Antibacterial chemotherapeutic agents

General Principles

Antimicrobial

Relevance

Populations of bacteria have been exposed to antibiotics for mellenia. Antibiotic resistance predates ANY clinical use. Our use of antibiotics does not CREATE resistance, we make it more prevalent.

Antimicrobial Pharmacodynamics ("activity")

Bacteriostatic antimicrobials

Bactericidal antimicrobials

Mechanisms of action

This figure relates antimicrobial classes to the mechasims and sites of action

Spectrum

Table 1. Antimicrobial spectrum of various antimicrobial classes.
 BacteriaMycoplasmaRickettsiaChlamydiaProtozoa
Aminoglycosides++   
Beta-lactams+    
Chloramphenicol++++ 
Lincosamides++  +
Macrolides++ + 
Pleuromutilins++ + 
Tetracyclines++++ 
Quinolones++++ 
Sulfonamides++ ++
Trimethoprim+   +
Adapted from Prescott, JF and Baggot, JD. Antimicrobial Therapy in Veterinary Medicine. Second Edition.

Table 2. Antibacterial spectrum (4 quadrants of "coverage")
 Aerobic bacteriaAnaerobic bacteria 
SpectrumGram
(+)
Gram
(-)
Gram
(+)
Gram
(-)
Examples
Broad + + + + cefoxitin, chloramphenicol, imipenam, tetracyclines, bacitracin
Intermediate + + + ± carbenicillin, ticarcillin, ceftiofur, amoxicillin/clavulanic acid, cephalosporins
+ ± + ± ampicillin, amoxicillin
Narrow   +     aztreonam, polymyxin
+ ± + ± benzyl penicillin G
+ +     aminoglycosides,sulfonamides, trimethoprim
+ +     fluoroquinolones
+   + + lincosamides, macrolides
+   +   vancomycin
    + + nitroimidazoles
± – variable activity

Facultative anaerobes

The classic "4 quadrants of coverage" do not account facultative anaerobes (e.g., E. coli). It is important to remember that facultative anaerobes are not anaerobes, they are aerobes that have the ability to live in an anaerobic environment. We culture them as aerobes, they (mostly) infect patients as aerobes and they respond to therapy as aerobes.

Bacterial resistance

Post-antibiotic effects (PAE)

Bacterial growth may be inhibited by some antibiotics even after concentrations fall (and should be ineffective).

Antimicrobial Drug Interactions

We combine antimicrobials for a number of reasons. An honest analysis suggests that we generally combine antimicrobials to increase the spectrum when we are confronted with "infection due to unknown." Most combinations are either "aditive or indifferent" (one drug to the other). We should not expect synergism and we rarely produce antagonism. The following results of such combinations are known to occur:

Additive / indifferent

action of the combination is equal to the sum of the actions of each component.

Synergism

action of the combination is significantly greater than the sum of the actions of each component.

Antagonism

action of the combination is significantly less than the sum of the actions of each component. Most commonly cited is "bacteriostatic drug inhibits action of bacteriocidal". Usually, bacteriostatic activity is sufficient for cure and you only waste money. Antagonism is only evident (clinically) when the patient is dependent on the antimicrobial for survival or cure.