Ofloxacin versus co-trimoxazole in the treatment of typhoid fever in children

Ofloxacin has been successfully used in the treatment of typhoid fever and Salmonella infections of adults for many years. However, it has rarely been tried for the typhoid fever of children. In the present study, the therapeutic efficacy of ofloxacin in the treatment of typhoid fever in children was compared to that of co-trimoxazole. Out of 41 patients with bacteriologically documented typhoid fever, those with co-trimoxazole-resistant strains received 20 mg/kg ofloxacin twice daily for 10 days, and those with co-trimoxazole-susceptible bacteria were given 60 mg/kg co-trimoxazole twice daily for 10 days. Both groups were compared according to the clinical variables (apyrexia, resolution of gastrointestinal, central nervous system reactions and articular symptoms) and the time when cultures became negative. All patients in both groups were cured without relapse. Apyrexia, resolution of gastrointestinal, central nervous system reactions and articular symptoms were obtained in a significantly shorter time with ofloxacin than with co-trimoxazole (P < 0.05). The interval between onset of therapy and the time when cultures became negative was significantly shorter in the ofloxacin group than in the co-trimoxazole group (P = 0.005). Ofloxacin seems to be a good alternative in the treatment of typhoid fever caused by co-trimoxazole resistant salmonellae in children aged less than 16 years. It is well tolerated by the patients and it causes no side effects with short-term usage.     

A comparative study of ofloxacin and cefixime for treatment of typhoid fever in children. The Dong Nai Pediatric Center Typhoid Study Group

BACKGROUND: Despite concerns about safety in children, fluoroquinolone antibiotics have become the treatment of choice in patients with multidrug-resistant typhoid fever in Vietnam. However, quinolone-resistant strains of Salmonella typhi have recently been reported from Vietnam; and if quinolone resistance becomes established, alternative oral treatment options will be needed. OBJECTIVE: Cefixime, an orally administered third generation cephalosporin, was compared with ofloxacin for the treatment of uncomplicated typhoid fever in children. METHODS: In an open trial children with suspected typhoid fever were randomized to receive either ofloxacin (10 mg/kg/day in two divided doses) for 5 days or cefixime (20 mg/kg/day in two divided doses) for 7 days. RESULTS: S. typhi was isolated from 82 patients (44 in the cefixime group, 38 in the ofloxacin group) and 70 (85%) of the isolates were multidrug-resistant. Median (95% confidence interval, range) fever clearance times were 4.4 (4 to 5.2, 0.2 to 9.9) days for ofloxacin recipients and 8.5 (4.2 to 9, 1.8 to 15.2) days for cefixime-treated patients (P < 0.0001). There were 11 treatment failures (10 acute and one relapse) in the cefixime group and 1 acute treatment failure in the ofloxacin group (mean difference, 22%; 95% confidence interval, 9 to 36%). CONCLUSION: Short course treatment with cefixime may provide a useful alternative treatment in cases of uncomplicated typhoid fever in children, but it is less effective than short course treatment with ofloxacin.     

阿奇霉素治疗儿童伤寒疗效观察

目的　近年来儿童伤寒耐药性明显升高,且对目前的替代剂头孢曲松和诺氟沙星的耐药菌株也有 增多的趋势,为探讨治疗儿童伤寒其它合适替代药物,该文采用阿奇霉素治疗儿童伤寒并观察其临床疗效、副作用和 耐受性。方法　45例确诊伤寒患儿,随机分为治疗组和对照组,治疗组23例,给予阿奇霉素治疗;对照组22例,给予 头孢曲松钠治疗。观察其临床疗效和副作用。结果　治疗组与对照组有效率分别为100%和90.9%,两组间差异无 显著性(P>0.05);治疗组与对照组退热时间分别为3.12±0.44d和3.18±0.53d,两组间差异无显著性(P>0.05)。 两组均未出现不良反应。结论　阿奇霉素治疗儿童伤寒具有良好疗效。     

Comparative efficacies of aztreonam and chloramphenicol in children with typhoid fever

We compared aztreonam with chloramphenicol in a randomized trial involving the treatment of 36 children with typhoid fever. Eighteen children were randomized to receive aztreonam, 150 mg/kg/day intravenously, and 18 to receive chloramphenicol, 100 mg/kg/day orally. On entry in the study the clinical characteristics of the two treatment groups were comparable. The duration of therapy was 14.9 +/- 3.6 days for the aztreonam group and 12.8 +/- 2.6 days for the chloramphenicol group. The mean duration of fever was 5.9 +/- 3.1 days and 4.05 +/- 2.1 days for aztreonam and chloramphenicol groups respectively (P greater than 0.05). Clinical cure was observed in all patients treated with aztreonam and in 17 of 18 children given chloramphenicol; one patient died in the latter group. There were no relapses in either group. We observed clinical adverse reactions during the treatment with aztreonam in 2 patients. All strains of Salmonella typhi were susceptible to aztreonam, 1 strain was resistant to chloramphenicol and 3 strains were resistant to ampicillin. Aztreonam appears to be a satisfactory alternative to chloramphenicol in cases of typhoid fever caused by resistant strains or when chloramphenicol is contraindicated.     

Double blind comparison of ibuprofen and paracetamol for adjunctive treatment of uncomplicated typhoid fever

BACKGROUND: Antipyretics reduce the prolonged, high fever characteristic of typhoid fever. The benefits of nonsteroidal drugs in this role have not been quantified. There have been concerns about the safety of antipyretics in typhoid. METHODS: In a double blind randomized study, 80 Vietnamese children with uncomplicated typhoid fever were randomized to receive identical syrup preparations of ibuprofen (10 mg/kg) or paracetamol (12 mg/kg) every 6 h until 36 h after defervescence. Children with a nalidixic acid-susceptible (Na) isolate of Salmonella typhi were treated with ofloxacin (15 mg/kg/day) for 3 days and those with a nalidixic acid-resistant (Na) isolate were treated for 7 days. RESULTS: S. typhi was isolated from 36 of 40 children randomized to ibuprofen (11 isolates Na) and 37 of 40 randomized to paracetamol (13 isolates Na). The median (range) fever clearance time (hours) was shorter in the ibuprofen group than the paracetamol group (68, 4 to 260 vs. 104, 12 to 404; P = 0.055) as was the area under the temperature time curve above 37 degree C (74, 0 to 237 vs. 127, 0 to 573; P = 0.013). The differences occurred predominantly in the children infected with a NaS. typhi whose infections responded more slowly to antibiotic treatment. There were no major side effects associated with the use of either drug. There were no differences between the two treatment arms in the concentrations of circulating interleukin-6 and tumor necrosis factor alpha during the course of treatment. CONCLUSION: The antipyretic effect of ibuprofen is superior to that of paracetamol in children with typhoid fever, particularly those with prolonged fever. Both antipyretics appeared to be safe.     

Cefpodoxime proxetil compared with cefixime for treatment of typhoid fever in children

In order to evaluate clinical and bacteriological efficacy of Cefpodoxime Proxetil (CP) in typhoid fever in comparison to cefixime (CF), we assessed 140 children with suspected typhoid fever. Fulfilling inclusion criteria finally 40 culture confirmed typhoid fever were allocated in randomized double blind clinical trial (RCT) to receive therapy with either oral CP (16 mg/kg/day, n = 21) or oral CF (20 mg/kg/day, n = 19) for 10 days. The two groups were comparable in their clinical and baseline characteristics. The clinical efficacy was similar in the two groups with only 2 (one in each group) clinical failures and all showing bacteriological eradication on subsequent blood culture. The time of defervescence was comparable in both groups (4.87 Fluconazole Prophylaxis against Fungal Colonization and Invasive Fungal Infection in Very Low Birth Weight Infants 2.33 vs 4.27 +/- 2.28 days, P = 0.308), with no relapse during 3 months follow up and no significant adverse effect. CP reduced the treatment cost by 33% in comparison to cefixime. Our study suggests CP is effective, safe and cheaper oral option for treatment of typhoid fever in children.     

Comparative trial of short-course ofloxacin for uncomplicated typhoid fever in Vietnamese children

An open, randomised comparison of 2 or 3 days of oral ofloxacin (10 mg/kg/day) for uncomplicated typhoid fever was conducted in 235 Vietnamese children. Multi-drug-resistant Salmonella typhi was isolated from 182/202 (90%) children and 5/166 (3%) tested isolates were nalidixic acid-resistant (Na(R)). Eighty-nine of 116 children randomised to 2 days and 107/119 randomised to 3 days were blood culture-positive and eligible for analysis. There were 12 (13.5%) failures in the 2-day group (six clinical failures, four blood culture-positive post treatment, two relapses) compared with eight (7.5%) failures in the 3-day group (four clinical failures, one blood culture-positive post treatment, three relapses) (OR 1.9, 95% CI 0.7-5.5,p = 0.17). There were no significant differences in the mean (95% confidence interval) fever clearance times (h) [92 (82-102) vs 101 (93-110), p = 0.18] or duration of hospitalisation (d) [7.6 (7.2-8.1) vs 8.0 (7.6-8.4), p = 0.19] between the two groups. There was one failure in the four eligible children infected with an Na(R) isolate of S. typhi. No adverse events were attributable to the ofloxacin. These results extend previous observations on the efficacy of short courses of ofloxacin for children with uncomplicated multi-drug-resistant typhoid fever.     

Typhoid fever, ciprofloxacin and growth in young children

Typhoid fever remains a significant public health problem in Southern Asia, particularly with the emergence of multi-resistant strains of Salmonella typhi in the late 1980s. Use of ciprofloxacin in children, although discouraged, is increasing and we aimed to assess whether its use affects growth or the prevalence of joint symptomology. Children under 6 years of age diagnosed as typhoid fever on the basis of a positive Widal test were recruited in the outpatient department of a paediatric teaching hospital after treatment had been initiated. During 6 months follow-up, prevalences of arthritis/arthralgia and ponderal, linear and knemometric growth were recorded. Seventy-five children were recruited (mean age 32 months, mean weight-for-height Z-score--1.3, mean height-for-age Z-score 1.4) and 29 (39%) of them received ciprofloxacin. No significant adverse effects on ponderal, linear or knemometric growth, or on the incidence of arthritis/arthralgia were found to be associated with the use of ciprofloxacin. Knemometric and ponderal catch-up growth was demonstrable 30 days after diagnosis but linear growth was still declining 3 months after diagnosis with catch-up growth demonstrable only after 6 months. We conclude that ciprofloxacin is commonly used in typhoid fever and has no adverse effects on growth or joint symptomology.     

头孢曲松与诺氟沙星对比治疗小儿耐药伤寒60例

目的 比较头孢曲松（罗氏分）与诺氟沙星治疗小儿耐药伤寒的疗效。方法 ６０例耐药伤寒患儿随机分为两组;头孢曲松组３０例,用头孢曲松〖１００ｍｇ／（ｋｇ．ｄ）,１次静脉给药〗,诺氟沙星组３０例,用诺氟沙星〖１０～２０ｍｇ／（ｋｇ．ｄ）,分２次口服〗。结果 头孢曲松总有效率为９３％（２８／３０）,而诺氟沙星组为８０％（２４／３０）（Ｐ〈０．０１）。结论 头孢曲松治疗小儿耐药伤寒效果优于诺氟沙星。     

Serum adenosine deaminase in the early diagnosis of typhoid fever.

To study the usefulness of the enzyme adenosine deaminase for the early diagnosis of typhoid fever, its activity in serum was assayed in 277 children admitted to the Hospital Guillermo Grant Benavente at Concepción, Chile, from March, 1988, to December, 1990. The children were distributed into seven groups: control, N = 82; bacteremia, N = 8; acute viral respiratory infection, N = 43; febrile children with miscellaneous etiologies, N = 49; pulmonary tuberculosis, N = 3; hepatitis A virus infection, N = 30; and typhoid fever, N = 62. The medium serum adenosine deaminase values were significantly higher in children with typhoid fever (P < 0.0001) in relation to the values in the control group (122.2 +/- 40.7 vs 28.1 +/- 8.4 units/liter at 37 degrees C). This test had a sensitivity of 91.9% and a specificity of 92.5% in identifying the patient with typhoid fever when using 80 units/liter as the cutoff values. The positive predictive value of the test was 83.8% and the negative predictive value was 96%. Determination of adenosine deaminase values in serum could be helpful in the early diagnosis of typhoid fever.     

Current perspectives of enteric fever: a hospital-based study from India

The last two decades have seen a change in the pattern of enteric fever with the emergence of multidrug-resistant strains (MDRS), particularly strains resistant to nalidixic acid. AIM: The aim of the study was to undertake a retrospective analysis of blood culture-confirmed cases of enteric fever diagnosed at Safdarjang Hospital, New Delhi, India from January 2001 to December 2003. METHODS: The epidemiological details, clinical features, treatment outcome and antimicrobial resistance patterns were studied. RESULTS: Of 377 blood culture-positive cases, 80.6% were Salmonella typhi and 19.4% Salmonella paratyphi A; 21.7% were children aged under 5 years and 6.1% were under 2 years. A significant decline in MDRS was observed, from 21.9% in 2001 to 12.4% in 2003 (p=0.04). There was a significant increase in nalidixic acid-resistant Salmonella (NARS) from 56.9% in 2001 to 88.9% in 2003 (p=0.0001). Complete resistance to ciprofloxacin (MIC>4 microg/ml) was detected in only two isolates, both Salmonella paratyphi A. Minimal inhibitory concentrations (MICs) of ciprofloxacin for NARS were increased (0.125-0.5 microg/ml) but were within National Committee for Clinical Laboratory Standards susceptibility ranges. NARS had a significantly longer fever defervescence time (7.7 vs 4.7 days, p<0.001) and hospital stay (12.1 vs 8.2 days, p<0.001), and higher rates of complications (55.5% vs 24.0%, p=0.014) and mortality than nalidixic acid-sensitive Salmonella (NASS). The rate of isolation of MDRS was higher in NARS than NASS (18.8% vs 7.3%, p=0.013). CONCLUSION: The high rate of occurrence of enteric fever in children <5 years and also of infections caused by Salmonella paratyphi A in India calls for critical re-assessment of vaccination strategy. Nalidixic acid resistance and rising MICs of fluoroquinolones in Salmonella spp pose a new global threat requiring debate on the optimum treatment of enteric fever.     

Can renal handling of phosphate predict response to growth hormone therapy in normal variant short children by short-term treatment?

We investigated if renal handling of phosphate could predict height velocity in 28 normal variant short children (16 boys and 12 girls). Before and after human growth hormone was given for four consecutive days, the ratio of maximum tubular reabsorption rate for phosphorus to glomerular filtration rate (TmP/GFR) was calculated. Based on increments in TmP/GFR (4TmP/GFR) with growth hormone administration, the patients were divided into two groups; children in whom the levels of ΔTmPiGFR were 0.8 mg/dl GF or more (group A, n = 7) and those with levels less than 0.8 mg/dl GF (group B, n = 21). All children in group A and some in group B ( n = 9) were injected with 0.5 IU/kg/week of recombinant human growth hormone for over one year. Height velocity during therapy was significantly greater in treated children in group A than in group B and was similar among treated (n = 9) and untreated ( n = 12) children in group B. The present study suggests that change in renal handling of phosphate during short-term growth hormone administration can serve to select normal variant short children who will respond well to growth hormone therapy.     

Acute osteomyelitis in the child with sickle cell disease in a tropical zone: value of oral fluoroquinolones]

AIM: This study was designed to assess the efficacy and the safety of fluoroquinolones in their compassionate use for acute osteomyelitis in children with sickle cell disease in a tropical country. PATIENTS AND METHODS: This study was non comparative, including twelve children (eight SS, three SC and one SEzerothalassemia) treated for acute osteomyelitis with oral ciprofloxacin or ofloxacin because of the following reasons: financial inability to afford conventional parenteral beta-lactams therapy (nine patients), refusal of hospitalization (two patients), and failure of conventional treatment (one patient). RESULTS: The mean age of patients was 9.5 +/- 2.6 years. The long bones were the predominantly site. Salmonella species were present in 75% of cases, followed by other enterobacteriaceae (16.7%), and Staphylococcus aureus (8.3%). Successful outcome occurred in all cases after three to four-weeks of treatment and 45 days of plaster immobilization. Transient bilateral Achilles tendon tendinitis was noted in a five-year-old patient. CONCLUSION: In economically developing countries, oral fluoroquinolones may be a therapeutic alternative for acute osteomyelitis in patients with sickle cell disease particularly in cases of financial hardship or failure with conventional therapy.     

Slowing of growth in height and weight on stimulants: a characteristic pattern

OBJECTIVE: The aims of the present study were to describe the growth pattern of children starting stimulant medication and to analyse the changes over time in height, weight and height velocity in a cohort of treated patients. METHODS: Retrospective review of growth data from files of all newly treated patients with attention-deficit/hyperactivity disorder in one paediatric practice. Forty-four boys and seven girls were treated for 6-42 months with either dexam-phetamine (n = 32) or methylphenidate (n = 19). RESULTS: During the first 6 months on stimulant medication 44 children (86%) had a height velocity below the age-corrected mean and there was weight loss in 39 (76%). The height and weight standard deviation score (SDS) showed a progressive decline that was statistically significant after 6 and 18 months (P < 0.001, paired t-test). The height velocity was significantly attenuated for the first 30 months (P < 0.01), being lowest during the first 6 months. The mean height deficit during the first 2 years was approximately 1 cm/year. The change in weight SDS was 2.4 times the change in height SDS after 30 months on treatment with a significant correlation (Pearson's correlation coefficient r = 0.88, P < 0.001). CONCLUSIONS: Stimulant medication is associated with a decrease in height and weight SDS during the first 6-30 months with a characteristic pattern on the growth chart.     

Chloramphenicol clearance in typhoid fever: Implications for therapy

We prospectively studied the pharmacokinetics of intravenous Chloramphenicol succinate (CS) in children (age 6 months-14 years) with culture proven typhoid fever (n=30) and non typhoidal illnesses (n=10). CS was administered in three different dosage regimens (50, 75 and 100 mg/kg/d-q 6 hourly). Liver function tests were monitored. Plasma trough and peak chloramphenicol concentrations were measured by HPLC analysis after 42 hrs. The 50 mg/kg/day dosage schedule was terminated midway through the study, as blood levels were consistently low and two patients with typhoid relapsed. children with typhoid has significantly lower clearance of CS in comparison with those with non-typhoidal illness (0.29±0.1 versus 0.5±0.37 1/kg/hr, P 0.05). There was no significant difference between mean peak and trough concentrations of chloramphenicol on 100 mg/kg/day and 75 mg/kg/day in children with typhoid. However, two children on 100 mg/kg/day dosage developed trough concentrations >20 mcg/ml. No correlation was found between CS clearance and serum bilirubin, SGPT (alanine transaminase) and alkaline phosphatase. Our data show altered clearance of CS in children with typhoid and suggests that 75 mg/kg/day may be a safer dose in children with hepatic dysfunction in typhoid.     

Ciprofloxacin treatment in preterm neonates in Bangladesh: lack of effects on growth and development

BACKGROUND: Quinolone-induced arthropathic toxicity in weight-bearing joints observed in juvenile animals during preclinical testing has largely restricted the routine use of ciprofloxacin in the pediatric age group. As histopathologic, radiologic and magnetic resonance imaging monitoring evidence has gathered supporting the safety of fluoroquinolones in children, many pediatricians have started to prescribe quinolones to some patients on a compassionate basis. OBJECTIVE: The objective of this study was to ascertain the safety of ciprofloxacin in preterm neonates <33 weeks gestational age treated at Dhaka Shishu (Children) Hospital in Bangladesh. METHODS: Long-term follow up was done to monitor the growth and development of preterm infants who were administered intravenous ciprofloxacin in the neonatal period. Ciprofloxacin was used only as a life-saving therapy in cases of sepsis produced by bacterial agents resistant to other antibiotics. Another group of preterm neonates with septicemia who were not exposed to ciprofloxacin, but effectively treated with other antibiotics and followed up, were matched with cases for gender, gestational age and birth weight and included as a comparison group. Forty-eight patients in the ciprofloxacin group and 66 patients in the comparison group were followed up for a mean of 24.7 +/- 18.5 months and 21.6 +/- 18.8 months, respectively. RESULTS: No osteoarticular problems or joint deformities were observed in the ciprofloxacin group during treatment or follow up. No differences in growth and development between the groups were found. CONCLUSIONS: Ciprofloxacin is a safe therapeutic option for newborns with sepsis produced by multiply resistant organisms.     

Growth in Children Treated for Acute Lymphoblastic Leukemia with and without Prophylactic Cranial Irradiation

ABSTRACT. Growth and weight gain were studied longitudinally over a period of four years in thirty-nine children treated for acute lymphoblastic leukemia. The children were divided into two groups according to treatment. Twenty-eight children were given prophylactic cranial irradiation and eleven children were treated without such irradiation. The duration of cytostatic treatment was three years in all cases. Average growth during the first two years was similar in the two groups, and the standard deviation scores (SDS) were below average. The rate of growth (in height) during the fourth year was significantly higher among those children who had not received cranial irradiation ( p <0.01). After four years the average attained height had declined 0.5 SD for children treated with cranial irradiation and 0.2 SD for children without such treatment. Weight velocity was significantly greater than the expected mean in the non-irradiated group during the first year and in the irradiated group during the fourth year of the study. Attained weight after four years had increased 0.4 SD more among those children who had not received irradiation. The results suggest that prophylactic cranial irradiation is responsible for the greater part of the prepubertal growth inhibition in these children.     

Problems in the clinical diagnosis of typhoid fever in children in the tropics

Between January 1976 and December 1978, the Microbiology Department of University College Hospital (UCH) Ibadan, isolated Salmonella typhi from the blood cultures of 93 children aged 0-14 years, who were admitted to the paediatric wards. Clinical case notes were retrieved and reviewed in 64 (68.8%) of them. Fifteen (23%) of the 64 children were less than one year of age while 22 (34%) were under the age of five years. The commonest presenting symptoms were fever, anorexia, diarrhoea and vomiting. A febrile convulsion was the presenting symptom in 13 (20%) of the patients, all of whom were under the age of five years. Hepatomegaly was almost twice as frequently observed as splenomegaly. Intestinal perforation was present in five of the patients. There was a high proportion of SS children who presented with fever, pallor, jaundice, generalized aches and pains and other clinical features of sickle cell disease and it is possible that such children are specially susceptible to typhoid fever. A clinical diagnosis of typhoid fever on admission was made in only 14 of the 64 children. Reasons are given for the low index of suspicion and it is suggested that any child with unremitting fever after adequate anti-malarial chemotherapy should be treated for enteric fever.     

Oral ciprofloxacin vs. intravenous ceftriaxone administered in an outpatient setting for fever and neutropenia in low-risk pediatric oncology patients: randomized prospective trial

BACKGROUND: Infections are one of the major complications in children undergoing chemotherapy. Monotherapy with either ciprofloxacin or ceftriaxone is safe and efficient in low-risk patients (solid tumors and stage I/II lymphomas). The same drugs may be used in an outpatient setting, decreasing costs and the risk of nosocomial infections. PROCEDURE: Low-risk patients (N = 70) with episodes of fever and neutropenia (N = 116) were randomized to receive either oral ciprofloxacin or intravenous ceftriaxone as outpatients. Only one patient had a central venous catheter. RESULTS: Episodes of fever and neutropenia were classified as fever of unknown origin (41% vs. 32%) or clinically documented infection (56% vs. 63%) in the ciprofloxacin and ceftriaxone groups, respectively. Most of these infections were of upper respiratory tract, skin, or gastrointestinal origin. The mean duration of neutropenia was 5 vs. 6 days. Fever persisted for 1-9 days (mean 2 vs. 3 days). Therapy was successful with no modifications in 83% vs. 75% of the episodes. Patients were admitted in 7% vs. 4% of the episodes. No bone or joint side effects were seen in either group. All patients survived. CONCLUSIONS: Outpatient therapy with either oral ciprofloxacin or intravenous ceftriaxone for fever and neutropenia is effective and safe in pediatric patients with solid tumors and stage I/II non-Hodgkin lymphoma (low-risk patients).     

Growth hormone (GH) treatment to final height in children with idiopathic short stature: evidence for a dose effect

OBJECTIVES: To investigate in an open-label randomized study, the effect of two doses of growth hormone (GH) on final height and height velocity during the first 2 years of treatment of children with idiopathic short stature (mean baseline height standard deviation score [SDS] -3.2). STUDY DESIGN: Patients were treated with GH at 0.24 mg/kg/week, 0.24 mg/kg/week for the first year and at 0.37 mg/kg/week thereafter (0.24-->0.37), or 0.37 mg/kg/week. Final height was evaluated in 50 patients at study completion (mean treatment duration, 6.5 years). RESULTS: Patients who received 0.37 mg/kg/week (n = 72) experienced a significantly greater increase in height velocity than those who received 0.24 mg/kg/week (n = 70) (treatment difference = 0.8 cm/year; P = .003) or 0.24-->0.37 mg/kg/week (n = 67) (treatment difference = 0.9 cm/year; P = .001). For the 50 patients for whom final height measurements were available, mean height SDS increased by 1.55, 1.52, and 1.85 SDS, respectively, for the three dose groups. For the primary comparison between the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups, the mean treatment difference (adjusted for differences in baseline predicted height SDS) was 0.57 SDS (3.6 cm; P = .025). Mean overall height gains (final height minus baseline predicted height) were 7.2 cm and 5.4 cm for the 0.37 mg/kg/week and 0.24 mg/kg/week dose groups, respectively, without dose effects on safety parameters. Final height measurements were within the normal adult height range for 94% of patients randomized to 0.37 mg/kg/week who continued to final height. CONCLUSION: GH treatment dose-dependently increases height velocity and final height in children with idiopathic short stature.