We appreciate Dr. Baxter's perspective on the use of aminoglycoside antibiotics in his practice. For the specific use of aminoglycosides in synergistic combination against gram-positive organisms, guidelines have recommended lower doses administered several times per day [1]. Similar dosing adjustments have not been established for synergistic use of once-daily aminoglycosides. All studies reviewed in our meta-analysis administered a once-daily aminoglycoside in combination with other antibiotics, usually ß-lactam drugs.

Although once-daily aminoglycosides reach peak levels (>6 to 10 mg/L for gentamicin and netilmicin) that are higher than those seen with conventional multiple-daily dosing methods and may reach lower trough levels faster than with these conventional methods, the ideal therapeutic range and monitoring variables for once-daily dosing remain to be determined. Some authors have advocated abandoning conventional monitoring of peak and trough levels in favor of achieving a target area under the serum concentration-time curve or an optimal serum concentration-time curve relative to the mean concentration [2, 3]. Others have alternatively monitored serum creatinine levels in patients at low risk for renal failure [4]. The studies that we systematically reviewed adjusted once-daily dosing to achieve trough levels that were similar to those of conventional aminoglycoside therapy in patients with normal renal function.

On the basis of current evidence, we suggest using once-daily aminoglycoside therapy plus other antibiotics according to the dosing regimens outlined in Table 1 of our meta-analysis; the goal would be to achieve serum trough levels of 2 mg/L for gentamicin and netilmicin and 5 mg/L for amikacin. Appropriate peak serum levels have not been established. Further research into the clinical significance of serum levels of aminoglycosides will help establish the appropriate therapeutic range for monitoring of once-daily dosing.