Can C Diff in Babies Go Away on Its Own

Pediatr Gastroenterol Hepatol Nutr. 2014 Jun; 17(2): lxxx–84.

Clostridium difficile in Children: To Treat or Not to Treat?

Jung Ok Shim

Partition of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Korea Academy Guro Hospital, Korea University College of Medicine, Korea.

Received 2014 Jun xiii; Accustomed 2014 Jun 26.

Abstruse

Clostridium difficile infection has been increasing since 2000 in children and in adults. Frequent antibiotics use, comorbidity, and the development of hypervirulent strains have increased the risk of infection. Despite the loftier carriage rates of C. difficile, infants rarely develop clinical infection. Discontinuing antibiotics and supportive management usually leads to resolution of illness. Antibiotics use should be stratified depending on the patient's age and severity of the disease.

Keywords: Clostridium difficile, Child, Anti-bacterial agents

EPIDEMIOLOGY AND PATHOGENESIS

Clostridium difficile is a gram-positive, spore forming bacterium usually spread through the fecal-oral route. It is non-invasive and presentation rages from asymptomatic carriage, to mild diarrhea, colitis, or pseudomembranous colitis caused by production of toxin A and B. C. difficile infection (CDI) is defined as the astute onset of diarrhea with documented toxigenic C. difficile or its toxin and no other cause for diarrhea. CDI increases morbidity and mortality, specially in hospitalized patients. CDI has been increasing since 2000 in both hospitalized patients and the general community in Asia, Europe, and Due north America. In adult patients, CDI increased 4-fold in Canada [i]. In Korea, the prevalence was 1.7 per 1,000 hospitalized adult patients in 2004 and ii.7 per 1,000 hospitalized adult patients in 2008 [2]. In pediatric patients, the United States Healthcare Cost and Utilization Projection Kids' Inpatient Database (HCUP-KID) reported 0.2% cases in hospitalized pediatric patients, and a significant increment from iii,565 cases in 1997 to seven,779 cases in 2006 [three].

The increase in CDI incidence is thought to be multifactorial, including increased antibody use such every bit cephalosporins and quinolone, an increasing elderly patient population, and the development of hypervirulent strains of C. difficile [4]. C. difficile colonizes in the intestine afterward disruption of normal intestinal microbiota. Frequent use of antibiotics increases the chance of colonization and toxin production by 2-xvi fold [five]. Astringent CDI is associated with hypervirulent strains such equally ribotype 027, North American pulsed-field gel electrophoresis blazon 1 (NAP1), and restriction endonuclease analysis B1. The NAP1 strain produces approximately 20-fold higher levels of toxins A and B due to a deletion in the toxin regulatory factor, tcdC [6]. Severe CDI outbreaks have been reported in Western countries, Japan and Korea. A fluoroquinolone-resistant strain of C. difficile (B1/NAP1/027) has been predominantly associated with these outbreaks [vii]. In 2008, European multicountry surveillance attributed 4.1 per 10,000 patient-days per hospital to CDI, and identified 65 dissimilar ribotypes. Of the cases analyzed, 22% of patients had died and C. difficile contributed at least in part to 40% of deaths. Infection by polymerase chain reaction-ribotypes is associated with complicated disease event [eight].

In 2010, the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America published clinical guidelines for CDI in adults [9]. They recommended metronidazole in mild to moderate disease, and vancomycin as a first-line therapy in astringent disease. However, at that place are sparse data and guidelines for handling of pediatric CDI.

CHARACTERISTICS OF CLOSTRIDIUM DIFFICILE IN CHILDREN

While the incidence of CDI in children also has been increasing, the severity of cases has not increased. In abrupt dissimilarity to developed data, HCUP-KID data reported no pregnant positive trends in mortality, rate of colectomy, or hospital days [3]. The percentage of NAP1 in pediatric CDI was 19.4% in a report [10], compared to more than l% in adults. The relatively low incidence of hypervirulent strains might explain the ascertainment that astringent cases in children take not increased. On the other mitt, asymptomatic colonization of C. difficile is common in early on infancy, and information technology often occurs in the first calendar week of life. The carrier rate is reported to exist 1% to 84% in healthy newborns and infants [xi,12], but it decreases to less than v% past 8 years of age. The about likely source in infants is from environmental contagion rather than directly maternal infant transmission. Chang et al. [13] reported that the toxin positivity rate is significantly higher in the infants with persistent C. difficile colonization than in those with transient colonization (66.7% vs. 24.5%, p=0.001). Exclusive breast-milk feeding decreases the take a chance of persistent colonization compared to formula or mixed feeding. The susceptibility to C. difficile colonization might exist because of the immaturity of the intestine and lack of protective intestinal microbiota [11]. Despite the loftier carriage rates, infants rarely develop clinical infection. The mechanisms for the resistance of infants to CDI are thought to be related to the immunoglobulin fractions of breast milk that inhibit the binding of toxin A to its intestinal receptor, and absence in the newborn gut of the intestinal receptor that binds C. difficile toxin A [11,14]. Risk factors of CDI in children are previous antibiotics employ, and predisposing comorbidities. A recent study of pediatric CDI cases reported 92% of children with previous antibiotics use, 60% with immunosuppressive treatment, 39% with a malignancy or organ transplantation, and 13% with inflammatory bowel disease [15]. While previous proton pump inhibitor use is known to exist associated with CDI in adults [16], the association with CDI in children is not established.

DIAGNOSIS OF CDI IN CHILDREN

Guidelines for diagnosis recommend that only stools from patients with diarrhea should exist tested for C. difficile and tests for cure should not be performed [i]. Endoscopic examination is not commonly recommended except in special cases. Toxigenic cultures and cytotoxin assays are the gold standard for CDI diagnosis. Nucleic acrid amplification tests for toxin genes are superior to the toxin A and B enzyme immunoassay (EIA) tests. Although the EIA test is highly specific, it is not highly sensitive in adults. C. difficile culture is non recommended because only the toxigenic organisms cause disease. Use of EIA in pediatric patients showed like results, although, Toltzis et al. [17] reported a positive predictive value of 64% in children. Children with fake-positive EIA results were significantly younger than those with truthful-positive tests. El Feghaly et al. [fifteen] reported that 24% of children with CDI had a concomitant viral co-infection and reported that norovirus genogroup 2 was the most common virus. Detection of C. difficile toxin in stool may not be the causative agent in children with diarrhea, particularly in young children. Stool exam for C. difficile in infants should be express.

TREATMENT

The use of antibiotics is non recommended in example of asymptomatic colonization with C. difficile. Eradication of C. difficile was attempted in one hospital to eliminate a potential reservoir for nosocomial outbreaks, but metronidazole was ineffective and vancomycin was merely of temporary effect [18].

General considerations for treatment of children with CDI include correction of fluid and electrolyte imbalances in addition to examination of the patient's medical tape for any history of antibiotics and proton pump inhibitor employ. Opiates for hurting command increment chance of ileus or toxic megacolon. Antimotility agents such equally loperamide should exist avoided.

The treatment of CDI in children is based on data from clinical trials in adults. Mild to moderate disease is defined as diarrhea (<six stools/day) without signs of systemic toxicity. Fever is ordinarily absent. Severe colitis is defined as frequent diarrhea (>vi stools/day) with severe abdominal pain and fever. Marked leukocytosis and azotemia may exist observed. Children with fulminant colitis show the most extreme manifestations such as hypotension, rise lactic acid levels, daze, and complete ileus or toxic megacolon. For children with moderate or severe disease, data-supported empirical antibody treatment should be started every bit soon as the diagnosis of CDI is suspected. Oral metronidazole at xxx mg/kg/day in 4 divided doses for 10-14 days is recommended in balmy-to-moderate disease. For severe colitis, oral vancomycin at xl mg/kg/solar day in four divided doses for 10-14 days is recommended. If necessary, subsequent adjuvant therapy with intravenous metronidazole and vancomycin memory enema (developed dose 0.v-ane.0 g in 100 mL of normal saline every iv-12 hours) may be considered [19].

In adult patients, metronidazole and vancomycin showed an initial high cure rate of 76-90% in 2007 [20]. Since then, the rate of treatment failure and affliction relapse with the employ of metronidazole has increased. NAP1 isolates may have reduced susceptibility to metronidazole [7]. Jardin et al. [21] compared treatment patterns and result of adult patients before and after implementation of severity-based CDI guidelines. Later on implementation of guidelines, the use of oral vancomycin was increased and the increased use was associated with decreased rates of refractory CDI.

Based on recent observational data, 53-63% of children with CDI are treated with metronidazole, and apply of oral vancomycin in children varies from 3.5-30% [19]. In a recent study, 27% of children with CDI were non treated with antibiotics, and the majority (42%) were treated with metronidazole, though 74% of children had severe colitis [22]. The American Clan of Pediatrics recommends discontinuation of antibiotics every bit the commencement stride in treating CDI, which may suffice in most instances [23]. Algorithm for CDI in children is suggested in Fig. 1.

Algorithm for management of children with unexplained diarrhea suspected Clostridium difficile infection.

Probiotics could exist started with antibiotic therapy to prevent antibody-associated diarrhea in children. The use of loftier-dose probiotics (five billion CFU/day) appears to be effective with the number needed to treat to preclude 1 case of diarrhea of 7 (95% conviction interval, six-ten) [24]. Studies of the consequence of probiotics in the handling of CDI are limited. In recurrent or astringent CDI, fecal microbiota transplantation might be effective. Donor-acquired feces are implanted into the gastrointestinal tract of the patient via a nasoduodenal catheters, retentiveness enema, duodenoscopy or colonoscopy. van Nood et al. [25] reported 81% resolution of recurrent CDI later the first infusion of feces in a small group of patients. Normal bowel flora serve as a defense force mechanism confronting pathogenic organisms and may effect in the elimination of C. difficile spores.

CONCLUSION

Cases of CDI in children are unlike from those in adults. Despite the high carriage rates of C. difficile, infants rarely develop clinical infection. Antibiotics should be stratified depending on the patient's age and case severity. Genetic epidemiology of hypervirulent strains may be helpful in pediatric patients with CDI.

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107224/