Experience with a once-daily aminoglycoside program administered to 2,184 adult patients

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: Ն60 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.

Influence of Hemodialysis on Gentamicin Pharmacokinetics, Removal During Hemodialysis, and Recommended Dosing

“…In addition, because the peak gentamicin serum concentration to minimum inhibitory concentration (MIC) ratio and area under the curve (AUC)/MIC ratio are the most important predictors of efficacy for aminoglycosides, opportunities to maximize therapeutic goals while minimizing risk of toxicity are important (18). Efforts to maximize these pharmacodynamic parameters have been successful in other populations (19,20), but not in patients receiving hemodialysis. This is due to the difficulty in achieving high peak/MIC ratios while minimizing "trough" concentrations with conventional dosing regimens.…”

Optimizing Antibiotic Pharmacodynamics for Clinical Practice

“…Using a fixed 7 mg/kg intravenous dose of gentamicin and a dosing interval nomogram based on estimated creatinine clearance of patients, Nicolau et al evaluated a once daily aminoglycoside dosing algorithm (referred to as the Hartford Nomogram) in 2,184 adult patients [42]. The investigators observed similar clinical response rates to historical data, but a reduced incidence of nephrotoxicity, which was 1.2% while using the Hartford Nomogram versus 3-5% historically.…”

Toxicity of single daily dose gentamicin in stem cell transplantation

“…Patients who received SDD gentamicin for Ͼ10 days in our study were more likely to develop ototoxicity. Nicholau et al 31 described a case of irreversible ototoxicity in a patient who received a once-daily aminoglycoside for 5 weeks. Viscoli et al 8 described an increase in peak serum amikacin concentration (37-44 mg/l) in pediatric BMT patients receiving once-daily amikacin for at least 9 days.…”