Multidrug-Resistance Organisms Multidrug-Resistance Organisms & & Clostridium difficileClostridium difficile

Presented by:

Peter NdarayaMercer College of Pharmacy

WellStar Hospital- Paulding

June 2009

ObjectivesObjectivesDescribe MDROsReview development of MDRO resistanceDescribe Clostridium difficilePresent a case of a patient with Clostridium

Difficile Associated Diarrhea (CDAD)

MDRO: DefinitionMDRO: Definition

Multidrug-Resistant Organisms (MDROs) are defined as microorganisms that are resistant to one or more classes of antimicrobial agents.

Three most common MDROs are:

1. Methicillin-Resistant Staph aureus (MRSA)

2. Vancomycin Resistant Enterococci: (VRE)

3. Extended Spectrum Beta-Lactamase producing Enterobacteria. (ESBLs)

CDC: Management of Multidrug-Resistant Organisms in Healthcare Settings, Healthcare Infection Control Advisory Committee, Jane D. Siegel et. al. pg 7-12

Epidemiology of MDROsEpidemiology of MDROs

Trends– Prevalence varies temporarily, by regions,

and by health care facilities.

– Type and level of care influence prevalence

– Prevalence in United States hospitals has increased steadily

CDC: Management of Multidrug-Resistant Organisms in Healthcare Settings, Healthcare Infection Control Advisory Committee, Jane D. Siegel et. al. pg 7-12

Epidemiology cont’dEpidemiology cont’d

Percentages of isolates of the organisms that developed

resistance in the United States

OrganismYear

MRSA VRE

1990 20-25% 1-15%

1999 > 50% 25%

2003 > 59.5% 28.5%

CDC: Management of Multidrug-Resistant Organisms in Healthcare Settings, Healthcare Infection Control Advisory Committee, Jane D. Siegel et. al. pg 7-12

Implication of MDROsImplication of MDROs

Increase hospital stay – Average 3-5 additional days

Increase hospital costs

Increase morbidity and mortality

CDC: Management of Multidrug-Resistant Organisms in Healthcare Settings, Healthcare Infection Control Advisory Committee, Jane D. Siegel et. al. pg 7-12

Causes of Resistance in MDROsCauses of Resistance in MDROs

Enzymatic degradationMutation at binding siteDown regulation of outer membrane

proteinsEfflux pumpsTransduction of genes

Bacteria Outer MembraneBacteria Outer Membrane Uppermost layer contains lipopolysaccharide (LPS) for Gram (-ve)

– Lipid portion is an endotoxin- stimulates immune response, fever…

Special channels (porins) allow passage of small molecules and drugs

Mechanisms of Resistance: EffluxMechanisms of Resistance: Efflux

Active, energy dependent pumps cause efflux of drugs

Bacterial Cytosol

PG layer

Outer membrane

drug

Efflux pump

Mechanisms of Resistance: EffluxMechanisms of Resistance: Efflux Active, energy dependent pumps can also cause efflux of

drugs

1.Methicillin-Resistant 1.Methicillin-Resistant Staph aureusStaph aureus (MRSA) (MRSA)

These are organisms that are not sensitive to common penicillin based drugs such as methicillin, amoxicillin, penicillin, oxacillin1

Normal flora- lives on human skin, noses, vaginal tract May cause infections if enters the body Contagious- through person to person contact Treatment - Vancomycin

2. Vancomycin Resistant Enterococci (VRE)2. Vancomycin Resistant Enterococci (VRE)

Enterococci resistant to Vancomycin Present in human body such as urinary tract and GI tract. Contagious Hospital patients can get it from contact via health care providers. Normal flora that may cause disease especially in vulnerable

populations:– Eg elderly, children and immunocompromised patients.

VREVRE cont’dcont’d

VRE include:– Enterococcus faecalis– Enterococcus faecium

Treated with Synercid (quinupristin and dalfopristin)

VRE can live on surfaces for up to 7 days!!!– Haemophilus influenzae lives about 2 days

Drugs.com: http://www.drugs.com/cg/vancomycin-resistant-enterococcus.html Accessed June1st 2009

Transmission of VRETransmission of VRE

Center for Disease Control and Prevention: http://www.cdc.gov/ncidod/eid/vol3no3/mcdonald.htm, Accessed June 17th 2009

VRE preventionVRE preventionStandard precautions

– Hand hygiene– Personal Protective Equipment (PPE)– Needlestick and sharps injury prevention.– Cleaning & disinfection– Respiratory hygiene (Cough Etiquette)– Waste disposal– Safe injection practices

Center for Disease Control and Prevention: http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf Accessed June 17th 2009

  Wisconsin Department of Health Services: http://dhs.wisconsin.gov/communicable/InfectionControl/StdPrecautions.htm, Accessed July 17th 2009.

3. Extended Spectrum Beta-Lactamase 3. Extended Spectrum Beta-Lactamase producing Enterobacteria. (ESBL)producing Enterobacteria. (ESBL)

ESBLs are plasmid-mediated beta lactamases described in gram negative bacilli2

– Eg. Klebsiella, Acinebacter

MOA – hydrolysis of beta- lactam ring in– Penicillins– Narrow spectrum cephalosporins

Beta-lactamase inhibitors inhibit ESBL producing strains– Clavulanic acid– Sulbactam

– Tazobactam.

Enzymatic degradation of ESBLs:Enzymatic degradation of ESBLs: Mechanisms of Mechanisms of -lactamase-lactamase

N

ON

O

OH

S CH3

CH3O

RH

-lactamase

CH2

OH-lactamase

CH2

OH

N

ON

O

OH

S CH3

CH3O

RH

-lactamase

CH2

OH H2O

N

ON

O

OH

S CH3

CH3O

RH

HOH

-lactamase

CH2

OH

+Hydrolysis of Oxyimino group

Penicillin drug

Inactivated drug

Other Drug Resistant DiseasesOther Drug Resistant Diseases

Extensively-Drug Resistant Tuberculosis (XDR-TB)– This is a TB causing organism that is resistant to almost

all drugs that are used to treat TB. Isoniazid Rifampin Fluoroquinolones At least one of: Amikacin, kanamycin, capreomycin

– The main cuasitive organism is Mycobacterium tuberculosis3

– Contagious through droplets but slower than viral infection such as flu

MDROs preventionMDROs prevention Observe the universal standard precautions Practice 200% percent safety rule Good hygiene practice

– Frequent hand wash– Cover cuts and scrapes– Do not share personal items eg razors

Do not pressure doctors for antibiotics Finish all antibiotic medications Health care providers to wash hands before touching patients Isolation for serious cases

Clostridium difficileClostridium difficile Clostridium difficile (C. diff) is a gram positive

bacteria of the clostridium genus. Contagious- especially in hospitals through contact Responsible for Clostridium difficile Infection (CDI)

– Infections include:Uncomplicated diarrhea (CDAD)Toxic megacolonPseudomembranous colitis

These diseases can lead to fulminant sepsis and death

Clostridium difficileClostridium difficile

Clostridium difficile: http://www.kaiscience.com/ph_163-Clostridium_difficile_Copyright_Dennis_Kunkel_Microscopy Accessed June 1st 2009

C. Diff is a gram positive rod of clostridium species

Toxic megacolonToxic megacolon

All Refer health: http://health.allrefer.com/health/toxic-megacolon-pictures-images.htm Accessed June 15th 2009l

Pseudomembranous colitisPseudomembranous colitis

http://www.tommyroshek.com/log/uploaded_images/pseudomembranes-748375.JPG Accessed, June 15th 2009

Pathogenesis of Pathogenesis of Clostridium difficile Clostridium difficile infectioninfection

American Family Physician: http://www.aafp.org/afp/20050301/921.html, Accessed June 14, 2009

13% with 2 weeks hospitalization50% after 4 weeks hospitalization

C. diffC. diff treatment treatment

1st line Metronidazole – Dose

Adults: 500 mg po TID for 10-14 days Children: 15-35 mg/kg/ day po TID

2nd line Vancomycin– Dose

Oral: 125-250mg po QID– Oral dosing is more effective than IV

Rectal enema: 500mg once daily

http://www.ohsu.edu/medicine/residency/handouts/pharmpearls/Gastrointestinal/GuidelinesForTreatmentOfCdiffi.pdf, Accessed June 17th 2009

Patient CasePatient Case

http://www.clipartguide.com/_pages/0060-0808-1313-1328.html, Accessed June 17th 2009

Ouch!!!

Patient CasePatient Case

CC-EE is a 68-year-old caucasian male who presented in the hospital with a chief complain of diarrhea and abdominal pain.

HPI- Came back to hospital 30 days since last discharge after C.diff colitis treatment. Has diarrhea x10 per day, watery stool, foul smell, abdominal pain on & off.

PMH- CAD, CABG, Diabetes mellitus, C. difficile colitis Allergies- sulfa, penicillin Vital Signs:

– Admission: BP=119/77, HR=66, R=20, T=97, pulse oximetry 98% on room air

– Current: BP=120/63, HR=60 irregular, R=20, O2 sat= 99% on room air Labs: WBC 6.8, Hb 14.0, hematorict 41, platelets 98, Sodium 136,

Potassium 4.3, Amylase 59, lipase 33,

Patient Case cont’dPatient Case cont’dHome Medications:

– Spironolactone 25mg 2 tablets p.o. daily– Coreg 3.125mg p.o. b.i.d.– Lasix 40mg p.o. daily– Novolin N 35 to 50 units SC b.i.d. p.r.n.– Lactinex– Glipizide– The patient says he is not taking asprin as it causes

nosebleeds

Patient case cont’dPatient case cont’d Hospital Medications:

– Insulin regular 1U-10U SC ACHS– Fondaparinux 2.5mg SC Q24H– Pantoprazole 40mg po ACB– Vancomycin 500mg/10ml po QID x 2 days– Metronidazole 500 mg IV Q6H X 3 days– Lactobacillus 1 cap po TID– Colesevelam 1,250mg po BIDWM– Spironolactone 50mg po Daily– Carvedilol 3.125mg po BID– Furosemide 40mg po Daily– Glipizide 5mg po ACB– Lidocaine 2% (lidocaine jet) prn

Assessment and PlanAssessment and Plan 1. Colitis, probably clostridium difficile.

– Patient was recently discharged with C.diff colitis. He had same symptoms: diarrhea and abdominal pain.

– He was started on Flagyl 500mg IV q8 hours and Vancomycin 500mg po q.i.d.

2. History of Coronary Artery Disease.– Patient is stable and will continue coreg– Not on any blood thinners

3. Diabetes Mellitus, type 1. He is currently on sliding scale insulin. Currently on liquid diet. His sugars will be monitiored closely.

4. Congestive heart failure. The patient is stable and will continue on Lasix, Adactone and coreg.

5. Thrombocytopenia. This is probably secondary to liver dysfunction. He is stable.

6. Skin ulcers. Wound care was consulted.

Clinical courseClinical course

The labs were positive for C. diff Had recurrent diarrhea.Was on metronidazole IV and vancomycin

IV one time but redeveloped diarrhea after one week.

Responded well to vancomycin

DischargeDischarge

Discharged after four days with;– Vancomycin 250mg p.o. qid x 3 weeks– Probiotics– Continue all other home medications prior to admission

Condition: At the time of discharge, the patient was afibrile, tolerating oral intake, no abdominal pain, still had diarrhea but formed stool

Recent labs: WBC 4.4, Hb 14, hematocrit 40

Patient case commentPatient case comment The patient had failed initial treatment with metronidazole. Patient was started on both metronidazole IV and oral

vancomycin. This was appropriate because the regimen provided double coverage and enhanced killing of C. diff.

The patient was discharged with vancomycin 250mg q.i.d. for 3 weeks. This was appropriate because the guidelines indicate for vancomycin when failure with metronidazole occurs after 5 days of treatment.4

According to the literature, there is evidence that probiotics can treat recurrent C.diff5. Therefore, inclusion of probiotics was appropriate.

Vancomycin may kill some of the normal flora and hence potential for C. diff overgrowth. Probiotics would re-establish normal flora and keep C.diff under control.

Home at last!Home at last!

ReferenceReference1. WebMD:

http://www.webmd.com/skin-problems-and-treatments/understanding-mrsa-methicillin-resistant-staphylococcus-aureus Accessed June 15th, 2009.

2. John Hopkins: http://www.hopkinsmedicine.org/heic/ID/esbl/ Accessed June 15th 2009

3. Healia: http://www.healia.com/healthguide/guides/tuberculosis/what-causes-tuberculosis Accessed June 15th 20094. http://www.ohsu.edu/medicine/residency/handouts/pharmpearls/Gastrointestinal/GuidelinesForTreatmentOfCdiffi.pdf,

Accessed June 17th 2009

5. Meta-Analysis of Probiotics for the Prevention of Antibiotic Associated Diarrhea and the Treatment of Clostridium difficile Disease; Lynne V. McFarland, American Journal of Gastroenterology. ISSN 0002-9270 pg 812-822