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Monitoring of aminoglycoside serum concentrations
Volume 111 Number 1
E d i t o r i a l correspondence
159
Monitoring of aminoglycoside serum concentrations Bone 2 Phase I 0.1 +0.1 0.2 9+0.2
2 9.2 _+7.5 3.5 _+1.3
Urine 3 58.2 _+25.0 35.0 _+9.4
Phase I 3.9 _+2.0 8.5 +3.4
2 18.6 _+7.2 24.4 _+4.l
K~, Blood/bone 2
K,0 Blood/urine
0.25 _+0.i 0.15 _+0.07
1.20 _+0.3 1.61 -+0.4
3 27.6 _+14.7 35.0 _+12.6
intercept (percen t of activity at time zero in blood) and of rate constants in the compartments (Table) showed increased bone uptake of 99mTc~Sn-MDP in children with thalassemia major. We conclude that in thalassemia this method is more sensitive than bone roentgenograms for quantitative evaluation of skeletal abnormalities.4 Moreover, we found that the increased bone turnover in thalassemia major is not correlated with age at onset of blood transfusions, but directly correlated with hemoglobin levels (r = 0.506, P <0.05). F. Schettini, M.D. M. Mele, M.D. D. De Mattia, M.D. G. Falcone, M.D. A. D'Addabbo, M.D. lnterdepartment Center o f Biocybernetics and Radioisotope Technics 1st Pediatric Clinic University o f Bari Policlinico, Piazza Giul(o Cesare 11 70124 Bari, Italy REFERENCES
1. Pootrakul P, Hungsprenges, S, Fucharoen S, et al. Relation betweeen erythropoiesis and bone metabolism in thalassemia. N Engl J reed 1981;304:1470. 2. Romeo MA, Azzia N, Micale C, Carozzo S, Schilir6 G. Proline, hydroxyproline, and ascorbic acid in thalassemia major. J PEDIATR 1986;109:399. 3. Conte E, Pieralice M. On the analysis of multi-component exponential 9 curves Qf radionuclides: a method to identify the order of a compartmental model directly from the tracer data. Rays (Roma) 1985;10(3):89. 4. Scutellari P, Orzincolo C, Calzolari F, Tilotta F. Le coste nelle/3-thalassemie: evoluzione deUe alterazioni in rapporto alia terapia trasfusionale. Radiol Med 1983;69:654.
To the Editor: The article by Massey et al. (J PEDIATR1986;109:897) proposed a n interesting guideline for monitoring patients rece!ving aminoglycosides. A clearer definition of the guidelines would seem appropriate if clinicians are to eliminate routine ordering of aminoglycoside serum concentrations for their patients. What agents do the authors believe are nephrotoxins of significance? Do they recommend that peak and trough data be obtained for patients who receive or are strong candidates to receive aminogly7 coside therapy for 10 days or longer? i f the course of therapy is to be 10 days, would not data early in therapy be more beneficial with regard to therapeutics in light of references provided by the authors on the need to achieve adequate serum concentrations? Do the authors recommend that no monitoring of renal function is necessary if therapy is for less than 10 days? Irreversible nephrotoxicity in the pediatric and adu!t patient is rare, especially now that patients are closely monitored; however, reversible nephrotoxicity must lengthen hospital stay and increase cost. On a larger scale, does the elimination of monitoring of serum concentrations really save money? Or does it accomplish this at the expense of the rare patient in whom nephrotoxicity develops and in those with therapeutic failure secondary to inadequate aminoglycoside therapy? Perhaps more data are needed. Richard L Sakai, Pharm.D. Director o f Pharmacy Visalia Community Hospital 1633 Court St. P.O. Box 911 Visalia, CA 93279-0911
Reply To the Editor: Our data demonstrated that the standard recommended 2.5 mg/kg q8h dosage regimen for tobramycin and gentamicin produced therapeutic peak concentrations for septicemia and soft tissue infections (>~4 ~g/mL) in all 67 patients in whom administration technique and sample timewere meticulously controlled. In addition, trough concentrations were within the safe range (<2 #g/mL) in all 62 patients between 3 months and 18 years with normal renal function who had received therapy fo r less than 10 days, even though 33 of these patients ~'eceived larger than recommended doses (mean ___SD 3.0 + 0.4 mg/kg) more frequently (q6h rather than q8h). Inasmuch as monitoring serum levels did not result in a change in dose, interval, BUN, or creatinine, and there was no clinical evidence of otovestibular toxicity, we concluded that the routine practice of measuring peak and trough concentrations in all patients receiving aminoglycosides was not cost effective. In contrast, we continue to recommend these measurements in those who might require a higher
E d i t o r i a l correspondence
159
Monitoring of aminoglycoside serum concentrations Bone 2 Phase I 0.1 +0.1 0.2 9+0.2
2 9.2 _+7.5 3.5 _+1.3
Urine 3 58.2 _+25.0 35.0 _+9.4
Phase I 3.9 _+2.0 8.5 +3.4
2 18.6 _+7.2 24.4 _+4.l
K~, Blood/bone 2
K,0 Blood/urine
0.25 _+0.i 0.15 _+0.07
1.20 _+0.3 1.61 -+0.4
3 27.6 _+14.7 35.0 _+12.6
intercept (percen t of activity at time zero in blood) and of rate constants in the compartments (Table) showed increased bone uptake of 99mTc~Sn-MDP in children with thalassemia major. We conclude that in thalassemia this method is more sensitive than bone roentgenograms for quantitative evaluation of skeletal abnormalities.4 Moreover, we found that the increased bone turnover in thalassemia major is not correlated with age at onset of blood transfusions, but directly correlated with hemoglobin levels (r = 0.506, P <0.05). F. Schettini, M.D. M. Mele, M.D. D. De Mattia, M.D. G. Falcone, M.D. A. D'Addabbo, M.D. lnterdepartment Center o f Biocybernetics and Radioisotope Technics 1st Pediatric Clinic University o f Bari Policlinico, Piazza Giul(o Cesare 11 70124 Bari, Italy REFERENCES
1. Pootrakul P, Hungsprenges, S, Fucharoen S, et al. Relation betweeen erythropoiesis and bone metabolism in thalassemia. N Engl J reed 1981;304:1470. 2. Romeo MA, Azzia N, Micale C, Carozzo S, Schilir6 G. Proline, hydroxyproline, and ascorbic acid in thalassemia major. J PEDIATR 1986;109:399. 3. Conte E, Pieralice M. On the analysis of multi-component exponential 9 curves Qf radionuclides: a method to identify the order of a compartmental model directly from the tracer data. Rays (Roma) 1985;10(3):89. 4. Scutellari P, Orzincolo C, Calzolari F, Tilotta F. Le coste nelle/3-thalassemie: evoluzione deUe alterazioni in rapporto alia terapia trasfusionale. Radiol Med 1983;69:654.
To the Editor: The article by Massey et al. (J PEDIATR1986;109:897) proposed a n interesting guideline for monitoring patients rece!ving aminoglycosides. A clearer definition of the guidelines would seem appropriate if clinicians are to eliminate routine ordering of aminoglycoside serum concentrations for their patients. What agents do the authors believe are nephrotoxins of significance? Do they recommend that peak and trough data be obtained for patients who receive or are strong candidates to receive aminogly7 coside therapy for 10 days or longer? i f the course of therapy is to be 10 days, would not data early in therapy be more beneficial with regard to therapeutics in light of references provided by the authors on the need to achieve adequate serum concentrations? Do the authors recommend that no monitoring of renal function is necessary if therapy is for less than 10 days? Irreversible nephrotoxicity in the pediatric and adu!t patient is rare, especially now that patients are closely monitored; however, reversible nephrotoxicity must lengthen hospital stay and increase cost. On a larger scale, does the elimination of monitoring of serum concentrations really save money? Or does it accomplish this at the expense of the rare patient in whom nephrotoxicity develops and in those with therapeutic failure secondary to inadequate aminoglycoside therapy? Perhaps more data are needed. Richard L Sakai, Pharm.D. Director o f Pharmacy Visalia Community Hospital 1633 Court St. P.O. Box 911 Visalia, CA 93279-0911
Reply To the Editor: Our data demonstrated that the standard recommended 2.5 mg/kg q8h dosage regimen for tobramycin and gentamicin produced therapeutic peak concentrations for septicemia and soft tissue infections (>~4 ~g/mL) in all 67 patients in whom administration technique and sample timewere meticulously controlled. In addition, trough concentrations were within the safe range (<2 #g/mL) in all 62 patients between 3 months and 18 years with normal renal function who had received therapy fo r less than 10 days, even though 33 of these patients ~'eceived larger than recommended doses (mean ___SD 3.0 + 0.4 mg/kg) more frequently (q6h rather than q8h). Inasmuch as monitoring serum levels did not result in a change in dose, interval, BUN, or creatinine, and there was no clinical evidence of otovestibular toxicity, we concluded that the routine practice of measuring peak and trough concentrations in all patients receiving aminoglycosides was not cost effective. In contrast, we continue to recommend these measurements in those who might require a higher