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Biomedical subjects

U B Schaad

Publications and source records attributed to U B Schaad.

At least 55 records · Page 3Linked to original sources
PubMed1996

Evaluation of the efficacy, safety and toleration of azithromycin vs. penicillin V in the treatment of acute streptococcal pharyngitis in children: results of a multicenter, open comparative study. The Swiss Tonsillopharyngitis Study Group.

BACKGROUND: For many years alternatives to penicillin have been studied for the management of pediatric group A beta-hemolytic Streptococcus (GABHS) pharyngitis. As a result of its pharmacokinetic profile azithromycin is unique among these alternative antimicrobials in allowing once daily dosing and shorter duration of treatment. However, the optimum dose (e.g. 10 or 12 mg/kg/day) and duration (e.g. 3 or 5 days) of azithromycin therapy have not been defined yet. METHODS: An open, comparative multicenter study was conducted in 343 children with clinical symptoms of GABHS pharyngitis and a positive culture to evaluate the efficacy and safety of azithromycin (10 mg/kg) once daily for 3 days compared with penicillin V three times daily for 10 days. RESULTS: Among the evaluable patients bacteriologic eradication documented at follow-up visits was inferior with azithromycin when compared with penicillin V therapy: at Days 9 to 20 (mean, 12 days), negative cultures in 65% (99 of 152 patients) vs. 82% (128 of 126 patients) (P < 0.001); and at Days 17 to 57 (mean, 25 days), in 55% vs. 80% (P < 0.001). Overall clinical success (cure or improvement) was achieved in 93% (149 of 160 patients) of azithromycin-treated and in 89% (143 of 160 patients) of penicillin-treated patients (P > 0.50). There was no correlation between bacteriologic response and clinical outcome, as assessed shortly after completion of therapy or during 6-month follow-up. Both treatments were well-tolerated. CONCLUSIONS: In the present study on GABHS pharyngitis in children, a once daily (10-mg/kg), 3-day oral regimen of azithromycin was as clinically effective and as safe as traditional penicillin but appeared inferior in eliminating GABHS from the throat.

Acute Disease↗
PubMed1996

Evidence for fluid volume depletion in hyponatraemic patients with bacterial meningitis.

Since the mechanisms underlying hyponatraemia in meningitis are poorly understood, we retrospectively reviewed the records of 187 paediatric patients with bacterial meningitis treated at the Department of Pediatrics, University of Bern, Switzerland, between 1982 and 1994. The degree of dehydration calculated from naked weight on admission and at 5 days was consistently (by 2.8 x 10(-2) and significantly more pronounced in 30 hyponatraemic (plasma sodium 130 mmol l-1 or less) than in 157 normonatraemic patients (plasma sodium 131 mmol l-1 or more). Furthermore, a tendency towards reduced sodium excretion was noted in hyponatraemic patients. The results suggest that in bacterial meningitis hyponatraemia is mostly induced by clinically latent fluid volume depletion.

Adolescent↗
PubMed1996

Pharmacokinetics of ciprofloxacin in pediatric cystic fibrosis patients.

The pharmacokinetic characteristics of ciprofloxacin were studied in 10 children with cystic fibrosis, aged from 6 to 16 years, who had completed the standard regimen of intravenous ceftazidime and amikacin. The aim of the investigation was to derive dosing guidelines for young cystic fibrosis patients to be treated with ciprofloxacin. Each child received ciprofloxacin given as two 30-min infusions (10 mg/kg of body weight each) 12 h apart; this was followed by the administration of oral ciprofloxacin (15 mg/kg every 12 h). Blood samples were taken after both infusions and after the first oral dose. A total of 232 ciprofloxacin concentrations (203 concentrations in plasma and 29 concentrations in urine) were analyzed by use of NONMEM and a two-compartment body model with seven parameters: total body clearance (CL), volume of the central compartment (V2), volume of the peripheral compartment (V3), intercompartmental clearance, renal clearance, absorption rate constant, and bioavailability. The influences of weight (range, 18 to 42 kg) and age (range, 6 to 16 years) were investigated. CL (in liters per hour) was found to be linearly correlated with weight (typical value of CL = 8.8 + 0.396. WT, where WT is weight; (interindividual coefficient of variation, 7.8%). V2 and V3 were directly proportional to weight, with slopes of 0.7 and 1.3 liters/kg, respectively. Interindividual variabilities were calculated to be 22.6 and 14.9% for V2 and V3, respectively. No dependency of the other pharmacokinetic parameters on age or weight was seen. Because of the high correlations between age and weight, only one covariable was necessary. Weight had the strongest effect. Bioavailability (population mean) was estimated to be 61.8%, and renal clearance (population mean) was estimated to be 11.4 liters/h. The residual (intraindividual) variability was 31.9%. The protein binding was about 34%, which is similar to the results obtained for adults. In order to define the appropriate dosage regimen for children suffering from cystic fibrosis, a formula was derived so that steady-state concentrations, similar to those obtained in adults after the administration of dosages of 400 mg three times daily intravenously and 750 mg twice daily orally, could be reached. The calculated total daily dose increased with increasing body weight. Given as milligrams per kilogram of body weight, the calculated dosage regimens suggest that for younger children (weight range, 14 to 28 kg), 28 to 20 mg/kg orally twice daily should be given, and for older children (weight range, 28 to 42 kg), 20 to 15 mg/kg orally twice daily should be given. For intravenous administration, dosages of 15 to 10 mg/kg twice daily are sufficient.

Administration, Oral↗
PubMed1996

[Aminoglycosides in pediatrics].

The aminoglycosides continue to be needed in hospital pediatrics. Their advantage is high predictability of both efficacy and toxicity. This review focuses on the background to the aminoglycosides and defines their present role in antibiotic therapy of pediatric patients. Both the beneficial and unfavourable characteristics of these antimicrobial agents are discussed. The clinical uses of aminoglycoside antibiotics and their possible modes of administration are also commented on. The author attempts to compare the currently available aminoglycosides gentamicin, tobramycin, amikacin and netilmicin in the light of their antibacterial activity in vitro, their clinical efficacy, and their ototoxic and nephrotoxic potential. For the future it is important not to lose sight of these backup drugs where appropriately and safely used. A possible renaissance of the aminoglycosides would require either a molecular miracle (new aminoglycosides with decreased toxicity and an increased spectrum of activity) or a bacterial revolt (rapid emergence of resistance of many gram-negative enteric bacilli to other antibiotic classes).

Aminoglycosides↗
PubMed1995

[Antibiotic treatment of urinary tract infections in hospitalized children].

From 1980 to 1991 237 patients (aged 1 week to 15 years) with moderate to severe urinary tract infection had been treated at the Department of Pediatrics University of Berne, Switzerland. Bacterial etiology, antimicrobial in vitro susceptibility tests, and drug management were retrospectively analyzed. 266 bacterial pathogens were isolated from these patients. Escherichia coli was the most frequent etiologic agent (203), followed by Enterococcus (21), Klebsiella (20), Proteus (12), Pseudomonas (6), Enterobacter (2) and Serratia (2). The overall in vitro susceptibility of these isolates was 61% for aminopenicillins, 80% for co-amoxiclav, 83% for co-trimoxazole and 92% for aminoglycosides. Aminoglycosides were ineffective in vitro only against enterococci. However, since all enterococcal strains were always sensitive to aminopenicillins, none of the pathogens was concomitantly resistant to both aminoglycosides and aminopenicillins. Parenteral therapy had been given initially in 141 patients (59%); aminopenicillin and aminoglycoside in 105, and aminopenicillin alone in 36 cases (cefuroxime instead of aminopenicillin in some patients with suspected allergy to penicillin). 96 patients (41%) were initially treated with oral antibiotics (cotrimoxazole, aminopenicillin or co-amoxiclav). The initial antimicrobial regimen had to be modified in 31 cases (13%). In children with moderate to severe urinary tract infection prompt sterilization of urine and kidneys will prevent or suppress renal tissue lesions. The in vitro susceptibility results observed in the pathogens isolated in the patients prompt us to suggest that the above mentioned goal can only be achieved by an initial regimen consisting of an aminopenicillin and an aminoglycoside compound administered parenterally.

Adolescent↗
PubMed1995

Mycobacterium genavense invasive infection in two children with AIDS: long-term followup.

Mycobacterium genavense is a rare cause of opportunistic infection in immunocompromised hosts. Follow up of two cases of M. genavense invasive infection in children with haemophilia A and AIDS are presented. One patient died 18 months after diagnosis of M. genavense infection of an indirectly related cause, probably of Pneumocystis carinii pneumonia. The second patient still attends our outpatient clinic and the infection is under control. Both presented with abdominal lymphomas and pain and a wasting syndrome. A combination of several drugs against atypical mycobacteria is used for treatment.

AIDS-Related Opportunistic Infections↗
PubMed1995

Effect of high-affinity anti-Pseudomonas aeruginosa lipopolysaccharide antibodies induced by immunization on the rate of Pseudomonas aeruginosa infection in patients with cystic fibrosis.

Patients with cystic fibrosis (CF; N = 26) and with no prior history of infection with Pseudomonas aeruginosa were immunized with an octavalent O-polysaccharide-toxin A conjugate vaccine. During the next 4 years, 16 patients (61.5%) remained free of infection and 10 (38.5%) became infected. Total serum antilipopolysaccharide (LPS) antibody levels induced by immunization were comparable in infected and noninfected patients. In contrast, 12 of 16 noninfected versus 3 of 10 infected patients (p = 0.024) mounted and maintained a high-affinity anti-LPS antibody response. When compared retrospectively with the rate in a group of age- and gender-matched, nonimmunized, noncolonized patients with CF, the rate at which P. aeruginosa infections were acquired was significantly lower (p < or = 0.02) among all immunized versus nonimmunized patients during the first 2 years of observation. Subsequently, only those immunized patients who maintained a high-affinity anti-LPS antibody response had a significant reduction (p < or = 0.014) in the rate of infection during years 3 and 4. Smooth, typeable strains of P. aeruginosa predominated among immunized patients; rough, nontypeable strains were most frequently isolated from nonimmunized patients. Mucoid variants were isolated from one immunized patient versus six nonimmunized patients. These results indicate that the induction of a high-affinity P. aeruginosa anti-LPS antibody response can influence the rate of infection in patients with CF.

Adolescent↗
PubMed1995

Steroid therapy for bacterial meningitis.

Routine dexamethasone therapy for bacterial meningitis in pediatric patients is controversial. Two experts debated this topic at the 1993 meeting of the Infectious Diseases Society of America. Both experts agreed that for management of Haemophilus influenzae meningitis, dexamethasone significantly reduced sensorineural hearing loss and probably reduced other long-term sequelae. Because relatively few patients with pneumococcal and meningococcal meningitis have been studied, no conclusions could be reached regarding the effectiveness of dexamethasone. Dr. Urs Schaad emphasized the impressive anti-inflammatory effects of dexamethasone in experimental pneumococcal meningitis and the lack of any adverse events when given to children for 2 or 4 days. He recommended routine use of dexamethasone in treating pediatric patients with bacterial meningitis. Dr. Sheldon Kaplan expressed concern regarding the effectiveness of steroids in treating pneumococcal meningitis, especially when penicillin-resistant and cephalosporin-resistant isolates are present, and he addressed the question of the long-term effects of administration of dexamethasone in children with viral meningitis. He advised against the routine use of dexamethasone for non-H. influenzae meningitis.

Dexamethasone↗
PubMed1995

[Congenital toxoplasmosis: pediatric approach. Consensus report of the Swiss infectious disease pediatricians].

The first part of this paper reviews: (1) the spectrum of clinical features of congenital toxoplasmosis; (2) the natural course of fetal infection; (3) the influence of antitoxoplasma therapy on the course of the disease; (4) methods for diagnosing the toxoplasma infection and assessing the severity of the disease; (5) currently used antitoxoplasma drugs and different therapeutic regimens. The second part suggests a practical approach to the problem of congenital toxoplasma infection, including diagnostic work-up, drug therapy, and follow-up. This practical approach is modulated according to the clinical syndrome in the infant and diagnostic and therapeutic considerations in the mother.

Coccidiostats↗
PubMed1994

[TBE-immunoglobulins--a critical assessment of efficacy].

Since there is no specific treatment for tick-borne encephalitis (TBE), immunoprophylaxis is used in endemic areas for controlling this disease. Active immunization has been shown to be effective and safe, and a restrictive immunization policy is generally accepted in Switzerland. However, the use of TBE-immunoglobulin for passive immunization after tick exposure is controversial. This article demonstrates that the published reports on the protection rate of TBE-immunoglobulin do not stand up to critical analysis. Efficacy has never been proved. Therefore, the use of TBE-immunoglobulin must be based upon practical or theoretical arguments. Routine administration of this preparation in endemic areas cannot be recommended.

Encephalitis Viruses, Tick-Borne↗
PubMed1994

A syndrome of primary combined immunodeficiency with microcephaly, cerebellar hypoplasia, growth failure and progressive pancytopenia.

A male infant with primary combined immunodeficiency, microcephaly with marked cerebellar hypoplasia, and growth failure of prenatal onset is presented. He developed progressive pancytopenia in the 3rd year of life and died at 42 months from disseminated aspergillosis. Laboratory studies and post mortem examination failed to reveal any known aetiology for his disorder. Hreidarsson et al. [3] previously described a syndrome of progressive pancytopenia with microcephaly, cerebellar hypoplasia and growth failure in three boys, with similar clinical and laboratory findings. Although extensive immunological investigations were not performed in those previous patients, recurrent infections in two of them are suggestive of immunodeficiency. In the light of the immunological findings in our patient, we propose that the condition of the four patients belongs to the same syndrome, which has to be considered as a primary combined immunodeficiency syndrome. This syndrome can be distinguished from the other known immunodeficiency syndromes by its associated characteristic features, namely microcephaly with cerebellar hypoplasia, growth failure of prenatal onset and progressive pancytopenia.

Cerebellum↗
PubMed1994

Immunization of noncolonized cystic fibrosis patients against Pseudomonas aeruginosa.

The long-term safety and immunogenicity of a polyvalent Pseudomonas aeruginosa conjugate vaccine was evaluated in 30 noncolonized cystic fibrosis patients. Four doses were administered over 3 years, and patients were followed for a mean of 38 months. No acute or long-term adverse effects were noted. Immunization engendered a significant antibody response to all vaccine components. A decline in titers during year 3 of observation was associated with a marked rise in the isolation of P. aeruginosa. This organism was isolated repeatedly from the respiratory tract of 4 patients and only once from 7 patients. The remaining patients were repeatedly culture-negative. Only 1 patient showed clinical deterioration associated with multiple isolations of P. aeruginosa.

Adolescent↗
PubMed1993

Dexamethasone therapy for bacterial meningitis in children. Swiss Meningitis Study Group.

Routine use of steroids as adjunctive treatment of bacterial meningitis remains controversial. We have carried out a prospective, placebo-controlled, double-blind study of dexamethasone in 115 children with acute bacterial meningitis in Switzerland. The patients were randomly assigned to receive either placebo (n = 55) or dexamethasone (n = 60) in addition to optimum antibiotic treatment (100 mg/kg daily ceftriaxone). Dexamethasone therapy (0.4 mg/kg) was started 10 min before the first dose of ceftriaxone and given every 12 h for 2 days. Baseline demographic, clinical, and laboratory features of the two groups were similar. After 24 h treatment meningeal inflammation as shown by cerebrospinal fluid (CSF) glucose concentration was significantly less with dexamethasone than with placebo (mean increase in glucose 63 [76] vs 40 [75]%, p = 0.008). However, other indices of inflammation showed similar changes in both groups. Addition of dexamethasone did not affect the rate at which CSF became sterile. Both groups showed prompt clinical responses and similar frequencies of complications (15 vs 12%). Monitoring for possible adverse effects of dexamethasone revealed no abnormalities. At follow-up examinations 3, 9, and 15 months after hospital discharge, 9 (16%) of 55 placebo recipients and 3 (5%) of 60 dexamethasone recipients had one or more neurological or audiological sequelae (p = 0.066); the relative risk of sequelae was 3.27 (95% CI 0.93-11.47). Our results and those of similarly designed studies lead us to believe that adjunctive dexamethasone therapy improves outcome from bacterial meningitis in infants and children. We recommend its use, preferably in the dose regimen used in this study.

Adolescent↗
PubMed1993

Invasive infection with Mycobacterium genavense in three children with the acquired immunodeficiency syndrome.

Three children with human immunodeficiency virus infection and invasive infection with Mycobacterium genavense are reported. Fever spikes, abdominal cramps and distension, diarrhea or ileus, and anemia were the predominant symptoms in the severely immunodeficient patients (CD4 lymphocytes < 0.04 x 10(9)/l). Numerous acid-fast bacilli were readily detectable by microscopy in stool samples and in lymph node biopsies, but cultures for mycobacteria remained negative. Mycobacterium genavense should be sought when invasive non-tuberculous mycobacteriosis is suspected and mycobacterial cultures from blood or other sites show limited growth. Multiple-drug regimens including amikacin, ethambutol, rifampin, and clarithromycin may be of benefit in controlling the infection, as observed in two patients.

AIDS-Related Opportunistic Infections↗