Skip to main content
SpringerLink
Log in

Selecting Antibacterials for Outpatient Parenteral Antimicrobial Therapy

Pharmacokinetic-Pharmacodynamic Considerations

  • Review Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Abstract

Some infectious diseases require management with parenteral therapy, although the patient may not need hospitalisation. Consequently, the administration of intravenous antimicrobials in a home or infusion clinic setting has now become commonplace. Outpatient parenteral antimicrobial therapy (OPAT) is considered safe, therapeutically effective and economical. A broad range of infections can be successfully managed with OPAT, although this form of treatment is unnecessary when oral therapy can be used. Many antimicrobials can be employed for OPAT and the choice of agent(s) and regimen should be based upon sound clinical and microbiological evidence. Assessments of cost and convenience should be made subsequent to these primary treatment outcome determinants. When designing an OPAT treatment regimen, the pharmacokinetic and pharmacodynamic characteristics of the individual agents should also be considered.

Pharmacokinetics (PK) is the study of the time course of absorption, distribution, metabolism and elimination of drugs (what the body does to the drug). Clinical pharmacokinetic monitoring has been used to overcome the pharmacokinetic variability of antimicrobials and enable individualised dosing regimens that attain desirable antimicrobial serum concentrations. Pharmacodynamics (PD) is the study of the relationship between the serum concentration of a drug and the clinical response observed in a patient (what the drug does to the body). By combining pharmacokinetic properties (peak [Cmax] or trough [Cmin] serum concentrations, half-life, area under the curve) and pharmacodynamic properties (susceptibility results, minimum inhibitory concentrations [MIC] or minimum bactericidal concentrations [MBC], bactericidal or bacteriostatic killing, post-antibiotic effects), unique PK/PD parameters or indices (t > MIC, Cmax/MIC, AUC24/MIC) can be defined.

Depending on the killing characteristics of a given class of antimicrobials (concentration-dependent or time-dependent), specific PK/PD parameters may predict in vitro bacterial eradication rates and correlate with in vivo microbiologic and clinical cures. An understanding of these principles will enable the clinician to vary dosing schemes and design individualised dosing regimens to achieve optimal PK/PD parameters and potentially improve patient outcomes. This paper will review basic principles of useful PK/PD parameters for various classes of antimicrobials as they may relate to OPAT.

In summary, OPAT has become an important treatment option for the management of infectious diseases in the community setting. To optimise treatment course outcomes, pharmacokinetic and pharmacodynamic properties of the individual agents should be carefully considered when designing OPAT treatment regimens.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. Rucker RW, Harrison GM. Outpatient intravenous medications in the management of cystic fibrosis. Pediatrics 1974; 54: 358–60

    PubMed  CAS  Google Scholar 

  2. Stiver HG, Telford GO, Mossey JM. Intravenous antibiotic therapy at home. Ann Intern Med 1978; 89: 690–3

    PubMed  CAS  Google Scholar 

  3. Antoniskis A, Anderson BC, Van Volkinberg EL, et al. Feasibility of outpatient self-administration of parenteral antibiotics. West J Med 1978; 128: 203–6

    PubMed  CAS  Google Scholar 

  4. Stiver HG, Trosky SK, Cote DD, et al. Self-administration of intravenous antibiotics: an efficient, cost-effective home care program. CMAJ 1982; 127: 207–11

    CAS  Google Scholar 

  5. Poretz DM, Eron LJ, Goldenberg RI, et al. Intravenous antibiotic therapy in an outpatient setting. JAMA 1982; 248: 336–9

    Article  PubMed  CAS  Google Scholar 

  6. Balinsky W, Nesbitt S. Cost-effectiveness of outpatient parenteral antibiotics: a review of the literature. Am J Med 1989; 87: 1–5

    Article  Google Scholar 

  7. Poretz DM, editor. Outpatient use of intravenous antibiotics. Am J Med 1994; 97 Suppl. 2A: 1–55

    Google Scholar 

  8. Stiver G, Wai A, Chase L, et al. Outpatient intravenous antibiotic therapy: the Vancouver Hospital experience. Can J Infect Dis 2000; 11 Suppl. A: 11A–4A

    Google Scholar 

  9. Williams DN, Rehm SJ, Tice AD, et al. Practice guidelines for community-based parenteral anti-infective therapy. Clin Infect Dis 1997; 25: 787–801

    Article  PubMed  CAS  Google Scholar 

  10. Wai AO, Frighetto L, Marra CA, et al. Cost analysis of an adult Outpatient Parenteral Antibiotic Therapy (OPAT) programme: a Canadian teaching hospital and Ministry of Health perspective. Pharmacoeconomics 2000; 18: 451–7

    Article  PubMed  CAS  Google Scholar 

  11. Thickson ND. Economics of home intravenous services. Pharmacoeconomics 1993; 3(3): 220–7

    Article  PubMed  CAS  Google Scholar 

  12. Hindes R, Winkler C, Kane P, et al. Outpatient intravenous antibiotic therapy in Medicare patients: cost-savings analysis. Infect Dis Clin Pract 1995; 4: 211–7

    Article  Google Scholar 

  13. Board N, Brennan NJ, Caplan GA. A randomised controlled trial of the costs of hospital as compared in the home for acute medical patients. Aust N Z J Public Health 2000; 24: 305–11

    Article  PubMed  CAS  Google Scholar 

  14. Tice AD. Pharmacoeconomic considerations in the ambulatory use of parenteral cephalosporins. Drugs 2000; 59: 29–35

    Article  PubMed  Google Scholar 

  15. Goodfellow A, Wai A, Chan E, et al. Cost-benefit, quality of life and willingness to pay analyses of the Home IV Antibiotic program: a Canadian perspective [abstract]. The Canadian Association for Population Therapeutics Conference; 2001 Apr 1–3; Banff, Alberta

  16. Amsden GW, Schentag JJ. Tables of antimicrobial agent pharmacology. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingston, 1995: 492–528

    Google Scholar 

  17. Karchmer AW. Cephalosporins. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingston, 1995: 492–528

    Google Scholar 

  18. Chambers HF. Penicillins. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and Practice of Infectious Diseases. 5th ed. Philadelphia: Churchill Livingston; 1995: 492–528

    Google Scholar 

  19. Gilbert DN. Aminoglycosides. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingston, 1995: 492–528

    Google Scholar 

  20. Andes DR, Craig WA. Pharmacokinetics and pharmacodynamics of outpatient intravenous antimicrobial therapy. Infect Dis Clin North Am 1998; 12: 849–60

    Article  PubMed  CAS  Google Scholar 

  21. Benet LZ, Oie S, Schwartz JB. Design and optimization of dosage regimens; pharmacokinetic data. (Appendix II). In: Hardman JG, Limbird LE, editors. Goodman and Gilman’s The pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill Health Professions Division, 1996: 1707–92

    Google Scholar 

  22. Gilbert DN, Moellering RC, Sande MA. The Sanford guide to antimicrobial therapy. 31st ed. Hyde Park, Vermont: Antimicrobial Therapy Inc., 2001: 56–7

    Google Scholar 

  23. Marra F, Jewesson PJ. Vancomycin serum concentration monitoring: the middle ground is best. Clin Drug Investig 1996; 12: 105–18

    Article  CAS  Google Scholar 

  24. Aminimanizani A, Beringer P, Jelliffe R. Comparative pharmacokinetics and pharmacodynamics of the newer fluoroquinolone antibacterials. Clin Pharmacokinet 2001; 40: 169–87

    Article  PubMed  CAS  Google Scholar 

  25. Manzella JP. Quinupristin-dalfopristin: a new antibiotic for severe gram-positive infections. Am Fam Phys 2001; 64: 1863–6

    CAS  Google Scholar 

  26. Jewesson PJ. Pharmaceutical, pharmacokinetic and other considerations for intravenous to oral stepdown therapy. Can J Infect Dis 1995; 6 Suppl. A: 11A–6A

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  28. Amsden GW, Schentag JJ. Tables of antimicrobial agent pharmacology. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingston, 1995: 247–64

    Google Scholar 

  29. Amsden GW, Schentag JJ. Tables of antimicrobial agent pharmacology. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingston, 1995: 233–46

    Google Scholar 

  30. Amsden GW, Schentag JJ. Tables of antimicrobial agent pharmacology. In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. 5th ed. Philadelphia: Churchill Livingston, 1995: 279–306

    Google Scholar 

  31. Lietman PS. Pharmacokinetics of antimicrobial agents. In Mandell GL, editors. Principles and practice of infectious diseases. 3rd ed. New York: Churchill Livingstone, 1990: 228–30

    Google Scholar 

  32. Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis 1998; 26: 1–10

    Article  PubMed  CAS  Google Scholar 

  33. Stein GE. Pharmacokinetics and pharmacodynamics of newer fluoroquinolones. Clin Infect Dis 1996; 23 Suppl. 1: S19–24

    Article  PubMed  CAS  Google Scholar 

  34. Paladino JA, Sperry HE, Backes JM, et al. Clinical and economic evaluation of oral ciprofloxacin after an abbreviated course of intravenous antibiotics. Am J Med 1991; 91: 462–70

    Article  PubMed  CAS  Google Scholar 

  35. Paladino JA, Zimmer GS, Schentag JJ. The economic potential of dual individualisation methodologies. Pharmacoeconomics 1996; 10: 539–45

    Article  PubMed  CAS  Google Scholar 

  36. Frighetto L, Nickoloff D, Martinusen SM, et al. Intravenous-to-oral stepdown program: four years of experience in a large teaching hospital. Ann Pharmacother 1992; 26: 1447–51

    PubMed  CAS  Google Scholar 

  37. Malfair SC, Frighetto L, Nickoloff DM, et al. Evaluation of the use of cefuroxime and cefuroxime axetil in an intravenous-oral stepdown program. Ann Pharmacother 1996; 30: 337–42

    PubMed  CAS  Google Scholar 

  38. Jewesson P. Cost-effectiveness and value of an IV switch. Pharmacoeconomics 1994; 5 Suppl. 2: 20–6

    Article  PubMed  CAS  Google Scholar 

  39. Paladino JA. Is more than one quinolone needed in clinical practice?. Ann Pharmacother 2001; 35: 1085–95

    Article  PubMed  CAS  Google Scholar 

  40. Pea F, Furlanut M. Pharmacokinetic aspects of treating infections in the intensive care unit: focus on drug interactions. Clin Pharmacokinet 2001; 40: 833–68

    Article  PubMed  CAS  Google Scholar 

  41. Gregg CR. Drug interactions and anti-infective therapies. Am J Med 1999; 106: 227–37

    Article  PubMed  CAS  Google Scholar 

  42. Gillum JG, Israel DS, Polk RE. Pharmacokinetic drug interactions with antimicrobial agents. Clin Pharmacokinet 1993; 25: 450–82

    Article  PubMed  CAS  Google Scholar 

  43. Michalets EL. Update: clinically significant cytochrome P-450 drug interactions. Pharmacotherapy 1998; 18: 84–112

    PubMed  CAS  Google Scholar 

  44. Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharma-codynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet 2000; 38(1): 41–57

    Article  PubMed  CAS  Google Scholar 

  45. Albengres E, Le Louet H, Tillement JP. Systemic antifungal agents: drug interactions of clinical significance. Drug Saf 1998; 18: 83–97

    Article  PubMed  CAS  Google Scholar 

  46. Lomaestro BM, Piatek MA. Update on drug interactions with azole antifungal agents. Ann Pharmacother 1998; 32: 915–28

    Article  PubMed  CAS  Google Scholar 

  47. Venkatakrishnan K, von Moltke LL, Greenblatt DJ. Effects of the antifungal agents on oxidative drug metabolism: clinical relevance. Clin Pharmacokinet 2000; 38: 111–80

    Article  PubMed  CAS  Google Scholar 

  48. Pai MP, Graci DM, Amsden GW. Macrolide drug interactions: an update. Ann Pharmacother 2000; 34: 495–513

    Article  PubMed  CAS  Google Scholar 

  49. Fish DN. Fluoroquinolone adverse effects and drug interactions. Pharmacotherapy 2001; 21: 253S–72S

    Article  PubMed  CAS  Google Scholar 

  50. Jewesson PJ. Overcoming antibiotic resistance: a physicians’ guide. Can J CME 1998; 3: 137–50

    Google Scholar 

  51. Ackerman BH, Dello Buono FA. In vitro testing of antibiotics. Pharmacotherapy 1996; 16: 201–17

    PubMed  CAS  Google Scholar 

  52. Hyatt JM, McKinnon PS, Zimmer GS, et al. The importance of pharmacokinetic/pharmacodynamic surrogate markers to outcome: focus on antibacterial agents. Clin Pharmacokinet 1995; 28: 143–60

    Article  PubMed  CAS  Google Scholar 

  53. Schentag JJ, Strenkoski-Nix LC, Nix DE, et al. Pharmacodynamic interactions of antibiotics alone and in combination. Clin Infect Dis 1998; 27: 40–6

    Article  PubMed  CAS  Google Scholar 

  54. White RL. What in vitro models of infection can and cannot do. Pharmacotherapy 2001; 21(11 Pt 2): 292S–301S

    Article  PubMed  CAS  Google Scholar 

  55. Jacobs MR. Optimisation of antimicrobial therapy using pharmacokinetic and pharmacodynamic parameters. Clin Microbiol Infect 2001; 7: 589–96

    Article  PubMed  CAS  Google Scholar 

  56. Sanchez-Navarro A, Sanchez Recio MM. Basis of anti-infective therapy: pharmacokinetic-pharmacodynamic criteria and methodology for dual dosage individualisation. Clin Pharmacokinet 1999; 37: 289–304

    Article  PubMed  CAS  Google Scholar 

  57. Li RC, Zhu M, Schentag JJ. Achieving an optimal outcome in the treatment of infections: the role of clinical pharmacokinetics and pharmacodynamics of antimicrobials. Clin Pharmacokinet 1999; 37: 1–16

    Article  PubMed  CAS  Google Scholar 

  58. Levison ME. Pharmacodynamics of antibacterial drugs. Infect Dis Clin North Am 2000; 14: 281–91

    Article  PubMed  CAS  Google Scholar 

  59. Li RC. New pharmacodynamic parameters for antimicrobial agents. Int J Antimicrob Agents 2000; 13: 229–35

    Article  PubMed  CAS  Google Scholar 

  60. Gunderson BW, Ross GH, Ibrahim KH, et al. What do we really know about antibiotic pharmacodynamics?. Pharmacotherapy 2001; 21(11 Pt 2): 302S–18S

    Article  PubMed  CAS  Google Scholar 

  61. Rodvold KA. Pharmacodynamics of antiinfective therapy: taking what we know to the patient’s bedside. Pharmacotherapy 2001; 21(11 Pt 2): 319S–30S

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  63. Burgess DS. Pharmacodynamic principles of antimicrobial therapy in the prevention of resistance. Chest 1999; 115(3 Suppl.): 19S–23S

    Article  PubMed  CAS  Google Scholar 

  64. Craig WA, Ebert SC. Killing and regrowth of bacteria in vitro: a review. Scand J Infect Dis Suppl 1990; 11: 319–26

    Google Scholar 

  65. Craig WA, Ebert SC. Killing and regrowth of bacteria in vitro: a review. Scand J Infect Dis Suppl 1991; 74: 63–70

    Google Scholar 

  66. Spivey JM. The postantibiotic effect. Clin Pharm 1992; 11: 865–75

    PubMed  CAS  Google Scholar 

  67. Verbist L. Relevance of antibiotic susceptibility testing for clinical practice. Eur J Clin Microbiol Infect Dis 1993; 12 Suppl. 1: S2–5

    Article  PubMed  Google Scholar 

  68. Schentag JJ, Smith IL, Swanson DJ, et al. Role for dual individualization with cefmenoxime. Am J Med 1984; 77: 43–50

    PubMed  CAS  Google Scholar 

  69. 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; 15 Suppl. A: 47–57

    Article  PubMed  CAS  Google Scholar 

  70. 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

    PubMed  CAS  Google Scholar 

  71. Schentag JJ, Nix DE, Forrest A, et al. AUIC: the universal parameter within the constraint of a reasonable dosing interval. Ann Pharmacother 1996; 30: 1029–31

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  74. Craig WA. Antimicrobial resistance issues of the future. Diagn Microbiol Infect Dis 1996; 25: 213–7

    Article  PubMed  CAS  Google Scholar 

  75. Craig WA, Andes D. Pharmacokinetics and pharmacodynamics of antibiotics in otitis media. Pediatr Infect Dis J 1996; 15: 255–9

    Article  PubMed  CAS  Google Scholar 

  76. Gilbert DN, Dworkin RJ, Raber SR, et al. Outpatient parenteral antimicrobial-drug therapy. N Engl J Med 1997; 337: 829–38

    Article  PubMed  CAS  Google Scholar 

  77. Servais H, Tulkens PM. Stability and compatibility of ceftazidime administered by continuous infusion to intensive care patients. Antimicrob Agents Chemother 2001; 45: 2643–7

    Article  PubMed  CAS  Google Scholar 

  78. Bodey GP, Ketchel SJ, Rodriguez V. A randomized study of carbenicillin plus cefamandole or tobramycin in the treatment of febrile episodes in cancer patients. Am J Med 1979; 67: 608–16

    Article  PubMed  CAS  Google Scholar 

  79. MacGowan AP, Bowker KE. Continuous infusion of betalactam antibiotics. Clin Pharmacokinet 1998; 35: 391–402

    Article  PubMed  CAS  Google Scholar 

  80. Burgess DS, Hastings RW, Hardin TC. Pharmacokinetics and pharmacodynamics of cefepime administered by intermittent and continuous infusion. Clin Ther 2000; 22: 66–75

    Article  PubMed  CAS  Google Scholar 

  81. Nicolau DP, Nightingale CH, Banevicius MA, et al. Serum bactericidal activity of ceftazidime: continuous infusion versus intermittent injections. Antimicrob Agents Chemother 1996; 40: 61–4

    PubMed  CAS  Google Scholar 

  82. Benko AS, Cappelletty DM, Kruse JA, et al. Continuous infusion versus intermittent administration of ceftazidime in critically ill patients with suspected gram-negative infections. Antimicrob Agents Chemother 1996; 40: 691–5

    PubMed  CAS  Google Scholar 

  83. Hanes SD, Wood GC, Herring V, et al. Intermittent and continuous ceftazidime infusion for critically ill trauma patients. Am J Surg 2000; 179: 436–40

    Article  PubMed  CAS  Google Scholar 

  84. Nicolau DP, McNabb J, Lacy MK, et al. Continuous versus intermittent administration of ceftazidime in intensive care unit patients with nosocomial pneumonia. Int J Antimicrob Agents 2001; 17: 497–504

    Article  PubMed  CAS  Google Scholar 

  85. McNabb JJ, Nightingale CH, Quintiliani R, et al. Cost-effectiveness of ceftazidime by continuous infusion versus intermittent infusion for nosocomial pneumonia. Pharmacotherapy 2001; 21: 549–55

    Article  PubMed  CAS  Google Scholar 

  86. Ambrose PG, Quintiliani R, Nightingale CH, et al. Continuous vs intermittent infusion of cefuroxime for the treatment of community-acquired pneumonia. Infect Dis Clin Pract 1998; 7: 463–70

    Article  Google Scholar 

  87. Grant EM, Kuti JL, Nicolau DP, et al. Clinical efficacy and pharmacoeconomics of a continuous-infusion piperacillin-tazobactam program in a large community teaching hospital. Pharmacotherapy 2002; 22: 471–83

    Article  PubMed  CAS  Google Scholar 

  88. MacGowan AP. Pharmacodynamics, pharmacokinetics, and therapeutic drug monitoring of glycopeptides. Ther Drug Monit 1998; 20: 473–7

    Article  PubMed  CAS  Google Scholar 

  89. Larsson AJ, Walker KJ, Raddatz JK, et al. The concentration-independent effect of monoexponential and biexponential decay in vancomycin concentrations on the killing of Staphylococcus aureus under aerobic and anaerobic conditions. J Antimicrob Chemother 1996; 38: 589–97

    Article  PubMed  CAS  Google Scholar 

  90. Duffull SB, Begg EJ, Chambers ST, et al. Efficacies of different vancomycin dosing regimens against Staphylococcus aureus determined with a dynamic in vitro model. Antimicrob Agents Chemother 1994; 38: 2480–2

    Article  PubMed  CAS  Google Scholar 

  91. Cantoni L, Wenger A, Glauser MP, et al. Comparative efficacy of amoxicillin-clavulanate, cloxacillin, and vancomycin against methicillin-sensitive and methicillin-resistant Staphylococcus aureus endocarditis in rats. J Infect Dis 1989; 159: 989–93

    Article  PubMed  CAS  Google Scholar 

  92. Schaad UB, McCracken Jr GH, Nelson JD. Clinical pharmacology and efficacy of vancomycin in pediatric patients. J Pediatr 1980; 96: 119–26

    Article  PubMed  CAS  Google Scholar 

  93. Zimmermann AE, Katona BG, Plaisance KI. Association of vancomycin serum concentrations with outcomes in patients with gram-positive bacteremia. Pharmacotherapy 1995; 15: 85–91

    PubMed  CAS  Google Scholar 

  94. Klepser ME, Kang SL, McGrath BJ, et al. Influence of vancomycin serum concentration on the outcome of gram-positive infections. Presented at The American College of Clinical Pharmacy Annual Winter Meeting; 1994 Feb 4–6; San Diego

  95. Rybak MJ, Capelletty MJ, Ruffing RC, et al. Influence of vancomycin serum concentrations on the outcome of patients being treated for Gram-positive infections [abstract]. Abstracts of the 37th Intersci Conf on Antimicrobial Agents Chemother. 1997 Sep 28–Oct 1: A46

  96. Edwards DJ, Pancorbo S. Routine monitoring of serum vancomycin concentrations: waiting for proof of its value. Clin Pharm 1987; 6: 652–4

    PubMed  CAS  Google Scholar 

  97. Freeman CD, Quintiliani R, Nightingale CH. Vancomycin therapeutic drug monitoring: is it necessary?. Ann Pharmacother 1993; 27: 594–8

    PubMed  CAS  Google Scholar 

  98. Moellering Jr RC. Monitoring serum vancomycin levels: climbing the mountain because it is there?. [published erratum appears in Clin Infect Dis 1994; 19: 379]. Clin Infect Dis 1994; 18: 544–6

    Article  PubMed  Google Scholar 

  99. Cantu TG, Yamanaka-Yuen NA, Lietman PS. Serum vancomycin concentrations: reappraisal of their clinical value. Clin Infect Dis 1994; 18: 533–43

    Article  PubMed  CAS  Google Scholar 

  100. Leader WG, Chandler MH, Castiglia M. Pharmacokinetic optimisation of vancomycin therapy. Clin Pharmacokinet 1995; 28: 327–42

    Article  PubMed  CAS  Google Scholar 

  101. Saunders NJ. Vancomycin administration and monitoring reappraisal. J Antimicrob Chemother 1995; 36: 279–82

    Article  PubMed  CAS  Google Scholar 

  102. Shalansky S. Rationalization of vancomycin serum concentration monitoring. Can J Hosp Pharm 1995; 48: 17–24

    Google Scholar 

  103. Begg EJ, Barclay ML, Kirkpatrick CM. The therapeutic monitoring of antimicrobial agents. Br J Clin Pharmacol 2001; 52 Suppl. 1: 35S–43S

    Article  PubMed  CAS  Google Scholar 

  104. Welty TE, Copa AK. Impact of vancomycin therapeutic drug monitoring on patient care. Ann Pharmacother 1994; 28: 1335–9

    PubMed  CAS  Google Scholar 

  105. Fernandez de Gatta MD, Calvo MV, Hernandez JM, et al. Cost-effectiveness analysis of serum vancomycin concentration monitoring in patients with hematologic malignancies. Clin Pharmacol Ther 1996; 60: 332–40

    Article  PubMed  CAS  Google Scholar 

  106. James JK, Palmer SM, Levine DP, et al. Comparison of conventional dosing versus continuous-infusion vancomycin therapy for patients with suspected or documented gram-positive infections. Antimicrob Agents Chemother 1996; 40: 696–700

    PubMed  CAS  Google Scholar 

  107. Klepser ME, Patel KB, Nicolau DP, et al. Comparison of bactericidal activities of intermittent and continuous infusion dosing of vancomycin against methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. Pharmacotherapy 1998; 18: 1069–74

    PubMed  CAS  Google Scholar 

  108. Lacy MK, Tessier PR, Nicolau DP, et al. Comparison of vancomycin pharmacodynamics (1g every 12 or 24 h) against methicillin-resistant staphylococci. Int J Antimicrob Agents 2000; 15: 25–30

    Article  PubMed  CAS  Google Scholar 

  109. Wysocki M, Thomas F, Wolff MA, et al. Comparison of continuous with discontinuous intravenous infusion of vancomycin in severe MRSA infections. J Antimicrob Chemother 1995; 35: 352–4

    Article  PubMed  CAS  Google Scholar 

  110. Albanese J, Leone M, Bruguerolle B, et al. Cerebrospinal fluid penetration and pharmacokinetics of vancomycin administered by continuous infusion to mechanically ventilated patients in an intensive care unit. Antimicrob Agents Chemother 2000; 44: 1356–8

    Article  PubMed  CAS  Google Scholar 

  111. Wysocki M, Delatour F, Faurisson F, et al. Continuous versus intermittent infusion of vancomycin in severe staphylococcal infections: prospective multicenter randomized study. Antimicrob Agents Chemother 2001; 45: 2460–7

    Article  PubMed  CAS  Google Scholar 

  112. Blaser J, Stone BB, Groner MC, et al. Comparative study with enoxacin and netilmicin in a pharmacodynamic model to determine importance of ratio of antibiotic peak concentration to MIC for bactericidal activity and emergence of resistance. Antimicrob Agents Chemother 1987; 31: 1054–60

    Article  PubMed  CAS  Google Scholar 

  113. Dudley MN, Blaser J, Gilbert D, et al. Combination therapy with ciprofloxacin plus azlocillin against Pseudomonas aeruginosa: effect of simultaneous versus staggered administration in an in vitro model of infection. J Infect Dis 1991; 164: 499–506

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  115. Drusano GL, Johnson DE, Rosen M, et al. Pharmacodynamics of a fluoroquinolone antimicrobial agent in a neutropenic rat model of Pseudomonas sepsis. Antimicrob Agents Chemother 1993; 37: 483–90

    Article  PubMed  CAS  Google Scholar 

  116. Leggett JE, Fantin B, Ebert S, et al. Comparative antibiotic dose-effect relations at several dosing intervals in murine pneumonitis and thigh-infection models. J Infect Dis 1989; 159: 281–92

    Article  PubMed  CAS  Google Scholar 

  117. Peloquin CA, Cumbo TJ, Nix DE, et al. Evaluation of intravenous ciprofloxacin in patients with nosocomial lower respiratory tract infections: impact of plasma concentrations, organism, minimum inhibitory concentration, and clinical condition on bacterial eradication. Arch Intern Med 1989; 149: 2269–73

    Article  PubMed  CAS  Google Scholar 

  118. Forrest A, Nix DE, Ballow CH, et al. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother 1993; 37: 1073–81

    Article  PubMed  CAS  Google Scholar 

  119. Forrest A, Chodosh S, Amantea MA, et al. Pharmacokinetics and pharmacodynamics of oral grepafloxacin in patients with acute bacterial exacerbations of chronic bronchitis. J Antimicrob Chemother 1997; 40 Suppl. A: 45–57

    Article  PubMed  CAS  Google Scholar 

  120. Preston SL, Drusano GL, Berman AL, et al. Pharmacodynamics of levofloxacin: a new paradigm for early clinical trials. JAMA 1998; 279: 125–9

    Article  PubMed  CAS  Google Scholar 

  121. Zhanel GG, Walters M, Laing N, et al. In vitro pharmacodynamic modelling simulating free serum concentrations of fluoroquinolones against multidrug-resistant Streptococcus pneumoniae. J Antimicrob Chemother 2001; 47: 435–40

    Article  PubMed  CAS  Google Scholar 

  122. Ambrose PG, Grasela DM, Grasela TH, et al. Pharmacodynamics of fluoroquinolones against Streptococcus pneumoniae in patients with community-acquired respiratory tract infections. Antimicrob Agents Chemother 2001; 45: 2793–7

    Article  PubMed  CAS  Google Scholar 

  123. Zhanel GG, Ennis K, Vercaigne L, et al. A critical review of fluoroquinolones: focus on respiratory tract infections. Drugs 2002; 62: 13–59

    Article  PubMed  CAS  Google Scholar 

  124. 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

    PubMed  CAS  Google Scholar 

  125. Craig WA, Redington J, Ebert SC. Pharmacodynamics of amikacin in vitro and in mouse thigh and lung infections. J Antimicrob Chemother 1991; 27 Suppl. C: 29–40

    Article  PubMed  CAS  Google Scholar 

  126. 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

    Article  PubMed  CAS  Google Scholar 

  127. Bayer AS, Norman D, Kim KS. Efficacy of amikacin and ceftazidime in experimental aortic valve endocarditis due to Pseudomonas aeruginosa. Antimicrob Agents Chemother 1985; 28: 781–5

    Article  PubMed  CAS  Google Scholar 

  128. Noone P, Parsons TM, Pattison JR, et al. Experience in monitoring gentamicin therapy during treatment of serious gramnegative sepsis. BMJ 1974; 1: 477–81

    Article  PubMed  CAS  Google Scholar 

  129. Moore RD, Smith CR, Lietman PS. The association of aminoglycoside plasma levels with mortality in patients with gramnegative bacteremia. J Infect Dis 1984; 149: 443–8

    Article  PubMed  CAS  Google Scholar 

  130. Moore RD, Smith CR, Lietman PS. Association of aminoglycoside plasma levels with therapeutic outcome in gram-negative pneumonia. Am J Med 1984; 77: 657–62

    Article  PubMed  CAS  Google Scholar 

  131. Deziel-Evans LM, Murphy JE, Job ML. Correlation of pharmacokinetic indices with therapeutic outcome in patients receiving aminoglycosides. Clin Pharm 1986; 5: 319–24

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  133. Kashuba AD, Bertino Jr JS, Nafziger AN. Dosing of aminoglycosides to rapidly attain pharmacodynamic goals and hasten therapeutic response by using individualized pharmacokinetic monitoring of patients with pneumonia caused by gram-negative organisms. Antimicrob Agents Chemother 1998; 42: 1842–4

    PubMed  CAS  Google Scholar 

  134. Kashuba AD, Nafziger AN, Drusano GL, et al. Optimizing aminoglycoside therapy for nosocomial pneumonia caused by gram-negative bacteria. Antimicrob Agents Chemother 1999; 43: 623–9

    PubMed  CAS  Google Scholar 

  135. Galloe AM, Graudal N, Christensen HR, et al. Aminoglycosides single or multiple daily dosing?: a meta-analysis on efficacy and safety. Eur J Clin Pharmacol 1995; 48: 39–43

    Article  PubMed  CAS  Google Scholar 

  136. Blaser J, Konig C. Once-daily dosing of aminoglycosides. Eur J Clin Microbiol Infect Dis 1995; 14: 1029–38

    Article  PubMed  CAS  Google Scholar 

  137. Barza M, Ioannidis JP, Cappelleri JC, et al. Single or multiple daily doses of aminoglycosides: a meta-analysis. BMJ 1996; 312(7027): 338–45

    Article  PubMed  CAS  Google Scholar 

  138. Munckhof WJ, Grayson ML, Turnidge JD. A meta-analysis of studies on the safety and efficacy of aminoglycosides given either once daily or as divided doses. J Antimicrob Chemother 1996; 37: 645–63

    Article  PubMed  CAS  Google Scholar 

  139. Hatala R, Dinh T, Cook DJ. Once-daily aminoglycoside dosing in immunocompetent adults: a meta-analysis. Ann Intern Med 1996; 124: 717–25

    PubMed  CAS  Google Scholar 

  140. Ferriols-Lisart R, Alos-Alminana M. Effectiveness and safety of once-daily aminoglycosides: a meta-analysis. Am J Health Syst Pharm 1996; 53: 1141–50

    PubMed  CAS  Google Scholar 

  141. Freeman CD, Strayer AH. Mega-analysis of meta-analysis: an examination of meta-analysis with an emphasis on once-daily aminoglycoside comparative trials. Pharmacotherapy 1996; 16: 1093–102

    PubMed  CAS  Google Scholar 

  142. Bailey TC, Little JR, Littenberg B, et al. A meta-analysis of extended-interval dosing versus multiple daily dosing of aminoglycosides. Clin Infect Dis 1997; 24: 786–95

    Article  PubMed  CAS  Google Scholar 

  143. Ali MZ, Goetz MB. A meta-analysis of the relative efficacy and toxicity of single daily dosing versus multiple daily dosing of aminoglycosides. Clin Infect Dis 1997; 24: 796–809

    Article  PubMed  CAS  Google Scholar 

  144. Rapp RP. Pharmacokinetics and pharmacodynamics of intravenous and oral azithromycin: enhanced tissue activity and minimal drug interactions. Ann Pharmacother 1998; 32: 785–93

    Article  PubMed  CAS  Google Scholar 

  145. Ebert S, Rikardsdottit S, Craig WA. Pharmacodynamic comparison of clarithromycin vs erythromycin [abstract]. In: Program and abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology, 1991: 509

    Google Scholar 

  146. Nightingale CH. Pharmacokinetics and pharmacodynamics of newer macrolides. Pediatr Infect Dis J 1997; 16: 438–43

    Article  PubMed  CAS  Google Scholar 

  147. Craig W, Rikardsdottir S, Watanabe Y. In vivo and in vitro postantibiotic effects (PAEs) of azithromycin [abstract]. In: Program and abstracts of the 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology, 1992: 45

    Google Scholar 

  148. Lewis RE, Klepser ME, Ernst EJ, et al. Evaluation of low-dose, extended-interval clindamycin regimens against Staphylococcus aureus and Streptococcus pneumoniae using a dynamic in vitro model of infection. Antimicrob Agents Chemother 1999: 43: 2005–9

    PubMed  CAS  Google Scholar 

  149. Nix DE, Tyrrell R, Muller M. Pharmacodynamics of metronidazole determined by a time-kill assay for Trichomonas vaginalis. Antimicrob Agents Chemother 1995; 39: 1848–52

    Article  PubMed  CAS  Google Scholar 

  150. Spence MR, Harwell TS, Davies MC, et al. The minimum single oral metronidazole dose for treating trichomoniasis: a randomized, blinded study. Obstet Gynecol 1997; 89(5 Pt 1): 699–703

    Article  PubMed  CAS  Google Scholar 

  151. Lamb HM, Figgitt DP, Faulds D. Quinupristin/dalfopristin: a review of its use in the management of serious gram-positive infections. Drugs 1999; 58: 1061–97

    Article  PubMed  CAS  Google Scholar 

  152. Delgado Jr G, Neuhauser MM, Bearden DT, et al. Quinupristin-dalfopristin: an overview. Pharmacotherapy 2000; 20: 1469–85

    Article  PubMed  CAS  Google Scholar 

  153. Rybak MJ, Houlihan HH, Mercier RC, et al. Pharmacodynamics of RP 59500 (quinupristin-dalfopristin) administered by intermittent versus continuous infusion against Staphylococcus aureus-infected fibrin-platelet clots in an in vitro infection model. Antimicrob Agents Chemother 1997; 41: 1359–63

    PubMed  CAS  Google Scholar 

  154. Craig W, Ebert S. Pharmacodynamic activities of RP 59500 in an animal infection model. Presented at the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 1993 Oct 17–20; New Orleans, LA

  155. Fantin B, Leclercq R, Merle Y, et al. Critical influence of resistance to streptogramin B-type antibiotics on activity of RP 59500 (quinupristin-dalfopristin) in experimental endocarditis due to Staphylococcus aureus. Antimicrob Agents Chemother 1995; 39: 400–5

    Article  PubMed  CAS  Google Scholar 

  156. Aeschlimann JR, Rybak MJ. Pharmacodynamic analysis of the activity of quinupristin-dalfopristin against vancomycin-resistant Enterococcus faecium with differing MBCs via time-killcurve and postantibiotic effect methods. Antimicrob Agents Chemother 1998; 42: 2188–92

    PubMed  CAS  Google Scholar 

  157. Dresser LD, Rybak MJ. The pharmacologic and bacteriologic properties of oxazolidinones, a new class of synthetic antimicrobials. Pharmacotherapy 1998; 18: 456–62

    PubMed  CAS  Google Scholar 

  158. Perry CM, Jarvis B. Linezolid: a review of its use in the management of serious gram-positive infections. Drugs 2001; 61: 525–51

    Article  PubMed  CAS  Google Scholar 

  159. Bain KT, Wittbrodt ET. Linezolid for the treatment of resistant gram-positive cocci. Ann Pharmacother 2001; 35: 566–75

    Article  PubMed  CAS  Google Scholar 

  160. Andes D, Van OML, Craig WA. Pharmacodynamic activity of a new oxazolidinone, linezolid, in an animal infection model [abstract A-9]. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy; 1998 Sep 24-26; San Diego

  161. Rybak MJ, Cappelletty DM, Moldovan T, et al. Comparative in vitro activities and postantibiotic effects of the oxazolidinone compounds eperezolid (PNU-100592) and linezolid (PNU-100766) versus vancomycin against Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus faecalis, and Enterococcus faecium. Antimicrob Agents Chemother 1998; 42: 721–4

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

Author information

Authors and Affiliations

  1. Clinical Service Unit Pharmaceutical Sciences, Vancouver Hospital and Health Sciences Centre, and Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada

    Richard S. Slavik &  Peter J. Jewesson

Authors
  1. Richard S. Slavik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter J. Jewesson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter J. Jewesson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Slavik, R.S., Jewesson, P.J. Selecting Antibacterials for Outpatient Parenteral Antimicrobial Therapy. Clin Pharmacokinet 42, 793–817 (2003). https://doi.org/10.2165/00003088-200342090-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-200342090-00002

Keywords

Search

Navigation