Bacterial Pathogenesis and Chemotherapy

Bacterial pathogenesis and chemotherapy
Terminology of Chemotherapy
Chemotherapy: The use of chemical substances or drugs to treat or prevent disease

Prophylaxis: Use of a drug to prevent potential for infection in a person at risk
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: Antimicrobial compounds synthesized entirely in the laboratory through chemical
reactions
Combined therapy (combination therapy): Protocol for taking at least two drugs at a time to
treat an infection.
Interactions between Drugs and Microbes

The goal of antimicrobial drugs is either to disrupt the cell processes or structures of bacteria,
fungi, and protozoa or to inhibit the virus multiplication cycle. All drugs should be selectively
toxic, which means they can kill or inhibit the growth of microbes without simultaneously
damaging host tissues. The best drugs are those that act specifically on microbial structures or
functions not found in vertebrate cells. The ideal antimicrobial is selectively toxic, highly
potent, stable, and soluble in the body’s tissues and fluids. It does not disrupt the immune
system or microflora of the host and is exempt from drug resistance.
Mechanisms of Drug Action

Most drugs that inhibit protein synthesis react with the ribosome-mRNA complex. Although
human cells also have ribosomes, the ribosomes of eukaryotes are different in size and
structure from those of prokaryotes, so these antimicrobials usually have a selective action
against bacteria. One potential therapeutic consequence of drugs that bind to the prokaryotic
ribosome is the damage they can do to eukaryotic mitochondria, which contain a prokaryotic
type of ribosome.
Antifungal Drugs
The great majority of chemotherapeutic drugs are designed to act on bacteria and are
generally ineffective in combating fungal infections. And because fungal and human cells are
so similar, drugs toxic to fungal cells are also capable of harming human tissues. Polyenes:
The example shown is amphotericin B, a complex steroidal antibiotic that inserts into fungal
cell membranes. Azoles: complex cyclic (ringed) compounds, such as ketoconazole which
inhibits synthesis of ergosterol, a component of the fungal cell membrane. Flucytosine: a
structural analog of cytosine that inhibits DNA and protein synthesis.
Antiparasitic Chemotherapy
Antimalarial Drugs: Quinine and Its Relatives
Quinine, a toxic chemical extracted from the bark of the cinchona tree, was the principal
treatment for malaria for hundreds of years, but it has largely been replaced by the
synthesized quinolines, mainly chloroquine and primaquine, which have less toxicity to
humans. The latest drug approved for treating uncomplicated malaria is a combination of
artimisinin and lumefantrine called Coartem. It was designed to prevent drug resistance and
has become the drug of choice in many parts of the world.
1|Page
Antiviral Chemotherapeutic Agents
The chemotherapeutic treatment of viral infections presents unique challenges. Selective
toxicity with regard to viral infection can be difficult to achieve because a single metabolic
system is responsible for the well-being of both virus and host. Unfortunately, vaccines are
unavailable for many serious viral diseases, creating a real need for antiviral medications.
Major modes of action include-barring penetration of the virus into the host cell; blocking
replication, transcription, and/or translation of viral genetic material; preventing the normal
maturation of viral particles
Although antiviral drugs protect uninfected cells by keeping viruses from being synthesized
and released, most are unable to eliminate extracellular viruses or those in a latent or
persistent state within the host’s DNA.
Alternative Antimicrobial Therapies

The technique called phage therapy, was first attempted over a hundred years ago after the
discovery of bacteriophages. The concept behind it is rather simple: When you expose
bacterial cells to their specific viruses, the viruses will invade and destroy them. If you apply
the viruses in large quantity to treat a human or animal infection, they could lyse the bacteria
and cure the infection. Other novel approaches to controlling infections include the use of
probiotics and prebiotics. Probiotics are preparations of live microorganisms that are fed to
animals and humans to modify the resident intestinal bacteria. These microorganisms can
replace microbes lost during antimicrobial therapy or simply augment the normal microbiota
that is already there. Culture-enriched dairy products are the latest commercial source of
probiotics.
Interactions between Microbes and Drugs: The Acquisition of Drug Resistance

The development of alternate enzymes that inactivate the drug (occurs only when new genes
are acquired)
Permeability or uptake of drug into bacterium is decreased or eliminated.
The microbe engages special drug transport pumps that remove the drug.
Binding sites for drug are decreased in number or affinity (can occur via mutation or
acquisition of new genes).
An affected metabolic pathway is shut down or an alternate pathway is used (occurs due to
mutation of original enzyme[s])
The Process of Selecting an Antimicrobial Drug

More sensitive and quantitative results can also be obtained with tube dilution tests. First the
antimicrobial compound is diluted serially in tubes of broth, and then each tube is inoculated
with a small uniform sample of pure culture, incubated, and examined for growth (turbidity).
The smallest concentration of drug in the series that visibly inhibits growth is called the
minimum inhibitory concentration, or MIC. The MIC is useful in determining the smallest
effective dosage of a drug and in providing a comparative index against other antimicrobials.
The MIC and the Therapeutic Index

It is best to choose the drug with high selective toxicity for the infectious agent and low
human toxicity.
The therapeutic index (TI) is defined as the ratio of the dose of the drug that is toxic to
humans as compared to its minimum effective (therapeutic) dose. The closer these two
figures are (the smaller the ratio), the greater is the potential for toxic drug reactions.
TI = Toxic dose / MIC
2|Page
Drug companies recommend dosages that will inhibit the microbes but not adversely affect
patient cells. When a series of drugs being considered for therapy have similar MICs, the
drug with the highest therapeutic index usually has the widest margin of safety.
When antimicrobial treatment fails, the failure is usually due to the inability of the drug to
diffuse into that body compartment (the brain, joints, skin); A few resistant cells in the
culture that did not appear in the sensitivity test; An infection caused by more than one
pathogen (mixed), some of which are resistant to the drug. If therapy does fail, a different
drug, combined therapy, or a different method of administration must be considered. Many
factors influence the choice of an antimicrobial drug besides microbial sensitivity to it. The
nature and spectrum of the drug, its potential adverse effects, and the condition of the patient
can be critically important. When several antimicrobial drugs are available for treating an
infection, final drug selection advances to a new series of considerations. In general, it is
better to choose the narrowest-spectrum drug of those that are effective if the causative agent
is known.
3|Page

Bacterial Pathogenesis and Chemotherapy

Uploaded by

Copyright:

Available Formats

Bacterial Pathogenesis and Chemotherapy

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Bacterial Pathogenesis and Chemotherapy

Uploaded by

Copyright:

Available Formats

Bacterial pathogenesis and chemotherapy

Chemotherapy: The use of chemical substances or drugs to treat or prevent disease

Interactions between Drugs and Microbes

Mechanisms of Drug Action

Alternative Antimicrobial Therapies

Interactions between Microbes and Drugs: The Acquisition of Drug Resistance

The Process of Selecting an Antimicrobial Drug

The MIC and the Therapeutic Index

You might also like