Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Drugs
Published in: Drugs 17/2005

01-12-2005 | Review Article

Continuous versus Intermittent Intravenous Administration of Antibacterials with Time-Dependent Action

A Systematic Review of Pharmacokinetic and Pharmacodynamic Parameters

Authors: Sofia K. Kasiakou, Kenneth R. Lawrence, Nicolaos Choulis, Dr Matthew E. Falagas

Published in: Drugs | Issue 17/2005

Login to get access

Abstract

We performed a systematic review of randomised clinical trials to evaluate the comparative pharmacokinetic and pharmacodynamic properties of the continuous versus intermittent mode of intravenous administration of various antibacterials. Data were identified from PubMed (January 1950 to January 2005), Current Contents, the Cochrane central register of controlled trials, and references from relevant articles and reviews. Seventeen randomised clinical trials comparing continuous with intermittent intravenous administration of the same antibacterial regimen and examining the pharmacokinetic and pharmacodynamic properties were included in this systematic review. We reviewed data regarding the clinical setting, number of participants, antibacterial agents and dosages used, as well as maximum serum concentration (Cmax), trough serum concentration (Cmin), steady-state or plateau serum concentration (Css), area under the concentrationtime curve (AUC), time above the minimum inhibitory concentration (MIC) [T > MIC], AUC: MIC, elimination rate constant, elimination half-life, volume of distribution and systematic clearance. The mean Cmax of the intermittently administered antibacterials was higher compared with Css achieved by the continuous infusion of the same antibacterial in all eligible studies (Cmax was on average 5.5 times higher than Css, range 1.9–11.2). Css was on average 5.8 times higher than the Cmin of the intermittently administered antibacterials (range 1.2–15.6). In three of six studies the length of time that the drug concentration was above the MIC of the responsible pathogens was longer in patients receiving the antibacterials continuously.
In conclusion, the reviewed data suggest that the continuous intravenous infusion of antibacterials with time-dependent bacterial killing seems to be superior than the intermittent intravenous administration, from a pharmacodynamic point of view, at least when treating bacteria with high MIC values for the studied antibacterials.
Literature
1.
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: 608–16PubMedCrossRef
2.
Eagle H, Fleischman R, Levy M. “Continuous” vs “discontinuous” therapy with penicillin: the effect of the interval between injections on therapeutic efficacy. N Engl J Med 1953; 248: 481–8PubMedCrossRef
3.
Feld R, Valdivieso M, Bodey GP, et al. A comparative trial of sisomicin therapy by intermittent versus continuous infusion. Am J Med Sci 1977; 274: 179–88PubMedCrossRef
4.
Lagast H, Meunier-Carpentier F, Klastersky J. Treatment of gram-negative bacillary septicemia with cefoperazone. Eur J Clin Microbiol 1983; 2: 554–8PubMedCrossRef
5.
Powell SH, Thompson WL, Luthe MA, et al. Once-daily vs continuous aminoglycoside dosing: efficacy and toxicity in animal and clinical studies of gentamicin, netilmicin, and tobramycin. J Infect Dis 1983; 147: 918–32PubMedCrossRef
6.
Thys JP, Vanderkelen B, Klastersky J. Pharmacological study of cefazolin during intermittent and continuous infusion: a crossover investigation in humans. Antimicrob Agents Chemother 1976; 10: 395–8PubMedCrossRef
7.
Buck C, Bertram N, Ackermann T, et al. Pharmacokinetics of piperacillin-tazobactam: intermittent dosing versus continuous infusion. Int J Antimicrob Agents 2005; 25: 62–7PubMedCrossRef
8.
Florea NR, Kotapati S, Kuti JL, et al. Cost analysis of continuous versus intermittent infusion of piperacillin-tazobactam: a time-motion study. Am J Health Syst Pharm 2003; 60: 2321–7PubMed
9.
Vuagnat A, Stern R, Lotthe A, et al. High dose vancomycin for osteomyelitis: continuous vs intermittent infusion. J Clin Pharm Ther 2004; 29: 351–7PubMedCrossRef
10.
Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis 1998; 26: 1–10PubMedCrossRef
11.
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: 521–7PubMed
12.
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: 691–5PubMed
13.
Bosso JA, Bonapace CR, Flume PA, et al. A pilot study of the efficacy of constant-infusion ceftazidime in the treatment of endobronchial infections in adults with cystic fibrosis. Pharmacotherapy 1999; 19: 620–6PubMedCrossRef
14.
Di Filippo A, De Gaudio AR, Novelli A, et al. Continuous infusion of vancomycin in methicillin-resistant staphylococcus infection. Chemotherapy 1998; 44: 63–8PubMedCrossRef
15.
Grant EM, Kuti JL, Nicolau DP, et al. Clinical efficacy and pharmacoeconomics of a continuous-infusion piperacillintazobactam program in a large community teaching hospital. Pharmacotherapy 2002; 22: 471–83PubMedCrossRef
16.
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: 1069–74PubMed
17.
Kasiakou SK, Sermaides GJ, Michalopoulos A, et al. Continuous versus intermittent intravenous administration of antibiotics: a meta-analysis of randomised controlled trials. Lancet Infect Dis 2005 Sep; 5(9): 581–9PubMedCrossRef
18.
Angus BJ, Smith MD, Suputtamongkol Y, et al. Pharmacokinetic-pharmacodynamic evaluation of ceftazidime continuous infusion vs intermittent bolus injection in septicaemic melioidosis. Br J Clin Pharmacol 2000; 49: 445–52PubMedCrossRef
19.
Bui KQ, Ambrose PG, Grant E, et al. Pharmacokinetics and pharmacoeconomic evaluation of ticarcillin-clavulanate administered as either continuous or intermittent infusion with once-daily gentamycin. Infect Dis Clin Pract 1999; 8: 449–55CrossRef
20.
Buijk SL, Gyssens IC, Mouton JW, et al. Pharmacokinetics of ceftazidime in serum and peritoneal exudate during continuous versus intermittent administration to patients with severe intraabdominal infections. J Antimicrob Chemother 2002; 49: 121–8PubMedCrossRef
21.
Burgess DS, Hastings RW, Hardin TC. Pharmacokinetics and pharmacodynamics of cefepime administered by intermittent and continuous infusion. Clin Ther 2000; 22: 66–75PubMedCrossRef
22.
Burgess DS, Waldrep T. Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam when administered by continuous infusion and intermittent dosing. Clin Ther 2002; 24: 1090–104PubMedCrossRef
23.
Byl B, Jacobs F, Wallemacq P, et al. Vancomycin penetration of uninfected pleural fluid exudate after continuous or intermittent infusion. Antimicrob Agents Chemother 2003; 47: 2015–7PubMedCrossRef
24.
Eriksson U, Seifert B, Schaffner A. Comparison of effects of amphotericin B deoxycholate infused over 4 or 24 hours: randomised controlled trial. BMJ 2001; 322: 579–82PubMedCrossRef
25.
Feld R, Rachlis A, Tuffneil PG, et al. Empiric therapy for infections in patients with granulocytopenia: continuous v interrupted infusion of tobramycin plus cefamandole. Arch Intern Med 1984; 144: 1005–10PubMedCrossRef
26.
Georges B, Archambaud M, Saivin S, et al. Continuous versus intermittent cefepime infusion in critical care: preliminary results. Pathol Biol (Paris) 1999; 47: 483–5
27.
Giacoia GP, Schentag JJ. Pharmacokinetics and nephrotoxicity of continuous intravenous infusion of gentamicin in low birth weight infants. J Pediatr 1986; 109: 715–9PubMedCrossRef
28.
Hanes SD, Wood GC, Herring V, et al. Intermittent and continuous ceftazidime infusion for critically ill trauma patients. Am J Surg 2000; 179: 436–40PubMedCrossRef
29.
Hitt CM, Nightingale CH, Quintiliani R, et al. Cost comparison of single daily i.v. doses of ceftriaxone versus continuous infusion of cefotaxime. Am J Health Syst Pharm 1997; 54: 1614–8
30.
Hollenstein U, Brunner M, Mayer BX, et al. Target site concentrations after continuous infusion and bolus injection of cefpirome to healthy volunteers. Clin Pharmacol Ther 2000; 67: 229–36PubMedCrossRef
31.
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: 696–700PubMed
32.
Jaruratanasirikul S, Sriwiriyajan S, Ingviya N. Continuous infusion versus intermittent administration of cefepime in patients with Gram-negative bacilli bacteraemia. J Pharm Pharmacol 2002; 54: 1693–6PubMedCrossRef
33.
Leder K, Turnidge JD, Korman TM, et al. The clinical efficacy of continuous-infusion flucloxacillin in serious staphylococcal sepsis. J Antimicrob Chemother 1999; 43: 113–8PubMedCrossRef
34.
Lemmen SW, Engels I, Daschner FD. Serum bactericidal activity of ceftazidime administered as continuous infusion of 3g over 24h versus intermittent bolus infusion of 2g against Pseudomonas aeruginosa in healthy volunteers. J Antimicrob Chemother 1997; 39: 841–2PubMedCrossRef
35.
Lipman J, Gomersall CD, Gin T, et al. Continuous infusion ceftazidime in intensive care: a randomized controlled trial. J Antimicrob Chemother 1999; 43: 309–11PubMedCrossRef
36.
Martin C, Cotin A, Giraud A, et al. Comparison of concentrations of sulbactam-ampicillin administered by bolus injections or bolus plus continuous infusion in tissues of patients undergoing colorectal surgery. Antimicrob Agents Chemother 1998; 42: 1093–7PubMed
37.
McNabb JJ, Nightingale CH, Quintiliani R, et al. Cost-effectiveness of ceftazidime by continuous infusion versus intermittent infusion for nosocomial pneumonia. Pharmacotherapy 2001; 21: 549–55PubMedCrossRef
38.
Mouton JW, Horrevorts AM, Mulder PG, et al. Pharmacokinetics of ceftazidime in serum and suction blister fluid during continuous and intermittent infusions in healthy volunteers. Antimicrob Agents Chemother 1990; 34: 2307–11PubMedCrossRef
39.
Naber KG, Adam D. Tissue concentrations of mezlocillin in benign hypertrophy of the prostate following intravenous bolus injection versus infusion. J Antimicrob Chemother 1983; 11 Suppl. C: 17–23PubMedCrossRef
40.
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: 497–504PubMedCrossRef
41.
Nicolau DP, Nightingale CH, Banevicius MA, et al. Serum bactericidal activity of ceftazidime: continuous infusion versus intermittent injections. Antimicrob Agents Chemother 1996; 40: 61–4PubMed
42.
Rappaz I, Decosterd LA, Bille J, et al. Continuous infusion of ceftazidime with a portable pump is as effective as thrice-a-day bolus in cystic fibrosis children. Eur J Pediatr 2000; 159: 919–25PubMedCrossRef
43.
Richerson MA, Ambrose PG, Bui KQ, et al. Pharmacokinetic and economic evaluation of piperacillin/tazobactam administered as either continuous or intermittent infusion with oncedaily gentamycin. Infect Dis Clin Pract 1999; 8: 195–200CrossRef
44.
Tarn VH, Louie A, Lomaestro BM, et al. Integration of population pharmacokinetics, a pharmacodynamic target, and microbiologic surveillance data to generate a rational empiric dosing strategy for cefepime against Pseudomonas aeruginosa. Pharmacotherapy 2003; 23: 291–5CrossRef
45.
Thalhammer F, Traunmuller F, El M, et al. Continuous infusion versus intermittent administration of meropenem in critically ill patients. J Antimicrob Chemother 1999; 43: 523–7PubMedCrossRef
46.
Thys JP, Mouawad E, Klastersky J. Concentrations of netilmicin in bronchial secretions and serum during intermittent vs continuous infusion: a crossover study in humans. J Infect Dis 1979; 140: 634PubMedCrossRef
47.
Vinks AA, Hollander JG, Overbeek SE, et al. Population pharmacokinetic analysis of nonlinear behavior of piperacillin during intermittent or continuous infusion in patients with cystic fibrosis. Antimicrob Agents Chemother 2003; 47: 541–7PubMedCrossRef
48.
Waltrip T, Lewis R, Young V, et al. A pilot study to determine the feasibility of continuous cefazolin infusion. Surg Infect (Larchmt) 2002; 3: 5–9CrossRef
49.
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: 2460–7PubMedCrossRef
50.
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: 352–4PubMedCrossRef
51.
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: 1356–8PubMedCrossRef
52.
Baririan N, Chanteux H, Viaene E, et al. Stability and compatibility study of cefepime in comparison with ceftazidime for potential administration by continuous infusion under conditions pertinent to ambulatory treatment of cystic fibrosis patients and to administration in intensive care units. J Antimicrob Chemother 2003; 51: 651–8PubMedCrossRef
53.
Berkhout J, Visser LG, van den Broek PJ, et al. Clinical pharmacokinetics of cefamandole and ceftazidime administered by continuous intravenous infusion. Antimicrob Agents Chemother 2003; 47: 1862–6PubMedCrossRef
54.
Bodey GP, Chang HY, Rodriguez V, et al. Feasibility of administering aminoglycoside antibiotics by continuous intravenous infusion. Antimicrob Agents Chemother 1975; 8: 328–33PubMedCrossRef
55.
Boselli E, Breilh D, Duflo F, et al. Steady-state plasma and intrapulmonary concentrations of cefepime administered in continuous infusion in critically ill patients with severe nosocomial pneumonia. Crit Care Med 2003; 31: 2102–6PubMedCrossRef
56.
Burgess DS, Summers KK, Hardin TC. Pharmacokinetics and pharmacodynamics of aztreonam administered by continuous intravenous infusion. Clin Ther 1999; 21: 1882–9PubMedCrossRef
57.
Byl B, Baran D, Jacobs F, et al. Serum pharmacokinetics and sputum penetration of amikacin 30 mg/kg once daily and of ceftazidime 200 mg/kg/day as a continuous infusion in cystic fibrosis patients. J Antimicrob Chemother 2001; 48: 325–7PubMedCrossRef
58.
Chabot GG, Pazdur R, Valeriote FA, et al. Pharmacokinetics and toxicity of continuous infusion amphotericin B in cancer patients. J Pharm Sci 1989; 78: 307–10PubMedCrossRef
59.
Colding H, Andersen GE. Administration of gentamicin and ampicillin by continuous intravenous infusion to newborn infants during parenteral nutrition. Scand J Infect Dis 1982; 14: 61–5PubMed
60.
Colding H, Moller S, Bentzon MW. Kinetics and dose calculations of ampicillin and gentamicin given as continuous intravenous infusion during parenteral nutrition in 88 newborn infants. Dev Pharmacol Ther 1983; 6: 365–73PubMed
61.
Connors JE, DiPiro JT, Hayter RG, et al. Assessment of cefazolin and cefuroxime tissue penetration by using a continuous intravenous infusion. Antimicrob Agents Chemother 1990; 34: 1128–31PubMedCrossRef
62.
Couldry R, Sanborn M, Klutman NE, et al. Continuous infusion of ceftazidime with an elastomeric infusion device. Am J Health Syst Pharm 1998; 55: 145–9PubMed
63.
Daenen S, Erjavec Z, Uges DR, et al. Continuous infusion of ceftazidime in febrile neutropenic patients with acute myeloid leukemia. Eur J Clin Microbiol Infect Dis 1995; 14: 188–92PubMedCrossRef
64.
Dalle JH, Gnansounou M, Husson MO, et al. Continuous infusion of ceftazidime in the empiric treatment of febrile neutropenic children with cancer. J Pediatr Hematol Oncol 2002; 24: 714–6PubMedCrossRef
65.
Egerer G, Goldschmidt H, Hensel M, et al. Continuous infusion of ceftazidime for patients with breast cancer and multiple myeloma receiving high-dose chemotherapy and peripheral blood stem cell transplantation. Bone Marrow Transplant 2002; 30: 427–31PubMedCrossRef
66.
Egerer G, Goldschmidt H, Salwender H, et al. Efficacy of continuous infusion of ceftazidime for patients with neutropenic fever after high-dose chemotherapy and peripheral blood stem cell transplantation. Int J Antimicrob Agents 2000; 15: 119–23PubMedCrossRef
67.
Facca B, Frame B, Triesenberg S. Population pharmacokinetics of ceftizoxime administered by continuous infusion in clinically ill adult patients. Antimicrob Agents Chemother 1998; 42: 1783–7PubMed
68.
Frame BC, Facca BF, Nicolau DP, et al. Population pharmacokinetics of continuous infusion ceftazidime. Clin Pharmacokinet 1999; 37: 343–50PubMedCrossRef
69.
Howden BP, Richards MJ. The efficacy of continuous infusion flucloxacillin in home therapy for serious staphylococcal infections and cellulitis. J Antimicrob Chemother 2001; 48: 311–4PubMedCrossRef
70.
Imhof A, Walter RB, Schaffner A. Continuous infusion of escalated doses of amphotericin B deoxycholate: an open-label observational study. Clin Infect Dis 2003; 36: 943–51PubMedCrossRef
71.
Issell BF, Keating MJ, Valdivieso M, et al. Continuous infusion tobramycin combined with carbenicillin for infections in cancer patients. Am J Med Sci 1979; 277: 311–8PubMedCrossRef
72.
Kuti JL, Nightingale CH, Knauft RF, et al. Pharmacokinetic properties and stability of continuous-infusion meropenem in adults with cystic fibrosis. Clin Ther 2004; 26: 493–501PubMedCrossRef
73.
Marshall E, Smith DB, O’Reilly SM, et al. Low-dose continuous-infusion ceftazidime monotherapy in low-risk febrile neutropenic patients. Support Care Cancer 2000; 8: 198–202PubMedCrossRef
74.
Pass SE, Miyagawa CI, Healy DP, et al. Serum concentrations of cefuroxime after continuous infusion in coronary bypass graft patients. Ann Pharmacother 2001; 35: 409–13PubMedCrossRef
75.
Pawlotsky F, Thomas A, Kergueris MF, et al. Constant rate infusion of vancomycin in premature neonates: a new dosage schedule. Br J Clin Pharmacol 1998; 46: 163–7PubMedCrossRef
76.
Speich R, Dutly A, Naef R, et al. Tolerability, safety and efficacy of conventional amphotericin B administered by 24-hour infusion to lung transplant recipients. Swiss Med Wkly 2002; 132: 455–8PubMed
77.
Vinks AA, Brimicombe RW, Heijerman HG, et al. Continuous infusion of ceftazidime in cystic fibrosis patients during home treatment: clinical outcome, microbiology and pharmacokinetics. J Antimicrob Chemother 1997; 40: 125–33PubMedCrossRef
78.
Young RJ, Lipman J, Gin T, et al. Intermittent bolus dosing of ceftazidime in critically ill patients. J Antimicrob Chemother 1997; 40: 269–73PubMedCrossRef
79.
Craig WA, Ebert SC. Continuous infusion of beta-lactam antibiotics. Antimicrob Agents Chemother 1992; 36: 2577–83PubMedCrossRef
80.
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: 483–90PubMedCrossRef
81.
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: 93–9PubMedCrossRef
82.
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: 2793–7PubMedCrossRef
83.
84.
Forrest A, Nix DE, Ballow CH, et al. Pharmacodynamics of intravenous ciprofloxacin in seriously ill patients. Antimicrob Agents Chemother 1993; 37: 1073–81PubMedCrossRef
85.
Burgess DS. Pharmacodynamic principles of antimicrobial therapy in the prevention of resistance. Chest 1999; 115: 19S–23SPubMedCrossRef
Metadata
Title
Continuous versus Intermittent Intravenous Administration of Antibacterials with Time-Dependent Action
A Systematic Review of Pharmacokinetic and Pharmacodynamic Parameters
Authors
Sofia K. Kasiakou
Kenneth R. Lawrence
Nicolaos Choulis
Dr Matthew E. Falagas
Publication date
01-12-2005
Publisher
Springer International Publishing
Published in
Drugs / Issue 17/2005
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.2165/00003495-200565170-00006

Other articles of this Issue 17/2005

Drugs 17/2005 Go to the issue

Review Article

Issues for Clinical Drug Development in Neurodegenerative Diseases

Leading Article

Tuberculosis Vaccines

Review Article

Pathophysiological Basis for Antioxidant Therapy in Chronic Liver Disease

Adis Drug Evaluation

Quetiapine

Review Article

Parathyroid Hormone as an Anabolic Skeletal Therapy

Current Opinion

Defining the Role of Mycophenolate Mofetil in the Treatment of Proliferative Lupus Nephritis