Randomized, controlled trial comparing once daily and three times daily gentamicin in children with urinary tract infections

OBJECTIVE: 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). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.     

Gentamicin dosage in newborn infants

Sixty nine pairs of trough and peak serum levels of gentamicin were determined in sixty three cases of gentamicin therapy of suspected sepsis in newborn babies (dosage 3.46 +/- 0.42 mg/kg/day given once a day). Eighty four percent of the trough levels were below 2 mg/l (mean: 1.39-0.60 mg/l). Ninety three percent of the peak levels were between 4 mg/l and 12 mg/l (mean: 7.38-2.35 mg/l). Three peak levels (four percent) were in the potentially toxic range (above 12 mg/l) and eleven trough levels (sixteen percent) were in the potentially toxic range (above 2 mg/l). On the basis of these observations the recommended gentamicin doses during the first two weeks of life is 3-4 mg/kg/day applied once a day. In immature babies with birth weights below 1500 g the daily doses should not exceed 3 mg/kg were as term babies especially during the second week of life should be treated with a daily gentamicin doses of near to 4 mg/kg/day.     

Pharmacokinetics of single daily dose gentamicin in children with cancer.

PURPOSE: To study the pharmacokinetics of single daily dose (SDD) gentamicin in children with cancer. METHODS: Serum concentrations of gentamicin were prospectively measured at 0.5, 8, 16, and 24 hours after a single daily dose of gentamicin 6 mg/kg, given as a 30-minute infusion in 18 febrile children with cancer and a central venous catheter. Then the peak (0.5-hour) and 12-hour serum concentrations of gentamicin were prospectively measured after a SDD of 7 mg/kg during 73 febrile episodes in 54 pediatric cancer patients with suspected infections. The aim was to achieve a peak serum concentration of 15 to 20 microg/mL 10 times the minimum inhibitory concentration (MIC) for sensitive Pseudomonas strains, resulting in good bactericidal activity and a long post-antibiotic effect (PAE) after a SDD of gentamicin. RESULTS: The mean serum peak gentamicin concentration 30 minutes after the end of the infusion of 6 mg/kg was 13.3 +/- 4.0 microg/mL. The mean serum concentration 16 hours after the infusion was 0.3 +/- 0.2 microg/mL. The mean peak and 12-hour serum concentration after SDD of 7 mg/kg was 17.2 +/- 3.9 microg/mL and 0.9 +/- 0.7 microg/mL, respectively. The mean peak serum concentration after SDD of 7 mg/kg in children younger than 5 years of age (16.1 +/- 3.5 microg/mL ) was significantly lower than that of children over 5 years of age (18.2 +/- 3.9 microg/mL; P = 0.02). The desired peak serum concentration was achieved in 67% of children younger and 84% of those older than 5 years of age. CONCLUSION: Adequate peak serum concentrations of gentamicin in children may be obtained with a SDD of 7 mg/kg. Children younger than 5 years of age achieve lower peak serum gentamicin concentration after SDD of 7 mg/kg than those older than 5 years.     

Individualizing gentamicin dosage in patients with cystic fibrosis: limitations to pharmacokinetic approach

Gentamicin serum concentrations were measured in 15 children and seven adults with cystic fibrosis and in eight children with other diseases. Potentially toxic trough concentrations occurred in three of the first nine patients studied, in whom the dose and a 4-hour dosing interval were prescribed on the basis of one-compartment pharmacokinetic calculations (Sawchuck-Zaske method). In contrast, final concentrations were within the accepted target ranges for the remaining 13 patients with cystic fibrosis, in whom the dose and interval were adjusted empirically on the basis of a single pair of "peak" and trough values. The mean +/- SD final dosage required to achieve target concentrations was 13.8 +/- 2.9 mg/kg/d for children and 11.8 +/- 1.1 mg/kg/d for adults (P greater than 0.05), generally divided into four doses at 6-hour intervals. Mean half-life and incremental increase in serum concentration from previous trough to subsequent "peak," an indirect measurement of volume of distribution, were not significantly different between children or adults with cystic fibrosis and pediatric control subjects; there was little interpatient variability in these values. Thus the high dosage requirements were related more to the higher target concentrations than to altered pharmacokinetic disposition in patients with cystic fibrosis. We conclude that the initial dose of gentamicin to achieve a peak of 8 to 12 micrograms/mL and a trough of less than 2.0 micrograms/mL in patients with cystic fibrosis should be 3 mg/kg administered every 6 hours in children and every eight hours in adults. Subsequent dosage adjustment should be made on the basis of a pair of peak and trough serum concentration measurements obtained after the fifth dose. Dosing intervals in this patient population generally should be no shorter than every 6 hours, even if the initial trough concentration is less than 1 microgram/mL.     

Incidence of potentially toxic concentrations of gentamicin in the neonate

The incidence of putatively toxic serum concentrations and the factors influencing their occurrence were investigated in a study of 91 neonates receiving parenteral gentamicin twice daily at a dose of mean (SD) 5.5 (0.1) mg/kg/day. Most neonates were preterm and of low birthweight. Serum concentrations, area under the curve (AUC), and clearance were calculated. Potentially toxic trough concentrations (greater than 2 mg/l) were recorded in 57 of 91 (63%) neonates; 24 of these had trough concentrations greater than 3 mg/l. These babies were of a significantly lower gestational age and were younger than the remainder of the population. Toxic trough concentrations were not accompanied by raised peak serum values. A wide variation in all pharmacokinetic variables was observed. Peak serum concentration was most highly correlated with dose, while trough concentration, AUC, and clearance were more dependent on postnatal age. Clearance of gentamicin decreased significantly with increasing serum urea and creatinine concentrations. Preterm neonates in the first week of life are likely to develop potentially toxic serum concentrations when receiving the currently recommended dose of gentamicin (5-6 mg/kg/day). To prevent accumulation the dosage interval may need to be increased to 18 hours in these babies.     

Incidence of potentially toxic concentrations of gentamicin in the neonate.

The incidence of putatively toxic serum concentrations and the factors influencing their occurrence were investigated in a study of 91 neonates receiving parenteral gentamicin twice daily at a dose of mean (SD) 5.5 (0.1) mg/kg/day. Most neonates were preterm and of low birthweight. Serum concentrations, area under the curve (AUC), and clearance were calculated. Potentially toxic trough concentrations (greater than 2 mg/l) were recorded in 57 of 91 (63%) neonates; 24 of these had trough concentrations greater than 3 mg/l. These babies were of a significantly lower gestational age and were younger than the remainder of the population. Toxic trough concentrations were not accompanied by raised peak serum values. A wide variation in all pharmacokinetic variables was observed. Peak serum concentration was most highly correlated with dose, while trough concentration, AUC, and clearance were more dependent on postnatal age. Clearance of gentamicin decreased significantly with increasing serum urea and creatinine concentrations. Preterm neonates in the first week of life are likely to develop potentially toxic serum concentrations when receiving the currently recommended dose of gentamicin (5-6 mg/kg/day). To prevent accumulation the dosage interval may need to be increased to 18 hours in these babies.     

Treatment of urinary tract infection with gentamicin once or three times daily

AIM: To examine the safety and efficacy of once-daily (OD) gentamicin treatment compared with conventional 8-hourly dosing (TDS) for urinary tract infection (UTI). METHODS: This was a prospective, randomized, controlled trial of children 1 mo to 13 y of age with presumed UTI. Children were randomly assigned to OD gentamicin 5 mg kg(-1) d(-1) or TDS gentamicin 6 mg kg(-1) d(-1) divided 8 hourly. Microbiological efficacy, nephrotoxicity, ototoxicity and renal scarring were assessed at the end of treatment. RESULTS: 210 patients with presumed UTI were recruited, of whom 172 were analysable (OD 84, TDS 88). The median age was 7 mo, 50% were male and 74% (n = 127) of patients had pyelonephritis. The majority of infections were due to Escherichia coli (n = 153, 89%), of which 9 (5.2%) were bacteraemic. Comparing the two groups, there was no significant difference in age, gender, duration of fever before admission, pyuria, nitrite positivity or initial total white blood cell count. All patients had negative urine cultures after 2-3 d of treatment, demonstrating 100% microbiological efficacy. There was no difference between the two groups in terms of ototoxicity, nephrotoxicity, duration of gentamicin treatment or time to fever defervescence. CONCLUSION: OD gentamicin is as efficacious as TDS gentamicin in the treatment of UTI in children, with no difference in ototoxicity and nephrotoxicity.     

Impact of zinc supplementation in malnourished children with acute watery diarrhoea

A double-blind, randomized, controlled clinical trial was conducted on 80 malnourished children with acute dehydrating diarrhoea to evaluate the efficacy of oral supplementation of zinc as an adjunct therapy to oral rehydration solution (ORS). After decoding it was observed that 44 children received zinc sulphate (177 mg/kg/day in three divided doses equivalent to 40 mg elemental zinc) in a syrup form and 36 children received only syrup placebo. Clinical parameters and microbiological findings of stool samples were comparable in the two groups at the time of enrollment. All the children (100 per cent) in the zinc supplemented group and 32 (89 per cent) children in the placebo group recovered within 5 days of hospitalization (p = 0.04). The zinc supplemented group had a significantly shorter duration of diarrhoea (70.4 +/- 10.0 vs. 103.4 +/- 17.1 h; p = 0.0001), passed less liquid stool (1.5 +/- 0.7 vs. 2.4 +/- 0.7kg; p=0.0001), consumed less oral rehydration solution (2.5 +/- 1.0 vs. 3.6 +/- 0.8 litre; p = 0.0001) and other liquids (867.0 +/- 466.1 vs. 1354.7 +/- 675.6 ml; p = 0.0001) as compared to the placebo group. Our findings suggest that zinc supplementation as an adjunct therapy to ORS has beneficial effects on the clinical course of dehydrating acute diarrhoea.     

Once daily dose gentamicin in neonates — is our dosing correct?

Aim:  The aim of this paper is to study the safety and efficacy (measured by therapeutic level) of once daily gentamicin in neonates ≥32 weeks of gestation and ≤7 days of age.
Setting:  Level II neonatal intensive care unit.
Subjects:  Neonates ≥32 weeks of gestation and ≤7 days of age treated with gentamicin for presumed sepsis.
Methods:  Gentamicin was administered by intravenous injection at 4 mg/kg/day once daily. Peak and trough gentamicin levels were measured at the third dose.
Results:  In neonates with gestational age between 32 and 36 weeks, 14 out of 65 (22%) had trough serum concentration >2 mg/L. Only 39 (60%) had peak and trough levels within the therapeutic range. All babies who had audiometric evaluation (62 out of 65) had normal hearing. Out of the 65 babies, 60 had paired serum creatinine levels estimated and none had evidence of renal dysfunction. Among term neonates, only 2 out of 50 had the trough serum concentration of >2 mg/L. In 38 (76%) of the 50 neonates, the trough serum gentamicin concentration was <2.0 mg/L and the peak level was <10 mg/L. Forty-eight babies had audiometric evaluation which was normal.
Conclusion:  A dose of 4 mg/kg/day produces serum gentamicin levels outside the therapeutic range in two-fifths of neonates between 32 and 36 ± 6 weeks. A single dose of 4 mg/kg/day of gentamicin is appropriate for term babies and probably excessive for 32–36 weeks' neonates.     

Once daily ceftriaxone and gentamicin for the treatment of febrile neutropenia.

AIMS: To evaluate the pharmacokinetics of once daily (OD) gentamicin and its effectiveness as part of an OD regimen for the empirical treatment of febrile neutropenia in children with cancer. SUBJECTS: 59 children aged 6 months to 16 years (mean (SD) 5.7 (4) years) with febrile neutropenia (neutrophil count < 0.5 x 10(9)/l) after chemotherapy. METHODS: Over one year, 113 febrile neutropenic episodes were treated empirically with an OD antibiotic regimen of ceftriaxone (80 mg/kg; maximum 4 g) and gentamicin (7 mg/kg; infused over 60 minutes, no maximum). The patients were assessed after 48 hours. RESULTS: 86 of the 113 episodes settled with the first line antibiotic regimen. In 29 episodes, blood cultures identified a causative bacterial pathogen; for 17 of these, the first line antibiotic regimen was adequate; in four episodes, although the episode settled, ceftriaxone was replaced by a more appropriate antibiotic and OD gentamicin was continued; in the remaining eight episodes, a glycopeptide antibiotic was deemed necessary. There was no failure of treatment in organisms sensitive to gentamicin, including Pseudomonas aeruginosa. In 27 episodes (24%), resolution was obtained by the empirical introduction of a second line regimen of ceftazidime and a glycopeptide antibiotic, and/or amphotericin. Gentamicin concentrations were measured in 110 episodes and they were all below the 24 hour line indicating that there was no need to change the dosing interval. In two episodes (2%), serum creatinine rose transiently by more than 50% of the baseline concentration. Although there was no vestibular toxicity, three of 30 children who underwent pure tone audiometry reported high frequency hearing loss in one ear. CONCLUSION: OD gentamicin can be used safely and effectively to treat febrile neutropenia in children with cancer. When used for a short period (< 5 days), in children not receiving other nephrotoxic drugs and who have normal serum creatinine, serum gentamicin estimations are unnecessary.     

Plasmodium falciparum inhibitory capacities of paired maternal-cord sera from south-west province, Cameroon

In malaria endemic areas, young children are protected against malaria attack during the first few weeks of life partially by transplacentally acquired antibodies. In this study, we show, using an in vitro assay, that part of these antibodies are involved with blocking the re-invasion of host red blood cells by erythrocytic merozoites. One hundred consecutive paired maternal-cord blood samples were collected at delivery and their plasma assayed for total IgG antibodies against crude blood stage antigens by the ELISA. The Ig fraction were precipitated from the plasma samples with (NH(4))(2)SO(4), purified on PD10 columns and used in vitro in determining the re-invasion inhibitory capacities. The mean (+/-SD) ELISA OD(405) IgG antibodies to crude blood stage antigens of maternal (0.476 +/- 0.48) and cord (0.421 +/- 0.39) plasma samples was not significantly different. However, the mean total protein concentration of the Ig fractions for maternal samples (15.82 +/- 3.85) was significantly higher (p=0.005) than that of paired cord samples (12.87 +/- 2.86 mg/ml). There was no correlation between anti-Plasmodium falciparum-specific IgG levels and total protein concentrations of the Ig fractions of both maternal and cord samples. The entire test Ig fractions were strongly inhibitory (>50 per cent) except for four paired maternal cord samples, which were moderately inhibitory (21--50 per cent) at the highest concentration tested (1:2 dilution). Furthermore, there was no correlation between maternal IgG levels and percentage re-invasion inhibition at the 1:2 dilution. The results suggest that mothers resident in malaria endemic areas possess naturally acquired re-invasion inhibitory antibodies and their foetuses can acquire these antibodies transplacentally, which may contribute to the relative protection observed in infants during their first few weeks of life.     

Plasma alpha-tocopherol (vitamin E) levels and tocopherol-lipid ratio among children with protein-energy malnutrition (PEM)

The fat-soluble vitamin E (alpha-tocopherol) status of 47 malnourished children was assessed and compared with that of a control group of ten age-matched normal children. Plasma levels of alpha-tocopherol, total lipid and the ratio of alpha-tocopherol to total lipid were determined. The plasma vitamin E level was low, with a value of less than 11.61 mumol/l (500 micrograms/dl) in 40 (85%) of the malnourished children while the remaining seven (15%) children had values that ranged between 11.61 and 17.20 mumol/l (500-741 micrograms/dl). On the other hand, the tocopherol/total lipid ratio was less than 0.8 mg/g of total lipid in only seven of the malnourished children. The remaining 40 (85%) subjects had values that ranged between 0.8 and 1.96 mg/g of total lipid, whereas in the control group, both the plasma tocopherol levels and the tocopherol/lipid ratio were greater than 11.61 mumol/l (500 micrograms/dl) and 0.8 mg/g of plasma total lipid respectively.     

Serum levels of gentamicin at peak and trough in neonates and infants

The peak and the trough levels of serum gentamicin were determined in 50 cases of neonates and infants by microbiological assay method. The peak levels in the neonates and the infants were 5.98±0.48 and 4.63±0.31 mcg/ml respectively. The trough levels in the corresponding group were 1.06±0.19 and 0.94±0.23 mcg/ml. The mean values of the peak and trough levels of the antibiotic were 5.57 and 1.02 mcg/ml respectively. It was observed that there was a significant lower peak concentration in the infants than in the neonates. A significantly higher peak concentration of gentamicin was observed in babies aged under 7 days than in those above 7 days. The route of administration (between I/M and I/V) did not seem to have any effect on the peak and trough levels of the antibiotics.     

Adenosine deaminase in childhood pulmonary tuberculosis: diagnostic value in serum.

The diagnostic value of serum adenosine deaminase (ADA) activity was evaluated in childhood pulmonary tuberculosis. Serum ADA levels were measured in 20 children diagnosed with pulmonary tuberculosis (group 1) and 150 children (group 2) including 128 with tuberculosis infection (Mantoux test positive) and 22 healthy children. In group 1, the mean serum ADA activity was 74.06 +/- 18.5 U/l, which was significantly (p < 0.001) higher than that of group 2 (40.36 +/- 12.0 U/l). A serum ADA level of > or = 53.76 U/l had a sensitivity of 100 per cent, specificity of 90.7 per cent, positive predictive value of 58.8 per cent, and a negative predictive value of 100 per cent in children with tuberculosis disease. To conclude, measurement of serum ADA activity was a useful diagnostic tool in childhood pulmonary tuberculosis.     

Extended interval dosing of gentamicin in premature neonates ≤ 28‐week gestation

Aim: To evaluate an extended interval dosing (EID) regimen of gentamicin in neonates ≤28‐week gestation. Methods: In 2008, an EID regimen for gentamicin was introduced for all neonates admitted to the NICU in Calgary. The dosing interval was based on a 22 h level after the first dose of 5mg/kg. We conducted an observational study in 33 infants ≤28‐week gestation on the EID regimen from the first day of life and compared gentamicin peak and trough levels with a historical control of 34 infants who received gentamicin in a dose of 2.5 mg/kg every 24 h (TID, traditional interval dosing). Results: In the EID group, based on the 22 h level, dosing interval was 36 h in 20 neonates and 48 h in 13 neonates. All neonates, except one, achieved therapeutic peak and trough levels. Compared to the TID group, the EID group had higher peak levels (median 9.8 μg/mL vs. 4.6 μg/mL, p < 0.001) with no difference in trough levels. With target peak levels of 5–12 μg/mL and trough levels of <2 μg/mL, a higher proportion of neonates in the TID group would need dose adjustment. Conclusion: In neonates ≤ 28‐week gestation, an EID regimen from day one of life, using a single level 22 h after the first dose for dosing interval, achieves therapeutic peak and trough levels and more optimum peak levels as compared to a TID regimen.     

Comparison of two gentamicin dosing schedules in very low birth weight infants

BACKGROUND: Several dosing schedules for gentamicin have been recommended for very low birth weight infants during the early neonatal period. We conducted a prospective, randomized, controlled trial to compare efficacy and pharmacokinetics of two dosing schedules in preterm neonates. METHODS: Fifty-eight very low birth weight infants (600 to 1500 g), prescribed gentamicin for treatment of suspected sepsis during the first week after birth, were randomized to receive either the new dosing schedule [every 48 h (q48h)] or the existing dosing schedule [every 24 h (q24h)]. Infants in the "q48h" group received gentamicin at 5.0 or 4.5 mg/kg/dose q48h depending on weight group and infants in the "q24h" group received 2.5 or 3.0 mg/kg/dose q24h. Peak and trough serum gentamicin concentrations were monitored. RESULTS: Peak serum gentamicin concentrations after the first dose were significantly higher in the q48h infants than in q24h infants (8.19 +/- 1.3 vs. 6.04 +/- 2.2, P = 0.00001). Ninety percent of all peak serum gentamicin concentrations in the q48h group were in a higher therapeutic range of 6 to 12 microg/ml as compared with 55% of q24h (P = 0.0005). None of the q48h infants had subtherapeutic serum gentamicin concentrations immediately after administration of the first dose as compared with 36% of q24h infants (P < 0.005). Eighteen percent of q24h infants continued to have peak serum gentamicin concentrations in subtherapeutic range even after the third dose at 48 h. Trough serum gentamicin concentrations were significantly lower in q48h infants than in q24h infants. However, 9 of 30 (30%) q48h infants had trough serum gentamicin concentrations of < or = 0.5 microg/ml before the dose at 48 h and 4 of the 9 had serum gentamicin concentrations of <1 microg/ml at 24 h after the first dose. CONCLUSIONS: The q48h dosing schedule of gentamicin given to very low birth weight infants during the first week after birth achieved therapeutic serum gentamicin concentrations and potentially higher peak to MIC ratios for microorganisms in all infants. However, nearly one-third of the infants had extremely low serum gentamicin concentrations before the next dose. A dosing interval of 36 h might be optimal for bactericidal activity and avoid bacterial growth during prolonged periods of extremely low serum gentamicin concentrations; this dosing interval warrants study.     

Pharmacokinetics of enprofylline administered intravenously and as a sustained-release tablet at steady state in children with asthma

The pharmacokinetics of enprofylline (3-propylxanthine) were studied in 10 children with asthma (mean age 7.9 years), after enprofylline 1 mg/kg given intravenously and after enprofylline 7.5 +/- 1.3 mg/kg given as a sustained-release tablet after 8 days of oral dosing twice daily. The mean +/- SD enprofylline serum elimination half-life was 1.06 +/- 0.20 hours, considerably shorter than the half-life reported in adults. The mean steady-state volume of distribution was 0.55 +/- 0.05 L/kg. The mean clearance rate was 0.44 +/- 0.06 L/hr/kg. The mean enprofylline serum concentration at steady state was 1.7 +/- 0.5 mg/L. The mean peak to trough ratio was 3.02 +/- 1.31. On the first and ninth study days, 87% +/- 8% and 90% +/- 16%, respectively, of the dose of enprofylline was recovered as unchanged drug in the urine. Enprofylline has a short half-life in children, but the sustained-release formulation provides stable serum concentrations and satisfactory relief of asthma throughout the 12-hour dosing interval.     

Comparison of serum concentrations of ceftazidime and tobramycin in newborn infants

Peak and trough serum concentrations of ceftazidime and tobramycin were determined in neonates with suspected septicaemia in an open randomized study. Mean peak serum levels were 85 (±4.4 SE) mg/l for ceftazidime and 5.8 (±0.3 SE) mg/l for tobramycin. The peak serum levels of ceftazidime were well above the reporte mminimal inhibitory concentration (MIC)₉₀ values of pathogenic bacteria encountered in neonates, while peak serum levels of tobramycin were lower than reported MIC₉₀ values for Klebsiella, Pseudomonas, Enterobacter and Serratia species. Nine of 33 tobramycin-treated patients had potentially toxic trough serum levels (>2mg/l) and nine had subtherapeutic peak serum levels (<4mg/l). The dosage of this antibiotic had to be changed frequently. In comparison only 2 of 29 ceftazidime-treated patients had subtherapeutic peak levels (<40mg/l) and none had potentially toxic trough levels (>40mg/l). Ceftazidime, in comparison with tobramycin, has a more favourable antibacterial spectrum and routine determinations of peak and trough serum levels should not be necessary.Abbreviations LBW low birth weight - MIC minimal inhibitory concentration     

Evaluation of the correlation between serum tumor necrosis factor-alpha and relative body mass index (RBMI) in childhood

OBJECTIVE: Obesity and malnutrition are the main nutritional problems of childhood. Tumor necrosis factor-alpha (TNFalpha) is a well-known cytokine with effects on adipose tissue. In this study relative body mass index (RBMI) and serum TNFalpha levels were compared in obese and malnourished children, and hyperinsulinism was evaluated in the obese children. SUBJECTS AND METHODS: Thirty-four children of whom 14 (9 M, 5 F) were obese, 10 (5 M, 5 F) were malnourished and 10 (4 M, 6 F) constituted the control group were evaluated. RBMI was used to define the groups according to the formula: patient's BMI/predicted BMI x 100. Mean RBMI values were 148.7 +/- 26, 77.6 +/- 4.63, and 100 +/- 8.2 in the obese, malnourished and control group, respectively. Mean ages of the obese, malnourished and control children were 9.75 +/- 2.59, 12.3 +/- 1.86 and 12.4 +/- 1.3 years, respectively. RESULTS: Higher serum TNFalpha levels were found in the obese children (20.94 +/- 0.38 pg/ml) in comparison with the control group (2.97 +/- 0.05 pg/ml) (p <0.001). Mean TNFalpha level in the malnourished group was 2.77 +/- 0.04 pg/ml, not statistically different from the control group (p >0.05). TNFalpha concentrations of the hyperinsulinemic and normoinsulinemic obese patients were not significantly different (p >0.05). CONCLUSION: We showed higher levels of serum TNFalpha in obese children. Increased TNFalpha levels do not always reflect hyperinsulinism. There was no difference in TNFalpha levels between the controls and the malnourished group.     

Chloramphenicol pharmacokinetics in African children with severe malaria

The objective of this study was to determine if the current dosage regimen for chloramphenicol CAP administered to children with severe malaria SM for presumptive treatment of concomitant bacterial meningitis achieves steady state plasma CAP concentrations within the reported therapeutic range of 10-25 mg/l. Fifteen children (11 male, 4 female) with a median age of 45 months (range: 10-108 months) and having SM, were administered multiple intravenous doses (25 mg/kg, 6 hourly for 72 h) of chloramphenicol sodium succinate CAPS for presumptive treatment of concomitant bacterial meningitis. Blood samples were collected over 72 h, and plasma CAPS, CAP and CSF CAP concentrations determined by high performance liquid chromatography. Average steady state CAP concentrations were approximately 17 mg/l, while mean fraction unbound (0.49) and CSF/plasma concentration ratio (0.65) were comparable to previously reported values in Caucasian children. Clearance was variable (mean = 4.3 l/h), and trough plasma concentrations during the first dosing interval were approximately 6 mg/l. Simulations indicated that an initial of loading dose of 40 mg/kg CAPS, followed by a maintenance dose of 25 mg/kg every 6 h would result in trough CAP concentrations of approximately 10 mg/l and peak concentrations <25 mg/l throughout the treatment period. The current dosage regimen for CAP needs to include a loading dose of 40 mg/kg CAPS to rapidly achieve plasma CAP concentrations within the reported therapeutic range.