Randomized controlled trial of once vs. twice daily gentamicin therapy in newborn. Gentamicin in neonatal infection: once versus twice daily dosage. Pharmacokinetics of once-daily dosing of gentamicin in neonates. Gentamicin therapy in preterms: a comparison of two dosage regimens. Once- versus twice-daily gentamicin dosing in neonates >/=34 Weeks' gestation: cost-effectiveness analyses. Once versus twice daily dose of gentamicin therapy in Thai neonates. Comparison of once-daily versus twice-daily gentamicin dosing regimens in infants > or = 2500 g. [Tolerability of once-daily-dosing of intravenous gentamicin in preterm neonates born at 32-37 weeks of gestation]. Randomized, controlled trial comparing once daily and three times daily gentamicin in children with urinary tract infections. Pharmacokinetics and antibacterial activity of daily gentamicin.
To compare the efficacy of once daily gentamicin administration to the conventional twice daily dosage schedule by estimation of serum gentamicin concentrations (SGC) in neonates.
                Randomized controlled trial.
                Medical college hospital.
                Seventy three neonates of gestational age>32 weeks at risk or with clinical features of sepsis.
                The subjects were divided into preterm and term groups. Babies in each of these groups were randomized to receive a single daily dose (4 mg/kg) or a twice daily dose (2.5 mg/kg) of injection gentamicin intravenously. Trough and peak SGC were estimated half an hour prior and one hour after the second dose. Statistical analysis was done using the equivalence method.
                In preterm as well as term babies, the mean peak and trough gentamicin levels were comparable in the two regimens. There is statistically significant evidence to show that the effect of once daily and twice daily dosage is similar.
                Once daily gentamicin administration is as effective as twice daily therapy and would be more cost effective. Fifty-four neonates were included and completed the study. Twenty-seven neonates were given 2.0-2.5 mg/kg of gentamicin twice daily while 27 neonates were given 4.0-5.0 mg/kg of gentamicin once daily. The twice daily dose and the once daily dose group had mean steady state gentamicin peak concentrations of 5.94 +/- 1.57 mg/l and 8.92 +/- 1.59 mg/l, respectively (p<0.05) while their trough concentrations were 1.44 +/- 0.49 mg/l and 0.90 +/- 0.35 mg/l, respectively (p<0.05). There were 3 neonates (11.11%) in the twice daily dose group whose peak and trough level were not within the desirable therapeutic range, two patients with too high trough level (>2 mg/l) and one with subtherapeutic peak level (<4 mg/l). Only one patient in the once daily group had undesirable trough level that was higher than 1.5 mg/l but less than 2 mg/l. Treatment with a once daily dose did not present more nephrotoxity than a twice daily dose regimen and had the tendency to have less effect on renal function. Once daily dosage can achieve the equivalent efficacy compared to a twice-daily dosage regimen. All neonates in twice daily and once daily dosage groups showed improvement in clinical outcome. Therefore, a once daily dose of gentamicin with 4.0-5.0 mg/kg could be an appropriate regimen in term neonates during the first 7 days of life. This regimen produces peak concentration that may have greater clinical efficacy and trough concentration with less toxicity than conventional dosing regimen. In a prospective, randomized trial of once-daily versus twice-daily intravenous or intramuscular dosing with gentamicin, 11 neonates received 5.0 mg/kg once daily and 15 received 2.5 mg/kg twice daily for 2 ro 3 days. The once-daily intravenous dosing group and the twice-daily intravenous or intramuscular dosing group, respectively, had mean steady-state gentamicin peak concentrations of 10.7 versus 6.6 micrograms/ml (p < 0.05), 6-hour postdosing concentrations of 4.7 versus 2.8 micrograms/ml (p < 0.05), trough concentrations of 1.7 versus 1.7 micrograms/ml, elimination half-life of 8.8 versus 5.4 hours (p < 0.05), and volume of distribution at steady state of 0.67 versus 0.46 L/kg. No nephrotoxic effects were identified in any group. Once-daily gentamicin therapy with 5.0 mg/kg in neonates achieves peak serum levels that are more suitable for optimal bacterial killing than those which traditional regimens achieve. Similar trough levels suggest that even larger doses and longer dosing intervals may be ideal in term neonates. To compare the pharmacokinetic profile of gentamicin given as a once daily dose as against the conventional twelve hourly dose in preterm neonates.
                Randomized double blind study.
                Tertiary level Neonatal Intensive Care Unit.
                Eighteen preterms admitted during the period January 1994 to May 1994.
                The babies were randomly assigned to receive either the once daily (plan O, 4 mg/kg Q 24 h) or the conventional (plan C, 2.5 mg/kg Q 12 h) gentamicin dosage regimen. Blood was collected for the first peak level one hour after the first dose of gentamicin. Trough and peak-2 levels were collected before and one hour after the dose due at 48 hours, respectively. Assays were done using fluorescence immunoassay and the pharmacokinetic estimations were calculated using the three measured levels on a simplified one-compartment open model. Serum concentration time curves were plotted using the computerized Bayesian forecasting. Student 't' and Mann-Whitney U tests were applied as required.
                Initial peak levels and steady state trough and peak levels in both groups.
                Optimum therapeutic peak level after the first dose was achieved only with the once daily gentamicin regimen (mean level 5.88 vs 3.88 micrograms/ml p = 0.000). Mean trough levels remained over 2 micrograms/ml in the conventional regimen (2.76 vs 1.96 micrograms/ml p = 0.019) group. Mean peak levels at the steady state were not significantly different in either regimen (6.65 vs 5.45 micrograms/ml in conventional p = 0.177). None of the neonates showed nephrotoxicity.
                Once daily dose (4 mg/kg) of gentamicin has logistic and monetary benefits in addition to the obvious pharmacokinetic advantage. To compare performance and cost analysis of two gentamicin regimens in infants >/=34 weeks' gestation requiring antibiotics for a 72-hour rule-out sepsis evaluation. A once-daily dosing (ODD) regimen of 4 mg/kg was compared with a standard twice-daily dosing (TDD) regimen of 2.5 mg/kg every 12 hours.
                Infants at two university-affiliated Level III nurseries were prospectively temporally allocated to receive ODD (n = 27) or TDD (n = 28) as part of their 72-hour empirical antibiotic regimen. Performance of dosing regimens was based on target serum gentamicin concentrations (SGC) established prospectively as a peak of 5 to 10 microgram/mL and a trough of </=2 microgram/mL. SGC were determined by fluorescence polarization immunoassay on day 3 of therapy. Cost data were obtained by distributing a questionnaire to 15 pediatric pharmacy practice sites. Inquiries were made regarding hospital cost of drug acquisition, drug supplies, drug preparation and administration, and serum concentration analysis. Performance and cost data were then used to do a cost-effectiveness analysis.
                Mean peak concentrations were higher with ODD (7.9 +/- 0.2 microgram/mL) than TDD (6.7 +/- 0.3 microgram/mL). Half of the patients in the TDD group had trough concentrations >2 microgram/mL, compared with none in the ODD group. Overall, 57% of the SGCs in the TDD group were outside the target concentration range versus 7% in the ODD group. Based on questionnaire results, a total 72-hour process cost of ODD versus TDD was compared for regimens with and without use of SGC analysis. If SGCs are obtained, more than 75% of the cost associated with gentamicin therapy is attributable to SGC analysis. Based on a cost-effectiveness analysis, ODD was the dominant dosing strategy in all categories analyzed.
                ODD of gentamicin at 4 mg/kg in neonates >/=34 weeks' gestation is the preferable treatment strategy based on: 1) significantly improved SGC performance compared with TDD; 2) elimination of the need for routine SGC collection in infants on short courses of therapy; and 3) significant antibiotic-associated hospital cost savings when compared with conventional therapy of TDD and SGC analysis. To compare the peak and trough gentamicin concentrations in neonates after a once (ODD) vs. twice daily dosing (TDD) to establish the appropriate dosage for Thai neonates.
                Neonates of gestational age > or = 34 weeks, or body weight > or = 2000 g, suspected of having bacterial infection were randomized to receive gentamicin intravenously, either 5 mg/kg every 24 hours or 2.5 mg/kg every 12 hours. The peak and trough serum gentamicin levels (SGLs) were measured. Serum creatinine cued nephrotoxicity.
                Neonates were evaluated and baseline characteristics between the groups were compared. The ODD and TDD group had a mean gentamicin peak and trough concentration of 10.1 +/- 3.0 vs. 7.8 +/- 2.0 microg/ml (p < 0.05) and 1.6 +/- 1.1 vs. 2.6 +/- 1.2 microg/ml (p < 0.05), respectively. The peak SGL of > or = 4 microg/ml was achieved in 100% vs. 96% of the ODD vs. TDD group, respectively. SGL troughs > or = 2 microg/ml were detected less often in the ODD group (22% vs. 68%, p < 0.05). Abnormal change in serum creatinine was not observed in either group.
                A once daily dose of gentamicin 5 mg/kg achieved a significantly higher peak SGL and safer trough than a twice-daily dose of 2.5 mg/kg albeit about a quarter of the ODD group had high troughs. A single daily dose of gentamicin 3.5-4 mg/kg/d in Thai neonates should be tested. There is no uniformity in the current recommendations of dosing regimen of gentamicin for neonates. We conducted a prospective, randomized, controlled trial to compare a once-daily dosing regimen to the twice-daily dosing regimen for neonates > or = 2500 g during the first 7 days after birth.
                Infants > or = 2500 g admitted to the Neonatal Intensive Care Unit and prescribed gentamicin for suspected bacterial infection were randomized to receive either 4 mg/kg every 24 hours, study group (n=20), or a standard regimen of 2.5 mg/kg every 12 hours, control group (n=21). Serum gentamicin concentrations (SGCs) were followed and gentamicin pharmacokinetics calculated on all infants.
                Peak SGC 30 minutes after the first dose was 8.2+/-1.7 microg/ml in the study group, compared to 6.4+/-1.5 microg/ml in the control group (p=0.001). Ninety-five percent of study group infants, compared to 81% of the control group, had peak SGCs in therapeutic range after the first dose. Peak SGC at 48 hours (steady state) was 8.9+/-1.5 in the study group and 6.8+/-1.1 in the control group (p=0.0001). On further analysis, a significantly higher percentage of infants in the study group, compared to the control group, had peak SGCs in higher therapeutic ranges of 6 to 12 microg/ml as well as 8 to 12 microg/ml. None of the study infants, compared to six control infants, had trough SGCs > or = 2 microg/ml at steady state. Thus, none of the study group infants, versus six of the control group infants, needed a dosing adjustment at 48 hours (p=0.02, Fisher's exact test).
                We found that 4 mg/kg gentamicin given every 24 hours achieved significantly higher peak SGCs and safe trough concentrations in all infants, compared to the twice-daily regimen of 2.5 mg/kg. We suggest that SGCs may not need to be followed in term infants prescribed a short course of this once-daily regimen for suspected early-onset sepsis if renal functions are normal. Gentamicin is an important factor in the empiric therapy of premature babies with suspected invasive bacterial infection. The aims of the study were to assess the tolerability of short course of gentamicin in preterm neonates.
                Preterm neonates aged 24 hours or less who were born at 32-37 weeks of gestation and weighed over 1500 grams were included in the study. Those infants suspected of having invasive non-CNS bacterial infection were assigned to treatment with ampicillin 50 mg/kg twice daily and either ODD (once daily dosing) or twice daily dosing (TDD) of gentamicin 5 mg/kg/day (17 and 18 patients, respectively). Neonates with shock, impaired renal function and known kidney, ear, and heart malformations, and metabolic disease were excluded from the study. At 72 to 96 hours of therapy, serum and urine creatinine, and sodium concentrations, peak (PGt) and though (TGt) serum levels of gentamicin, and urinary lysosyme secretion were measured. Fractional excretion of sodium (FeNa), and glomerullar filtration rate (GFR) were calculated for each infant. Audiometric evaluation was performed at 1 to 2 months of age.
                For the ODD and TDD groups respectively, the values of serum creatinine, FENa, GFR, and urinary lyzozim were similar. The mean SD PGt levels were 9.9 +/- 4.6 vs 5.9 +/- 1.9 g/ml (p < 0.04), and that of the TGt levels was 1.55 +/- 0.55 vs 2.4 +/- 0.9 micrograms/ml (p = 0.028), Ten (55.6%) vs 3(23.1%) of the TDD and ODD groups respectively had TGt levels above 2 micrograms/ml (p = 0.035). Audiometric evaluation was normal in all infants.
                Short course of ODD of gentamicin could be safe and potentially more effective in preterm babies. To undertake population pharmacokinetic modeling and to determine the safety and efficacy of once daily (OD) gentamicin dosing in children with severe urinary tract infections (UTI).
                An open, randomized, controlled trial comparing OD with three times daily (TD) gentamicin dosing in hospitalized children ages 1 month to 12 years with UTI. Daily doses (milligrams per kg per day) of gentamicin in both groups were 7.5 (<5 years old), 6.0 (5 to 10 years old) and 4.5 (>10 years old).
                There were 179 children enrolled (90 OD, 89 TD). Baseline clinical characteristics and pathogens were similar, except that circulatory compromise and renal cortical scintigraphic defects were more common in the OD group. Median gentamicin treatment durations were 3.0 (OD) and 2.7 (TD) days. Mean peak gentamicin concentrations were 17.3 (OD) vs. 6.4 (TD) mg/l; 99% of peak concentrations were >7 mg/l in the OD group whereas 16% of peak concentrations were <5 mg/l in the TD group. Mean trough concentrations were 0.35 (OD) vs. 0.55 (TD) mg/l. In the OD group 4% of trough concentrations were > or = 2 mg/l, whereas in the TD group only 0.7% were > or = 2 mg/l. Age or prior elevated peak concentrations did not predict high trough concentrations. Population pharmacokinetic modeling of the data fitted a one-compartment model with first order elimination. There were no clinical or bacteriologic failures. The two disease-related complications were confined to the OD group. No nephro- or ototoxicity was identified.
                With age-appropriate dosing and measurement of serum trough concentrations before the second dose, OD gentamicin is safe and effective for the treatment of UTI requiring parenteral treatment in children aged 1 month to 12 years. Twenty full term neonates with suspected bacterial infection were randomly assigned to a once daily or a twice daily dosage regimen with gentamicin (4 mg/kg/day). Concomitantly all patients were treated with ampicillin (200 mg/kg/day). The gentamicin concentration time curves were analysed by an open two compartment model under steady state conditions on day 4 of treatment. The mean theoretical maximum serum concentration in the group taking gentamicin once daily (10.9 micrograms/ml) was significantly higher than in the group taking it twice daily (7.4 micrograms/ml). Potentially toxic serum concentrations were never reached. Mean trough concentrations were comparable in both groups (once daily 0.8 micrograms/ml; twice daily 1.0 micrograms/ml). Urinary alanine aminopeptidase excretion increased during and even two days after end of treatment in both groups without any significant differences. The results of the dynamic in vitro model revealed that both dosage schedules showed comparable bactericidal effects on pathogens inhibited by low concentrations of gentamicin like Escherichia coli and Staphylococcus aureus. However the once daily regimen was significantly superior in isolates with high minimal inhibitory concentrations.
There is insufficient evidence from the currently available RCTs to conclude whether 'once a day' or 'multiple doses a day' regimen of gentamicin is superior in treating proven neonatal sepsis. However, data suggests that pharmacokinetic properties of 'once a day' gentamicin regimen are superior to 'multiple doses a day' regimen in that it achieves higher peak levels while avoiding toxic trough levels. There is no change in nephrotoxicity or auditory toxicity. Based on this assessment of pharmacokinetics, 'once a day regimen' may be superior in treating neonatal sepsis in neonates greater than 32 weeks gestation.