Dear Editor

We are grateful to Dr Sunil for highlighting the issue of concommitent aminogycoside use with vancomycin. We agree that sick preterms are different and that it would be imprudent to abandon measuring vancomycin serum levels altogether. However, we do not change our recommendation that trough levels are sufficient in most cases. We are not aware of any data showing that concommitent use of aminoglycosides changes either the desired thereapeutic or safety range used for vancomycin in infants, although we agree that if a toxic level is reached then the harm may be more severe. As we explained in our paper peak levels are a poor measure of possible toxic levels compared to trough concentrations. They are mainly of use to ensure an adequate minimal inhibitory serum concentration has been reached. As aminoglycosides will not directly influence the vancomycin peak level alone we can see no strong reason to measure them when these drugs are given together.

Dear Editor

The purpose of measuring serum levels of a drug is either to monitor the toxicity of the drug or the therapeutic concentration for a particular condition. Emergence of infections with beta-lactam-resistant Staphylococcus epidermidis, Staphylococcus aureus, and Enterococcus sp. has led to the frequent use of vancomycin in neonates. Vancomycin historically has had a reputation for toxicity. Many of its original adverse reactions, including ototoxicity and nephrotoxicity, were probably due impurities in the formulation.[1] Now, that a more purified form is available, these adverse reactions are uncommon; however, concomitant administration with aminoglycosides or other nephrotoxins may increase the risk of toxicity.[2] Effective drug therapy is measured by response, not by achievement of a particular circulating drug concentration. Because the association between vancomycin peak concentrations and toxicity is poor, some have recommended measuring trough concentration only [3] as your study is clearly documenting, but others have suggested not measuring any concentrations in the majority of children with normal renal function.[4] However, in critically ill premature neonates, poor glomerular filtration rate with prematurity and compromised cardiovascular function, it remains prudent to measure both peak and trough concentrations in those with poor or changing renal function. Caution must be exercised when other nephrotoxic or ototoxic drugs such as aminoglycisides are administered concurrently.[5] In your study, you have not mentioned about the concomittent use of aminoglycoside.

References

(1) Baillie GR, Neal D. Vancomycin ototoxicity and nephrotoxicity. A review. Med Toxicol Adv Drug Exp 1988;3:376-386.

(2) Rybak MJ, Albrecht LM, Boike SC, Chandrasekar PH. Nephrotoxicity of vancomycin, alone and with an aminoglycoside. J Antimicrob Chemother 1990;25:679-687.

(3) Saunders NJ. Why monitoring peak vancomycin concentration? Lancet 1994;344:1748-1750.

(4) Thomas MP, Steele RW. Monitoring serum vancomycin concentrations in children. Is it necessary? Pediatr Infect Dis J 1998;17:351-352.

(5) Moellering RC, Krogstad DJ, and Greenblatt DJ. Vancomycin therapy in patients with impaired renal function: a nomogram for dosage. Ann Intern Med 1981;94:343-346.