Intro

Question 1

Antibiotic - Def’n

Answer 1

a substance created by a microorganism to inhibit or

kill another microorganism

Question 2

Antibacterial - Def’n

Answer 2

a substance that inhibits or kills bacteria

Question 3

Antifungal - Def’n

Answer 3

a substance that inhibits or kills fungi or spores

Question 4

Antiviral - Def’n

Answer 4

a substance that inhibits the development and

transmission of viruses

Question 5

Antiprotozoal - Def’n

Answer 5

a substance that inhibits or kills protozoa

Question 6

Anti-infective - Def’n

Answer 6

a substance that inhibits, prevents, or kills the

source of an infection

Question 7

Antiseptic - Def’n

Answer 7

a substance that is applied to living tissue/skin to

prevent, treat, or reduce infection

Question 8

Disinfectant - Def’n

Answer 8

a substance that is applied to inanimate

objects/surfaces to kill microbes

Question 9

Antimicrobial - Def’n

Answer 9

a substance that inhibits or kills microbes

Question 10

Draw the web showing relationship between infectious diseases term

Answer 10

Antimicrobials -> Biocides, antiseptics, anti-infectives -> antibacterials->antibiotics, antivirals, antifungals

Question 11

WHO Leading Causes of Death

Answer 11

1. Ischaemic heart disease 2. Stroke 3. Chronic obstructive pulmonary disease 4. lower respiratory infections 5. neonatal conditions 6. Trachea, bronchus, lung cancers 7. Alzheimer’s 8. Diarrhoeal diseases 9. Diabetes mellitus 10. Kidney diseases

Question 12

Antimicrobial Resistance - what are some examples of antimicrobial resistant bacteria

Answer 12

PRSA, MRSA, VRE, VRSA, ESBL, AmpC, KPC, NDM-1

Question 13

Bacterial Resistance - 4 types/ways that there is resistance

Answer 13

Intrinsic resistance, (Cell wall, mechanism they already have
Some agents target cell wall)

acquired resistance (mutation), selection of resistant strains with antibacterial use (misuse), Spread and Clonal Spread

Question 14

Bacterial resistance - ex of decreased permeability

Answer 14

Cell wall changes (e.g., vancomycin)
Porin channel changes (e.g., imipenem)
Biofilm production
Prevents antibacterial geint into the biofilm

Question 15

Bacterial resistance - ex of Enzyme modification

Answer 15

β-lactamases (e.g., penicillin)
Aminoglycoside-modifying enzymes
Methylation (e.g., clarithromycin)

Question 16

Bacterial resistance - Target site changes

Answer 16

Alteration of penicillin binding proteins
Ribosomal modification (e.g., clindamycin)

Question 17

Bacterial resistance - Active efflux

Answer 17

Tetracycline efflux

Fluoroquinolone efflux

Question 18

Antibacterial Development - economic viability?

Answer 18

Antibacterial development is no longer an economically wise investment for pharmaceutical companies.

• the only drugs that lose benefit by extensive use
• given in short courses vs drugs like atorvastatin for decades
• and are relatively cheap (peak charge of $1,000-$3,000/course vs chemotherapy at sometimes > $80,0000 / course)

Question 19

What are some costs to antibiotic resistance?

Answer 19

• Increased use of broad spectrum antibacterials
• Increased use of IV antibacterials
• Increased hospitalization
• Increased costs of hospitalization
• Increased Infection Control
• Diminished quality of life
• Increased morbidity and mortality

Question 20

Antibacterials in Agriculture - how many antibacterials are used (%) and what are they used for?

Answer 20

80-88% of all antibacterials sold are administered to food animals
 Used for growth promotion

Question 21

What is the cycle of antibacterials from agriculture?

Answer 21

> 90% antibacterials given to animals excreted in urine and stool which is Excreted into soil, surface runoff, and ground water and widely dispersed through fertilizer
Humans consume the animals, and the possibly contaminated water

Question 22

Steps to reduce antibacterial resistance

Answer 22

• Use antibacterials only when necessary
• Do not use antibacterials for viral infections
• Use antibacterials for appropriate duration
• Ensure patient adherence
• Use antibacterials with the narrowest spectrum of activity possible
• Prevent the spread of infections – handwashing, cleaning services
• Prevent Infections - Vaccinate Strict infection control procedures
• Guidelines
• Drug formularies
• Antibacterial Cycling ?
• Regulatory policies
• Improved diagnostics
• Educate the public, health care professionals
• Reduce agricultural use of antibacterials

Question 23

Relationships in an infected patient - 3 pillars (Host, antibiotic, pathogen)

Answer 23

HOST -> PK -> ANTIBIOTIC -> PD -> PATHOGEN -> Infectious Disease. PATHOGEN -> resistance -> ANTIBIOTIC -> toxicodynamics -> HOST -> immune response

Question 24

Factors in Choosing Antimicrobial Therapy - some general ones

Answer 24

What disease is being treated? Should it be treated
with antibacterials?
 What are the suspected organisms?
 How ill is the patient?
 Are there cultures to direct antibacterial choice?
 Is the patient immunocompromised?
 What are the current susceptibility patterns by site?
 What are the advantages/disadvantages of the
available choices of susceptible antibacterials?
 What are the cost issues?

Question 25

Administrative factors in Choosing | Antimicrobial Therapy

Answer 25

What route of administration should be used?  e.g., IV, IM, PO, or topical  Are there any issues limiting route of administration?  e.g., severity of infection, site of infection, ability to swallow, ability to absorb drug p.o, I.M, or rectally; do we want the drug to stay in the GI tract  Are there taste issues with oral medications  What is the evidence regarding choice of antibacterial in this particular case?  Are there good evidence-based guidelines to support your choice? Are they up to date?  What is the site and severity of the infection?  What dose should be used for this patient?  Does the dose need to be adjusted based on renal function or hepatic function of the patient?  Does the drug have any toxicities or allergies or special circumstances (e.g., pregnancy) that would preclude use of this drug in this patient?  Is there any way that this infection could be prevented or spread of the infection be prevented?  How long should treatment continue?  How should progress be monitored in this patient?

Question 26

Site-specific factors - Eye, Brain, and Prostate (why is it difficult site)

Answer 26

 non-fenestrated capillaries  impede drug diffusion (antibacterial delivery difficult)  Infections difficult to treat  Need to take into consideration the pharmacokinetics of the antibacterial  May require direct injection of antibacterials  e.g., intravitreal, intraventricular

Question 27

What is biofilm

Answer 27

In humans, biofilm frequently forms on foreign substances inserted or implanted into the body if they come in contact with bacterial organisms  IV catheters, urinary catheters, dialysis catheters  Artificial joints (knee, hip), artificial heart valve  Biofilm may also form on some tissues in the body resulting in infections that are very difficult to treat  e.g., lung tissues in cystic fibrosis

Question 28

What is "sessile" bacteria

Answer 28

“Sessile” bacteria within biofilm become resistant to antibacterial therapy and may require 10 – 1000 higher concentrations of antibacterial than free “planktonic” bacteria  We usually cannot achieve these concentrations clinically

Question 29

Anti-bacterial Combinations (4 reasons why to do it)

Answer 29

 To broaden empiric coverage  For polymicrobial coverage  To prevent emergence of resistance  Synergy

Question 30

What is the concept and combination for synergy

Answer 30

Superior to the sum of effects of both | antibacterials given separately, 1 + 1 > 2

Question 31

What is the concept and combination for addition

Answer 31

Superior to either antibacterial given separately (but less than the sum of the effects of both antibacterials), 1+ 1 > 1-2

Question 32

What is the concept and combination for indifference

Answer 32

Equal to either antibacterial alone 1 + 1 = 1

Question 33

What is the concept and combination for antagonism

Answer 33

Inferior to either antibacterial alone, 1 + 1 < 1

Question 34

What are the 3 graphs showing in vitro combinations for indifference, synergism or antagonism?

Answer 34

Draw graphs A,B,C or explain relationships on Slide 51 of Intro.

Question 35

What are some ex of synergistic combinations in the clinical setting?

Answer 35

 Penicillin + aminoglycoside against enterococci  Combination antipseudomonals (e.g., piperacillin + aminoglycoside)  Sulfonamides + trimethoprim  β-lactam + β-lactamase inhibitor

Question 36

Disadvantages of Anti-bacterial Combinations

Answer 36

``` Antagonism  Examples:  Penicillin + tetracycline  Gentamicin + chloramphenicol Cost Adverse effects ```

Question 37

Drug Interactions of Anti-bacterial Combinations - Oral anticoagulants - things to consider

Answer 37

 Antibacterial inhibits Vitamin K synthesis in GI tract -risk - enhanced anticoagulant effect  Effect of fever, infection?  Recommendation – Stockley’s Drug Interaction -Monitor after 3 – 5 days -Monitor INR carefully with sulfonamides and reduce dose -Monitor INR carefully with metronidazole

Question 38

Oral Contraceptives Metabolism

Answer 38

Enterohepatic recycling of conjugates (from minor pathway)  Conjugates excreted into GI tract via bile duct  Conjugate broken down by bacteria in GI tract  Free estrogen reabsorbed  Antibacterials may reduce bacteria in GI tract and interfere with enterohepatic recycling (reduce systemic estrogens and may result in OC failure)  Some antibacterials increase metabolism of ethinylestradiol (e.g., rifampin, rifabutin)  Antibacterials frequently cause diarrhea and/or vomiting that may decrease OC absorption

Question 39

Antibacterial/OC Interaction - evidence and conslusion?

Answer 39

Likely to reduce birth control pill effectiveness ->  Rifampin, (rifabutin) Associated with OC failure in > 3 case reports ->  Ampicillin, amoxacillin, griseofulvin, metronidazole, tetracycline Associated with OC failure in 1 case report ->  Cephalexin, Clindamycin, Dapsone, Erythromycin, Isoniazid, Pen V, TMP/SMX The evidence regarding oral contraceptives and its effectiveness with concomitant ingestion of antibacterials is conflicting.  Until evidence becomes clearer, patients should be aware of this possible interaction.

Question 40

Additional Considerations with Antimicrobial Therapy

Answer 40

 Allergic Reactions  Documentation of type of reaction is very important  Specific Toxicities  e.g., nephrotoxicity with aminoglycosides  Antibacterial Resistance !!!!!!