Abstract
Once-daily aminoglycoside (ODA) regimens have been instituted to maximize bacterial killing by optimizing the peak concentration/MIC ratio and to reduce the potential for toxicity. We initiated an ODA program at our institution that utilizes a fixed 7-mg/kg intravenous dose with a drug administration interval based on estimated creatinine clearance: > or = 60 ml/min every 24 h (q24h), 59 to 40 ml/min q36h, and 39 to 20 ml/min q48h. Subsequent interval adjustments are made by using a single concentration in serum and a nomogram designed for monitoring of ODA therapy. Since initiation of the program, 2,184 patients have received this ODA regimen. The median dose was 450 (range, 200 to 925) mg, while the median length of therapy was 3 (range, 1 to 26) days. The median age of the population was 46 (range, 13 to 97) years. Gentamicin accounted for 94% of the aminoglycoside use, and the majority (77%) of patients received the drug q24h. The 36-, 48-, and > 48-h intervals were used for 15, 6, and 2% of this population, respectively. Three patients exhibited clinically apparent ototoxicity. Twenty-seven patients (1.2%) developed nephrotoxicity (the Hartford Hospital historical rate is approximately 3 to 5%) after a median of 7 (range, 3 to 19) days of therapy. On the basis of a prospective evaluation of 58 patients and follow-up of additional patients via clinician reports, we have noted no apparent alterations in clinical response with our ODA program. This ODA program appears to be clinically effective, reduces the incidence of nephrotoxicity, and provides a cost-effective method for administration of aminoglycosides by reducing ancillary service time and serum aminoglycoside determinations.
MeSH Terms
Adolescent
Adult
Aged
Aged, 80 and over
Aging/physiology
Aminoglycosides
Anti-Bacterial Agents/administration & dosage,adverse effects,pharmacokinetics
Bacterial Infections/drug therapy,metabolism
Cost-Benefit Analysis
Creatinine/blood
Humans
Kidney Diseases/chemically induced
Middle Aged
Prospective Studies
Chemicals
Aminoglycosides
Anti-Bacterial Agents
Creatinine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Nicolau D P
Department of Pharmacy, Hartford Hospital, Connecticut 06102, USA.
Freeman C D
Belliveau P P
Nightingale C H
Ross J W
Quintiliani R
References (26)
26 references, click to expand
-
Prediction of creatinine clearance from serum creatinine.
Nephron. 1976;16(1):31-41
PMID: 1244564
-
Once versus thrice daily gentamicin in patients with serious infections.
Lancet. 1993 Feb 6;341(8841):335-9
PMID: 8094114
-
A randomized comparative trial of three aminoglycosides--comparison of continuous infusions of gentamicin, amikacin and sisomicin combined with carbenicillin in the treatment of infections in neutropenic patients with malignancies.
Medicine (Baltimore). 1979 Mar;58(2):159-70
PMID: 431401
-
The influence of dosage regimen on experimental gentamicin nephrotoxicity: dissociation of peak serum levels from renal failure.
J Infect Dis. 1979 Oct;140(4):576-80
PMID: 512417
-
Gentamicin dosage requirements: wide interpatient variations in 242 surgery patients with normal renal function.
Surgery. 1980 Feb;87(2):164-9
PMID: 7355388
-
Basic pharmacokinetics.
Ther Drug Monit. 1986;8(1):47-58
PMID: 3515640
-
Clinical response to aminoglycoside therapy: importance of the ratio of peak concentration to minimal inhibitory concentration.
J Infect Dis. 1987 Jan;155(1):93-9
PMID: 3540140
-
The aminoglycosides: streptomycin, kanamycin, gentamicin, tobramycin, amikacin, netilmicin, and sisomicin.
Mayo Clin Proc. 1987 Oct;62(10):916-20
PMID: 3657309
-
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 Jul;31(7):1054-60
PMID: 3116917
-
Mechanism of bactericidal action of aminoglycosides.
Microbiol Rev. 1987 Sep;51(3):341-50
PMID: 3312985
-
Prospective comparison of traditional and pharmacokinetic aminoglycoside dosing methods.
Crit Care Med. 1988 Sep;16(9):840-3
PMID: 3402229
-
Netilmicin in the treatment of gram-negative bacteremia: single daily versus multiple daily dosage.
J Infect Dis. 1989 May;159(5):931-7
PMID: 2708843
-
Pharmacokinetic monitoring of nephrotoxic antibiotics in surgical intensive care patients.
J Trauma. 1989 Nov;29(11):1462-8; discussion 1468-70
PMID: 2585556
-
Does administration of an aminoglycoside in a single daily dose affect its efficacy and toxicity?
J Antimicrob Chemother. 1990 Jan;25(1):159-73
PMID: 2108113
-
Failure of a nomogram to achieve target aminoglycoside concentrations.
Br J Clin Pharmacol. 1990 Apr;29(4):495-6
PMID: 2328198
-
Prospective randomized study of once-daily versus thrice-daily netilmicin regimens in patients with intraabdominal infections.
Eur J Clin Microbiol Infect Dis. 1990 Mar;9(3):161-8
PMID: 2186909
-
Once-daily dosing regimen for aminoglycoside plus beta-lactam combination therapy of serious bacterial infections: comparative trial with netilmicin plus ceftriaxone.
Am J Med. 1990 Jul;89(1):58-66
PMID: 2195890
-
Pharmacodynamic properties of antibiotics: application to drug monitoring and dosage regimen design.
Infect Control Hosp Epidemiol. 1990 Jun;11(6):319-26
PMID: 2165081
-
Once-daily aminoglycoside therapy.
Antimicrob Agents Chemother. 1991 Mar;35(3):399-405
PMID: 2039189
-
Killing and regrowth of bacteria in vitro: a review.
Scand J Infect Dis Suppl. 1990;74:63-70
PMID: 2097720
-
The postantibiotic effect: a review of in vitro and in vivo data.
DICP. 1991 Feb;25(2):153-63
PMID: 2058187
-
Clinical and bacteriological efficacy, and practical aspects of amikacin given once daily for severe infections.
J Antimicrob Chemother. 1991 May;27 Suppl C:91-103
PMID: 1856149
-
A critical reevaluation of the "therapeutic range" of aminoglycosides.
Clin Infect Dis. 1992 Jan;14(1):320-39
PMID: 1571447
-
Comparison of gentamicin dosing regimens using an in-vitro model.
J Antimicrob Chemother. 1992 Apr;29(4):427-33
PMID: 1607331
-
Prediction of glomerular filtration rate using aminoglycoside clearance in critically ill medical patients.
Ann Pharmacother. 1992 Oct;26(10):1205-10
PMID: 1421639
-
Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: gentamicin in burn patients.
J Pharmacokinet Biopharm. 1976 Apr;4(2):183-95
PMID: 950590