Microbio - Chapter 15 Antimicrobial Drugs

______ are drugs against microbes

Antimicrobials

Antimicrobials are therapeutic compounds that _____ microbes or ______ to prevent pathogenic action

kill; inhibit their growth

Alexander Fleming noticed a plate of

Staphylococcus aureus was contaminated with mold and the bacteria were unable to grow near the mold

Mold ______ that could interfere with bacterial growth

excreted acompound

Named ______ after the species of contaminating mold

penicillin

____ was the 1st antibiotic tested clinically and mass produced

Penicillin

What are the basic criteria for drugs used as chemo-therapeutic agents?

1. effective against microbes

2. nontoxic to the host

3. able to be purified in high amounts

_______ is the range of different microbes against which an antimicrobial agent acts

Spectrum of activity

______ spectrum drugs are effective against a broad range of microbes

Broad

____ spectrum are antimicrobials that target a limited range of microbes

Narrow

______ spectrum drugs are effective against a single organism/disease

Limited

Why are narrow spectrum drugs preferred?

They present less disruption to the normal microbiota

_______ is medical treatment with a broad spectrum drug initiation while waiting for culture results

Empiric therapy

Broad spectrum antimicrobials may lead to the development of

superinfection

Ideal antimicrobials should meet as many of the following criteria as possible

1 Nontoxic to the host and without undesirable side effects

2. Nonallergenic to the host

3. Not eliminate the normal microbiota of the host

4. Able to reach the infected part of the human body

5. Inexpensive and easy to produce

6. Chemically-stable (have a long shelf-life)

7. Microbial resistance is uncommon and unlikely to develop

______ antimicrobials are substances produced by microorganisms that inhibit other living microorganisms

Naturally occurring (soil-dwelling microbes)

_______ antimicrobials are manufactured by chemical processes

Synthetic

______ antimicrobials have chemical modification of naturally occurring antibiotics

Semi-synthetic

_________ drugs result from each successive round of chemical modification

Next generation

Selective toxicity

inhibit/kill pathogen with little to no toxic effects on the patient

Selective toxicity is achieved by _______ for the drug in the microbe that do not exist in the patient

exploiting vulnerable targets

What bacteria processes are unique

cell wall synthesis, protein synthesis, or nucleic acid synthesis

The ratio of the toxic dose (to the patient) to the therapeutic dose (to eliminate the infection)

TI - Therapeutic Index

TI estimated the ________ of a drug

margin of safety

Margin of safety is the dose range where

drug efficacy is optimized while side effects are minimized

Drugs with a ____ TI have a large margin of safety and less danger of producing toxic effects

wide/high

Which organs are most susceptible to damage along with the microbiota?

Kidneys and liver

____ toxic to the liver

Hepatotoxic drugs

Toxic to the kidneys

Nephrotoxic

What is the preferred administration route?

oral administration

Why is oral administration preferred?

Easiest, most convenient, least cost

However, oral drugs must be

stable in the acidic environment of the stomach

Sufficiently absorbed in the intestines but not irritating to GI mucosa

____ administration is any route not involving the intestines

Parenteral

Advantages of parenteral administration include

Rapid absorption and faster onset of drug action

Intradermal/subcutaneously

under the skin

intravenously

into a vein

intramuscularly

into the muscle tissue

Half life is the time it takes for

half of a drug dose to be eliminated or deactivated by the body

____ half life requires frequent administration

short

antibiotics used to prevent infection

prophylaxis (broad)

____ therapy when organism is unknown but syndrome is known

Empirical (broad)

____ therapy when organism is known but susceptibility is unknown

Pathogen directed (narrow)

_____ therapy when organism is known and susceptibility is known

Susceptibility-guided (narrow and the goal)

______ stops the growth of bacteria

Bacteriostatic

______ kills the bacteria

Bactericidal

Bacteriostatic tend to target

bacterial protein/folic acid synthesis and metabolic pathways

With _______ antibacterial drugs, patient’s own immune system kills of the bacteria

bacteriostatic

Bactericidal tend to target

bacterial cell walls, cell membranes, or nucleic acids

What is the largest family of antibacterial drugs?

Beta-lactam superfamily

____ drugs do not destroy their target pathogen

Antiviral

What is the goal of antiviral drugs?

To inhibit viral development to treat active infection

Why is it hard to design safe and effective antiviral drugs?

Because viruses utilize host cell machinery for replication, making it challenging to target them without harming host cells.

Antiviral drugs can target

viral replication cycle

Antiviral drugs can stimulate

the host’s anti-viral immune system

____ the primary and most effective wat to reduce severe viral infection

Vaccinations

Drugs that target eukaryotic pathogens are limited by their

toxicity to host cells

Many eukaryotic drugs have a very narrow

therapeutic index

Mycoses

fungal infections

Antifungals target

fungal specific compounds

Antifungals interfere with _______ and _____ synthesis

Nucleic Acid - leads to failure of fungal cell replication

Cell wall - glucans/chitin

Antifungals also interfere with ______ causing death

cell membrane stability and structure - targets ergosterol

Eukaryotic parasites have a complex life cycle so drugs that target one stage may be

ineffective against other stages

Antiparasitic drugs target

intracellular components

Antiparasitic drugs function to

stun or kill

_____ drugs are limited by their toxicity

Antiparasitic

What does MIC stand for?

Minimum Inhibitory Concentration

_____ disk diffusion test determine susceptibility

Kirby Bauer

_____ test determines susceptibility and MIC

Epsilometer (E-test)

Describe Kirby Bauer Test

1. Drug-infused disks are placed on a freshly inoculated agar surface

2. Plates are incubated to allow for bacterial growth and drug diffusion from the disc

3. Zone of inhibition appears if the bacteria are prevented from growing

What is the zone of inhibition used for?

Compare diameter zone to a standard table

Determines if susceptible, resistant, or intermediate

What does MBC stand for?

Minimum Bactericidal Concentration

MIC determines the

lowest concentration of an antimicrobial agent that prevents visible growth

MBC determines the

lowest concentration of an antimicrobial agent required to kill the organsim

____ occurs when a microbe is not affected by a drug therapy that is intended to inhibit or eliminate the pathogen

Antimicrobial resistance

_____ resistance is natural resistance to antimicrobial drugs based on inherent microbial structure

Intrinsic resistance

Intrinsic resistance makes certain pathogens/infections _______

harder to treat/eliminate

IR - lacks a PG therefore intrinsically resistant to drugs that target CW synthesis

Mycoplasma pneumoniae

IR - forms endospores and resist to most antibiotics

Clostridium difficile

IR - waxy cell wall enriched with mycolic acid

Mycobacterium tuberculosis

Acquired resistance is acquired by

genetic mutation or acquisition of resistance genes

Acquired resistance occurs when drug concentration levels within the cell are

Kept below the MIC

How does acquired resistance work?

alter drug’s target

inactivate drug

reduced drug concentrations inside the cell (block entry or pump drug out)

strains of bacteria, viruses, parasites, and fungi that are resistant to the antimicrobials commonly used to treat the infections they cause

super bugs

results when superbugs emerge from the initial infection resistant to the treatment and become the primary cause of a second infection

superinfections

Antibiotic resistance is fueled by

natural selection