Intro Flashcards
Antibiotic - Def’n
a substance created by a microorganism to inhibit or
kill another microorganism
Antibacterial - Def’n
a substance that inhibits or kills bacteria
Antifungal - Def’n
a substance that inhibits or kills fungi or spores
Antiviral - Def’n
a substance that inhibits the development and
transmission of viruses
Antiprotozoal - Def’n
a substance that inhibits or kills protozoa
Anti-infective - Def’n
a substance that inhibits, prevents, or kills the
source of an infection
Antiseptic - Def’n
a substance that is applied to living tissue/skin to
prevent, treat, or reduce infection
Disinfectant - Def’n
a substance that is applied to inanimate
objects/surfaces to kill microbes
Antimicrobial - Def’n
a substance that inhibits or kills microbes
Draw the web showing relationship between infectious diseases term
Antimicrobials -> Biocides, antiseptics, anti-infectives -> antibacterials->antibiotics, antivirals, antifungals
WHO Leading Causes of Death
- 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
Antimicrobial Resistance - what are some examples of antimicrobial resistant bacteria
PRSA, MRSA, VRE, VRSA, ESBL, AmpC, KPC, NDM-1
Bacterial Resistance - 4 types/ways that there is resistance
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
Bacterial resistance - ex of decreased permeability
Cell wall changes (e.g., vancomycin)
Porin channel changes (e.g., imipenem)
Biofilm production
Prevents antibacterial geint into the biofilm
Bacterial resistance - ex of Enzyme modification
β-lactamases (e.g., penicillin)
Aminoglycoside-modifying enzymes
Methylation (e.g., clarithromycin)
Bacterial resistance - Target site changes
Alteration of penicillin binding proteins Ribosomal modification (e.g., clindamycin)
Bacterial resistance - Active efflux
Tetracycline efflux
Fluoroquinolone efflux
Antibacterial Development - economic viability?
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)
What are some costs to antibiotic resistance?
- 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
Antibacterials in Agriculture - how many antibacterials are used (%) and what are they used for?
80-88% of all antibacterials sold are administered to food animals
Used for growth promotion
What is the cycle of antibacterials from agriculture?
> 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
Steps to reduce antibacterial resistance
- 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
Relationships in an infected patient - 3 pillars (Host, antibiotic, pathogen)
HOST -> PK -> ANTIBIOTIC -> PD -> PATHOGEN -> Infectious Disease. PATHOGEN -> resistance -> ANTIBIOTIC -> toxicodynamics -> HOST -> immune response
Factors in Choosing Antimicrobial Therapy - some general ones
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?
Administrative factors in Choosing
Antimicrobial Therapy
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?
Site-specific factors - Eye, Brain, and Prostate (why is it difficult site)
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
What is biofilm
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
What is “sessile” bacteria
“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
Anti-bacterial Combinations (4 reasons why to do it)
To broaden empiric coverage
For polymicrobial coverage
To prevent emergence of resistance
Synergy
What is the concept and combination for synergy
Superior to the sum of effects of both
antibacterials given separately, 1 + 1 > 2
What is the concept and combination for addition
Superior to either antibacterial given
separately (but less than the sum of the
effects of both antibacterials), 1+ 1 > 1-2
What is the concept and combination for indifference
Equal to either antibacterial alone 1 + 1 = 1
What is the concept and combination for antagonism
Inferior to either antibacterial alone, 1 + 1 < 1
What are the 3 graphs showing in vitro combinations for indifference, synergism or antagonism?
Draw graphs A,B,C or explain relationships on Slide 51 of Intro.
What are some ex of synergistic combinations in the clinical setting?
Penicillin + aminoglycoside against enterococci
Combination antipseudomonals (e.g., piperacillin +
aminoglycoside)
Sulfonamides + trimethoprim
β-lactam + β-lactamase inhibitor
Disadvantages of Anti-bacterial Combinations
Antagonism Examples: Penicillin + tetracycline Gentamicin + chloramphenicol Cost Adverse effects
Drug Interactions of Anti-bacterial Combinations - Oral anticoagulants - things to consider
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
Oral Contraceptives Metabolism
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
Antibacterial/OC Interaction - evidence and conslusion?
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.
Additional Considerations with Antimicrobial Therapy
Allergic Reactions
Documentation of type of reaction is very important
Specific Toxicities
e.g., nephrotoxicity with aminoglycosides
Antibacterial Resistance !!!!!!
