MDROsIt’s not just about MRSA

Titus L. Daniels, MD MPHAssistant Professor of Medicine (Infectious Diseases) – VUSMAssociate Hospital Epidemiologist – Vanderbilt Medical Center

Hospital Epidemiologist – Williamson Medical Center

APIC Annual Conference – June 10, 2009

Disclosers

Acknowledgements

• Vicki Brinsko • Amy Dziewior• Tracy Hann• Lorrie Ingram

• Jan Szychowski• Kathie Wilkerson• Vicki Sweeney

MDROs

•MRSA = Methicillin – resistant Staphylococcus aureus

• VRE = Vancomycin – resistant enterococcus

• CDAD = C. difficile associated diarrhea

•MDRGN = Multi‐drug resistant Gram‐negatives

An example

77 y/o male 

Hospitalized much of the prior 90 days

Slowly recovering

Now extubated

Sitting up, working with physical therapy

Eating well, gaining weight

Family reporting “best he’s looked in a year”

Plans for rehab transfer in 2‐3 days

Then…

Diarrhea develops

Intubated again as sepsis develops

C. difficile test is positive

Toxic megacolon develops

Patients dies 48 hours later

Why did this happen?

3 days before diarrhea started…

–Patient in adjacent room diagnosed with C. difficile diarrhea

–Staff repeatedly observed not adhering to hand hygiene or isolation practices

–Shared staff documented

CDAD

• Clostridium difficile–Gram positive spore forming organism

• Known pathogen since 1978

•Many consider a strict iatrogenic pathogen

• Previously easily recognized and treated

“New” strain

• Increased toxin production – as much as 20x

• Toxin appears more virulent

• Toxin is less likely to be “turned” off

• Resistant to fluoroquinolone antibiotics

• Organism associated with hypersporulation

Rates of CDAD – United States

Diagnosis

• Relatively straight‐forward– Use of enzyme based tests most common

– Detection of toxin is important

– False negative results occur up to 20%

• Clinical suspicion and probabilities should not be swayed substantially by negative testing

Treatment

• Optimal treatment options are evolving

•Most experts recommend:– Vancomycin orally + metronidazole IV for severe disease

–Metronidazole for mild‐moderate disease•Oral is most effective

• IV is an alternative

• Use of probiotics?

STOPother antimicrobials

VRE

•Gram positive bacteria

•Related to the Streptococci

•Long considered of “low”virulence

•Widely recognized cause of healthcare‐associated infections

VRE Epidemiology

Does VRE matter?

Chance of death with VRE is 

2.5 times greaterthan with non‐VRE

True MDROs

Gram‐negative bacteria–Klebsiella pneumoniae

–Pseudomonas aeruginosa

–Acinetobacter baumanniiTroops in Iraq Bring Resistant Bacteria Home

Sciences and MedicineMilitary Chases Mystery Infection

Drug resistant bacteria 

≠NEW

A quick primer

Resistance among “key” pathogens

Am J Infect Control 2004;32(8):470–485.

Imipenem resistance

Livermore. Ann Med 2003;35:226-234

Intermediate resistance Fully resistantThe Surveillance Network. >250 hospitals in US; >2000 reported infections annually

Resistance in U.S. ICUs

• 1994 ‐ 2004• > 300 intensive care units• 8537 isolates 

– ~ 3600 resistant to at least one principal agent

• Fluoroquinolone resistance: 49.5 ‐ 73%• β‐lactam resistance: 39 ‐ 66%• Aminoglycoside resistance: 19 ‐ 30.5%• Carbapenem resistance: 9 ‐ 38.5%

Carey, et al. Abstract K-1495. 46th ICAAC; Sept. 2006

Even more concerning…

•Emergence of carbapenemases–KPC = Klebsiella pneumoniaecarbapenemase

–CRE = carbapenem resistant Enterobacteriacae

Deaths associated with bacteria

PathogenBSIs per 

10,000 adm% Total BSI n=20,978

% ICU BSI n=10,515

% Non‐ICU BSI n=10,442

% Total Crude Mortality

% ICU Crude Mortality

% Non‐ICU Mortality

CNS 15.8 31.3 35.9 26.6 20.7 25.7 13.8

S. aureus 10.3 20.2 16.8 23.7 25.4 34.4 18.9

Enterococcus 4.8 9.4 9.8 9 33.9 43 24

Ps. aeruginosa  2.1 4.3 4.7 3.8 38.7 47.9 27.6

Enterobacter 1.9 3.9 4.7 3.1 26.7 32.5 18

Klebsiella 2.4 4.8 4 5.5 27.6 37.4 20.3

E. coli 2.8 5.6 3.7 7.6 22.4 33.9 16.9

Serratia 0.9 1.7 2.1 1.3 27.4 33.9 17.1

A. baumannii 0.6 1.3 1.6 0.9 34.0 43.4 16.3

Wisplinghoff, et al. Clin Infect Dis 2004;39:309-17

24,179 BSIs from SCOPE Project

38.7% Pseudomonas aeruginosa34.0% Acinetobacter baumannii33.9% Enterococcus

Another example…

22 y/o male 

75% burns from explosion

Hospitalized in burn unit 47 days

Fever develops

Cultures obtained

Empiric antibiotics started

Blood cultures return positive for A. baumannii

• Amikacin = R

• Gentamicin = R

• Tobramycin = R

• Cefepime = R

• Imipenem = R

• Meropenem = R

• Amp/Sulbactam = R

• Pip/tazobactam = R

• Levofloxacin = R

• Tigecycline = R

Colistin = R

Now what do we do

Prevention

•Hand hygiene

• Isolation practices– Isolation based on syndromes or diagnoses

–When to stop

–Visitors 

• Environmental cleaning

Antimicrobial Stewardship

What is stewardship?

A practice that ensures the optimal selection, dose, and duration of an antimicrobial therapy that leads to the best clinical outcome for the treatment or prevention of infection while producing the fewest toxic effects and the lowest risk for subsequent resistance. (Gerding, 2001)

Use drives resistance

Relationship of use to resistance

Paul, et al. J Hosp Infect 2005;60:256-60

There are NO antibiotics in development with novel mechanisms of action

Why is stewardship important?

Are we returning to the pre‐antibiotic era?

Does this matter to the IP?

Infection Prevention

• Decrease in C. difficile infections

• Decrease in resistant Enterobacteriacae

• Trend toward reduced VRE infections

• No impact on MRSA infections

Why aren’t we ALL doing this?

• Physician automony

• Perceived financial costs

• Institutional infrastructure– Administrative “buy‐in”

– Computerized vs. paper charting/orders

– Pharmacy staff/time

– Infectious Diseases/Epidemiologist availability

Competing Interests

50% did NOT have CAP30% of these died

Summary

•MDROs increasing

•Mortality with resistance greater?

• Prevention is becoming the only option for many pathogens (i.e. Gram‐negatives)

• Antimicrobial stewardship and infection prevention are linked

EVERYPatient.

EVERYTime.

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