Chapter 10: Antimicrobial Treatment

What is folic acid?

Folic acid is a complex, enzyme catalyzed synthesis of DNA. It helps in the biosynthesis of the building blocks of DNA.

Why do fungal infections require special agents to be treated in chemotherapy?

Fungal cells are eukaryotic, so the drugs designed for bacteria are ineffective against fungi. Drugs toxic to fungal cells can also harm human tissue.

What would drugs target that would be most toxic to humans?

If drugs were to target characteristics that were similar in both the host cell and the infectious agent, then it would be detrimental. (ex. the cytoplasmic membrane)

Which organisms is testing for drug susceptibility needed for?

-Staphylococcus species -Neisseria gonorrhoeae -Enterococcus faecalis -Aerobic, gram-negative intestinal bacilli Testing for fungal and protozoal infection is difficult and unnecessary.

What factors must be known before antimicrobial therapy?

-the identity of the microorganism causing the disease -the degree of the microorganism's susceptibility to various drugs -the overall medical condition of the patient

What are the characteristics of the ideal antimicrobial drug?

-toxic to microbe but nontoxic to host cells -microbicidal rather than microbistatic -relatively soluble; functions even when highly diluted -remains potent long enough -does not lead to antimicrobial resistance -complements or assists activities of the host's defenses -remains active in tissues and body fluids -readily delivered to sight of infection -reasonably priced -does not disrupt the host's health by causing allergies or predisposing it to other infections

What do antibiotics act of in bacteria?

Antibiotics act on the small subunit of the 70S ribosomes in prokaryotic cells.

Define antibiotics/ its origins.

Antibiotics are natural metabolic products of bacteria and fungi, that are produced to inhibit the growth of competing microbes in the same habitat. Bacteria in the genera Streptomyces and Bacillus. Molds in the genera Penicillium and Cephalosporium.

Define antimicrobial resistance.

Antimicrobial resistance is an adaptive response in which microorganisms begin to tolerate an amount fo drug that would normally be inhibitory. This is due to genetic versatility and adaptability of microbial populations.

Define broad spectrum (extended spectrum).

Antimicrobials effective against a wide variety of microbial types.

What is a superinfection?

Superinfection occurs when microbes that were once small in number overgrow when normal resident biota are destroyed by broad spectrum antimicrobials Broad spectrum antimicrobials could destroy good bacteria, making the resistant bad bacteria more susceptible for growth.

What is the Kirby-Bauer technique?

The Kirby-Bauer technique is an agar diffusion test that provides useful data on antimicrobial susceptibility; whether or not bacteria is resistant or susceptible(meaning it can be harmed by the drug) to the drug.

What is the usage of penicillin?

Penicillins are drugs with selective toxicity that blocks the synthesis of the bacterial cell wall. It mostly targets the chemical peptidoglycan, which humans lack, so we're unaffected by the drug.

Define prophylaxis.

Use of a drug to prevent a person at risk.

Why is it challenging to perform chemotherapeutic treatment of viruses?

Virus infectious agents rely on the host cells for the majority of their metabolic function, so disrupting the viruses metabolism would mean destroying the host cell's metabolism.

What are prebiotics?

Prebiotics are nutrients that encourage the growth of beneficial microbes in the intestine.

Explain microbe resistance through horizontal transfer.

Resistance (R) factors: plasmids(circular DNA strands) containing antibiotic resistance genes. This can occur through conjugations(merging of cells), transformation(a dead cell transferring genes to another), or transduction(replication and transfer of gene) Transposons also duplicate and insert genes for drug resistance into plasmids.

Define selective toxicity.

Selective toxicity means to kill or inhibit microbial cells without damaging host tissues.

Define Synthetic drugs.

drugs produced entirely from chemical reactions.

Define Synthetic drugs.

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

What are the actions of antiviral drugs?

-Antiviral drugs inhibit viral entry through receptor, fusion and uncoating inhibitors. -inhibits nucleic acid synthesis -inhibits assembly and release

What are new approaches to antimicrobial treatment?

-Using RNA interference strategies: small pieces of RNA regulate the expression of genes, used to shut down metabolism of pathogenic microbes -mimicking defense peptides

What is the goal of antimicrobial drugs?

-disrupt cell processes or structures of bacteria, fungi, or protozoa -inhibit viral replication -interfere with functions of enzymes required to synthesize or assemble macromolecules -destroy structures already formed in the cell

What are the challenges in antihelminthic drug therapy?

-flukes, tapeworms and roundworms are larger parasites -their physiology is similar to humans -blocking reproduction does not affect adult worms (most effective drugs immobilize, disintegrate, or inhibit the metabolism of all stages of the life cycle.

What can failure of antimicrobial treatment be due to?

-inability of the drug to diffuse throughout the body -resistant microbe in the infection that did not make it into the sample collected for testing -an infection caused by more than one pathogen (mixed), some of which are resistant to the drug -patients did not take the antimicrobials correctly

What are the five major metabolic targets of antimicrobial agents?

-inhibition of cell wall synthesis (ex. penicillin targets cell walls) -inhibition of nucleic acid structure or function (DNA and RNA) -inhibition of protein synthesis -interfering with cytoplasmic membrane structure and function -inhibition of folic acid synthesis (inhibits enzymes by blocking pathways and inhibiting metabolism)

What are biofilm treatment strategies?

-interrupting quorum sensing pathways -adding DNAse to antibiotics aids penetration through extracellular debris -impregnating devices with antibiotics prior to implantation Some antibiotics cause biofilms to form at a higher rate than they normally would.

Discuss 5 mechanisms that microbes use for drug resistance.

-new enzymes are synthesized, inactivating the drug (through new genes) (ex. bacterial exoenzymes called beta-lactamases or pencillinases hydrolyze the beta-lactam ring structure of some penicillins and cephalosporins, rendering the drugs inactive) -permeability of the drug decreases (through mutation). This could be due to a change in receptors for the drug -drug is immediately eliminated (through new genes) (ex. many bacteria possess multidrug-resistant(MDR) pumps that actively transports drugs outside of the cell (gram negative or gram positive cells) -binding sites of drugs decreased (through mutation or new genes) (ex. erythromycin and clindamysin resistance is associated with the alteration of the 50S subunit) -an affected metabolic pathway is shut down or an alternate pathway is used (occurs via mutation of original enzymes) (ex. sulfonamide and trimethoprim resistance develop when microbes deviate from the usual patterns of folic acid synthesis)

Bacteria in biofilms

-often unaffected by antimicrobials -antibiotics cannot penetrate sticky extracellular material surrounding biofilms -have different susceptibility profiles than free-living bacteria

Penicillin

-original penicillin was narrow spectrum and susceptible to microbial counterattacks. -gram positive bacteria (strep throat, staph infections) -effective against bacterial infections -can be hydrolyzed by penicillinase

What are the precautions taken before prescribing an antibiotic?

-preexisting conditions that might affect the drugs activity -history of allergy to a certain class of drugs -underlying liver or kidney disease -infants, elderly, pregnant -intake of other drugs increase toxicity or failure of one or more drugs -some drug combos have synergistic effect, may allow for reduced dosages

How does antibiotic resistance happen?

1. Only a few bacteria are drug resistant in a sample. 2. Antibiotics kill the bacteria that is not drug resistant along with some good bacteria which protects the cell from infection. 3. Resistant bacteria are now able to grow and take over. 4. The resistant bacteria passes on its resistance traits to other bacteria.

How can a microbe develop resistance?

A microbe can become newly resistant through spontaneous mutations in critical chromosomal genes or through the acquisition of entire new genes or sets of genes via horizontal transfer. Persisters can also slow or stop their metabolisms so they cannot be harmed by the antibiotic. Slight changes can be overcome with larger doses.

What can be prevented through the use of vaccines?

Measles, mumps and hepatitis.

What are agents that treat helminthic infections?

Mebendazole and albendazole inhibit microtubules or worms, eggs, and larvae. Pyrantel paralyzes the muscles of intestinal roundworms. Praziquantel: tapeworm and fluke infections

What is the tube dilution test?

More sensitive and quantitative than the Kirby-Bauer test. Antimicrobials are diluted serially in tubes of broth. Each tube is inoculated with a small uniform sample of pure culture, incubated and examined.

What are probiotics?

Probiotics are preparations of live microorganisms fed to animals and humans to improve intestinal biota. -it can replace microbes lost during antimicrobial treatment -augment biota already there -useful in the management of food allergies

What are two example of antimalarial drugs?

Quinine has been the principal treatment for malaria. Depending on the stage in the life cycle different drugs are used. Artemisinin is another staple drug. Artemisinin combination therapy (ACT) is artemisinin with quinine derivatives or other drugs.

What is the goal of antimicrobial chemotherapy?

The goal of antimicrobial chemotherapy is to administer a drug to an infected person that destroys the infective agent without harming the host's cells. It should remain active in the body for as long as its needed and be easily broken down and excreted.

What is the minimum inhibitory concentration(MIC)?

The minimum inhibitory concentration is the smallest concentration (highest dilution) of drug that visibly inhibits growth. It is useful in determining the smallest effective dosage and providing a comparative index against other antimicrobials.

Explain the Kirby-Bauer technique.

The surface of an agar plate is spread with test bacterium. Small discs containing a prepared amount of antibiotics 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. This method is less effective for anaerobic, highly fastidious, or slow growing bacteria.

What is the therapeutic index?

Therapeutic index is the ratio of the dose of the drug that is toxic to humans as compared to the minimum effective (therapeutic) dose. (dose that is toxic to humans/minimum effective dose) the lower the number the risker and more toxic the drug could be . A high therapeutic index has the highest margin of safety.

What are the goals of chemotherapy?

To disrupt the structure or function of an organism to the point where it can no longer survive.

Define narrow spectrum (limited spectrum).

antimicrobials effective against a limited array of microbial types

Define antimicrobials.

any antimicrobial drug, regardless of origin.

Define antimicrobial chemotherapy.

the use of drugs to control infection.