Advertisement

Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Delivering Antibacterials to the Lungs

Considerations for Optimizing Outcomes

  • 29 Accesses

  • 26 Citations

Abstract

An important determinant of clinical outcome of a lower respiratory tract infection may be sterilization of the infected lung, which is also dependent on sustained antibacterial concentrations achieved in the lung. For this reason, recently there has been increased interest in measuring the concentration of antimicrobial agents at different potential sites of infection in the lung. Levels of antibacterials are now measured in bronchial mucosa, epithelial lining fluid (ELF) and alveolar macrophages, as well as in sputum. Penicillins and cephalosporins reach only marginal concentrations in bronchial secretions, whereas fluoroquinolones and macrolides have been shown to achieve high concentrations. The extent of penetration of different antibacterials into the bronchial mucosa is relatively high. This is also true for β-lactams, although their tissue concentrations never reach blood concentrations. Antibacterials penetrate less into the ELF than into the bronchial mucosa, but fluoroquinolones appear to concentrate more into alveolar lavage than into bronchial mucosa.

Pulmonary pharmacokinetics is a very useful tool for describing how drugs behave in the human lung, but it does not promote an understanding of the pharmacological effects of a drug. More important, instead, is the correlation between pulmonary disposition of the drug and its minimum inhibitory concentration (MIC) values for the infectious agent. The addition of bacteriological characteristics to in vivo pharmacokinetic studies has triggered a ‘pharmacodynamic approach’. Pharmacodynamic parameters integrate the microbiological activity and pharmacokinetics of an anti-infective drug by focusing on its biological effects, particularly growth inhibition and killing of pathogens.

Drugs that penetrate well and remain for long periods at the pulmonary site of infection often induce therapeutic responses greater than expected on the basis of in vitro data. However, although the determination of antibacterial concentrations at the site of infection in the lung has been suggested to be important in predicting the therapeutic efficacy of antimicrobial treatment during bacterial infections of the lower respiratory tract, some studies have demonstrated that pulmonary bacterial clearance is correlated more closely to concentrations in the serum than to those in the lung homogenates, probably because they better reflect antibacterial concentation in the interstitial fluid.

This is a preview of subscription content, log in to check access.

Table I
Fig. 1
Fig. 2
Fig. 3
Table II
Table III
Fig. 4
Fig. 5

References

  1. 1.

    Cazzola M. Problems and prospectives in the antibiotic treatment of lower respiratory tract infections. Pulm Pharmacol 1994; 7: 139–52

  2. 2.

    Veber B, Vallée E, Desmont JM, et al. Correlation between macrolide lung pharmacokinetics and therapeutic efficacy in a mouse model of pneumococcal pneumonia. J Antimicrob Chemother 1993; 32: 473–82

  3. 3.

    Honeybourne D. Antibiotic penetration in the respiratory tract and implications for the selection of antimicrobial therapy. Curr Opin Pulm Med 1997; 3: 170–4

  4. 4.

    Valcke Y, Pauwels R, van der Straeten M. Pharmacokinetics of antibiotics in the lungs. Eur Respir J 1990; 3: 715–22

  5. 5.

    Baldwin DR, Honeybourne D, Wise R. Pulmonary disposition of antimicrobial agents in vivo: observations and clinical relevance. Antimicrob Agents Chemother 1992; 36: 1176–80

  6. 6.

    Honeybourne D, Baldwin DR. The site concentrations of antimicrobial agents in the lungs. J Antimicrob Chemother 1992; 30: 249–60

  7. 7.

    Cruciani M, Gatti G, Cazzadori A, et al. Pharmacokinetics of antimicrobial agents in the respiratory tract. Zentralbl Bakteriol 1996; 284: 1–31

  8. 8.

    Bergogne-Bérézin E. New concepts in the pulmonary disposition of antibiotics. Pulm Pharmacol 1995; 8: 65–81

  9. 9.

    Stewart SM, Fisher M, Young JE, et al. Amoxycillin levels in sputum, serum and saliva. Thorax 1974; 29: 110–4

  10. 10.

    Marlin GE, Burgess KR, Burgoyne J, et al. Penetration of piperacillin into bronchial mucosa and sputum. Thorax 1981; 36: 774–80

  11. 11.

    Muller-Serieys C, Bergogne-Bérézin E, Rowan C, et al. Imipenem penetration into bronchial secretions. J Antimicrob Chemother 1987; 20: 618–9

  12. 12.

    Lovering AM, Pycock CJ, Harvey JE, et al. The pharmacokinetics and sputum penetration of ampicillin and amoxycillin following simultaneous i.v. administration. J Antimicrob Chemother 1990; 25: 385–92

  13. 13.

    Hill SL, Bilton D, Johnson MM, et al. Sputum and serum pharmacokinetics of loracarbef (LY163892) in patients with chronic bronchial sepsis. J Antimicrob Chemother 1994; 33: 129–36

  14. 14.

    Cazzola M, Matera MG, Polverino M, et al. Pulmonary penetration of ceftazidime. J Chemother 1995; 7: 50–4

  15. 15.

    Jehl F, Muller-Serieys C, de Larminat V, et al. Penetration of piperacillintazobactam into bronchial secretions after multiple doses to intensive care patients. Antimicrob Agents Chemother 1994; 38: 2780–4

  16. 16.

    Bergogne-Berezin E, Morel C, Benard Y, et al. Pharmacokinetic study of beta-lactam antibiotics in bronchial secretions. Scand J Infect Dis 1978; Suppl. 14: 267–72

  17. 17.

    Bergogne-Bérézin E, Berthelot G, Even P, et al. Penetration of ciprofloxacin into bronchial secretions. Eur J Clin Microbiol 1986; 5: 197–200

  18. 18.

    Davies B, Maesen FPV, Geraedts W, et al. Penetration of ofloxacin from serum to sputum. Drugs 1987; 34Suppl. 1: 26–2

  19. 19.

    Bergogne-Bérézin E, Muller-Serieys C, Kafe H, et al. Penetration of lomefloxacin into bronchial secretions following single and multiple oral administration. Am J Med 1992; 92Suppl. 4A: S8–11

  20. 20.

    Fujita A, Miya T, Tanaka R, et al. Levofloxacin concentrations in serum, sputum and lung tissue: evaluation of its efficacy according to breakpoint. Jpn J Antibiot 1999; 52: 661–6

  21. 21.

    Cazzola M, Matera MG, Tufano MA, et al. Pulmonary disposition of lomefloxacin in patients with acute exacerbation of chronic obstructive pulmonary disease. A multiple-dose study. J Chemother 2001; 13: 407–12

  22. 22.

    Begg EJ, Robson RA, Saunders DA, et al. The pharmacokinetics of oral fleroxacin and ciprofloxacin in plasma and sputum during acute and chronic dosing. Br J Clin Pharmacol 2000; 49: 32–8

  23. 23.

    Pennington JE, Reynold HY. Concentrations of gentamicin and carbenicillin in bronchial secretions. J Infect Dis 1973; 128: 63–8

  24. 24.

    Gartmann J. Doxycycline concentrations in lung tissue, bronchial wall, bronchial secretions. Chemotherapy 1975; 21: 19–26

  25. 25.

    Odio W, Vanlaer E, Klastersky J. Concentrations of gentamicin in bronchial secretions after intramuscular and endotracheal administration. J Clin Pharmacol 1975; 15: 518–24

  26. 26.

    Dull WL, Alexander MR, Kasik JE. Bronchial secretion levels of amikacin. Antimicrob Agents Chemother 1979; 16: 767–71

  27. 27.

    Valcke YJ, Vogelaers DP, Colardyn FA, et al. Penetration of netilmicin in the lower respiratory tract after once-daily dosing. Chest 1992; 101: 1028–32

  28. 28.

    Santre C, Georges H, Jacquier JM, et al. Amikacin levels in bronchial secretions of 10 pneumonia patients with respiratory support treated once daily versus twice daily. Antimicrob Agents Chemother 1995 39: 264–7

  29. 29.

    Marlin GE, Davies PR, Rutland J, et al. Plasma and sputum erythromycin concentrations in chronic bronchitis. Thorax 1980; 35: 441–5

  30. 30.

    Bergogne-Bérézin E. Tissue distribution of macrolide antibiotics. In: Bryskier AJ, Butzler J-P, Neu HC, et al., editors. Macrolides: chemistry, pharmacology and clinical uses. Paris: Arnette Blackwell, 1993: 84

  31. 31.

    Matera MG, Tufano MA, Polverino M, et al. Pulmonary concentrations of dirithromycin and erythromycin during acute exacerbation of mild chronic obstructive pulmonary disease. Eur Respir J 1997; 10: 97–102

  32. 32.

    Baldwin DR, Wise R, Andrews JM, et al. Azithromycin concentrations at the sites of pulmonary infection. Eur Respir J 1990; 3: 886–90

  33. 33.

    Cazzola M, Matera MG, Tufano MA, et al. Pulmonary penetration of dirithromycin in patients suffering from acute exacerbation of chronic bronchitis. Pulm Pharmacol 1994; 7: 377–81

  34. 34.

    Honeybourne D. Antibiotic penetration into lung tissue. Thorax 1994; 49: 104–6

  35. 35.

    Wise R, Baldwin DR, Honeybourne D. Penetration of antibiotics into the bronchial mucosa. Res Clin Forums 1990; 12(4): 95–100

  36. 36.

    Baldwin DR, Andrews JM, Wise R, et al. Bronchoalveolar distribution of cefuroxime axetil and in vitro efficacy of observed concentrations against respiratory pathogens. J Antimicrob Chemother 1992; 30: 377–85

  37. 37.

    Wise R, Honeybourne D. Antibiotic penetration into the respiratory tract. A basis for rational therapy. J Chemother 1995; 4: 28–32

  38. 38.

    Wise R. The pharmacokinetics of the oral cephalosporins: a review. J Antimicrob Chemother 1990; 26Suppl. E: 13–20

  39. 39.

    Baldwin DR, Wise R, Andrews JM, et al. Concentrations of cefpodoxime in serum and bronchial mucosal biopsies. J Antimicrob Chemother 1992; 30: 67–71

  40. 40.

    Krumpe P, Lin C-C, Radwanski E, et al. The penetration of ceftibuten into the respiratory tract. Chest 1999 116: 369–74

  41. 41.

    Baldwin DR, Wise R, Andrews JM, et al. Comparative bronchoalveolar concentrations of ciprofloxacin and lomefloxacin following oral administration. Respir Med 1993; 87: 595–601

  42. 42.

    Cook PJ, Andrews JM, Wise R, et al. Concentrations of OPC-17116, a new fluoroquinolone antibacterial, in serum and lung compartments. J Antimicrob Chemother 1995; 35: 317–26

  43. 43.

    Wise R, Honeybourne D. A review of the penetration of sparfloxacin into the lower respiratory tract and sinuses. J Antimicrob Chemother 1996; 37: 57–63

  44. 44.

    Andrews JM, Honeybourne D, Brenwald NP, et al. Concentrations of trovafloxacin in bronchial mucosa, epithelial lining fluid, alveolar macrophages and serum after administration of single or multiple oral doses to patients undergoing fibre-optic bronchoscopy. J Antimicrob Chemother 1997; 39: 797–802

  45. 45.

    Andrews JM, Honeybourne D, Jevons G, et al. Concentrations of levofloxacin (HR 355) in the respiratory tract following a single oral dose in patients undergoing fibre-optic bronchoscopy. J Antimicrob Chemother 1997; 40: 573–7

  46. 46.

    Soman A, Honeybourne D, Andrews J, et al. Concentrations of moxifloxacin in serum and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy. J Antimicrob Chemother 1999; 44: 835–8

  47. 47.

    Honeybourne D, Andrews JM, Cunningham B, et al. The concentrations of clinafloxacin in alveolar macrophages, epithelial lining fluid, bronchial mucosa and serum after administration of single 200 mg oral doses to patients undergoing fibre-optic bronchoscopy. J Antimicrob Chemother 1999 43: 153–5

  48. 48.

    Honeybourne D, Banerjee D, Andrews J, et al. Concentrations of gatifloxacin in plasma and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy. J Antimicrob Chemother 2001; 48: 63–6

  49. 49.

    Gotfried MH, Danziger LH, Rodvold KA. Steady-state plasma and intrapulmonary concentrations of levofloxacin and ciprofloxacin in healthy adult subjects. Chest 2001; 119: 1114–22

  50. 50.

    Lamy P, Anthoine D, Zuck P, et al. Etude pharmacocinétique de la spiramycine en pathologie infectieuse respiratoire. Ann Med 1977; 16: 109–12

  51. 51.

    Chastre J, Brun P, Fourtillan JB, et al. Pulmonary disposition of roxithromycin (RU 28965), a new macrolide antibiotic. Antimicrob Agents Chemother 1987; 31: 1312–6

  52. 52.

    Mattie H, Hoogeterp JJ, Kaajan JPG, et al. The penetration of erythromycin into human bronchial mucosa. Br J Clin Pharmacol 1987; 24: 179–83

  53. 53.

    Cars O. Distribution of antibiotics into tissues and cells. Medical Masterclasses 1993; 1(3): 2–9

  54. 54.

    Staehelin LA. Structure and function of intercellular junctions. Intern Ren Cytol 1974; 39: 191–283

  55. 55.

    Baldwin DR, Wise R, Andrews JM, et al. Concentrations of antimicrobials in the pulmonary alveolar epithelial lining. Res Clin Forums 1990; 12(4): 103–13

  56. 56.

    Baldwin DR, Andrews JM, Wise R, et al. Bronchoalveolar distribution of cefuroxime axetil and in-vitro efficacy of observed concentrations against respiratory pathogens. J Antimicrob Chemother 1992; 30: 377–85

  57. 57.

    Cook PJ, Andrews JM, Woodcock J, et al. Concentration of amoxycillin and clavulanate in lung compartments in adults withoutpulmonary infection. Thorax 1994; 49: 1134–8

  58. 58.

    Cook PJ, Andrews JM, Wise R, et al. Distribution of cefdinir, a third generation cephalosporin antibiotic, in serum and pulmonary compartments. J Antimicrob Chemother 1996; 37: 331–9

  59. 59.

    Allegranzi B, Cazzadori A, Di Perri G, et al. Concentrations of single-dose meropenem (1 g iv) in bronchoalveolar lavage and epithelial lining fluid. J Antimicrob Chemother 2000; 46: 319–22

  60. 60.

    Panteix G, Harf R, de Montclos H, et al. Josamycin pulmonary penetration determined by broncho-alveolar lavage in man. J Antimicrob Chemother 1988; 22: 917–21

  61. 61.

    Conte Jr JE, Golden J, Duncan S, et al. Single-dose intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime in volunteer subjects. Antimicrob Agents Chemother 1996; 40: 1617–22

  62. 62.

    Khair OA, Andrews JM, Honeybourne D, et al. Lung concentrations of telithromycin after oral dosing. J Antimicrob Chemother 2001; 47: 837–40

  63. 63.

    Carcas AJ, Garcia-Satue JL, Zapater P, et al. Tobramycin penetration into epithelial lining fluid of patients with pneumonia. Clin Pharmacol Ther 1999; 65: 245–50

  64. 64.

    Tulkens PM. Intracellular distribution and activity of antibiotics. Eur J Clin Microbiol Infect Dis 1991; 10: 100–6

  65. 65.

    Honeybourne D. Antibiotic penetration in the respiratory tract and implications for the selection of antimicrobial therapy. Curr Opin Pulm Med 1997; 3: 170–4

  66. 66.

    Plouffe J, Schwartz DB, Kolokathis A, et al. Clinical efficacy of intravenous followed by oral azithromycin monotherapy in hospitalized patients with community-acquired pneumonia. The Azithromycin Intravenous Clinical Trials Group. Antimicrob Agents Chemother 2000; 44: 1796–802

  67. 67.

    Cazzola M, Caputi M, Santangelo G, et al. A five-day course of dirithromycin in the treatment of acute exacerbation of severe chronic obstructive pulmonary disease. J Chemother 1997; 9: 279–84

  68. 68.

    Bergogne-Bérézin E. Predicting the efficacy of antimicrobial agents in respiratory infections — is tissue concentration a valid measure? J Antimicrob Chemother 1995; 35: 363–71

  69. 69.

    Neu HC. Activity of macrolides against common pathogens in vitro. In: Bryskier AJ, Butzler J-P, Neu HC, et al., editors. Macrolides: chemistry, pharmacology and clinical uses. Paris: Arnette-Blackwell, 1993: 82

  70. 70.

    Sides GD, Cerimele BJ, Black HR, et al. Pharmacokinetics of dirithromycin. J Antimicrob Chemother 1993; 31Suppl. C: 65–75

  71. 71.

    Panteix G, Harf R, Desnottes JF, et al. Accumulation of pefloxacin in the lower respiratory tract demonstrated by bronchoalveolar lavage. J Antimicrob Chemother 1994; 33: 979–85

  72. 72.

    Nolting A, Costa TD, Vistelle R, et al. Determination of free extracellular concentrations of piperacillin by microdialysis. J Pharm Sci 1996; 85: 369–72

  73. 73.

    Müller M, Haag O, Burgdorff T, et al. Characterization of peripheral-compartment kinetics of antibiotics by in vivo microdialysis in humans. Antimicrob Agents Chemother 1996; 40: 2703–9

  74. 74.

    Bergogne-Bérézin E, Vallée E. Pharmacokinetics of antibiotics in respiratory tissues and fluids. In: Pennington JE, editor. Respiratory infections: diagnosis and management. 3rd ed. New York: Raven Press, 1994: 715–40

  75. 75.

    Ellner PD, Neu HC. The inhibitory quotient. A method for interpreting minimum inhibitory concentration data. JAMA 1981; 246: 1575–8

  76. 76.

    Cazzola M. Pulmonary pharmacokinetics of dirithromycin allow a 5-day treatment of acute bacterial exacerbation of chronic bronchitis. Drugs Today 1995; 31: 105–9

  77. 77.

    Cunha BA. Antibiotic pharmacokinetic considerations in pulmonary infections. Semin Respir Infect 1991; 6: 168–82

  78. 78.

    Fraschini F, Scaglione F, Cogo R, et al. Bactericidal effect of ceftriaxone versus imipenem plus cilastin in bronchial secretion. Chemotherapy 1988; 34Suppl. 1:3–15

  79. 79.

    Maesen FPV, Beeuwkes H, Davies BI, et al. Bacampicillin in acute exacerbations of chronic bronchitis: a dose-range study. J Antimicrob Chemother 1976; 2: 279–85

  80. 80.

    Maesen FPV, Geraedts WH, Davies BI. Cefaclor in the treatment of chronic bronchitis. J Antimicrob Chemother 1990; 26: 456–7

  81. 81.

    Cazzola M, Matera MG, Noschese P. Parenteral antibiotic therapy in the treatment of lower respiratory tract infections. Strategies to minimize the development of antibiotic resistance. Pulm Pharmacol Ther 2000; 13: 249–56

  82. 82.

    Delacher S, Derendorf H, Hollenstein U, et al. A combined in vivo pharmacokinetic-in vitro pharmacodynamic approach to simulate target site pharmacodynamics of antibiotics in humans. J Antimicrob Chemother 2000; 46: 733–9

  83. 83.

    Craig WA, Ebert SC. Killing and regrowth of bacteria in vitro: a review. Scand J Infect Dis 1990; 74 Suppl.: 63–70

  84. 84.

    Bustamante CI, Drusano GL, Tatem BA, et al. Post-antibiotic effect of imipenem on Pseudomonas aeruginosa. Antimicrob Agents Chemother 1984; 26: 678–82

  85. 85.

    Craig WA. Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regimens for broad-spectrum cephalosporins. Diagn Microbiol Infect Dis 1995; 22: 89–96

  86. 86.

    Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis 1998; 26: 1–12

  87. 87.

    Turnidge JD. The pharmacodynamics of β-lactams. Clin Infect Dis 1998; 27: 10–22

  88. 88.

    Drusano G L. Human pharmacodynamics of β-lactams, aminoglycosides and their combination. Scand J Infect Dis 1990; 74: 235–48

  89. 89.

    Schentag JJ, Swanson DJ, Smith IL. Dual individualization: antibiotic dosage calculation from the integration of in-vitro pharmacodynamics and in-vivo pharmacokinetics. J Antimicrob Chemother 1985; 15Suppl. A: 47–57

  90. 90.

    Nix DE, Schentag JJ. Role of pharmacokinetics and pharmacodynamics in the design of dosage schedules for 12-h cefotaxime alone and in combination with other antibiotics. Diagn Microbiol Infect Dis 1995; 22: 71–6

  91. 91.

    Lacy MK, Nicolau DP, Nightingale CH, et al. The pharmacodynamics of aminoglycosides. Clin Infect Dis 1998; 27: 23–7

  92. 92.

    Lode H, Borner K, Koeppe P. Pharmacodynamics of fluoroquinolones. Clin Infect Dis 1998; 27: 33–9

  93. 93.

    Turnidge J. Pharmacokinetics and pharmacodynamics of fluoroquinolones. Drugs 1999; 58Suppl. 2: 29–36

  94. 94.

    Moore RD, Lietman PS, Smith CR. Clinical response to aminoglycoside therapy: Importance of the ratio of peak concentration to minimum inhibitory concentration. J Infect Dis 1987; 155: 93–9

  95. 95.

    Preston SL, Drusano GL, Berman AL, et al. Pharmacodynamics of levofloxacin. JAMA 1998; 279: 125–9

  96. 96.

    Schentag JJ, Gilliland KK, Paladino JA. What have we learned from pharmacokinetic and pharmacodynamic theories? Clin Infect Dis 2001; 32Suppl. 1: S39–46

  97. 97.

    Lister PD, Sanders CC. Pharmacodynamics of levofloxacin and ciprofloxacin against Streptococcus pneumoniae. J Antimicrob Chemother 1999; 43: 79–86

  98. 98.

    Hoang AD, Peterson M, Hovde LB, et al. Investigation of AUC/MIC ratio as a generic predictor of fluoroquinolone activity against Staphylococcus aureus using trovafloxacin, ciprofloxacin, sparfloxacin, and levofloxacin in an in vitro pharmacodynamic model [abstract]. Program and abstracts of the 98th General Meeting of the American Society for Microbiology. Washington, DC: American Society for Microbiology, 1998: 50

  99. 99.

    Craig WA. Postantibiotic effects and the dosing of macrolides, azalides, and streptogramins. In: Zinner SH, Young LS, Acar JF, et al., editors. Expanding indications for the new macrolides, azalides, and streptogramins. New York: Marcel Dekker, 1997: 27–38

  100. 100.

    Patel KB, Xuan D, Tessier PR, et al. Comparison of bronchopulmonary pharmacokinetics of clarithromycin and azithromycin. Antimicrob Agents Chemother 1996; 40: 2375–9

  101. 101.

    Schentag JJ, Nix DE, Adelman MH. Mathematical examination of dual individualization principles (I): relationships between AUC above MIC and area under the inhibitory curve for cefmenoxime, ciprofloxacin and tobramycin. DICP 1991; 25: 1050–7

  102. 102.

    Schentag JJ, Gilliland KK, Paladino JA. Fluoroquinolone pharmacodynamics [reply]. Clin Infect Dis 2001; 33: 2092–6

  103. 103.

    Dalla Costa TD, Derendorf H. AUIC: a general target for the optimization of dosing regimens of antibiotics? Ann Pharmacother 1996; 30: 1024–8

  104. 104.

    Drusano GL, Preston SL, Owens Jr RC, et al. Fluoroquinolone pharmacodynamics. Clin Infect Dis 2001; 33: 2091–2

  105. 105.

    Odenholt-Tornqvist I, Lowdin E, Car O. Pharmacodynamic effects of subinhibitory concentrations of β-lactam antibiotics in vitro. Antimicrob Agents Chemother 1991; 35: 1834–9

  106. 106.

    Cazzola M, Matera MG, Donner CF. Pharmacokinetics and pharmacodynamics of newer oral cephalosporins: implication for treatment of community-acquired lower respiratory tract infections. Clin Drug Invest 1998; 16: 335–46

  107. 107.

    Vogelman B, Gudmundsson S, Leggett J, et al. Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model. J Infect Dis 1988; 158: 831–47

  108. 108.

    Cazzola M, Noschese P, Vinciguerra A, et al. Le correlazioni esistenti tra farmacocinetica polmonare e farmacodinamica permettono di ipotizzare l’utilizzo del ceftazidime alla dose di 1 g una sola volta al giorno nel trattamento delle riacutizzazioni batteriche della broncopneumopatia cronica ostruttiva con danno funzionale moderato. Minerva Med 1998; 89: 15–22

  109. 109.

    Thomas JK, Forrest A, Bhavnani SM, et al. Pharmacodynamic evaluation of factors associated with the development of bacterial resistance in acutely ill patients during therapy. Antimicrob Agents Chemother 1998; 42: 521–7

  110. 110.

    Highet VS, Forrest A, Ballow CH, et al. Antibiotic dosing issues in lower respiratory tract infection: population-derived area under inhibitory curve is predictive of efficacy. J Antimicrob Chemother 1999; 43: 55–63

  111. 111.

    Cazzola M, Di Perna F, Boveri B, et al. Interrelationship between the pharmacokinetics and pharmacodynamics of cefaclor advanced formulation in patients with acute exacerbation of chronic bronchitis. J Chemother 2000; 12: 216–22

  112. 112.

    Vallee E, Azoulay-Dupuis E, Bauchet J, et al. Kinetic disposition of temafloxacin and ciprofloxacin in a murine model of pneumococcal pneumonia. Relevance for drug efficacy. J Pharmacol Exp Ther 1992; 262: 1203–8

  113. 113.

    Drusano GL, Craig WA. Relevance of pharmacokinetics and pharmacodynamics in the selection of antibiotics for respiratory tract infections. J Chemother 1997; 9Suppl. 3: 38–44

  114. 114.

    Craig WA. Outpatient parenteral antibiotic therapy. Management of serious infections. Part I: medical, socioeconomic, and legal issues. Selecting the antibiotic. Hosp Pract (Off Ed) 1993; 28Suppl. 1: 16–20

  115. 115.

    Baquero F, Negri MC. Strategies to minimize the development of antibiotic resistance. J Chemother 1997; 9Suppl. 3: 29–37

  116. 116.

    Vondracek TG. β-lactam antibiotics: is continuous infusion the preferred method of administration? Ann Pharmacother 1995; 9: 415–24

  117. 117.

    Mouton JW, Vinks AA. Is continuous infusion of β-lactam antibiotics worthwhile?. Efficacy and pharmacokinetic considerations. J Antimicrob Chemother 1996; 38: 5–15

  118. 118.

    Cazzola M, Matera MG. Interrelationship between pharmacokinetics and pharmacodynamics in the design of dosage regimens for treating acute exacerbations of chronic bronchitis. Respir Med 1998; 92: 895–901

Download references

Acknowledgements

The authors have received no funding for the preparation of this manuscript and have no conflicts of interest directly relevant to it.

Author information

Correspondence to Dr Mario Cazzola.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Cazzola, M., Blasi, F., Terzano, C. et al. Delivering Antibacterials to the Lungs. Am J Respir Med 1, 261–272 (2002). https://doi.org/10.1007/BF03256617

Download citation

Keywords

  • Minimum Inhibitory Concentration
  • Azithromycin
  • Lower Respiratory Tract Infection
  • Cefaclor
  • Epithelial Line Fluid