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Biomedical subjects

H R Stutman

Publications and source records attributed to H R Stutman.

At least 55 records · Page 3Linked to original sources

Second episodes of Haemophilus influenzae type b disease following rifampin prophylaxis of the index patients.

Patients treated for Haemophilus influenzae type b disease frequently remain nasopharyngeal carriers of that organism and fail to develop protective concentrations of serum antibody. It has been suggested that rifampin prophylaxis of the index patient may prevent recurrence of disease by eliminating type b Haemophilus carriage. We report nine children who developed second episodes of disease 1 week or more after receiving rifampin prophylaxis. The median interval between the last dose of rifampin and admission to the hospital for the second episode was 70 days (range, 9 to 138). Analysis of biotypes and outer membrane protein polyacrylamide gel electrophoresis patterns of paired isolates from eight cases revealed that the second episodes in two of the children were caused by acquisition of new type b Haemophilus strains, whereas the second episodes in the remaining six children were caused by isolates which were indistinguishable from the respective isolates from the first episodes. Rifampin prophylaxis of the index patient may prevent some episodes of recurrent disease. However, in some patients who have received prophylaxis, second episodes can occur, probably as a result of reacquisition of the organism from contacts who did not receive rifampin or from acquisition of new type b strains.

Bacterial Outer Membrane Proteins↗

Pulmonary infections in children with cystic fibrosis.

Bronchopulmonary infections continue to be the major determinant of morbidity and mortality in patients with cystic fibrosis (CF). The basic pathogenesis of disease includes abnormal secretions and impaired mucociliary clearance. Colonization of the tracheobronchial tract with bacteria is then associated with a cycle of infection, inflammation and airway obstruction eventually leading to respiratory insufficiency. Early clinical features include persistent cough and failure to thrive. Hyperinflation and bronchial thickening are early radiographic changes suggestive of CF. Staphylococcus aureus is commonly the initial respiratory pathogen. Subsequently, Hemophilus influenzae and Pseudomonas aeruginosa colonize the respiratory tract. In addition, respiratory viruses and other pathogens such as Legionella and mycoplasma are implicated in the etiology of pulmonary infections. The culture of respiratory secretions such as sputum are important guidelines to the etiology of pulmonary infection in CF. The laboratory must be aware of the pathogens that are typical of this disease and use appropriate techniques and media. In large part, advances in treatment in CF over the past two decades are due to the availability of increasingly potent antibiotic agents. However, effective treatment must be multifaceted and include a variety of nonantimicrobial therapies. Different approaches to the antibiotic therapy of pulmonary infection in CF, including prevention, suppression, and definitive treatment are discussed. In addition to traditional antibiotic therapy, a variety of newer methods of therapy in CF are discussed. These include oral antipseudomonal antibiotics, corticosteroid therapy, aerosolized antibiotics, and continuous antimicrobial prophylaxis.

Anti-Bacterial Agents↗

Aztreonam therapy for serious gram-negative infections in children.

Fifty-nine children were enrolled in an open trial of aztreonam, a monocyclic beta-lactam, therapy for serious gram-negative infections. Thirty-six infections were microbiologically evaluable and received five or more days of therapy. Patients' ages ranged from 3 days to 12 years, and diagnoses included pyelonephritis or cystitis (20), deep soft tissue or joint infection (seven), septicemia (four), pneumonia (three), peritonitis, and epiglottitis. Causative bacteria included Escherichia coli and other Enterobacteriaceae, Pseudomonas aeruginosa, and Haemophilus influenzae. The standard regimen was 30 mg/kg every six or eight hours intravenously. All isolates were aztreonam-susceptible and were eradicated during therapy. Two patients had microbiologic relapses: a patient with Salmonella choleraesuis meningitis who was initially treated for only ten days and a patient with E coli pyelonephritis. Clinical cure was achieved in 31 of 36 children. Pharmacokinetic studies performed in six children demonstrated no difference in serum concentrations or pharmacokinetic variables between day 1 and day 7 of therapy. Although several patients had transient eosinophilia (eight), elevated levels of aminotransferase (seven), or thrombocytosis (ten), no clinically significant adverse effects were noted. In this initial, uncontrolled study, aztreonam was effective and safe in the treatment of a variety of serious gram-negative infections in children.

Aztreonam↗

Cefuroxime versus ampicillin plus chloramphenicol in childhood bacterial meningitis: a multicenter randomized controlled trial.

In a multicenter randomized trial, 107 children with bacterial meningitis were initially given either cefuroxime or ampicillin plus chloramphenicol. Patients were alternately assigned to 7- or 10-day courses of the designated antimicrobial regimen. CSF isolates included Haemophilus influenzae type b (89, of which 25% were beta-lactamase positive), Streptococcus pneumoniae, and Neisseria meningitidis. Although mean CSF bactericidal titers against Haemophilus isolates were 1:6 in each treatment group, H. influenzae was cultured from CSF in four of 39 patients receiving cefuroxime, 24 to 48 hours after initiation of therapy, compared with none of 40 patients given ampicillin plus chloramphenicol (P = 0.11). Clinical cure rates were similar (95%); one death occurred in each group. One child given cefuroxime had persistent meningitis after 5 days of therapy, and mastoiditis with secondary bacteremia developed in one on day 10. Three patients had relapse or reinfection. One patient who received cefuroxime for 10 days had a relapse of epiglottitis 17 days later, and of the patients given ampicillin plus chloramphenicol, one had a relapse of meningitis 1 week after 7 days of therapy, and bacteremia developed in one 42 days after completion of 10 days of therapy. No increase in either in-hospital complications or relapses occurred with a 7-day treatment course. Proof of the equivalence of the antibiotic regimens and the efficacy of 7-day courses of treatment, as well as the consequences of delayed CSF sterilization, will require additional investigation.

Adolescent↗

Single-dose pharmacokinetics of imipenem-cilastatin in pediatric patients.

The single-dose pharmacokinetics of two dosages of imipenem-cilastatin (1:1), 10 and 25 mg/kg, were studied in ten children. Plasma concentrations, half-lives, and areas under the curve of both imipenem and cilastatin was significantly greater at the 25 mg/kg dosage but the half-lives and clearances of the two drugs were similar to each other only at the larger dose. After a 25 mg/kg dose, the mean peak and trough (6 hr) plasma concentrations of imipenem were 78.8 and 0.68 micrograms/ml, respectively, and the half-lives of imipenem and cilastatin were 1.12 and 0.97 hr, respectively. Urinary excretion of imipenem was 43-47% during the 6 hr following administration of either dosage. No clinical or laboratory toxicity was noted. A 25 mg/kg dose of imipenem-cilastatin maintains serum concentrations of imipenem above the minimum inhibitory concentration (MIC) of potential pathogens for 4-6 hr and seems appropriate for multiple-dose studies. Our data suggest that a minimum dosage, greater than 10 mg/kg, of cilastatin may be required to prolong the half-life of imipenem to adult values.

Child↗

Bacterial arthritis.

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Anti-Bacterial Agents↗

Penetration of latamoxef, cefoperazone and piperacillin into the sputum of patients with cystic fibrosis.

Concentrations of latamoxef, cefoperazone and piperacillin, administered intravenously, were measured in serum and sputum of cystic fibrosis patients with recurrent pulmonary infections, chronically colonized with Pseudomonas aeruginosa. Serum pharmacokinetic data were consistent with prior reports. Peak sputum to peak serum concentrations were approximately 3% for each antimicrobial. However, the more prolonged sputum concentrations of piperacillin were reflected in greater areas under the sputum concentration-time curve and a longer duration above the MIC50 of tested P. aeruginosa strains for that drug.

Adolescent↗

Potential of moxalactam and other new antimicrobial agents for bilirubin-albumin displacement in neonates.

The effects of several novel antibiotics on in vitro binding of bilirubin to human serum albumin were investigated. At physiologic bilirubin-albumin ratios and pH values, aztreonam, imipenem, azlocillin, enoxacin and ciprofloxacin did not compete with bilirubin at drug concentrations less than 900 micrograms/mL. Cefoperazone caused an apparent increase in unbound bilirubin only at concentrations greater than 35 microM (330 micrograms/mL). Moxalactam, however, caused a linear increase in unbound bilirubin, greater than that seen with sulfisoxazole, over the entire range of antibiotic concentrations. These results may have implications for the use of these newer antimicrobial agents in neonatal infections.

Anti-Bacterial Agents↗

Hemophilus influenzae type b meningitis in infant rabbits. Pathogenesis and therapy.

A model of human Hemophilus influenzae type b meningitis was developed in infant rabbits infected intranasally. The pathogenesis and course resembled that in human beings; bacteremia was followed by meningitis with a high mortality. Pretreatment of the nasopharyngeal mucosa with 0.5% trypsin or normal saline significantly increased the rate of bacteremia. Death was age related. Intranasal challenge with type f and nontypeable H influenzae was associated with transient bacteremia. Our results suggest that factors on the respiratory tract epithelial cell surface influence colonization and infection with H influenzae type b and confirm the importance of other host and parasite factors. Intravenous aztreonam resulted in a peak CSF concentration that was 6% to 7% of the serum concentration in infected meninges but only 2% to 3% in normal meninges. Aztreonam reduced mortality in established H influenzae type b meningitis from 88% in untreated animals to 9%.

Animals↗

In vitro antimicrobial activity of aztreonam alone and in combination against bacterial isolates from pediatric patients.

We examined 134 pediatric clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa, and gram-positive cocci for susceptibility to aztreonam alone and in combination with seven other antibiotics. All 98 gram-negative isolates were susceptible to aztreonam with similar inhibitory and bactericidal activity. Combinations of aztreonam with cefoxitin, ampicillin, or clindamycin were generally indifferent or additive. Synergism was occasionally seen against enteric organisms with aztreonam plus cefoxitin or clindamycin. Combinations of tobramycin and aztreonam were synergistic (62%) against P. aeruginosa; aztreonam plus piperacillin or ticarcillin was additive. Aztreonam did not affect the activity of nafcillin against Staphylococcus aureus, or of ampicillin against species of Streptococcus group B or D. Antagonism was seen only with aztreonam plus cefoxitin against Enterobacter species, but not at clinically significant concentrations. Several combinations of antibiotics with aztreonam should be appropriate for initial therapy of infections in children without major risks of antibacterial antagonism.

Anti-Bacterial Agents↗

Single-dose pharmacokinetics of aztreonam in pediatric patients.

Single intravenous doses (30 mg/kg) of aztreonam, a novel monobactam antibiotic, were administered to 29 children from 2 days to 11 years old. Serum, urine, and, when possible, cerebrospinal fluid samples were analyzed by high-pressure liquid chromatography and microbiological methods. The concentration of aztreonam in serum 15 min after drug administration was approximately 100 micrograms/ml in all age groups. The elimination half-life varied inversely, and the clearance from serum varied directly, with age. Aztreonam pharmacokinetics in 2- to 12-year-olds were similar to those in adults. The concentration in urine was high and prolonged, with potentially therapeutic concentrations still present 12 to 24 h after infusion in all age groups. Penetration into cerebrospinal fluid averaged 17.3% in children with inflamed meninges. Standard clinical and laboratory measurements revealed no untoward reactions. The 30-mg/kg dose of aztreonam produced potentially therapeutic concentrations in serum, urine, and cerebrospinal fluid. A dosage schedule of every 6 to 8 h in older children and every 8 to 12 h in neonates is suggested for multiple-dose clinical trials.

Age Factors↗

Phaeohyphomycosis of the maxilloethmoid sinus caused by Drechslera spicifera: a new fungal pathogen.

"Phaeohyphomycosis" refers to soft tissue and systemic infections caused by dematiacious septate fungi. Drechslera spicifera, a dematiacious fungus, rarely pathogenic in humans was found to cause maxilloethmoid sinus disease in two immunocompetent children. The clinical presentation was similar to noninvasive aspergillosis. Intracavitary surgical excision without adjuvant chemotherapy resulted in apparent cure. The microbiologic and clinicopathologic aspects of this mycotic sinus disease are reviewed and discussed in relation to the entire spectrum of human disease reported which has been attributed to this organism.

Adult↗