***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: OBJECTIVE 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 . DESIGN R and omized controlled trial . SETTING Medical college hospital . SUBJECTS Seventy three neonates of gestational age>32 weeks at risk or with clinical features of sepsis . METHODS The subjects were divided into preterm and term groups . Babies in each of these groups were r and omized 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 . RESULTS 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 . CONCLUSION Once daily gentamicin administration is as effective as twice daily therapy and would be more cost effective This article reports the results of a four-year follow-up study initiated in 1970 on the long-term effects of gentamicin and kanamycin use in newborn infants .  Audiometric , vestibular , and psychometric evaluations were performed on  gentamicin-treated , kanamycin-treated , and untreated , matched control infants and children . No substantial sensorineural hearing loss or vestibular dysfunction was identified in these patients that could be attributed to aminoglycoside therapy . Performances on the Illinois Test of Psycholinguistic Abilities , Beery Test of Visual Motor Integration , the Peabody Picture Vocabulary Test , and on fine and gross motor examinations were comparable for the three study groups 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 Neonates , especially preterms , are known to have low glomerular filtration rates ( GFR ) . This may result in elevated trough concentrations during multiple administration of aminoglycosides ( AGs ) , potentially leading to nephro- and ototoxic reactions . The once-daily administration ( q.d . ) of AGs has been shown to be equally or better tolerated in adults and children than the conventional schedules ( twice daily , b.i.d . ; thrice daily , t.i.d . ) , while offering potential pharmacodynamic and nursing advantages . No data , however , are available for neonates . As a consequence , this pilot study was conducted in order to assess the tolerance of the once-a-day administration of amikacin in comparison with the twice daily dose regimen , in relation to the pharmacokinetics of the drug under these two schedules . 22 Male neonates ( gestational age > or = 34 weeks ; postnatal age < or = 2 days ) were r and omized to receive amikacin ( AK ) ( 15 mg/kg/day ) q.d . ( n = 10 ) or b.i.d . ( n = 12 ) together with ampicillin ( 50 mg/kg/12 h ) . AK plasma levels were measured at days 1 , 3 , 5 and 7 of treatment just before the next dose ( trough level ) and 1 h after completion of infusion ( peak level ) and after 3 and 6 h only at day 1 . Due to the small size of the sample s , no difference in efficacy could be assessed and was not the aim per se . Glomerular dysfunction was assessed by creatinine clearance , and tubular injuries by the urinary excretion of proteins ( retinol binding protein , beta 2-microglobulin , clara cell protein ( P1 ) and microalbumin ) , enzymes ( N-acetyl-beta-D-glucosaminidase , alkaline phosphatase , alanine aminopeptidase , and gamma-glutamyltransferase ) , and total phospholipids ( TPL ) in urine . Ototoxicity was assessed by brainstem auditory evoked potentials ( BAEPs ) at days 0 , 3 and 9 of therapy . Eight healthy neonates served as controls . All patients showed a normal and similar increase of GFR during the first postnatal days . Proteinuria did not increase , but enzymuria and TPL increased significantly during the treatment in both AK groups without significant difference between groups . BAEPs at day 9 were not significantly different between treated and untreated patients . We conclude from this pilot study that , in the absence of more toxicity , the q.d . administration of AK in neonates of > or = 34 weeks of gestational age may be recommended over its bid schedule in view of its potential advantages In a prospect i ve , r and omized 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 OBJECTIVE : There is no uniformity in the current recommendations of dosing regimen of gentamicin for neonates . We conducted a prospect i ve , r and omized , controlled trial to compare a once-daily dosing regimen to the twice-daily dosing regimen for neonates ≥2500 g during the first 7 days after birth . STUDY DESIGN : Infants ≥2500 g admitted to the Neonatal Intensive Care Unit and prescribed gentamicin for suspected bacterial infection were r and omized to receive either 4 mg/kg every 24 hours , study group ( n=20 ) , or a st and ard 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 . RESULTS : Peak SGC 30 minutes after the first dose was 8.2±1.7 μg/ml in the study group , compared to 6.4±1.5 μg/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 μg/ml as well as 8 to 12μg/ml . None of the study infants , compared to six control infants , had trough SGCs ≥2 μg/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 ) . CONCLUSION : 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 Objective . We developed a simplified gentamicin dosing protocol for all neonates using a loading dose and once-daily dosing that would have an equal or lower incidence of toxicity and an equal or improved effectiveness compared with a regimen with no loading dose that included use of divided daily dosing . Methods . All neonatal intensive care unit patients with a postnatal age ≤7 days and started on gentamicin therapy at the discretion of the attending neonatologist were evaluated in this comparative cohort study . All peak and trough serum drug levels ( SDL ) , pertinent demographic data , and markers of potential nephrotoxicity , ototoxicity , and cure were tracked prospect ively during 132 consecutive , nonr and omized courses of therapy on a new gentamicin protocol . These were compared with data retrieved retrospectively throughout 103 consecutive , nonr and omized courses of therapy in a control group . Results . Initial measured peak SDL were higher ( 7.8 ± 1.1 μg/mL vs 6.1 ± 1.0 μg/mL ) and trough SDL were lower ( 0.9 ± 0.2 μg/mL vs 2.7 ± 0.6 μg/mL ) in the protocol term subset , compared with the control term subset ( gestational age , ≥37 weeks ; weight , ≥2500 g ) . One hundred percent of the initial and maintenance peak SDL in term protocol neonates were 5 to 12 μg/mL ; compared with 84 % of the initial and 61 % of maintenance peak SDL in the term control group . One hundred percent of the initial and maintenance trough SDL were in the desired range of < 2 μg/mL in term protocol neonates ; compared with 70 % of the initial and 94 % of maintenance trough SDL in the term control group . No significant differences were found in any SDL in low birth weight neonates ( gestational age < 37 weeks or weight < 2500 g and > 1500 g ) in the protocol compared with the control group . The very low birth weight ( weight < 1500 g ) protocol neonates had a significantly higher mean initial trough SDL ( 2.3 ± 0.7 μg/mL vs 1.5 ± 0.6 μg/mL ) and a lower incidence of initial trough SDL < 2.0 μg/mL ( 30 % vs 95 % ) than very low birth weight neonates in the control group . No differences were seen between groups in incidence of significant rise in serum creatinine or failure of hearing screen . Conclusion . A loading dose followed by once-daily dosing was shown to result in SDL in the safe and therapeutic range in all term neonates in this study . In low birth weight neonates , this regimen result ed in peak and trough SDL throughout therapy that were similar to those observed in the control group . Delaying the initiation of maintenance once-daily dosing until 36 to 48 hours after the loading dose would be expected to result in a higher incidence of initial trough SDL in target range for very low birth weight neonates Twenty full term neonates with suspected bacterial infection were r and omly 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 
    Output:
    
Extended interval dosing of aminoglycosides in neonates is safe and effective , with a reduced risk of serum drug concentrations outside the therapeutic range