P. Joan Chesney

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.

An enterotoxin-like protein in Staphylococcus aureus strains from patients with toxic shock syndrome.

An enterotoxin-like protein, tentatively labeled enterotoxin F, was isolated from Staphylococcus aureus strains taken from patients with toxic shock syndrome. Antibodies specific for enterotoxin F were prepared in rabbits. Use of these antibodies showed that 130 (91.5%) of 142 S. aureus strains from patients with toxic shock syndrome produced enterotoxin F. Strains from toxic shock patients in eight other countries were identified as enterotoxin F producers. Only a small number of S. aureus strains from sources other than patients with toxic shock syndrome were found to produce enterotoxin F. Twenty-one of 111 controls had low antibody titers (less than 1:100) to enterotoxin F whereas 86 of 92 toxic shock patients had low acute phase antibody titers (less than 1:100) to enterotoxin F. Eight of 52 patients had serum conversion as shown by an increase in antibody titer to enterotoxin F in sera taken 21 to 60 days after onset of the illness. It may be possible to identify persons susceptible to toxic shock syndrome by measuring their antibody titer to enterotoxin F.

The Food and Drug Administration’s Deliberations on Antidepressant Use in Pediatric Patients

On February 2, 2004, the Food and Drug Administration organized a joint meeting of the Neuro-Psychopharmacologic Advisory Committee and Pediatric Subcommittee of the Anti-Infective Drugs Advisory Committee to examine the occurrence of suicidality in clinical trials that investigate the use of the newer antidepressant drugs in pediatric patients. Committee members reconvened on September 13–14, 2004, and concluded that there was a causal link between the newer antidepressants and pediatric suicidality. This article provides a summary of the Food and Drug Administration deliberations for the pediatric clinician. We also provide research, regulation, education, and practice implications for care for children and adolescents who may be eligible for treatment with these medications.

Toxic Shock Syndrome: Management and Long-Term Sequelae

Little information is available on the optimal management of toxic shock syndrome and on its sequelae. The most appropriate antibiotic treatment, the efficacy of colloid infusions, and the potential role of gamma globulin preparations have not yet been completely ascertained. Coagulase-positive staphylococci associated with toxic shock syndrome had minimal inhibitory concentrations of 0.06 microgram/mL or less to rifampin, 0.25 microgram/mL or less to gentamicin, and 0.50 microgram/mL or less to both nafcillin and clindamycin. In the 36 patients studied abnormal chest roentgenograms were commoner in those who had received albumin than in those who had not. Radioimmunoassay showed antibody titers to staphylococcal enterotoxin F, a marker protein in toxic shock syndrome, of 1:4000 or more for intravenous gamma globulin (12/15 lots) and 1:40 000 or more for intramuscular gamma globulin. Major sequelae of toxic shock syndrome include late-onset rash, compromised renal function, cyanotic extremities, and prolonged neuromuscular abnormalities.

Penicillin- and cephalosporin-resistant strains of Streptococcus pneumoniae causing sepsis and meningitis in children with sickle cell disease☆☆☆★

OBJECTIVE We investigated the possibility that antimicrobial-resistant pneumococci were causing invasive disease in children with sickle-cell disease (SCD). STUDY DESIGN Records of all children with SCD observed at the Mid-South Sickle Cell Center (MSSCC) at LeBonheur Childrens Medical Center were reviewed from January 1990 to June 1994. Children with SCD and pneumococcal sepsis were identified. The Streptococcus pneumoniae isolates from these children were examined for serotype and antimicrobial susceptibilities. Two additional children not observed in the MSSCC had pneumococcal sepsis caused by penicillin-resistant isolates and were also included. RESULTS Antimicrobial susceptibility testing of the six penicillin-resistant isolates revealed that four were resistant to trimethoprim-sulfamethoxazole, two to erythromycin, and one to clindamycin. The two isolates that were resistant to ceftriaxone also were multiply resistant. From the MSSCC, 26 children had pneumococcal sepsis during the 4 1/2-year period studied. Five of these children (19%) died. Four (15%), including one who died, were infected with penicillin-resistant strains. CONCLUSION Pneumococcal sepsis, meningitis, and infections of other foci in children with SCD may be caused by S. pneumoniae that is resistant to one or more antimicrobial agents, including penicillin. The addition of vancomycin to the antibiotics currently used for initial management should be considered in areas where the antibiotic resistance of S. pneumoniae is prevalent.

Successful treatment of Candida meningitis with amphotericin B and 5-fluorocytosine in combination.

The combined use of amphotericin B and 5-fluorocytosine in the treatment of two children with Candida albicans meningitis is described. Therapy consisted of nine to 13 days of iv amphotericin B, combined with, or followed by six to nine weeks of oral 5-FC. Each organism was sensitive to 5-FC before starting therapy. Resistance did not develop during therapy. CSF administration was not necessary and toxic reactions were minimal and transient; neither patient has suffered a recurrence four years and 14 months, respectively, after discontinuance of therapy. The combination of short-term therapy with iv amphotericin B plus long-term oral 5-FC was successful in these two patients.

Intranuclear inclusions in megakaryocytes in congenital cytomegalovirus infection

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Toxic-shock syndrome: A commentary and review of the characteristics of Staphylococcus aureus strains

SummaryToxic-shock syndrome (TSS) was first identified in 1978 in children as a toxin-mediated illness associated withStaphylococcus aureus. Extensive publicity ensued when the strong association of this disease with menses and tampon use was recognized in 1980. Since that time, investigation into the epidemiology, clinical manifestations and pathogenesis of TSS has coincided with a decreasing incidence of disease. A unique exotoxin has been isolated under varying physico-chemical conditions from TSS-associated strains ofS. aureus and its effect on immune function and other parameters bothin vitro andin vivo described. In addition, TSS-associatedS. aureus strains have been found to have characteristic heavy metal susceptibility patterns, to be lysogenized and to show decreased hemolysis on sheep blood agar. Preliminary results of the prevalence of TSS-associated strains ofS. aureus and of the theories of pathogenesis are reviewed.ZusammenfassungDas Syndrom des toxischen Schocks (TSS) wurde erstmals 1978 bei Kindern als Toxin-vermittelte, mitStaphylococcus aureus assoziierte Krankheit identifiziert. Die 1980 erkannte, enge Assoziation dieser Krankheit mit Menses und Tampongebrauch erregte erhebliches öffentliches Interesse. Seitdem wurde intensiv über die Epidemiologie, die klinischen Manifestationsformen und die Pathogenese des TSS geforscht; gleichzeitig nahm die Inzidenz an Erkrankungen ab. Aus TSS-assoziierten Stämmen vonS. aureus wurde unter verschiedenen physikalisch-chemischen Bedingungen ein besonderes Exotoxin isoliert, und es wurden seineIn vitro- undIn vitro-Wirkungen auf immunologische Funktionen und andere Parameter beschrieben. Außerdem wurde herausgefunden, daß ASS-assoziierteS. aureus-Stämme ein charakteristisches Empfindlichkeitsprofil gegenüber Schwermetallen haben, lysogeniert werden und auf Schafblutagar verminderte Hämolyse zeigen. Die vorläufigen Ergebnisse von Studien zur Prävalenz TSS-assoziierter Stämme vonS. aureus und Theorien zur Pathogenese werden in einer Übersicht dargestellt.Toxic-shock syndrome (TSS) was first identified in 1978 in children as a toxin-mediated illness associated withStaphylococcus aureus. Extensive publicity ensued when the strong association of this disease with menses and tampon use was recognized in 1980. Since that time, investigation into the epidemiology, clinical manifestations and pathogenesis of TSS has coincided with a decreasing incidence of disease. A unique exotoxin has been isolated under varying physico-chemical conditions from TSS-associated strains ofS. aureus and its effect on immune function and other parameters bothin vitro andin vivo described. In addition, TSS-associatedS. aureus strains have been found to have characteristic heavy metal susceptibility patterns, to be lysogenized and to show decreased hemolysis on sheep blood agar. Preliminary results of the prevalence of TSS-associated strains ofS. aureus and of the theories of pathogenesis are reviewed. Das Syndrom des toxischen Schocks (TSS) wurde erstmals 1978 bei Kindern als Toxin-vermittelte, mitStaphylococcus aureus assoziierte Krankheit identifiziert. Die 1980 erkannte, enge Assoziation dieser Krankheit mit Menses und Tampongebrauch erregte erhebliches öffentliches Interesse. Seitdem wurde intensiv über die Epidemiologie, die klinischen Manifestationsformen und die Pathogenese des TSS geforscht; gleichzeitig nahm die Inzidenz an Erkrankungen ab. Aus TSS-assoziierten Stämmen vonS. aureus wurde unter verschiedenen physikalisch-chemischen Bedingungen ein besonderes Exotoxin isoliert, und es wurden seineIn vitro- undIn vitro-Wirkungen auf immunologische Funktionen und andere Parameter beschrieben. Außerdem wurde herausgefunden, daß ASS-assoziierteS. aureus-Stämme ein charakteristisches Empfindlichkeitsprofil gegenüber Schwermetallen haben, lysogeniert werden und auf Schafblutagar verminderte Hämolyse zeigen. Die vorläufigen Ergebnisse von Studien zur Prävalenz TSS-assoziierter Stämme vonS. aureus und Theorien zur Pathogenese werden in einer Übersicht dargestellt.

Liver Physiology and Disease Acute Cholestasis in Patients with Toxic-Shock Syndrome

Serum liver function tests were performed in 22 females fulfilling the criteria for toxic-shock syndrome. All patients showed evidence of hepatic dysfunction during their hospital course. These findings included hyperbilirubinemia in the absence of laboratory evidence for significant hemolysis, mild elevation of the transaminases, threefold increase in their serum bile salt concentration, and hypoalbuminemia. These findings are best explained by hypoperfusion of the liver and a canalicular injury secondary to staphylococcal exotoxin. Cholestasis appears to be a universal finding in toxic-shock syndrome.

Possible Host-Defense Mechanisms in Toxic Shock Syndrome

Abstract Future research activity in toxic shock syndrome should provide further understanding of the ways different host-defense mechanisms are involved in toxic shock syndrome; such efforts must ...