Exam 3 - Antimicrobials and Resistance

antimicrobial drugs

drugs is used to control an infection, inhibits or kills microorganisms

antibiotics

natural antimicrobials

synthetics

man-made antimicrobials

semi synthetics

antibiotics which have been chemically modified

broad spectrum agents

target a wide variety of pathogenic bacteria

narrow spectrum agents

target only a narrow subset of pathogens

where did antimicrobials come from

Fleming's discovery of penicillin

main sources of useful antibiotics

Streptomyces and Bacillus (bacteria), Penicillium and Cephalosporium (fungi)

main trick to designing an antibiotics

finding something the target pathogen has but the host cell does not

major concern of antibiotics

toxicity to host

therapeutic index

ratio of a drug's toxic dose to its minimum therapeutic dose, the larger the therapeutic index the safer the drug

five main approaches of antibiotics

inhibition of cell wall formation, cell membrane function, DNA synthesis, ribosomes/protein synthesis, metabolic pathways

beta-lactam antibiotics function

inhibitors of cell wall synthesis

four types of beta-lactam inhibitors

penicillins, cephalosporins, monobactams, carbapenems

Penicllin Family

penicillin, amoxicillin, ampicillin, carbenicillin

where did fleming first locate penicillin

on a fungus - blue with white ring surrounding

two bacterial sources of useful antibiotics

streptomyces and bacillus

two fungal sources of useful antibiotics

penicillium and cephalosporium

what do antimicrobial drugs target

bacterial cellular targets

common component in penicillin family

beta lactam ring and thiazolidine group

cephalosporins

have two sites of placement of r groups at positions of 3 and 7

cephalosporin second ring

six membered opposed to five

advantage of two r groups in cephalosporins

several generations of molecules with greater versatility in function and complexity in structure

metabolic pathway inhibitors

trimethoprim and sulfanilamides

sulfanilamides are also called

sulfa drugs

protein synthesis inhibitors - 50s ribosomal subunit

chloramphenicol, macrolides, lincosamides

protein synthesis inhibitors - 30s ribosomal subunit

ahminoglycosides and tetracyclines

semisynthetic drugs derived from a natural antibiotic made by streptomyces

tetracyclines

ribosome-binding, bacteriostatic, broad spectrum

tetracyclines

pyrimidine examples

thymine, cytosine, and uracil

do sulfa drugs and trimethoprim inhibit the same spot on the metabolic pathway

no

how do sulfa drugs inhibit metabolic pathway

take up active site PABA usually uses

Human pathogens have been constantly developing antibiotic __________________ since the beginning of antibiotic therapy

Resistance - quite quickly

At Rockingham Memorial Hospital, for example, ____% of Staphylococcus aureus strains isolated in 1999 were resistant to penicillin, ampicillin, and amoxicillin.

88

Most antibiotic resistance has been observed in gram-_________________ organisms

negative

There is an observed ____________ growth in resistance when microbes are exposed for long periods of time

exponential

Development of resistant bacteria (in Diarrheal patients) is proportional to what?

antibiotic use

What has been a large factor in the rise of antibiotic resistance in microbials?

inappropriate prescriptions and use of antibiotics & patients not completing entire courses of antibiotics

More than _____ million unnecessary antibiotic prescriptions are written each year for patients outside of hospitals

50

100% of antibiotic prescriptions for what were completely unnecessary and increased resistance of bacteria responsible?

common cold

In 2001, 84% of all antibiotics produced in the U.S. were used for?

Agriculture

70% non-therapeutic livestock use

Under dosage of antibiotics do what?

Expose microbes to nonlethal quantities, making them resistant

what is non-therapeutic use for animals

not used to prevent disease, used to ensure growth in animals

vitamin in chicken feet

vitamin T

one health concept

recognizes that the health of people is connected to the health of animals and the environment

6 out of every 10 infectious diseases in humans are spread from

animals, zoonotic

a major factor in the rise of antibiotic resistance in bacteria

horizontal transfer of resistance genes

erythromycin and azithromycin

macrolides

ribosome binding antibiotic derived from streptomyces erythreaus, bacteriostatic

macrolides

impair proofreading, resulting in production of faulty proteins

aminoglycosides

blocks the binding of tRNAs inhibiting protein synthesis

tetracyclines

derived from streptomyces, ribosome binding, bacteriaCIDAL

aminglycosides

ciprofloxacin, nalidixic acid

fluoroquinolones

relatively new, introduced 15 years ago

fluoroquinolones

completely synthetic, broad spectrum specifically gram negatives, inhibits DNA replication

fluoroquinolones

newer classes of antibiotics

synercid and zyvox

narrow spectrum primarily against gram positive pathogens

synercid and syvox

what are the three most produced and use antibiotics worldwide

37% - cephalosporins, 17% - penicillins, 14% - quinolones

majority of antibiotics used worldwide have what function

inhibits cell wall formation (peptidoglycan)

antimicrobial arms race

-we discover a new class of antibiotics

-the target develops resistance

-we modify the drug

-the target develops resistance to the modification

-and so on

What has happened to antimicrobial approval by FDA over the years?

Rapid decrease in amount of antimicrobial approvals

Linezolid resistance was developed in Staph how long after introduction?

little over a year

beta-lactam

An antibiotic

beta-lactamase

produced by bacteria to fight an antibiotic

beta-lactamase inhibitor

produced by humans to fight the product produced by bacteria to fight an antibiotic

Host/drug reactions (adverse or "side" effects)

tissue toxicity, allergic reactions, disruption of normal flora

Host/drug reactions involving tissue toxicity can affect

Kidneys, liver, heart, skin, nerves, teeth and bones

mechanisms of antimicrobial resistance

enzymatic destruction of drug, blocked penetration of drug, target modification, efflux pump

host/drug reactions allergic

sensitized on first contact, often due to reaction to a metabolic byproduct

'mucking with the microbial ecology of our bodies' applies to what host/drug reactions to antibiotics

disruption of normal flora to the body

Disruption of "normal flora" of the body, a host/drug reaction to antibiotics, is a frequent cause of what?

diarrhea

Superinfection

secondary infection caused by destruction of normal microflora

steps to picking the right antimicrobial drug

identify the agent, determine the susceptibility of the agent

How to determine susceptibility of an agent when choosing the right antimicrobial drug?

Kirby-Bauer susceptibility test

What is the minimum inhibitory concentration (MIC)?

The highest dilution of a drug where it VISIBLY inhibits growth of a particular microorganism