1. WHEN ANTIBIOTICS DO MORE HARM THAN GOOD ID Conference Reinalyn Cartago MD Jerome Ramos MD April 29, 2010

2. To identify risk factors for acquiring Clostridium difficile infection (CDI) To explain diagnosis and management of CDI in adult patients To compare diagnosis and management of CDI in our institution with that of the current guidelines To identify methods of infection prevention and control as well as environmental management of the pathogen OBJECTIVES

3. I. E. 71/M Misamis Occidental presently residing in Marikina City GENERAL DATA

4. DIARRHEA CHIEF COMPLAINT

5. No known co-morbids Alcoholic beverage drinker 40 pack yr smoker Good Functional Capacity PROFILE

7. Self-medicated with:

8. Clarithromycin (5 doses)

9. Clindamycin (5 doses)

12. Holoabdominal UTZ liver parenchymal disease; moderate ascites; UR GB, Pancreas, spleen, kindneys and urinary bladder Abdominal CT Scan minimal ascites; fecal stasis; adynamicileus; mild to mod bilateral pleural effusion; non-focal thickening on antero-lateral abd wall

13. (+) Generalized body malaise, anorexia, undocumented weight loss (+) dysphagia/ odynophagia (-) cough/ colds; no DOB (-) angina chest pain; no orthopnea; no PND; no easy fatigability (-) no urinary changes (-) edema REVIEW OF SYSTEMS

14. Not a known hypertensive, diabetic and asthmatic No known allergies 1970’s – admitted for typhoid fever PAST MEDICAL HISTORY

15. No known heredo-familial diseases No history of Cancer No similar illness in the family FAMILY HISTORY

16. Alcoholic beverage drinker 40 pack yr smoker Denies illicit drug use PERSONAL/SOCIAL HISTORY

17. COURSE IN THE WARDS

18. Awake, weak looking, not in distress 110/70 79 18 afebrile AS, PC, (-) CLAD ECE, CBS AP, DHS, normal rate, irregular rhythm, no murmurs/thrills Globular, soft, nontender abdomen DRE: (+) redundant mucosa vs mass FEP, PNB, (+) grade 2 bipedal edema ASSESSMENT: Diarrhea probably secondary to overflow secondary to PGO r/o Colonic New Growth Amoebic Colitis T/C PGO T/C CLD R/O Typhoid Fever ADMISSION NPO Metronidazole 500mg IV q6 Lansoprazole 30mg/tab, 1 tab SL

19. (07/23/08) WBC 21.10/ RBC 4.69/ HGb 143/ HCT 0.423/ Platelets 355/ neut 0.887/ lymph 0.043/ mono 0.064/ eos 0/ baso 0.006 BUN 6.34 crea 123 alkphos 109 ast 60 alt 53 Na 133 K 4.9 Cl 101 PT 12.1/ 17.6/ 0.48/ 1.70 Fecalysis : Brown/ watery/mucoid/ 0-2 RBC/ 38-40 WBC; no ova or parasites; (+) occult blood LABS

20. D1 D2 D3 D4 D5 D6 D7 D8 D9 (+) Loose watery stools – 4 episodes per day; Non-bloody Afebrile Started OF feeding Ciprofloxacin 200mg IV q12h Cleared for Colonoscopy

21. (07/24/08) DAY 1 BUN 6.38 crea 101 Ca 1.79 Mg 0.83 K 4.7 Anti HBc total – NR; Anti HCV – NR Salmonella IgG – R; IgM – NR Stool CS - No enteric pathogen isolated Holoab UTZ - N (07/25/08) DAY 2 HgbA1c 6.5 Alb 18 Urinalysis - Y/ Clear/ 1.020/ 6.0/ (-) sugar and protein/ (-) RBC and WBC/ (-) cast and crystals/ (-) EC LABS

23. NGT opened to drain

24. with relief of abdominal pain

25. 200cc residuals; minimal coffee ground

26. Omeprazole 40 mg IV q12

28. EGD, Colonoscopy

32. Discontinued Ciprofloxacin

33. Esomeprazole 40mg/tab q12hEGD hiatal hernia; reflux esophagitis; gastroduodenitis; duodenal polyps

36. stools occurring once a day, formed

37. abdominal pain completely resolved

39. SUMMARY OF COURSE HOSPITAL DAY Metronidazole 500mg IV q6h Metronidazole 500mg /tab , 1 tab q6h Ciprofloxacin 200 mg IV q12h Vancomycin 500mg IV q12h BM x 9 BM x 1 Resolution of LBM LBM x 4 WBC 21.1 WBC 7.57 WBC 6.77

40. TAKE HOME MEDS: Esomeprazole 40 mg/tab, BID Rebamipide 100 mg/tab, TID x 2 wks Metronidazole 500 mg/tab, TID x 2 more days Mebeverine tab, TID x 1 week

41. FINAL DIAGNOSIS PSEUDOMEMBRANOUS COLITIS

42. What are possible causes of chronic diarrhea in an elderly patient with questionable history of prolonged antibiotic use? ISSUES

43. For patients with CDI, is there a need to do toxin assay if colonoscopy already reveals pseudomembranes? Is it prudent to treat patients as CDI based on clinical grounds only? ISSUES

44. Is there a need to give both Metronidazole and Vancomycin in our patient? What is the appropriate route and duration of treatment of CDI ISSUES

45. DISCUSSION

46. 20% - 30% of antibiotic associated diarrhea Few surveillance data in US 3.4 – 8.4 per 1,000 admissions in Canada Clinical Practice Guidelines for Clostridium difficileInfection in Adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) EPIDEMIOLOGY

47. Atlanta GA--rates of Clostridium difficile infections (CDI) surpassed infection rates for methicillin-resistant Staphylococcus aureus (MRSA) in South East US Hospitals Becky Miller, MD, Duke Infection Control Outreach Network, Duke University, 2009. EPIDEMIOLOGY

48. “CDAD should probably not be the first consideration when a patient in the ICUs of UP-PGH (2004) develops Nosocomial Diarrhea” “…at least 2 specimens should be sent for C. difficile testing if the suspicion for CDAD is strong” Gutierrez MD., UP-PGH, 2004 EPIDEMIOLOGY

49. Exposure to antimicrobial agents Clindamycin, Ampicillin, Cephalosporins, Fluoroquinolones Advanced Age Greater severity of underlying illness Duration of Hospitalization Gastric Surgery Use of rectal thermometers Enteral tube feeding Antacids, PPI RISK FACTORS

50. PATHOGENESIS

51. What are possible causes of chronic diarrhea in an elderly patient with questionable history of prolonged antibiotic use? ANSWERS TO ISSUES

52. For patients with CDI, is there a need to do toxin assay if colonoscopy already reveals pseudomembranes? Is it prudent to treat patients as CDI based on clinical grounds only? ANSWERS TO ISSUES

53. Is there a need to give both Metronidazole and Vancomycin in our patient? What is the appropriate route and duration of treatment of CDI ANSWERS TO ISSUES

54. THANK YOU!!!

55. 6% rate of resistance to metronidazoleamong 78 isolates of C. difficile Peláezet al.,38th ICAAC In 1997, high-level metronidazoleresistance demonstrated in C. difficile isolates obtained from horses S. S. Jang, et al. 35th Annual Meeting of Infectious Diseases Society of America 1997, Clin. Infect. Dis. 25(Suppl. 2):S266–S267, 1997] Highest rate of metronidazole resistance was observed in HIV-infected patients T. Peláez, L. Alcalá, R. Alonso,* M. Rodríguez-Créixems, J. M. García-Lechuz, and E. Bouza, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, June 2002, p. 1647–1650 METRONIDAZOLE RESISTANCE

56. “…clinical isolates of Clostridium difficile with resistance to metronidazole is 6.3%.” not due to the presence of nimgenes resistance to metronidazole in toxigenic C. difficile isolates is heterogeneous prolonged exposure to metronidazole can select for in vitro resistance routine performance of the disk diffusion method (5-microg metronidazole disk) J Clin Microbiol. 2008 Sep;46(9):3028-32. Epub 2008 Jul 23 METRONIDAZOLE RESISTANCE

57. Oral rifaximin (Xifaxan®; Salix Pharmaceuticals, Inc, Morrisville, NC) 1200 mg/d for 14 days Gut-selective, non-systemic antibiotic METRONIDAZOLE RESISTANCE