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
MDRO(multidrug resistant
organisms
In addition to MRSA and VRE, certain
gram negative bacteria(GNB), including
those producing extended spectrum betalactamases (ESBLs) and others that are
resistant to multiple classes of
antimicrobial agents, are of particular
concern
MDRO(multidrug resistant
organisms
Drug-resistant pathogens are a growing
threat to all people, especially in
healthcare settings.
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
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
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.
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
Methicillin
Resistant 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 >50% 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 .
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Methicillin-Resistant Staphylococcus aureus
(MRSA) Among Intensive Care Unit Patients,
1995-2004
60
50
40
30
20
10
Year
20
04
20
03
20
02
20
01
20
00
19
99
19
98
19
97
19
96
0
19
95
Percent Resistance
70
Source: National Nosocomial Infections Surveillance (NNIS) System
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 <1% to approximately 15%
VRE accounted for almost 25% of
enterococcus isolates in NNIS ICUs in
1999 and 28.5% in 2003 .
Vancomycin-Resistant Enterococci (VRE) Among Intensive Care Unit
Patients,1995-2004
30
25
20
15
10
5
Year
20
04
20
03
20
02
20
01
20
00
19
99
19
98
19
97
19
96
0
19
95
Percent Resistance
35
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
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
3rd Generation Cephalosporin-Resistant Klebsiella pneumoniae Among
Intensive Care Unit Patients, 1995-2004
Percent Resistance
30
25
20
15
10
5
Year
20
04
20
03
20
02
20
01
20
00
19
99
19
98
19
97
19
96
19
95
0
Source: National Nosocomial Infections Surveillance (NNIS) System
Year
20
04
20
03
20
02
20
01
20
00
19
99
19
98
19
97
19
96
40
35
30
25
20
15
10
5
0
19
95
Percent Resistance
Fluoroquinolone-Resistant Pseudomonas aeruginosa Among Intensive
Care Unit Patients, 1995-2004
Campaign to Prevent
Antimicrobial Resistance
Clinicians hold the solution!
Risk factors that promote antimicrobial resistance in
healthcare settings include
Extensive use of antimicrobials
Transmission of infection
Susceptible hosts
Key Prevention Strategies
Clinicians hold the solution!
" Prevent infection "
Diagnose and treat infection effectively “
Use antimicrobials wisely “
Prevent transmission
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
Selection for antimicrobialresistant Strains
Resistant Strains
Rare
Antimicrobial
Exposure
Resistant Strains
Dominant
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
Emergence of Antimicrobial
Resistance Susceptible Bacteria
Resistant Bacteria
Resistance Gene Transfer
New Resistant Bacteria
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)
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
Beta-lactam Antibiotics
Examples
•Penicillins:
–Penicillin, amoxicillin, ampicillin
•Cephalosporins:
–Cephalexin,Cefuroxime,Ceftriaxone
•Carbapenems:
–Imipenem, meropenem
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!
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 betalactamase 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 )
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
ESBL?
If an ESBL is detected, all penicillins,
cephalosporins, and aztreonam should be
reported as “resistant”, regardless of in
vitro susceptibility test results
ESBL?
However: ESBL producing organisms are
still susceptible to:
•Cephamycins:
–Cefoxitin
–Cefotetan
•Carbapenems:
–Meropenem
–Imipenem
Carbapenems are becoming the therapeutic option of choice
ESBL?
Take home message
ESBLs are harbingers of multi-drug
resistance
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
Antimicrobial Resistance:
Key Prevention Strategies
Susceptible pathogen
Pathogen
Prevent
Infection
Prevent
Transmission
Infection
Antimicrobial
Resistance
Effective
Diagnosis
& Treatment
Optimize
Use
Antimicrobial Use
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Use Antimicrobials Wisely
Prevent Infection
5. Practice antimicrobial control
6. Use local data
1. Vaccinate
7. Treat infection, not contamination
2. Get the catheters out 8. Treat infection, not colonization
9. Know when to say “no” to vanco
10. Stop treatment when infection is
cured or unlikely
Diagnose and Treat
Infection
Effectively
Prevent Transmission
3. Target the pathogen
11. Isolate the pathogen
4. Access the experts
12. Break the chain of
contagion
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
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 atrisk patients before discharge
get influenza vaccine annually
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Step 1: Vaccinate
Need for Healthcare Personnel Immunization
Programs: Influenza Vaccination Rates (1996-97)
% Vaccinated
All adults > 65 yrs. of age
63%
Healthcare personnel at high
risk*
38%
All healthcare personnel**
34%
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Step 1: Vaccinate
Need for Hospital-Based Vaccination:
Post-discharge Vaccination Status of Hospitalized Adults
Influenza
Vaccine
Pneumococcal
Vaccine
Age 18-64 years
with medical risk*
17% vaccinated
31% vaccinated
Age > 65 years*
45% vaccinated
68% vaccinated
Hospitalized for
pneumonia
during influenza
season**
35% vaccinated
20% vaccinated
Population
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
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
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Step 2: Get the catheters out
Biofilm on Intravenous Catheter Connecter 24 hours
after Insertion
Scanning
Electron Micrograph
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
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
12 Steps to Prevent Antimicrobial
Resistance: Hospitalized Adults
Step 3: Target the pathogen
Inappropriate Antimicrobial Therapy:
Impact on Mortality
600
17.7% mortality
500
Relative Risk = 2.37
(95% C.I. 1.83-3.08; p < .001)
400
300
200
42.0% mortality
# Survivors
# Deaths
100
0
Inappropriate
Therapy
Appropriate
Therapy
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Step 3: Target the pathogen
Inappropriate Antimicrobial Therapy: Prevalence among Intensive Care
Patients
50%
45.2%
40%
34.3%
30%
20%
Inappropriate
Antimicrobial Therapy
(n = 655 ICU patients with infection
Community-onset infection
17.1%
Hospital-onset infection
Hospital-onset infection after
initial community-onset infection
10%
0%
Patient Group
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Diagnose & Treat
Infection Effectively
Step 4:
Access the experts
Fact: Infectious diseases expert input
improves the outcome of serious
infections.
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Step 4: Access the experts
Infectious Diseases Expert Resources
Infectious Diseases
Specialists
Healthcare
Epidemiologists
Clinical
Pharmacists
Infection Control
Professionals
Optimal
Patient Care
Clinical
Microbiologist
s Surgical Infection
Experts
Clinical
Pharmacologists
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Use Antimicrobials Wisely
Step 5: Practice
antimicrobial control
Fact: Programs to improve
antimicrobial use are effective.
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
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.
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
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
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Use Antimicrobials Wisely
Step 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
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Use Antimicrobials
Wisely
Step 9: Know when to say
“no” to vanco
Fact: Vancomycin overuse promotes
emergence, selection,and
spread of resistant pathogens.
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Step 9: Know when to say “no” to vanco
Evolution of Drug Resistance in S. aureus
Penicillin
Methicillin
MethicillinPenicillin-resistant
S. aureus
resistant
[1950s]
[1970s]
S. aureus
S. aureus (MRSA)
[1997]
Vancomycin
[1990s]
Vancomycin-
resistant
S. aureus
[ 2002 ]
Vancomycin
intermediateresistant
S. aureus
(VISA)
Vancomycin-resistant
enterococci (VRE)
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Step 10: Stop treatment when infection is cured or unlikely
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
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Step 11: Isolate the pathogen
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
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Prevent Transmission
Step 12: Break the chain
of contagion
Fact: Healthcare personnel can
spread antimicrobial-resistant
pathogens from patient-topatient.
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Step 12: Break the chain of contagion
Improved Patient Outcomes associated with
Proper Hand Hygiene
Chlorinated lime hand antisepsis
Ignaz Philipp
Semmelweis
(1818-65)
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 culturenegative 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.
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
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
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings
Prevention
IS PRIMARY!
Protect patients…protect healthcare personnel…
promote quality healthcare!
The End!
•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.