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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 beta-
lactamases (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


                     70
                     60
Percent Resistance




                     50
                     40
                     30
                     20
                     10
                     0
                       95



                                     97



                                                   99

                                                          00




                                                                               03

                                                                                      04
                              96



                                            98




                                                                 01

                                                                        02
                     19

                            19

                                   19



                                                 19

                                                        20



                                                                      20

                                                                             20

                                                                                    20
                                          19




                                                               20




                                                        Year
                      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




                         35
    Percent Resistance


                         30
                         25
                         20
                         15
                         10
                         5
                         0




                                                                                          04
                           95

                                  96

                                         97

                                                98

                                                       99

                                                              00

                                                                     01

                                                                            02

                                                                                   03
                                              19




                                                                                        20
                         19

                                19

                                       19



                                                     19

                                                            20

                                                                   20

                                                                          20

                                                                                 20
                                                            Year
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


                             30
                             25
        Percent Resistance




                             20
                             15
                             10
                             5
                             0
                               95



                                             97



                                                           99

                                                                  00




                                                                                       03

                                                                                              04
                                      96



                                                    98




                                                                         01

                                                                                02
                             19

                                    19

                                           19



                                                         19

                                                                20



                                                                              20

                                                                                     20

                                                                                            20
                                                  19




                                                                       20



                                                                Year
 Source: National Nosocomial Infections Surveillance (NNIS) System
Fluoroquinolone-Resistant Pseudomonas aeruginosa Among Intensive
                  Care Unit Patients, 1995-2004



                             40
                             35
        Percent Resistance



                             30
                             25
                             20
                             15
                             10
                              5
                              0
                               95

                                      96




                                                                                02

                                                                                       03

                                                                                              04
                                             97

                                                    98

                                                           99

                                                                  00

                                                                         01
                             19

                                    19

                                           19

                                                  19

                                                         19

                                                                20

                                                                       20

                                                                              20

                                                                                     20

                                                                                            20
                                                                Year
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 antimicrobial-
            resistant Strains




                                                                      xx
                                                                            x
                                                                            x
   Resistant Strains




                                                              xx
         Rare

                   x
                             Antimicrobial                      xx
                    x        Exposure                                      xx

                                                         Resistant Strains
                                                            Dominant
Campaign to Prevent Antimicrobial Resistance in Healthcare Settings



       Emergence of Antimicrobial
             Resistance Susceptible Bacteria

 Resistant Bacteria

                                   Mutations


                                                                         XX

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 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 )
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                                                             Prevent
Transmission                                                             Infection
                                                                         Infection
     Antimicrobial
      Resistance

                                                                         Effective
 Optimize                                                                Diagnosis
     Use                                                                 & Treatment

                                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
1. Vaccinate             6. Use local data
                         7. Treat infection, not contamination
2. Get the catheters out 8. Treat infection, not colonization
                                        9. Know when to say “no” to vanco
Diagnose and Treat                      10. Stop treatment when infection is
Infection                                   cured or unlikely
Effectively
                       Prevent Transmission
3. Target the pathogen
4. Access the experts   11. Isolate the pathogen
                        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 at-
              risk 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
                                                                    38%
risk*
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                    Pneumococcal
Population                             Vaccine                      Vaccine
Age 18-64 years                        17% vaccinated               31% vaccinated
with medical risk*
Age > 65 years*                        45% vaccinated               68% vaccinated
Hospitalized for
pneumonia                              35% vaccinated               20% vaccinated
during influenza
season**
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    Relative Risk = 2.37
No. Infected




               500
                                                          (95% C.I. 1.83-3.08; p < .001)
  Patients




               400

               300

               200
                     42.0% mortality                             # Survivors
               100                                               # Deaths
                0
                      Inappropriate       Appropriate
                        Therapy            Therapy
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
                    Step 3: Target the pathogen


Inappropriate Antimicrobial Therapy: Prevalence among Intensive Care
                               Patients


                                                                 Inappropriate
                     50%                                         Antimicrobial Therapy
                                                     45.2%       (n = 655 ICU patients with infection
  % inappropriate




                     40%
                                            34.3%
                     30%                                                  Community-onset infection

                     20%
                                  17.1%                                   Hospital-onset infection

                     10%                                                  Hospital-onset infection after
                                                                          initial community-onset infection
                      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                                           Infection Control
    Epidemiologists                                          Professionals

    Clinical                 Optimal
Pharmacists                 Patient Care
                                                           Clinical
              Clinical                                     Pharmacologists
        Microbiologist
                     s Surgical Infection
                           Experts
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
                    Penicillin-resistant           Methicillin-
S. aureus                                          resistant
           [1950s]      S. aureus        [1970s]
                                                    S. aureus (MRSA)

                                                                      Vancomycin
                                                    [1997]

                                                                     [1990s]

  Vancomycin                        Vancomycin             Vancomycin-resistant
       -     [ 2002 ]
                                    intermediate-           enterococci (VRE)
   resistant                          resistant
    S. aureus                         S. aureus
                                       (VISA)
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-to-
          patient.
12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults
Step 12: Break the chain of contagion


     Improved Patient Outcomes associated with
               Proper Hand Hygiene




                                                           Ignaz Philipp
                                                           Semmelweis
                                                                  (1818-65)
  Chlorinated lime hand antisepsis
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.
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

Problem!
                 Palestine
  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.

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Management mdromultidrug-resistant-organisms-health-care-facilities

  • 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. 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 .
  • 9. 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Methicillin-Resistant Staphylococcus aureus (MRSA) Among Intensive Care Unit Patients, 1995-2004 70 60 Percent Resistance 50 40 30 20 10 0 95 97 99 00 03 04 96 98 01 02 19 19 19 19 20 20 20 20 19 20 Year 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 <1% 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 35 Percent Resistance 30 25 20 15 10 5 0 04 95 96 97 98 99 00 01 02 03 19 20 19 19 19 19 20 20 20 20 Year
  • 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. 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults 3rd Generation Cephalosporin-Resistant Klebsiella pneumoniae Among Intensive Care Unit Patients, 1995-2004 30 25 Percent Resistance 20 15 10 5 0 95 97 99 00 03 04 96 98 01 02 19 19 19 19 20 20 20 20 19 20 Year Source: National Nosocomial Infections Surveillance (NNIS) System
  • 14. Fluoroquinolone-Resistant Pseudomonas aeruginosa Among Intensive Care Unit Patients, 1995-2004 40 35 Percent Resistance 30 25 20 15 10 5 0 95 96 02 03 04 97 98 99 00 01 19 19 19 19 19 20 20 20 20 20 Year
  • 15. Campaign to Prevent Antimicrobial 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. Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Selection for antimicrobial- resistant Strains xx x x Resistant Strains xx Rare x Antimicrobial xx x Exposure xx Resistant Strains Dominant
  • 19. Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Emergence of Antimicrobial Resistance Susceptible Bacteria Resistant Bacteria Mutations XX Resistance Gene Transfer New Resistant 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. Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Antimicrobial Resistance: Key Prevention Strategies Susceptible pathogen Pathogen Prevent Prevent Transmission Infection Infection Antimicrobial Resistance Effective Optimize Diagnosis Use & Treatment Antimicrobial Use
  • 30. 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 1. Vaccinate 6. Use local data 7. Treat infection, not contamination 2. Get the catheters out 8. Treat infection, not colonization 9. Know when to say “no” to vanco Diagnose and Treat 10. Stop treatment when infection is Infection cured or unlikely Effectively Prevent Transmission 3. Target the pathogen 4. Access the experts 11. Isolate the pathogen 12. Break the chain of contagion
  • 31. 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 at- risk patients before discharge get influenza vaccine annually
  • 32. 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 38% risk* All healthcare personnel** 34%
  • 33. 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Step 1: Vaccinate Need for Hospital-Based Vaccination: Post-discharge Vaccination Status of Hospitalized Adults Influenza Pneumococcal Population Vaccine Vaccine Age 18-64 years 17% vaccinated 31% vaccinated with medical risk* Age > 65 years* 45% vaccinated 68% vaccinated Hospitalized for pneumonia 35% vaccinated 20% vaccinated during influenza season**
  • 34. 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
  • 35. 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
  • 36. 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
  • 37. 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Step 3: Target the pathogen Inappropriate Antimicrobial Therapy: Impact on Mortality 600 17.7% mortality Relative Risk = 2.37 No. Infected 500 (95% C.I. 1.83-3.08; p < .001) Patients 400 300 200 42.0% mortality # Survivors 100 # Deaths 0 Inappropriate Appropriate Therapy Therapy
  • 38. 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Step 3: Target the pathogen Inappropriate Antimicrobial Therapy: Prevalence among Intensive Care Patients Inappropriate 50% Antimicrobial Therapy 45.2% (n = 655 ICU patients with infection % inappropriate 40% 34.3% 30% Community-onset infection 20% 17.1% Hospital-onset infection 10% Hospital-onset infection after initial community-onset infection 0% Patient Group
  • 39. 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.
  • 40. 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Step 4: Access the experts Infectious Diseases Expert Resources Infectious Diseases Specialists Healthcare Infection Control Epidemiologists Professionals Clinical Optimal Pharmacists Patient Care Clinical Clinical Pharmacologists Microbiologist s Surgical Infection Experts
  • 41. 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Use Antimicrobials Wisely Step 5: Practice antimicrobial control Fact: Programs to improve antimicrobial use are effective.
  • 42. 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.
  • 43. 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
  • 44. 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
  • 45. 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.
  • 46. 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 Penicillin-resistant Methicillin- S. aureus resistant [1950s] S. aureus [1970s] S. aureus (MRSA) Vancomycin [1997] [1990s] Vancomycin Vancomycin Vancomycin-resistant - [ 2002 ] intermediate- enterococci (VRE) resistant resistant S. aureus S. aureus (VISA)
  • 47. 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
  • 48. 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
  • 49. 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-to- patient.
  • 50. 12 Steps to Prevent Antimicrobial Resistance: Hospitalized Adults Step 12: Break the chain of contagion 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 Problem! Palestine 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. Campaign to Prevent Antimicrobial Resistance in Healthcare Settings Prevention IS PRIMARY! Protect patients…protect healthcare personnel… promote quality healthcare!
  • 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.

Notes de l'éditeur

  1. The proportion of hospital-onset infections that are due to a resistant organism has increased at an alarming rate. The next four slides show trends in antimicrobial resistance among pathogens causing infections in ICU patients. These trends are based on data from the CDC’s National Nosocomial Infections Surveillance (NNIS) system. Shown on this slide are trends in the proportion of Staphylococcus aureus infections caused by methicillin-resistant strains. From 1995 through 2004, the percent of S. aureus infections caused by methicillin-resistant strains increased from approximately 40% to 60%.
  2. During the same time period, there also was a significant increase in the proportion of gram-negative pathogens (e.g., Klebsiella spp. and Enterobacteriaceae) that had acquired extended-spectrum beta-lactamases (ESBLs). Shown above are trends in 3 rd generation cephalosporin resistance among Klebsiella pneumoniae . As of 2004, approximately 25% of K. pneumoniae isolates causing infections in ICUs were resistant to 3 rd generation cephalosporins.
  3. Once resistant strains of bacteria are present in a population, exposure to antimicrobial drugs favors their survival. Reducing antimicrobial selection pressure is one key to preventing antimicrobial resistance and preserving the utility of available drugs for as long as possible.
  4. 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.
  5. Once a pathogen produces infection, antimicrobial treatment may be essential. However, antimicrobial use promotes selection of antimicrobial-resistant strains of pathogens. As the prevalence of resistant strains increases in a population, subsequent infections are increasingly likely to be caused by these resistant strains. Fortunately, this cycle of emerging antimicrobial resistance / multi-drug resistance can be interrupted. Preventing infections in the first place will certainly reduce the need for antimicrobial exposure and the emergence and selection of resistant strains. Effective diagnosis and treatment will benefit the patient and decrease the opportunity for development and selection of resistant microbes; this requires rapid accurate diagnosis, identification of the causative pathogen, and determination of its antimicrobial susceptibility. Optimizing antimicrobial use is another key strategy; optimal use will ensure proper patient care and at the same time avoid overuse of broad-spectrum antimicrobials and unnecessary treatment. Finally, preventing transmission of resistant organisms from one person to another is critical to successful prevention efforts.
  6. These 12 steps to Prevent Antimicrobial Resistance among hospitalized adults are action steps that clinicians can and should take now. They are designed to optimize patient safety and the outcome of infectious disease management. Together, these steps can prevent the emergence and spread of antimicrobial-resistant pathogens.
  7. The Advisory Committee on Immunization Practices (ACIP) recommends standing orders for influenza and pneumococcal vaccinations to improve vaccination of hospitalized patients before discharge. In addition, ACIP and the Healthcare Infection Control Practices Advisory Committee (HICPAC) recommend that healthcare personnel should receive an annual influenza vaccine to protect patients and other healthcare personnel.
  8. Outbreaks of influenza in hospitals have been linked to transmission from otherwise healthy healthcare personnel and are a major patient safety issue. The Advisory Committee on Immunization Practices (ACIP) recommends that healthcare personnel with patient care duties receive an annual influenza vaccine. However, vaccination rates among healthcare personnel are extremely poor; less than 40% of personnel are immunized in most facilities. * One or more high-risk medical conditions including diabetes, current cancer treatment, or chronic heart, lung, or kidney disease. ** Healthcare workers included persons currently employed in healthcare occupations, regardless of setting, and persons currently employed in healthcare settings without a healthcare occupation.
  9. Hospitalization represents a “missed opportunity” for vaccination. Discharged patients are unlikely to have received pneumococcal vaccine even when they are at high risk. Older hospital patients are more likely to have received influenza vaccine than younger patients, but a significant proportion in both groups was not vaccinated in either group.
  10. The most effective way to decrease device-associated infections is to decrease device utilization. In other words, get the catheters out ! Catheters should only be used when essential to patient care, not for convenience or as a “routine” practice. In some cases, antimicrobial-impregnated catheters may be warranted to prevent infections. Proper insertion and catheter care may decrease contamination and infection risk. The need for a catheter should be assessed on a daily basis so that unnecessary catheters will be recognized and removed.
  11. All invasive medical devices support the development of biofilms. Biofilm is a complex three-dimensional structure that consists of cells, bacteria, and extracellular matrix materials. In this scanning electron micrograph, many bacteria are seen in a matrix of material that also contains a red blood cell. This biofilm developed within 24 hours of catheter insertion. Biofilms may promote development of antimicrobial-resistant infections in several ways: Serving as a nidus for deposition and growth of resistant strains that then are released to cause infection; Creating a permeability barrier to antimicrobial diffusion, so that bacteria imbedded in the biofilm may be exposed to sub-inhibitory concentrations of drug that promotes emergence of resistance; Providing a matrix in which bacteria can exchange resistance factors. Biofilms cannot be prevented but some strategies may decrease the rate at which biofilms are formed and decrease bacterial colonization of biofilms.
  12. Correct diagnosis of the causative pathogen is necessary to ensure appropriate antimicrobial therapy. Hence, cultures are almost always indicated when managing hospitalized adults with known or suspected infection. Empiric antimicrobial therapy should be selected to target likely pathogens and be consistent with local antimicrobial susceptibility data. Definitive therapy should target known pathogens once they are identified and their antimicrobial susceptibility test results are known.
  13. Several studies suggest that input from professionals with infectious diseases expertise can improve patient outcomes, improve antimicrobial use, decrease treatment costs, and decrease the length of hospital stay.
  14. Infectious diseases specialists are one important resource for providing input, but many other professionals also contribute to optimal care for patients with infections. Like all patient safety endeavors, multidisciplinary collaboration is key!
  15. The importance of wise use of antimicrobials has been emphasized for many years. Many hospital-based programs to improve antimicrobial utilization have been implemented.
  16. Antimicrobial susceptibility data are often aggregated into “antibiograms”, which provide a summary picture of common organisms and their susceptibility to many antimicrobial drugs. Antibiograms provide a starting point for making decisions about empiric antimicrobial treatment, but do not necessarily reliably predict susceptibility of pathogens from a given patient because the data are not stratified by relevant characteristics that may affect the prevalence of resistance.
  17. Optimizing skin antisepsis is the first critical step in obtaining blood samples for culture. Proper specimen collection and management is key to preventing contaminated cultures.
  18. Clinical criteria and additional laboratory data can help distinguish infection from colonization. Improving the specificity of diagnostic criteria for infection can help reduce unnecessary antimicrobial use.
  19. Emergence of vancomycin resistance among gram-positive organisms is a major threat to patient safety in hospitals. Overuse of vancomycin promotes selection and spread of these resistant organisms.
  20. Introduction of every new class of antimicrobial drug is followed by emergence of resistance. By the 1950s, penicillin-resistant S. aureus were a major threat in hospitals and nurseries. By the 1970s, methicillin-resistant S. aureus had emerged and spread, a phenomenon that encouraged widespread use of vancomycin. In the 1990s, vancomycin-resistant enterococci emerged and rapidly spread; most of these organisms are resistant to other traditional first-line antimicrobial drugs. At the end of the century, the first S. aureus strains with reduced susceptibility to vancomycin were documented, prompting concerns that S. aureus fully resistant to vancomycin may be on the horizon. In June 2002 the first case of vancomycin-resistant S. aureus was detected.
  21. Stopping treatment when infection is unlikely or not diagnosed does not lead to harm and in fact, might benefit patients.
  22. Adherence to common-sense measures to isolate antimicrobial-resistant organisms before they are transferred to other patients or become endemic in a facility is essential. When in doubt about appropriate isolation procedures, consultation with an infection control professional is indicated.
  23. Healthcare personnel are important components of the chain of transmission in hospitals. Antimicrobial-resistant pathogens from one patient are transmitted to another when lapses in proper hand hygiene and other infection control practices occur. Healthcare personnel can also transmit their own flora and infectious pathogens to patients.
  24. Ignaz Philipp Semmelweis (1818-65), a Hungarian obstetrician, introduced antiseptic hand hygiene techniques. 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 12% to less than 1% after this hand hygiene intervention was implemented.
  25. Prevention is Primary!