Gary D. Overturf

Prevention of respiratory syncytial virus infections: Indications for the use of palivizumab and update on the use of RSV-IGIV

The Food and Drug Administration recently approved the use of palivizumab (palē-vizhū-mäb), an intramuscularly administered monoclonal antibody preparation. Recommendations for its use are based on a large, randomized study demonstrating a 55% reduction in the risk of hospitalization attributable to respiratory syncytial virus (RSV) infections in high-risk pediatric patients. Infants and children with chronic lung disease (CLD), formerly designated bronchopulmonary dysplasia, as well as prematurely born infants without CLD experienced a reduced number of hospitalizations while receiving palivizumab compared with a placebo. Both palivizumab and respiratory syncytial virus immune globulin intravenous (RSV-IGIV) are available for protecting high-risk children against serious complications from RSV infections. Palivizumab is preferred for most high-risk children because of ease of administration (intramuscular), lack of interference with measles–mumps–rubella vaccine and varicella vaccine, and lack of complications associated with intravenous administration of human immune globulin products. RSV-IGIV, however, provides additional protection against other respiratory viral illnesses and may be preferred for selected high-risk children including those receiving replacement intravenous immune globulin because of underlying immune deficiency or human immuno-deficiency virus infection. For premature infants about to be discharged from hospitals during the RSV season, physicians could consider administering RSV-IGIV for the first month of prophylaxis. Most of the guidelines from the American Academy of Pediatrics for the selection of infants and children to receive RSV-prophylaxis remain unchanged. Palivizumab has been shown to provide benefit for infants who were 32 to 35 weeks of gestation at birth. RSV-IGIV is contraindicated and palivizumab is not recommended for children with cyanotic congenital heart disease. The number of patients with adverse events judged to be related to palivizumab was similar to that of the placebo group (11% vs 10%, respectively); discontinuation of injections for adverse events related to palivizumab was rare.

Intramuscular versus oral antibiotic therapy for the prevention of meningitis and other bacterial sequelae in young, febrile children at risk for occult bacteremia

Because studies of the treatment of children with occult bacteremia have yielded conflicting results, we compared ceftriaxone with amoxicillin for therapy. Inclusion criteria were age 3 to 36 months, temperature > or = 39 degrees C, an acute febrile illness with no focal findings or with otitis media (6/10 centers), and culture of blood. Subjects were randomly assigned to receive either ceftriaxone, 50 mg/kg intramuscularly, or amoxicillin, 20 mg/kg/dose orally for six doses. Of 6733 patients enrolled, 195 had bacteremia and 192 were evaluable: 164 Streptococcus pneumoniae, 9 Haemophilus influenzae type b, 7 Salmonella, 2 Neisseria meningitidis, and 10 other. After treatment, three patients receiving amoxicillin had the same organism isolated from their blood (two H. influenzae type b, one Salmonella) and two from the spinal fluid (two H. influenzae type b), compared with none given ceftriaxone. Probable or definite infections occurred in three children treated with ceftriaxone and six given amoxicillin (adjusted odds ratio 0.43, 95% confidence interval 0.08 to 1.82, p = 0.31). The five children with definite bacterial infections (three meningitis, one pneumonia, one sepsis) received amoxicillin (adjusted odds ratio 0.00, 95% confidence interval 0.00 to 0.52, p = 0.02). Fever persisted less often with ceftriaxone (adjusted odds ratio 0.52, 95% confidence interval 0.28 to 0.94, p = 0.04). Although the difference in total infections was not significant, ceftriaxone eradicated bacteremia, prevented significantly more definite focal bacterial complications, and was associated with less persistent fever.

Varicella vaccine update

Recommendations for routine varicella vaccination were published by the American Academy of Pediatrics in May 1995, but many eligible children remain unimmunized. This update provides additional information on the varicella disease burden before the availability of varicella vaccine, potential barriers to immunization, efforts to increase the level of coverage, new safety data, and new recommendations for use of the varicella vaccine after exposure and in children with human immunodeficiency virus infections. Pediatricians are strongly encouraged to support public health officials in the development and implementation of varicella immunization requirements for child care and school entry.

Hepatitis C virus infection

Hepatitis C virus (HCV) has become the most significant cause of chronic liver disease of infectious etiology in the United States. The recognition that HCV can be transmitted perinatally or through blood transfusions warrants particular attention by the pediatrician. The American Academy of Pediatrics recommends screening infants born to HCV-infected mothers and persons with risk factors for HCV infection such as injection drug use, transfusion of ≥1 U of blood or blood products before 1992, or hemodialysis should be screened for anti-HCV. Also, persons who received clotting factor concentrates before 1987, when effective inactivation procedures were introduced, also should be screened. Guidelines for counseling families of HCV-infected children are provided.

Severe invasive group a streptococcal infections: A subject review

The course of severe invasive group A β-hemolytic streptococcal (GABHS) infections is often precipitous, requiring prompt diagnosis and rapid initiation of appropriate therapy. Therefore, physicians must have a high index of suspicion of this disease, particularly in patients at increased risk (eg, those with varicella or diabetes mellitus). Although a relationship between the use of nonsteroidal antiinflammatory drugs and severe invasive GABHS infections has been suggested, at present data on which to base a clinical decision about the use or restriction of nonsteroidal antiinflammatory drugs in children with varicella are insufficient. When necrotizing fasciitis is suspected, prompt surgical drainage, debridement, fasciotomy, or amputation often is necessary. Many experts recommend intravenously administered penicillin G and clindamycin for the treatment of invasive GABHS infections on the basis of animal studies. Some evidence exists that intravenous immunoglobulin given in addition to appropriate antimicrobial and surgical therapy may be beneficial. Although chemoprophylaxis for household contacts of persons with invasive GABHS infections has been considered by some experts, the limited available data indicate that the risk of secondary cases is low (2.9 per 1000) and data about the effectiveness of any drug are insufficient to make recommendations. Because of the low risk of secondary cases of invasive GABHS infections in schools or child care facilities, chemoprophylaxis is not indicated in these settings. Routine immunization of all healthy children against varicella is recommended and is an effective means to decrease the risk of invasive GABHS infections.

Prophylaxis of varicella in high-risk children: Dose-response effect of zoster immune globulin

Immunodeficient patients who were presumed to be susceptible received zoster immune globulin prophylaxis after exposure to varicella. The highest clinical attack rate (35.9%) was seen in household contacts; the lowest attack rate (0%) was observed in children exposed at school. Among household contacts, 48 of 100 patients who received high titer ZIG (reciprocal complement fixation titer greater than or equal to 2,560) developed fourfold rises in serum CF antibody between pre- and 48-hour post-treatment specimens, compared to only one of 34 patients treated with lower titer ZIG lots (P less than 0.001). Patients who developed fourfold antibody rises were significantly less likely to contract clinical varicella (P less than 0.01). Patients who received high titer ZIG also had significantly lower risks of death (P = 0.025) and complications (P = 0.006). Among ZIG-treated patients who contracted clinical varicella, 80% developed mild disease (less than 100 pox), and the median incubation period was prolonged. Immunodeficient children exposed to varicella benefit from ZIG prophylaxis and higher titer ZIG is of greatest benefit.

Indications for the Immunological Evaluation of Patients with Meningitis

Although people with bacterial meningitis lack adequate protective antibody against the invading pathogen, most do not have an underlying immunodeficiency. Certain comorbid conditions increase the risk for development of bacterial sepsis and meningitis. In addition, certain congenital complement deficiencies, defects of antibody production, or asplenia may be first recognized by the occurrence of bacterial meningitis, particularly when it occurs in infants or young children. Deficiencies of the terminal components of complement (C5-C9) or properdin have been associated with recurrent or invasive neisserial infections, and asplenia, agammaglobulinemia, and deficiencies of the early components of complement (e.g., C1-C3) are associated with risks of infections caused by Streptococcus pneumoniae, Haemophilus influenzae, and meningococci. The presence of congenital or acquired immunodeficiencies should be considered in persons who present with bacterial meningitis on the basis of the etiology, clinical epidemiology, and presence of other risk factors.

Prevention of lyme disease

Lyme disease is currently the most frequently reported vector-borne illness in the United States, accounting for more than 95% of such cases. The purpose of this report is to provide recommendations for preventing Lyme disease, including the use of Lyme disease vaccine. Individuals can reduce their risk of Lyme disease by avoiding tick-infested habitats when in endemic areas. If exposure to tick-infested habitats cannot be avoided, individuals may reduce their risk of infection by using repellents, wearing protective clothing, and regularly checking for and removing attached ticks. Morbidity from Lyme disease can be reduced significantly by detecting and treating the infection in its early stages; early and appropriate treatment almost always results in a prompt and uncomplicated cure. A Lyme disease vaccine (LYMErix, SmithKline Beecham, Collegeville, PA) was licensed by the US Food and Drug Administration on December 21, 1998, for persons 15 to 70 years of age. This vaccine seems to be safe and effective, but whether its use is cost-effective has yet to be clearly established. Use of this vaccine causes false-positive enzyme immunoassay results for Lyme disease. Lyme disease can be diagnosed in vaccinated persons by immunoblot testing. Decisions about the use of this vaccine should be based on an assessment of a persons risk as determined by activities and behaviors relating to tick exposure in endemic areas. This vaccine should be considered an adjunct to, not a replacement for, the practice of personal protective measures against tick exposure and the early diagnosis and treatment of Lyme disease.

Treatment of bacterial meningitis with ceftizoxime.

Ceftizoxime was evaluated in the treatment of 18 patients (6 adults and 12 children) with bacterial meningitis. In seven patients Haemophilus influenzae was the causative agent, in three Neisseria meningitidis, in five Streptococcus pneumoniae, and in one each alpha-streptococcus and Escherichia coli; one case was culture negative. Ceftizoxime was administered intravenously in doses of 200 mg/kg per day. Clinical response was appropriate in all patients with a mean time of defervescence of 3.7 days, and sterile cerebrospinal fluid was obtained from all patients at 24 to 36 h after initiation of therapy. The mean concentration of ceftizoxime in 46 cerebrospinal fluid samples obtained during therapy was 8.53 micrograms/ml (range, less than 0.5 to 29.0 micrograms/ml). Ceftizoxime concentrations in cerebrospinal fluid samples were ten- to several hundredfold the bactericidal concentrations of the pathogens isolated from the cerebrospinal fluid. Ceftizoxime penetrates the meninges well during acute infection and appears to be an excellent candidate antibiotic in the treatment of bacterial meningitis.

Neonatal necrotizing enterocolitis associated with delta toxin-producing methicillin-resistant Staphylococcus aureus

Delta toxin-producing coagulase-negative staphylococci previously have been associated with necrotizing enterocolitis in neonates. We identified three preterm infants (body weight, 845 +/- 59 g) infected with methicillin-resistant Staphylococcus aureus (MRSA) who had a similar clinical syndrome, characterized by pustular dermatitis, bacteremia and necrotizing enterocolitis accompanied by gastric residua, abdominal distention, hematochezia and pneumatosis intestinalis. MRSA was recovered from all three infants at infected skin sites, blood or venous catheters and from two of three infants in stool specimens. Two infants also had Staphylococcus epidermidis isolated from stool. All MRSA isolates had identical microbiologic profiles: four plasmids with identical molecular weights; coproduction of enterotoxins A and B; and the same antibiotic susceptibilities. Of one skin isolate, two blood isolates and two stool isolates of MRSA that were tested, all had characteristic delta toxin hemolytic activity. All culture supernatants of these isolates evaluated for delta toxin were positive by Western blot analysis. The two strains of S. epidermidis isolated from stool were negative for delta-like toxin by a standardized enzyme-linked immunoassay. The clustering of these cases, the similarity of the clinical syndrome, and the prior association of necrotizing enterocolitis with delta-like toxins produced by S. epidermidis, suggest that delta toxin-producing MRSA (or other S. aureus isolates) also may be etiologic agents in some cases of necrotizing enterocolitis in newborns.