MDRO(multidrug resistant organisms)

1
MDRO(multidrug resistant organisms)

• Definition
• microorganisms, predominantly bacteria, that
  are resistant to one or more classes of
  antimicrobial agents. Although the names of
  certain MDROs describe resistance to only one
  agent (e.g., MRSA,VRE), these pathogens are
  frequently resistant to most available
  antimicrobial agents

2
MDRO(multidrug resistant organisms

• In addition to MRSA and VRE, certain gram
  negative bacteria(GNB), including those producing
  extended spectrum beta-lactamases (ESBLs) and
  others that are resistant to multiple classes of
  antimicrobial agents, are of particular concern

3
MDRO(multidrug resistant organisms

• Drug-resistant pathogens are a growing threat
  to all people, especially in healthcare settings.

4
MDRO(multidrug resistant organisms

• Each year nearly 2 million patients in the
  United States get an infection in a hospital. Of
  those patients, about 90,000 die as a result of
  their infection. More than 70 of the bacteria
  that cause hospital-acquired infections are
  resistant to at least one of the drugs most
  commonly used to treat them. Persons infected
  with drug-resistant organisms are more likely to
  have longer hospital stays and require treatment
  with second- or third-choice drugs that may be
  less effective, more toxic, and/or more expensive

5
Clinical importance of MDROs

• - In most instances, MDRO infections have
  clinical manifestations that are similar to
  infections caused by susceptible pathogens.
  However, options for treating patients with these
  infections are often extremely limited. Although
  antimicrobials are now available for treatment of
  MRSA and VRE infections, resistance to each new
  agent has already emerged in clinical isolates.
• - Similarly, therapeutic options are limited
  for ESBL-producing isolates of gram-negative
  bacilli

6
Clinical importance of MDROs

• -These limitations may influence antibiotic
  usage patterns in ways that suppress normal flora
  and create a favorable environment for
  development of colonization when exposed to
  potential MDR pathogens (i.e., selective
  advantage).
• -Increased lengths of stay, costs, and
  mortality also have been associated with MDROs.

7
Clinical importance of MDROs

• The type and level of care influence the
  prevalence of MDROs. ICUs, especially those at
  tertiary care facilities, may have a higher
  prevalence of MDRO infections than do non-ICU
  settings

8
MethicillinResistant Staph (MRSA)

• MRSA was first isolated in the United States
  in 1968.
• By the early 1990s, MRSA accounted for
  20-25 of Staphylococcus aureus isolates from
  hospitalized patients. In 1999, MRSA accounted
  for gt50 of S. aureus isolates from patients in
  ICUs in the National Nosocomial Infection
  Surveillance (NNIS) system in 2003, 59.5 of S.
  aureus isolates in NNIS ICUs were MRSA .

9
Methicillin-Resistant Staphylococcus
aureus(MRSA) Among Intensive Care Unit
Patients,1995-2004
Source National Nosocomial Infections
Surveillance (NNIS) System
10
Vancomycin-Resistant enterococcus (VRE)

• A similar rise in prevalence has occurred with
  VRE . From 1990 to 1997, the prevalence of VRE in
  enterococcal isolates from hospitalized patients
  increased from lt1 to approximately 15
• VRE accounted for almost 25 of enterococcus
  isolates in NNIS ICUs in 1999 and 28.5 in 2003 .

11
Vancomycin-Resistant Enterococci (VRE) Among
Intensive Care Unit Patients,1995-2004
12
Gram-negative resistant Bacteria

• -GNB resistant to ESBLs, fluoroquinolones,
  carbapenems, and aminoglycosides also have
  increased in prevalence.
• For example, in 1997, the SENTRY
  Antimicrobial Surveillance Program found that
  among K. pneumoniae strains isolated in the
  United States, resistance rates to ceftazidime
  and other third-generation cephalosporins were
  6.6, 9.7, 5.4, and 3.6 for bloodstream,
  pneumonia, wound, and urinary tract infections,
  respectively .
• In 2003, 20.6 of all K. pneumoniae isolates
  from NNIS ICUs were resistant to these drugs

13
3rd Generation Cephalosporin-Resistant Klebsiella
pneumoniae Among Intensive Care Unit Patients,
1995-2004
Source National Nosocomial Infections
Surveillance (NNIS) System
14
Fluoroquinolone-Resistant Pseudomonas aeruginosa
Among Intensive Care Unit Patients, 1995-2004
15
Campaign to PreventAntimicrobial Resistance

• Clinicians hold the solution!

16
Risk factors that promote antimicrobial
resistance in healthcare settings include

• Extensive use of antimicrobials
  Transmission of infection
• Susceptible hosts

17
Key Prevention Strategies
Clinicians hold the solution!

" Prevent infection " Diagnose and
treat infection effectively Use
antimicrobials wisely Prevent transmission
18
Selection for antimicrobial-resistant Strains
19
Emergence of Antimicrobial Resistance
Campaign to Prevent Antimicrobial Resistance in
Healthcare Settings
Susceptible Bacteria
20
Plasmids

• Rings of extra chromosomal DNA
• Can be transferred between different species
  of bacteria
• Carry resistance genes
• Most common and effective mechanism of
  spreading resistance from bacteria to bacteria
  (Bacterial Conjugation)

21
Beta-Lactamases What are they ?

• Enzymes produced by certain bacteria that
  provide resistance to certain antibiotics
• Produced by both gram positive and gram
  negative bacteria
• Found on both chromosomes and plasmids

22

• Beta-lactam Antibiotics
• Examples
• Penicillins
• Penicillin, amoxicillin, ampicillin
• Cephalosporins
• Cephalexin,Cefuroxime,Ceftriaxone
• Carbapenems
• Imipenem, meropenem

23
Beta-Lactamases

• Mechanism of Action
• Hydrolysis of beta-lactam ring of basic
  penicillin structure
• Hydrolysis adding a molecule of H2O to C-N
  bond with enzyme action
• This opens up the ring, thus making the drug
  ineffective!

24
ESBL?

• Resistance that is produced through the
  actions of beta lactamases.
• Extended spectrum cephalosporins, such as the
  third generation cephalosporins, were originally
  thought to be resistant to hydrolysis by
  beta-lactamases!
• Not so!
• mid 1980's it became evident that a new type
  of beta-lactamase was being produced by
  Klebsiella E coli that could hydrolyze the
  extended spectrum cephalosporins.
• These are collectively termed the
• 'extended spectrum beta-lactamases '( ESBL's
  )

25
ESBL?

• The story is more
  complicated.
• Multiple antimicrobial resistance is often
  a characteristic of ESBL producing gram-negative
  bacteria.
• Ceftazidime
• Cefotaxime
• Ceftriaxone
• Aztreonam
• Genes encoding for ESBLs are frequently
  located on plasmids that also carry resistance
  genes for
• Aminoglycosides
• Tetracycline
• TMP-SULFA
• Chloramphenicol
• Fluoroquinolones

26
ESBL?

• If an ESBL is detected, all penicillins,
  cephalosporins, and aztreonam should be reported
  as resistant, regardless of in vitro
  susceptibility test results

27
ESBL?

• However ESBL producing organisms are still
  susceptible to
• Cephamycins
• Cefoxitin
• Cefotetan
• Carbapenems
• Meropenem
• Imipenem
• Carbapenems are becoming the therapeutic
  option of choice

28
ESBL?

• Take home message
• ESBLs are harbingers of multi-drug
  resistance

29
Antimicrobial Resistance Key Prevention
Strategies
Pathogen
Susceptible pathogen
30
12 Steps to Prevent Antimicrobial Resistance
Hospitalized Adults

• 5. Practice antimicrobial control
• 6. Use local data
• 7. Treat infection, not contamination
• 8. Treat infection, not colonization
• 9. Know when to say no to vanco
• 10. Stop treatment when infection is cured or
  unlikely
• 11. Isolate the pathogen
• 12. Break the chain of
• contagion

Use Antimicrobials Wisely

• 1. Vaccinate
• 2. Get the catheters out
• 3. Target the pathogen
• 4. Access the experts

Prevent Infection
Diagnose and Treat Infection Effectively
Prevent Transmission
31
Prevent Infection Step 1 Vaccinate
Fact Pre-discharge influenza and pneumococcal
vaccination of at-risk hospital patients and
influenza vaccination of healthcare personnel
will prevent infections.

• Actions
• give influenza / pneumococcal vaccine to at-risk
  patients before discharge
• get influenza vaccine annually

32
Need for Healthcare Personnel Immunization Program
s Influenza Vaccination Rates (1996-97)
33
Need for Hospital-Based VaccinationPost-discharg
e Vaccination Status of Hospitalized Adults

• Influenza Pneumococcal
• Population Vaccine Vaccine
• Age 18-64 years 17 vaccinated 31 vaccinated
• with medical risk
• Age gt 65 years 45 vaccinated 68 vaccinated
• Hospitalized for
• pneumonia 35 vaccinated 20 vaccinated
• during influenza season

34
Prevent Infection Step 2 Get the catheters out

• Fact Catheters and other invasive devices are
  the 1 exogenous cause of hospital-onset
  infections.
• Actions
• use catheters only when essential
• use the correct catheter
• use proper insertion catheter-care protocols
• remove catheters when not essential

• Link to Guidelnes for the Prevention of
  Intravascular Catheter-related Infections

35
Biofilm on Intravenous Catheter Connecter 24
hours after Insertion
Scanning Electron Micrograph
36
Diagnose Treat Infection Effectively Step 3
Target the pathogen

• Fact Appropriate antimicrobial therapy saves
  lives.
• Actions
• culture the patient
• target empiric therapy to likely pathogens and
  local antibiogram
• target definitive therapy to known pathogens and
  antimicrobial susceptibility test results

37
12 Steps to Prevent Antimicrobial Resistance
Hospitalized Adults Step 3 Target the pathogen
Inappropriate Antimicrobial Therapy
Impact on Mortality
38
Inappropriate Antimicrobial Therapy Prevalence
among Intensive Care Patients
Inappropriate Antimicrobial Therapy (n 655
ICU patients with infection
45.2
34.3
Community-onset infection Hospital-onset
infection Hospital-onset infection after
initial community-onset infection
inappropriate
17.1
Patient Group
39
Diagnose Treat Infection Effectively Step 4
Access the experts

• Fact Infectious diseases expert input improves
  the outcome of serious infections.

40
Infectious Diseases Expert Resources
41
Use Antimicrobials Wisely Step 5 Practice
antimicrobial control

• Fact Programs to improve antimicrobial use are
  effective.

42
Use Antimicrobials Wisely Step 6 Use local data

• Fact The prevalence of resistance can vary by
  time, locale, patient population, hospital unit,
  and length of stay.

43
Use Antimicrobials Wisely Step 7 Treat
infection, not contamination

• Fact A major cause of antimicrobial overuse is
  treatment of contaminated cultures.
• Actions
• use proper antisepsis for blood other cultures
• culture the blood, not the skin or catheter hub
• use proper methods to obtain process all
  cultures

• Link to CAP standards for specimen collection
  and management

44
Use Antimicrobials WiselyStep 8 Treat
infection, not colonization

• Fact A major cause of antimicrobial overuse is
  treatment of colonization.
• Actions
• treat bacteremia, not the catheter tip or hub
• treat pneumonia, not the tracheal aspirate
• treat urinary tract infection, not the indwelling
  catheter

• Link to IDSA guideline for evaluating fever in
  critically ill adults

45
Use Antimicrobials Wisely Step 9 Know when to
say no to vanco

• Fact Vancomycin overuse promotes emergence,
  selection,and spread of resistant pathogens.

46
Evolution of Drug Resistance in S. aureus
Penicillin
Penicillin-resistant
S. aureus
1950s
S. aureus
47
Use Antimicrobials Wisely Step 10 Stop
antimicrobial treatment

• Fact Failure to stop unnecessary antimicrobial
  treatment contributes to overuse and resistance.
• Actions
• when infection is cured
• when cultures are negative and infection is
  unlikely
• when infection is not diagnosed

48
Prevent Transmission Step 11 Isolate the
pathogen

• Fact Patient-to-patient spread of pathogens can
  be prevented.
• Actions
• use standard infection control precautions
• contain infectious body fluids
• (use approved airborne/droplet/contact isolation
  precautions)
• when in doubt, consult infection control experts

49
Prevent Transmission Step 12 Break the chain of
contagion

• Fact Healthcare personnel can spread
  antimicrobial-resistant pathogens from
  patient-to-patient.

50
Improved Patient Outcomes associated with Proper
Hand Hygiene
Ignaz Philipp
Semmelweis (1818-65)
Chlorinated lime hand antisepsis
51
Prevention and Control of MDRO transmission

• Successful control of MDROs has been documented
  using a variety of combined interventions.
• These include
• - Improvements in hand hygiene,
• - Use of Contact Precautions until patients are
  culture-negative for a target MDRO,
• - Active surveillance cultures (ASC),
• - Education,
• - Enhanced environmental cleaning, and
  improvements in communication about patients with
  MDROs within and between healthcare facilities.

52
Infection control practices and the campaign to
prevent multi-drug resistance in Palestine

• Problem!
• Unrestricted use of antibiotics in the
  community
• Role of physicians-evidence based guidelines and
  protocols
• Role of pharmacists-policies (antibiotics should
  not be over the counter drugs!)
• Role of public-education
• Role of the ministry of health-rules and
  regulations

53
Infection control practices and the campaign to
prevent multi-drug resistance in Palestine

• Problem!
• Lack of National Nosocomial Infection
  Surveillance (NNIS) system (governmental and
  non-governmental)
• Problem!
• Do we have adequate Infectious Diseases
  Expert Resources ?
• - Infectious Diseases Specialists
• - Infection Control Professionals
• - Clinical Pharmacologists
• - Clinical Microbiologists
• - Health care Epidemiologists

54
Prevention IS PRIMARY!
1
Protect patientsprotect healthcare
personnel promote quality healthcare!
55
The End!
56

• Bacteria have evolved numerous mechanisms to
  evade antimicrobial drugs. Chromosomal mutations
  are an important source of resistance to some
  antimicrobials. Acquisition of resistance genes
  or gene clusters, via conjugation, transposition,
  or transformation, accounts for most
  antimicrobial resistance among bacterial
  pathogens. These mechanisms also enhance the
  possibility of multi-drug resistance.