Clinical profile of pediatric patients hospitalized with respiratory syncytial virus infection.

To update the clinical profile of pediatric patients hospitalized with RSV infection, we retrospectively reviewed the records of 246 children (male:female ratio 1.44:1) admitted during one season to a tertiary-care hospital. The most common admitting diagnoses were bronchiolitis (37.4%), pneumonia (32.5%), and possible septicemia (13%). Median age was 3 months; median length of stay, three days. Twice as many minorities were admitted with RSV infection as all other admissions during the same year. Family history of asthma, while common (35%), did not affect length of stay or complications. Of the 38 (15%) patients requiring intensive care, 29 (76%) underwent ventilation. Patients with underlying cardiopulmonary disease had more complications, were more likely to require intensive care (about 50%), and had significantly longer hospital stays than others. All three patients (1.2%) who died had congenital heart disease. Common risk factors included young age, chronic cardiopulmonary disease, male sex, and possibly family history of asthma. Although the most typical clinical diagnoses remain bronchiolitis and pneumonia, a systemic illness resembling the sepsis syndrome has emerged at our institution as a significant clinical presentation.

Ribavirin effect on pulmonary function in young infants with respiratory syncytial virus bronchiolitis.

To assess the effect of ribavirin on pulmonary function in infants with respiratory syncytial virus bronchiolitis, we performed a randomized (nonmatched), double blinded, placebo-controlled study of 19 infants with RSV bronchiolitis. Infants with underlying respiratory, cardiac or immunologic disease were excluded. Patients were given ribavirin (10) or placebo (9) via an aerosol generator for 18 hours/day for 3 days. Pulmonary function (dynamic compliance, total lung resistance) was calculated using a pneumotachographic method on Days 1, 2 and 7. Differences between groups on clinical criteria were not found. Approximately one-half of each group showed increased compliance and decreased lung resistance after 24 to 48 hours of therapy. By Day 7 compliance had increased 30% in the placebo group and 210% in the ribavirin-treated infants (P = 0.05). Significant differences in the rate of change of lung resistance were not seen by Day 7. We conclude that previously noted improvements in the early course of respiratory syncytial virus bronchiolitis treated with ribavirin do not appear to be a result of measurable changes in pulmonary function. However, paradoxical increases in airway resistance were not found in patients treated with ribavirin.

Vitamin A levels in children with measles in Long Beach, California.

Studies from Africa suggest that vitamin A supplementation may reduce morbidity and mortality rates associated with measles among poorly nourished children. We studied 20 children with measles in Long Beach, Calif., and found that 50% (95% confidence interval; 28% to 72%) were vitamin A deficient. This frequency among presumably well nourished American children supports evaluation of vitamin A status as a part of acute management of measles in the United States.

Cefepime. Pharmacokinetics and clinical response in patients with cystic fibrosis.

OBJECTIVE: To measure first-dose and steady-state plasma, urine, and sputum concentrations of cefepime and make preliminary assessments of the clinical efficacy of cefepime in patients with cystic fibrosis. DESIGN: Open noncomparative clinical trial. SETTING: Memorial Miller Children's Hospital of Long Beach, Calif. PARTICIPANTS: Twelve patients, aged 4 to 41 years, with a confirmed diagnosis of cystic fibrosis and chronic bronchopulmonary infections. INTERVENTIONS: Patients received cefepime at 50 mg/kg per dose (maximum dose, 2 g per dose) given intravenously every 8 hours. Clinical evaluations, pulmonary function tests, quantitative sputum cultures, and sensitivity testing were performed before, at the end of, and 2 weeks after therapy. MEASUREMENTS AND MAIN RESULTS: Mean (+/- SD) peak plasma concentrations after the first dose were 148.2 (36.6) mg/L; the following other values were included: half-life, 1.59 (0.46) hours; area under the curve, 292 (94) microgram/h per milliliter; total-body clearance, 3.01 (1.46) mL/min per kilogram; volume of distribution at steady state, 0.32 (0.10) L/kg; and percent of dose recovered in urine, 52% (27%). Steady-state and first-dose values were similar. Trough levels varied from 6.4 to 7.2 mg/L. Mean (+/- SD) sputum concentrations at steady state varied from 6.3 (5.4) to 4.8 (2.3) mg/L. At completion of therapy, nine of 10 patients' conditions were improved as indicated by clinical scores (greater than 10 points), forced vital capacity (greater than 10%), and a greater than or equal to 1 log decrease in sputum bacterial concentration. Cefepime was well tolerated in 10 patients, but rash and light-headedness developed in two patients. Pseudomonas aeruginosa minimum inhibitory concentration90 increased from the start (64 mg/L) to the end of therapy (256 mg/L) and was unchanged 2 weeks later. CONCLUSION: Based on these data and the potential advantage of a single agent for the treatment of mixed infections (Staphylococcus aureus and P aeruginosa), comparative clinical trials of cefepime and standard therapy for bronchopulmonary exacerbations in patients with cystic fibrosis appear to be warranted.

Bacterial meningitis--an update.

This report emphasizes new clinical information about bacterial meningitis in infants and children. Important elements of diagnosis include examination for the presence of shock and increased intracranial pressure. In such cases, initial treatment should focus on appropriate fluid therapy, administration of oxygen, reduction of intracranial pressure and use of corticosteroids. Currently, antibiotics of choice include ampicillin plus either cefotaxime or ceftriaxone in young infants, and one of these cephalosporins in older patients (beyond 3 months of age). Shorter durations of therapy (5 to 7 days for meningococcus, 7 days for haemophilus and 7-10 days for pneumococcus) are now commonly employed. In many centers, dexamethasone is started before the first dose of antibiotic and continued for 4 days to reduce neurologic and audiologic sequelae. Future trends will include studies of endotoxin neutralizers and non-steroidal anti-inflammatory drugs to reduce further tissue injury in meningitis. Prevention of meningitis is the ultimate goal. Since Haemophilus influenzae vaccination can now begin at 2 months, this approach may bring important results soon.

Measles.

Measles has become epidemic over most of the world, with an important increase in the number of cases and associated morbidity and mortality in the United States since 1986. The two major factors responsible for this rise in the number of cases are, first, the increase in unvaccinated preschool-age children and, second, vaccine nonresponders (approximately 5%). The highest attack rate occurred in teenagers (15 to 19 years old) and in nine states (82% of cases). This situation has prompted revised immunization recommendations for those counties reporting more than five cases of measles among preschool-age children during each of the previous 5 years. In these counties, a first dose with monovalent measles vaccine is recommended at 9 months of age, followed by a second dose with measles, mumps, and rubella vaccine at 15 months of age, and revaccination of all children at the time of school entry. Recent publications regarding the use of vitamin A and certain antiviral agents are encouraging and are discussed in the manuscript. All cases of measles should be reported and investigated promptly. A good outbreak-control program will depend on the rapid recognition of the disease, a team approach, and prompt vaccination or IgG administration to susceptible persons.

In-vitro activity of cefprozil (BMY 28100) and loracarbef (LY 163892) against pathogens obtained from middle ear fluid.

We compared the in-vitro activities of cefprozil, a novel oral cephalosporin, and of loracarbef, a new oral carbacephem, with other agents against middle ear fluid isolates obtained from children with acute otitis media. These included Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis. Cefprozil activity (MIC50 and MIC90) against S. pneumoniae was 0.25 and 0.50 mg/l; against H. influenzae 8 and 16 mg/l; against B. catarrhalis 2 and 2 mg/l. Loracarbef activity (MIC50 and MIC90) against S. pneumoniae was 1 and 2 mg/l; against H. influenzae 8 and 16 mg/l; against B. catarrhalis 1 and 8 mg/l. Cefprozil was four-fold more active against S. pneumoniae than loracarbef but similar to amoxycillin, amoxycillin/clavulanate, cefaclor, cefixime, cefuroxime and trimethoprim/sulfamethoxazole (TMP/SMX). Against H. influenzae, cefprozil was similar to loracarbef and other agents through less active than TMP/SMX and cefixime. Against B. catarrhalis, cefprozil was four-fold more active than loracarbef, cefaclor and cefixime but similar to the comparative antibiotics. Cefprozil and loracarbef activities were unaffected at pH 6 and 8 or in the presence of human serum, but there was a major diminution of activity for both agents at pH 5 and at inoculum sizes greater than or equal to 10(7) cfu/ml. Cefoprozil and loracarbef have consistent activity against middle ear pathogens and further pharmacokinetic and clinical studies appear warranted.

In vitro activity of tosufloxacin, a new quinolone, against respiratory pathogens derived from cystic fibrosis sputum.

By using broth microdilution methods, the in vitro activity of tosufloxacin (A-64730), a new quinolone, was compared with those of other agents, including five quinolones, against geographically diverse cystic fibrosis sputum isolates obtained from 26 cystic fibrosis centers in the United States. These included Pseudomonas aeruginosa, conventional as well as especially resistant (ceftazidime, aztreonam, gentamicin, and/or tobramycin) isolates: Escherichia coli; Pseudomonas cepacia; Staphylococcus aureus; and Haemophilus influenzae. Tosufloxacin MICs for 50 and 90% of isolates of standard P. aeruginosa were 0.5 and 2.0 mg/liter, for resistant P. aeruginosa they were 4.0 and greater than 16.0 mg/liter, for E. coli they were less than or equal to 0.016 mg/liter, for P. cepacia they were 4.0 and 8.0 mg/liter, for S. aureus they were 0.063 and 0.063 mg/liter, and for H. influenzae they were less than or equal to 0.016 and 0.032 mg/liter, respectively. Tosufloxacin activities against standard and resistant strains of P. aeruginosa were similar to those of comparative quinolones. Against E. coli, tosufloxacin activity was similar to those of other quinolones. Against S. aureus, tosufloxacin activity was similar to those of trimethoprim-sulfamethoxazole and cephalexin, but tosufloxacin was more active than other agents. Against H. influenzae, tosufloxacin activity was similar to those of other quinolones. There was minor diminution of activity at pH 8.2 but major diminution of activity at pH 5.2 and at inoculum sizes of greater than or equal to 10(7) CFU/ml. Activity was unaffected by sputum but was enhanced by serum and by the omission of cation supplementation. Tosufloxacin has consistent activity against common cystic fibrosis pathogens. Its high degree of activity against S. aureus with activity maintained against P. aeruginosa and other gram-negative bacteria of interest suggests that further in vitro studies and assessment of activity in in vivo models of cystic fibrosis pulmonary infections are warranted.

Comparative in vitro activity of a new quinolone, fleroxacin, against respiratory pathogens from patients with cystic fibrosis.

We evaluated fleroxacin, a newer fluoroquinolone, against isolates from sputum from patients with cystic fibrosis. These isolates included rough and mucoid Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli. Selected isolates were tested by the broth microdilution method to examine the influence of various pHs, inoculum sizes, and biological fluids (serum or sputum from patients with cystic fibrosis). Fleroxacin MICs for 50 and 90% of isolates of P. aeruginosa were 2.0 and 4 micrograms/ml, those for P. cepacia were 2 and 16 micrograms/ml, those for S. aureus were 0.5 and 1 microgram/ml, those for H. influenzae were 0.06 and 0.06 micrograms/ml, and those for E. coli were 0.01 and 0.03 micrograms/ml, respectively. Fleroxacin activity against mucoid P. aeruginosa was similar to the activities of enoxacin and ofloxacin but eightfold lower than that of ciprofloxacin. It was twofold more active than norfloxacin and enoxacin but was twofold less active than ciprofloxacin, ofloxacin, and nafcillin against S. aureus. Fleroxacin inhibitory activity against P. cepacia was two- to fourfold lower than that of ciprofloxacin but eightfold greater than those of the other quinolones tested. Alterations in pH, diluent, and inoculum size did not significantly affect fleroxacin activity. These results, combined with available pharmacokinetic and tissue distribution data, support the need for clinical evaluation of fleroxacin in pulmonary infections in patients with cystic fibrosis.

In vitro activity of E-1040, a 3-substituted cephalosporin, against pathogens from cystic fibrosis sputum.

On the basis of preliminary in vitro data, we evaluated E-1040, a new cephalosporin, against 188 cystic fibrosis (CF) sputum isolates obtained from 26 CF centers in the United States. These isolates included mucoid and nonmucoid Pseudomonas aeruginosa, Pseudomonas cepacia, Staphylococcus aureus, Haemophilus influenzae, and Escherichia coli. In addition to MICs measured under standard conditions, selected isolates were tested at various pH values, inoculum sizes, and diluent (CF serum and sputum) conditions. E-1040 activities (MICs for 50 and 90% of the strains) against the isolates were as follows: P. aeruginosa (mucoid and nonmucoid), 1 and 4 micrograms/ml; P. cepacia, 4 and 16 micrograms/ml; S. aureus, 8 and 8 micrograms/ml; H. influenzae, 1 and 4 micrograms/ml; and E. coli, less than or equal to 0.12 and less than or equal to 0.12 microgram/ml. E-1040 activity against mucoid P. aeruginosa was 4-fold greater than that of aztreonam, 16-fold greater than that of ceftazidime, and 32-fold greater than that of piperacillin. E-1040 was similar to other broad-spectrum cephalosporins against S. aureus, H. influenzae, and E. coli. Bactericidal activity was less than or equal to 1 dilution of MIC for 88% of the strains, although kinetic studies with mucoid strains of P. aeruginosa demonstrated effective killing only at eight times the MIC. Variations in pH from 5 to 8, in inoculum size from 10(3) to 10(7) CFU/ml, and in diluent (CF serum or CF sputum) did not affect E-1040 activity.

Invasive Haemophilus influenzae type B infections: a continuing challenge.

Invasive Haemophilus influenzae type b infections are a major cause of severe infections in children between 2 months and 5 years of age. Meningitis, arthritis, pneumonia, cellulitis, osteomyelitis, and epiglottitis affect approximately 25,000 patients annually and are a major cause of mortality and morbidity in children. H. influenzae type b clinical syndromes, diagnostic methods, epidemiology, immunity, and treatment are discussed in this review. Although potent antibiotics have long been available for treatment, mortality and morbidity rates have not declined substantially in the last 15 years. Prevention of disease is therefore a continuous medical challenge. Secondary cases can be prevented by identification of the high-risk groups and the application of appropriate techniques, including antimicrobial prophylaxis. Primary prevention is the major goal of current research. H. influenzae type b vaccines currently are available for protection of infants 18 months of age and older. Prevention of primary and secondary disease and future developments, including new vaccine strategies, are stressed.