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Biomedical subjects

W J Barson

Publications and source records attributed to W J Barson.

At least 37 records · Page 2Linked to original sources

Pharmacokinetics, cerebrospinal fluid concentration, and safety of intravenous rifampin in pediatric patients undergoing shunt placements.

The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal fluid concentrations and safety of intravenous rifampin in pediatric patients undergoing shunt placement. Nine patients (mean age 5.6 y) received a single dose of rifampin, 20 mg.kg-1, administered intravenously 1 h prior to surgery. The peak serum concentrations ranged from 13.5-26.7 micrograms.ml-1; cerebrospinal fluid concentrations ranged from 0.12-3.0 (mean: 1.4) micrograms.ml-1. The mean total clearance, apparent distribution volume, and elimination half-life were 0.29 l.kg-1.h-1, 1.11.kg-1, and 2.8 h. The concentrations of rifampin achieved in the cerebrospinal fluid exceeded the minimum inhibitory concentrations by 100- to 1000-fold against Staphylococcus epidermidis. However, 5 of 9 patients developed cutaneous reactions during intravenous rifampin prophylactic therapy. Because of the high frequency of adverse effects and more than adequate rifampin concentrations achieved in the cerebrospinal fluid, rifampin doses lower than that used in this study may be evaluated in future studies.

Adolescent↗

Pharmacokinetics and cerebrospinal fluid concentration of nafcillin in pediatric patients undergoing cerebrospinal fluid shunt placement.

Postoperative infection is among the most common complications in patients with cerebrospinal fluid shunt placement. Nafcillin is often used for prophylaxis but not pharmacokinetic data are available perioperatively in pediatric patients. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal concentrations of nafcillin. Ten patients (mean age 8.0 +/- 5.6 years) received three doses of intravenous nafcillin, 50 mg/kg every 6 h; the first dose was administered 1 h prior to surgery. Multiple blood samples were collected during and after surgery and the cerebrospinal fluid sample was obtained at the time of shunt insertion. Urine samples were collected for 24 h after initiation of nafcillin. Nafcillin was analyzed with an HLPC method. The peak serum concentrations ranged from 22 to 107 micrograms/ml; cerebrospinal fluid concentrations ranged from 0.02 to 0.30 (mean 0.16 +/- 0.11) micrograms/ml. The mean total clearance, renal clearance, apparent volume of distribution, and elimination half-life were 0.90 +/- 0.55 l/kg/h, 0.12 +/- 0.04 l/kg/h, 0.70 +/- 0.52 l/kg, and 0.5 +/- 0.1 h, respectively. 16% of total nafcillin dose was excreted in the urine. A 4-fold variability in total clearance and a 10-fold variation in cerebrospinal fluid concentrations of nafcillin was observed in these patients. Further, the concentrations of nafcillin attained in the cerebrospinal do not appear to be adequate, based on its minimum inhibitory concentration of 0.5 micrograms/ml against very susceptible staphylococci. These data, in addition to the fact that an increasing number of staphylococci are becoming resistant to nafcillin, question the usefulness of prophylactic nafcillin in pediatric patients undergoing shunt procedures.

Adolescent↗

Pharmacokinetics and cerebrospinal fluid (CSF) concentrations of vancomycin in pediatric patients undergoing CSF shunt placement.

Staphylococcus epidermidis has been established as the common pathogen causing cerebrospinal fluid shunt infections. In addition, clinical isolates of S. epidermidis from infected shunts are typically resistant to methicillin. Vancomycin is often used for neurosurgical prophylaxis due to its excellent in vitro activity against methicillin-resistant staphylococci. Limited data are available about the pharmacokinetics and cerebrospinal fluid concentrations of vancomycin in pediatric patients intraoperatively. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal fluid concentrations of vancomycin. Eight patients (mean age 8.3 +/- 7.0 years) received three doses of intravenous vancomycin, 15 mg/kg every 6 h. The first dose was administered 1 h prior to surgery. Blood samples were collected at 0, 0.5, 1, 2, 4, and 5 h after the end of the infusion. A cerebrospinal fluid sample was collected at the time of shunt insertion. Urine samples were collected over a 24-hour period. Vancomycin was measured with a fluorescence polarization immunoassay. The peak serum concentrations ranged from 15.6 to 33.7 micrograms/ml; cerebrospinal fluid concentrations ranged from less than 0.6 to 0.8 microgram/ml. The mean total clearance, renal clearance, apparent volume of distribution, and elimination half-life were 0.11 +/- 0.05 l/h/kg, 0.07 +/- 0.02 l/h/kg, 0.54 +/- 0.15 l/kg, and 4.8 +/- 4.0 h, respectively. Approximately 70% of total vancomycin dose was excreted in the urine. A 2- to 5-fold variation in total clearance and a 2.5-fold variability in renal clearance were observed. Low cerebrospinal fluid concentrations of vancomycin were present at the time of shunt insertion in these pediatric patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Acute scrotum due to Haemophilus influenzae type b.

The acute scrotum in infants and children is generally due to torsion of the spermatic cord, torsion of the appendix testis, or acute epididymitis. An infant is presented who was found to have epididymitis and a scrotal abscess due to Haemophilus influenzae type b at the time of surgical exploration for suspected torsion of the spermatic cord.

Abscess↗

Puncture wound osteochondritis of the foot caused by CDC group Vd.

A case of puncture wound osteochondritis of the foot caused by CDC group Vd is presented because of the unusual nature of the infecting organism. This organism may be confused with Pseudomonas aeruginosa, the usual pathogen responsible for this type of infection, but does not have a similar antimicrobial susceptibility profile. For this reason, it is important to obtain appropriate culture specimens and to identify and test the susceptibility of bacterial isolates from cases of puncture wound-associated osteochondritis so that optimal therapeutic regimens can be determined.

Adolescent↗

Onset of Hemophilus influenzae type-b meningitis during cefaclor therapy for preseptal cellulitis.

Second generation cephalosporins are frequently used for the treatment of bacteremic Hemophilus influenzae type b infections. "Breakthrough" meningitis during cefamandole therapy has documented the need for adequate cerebrospinal fluid penetration by these antibiotics if they are to be used in the therapy of Hemophilus infections. A child with H. influenzae type b preseptal cellulitis is reported who initially responded to treatment with intravenous cefuroxime and oral cefaclor. However, while still receiving cefaclor, the child was readmitted with H. influenzae meningitis. Microtiter broth dilution susceptibility testing performed during the second admission showed the isolate to be relatively resistant to cefuroxime (minimum bactericidal concentration [MBC] = 4 micrograms/ml) and resistant to cefaclor (MBC greater than 16 micrograms/ml). This experience documents the need to monitor the clinical response closely during therapy of H. influenzae bacteremic infections with these second generation cephalosporin treatment regimens. In addition, attention should be paid to minimum inhibitory concentrations of these cephalosporins, since variations in H. influenzae type b susceptibility to these agents may limit their efficacy.

Cefaclor↗

Management of infections in children with cancer.

Infectious complications remain a frequent cause of morbidity and mortality in children with cancer, especially in those who are granulocytopenic. Physicians caring for these children must approach each new febrile episode as if it were life threatening. Questions concerning the present illness must be comprehensive. The physical examination should be done in a compulsive manner because the more obvious signs of inflammation are often absent because of granulocytopenia. Immediate initiation of broad-spectrum intravenous antibiotic coverage is required once the appropriate specimens for diagnostic microbiology studies have been obtained. Because these patients may exhibit either dramatic or, more often, only subtle clinical findings, they must be monitored closely and have a complete physical examination at least daily. The laboratory studies frequently determine the etiology of the fever. Therapy can then be modified, based upon the particular pathogen isolated or the type of infection identified. Because bacterial infections are responsible for most infectious febrile episodes in the granulocytopenic child with cancer, appropriate antibiotic therapy usually is curative. However, some patients remain febrile and granulocytopenic without explanation. These patients frequently have a fungal infection and respond to amphotericin B therapy. Our present armamentarium of antimicrobial agents against the common pathogens encountered in cancer patients, except for cytomegalovirus, is adequate. Future advances in therapy of infections in children with cancer will probably be in the area of immunotherapy. This would include both passive administration of products to strengthen a debilitated immune system, together with active immunization with the aim to prevent infectious complications. Prevention of infection in the cancer population may be one of the keys to producing longer remissions and prolonged overall survival, by enabling pediatric oncologists to administer more intensive induction chemotherapy.

Agranulocytosis↗

Ceftriaxone kinetics and cerebrospinal fluid penetration in infants and children with meningitis.

20 patients (0.4-5.6 years old) receiving ceftriaxone for the treatment of bacterial meningitis were studied. Simultaneous serum and cerebrospinal fluid concentrations of ceftriaxone were determined by HPLC in 15 patients at 11.4-12.8 h after an intravenous loading dose of 75 mg/kg. Serum and cerebrospinal fluid concentrations ranged from 20.5 to 44.9 (31.3 +/- 7.8) and from 1.1 to 8.0 (3.7 +/- 1.8) micrograms/ml, respectively. Cerebrospinal fluid concentrations ranged from 3 to 25% (12 +/- 6%) of the simultaneous serum concentrations. In 6 patients, serum and cerebrospinal fluid concentrations were determined after maintenance doses of 50 mg/kg/12 h. Serum and cerebrospinal fluid concentrations ranged from 120 to 144 and 2.3-4.9 micrograms/ml at 1.8-5.5 h after the first maintenance dose in 2 patients; 74-139 and 5.7-7.9 micrograms/ml at 1.3-5.8 h after the second dose in 3 patients and was 101 and 4.1 micrograms/ml at 4 h after the 3rd dose in 1 patient. Multiple blood samples were collected after the loading dose in 5 patients and after 9-10 days of maintenance doses in 3 patients. Steady-state peak and trough serum concentrations ranged from 295 to 440 and 32.6-44.8 micrograms/ml, respectively. After the loading and maintenance dose at steady-state, total body clearance averaged 1.17 and 0.64 ml/min (p = 0.01); apparent volume of distribution averaged 0.37 and 0.26 l/kg (p greater than 0.05); and elimination half-life averaged 3.7 and 4.6 h (p = 0.01), respectively. These results suggest that (1) adequate cerebrospinal fluid concentrations of ceftriaxone can be achieved in patients with meningitis with the dosage regimen studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Ceftriaxone↗

Coxsackievirus B2 infection in a neonate with incontinentia pigmenti.

Because of the concern for herpes simplex virus infection in the neonate, the presence of neonatal vesiculobullous lesions is a critical finding. However, there are other etiologies for these lesions. A case of a neonate with a vesicular rash and meningoencephalitis which was initially thought due to herpes is presented. The infant was ultimately determined to have incontinentia pigmenti and a concomitant coxsackievirus B2 infection.

Acute Disease↗

Cefuroxime therapy for bacteremic soft-tissue infections in children.

Although it is used extensively in Europe, there is a limited amount of published data concerning pediatric clinical experience with cefuroxime in the United States. Thirty-six children, ranging from 3.5 to 57 months of age, received intravenous cefuroxime (75 mg/kg/day in three divided doses) for soft-tissue infections of the face or epiglottis. Infections treated included preseptal (19 patients) and buccal (13 patients) cellulitis and epiglottitis (four patients). Blood cultures were positive in 22 patients, yielding Haemophilus influenzae type b in 17 (four were beta-lactamase-positive), Streptococcus pneumoniae in four; and beta-lactamase-positive, nontypable H influenzae in one. An additional five patients with buccal cellulitis had negative blood cultures but H influenzae type b antigenuria. A satisfactory clinical response was noted in all patients, and repeated blood cultures performed in initially bacteremic patients were sterile. Cefuroxime therapy was well tolerated, and abnormal laboratory results were infrequent, except for absolute granulocytopenia (granulocytes, less than 1,500/cu mm), which occurred in six patients but could not be ascribed to a drug effect because of the uncontrolled design of our study. Treatment with cefuroxime appears to be a safe and effective therapy for pediatric soft-tissue infections due to H influenzae and S pneumoniae.

Cefuroxime↗

Ceftriaxone: a third-generation cephalosporin.

Ceftriaxone is a new third-generation cephalosporin with excellent activity against many gram-negative, and reasonable activity against most gram-positive microorganisms. Clinical studies have demonstrated its efficacy and safety in patients with bacterial meningitis; respiratory tract, urinary tract, soft tissue, bone and joint infections; and gonorrhea. Ceftriaxone has been well tolerated except for diarrhea, which in most cases has not required a change in therapy. The long elimination half-life of ceftriaxone has allowed twice- and once-daily administration, the latter potentially resulting in substantial cost savings. Because of its documented efficacy, safety, and convenient dosing schedule, ceftriaxone may become the preferred third-generation cephalosporin for the treatment of a variety of serious infections.

Adult↗

Moxalactam epimer kinetics in children.

The kinetics of the R and S epimers of moxalactam were followed after single intravenous doses of 50 mg/kg to 12 patients, 8 to 45 mo old, with cellulitis or epiglottitis. High-pressure liquid chromatography was used to determine serum concentrations. Total body clearance and apparent volume of distribution of the R epimer were higher than those of the S epimer (P less than 0.004). Total body clearance of R, S, and R + S moxalactam ranged from 29.01 to 183.7, 19.00 to 79.95, and 23.34 to 113.6 ml/min/m2. Mean elimination half-lives of R, S, and R + X moxalactam were 2.04, 2.26, and 2.24 hr. The higher incidence of the more active R epimer and the 500% interpatient variation in clearance may indicate a need for monitoring serum and cerebrospinal fluid concentrations in patients with severe unresponsive central nervous system infectious treated with moxalactam.

Anti-Bacterial Agents↗