Single-Dose Pharmacokinetics of Intravenous Sulbactam in Pediatric Patients

The pharmacokinetics of intravenously administered sulbactam were studied in 17 pediatric patients two to 14 years of age. Single doses of 12.5 or 25 mg/kg were infused over 3 min, and in previously healthy children, mean peak plasma concentrations 5 min after dosing were 71 and 163 µg/ml, respectively. Noncompartmental and compartmental calculations resulted in similar pharmacokinetic parameters. Linear pharmacokinetics were found in the concentration range studied. The mean terminal-phase half-life was 1.75hr, the mean total plasma clearance was 180 ml/min per 1.73 m2, and the mean apparent volume of distribution was 340 ml/kg. Approximately 70%-80% of an intravenous dose was excreted unchanged in the urine. In children with cystic fibrosis, both total plasma clearance and apparent volume of distribution weresignificantly increased. The data support the intravenous administration of 12.5-25 mg of sulbactam/kg every 6 to 8 hr for assessing the adequacy of this drug as an adjunct to β-lactam therapy for various bacterial infections in childre

Sequential intravenous-oral amoxycillin/clavulanate (Augmentin) therapy in paediatric hospital practice

The efficacy and safety of intravenous and sequential intravenous-oral clavulanate-potentiated amoxycillin therapy was evaluated in 71 hospitalized paediatric patients, one month to 16 years of age. The infections treated included peritonsillar abscess (2 patients), purulent tracheitis (1), acute epiglottitis (24), pneumonia (31), pansinusitis (4), mastoiditis (1), cellulitis (4), lymphadenitis (2) and pyelonephritis (2). The severity of disease was rated as moderate in 31 patients (44%), and as severe in 40 (56%). Bacterial pathogens could be cultured in 26 cases (37%). The response to therapy was prompt and followed by clinical cure in each patient. Adverse drug effects included phlebitis (in 6%), mild gastrointestinal complaints (6%), rash (4%) and transient neutropenia and elevation of transaminases (one case each). It is concluded that amoxycillin/clavulanate is effective and safe treatment for bacterial infections of the respiratory tract, urinary tract, skin or soft tissues in childre

Pharmacokinetics of a syrup formulation of amoxycillin-potassium clavulanate in children

The pharmacokinetics of a syrup formulation consisting of four parts of amoxycillin and one part of potassium clavulanate (Augmentin) were studied in 11 paediatric patients, 3 to 14 years of age. Single oral doses of 25 mg of Augmentin per kg body weight (20 mg of amoxycillin per kg plus 5 mg of potassium clavulanate per kg, i.e. 1 mg of the syrup per kg) were administered on an empty stomach, and were well accepted and tolerated. Mean peak plasma concentrations 60-90 min after dosing were 7.2 mg/l for amoxycillin and 2-0 mg/l for clavulanic acid. Mean terminal phase plasma half-lifes were 1.4 and 1.0 h, respectively. It is concluded that 25-mg/kg doses of this syrup formulation of Augmentin administered three times daily should be adequate therapy for various childhood bacterial infection

Granulocyte Neutral Proteases and Pseudomonas Elastase as Possible Causes of Airway Damage in Patients with Cystic Fibrosis

We studied the possible role of granulocyte neutral proteases as mediators of airway destruction in patients with cystic fibrosis (CF) who were infected with Pseudomonas aeruginosa. We measured the enzymatic activities of bronchial secretions on purified radioactively labeled complement component three (C3), elastin, and a granulocyte elastase-specific substrate. Bronchial secretions from 18 patients with CF who were infected with P aeruginosa had a significantly higher mean value for C3 cleaving, elastolytic, and granulocyte elastase-like activity than did two control groups. High enzymatic activities were observed in patients with CF who have advanced bronchial disease (that had been determined by a clinical scoring system). Kinetics of proteolysis of radioactively labeled C3 and inhibition profiles of the activities of the three enzymatic activities studied suggest that they are mainly derived from granulocytes. In addition, 20 of 31 strains of P aeruginosa isolated from patients with CF inactivated purified α1-antiprotease in vitro. We postulate that granulocyte neutral proteases and P aeruginosa may act synergistically in the airways of patients with CF and may contribute to the destruction of elastin and inactivation of C

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 meningiti

Affinity Constants of Naturally Acquired and Vaccine-Induced Anti-Pseudomonas aeruginosa Antibodies in Healthy Adults and Cystic Fibrosis Patients

Naturally acquired anti-Pseudomonas aeruginosa antibody fails to afford protection against repeated P. aeruginosa bronchopulmonary exacerbations in cystic fibrosis (CF) patients. In an effort to explain this phenomenon, the titer and affinity constants of serum anti-lipopolysaccharide (LPS) IgG were determined in five study groups: healthy adults before and after immunization with a polyvalent LPS-based vaccine, healthy noncolonized CF patients before and after immunization, nonimmunized CF patients with significantly elevated anti-LPS antibody titers without documented colonization, recently colonized CF patients before and after immunization, and nonimmunized CF patients chronically colonized with P. aeruginosa. Immunization elicited a significant rise in total anti-LPS immunoglobulin levels and affinity constants in both healthy adults and CF patients. Although chronically colonized patients had elevated levels of total anti-LPS antibody, these antibodies possessed affinities at least tOO-fold less than those of vaccine-induced antibodie

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. aeruginos

The Battle against Emerging Antibiotic Resistance: Should Fluoroquinolones Be Used to Treat Children?

Inappropriate use of antibiotic drugs in humans and animals has led to widespread resistance among microbial pathogens. Resistance is the phenotypic expression corresponding to genetic changes caused by either mutation or acquisition of new genetic information. In some cases, multidrug resistance occurs. Streptococcus pneumoniae is one of the most important respiratory pathogens, playing a major role in both upper and lower respiratory tract infections. Pneumococcal resistance to antimicrobials may be acquired by means of horizontal transfer followed by homologous recombination of genetic material from the normal flora of the human oral cavity or by means of mutation. Resistance to penicillins and macrolides has been increasing for some time, but, recently, fluoroquinolone resistance has become an issue as well. We are concerned that, if fluoroquinolones are approved for use in children, their widespread use will result in rapid emergence of pneumococcal resistance, because children are more often colonized in the nasopharynx with high-density populations of pneumococci than are adult