Ch. 10 Antimicrobial Treatment

Goal of antimicrobial chemotherapy:

Administer a drug to an infected person that destroys the infective agent without harming the host's cells

A drug must be able to:

- be easy to administer and able to reach the infectious agent anywhere in the body

- be absolutely toxic to the infectious agent and absolutely nontoxic to the host

- remain in the body as long as needed and be safely and easily broken down and excreted

Characteristics of the Ideal Antimicrobial Drug

- Toxic to the microbe but nontoxic to the host

- Microbicidal rather than microbiostatic

- Relatively soluble; functions even when highly diluted in body fluids

- Remains potent long enough to act and is not broken down or excreted prematurely

- Does not lead to the development of antimicrobial resistance

- Complements or assists the activities of the host's defenses

- Remains active in tissues and body fluids

- Readily delivered to the site of infection

- Reasonably priced

- Does not disrupt the host's health by causing allergies or predisposing the host to other infections

Prophylaxis

use of a drug to prevent infection of a person at risk

Anitmicrobial chemotherapy

the use of drugs to control infection

Antimicrobials

all-inclusive term for any antimicrobial drug, regardless of its origin

Antibiotics

substances produced by the natural metabolic processes of some microorganisms that can inhibit or destroy other microorganisms

semisynthetic drugs

drugs that are chemically modified in the laboratory after being isolated from natural sources

synthetic drugs

drugs produced entirely by chemical reactions

Antimicrobial drugs have reduced the incidence of certain __________ but they have not eradicated infectious __________ and probably never will.

infections, diseases

The introductions of modern drugs to control infections was a medical revolution in the _______

1940s

Narrow spectrum (limited spectrum)

antimicrobials effective against a limited array of microbial types- for example, a drug effective mainly on gram-positive bacteria

Broad spectrum (extended spectrum)

antimicrobial effective against a wide variety of microbial types- for example a drug effective against both gram positive and gram negative bacteria

Antibiotics are natural metabolic products of __________ and _______.

bacteria, fungi

Antibiotics are produced to ________ the growth of competing _________ in the same habitat (antagonism).

inhibit, microbes

The greatest numbers of antibiotics are derived from:

- bacteria in the genera Streptomyces and Bacillus

- molds in the genera Penicillium and Cephalosporium

Before actual antimicrobial therapy can begin, three factors must be known:

- the identity of the microorganism causing the infection

- the degree of the microorganism's susceptibility (or sensitivity) to various drugs

- the overall medical condition of the patient

Identification of infectious agents should begin...

ASAP

Identifying agents should occur before _________________ drug is given, before their numbers are ___________.

antimicrobial, reduced

Direct examination of body fluids, ________, or _______ samples is a rapid method for ____________

sputum, stool, detection

Doctors often begin therapy on the basis of immediate __________ and informed _________.

findings, guesses

If the infectious agent is not or cannot be isolated, ______________ statistics may be required.

epidemiological

Testing for Drug Susceptibility:

Testing is necessary for the following organisms:

- Staphylococcus species

- Neisseria gonorrhoeae

- Streptococcus faecalis

- Aerobic, gram-negative intestinal bacilli

Testing for ________ or __________ infections is difficult and unnecessary.

fungal, protozoa

- surface of an agar plate is spread with test bacterium

- small discs containing a prepared amount of antibiotic are placed on the plate

- zone of inhibition surrounding the discs is measured and compared with a standard for each drug

- antibiogram provides data for drug selection

Kirby-Bauer Technique

This method is less effective for anaerobic, highly fastidious, or slow-growing bacteria:

kirby-bauer technique

therapeutic index

the ratio of the dose that is toxic to humans as compared to its minimum effective (therapeutic) dose

The SMALLER the ratio, the GREATER the potential for

toxic drug reactions

When TI = 1.1

it is a risky choice

When TI = 10

it is a safer choice

The drug with the highest TI has the __________ margin of safety.

widest

Before prescribing an antibiotic,

the physician must take a careful history of the patient to discover any preexisting conditions that might influence the activity of the drug or the response of the patient

Which of the following antibiotics would be the safest choice for a patient with no exceptional medical history? Why?

Drug B: Zone of inhibition 20mm, TI: 12

1 multiple choice option

Drugs most toxic to humans:

- Drugs that act upon a structure common to both the ineffective agent & then host cell (cell membrane)

Goals of antimicrobial drugs:

- Disrupt cell processes or structures

- Inhibit virus replication

- Interfere with the function of enzymes

- Destroy structures already formed in the cell

Selectively toxic

kills or inhibit microbial cells without damaging host tissues

Drugs with excellent selective toxicity block __________ of the bacterial ______ _______ (penicillins)

cell wall

Minimum inhibitory concentration (MIC):

the smallest concentration (highest dilution) of drug that visibly inhibits growth

Minimum bactericidal concentration (MBC)

the smallest concentration of drug needed to kill test bacteria

Human cells lack the chemical ________________ and are unaffected by penicillins.

peptidoglycan

As the characteristics of the infectious agent become more and more similar to the host cell, ____________ __________ becomes more difficult to achieve.

selective toxicity

Drugs that target the cell wall:

- penicillins - cephalosporins

- carbapenems - bacitracin

- isoniazid - vancomycin

- fosfomycin tromethamine

Drugs that target protein synthesis:

- Aminoglycosides

- Tetracyclines

- Glycylcyclines

- Macrolides

Aminoglycosides

insert on sites on the 30S subunit and cause the misreading of the mRNA, leading to abnormal proteins (ie. streptomycin)

Macrolides

inhibit translocation of the subunit during translation (ie. erythromycin)

Tetracyclines and Glycylcyclines

block the attachment of tRNA on the A acceptor site and stop further protein synthesis

Drugs that target DNA or RNA

- Fluoroquinolones

- Sulfonamides

Fluoroquinolones

inhibit DNA unwinding enzymes or helicases, thereby stopping DNA transcription

Sulfonamides

interfere with folate metabolism by blocking enzymes required for the synthesis of tetrahydrofolate, which is needed by the cells for folic acid synthesis and eventual production of DNA, RNA, and amino acids

Drugs that target cytoplasmic or cell membranes:

polymyxins (colistins)

Polymyxins (colistins)

interact with membrane phospholipids; distort the cell surface and cause leakage of protein and nitrogen bases, particularly in gram-negative bacteria (ie. polymyxins B and daptomycin)

Which of the following antibiotic modes of action will have the least toxic effect on a human cell?

Antibiotic C: acts on the peptidoglycan cell wall

2 multiple choice options

Broad-spectrum drugs

effective against more than one group of bacteria

Narrow-spectrum drug

targets a specific group

Fungi cells are __________ and thus present problem in drug treatment.

eukaryotic

Drugs designed to act on bacteria are ____________ against fungi.

ineffective

The similarities between fungi and human cells means that drugs _______ to fungi will harm human ________.

toxic, tissue

Antimalarial drugs:

quinine and artemisinin

Quinine

- Principal treatment of malaria for hundreds of years

- Has been replaced by synthesized quinolones, chloroquine and primaquine

- Several species of Plasmodium and many stages in its life cycle means that no drug is universally effective

Artemisinin

has become the staple for malaria treatment in most parts of the world for centuries in Chinese traditional medicine

Metronidazole

a widely used amoebicide that is effective in treating intestinal infections and hepatic disease caused by Entamoeba histolytica; can also treat Giardia lamblia and Trichomonas vaginalis

Other drugs with antiprotozoal activities are

quinacrine, sulfonamides, and tetracyclines

Flukes tapeworms, and roundworms are larger ___________ their physiology is much more similar to _________.

parasites, humans

The strategy to block ___________ of __________ adult worms is usually not successful in eradicating them.

reproduction, helminthic

The most effective anti-helminthic drugs _________, __________, or ________ the metabolism of all stages of the life cycle.

immobilize, disintegrate, inhibit

Chromosomal drug resistance:

- usually results from random mutation

- slight changes in drug sensitivity can be overcome with larger doses of the drug

- "persister": slowing or stopping of metabolism so that the microbe cannot be harmed by the antibiotic

The CDC has categorized resistance into three groups term hazard levels:

concerning, serious, urgent

Urgent threats:

- Clostridium difficile (C. diff)

- Carbapenem-resistant Enterobacteriaceae (CRE)

- Drug-resistant Neisseria gonorrhoeae

Serious threats:

- Multidrug-resistant Acinetobacter

- Drug-resistant Campylobacter

- Fluconazole-resistant Candida

- Many more

Concerning threats:

- Vancomycin-resistant Staphylococcus aureus (VRSA)

- Erythromycin-resistant Group A Streptococcus

- Clindamycin-resistant Group B Streptococcus

Probiotics

preparation of live microorganisms fed to animals and humans to improve intestinal biota

Probiotics can replace _________ lost during antimicrobial therapy

microbes

Probiotics augment _______ already there. It is safe and in some cases __________.

biota, effective

Probiotics are useful in the management of ______ ________.

food allergies

Prebiotics

nutrients that encourage the growth of beneficial microbes in the intestine

Certain sugars such as _________ encourage the growth of Bifidobacterium in the large intestine and discourage the growth of ___________ ___________.

fructans, potential pathogens

Which of the following mechanisms of of antibiotic resistance act specifically on penicillins and cephalosporins?

B) Enzymes are synthesized, inactivating the drug

3 multiple choice options