Clinical Pharmacology of Tobramycin in Newborns

Kaplan, J. Martin; McCracken, George H.; Thomas, Marion L.; Horton, Linda; Davis, N.R.

doi:10.1001/archpedi.1973.04160050012003

Cited by 27 publications

(11 citation statements)

References 12 publications

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“…In general, serum half-life values correlated inversely with these three parameters. These pharmacokinetic relationships have also been demonstrated for the other aminoglycosides in neonates (6,7,11,13). The larger volume of distribution observed in low-birth weight babies of younger gestational and chronological ages most likely reflects the increased extracellular fluid volume characteristic of these immature infants.…”

Section: Resultsmentioning

confidence: 62%

“…An average serum concentration of 2.2 ug/ml was noted 12 h after the dose at the beginning of therapy compared with 5.6 ,ug/ml on the last day. This was unexpected in light of our previous studies of aminoglycosides in neonates (7,11,13). This occurred in the same group of infants whose serum creatinine levels were 21.0 mg/dl or did not show the usual decline observed in the first 2 weeks of life and who required mechanical ventilation during the course of netilmicin therapy.…”

Section: Netilmicin In Newborn Infants 251mentioning

confidence: 79%

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Pharmacokinetic Properties of Netilmicin in Newborn Infants

Siegel

McCracken

Thomas

et al. 1979

Antimicrob Agents Chemother

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Netilmicin and gentamicin susceptibilities of 258 gram-negative organisms and 25 strains of Staphylococcus aureus were nearly identical. The pharmacokinetic properties of netilrnicin were evaluated in 101 newborn infants and related to birth weight, gestational age, chronological age, and route of administration. Mean peak serum concentrations of 5.6 to 6.9 and 7.8 to 8.4 ,ug/ml were observed 30 min after 3-and 4-mg/kg doses, respectively, were given intramuscularly. The peak concentrations were directly related to gestational age. The average serum half-life values varied from 3.4 to 4.7 h and in general were inversely related to birth weight, gestational age, and postnatal age. The pharmacokinetics of netilmicin in 10 infants were similar after intramuscular and intravenous administration. A comparative study of netilmicin and gentamicin in seven neonates revealed greater variability in serum concentrations of gentamicin and a shorter half-life for netilmicin. There was evidence of accumulation of netilmicin in 12 low-birth weight, premature infants who received 4-mg/kg doses for an average of 6.4 days. Serum and urine levels of netilmicin were measured up to 11 days after discontinuation of the drug. These data are well characterized by a two-compartment model. Additional studies of efficacy and long-term toxicity of netilmicin in neonates are necessary.Netilmicin is a new semisynthetic aminoglycoside that is a 1-N-ethyl sisomicin derivative produced by Micromonospora inyoensis. Its antimicrobial spectrum is similar to that of gentamicin with an added advantage that an increasing number of Enterobacteriaceae possess adenylating enzymes mediating resistance to gentamicin, but not to netilmicin (4,10,16,21,28). Animal studies indicate that substantially less ototoxicity and nephrotoxicity result from repeated doses of netilmicin than of gentamicin (9,12,16). In an experimental rabbit model ofEscherichia coli meningitis, netilmicin has also been shown to have greater bactericidal activity in cerebrospinal fluid' than does gentamicin (24). These observations suggest that netilmicin may be potentially useful for therapy of neonatal bacterial infections.In this study we have evaluated the pharmacokinetics of netilnicin in 101 neonates and related these properties to birth weight, gestational age, chronological age, and route of administration. We have also measured netilmicin in serum and/or urine for as long as 12 days after discontinuation of therapy and have fit these data to a two-compartment model as has been described for aminoglycosides in older children and adults (3,17,20,25,30). MATERIALS AND METHODSSusceptibility studies. The susceptibilities to gentamicin and netilmicin of 258 gram-negative organisms and 25 Staphylococcus aureus strains isolated from blood, cerebrospinal fluid, or urine of sick neonates and from rectal culture of normal newborns were determined by a modified agar plate dilution method (1) with a multiple inoculating apparatus (27). Serial twofold dilutions of laboratory standards of net...

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Section: Resultsmentioning

confidence: 62%

Section: Netilmicin In Newborn Infants 251mentioning

confidence: 79%

Pharmacokinetic Properties of Netilmicin in Newborn Infants

Siegel

McCracken

Thomas

et al. 1979

Antimicrob Agents Chemother

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“…The difference in these findings is not explained by the present study. The clinical pharma cology of tobramycin iii adults and newborn has been well studied [10,17] and indicates that serum concentrations of 3-6 //g/ml are achievable with tobramycin; this suggests that clinical correlates of the in vitro activity are to be expected. The toxicity and other properties of the drug are very similar to gentamicin.…”

Section: Discussionmentioning

confidence: 99%

Antibacterial Activity of Tobramycin against Gram-Negative Bacteria and the Combination of Ampicillin/Tobramycin against <i>E. coli</i>

Laxer¹,

Mackay²,

Marks³

1975

Chemotherapy

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The antibacterial activity of tobramycin, gentamicin, erythromycin, cloxacillin, kanamycin, cephalexin, penicillin, carbenicillin and polymyxin were compared against 303 clinical bacterial isolates from a pediatric hospital patient population. Standard disk diffusion and agar-dilution methods were employed. Significant activity was demonstrated for tobramycin against Pseudomonas, Klebsiella, Escherichia coli and both Staphylococcus aureus and albus. Tobramycin was significantly more active against Pseudomonas than gentamicin or the other antibiotics tested. Comparable activity to gentamicin was present for the other types of bacteria. Cross-resistance was not encountered between tobramycin and gentamicin. 30 isolates of E. coli were tested against the combination of tobramycin and ampicillin by the growth-curve method. Synergism was demonstrated in 4 isolates, antagonism in 1 and an additive effect in 25. A bactericidal effect was present at 24 h against 17 isolates with tobramycin alone and against 25 isolates when combined with ampicillin. These results provide in vitro rationale for the consideration of tobramycin for clinical use in patients with Pseudomonas infections and for the combination of ampicillin and tobramycin for the treatment of selected E. coli infections.

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“…After it had crossed the placenta to the fetus, TBM was cleared from the fetal serum within 17 h, with a tl2 of 5.25 h. Kaplan and co-workers (5) reported that the TBM serum t12 for small premature infants is 8. Fetal renal tissue concentrations of TBM were high and were found to increase significantly for as long as 34 h, whereas both fetal serum and urine concentrations steadily declined to nondetectable levels by 17 and 21.6 h, respectively.…”

Section: Discussionmentioning

confidence: 99%

Tobramycin: Maternal-Fetal Pharmacology

Bernard

Garcia-Cázares

Ballard

et al. 1977

Antimicrob Agents Chemother

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To investigate the maternal-fetal transfer of tobramycin (TBM) and its distribution in the fetus, a single dose of 2 mg/kg was administered intramuscularly to 35 pregnant patients (13 first trimester, 22 second trimester) 0.5 to 34 h before hysterectomy. TBM concentration was assayed microbiologically in maternal serum, fetal tissues (placenta, brain, lung, liver, and kidney), and fluids (amniotic, cerebrospinal fluid [CSF], urine, and serum). Mean maternal serum half-life (1.54 h) and mean peak serum concentration ofTBM were within ranges reported for nonpregnant adults. In fetal serum, half-life was 5.2 h, and TBM levels did not exceed 0.58 ,g/ml. For intervals up to 34 h, the mean TBM concentration in placental tissues was 1.4 gg/g. Concentration differences related to fetal maturation were found for fetal CSF, amniotic fluid, and fetal kidney. No antimicrobial activity was found in the fetal CSF of >16 weeks' gestation. TBM was present predominantly in the second trimester amniotic fluid specimens. Fetal kidney concentrations reached 7.2 ug/g at 34 h after maternal drug administration. Higher TBM concentrations were related to advanced maturation ofthe fetal kidney. Second trimester fetal urine concentrations for TBM ranged from 0.1 to 3.4 gg/ml, and the fetal urinary half-life was 3.7 h. Knowledge of fetal pharnacology is essential for weighing the fetal benefits or risks of antimicrobial therapy for the infected gravid patient.

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Clinical Pharmacology of Tobramycin in Newborns

Cited by 27 publications

References 12 publications

Pharmacokinetic Properties of Netilmicin in Newborn Infants

Pharmacokinetic Properties of Netilmicin in Newborn Infants

Antibacterial Activity of Tobramycin against Gram-Negative Bacteria and the Combination of Ampicillin/Tobramycin against <i>E. coli</i>

Tobramycin: Maternal-Fetal Pharmacology

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