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Atsushi Kawano BSc, MSc, BSc (Pharmacy Candidate) PHARM 415B Symposium Presentation February 15th, 2013

Learning Objectives
Review bacterial cell components Describe antibiotic classes Develop a thinking process to approach any infectious disease

Discuss the role of pharmacists in antimicrobial stewardship initiatives

DISCLAIMER! This presentation does NOT go into significant detail about individual antibiotic classes (please see my website: abx4dummies.weebly.com for spectrum of activity). Rather, this presentation intends to promote a thought process to help pick the right drug for the right bug!

What do you remember from PHARM 232/233L?

Accessed from: http://pathmicro.med.sc.edu/fox/culture.htm

What do you remember from PHARM 232/233L?

1. Funahara, Y., Nikaido, H., 1980. Asymmetric localization of lipopolysaccharides on the outer membrane of Salmonella typhimurium. J. Bacteriol. 141, 14631465. 2. Nikaido, H., 2003. Molecular basis of bacterial outer membrane permeability revisited. Microbiol. Mol. Biol. Rev. 67, 593656.

What do you remember from PHARM 232/233L?1

Modified from Wright, 2010

Key points about bacteria1


Bacteria can be broadly classified as either gram-positive or gram-negative based on cell components* Antibiotics attack unique bacterial features Bacteria can become resistant to antibiotics through various mechanisms Need to understand these concepts to understand antibiotics! *Atypical bacteria are not discussed in this presentation

Examples of some common bacteria causing infectious disease

Gram-Positive Bacteria

Gram-Negative Bacteria

Staphylococcus aureus Streptococcus pneumoniae Enterococcus faecalis Clostridium Difficile

Haemophilus influenzae Escherichia coli Pseudomonas aeruginosa Neisseria meningitidis

What do you remember from Slides 4-8?

Case scenario: You are the new infectious disease (ID) pharmacy student at a local hospital. The pharmacy manager hands you the morning microbiology results (see next slide). The pharmacy manager wants to know

What do you remember from Slides 4-8?

Whats the difference between gram-positive and gramnegative bacteria? This bacteria used to be susceptible to ceftriaxone, but its resistant now. Generally speaking, what can bacteria do to become resistant to antibiotics?

Simplified approach to ID

Need to ask these simple questions


Is there an infection? What are the usual bugs? Whats the source of the infection? What drugs can be for the bugs?

1. Is there an infection?

Signs and Symptoms


blood pressure, temperature, heart rate, white count, respiratory rate, presence of pus, diarrhea, etc

Laboratory Findings
Cultures from blood, wound, urine, catheter tips, etc

Know your patient!

2. What are the usual bugs?

For each type of infection, there are commonly associated bacteria that are responsible for the majority of the cases
Community Acquired Pneumonia

Presumptive Pathogens2

Outpatient

Streptococcus pneumoniae Haemophilus influenza Mycoplasma pneumoniae Chlamydophila pneumoniae


Respiratory viruses

2. What are the usual bugs?

Never forget to think of the bug before thinking about the drug
Example: Based on what you know from IPFC and/or COOP, does the ciprofloxacin susceptibility seem a little off to you?

2. What are the usual bugs?

2. What are the usual bugs?

Know your resources!3-5

and many more!

Know your resources!4

Know your resources!4

What do you remember from Slides 11-19?

Case scenario: You survived your first month of COOP as an ID pharmacy student! Now youre doing a one week rotation with the ID pharmacist. Youre assigned to follow a patient with a positive Clostridium Difficle result. Take a look at the microbiology results and medication history. Does this patient actually have a C. Difficle infection?

What do you remember from Slides 11-19?


Patient: Male 54 y.o Chief Complaint: Recent onset of diarrhea Past Medical History: Liver cirrhosis Current Medications: Titrating dose of lactulose

Vital Signs: BP 130/80, HR 70 bbm, regular, Temperature 37.5C


Blood work: WBC 5.0 x 109/L Microbiology: C. Difficle Positive

What do you remember from Slides 11-19?


Patient: Male 54 y.o Chief Complaint: Recent onset of diarrhea Past Medical History: Liver cirrhosis Current Medications: Titrating dose of lactulose

Vital Signs: BP 130/80, HR 70 bbm, regular, Temperature 37.5C


Blood work: WBC 5.0 x 109/L Microbiology: C. Difficle Positive

3. Whats the source of the infection?

Its easy to treat a culture, but harder to find a source of infection Infections usually occur because of physical and/or immunological compromise No point in treating an infection if circumstances allow it to come back!

3. Whats the source of the infection?6

Source control
all physical measures undertaken to eliminate a

source of infection, to control ongoing contamination, and to restore premorbid anatomy and function

Examples:
Drainage Debridement/ Device removal Decompression Restoration of anatomy/function

4. What drugs can be used for the bugs?1

How do you pick the right drug for the right bug?

Spectrum of Activity (abx4dummies.weebly.com)


Guidelines
Pharmacokinetics (PK)

Pharmacodynamics (PD)
Bactericidal? Bacteriostatic?

How good are guidelines?7

How good are guidelines?7

Khan et al. found that


More than 50% of the recommendations were derived from expert opinion Use of an alternative grading system (i.e. GRADE) may provide more accurate information regarding the quality of study

Bottom line: Guidelines are a good starting point, but they are not always the answer!

Pharmacokinetics and Pharmacodynamics8

Pharmacokinetics (PK)
Relates to ADME parameters to antibiotic concentration in serum and tissues Dose-adjustments

Pharmacodynamics (PD)
Antibiotic and microorganism

Concentration-dependent versus Timedependent killing

Concentration- vs. Time- Dependent Antimicrobial Activity9

What do you remember from Slides 23-30?

Case scenario: Your preceptor (MS) wants to know that youve been keeping up with your readings. Youre told that a presumptive meningitis patient (20 month old) is treated with piperacillintazobactam. MS wants to know whats wrong with this statement. Whats your thinking process to answer this question?

What do you remember from Slides 23-30?

For each type of infection, there are commonly associated bacteria that are responsible for the majority of the cases
Meningitis Presumptive Pathogens11

20 month old patient

Streptococcus agalactiae Streptococcus pneumoniae Neisseria meningtidis Listeria monocytogenes Haemophilus influenzae Escherichia coli

What do you remember from Slides 23-30?3,11

Piperacillin-Tazobactam
Covers Streptococcus agalactiae, Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli

What do you remember from Slides 23-30?3,11

Piperacillin-Tazobactam
Covers Streptococcus agalactiae, Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli

Pharmacokinetics
Distribution DOES NOT CROSS BLOOD BRAIN BARRIER

Bactericidal vs. Bacteriostatic10

Bactericidal Kills Bacteria

Bacteriostatic Inhibits Bacteria


Based on in vitro assessment of minimal bactericidal concentration (MBC) and minimal inhibitory concentration (MIC)

In vitro assessment does NOT predict


clinical outcomes!

Antimicrobial Stewardship Principles12

Antimicrobial stewardship principles attempt to


Find the most appropriate drug for the bug Optimize patient outcomes

Avoid collateral damage


Minimize costs

How can pharmacists help?

Pharmacists and Antimicrobial Stewardship Principles12

Document antibiotic use for patients


i.e. What antibiotics have been used in the last 3-6 months?

Understand antibiotic PK/PD properties


i.e. Is the drug going to reach the target site?

Question every antibiotic!


Know your patients!

Take home messages

Need to understand the bug before picking the drug


i.e. Look at resistance patterns

Ask the right questions about the antibiotics Antimicrobial Stewardship principles are important because the bugs are changing!

References
1. Wright GD. Q&A: antibiotic resistance: where does it come from and what can we do about it? BMC Biol 2010; 8:123. 2. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Disease Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44:S27-72. 3. Mandell GL, Bennett JE, Dolin R. Mandell, Douglas, and Bennetts principles and practice of infectious diseases. 9th ed. Philadelphia: Churchill Livingstone/Elsevier; 2009. 4. Gilbert DN, Moellering RC, Eliopoulos GM, et al. The sanford guide to antimicrobial therapy. 42nd ed. Sperryville: Antimicrobial Therapy; 2012. 5. Anti-infective Review Panel. Anti-infective guidelines for community-acquired infections. Toronto: MUMS Guideline Clearinghouse; 2012. 6. De Waele JJ. Early source control in sepsis. Langenbecks Arch Surg 2010; 395:489-494. 7. Khan AR, Khan S, Zimmerman V, et al. Quality and strength of evidence of the Infectious Diseases Society of America clinical practice guidelines. Clin Infect Dis 2010; 51(10):1147-56. 8. Van Bambeke F, Barcia-Macay M, Lemaire S, et al. Cellular pharmacodynamics and pharmacokinetics of antibiotics: current views and perspectives. Curr Opin Drug Discov Devel 2006; 9(2):218-30. 9. Roberts JA, Lipman J. Pharmacokinetics issues for antibiotics in the critically ill patient. Crit Care Med. 2009; 37:840-851. 10.Pankey GA, Sabath LD. Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of gram-positive bacterial infections. Clin Infect Dis 2004; 38:864-70. 11. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004; 39:1267-84. 12.Dresser L. Practice spotlight: pharmacists in an antimicrobial stewardship program. Can J Hosp Pharm 2010; 63(4):328-329.

abx4dummies.weebly.com
What am I? Hint 1: Gram-positive cocci in groups Hint 2: -lactam antibiotics are no match for me!

Questions?

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