Lecture 1 - Infectious Diseases/Antimicrobial Stewardship

what is the definition of antibiotic

a substance created by a microorganism to inhibit or kill another microorganism

what is the definition of antibacterial

a substance that inhibits or kills bacteria (usually synthetic, more specific)

what are the 2 types of bacterial resistance

intrinsic resistance

acquired resistance

what is acquired resistance

transfer of resistant genes from other bacteria by transduction, transformation, or conjugation

what are the 4 mechanisms of bacterial resistance

decreased permeability

enzyme modification

target site changes

active efflux

what are ways bacteria can decrease the permeability of antibacterials

cell wall changes (e.g. vancomycin)

porin channel changes (e.g. imipenem)

biofilm production

what are ways bacteria modify enzymes to decrease the effectiveness of antibacterials

beta-lactamases (e.g., penicillin)

aminoglycoside-modifying enzymes

methylation (e.g. clarithromycin)

what are target site changes that can decrease the effectiveness of antibacterials

alteration of penicillin binding proteins

ribosomal modification (e.g. clindamycin)

what are ways bacteria actively efflux antimicrobials

tetracycline efflux

fluoroquinolone efflux

what are the consequences of antibacterial 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

what are issues with antibacterials in agriculture

level required to promote growth has increased 20-fold since 1950

high rates of resistance in intestinal flora of farm animals and farmers

molecular methods show resistant organisms in farm animals reach consumers in meat products

>90% of antibacterials given to animals excreted in urine/stool → excreted into soil, surface runoff, widely dispersed through fertilizer

what are ways to practice antimicrobials stewardship

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

what is a common myth about reducing antibacterial resistance (exam question)

stopping antibacterial treatment early results in bacterial resistance development - FALSE

longer durations are more likely to do this (selective pressure)

what are other ways to reduce antibacterial resistance

strict infection control procedures

antibacterial cycling?

regulatory policies

improved diagnostics

educate the public, healthcare professionals

reduce agricultural use of antibacterials

what are factors to consider when choosing antimicrobial therapy

disease is being treated? should it be treated with antibacterials?

suspected organisms? cultures to direct antibacterial choice? current susceptibility patters by site?

how ill is the patient? is the patient immunocompromised?

what are the advantages/disadvantages of the available choices of susceptible antibacterials? cost considerations?

route of administration? issues limiting route of administration (severity, site, NPO, etc)?

evidence? evidence based guidelines?

dose (renal/hepatic function)? duration of treatment? monitoring?

drug toxicity/alergies? pregnancy?

prevention?

what are site-specific factors for eye, brain, prostate

non-fenestrated capillaries - impede drug diffusion making antibacterial delivery difficult

need to consider PK of the antibacterial - may required direct injection

when are biofilms formed in humans

on foreign substances inserted or implanted into the body if they come in contact with bacterial organisms

• e.g. IV catheters, urinary catheters, dialysis catheters, artificial joints, artificial heart valve

may form on some tissues resulting in infections that are difficult to treat e.g. lung tissues in cystic fibrosis

what are concerns with antibacterial resistance for biofilms

sessile bacteria within biofilm become resistant to antibacterial therapy

when might antibacterial combinations be needed

to broaden empiric coverage

for polymicrobial coverage

to prevent emergence of resistance (less commom, sometimes in TB)

synergy

what is synergy

combination is superior to the sum of effects of both antibacterials given separately

what is addition

combination is superior to either antibacterial given seperately but less that the sum of effects)

what is indifference

combining is equal to either antibacterial alone

what is antagonism

combination is inferior to either antibacterial alone

what are disadvantages of antibacterial combinations

antagonism - e.g. penicillin + tetracycline, gentamycin + chlormphenicol

cost

adverse effects

what are considerations for anticoagulants in antimicrobial therapy

antibacterial inhibits vitamin K synthesis in GI tract - risk of increased anticoagulant effect

monitor INR

what is the drug interaction of oral contraceptives with antimicrobial therapy

free estrogen is reabsorbed in GI by enterohepatic recycling

antibacterials may reduce bacteria in GI tract and interfere with enterohepatic recycling

some antibacterials cause increased metabolism of estrogens

some antibacterials cause diarrhea or vomiting that may decrease absorption