Antimicrobial Stewardship Quiz

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Practice Points on Antimicrobials - 1

• Presented by Dr. Jonathan Penm
• Email: [email protected]
• Twitter: @JonPenm

Learning Objectives

• Understand antimicrobial stewardship program strategies and how to improve antimicrobial use.
• Become familiar with common infectious disease pathogens.
• Identify conditions/pathogens responsive to beta-lactams.
• Compare and contrast beta-lactam drugs.
• Apply formulary restrictions to beta-lactams.

Previous Lectures

• Antimicrobial resistance is a global concern.
• This lecture series focuses on practical antimicrobial stewardship programs, point-of-care interventions, empirical vs directed therapy, and IV-to-oral conversions.
• Lectures will explain when to use specific antimicrobials, their spectrum of activity, and formulary restrictions.

Antimicrobial Stewardship Programs

• Required for all Australian accredited hospitals.
• Led by a multidisciplinary team, including a doctor and pharmacist, to manage antimicrobial use.
• Improve appropriate use, updates policies and educates staff.
• Evaluate antimicrobial use and resistance patterns.
• Studies show they reduced antimicrobial use by 22-36% and resistance rates.

Empirical vs Directed Therapy

• Empirical therapy: Treatment based on most likely pathogens and their susceptibility.
• Directed therapy: Treatment based on the results of culture and susceptibility tests.

Essential Strategies for Antimicrobial Stewardship Programs

• Guidelines based on local microbiology and susceptibility.
• Formulary restrictions.
• Reviewing antimicrobial prescribing.
• Direct feedback to prescribers.
• Point-of-care interventions (e.g., IV-to-oral switch, directed therapy, dose optimization).
• Clinical microbiology monitoring.
• Monitor antimicrobial use and outcomes.

When to Use Broad Spectrum Agents (e.g., Sepsis)

• Often used in life-threatening conditions like sepsis.
• The optimal time to start broad spectrum antimicrobial treatment is crucial for patient outcomes.

Sepsis

• Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection.
• Measured by PaO2 (partial pressure of oxygen in the alveoli), Glasgow coma scale, mean arterial pressure, platelets, bilirubin, and creatinine.

Which Antimicrobial to Use?

• Essential steps to determine appropriate treatment:
• Identify the condition being treated.
• Perform a Gram stain to classify bacteria as Gram-positive or Gram-negative.
• The structure of peptidoglycan differs between Gram-positive and Gram-negative bacteria, affecting antimicrobial susceptibility.

Gram Stain

• Used to classify bacteria as Gram-positive or Gram-negative.

Gram Stain - Gram Positive

• Includes Staphylococcus, Streptococcus, and Enterococcus.

Gram Stain - Gram Negative

• Includes Enterobacteriaceae (e.g., E. coli, Klebsiella), ESCAPPMs (e.g., Enterobacter, Serratia, Citrobacter, and others), and environmental bacteria (e.g., Acinetobacter, Pseudomonas, and Morganella.)

Gram Stain - Anaerobes

• Includes both Gram-positive and Gram-negative types in various locations like the bowel and mouth.
• Examples include Actinomyces, Bacteroides, and Peptostreptococcus spp. , and Clostridium difficile.

Beta-lactams

• Include penicillins, cephalosporins, monobactams, and carbapenems.

Penicillins

• Oral penicillins (natural and penicillinase-resistant)
• Intravenous penicilins (natural and penicillinase-resistant)
• Aminopenicillins are also included.

Penicillinase-Resistant Penicillins

• Active against Gram-positive cocci, including Streptococcus and Staphylococcus species.
• Available in oral and intravenous forms.
• Ideal for Staphylococcus infections like cellulitis.

Aminopenicillins

• Active against Gram-positive cocci (e.g., Streptococcus) and some Gram-negative rods (e.g., Haemophilus influenzae).
• Common oral medications include Amoxicillin.
• IV Ampicillin therapy is also available.
• Used to treat pneumonia (often caused by Streptococcus pneumoniae and Haemophilus influenzae).

Beta-Lactamase Inhibitors

• Clavulanic acid and Tazobactam are examples.
• These are added to penicillins to enhance their effectiveness against bacteria that produce Beta-lactamases.
• Extended spectrum of action, encompassing aerobic Gram-positive and Gram-negative bacteria.

Cephalosporins

• Classified into generations, with higher generations covering more Gram-negative bacteria.
• Commonly used for penicillin allergies.
• Some examples of oral cephalosporins include Cefalexin and Cefaclor.
• IV Cephazolin, and Cefotaxime.

Beta-lactam Allergies

• IgE-mediated reactions (e.g., urticaria, angioedema, bronchospasm, anaphylaxis) can occur with beta-lactam use.
• Delayed reactions (e.g., rashes) can also happen several days after treatment.
• Avoid both penicillins and cephalosporins in patients with a history of these allergies.

Cross-reactivity Between Beta-lactams

• Old theory linked cross-reactivity to the beta-lactam ring.
• Modern evidence points to the R1 side chain as a more significant factor.
• Cefazolin (R1 side chain) shows low cross-reactivity with other beta-lactams.

Extended Spectrum Beta-Lactamase (ESBL)

• ESBL-producing organisms inactivate various beta-lactam antibiotics, including 3rd and 4th generation cephalosporins, penicillin and most beta-lactamases inhibitors.
• They are often found in Gram-negative bacteria, such as E. coli, Klebsiella.
• Additional treatment strategies are often needed in the case of ESBL and severe infection.

Carbapenems

• Imipenem, meropenem, and ertapenem are examples.
• Primarily reserved for treating bacteria that produce ESBL or when broad-spectrum coverage is necessary.
• Effective against Gram negative, Gram positive, and anaerobic bacteria.

Macrolides

• Azithromycin, Clarithromycin, Erythromycin, Roxithromycin are examples.
• Primarily affects aerobic G-ve bacteria.
• Can be used in penicillin allergies.
• Also beneficial for atypical bacteria that cause pneumonia (e.g., Mycoplasma, Legionella, Chlamydia)
• Interactions include elevated QT interval

Quinolones

• Include Norfloxacin, Ciprofloxacin, Moxifloxacin.
• Cipro/Norfloxacin is effective against Gram-negative bacteria, including Pseudomonas species
• Moxifloxacin covers a wider range of bacteria (Gram-positive, Gram-negative, anaerobes, atypical bacteria) but has less activity against Pseudomonas.
• Common side effects include peripheral neuropathy and tendon damage, therefore should be used carefully.

Aminoglycosides

• Amikacin, Gentamicin, and Tobramycin are examples.
• Used in severe Gram-negative bacterial infections.
• Often given intravenously, not orally absorbed.
• ADRs include nephrotoxicity and ototoxicity.

Vancomycin Monitoring

• Monitoring is essential for >48 hours of use.
• AUC/MIC ratio best predicts vancomycin efficacy.
• Regular blood monitoring to track levels from 30 minutes to 14 hours after dosing is necessary and recommended.

IV to Oral Switch

• Decisions on IV-to-oral switching rely on specific clinical criteria, including clinical improvement, resolution of fever and no instability.
• Consider the duration of IV treatment with known potential risks.
• Important to consider the patient's overall condition.

Clinical Use of Antimicrobials

• Sepsis: Life-threatening requires rapid IV administration of broad spectrum coverage (e.g., gentamicin, flucloxacillin). Antibiotics should be chosen based on the suspected source/cause.
• Febrile neutropenia: Treat broadly initially covering all Gram-positive, Gram-negative and anaerobes with the need to cover Pseudomonas aeruginosa more specifically

Formulary Restrictions

• Hospital formulary listing only medicines with established efficacy and safety, reviewed annually to reflect current evidence.
• Traffic light system to control the use of medications based on urgency and safety.

Summary Table (page 33)

• Summary of bacteria types and associated coverage by various groups.

Class Questions

• General questions related to the topic to be discussed in class.