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Biomedical subjects

S Shelton

Publications and source records attributed to S Shelton.

At least 55 records · Page 3Linked to original sources
PubMed1982

Benefits and risks of sequential parenteral--oral cephalosporin therapy for suppurative bone and joint infections.

Seventy-five infants and children with suppurative skeletal infections were managed with a sequential parenteral-oral regimen of cephalosporin antibiotic therapy. Initially, parenteral antibiotics (cefamandole for 48 patients and cefuroxime for 27 patients) were given for a median of 5 days. Oral therapy was with large doses of cefaclor (150 mg/kg/day) or cephalexin (100 mg/kg/day). Eight patients (11%) had inadequate serum bactericidal activity with cefaclor. Six of them were successfully managed with alternative oral antibiotics, and parenteral therapy resumed in one patient. Chronic disease developed in a child who was continued on oral cloxacillin therapy in spite of absent serum bactericidal activity. It is concluded that oral therapy can be successful for the majority of patients but that it is hazardous and not indicated if careful laboratory monitoring of compliance and serum bactericidal activity cannot be performed.

Acute Disease↗
PubMed1982

Pharmacokinetics of potassium clavulanate in combination with amoxicillin in pediatric patients.

Two dosages of a liquid suspension formulation of amoxicillin and potassium clavulanate were tested in 34 infants and children. The smaller dosage resulted in suboptimal plasma concentrations. With a greater dosage (3.3 mg of clavulanate per kg and 13.3 mg of amoxicillin per kg), the mean peak plasma concentrations were 1.6 micrograms clavulanic acid per ml and 4.9 micrograms amoxicillin per ml.

Amoxicillin↗
PubMed1982

Pharmacokinetics and cerebrospinal fluid bactericidal activity of ceftriaxone in the treatment of pediatric patients with bacterial meningitis.

Single-dose pharmacokinetics of ceftriaxone were determined in 19 patients with proven bacterial meningitis. The dosage was 50 mg of ceftriaxone per kg. The plasma concentration time curve declined in a biexponential manner. The mean peak plasma concentration was 207 micrograms/ml, and the elimination half-life was 4 h. In 12 patients, multiple-dose pharmacokinetics were determined after a loading dose of 75 mg of ceftriaxone per kg, followed by 50-mg/kg doses every 8 h in 5 patients or every 12 h in 7 patients. The mean peak plasma concentration was 230 micrograms/ml after the first dose and 263 micrograms/ml after the last dose. Of 12 patients, 5 had trough values that were larger after multiple doses than after a single dose. Mean penetration of ceftriaxone into cerebrospinal fluid was 3.1%. The median cerebrospinal fluid bactericidal titer against the patients pathogens was greater than 1:1,024 and less than 1:2,048. The drug was well tolerated without adverse effects.

Bacteria↗
PubMed1982

Pharmacokinetics of cefuroxime in infants and children with bacterial meningitis.

A total of 38 patients with bacterial meningitis received either 50 or 75 mg of cefuroxime per kg of body weight given as a 15-min intravenous infusion during the first to third days of therapy. The mean peak plasma concentrations of cefuroxime after doses of 50 and 75 mg/kg were 105 and 152 micrograms/ml, respectively. In five patients, pharmacokinetic values were determined after multiple doses of 50 mg of cefuroxime per kg every 6 h. The mean peak plasma concentrations were 120 micrograms/ml after the first dose and 130 micrograms/ml after the last dose. The concentrations at 6 h were 3.25 and 11.0 micrograms/ml after the first and last doses, respectively. The elimination half-life was approximately 1.5 h, and the apparent volume of distribution was 650 ml/kg. The plasma clearance rate was 195 to 198 ml/min per 1.73 m2. Penetration into the cerebrospinal fluid, expressed as the ratio of the cerebrospinal fluid to serum areas under the curve times 100, was 6.4% in patients given 50 mg of cefuroxime per kg and 10% in those who received 75 mg/kg. The cerebrospinal bactericidal activity in 27 patients was less than or equal to 1:8; only 2 patients had bactericidal activity of less than or equal to 1:2.

Cefuroxime↗
PubMed1981

The dexamethasone suppression test as a measure of hypothalamic-pituitary feedback sensitivity and its relationship to behavioral arousal.

A nonhuman primate model was used to evaluate the value of the dexamethasone suppression test as an index of hypothalamic-pituitary-adrenal responsiveness to arousal. In 8 rhesus monkeys plasma cortisol was suppressed by dexamethasone in a dose-dependent fashion at doses between 0.75 and 33 microgram/kg. A replication study was performed 5 months later using a single dexamethasone dose (17 microgram/kg) known to produce maximal plasma cortisol suppression. This yielded highly correlated results (r = 0.91, p less than 0.005) suggesting that dexamethasone suppressibility may be a stable characteristic of individual animals. In 9 other animals whose arousal responses to a stressful procedure (nasogastric tube insertion) had been rated daily over a previous 3-month period, baseline plasma cortisol levels and the percent suppression of plasma cortisol by dexamethasone were evaluated. Baseline plasma cortisol levels did not significantly correlate with the degree of dexamethasone-suppression and the mean arousal ratings within animals. However, the postdexamethasone percent of baseline cortisol did correlate significantly (r = 0.75, p less than 0.025) with individual mean arousal ratings. These preliminary results suggest that assessment of the sensitivity of an individual's hypothalamic-pituitary glucocorticoid feedback system may be a better predictor than its baseline cortisol concentrations of its degree of behavioral arousal to stress.

Animals↗
PubMed1980

In vitro susceptibility of gram-negative bacilli from pediatric patients to moxalactam, cefotaxime, Ro 13-9904, and other cephalosporins.

Moxalactam, Ro 13-9904, cefotaxime, cefoperazone, older cephalosporins, and four aminoglycosides were tested in vitro against 432 strains of gram-negative bacteria isolated from pediatric patients. The new drugs were uniformly active against coliform bacilli obtained from patients with meningitis and against aminoglycoside-resistant coliform bacilli.

Bacteria↗
PubMed1978

Comparison of human rotavirus disease in tropical and temperate settings.

Human rotaviruses (HRV) are a common cause of acute nonbacterial gastroenteritis in pediatric patients. A prospective study of HRV disease in a temperate (Dallas) and a tropical (San Jose, Costa Rica) setting demonstrated differences in seasonal distribution. In both locales, HRV accounted for 50% to 60% of acute nonbacterial gastroenteritis episodes from December through February; this period corresponded to the cooler months of winter in Dallas and to the dry season in San Jose. During the rest of the observation year, the virus was not recovered from any Dallas patients, but was found in 30% to 40% of Costa Rican patients in every month but May. Signs, symptoms, and laboratory values suggest the small bowel as the major site of pathophysiology; mucosal disruption may occur in some cases.

Acute Disease↗
PubMed1978

Oral antibiotic therapy for skeletal infections of children. I. Antibiotic concentrations in suppurative synovial fluid.

To evaluate the feasibility of oral antibiotic treatment for pyogenic arthritis, one or more oral doses of antibiotics were substituted for the drugs being used for parenteral therapy. Synovial fluid and serum specimens obtained at randomized times after an oral dose of ampicillin, cephalexin, cloxacillin, dicloxacillin, or penicillin G were assayed for antibiotic content and antibacterial activity. Seventy specimens from 21 infants and children were studied. Peak synovial fluid concentrations were greater than 60% of peak serum concentrations with all drugs tested and there was adequate inhibitory activity against bacteria commonly causing arthritis. The degree of antibiotic binding to serum protein had no apparent effect on the degree of penetration into pyogenic synovial fluid.

Administration, Oral↗
PubMed1978

Clinical pharmacology and efficacy of ticarcillin in infants and children.

Ticarcillin was evaluated in 82 neonates and young infants with suspected sepsis and in 16 older children with chronic Pseudomonas infection of the mastoids. The infants also received kanamycin. Individual ticarcillin doses of 75 or 100 mg/kg were given every four, six, or eight hours by intramuscular injection or by a 30-minute intravenous infusion. Mean plasma concentrations one hour after a dose were from 125 to 189 microgram/ml, depending on dosage, age, and maturity. Mean plasma half-lives were approximately 5 hours in the first week of life, 2 hours in infants from 1 to 8 weeks, and 0.9 hours in older children. Volume of distribution was approximately twice as great in infants as in children, and plasma clearance rates correlated inversely with age. Limited efficacy data suggest that ticarcillin is a suitable alternative to ampicillin or carbenicillin, when given concurrently with an aminoglycoside, for newborn infections. When given for several days before mastoidectomy and tympanoplasty, ticarcillin sterilized the mastoids in the majority of patients. A new dosage schedule for ticarcillin in pediatric patients is proposed.

Adolescent↗
PubMed1975

Clinical pharmacology of ticarcillin in the newborn infant: relation to age, gestational age, and weight.

Ticarcillin, a new penicillin derivative with greater in vitro activity against Pseudomonas than carbenicillin, was given as a single dose of 50 mg/kg intramuscularly on 61 occasions to 54 neonates and young infants. The serum concentrations and rate of elimination varied considerably depending upon gestational age, chronological age, and body weight. Peak serum concentrations depended principally upon the volume of distribution which approximated the extracellular fluid volume of the neonate. The plasma clearance and serum half-life of the drug were determined. From these pharmacokinetic data appropriate groupings according to age and body weight were made and dosages and intervals of administration predicted for clinical trials of efficacy with repeated doses.

Age Factors↗
PubMed1972

Pharmacokinetics of carbenicillin in neonates of normal and low birth weight.

A single intramuscular dose of 100 mg carbenicillin/kg produced measured peak concentrations of approximately 150 to 175 mug/ml in newborn infants. The carbenicillin serum half-life of 1.0 hr in normal adults was prolonged to 2.7 hr in infants of normal birth weight and to 4.0 hr in babies of low birth weight in the first week of life. One-third of a dose administered to babies of low birth weight and two-thirds of that given to babies weighing over 2,500 g was excreted by the kidney in 12 hr. Postadministration 6-hr urinary carbenicillin concentrations averaged 1,399 mug/ml after an intramuscular dose of 50 mg/kg and 2,689 mug/ml after a 100 mg/kg injection. Although carbenicillin is excreted by both glomerular and tubular mechanisms in adults, serum half-life and urinary carbenicillin excretion correlated well with creatinine clearance. Recommendations for dosage of carbenicillin and intervals of administration in the neonatal period are made based upon mathematical predictions from pharmacokinetic data.

Anti-Bacterial Agents↗
PubMedDate not supplied

Oral or intravenous trimethoprim-sulfamethoxazole therapy for shigellosis.

A review of the literature concerning shigellosis treated with trimethoprim-sulfamethoxazole (TMP-SMZ) revealed comparative studies of 149 cases and noncomparative studies of 147 cases. Bacteriologic and clinical success rates were greater than or equal to 90% and TMP-SMZ compared favorably with alternative drug therapy. In the present study TMP-SMZ was given intravenously as initial therapy to 11 children hospitalized for severe shigella colitis. Bacteriologic and clinical responses were comparable to those observed with oral TMP-SMZ therapy. Pharmacokinetic studies revealed substantial differences between the responses of these children and those reported for adult patients; a higher ratio of SMZ to TMP (50:1) was found in children. It is concluded that TMP-SMZ is effective therapy for shigellosis and is the drug of choice in areas where ampicillin resistance is prevalent.

Administration, Oral↗
PubMedDate not supplied

Cefuroxime therapy for pneumonia in infants and children.

Because Streptococcus pneumoniae, Haemophilus influenzae b and Staphylococcus aureus are the major causes of bacterial pneumonia in infancy, we customarily have given a beta-lactam antibiotic and chloramphenicol as initial antibiotic therapy. Cefuroxime (75 mg/kg/day divided every 8 hours iv or im) was evaluated as single drug therapy in an open study of 100 infants and children with suspected bacterial pneumonia. The mean serum concentration of cefuroxime 30 minutes after a 15-minute infusion of 25 mg/kg iv was 29.1 micrograms/ml, and the volume of distribution was 695 ml/kg. Pleural fluid concentrations in 3 specimens were 2.2, 8.5 and 11 micrograms/ml. Median age of patients was 15 months. Bacterial etiology was established in 20 patients: H. influenzae b (8 patients); pneumococcus (8 patients); S. aureus (2 patients); Group A streptococcus (1 patient); Neisseria meningitidis B (1 patient). All organisms were susceptible to 1.25-micrograms/ml doses or less of cefuroxime. The mean number of days was 3.1 until patients became afebrile and 5.1 until respiratory symptoms were gone. Eosinophilia occurred in 10 patients. Cefuroxime is safe and effective single drug therapy for pneumonia in infants and children.

Cefuroxime↗
PubMedDate not supplied

Relatively penicillin-resistant pneumococcal infections in pediatric patients.

Two hundred fifty-eight isolates of Streptococcus pneumoniae obtained from 232 infants and children at Children's Medical Center, Dallas, from November 1, 1981, to March 31, 1983, were screened for susceptibility to penicillin. On 1-microgram oxacillin disks 21 strains (8%) had zones of inhibition of 17 mm or less, and the tube-dilution minimal inhibitory concentrations of penicillin were from 0.125 to 0.5 micrograms/ml. These strains were designated as relatively resistant S. pneumoniae (RRSP). Prior therapy with a beta-lactam agent had occurred in 56% of patients with RRSP disease compared with 14% of randomly selected children with infections due to susceptible strains of S. pneumoniae (P = 0.009). Fifteen children (6%) had diseases due to RRSP ranging from sepsis or meningitis to otitis media or conjunctivitis. Four children, including the two patients with meningitis, had unsatisfactory responses to therapy with a beta-lactam antibiotic. Vancomycin or chloramphenicol is preferred for therapy of disease due to RRSP.

Anti-Bacterial Agents↗