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Dr. Soha Al-Marsafy
Infection control consultant
Member of GAHAR accreditation standards
development for hospitals
Antimicrobial resistance
know how to fight your enemy
•Antimicrobial
resistance (AMR)
What
•overuse & misuse
of antimicrobials
Why
•All people
Who
•to do to prevent
what
•Control & treat
How
Resistance is not new
What is antimicrobial resistance
(AMR)?
• The inherited or acquired ability of
microorganisms to resist the action of
the antimicrobial agent
• Sometimes, microorganisms develop
resistance to more than one
antimicrobial agent, and are referred
to as “superbugs”.
• 700,000 people die of AMR every year
because available antimicrobial drugs
have become less effective at killing
resistant pathogens.
• A list of 18 bacteria & fungi by the CDC
that endanger human health, classifying
them as either:
• Urgent threats
• Serious threats
• concerning threats
• Urgent threats
• Candida auris
• Carbapenem-resistant Enterobacteriaceae
• Drug-resistant Neisseria gonorrhoeae
• Serious threats
• ESBL-producing Enterobacteriaceae
• Vancomycin-resistant Enterococci (VRE)
• Methicillin-resistant Staphylococcus aureus
(MRSA)
• Concerning threats
• Clindamycin-resistant group B Streptococcus
“Antibiotics are like fire extinguishers.
We don’t want to use them all the time
but we are happy we have them on the
wall.”
John Rex
Sledgehammer
• Antibiotics can be broad Affect many
different species of bacteria
• BUT broad spectrum antibiotics contribute
more to resistance
Broad Spectrum Antibiotics
Scalpel
• More targeted Antibiotics can be narrow
spectrum
• Effect one or two kinds of bacteria
• Narrow spectrum antibiotics
contribute less to resistance
Narrow Spectrum Antibiotics
Superbugs Are Growing More Resistant to
Hand Sanitizer, Scientists Warn
DAVID NIELD
3 AUG 2018
• Proteases - Pumps - Porins
• Penicillin-binding protein (PBP) change
• Point mutations & target modifications
• PRE-DETERMINED
• PLASMID-MEDIATED
The ‘Ps’ of resistance
SHARING THE RESTISTANCE
AHRQ SAFETY PROGRAM FOR LONG-TERM CARE:
HAIs/CAUTI
Centers for Disease Control and Prevention. Antibiotic Resistance Threats
in the United States, 2013.
Antimicrobial Resistance (AMR)
a plasmid-borne colistin resistance
gene, mcr-1, heralds the emergence
of truly pan-drug resistant bacteria
Colistin-resistant E.Coli infection;
female 46 years old patient in 2016
McGann P, et al. Antimicrob Agents Chemother. 2016. pii: AAC.01103
become
antibiotic
resistant
Resistant
bacteria
can spread
like other
microbes
e.g. by
shaking
hands
Resistant
bacteria
can be
carried by
anyone
healthy
or
ill
The use of
antibiotics
in animals
and
agriculture
contributes
to the
problem
The more a
person takes
antibiotics,
the more
likely they
are to carry
antibiotic
resistant
THE BUGS ARE WINNING??!!
Resistant infections
• More difficult to treat
• Other antibiotics need to be used which may not
work as well or can be more toxic
• More coast on the patient and hospital
• Usually require longer hospital stays
• More likely to spread to others
Fighting Back!
AMR
PREVENTION CONTROL
PREVENTION
1. Prevent infections, prevent the spread of resistance
2. Developing new drugs and diagnostic tests
3. IMPROVING ANTIBIOTIC PRESCRIBING
(STEWARDSHIP)
4. Tracking the outcomes
The CDC has recommended four necessary
actions to prevent antimicrobial resistance
HOW TO START AN
ANTIMICROBIAL
STEWARDSHIP IN
YOUR INSTITUTION
ANTIMICROBIAL STEWARDSHIP
• Antimicrobial stewardship is an activity
that promotes
–Appropriate selection of antimicrobials
–Appropriate dosing of antimicrobials
–Appropriate route and duration of
antimicrobial therapy
GOALS OF ANTIMICROBIAL
STEWARDSHIP
What is antimicrobial stewardship?
Antibiotic stewardship refers to a set of commitments and activities
designed to “optimize the treatment of infections while reducing the
adverse events associated with antibiotic use.”
The goal is…
– to have the RIGHT DRUG
– for the RIGHT PERSON
– over the RIGHT TIME FRAME
AHRQ SAFETY PROGRAM FOR LONG-TERM CARE:
HAIs/CAUTI
GOALS OF ANTIMICROBIAL
STEWARDSHIP
• Primary goal
Optimize clinical outcomes
• Secondary goal
Reduce healthcare costs without adversely
impacting the quality of care
Hand hygiene
 Apply to all patients receiving care in hospitals,
regardless of their diagnosis or presumed infection
status
 Designed to reduce the risk of transmission of
microorganisms from both recognized and
unrecognized sources of infections
 Under standard precautions, blood and body fluids
of all patients are considered potentially infectious
Standard Precautions
Isolation precaution
Proper use of antibiotics
Difference between colonization & infection
Colonization Infection
Normal white count, no
left shift.
WBCs elevated or
decreased with left shift.
Normothermia. Hyperthermia or
hypothermia.
Usually not associated
with heavy growth of
pathogen on gram
stain.
More often associated with
heavy growth of pathogen
and a gram stain.
Not associated with
other signs of an
infection.
Usually associated with
other signs of infection.
1- colonization usually occurs in patients who are
chronically ill with chronic tracheostomies or
chronically ventilated
2- mixed flora may grow on gram stain in absence of
infection
3- squamous epithelial cells > 10 = contamination
4- some organisms are almost never considered
pulmonary pathogen ( coagulase –ve staph ,
enterococcus , gram + ve bacilli ( except Nocardia ) ,
streptococcus except ( pneumoniae , agalactiae ,
pyogenes , anginosus ) & candida spp
29
Sputum cultures :
Signs and symptoms must be present :
1- leucocytosis or left shift
2- fever , chills
3- cough , SOB
4- decrease oxygen saturation
5- increase purulent secretions
6- increase suction needs in trachestomy and
ventilated patients
30
Blood cultures :
False positive :
1- bacterial growth occurs after 72 hr of
incubation
2- if common skin commensals ( eg staph
coagulase –ve ) appear except in prescence of
prosethtic material + signs of infection or two
blood c/s from two separate sites at two
different times
3- only one set positive out of two or more
31
3. Converting from intravenous to oral antibiotic
administration
1. Initiating empiric therapy
2. Tailoring antibiotic therapy ("antibiotic time-out")
Management of patients with suspected or
proven bacterial infection consists of initiation
of empiric therapy ( prior to availability of
definitive microbiology data), followed by
adjustment once microbiology data become
available definitive treatment.
4. Using the shortest effective duration of therapy
5. Pharmacokinetic monitoring
– Hospital -acquired pneumonia
– Urinary tract infections
– Skin and soft tissue infections
– Empiric coverage of MRSA infections
– Surgical prophylaxis
Facility-specific clinical practice guidelines and
pathways for these common infections
(ANTIBIOTIC POLICY)
Based on susceptibility patterns, and drug
availability
IN OUR HOSPITAL
Combination therapy
•Synergistic (1+1>2); Additive (1+1=2);
Antagonistic(1+1<2)
•Combination of 2 static drugs are usually additive
(exception Sulfonamide with Trimethoprim is
synergistic)
•Combination of 2 –cidal drugs with different MOA is
additive or synergistic
•Combination of –cidal + -static is ANTAGONISTIC
(rarely additive if organism is less sensitive to-cidal)
•e.g. Penicillin + Tetracycline ANTAGONISTIC but
Rifampicin + Dapsone in leprosy is additive
Pharmacokinetics
•ABSORBTION
•Oral route: used in non life threatening infections
•Intravenous route: serious life threatening infections.
•Topical: localized infection
•DISTRIBUTION
•The drug must reach the required site of action at
adequate dose in adequate amounts in the active form for
sufficient time like CNS, eye, prostate gland. Like : use of
inhalation antibiotic in complicated pneumonia.
•Pus cavities are avascular; low concentrations of
antibiotics are achieved. Incision and drainage of pus is
done prior to antibiotics.
Antimicrobial coverage :
2- MRSA :
Vancomycin - linezolide ,
tygecycline - ceftaroline -
septrin - clindamycin -
teicoplanin
1- pseudomonas :
Tazocin-aminoglycosides -
ceftazidime - cefepime -
fluoroquinolones –
Carbapenem - ceftolozane-
tazobactam - Polymixin
3- anaerobes :
Metronidazole - dalacin –
tazocin- unasyn - augmentin -
carbapenem -moxifloxacin -
tygacil
36
Antibiogram
summary of antibiotic susceptibility data for bacterial
isolates recovered by a microbiology laboratory over a
defined period of time (usually one year).
Antibiograms may be used by pharmacist
1. to guide choice of empiric antibiotic therapy
2. to develop facility-specific clinical protocols
3. to monitor resistance trends.
The data are most useful when stratified by inpatient
versus outpatient source, hospital site (eg, intensive
care unit, general ward, emergency department)
and population (eg, pediatric versus adult)
Antibiogram
1.Analyze and present a cumulative
antibiogram report at least annually
2. Include only final, verified test results.
3. Include data for species with ≥30 isolates.
4. Include only diagnostic (not surveillance) cultures.
5. Eliminate duplicates by including only the
first isolate of
a species/patient/analysis period,
irrespective of site or antibiotic
susceptibility profile.
6. Include only antibiotic agents routinely tested and
calculate the percent susceptible from results
reported.
The Clinical and Laboratory Standards Institute guideline on
antibiogram preparation recommends the following:
39
aimed.
net.au
Process measures
Monitor antibiotic use prescribing
Antibiotic use : Controversy regarding best
methods for monitoring use
• DDD = defined daily dose
• DOT = days of therapy
Outcomes measures
TODAY’S FOCUS
What is antimicrobial stewardship?
Antibiotic stewardship refers to a set of commitments and activities
designed to “optimize the treatment of infections while reducing
the adverse events associated with antibiotic use.”
The goal is…
– to have the RIGHT DRUG
– for the RIGHT PERSON
– over the RIGHT TIME FRAME
TODAY’S FOCUS
• Penicillin allergy
• Up to 10% of the general population and 15%
of hospitalized patients list penicillin as an
allergy
PENICILLIN ALLERGY
• Penicillin “allergic” patients are more likely to
– Received fluroquinolones, vancomycin, clindamycin
– Harbor drug resistant organisms such as MRSA and VRE
– Develop C diff colitis
• Increased mortality
– Experience --
• treatment failure, infection recurrence, death from MSSA
bacteremia
• treatment failure in gram negative bacteremia
• a delay in empiric antimicrobial treatment
• a surgical site infection
PENICILLIN ALLERGY
• Pencillin “allergic” patients are more likely to
– Develop new antibiotic “allergies” with alternative therapies
– Have an allergic reaction to vancomycin than cefazolin
– Have side effects or toxicities from second-line therapies
• Penicillin allergic patients have higher drug costs
– Higher outpatient antibiotic costs per patient
– $300 more per patient per day of inpatient antibiotic therapy
– $1253 more in length of stay costs per patient per admission
• Penicillin allergic patients have longer hospital stays
– 10% longer hospital stays, estimated cost of $21.5 million per
year.
PENICILLIN ALLERGY: ACCURATE
DIAGNOSIS?
• Less than 10% of these allergies are confirmed
when tested
• Childhood viral rashes are often misdiagnosed
as drug rashes
– Only 7-16% of kids with “drug allergy” during an
infection later test positive to the drug.
• Even if a patient is truly allergic, most people
“outgrow” penicillin allergy
– Over 50% of people with confirmed allergy to
penicillin ‘lose their allergy’ after 5 years
BETA LACTAMS
CEPHALOPSORIN VS PENICILLIN
• Overall cross-reactivity based on multiple
studies is actually very low:
– Reported (but unconfirmed) penicillin allergy:
0.1%
– Confirmed penicillin allergy: 2%
– Above exclude patients with penicillin anaphylaxis
PENICILLIN ALLERGY
OUR EFFORTS
• Cascading susceptibilities
• Drug desensitization
• Drug challenge
Cascading Susceptibilities
• Definition
– a strategy of reporting antimicrobial susceptibility
test results in which secondary (e.g., broader-
spectrum, more costly) agents may only be
reported if an organism is resistant to primary
agents within a particular drug class
Old New
Graded Challenge/Test Doses
1%/10%/20%
Scheduled Maintenance Dosing
Ampicillin 2000 mg IV once
Observe for 30 minutes
Ampicillin 200 mg IV once
Observe for 30 minutes
Ampicillin 20 mg IV once
Observe for 30 minutes
Monitoring
• Vital signs every 30 minutes
• Rescue meds available
(diphenhydramine,
epinephrine,
methylprednisolone)
• Update allergy profile after
challenge
Graded Challenge (GC)
• Non-life threatening reaction and using agent with
similar side chain
• Severe Type1 IgE mediated allergy and using Agent
with dissimilar side- chain
When to Use
• Severe-delayed reactions such as SJS or DRESS
• When a reaction is likely (a recent reaction to the
same agent)
Contraindications
• Tests for existence of true allergy
• Allows allergy de-labeling
Pros/Cons
Desensitization
Monitoring
• Requires 1:1 nursing ratio
• ICU admission likely
required
• Airway box at bedside
• Vital signs every 30 minutes
• Rescue meds available
(diphenhydramine,
epinephrine,
methylprednisolone)
• Desensitization establishes a
temporary tolerance so allergy
on profile is relevant and should
remain there
18 step process
1. Ampicillin IV Desensitization Protocol (Goal dose 2 grams)
1. 0.01 mg (0.01mg/mL) IV once in 50 mL of 0.9% NS
2. 0.02 mg (0.01 mg/mL) IV once in 50 mL of 0.9% NS once, 15 min after previous dose
3. 0.04 mg (0.01 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
4. 0.08 mg (0.01 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
5. 0.16 mg (0.1 mg/mL)IV once in 50 mL of 0.9% NS, 15 min after previous dose
6. 0.32 mg (0.1 mg/mL) IV once in 50 mL of 0.9% NS , 15 min after previous dose
7. 0.64 mg (0.1 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
8. 1.2 mg (0.1 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
9. 2.4 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
10. 4.8 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
11. 10 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
12. 20 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
13. 40 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
14. 80 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
15. 160 mg (250mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
16. 320 mg (250 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
17. 640 mg (250 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose
18. 1600 mg (250 mg/mL) IV once 50 mL of 0.9% NS, 15 min after previous dose
Additional Information About
Infections and Symptom
Management
Monthly Meetings
 Be held monthly to review progress
 All individuals responsible for the QI
program should attend the meetings
Fever and Older Adults
 Do you know why a resident DOES NOT
need a fever to have an infection?
• Fever may be absent in 30-50% of older
adults with serious infections
• Factors such as chronic diseases,
medications, and time of day can affect
an older person’s temperature
Suspected UTI
Cloudy or Smelly Urine:
To Culture or Not?
 Urine changes have many causes
• foul-smelling urine may be caused by dehydration,
hygiene, medication, diet, or infection
 Will overdiagnose infection in one-third of cases
 Improved toileting and fluid intake is often better
treatment than antibiotics; hydration and perineal
hygiene can prevent recurrence
 Culture should be ordered only if new urinary
symptoms are present
*Archives of Internal Medicine. 160: 678-682, 2000.
When to Order a Urine Culture
Diagnostic Pathway
Fever of >37.9°C (100 °F) or 1.5°C (2.4 °F) increase above
baseline, on 2 occasions over the last 12 h?
2 or more symptoms/signs
of other infection?
Do not order
urine culture
YES
Order urine culture if you
observe 1 or more:
• New onset burning urination
(dysuria)
• Urinary catheter
• New or worsening:
oUrgency
oFrequency
oFlank pain
oGross hematuria
oUrinary incontinence
oSuprapubic pain
NO
YES
Order urine culture if you
observe 2 or more:
• New onset burning urination
(dysuria)
• New or worsening:
oUrgency
oFrequency
oFlank pain
oGross hematuria
oUrinary incontinence
oSuprapubic pain
NO
Order urine culture if
you observe 1 or more:
• New CVA tenderness
• Shaking chills (rigors)
• New onset of delirium
Urinary catheter?
Suspected Respiratory Infection
 Symptomatic care:
• Monitor vital signs
• Encourage fluid intake
• Acetaminophen 650 mg q 6 hrs PRN for fever
and pain reduction
• Nasal saline 2 sprays to each nostril PRN for
nasal congestion
• Guaifenesin 2 teaspoons every 4 hours as
needed for cough
• Antihistamines, especially Benadryl, should
be AVOIDED
Suspected Skin/Soft Tissue Infection
 Appropriate care:
• Mobility – encourage mobility (passive
or active)
• Acetaminophen 650 mg as needed or
prior to cleaning/dressing changes
• Cleanse wounds with each dressing
change with saline or warm water; do
not use antiseptic cleansers
• Apply dressing as needed
Infectious Diseases Society of America
2022 Guidance on the Treatment of
• Extended-Spectrum β-lactamase
Producing Enterobacterales (ESBL-E)
• Carbapenem-Resistant Enterobacterales
(CRE),
• Pseudomonas aeruginosa with Difficult-
to-Treat Resistance (DTR-P. aeruginosa)
Preferred Antibiotics for the Treatment of
Infections Caused by MDR P. aeruginosa
P. aeruginosa isolates test susceptible to
traditional non-carbapenem β-lactam
agents (ie, piperacillin-tazobactam,
ceftazidime, cefepime, aztreonam), they
are preferred over carbapenem therapy.
P. aeruginosa isolates resistant to carbapenems but
susceptible to traditional β-lactams, use of a novel
β-lactam agent that tests susceptible
(eg, ceftolozane-tazobactam, ceftazidime-
avibactam, imipenem-cilastatin-relebactam) is also
a reasonable treatment option

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AMR.pptx

  • 1. Dr. Soha Al-Marsafy Infection control consultant Member of GAHAR accreditation standards development for hospitals Antimicrobial resistance know how to fight your enemy
  • 2. •Antimicrobial resistance (AMR) What •overuse & misuse of antimicrobials Why •All people Who •to do to prevent what •Control & treat How
  • 4. What is antimicrobial resistance (AMR)? • The inherited or acquired ability of microorganisms to resist the action of the antimicrobial agent • Sometimes, microorganisms develop resistance to more than one antimicrobial agent, and are referred to as “superbugs”.
  • 5. • 700,000 people die of AMR every year because available antimicrobial drugs have become less effective at killing resistant pathogens. • A list of 18 bacteria & fungi by the CDC that endanger human health, classifying them as either: • Urgent threats • Serious threats • concerning threats
  • 6. • Urgent threats • Candida auris • Carbapenem-resistant Enterobacteriaceae • Drug-resistant Neisseria gonorrhoeae • Serious threats • ESBL-producing Enterobacteriaceae • Vancomycin-resistant Enterococci (VRE) • Methicillin-resistant Staphylococcus aureus (MRSA) • Concerning threats • Clindamycin-resistant group B Streptococcus
  • 7. “Antibiotics are like fire extinguishers. We don’t want to use them all the time but we are happy we have them on the wall.” John Rex
  • 8. Sledgehammer • Antibiotics can be broad Affect many different species of bacteria • BUT broad spectrum antibiotics contribute more to resistance Broad Spectrum Antibiotics
  • 9. Scalpel • More targeted Antibiotics can be narrow spectrum • Effect one or two kinds of bacteria • Narrow spectrum antibiotics contribute less to resistance Narrow Spectrum Antibiotics
  • 10. Superbugs Are Growing More Resistant to Hand Sanitizer, Scientists Warn DAVID NIELD 3 AUG 2018
  • 11. • Proteases - Pumps - Porins • Penicillin-binding protein (PBP) change • Point mutations & target modifications • PRE-DETERMINED • PLASMID-MEDIATED The ‘Ps’ of resistance
  • 12. SHARING THE RESTISTANCE AHRQ SAFETY PROGRAM FOR LONG-TERM CARE: HAIs/CAUTI Centers for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013.
  • 13. Antimicrobial Resistance (AMR) a plasmid-borne colistin resistance gene, mcr-1, heralds the emergence of truly pan-drug resistant bacteria Colistin-resistant E.Coli infection; female 46 years old patient in 2016 McGann P, et al. Antimicrob Agents Chemother. 2016. pii: AAC.01103
  • 14. become antibiotic resistant Resistant bacteria can spread like other microbes e.g. by shaking hands Resistant bacteria can be carried by anyone healthy or ill The use of antibiotics in animals and agriculture contributes to the problem The more a person takes antibiotics, the more likely they are to carry antibiotic resistant THE BUGS ARE WINNING??!!
  • 15. Resistant infections • More difficult to treat • Other antibiotics need to be used which may not work as well or can be more toxic • More coast on the patient and hospital • Usually require longer hospital stays • More likely to spread to others
  • 16.
  • 18. PREVENTION 1. Prevent infections, prevent the spread of resistance 2. Developing new drugs and diagnostic tests 3. IMPROVING ANTIBIOTIC PRESCRIBING (STEWARDSHIP) 4. Tracking the outcomes The CDC has recommended four necessary actions to prevent antimicrobial resistance
  • 19. HOW TO START AN ANTIMICROBIAL STEWARDSHIP IN YOUR INSTITUTION
  • 20. ANTIMICROBIAL STEWARDSHIP • Antimicrobial stewardship is an activity that promotes –Appropriate selection of antimicrobials –Appropriate dosing of antimicrobials –Appropriate route and duration of antimicrobial therapy
  • 21. GOALS OF ANTIMICROBIAL STEWARDSHIP What is antimicrobial stewardship? Antibiotic stewardship refers to a set of commitments and activities designed to “optimize the treatment of infections while reducing the adverse events associated with antibiotic use.” The goal is… – to have the RIGHT DRUG – for the RIGHT PERSON – over the RIGHT TIME FRAME AHRQ SAFETY PROGRAM FOR LONG-TERM CARE: HAIs/CAUTI
  • 22. GOALS OF ANTIMICROBIAL STEWARDSHIP • Primary goal Optimize clinical outcomes • Secondary goal Reduce healthcare costs without adversely impacting the quality of care
  • 24.  Apply to all patients receiving care in hospitals, regardless of their diagnosis or presumed infection status  Designed to reduce the risk of transmission of microorganisms from both recognized and unrecognized sources of infections  Under standard precautions, blood and body fluids of all patients are considered potentially infectious Standard Precautions
  • 25.
  • 27. Proper use of antibiotics
  • 28. Difference between colonization & infection Colonization Infection Normal white count, no left shift. WBCs elevated or decreased with left shift. Normothermia. Hyperthermia or hypothermia. Usually not associated with heavy growth of pathogen on gram stain. More often associated with heavy growth of pathogen and a gram stain. Not associated with other signs of an infection. Usually associated with other signs of infection.
  • 29. 1- colonization usually occurs in patients who are chronically ill with chronic tracheostomies or chronically ventilated 2- mixed flora may grow on gram stain in absence of infection 3- squamous epithelial cells > 10 = contamination 4- some organisms are almost never considered pulmonary pathogen ( coagulase –ve staph , enterococcus , gram + ve bacilli ( except Nocardia ) , streptococcus except ( pneumoniae , agalactiae , pyogenes , anginosus ) & candida spp 29
  • 30. Sputum cultures : Signs and symptoms must be present : 1- leucocytosis or left shift 2- fever , chills 3- cough , SOB 4- decrease oxygen saturation 5- increase purulent secretions 6- increase suction needs in trachestomy and ventilated patients 30
  • 31. Blood cultures : False positive : 1- bacterial growth occurs after 72 hr of incubation 2- if common skin commensals ( eg staph coagulase –ve ) appear except in prescence of prosethtic material + signs of infection or two blood c/s from two separate sites at two different times 3- only one set positive out of two or more 31
  • 32. 3. Converting from intravenous to oral antibiotic administration 1. Initiating empiric therapy 2. Tailoring antibiotic therapy ("antibiotic time-out") Management of patients with suspected or proven bacterial infection consists of initiation of empiric therapy ( prior to availability of definitive microbiology data), followed by adjustment once microbiology data become available definitive treatment. 4. Using the shortest effective duration of therapy 5. Pharmacokinetic monitoring
  • 33. – Hospital -acquired pneumonia – Urinary tract infections – Skin and soft tissue infections – Empiric coverage of MRSA infections – Surgical prophylaxis Facility-specific clinical practice guidelines and pathways for these common infections (ANTIBIOTIC POLICY) Based on susceptibility patterns, and drug availability IN OUR HOSPITAL
  • 34. Combination therapy •Synergistic (1+1>2); Additive (1+1=2); Antagonistic(1+1<2) •Combination of 2 static drugs are usually additive (exception Sulfonamide with Trimethoprim is synergistic) •Combination of 2 –cidal drugs with different MOA is additive or synergistic •Combination of –cidal + -static is ANTAGONISTIC (rarely additive if organism is less sensitive to-cidal) •e.g. Penicillin + Tetracycline ANTAGONISTIC but Rifampicin + Dapsone in leprosy is additive
  • 35. Pharmacokinetics •ABSORBTION •Oral route: used in non life threatening infections •Intravenous route: serious life threatening infections. •Topical: localized infection •DISTRIBUTION •The drug must reach the required site of action at adequate dose in adequate amounts in the active form for sufficient time like CNS, eye, prostate gland. Like : use of inhalation antibiotic in complicated pneumonia. •Pus cavities are avascular; low concentrations of antibiotics are achieved. Incision and drainage of pus is done prior to antibiotics.
  • 36. Antimicrobial coverage : 2- MRSA : Vancomycin - linezolide , tygecycline - ceftaroline - septrin - clindamycin - teicoplanin 1- pseudomonas : Tazocin-aminoglycosides - ceftazidime - cefepime - fluoroquinolones – Carbapenem - ceftolozane- tazobactam - Polymixin 3- anaerobes : Metronidazole - dalacin – tazocin- unasyn - augmentin - carbapenem -moxifloxacin - tygacil 36
  • 37. Antibiogram summary of antibiotic susceptibility data for bacterial isolates recovered by a microbiology laboratory over a defined period of time (usually one year). Antibiograms may be used by pharmacist 1. to guide choice of empiric antibiotic therapy 2. to develop facility-specific clinical protocols 3. to monitor resistance trends. The data are most useful when stratified by inpatient versus outpatient source, hospital site (eg, intensive care unit, general ward, emergency department) and population (eg, pediatric versus adult)
  • 38. Antibiogram 1.Analyze and present a cumulative antibiogram report at least annually 2. Include only final, verified test results. 3. Include data for species with ≥30 isolates. 4. Include only diagnostic (not surveillance) cultures. 5. Eliminate duplicates by including only the first isolate of a species/patient/analysis period, irrespective of site or antibiotic susceptibility profile. 6. Include only antibiotic agents routinely tested and calculate the percent susceptible from results reported. The Clinical and Laboratory Standards Institute guideline on antibiogram preparation recommends the following:
  • 40. Process measures Monitor antibiotic use prescribing Antibiotic use : Controversy regarding best methods for monitoring use • DDD = defined daily dose • DOT = days of therapy Outcomes measures
  • 41. TODAY’S FOCUS What is antimicrobial stewardship? Antibiotic stewardship refers to a set of commitments and activities designed to “optimize the treatment of infections while reducing the adverse events associated with antibiotic use.” The goal is… – to have the RIGHT DRUG – for the RIGHT PERSON – over the RIGHT TIME FRAME
  • 42. TODAY’S FOCUS • Penicillin allergy • Up to 10% of the general population and 15% of hospitalized patients list penicillin as an allergy
  • 43. PENICILLIN ALLERGY • Penicillin “allergic” patients are more likely to – Received fluroquinolones, vancomycin, clindamycin – Harbor drug resistant organisms such as MRSA and VRE – Develop C diff colitis • Increased mortality – Experience -- • treatment failure, infection recurrence, death from MSSA bacteremia • treatment failure in gram negative bacteremia • a delay in empiric antimicrobial treatment • a surgical site infection
  • 44. PENICILLIN ALLERGY • Pencillin “allergic” patients are more likely to – Develop new antibiotic “allergies” with alternative therapies – Have an allergic reaction to vancomycin than cefazolin – Have side effects or toxicities from second-line therapies • Penicillin allergic patients have higher drug costs – Higher outpatient antibiotic costs per patient – $300 more per patient per day of inpatient antibiotic therapy – $1253 more in length of stay costs per patient per admission • Penicillin allergic patients have longer hospital stays – 10% longer hospital stays, estimated cost of $21.5 million per year.
  • 45. PENICILLIN ALLERGY: ACCURATE DIAGNOSIS? • Less than 10% of these allergies are confirmed when tested • Childhood viral rashes are often misdiagnosed as drug rashes – Only 7-16% of kids with “drug allergy” during an infection later test positive to the drug. • Even if a patient is truly allergic, most people “outgrow” penicillin allergy – Over 50% of people with confirmed allergy to penicillin ‘lose their allergy’ after 5 years
  • 47. CEPHALOPSORIN VS PENICILLIN • Overall cross-reactivity based on multiple studies is actually very low: – Reported (but unconfirmed) penicillin allergy: 0.1% – Confirmed penicillin allergy: 2% – Above exclude patients with penicillin anaphylaxis
  • 49. OUR EFFORTS • Cascading susceptibilities • Drug desensitization • Drug challenge
  • 50. Cascading Susceptibilities • Definition – a strategy of reporting antimicrobial susceptibility test results in which secondary (e.g., broader- spectrum, more costly) agents may only be reported if an organism is resistant to primary agents within a particular drug class
  • 52. Graded Challenge/Test Doses 1%/10%/20% Scheduled Maintenance Dosing Ampicillin 2000 mg IV once Observe for 30 minutes Ampicillin 200 mg IV once Observe for 30 minutes Ampicillin 20 mg IV once Observe for 30 minutes Monitoring • Vital signs every 30 minutes • Rescue meds available (diphenhydramine, epinephrine, methylprednisolone) • Update allergy profile after challenge
  • 53. Graded Challenge (GC) • Non-life threatening reaction and using agent with similar side chain • Severe Type1 IgE mediated allergy and using Agent with dissimilar side- chain When to Use • Severe-delayed reactions such as SJS or DRESS • When a reaction is likely (a recent reaction to the same agent) Contraindications • Tests for existence of true allergy • Allows allergy de-labeling Pros/Cons
  • 54. Desensitization Monitoring • Requires 1:1 nursing ratio • ICU admission likely required • Airway box at bedside • Vital signs every 30 minutes • Rescue meds available (diphenhydramine, epinephrine, methylprednisolone) • Desensitization establishes a temporary tolerance so allergy on profile is relevant and should remain there 18 step process 1. Ampicillin IV Desensitization Protocol (Goal dose 2 grams) 1. 0.01 mg (0.01mg/mL) IV once in 50 mL of 0.9% NS 2. 0.02 mg (0.01 mg/mL) IV once in 50 mL of 0.9% NS once, 15 min after previous dose 3. 0.04 mg (0.01 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose 4. 0.08 mg (0.01 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose 5. 0.16 mg (0.1 mg/mL)IV once in 50 mL of 0.9% NS, 15 min after previous dose 6. 0.32 mg (0.1 mg/mL) IV once in 50 mL of 0.9% NS , 15 min after previous dose 7. 0.64 mg (0.1 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose 8. 1.2 mg (0.1 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose 9. 2.4 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose 10. 4.8 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose 11. 10 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose 12. 20 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose 13. 40 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose 14. 80 mg (10 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose 15. 160 mg (250mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose 16. 320 mg (250 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose 17. 640 mg (250 mg/mL) IV once in 50 mL of 0.9% NS, 15 min after previous dose 18. 1600 mg (250 mg/mL) IV once 50 mL of 0.9% NS, 15 min after previous dose
  • 55. Additional Information About Infections and Symptom Management
  • 56. Monthly Meetings  Be held monthly to review progress  All individuals responsible for the QI program should attend the meetings
  • 57. Fever and Older Adults  Do you know why a resident DOES NOT need a fever to have an infection? • Fever may be absent in 30-50% of older adults with serious infections • Factors such as chronic diseases, medications, and time of day can affect an older person’s temperature
  • 58. Suspected UTI Cloudy or Smelly Urine: To Culture or Not?  Urine changes have many causes • foul-smelling urine may be caused by dehydration, hygiene, medication, diet, or infection  Will overdiagnose infection in one-third of cases  Improved toileting and fluid intake is often better treatment than antibiotics; hydration and perineal hygiene can prevent recurrence  Culture should be ordered only if new urinary symptoms are present *Archives of Internal Medicine. 160: 678-682, 2000.
  • 59. When to Order a Urine Culture Diagnostic Pathway Fever of >37.9°C (100 °F) or 1.5°C (2.4 °F) increase above baseline, on 2 occasions over the last 12 h? 2 or more symptoms/signs of other infection? Do not order urine culture YES Order urine culture if you observe 1 or more: • New onset burning urination (dysuria) • Urinary catheter • New or worsening: oUrgency oFrequency oFlank pain oGross hematuria oUrinary incontinence oSuprapubic pain NO YES Order urine culture if you observe 2 or more: • New onset burning urination (dysuria) • New or worsening: oUrgency oFrequency oFlank pain oGross hematuria oUrinary incontinence oSuprapubic pain NO Order urine culture if you observe 1 or more: • New CVA tenderness • Shaking chills (rigors) • New onset of delirium Urinary catheter?
  • 60. Suspected Respiratory Infection  Symptomatic care: • Monitor vital signs • Encourage fluid intake • Acetaminophen 650 mg q 6 hrs PRN for fever and pain reduction • Nasal saline 2 sprays to each nostril PRN for nasal congestion • Guaifenesin 2 teaspoons every 4 hours as needed for cough • Antihistamines, especially Benadryl, should be AVOIDED
  • 61. Suspected Skin/Soft Tissue Infection  Appropriate care: • Mobility – encourage mobility (passive or active) • Acetaminophen 650 mg as needed or prior to cleaning/dressing changes • Cleanse wounds with each dressing change with saline or warm water; do not use antiseptic cleansers • Apply dressing as needed
  • 62. Infectious Diseases Society of America 2022 Guidance on the Treatment of • Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E) • Carbapenem-Resistant Enterobacterales (CRE), • Pseudomonas aeruginosa with Difficult- to-Treat Resistance (DTR-P. aeruginosa)
  • 63. Preferred Antibiotics for the Treatment of Infections Caused by MDR P. aeruginosa P. aeruginosa isolates test susceptible to traditional non-carbapenem β-lactam agents (ie, piperacillin-tazobactam, ceftazidime, cefepime, aztreonam), they are preferred over carbapenem therapy.
  • 64. P. aeruginosa isolates resistant to carbapenems but susceptible to traditional β-lactams, use of a novel β-lactam agent that tests susceptible (eg, ceftolozane-tazobactam, ceftazidime- avibactam, imipenem-cilastatin-relebactam) is also a reasonable treatment option

Editor's Notes

  1. What is the problem? Why is the use of antimicrobials important in AMR? Who does it affect? Where is AMR an issue? When do we need action on AMR? Reference Image https://www.thehindubusinessline.com/opinion/invisible-threat-of-antimicrobial-resistance/article9964030.ece
  2. In an interview shortly after winning the Nobel Prize in 1945 for discovering penicillin, Alexander Fleming said: “The thoughtless person playing with penicillin treatment is morally responsible for the death of the man who succumbs to infection with the penicillin-resistant organism.” You may wish to play this TED talk on antibiotic resistance - https://www.youtube.com/watch?v=o3oDpCb7VqI&app=desktop
  3. Reference Image - https://www.australiansafetysigns.net.au/products/fire-fire-extinguisher
  4. Reference Image - https://ajp.com.au/columns/opinion/wielding-the-sledgehammer/
  5. Reference Image - https://www.patentearth.com/blog/history-of-the-scalpel-the-original-surgical-instrument.html
  6. Here’s how antibiotic resistance develops. In field 1, we can see a bunch of bacteria, much like what is in the normal human gut. If you give the resident antibiotics, only a few bacteria survive—and these tend to be resistant to that antibiotic. These resistant bacteria multiply and take over. Even worse, in panel 4, the resistant bacteria share their resistance traits with other bacteria, now making them resistant too. This can also happen in the human intestine. Every course of antibiotics carries these risks—and nursing home residents get a lot of antibiotics each year. Many of these rounds of antibiotics are unnecessary. And that is why we are talking about antibiotic stewardship today. We are learning when to give antibiotics and when to withhold antibiotics.
  7. 2. The mechanism that cause bacteria to become resistance to antibiotics can spread fast across the globe. The recent discovery of new gene known as mcr -1—which can make bacteria resistant to colistin, a last-resort drug for some multidrug-resistant infections is a case in point. The gene was first discovered in China in November last year. Within three months, investigators in Europe found that the gene had spread to other parts of the world and mcr -1 was associated with E. Coli infection in a patient in a military facility in Pennslvania
  8. All exposure to antibiotics can lead to resistant microbes which can be carried by anyone and passed on in simple ways to anyone who may then become ill. A person can be either ‘colonised’ or ‘infected’ with resistant bacteria. ‘Colonised’ means that a person has the bacteria present on the skin, in body openings or in the gut, but has no signs of infection. 'Infected’ means that a person has signs of an infection, such as fever or pus from a wound. So a “healthy” person may be colonised with resistant bacteria and pass this on to anyone who could develop an infection. Also, if that “healthy” person were to develop an infection themselves which would be more serious as they are have resistant bacteria. References: https://www.gosh.nhs.uk/conditions-and-treatments/general-medical-conditions/resistant-bugs-antibiotic-resistance-and-multidrug-resistant-organisms https://www.cedars-sinai.org/health-library/diseases-and-conditions/a/antibiotic-resistance.html Images: https://lovepik.com/image-400225679/bacteria.html ; http://clipart-library.com/free/shaking-hands-clipart-black-and-white.html ; https://www.creativefabrica.com/product/icon-set-time-5-oclock/ ; http://learnonlinedevelopments.blogspot.com/2013/04/free-people-graphic-image.html
  9. More difficult to treat Hospital rather than community Broader spectrum antibiotics, worsening resistance Antibiotics with more side effects Reference: Image - https://health.usnews.com/wellness/articles/2016-11-30/what-to-expect-when-your-loved-one-is-in-the-icu
  10. So what is antibiotic stewardship? [CLICK] Antibiotic stewardship is a set of commitments and activities designed to optimize the treatment of infections while reducing the harmful events that can be associated with antibiotic use. [CLICK] Basically, it is having the right drug, for the right person, over the right time frame.
  11. Monthly meetings should be held to review progress and address any challenges. Staff champions as well as any staff involved should attend the monthly meetings.
  12. Often the trigger for a urine culture is a call from a facility saying that the resident’s urine is cloudy or foul-smelling. The scientific literature has quite a bit to say on cloudy, smelly urine. It shows that: - Most symptomatic UTIs are accompanied by cloudy or smelly urine. However, there are many other causes of changes in the urine, such as poor oral intake, dehydration, crystalization after urine passage, and other non-infectious causes. Studies have shown that a positive culture obtained solely because of a change in urine appearance will over-diagnose infection at least one-third of the time. - For this reason, most experts have concluded that the evidence supports managing malodorous urine not with a culture but with increased fluid intake and improved toileting, and reserving cultures for residents with urinary tract symptoms such as dysuria or new incontinence.