Chapter 20 Antimicrobial Drugs

Broad-spectrum

effective against a wide range of microorganisms.

Bacteriostatic

Prevent microbes from growing

Bactericidal

Kill microbes directly

Superinfection

occur when a pathogen develops resistance to the drug being used or when normally resistant microbiota multiply excessively.

Narrow-spectrum

affect only a select group of microbes like gram+ cells.

Why are fungal, protozoan, and helminthic infections harder to treat?

Because these types of bacteria have eukaryotic cells

Chemotherapy

the use of drugs to treat a disease

Antimicrobial drugs

generally act either by directly killing microorganisms (bactericidal) or by inhibiting their growth (Bacteriostatic)

Antibiotic

a substance produced by a microbe that, in small amounts, inhibits another microbe

Selective toxicity

killing harmful microbes without damaging the host

Narrow spectrum is to __________ as broad spectrum is to ___________.

Bactericidal; bacteriostatic

What are the 5 main targets of antimicrobial drugs?

Cell wall synthesis, Cell membrane function, Nucleic acid synthesis, Protein synthesis, and Action as antimetabolites

Inhibitors of cell wall synthesis

BICVP: Bacitracin, Isoniazid, Cephalosporins, Vancomycin, Penicillins

Inhibitors of protein synthesis:

Chloramphenicol, Tetracyclines, Aminoglycosides inhibit protein synthesis at 70s ribosomes.

Inhibitors of nucleic acid synthesis:

Rifamycin - inhibits mRNA synthesis; its used to treat TB.

Quinolones and fluoroquinolones inhibit DNA gyrase fir treating UTIs.

Rifamycin: Inhibitor of NA synthesis

RIFAMPIN: inhibits RNA polymerase/transcription. Ideal treatment: Mycobacterium (Leprosy, TB)

Injury to the Plasma membrane

Lipopeptides polymyxin B and bacteria cause damage to plasma membrane

Disruptor of cell membrane:

Polymyxin

What are the 4 major groups of Antimicrobial drugs?

1. Antibacterial, 2. Antifungal, 3. Antiparasitic, 4. Antiviral

What are b-lactamases (penicillinase) & be able to name two techniques that limit their activity?

Penicillinases are bacterial enzymes that destroy natural penicillins. All penicillins contain a B-lactam ring.

Carbapenems

are broad-spectrum antibiotics that inhibit cell wall synthesis.

Mono-bactams aztreonam

affects only gram-negative bacteria

Synergism

occurs when the effect of two drugs together is greater than the effect of either alone

What are the differences in the information provided by the disk diffusion test, e test and broth dilution tests

In the disk-diffusion test (Kirby-Bauer) a bacterial culture is inoculated on an agar medium and filter paper disks impregnated with chemotherapeutic agents are overlaid on the culture. After incubation the diameter of the zone of inhibition is used to determine whether the organism is sensitive, intermediate, or resistance to the deug. MIC is the lowest concentration of a drug capusle.

MIC can be estimated using the E Test

Broth-dilution: the microorganism is grown in liquid media with different concentrations. Lowest concentration that kills bacteria is called the minimal bactercidal concentration MBC.

Effect of combination of drugs

Some combination of drugs are synergistic; they are more effective when taken together.

Some combination of drugs are antagonistic; when taken together both drugs become less effective than when taken alone.

Antagonism

occurs when the effect of two drugs together is less than the effect of either alone

The future of chemotherapeutic agents

New agents include antimicribial peptides, bacteriocins and bacteriophages. Virulence factors rather than cell grotwth factors may provide new targets.

Why shouldn't rifampin be used alone?

Because many Gram(-) are resistant due to it not crossing their outer membrane. Others will develop a resistance by altering its target.

What mechanisms are used by bacteria to resist antibiotics?

The discriminating use of drugs in appropiate concentration and dosages can minimize resistance.

What factors promote antibiotic resistance?

Superbugs are bacteria that are resistance to several anitbiotics. Drug resistance factors are transferred horizontally between bacteria. Resistance factors may be due to enzymatic destruction of a drug, prevention of penetration of the drug due to its target site, cellular or metabolic changes at target sites, altering the target site or rapid efflux of the antibiotic.

Why should you not use Colistin as a first line of defense? (It is a polymyxin)

Because it is HIGHLY nephrotoxic. Good as a last resort.

What is the general mechanism of antibiotics that affect the cytoplasmic membrane?

They interact with the phospholipids and increase the cell permeability, resulting in apoptosis. Can be stopped by inability to reach inner membrane (via outer or thick peptidoglycan)

What is an antimicrobial drug?

An antimicrobial drug is a chemical substance that destroys pathogenic microorganisms with minimal damage to host tissues.

What do chemotherapeutic agents include?

Chemotherapeutic agents include chemicals that combat disease in the body.

Who developed the concept of chemotherapy?

Paul Ehrlich developed the concept of chemotherapy to treat microbial diseases; he predicted the development of chemotherapeutic agents, which would kill pathogens without harming the host.

When did sulfa drugs come into prominence?

In the 1930s

What was the first anitbiotic discovered and who discovered it?

Alexander Fleming discovered the first antibiotic, Penicillin, in 1928; it's first clincal trials were done in 1940. (WWI)