netilmicin and Infant--Premature--Diseases

The aim of this study was to validate a simplified high-dosage, extended-interval netilmicin dosage regimen for infants. A total of 129 infants receiving 163 treatment courses of netilmicin (6 mg kg every 24 or 36 h depending on gestational age (GA), postnatal age and postmenstrual age) was analysed. Serum netilmicin concentrations were monitored before (Cmin), 30 min (C0.5h) after and 7.5 h (C7.5h) after the third dose. In 110 patients during first week of life mean C0.5h was 10.5 mg/l. Mean C0.5h was significantly lower (9.0 mg/l) in 38 infants older than 1 week of age. 14 of 15 patients with Cmin levels > or = 2 mg/l receiving netilmicin every 36 h were < 28 weeks of gestation. In the first week of life significant correlations between GA and elimination half-life (p < 0.001) and between plasma creatinine and elevated Cmin (p < 0.002) were found, but no correlation between C0.5h and GA. In this high-dosage regimen a dosing interval of 48 h for GA < 29 weeks, 36 h for GA 29-36 weeks and 24 h for full term babies seems appropriate, during first week of life, to avoid the majority of elevated trough levels and still obtain maximal therapeutic efficacy.

Topics: Ampicillin; Anti-Bacterial Agents; Bacteremia; Cloxacillin; Drug Administration Schedule; Drug Therapy, Combination; Female; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Infections; Netilmicin

The effect of three different aminoglycosides on renal function was evaluated in 30 premature infants of similar gestational age who were treated within 24 h of birth with either amikacin (10 infants, group A), gentamicin (10 infants, group B) or netilmicin (10 infants, group C), for a period of 7 days. Ten infection-free premature infants of similar post-conceptional age were used as controls. Serial determinations of plasma creatinine concentration (PCr), as well as the fractional excretion of sodium (FENa), potassium, magnesium (FEMg), phosphate (FEP) and uric acid (FEUA), and the urinary excretion of calcium (UCa/UCr ratio) were assessed before, during and after treatment. During the treatment period a significant increase in FENa, FEMg and UCa/UCr was observed in group B (P < 0.05 and P < 0.01, respectively) and an increase in FENa and UCa/UCr in group C (P < 0.01) compared with controls. These disturbances were observed with trough concentrations of aminoglycosides but were accentuated at peak serum concentrations and were restored to normal 2 days after stopping therapy. In addition, a significant correlation was demonstrated between FENa, FEMg and UCa/UCr ratio in treated patients. PCr levels decreased similarly in all patient groups, but in 8 of 30 infants (27%) they remained elevated and returned to control values only 10 days after stopping therapy. Such renal functional disturbances, although transient, may result in significant electrolyte and mineral imbalance in the sick premature infant.

Topics: Amikacin; Calcium; Case-Control Studies; Creatinine; Gentamicins; Humans; Infant, Newborn; Infant, Premature, Diseases; Infections; Kidney; Kidney Function Tests; Magnesium; Netilmicin; Phosphorus; Potassium; Sodium; Uric Acid

Aminoglycosides are commonly used antibiotics with excellent renal parenchymal penetration. Their clinical effectiveness is counter balanced with the risk of renal toxicity, which develops in a dose-dependent fashion. Aminoglycoside-induced renal tubular dysfunction could result in diffuse damage or manifest as a Fanconi-like syndrome, Bartter-like syndrome (BLS), or distal renal tubular acidosis.(1-4) Although tubulopathy associated with amikacin and gentamicin was reported in adults and rarely children, to the best of our knowledge, netilmicin-associated BLS neither in adults nor in children has been reported in the literature. We here report a 30-week, 770 g male preterm infant who developed BLS just after netilmicin treatment for neonatal sepsis and recovered 6 weeks after the drug cessation.

Topics: Adult; Anti-Bacterial Agents; Bartter Syndrome; Female; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Kidney Diseases; Male; Netilmicin; Pregnancy; Sepsis

The effect of aminoglycoside administration on kidney functional maturation was evaluated in groups of 30 preterm and 30 fullterm infants who were treated for 7 days because of suspected infection. One of three different aminoglycosides was administered to each subgroup of ten preterm and ten fullterm infants. Changes in tubular function in groups of ten preterm and ten fullterm infants who were not given antibiotics were also compared. The mean gestational age for preterm infants from 32.5 to 33.6 weeks and for fullterm infants between 39.2 and 39.5 weeks. The renal tubular function was assessed by examining the fractional excretion of sodium (FENa), potassium (FEK), phosphorus (FEP), magnesium (FEMg) and uric acid (FEUA) as well as by the urinary excretion of calcium as the calcium/creatinine (UCa/UCr) ratio. Gentamicin affected the normal plasma creatinine (PCr) decline in both treated groups (fullterm and preterm). Disturbances in FENa and UCa/UCr were more pronounced in treated preterm than in fullterm infants especially after netilmicin and gentamicin administration. FEMg was significantly affected in preterm infants treated with gentamicin. The findings of this study indicate that the effect of aminoglycosides on tubular function is dependent upon kidney maturity and the type of the aminoglycoside used for therapy.

Topics: Amikacin; Aminoglycosides; Anti-Bacterial Agents; Gentamicins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infections; Kidney; Kidney Function Tests; Netilmicin; Phosphorus; Potassium; Sodium; Uric Acid

A fatal case of fulminant hepatic failure that occurred in the neonatal period is reported in a premature infant born after 27 4/7-weeks' gestation. Immediately after birth the infant had severe hypoxia and hypotension resulting from birth asphyxia, hypovolemic shock, and septicemia. At autopsy, histological appearance of the liver showed virtually total hepatocellular necrosis without features of fibrosis. Although the exact cause of hepatocellular injury cannot be fully ascertained, it is assumed that hypoxia and hypotension must have been the predominant factors leading to massive hepatic necrosis.

Topics: Acyclovir; Alanine Transaminase; Aspartate Aminotransferases; Bicarbonates; Cloxacillin; Dopamine; Female; Fetal Hypoxia; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Infant, Premature, Diseases; Liver; Male; Necrosis; Netilmicin; Pancuronium; Partial Thromboplastin Time; Penicillins; Pregnancy; Prothrombin Time; Sepsis; Shock; Sodium; Sodium Bicarbonate

We tried to adapt the dose of netilmicin in an intensive care unit on 41 newborns, under 8 days of age. Individual pharmacokinetic parameters were calculated after the first intramuscular dose administration and the initial dose (3 mg/kg/twice a day) was modified in 17 cases. Methodologic problems but mainly great variations in physiology and pathology explain the difficulties in predicting the serum concentration (peak and valley) on the 7th day. A decrease in the daily dose for the preterm infant, compared to the one used in full-term infant, and a drug concentration monitoring are advised.

Topics: Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Postmature; Infant, Premature, Diseases; Intensive Care Units, Neonatal; Kinetics; Netilmicin

The pharmacokinetics of netilmicin were analyzed in 30 children, including 13 premature and seven gestationally mature newborns. Ten were children ranging in age from 3.5 months to 13 years. The newborns exhibited more variation in serum levels than the older children, and the premature babies more than those born at term. The serum half-life (t1/2), tended to show higher values in premature than in mature newborns, although this was not statistically significant. The newborns had a t1/2 of 5.9 hours, compared to 2.5 hours in the older children. There was no statistically significant difference in distribution volumes or coefficients between the two groups of newborns who had an insignificantly higher relative apparent beta-phase distribution volume coefficient of 0.420 l/kg, compared to 0.377 l/kg in the older children. All had distribution coefficient values within the same range. The total body clearance in absolute terms, and when referred to body surface of 1.73 m2, was significantly lower in the newborns than in the older children, but the clearance, when referred to body weight, was of the same order in the babies and older children. The age differences affect dosage. Dosage schedules based on pharmacokinetics are proposed for gestationally premature babies, mature newborns, and older children. Premature infants can receive 2.5 mg/kg body weight and gestationally mature newborns 3.0 mgkg, both every 12 hours; the monitoring of serum concentrations is mandatory. Children aged three months and older can receive 3.0 mg/kg every eight hours.

Topics: Adolescent; Age Factors; Bacterial Infections; Body Surface Area; Body Weight; Child; Child, Preschool; Gentamicins; Gestational Age; Half-Life; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Kinetics; Netilmicin