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Clinical Pharmacokinetics

, Volume 58, Issue 2, pp 143–156 | Cite as

Four Decades of β-Lactam Antibiotic Pharmacokinetics in Cystic Fibrosis

  • Jürgen B. BulittaEmail author
  • Yuanyuan Jiao
  • Stefanie K. Drescher
  • Antonio Oliver
  • Arnold Louie
  • Bartolome Moya
  • Xun Tao
  • Mathias Wittau
  • Brian T. Tsuji
  • Alexandre P. Zavascki
  • Beom Soo Shin
  • George L. Drusano
  • Fritz Sörgel
  • Cornelia B. Landersdorfer
Review Article

Abstract

The pharmacokinetics (PK) of β-lactam antibiotics in cystic fibrosis (CF) patients has been compared with that in healthy volunteers for over four decades; however, no quantitative models exist that explain the PK differences between CF patients and healthy volunteers in older and newer studies. Our aims were to critically evaluate these studies and explain the PK differences between CF patients and healthy volunteers. We reviewed all 16 studies that compared the PK of β-lactams between CF patients and healthy volunteers within the same study. Analysis of covariance (ANCOVA) models were developed. In four early studies that compared adolescent, lean CF patients with adult healthy volunteers, clearance (CL) in CF divided by that in healthy volunteers was 1.72 ± 0.90 (average ± standard deviation); in four additional studies comparing age-matched (primarily adult) CF patients with healthy volunteers, this ratio was 1.46 ± 0.16. The CL ratio was 1.15 ± 0.11 in all eight studies that compared CF patients and healthy volunteers who were matched in age, body size and body composition, or that employed allometric scaling by lean body mass (LBM). Volume of distribution was similar between subject groups after scaling by body size. For highly protein-bound β-lactams, the unbound fraction was up to 2.07-fold higher in older studies that compared presumably sicker CF patients with healthy volunteers. These protein-binding differences explained over half of the variance for the CL ratio (p < 0.0001, ANCOVA). Body size, body composition and lower protein binding in presumably sicker CF patients explained the PK alterations in this population. Dosing CF patients according to LBM seems suitable to achieve antibiotic target exposures.

Notes

Acknowledgements

The authors thank Mr. Ingo Menhard for support with the graphics design, and Ms. Ann Ross for technical support during the submission of this review.

Compliance with ethical standards

Conflict of interest

Jürgen B. Bulitta, Yuanyuan Jiao, Stefanie K. Drescher, Antonio Oliver, Arnold Louie, Bartolome Moya, Xun Tao, Mathias Wittau, Brian T. Tsuji, Alexandre P. Zavascki, Beom Soo Shin, George L. Drusano, Fritz Sörgel, and Cornelia B. Landersdorfer declare no conflicts of interest relevant to the contents of this review.

Funding

This work was partly supported by Australian National Health and Medical Research Council (NHMRC) project grants (APP1045105 to JBB and CBL, and APP1101553 to CBL and JBB). NHMRC career development fellowships supported JBB (APP1084163) and CBL (APP1062509).

References

  1. 1.
    Touw DJ, Vinks AA, Mouton JW, Horrevorts AM. Pharmacokinetic optimisation of antibacterial treatment in patients with cystic fibrosis. Current practice and suggestions for future directions. Clin Pharmacokinet. 1998;35(6):437–59.Google Scholar
  2. 2.
    Rey E, Treluyer JM, Pons G. Drug disposition in cystic fibrosis. Clin Pharmacokinet. 1998;35(4):313–29.Google Scholar
  3. 3.
    Anderson BJ, Holford NH. Mechanism-based concepts of size and maturity in pharmacokinetics. Annu Rev Pharmacol Toxicol. 2008;48:303–32.Google Scholar
  4. 4.
    West GB, Brown JH, Enquist BJ. A general model for the origin of allometric scaling laws in biology. Science. 1997;276(5309):122–6.Google Scholar
  5. 5.
    Milatovic D, Braveny I. Development of resistance during antibiotic therapy. Eur J Clin Microbiol. 1987;6(3):234–44.Google Scholar
  6. 6.
    Carmeli Y, Troillet N, Karchmer AW, Samore MH. Health and economic outcomes of antibiotic resistance in Pseudomonas aeruginosa. Arch Intern Med. 1999;159(10):1127–32.Google Scholar
  7. 7.
    Livermore DM. Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare? Clin Infect Dis. 2002;34(5):634–40.Google Scholar
  8. 8.
    Hoiby N. Antibiotic therapy for chronic infection of pseudomonas in the lung. Annu Rev Med. 1993;44:1–10.Google Scholar
  9. 9.
    Canton R, Cobos N, de Gracia J, Baquero F, Honorato J, Gartner S, et al. Antimicrobial therapy for pulmonary pathogenic colonisation and infection by Pseudomonas aeruginosa in cystic fibrosis patients. Clin Microbiol Infect. 2005;11(9):690–703.Google Scholar
  10. 10.
    Bulitta JB, Landersdorfer CB, Forrest A, Brown SV, Neely MN, Tsuji BT, et al. Relevance of pharmacokinetic and pharmacodynamic modeling to clinical care of critically ill patients. Curr Pharm Biotechnol. 2011;12(12):2044–61.Google Scholar
  11. 11.
    Drusano GL, Bonomo RA, Bahniuk N, Bulitta JB, Vanscoy B, Defiglio H, et al. Resistance emergence mechanism and mechanism of resistance suppression by tobramycin for cefepime for Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2012;56(1):231–42.Google Scholar
  12. 12.
    Landersdorfer CB, Ly NS, Xu H, Tsuji BT, Bulitta JB. Quantifying subpopulation synergy for antibiotic combinations via mechanism-based modeling and a sequential dosing design. Antimicrob Agents Chemother. 2013;57(5):2343–51.Google Scholar
  13. 13.
    Yadav R, Landersdorfer CB, Nation RL, Boyce JD, Bulitta JB. Novel approach to optimize synergistic carbapenem-aminoglycoside combinations against carbapenem-resistant Acinetobacter baumannii. Antimicrob Agents Chemother. 2015;59(4):2286–98.Google Scholar
  14. 14.
    Ly NS, Bulitta JB, Rao GG, Landersdorfer CB, Holden PN, Forrest A, et al. Colistin and doripenem combinations against Pseudomonas aeruginosa: profiling the time course of synergistic killing and prevention of resistance. J Antimicrob Chemother. 2015;70(5):1434–42.Google Scholar
  15. 15.
    Yadav R, Bulitta JB, Nation RL, Landersdorfer CB. Optimization of synergistic combination regimens against carbapenem- and aminoglycoside-resistant clinical Pseudomonas aeruginosa isolates via mechanism-based pharmacokinetic/pharmacodynamic modeling. Antimicrob Agents Chemother. 2016;61(1):pii:e01011-16.Google Scholar
  16. 16.
    Yadav R, Bulitta JB, Schneider EK, Shin BS, Velkov T, Nation RL, et al. Aminoglycoside concentrations required for synergy with carbapenems against Pseudomonas aeruginosa determined via mechanistic studies and modeling. Antimicrob Agents Chemother. 2017;61(12):e00722–17.Google Scholar
  17. 17.
    Landersdorfer CB, Yadav R, Rogers KE, Kim TH, Shin BS, Boyce JD, et al. Combating carbapenem-resistant acinetobacter baumannii by an optimized imipenem-plus-tobramycin dosage regimen: prospective validation via hollow-fiber infection and mathematical modeling. Antimicrob Agents Chemother. 2018;62(4): pii: e02053-17.Google Scholar
  18. 18.
    Drusano GL, Liu W, Fregeau C, Kulawy R, Louie A. 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.Google Scholar
  19. 19.
    Jumbe N, Louie A, Leary R, Liu W, Deziel MR, Tam VH, et al. Application of a mathematical model to prevent in vivo amplification of antibiotic-resistant bacterial populations during therapy. J Clin Invest. 2003;112(2):275–85.Google Scholar
  20. 20.
    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(12):481–8.Google Scholar
  21. 21.
    Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis. 1998;26(1):1–12.Google Scholar
  22. 22.
    Drusano GL. Antimicrobial pharmacodynamics: critical interactions of ‘bug and drug’. Nat Rev Microbiol. 2004;2(4):289–300.Google Scholar
  23. 23.
    Blaser J. In-vitro model for simultaneous simulation of the serum kinetics of two drugs with different half-lives. J Antimicrob Chemother. 1985;15(Suppl A):125–30.Google Scholar
  24. 24.
    Grasso S, Meinardi G, de Carneri I, Tamassia V. New in vitro model to study the effect of antibiotic concentration and rate of elimination on antibacterial activity. Antimicrob Agents Chemother. 1978;13(4):570–6.Google Scholar
  25. 25.
    Louie A, Bied A, Fregeau C, Van Scoy B, Brown D, Liu W, et al. Impact of different carbapenems and regimens of administration on resistance emergence for three isogenic Pseudomonas aeruginosa strains with differing mechanisms of resistance. Antimicrob Agents Chemother. 2010;54(6):2638–45.Google Scholar
  26. 26.
    Zobell JT, Waters CD, Young DC, Stockmann C, Ampofo K, Sherwin CM, et al. Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. Cephalosporins and penicillins. Pediatr Pulmonol. 2013;48(2):107–22.Google Scholar
  27. 27.
    Zobell JT, Young DC, Waters CD, Stockmann C, Ampofo K, Sherwin CM, et al. Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: I. Aztreonam and carbapenems. Pediatr Pulmonol. 2012;47(12):1147–58.Google Scholar
  28. 28.
    Davis AM, Webborn PJ, Salt DW. Robust assessment of statistical significance in the use of unbound/intrinsic pharmacokinetic parameters in quantitative structure-pharmacokinetic relationships with lipophilicity. Drug Metab Dispos. 2000;28(2):103–6.Google Scholar
  29. 29.
    Benet LZ, Hoener BA. Changes in plasma protein binding have little clinical relevance. Clin Pharmacol Ther. 2002;71(3):115–21.Google Scholar
  30. 30.
    Pang KS, Rowland M. Hepatic clearance of drugs: I. Theoretical considerations of a “well-stirred” model and a “parallel tube” model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance. J Pharmacokinet Biopharm. 1977;5(6):625–53.Google Scholar
  31. 31.
    Zou P, Yu Y, Zheng N, Yang Y, Paholak HJ, Yu LX, et al. Applications of human pharmacokinetic prediction in first-in-human dose estimation. AAPS J. 2012;14(2):262–81.Google Scholar
  32. 32.
    Berg U, Kusoffsky E, Strandvik B. Renal function in cystic fibrosis with special reference to the renal sodium handling. Acta Paediatr Scand. 1982;71(5):833–8.Google Scholar
  33. 33.
    Beringer PM, Kriengkauykiat J, Zhang X, Hidayat L, Liu S, Louie S, et al. Lack of effect of P-glycoprotein inhibition on renal clearance of dicloxacillin in patients with cystic fibrosis. Pharmacotherapy. 2008;28(7):883–94.Google Scholar
  34. 34.
    Jusko WJ, Mosovich LL, Gerbracht LM, Mattar ME, Yaffe SJ. Enhanced renal excretion of dicloxacillin in patients with cystic fibrosis. Pediatrics. 1975;56(6):1038–44.Google Scholar
  35. 35.
    Yaffe SJ, Gerbracht LM, Mosovich LL, Mattar ME, Danish M, Jusko WJ. Pharmacokinetics of methicillin in patients with cystic fibrosis. J Infect Dis. 1977;135(5):828–31.Google Scholar
  36. 36.
    Arvidsson A, Alvan G, Strandvik B. Difference in renal handling of cefsulodin between patients with cystic fibrosis and normal subjects. Acta Paediatr Scand. 1983;72(2):293–4.Google Scholar
  37. 37.
    Spino M, Chai RP, Isles AF, Thiessen JJ, Tesoro A, Gold R, et al. Cloxacillin absorption and disposition in cystic fibrosis. J Pediatr. 1984;105(5):829–35.Google Scholar
  38. 38.
    Leeder JS, Spino M, Isles AF, Tesoro AM, Gold R, MacLeod SM. Ceftazidime disposition in acute and stable cystic fibrosis. Clin Pharmacol Ther. 1984;36(3):355–62.Google Scholar
  39. 39.
    de Groot R, Hack BD, Weber A, Chaffin D, Ramsey B, Smith AL. Pharmacokinetics of ticarcillin in patients with cystic fibrosis: a controlled prospective study. Clin Pharmacol Ther. 1990;47(1):73–8.Google Scholar
  40. 40.
    Huls CE, Prince RA, Seilheimer DK, Bosso JA. Pharmacokinetics of cefepime in cystic fibrosis patients. Antimicrob Agents Chemother. 1993;37(7):1414–6.Google Scholar
  41. 41.
    Hedman A, Alvan G, Strandvik B, Arvidsson A. Increased renal clearance of cefsulodin due to higher glomerular filtration rate in cystic fibrosis. Clin Pharmacokinet. 1990;18(2):168–75.Google Scholar
  42. 42.
    Hamelin BA, Moore N, Knupp CA, Ruel M, Vallee F, LeBel M. Cefepime pharmacokinetics in cystic fibrosis. Pharmacotherapy. 1993;13(5):465–70.Google Scholar
  43. 43.
    Christensson BA, Ljungberg B, Eriksson L, Nilsson-Ehle I. Pharmacokinetics of meropenem in patients with cystic fibrosis. Eur J Clin Microbiol Infect Dis. 1998;17(12):873–6.Google Scholar
  44. 44.
    Vinks AA, van Rossem RN, Mathot RA, Heijerman HG, Mouton JW. Pharmacokinetics of aztreonam in healthy subjects and patients with cystic fibrosis and evaluation of dose-exposure relationships using monte carlo simulation. Antimicrob Agents Chemother. 2007;51(9):3049–55.Google Scholar
  45. 45.
    Bulitta JB, Duffull SB, Kinzig-Schippers M, Holzgrabe U, Stephan U, Drusano GL, et al. Systematic comparison of the population pharmacokinetics and pharmacodynamics of piperacillin in cystic fibrosis patients and healthy volunteers. Antimicrob Agents Chemother. 2007;51(7):2497–507.Google Scholar
  46. 46.
    Bulitta JB, Duffull SB, Landersdorfer CB, Kinzig M, Holzgrabe U, Stephan U, et al. Comparison of the pharmacokinetics and pharmacodynamic profile of carumonam in cystic fibrosis patients and healthy volunteers. Diagn Microbiol Infect Dis. 2009;65(2):130–41.Google Scholar
  47. 47.
    Bulitta JB, Landersdorfer CB, Huttner SJ, Drusano GL, Kinzig M, Holzgrabe U, et al. Population pharmacokinetic comparison and pharmacodynamic breakpoints of ceftazidime in cystic fibrosis patients and healthy volunteers. Antimicrob Agents Chemother. 2010;54(3):1275–82.Google Scholar
  48. 48.
    Bulitta JB, Kinzig M, Landersdorfer CB, Holzgrabe U, Stephan U, Sorgel F. Comparable population pharmacokinetics and pharmacodynamic breakpoints of cefpirome in cystic fibrosis patients and healthy volunteers. Antimicrob Agents Chemother. 2011;55(6):2927–36.Google Scholar
  49. 49.
    Bulitta JB, Holford NHG. Population pharmacokinetic and pharmacodynamic methods. In: D’Agostino RB, Sullivan L, Massaro J (eds). Wiley encyclopedia of clinical trials. Hoboken: Wiley Inc; 2008.Google Scholar
  50. 50.
    Anonymous. Cystic fibrosis foundation patient registry 1997 annual data report. Bethesda: Cystic Fibrosis Foundation; 1998.Google Scholar
  51. 51.
    Stephenson AL, Tom M, Berthiaume Y, Singer LG, Aaron SD, Whitmore GA, et al. A contemporary survival analysis of individuals with cystic fibrosis: a cohort study. Eur Respir J. 2015;45(3):670–9.Google Scholar
  52. 52.
    Frederiksen B, Lanng S, Koch C, Hoiby N. Improved survival in the Danish center-treated cystic fibrosis patients: results of aggressive treatment. Pediatr Pulmonol. 1996;21(3):153–8.Google Scholar
  53. 53.
    Prandota J. Drug disposition in cystic fibrosis: progress in understanding pathophysiology and pharmacokinetics. Pediatr Infect Dis J. 1987;6(12):1111–26.Google Scholar
  54. 54.
    Strober W, Peter G, Schwartz RH. Albumin metabolism in cystic fibrosis. Pediatrics. 1969;43(3):416–26.Google Scholar
  55. 55.
    Abman SH, Reardon MC, Accurso FJ, Hammond KB, Sokol RJ. Hypoalbuminemia at diagnosis as a marker for severe respiratory course in infants with cystic fibrosis identified by newborn screening. J Pediatr. 1985;107(6):933–5.Google Scholar
  56. 56.
    Krueger WA, Bulitta J, Kinzig-Schippers M, Landersdorfer C, Holzgrabe U, Naber KG, et al. Evaluation by monte carlo simulation of the pharmacokinetics of two doses of meropenem administered intermittently or as a continuous infusion in healthy volunteers. Antimicrob Agents Chemother. 2005;49(5):1881–9.Google Scholar
  57. 57.
    Bulitta J, Kinzig M, Jakob V, Holzgrabe U, Sörgel F, Holford NHG. Nonlinear pharmacokinetics of piperacillin in healthy volunteers—implications for optimal dosage regimens. Br J Clin Pharmacol. 2010;70(11):682–93.Google Scholar
  58. 58.
    Landersdorfer CB, Bulitta JB, Kirkpatrick CM, Kinzig M, Holzgrabe U, Drusano GL, et al. Population pharmacokinetics of piperacillin at two dose levels: influence of nonlinear pharmacokinetics on the pharmacodynamic profile. Antimicrob Agents Chemother. 2012;56(11):5715–23.Google Scholar
  59. 59.
    Lodise TP Jr, Lomaestro B, Rodvold KA, Danziger LH, Drusano GL. Pharmacodynamic profiling of piperacillin in the presence of tazobactam in patients through the use of population pharmacokinetic models and Monte Carlo simulation. Antimicrob Agents Chemother. 2004;48(12):4718–24.Google Scholar
  60. 60.
    Vinks AA, Den Hollander JG, Overbeek SE, Jelliffe RW, Mouton JW. Population pharmacokinetic analysis of nonlinear behavior of piperacillin during intermittent or continuous infusion in patients with cystic fibrosis. Antimicrob Agents Chemother. 2003;47(2):541–7.Google Scholar
  61. 61.
    Oliver A, Canton R, Campo P, Baquero F, Blazquez J. High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Science. 2000;288(5469):1251–4.Google Scholar
  62. 62.
    Rees VE, Bulitta JB, Oliver A, Tsuji BT, Rayner CR, Nation RL, et al. Resistance suppression by high-intensity, short-duration aminoglycoside exposure against hypermutable and non-hypermutable Pseudomonas aeruginosa. J Antimicrob Chemother. 2016;71(11):3157–67.Google Scholar
  63. 63.
    Landersdorfer CB, Rees VE, Yadav R, Rogers KE, Kim TH, Bergen PJ, et al. Optimization of a meropenem-tobramycin combination dosage regimen against hypermutable and nonhypermutable Pseudomonas aeruginosa via mechanism-based modeling and the hollow-fiber infection model. Antimicrob Agents Chemother. 2018;62(4): pii:e02055-17.Google Scholar
  64. 64.
    Ciofu O, Rojo-Molinero E, Macia MD, Oliver A. Antibiotic treatment of biofilm infections. APMIS. 2017;125(4):304–19.Google Scholar
  65. 65.
    Hoiby N, Bjarnsholt T, Moser C, Bassi GL, Coenye T, Donelli G, et al. ESCMID guideline for the diagnosis and treatment of biofilm infections 2014. Clin Microbiol Infect. 2015;21(Suppl 1):S1–25.Google Scholar
  66. 66.
    Lopez-Causape C, Rojo-Molinero E, Macia MD, Oliver A. The problems of antibiotic resistance in cystic fibrosis and solutions. Expert Rev Respir Med. 2015;9(1):73–88.Google Scholar
  67. 67.
    Lim LM, Ly N, Anderson D, Yang JC, Macander L, Jarkowski A 3rd, et al. Resurgence of colistin: a review of resistance, toxicity, pharmacodynamics, and dosing. Pharmacotherapy. 2010;30(12):1279–91.Google Scholar
  68. 68.
    Nation RL, Li J. Colistin in the 21st century. Curr Opin Infect Dis. 2009;22(6):535–43.Google Scholar
  69. 69.
    Tod M, Padoin C, Petitjean O. Clinical pharmacokinetics and pharmacodynamics of isepamicin. Clin Pharmacokinet. 2000;38(3):205–23.Google Scholar
  70. 70.
    Tsuji BT, Brown T, Parasrampuria R, Brazeau DA, Forrest A, Kelchlin PA, et al. Front-loaded linezolid regimens result in increased killing and suppression of the accessory gene regulator system of Staphylococcus aureus. Antimicrob Agents Chemother. 2012;56(7):3712–9.Google Scholar
  71. 71.
    Tsuji BT, Bulitta JB, Brown T, Forrest A, Kelchlin PA, Holden PN, et al. Pharmacodynamics of early, high-dose linezolid against vancomycin-resistant enterococci with elevated MICs and pre-existing genetic mutations. J Antimicrob Chemother. 2012;67(9):2182–90.Google Scholar
  72. 72.
    Boak LM, Rayner CR, Grayson ML, Paterson DL, Spelman D, Khumra S, et al. Clinical population pharmacokinetics and toxicodynamics of linezolid. Antimicrob Agents Chemother. 2014;58(4):2334–43.Google Scholar
  73. 73.
    Okusanya OO, Tsuji BT, Bulitta JB, Forrest A, Bulik CC, Bhavnani SM, et al. Evaluation of the pharmacokinetics-pharmacodynamics of fusidic acid against Staphylococcus aureus and Streptococcus pyogenes using in vitro infection models: implications for dose selection. Diagn Microbiol Infect Dis. 2011;70(1):101–11.Google Scholar
  74. 74.
    Tsuji BT, Okusanya OO, Bulitta JB, Forrest A, Bhavnani SM, Fernandez PB, et al. Application of pharmacokinetic-pharmacodynamic modeling and the justification of a novel fusidic acid dosing regimen: raising Lazarus from the dead. Clin Infect Dis. 2011;52(Suppl 7):S513–9.Google Scholar
  75. 75.
    Bulitta JB, Okusanya OO, Forrest A, Bhavnani SM, Clark K, Still JG, et al. Population pharmacokinetics of fusidic acid: rationale for front-loaded dosing regimens due to autoinhibition of clearance. Antimicrob Agents Chemother. 2013;57(1):498–507.Google Scholar
  76. 76.
    Craft JC, Moriarty SR, Clark K, Scott D, Degenhardt TP, Still JG, et al. A randomized, double-blind phase 2 study comparing the efficacy and safety of an oral fusidic acid loading-dose regimen to oral linezolid for the treatment of acute bacterial skin and skin structure infections. Clin Infect Dis. 2011;52(Suppl 7):S520–6.Google Scholar
  77. 77.
    Bulitta JB, Yang JC, Yohonn L, Ly NS, Brown SV, D’Hondt RE, 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(5):2051–62.Google Scholar
  78. 78.
    Bergen PJ, Bulman ZP, Landersdorfer CB, Smith N, Lenhard JR, Bulitta JB, et al. Optimizing polymyxin combinations against resistant gram-negative bacteria. Infect Dis Ther. 2015;4(4):391–415.Google Scholar
  79. 79.
    Bulitta JB, Ly NS, Landersdorfer CB, Wanigaratne NA, Velkov T, Yadav R, et al. Two mechanisms of killing of Pseudomonas aeruginosa by tobramycin assessed at multiple inocula via mechanism-based modeling. Antimicrob Agents Chemother. 2015;59(4):2315–27.Google Scholar
  80. 80.
    Mohamed AF, Nielsen EI, Cars O, Friberg LE. Pharmacokinetic-pharmacodynamic model for gentamicin and its adaptive resistance with predictions of dosing schedules in newborn infants. Antimicrob Agents Chemother. 2012;56(1):179–88.Google Scholar
  81. 81.
    Barclay ML, Begg EJ, Chambers ST, Peddie BA. The effect of aminoglycoside-induced adaptive resistance on the antibacterial activity of other antibiotics against Pseudomonas aeruginosa in vitro. J Antimicrob Chemother. 1996;38(5):853–8.Google Scholar
  82. 82.
    Barclay ML, Begg EJ, Chambers ST, Thornley PE, Pattemore PK, Grimwood K. Adaptive resistance to tobramycin in Pseudomonas aeruginosa lung infection in cystic fibrosis. J Antimicrob Chemother. 1996;37(6):1155–64.Google Scholar
  83. 83.
    Hocquet D, Vogne C, El Garch F, Vejux A, Gotoh N, Lee A, et al. MexXY-OprM efflux pump is necessary for a adaptive resistance of Pseudomonas aeruginosa to aminoglycosides. Antimicrob Agents Chemother. 2003;47(4):1371–5.Google Scholar
  84. 84.
    Bergen PJ, Bulitta JB, Forrest A, Tsuji BT, Li J, Nation RL. Pharmacokinetic/pharmacodynamic investigation of colistin against Pseudomonas aeruginosa using an in vitro model. Antimicrob Agents Chemother. 2010;54(9):3783–9.Google Scholar
  85. 85.
    Ly NS, Yang J, Bulitta JB, Tsuji BT. Impact of two-component regulatory systems PhoP-PhoQ and PmrA-PmrB on colistin pharmacodynamics in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2012;56(6):3453–6.Google Scholar
  86. 86.
    Carmeli Y, Troillet N, Eliopoulos GM, Samore MH. Emergence of antibiotic-resistant Pseudomonas aeruginosa: comparison of risks associated with different antipseudomonal agents. Antimicrob Agents Chemother. 1999;43(6):1379–82.Google Scholar
  87. 87.
    Krilov LR, Blumer JL, Stern RC, Hartstein AI, Iglewski BN, Goldmann DA. Imipenem/cilastatin in acute pulmonary exacerbations of cystic fibrosis. Rev Infect Dis. 1985;7(Suppl 3):S482–9.Google Scholar
  88. 88.
    Fink MP, Snydman DR, Niederman MS, Leeper KV Jr, Johnson RH, Heard SO, et al. Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group. Antimicrob Agents Chemother. 1994;38(3):547–57.Google Scholar
  89. 89.
    Iyobe S, Watanabe M, Mitsuhashi S, Inoue M. Estimation of outer membrane permeability of carbapenem antibiotics to Pseudomonas aeruginosa. J Infect Chemother. 1999;5(3):168–70.Google Scholar
  90. 90.
    Yadav R, Bulitta JB, Wang J, Nation RL, Landersdorfer CB. Evaluation of pharmacokinetic/pharmacodynamic model-based optimized combination regimens against multidrug-resistant Pseudomonas aeruginosa in a murine thigh infection model by using humanized dosing schemes. Antimicrob Agents Chemother. 2017;61(12): pii:e01268-17.Google Scholar
  91. 91.
    Zavascki AP, Bulitta JB, Landersdorfer CB. Combination therapy for carbapenem-resistant Gram-negative bacteria. Exp Rev Anti Infect Ther. 2013;11(12):1333–53.Google Scholar
  92. 92.
    Zavascki AP, Klee BO, Bulitta JB. Aminoglycosides against carbapenem-resistant Enterobacteriaceae in the critically ill: the pitfalls of aminoglycoside susceptibility. Exp Rev Anti Infect Ther. 2017;15(6):519–26.Google Scholar
  93. 93.
    Rolinson GN, Sutherland R. The binding of antibiotics to serum proteins. Br J Pharmacol Chemother. 1965;25(3):638–50.Google Scholar
  94. 94.
    Libke RD, Clarke JT, Ralph ED, Luthy RP, Kirby WM. Ticarcillin vs carbenicillin: clinical pharmacokinetics. Clin Pharmacol Ther. 1975;17(4):441–6.Google Scholar
  95. 95.
    Sutherland R, Burnett J, Rolinson GN. Alpha-carboxy-3-thienylmethylpenicillin (BRL 2288), a new semisynthetic penicillin: in vitro evaluation. Antimicrob Agents Chemother (Bethesda). 1970;10:390–5.Google Scholar
  96. 96.
    Roos JF, Bulitta J, Lipman J, Kirkpatrick CM. Pharmacokinetic-pharmacodynamic rationale for cefepime dosing regimens in intensive care units. J Antimicrob Chemother. 2006;58(5):987–93.Google Scholar
  97. 97.
    Benko AS, Cappelletty DM, Kruse JA, Rybak MJ. Continuous infusion versus intermittent administration of ceftazidime in critically ill patients with suspected gram-negative infections. Antimicrob Agents Chemother. 1996;40(3):691–5.Google Scholar
  98. 98.
    Sorgel F, Kinzig M. The chemistry, pharmacokinetics and tissue distribution of piperacillin/tazobactam. J Antimicrob Chemother. 1993;31(Suppl A):39–60.Google Scholar
  99. 99.
    McNulty CA, Garden GM, Ashby J, Wise R. Pharmacokinetics and tissue penetration of carumonam, a new synthetic monobactam. Antimicrob Agents Chemother. 1985;28(3):425–7.Google Scholar
  100. 100.
    Strenkoski LC, Nix DE. Cefpirome clinical pharmacokinetics. Clin Pharmacokinet. 1993;25(4):263–73.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Jürgen B. Bulitta
    • 1
    Email author
  • Yuanyuan Jiao
    • 1
  • Stefanie K. Drescher
    • 1
  • Antonio Oliver
    • 2
  • Arnold Louie
    • 3
  • Bartolome Moya
    • 1
  • Xun Tao
    • 1
  • Mathias Wittau
    • 4
  • Brian T. Tsuji
    • 5
  • Alexandre P. Zavascki
    • 6
  • Beom Soo Shin
    • 7
  • George L. Drusano
    • 3
  • Fritz Sörgel
    • 8
    • 9
  • Cornelia B. Landersdorfer
    • 10
  1. 1.Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of PharmacyUniversity of FloridaOrlandoUSA
  2. 2.Servicio de MicrobiologíaHospital Son EspasesPalma de MallorcaSpain
  3. 3.Institute for Therapeutic Innovation and Department of Medicine, College of MedicineUniversity of FloridaOrlandoUSA
  4. 4.Department of Visceral SurgeryUniversity of UlmUlmGermany
  5. 5.School of Pharmacy and Pharmaceutical SciencesUniversity at BuffaloBuffaloUSA
  6. 6.Department of Internal Medicine, Medical SchoolUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  7. 7.School of PharmacySungkyunkwan UniversitySuwonKorea
  8. 8.Institute for Biomedical and Pharmaceutical ResearchNürnberg-HeroldsbergGermany
  9. 9.Department of PharmacologyUniversity of Duisburg-EssenEssenGermany
  10. 10.Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical SciencesMonash UniversityParkvilleAustralia

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