1. MDROs 101 Multidrug-Resistant Organisms
By Dr. Sherif Ibrahim

2. Review epidemiology of MDROs
Objectives
Review epidemiology of MDROs
Reservoir
Mode of transmission
Type of infection
Role of environment
Review specific MDROs
Prevention strategies
Contact Precautions
Exercise

3. Multi-Drug Resistant Organisms (MDROs) Epidemiology
Definition:
microorganisms, predominantly bacteria, that are resistant to one or more classes of antimicrobial agents
Importance:
Limited options for treatment
Increase the length of stay and cost of hospitalization
Increase admission to and stay in ICU
High mortality rates

4. MDROs - Epidemiology Transmission:
Mainly person to person through hands of healthcare personnel (HCP)
Contact with contaminated environmental surfaces
Transmission depends on
Availability of vulnerable patients
Antimicrobial pressure
Colonization pressure
Adherence to infection control measures
Frequent movement among healthcare facilities
Colonization Pressure: It is defined as the proportion of patients colonized with a particular organism in a defined geographic area within a hospital/healthcare facility during a specified time period
Antimicrobial Pressure: Increased antimicrobial use leads to selective pressure on normal flora resulting in emergence of MDROs

5. MDROs – Epidemiology Reservoirs Risk factors
Infected and colonized patients
Contaminated environmental surfaces & patient care equipment
Risk factors
Colonization, age > 65, ICU admission, long hospital stay, frequent hospitalizations, invasive procedures, indwelling devices, underlying diseases, enteral feeding, LTCFs, antimicrobial exposure

6. MDROs – Epidemiology
Infected: a person who has culture-positive for an MDRO and displays signs or symptoms of infection
Colonized: a person who has culture- positive for an MDRO but has no signs or symptoms of infection

7. Important MDROs ESCAPE
Enterococcus faecium (VRE) Staphylococcus aureus (MRSA) Clostridium difficile (C. Diff) Acinetobacter baumannii Pseudomonas aeruginosa Enterobacteriaceae (CRKP/CRE)

8. Gram Positive MDROs
Methicillin‐Resistant Staphylococcus aureus (MRSA)
Vancomycin‐Resistant Enterococci (VRE)

9. MRSA – Epidemiology Staph aureus (SA) resistant to beta‐lactams.
Nasal colonization  general population
25-30 % for SA
< 2% for MRSA
Other colonization sites: rectum, axilla, throat, wounds
Higher carriage among HCP, dialysis patients, diabetics, IV drug users
Reservoirs: ……. and……...
Transmission…… and………
MRSA carriage varied substantially across 10 nursing homes. Overall point prevalence was 31% (range, 7%–52%)
Versus 6% in hospitals and 9%–24% in intensive care units.
Reservoirs: colonized and infected individuals (frequent contact with the healthcare system)
Transmission: Person to person mainly through hands of HCP and direct contact with contaminated environmental services.
Beta-Lactams: penicillins, cephalosporins, cephamycins, carbapenems, monobactams

10. MRSA – Epidemiology 49-65 % of HA-Staph infections NHSN
94,360 invasive MRSA infections annually/US
18,650 associated deaths
86% of all invasive MRSA are HAIs
Staphylococcus aureus
Intrinsic virulence
Cause a wide range of life threatening infections
Adapt to different environmental conditions
Can survive in the environment 1-56 days
Predominant pathogen in HAIs
a survey of 463 hospitals in  565 of device-associated SA infections are MRSA
MRSA can be carried in the nares for more than 1 year; in one study, subsequent MRSA infections occurred in 29% of patients within 18 months of a previous colonization or infection

11. Prevention and Control
MRSA colonization generally precedes infection
Risk of developing MRSA infection among colonized individuals is 29% in 18 months
Rationale for prevention
Prevent transmission from colonized to un-colonized individuals
Prevent infection in colonized individuals
MRSA-specific strategies (Decolonization)
Non MRSA-specific strategies (reduce device- associated infections)

12. Vancomycin‐Resistant Enterococci (VRE) Epidemiology
Aerobic Gram positive cocci that inhabitant of GI tract and female genital tract
Endemic in most U.S. hospitals
25% all enterococcal isolates are VRE
Resistance is commonly seen in isolates of E. faecium than E. faecalis
Risk factors (Host, Healthcare facility, Antimicrobial exposure)

13. VRE Epidemiology Reservoirs: ….. and …….. Transmission: ……and ……
Common sites of infection: urinary tract, surgical wound, blood stream
Mortality rate is 2 times higher in VRE than VSE infections
Survives on environment  days – weeks
Reservoirs: colonized and infected individuals (frequent contact with the healthcare system)
Transmission: Person to person mainly through hands of HCP and direct contact with contaminated environmental services.
Resistance develops due to acquisition of van gene clusters on mobile genetic elements that are transferable between enterococcal strains
Host Related Risk Factors: VRE colonization , Enterococcal stool density, Immunodeficiency, Transplant recipient, Clostridium difficile diarrhea , Renal insufficiency, Severity of underlying illness
Healthcare facilities: ICU Admission, Proximity to a patient with VRE, Length of hospitalization, Multiple unit stays, Enteral feedings (Total perienteral nutrition)
Medications: Number, type, and duration of antibiotic therapy, Vancomycin use, 3rd Generation Cephalosporin utilization, Anti-anaerobic antibiotics (such as Clindamycin), Flouroquinolones (such as Ciprofloxacin)

14. Gram Negative MDROs Glucose fermenter (Enterobacteriaceae)
Foodborne (Salmonella, Shigella)
Healthcare-associated Enterobacter species (E. cloacae)
Community and Healthcare-associated
Klebsiella species (K. pneumoniae)
Escherichia coli
Non–glucose fermenters
Acinetobacter baumannii
Pseudomonas aeruginosa

15. Enterobacteriaceae Epidemiology
Normal human gut flora
Environment (soil & water)
Important cause of community and HA infections
Wide range of infections (UTI, Bacteremia, pneumonia, wound infection)
E. coli most common cause of outpatient UTIs
E coli and Klebsiella accounted for 15% all HAIs reported to NHSN 2007
Risk of Enterobacteriaceae infections high among patients with a pathologic intra-abdominal condition /surgery.
Urinary tract infection both catheterized and non catheterized patients because of the proximity of the urethral meatus to the anus. Recent Prolonged hospitalization, LTCF

16. Development of Antimicrobial-Resistant Enterobacteriaceae
B lactamases  resistant to B-lactams for decades
Extended spectrum B-lactamases (ESBL)  resistant to 3rd generation cephalosporins, monobactams
Usually nosocomial however 34% from patients with no healthcare contact
Carbapenems  the last line of defense for treatment

17. Development of Antimicrobial-Resistant Enterobacteriaceae
Carbapenem-Resistant Enterobacteriaceae (CRE)
Resistance  production of a carbapenemase also known as KP carbapenemase (KPC)
Resides on transferable plasmids wide spread transmission
Limits options for treatment (Polymyxins problems with nephrotoxicity)
Reservoirs: ……..and …..
Transmission; …..and ……
Resistance mainly occurs in KP, reported in other Enterobecteriacea, few reports in Pseudomonas
Reservoirs: colonized and infected individuals (frequent contact with the healthcare system)
Transmission: Person to person mainly through hands of HCP and direct contact with contaminated environmental services.

18. Geographical Distribution of KPC-Producers
Sporadic isolate(s)
2001
Centers for Disease Control and Prevention. 18 18

19. Geographical Distribution of KPC-Producers
Widespread
Sporadic isolate(s)
2006
Centers for Disease Control and Prevention. 19 19

20. Geographical Distribution of KPC-Producers
Sporadic and Widespread isolate(s)
2010
Centers for Disease Control and Prevention. 20 20

21. Susceptibility Profile of KPC-Producing KP
Antimicrobial
Interpretation
Amikacin I
Chloramphenicol R
Amox/clav
Ciprofloxacin
Ampicillin
Ertapenem
Aztreonam
Gentamicin
Cefazolin
Imipenem
Cefpodoxime
Meropenem
Cefotaxime
Pipercillin/Tazo
Cetotetan
Tobramycin
Cefoxitin
Trimeth/Sulfa
Ceftazidime
Polymyxin B
MIC >4mg/ml
Ceftriaxone
Colistin
Cefepime
Tigecycline S

22. Mortality Associated with CRKP48 20 38 12
OR 3.71 ( )
OR 4.5 ( )

23. CRKP in Long-Term Care Facilities
Few clinical cases  large reservoir of colonized patients in LTCFs.
Colonization rate was as high as 49% in one outbreak
Recipe for CRKP outbreaks:
Infection control breaches (lack of compliance)
Unrecognized colonized residents serving as reservoirs for transmission

24. MDR- Acinetobacter baumannii (Ab) Epidemiology
Non-motile gram negative bacteria (32 species)
Ubiquitous  widely distributed in nature (soil, water, food, sewage) & the hospital environment
MDR-Ab is primarily a nosocomial pathogen
Long survival time on inanimate surfaces extensive environmental contamination
Transmission …. and……
Reservoirs: …… and …..
Reservoirs: colonized and infected individuals (frequent contact with the healthcare system)
Transmission: Person to person mainly through hands of HCP and direct contact with contaminated environmental services.
In vitro survival time 329 days
11 days survival on Formica, 12 days on stainless steel
Up to 4 months on dry surfaces
(Wagenvoort JHT, Joosten EJAJ. J Hosp Infect 2002;52: )
(Webster C et al. Infect Control Hosp Epidemiol 2000;21:246)
(Wendt C et al. J Clin Microbiol 1997;35: )
32 species >2/3 of Acinetobacter infections are due to A. baumanii
The bacteria colonize the pharynx intermittently in 7% of the general population and in addition can be isolated from sputum, urine, stool, and vaginal discharges
MDR-AB carriage and natural history have not been well studied
Skin colonization are 25 to 40% among healthy individuals and up to 75% for hospitalized patients

25. MDR- Ab Epidemiology Widespread environmental contamination
Respiratory care equipment
Bed rails, Bedside tables,
Mattresses, Pillows
Curtains, door handles
Keyboards
Floor mops, sinks
Air humidifiers
Patient care items
Wound care procedures
Equipment carts,
Infusion pumps
Patient monitors and X-ray board
The bacteria colonize the pharynx intermittently in 7% of the general population and in addition can be isolated from sputum, urine, stool, and vaginal discharges
MDR-AB carriage and natural history have not been well studied
Skin colonization are 25 to 40% among healthy individuals and up to 75% for hospitalized patients
Most common gram negative carried by skin of HCP
Frequently colonizes tracheostomy site
Chlorohexidine resistance

26. MDR- Ab Epidemiology MDR- Acinetobacter mainly causes HAIs
Pneumonia (Ventilator-associated pneumonia)
Urinary tract
Bacteremia
Meningitis
Skin/wound infections
MDR- Acinetobacter infections
Acute care (ICUs) traditionally, associated with outbreaks
LTAC & LTCFs
Injured military personnel
Outbreaks  mortality rates up to 75%

27. MDR- Pseudomonas aeruginosa Epidemiology
Aerobic gram-negative rods
Ubiquitous in soil and water
Moist environment (hydrophilic) (e.g. sink drains, vegetables, river water, etc.)
P. aeruginosa is an opportunistic infection  rarely colonize healthy individuals
At Risk individuals:
Immuno-compromised
Burn patients
Patients on mechanical ventilation
Cystic fibrosis patients

28. P. aeruginosa Epidemiology
10% of all hospital-acquired infections
Often cause severe life threatening HAIs
Can be found everywhere
Can be community acquired
In healthcare facilities: respiratory equipment, food, sinks, taps, toilets, weak disinfectants, showers and mops, uncooked vegetables, flower water
Transmission …..and ……….
Reservoirs ……. and …………
Colonization precedes infection in 50% of cases
Reservoirs: colonized and infected individuals (frequent contact with the healthcare system)
Transmission: Person to person mainly through hands of HCP and direct contact with contaminated environmental services.
colonization  moist areas axilla, ears, perineum

29. Prevention Strategies (MDROs)
Core Measures
Administrative support
Surveillance
Patient placement
Patient/staff cohorting
Hand hygiene
Contact precautions
Protocol for lab notification
Dedicated equipment
Device use
Environmental measures
Monitor compliance
Education
Antimicrobial stewardship
Supplemental Measures
Preemptive isolation
Active surveillance culture
Chlorohexidine bathing

30. C. difficile : Epidemiology
Gram positive spore forming bacillus (rods)
Obligate anaerobe
Part of the GI Flora in
1-3% of healthy adult
70% of children < 12 months
Some strains produce toxins A & B
Toxins-producing strains cause C. diff Infection (CDI)
CDI ranges from mild, moderate, to severe and even fatal illness
G positive means (Dark blue when use gram stain
Obligate anaerobes does not require O2 to survive
Toxins are required to cause disease. A is the major toxins B can also cause the same illness as A
CDI used to be called CDAD

31. C. difficile Epidemiology
Transmission
Fecal – oral route
Contaminated hands of healthcare workers
Contaminated environmental surfaces.
Person to person in hospitals and LTCFs
Reservoir:
Human: colonized or infected persons
Contaminated environment
C. diff spores can survive for up 5 months on environmental surfaces.
surfaces, devices commodes, bathing tubs, and electronic rectal thermometers)
Source of infection can be endogenous or exogenous

32. C. difficile: Epidemiology
A common cause of nosocomial antibiotic- associated diarrhea (AAD)
Most common infectious cause of acute diarrheal illness in LTCFs
The only nosocomial organism that is anaerobic and forms spores
Infective dose is < 10 spores

33. Number of annual deaths
CDI: Impact
Number of annual cases
Cost
Number of annual deaths
Hospital-onset, hospital acquired (HO-HA)
165,000
$ 1.3 B
9000
Nursing home-onset
$ 2.2 B
16,500

34. Clinical Manifestations
Illness caused by toxin-producing strains of C. difficile ranges from
Asymptomatic carriers = Colonized
Mild or moderate diarrhea
Pseudo membranous colitis that can be fatal
A median time between exposure to onset of CDI symptoms is of 2–3 days
Risk of developing CDI after exposure ranges between days to 10 weeks

35. Rationale for Preventive strategies
Colonized
no symptoms
Antimicrobial stewardship
Antimicrobials
C Diff exposure & acquisition
Patients acquire C diff at the HCF 1- contact with a healthcare worker with transient hand colonization,
2 contact with the contaminated environment, or (3) by direct contact with a patient with CDI.
The rate of acquisition during hospitalization increases linearly with time and can be as high as 40%
after 4 weeks of hospitalization
Optimizing Environmental cleaning and Hand Hygiene
Admitted to healthcare facility
Infected
Symptomatic

36. Preventive Strategies: C. Diff
Core Measures
Surveillance
Contact Precautions (CP) for duration of diarrhea
Hand hygiene (HH)
Dedicated equipment
Cleaning and disinfection of equipment and environment
Laboratory-based alert system for immediate notification
Educate HCP, housekeeping, admin staff, patients, families, visitors, about CDI
Monitor compliance
Supplemental Measures
Extend (CP) beyond duration of diarrhea (48 hours)
Presumptive isolation for symptomatic patients
Implement soap and water for HH before exiting room of a patient with CDI
Implement universal glove use on units with high CDI rates
Use sodium hypochlorite (bleach) - containing agents for environmental cleaning
Implement an antimicrobial stewardship program

37. Contact Precautions (CP)
Patient placement (factors to consider)
Hand hygiene (HH)
Gloves
Don gloves upon room entry
Change gloves after contact with infectious materials
Change gloves when moving from contaminated to non contaminated site
Remove gloves and HH before leaving the room or caring for another patient
Gowns
Don gown upon room entry
Remove and discard gloves before removing gown
Discarding gown before exiting the room
After gown and gloves removal HH make sure not to touch any potentially contaminated environmental surface in the room
Dedicated equipment (BP cuff, stethoscope, thermometer, etc.)

38. Contact Precautions in LTCFs
Challenges of implementing CP in LTCFs
Contact Precautions should be used for the following residents with MDROs
Dependent on HCP in their activities of daily life
Ventilator-dependent
Incontinent of stool
Wound with difficult to contain discharge
Contact Precautions can be relaxed for all others residents with MDROs (consider resident’s mental status and personal hygiene)
Standard precautions should be observed all times
Dedicated equipment
Signage for HCP and visitors

39. Conclusion
MDROs represent a major clinical and infection control challenge particularly in LTCFs
You cannot do it alone  Regional approach
Aggressive infection control approach works
Appropriate antimicrobial use
Training and education (HCP, Patients, Families)
Communications (intrafacility and interfacilities)

40. Exercise
During morning rounds you were assigned rooms 103 and 107 for the day
Room 103
Under contact precautions
Has 2 patients
Patient #1 was recently treated for CRKP UTI, has a Foley catheter and is stool incontinent
Patient # 2 is CRKP colonized and has a deep bedsore in the right buttock
Room # 107
Has two residents admitted for short term rehabilitation S/P total knee replacement. One of them is stool incontinent

41. Questions
What type of precautions would you use upon entering Room 103 and why?
How is this type of organism transmitted?
What type of precautions will you be using for room 107 and why?
Do you think it is a good practice to provide care for these two rooms in the same day? Please explain why and what is the best practice in this situation?
Patient # 2 in room 103 is ambulatory and he wants to go to the activity room. What would you do?
In the schedule, all four patients are due for bathing. Specify who would go first.

42. Questions

43. Resources and References
SHEA/APIC Guideline: Infection Prevention and Control in the Long- Term Care Facility tion%20Control%20Jul08.pdf
Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings
Management of Multidrug-Resistant Organisms In Healthcare Settings,
DIDE Website
CDC Healthcare-Associated Infections
CDC SHEA “Train the Trainer” May 2011
Epidemiology and Prevention of Common Emerging MDROs “Alex Kallen, MD, MPH” DHQP, CDC