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Continuous versus intermittent infusions of antibiotics for the treatment of severe acute infections

  1. Jennifer R Shiu1,
  2. Erica Wang2,
  3. Aaron M Tejani3,*,
  4. Michael Wasdell4

Editorial Group: Cochrane Injuries Group

Published Online: 28 MAR 2013

Assessed as up-to-date: 13 SEP 2012

DOI: 10.1002/14651858.CD008481.pub2


How to Cite

Shiu JR, Wang E, Tejani AM, Wasdell M. Continuous versus intermittent infusions of antibiotics for the treatment of severe acute infections. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD008481. DOI: 10.1002/14651858.CD008481.pub2.

Author Information

  1. 1

    Alberta Health Services, Edmonton, Canada

  2. 2

    Interior Health Authority, Kelowna General Hospital, Kelowna, Canada

  3. 3

    University of British Columbia, Therapeutics Initiative, Vancouver, BC, Canada

  4. 4

    Bridgepoint Collaboratory for Research and Innovation Bridgepoint Health, Toronto, Canada

*Aaron M Tejani, Therapeutics Initiative, University of British Columbia, 2176 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada. Aaron.Tejani@fraserhealth.ca.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 28 MAR 2013

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References

References to studies included in this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
  5. References to other published versions of this review
Adembri 2008 {published data only}
  • Adembri C, Fallani S, Cassetta MI, Arrigucci S, Ottaviano A, Pecile P, Mazzei T, De Gaudio R, Novelli A. Linezolid pharmacokinetic/pharmacodynamic profile in critically ill septic patients: intermittent versus continuous infusion. International Journal of Antimicrobial Agents 2008;31(2):122-9.
Angus 2000 {published data only}
Bodey 1979 {published data only}
  • Bodey GP, Ketchel SJ, Rodriguez V. A randomized study of carbenicillin plus cefamandole or tobramycin in the treatment of febrile episodes in cancer patients. American Journal of Medicine 1979;67(4):608-16.
Buck 2005 {published data only}
  • Buck C, Bertram N, Ackermann T, Sauerbruch T, Derendorf H, Paar WD. Pharmacokinetics of piperacillin-tazobactam: intermittent dosing versus continuous infusion. International Journal of Antimicrobial Agents 2005;25(1):62-7.
Chytra 2012 {published and unpublished data}
  • Chytra I, Stepan M, Benes J, Pelnar P, Zidkova A, Bergerova T, Pradl R, Kasal E. Clinical and microbiological efficacy of continuous versus intermittent application of meropenem in critically ill patients: a randomized open-label controlled trial. Critical Care 2012;16:R113 (Epub ahead of print).
Cousson 2005 {published and unpublished data}
  • Cousson J, Floch T, Vernet-Garnier V, Appriou M, Petit JS, Jovenin N, Lamiable D, Hoizey G. Pharmacodynamic interest of ceftazidime continuous infusion vs intermittent bolus administration in patients with severe nosocomial pneumonia (French). Pathologie Biologie 2005;53:546-50.
DeJongh 2008 {published and unpublished data}
  • De Jongh R, Hens R, Basma V, Mouton JW, Tulkens PM, Carryn S. Continuous versus intermittent infusion of temocillin, a directed spectrum penicillin for intensive care patients with nosocomial pneumonia: stability, compatibility, population pharmacokinetic studies and breakpoint selection. Journal of Antimicrobial Chemotherapy 2008;61(2):382-8.
Feld 1977 {published data only}
  • Feld R, Valdivieso M, Bodey GP, Rodriguez V. A comparative trial of sisomicin therapy by intermittent versus continuous infusion. The American Journal of the Medical Sciences 1977;274(2):179-88.
Feld 1984 {published data only}
  • Feld R, Rachlis A, Tuffnell PG, Duncan I, Moran L, Pinfold P, DeBoer G. Empiric therapy for infections in patients with granulocytopenia. Continuous v interrupted infusion of tobramycin plus cefamandole. Archives of Internal Medicine 1984;144(5):1005-10.
Georges 2005 {published data only}
  • Georges B, Conil JM, Cougot P, Decun JF, Archambaud M, Seguin T, Chabanon G, Virenque C, Houin G, Saivin S. Cefepime in critically ill patients: continuous infusion vs. an intermittent dosing regimen. International Journal of Clinical Pharmacology and Therapeutics 2005;43(8):360-9.
Hanes 2000 {published data only}
  • Hanes SD, Wood GC, Herring V, Croce MA, Fabian TC, Pritchard E, Boucher BA. Intermittent and continuous ceftazidime infusion for critically ill trauma patients. The American Journal of Surgery 2000;179(6):436-40.
Lagast 1983 {published data only}
Lau 2006 {published data only}
  • Lau WK, Mercer D, Itani KM, Nicolau DP, Kuti JL, Mansfield D, Dana A. Randomized, open-label, comparative study of piperacillin-tazobactam administered by continuous infusion versus intermittent infusion for treatment of hospitalized patients with complicated intra-abdominal infection. Antimicrobial Agents and Chemotherapy 2006;50(11):3556-61.
Lipman 1999 {published data only}
Lubasch 2003 {published data only}
  • Lubasch A, Luck S, Hartmut L, Mauch H, Lorenz J, Bolcskei P, Welte T. Optimizing ceftazidime pharmacodynamics in patients with acute exacerbation of severe chronic bronchitis. Journal of Antimicrobial Chemotherapy 2003;51:659-64.
Nicolau 1999a {published data only}
  • Nicolau DP, McNabb J, Lacy MK, Li J, Quintiliani R, Nightingale CH. Pharmacokinetics and pharmacodynamics of continuous and intermittent ceftazidime during the treatment of nosocomial pneumonia. Clinical Drug Investigation 1999;18(2):133-9.
Nicolau 1999b {published data only}
  • Nicolau DP, Lacy MK, McNabb J, Quintiliani R, Nightingale CH. Pharmacokinetics of continuous and intermittent ceftazidime in intensive care unit patients with nosocomial pneumonia. Infectious Diseases in Clinical Practice 1999;8(1):45-9.
Nicolau 2001 {published data only}
  • Nicolau DP, McNabb J, Lacy MK, Quintiliani R, Nightingale CH. Continuous versus intermittent administration of ceftazidime in intensive care unit patients with nosocomial pneumonia. International Journal of Antimicrobial Agents 2001;17(6):497-504.
Okimoto 2009 {published data only}
  • Okimoto N, Ishiga M, Nanba F, Kibayashi T, Kishimoto M, Kurihara T, Honda Y, Asaoka N, Tamada S. Clinical effects of continuous infusion and intermittent infusion of meropenem on bacterial pneumonia in the elderly (Japanese). Nihon Kokyuki Gakkai Zasshi 2009;47(7):553-7.
Pedeboscq 2001 {published and unpublished data}
  • Pedeboscq S, Dubau B, Frappier S, Hernandez V, Veyssieres D, Winnock S, Pometan JP. Comparison of 2 administration protocols (continuous or discontinuous) of a time-dependent antibiotic, Tazocin (French). Pathologie Biologie (Paris) 2001;49(7):540-7.
Rafati 2006 {published data only}
  • Rafati MR, Rouini MR, Mojtahedzadeh M, Najafi A, Tavakoli H, Gholami K, Fazeli MR. Clinical efficacy of continuous infusion of piperacillin compared with intermittent dosing in septic critically ill patients. International Journal of Antimicrobial Agents 2006;28(2):122-7.
Roberts 2007 {published and unpublished data}
  • Roberts JA, Boots R, Rickard CM, Thomas P, Quinn J, Roberts DM, Richards B, Lipman J. Is continuous infusion ceftriaxone better than once-a-day dosing in intensive care? A randomized controlled pilot study. Journal of Antimicrobial Chemotherapy 2007;59(2):285-91.
Roberts 2009b {published and unpublished data}
  • Roberts JA, Kirkpatrick CMJ, Roberts MS, Robertson TA, Dalley AJ, Lipman J. Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte Carlo dosing simulations and subcutaneous tissue distribution. Journal of Antimicrobial Chemotherapy 2009;64(1):142-50.
Roberts 2009c {published and unpublished data}
  • Roberts JA, Roberts MS, Robertson TA, Dalley AJ, Lipman J. Piperacillin penetration into tissue of critically ill patients with sepsis-bolus versus continuous administration?. Critical Care Medicine 2009;37(3):926-33.
Roberts 2010 {published and unpublished data}
  • Roberts JA, Kirkpatrick CMJ, Roberts MS, Dalley AJ, Lipman J. First-dose and steady-state population pharmacokinetics and pharmacodynamics of piperacillin by continuous or intermittent dosing in critically ill patients with sepsis. International Journal of Antimicrobial Agents 2010;35:156-63.
Sakka 2007 {published data only}
  • Sakka SG, Glauner AK, Bulitta JB, Kinzig-Schippers M, Pfister W, Drusano GL, Sorgel F. Population pharmacokinetics and pharmacodynamics of continuous versus short-term infusion of imipenem-cilastatin in critically ill patients in a randomized, controlled trial. Antimicrobial Agents and Chemotherapy 2007;51(9):3304-10.
van Zanten 2007 {published and unpublished data}
  • van Zanten ARH, Oudijk M, Nohlmans-Paulssen MKE, van der Meer YG, Girbes ARJ, Polderman KH. Continuous vs. intermittent cefotaxime administration in patients with chronic obstructive pulmonary disease and respiratory tract infections: pharmacokinetics/pharmacodynamics, bacterial susceptibility and clinical efficacy. British Journal of Clinical Pharmacology 2007;63(1):100-9.
Wright 1979 {published data only}
  • Wright JP, Potgieter PD, Forder AA, Botha P, Brinkworth G, Elisha G, Ferguson AD. Gentamicin and penicillin in the treatment of severe respiratory infections. South African Medical Journal 1979;55(6):197-200.
Wysocki 2001 {published and unpublished data}
  • Wysocki M, Delatour F, Faurisson F, Rauss A, Pean Y, Misset B, Thomas F, Timsit JF, Similowski T, Mentec H, Mier L, Dreyfuss D, and the study group. Continuous versus intermittent infusion of vancomycin in severe staphylococcal infections: prospective multicenter randomized study. Antimicrobial Agents and Chemotherapy 2001;45(9):2460-7.

References to studies excluded from this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
  5. References to other published versions of this review
Adembri 2010 {published data only}
  • Adembri C, Ristori R, Chelazzi C, Arrigucci S, Cassetta MI, De Gaudio AR, Novelli A. Cefazolin bolus and continuous administration for elective cardiac surgery: improved pharmacokinetic and pharmacodynamic parameters. Journal of Thoracic and Cardiovascular Surgery 2010;140:471-5.
Ambrose 1998 {published data only}
  • Ambrose PG, Quindliani R, Nightingale CH, Nicolau DP. Continuous vs. intermittent infusion of cefuroxime for the treatment of community-acquired pneumonia. Infectious Diseases in Clinical Practice 1998;7(9):463-70.
Benko 1996 {published data only}
  • Benko A, Cappelletty D, Kruse J, Rybak M. Continuous infusion versus intermittent administration of ceftazidime in critically ill patients with suspected gram-negative infections. Antimicrobial Agents and Chemotherapy 1996;40(3):691-95.
Bosso 1999 {published data only}
Buijk 2002 {published data only}
  • Buijk SLCE, Gyssens IC, Mouton JW, Van Vliet A, Verbrugh HA. Pharmacokinetics of ceftazidime in serum and peritoneal exudate during continuous versus intermittent administration to patients with severe intra-abdominal infections. Journal of Antimicrobial Chemotherapy 2002;49(1):121-8.
Burgess 2002 {published data only}
  • Burgess D, Waldrep T. Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam when administered by continuous infusion and intermittent dosing. Clinical Therapeutics 2002;24(7):1090-1104.
DeRyke 2006 {published data only}
  • DeRyke CA, Kuti JL, Mansfield D, Dana A, Nicolau DP. Pharmacoeconomics of continuous versus intermittent infusion of piperacillin-tazobactam for the treatment of complicated intraabdominal infection. American Journal of Health System Pharmacy 2006;63(8):750-5.
Georges 1999 {published data only}
  • Georges B, Archambaud M, Saivin S, Decun J, Cougot P, Mazerolles M, Andrieu P, Suc C, Houin G, Chabanon G, Virenque C. Continuous versus intermittent cefepime infusion in critical care. Preliminary results (French). Pathologie Biologie 1999;47(5):483-85.
Grant 2002 {published data only}
Hutschala 2009 {published data only}
  • Hutschala D, Kinstner C, Skhirdladze K, Thalhammer F, Muller M, Tschernko E. Influence of vancomycin on renal function in critically ill patients after cardiac surgery. Anesthesiology 2009;111:356-65.
James 1996 {published data only}
  • James J, Palmer S, Levine D, Rybak M. Comparison of conventional dosing versus continuous-infusion vancomycin therapy for patients with suspected or documented gram-positive infections. Antimicrobial Agents and Chemotherapy 1996;40(3):696-700.
Jaruratanasirikul 2002 {published data only}
Jaruratanasirikul 2005 {published data only}
  • Jaruratanasirikul S, Sriwiriyajan S, Punyo J. Comparison of the pharmacodynamics of meropenem in patients with ventilator-associated pneumonia following administration by 3-hour infusion or bolus injection. Antimicrobial Agents and Chemotherapy 2005;49(4):1337-39.
Jaruratanasirikul 2009 {published data only}
  • Jaruratanasirikul S, Sudsai T. Comparison of the pharmacodynamics of imipenem in patients with ventilator-associated pneumonia following administration by 2 or 0.5h infusion. Journal of Anitimicrobial Chemotherapy 2009;63:560-63.
Jaruratanasirikul 2010 {published data only}
  • Jaruratanasirikul S, Julamanee J, Sudsai T, Saengsuwan P, Jullangkoon M, Ingviya N, Jarumanokul R. Comparison of continuous infusion versus intermittent infusion of vancomycin in patients with methicillin-resistant Staphylococcus aureus. Journal of the Medical Association of Thailand 2010;93(2):172-6.
Kirkpatrick 2001 {published data only}
  • Kickpatrick C, Howard G, Vella-Brincat J. Comment: serum concentrations of cefuroxime after continuous infusion in coronary bypass graft patients. The Annals of Pharmacotherapy 2001;53:1295-96.
Klepser 1998 {published data only}
  • Klepser M, Patel K, Nicolau D, Quintiliani R, Nightingale C. Comparison of bactericidal activities of intermittent and continuous infusion dosing of vancomycin against methicillin-resistant staphylococcus aureus and enterococcus faecalis. Pharmacotherapy 1998;18(5):1069-74.
Kojika 2005 {published data only}
  • Kojika M, Sato N, Hakozaki M, Suzuki Y, Takahasi G, Endo S, Suzuki K, Wakabayasi G. A preliminary study of the administration of carbapenem antibiotics in sepsis patients on the basis of administration time. The Japanese Journal of Antibiotics 2005;58(5):452-7.
Langgartner 2007 {published data only}
  • Langgartner J, Lehn N, Gluck T, Herzig H, Kees F. Comparison of the pharmacokinetics of piperacillin and sulbactam during intermittent and continuous intravenous infusion. Chemotherapy 2007;53:370-77.
Li 2005 {published data only}
  • Li C, Kuti JL, Nightingale CH, Mansfield DL, Dana A, Nicolau DP. Population pharmacokinetics and pharmacodynamics of piperacillin/tazobactam in patients with complicated intra-abdominal infection. Journal of Antimicrobial Chemotherapy 2005;56(2):388-95.
Lorente 2006 {published data only}
  • Lorente L, Lorenzo L, Martin MM, Jimenez A, Mora ML. Meropenem by continuous versus intermittent infusion in ventilator-associated pneumonia due to gram-negative bacilli. Annals of Pharmacotherapy 2006;40:219-23.
Martin 1998 {published data only}
  • Martin C, Cotin A, Giraud A, Beccani-Argeme M, Alliot P, Mallet MN, Argeme M. Comparison of concentrations of sulbactam-ampicillin administered by bolus injections or bolus plus continuous infusion in tissues of patients undergoing colorectal surgery. Antimicrobial Agents and Chemotherapy 1998;42(5):1093-97.
McNabb 2001 {published data only}
Nicasio 2007 {published data only}
Pass 2001 {published data only}
  • Pass SE, Miyagawa CI, Healy DP, Ivey TD. Serum concentrations of cefuroxime after continuous infusion in coronary bypass graft patients. Annals of Pharmacotherapy 2001;35:409-13.
Schuster 2009 {published data only}
  • Schuster KM, Wilson D, Schulman CI, Pizano LR, Ward CG, Namias N. Continuous infusion oxacillin for the treatment of burn wound cellulitis. Surgical Infections 2009;10(1):41-5.
Seguin 2009 {published data only}
  • Seguin P, Verdier M, Chanavaz C, Engrand C, Laviolle B, Donnio P, Malledant Y. Plasma and peritoneal concentration following continuous infusion of cefotaxime in patients with secondary peritonitis. Journal of Antimicrobial Chemotherapy 2009;63:564-67.
Thalhammer 1999 {published data only}
  • Thalhammer F, Traunmuller F, El Menyawi I, Frass M, Hollenstein U, Locker G, Stoiser B, Staudinger T, Thalhammer-Scherrer R, Burgmann H. Continuous infusion versus intermittent administration of meropenem in critically ill patients. Journal of Antimicrobial Chemotherapy 1999;43:523-27.
Vinks 2003 {published data only}
  • Vinks A, Hollander J, Overbeek S, Jelliffe R, Mouton J. Population pharmacokinetic analysis of nonlinear behavior of piperacillin during intermittent of continuous infusion in patients with cystic fibrosis. Antimicrobial Agents and Chemotherapy 2003;47(2):541-47.
Vuagnat 2004 {published data only}
Waltrip 2002 {published data only}
  • Waltrip T, Lewis R, Young V, Farmer M, Clayton S, Myers S, Gray L, Galandiuk S. A pilot study to determine the feasibility of continuous cefazolin infusion. Surgical Infections 2002;3(1):5-9.

References to ongoing studies

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
  5. References to other published versions of this review
Cousson 2010 {unpublished data only}
  • Cousson J, Floch T, Hoizey G, Nicolai F, Guillard T, Vernet-Garnier V. Comparison of pharmacodynamic interest of ceftazidime continuous infusion vs intermittent bolus administration in epithelial lining fluid concentrations of patients with severe nosocomial pneumonia. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (poster) 2010.
NCT00891423 {unpublished data only}
  • Johnson P. A Randomised controlled crossover pilot study of meropenem standard 30 minute infusion versus prolonged 3 hour infusion in intensive care patients. Available at http://www.clinicaltrials.gov, last updated July 2012. Accessed November 14, 2012.
NCT01158937 {unpublished data only}
  • Cortes D. Pharmacokinetic study of extended infusion meropenem in adult cystic fibrosis patients with exacerbation of pulmonary infection. Available at http://www.clinicaltrials.gov, last updated June 2012. Accessed November 14, 2012.
NCT01198925 {unpublished data only}
  • Decruyenaere J. Assessment of the optimal dosing of piperacillin-tazobactam in intensive care unit patients: extended versus continuous infusion. Available at http://www.clinicaltrials.gov, last updated July 2012. Accessed November 14, 2012.
NCT01379157 {unpublished data only}
  • Jaruratanasirikul S. The pharmacodynamics of imipenem in critically ill patients with ventilator-associated pneumonia following administration by 4h or 0.5h infusion. Available at http://www.clinicaltrials.gov, last updated December 2011. Accessed November 14, 2012.
NCT01577368 {unpublished data only}
  • Gil-Navarro MV. Efficacy and safety of piperacillin-tazobactam continuous infusion vs intermittent infusion for complicated or nosocomial Pseudomonas aeruginosa infection or suspected infection. Available at http://www.clinicaltrials.gov, last updated April 2012. Accessed November 14, 2012.
NCT01667094 {unpublished data only}
  • Peleg A. Continuous infusion anti-pseudomonal beta-lactams for the treatment of acute, infective pulmonary exacerbations in cystic fibrosis: a prospective randomised controlled trial. Available at http://www.clinicaltrials.gov, last updated August 2012. Accessed November 14, 2012.
NCT01720940 {unpublished data only}
  • Fisher D. Reducing nephrotoxicity of vancomycin: a prospective, randomised study of continuous versus intermittent infusion of vancomycin. Available at http://www.clinicaltrials.gov, last updated November 2012. Accessed November 14, 2012.

Additional references

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
  5. References to other published versions of this review
Ariano 2010
  • Ariano R, Zelenitsky S, McCormack J. Should IV antibiotics be administered by prolonged infusion?. Canadian Journal of Hospital Pharmacy 2010;63(3):246-9.
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Craig 1998
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Florea 2003
  • Florea NR, Kotapati S, Kuti JL, Geissler EC, Nightingale CH, Nicolau DP. Cost analysis of continuous versus intermittent infusion of piperacillin–tazobactam: a time–motion study. American Journal of Health System Pharmacy 2003;60(22):2321-7.
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Nicolau 1996
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Roberts 2008
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Roberts 2009a
Rosenthal 2012
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References to other published versions of this review

  1. References to studies included in this review
  2. References to studies excluded from this review
  3. References to ongoing studies
  4. Additional references
  5. References to other published versions of this review
Yu 2010
  • Yu IS, Tejani AM, Wasdell M. Continuous versus intermittent infusions of antibiotics for the treatment of severe acute infections (Protocol). Cochrane Database of Systematic Reviews 2010, Issue 4. [DOI: 10.1002/14651858.CD008481]