1. Pharmacokinetics and Pharmacodynamics: Optimal Antimicrobial Therapy in the Intensive Care Unit 
Thomas P. Lodise, PharmD, G.L. Drusano, MD 
Critical Care Clinics 
Volume 27, Issue 1, Pages 1-18 (January 2011)
DOI: /j.ccc
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2. Fig. 1 Common pharmacodynamic indices.
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3. Fig. 2
Emergence of resistance to meropenem (A) and tobramycin (B) in the wild-type isolate Pseudomonas aeruginosa PA01.
(Reprint from Drusano GL, Liu W, Fregeau C, et al. Differing effects of combination chemotherapy with meropenem and tobramycin on cell kill and suppression of resistance of wild-type Pseudomonas aeruginosa PAO1 and its isogenic MexAB efflux pump-overexpressed mutant. Antimicrob Agents Chemother 2009;53(6):2266–73 [Figure 2]; with permission.)
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4. Fig. 3
Probability of achieving 50% fT>MIC for piperacillin/tazobactam regimens containing piperacillin 16 g/d.
(Reprint from Kim A, Sutherland CA, Kuti JL, et al. Optimal dosing of piperacillin-tazobactam for the treatment of Pseudomonas aeruginosa infections: prolonged or continuous infusion? Pharmacotherapy 2007;27(11):1490–7 [Figure 2]; with permission.)
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5. Fig. 4
Comparison of outcomes of patients with APACHE II scores ≥17 and patients with APACHE II scores <17 (the Classification and Regression Tree [CART]-derived breakpoint) who received either an extended infusion of piperacillin-tazobactam or an intermittent infusion of piperacillin-tazobactam. LOS, length of stay. aExcludes patients who died within 14 days of collection of P aeruginosa–positive culture sample. bComparison between patients with an APACHE II score <17 and patients with an APACHE II score ≤17 was P<.05. cComparison between the extended group and the intermittent infusion group was P<.05.
(Reprint from Lodise TP Jr, Lomaestro B, Drusano GL. Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy. Clin Infect Dis 2007;44(3):357–63 [Figure 2]; with permission.)
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6. Fig. 5
(A) Levofloxacin clinical outcome probabilities of successful outcome (n = 134 patients; 7 clinical failures). The probability curve for successful clinical outcome versus the ratio of the peak plasma concentration to the minimum inhibitory concentration (peak/MIC) is shown. Breakpoints for the pharmacologic variables indicate the value for which there is a significantly increased probability of successful outcome as determined by classification and regression tree analysis. The figure illustrates the probability curves for successful clinical outcome including peak/MIC ratio and 3 infection sites. (Reprint from Preston SL, Drusano GL, Berman AL, et al. Pharmacodynamics of levofloxacin: a new paradigm for early clinical trials. JAMA 1998;279(2):125–9 [Figure 1]; with permission.) (B) Probability of eradication of the pathogen, as a function of age and whether the patient achieves an area under the curve (AUC):MIC ratio of ≥87. Patients with younger age and who achieve an AUC:MIC ratio of ≥87 have a significantly higher probability of achieving eradication of their pathogen. Classification and regression tree analysis identified the breakpoint for age as 67 years. (Reprint from Drusano GL, Preston SL, Fowler C, et al. Relationship between fluoroquinolone area under the curve: minimum inhibitory concentration ratio and the probability of eradication of the infecting pathogen, in patients with nosocomial pneumonia. J Infect Dis 2004;189(9):1590–97 [Figure 1]; with permission.)
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7. Fig. 6
Probability of temperature resolution by days 5, 7, and 9 of aminoglycoside therapy as determined by logistic regression analysis. Use of AUC0-24/MIC as a predictor variable. Squares indicate breakpoints for the significant predictors as determined by CART analysis.
(Reprint from Kashuba AD, Nafziger AN, Drusano GL, et al. Optimizing aminoglycoside therapy for nosocomial pneumonia caused by gram-negative bacteria. Antimicrob Agents Chemother 1999;43(3):623–29 [Figure 1]; with permission.)
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8. Fig. 7
(A) Curve of probability of development of aminoglycoside nephrotoxicity for patients receiving the drug on a twice-daily basis as estimated by multivariate logistic regression analysis. The probability rises as a function of increasing daily exposure to aminoglycoside, as indexed to the AUC. Concurrent vancomycin use provides a marked increase in the probability of nephrotoxicity for equivalent exposure to aminoglycosides, as indexed to the daily AUC. (B) Once-daily administration shifts the curves of probability of nephrotoxicity as influenced by daily aminoglycoside AUC to the right. (Reprint from Rybak MJ, Abate BJ, Kang SL, et al. Prospective evaluation of the effect of an aminoglycoside dosing regimen on rates of observed nephrotoxicity and ototoxicity. Antimicrob Agents Chemother 1999;43(7):1549–55 [Figure 1]; with permission.) (C) Effect of concurrent vancomycin use on the time to the occurrence of nephrotoxicity in patients receiving a twice-daily aminoglycoside regimen. (Reprint from Drusano GL, Ambrose PG, Bhavnani SM, et al. Back to the future: using aminoglycosides again and how to dose them optimally. Clin Infect Dis 2007;45(6):753–60 [Figure 2]; with permission.)
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9. Fig. 8
(A) Stratified Kaplan-Meier analysis of time to nephrotoxicity for patients treated with linezolid (stratum 0), those treated with a standard dose of vancomycin (<4 g/d) (stratum 1), and a those treated with a high dose of vancomycin (≥4 g/d) (stratum 2). The overall differences are significant (P<.001 by Mantel test). Pairwise analysis demonstrated that strata 0 and 1 are not different. Strata 0 and 2 and strata 1 and 2 are significantly different. For the pairwise analyses, α-decay was performed by Bonferroni adjustment. (Reprint from Lodise TP, Lomaestro B, Graves J, et al. Larger vancomycin doses [at least four grams per day] are associated with an increased incidence of nephrotoxicity. Antimicrob Agents Chemother 2008;52(4):1330–36 [Figure 1]; with permission.) (B) Graphic representation of the logistic regression–derived nephrotoxicity probability functions. ICU, intensive care unit. (Reprint from Lodise TP, Patel N, Lomaestro BM, et al. Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. Clin Infect Dis 2009;49(4):507–14 [Figure 3]; with permission.)
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