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Biomedical subjects

M D Reed

Publications and source records attributed to M D Reed.

At least 91 records · Page 5Linked to original sources
PubMed1987

The clinical pharmacology of vancomycin in seriously ill preterm infants.

The first dose and steady state pharmacokinetics of vancomycin were studied in 16 seriously ill preterm infants (less than or equal to 34 wk gestational age) with documented Staphylococcus epidermidis infections. One infant was dropped from the study due to peripheral flushing occurring during administration of the first dose. Individual vancomycin doses ranged from 9.8 to 17.8 mg/kg and were infused intravenously over 15-37 min. Fifteen infants were studied after the first dose of vancomycin, whereas only 12 of these 15 were able to be studied under steady state conditions. Vancomycin half-life, steady-state volume of distribution, and body clearance averaged 6.0 h, 0.53 liter/kg, and 1.22 ml/min after the first dose and only slight differences were observed in these parameter estimates under steady state conditions. However, substantial accumulation of vancomycin in serum was observed with multiple dosing. Complete 8-h urine collections were possible in 12 of 15 premature infants after the first dose of vancomycin. Overall, 44.6% of the dose was recovered in the urine with a corresponding vancomycin renal ClR averaging 0.88 ml/min. Vancomycin body Cl correlated directly with renal ClR (r = 0.88, p less than 0.001) and body weight (r = 0.8, p less than 0.001). Vancomycin pharmacokinetic parameter estimates Vdss and Cl correlated directly with body weight, surface area, and postconceptional age. No significant relationships were observed between these parameter estimates and gestational age or postnatal age. Fourteen of 15 infants were treated successfully for their underlying infectious process. These data support the use of lower doses of vancomycin than previously recommended for the treatment of preterm infants.

Female↗
PubMed1986

Cephalosporin therapeutics in cystic fibrosis.

Cephalosporins modified at the C-3 and C-7 positions of the cephem-nucleus have high antimicrobial activity and are safe. With evolution through first, second, and third generations, they have gained increasing gram-negative activity, but often at the expense of potency against gram-positive organisms. All third-generation cephalosporins have some intrinsic anti-Pseudomonas activity, indicating their potential benefit in the treatment of acute pulmonary exacerbations in patients with cystic fibrosis. Rational therapy in this clinical setting requires recognition of the pharmacodynamic and pharmacokinetic idiosyncrasies intrinsic to this patient population. When these priorities are recognized, only two of the available agents, cefsulodin and ceftazidime, appear to be of any therapeutic value. Both agents have been evaluated extensively in the treatment of acute pulmonary exacerbation in cystic fibrosis, and both have been found to be safe and effective.

Cefsulodin↗
PubMed1986

Barbiturate and nonbarbiturate sedative hypnotic intoxication in children.

This article reviews the pharmacology, toxicology, and treatment of both barbiturate and nonbarbiturate sedative hypnotic overdose. Although poisoning with these agents has declined over recent years, intoxication with them can still result in a life-threatening situation requiring immediate assessment and treatment.

Anti-Anxiety Agents↗
PubMed1986

Developmental pharmacology and therapeutics of piperacillin in gram-negative infections.

Twenty children ranging in age from 1 week to 19 years with documented or suspected bacterial infections arising outside the central nervous system were studied. Pharmacokinetic analysis was possible in 15 children; 8 after the first dose, 6 during steady-state conditions, and 4 on both occasions. Data were obtained utilizing noncompartmental pharmacokinetic methods. Peak piperacillin serum concentrations ranged from 51 to 232 mg/l and correlated directly (r = 0.75) with the dose administered. In children with normal renal function, there was an age-dependent decrease in elimination half-life and apparent steady-state volume of distribution, whereas plasma clearance increased logarithmically. All but 1 child responded favorably to piperacillin therapy, and 1 child with a urinary tract infection relapsed 10 days after discontinuation of the therapy. Although improved clinically, piperacillin monotherapy failed to eradicate pathogens in 2 children. No adverse clinical or biochemical effects were observed in any child.

Adolescent↗
PubMed1986

Current concepts in clinical therapeutics: bacterial meningitis in infants and children.

The epidemiology and incidence, etiology, pathogenesis and pathophysiology, clinical presentation, diagnosis, principles of therapy, and treatment of bacterial meningitis in infants and children are reviewed. Bacterial meningitis is a major cause of morbidity and mortality, and most cases occur in children less than five years old. Haemophilus influenzae type b, Neisseria meningitidis, and Streptococcus pneumoniae are the major pathogens involved. Bacteremia or colonization of the upper-respiratory-tract epithelium often precedes meningitis. Defense mechanisms are poor in the cerebrospinal fluid; once an organism penetrates the blood-brain barrier, infection may follow quickly. Clinical signs and symptoms are somewhat nonspecific, with lethargy, restlessness, and poor feeding prominent; diagnosis often relies on the patient history along with preliminary results of lumbar punctures. Therapy is based on pharmacologic and pharmacodynamic principles concerning the available antimicrobial agents, the blood-brain barrier, and supportive therapy. Effective antimicrobial therapy requires attainment of adequate bactericidal activity in the cerebrospinal fluid; penetration of agents into the brain depends on their physico-chemical characteristics. Antibiotic therapy must generally be started before culture results are available, making empiric therapy based on the child's age, history, and underlying conditions important. Established therapeutic agents include penicillins, aminoglycosides, and chloramphenicol, though newer expanded-spectrum cephalosporins such as cefuroxime, ceftriaxone, and cefotaxime are being used with increasing frequency. However, the use of these newer, more potent antimicrobial agents have not appreciably altered associated morbidity and mortality. Aggressive supportive care and evaluation of newer nonantibiotic treatments should be addressed in future studies of bacterial meningitis in infants and children.

Anti-Bacterial Agents↗
PubMed1986

Continuous nasogastric administration of activated charcoal for the treatment of theophylline intoxication.

Two adolescents with serum theophylline concentrations in excess of 100 mg/L were treated with continuous nasogastric infusion of activated charcoal after an intentional overdose. In both cases, nasogastric boluses of 20 to 50 gm of charcoal resulted in prompt emesis of stomach contents despite the presence of a functional nasogastric tube. For nasogastric infusion, activated charcoal was diluted in 0.9% sodium chloride and infused at a rate of 0.25 to 0.5 gm/kg/hr up to a maximal rate of 50 gm/hr. Despite the high initial serum concentrations, the theophylline elimination half-lives during the first 20 hours after the start of charcoal were 7.7 and 13.5 hours. Subsequently, this decreased to 2.6 and 3.2 hours. No serious neurologic, cardiovascular, or metabolic derangements were observed. Continuous nasogastric infusions of activated charcoal may be safe and effective alternatives to charcoal hemoperfusion in patients with theophylline overdose.

Administration, Intranasal↗
PubMed1985

Ceftazidime therapy in patients with cystic fibrosis and multiply-drug-resistant pseudomonas.

The in vitro activity of ceftazidime against Pseudomonas aeruginosa and P. cepacia isolates from patients with cystic fibrosis was compared with that of other antipseudomonal drugs. Ceftazidime was as potent as imipenem against P. aeruginosa and the only drug effective against P. cepacia. An evaluation of the elimination kinetics of ceftazidime in 20 cystic fibrosis patients revealed an elimination half-life of 1.76 hours, an apparent distribution volume of 0.27 liters/kg, and a serum clearance rate of 133.9 ml/minute/1.73m2. Urinary recovery of ceftazidime was 87 percent within the first 24 hours after administration of the drug, with 65 percent recovered in the first two-hour fraction. Probenecid administration had no effect on the elimination kinetics of ceftazidime. Forty-three patients who had either shown no response to conventional therapy or had sputum Pseudomonas isolates that were susceptible only to ceftazidime received 75 courses of therapy. In 67 percent of these patients, the clinical response, when evaluated using an objective clinical efficacy scoring system, was considered favorable. Clinical failures were not associated with the development of drug resistance. Thus, ceftazidime can be recommended for the treatment of acute pulmonary exacerbations in patients with cystic fibrosis.

Adolescent↗
PubMed1985

Pharmacokinetic determination of ranitidine pharmacodynamics in pediatric ulcer disease.

The pharmacokinetics and pharmacodynamics of ranitidine were evaluated during three methods of administration in 12 children ranging in age from 3.5 to 16 years with documented gastric or duodenal ulcer disease. First, a continuous intravenous infusion of ranitidine was administered to determine the serum concentration necessary to suppress gastric acid secretion by at least 90%. From these data a therapeutic dose of ranitidine was calculated and administered on separate days via the intravenous bolus and oral routes. Half-life, volume of distribution, and clearance values for ranitidine were the same after intravenous bolus and oral doses (1.8 vs 2.0 hours, 2.3 vs 2.5 L/kg, and 794.7 vs 788.0 ml/min/1.73 m2, respectively). The bioavailability of ranitidine given orally averaged 48%. Serum ranitidine concentrations necessary to inhibit gastric acid secretion by at least 90% ranged between 40 and 60 ng/ml for all children studied. No adverse clinical or biochemical effects were observed in any child during the 6 weeks of orally administered treatment. Endoscopic reevaluation after 6 weeks indicated complete healing of initial ulcers.

Adolescent↗
PubMed1985

The posterolateral and the retrorenal colon: implication in percutaneous stone extraction.

Increasing experience with percutaneous nephrolithotomy has fostered an aggressive approach to most renal calculi. We report a case of a stone in a horseshoe kidney. Computerized tomography before anticipated percutaneous stone extraction revealed the colon to be positioned posterior to the left portion of the horseshoe kidney. The posterior position of the colon prevented percutaneous access to the kidney. Computerized tomography should be performed in patients with stones in horseshoe kidneys and other fusion anomalies before elective percutaneous stone extraction is done.

Adult↗
PubMed1985

Pharmacokinetics of imipenem and cilastatin in patients with cystic fibrosis.

The pharmacokinetics of imipenem, a new carbapenem antibiotic, and cilastatin, a metabolic inhibitor, were evaluated in 17 patients with cystic fibrosis. Imipenem and cilastatin were combined in a ratio of 1:1 in the infusion solution, and patients intravenously received 30, 60, or 90 mg of imipenem per kg of body weight per day, divided into four equal doses. Pharmacokinetic evaluation after the first dose and again under steady-state conditions revealed biodisposition characteristics which were similar and independent of the daily dose administered. Cilastatin concentrations in serum paralleled those of imipenem. A linear relationship between dose and area under the serum concentration-time curve for both compounds was observed, suggesting a first-order pharmacokinetic process. A total of 50 and 78% of the doses of imipenem and cilastatin, respectively, were recovered unchanged in the urine. The renal clearances of imipenem and cilastatin averaged 54 and 88%, respectively, of the serum clearance. These data suggest that an extrarenal mechanism may be involved in the overall elimination of imipenem. No patient experienced any clinical or biochemical abnormalities during drug therapy.

Anti-Bacterial Agents↗
PubMed1985

Pharmacokinetics and cerebrospinal fluid penetration of ceftazidime in children with meningitis.

The single dose pharmacokinetics and cerebrospinal fluid (CSF) penetration of ceftazidime were determined in 10 children with bacterial meningitis. Serum ceftazidime pharmacokinetics showed a distinct age dependence in which the clearance in children less than 1 month of age was markedly reduced. Ceftazidime concentrations in CSF, which ranged from 1.4-8.5 micrograms/ml, exceeded the minimum bactericidal concentrations for infecting pathogens throughout the 8-hour sampling period. These concentrations were found to be independent of CSF cell count, protein concentration or the day of therapy on which the study was performed. The ratio of CSF to serum ceftazidime concentration increased with time, suggesting that ceftazidime was cleared more slowly from CSF than from peripheral blood. Our data support the initiation of a study comparing the efficacy of ceftazidime to conventional therapy in children with bacterial meningitis.

Age Factors↗
PubMed1985

Evaluation of antibiotics for home care programs.

A number of antimicrobial agents have been used successfully to treat patients with chronic infectious diseases in the home health care environment. This diversity in types of antibiotics used reflects more than ten years' development of active home medical care programs. With continuing experience, it is clear that the number and types of antibiotics available on formulary for routine use in home programs can be condensed. Since a patient should in most cases be treated in the home environment with the same antibiotic that has demonstrated efficacy and safety upon initial therapy during hospitalization, the selection of available antibiotics will affect the hospital's formulary selection process. This process must critically evaluate the documented efficacy and safety of each agent, since the drug's primary use will be in a relatively uncontrolled environment, devoid of continuous professional assessment. The beta-lactam antibiotics appear to be preferred agents for outpatient use, particularly as monotherapy. These agents offer desirable in vitro activity and potency, ease of administration, overall efficacy, and safety. However, despite a preference for beta-lactam antibiotics, additional and alternative agents must be routinely available in program formularies.

Anti-Bacterial Agents↗
PubMed1984

Dosing implications of rapid elimination of trimethoprim-sulfamethoxazole in patients with cystic fibrosis.

The first-dose and steady-state pharmacokinetics of trimethoprim and sulfamethoxazole were determined in 14 patients with cystic fibrosis. When pharmacokinetic data from the first dose were compared with those at steady state, both TMP and SMZ showed expected accumulations in serum concentrations and decreases in total body clearance. The area under the SMZ serum concentration-time curve was significantly greater at steady state, suggesting drug accumulation during long-term therapy. When pharmacokinetic characteristics for TMP and SMZ obtained in patients with cystic fibrosis were compared with those reported for normal adults, the patients were found to have shorter elimination half-lives and greater plasma clearances. In addition, the apparent volume of distribution for TMP was smaller for patients with cystic fibrosis than for normal adults, consistent with their reduced mass of adipose tissue. Our data support the need for increased dosing or decreased dosing intervals when administering TMP-SMZ to patients with cystic fibrosis.

Adolescent↗
PubMed1984

Comparison of the efficacy and safety of ceftriaxone to ampicillin/chloramphenicol in the treatment of childhood meningitis.

Ceftriaxone is a new cephalosporin with a broad spectrum of antibacterial activity and unique serum and CSF pharmacokinetics. The drug was compared in a randomized fashion with ampicillin and chloramphenicol in the treatment of 19 children with Haemophilus influenzae type b meningitis. Ceftriaxone was also administered non-randomly to six other patients including three children with Gram-negative meningitis. Among the children with H. influenzae meningitis, no deaths were noted and the outcomes of the study and the control groups were similar. Ninety per cent of the isolates of H. influenzae were inhibited by 0.0625, 1 and 1 mg/l of ceftriaxone, ampicillin and chloramphenicol respectively. One child with pneumococcal meningitis and two children with meningococcal meningitis recovered rapidly and without incident during ceftriaxone therapy. Three children with Gram-negative meningitis caused by multiply-drug resistant organisms were bacteriologically cured within five days of the onset of therapy. Persistent pleocytosis and neurological disabilities were noted in two at the conclusion of therapy. Ceftriaxone, as a single agent, was comparable in efficacy with traditional antimicrobial therapy usually employed in childhood meningitis.

Adolescent↗
PubMed1984

Single-dose pharmacokinetics of cefsulodin in patients with cystic fibrosis.

The single-dose pharmacokinetics of cefsulodin were evaluated in 12 patients with cystic fibrosis. Each patient received 3 g of cefsulodin intravenously over 30 min. Multiple plasma and urine samples were obtained during the 6-h study period for the determination of cefsulodin. Pharmacokinetic parameters were determined by model-independent methods. Mean values for t1/2, Vss, and CLp were 1.53 h, 0.242 liters/kg, and 117.3 ml/min per 1.73 m2, respectively. Six-hour urine recovery revealed 73.2% of the administered dose with a corresponding cefsulodin urinary clearance of 75.1 ml/min. These pharmacokinetic data in patients with cystic fibrosis appear consistent with data reported for unaffected individuals.

Adolescent↗
PubMed1984

Ceftazidime as initial therapy for suspected bacterial infections in hospitalized pediatric patients.

Ceftazidime, a new beta-lactam antibiotic, was used to treat 60 children with suspected bacterial infections occurring outside the central nervous system. The patients ranged in age from 0.1 to 21 years and received 30 mg of ceftazidime per kg up to a total single dose of 1 g administered every 8 h. Fifty-three pathogens were isolated from 43 children before the initiation of therapy. All children responded clinically, although one child failed bacteriologically and five children were considered colonized at the end of ceftazidime therapy. Adverse reactions associated with ceftazidime administration were primarily alterations in laboratory parameters and were clinically insignificant. Ceftazidime administered on an 8-h dosing regimen is effective monotherapy for the treatment of childhood infections.

Adolescent↗
PubMed1984

Evaluation of latamoxef as initial therapy of bone and joint infections in childhood.

The efficacy and pharmacokinetics of latamoxef were evaluated during initial therapy of bacteriologically proven bone and joint infections in children. Pharmacokinetic evaluation revealed no significant difference in latamoxef biodisposition after the first dose or at steady state. Peak serum concentrations exceeded 140 mg/l and 8-hour trough concentrations averaged 6.5 mg/l. The patients were infected with a variety of gram-positive and gram-negative pathogens. All were sensitive to readily achievable serum concentrations of latamoxef; moreover, the serum concentration remained above the MIC of the most resistant organism for at least 7 h after each dose. All patients responded favorably to initial therapy and there have been no relapses in more than 2 years of clinical follow-up.

Adolescent↗