Use of Antimicrobials and Toxicity

Broad-spectrum antibacterial agents kill most bacteria including gram-positive rods and cocci, gram-negative rods and cocci, and often anaerobes too. Narrow-spectrum agents kill a narrow range of microbes, e.g. benzylpenicillin is mainly active against gram-positive cocci. By and large a narrow-spectrum antimicrobial is less likely to disrupt a patient’s normal flora than a broad-spectrum agent. Hence, if the likely organism is causing an infection it is best to give a narrow-spectrum antimicrobial to treat that specific organism. If a patient presents ‘septic’ and the source of infection is unknown, relevant cultures should be taken followed by broad-spectrum antimicrobial cover. This can later be modified either when the source of infection is found or as a result of microbiology culture results. ● Agents mostly active against gram-positive bacteria include: ■ Penicillin (Also active against Neisseria spp.). ■ Fusidic acid. ■ Macrolides (Also active against Legionella, Campylobacter, Bordetella spp.). ■ Clindamycin. ■ Glycopeptides. ■ Oxazolidinones. ■ Streptogramins. ● Agents mainly active against gram-negative bacteria include: ■ Polymyxin. ■ Trimethoprim. ■ Aminoglycosides (also active against staphylococci and show synergy when combined with beta-lactams against/glycopeptides against streptococci). ■ Monobactams. ■ Temocillin. ● Broad-spectrum antimicrobials include: ■ Beta-lactam plus beta-lactamase inhibitor combinations. ■ Cephalosporins. ■ Carbapenems. ■ Chloramphenicol, Tetracyclines/Glycyclines. A bactericidal agent is a compound that actively kills multiplying bacteria. A bacteriostatic compound inhibits the growth of bacteria. Whether or not an antimicrobial is bactericidal or bacteriostatic depends on a variety of things, including the type of agent, its concentration, and the organism it is being used to treat. It is especially important to try and use a bactericidal agent if the patient’s immune system is impaired or the infection is at a site where it is difficult for the immune system to access, e.g. the heart valves in bacterial endocarditis, the meninges in meningitis. Examples of each are given here: ● Bactericidal agents include beta-lactams, glycopeptides, fluoroquinolones, and aminoglycosides. ● Bacteriostatic agents include macrolides, clindamycin, tetracyclines, trimethoprim, and sulphonamides. The therapeutic index of a drug is the ration of the concentration of drug likely to be toxic to the patient divided by the concentration of drug likely to be clinically effective.