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WHEN ANTIBIOTICS DO MORE HARM THAN GOOD ID Conference Reinalyn Cartago MD Jerome Ramos MD April 29, 2010
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
I. E. 71/M Misamis Occidental presently residing in Marikina City GENERAL DATA
DIARRHEA CHIEF COMPLAINT
No known co-morbids Alcoholic beverage drinker 40 pack yr smoker Good Functional Capacity PROFILE
HISTORY OF PRESENT ILLNESS 3 months PTA ,[object Object]
Self-medicated with:
Clarithromycin (5 doses)
Clindamycin (5 doses)
 Co-trimoxazole   unrecalled     dose and       duration  ,[object Object],odynophagia ,[object Object],   well
2 weeks PTA - consult and  subsequent   admission at a local hospital  - management unrecalled - Holoabdominal Ultrasound  and Abdominal CT        -  transferred to PGH 3 weeks PTA - LBM – 10x/day - undocumented fever ,[object Object],  bowel movement - increasing abdominal girth - occlvomiting ,[object Object],  decrease in caliber of stool HISTORY OF PRESENT ILLNESS
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
(+) 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
Not a known hypertensive, diabetic and asthmatic No known allergies 1970’s – admitted for typhoid fever PAST MEDICAL HISTORY
No known heredo-familial diseases No history of Cancer No similar illness in the family FAMILY HISTORY
Alcoholic beverage drinker 40 pack yr smoker Denies illicit drug use PERSONAL/SOCIAL HISTORY
COURSE IN THE WARDS
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
(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
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
(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
D1          D2         D3           D4            D5          D6          D7          D8          D9 DAY 4 ,[object Object]
 NGT opened to drain
 with relief of abdominal pain
 200cc residuals;  minimal coffee ground
Omeprazole 40 mg IV q12
Rebamipide 100mg/tab, 1 tab TIDDAY 5 ,[object Object]
 EGD, Colonoscopy
 Blood CS,[object Object]
D1          D2         D3           D4            D5          D6          D7          D8          D9 COLONOSCOPY Nodular mucosa with yellowish exudates from rectum to cecum, more severe on the left side CLINICAL IMPRESSION: Pseudomembranous Colitis; Internal Hemorrhoids DAY 5 ,[object Object]
Start Vancomycin 500 mg IV   q12h as continuous IV Infusion     to run for 1 h ,[object Object]
Discontinued Ciprofloxacin
Esomeprazole 40mg/tab q12hEGD  hiatal hernia; reflux esophagitis; gastroduodenitis; duodenal polyps
D1          D2         D3           D4            D5          D6          D7          D8….D17 ,[object Object],crea 101 BUN 3.49 Na 143 K 3.0 ,[object Object],crea 90 Mg 0.77 K 3.6 ,[object Object],	Alb 18 Ca 1.79 Na 139 WBC 6.77/ HGb 117/ HCT 0.36/ neut 0.630/ lymph 0.230/            mono 0.100/ eos 0.030/ baso 0.010 ,[object Object],Phos 0.81 ,[object Object]
 stools occurring once a day, formed
 abdominal pain completely resolved
 DAT well-toleratedDAY 10 - Metronidazole IV shifted to 500mg/tab, 1 tab q6 ,[object Object],- eventually discharged improved and well
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
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
FINAL DIAGNOSIS PSEUDOMEMBRANOUS COLITIS

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Clostridium difficile infection (cdi)

  • 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
  • 5. No known co-morbids Alcoholic beverage drinker 40 pack yr smoker Good Functional Capacity PROFILE
  • 6.
  • 10.
  • 11.
  • 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
  • 22.
  • 23. NGT opened to drain
  • 24. with relief of abdominal pain
  • 25. 200cc residuals; minimal coffee ground
  • 27.
  • 29.
  • 30.
  • 31.
  • 33. Esomeprazole 40mg/tab q12hEGD hiatal hernia; reflux esophagitis; gastroduodenitis; duodenal polyps
  • 34.
  • 35.
  • 36. stools occurring once a day, formed
  • 37. abdominal pain completely resolved
  • 38.
  • 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
  • 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
  • 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
  • 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
  • 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