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8 Craig10080CephalosporinsPenicillins60402000 20 40 60 80 100FIGURE 4 Relationship between percentageof time serum levels ofb-lactams that exceed the MIC andsurvival in animal models infectedwith Streptococcus pneumoniae.Abbreviation: FPO. Source: FromRefs. 41, 42.20% or less of the dosing interval. As soon as the percentage of time above MICreached 40% to 50% or higher, survival was in the order of 90% to 100%.The PK/PD indice that best correlates with the efficacy of the fluoroquinolonesis the 24-hour AUC/MIC ratio (12,38,43). The magnitude of this PK/PDindice required to produce a bacteriostatic effect in animal infection models variedfor most organisms from 25 to 50 (12). These values are equivalent to averagingone to two times the MIC over a 24-hour period [i.e., (1–2 · MIC) · 24 hour =24–48]. The relationship between 24-hour AUC/MIC values and outcome forfluoroquinolones as reported in the literature from studies that treated animals forat least two days, reported survival results at the end of therapy, and provided PKdata is illustrated in Figure 5 (12,38).The infections in these studies included pneumonia, peritonitis, and sepsisproduced by gram-negative bacilli and a few gram-positive cocci in immunosuppressedmice, rats, and guinea pigs. In general, 24-hour AUC/MIC ratios less than30 were associated with greater than 50% mortality, whereas AUC/MIC values of100 or greater were associated with almost no mortality. A value of 100 is10080Mortality (%)60402001 10 10024-hour AUC/MIC1000FIGURE 5 Relationship between24-hour AUC/MIC forfluoroquinolones and survivalin immunosuppressed animalsinfected with gram-negativebacilli and a few gram-positivecocci. Abbreviations: AUC, areaunder the concentration-versustimecurve; FPO; MIC, minimuminhibitory concentration.Source: From Refs. 12, 38.