1. Managing MDROs in LTCFs
Nimalie D. Stone, MD/MS
Medical Epidemiologist for LTC
GA LTC IC course
Winter/Spring 2011
National Center for Emerging and Zoonotic Infectious Diseases
Division of Healthcare Quality Promotion

2. Objectives
Review basics about common bacteria which can develop antibiotic resistance in the healthcare setting
Discuss mechanisms by which antibiotic resistance emerges and spreads
Identify strategies for preventing MDRO transmission

3. Basics on Bacteria
Gram Stain
Positive
(purple)
Gram Stain
Negative
(pink/red)
Bacteria have different characteristics that allow us to identify them in the lab
Growth patterns, structure of the cell
We use these characteristics to develop antibiotics

4. Common types of Bacteria
Gram positive
Most are cocci, “round bacteria”
Streptococcus, Staphylococcus, Enterococcus
Clostridium difficile (C. diff) is a Gram positive rod
Gram negative
Most are baccili, “rod-shaped bacteria”
Enterobacteriaceae: E coli, Klebsiella, Enterobacter , Proteus
Pseudomonas

5. Normal Bacterial Carriage
People have bacteria living in and on us all the time
Some live on our skin, some in our nose and throats, others in our bowels
Our bodies need these bacteria to help us
Some digest food/nutrients, others block bad bugs
These “colonizing” bacteria aren’t harmful
Only bacteria that invade our system and cause illness need to be treated

6. Antibiotics 101 Antibiotics are drugs that treat and kill bacteria
They are grouped into classes based on their structure and activity
Narrow-spectrum target a few specific bacteria
Broad-spectrum can kill a wide variety of bacteria
Infection prevention programs track certain “bug-drug” combinations for evidence that the bacteria is getting resistant
Bacteria with resistance can cause patients to have more severe, costly infections which are harder to treat

7. Antibiotic Classes Penicillins Cephalosporins (cousins to penicillins)
Examples: Penicillin, amoxicillin, ampicillin, methicillin
Penicillins can be combined with a drug to help them overcome certain bacterial resistance
Amoxicillin + Clavulante = Augmentin;
Piperacillin + tazobactam = Zosyn
Cephalosporins (cousins to penicillins)
1st generation (more gram positive activity): Cephalexin, Cefazolin
3rd/4th generation (more gram negative): Ceftriaxone, Ceftazidime

8. Antibiotic Classes (cont)
Carbapenems
Examples: Imipenem, meropenem, ertapenem
Extremely broad-spectrum, among the most powerful antibiotics we currently
Miscellaneous drugs with only gram positive activity: Vancomycin, linezolid, daptomycin
Vancomycin is the primary treatment for Methicillin-resistant Staphylococcus aureus (MRSA)
Oral vancomycin is ONLY used to treat C difficile;
IV Vancomycin must be used to treat all other infections
Enterococci that develop resistance to Vancomycin are called Vancomycin-resistant enterococci (VRE)

9. Antibiotic Classes (cont)
Fluoroquinolones
1st generation (Ciprofloxacin) mostly gram neg activity, often used for UTI treatment
2nd/3rd gen (Levofloxacin/Moxifloxacin) have broader activity, can cover Streptococcus pneumoniae and other respiratory/sinus bacteria
Aminoglycosides
Examples: Gentamicin, Tobramycin, Amikacin
Excellent gram negative drugs – especially for urinary tract
Aren’t used as much because can be toxic to the kidneys, need to be monitored when used

10. Antibiotic Classes (cont)
Miscellaneous drugs
Trimethoprim/Sulfamethoxazole (Bactrim): Considered by many to be narrow spectrum, but has Gram neg and Gram pos activity, used to treat UTIs, also good for MRSA skin infections
Azithromycin (“Z-pack”): Also considered more narrow spectrum, good for respiratory/sinus infections
Metronidazole (Flagyl): One of the main treatments for C. difficile infections

11. Mechanisms of antibiotic resistance
Production of proteins that destroy antibiotics
Beta-lactamases
Carbapenemases
Change their cell structure so antibiotics can’t bind and block their function
Reduce their antibiotic exposure
Pump drugs out
Increase cell barriers to keep drug out

13. Snapshot of resistance patterns: Facility antibiograms
A yearly summary of the common bacteria from facility cultures and their susceptibility patterns to antibiotics
Allows you to see trends in resistance over time
Ask your microbiology lab about it

14. Defining Multidrug-resistance
Resistant to treatment by several antibiotics from unrelated classes
Sometimes just one key drug resistance will define an important MDRO, for example, Methicillin-resistance in Staph aureus
Sometimes bacteria acquire resistance to several classes, often seen in gram negative rods
Cephalosporin-resistance is a big concern in bacteria like E coli/Klebsiella which often cause UTIs
Pseudomonas will be resistant to fluoroquinolones, penicillins, cephalosporins, and carbapenems

15. ABC’s of MDROs Bacteria Abbrev. Antibiotic Resistance
Staphylococcus aureus
MRSA
Methicillin-resistant
Enterococcus (faecalis/faecium)
VRE
Vancomycin-resistant
Enterobacteriaceae
(E coli/Klebsiella, etc)
CRE (KPC)
Carbapenem-resistant
Pseudomonas/ Acinetobacter
MDR
Many drug classes

16. Staphylococcus aureus
Derived from the Greek word Staphyle: “Bunch of grapes” and aureus: “gold”
Part of the normal colonizing bacteria on our skin and in the nose
Though it colonizes many people, it may not cause infection unless the skin gets broken or the immune system gets weak

17. Methicillin-resistant Staphylococcus aureus (MRSA): An ongoing problem
First emerged in the US healthcare setting in 1968
Outbreaks linked to transmission via healthcare workers
Prevalence in nursing homes, 20-50%
Community-acquired strains are adding to the burden of infection in the healthcare setting
Increasing public and legislative pressure to address the transmission of MRSA in healthcare

18. Risk Factors for Healthcare- associated MRSA infections
Previous hospitalization
Increased length of stay prior to onset of infection
Surgery
Enteral feeding
Prior antibiotics
Invasive devices
History of MRSA colonization
Residence in a long-term care facility
1. Graffunder EM & Venezia RA. J Antimic Chemo 2002;49: Oztoprak, N. et al. Am J Infec Cont. 2006; 34: Wertheim et al. Lancet 2005; 5: Bader, M. Inf Cont Hosp Epi. 2006; 27:

19. Clostridium difficile
Gram positive rod which grows best without oxygen (anaerobic)
C. diff has a special growth characteristic called “spores”
Hard outer shells in which sleeping bacteria can survive in the environment for long periods
Spores are shed in large numbers during the diarrhea caused by C diff infection (CDI)

20. Steps to C. diff Infection (CDI)
Acquisition of C. difficile
Antibiotic therapy
Changes normal colonic bacteria
C diff over grows and produces toxin

21. More than half of healthcare associated CDI cases occur in long-term care facilities
A significant number of individuals admitted to LTC are colonized with C difficile
Up to 20% acquire it while in nursing homes
CDI is the most commonly identified cause of acute diarrheal illness in the LTC population

22. CDI risk factors causing disease
Poutanen & Simor. CMAJ :51-8

23. Exposures and risk factors related to CDI in older adults
Simor. JAGS. 2010, e publ

24. C diff. prevention challenges
Spores are not killed by alcohol hand rubs; the act rubbing your hands with soap under water removes the spores
Spores are resistant to common cleaners and require bleach to be effectively killed

25. Managing a resident with C diff.
The goal of therapy for C diff infection is to stop the symptoms of diarrhea, abdominal upset and fever
Once the diarrhea has resolved, the resident is safe to move about the facility
Residents can carry C.diff in their bowels (colonized) for months after their diarrhea resolves
After being treating a resident for CDI, there is NO VALUE in sending multiple C diff stool studies to see if “the infection has cleared”
Often you’ll continue to get positive results which prompt unnecessary additional treatment

26. Carbapenemase producing GNRs
Carbapenemases are protein enzymes that break down all penicillins, cephalosporins and carbapenems
There are different types of these enzymes some found in bugs like Acinetobacter and Pseudomonas ; others found in bugs like Klebsiella
The genetic material also tends to carry resistance to other antibiotic classes like fluoroquinolones and aminoglycosides
What’s really scary is that the resistance genes can be easily shared to other bacteria
Especially since we have lots of gram-negative bacteria colonizing our bowels
Walsh, TR. Current Opin Infect Dis 2008;21:367-71

27. Monitor your culture reports for Carbapenem-resistant GNRs
Widely reported in the US and specifically Georgia
Ask your referral hospitals if they have had problems
Being aware of new resistance patterns in your residents will help you prevent spread
States reporting Carbapenem-Resistant Enterobacteriaceae (CRE)

28. Case of an emerging MDRO….
Lab examined all the Acinetobacter cultured from people at 4 local hospitals over 5 years
Classified as hospital-associated, NH-associated, or community-associated
Wanted to see how antibiotic resistance emerged in this community

29. Multidrug-resistance emerged quickly
Over 5 year period, antibiotic resistance increased dramatically
In the last 2 years of the study pan-resistant bacteria emerged
Culture sources: Respiratory secretions (56%); Wounds (22%); Urine (12%)
Sengstock DM, et al. Clin Infect Dis (12):

30. Healthcare facilities are the source of MDROs
All the highly resistant bacteria were coming from patients in the hospital or those in the nursing homes – NOT from people living at home
Sengstock DM, et al. Clin Infect Dis (12):

31. MDROs in the healthcare setting
DEVELOPMENT
Antibiotic pressure
Most common predictor of antibiotic resistance is prior antibiotic use
Device utilization
Biofilm formation on central lines, urinary catheters, etc.
SPREAD
Patient to patient transmission via healthcare workers
Environmental / equipment contamination
Role of colonization pressure on acquisition
Step one in our fight against drug-resistant bacteria is understanding the ways in which they develop and spread in our healthcare facilities and community 31

32. Resistance from antibiotic pressure
At first most of the bacteria can be killed by the drug (green)
But, once they are wiped out, the resistant bugs take over (red)

33. Antibiotic use drives resistance
On this graph you can see that after a few years of increasing antibiotic use – they start seeing a rise in the fraction of bacteria resistant to that antibiotic in the community
Johnson et al. Am J. Med. 2008; 121: 33

34. Biofilm formation on device surfaces
A biofilm is a slime layer that bacteria form on the plastic surfaces of devices that we place in our patients. This is why over time, all people with chronic devices have bacteria colonizing those devices
Biofilm: An collection of bacteria within a sticky film that forms a community on the surface of a device 34

35. Biofilm on an indwelling catheter
When you take out one of those devices and look at its surface under a really powerful microscope, you can actually see the slime layer of bacteria that has formed
Tenke, P et al. World J. Urol. 2006; 24: 13-20 35

36. Resistance develops within biofilms
Bacteria within a biofilm are grow every differently from those floating around freely
These changes in their growth make our antibiotics less effective
Antibiotics can’t penetrate the biofilm to get to the bacteria
This leads to much less drug available to treat the bugs
Bacteria within the biofilm can talk to each other and share the traits that allow some to be resistant
Over time more and more of them become resistant as well
Tenke, P et al. World J. Urol. 2006; 24: 13-20

37. Improved Patient Outcomes Associated with Hand Hygiene
Ignaz Philipp Semmelweis ( ), a Hungarian obstetrician, postulated his theory on antiseptic hand hygiene techniques in 1847.
Semmelweis noted that post-partum women examined by medical students who did not wash their hands after performing autopsies had high mortality rates.
He required students to clean their hands with chlorinated lime before examining patients.
Maternal mortality declined from 18% to 1% after this hand hygiene intervention was implemented.
Ignaz Philipp Semmelweis
( )
Chlorinated Lime Hand Antisepsis
Adapted from CDC. Prevent Antimicrobial Resistance: A Campaign for Clinicians. April 2002.

39. Bacterial contamination of HCW hands prior to hand hygiene in a LTCF
Gram negative bacteria were the most common bugs cultured from hands of staff
Most Gram neg. bacteria live in the bowls or colonize the urine!!!
Mody L, et al. InfectContHospEpi. 2003; 24:

40. Hand Hygiene
Most effective and least costly means of preventing the transmission of MDROs
Yet, compliance still ranges between ~30-60%
Instructor Notes:
Consistent use by staff of proper hygienic practices and techniques is critical to preventing the spread of infections. 40 40

41. Alcohol-based hand rub improves compliance and decontamination
Mody L, et al. InfectContHospEpi. 2003; 24:

42. Decreased MRSA infections associated with increased hand hygiene compliance
Pittet, D et al.Lancet 2000;356:

43. 43

44. The invisible reservoir of MDROs
X marks the locations where VRE was isolated in this room
Image from Abstract: The Risk of Hand and Glove Contamination after Contact with a VRE (+) Patient Environment. Hayden M, ICAAC, 2001, Chicago, IL.
Slide courtesy of Teresa Fox, GA Div PH 44

45. Duration of environmental contamination by MDROs45

46. Colonization pressure on risk of acquisition
Colonization pressure: Presence of other MDRO carriers on a unit will increase the risk of MDRO acquisition to a non-carrier close by
Studies have demonstrated the impact of colonization pressure on acquisition of MRSA, VRE and CDI
Both asymptomatic carriers (colonized) and actively infected individuals can be a source for transmission (spread) on a unit
Williams VR et al. Am J Infect Control Mar;37(2):106-10
Bonten MJ et al. Arch Intern Med May 25;158(10):
Dubberke ER et al. Arch Intern Med May 28;167(10):1092-7

47. Colonization pressure: C.diff example
Unit A
Fewer patients with active CDI
=lower risk of acquiring CDI
Unit B
More patients with active CDI
=higher risk of acquiring CDI
CDI pressure
=1 × days in unit
=5 × days in unit
Dubberke ER, et al. Clin Infect Dis. 2007;45:
Dubberke ER et al. Arch InternMed.2007;167(10):1092-7 47

48. Key MDRO Prevention Strategies
Assessing hand hygiene practices
Implementing Contact Precautions
Recognizing previously colonized patients
Rapidly reporting MDRO lab results
Strategically place residents based on MDRO risk factors
Careful device utilization
Antibiotic stewardship
Inter-facility communication

49. Assessing Hand Hygiene
Hand hygiene should be a cornerstone of prevention efforts
As part of a hand hygiene intervention, consider:
Ensuring easy access to soap and water/alcohol-based hand gels
Observation of practices - particularly around high-risk situations (before and after contact with colonized or infected patients)
Feedback – “Just in time” feedback if failure to perform hand hygiene observed

50. Implementing Contact Precautions
Involves use of gown and gloves for patient care
Don equipment prior to room entry
Remove prior to room exit
Selective roommate placement for MDRO colonized/infected individuals
Observation of practices - particularly around high-risk situations
Use of dedicated non-essential items may help decrease transmission due to contamination
Blood pressure cuffs; Stethoscopes; IV poles and pumps

51. Recognizing Prior Colonization
Individuals can be colonized with MDROs for months
Being able to identify previously colonized or infected individuals allows for application of appropriate interventions in a timely fashion
Being an MDRO carrier should not prevent a resident from being admitted to a LTCF,
Knowledge allows us to plan for them to have the safest care
For every resident carrying an MDRO that we know about, there are probably 3 others we don’t know

52. Strategic placement of residents based on risk factors
Base new roommate assignments on resident characteristics
Wounds, devices, current antibiotics, incontinence are all risks for being an MDRO carrier or acquiring a new MDRO
Try to avoid placing two high risk residents together
Don’t necessarily change stable room assignments just because of a new culture result unless it now poses new risk
Roommates who’ve been together for a long time have already had opportunity to share organisms in the past (even if you only learned about it recently)

53. Prompt Recognition of MDROs in Laboratory Reports
Facilities should have a mechanism for rapidly communicating positive MDRO lab results to clinical area
Allows for rapid initiation of interventions on newly identified MDRO carriers
Consider implementing precautions while waiting for results from the lab if an MDRO is possible
For example, contact precautions for a resident with diarrhea while waiting for results of a C diff stool study

54. Careful Device Utilization
Know the population of residents with indwelling medical devices
May require focused infection surveillance
Continually assess the ongoing need for devices
Develop a bladder protocol for urinary catheter removal
Resist the temptation to retain IV lines beyond the duration of treatment “just in case”
Ensure staff are comfortable and trained on handling/maintenance of medical devices

55. Antibiotic Stewardship
Careful antibiotic use is a critical component in the control of MDROs
Know the frequency/indications for antibiotic use by medical providers in your facility
Apply criteria to assess utilization in a standard way
Develop standard protocols for communicating concerns and assessing residents who are suspected to have an infection between nursing and medical staff
Ensure documentation of signs/symptoms is complete

56. Case study on care transitions
A LTC resident was transferred to a local ED with worsening lower extremity swelling and shortness of breath
Resident’s history included coronary heart disease, Diabetes with neuropathy, enlarged prostate
Diagnosed with worsening heart failure admitted to ICU for cardiac monitoring and fluid management
A urinary catheter was placed at the time of admission and a specimen was sent for UA/culture in ED.
Based on the UA, the patient was started on antibiotics

57. Case study (continued)
After treatment for heart failure and the positive urine culture, the resident was discharged backed to the LTC facility with the catheter in place.
Prior to removing the urinary catheter a repeat culture was sent which grew VRE
A second course of antibiotics was initiated
Two weeks later the resident developed diarrhea and fever
Stool sample was positive C. Diff toxin test.

58. Issues raised by our case
Is the practice of screening urine cultures on admission a valuable strategy?
What are the pros/cons
Did the resident continue to need the urinary catheter once the CHF was managed?
How is resident functionality communicated at time of transfer
How are antibiotics used in both acute/LTC facilities in this shared population?
Who is accountable for the complications of antibiotic use?

59. Inter-facility Communication
Mechanism for communicating MDRO carriage and other risk factors at time of transfer between facilities
Critical components:
MDRO history of current infection or carriage
Device utilization
Current antibiotic treatments (indication/duration)
Bedside care issues (wounds, continence, etc)

61. Summary of Prevention Strategies
Assessing hand hygiene practices
Implementing Contact Precautions
Recognizing previously colonized patients
Rapidly reporting MDRO lab results
Strategically place residents based on MDRO risk factors
Careful device utilization
Antibiotic stewardship
Inter-facility communication

62. Story of Success…
Describes the impact of regionally implemented infection control strategies to address VRE emerging in the Siouxland region of Iowa, Nebraska and S. Dakota
Three annual point prevalence surveys (active surveillance) for VRE among patients/residents in participating acute/long-term care facilities

63. IC practice guidelines for facilities
Ostrowsky BE et al. New Eng J Med :

64. VRE prevalence decreased following prevention intervention
32 Facilities participated in 1997 and 1998 (4 acute/ 28 LTC) vs. 30 in1999 (4 acute/ 26 LTC)
Overall 85%-89% of eligible patients/ residents cultured each year
52-59% in acute care
90-95% in LTC
Ostrowsky BE et al. New Eng J Med :

65. Critical message about collaboration
Ostrowsky BE et al. New Eng J Med :

66. Thank you!!
with questions/comments
National Center for Emerging and Zoonotic Infectious Diseases
Division of Healthcare Quality Promotion