by the US Food and Drug Administration, is expensive, and is not routinely covered by insurance.
Bezlotoxumab is a humanized monoclonal antibody against toxin B. In 2016, it was approved by the FDA for the prevention of C. difficile infection in high-risk adults who are receiving standard-of-care antibiotics (eg, vancomycin, fidaxomicin). In two randomized trials in 2655 adult patients, the addition of bezlotoxumab to standard-of-care antibiotics reduced the rate of recurrent C. difficile infection (16 to 17 percent versus 26 to 28 percent) [58].
The safety, pharmacokinetics, and efficacy of bezlotoxumab were studied in a randomized trial of 148 children age 1 to <18 years with a current C. difficile infection [59]. Children receiving bezlotoxumab had similar rates of adverse events as those in the placebo group, and no patient discontinued treatment due to an adverse event. Rates of recurrent C. difficile infection were not significantly better compared with placebo (11.2 versus 14.7 percent), although there were too few events to detect a statistical difference.
●Other options – Other options for the treatment of subsequent recurrences in children and adolescents include:
•Rifaximin – Rifaximin is a nonabsorbable, broad-spectrum, rifamycin antibiotic with a good safety profile, minimal drug interactions, and high activity against most strains of C. difficile [60]. A course of rifaximin following standard treatment for C. difficile ("rifaximin chaser") was associated with eradication of infection and decreased rates of relapse [61,62]. Rifaximin is approved in the United States for treatment of travelers' diarrhea in individuals ≥12 years of age; it has additional indications in other countries. Previous treatment with a rifamycin increases the risk of rifaximin resistance in the infecting strain of C. difficile. Rifaximin also has the potential to induce resistance to rifamycins [63,64].
•Nitazoxanide – Nitazoxanide is available for the treatment of diarrhea from Cryptosporidium and Giardia in patients ≥1 year of age. It is broadly active against most anaerobic bacteria [65]. In randomized trials, nitazoxanide produced cure and relapse rates similar to metronidazole and vancomycin for initial treatment of C. difficile infection [66,67]. Adult patients unresponsive to, or relapsing after, metronidazole treatment had a 66 percent response to one or more courses of nitazoxanide 500 mg twice per day [68].
•Teicoplanin – Teicoplanin is a glycopeptide antibiotic (similar to vancomycin) that is inexpensive and available in some countries for the treatment of gram-positive organisms. It is not available in the United States. Teicoplanin appears to be at least as efficacious as vancomycin with fewer adverse effects [23,25].
There are limited data on the use of teicoplanin in children with C. difficile infection.
•Fecal microbiota transplantation – FMT is a procedure in which fecal matter obtained from a healthy donor is administered to a recipient. Several routes of administration have been described, including nasogastric/jejunal tubes, enema, colonoscopy, and oral capsules [69]. Randomized and observational studies have found FMT to be effective in the treatment of recurrent C. difficile infection in adults.
In a retrospective multicenter study, 81 percent (271 of 335) of children with recurrent C. difficile infection were cured with a single FMT [70]. Factors associated with increased odds of success included lack of feeding tube, receipt of fresh donor stool (versus thawed, previously frozen stool), delivery via colonoscopy, and lower number of episodes before FMT. Serious adverse events were uncommon, occurring in 4.7 percent of recipients [70]. Prospective, controlled trials of FMT for C. difficile infection have not been performed in children.
A joint position paper from North American and European Pediatric Gastroenterology organizations provides guidance on the use of FMT for recurrent C. difficile infection in children [69]. Given the many clinical and regulatory issues, FMT should only be performed at established centers with experience with FMT. An international multidisciplinary panel of experts in pediatric oncology and infectious diseases recommends against FMT for the treatment of C. difficile infection in children and adolescents with cancer and those who have received hematopoietic cell transplantation [16]. (See 'Society guideline links' below.)
FMT is discussed in detail separately. (See "Fecal microbiota transplantation for treatment of Clostridioides difficile infection".)
ALTERNATIVE THERAPIES — Several alternatives to antimicrobial therapy for C. difficile infection are being investigated, including toxin binding agents, intravenous immune globulin, and probiotics.
We suggest not using these therapies for the treatment of children with C. difficile infection because their efficacy and safety have not been established. An international multidisciplinary panel of experts in pediatric oncology and infectious diseases also suggests that these therapies not be used for the treatment of C. difficile infection in children and adolescents with cancer and those who have received hematopoietic cell transplantation [16].
The alternative therapies are discussed separately. (See "Clostridioides difficile infection in adults: Treatment and prevention", section on 'Alternative therapies'.)
PREVENTION OF RECURRENCE — Patients remain vulnerable to recurrence for many weeks following treatment of C. difficile infection. During this period of vulnerability, the following preventive measures may reduce the risk of recurrence:
●Avoidance of antimicrobial treatment; if antimicrobial treatment is necessary in a high-risk patient, we suggest tailoring therapy to achieve the narrowest spectrum and shortest duration possible [7] (see 'Discontinuation of inciting antibiotics' above)
●Following proper hand hygiene with close attention to environmental cleaning, particularly where toileting and diaper changing occur (see "Clostridioides difficile infection: Prevention and control", section on 'Hand hygiene')
●Avoidance of gastric acid suppression (ie, proton pump inhibitors and histamine-2 receptor antagonists) [71] (see "Clostridioides difficile infection in children: Microbiology, pathogenesis, and epidemiology", section on 'Other risk factors')
OUTCOME — Most children with C. difficile infection recover without sequelae [2,48,72]. However, among hospitalized children, C. difficile infection is associated with increased in-hospital mortality, length of stay, and hospital cost [73]. In a multicenter cohort of 7318 children hospitalized with C. difficile infection during 2006 through 2011, the 30-day all-cause mortality rate was 1.5 percent; risk factors for death included older age, gastric acid suppression, select chronic conditions (malignancy, cardiovascular disease, hematology/immunologic conditions), and more severe underlying illness [74].
PREVENTION — The prevention of C. difficile infection is discussed separately. (See "Clostridioides difficile infection: Prevention and control".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Clostridioides difficile infection".)
SUMMARY AND RECOMMENDATIONS
●General measures
•Discontinue inciting antibiotics (preferred) or modify antimicrobial therapy to achieve the narrowest spectrum and shortest duration possible. (See 'Discontinuation of inciting antibiotics' above.)
•Correct fluid losses and electrolyte imbalances. (See 'Supportive care' above and "Clinical assessment of hypovolemia (dehydration) in children" and "Treatment of hypovolemia (dehydration) in children in resource-abundant settings".)
•Hospitalization may be warranted for children with (see 'Indications for hospitalization' above):
-Dehydration
-Moderate to marked toxicity
-Severe or fulminant disease (table 1)
-Poor access to follow-up care
●Indications for antimicrobial therapy – We initiate antimicrobial therapy in children with documented symptomatic C. difficile infection (table 2).
Empiric antimicrobial therapy may be warranted if there is a delay in laboratory confirmation or for severe or fulminant disease (table 1).
●Antimicrobial therapy for initial episode
•Mild or moderate disease – For children and adolescents with mild or moderate C. difficile disease (table 1), we suggest oral vancomycin, metronidazole, or fidaxomicin (table 3) (Grade 2B). (See 'Mild or moderate disease' above.)
•Severe disease – For children and adolescents with severe C. difficile disease (table 1), we suggest oral vancomycin as the initial drug of choice (table 3) (Grade 2B). (See 'Severe disease' above.)
•Fulminant disease – For children and adolescents with fulminant C. difficile disease, we suggest the combination of intravenous metronidazole and either oral or rectal vancomycin (for children unable to tolerate oral therapy) (table 3) (Grade 2C). (See 'Fulminant disease' above.)
●Response to treatment – We assess the response to treatment for C. difficile infection clinically. Symptoms generally improve within 48 to 72 hours after initiation of antibiotic therapy, but diarrhea may not fully resolve for four to five days. We do not obtain follow-up stool studies. (See 'Response to treatment' above.)
Progression of disease while on treatment or failure to improve after several days of therapy defines treatment failure. Treatment failure is uncommon in children. Children with treatment failure should be evaluated (or reevaluated) for other causes of diarrhea. (See "Clostridioides difficile infection in children: Clinical features and diagnosis", section on 'Differential diagnosis' and 'Management of treatment failure' above.)
●Management of recurrence – Recurrence of C. difficile infection after completion of antibiotic treatment may represent a relapse of the previous infecting strain or reinfection with a new strain. (See 'Management of recurrence' above.)
•Initial recurrence – For the first recurrence of C. difficile infection in children, we suggest a second course of treatment with the same regimen used for the initial episode (table 3) (Grade 2C).
•Subsequent recurrences – For children with subsequent recurrences of C. difficile infection, we suggest pulse-tapered oral vancomycin or oral fidaxomicin (table 3) (Grade 2C). (See 'Management of recurrence' above.)
●Prevention of recurrence – Patients remain vulnerable to recurrent infection for many weeks following treatment for C. difficile infection. Avoid antibiotics if possible during the period of vulnerability. (See 'Prevention of recurrence' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Michael Cooperstock, MD, MPH, who contributed to an earlier version of this topic review.
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