ANTI-INFECTIVE THERAPY 5 MIC mbc exceed the MIC. High peak levels of these antibiotics may be more effective than low peak levels at curing inf Inoculate all tubes with 104 bacteria incubate 38C X 12 hrs tions. Therefore, for treatment with aminoglycosides and Clea fluoroquinolones Cmax/MIC and AUC/MIC are more helpful for maximizing effectiveness. In the rested to achieve maximal effectiveness when Cmax/MIC is 10 to 12. For fluoroquinolones, best outcomes in com- munity-acquired pneumonia may be achieved when the AUC/MIC is >34. To prevent the development of Auc roquinolone resistance to S pneumoniae, in vitro studies have suggested that AUC/MIC should be >50. For ug/ml p aeruginosa, an AUC/MIC Minimal Inhibitory Concentration( MIC)=2uIgml In vitro studies also demonstrate that aminoglycosides when the antibiotic is removed, a delay in the recovery of th ccurs ram-negative bacteria demon strate a delay of 2 to 6 hours in the recovery of active no delay after penicillins and cephalosporins. But per cillin and cephalosporins generally cause a 2-hour delay in the recovery of gram-positive or Figure 1-2. Understanding the minimum inhibitory effect can be dosed less frequently; those with no post concentration and the minimal bactericidal antibiotic effect should be administered by constant therapeutic approaches, it must be kept in mind that con- centration-dependent killing and post-antibiotic effect are importance for these antibiotics, and serum concentra- both in vitro phenomena, and treatment strategies based e s times to enhance penetration into less permeable body sites. human clinical trials oroquinolones demonstrate concentration-dei killing. In vitro studies show that these antibiotics demonstrate greater killing the more thei r concentrations KEY POINTS About Antibiotic Dosing 1. Absorption, volume of distribution, metabolism, and excretion all affect serum antibiotic levels the Curve 2. Mean inhibitory concentration(MIC)is helpf in guiding antibiotic choice. 3. To maximize success with B-lactam antibiotics serum antibiotic levels should be above the mic for at least 50% of the time (t>mic >50%6) 4. To maximize success with aminoglycosides and fluoroquinolones, high peak concentration, Time above MIc Cmax/MIC, and high AUC/MIC ratio are recom- mended Drug dependent killing and post-antibiotic effect for minoglycosides and fluoroquinolones remain to be proven by dinical trials. Figure 1-3. Pharmacokinetics of a typical antibiotic.importance for these antibiotics, and serum concentra￾tions above 8 times the MIC are of no benefit other than to enhance penetration into less permeable body sites. Unlike
-lactam antibiotics, aminoglycosides and flu￾oroquinolones demonstrate concentration-dependent killing. In vitro studies show that these antibiotics demonstrate greater killing the more their concentrations exceed the MIC. High peak levels of these antibiotics may be more effective than low peak levels at curing infec￾tions. Therefore, for treatment with aminoglycosides and fluoroquinolones Cmax/MIC and AUC/MIC are more helpful for maximizing effectiveness. In the treatment of gram-negative bacteria, aminoglycosides have been sug￾gested to achieve maximal effectiveness when Cmax/MIC is 10 to 12. For fluoroquinolones, best outcomes in com￾munity-acquired pneumonia may be achieved when the AUC/MIC is 34. To prevent the development of fluo￾roquinolone resistance to S. pneumoniae, in vitro studies have suggested that AUC/MIC should be 50. For P. aeruginosa, an AUC/MIC of 200 is required. In vitro studies also demonstrate that aminoglycosides and fluoroquinolones demonstrate a post-antibiotic effect: when the antibiotic is removed, a delay in the recovery of bacterial growth occurs. Gram-negative bacteria demon￾strate a delay of 2 to 6 hours in the recovery of active growth after aminoglycosides and fluoroquinolones, but no delay after penicillins and cephalosporins. But peni￾cillins and cephalosporins generally cause a 2-hour delay in the recovery of gram-positive organisms. Investigators suggest that antibiotics with a significant post-antibiotic effect can be dosed less frequently; those with no post￾antibiotic effect should be administered by constant infusion. Although these in vitro effects suggest certain therapeutic approaches, it must be kept in mind that con￾centration-dependent killing and post-antibiotic effect are both in vitro phenomena, and treatment strategies based on these effects have not been substantiated by controlled human clinical trials. ANTI-INFECTIVE THERAPY / 5 Figure 1–2. Understanding the minimum inhibitory concentration and the minimal bactericidal concentration. 1. Absorption, volume of distribution, metabolism, and excretion all affect serum antibiotic levels. 2. Mean inhibitory concentration (MIC) is helpful in guiding antibiotic choice. 3. To maximize success with
-lactam antibiotics, serum antibiotic levels should be above the MIC for at least 50% of the time (T>MIC 50%). 4. To maximize success with aminoglycosides and fluoroquinolones, high peak concentration, Cmax/MIC, and high AUC/MIC ratio are recom￾mended. 5. The clinical importance of concentration￾dependent killing and post-antibiotic effect for aminoglycosides and fluoroquinolones remain to be proven by clinical trials. KEY POINTS About Antibiotic Dosing Figure 1–3. Pharmacokinetics of a typical antibiotic.