Fundamentals of Chemotherapy

Chemotherapy began with Paul Ehrlich.

Bactericidal drugs kill organisms and more effective during logarithmic growth, since the increased metabolic activity provides maximum susceptibility. Bacteriostatic antimicrobials only prevent bacterial growth.

The use of antibiotics in fixed dosage combinations is to be avoided. However, the simultaneous administration of two or more antibiotics may be justified in certain situations.

Natural resistance depends on the absence of a metabolic process affected by the antibiotic in question.

Due to three mechanisms:

1. non-susceptible metabolism;

2. ability of the organism to destroy the drug (penicillinase);

3. inability of the drug to penetrate to an appropriate location in the parasite.

Acquired resistance can arise through mutation, adaptation, or through development of infectious (multiple) drug resistance. Many gram-negative bacilli have genetic material (R factors) what is separate from the chromosomes but that mediates resistance to many different antibiotics. The R factors can be transferred from one bacterium to another (conjugation). Bacteriophages can transfer DNA via transduction to impart resistance to penicillin, erythromycin, tetracycline, and chloramphenicol. Transposition can also occur.

In general, the selection of an antibiotic should be based upon an etiologic diagnosis. Although sensitivity determinations are desirable in infections caused by E. coli, Proteus, P. aeruginosa, and Staphylococcus, they are not absolutely necessary in infections caused by some organisms that are usually sensitive to penicillin.

An antibacterial drug usually causes significant clinical improvement within 12-24 hrs. If no clinical improvement is obvious after 48-72 hrs of full therapy, it can usually be concluded that the organisms are resistant or an abscess exists.

Chemotherapeutic agents should be measured using viability.

Bacteriologic diagnosis: Disk diffusion method provides quick, basic information as to whether an organism is susceptible or resistant to a particular antibiotic. Tube dilution method provides exact concentration of antibiotic needed to kill bacteria.

In general, there is no place for prophylaxis unless it is directed against one particular organism, or a small group of organisms.

Adverse drug effects: Superinfection is the appearance of both microbiological and clinical evidence of a new infection with pathogenic microorganisms or fungi; caused by inappropriate drug use, drug resistance, inadequate dosing, or possibly catheterization. Hypersensitivity reactions can develop to most antibacterial drugs, particularly in atopic individuals.

Category: Pharmacology Notes