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Confirm need: identify target; keys to appropriate antimicrobial use


The term "bactericidal" is somewhat abused. Veterinarians will reach for a drug that is "cidal" rather than "static", assuming that the ability of the drug to kill rather than simply inhibit organisms will increase the risk of therapeutic efficacy. This may be true, but only if concentrations of the drug achieved at the site of infection are sufficient to kill the microbe. The term "bactericidal" is an in vitro definition and is based on killing rates (e.g., 99.9 percent reduction in bacterial inoculum within a 24-hour period of exposure) as well as the proximity of the minimum bactericidal concentration (MBC) of a drug to the MIC. The MBC is determined following tube dilution procedures; tubes with no observable growth are inoculated on agar gel. If no organism grows on the agar, the organisms were killed in the test tube. The tube with the lowest concentration of drug that yields no growth on the agar gel contains the MBC of drug. For drugs considered bactericidal, the MBC is within one tube dilution of the MIC, meaning, the organisms were not simply inhibited, but rather, were killed.

For "bacteriostatic" drugs, growth on the agar plate will occur for several tube dilutions above the MIC, indicating that organisms were not killed. However, bacteriostatic drugs are capable of killing [e.g., some organisms are exquisitely sensitive to the effects of selected drugs; some static drugs are accumulated to concentrations that are likely to be cidal (e.g., macrolides and lincosamides in phagocytes; urine concentration)]. However, killing concentrations are generally more likely achieved for a cidal drug compared to a static concentration. On the other hand, a cidal drug may not kill if concentrations are not sufficient, or if conditions preclude its actions (e.g., slow growth in an anaerobic environment; combination with growth inhibitors). Thus, cidal effects will occur only if adequate concentrations (i.e., MIC/MBC) are achieved at the site. The bactericidal nature of a drug often reflects its mechanism of action.

Drugs that target ribosomes (e.g., tetracyclines, macrolides, lincosamides, chloramphenicol) often simply inhibit the growth of the organism, and, because a much higher drug concentration is necessary to kill the organism, in vitro, the MIC is distant from the MBC. Clinically, host defenses must eradicate the infection following treatment with these drugs unless exceptionally high concentrations (i.e., the MBC) of these drugs are achieved in tissues. An exception is made for aminoglycosides, whose ribosomal inhibition is so effective that the organism dies.

Drugs that target cell walls (beta lactams including penicillins and cephalosporins; vancomycin), cell membranes (bacitracin, polymixin and colistin), and DNA (enrofloxacin, metronidazole) and RNA (rifampin) are defined in vitro as bactericidal. Combinations of static drugs can often result in "cidal" actions. For example, sulfonamides (which target folic acid synthesis) are "static", but when used in combination with diaminopyrimidines (e.g., trimethoprim), the combination is defined in vitro as cidal.

Attaining bactericidal concentrations of an antimicrobial is critical for those infections for which host killing is likely to be impaired. These include, but are not limited to, infections in immune-compromised animals (e.g., viral infection like parvovirus, panleukopenia, FIV, FeLV), animals receiving glucocorticoids or in systems characterized by derangements in local immunity (i.e., CNS infection for which a marked inflammatory response can be life threatening; osteomyelitis; peritonitis, bacteremia/sepsis, many chronic infections).

Dr. Johnny Hoskins is owner of DocuTech Services. He is a diplomate of the American College of Veterinary Internal Medicine with specialities in small animal pediatrics. He can be reached at (225) 955-3252, fax: (214) 242-2200


Source: DVM360 MAGAZINE,
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