Advanced search
Publication Cover
Expert Opinion on Drug Metabolism & Toxicology Volume 12, 2016 - Issue 1
Submit an article Journal homepage
1,420
Views
40
CrossRef citations to date
0
Altmetric
Reviews

Pharmacokinetics and pharmacodynamics in antibiotic dose optimization

Sherwin KB SyDepartment of Pharmaceutics, College of Pharmacy, University of Florida, PO Box 100494, Gainesville, FL32610, USA;Post-Graduate Program in Biostatistics, Universidade Estadual de Maringá, Maringá, PR, Brazil
,
Luning ZhuangDepartment of Pharmaceutics, College of Pharmacy, University of Florida, PO Box 100494, Gainesville, FL32610, USA;Division of Pharmacometrics, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA
&
Hartmut DerendorfDepartment of Pharmaceutics, College of Pharmacy, University of Florida, PO Box 100494, Gainesville, FL32610, USACorrespondence[email protected]
Pages 93-114 | Published online: 14 Dec 2015

Bibliography

  • Papers of special note have been highlighted as
  • • of interest
  • •• of considerable interest
  • Asin-Prieto E, Rodriguez-Gascon A, Isla A. Applications of the pharmacokinetic/pharmacodynamic (PK/PD) analysis of antimicrobial agents. J Infect Chemother. 2015;45:504–511.
  • Sy SK, Derendorf H. Pharmacometrics in bacterial infections. In: Schmidt S, Derendorf H, editors. Applied pharmacometrics. 1st ed. New York (NY): Springer; 2014. p. 229–258.
  • Nielsen EI, Friberg LE. Pharmacokinetic-pharmacodynamic modeling of antibacterial drugs. Pharmacol Rev. 2013;65:1053–1090.

••A very thorough review of antimicrobial pharmacokinetic–pharmacodynamic research up until 2013

  • Heerdink ER, Urquhart J, Leufkens HG. Changes in prescribed drug doses after market introduction. Pharmacoepidemiol Drug Saf. 2002;11:447–453.
  • Sy SK, Wang X, Derendorf H. Introduction to pharmacometrics and quantitative pharmacology with an emphasis on physiologically based pharmacokinetics. In: Derendorf H, Schmidt S, editors. Applied pharmacometrics. New York (NY): Springer; 2014. p. 1–64.

• Provides a concise overview of pharmacokinetic modeling approach in general

  • Wu B, Sy SK, Derendorf H. Principles of applied pharmacokinetic–pharmacodynamic modeling. In: Vinks AA, Derendorf H, Mouton JW, editors. Fundamentals of antimicrobial pharmacokinetics and pharmacodynamics. New York (NY): Springer; 2014. p. 63–79.
  • Jorgensen JH, Ferraro MJ. Antimicrobial susceptibility testing: a review of general principles and contemporary practices. Clin Infect Dis. 2009;49:1749–1755.
  • Eagle H, Fleischman R, Musselman AD. The effective concentrations of penicillin in vitro and in vivo for streptococci, pneumococci, and Treponema pallidum. J Bacteriol. 1950;59:625–643.
  • Eagle H, Fleischman R, Musselman AD. Effect of schedule of administration on the therapeutic efficacy of penicillin; importance of the aggregate time penicillin remains at effectively bactericidal levels. Am J Med. 1950;9:280–299.
  • Eagle H, Fleischman R, Levy M. “Continuous” vs. “discontinuous” therapy with penicillin; the effect of the interval between injections on therapeutic efficacy. N Engl J Med. 1953;248:481–488.
  • Eagle H, Fleischman R, Levy M. On the duration of penicillin action in relation to its concentration in the serum. J Lab Clin Med. 1953;41:122–132.
  • Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998;26:1–10; quiz 11–12.
  • Mouton JW, Dudley MN, Cars O, et al. Standardization of pharmacokinetic/pharmacodynamic (PK/PD) terminology for anti-infective drugs: an update. J Antimicrob Chemother. 2005;55:601–607.
  • Ambrose PG, Bhavnani SM, Rubino CM, et al. Pharmacokinetics-pharmacodynamics of antimicrobial therapy: it’s not just for mice anymore. Clin Infect Dis. 2007;44:79–86.
  • Bustamante CI, Drusano GL, Tatem BA, et al. Postantibiotic effect of imipenem on Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1984;26:678–682.
  • Andes D, Craig WA. Animal model pharmacokinetics and pharmacodynamics: a critical review. Int J Antimicrob Agents. 2002;19:261–268.
  • Craig WA, Ebert SC. Killing and regrowth of bacteria in vitro: a review. Scand J Infect Dis Suppl. 1990;74:63–70.
  • Andes D, Van Ogtrop ML, Peng J, et al. In vivo pharmacodynamics of a new oxazolidinone (linezolid). Antimicrob Agents Chemother. 2002;46:3484–3489.
  • Nielsen EI, Cars O, Friberg LE. Pharmacokinetic/pharmacodynamic (PK/PD) indices of antibiotics predicted by a semimechanistic PKPD model: a step toward model-based dose optimization. Antimicrob Agents Chemother. 2011;55:4619–4630.
  • Corvaisier S, Maire PH, Bouvier d’Yvoire MY, et al. Comparisons between antimicrobial pharmacodynamic indices and bacterial killing as described by using the Zhi model. Antimicrob Agents Chemother. 1998;42:1731–1737.
  • Rybak MJ, Lomaestro BM, Rotschafer JC, et al. Vancomycin therapeutic guidelines: a summary of consensus recommendations from the infectious diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. Clin Infect Dis. 2009;49:325–327.
  • Moise-Broder PA, Forrest A, Birmingham MC, et al. Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections. Clin Pharmacokinet. 2004;43:925–942.
  • Kullar R, Leonard SN, Davis SL, et al. Validation of the effectiveness of a vancomycin nomogram in achieving target trough concentrations of 15–20 mg/L suggested by the vancomycin consensus guidelines. Pharmacotherapy. 2011;31:441–448.
  • Wong-Beringer A, Joo J, Tse E, et al. Vancomycin-associated nephrotoxicity: a critical appraisal of risk with high-dose therapy. Int J Antimicrob Agents. 2011;37:95–101.
  • Toutain PL, Bousquet-Melou A, Martinez M. AUC/MIC: a PK/PD index for antibiotics with a time dimension or simply a dimensionless scoring factor? J Antimicrob Chemother. 2007;60:1185–1188.
  • Booker BM, Smith PF, Forrest A, et al. Application of an in vitro infection model and simulation for reevaluation of fluoroquinolone breakpoints for Salmonella enterica serotype typhi. Antimicrob Agents Chemother. 2005;49:1775–1781.
  • Dudhani RV, Turnidge JD, Coulthard K, et al. Elucidation of the pharmacokinetic/pharmacodynamic determinant of colistin activity against Pseudomonas aeruginosa in murine thigh and lung infection models. Antimicrob Agents Chemother. 2010;54:1117–1124.
  • Dudhani RV, Turnidge JD, Nation RL, et al. fAUC/MIC is the most predictive pharmacokinetic/pharmacodynamic index of colistin against Acinetobacter baumannii in murine thigh and lung infection models. J Antimicrob Chemother. 2010;65:1984–1990.
  • Guyonnet J, Manco B, Baduel L, et al. Determination of a dosage regimen of colistin by pharmacokinetic/pharmacodynamic integration and modeling for treatment of G.I.T. disease in pigs. Res Vet Sci. 2010;88:307–314.
  • Bergen PJ, Bulitta JB, Forrest A, et al. Pharmacokinetic/pharmacodynamic investigation of colistin against Pseudomonas aeruginosa using an in vitro model. Antimicrob Agents Chemother. 2010;54:3783–3789.
  • Helfand MS, Bonomo RA. Current challenges in antimicrobial chemotherapy: the impact of extended-spectrum beta-lactamases and metallo-beta-lactamases on the treatment of resistant Gram-negative pathogens. Curr Opin Pharmacol. 2005;5:452–458.
  • Leflon-Guibout V, Bonacorsi S, Clermont O, et al. Pyelonephritis caused by multiple clones of Escherichia coli, susceptible and resistant to co-amoxiclav, after a 45 day course of co-amoxiclav. J Antimicrob Chemother. 2002;49:373–377.
  • Leflon-Guibout V, Ternat G, Heym B, et al. Exposure to co-amoxiclav as a risk factor for co-amoxiclav-resistant Escherichia coli urinary tract infection. J Antimicrob Chemother. 2002;49:367–371.
  • Sanders CC, Iaconis JP, Bodey GP, et al. Resistance to ticarcillin-potassium clavulanate among clinical isolates of the family Enterobacteriaceae: role of PSE-1 beta-lactamase and high levels of TEM-1 and SHV-1 and problems with false susceptibility in disk diffusion tests. Antimicrob Agents Chemother. 1988;32:1365–1369.
  • Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother. 2010;54:969–976.
  • Strayer AH, Gilbert DH, Pivarnik P, et al. Pharmacodynamics of piperacillin alone and in combination with tazobactam against piperacillin-resistant and -susceptible organisms in an in vitro model of infection. Antimicrob Agents Chemother. 1994;38:2351–2356.
  • Livermore DM. Determinants of the activity of beta-lactamase inhibitor combinations. J Antimicrob Chemother. 1993;31(Suppl A):9–21.
  • VanScoy B, Mendes RE, McCauley J, et al. Pharmacological basis of beta-lactamase inhibitor therapeutics: tazobactam in combination with Ceftolozane. Antimicrob Agents Chemother. 2013;57:5924–5930.
  • VanScoy B, Mendes RE, Nicasio AM, et al. Pharmacokinetics-pharmacodynamics of tazobactam in combination with ceftolozane in an in vitro infection model. Antimicrob Agents Chemother. 2013;57:2809–2814.
  • Louie A, Castanheira M, Liu W, et al. Pharmacodynamics of beta-lactamase inhibition by NXL104 in combination with ceftaroline: examining organisms with multiple types of beta-lactamases. Antimicrob Agents Chemother. 2012;56:258–270.
  • Coleman K, Levasseur P, Girard AM, et al. Activities of ceftazidime and avibactam against beta-lactamase-producing Enterobacteriaceae in a hollow-fiber pharmacodynamic model. Antimicrob Agents Chemother. 2014;58:3366–3372.
  • Dose finding for a β-lactam – β-lactamase inhibitor combination. [cited 2014 Nov]. http://www.ema.europa.eu/docs/en_GB/document_library/Presentation/2015/01/WC500179802.pdf
  • Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44(Suppl 2):S27–S72.
  • Louie A, Liu W, Fikes S, et al. Impact of meropenem in combination with tobramycin in a murine model of Pseudomonas aeruginosa pneumonia. Antimicrob Agents Chemother. 2013;57:2788–2792.
  • Joly-Guillou ML, Wolff M, Farinotti R, et al. In vivo activity of levofloxacin alone or in combination with imipenem or amikacin in a mouse model of Acinetobacter baumannii pneumonia. J Antimicrob Chemother. 2000;46:827–830.
  • Paul M, Dickstein Y, Schlesinger A, et al. Beta-lactam versus beta-lactam-aminoglycoside combination therapy in cancer patients with neutropenia. Cochrane Database Syst Rev. 2013;6:CD003038.
  • Paul M, Lador A, Grozinsky-Glasberg S, et al. Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis. Cochrane Database Syst Rev. 2014;1:CD003344.
  • Levison ME. Pharmacodynamics of antimicrobial drugs. Infect Dis Clin North Am. 2004;18:451–465.
  • Brentnall C, Cheng Z, McKellar QA, et al. Pharmacodynamics of oxytetracycline administered alone and in combination with carprofen in calves. Vet Rec. 2012;171:273.
  • Ziv G, Sulman FG. Binding of antibiotics to bovine and ovine serum. Antimicrob Agents Chemother. 1972;2:206–213.
  • Nouws JF, Vree TB, Termond E, et al. Pharmacokinetics and renal clearance of oxytetracycline after intravenous and intramuscular administration to dairy cows. Vet Q. 1985;7:296–305.
  • Buyck JM, Plesiat P, Traore H, et al. Increased susceptibility of Pseudomonas aeruginosa to macrolides and ketolides in eukaryotic cell culture media and biological fluids due to decreased expression of oprM and increased outer-membrane permeability. Clin Infect Dis. 2012;55:534–542.
  • Pruul H, McDonald PJ. Potentiation of antibacterial activity of azithromycin and other macrolides by normal human serum. Antimicrob Agents Chemother. 1992;36:10–16.
  • Ericsson HM, Sherris JC. Antibiotic sensitivity testing. Report of an international collaborative study. Acta Pathol Microbiol Scand B: Microbiol Immunol. 1971;217(Suppl 217):1+.
  • Aliabadi FS, Landoni MF, Lees P. Pharmacokinetics (PK), pharmacodynamics (PD), and PK-PD integration of danofloxacin in sheep biological fluids. Antimicrob Agents Chemother. 2003;47:626–635.
  • Blaser J, Stone BB, Zinner SH. Two compartment kinetic model with multiple artificial capillary units. J Antimicrob Chemother. 1985;15(Suppl A):131–137.
  • Crandon JL, Nicolau DP. Human simulated studies of aztreonam and aztreonam-avibactam to evaluate activity against challenging gram-negative organisms, including metallo-beta-lactamase producers. Antimicrob Agents Chemother. 2013;57:3299–3306.
  • Bulitta JB, Ly NS, Yang JC, et al. Development and qualification of a pharmacodynamic model for the pronounced inoculum effect of ceftazidime against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2009;53:46–56.
  • Sy SK, Beaudoin ME, Nichols WW, et al. Avibactam and ceftazidime combination against multidrug resistant organisms in an in vitro pharmacokinetic/pharmacodynamic model. In: 54th interscience conference of antimicrobial agents and chemotherapy; 2014. Washington (DC); 2014 Sept 5–9, p. abstr A–1344.
  • Sy SK, Beaudoin ME, Schuck VJ, et al. Modeling the potentiation of in vitro aztreonam activities by avibactam against four beta-lactam-resistant bacterial strains. In: 53rd interscience conference of antimicrobial agents and chemotherapy; 2013. Denver (CO); 2013 Sept 10–13; p. abstr A–1014.
  • Gershenfeld NA. The nature of mathematical modeling. Cambridge (UK): Cambridge University Press; 1999.
  • Udekwu KI, Parrish N, Ankomah P, et al. Functional relationship between bacterial cell density and the efficacy of antibiotics. J Antimicrob Chemother. 2009;63:745–757.
  • Mouton JW, Vinks AA. Pharmacokinetic/pharmacodynamic modelling of antibacterials in vitro and in vivo using bacterial growth and kill kinetics: the minimum inhibitory concentration versus stationary concentration. Clin Pharmacokinet. 2005;44:201–210.
  • Tam VH, Ledesma KR, Vo G, et al. Pharmacodynamic modeling of aminoglycosides against Pseudomonas aeruginosa and Acinetobacter baumannii: identifying dosing regimens to suppress resistance development. Antimicrob Agents Chemother. 2008;52:3987–3993.
  • Treyaprasert W, Schmidt S, Rand KH, et al. Pharmacokinetic/pharmacodynamic modeling of in vitro activity of azithromycin against four different bacterial strains. Int J Antimicrob Agents. 2007;29:263–270.
  • Zhuang L, Sy SK, Xia H, et al. Evaluation of in vitro synergy between vertilmicin and ceftazidime against Pseudomonas aeruginosa using a semi-mechanistic pharmacokinetic/pharmacodynamic model. Int J Antimicrob Agents. 2015;45:151–160.

••One of the first articles to successfully characterize whether a combination is synergistic, antabonistic or additive using modeling

  • Greco WR, Bravo G, Parsons JC. The search for synergy: a critical review from a response surface perspective. Pharmacol Rev. 1995;47:331–385.

• Provides the mathematical foundation for qualifying synergistic activities of combination therapy

  • Maiwald T, Timmer J. Dynamical modeling and multi-experiment fitting with PottersWheel. Bioinformatics. 2008;24:2037–2043.
  • Hengl S, Kreutz C, Timmer J, et al. Data-based identifiability analysis of non-linear dynamical models. Bioinformatics. 2007;23:2612–2618.
  • Kohanski MA, Dwyer DJ, Collins JJ. How antibiotics kill bacteria: from targets to networks. Nat Rev Microbiol. 2010;8:423–435.
  • Topfer N, Jozefczuk S, Nikoloski Z. Integration of time-resolved transcriptomics data with flux-based methods reveals stress-induced metabolic adaptation in Escherichia coli. BMC Syst Biol. 2012;6:148.
  • Muller M, Dela Pena A, Derendorf H. Issues in pharmacokinetics and pharmacodynamics of anti-infective agents: distribution in tissue. Antimicrob Agents Chemother. 2004;48:1441–1453.
  • Plock N, Kloft C. Microdialysis–theoretical background and recent implementation in applied life-sciences. Eur J Pharm Sci. 2005;25:1–24.
  • Barbour A, Schmidt S, Rout WR, et al. Soft tissue penetration of cefuroxime determined by clinical microdialysis in morbidly obese patients undergoing abdominal surgery. Int J Antimicrob Agents. 2009;34:231–235.
  • Sauermann R, Burian B, Burian A, et al. Tissue pharmacokinetics of ertapenem at steady-state in diabetic patients with leg infections. J Antimicrob Chemother. 2013;68:895–899.
  • Hutschala D, Skhirtladze K, Kinstner C, et al. In vivo microdialysis to measure antibiotic penetration into soft tissue during cardiac surgery. Ann Thorac Surg. 2007;84:1605–1610.
  • Velissaris D, Karamouzos V, Marangos M, et al. Pharmacokinetic changes and dosing modification of aminoglycosides in critically ill obese patients: a literature review. J Clin Med Res. 2014;6:227–233.
  • De Kock L, Sy SK, Rosenkranz B, et al. Pharmacokinetics of para-aminosalicylic acid in HIV-uninfected and HIV-coinfected tuberculosis patients receiving antiretroviral therapy, managed for multidrug-resistant and extensively drug-resistant tuberculosis. Antimicrob Agents Chemother. 2014;58:6242–6250.
  • Sy SK, De Kock L, Diacon AH, et al. N-acetyltransferase genotypes and the pharmacokinetics and tolerability of para-aminosalicylic acid in patients with drug-resistant pulmonary tuberculosis. Antimicrob Agents Chemother. 2015;59:4129–4138.
  • Goff DA, Nicolau DP. When pharmacodynamics trump costs: an antimicrobial stewardship program’s approach to selecting optimal antimicrobial agents. Clin Ther. 2013;35:766–771.
  • Mouton JW, Punt N, Vinks AA. Concentration-effect relationship of ceftazidime explains why the time above the MIC is 40 percent for a static effect in vivo. Antimicrob Agents Chemother. 2007;51:3449–3451.
  • Kong X, Wen JQ, Qi RF, et al. Diffuse interstitial brain edema in patients with end-stage renal disease undergoing hemodialysis: a tract-based spatial statistics study. Medicine. 2014;93:e313.
  • Gupta V, Yassin MH. Infection and hemodialysis access: an updated review. Infect Disord Drug Targets. 2013;13:196–205.
  • Sowinski KM, Magner SJ, Lucksiri A, et al. Influence of hemodialysis on gentamicin pharmacokinetics, removal during hemodialysis, and recommended dosing. Clin J Am Soc Nephrol. 2008;3:355–361.
  • Teigen MM, Duffull S, Dang L, et al. Dosing of gentamicin in patients with end-stage renal disease receiving hemodialysis. J Clin Pharmacol. 2006;46:1259–1267.
  • Begg EJ, Barclay ML, Duffull SB. A suggested approach to once-daily aminoglycoside dosing. Br J Clin Pharmacol. 1995;39:605–609.
  • Plajer SM, Chin PK, Vella-Brincat JW, et al. Gentamicin and renal function: lessons from 15 years’ experience of a pharmacokinetic service for extended interval dosing of gentamicin. Ther Drug Monit. 2015;37:98–103.
  • Zhuang L, Xia H, He Y, et al. Derendorf H. Evaluation of dosing strategy of gentamicin in patients with end-stage renal disease receiving hemodialysis using semi-mechanistic pharmacokinetic/pharmacodynamic model. J Antimicrob Chemother. Forthcoming 2016.
  • Crandon JL, Schuck VJ, Banevicius MA, et al. Comparative in vitro and in vivo efficacies of human simulated doses of ceftazidime and ceftazidime-avibactam against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2012;56:6137–6146.
  • Housman ST, Crandon JL, Nichols WW, et al. Efficacies of ceftazidime-avibactam and ceftazidime against Pseudomonas aeruginosa in a murine lung infection model. Antimicrob Agents Chemother. 2014;58:1365–1371.
  • Li J, Knebel W, Riggs M, et al. Population pharmacokinetic modeling of ceftazidime (CAZ) and avibactam (AVI) in healthy volunteers and patients with complicated intra-abdominal infection (cIAI). In: 52nd annual interscience conference on antimicrobial agents and chemotherapy; 2012 Sep 8–12. San Francisco (CA); 2012. p. abstr A–634.
  • Baquero F. Resistance to quinolones in gram-negative microorganisms: mechanisms and prevention. Eur Urol. 1990;17(Suppl 1):3–12.
  • Baquero F, Negri MC. Strategies to minimize the development of antibiotic resistance. J Chemother. 1997 May;9(Suppl 3):29–37.
  • Khachman D, Conil JM, Georges B, et al. Optimizing ciprofloxacin dosing in intensive care unit patients through the use of population pharmacokinetic-pharmacodynamic analysis and Monte Carlo simulations. J Antimicrob Chemother. 2011;66:1798–1809.
  • Lee HH, Molla MN, Cantor CR, et al. Bacterial charity work leads to population-wide resistance. Nature. 2010;467:82–85.
  • Tam VH, Louie A, Deziel MR, et al. The relationship between quinolone exposures and resistance amplification is characterized by an inverted U: a new paradigm for optimizing pharmacodynamics to counterselect resistance. Antimicrob Agents Chemother. 2007;51:744–747.

••Explains the relationship between resistance amplification and drug dose, which provides a basis for high initial antibiotic dose in treatment regimens to eradicate infection quickly before bacteria has the chance to develop drug resistance

  • Juan C, Macia MD, Gutierrez O, et al. Molecular mechanisms of beta-lactam resistance mediated by AmpC hyperproduction in Pseudomonas aeruginosa clinical strains. Antimicrob Agents Chemother. 2005;49:4733–4738.
  • Dong Y, Zhao X, Domagala J, et al. Effect of fluoroquinolone concentration on selection of resistant mutants of Mycobacterium bovis BCG and Staphylococcus aureus. Antimicrob Agents Chemother. 1999;43:1756–1758.
  • Dong Y, Zhao X, Kreiswirth BN, et al. Mutant prevention concentration as a measure of antibiotic potency: studies with clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2000;44:2581–2584.
  • Zhao X, Drlica K. Restricting the selection of antibiotic-resistant mutants: a general strategy derived from fluoroquinolone studies. Clin Infect Dis. 2001;33(Suppl 3):S147–S156.
  • Firsov AA, Vostrov SN, Lubenko IY, et al. In vitro pharmacodynamic evaluation of the mutant selection window hypothesis using four fluoroquinolones against Staphylococcus aureus. Antimicrob Agents Chemother. 2003;47:1604–1613.
  • Drlica K. The mutant selection window and antimicrobial resistance. J Antimicrob Chemother. 2003;52:11–17.
  • Andersson DI. Persistence of antibiotic resistant bacteria. Curr Opin Microbiol. 2003;6:452–456.
  • Andersson DI. The biological cost of mutational antibiotic resistance: any practical conclusions? Curr Opin Microbiol. 2006;9:461–465.
  • Andersson DI, Hughes D. Antibiotic resistance and its cost: is it possible to reverse resistance? Nat Rev Microbiol. 2010;8:260–271.
  • Jumbe LN, Drusano GL. A model-based PK/PD antimicrobial chemotherapy drug development platform to simultaneously combat infectious diseases and drug resistance. In: Kimko HHC, Peck CC, editors. Clinical Trial Simulations. New York (NY): Springer; 2011. p. 251–279.
  • Nielsen EI, Viberg A, Lowdin E, et al. Semimechanistic pharmacokinetic/pharmacodynamic model for assessment of activity of antibacterial agents from time-kill curve experiments. Antimicrob Agents Chemother. 2007;51:128–136.
  • Mohamed AF, Nielsen EI, Cars O, et al. Pharmacokinetic-pharmacodynamic model for gentamicin and its adaptive resistance with predictions of dosing schedules in newborn infants. Antimicrob Agents Chemother. 2012;56:179–188.
  • Nguyen TT, Guedj J, Chachaty E, et al. Mathematical modeling of bacterial kinetics to predict the impact of antibiotic colonic exposure and treatment duration on the amount of resistant enterobacteria excreted. PLoS Comput Biol. 2014;10:e1003840.
  • Tam VH, Louie A, Deziel MR, et al. Bacterial-population responses to drug-selective pressure: examination of garenoxacin’s effect on Pseudomonas aeruginosa. J Infect Dis. 2005;192:420–428.
  • Tam VH, Louie A, Fritsche TR, et al. Impact of drug-exposure intensity and duration of therapy on the emergence of Staphylococcus aureus resistance to a quinolone antimicrobial. J Infect Dis. 2007;195:1818–1827.
  • Jumbe N, Louie A, Leary R, et al. Application of a mathematical model to prevent in vivo amplification of antibiotic-resistant bacterial populations during therapy. J Clin Invest. 2003;112:275–285.
  • Bulitta JB, Yang JC, Yohonn L, et al. Attenuation of colistin bactericidal activity by high inoculum of Pseudomonas aeruginosa characterized by a new mechanism-based population pharmacodynamic model. Antimicrob Agents Chemother. 2010;54:2051–2062.
  • Sandri AM, Landersdorfer CB, Jacob J, et al. Population pharmacokinetics of intravenous polymyxin B in critically ill patients: implications for selection of dosage regimens. Clin Infect Dis. 2013;57:524–531.
  • Nation RL, Li J, Cars O, et al. Framework for optimisation of the clinical use of colistin and polymyxin B: the Prato polymyxin consensus. Lancet Infect Dis. 2015;15:225–234.
  • Sandri AM, Landersdorfer CB, Jacob J, et al. Pharmacokinetics of polymyxin B in patients on continuous venovenous haemodialysis. J Antimicrob Chemother. 2013;68:674–677.
  • Asin-Prieto E, Rodriguez-Gascon A, Troconiz IF, et al. Population pharmacokinetics of piperacillin and tazobactam in critically ill patients undergoing continuous renal replacement therapy: application to pharmacokinetic/pharmacodynamic analysis. J Antimicrob Chemother. 2014;69:180–189.
  • Johnson CA, Halstenson CE, Kelloway JS, et al. Single-dose pharmacokinetics of piperacillin and tazobactam in patients with renal disease. Clin Pharmacol Ther. 1992;51:32–41.
  • Udy AA, Lipman J, Jarrett P, et al. Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance? Crit Care. 2015;19:28.
  • Chung EK, Cheatham SC, Fleming MR, et al. Population pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese and nonobese patients. J Clin Pharmacol. 2015;55:899–908.
  • Sturm AW, Allen N, Rafferty KD, et al. Pharmacokinetic analysis of piperacillin administered with tazobactam in critically ill, morbidly obese surgical patients. Pharmacotherapy. 2014;34:28–35.
  • Deman H, Verhaegen J, Willems L, et al. Dosing of piperacillin/tazobactam in a morbidly obese patient. J Antimicrob Chemother. 2012;67:782–783.
  • Drusano GL. Antimicrobial pharmacodynamics: critical interactions of ‘bug and drug’. Nat Rev Microbiol. 2004;2:289–300.
  • Singh R, Kim A, Tanudra MA, et al. Pharmacokinetics/pharmacodynamics of a beta-lactam and beta-lactamase inhibitor combination: a novel approach for aztreonam/avibactam. J Antimicrob Chemother. 2015;70:2618–2626.
  • Safdar N, Andes D, Craig WA. In vivo pharmacodynamic activity of daptomycin. Antimicrob Agents Chemother. 2004;48:63–68.
  • Greenberg RN, Benes CA. Time-kill studies with oxacillin, vancomycin, and teicoplanin versus Staphylococcus aureus. J Infect Dis. 1990;161:1036–1037.
  • Brink AJ, Richards GA, Cummins RR, et al. Recommendations to achieve rapid therapeutic teicoplanin plasma concentrations in adult hospitalised patients treated for sepsis. Int J Antimicrob Agents. 2008;32:455–458.
  • Lodise TP, Butterfield JM, Hegde SS, et al. Telavancin pharmacokinetics and pharmacodynamics in patients with complicated skin and skin structure infections and various degrees of renal function. Antimicrob Agents Chemother. 2012;56:2062–2066.
  • Sakoulas G, Moise-Broder PA, Schentag J, et al. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus aureus bacteremia. J Clin Microbiol. 2004;42:2398–2402.
  • Burgess DS, Frei CR, Lewis Ii JS, et al. The contribution of pharmacokinetic-pharmacodynamic modelling with Monte Carlo simulation to the development of susceptibility breakpoints for Neisseria meningitidis. Clin Microbiol Infect. 2007;13:33–39.
  • Noreddin AM, El-Khatib WF, Aolie J, et al. Pharmacodynamic target attainment potential of azithromycin, clarithromycin, and telithromycin in serum and epithelial lining fluid of community-acquired pneumonia patients with penicillin-susceptible, intermediate, and resistant Streptococcus pneumoniae. Intj Infect Dis. 2009;13:483–487.
  • Matsumoto K, Shigemi A, Takeshita A, et al. Analysis of thrombocytopenic effects and population pharmacokinetics of linezolid: a dosage strategy according to the trough concentration target and renal function in adult patients. Int J Antimicrob Agents. 2014;44:242–247.
  • Schentag JJ. Pharmacokinetic and pharmacodynamic surrogate markers: studies with fluoroquinolones in patients. Am J Health Syst Pharm. 1999;56:S21–S24.
  • Aminimanizani A, Beringer P, Jelliffe R. Comparative pharmacokinetics and pharmacodynamics of the newer fluoroquinolone antibacterials. Clin Pharmacokinet. 2001;40:169–187.
  • Andes D, Craig WA. Pharmacodynamics of the new fluoroquinolone gatifloxacin in murine thigh and lung infection models. Antimicrob Agents Chemother. 2002;46:1665–1670.
  • Forrest A, Nix DE, Ballow CH, et al. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother. 1993;37:1073–1081.
  • Ernst EJ, Klepser ME, Petzold CR, et al. Evaluation of survival and pharmacodynamic relationships for five fluoroquinolones in a neutropenic murine model of pneumococcal lung infection. Pharmacotherapy. 2002;22:463–470.
  • Meagher AK, Passarell JA, Cirincione BB, et al. Exposure-response analyses of tigecycline efficacy in patients with complicated skin and skin-structure infections. Antimicrob Agents Chemother. 2007;51:1939–1945.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.