Antimicrobial Stewardship Training

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Antimicrobial Stewardship Training
Part 1 Review of
Basic Principles and Selected
Antimicrobials By Keith Teelucksingh, PharmD
Infectious Disease Pharmacist, Kaiser Permanente
Vallejo With contributions by Linh Van,
PharmD Infectious Disease Pharmacist, Kaiser
Permanente Oakland
This course is accepted by the California State
Board of Pharmacy for 2.0 hours of credit.
Provider 127 Accredited by CAPE Coursework
expires 1/1/2011
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Antimicrobial Stewardship Training

• An Antimicrobial Stewardship program is a an
  overarching program to change and direct
  antimicrobial use at a heath care institution.1
• A series of training programs have been developed
  to enhance pharmacists knowledge and expertise
  in providing antimicrobial stewardship at Kaiser
  Permanente hospitals.
• 1 MacDougall C, Polk R. Antimicrobial Stewardship
  Programs in Health Care Systems. Clin. Microbiol.
  Rev. Vol. 18 Oct 2005, p. 638-656

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Antimicrobial Stewardship Training

• Part 1 Review of Basic Principles and Selected
  Antimicrobials
• Provides core background information in three
  modules
• Microbiology Lab review
• Antibiotic review
• Allergy review

?See Notes
4
Module 1 (of 3) Microbiology Lab Review

• Goal
• The goal of the Microbiology Lab Review module is
  to review and enhance pharmacists basic
  understanding of microbiology in the clinical
  setting.

? See Notes
5
Objectives

• Upon completion of this module, the participant
  will be able to
• Differentiate between gram-positive and
  gram-negative bacteria and name pertinent species
  from each group.
• Be able to interpret blood, urine, tissue and
  sputum culture results.
• Define contamination and colonization.
• Explain the purpose of urinalysis.
• Be able to name some species of
  Coagulase-negative Staphylococcus (CoNS) and
  explain the significance of isolating CoNS from
  blood cultures.

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Definitions

• Infectious Disease an interaction with a
  microbe that causes damage to the host.1
• Pathogen any microorganism that has the
  capacity to cause disease.1
• Virulence properties that enable a microorganism
  to establish itself on or within a host of a
  particular species and enhance its potential to
  cause disease.

1. Mandell, Bennett, Dolin Principles and
Practice of Infectious Diseases, 6th Ed.
?See Notes
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Definitions

• Microbiology results will be reported similar to
  this

Organism Staphylococcus aureus Organism Staphylococcus aureus Organism Staphylococcus aureus
Drug MIC Result
Penicillin gt8 R
Ampicillin gt8 R
Oxacillin lt0.25 S
Clindamycin lt1 S
Tetracycline lt1 S
Trimeth/sulfa lt0.5/9.5 S
?See Notes
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Definitions

• Susceptible (S) implies that an infection due to
  the isolate may be appropriately treated with the
  dosage of antimicrobial agent recommended for
  that type of infection.
• Only use an antibiotic that is reported as
  susceptible.
• Intermediate (I) implies that an infection due
  to the isolate may be appropriately treated in
  body sites where the drugs are physiologically
  concentrated or when a high dosage of drug can be
  used (i.e., urinary tract).

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Definitions

• Resistant (R) isolates that are not inhibited by
  the usually achievable concentrations of the
  agent with normal dosage schedules and/or fall in
  the range where specific microbial resistance
  mechanisms are likely (e.g., ß-lactamases).
• Minimum inhibitory concentration (MIC) the
  lowest concentration of the antimicrobial agent
  that prevents visible growth after an incubation
  period.
• Breakpoint discriminatory antimicrobial
  concentration used in the interpretation of
  results of susceptibility testing to define
  isolates as susceptible, intermediate or
  resistant. That is, the MIC where a bacteria goes
  from S to either I or R.

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Gram Stain

• Provides for rapid identification of presumed
  pathogen
• Gram Positive () versus Gram negative (-)
• Gives idea of morphology or arrangement of
  bacteria
• cocci vs. rod
• cluster, pairs, chain
• Aids in selecting appropriate empiric antibiotic
  choices

• Can be performed on any body fluid
• Only useful as preliminary guide NOT definitive

?See Notes
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Gram Stain

• Application of series of dyes that affix to the
  peptidoglycan in bacterial cell wall
• Purple
• Gram Positive
• Pink
• Gram Negative

Bacteria isolated and colored with Gram stain.
Gram-positive cocci, Staphylococcus aureus, from
a lab culture.
Gram-negative bacilli with a capsule, Klebsiella
pneumoniae, from a pneumonia lung abscess
(magnified 1,000).
?See Notes
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Bacterial Morphology

• Shapes
• cocci round
• bacilli rods
• coccobacilli ovoid
• fusiform pointed-end
• Arrangements
• single
• pairs
• clusters
• chains

?See Notes
13
Microbiology Common Pathogens

• Gram-Positive Cocci
• Clusters
• Staphylococcus spp.
• Pairs or chains
• Streptococcus spp. including
  S. pneumoniae, S. viridans
• Enterococcus spp.
• Other species
• Micrococcus spp.

Staphylococcus aureus
?See Notes
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Microbiology Common Pathogens

• Gram-Positive Bacilli (Rods)
• Diphtheroids
• Corynebacterium spp.
• Proprionibacterium acnes
• Large, with spores
• Clostridium spp (anaerobic)
• Bacillus spp
• Branching, beaded, rods
• Nocardia spp.
• Actinomyces spp.
• Other
• Listeria spp.
• Lactobacillus spp. (vaginal flora)

Clostridium difficile
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Common Bacteria and Classifications
Adapted from Jeff Kuper, Pharm.D., BCPS
?See Notes
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Microbiology Common Pathogens

• Gram-Negative Cocci
• Diplococci
• Pairs
• Neisseria meningitidis
• Neisseria gonorrhea
• Other
• Acinetobacter spp. (technically a rod but can
  appear as cocci or bacilli)

Neisseria gonorrhoeae
Acinetobacter baumannii
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Microbiology Common Pathogens

• Gram-Negative Bacilli (Rods)
• Lactose fermenters
• Enterobacteriaceae (enteric Gm -)
• Serratia spp.
• Proteus spp.
• Enterobacter spp.
• Escherichia coli
• Citrobacter spp.
• Klebsiella spp.
• Nonfermenters
• Acinetobacter baumannii
• Pseudomonas aeruginosa
• Stenotrophomonas maltophilia

Pseudomonas aeruginosa
?See Notes
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Microbiology Common Pathogens

• Anaerobes
• Gm
• Clostridium spp. (rods/bacilli)
• Peptostreptococcus (cocci)
• Gm -
• Bacteroides spp. (rods/bacilli)
• e.g. B. fragilis
• Prevotella spp. (rods/bacilli)

Clostridium difficile adhering to microvilli in
the gut
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Microbiology Common Pathogens

• Atypical bacteria
• Mycoplasma pneumoniae
• Legionella pneumophilia
• Chlamydia pneumoniae
• These bacteria are hard to culture on standard
  media, hence the name atypical.
• Commonly implicated in infections like
  community-acquired pneumonia (CAP).

Legionella pneumophilia
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Program Learning

1. What type of bacteria is Bacteroides fragilis?
2. How does the group of Enterobacteriaciae appear
   on gram stain?
3. Name some atypical bacteria. What types of
   infections do atypical bacterial cause?

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Program Learning Answers

• What type of bacteria is Bacteroides fragilis?
  An anaerobic gram-negative rod.
• How does the group of Enterobacteraciae appear on
  gram stain?
  Gram-negative and appear
  pink.
• Name some atypical bacteria. What types of
  infections do atypical bacterial cause?
  Legionella pneumophilia,
  Chlamydia pneumoniae, Mycoplasma pneumoniae.
  These are mostly associated with
  community-acquired pneumonia.

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Colonization

• The presence of bacteria on a body surface or
  mucous membrance without causing
  disease/infection.
• Upper respiratory tract (URT) Strep.
  viridans, Candida spp
• Skin S. epidermidis, Corynebacterium spp., S.
  aureus
• GI tract E. coli, K. pneumoniae, Candida spp.,
  Bacteroides spp.
• Urogential Lactobacillus (vaginal flora)

S. epidermidis. CDC.
?See Notes
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Colonization

• The presence of bacteria/organisms in a culture
  does not necessarily mean they are pathogenic.
• It is up to the clinician to interpret the
  culture result and clinically correlate to the
  patients signs and symptoms.

?See Notes
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Colonization

• The following are considered sterile sites and
  are not prone to colonization
• Blood
• Brain
• Muscle
• CSF
• Synovial fluid

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Contamination

• An organism that is introduced at some point
  during the culturing process not related to or
  causing an infectious process.
• Examples Improperly prepped skin prior to
  venipuncture, drawn from dirty IV line, poor
  lab technique ? contamination on Petri dish).
• Example skin flora (S. epidermidis) being
  isolated in blood cultures.

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Blood Cultures

• Definitive means of identifying most likely
  pathogens.
• Most pathogens will grow within first 1224 hours
  of collection (Candida, anaerobes may take
  longer).
• Incubated for five days by laboratory.
• Should be taken PRIOR to initiation of
  antibiotics.
• Growth may be inhibited by antibiotics.

?See Notes
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Blood Cultures

• Common contaminants
• Gm cocci Coagulase neg Staph (CoNS)
  S. epidermidis, S. hominis, S.capitis, S.
  warneri
• Gm rods Corynebacterium spp., Micrococcus
  spp., Bacillus spp. (not anthracis)

?See Notes
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Adapted from Jeff Kuper, Pharm.D., BCPS
?See Notes
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Blood Cultures

• The following should NEVER be considered
  contaminants
• Staphylococcus aureus
• Gram rods/bacilli
• Candida spp.

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Blood Cultures

• So whats the significance of isolating a
  Coagulase negative Staphylococcus spp. (CoNS)
  species from blood cultures?

?See Notes
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Blood Cultures Significance of CoNS

• Assess how many blood cultures are positive vs.
  how many were drawn.
• There should be a low suspicion for true
  infection if only one blood culture from multiple
  sets drawn around the same time period are
  positive for CoNS
• There should be a low suspicion if only one
  culture is positive and cultures were drawn from
  separate sites (e.g., one from IV line, one from
  peripheral site). See next slide for more
  information.

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Blood Cultures Significance of CoNS

• What disease state/infection being treated?
• Patients with an indwelling central line,
  hemodialysis catheter may be more at risk of
  infection.
• Patients with foreign material (especially
  cardiac), bone/joint infections may have positive
  blood cultures for CoNS.

?See Notes
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Blood Cultures Significance of CoNS

• What constitutional symptoms does the patient
  have?
• Fever, leukocytosis
• What type of patient?
• Immunocompetent
• Immunocompromised
• Chemotherapy/meds
• Disease state (advanced HIV)
• Transplant
• Neutropenic

?See Notes
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Blood Cultures Significance of CoNS

• In general, a solitary peripheral blood culture
  positive for CoNS in an immunocompetent patient
  should be regarded as a contaminant if
• No other blood cultures drawn in a reasonable
  time frame are also growing CoNS.
• The patient does not have prosthetic material
  present or does not have a central line/catheter.
• If another source of infection is identified to
  account for the patients constitutional
  symptoms.
• If patient has no signs or symptoms of infection.

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Blood Cultures Significance of CoNS
Just as in any clinical situation where the case
is not straightforward or there are questions

• If ever in doubt, present case to ID physician.

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Urine Culture

• Urine samples are held for 24 hours by
  microbiology lab.
• Bacterial growth expressed as colony counts,
  i.e., gt100,000 colony forming units (CFU).
• Should always have a corresponding urinalysis
  (UA) performed for microscopy.
• If gt2 bacteria are isolated from a urine culture,
  the lab will not perform any further work-up on
  the specimen.

?See Notes
37
Urine Culture

• Why perform a UA?
• The examination of fluid microscopy allows for
  some differentiation between infection vs.
  colonization vs. contamination.
• Infected fluid should have WBC, neutrophils or
  other inflammatory markers.
• Uninfected fluids generally are devoid of these
  markers.
• Keep in mind that immunocompromised patients may
  not be able to mount a strong enough immune
  response to produce these markers.

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Urine Culture Interpreting the UA

• How many WBCs in urine?
• How many epithelial/squamous cells present?
• The lower the number, the cleaner the sample
  (i.e., you can probably trust culture result).
• The higher the number increases risk of
  contamination with colonizing flora (i.e., sample
  taken too early in the urine stream)
• What amount of leukocyte esterase present?
• Given as trace, small, moderate and large.
• Found in certain WBC, sign of inflammation.

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Tissue Culture

• Preliminary report available at 24 hours,
  incubated for 72 hours total.
• Lab will quantify growth of organism rare,
  light, moderate and heavy.
• Tissue sample is plated onto agar plate.
• Quantification of growth on plate gives some idea
  of the bacterial burden of a sample.

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Tissue Culture

• These cultures can vary in quality
• Some may be superficial samples (i.e., more prone
  to contamination or colonization) others may be
  deep tissue samples or cultures from an operation
  (i.e., less likely to be contaminated or
  colonized).
• The presence of cellulitis, pus, exposed bone can
  help distinguish true infection from
  contamination or colonization.
• Read the MD note carefully and get some idea of
  what the area looks like, whether the MD thinks
  the area looks clinically infected or not.

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Sputum Culture

• Gram stain done initially by lab to assess
  quality of specimen.
• If gt 10 epithelial cells, sample is not worked
  up
• Sample not indicative of lower airway secretion.
• May be prone to contamination.
• Patients with pulmonary infection should have
  purulent sputum.
• Presence of WBC on gram stain.

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Program Learning

1. Name some organisms that are commonly found on
   the skin.
2. True or False Coagulase positive Staphylococci
   growing from a blood culture should be considered
   a contaminant.
3. Which microbes may take longer to grow out in
   blood cultures?
4. True or False It is common for CSF and synovial
   fluid to be colonized with bacteria.

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Program Learning Answers

1. Name some organisms that are commonly found on
   the skin
   S. epidermidis, S.
   aureus, Corynebacterium spp.
2. True or False Coagulase positive Staphylococci
   growing from a blood culture should be considered
   a contaminant.
   False CoNS are usually
   contaminants. Staphylococcus aureus is coagulase
   and should never be considered a contaminant
   when isolated from the blood.

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Program Learning Answers

1. Which microbes may take longer to grow out in
   blood cultures?
   Anaerobes and Candida spp. take
   longer to grow out in blood cultures.
2. True or False It is common for CSF and synovial
   fluid to be colonized with bacteria.
   CSF and synovial fluid
   are considered sterile sites and are not commonly
   colonized.

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References

• Mandell, Bennett Dolin. Principles and Practice
  of Infectious Disease. 7th ed. http//cl.kp.org
  (accessed Oct. 14, 2009).
• Kaiser Permanente Laboratory Manual Information
  - Northern California. http//cl.kp.org (accessed
  Oct. 14, 2009).
• Mermel, L. et al. Clinical Practice Guidelines
  for the Diagnosis and Management of Intravascular
  catheter-related infection 2009 Update by the
  Infectious Diseases Society of America. Clin
  Infect Dis. 2009491-45.

This concludes Module 1, the Microbiology Lab
Review. Please proceed to Modules 2 and 3.