Dosing and administration of parenteral aminoglycosides
- Richard H Drew, PharmD, MS, FCCP
Richard H Drew, PharmD, MS, FCCP
- Professor, Campbell University College of Pharmacy and Health Sciences
- Associate Professor and Clinical Pharmacist, Infectious Diseases
- Duke University Medical Center
The traditional approach to parenteral aminoglycoside dosing in adults involves the administration of a weight-based dose divided two to three times daily in patients with normal renal function. The dose is reduced and/or dosing interval extended in patients with decreased renal function. Extended-interval aminoglycoside therapy (also known as once-daily aminoglycosides, single daily aminoglycoside dosing, consolidated or high-dose aminoglycoside therapy) utilizes a higher weight-based dose administered at an extended interval (every 24 hours for those with normal renal function and longer for those with renal dysfunction). Extended-interval aminoglycoside therapy (utilizing higher single doses) should not be confused with traditional, intermittent dosing with lower individual doses administered at 24-hour intervals because of renal impairment.
This topic discusses the efficacy and safety, patient selection, and implementation of these two dosing strategies. Other (general) information about aminoglycosides is found elsewhere. (See "Aminoglycosides".)
This topic refers to dosing of aminoglycosides for the treatment of typical bacterial infections. Dosing of aminoglycosides in the treatment of mycobacterial infections, tularemia, plague, and brucella are discussed in the topics dedicated to those infections.
Of note, for most of these situations, with the exception of urinary tract infections, aminoglycosides are generally used in combination with other agents that have gram-negative activity, regardless of dosing method. (See "Aminoglycosides", section on 'Clinical use'.)
The rapid attainment of therapeutic concentrations of aminoglycosides has been correlated with improved patient outcomes. Thus, dosing should be optimized to achieve this effect. Additionally, dosing should be tailored to minimize aminoglycoside toxicity. The following general principles apply to all patients, regardless of whether traditional intermittent versus extended-interval daily dosing strategies are used:
- Trissel LA. Handbook on Injectable Drugs, 14th Ed, American Society of Health-System Pharmacists, Bethesda 2007.
- Gault MH, Longerich LL, Harnett JD, Wesolowski C. Predicting glomerular function from adjusted serum creatinine. Nephron 1992; 62:249.
- Hatala R, Dinh T, Cook DJ. Once-daily aminoglycoside dosing in immunocompetent adults: a meta-analysis. Ann Intern Med 1996; 124:717.
- Barza M, Ioannidis JP, Cappelleri JC, Lau J. Single or multiple daily doses of aminoglycosides: a meta-analysis. BMJ 1996; 312:338.
- Ferriols-Lisart R, Alós-Almiñana M. Effectiveness and safety of once-daily aminoglycosides: a meta-analysis. Am J Health Syst Pharm 1996; 53:1141.
- 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.
- Contopoulos-Ioannidis DG, Giotis ND, Baliatsa DV, Ioannidis JP. Extended-interval aminoglycoside administration for children: a meta-analysis. Pediatrics 2004; 114:e111.
- Rao SC, Ahmed M, Hagan R. One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates. Cochrane Database Syst Rev 2006; :CD005091.
- Smyth AR, Bhatt J. Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis. Cochrane Database Syst Rev 2012; :CD002009.
- French LM, Smaill FM. Antibiotic regimens for endometritis after delivery. Cochrane Database Syst Rev 2004; :CD001067.
- Mavros MN, Polyzos KA, Rafailidis PI, Falagas ME. Once versus multiple daily dosing of aminoglycosides for patients with febrile neutropenia: a systematic review and meta-analysis. J Antimicrob Chemother 2011; 66:251.
- Giuliano RA, Verpooten GA, De Broe ME. The effect of dosing strategy on kidney cortical accumulation of aminoglycosides in rats. Am J Kidney Dis 1986; 8:297.
- Giuliano RA, Verpooten GA, Verbist L, et al. In vivo uptake kinetics of aminoglycosides in the kidney cortex of rats. J Pharmacol Exp Ther 1986; 236:470.
- Rybak MJ, Abate BJ, Kang SL, et al. Prospective evaluation of the effect of an aminoglycoside dosing regimen on rates of observed nephrotoxicity and ototoxicity. Antimicrob Agents Chemother 1999; 43:1549.
- Smyth A, Tan KH, Hyman-Taylor P, et al. Once versus three-times daily regimens of tobramycin treatment for pulmonary exacerbations of cystic fibrosis--the TOPIC study: a randomised controlled trial. Lancet 2005; 365:573.
- Mulheran M, Hyman-Taylor P, Tan KH, et al. Absence of cochleotoxicity measured by standard and high-frequency pure tone audiometry in a trial of once- versus three-times-daily tobramycin in cystic fibrosis patients. Antimicrob Agents Chemother 2006; 50:2293.
- Nicolau DP, Wu AH, Finocchiaro S, et al. Once-daily aminoglycoside dosing: impact on requests and costs for therapeutic drug monitoring. Ther Drug Monit 1996; 18:263.
- Gilbert DN, Lee BL, Dworkin RJ, et al. A randomized comparison of the safety and efficacy of once-daily gentamicin or thrice-daily gentamicin in combination with ticarcillin-clavulanate. Am J Med 1998; 105:182.
- Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 2013; 70:195.
- Gentamicin (gentamicin sulfate). US FDA approved product information. National Library of Medicine. Available online at www.dailymed.nlm.nih.gov (Accessed on September 25, 2013).
- Tobramycin (tobramycin sulfate). US FDA approved product information. National Library of Medicine. Available online at www.dailymed.nlm.nih.gov (Accessed on September 25, 2013).
- Kashuba AD, Nafziger AN, Drusano GL, Bertino JS Jr. Optimizing aminoglycoside therapy for nosocomial pneumonia caused by gram-negative bacteria. Antimicrob Agents Chemother 1999; 43:623.
- Nicolau DP, Freeman CD, Belliveau PP, et al. Experience with a once-daily aminoglycoside program administered to 2,184 adult patients. Antimicrob Agents Chemother 1995; 39:650.
- Karlowsky JA, Zhanel GG, Davidson RJ, Hoban DJ. Once-daily aminoglycoside dosing assessed by MIC reversion time with Pseudomonas aeruginosa. Antimicrob Agents Chemother 1994; 38:1165.
- Morris JT, Cooper RH. Intravenous streptomycin: a useful route of administration. Clin Infect Dis 1994; 19:1150.
- Isemann BT, Kotagal UR, Mashni SM, et al. Optimal gentamicin therapy in preterm neonates includes loading doses and early monitoring. Ther Drug Monit 1996; 18:549.
- McDade EJ, Wagner JL, Moffett BS, Palazzi DL. Once-daily gentamicin dosing in pediatric patients without cystic fibrosis. Pharmacotherapy 2010; 30:248.
- Zaske DE. Aminoglycosides. In: Applied Pharmacokinetics, 3rd Ed, William EE, Schentag EJ, Jusko WJ (Eds), Applied Therapeutics Inc, Vancouver, WA 1994.
- Dager WE, King JH. Aminoglycosides in intermittent hemodialysis: pharmacokinetics with individual dosing. Ann Pharmacother 2006; 40:9.
- Roberts JA, Field J, Visser A, et al. Using population pharmacokinetics to determine gentamicin dosing during extended daily diafiltration in critically ill patients with acute kidney injury. Antimicrob Agents Chemother 2010; 54:3635.
- Buijk SE, Mouton JW, Gyssens IC, et al. Experience with a once-daily dosing program of aminoglycosides in critically ill patients. Intensive Care Med 2002; 28:936.
- Sexton DJ, Tenenbaum MJ, Wilson WR, et al. Ceftriaxone once daily for four weeks compared with ceftriaxone plus gentamicin once daily for two weeks for treatment of endocarditis due to penicillin-susceptible streptococci. Endocarditis Treatment Consortium Group. Clin Infect Dis 1998; 27:1470.
- GENERAL PRINCIPLES
- Dosing weight
- Creatinine clearance estimation
- Monitoring for toxicity
- TRADITIONAL VERSUS EXTENDED-INTERVAL DOSING
- - Nephrotoxicity
- - Ototoxicity
- Convenience and cost
- SELECTION OF DOSING STRATEGY
- GENTAMICIN AND TOBRAMYCIN DOSING IN ADULTS
- Traditional dosing and monitoring
- - Loading dose
- - Initial maintenance dose and dosing interval
- - Drug concentration monitoring
- "Target" concentrations
- - Dosing adjustments
- - Frequency of monitoring
- Extended-interval dosing and monitoring
- - Initial dose and dosing interval
- - Drug concentration monitoring
- Target concentrations
- Nomogram-based monitoring
- Individualized monitoring
- AMIKACIN DOSING IN ADULTS
- STREPTOMYCIN DOSING IN ADULTS
- DOSING FOR SPECIAL CIRCUMSTANCES
- Neonates and children
- Peritoneal dialysis
- Intermittent hemodialysis
- Continuous AV hemofiltration
- Cystic fibrosis
- Burn patients
- Septic patients
- Elderly patients
- Synergy for gram-positive infections
- SUMMARY AND RECOMMENDATIONS