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Biomedical subjects

S C Aronoff

Publications and source records attributed to S C Aronoff.

54 records · Page 3Linked to original sources
PubMed1984

In vitro activities of aztreonam, piperacillin, and ticarcillin combined with amikacin against amikacin-resistant Pseudomonas aeruginosa and P. cepacia isolates from children with cystic fibrosis.

Amikacin, combined with aztreonam, piperacillin, or ticarcillin, synergistically inhibited amikacin-resistant sputum isolates of Pseudomonas aeruginosa and P. cepacia from children with cystic fibrosis. Ticarcillin-amikacin was the least active combination. Aminoglycoside resistance should not preclude the use of beta-lactam-aminoglycoside combinations in the treatment of pulmonary infections in cystic fibrosis.

Amikacin↗
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

Comparative activities of the beta-lactamase inhibitors YTR 830, sodium clavulanate, and sulbactam combined with amoxicillin or ampicillin.

YTR 830, a new beta-lactamase inhibitor, was compared with clavulanic acid and sulbactam against aminopenicillin-resistant clinical isolates. At a concentration of 8 micrograms/ml, YTR 830 was as effective as clavulanate or sulbactam in reducing the aminopenicillin MICs. Combined with amoxicillin, YTR 830 is a potentially useful agent for therapy of many bacterial infections.

Amoxicillin↗
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↗
PubMed1984

Moxalactam therapy of serious pediatric infections.

Forty children with documented or suspected bacterial infections arising outside the central nervous system (CNS) were studied. Fifteen different pathogens for a total of 30 isolates were obtained from multiple sources. Staphylococcus aureus (minimum inhibitory concentrations 4-8 micrograms/ml) was the most common pathogen isolated, involving seven patients. Each patient received moxalactam 50 mg/kg iv over 15 minutes q8h and responded favorably to therapy, exhibiting bacteriologic and/or clinical cures. Toxicity associated with moxalactam occurred in only two patients and necessitated discontinuation of drug therapy. Moxalactam 50 mg/kg iv q8h is effective therapy for non-CNS infections occurring in infants and children.

Bacteria↗
PubMed1983

Developmental pharmacokinetics of moxalactam.

A pharmacokinetic evaluation of moxalactam was performed with 30 infants and children with documented or suspected bacterial infections arising outside the central nervous system. Each child received 50 mg of moxalactam per kg infused intravenously over a period of 15 min every 8 h. A total of 26 children were studied after receiving the first dose; 20 of these, along with 4 additional patients, were evaluated after receiving continuous therapy for at least 3 days. After the first dose, the elimination half-life, apparent volume of distribution, and plasma clearance averaged 1.59 h, 0.331 liter/kg, and 100.9 ml/min per 1.73 m2, respectively. The biodisposition of the moxalactam epimers was also evaluated, with similar overall results. No differences in pharmacokinetic parameters were observed when the first-dose values were compared with those obtained at the steady state. Age-dependent changes in moxalactam elimination were observed for children of less than or equal to 1 year of age, suggesting that a dosage reduction may be necessary for children of less than or equal to 2 months of age.

Adolescent↗
PubMed1983

Efficacy and safety of ceftriaxone in serious pediatric infections.

Thirty-four patients aged 1 month to 19 years were treated with ceftriaxone for suspected bacterial infections. Bacterial pathogens were isolated from 25 children. The overall bacterial cure rate was 88%, with an overall clinical response rate of 96%. No side effects requiring cessation of therapy were observed. Ceftriaxone proved to be safe and effective in the treatment of serious infections in children.

Adolescent↗
PubMed1975

Failure of neutrophilia to increase the number of neutrophils entering a peritoneal exudate in mice.

Neutrophilia, produced by bleeding or by parasitic infection, did not result in a larger than normal number of cells migrating into endotoxin-induced peritoneal exudates. These results fail to support but do not disprove the concept that neutrophil loss from the blood may be controlled primarily by changes in the fractional turnover rate rather than by blood pool size. They indicate that the failure of exudate neutrophils to increase in proportion to blood neutrophils in patients with chronic myeloid leukemia may not be an abnormality as interpreted previously.

Animals↗
PubMedDate not supplied

Single-dose pharmacokinetics of aztreonam in children with cystic fibrosis.

The single-dose pharmacokinetics of aztreonam was evaluated in 10 clinically stable subjects with cystic fibrosis. Each child received 30 mg aztreonam/kg intravenously over 2 to 3 minutes. Multiple timed blood samples were obtained over 8 hours for determination of aztreonam elimination kinetics; all urine excreted for 24 hours was collected in timed aliquots for the determination of aztreonam and its microbiologically inactive metabolite, SQ 26,992. Aztreonam pharmacokinetic parameters were determined by model-independent methods. Mean t1/2, steady-state volume distribution, and body clearance were 1.3 hr, 0.25 L/kg, and 127.2 ml/min/1.73m2, respectively. In 9 of the 10 subjects, two-compartment pharmacokinetic analysis was possible and compared favorably with model-independent parameter estimates. Twenty-four-hour urinary recovery of aztreonam was 76.3% of the administered dose; 2.6% was recovered as the metabolite SQ 26,992. The renal clearance of aztreonam averaged 92.5 ml/min/1.73m2. When these data are combined with in vitro susceptibility data for aztreonam against Pseudomonas aeruginosa isolated from the sputum of patients with cystic fibrosis, a dose of 200 mg aztreonam/kg/day divided six hourly would be predicted to maintain serum concentrations above the minimum inhibitory concentration (MIC) for these organisms for the majority of the dosing interval.

Adolescent↗
PubMedDate not supplied

Differences in drug susceptibility between isolates of Pseudomonas cepacia recovered from patients with cystic fibrosis and other sources and its relationship to beta-lactamase focusing pattern.

Pseudomonas cepacia, a significant pulmonary pathogen among children with cystic fibrosis (CF), often possesses an inducible beta-lactamase. The beta-lactamase isoelectric focusing pattern and beta-lactam susceptibility of CF and non-CF isolates of P. cepacia were compared. Against all of the test strains, ceftazidime and piperacillin were more effective than aztreonam. More CF isolates were resistant to 8 micrograms/ml of ceftazidime than non-CF isolates. Isoelectric focusing of cefoxitin-induced, cell-free preparations of the CF isolates produced significantly more bands than comparable preparations of non-CF isolates. Organisms producing a beta-lactamase band that focused in the pH range of 8.5 to 8.7 were significantly more resistant to 8 micrograms/ml of ceftazidime than other isolates. The increased resistance of CF isolates of P. cepacia to ceftazidime may be the result of the production of a specific bacterial beta-lactamase.

Anti-Bacterial Agents↗
PubMedDate not supplied

The effect of alginate on the invasion of cystic fibrosis respiratory epithelial cells by clinical isolates of Pseudomonas aeruginosa.

Chronic infection in the cystic fibrosis (CF) lung is characterized by Pseudomonas aeruginosa strains that overproduce the mucoid exopolysaccharide, alginate. Previous experiments have shown that long-term survival of P. aeruginosa in the CF lung may be facilitated by increased adherence and decreased invasion of respiratory epithelial cells. Therefore, mucoid and nonmucoid clinical isolates of P. aeruginosa were assayed for their ability to associate with and invade the CF respiratory epithelial cell line, CF/T43. Association assays and gentamicin exclusion assays demonstrated that mucoid P. aeruginosa associates with and invades CF/T43 cell monolayers significantly less than nonmucoid P. aeruginosa strains (P = .004, .02). Fluorescence microscopy invasion assays confirmed these results. The differences in association and invasion by the P. aeruginosa strains were not due to differences in lipopolysaccharide phenotype or cytotoxicity for CF/T43 respiratory epithelial cells. Exogenous bacterial alginate had no effect on the invasion of CF respiratory epithelia by a nonmucoid strain. Invasion assays with the wild-type P. aeruginosa strain PAO1 and isogenic algU and mucA mutant strains failed to show differences in invasion (P = .25). We conclude that (i) mucoid P. aeruginosa isolates associate with and invade CF/T43 respiratory epithelial cells with less efficiency than nonmucoid P. aeruginosa, (ii) these differences are not due to variations in lipopolysaccharide phenotype between strains, (iii) neither exogenous nor endogenous alginate affects the ability of P. aeruginosa to invade CF/T43 respiratory epithelial cells, and (iv) invasion of CF/T43 respiratory epithelial cells by a laboratory reference strain of P. aeruginosa does not appear to be regulated by AlgU.

Alginates↗
PubMedDate not supplied

Efficacy and safety of sequential treatment with parenteral sulbactam/ampicillin and oral sultamicillin for skeletal infections in children.

Nine children with osteomyelitis and/or septic arthritis were treated sequentially with parenteral sulbactam/ampicillin and oral sultamicillin. Causative pathogens were identified in six cases; all were susceptible to the combination of ampicillin and sulbactam. The mean duration of parenteral therapy was 7.1 days (6-11 days), and the average hospital stay was 10.3 days (6-18 days). Peak serum bactericidal titers of greater than or equal to 1:8 were achieved in all patients during parenteral therapy; only one child receiving oral therapy did not achieve a titer of greater than or equal to 1:4. At follow-up, all of the children were cured clinically and there was no evidence of relapse. Adverse reactions to oral therapy were minimal. The regimen of parenteral sulbactam/ampicillin and oral sultamicillin used sequentially is effective and safe for the treatment of skeletal infections in children. The use of this approach significantly reduced the duration of hospitalization.

Administration, Oral↗
PubMedDate not supplied

Evaluation of moxalactam.

The mechanism of action, antibacterial spectrum, pharmacokinetics, current dosage recommendations, adverse reactions, therapeutic uses, and pharmaceutical considerations of moxalactam disodium are reviewed. Moxalactam is a synthetically derived, structurally unique beta-lactam antibiotic. Its antimicrobial activity encompasses a wide spectrum and includes some strains of pseudomonal species. Administered by i.v. or i.m. injection, moxalactam is widely distributed to body fluids and tissues. Its elimination half-life is longer than those of first- and second-generation cephalosporins. Usually administered in two or three divided doses daily, moxalactam has been shown to be effective against specific organisms in a variety of infections, including lower respiratory, urinary-tract, intra-abdominal, central nervous system, skin and skin-structure, and bone and joint infections, and bacterial septicemia. Adverse reactions associated with moxalactam administration have been limited and appear similar to those experienced following the use of other beta-lactam antibiotics. Because of its wide spectrum of activity, colonization of resistant organisms and (to a lesser extent) superinfection may complicate therapy. Early clinical experience indicates that moxalactam is effective for the treatment of a number of bacterial infections, including those involving the abdominal cavity and respiratory and urinary tracts. More experience is necessary to delineate its most appropriate roles in specific infectious processes.

Bacteria↗
PubMedDate not supplied

Single-dose plasma and cerebrospinal fluid pharmacokinetics of ceftriaxone in infants and children.

Pharmacokinetic variables were studied in children with central nervous system infections who received a single dose of ceftriaxone sodium. After initial lumbar puncture of children with documented or suspected bacterial meningitis, ventriculitis, or both, therapy was initiated with i.v. ampicillin and chloramphenicol. Children were randomly selected to receive a single i.v. dose of ceftriaxone. Concentrations of ceftriaxone were measured in plasma at intervals from 0 to 720 minutes after the beginning of the infusion and in cerebrospinal fluid (CSF) at one to five hours after the dose. Blood samples were obtained immediately after the second lumbar puncture for assessment of drug penetration into CSF. Elimination rate constant, elimination half-life, apparent volume of distribution, and plasma clearance were determined from samples obtained 30-720 minutes after the start of the infusion. In two children with ventriculoperitoneal shunts, serial determinations of ceftriaxone in CSF were obtained. All eight children who received 75 mg/kg and five of eight who received 50 mg/kg had positive CSF cultures. Volume of distribution was less after the 50 mg/kg dose than after the 75 mg/kg dose. In the children with shunts, adequate CSF drug concentrations were maintained throughout 12 hours of testing. These data support a 12-hour dosage interval, but clinical studies are needed to evaluate efficacy of the drug at both 12-hour and 24-hour dosage regimens.

Adolescent↗