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J L Blumer

Publications and source records attributed to J L Blumer.

160 records · Page 9Linked to original sources
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

Therapeutic evaluation of piperacillin for acute pulmonary exacerbations in cystic fibrosis.

The efficacy and pharmacokinetics of piperacillin monotherapy were studied in 46 patients with cystic fibrosis. Two patients were dropped from the study within 24 hr of enrollment because of drug-associated nausea and vomiting. Initially fourteen older patients (greater than 12 years) receiving piperacillin 450 mg/kg/day underwent a preliminary evaluation. Based on the results, 30 younger patients (less than or equal to 12 years) randomized in a double-blind fashion received either 600 or 900 mg/kg/day of piperacillin in six divided doses. Pharmacokinetic parameter estimates for t1/2 Vdss, and Cl were similar for first dose and steady-state evaluations. In 27 patients, approximately 43% of the administered dose was recovered in the urine after 4 hr. Piperacillin CiR averaged 49% of the total Cl. No difference in overall clinical efficacy could be identified between 600 and 900 mg/kg/day of piperacillin using two different objective scoring systems. Although a reduction in sputum Pseudomonas colony counts was greater following the 900 mg/kg/day regimen, this appeared to be independent of clinical effect. In 14 patients (32%), a distinct adverse serum-sicknesslike reaction was observed. The incidence of this reaction appeared to increase as the dose of piperacillin increased. All signs and symptoms of this reaction resolved within 36 hr of discontinuing piperacillin administration but recurred immediately on rechallenge in four patients. All patients with the adverse reaction were subsequently treated with beta-lactam antibodies without ill effect. Overall, clinical improvement appeared to be independent of the piperacillin dose. Our data support the use of total daily piperacillin dosages not exceeding 600 mg/kg.

Adolescent↗
PubMedDate not supplied

Comparison of the efficacy and tolerability of once-daily ceftibuten and twice-daily cefprozil in the treatment of children with acute otitis media.

In this multicenter, randomized, single (investigator)-masked study, the efficacy and tolerability of once-daily ceftibuten and twice-daily cefprozil were compared in the treatment of acute otitis media in patients 6 months to 10 years of age. Ceftibuten oral suspension 9 mg/kg once daily (maximum dose, 400 mg/d) and cefprozil oral suspension 15 mg/kg twice daily (maximum dose, 1000 mg/d) were given for 10 days. Clinical response, evaluated at the posttreatment visit (days 14 to 16), was rated as clinical cure, improvement, failure, relapse/recurrence, or not assessable. The clinical response was considered successful if the posttreatment assessment was clinical cure or clinical improvement and unsuccessful if the assessment was clinical failure, relapse/recurrence, or not assessable. Tolerability was evaluated by observed and spontaneously reported adverse events. A total of 205 patients were enrolled in the study. The ceftibuten group (51 males, 51 females; mean age, 4.8 years, range, 0.5 to 10.7 years) was similar in demographic characteristics to the cefprozil group (60 males, 43 females; mean age, 4.8 years, range, 0.7 to 10.7 years). In the ceftibuten-treated group, 83.3% (85) of the 102 patients had a successful response compared with 82.5% (85) of the 103 patients in the cefprozil-treated group. The incidence of treatment-related adverse events was similar in both groups, occurring in 5.9% (6) of the ceftibuten-treated patients and 5.8% (6) of the cefprozil-treated patients. Once-daily ceftibuten oral suspension was as effective and well tolerated as twice-daily cefprozil in the treatment of acute otitis media in children. The once-daily dosing schedule for ceftibuten therapy may aid patient compliance, particularly in the pediatric population. Ceftibuten should prove to be a useful alternative in the treatment of acute otitis media.

Acute Disease↗
PubMedDate not supplied

Imipenem/cilastatin in acute pulmonary exacerbations of cystic fibrosis.

Nineteen patients with pulmonary exacerbations of cystic fibrosis due to Pseudomonas aeruginosa were given imipenem/cilastatin for six to 10 days at dosages of 30-90 mg/kg per day. Mean Shwachman scores rose from 46.6 to 50.3 (P less than .001), clinical efficacy scores from 34.3 to 43.3 (P less than .001), vital capacity from 53.7% to 58.5% of the predicted value (P less than .01), forced expiratory volume in 1 sec from 39.5% to 42.6%, and partial pressure of oxygen in arterial blood from 68.2 mm Hg to 72.6 mm Hg. Treatment failed in only two instances. The concentration of P. aeruginosa in the sputum decreased to a modest extent (8.5 log10 cfu/ml on day 1, 8.1 log10 cfu/ml on day 10; P greater than .1). Four patients had imipenem-resistant strains of P. aeruginosa at the start of therapy, and 11 additional patients developed resistant strains during treatment; in eight patients greater than 90% of all Pseudomonas organisms in the sputum were resistant at the end of therapy. Six patients acquired Candida in their sputum. There was no correlation between bacteriologic improvement or the development of resistance to imipenem and either clinical outcome or improvement in pulmonary function. In summary, imipenem/cilastatin therapy is associated with a good clinical outcome in patients with cystic fibrosis, but resistance emerges rapidly.

Adolescent↗
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

Comparison of cefaclor and trimethoprim-sulfamethoxazole in the treatment of acute otitis media.

The efficacy and safety of cefaclor and trimethoprim-sulfamethoxazole (TMP-SMX) were compared in 100 children with acute otitis media assigned to the two treatment groups in a double-blind, randomized fashion. Treatment was for 10 days. Each patient had a diagnostic tympanocentesis before starting therapy. Pathogens were isolated from the middle ear aspirate in 49% of the cases, and organisms considered nonpathogenic were isolated as pure cultures from an additional 19%. Of the 100 patients 4 of 50 in the cefaclor group and 2 of 50 in the TMP-SMX group were considered treatment failures. In three of the four failures with cefaclor, compliance with the first course of therapy could not be ascertained. All six patients showed a good therapeutic response to an additional 10-day course of cefaclor. We conclude that cefaclor and TMP-SMX have essentially equivalent efficacy in the treatment of acute otitis media.

Acute Disease↗
PubMedDate not supplied

Skin and soft tissue infections: pharmacologic approaches.

Skin and soft tissue infections are common infectious problems in pediatric practice. Recent clinical and pharmacologic evaluations of several new antimicrobial agents have shed new light on the pathogenesis and management of these infections. Staphylococcus aureus now appears to be the most common bacterial isolate in children with impetigo. In patients hospitalized because of skin and soft tissue infections, S. aureus and Haemophilus influenzae type b remain the predominant pathogens. Rational therapeutic approaches to these infections require a recognition of the interplay among the pharmacodynamic, pharmaceutic and pharmacokinetic determinants of effective antimicrobial therapy. Using this approach the therapeutic questions regarding "what drug," "what dose" and "how long to treat" can be approached. Drugs such as the aminopenicillin-beta-lactamase inhibitor combinations may offer rational outpatient therapeutic alternatives, while parenteral cefuroxime and ceftriaxone are more probably the drugs of choice for parenteral therapy. In an age when cost effectiveness must prevail, strategies using ceftriaxone for both inpatient and outpatient management may provide the safest and most cost-effective therapy.

Anti-Bacterial Agents↗
PubMedDate not supplied

Pharmacological treatment of depression in children and adolescents.

Major depression is a common disorder during childhood and adolescence. Over the past decade, many new antidepressants have been marketed in the US. In adults, these newer agents have been shown to be as effective as the prototypic tricyclic antidepressants (TCAs). Further, when compared with the TCAs these medications are better tolerated and are safer in overdose. Although TCAs are effective in the treatment of depressed adults, controlled clinical trials have not demonstrated their efficacy in either children or adolescents. In addition, concerns about the safety of TCAs and the monoamine oxidase inhibitors has left disappointingly few pharmacological treatment options available for depressed children and adolescents. For this reason, clinicians have begun to prescribe the newer agents for this population, despite the fact that relatively little is known about their disposition, safety or effectiveness in the young. Investigators have begun to examine whether the use of newer antidepressant medications such as fluoxetine, sertraline, paroxetine, fluvoxamine, nefazodone, and venlafaxine is truly indicated for children and adolescents with major depression. Pharmacokinetic studies of sertraline, paroxetine and nefazodone have been performed in depressed youths. The results of these studies have provided data for rational administration strategies for these agents. They have also provided evidence that these agents may be well tolerated in children and adolescents. Further evidence that these agents are often well tolerated when prescribed to depressed youths has been obtained from both open-label and double-blind studies. Published studies have generally shown that open-label treatment with these newer agents often leads to symptom amelioration in paediatric patients with major depression. Since high rates of placebo response are often seen in depressed children and adolescents, results from these studies cannot be interpreted to suggest that these medications have true antidepressant efficacy in this population. At present, the results of only two such studies have been published. The results of one of these trials are difficult to interpret because of methodological considerations. The other study reported that treatment with fluoxetine was superior to placebo. This paper critically reviews what has been published about the pharmacological treatment of depressed paediatric patients and provides some guidance to the use of antidepressants in this patient population, paying particular attention to what is known about the newer antidepressants as well as considering directions for future research.

Adolescent↗
PubMedDate not supplied

High-dose i.v. thiotepa and cryopreserved autologous bone marrow transplantation for therapy of refractory cancer.

Twenty-five patients with malignancies resistant to conventional chemoradiation therapy or for which no effective therapy is known were treated with escalating doses of thiotepa (135-1215 mg/m2 iv over 3 days) followed by reinfusion of previously cryopreserved autologous bone marrow. The hematological and nonhematological toxic effects, therapeutic effects, and pharmacokinetics of this regimen were evaluated. Granulocyte (greater than 500/microliter) and platelet (greater than 20,000/microliter) count recovery occurred at a median of 16 (range, 11-38) and 18.5 (range, 11-40) days after marrow reinfusion, respectively. Six patients experienced severe infection, four of which were fatal. One patient died due to intracranial hemorrhage. Toxicity to the gastrointestinal and central nervous systems was dose-limiting, and the maximum tolerated dose of thiotepa was 1005 mg/m2. Objective tumor regression occurred in six of the patients. Serum thiotepa concentration peaked immediately after infusion and declined rapidly in a biphasic manner. No relationship between thiotepa serum concentration or pharmacokinetic parameter estimates was observed for tumor response or toxicity. High-dose thiotepa and autologous bone marrow transplantation may represent an alternative therapeutic modality for patients with advanced cancer.

Adolescent↗
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↗
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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↗
PubMedDate not supplied

Meta-analysis in the evaluation of treatment for streptococcal pharyngitis: a review.

Penicillin has been first-line therapy for the treatment of streptococcal pharyngitis for more than 40 years. Since the 1980s, there have been a number of reports suggesting that bacteriologic failure rates with penicillin may be rising. A number of alternative therapies have been proposed, including oral cephalosporins. To evaluate the efficacy of these agents, two meta-analyses have recently been performed. In the meta-analysis performed by Pichichero and Margolis, oral cephalosporins were reported to achieve a significantly greater bacteriologic cure rate than penicillin (92% with cephalosporins vs 84% with penicillin, P < 0.0001) when results from 19 studies were analyzed. A separate meta-analysis performed by Deeter et al reported that the oral cephalosporin cefadroxil monohydrate achieved significantly greater bacteriologic cure rates (94.8% cefadroxil vs 87.5% penicillin, P < 0.05) than oral penicillin when 9 trials in 1406 patients with streptococcal pharyngitis were analyzed. A review of 65 studies of the use of penicillin for the treatment of streptococcal pharyngitis has shown that bacteriologic failure rates in the period 1980 to 1993 were approximately 12% to 13%, slightly but not significantly greater than during the period 1953 through 1979. Oral cephalosporins such as cefadroxil monohydrate provide reasonable alternatives for the treatment of streptococcal pharyngitis.

Administration, Oral↗
PubMedDate not supplied

Comparative evaluation of cefadroxil and cephalexin in children and adolescents with pyodermas. Cefadroxil Once Daily Pyoderma Study Group.

This randomized, multicenter study compared the safety and efficacy of cefadroxil with that of cephalexin for the treatment of pyodermas in children and adolescents (1-18 years of age). Cefadroxil was given as a single oral daily dose of 30 mg/kg, and cephalexin 30 mg/kg/day was given in two divided doses. The maximum daily dose for both drugs was 1 gm, and treatment was administered for 10 days. Clinical and bacteriologic evaluations were made on days 4 or 5 during therapy and 2 to 4 days after therapy was completed. Of the 462 patients enrolled in the study, 156 patients in the cefadroxil group and 133 patients in the cephalexin group were evaluable. Staphylococcus aureus (56% of isolates) and Streptococcus pyogenes (39% of isolates) were isolated most frequently. The bacteriologic response was statistically greater in the patients treated with cefadroxil than in those treated with cephalexin (96% versus 89%; P = 0.042). A satisfactory clinical response was reported in 147 (94%) cefadroxil-treated patients and 122 (92%) cephalexin-treated patients (P = 0.476). The overall effective response to treatment was significantly higher with cefadroxil than with cephalexin (94% versus 86%; P = 0.024). Compliance with 9 or 10 days of therapy was similar in both treatment groups, although there was a difference between the two treatment groups with respect to completion of medication regimen: 95% of patients taking cefadroxil once daily--versus 65% of patients taking cephalexin twice daily--took 100% of their medication (P < 0.0001). Adverse events were infrequent and mild. The results of this study demonstrate that once-daily cefadroxil offers greater bacteriologic eradication and a better overall effective response than twice-daily cephalexin for the treatment of pyodermas caused by gram-positive pathogens in children and adolescents.

Adolescent↗
PubMedDate not supplied

Pharmacokinetics of azithromycin after single- and multiple-doses in children.

STUDY OBJECTIVE: To characterize the disposition and tolerance of azithromycin after single and multiple oral doses of 12 mg/kg in children with and without cancer. DESIGN: Open-label, nonrandomized pharmacokinetic study. SETTING: Two pediatric hospitals. PATIENTS: Twelve children with cancer admitted to the inpatient unit for empiric antibiotic treatment of febrile neutropenia, and 16 hospitalized patients receiving antibiotic therapy INTERVENTIONS: Patients received azithromycin suspension either as a single dose or daily dose every morning for 5 consecutive days. Serial blood samples were collected up to 120 hours after a single dose or during and after multiple doses to characterize the pharmacokinetic parameters estimated for a two-compartment absorption model. MEASUREMENTS AND MAIN RESULTS: All 28 patients were evaluable for safety. Azithromycin was well tolerated except in one patient with cancer who experienced abdominal cramps and withdrew from the study. Pharmacokinetic results were not determined in five patients because of insufficient concentration-time data. The mean +/- SD estimates of oral clearance, terminal half-life, maximum concentration in serum (Cmax), and time to achieve Cmax in the 23 evaluable patients were 4.83 +/- 3.59 L/hour/kg, 54.5 +/- 36.4 hours, 318.2 +/- 174.5 microg/L, and 2.4 +/- 1.1 hours, respectively. These estimates did not differ between single-dose (14 patients) and multiple-dose (9 patients) groups. Pharmacokinetic parameters were not different between the 11 children with cancer and the 12 without cancer. CONCLUSION: Azithromycin 12 mg/kg results in proportionately higher serum concentrations than previously published results for lower doses (5 mg/kg). Variability in concentration profiles among patients is substantial, and age or other yet unidentified clinical factors may explain some of the differences observed.

Adolescent↗