Single-dose ceftriaxone kinetics in the newborn.

Ceftriaxone kinetics were characterized after a single, 2-minute, intravenous infusion of 50 mg/kg to 20 sick infants 1 to 8 days old who weighed 1.78 to 4.36 kg. Plasma binding parameters could be determined by equilibrium dialysis in 16 of the infants, in whom kinetic parameters for free ceftriaxone in plasma were also determined. Compared with corresponding values in adults, the elimination t1/2 was longer in infants (19 and 8.4 hours) because of reduced total systemic clearance (4.48 and 8.51 ml/min/m2). The apparent steady-state volume of distribution was of the same order in infants and adults (5,130 and 5,350 ml/m2). Both renal and nonrenal clearance of free ceftriaxone were reduced in infants, but these decreases were partially offset by an increased free fraction; plasma binding affinity and capacity constants for infants were about half the adult values. The mean fraction of dose excreted unchanged in urine was estimated at 70% in the neonates and 46% in adults. There were no clinically significant correlations between the kinetic parameters and either age since birth or age since conception. The fraction of free ceftriaxone in plasma inversely correlated with age since conception and was lower in female infants, which decreased the systemic clearance and volume of distribution of total drug in the female infants compared with the male infants. Values for the volume of distribution and clearance parameters were not related to body size (weight or body surface area). From our results, a ceftriaxone dosage of 50 to 100 mg/day is recommended during the first week of life for newborn infants who weigh between 1.8 and 4.4 kg. Impaired renal function may require a reduction in dosage.

Solubilization of immune precipitates by complement in the absence of properdin or factor D.

Various experiments have demonstrated that immune precipitates (IPs) are not solubilized by complement in the absence of alternative pathway function. To determine whether the characteristics of the IPs were responsible for these observations, we studied the solubilization (Sol) of IPs formed by bovine serum albumin (BSA)-rabbit antiBSA and tetanus toxoid (TT)-human antiTT. Sera deficient in properdin solubilized a fraction of BSA-antiBSA precipitates, although only when the IPs were formed in antibody excess. The same sera solubilized TT-antiTT precipitates with some delay but almost as efficiently as normal serum. Factor D-depleted serum solubilized a fraction of TT-antiTT precipitates too, indicating that Sol may proceed through activation of the classical pathway only. Thus, the requirements for complement-mediated Sol depend on the characteristics of the IPs and do not necessarily include alternative pathway function.

Recrudescence and relapse in bacterial meningitis of childhood.

Antibiotic therapy of bacterial meningitis in children may be complicated by reappearance of bacteria in cerebrospinal fluid during therapy (recrudescence) or within three weeks after therapy is stopped (relapse). Clinical and laboratory features of six children with recrudescence and of 21 children with relapse were reviewed. These complications occurred mainly in infants less than 2 years of age and comprised less than 1% of all cases of bacterial meningitis. Neither the initial nor the follow-up CSF findings were predictive of recrudescence or relapse. Prolonged or secondary fever was unrelated to these complications. Recrudescence was usually caused by inappropriate therapy whereas relapse after adequate therapy of bacterial meningitis was usually ascribed to persistence of infection in meningeal or parameningeal foci. Relapse did not become manifest until three or more days after discontinuation of therapy. It is concluded that routine examination of CSF at the end of adequate anti-microbial therapy is not necessary or useful when the patient has exhibited a satisfactory clinical response. Furthermore, the commonly recommended observation period of 48 hours in the hospital after discontinuation of therapy is not justified for a patient who has had an uneventful course.

Pyogenic arthritis of the sacroiliac joint in pediatric patients.

Clinical manifestations, diagnostic studies, and management of pyogenic sacroiliitis were reviewed in 77 pediatric patients. This infection occurs primarily in late childhood, is more common in boys, and has a subacute onset in about two thirds of cases. Recognition of the characteristic signs and symptoms of sacroiliac involvement coupled with radioisotope bone scanning substantially reduces the delay in correct diagnosis that averaged 3.9 weeks in all patients (4.8 weeks in those without and 1.7 weeks in those with bone scans performed). Joint aspiration under biplane fluoroscopic control and culture of the aspirated material is indicated in establishing the specific etiologic agent which is Staphylococcus aureus in most cases. Adequate management of pyogenic sacroiliitis consists of appropriately monitored antibiotic treatment and, if present, evacuation of pus. The use of spica cast immobilization offers no apparent beneficial effect. Indications for surgery include drainage of pus and removal of sequestered bone. With adequate management the prognosis of suppurative sacroiliitis in pediatric patients is excellent, despite persistent abnormal radiographic findings in most patients.

Use of the quinolones in paediatrics.

For many years, quinolone-induced cartilage toxicity observed in experiments involving immature animals has represented an indisputable contraindication for the use of these promising antimicrobials in prepubertal patients. Clinical, magnetic resonance imaging and histopathological monitoring of patients receiving ciprofloxacin at the University of Berne, together with published data, suggest that the quinolones do not cause arthropathy in humans. Conditions that potentially qualify for quinolone use (especially ciprofloxacin) in children include oral antipseudomonal (or antistaphylococcal) therapy for pulmonary exacerbations in cystic fibrosis, and complicated urinary tract, skeletal, aural and shunt infections. In addition to these rarer indications, there is an urgent need for the quinolones in developing countries for children with endemic and epidemic shigellosis and invasive salmonellosis. At present, these compounds are not approved for paediatric use and therefore must be administered as part of a controlled study or on a compassionate use basis in individual patients.

Toward an integrated program for patient care in pediatric infections.

BACKGROUND: Clinicians and scientists have important and complementary roles to play in improving the management of pediatric infectious diseases. The clinician's role is to provide optimal care for the individual patient, whereas the scientist is closely involved in teaching and research. OBJECTIVES: To review the current challenges in the management of childhood infections and the contributions of different groups to meeting these challenges. DISCUSSION: The pattern of infectious diseases in children is constantly changing, emphasizing the importance of microbiologic research in meeting these challenges. In the clinical setting the research results must be applied and integrated in routine practice. The development and successful clinical use of new diagnostic techniques, new antibiotics and new vaccines provide good examples of the teamwork between scientists and clinicians, which is essential for progress in the field of common childhood infectious diseases. The most urgent challenges in this area that now face physicians are the increasing prevalence of antibiotic-resistant bacteria, especially the spread of penicillin-resistant Streptococcus pneumoniae, and the growing numbers of immunocompromised children. Devising and implementing strategies to meet these demands will require a continuing commitment from pediatricians and microbiologists.

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.

Treatment of respiratory syncytial virus bronchiolitis: 1995 poll of members of the European Society for Paediatric Infectious Diseases.

BACKGROUND: Among the lower respiratory tract infections during infancy requiring hospitalization, respiratory syncytial virus (RSV) bronchiolitis is the most frequent disease entity. Nevertheless treatment remains controversial. METHODS: A poll among the European Society for Paediatric Infectious Diseases (ESPID) members was conducted to determine the respective local and national treatment policies of RSV bronchiolitis. RESULTS: The questionnaire was returned by 88 centers represented in ESPID (response rate 64%). Ribavirin was used occasionally for high risk patients in 34 centers although 16 hospitals follow the guidelines of the Red Book Committee of the American Academy of Pediatrics. There were no centers using ribavirin for all patients. Bronchodilator treatment was used universally in various combinations for all patients in 54 centers and for all high risk patients in 15. Corticosteroids were used by > 80% of ESPID colleagues in various combinations of administration routes. CONCLUSION: The lack of effective treatment for RSV bronchiolitis and the controversy in the literature concerning antiviral, bronchodilator and antiinflammatory therapy leads to inconsistent treatment strategies.

Clinical, radiologic and magnetic resonance monitoring for skeletal toxicity in pediatric patients with cystic fibrosis receiving a three-month course of ciprofloxacin.

Because of arthropathic toxicity observed in growing animals the quinolone antibiotics are not recommended for use in children. Recently, magnetic resonance imaging performed in juvenile animals was found to predict ciprofloxacin-induced cartilage damage at the knee joint. We conducted clinical, laboratory, radiologic and magnetic resonance imaging investigations in 13 prepubertal (age range, 6 to 13 years) and 5 postpubertal patients (age range, 14 to 24 years) with cystic fibrosis at the start and the end of a 3-month course of ciprofloxacin (30 mg/kg of body weight/day, administered orally in two equal doses) and at follow-up 4 to 6 months later. Our comprehensive monitoring gave no evidence for arthropathogenicity. Detailed physical skeletal function tests, height velocity values, laboratory studies of bone metabolism and conventional radiographs of both knees revealed no abnormalities. Moreover the serial magnetic resonance images of the left knee demonstrated lack of joint effusion, intact two-layer appearance of the cartilage and unaffected thickness of the articular cartilage measured at five anatomically different points. Our results together with the published data on quinolone use in pediatrics suggest that ciprofloxacin does not cause arthropathy in humans.

Ciprofloxacin as antipseudomonal treatment in patients with cystic fibrosis.

OBJECTIVE: The efficacy and safety of oral ciprofloxacin as a maintenance antipseudomonal therapy were evaluated in 44 patients with cystic fibrosis who had completed a 14-day regimen of intensive hospital therapy with intravenous ceftazidime and amikacin, supplemented by amikacin inhalation therapy. METHODS: Twenty-one patients were randomly assigned to oral ciprofloxacin alone (Group I) and 23 received ciprofloxacin plus inhaled amikacin (Group II). RESULTS: Negative sputum cultures were achieved in 34 patients (77%) at the end of intensive therapy (19 Group I and 15 Group II) and were sustained after 3 months of maintenance therapy in 5 of the 19 responders in Group I (26%) and in 8 of the 15 responders in Group II (53%). Resistance to ciprofloxacin was found in 7 of 31 (23%) sputum isolates at the end of ciprofloxacin therapy. During maintenance therapy, continued improvement in clinical symptoms was observed in 14 patients in both treatment groups; 6 in each group had further improvements whereas only 4 patients were clinical failures. There was no correlation between clinical outcome and either elimination of Pseudomonas aeruginosa from sputum culture or development of ciprofloxacin resistance. Both maintenance regimens were well-tolerated by this population of patients which included 28 children younger than 15 years of age. There were no severe or serious adverse events, no signs of quinolone-related arthropathy and no growth impairment. CONCLUSION: Ciprofloxacin was efficacious, safe and well-tolerated as maintenance antipseudomonal therapy in cystic fibrosis patients. These results suggest further evaluation of ciprofloxacin as an oral maintenance therapy is warranted.

Oral ciprofloxacin vs. intravenous ceftazidime plus tobramycin in pediatric cystic fibrosis patients: comparison of antipseudomonas efficacy and assessment of safety with ultrasonography and magnetic resonance imaging. Cystic Fibrosis Study Group.

BACKGROUND: More data on the efficacy and safety of ciprofloxacin in pediatric cystic fibrosis patients are needed. METHODS: One hundred eight pediatric cystic fibrosis patients (ages 5 to 17 years) with acute bronchopulmonary exacerbations entered a randomized multicenter trial designed to compare the safety and efficacy of antipseudomonas therapy with oral ciprofloxacin (15 mg/kg twice daily; maximum dosage 750 mg twice daily) or intravenous ceftazidime plus tobramycin (CAZ/TM) for 14 days. RESULTS: Clinical improvement was observed in 93% of patients treated with oral ciprofloxacin and in 96% of those receiving parenteral therapy. Transient suppression of Pseudomonas aeruginosa was achieved in 63% of patients at the end of the course of iv CAZ/TM therapy and in 24% receiving ciprofloxacin. Ultrasound examination and nuclear magnetic resonance imaging scans showed no evidence of cartilage toxicity in any of the ciprofloxacin-treated patients. Musculoskeletal adverse events were reported with similar frequency in the two groups of patients (7% in the group receiving ciprofloxacin therapy and 11% in the IV CAZ/TM group). The only sustained musculoskeletal symptom was a case of synovitis in a patient receiving parenteral CAZ/TM. CONCLUSION: Ciprofloxacin thus appears to be safe and effective for use in young patients with bronchopulmonary exacerbation of cystic fibrosis.

Seroprevalence of varicella-zoster virus immunoglobulin G antibodies in Swiss adolescents and risk factor analysis for seronegativity.

BACKGROUND: Little is known about the seroprevalence of anti-varicella-zoster virus (VZV) serum antibodies in adolescents in Switzerland as in most other European countries. METHODS: Serum specimens from 13- to 15-year-old students from eight urban and rural areas in Switzerland, obtained as part of an allergy risk assessment study project (SCARPOL), were available for analysis of IgG antibodies against VZV by enzyme-linked immunosorbent assay (ELISA) and confirmation by fluorescent antibody staining of membrane antigen in a subcohort. Serum specimens and comprehensive sociodemographic data had been collected during two study periods between 1992 and 1995. RESULTS: Data and serum specimens were available from 1709 and 1788 subjects, respectively. Seroprevalence of anti-VZV antibodies as measured by ELISA was 95.5% (95% confidence interval, 94.5 to 96.4). When serum specimens that were indeterminate by ELISA were tested by FAMA, seroprevalence was 96.5% (95% confidence interval, 95.7 to 97.4). After logistic regression analysis, the number of siblings was the only factor that significantly influenced the presence of VZV antibodies (90.1% in those with no siblings, >96% with 1 or more siblings), whereas residence (urban vs. rural), parental education, nationality and gender did not. CONCLUSIONS: Seroprevalence of anti-VZV serum antibodies is comparatively high among Swiss adolescents. Individuals who grow up without siblings have a significant risk of evading natural VZV infection in childhood, and they therefore form a potential target group for varicella immunization in Switzerland.

Aerosolized immunoglobulin treatment of respiratory syncytial virus infection in infants.

BACKGROUND: Recent studies in animals with experimental respiratory syncytial virus (RSV) infection indicate that passive immunization by intranasal or intratracheal application of gamma-globulins (immunoglobulins) may be beneficial for treatment of infants with lower respiratory tract infection caused by RSV. METHODS: We conducted a placebo-controlled, randomized multicenter study involving 68 infants with proven RSV infection admitted to 5 pediatric centers in Switzerland from November 1, 1992, through April 30, 1993. Treatment was carried out with aerosolized human IgG (Sandoglobulin) by assisted ventilation. On the day of hospital admission a single dose of 0.1 g of IgG per kg of body weight in a 5% solution or an identical amount of placebo, each delivered in 2 parts, was given. RESULTS: The two groups did not differ substantially in their response to the aerosol received. The rate of improvement for symptoms of respiratory tract infection, oxygen requirement and length of hospital stay were comparable for both groups. There was a significant reduction (P < 0.05) in the frequency of apneic spells observed in the treatment group by Day 3 posttreatment. Aerosol therapy was generally well-tolerated in nonintubated infants, but some severe side effects (increased oxygen requirements in two patients, pneumothorax in one patient) were observed in two of three intubated and ventilated infants treated with IgG. CONCLUSIONS: Aerosolized immunoglobulin in the dosage used had no substantial beneficial effect on RSV bronchiolitis. Despite these findings passive immunotherapy for treatment of RSV-induced lower respiratory tract infection deserves further evaluation before being discarded as ineffective.

Cefepine vs. ceftazidime treatment of pyelonephritis: a European, randomized, controlled study of 300 pediatric cases. European Society for Paediatric Infectious Diseases (ESPID) Pyelonephritis Study Group.

BACKGROUND: Cefepime has been used in clinical therapeutic trials for meningitis, serious infection and febrile neutropenia, comprising more than 800 pediatric patients. This agent has also been used in patients 12 years of age and older with uncomplicated and complicated urinary tract infections including pyelonephritis, but not in younger patients. In this study the safety and efficacy of cefepime were compared with those of ceftazidime for treatment of pyelonephritis in pediatric patients younger than 12 years of age. METHODS: Two hundred ninety-nine pediatric patients (ages 1 month to 12 years) with pyelonephritis (300 episodes) were enrolled in a randomized, open label, multicenter trial. Individual results were evaluated by a blinded committee of experts. Cefepime was compared with ceftazidime, both administered parenterally at 50 mg/kg every 8 h. Patients were to receive the assigned study drug until at least 48 h after becoming afebrile. The i.v. treatment was then to be continued or replaced by oral trimethoprimsulfamethoxazole for a maximum of 12 to 14 days. RESULTS: The predominant causative pathogens were Escherichia coli, 88%; Proteus spp., 6%; Pseudomonas aeruginosa, 2%; and Klebsiella spp., 2%. Bacteriologic eradication was achieved in 96 and 94% of cefepime and ceftazidime patients, respectively, at the end of i.v. study drug treatment and was maintained in 94 and 91%, respectively, at the end of total study therapy. After study therapy bacteriologic eradication was maintained after 4 to 6 weeks in 86% of cefepime cases and in 83% of ceftazidime cases. A satisfactory clinical response occurred in 98 and 96% of cefepime and ceftazidime patients, respectively, at the end of i.v. treatment and in 93% at the end of total study therapy in both treatment arms. Drug-related clinical adverse events occurred in 14 cefepime patients (91%) and in 10 ceftazidime patients (7%). CONCLUSIONS: Cefepime and ceftazidime are equally safe and efficacious treatment for pyelonephritis in pediatric patients.

Acute encephalitis in Swiss children: aetiology and outcome.

Since published data on the course and prognosis of encephalitis in Central Europe is limited, we retrospectively evaluated 104 children with either acute strict sense encephalitis (n = 80) or acute cerebellar ataxia (n = 24) treated at the Department of Pediatrics, University of Bern, Switzerland, between 1980 and 1991. Of the 80 patients with strict sense encephalitis, four (5%) died acutely and 28 (36%) of 78 followed up had sequelae - eight patients with severe, six with moderate and 14 with mild sequelae. Young age and seizures were shown to correlate with poor outcome. Among the 24 patients with acute cerebellar ataxia, there was no fatal outcome and none developed severe residua, but six had mild and one had moderate sequelae. Initial cerebrospinal fluid white cell count was significantly higher in these children with sequelae compared with those without any sequelae after acute cerebellar ataxia.

Diagnosis of acute haematogenous osteomyelitis and septic arthritis: 20 years experience at the University Children's Hospital Basel.

OBJECTIVE: To review the diagnostic experience with acute haematogenous osteomyelitis (AHOM) and/or septic arthritis at our institution. METHODS: Retrospective review of the medical records of those patients with a bacteriologically and/or radiologically confirmed diagnosis, hospitalised in the University Children's Hospital Basel, Switzerland between January 1980 and July 2000. RESULTS: 90 patients (61% males), 4 weeks to 14 years of age, met the inclusion criteria. Median duration of disease prior to hospitalisation was 3 days (range 0-14); 88% were admitted during the first week after onset of complaints. 81 patients received no antimicrobial therapy prior to hospitalisation and are the subject of this presentation. ESR (1st hour in mm; median 36; range 11-124), CRP (mg/l; median 64; range 0-221) and WBC (x 10(9)/l; median 13; range 5-34) were elevated in 100%, 82% and 58% of patients, respectively. Blood cultures (BC) and/or tissue cultures (TC) were performed in 79 (98%) patients. Overall, bacteria were isolated from 53 patients (65%) with Staph. aureus as the most frequent organism (n = 31; 50%). BC were performed in 67 patients and yielded 35 (52%) positive cultures; TC (n = 47) yielded 27 (57%) isolates. In 34 patients with both BC and TC performed, only 12 (35%) were positive in both tests. Diagnostic findings were observed in 23 (59%) of 39 plain radiographs, 31 (56%) of 55 sonograms, 39 (89%) of 44 99mTc-labeled bone scans and 4 (100%) of 4 MRI. 41 patients with diagnostic radiological findings had consecutive TC yielding 30 (73%) bacteriological isolates. Median duration of hospitalisation was 15 days (range 2-66). CONCLUSION: Our data indicate that the diagnostic procedures of choice should be 1) early bone scan or MRI, 2) BC and 3) TC. Of supportive laboratory parameters, ESR and CRP were most valuable in our hands.

Acute streptococcal tonsillopharyngitis: a review of clinical efficacy and bacteriological eradication.

This review evaluates studies published between January 1997 and August 2003 comparing clinical outcome and bacteriological eradication rates for patients with acute streptococcal tonsillopharyngitis treated with penicillin or other antimicrobial agents. Studies were identified using MEDLINE, and clinical outcome and bacteriological eradication at end of treatment and 2 weeks after end of treatment were ascertained. Any longer-term follow-up was also noted, along with treatment-related adverse events and compliance. Clinical efficacy rates between penicillin and comparator antibiotics were generally high and similar. Bacterial eradication rates were more variable and, 2 weeks after treatment, ranged from 64% to 93% for penicillin and 31% to 98% for comparators. Simpler dosing schedules and shorter therapy durations produced higher compliance rates. This review highlights the similarities and differences between treatment with penicillin and a wide range of comparator antibiotics. Therapy for acute group A streptococcal pharyngitis should combine excellent clinical efficacy, high bacteriological eradication rates, good tolerance and a simple, convenient dosing regimen.

Antibiotic therapy of childhood pneumonia.

Antibiotic therapy of childhood pneumonia must be based on various factors. Among them, clinical skills, diagnostic studies, knowledge of possible etiologic agents and their in-vitro susceptibility, and avoidance of antibiotic overuse are of greatest importance. The challenge of selective treatment is the reality in developed countries. The equation of pneumonia with antibiotic therapy can no longer be accepted as absolute. If antibiotic therapy is indicated, a new macrolide is usually the drug of choice.

[Group A streptococci 1992--a challenge for general practice, hospital and research]. / A-Streptokokken 1992--Herausforderung für Praxis, Spital und Forschung.

Group A streptococci continue to frequently cause a wide array of infectious diseases. Prompt and reliable diagnosis of such patients and their adequate management are often complex and require substantial degree of both knowledge and suspicion. Modern aspects concerning acute streptococcal pharyngitis, invasive infections, and rheumatic fever represent important challenges for medical doctors working in private praxis, hospital and research. Major achievements in better understanding streptococcal infection include the complex pathogenicity of M-proteins, the perplexing results of uncritically performed throat cultures, the questionable therapeutic dominance of penicillin, and the prospect for active immunization. These changes certainly imply relevant adaption in managing group A streptococcal infections.

[Childhood meningitis]. / Meningitis im Kindesalter.

Early and reliable diagnosis, prompt and adequate treatment, and intensive monitoring are the mainstays for normal outcome of patients with meningitis. Major progress has been achieved during the last 5-10 years. The successful implementation of the active immunization against Haemophilus influenzae type b has dramatically changed the epidemiology of bacterial meningitis: total incidence has been cut in half and approximately half of the cases now occur in adults. Important new insights into the pathogenesis and the pathophysiology have been gained resulting in specific supportive and antiinflammatory measures. Emergence of antibiotic-resistance in meningitis pathogens have lead to modified antimicrobial therapies. Knowledge about factors associated with a poor prognosis is important in selecting patients for more intensive surveillance and treatment, and in identifying candidates for new preventive or therapeutic strategies.