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At the MIC the antibiotic is inhibiting growth, but it may or may not actually be killing the organism. Antibiotics that inhibit growth of the organism without killing it are termed bacteriostatic. If antibiotics are taken away, the organisms can begin growing again. However, bacteriostatic antibiotics usually are successful in treating infections because they allow the patient’s immune system to catch up and kill off the organisms. Other antibiotics are considered bactericidal; their action kills the organisms without any help from the immune system. For most infections, outcomes using appro-priate bacteriostatic versus bactericidal drugs are similar; however, for certain infections bactericidal drugs are preferred. These infections include endocarditis, meningitis, osteomyelitis, and infections in neutropenic patients. For these infections, there is reduced contribution from the immune system because of the anatomic location or the immuno-suppression of the patient. Bactericidal activity is determined by taking a sample of the broth at the MIC and below and spreading the broth on agar plates (Figure 3-1). The number of bacterial colonies on the plates are counted and the concentration corresponding to a 99.9% reduction in the original bacterial inoculum is considered to be the minimum bactericidal concentration (MBC). When the MBC is 4 times or less the MIC, the drug is considered to be bactericidal; if the MBC/MIC ratio is greater than 4, it is considered bacteriostatic. Table 3-2 lists drugs according to whether they are generally considered bacteriostatic or bactericidal; however, it should be noted that this activity can vary based on the pathogen being treated, the achievable dose, and the growth phase of the organism.
Besides differing in whether they kill bacteria or merely inhibit their growth, antibiotics also differ in how they manifest their effects over time. Careful studies have revealed that for certain antibiotics, activity against bacteria correlates with the duration of time that the concentration of the drug remains above the MIC (time-dependent activity). For other antibiotics, antibacterial activity correlates not with the time above the MIC but with the ratio of the peak concentration of the drug to the MIC (concentration-dependent or time-independent activity). For some antibiotics, the best predictor of activity is the ratio of the area under the concentration-time curve to the MIC.