Skip to main content
Log in

Community-Based Parenteral Anti-Infective Therapy (CoPAT)

Pharmacokinetic and Monitoring Issues

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

Abstract

Community-based parenteral anti-infective therapy (CoPAT) has, over the past 20 years, increased rapidly in many parts of the world including North America, Europe, South America and Australia. CoPAT is a multidisciplinary activity demanding close cooperation between nurses, pharmacists and physicians, as well as with the patient. The selection of an anti-infective drug for use outside the hospital setting must take into account not only the therapeutic effectiveness, cost effectiveness and safety of the drug, but also pharmacological factors such as the dosage schedule and the stability of the drug. Dosage schedules vary with pharmacokinetic factors (e.g. the use of drugs with long half-lives are favoured by CoPAT programmes) and pharmacodynamic features (e.g. once daily gentamicin therapy is attractive and practical because of concentration-dependent bactericidal killing and prolonged post-antibiotic effect). With selected drugs, the renal and, to a lesser degree, liver function of the patient will influence the dosage schedule.

The mode of intravenous (IV) drug administration will vary with volume considerations (limiting the use of syringe-infusion therapy for some drugs), stability issues (prevents drugs that are stable at room temperature for less than 24 hours from being used in multidose computerised delivery systems), as well as patient factors (ability to self administer an IV drug). Monitoring serum antimicrobial concentrations is undertaken to assure effectiveness and avoid toxicity, and is indicated for drugs with a narrow therapeutic window, such as the aminoglycosides. With the advent of the single daily dose administration of aminoglycosides, checking serum concentrations at the mid-point, i.e. 6 to 14 hours following administration of the first dose, is one approach. Because the toxic effects of vancomycin have been overstated, serum concentrations should only be obtained for defined indications primarily to assure therapeutic effectiveness.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  3. Kind AC, Williams DN, Persons G, et al. Intravenous antibiotic therapy at home. Arch Intern Med. 1979; 139: 413–5.

    Article  PubMed  CAS  Google Scholar 

  4. 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 

  5. Rehm SJ, Weinstein AJ. Home intravenous antibiotic therapy: a team approach. Ann Intern Med. 1983; 99: 388–92.

    PubMed  CAS  Google Scholar 

  6. Tice AD. An office model of outpatient parenteral antibiotic therapy. Rev Infect Dis. 1991; 13 Suppl. 2: S184–8.

    Article  PubMed  Google Scholar 

  7. Tice AD. The team concept: symposium on outpatient parenteral antibiotic therapy. Hosp Pract. 1993; 28 Suppl. I: 6–10.

    Google Scholar 

  8. Baumgartner JD, Glauser MP. Single daily dose treatment of severe refractory infections with ceftriaxone. Arch Intern Med. 1983; 143: 1868–73.

    Article  PubMed  CAS  Google Scholar 

  9. Winter RJD, Deacock SJ, George RJD, et al. Self-administered home intravenous antibiotic therapy in bronchiectasis and adult cystic fibrosis. Lancet. 1984; I: 1338–9.

    Article  Google Scholar 

  10. Grayson ML, Silvers J, Turnidge J. Home intravenous antibiotic therapy: a safe and effective alternative to inpatient care. Med J Aust. 1995; 162: 249–53.

    PubMed  CAS  Google Scholar 

  11. Kayley J, Berendt AR, Snelling MJM, et al. Antimicrobial practice. Safe intravenous antibiotic therapy at home: experience of a UK based programme. J Antimicrob Chemother. 1996; 37: 1023–9.

    Article  PubMed  CAS  Google Scholar 

  12. 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 

  13. Francioli P, Etienne J, Hoigne R, et al. Treatment of streptococcal endocarditis with a single daily dose of ceftriaxone sodium for four weeks: efficacy and outpatient treatment feasibility. JAMA. 1992; 267: 264–7.

    Article  PubMed  CAS  Google Scholar 

  14. Stamboulian D, Bonhevi P, Arevalo C, et al. Antibiotic management of outpatients with endocarditis due to penicillin-susceptible streptococci. Rev Infect Dis. 1991; 13 Suppl. 2: S160–3.

    Article  PubMed  Google Scholar 

  15. 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 

  16. Pallares R, Linares J, Vadillo M, et al. Resistance to penicillin and cephalosporin and mortality from severe pneumococcal phenomena in Barcelona Spain. N Engl J Med 1995: 333(24): 474–80.

    Article  PubMed  CAS  Google Scholar 

  17. Hoffman J, Cetron MS, Farley MN, et al. The prevalence of drug-resistant streptococcus pneumoniae in Atlanta. N Engl J Med. 1995; 333(24): 481–6.

    Article  Google Scholar 

  18. Recommendations of the Hospital Infection Control Practices Advisory Committee. Recommendations for preventing the spread of vancomycin resistance. MMWR Morb Mortal Wkly Rep. 1994; 44: 1–13.

    Google Scholar 

  19. Centers for Disease Control and Prevention. Interim guidelines for prevention and control of staphylococcal infection associated with reduced susceptibility to vancomycin. MMWR Morb Mortal Wkly Rep. 1997; 46: 626–8.

    Google Scholar 

  20. Poretz DM. The infusion center: a model for outpatient parenteral antibiotic therapy. Rev Infect Dis. 1991; 13 Suppl. 2: S142–46.

    Article  PubMed  Google Scholar 

  21. Tice AD. The office and clinic model for OPAT. Report: a special report from Scientific American Medicine. Proceedings of an OPAT Advisory Board Meeting; 1996 May 16–18; Chicago.

    Google Scholar 

  22. Williams DN. Home intravenous antibiotic therapy (HIVAT): indications, patients and antimicrobial agents. Int J Antimicrob Agents. 1995; 5: 3–8.

    Article  PubMed  CAS  Google Scholar 

  23. Craig WA. Antibiotic selection factors and description of a hospital-based outpatient antibiotic therapy program in the USA. Eur J Clin Microbiol Infect Dis. 1995; 14: 636–42.

    Article  PubMed  CAS  Google Scholar 

  24. Deguchi Y, Terasaki T, Yamada H, et al. An application of microdialysis to drug tissue distribution study: in vivo evidence for free-ligand hypothesis and tissue binding of betalactam antibiotics in interstitial fluids. J Pharmacobiodyn. 1992; 15: 78–89.

    Article  Google Scholar 

  25. Shyu WC, Quintiliani R, Nightengale CH, et al. Effect of protein binding on drug penetration into blister fluid. Antimicrob Agents Chemother. 1988; 32: 128–30.

    Article  PubMed  CAS  Google Scholar 

  26. Scaglione F. Predicting the clinical efficacy of antibiotics: toward definitive criteria. Pediatr Infect Dis J. 1997; 16: 556–9.

    Google Scholar 

  27. Hyatt JM, McKinnon PS, Zimmer GS, et al. The importance of pharmacokinetic/pharmacodynamic surrogate markers to outcome: focus on antibacterial agents. Clin Pharmacokinet Concepts. 1995; 28(2): 143–60.

    Article  CAS  Google Scholar 

  28. Forrest A, Nix DE, Ballow CH, et al. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother. 1993; 37(5): 1073–81.

    Article  PubMed  CAS  Google Scholar 

  29. Dalla Costa T, Derendorf H. AUIC: a general target for the optimization of dosing regimens of antibiotics. Ann Pharmacother. 1996; 30: 1024–31.

    PubMed  CAS  Google Scholar 

  30. Dudley MN, Mandler HD, Gilbert D, et al. Pharmacokinetics and pharmacodynamics of intravenous ciprofloxacin. Am J Med. 1987; 82 Suppl. 4A: 363–8.

    PubMed  CAS  Google Scholar 

  31. Follath F, Bindschedler M, Wenk M, et al. Clinical efficacy of ciprofloxacin in pseudomonas infections. In: Neu HC, Wevta H, editors. Proceedings of the First International Ciprofloxacin Workshop. Amsterdam: Elsevier Science Publishing, 1989: 411–3.

    Google Scholar 

  32. 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 bactericical activity and emergence of resistance. Antimicrob Agents Chemother. 1987; 31: 1054–60.

    Article  PubMed  CAS  Google Scholar 

  33. 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(1): 93–9.

    Article  PubMed  CAS  Google Scholar 

  34. 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: 608–11.

    Article  PubMed  CAS  Google Scholar 

  35. Craig WA, Ebert SC. Continuous infusion of beta-lactam antibiotics. Antimicrob Agents Chemother. 1992; 36(12): 2577–83.

    Article  PubMed  CAS  Google Scholar 

  36. Mouton JW, Vinks AA. Is continuous infusion of beta-lactam antibiotics worthwhile? Efficacy and pharmacokinetic considerations. J Antimicrob Chemother. 1996; 38(1): 5–15.

    Article  PubMed  CAS  Google Scholar 

  37. Klepser ME, Kang SL, McGrath BJ, et al. Influence of vancomycin serum concentration on the outcome of gram-positive infections. American College of Clinical Pharmacy Annual Winter Meeting; 1994 Feb 6–9, San Diego.

    Google Scholar 

  38. Livernese LL, Benz RL, Ingerman MJ, et al. Antibacterial agents in renal failure. Infect Dis Clin North Am. 1995; 9(3): 591–614.

    Google Scholar 

  39. Bennett WM, Aronoff JR, Golper TA, et al., editors. Drug prescribing in renal failure: dosing guidelines for adults. 3rd ed. Philadelphia: American College of Physicians, 1994.

    Google Scholar 

  40. Haug MT III, Slug PH. Antibiotic pharmacokinetics. In: Sivak ED, Higgins TL, Seiver A, editors. The high risk patient: management of the critically ill. Baltimore: Williams & Wilkins, 1995: 1338–64.

    Google Scholar 

  41. Tschida SJ, Vance-Bryan K, Zaske DE. Anti-infective agents and hepatic disease. Med Clin North Am. 1995; 79(4): 895–917.

    PubMed  CAS  Google Scholar 

  42. Cockroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976; 16: 31–41.

    Article  Google Scholar 

  43. Wu G, Furlanut M. Predictions of serum vancomycin concentrations by means of six different equations for calculation of creatinine clearance. Int J Clin Pharmacol Res. 1997; 17(1): 1–10.

    PubMed  CAS  Google Scholar 

  44. Jelliffe RW, Schumitzky A, Bayard D, et al. Model-based, goaloriented, individualized drug therapy: linkage of population modelling, new ‘multiple model’ dosage design, bayesian feedback and individualized target goals. Clin Pharmacokinet. 1998; 34(1): 57–77.

    Article  PubMed  CAS  Google Scholar 

  45. Nicolau DP, Freeman CD, Belliveau PP, et al. Experience with once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents Chemother. 1995; 39: 650–5.

    Article  PubMed  CAS  Google Scholar 

  46. Nicolau DP, Nightingale CH, Banevicns MA, et al. Serum bactericidal activity of ceftazidime: continuous infusion versus intermittent injections. Antimicrob Agents Chemother 1996 Jan; 40(1): 61–4.

    PubMed  CAS  Google Scholar 

  47. Weinstein MP, Stratton CW, Hawley HB, et al. Multicenter collaborative evaluation of a standardized serum bactericidal test as a predictor of therapeutic efficacy in acute and chronic osteomyelitis. Am J Med. 1987; 83(2): 218–22.

    Article  PubMed  CAS  Google Scholar 

  48. Vinks AA, Brimicombe RW, Heijerman H, et al. Continuous infusion of ceftazidime in cystic fibrosis patients during home treatment: clinical outcome microbiology and pharmacokinetics. J Antimicrob Chemother 1997: 40(1): 125–33.

    Article  PubMed  CAS  Google Scholar 

  49. Nadworny HA, Markowitz A. Parenteral antibiotic therapy at home: experience with intramuscular cefonicid. Clin Ther. 1987; 10: 82–91.

    PubMed  CAS  Google Scholar 

  50. Dagan R, Philip M, Watemberg NM, et al. Outpatient treatment of serious outpatient community-acquired pediatric infections using once-daily intramuscular ceftriaxone. Pediatr Infect Dis J. 1984; 3: 514–7.

    Article  Google Scholar 

  51. Russo TA, Cook S, Gorbach SL. Intramuscular ceftriaxone in home parenteral therapy. Antimicrob Agents Chemother. 1988; 32(4): 1439–40.

    Article  PubMed  CAS  Google Scholar 

  52. Wagner DK, Collier BD, Rytel MW. Long-term intravenous antibiotic therapy in chronic osteomyelitis. Arch Intern Med. 1985; 145: 1073–8.

    Article  PubMed  CAS  Google Scholar 

  53. Siber GR, Echeverria P, Smith AL, et al. Pharmacokinetics of gentamicin in children and adults. J Infect Dis. 1975; 132(6): 637–51.

    Article  PubMed  CAS  Google Scholar 

  54. Edelstein HE, Oster SE, Chirurgi VA, et al. Intravenous or intramuscular teicoplanin once daily for skin and soft-tissue infections. DICP Ann Pharmacother. 1991; 25: 914–8.

    CAS  Google Scholar 

  55. Verbist L, Tjandramaga B, Hendrickx B, et al. In vitro activity and human pharmacokinetics of teicoplanin. Antimicrob Agents Chemother. 1984; 26: 881–6.

    Article  PubMed  CAS  Google Scholar 

  56. McNulty Jr TJ. Initiation of antimicrobial therapy in the home. Am J Hosp Pharm. 1993; 50: 773–4.

    Google Scholar 

  57. O’sullivan TL, Ruffing MJ, Lamp KC, et al. Prospective evaluation of Red Man Syndrome in patients receiving vancomycin. J Infect Dis. 1993; 168: 773–6.

    Article  PubMed  Google Scholar 

  58. Trissel LA. Handbook of injectable drugs. 9th ed. Bethesda: American Society of Health-System Pharmacists, 1996.

    Google Scholar 

  59. King JC. King guide to parenteral admixtures. St Louis: King Guide Publications, 1996.

    Google Scholar 

  60. Tice AD. Handbook of outpatient parenteral therapy for infectious diseases. New York: Scientific American, 1997.

    Google Scholar 

  61. Stiles ML, Allen Jr LV, Prince SJ. Stability of various antibiotics kept in an insulated pouch during administration via portable infusion pump. Am J Health Syst Pharm. 1995; 52: 70–4.

    PubMed  CAS  Google Scholar 

  62. Neftel KA, Walti M, Spengler H, et al. Effect of storage of penicillin-G solutions on sensitization to penicillin-G after intravenous administration. Lancet 1982; I (8279): 986–8.

    Article  Google Scholar 

  63. Neftel KA, Walti M, Schulthess HK, et al. Adverse reactions following intravenous penicillin-G relate to degradation of the drug in vitro. Klin Wochenschr. 1984; 62(1): 25–9.

    Article  PubMed  CAS  Google Scholar 

  64. Moellering Jr RC. Monitoring serum vancomycin levels: climbing the mountain because it is there? [editorial]. Clin Infect Dis. 1994; 18: 544–6.

    Article  PubMed  Google Scholar 

  65. Moellering Jr RC, Krogstad DJ, Greenblatt DJ. Vancomycin therapy in patients with impaired renal function: a nomogram for dosage. Ann Intern Med. 1981; 94: 343–6.

    PubMed  Google Scholar 

  66. 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(3): 696–700.

    PubMed  CAS  Google Scholar 

  67. Wood MJ. The comparative efficacy and safety of teicoplanin and vancomycin. J Antimicrob Chemother. 1996; 37: 209–22.

    Article  PubMed  CAS  Google Scholar 

  68. 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 

  69. 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 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David N. Williams.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Williams, D.N., Raymond, J.L. Community-Based Parenteral Anti-Infective Therapy (CoPAT). Clin Pharmacokinet 35, 65–77 (1998). https://doi.org/10.2165/00003088-199835010-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-199835010-00005

Keywords

Navigation