WHEN ANTIBIOTICS DO MORE HARM THAN GOOD

ID ConferenceReinalyn Cartago MD

Jerome Ramos MDApril 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- (+) odynophagia/

dysphagia- Self-medicated with:

- Clarithromycin (5 doses)

- Clindamycin (5 doses)

- Co-trimoxazole unrecalled dose and duration

-Noted resolution of odynophagia

- asymptomatic and 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

- diffuse abdominal pain relieved by bowel movement- increasing abdominal girth- occl vomiting

- NO hematochezia/ melena; nor 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; adynamic

ileus; 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 PGOT/C CLDR/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 alk phos 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

- Severe abdominal pain- NGT opened to drain

- with relief of abdominal pain- 200cc residuals; minimal coffee ground

- Omeprazole 40 mg IV q12 - Rebamipide 100mg/tab, 1 tab TID

DAY 5- 9 episodes of loose watery stools- EGD, Colonoscopy - Blood CS

Blood CS x 1 (07/27/08) DAY 4◦ Staphylococcus haemolyticus after 18.9 h of incubation

S: Vancomycin

Biopsy (07/28/10) DAY 5◦ Duodenum – tubulovillous adenoma◦ Acute on chronic colitis

(07/28/08) ◦ WBC 7.57/ RBC 4.67/ HGb 138/ HCT 0.42/neut 0.760/

lymph 0.120/ mono 0.100/ eos 0.010/ baso 0.010◦ Alb 17 Ca 1.76 Mg 0.90 Na 132 K 3.6

LABS

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

EGD

hiatal hernia; reflux esophagitis; gastroduodenitis; duodenal polyps

DAY 5- Meds revised:oStart Vancomycin 500 mg IV q12h as continuous IV Infusion to run for 1 hoMetronidazole IV continuedoDiscontinued CiprofloxacinoEsomeprazole 40mg/tab q12h

D1 D2 D3 D4 D5 D6 D7 D8….D17

DAY 10- Metronidazole IV shifted to 500mg/tab, 1 tab q6

-Noted improvement on bowel movement- stools occurring once a day, formed

- abdominal pain completely resolved- DAT well-tolerated

-Completed 10 days of Vancomycin IV - eventually discharged improved and well

-07/30/08 crea 101 BUN 3.49 Na 143 K 3.0

- 08/02/08 crea 90 Mg 0.77 K 3.6

- 08/03/08Alb 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

-08/04/08 Phos 0.81

01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 17

SUMMARY OF COURSEHOSPITAL DAY

Metronidazole 500mg IV q6h

Metronidazole 500mg /tab , 1 tab q6h

Ciprofloxacin200 mg IV

q12h

Vancomycin 500mg IV q12h

LBM x 4BM x 9

BM x 1

Resolution of LBM

WBC21.1

WBC7.57

WBC6.77

TAKE HOME MEDS:

Esomeprazole 40 mg/tab, BIDRebamipide 100 mg/tab, TID x 2 wksMetronidazole 500 mg/tab, TID x 2 more daysMebeverine tab, TID x 1 week

FINAL DIAGNOSIS

PSEUDOMEMBRANOUS COLITIS

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

ISSUES

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

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

DISCUSSION

20% - 30% of antibiotic associated diarrhea Few surveillance data in US

3.4 – 8.4 per 1,000 admissions in CanadaClinical Practice Guidelines for Clostridium difficile Infection in Adults: 2010 Update by the Society for Healthcare

Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA)

EPIDEMIOLOGY

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

“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

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

PATHOGENESIS

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

ANSWERS TO ISSUES

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

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

THANK YOU!!!

6% rate of resistance to metronidazole among 78 isolates of C. difficile

◦ Peláez et al.,38th ICAAC

In 1997, high-level metronidazole resistance 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

“…clinical isolates of Clostridium difficile with resistance to metronidazole is 6.3%.”◦ not due to the presence of nim genes◦ 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

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

METRONIDAZOLE RESISTANCE