Pediatr Gastroenterol Hepatol Nutr.  2017 Mar;20(1):47-54. 10.5223/pghn.2017.20.1.47.

Effect of Metronidazole in Infants with Bowel Habit Change: Irrelative to the Clostridium difficile Colonization

• Kim EJ
• Lee SH
• Tchah H
• Ryoo E

• KMID: 2375278
• DOI: http://doi.org/10.5223/pghn.2017.20.1.47

Abstract

PURPOSE
Clinical symptoms associated with Clostridium difficile infection (CDI) can vary widely. Carrier state without apparent symptoms is relatively common during infancy. The objective of this study was to determine the association of C. difficile colonization with bowel habit change and the effect of C. difficile colonization treatment on restoration of normal bowel habit.
METHODS
Between 2006 and 2014, infants at 1 to 12 months of age with diarrhea for more than 2 weeks who did not improve with conservative care were recruited from Gachon University Gil Medical Center. Infants who were followed up for at least 7 days were included. The presence or absence of C. difficile colonization, effect of metronidazole, and other medical records were reviewed. To determine the association between CDI and bowel habit change, logistic regression analysis was used.
RESULTS
Of a total of 126 infants, 74 (58.7%) were male patients. Of the 126 patients, 27 (21.4%) had C. difficile colonization. Significant (p<0.05) risk factors for C. difficile colonization included artificial milk feeding (odds ratio [OR], 4.310; 95% confidence interval [CI], 1.564-11.878), prior rotavirus vaccination (OR, 4.322; 95% CI, 1.018-18.349), and antibiotic use (OR, 4.798; 95% CI, 1.430-16.101). There was improvement in bowel habit after metronidazole therapy (OR, 0.34; 95% CI, 0.15-0.79; p<0.05), regardless of the presence or absence of C. difficile colonization,
CONCLUSION
There was no significant correlation between bowel habit change and C. difficile colonization during infancy. However, metronidazole can be used as an optional method to manage functional gastrointestinal disorders.

Keyword

Infant; Clostridium difficile; Gastrointestinal diseases; Metronidazole

MeSH Terms

Carrier State
Clostridium difficile*
Clostridium*
Colon*
Diarrhea
Gastrointestinal Diseases
Humans
Infant*
Logistic Models
Male
Medical Records
Methods
Metronidazole*
Milk
Risk Factors
Rotavirus
Vaccination
Metronidazole

Figure

• 

  Fig. 1 A flow chart of the protocol of the present study.

Reference

1. Pezzella V, De Martino L, Passariello A, Cosenza L, Terrin G, Berni Canani R. Investigation of chronic diarrhoea in infancy. Early Hum Dev. 2013; 89:893–897.

2. Langley JM, LeBlanc JC, Hanakowski M, Goloubeva O. The role of Clostridium difficile and viruses as causes of nosocomial diarrhea in children. Infect Control Hosp Epidemiol. 2002; 23:660–664.

3. Kim J, Smathers SA, Prasad P, Leckerman KH, Coffin S, Zaoutis T. Epidemiological features of Clostridium difficile-associated disease among inpatients at children's hospitals in the United States, 2001-2006. Pediatrics. 2008; 122:1266–1270.

4. Sammons JS, Toltzis P, Zaoutis TE. Clostridium difficile infection in children. JAMA Pediatr. 2013; 167:567–573.

5. Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med. 2015; 372:1539–1548.

6. Rousseau C, Poilane I, De Pontual L, Maherault AC, Le Monnier A, Collignon A. Clostridium difficile carriage in healthy infants in the community: a potential reservoir for pathogenic strains. Clin Infect Dis. 2012; 55:1209–1215.

7. Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med. 1994; 330:257–262.

8. Schutze GE, Willoughby RE. Clostridium difficile infection in infants and children. Pediatrics. 2013; 131:196–200.

9. Sandora TJ, Fung M, Flaherty K, Helsing L, Scanlon P, Potter-Bynoe G, et al. Epidemiology and risk factors for Clostridium difficile infection in children. Pediatr Infect Dis J. 2011; 30:580–584.

10. Rasquin-Weber A, Hyman PE, Cucchiara S, Fleisher DR, Hyams JS, Milla PJ, et al. Childhood functional gastrointestinal disorders. Gut. 1999; 45:Suppl 2. II60–II68.

11. Almeida R, Gerbaba T, Petrof EO. Recurrent Clostridium difficile infection and the microbiome. J Gastroenterol. 2016; 51:1–10.

12. Rineh A, Kelso MJ, Vatansever F, Tegos GP, Hamblin MR. Clostridium difficile infection: molecular pathogenesis and novel therapeutics. Expert Rev Anti Infect Ther. 2014; 12:131–150.

13. Rousseau C, Levenez F, Fouqueray C, Doré J, Collignon A, Lepage P. Clostridium difficile colonization in early infancy is accompanied by changes in intestinal microbiota composition. J Clin Microbiol. 2011; 49:858–865.

14. Benson L, Song X, Campos J, Singh N. Changing epidemiology of Clostridium difficile-associated disease in children. Infect Control Hosp Epidemiol. 2007; 28:1233–1235.

15. Cohen MB. Clostridium difficile infections: emerging epidemiology and new treatments. J Pediatr Gastroenterol Nutr. 2009; 48:Suppl 2. S63–S65.

16. Owens RC Jr, Donskey CJ, Gaynes RP, Loo VG, Muto CA. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis. 2008; 46:Suppl 1. S19–S31.

17. Benno Y, Sawada K, Mitsuoka T. The intestinal microflora of infants: composition of fecal flora in breast-fed and bottle-fed infants. Microbiol Immunol. 1984; 28:975–986.

18. Rolfe RD, Song W. Immunoglobulin and non-immunoglobulin components of human milk inhibit Clostridium difficile toxin A-receptor binding. J Med Microbiol. 1995; 42:10–19.

19. Sekirov I, Russell SL, Antunes LC, Finlay BB. Gut microbiota in health and disease. Physiol Rev. 2010; 90:859–904.

20. Ang L, Arboleya S, Lihua G, Chuihui Y, Nan Q, Suarez M, et al. The establishment of the infant intestinal microbiome is not affected by rotavirus vaccination. Sci Rep. 2014; 4:7417.

21. Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol. 2007; 102:2047–2056. quiz 2057.

22. Mezoff EA, Cohen MB. Acid suppression and the risk of Clostridium difficile infection. J Pediatr. 2013; 163:627–630.

23. Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA. 2005; 294:2989–2995.

24. Evans CT, Johnson S. Prevention of Clostridium difficile infection with probiotics. Clin Infect Dis. 2015; 60:Suppl 2. S122–S128.

25. Johnston BC, Ma SS, Goldenberg JZ, Thorlund K, Vandvik PO, Loeb M, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Ann Intern Med. 2012; 157:878–888.

26. Allen SJ, Wareham K, Wang D, Bradley C, Hutchings H, Harris W, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013; 382:1249–1257.

27. Na JY, Park JM, Lee KS, Kang JO, Oh SH, Kim YJ. Clinical characteristics of symptomatic Clostridium difficile infection in children: conditions as infection risks and whether probiotics is effective. Pediatr Gastroenterol Hepatol Nutr. 2014; 17:232–238.

28. Pant C, Deshpande A, Altaf MA, Minocha A, Sferra TJ. Clostridium difficile infection in children: a comprehensive review. Curr Med Res Opin. 2013; 29:967–984.

29. Loo VG, Bourgault AM, Poirier L, Lamothe F, Michaud S, Turgeon N, et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med. 2011; 365:1693–1703.

30. Hung YP, Lee JC, Lin HJ, Liu HC, Wu YH, Tsai PJ, et al. Clinical impact of Clostridium difficile colonization. J Microbiol Immunol Infect. 2015; 48:241–248.

31. Halvorson HA, Schlett CD, Riddle MS. Postinfectious irritable bowel syndrome--a meta-analysis. Am J Gastroenterol. 2006; 101:1894–1899.

32. Thabane M, Kottachchi DT, Marshall JK. Systematic review and meta-analysis: the incidence and prognosis of post-infectious irritable bowel syndrome. Aliment Pharmacol Ther. 2007; 26:535–544.

33. Lembo A, Pimentel M, Rao SS, Schoenfeld P, Cash B, Weinstock LB, et al. Repeat treatment with rifaximin is safe and effective in patients with diarrhea-predominant irritable bowel syndrome. Gastroenterology. 2016; pii: S0016-5085(16)34926-5. DOI: 10.1053/j.gastro.2016.08.003. [Epub ahead of print].

34. Pérez-Cobas AE, Artacho A, Ott SJ, Moya A, Gosalbes MJ, Latorre A. Structural and functional changes in the gut microbiota associated to Clostridium difficile infection. Front Microbiol. 2014; 5:335.