Flucloxacillin associated neutropenia in children treated for bone and joint infections.

OBJECTIVE: This report describes episodes of acute neutropenia associated with flucloxacillin use in children treated for bone and joint infections. METHODS: A retrospective chart audit was performed on eight children who developed neutropenia when treated with flucloxacillin. RESULTS: Eight children (aged 1 month to 13 years) had a diagnosis of neutropenia attributed to treatment with flucloxacillin, seven of whom received parenteral therapy. The time to onset of neutropenia averaged 27 days, with neutrophil counts returning to normal limits in all patients after 2 to 9 days. Two children were asymptomatic when the neutropenia was detected. The average flucloxacillin dose used was 65% (range 20-100%) of the recommended maximum dose. CONCLUSIONS: These cases suggest that flucloxacillin should be used with greater caution and guidelines for dosing and clinical monitoring (regular neutrophil counts) need to be reassessed, despite none of these patients experiencing serious sequelae.

Prospective study of 125 cases of Staphylococcus aureus bacteremia in children in New Zealand.

BACKGROUND: Staphylococcus aureus bacteremia is a common complication of S. aureus infection. There are few pediatric studies defining the incidence and associated morbidity and mortality of S. aureus bacteremia and no such New Zealand studies. We conducted a prospective study of S. aureus bacteremia in children in New Zealand. METHODS: From July 1, 1996 to December 31, 1998, we included all children < 16 years of age with S. aureus bacteremia in Auckland and Christchurch. Relevant information regarding patient demographics, clinical course and outcome and laboratory results was recorded. RESULTS: One hundred twenty-five cases of true S. aureus bacteremia were identified. There were 4 deaths within 30 days of the onset of bacteremia. Fourteen (11%) of the children were < 1 month of age. Maori children (relative risk, 2.0; 95% confidence interval, 1.3 to 3.2) were twice as likely and Pacific Island children (relative risk, 2.5; 95% confidence interval, 1.6 to 3.8) 2.5 times as likely as white children to acquire S. aureus bacteremia. The peak incidence of S. aureus bacteremia was observed in Pacific Island children < 1 year of age (105 cases/100,000 children/year). Twenty-seven percent of cases were related to intravenous catheters. Seventy percent of cases were community-acquired. Ninety-eight percent of non-catheter-related cases in children > 1 month of age were community-acquired. There was a low rate of methicillin resistance (6%). CONCLUSIONS: S. aureus bacteremia is largely community-acquired in children in New Zealand and is more common in Pacific Island and Maori populations. Although there is a low associated mortality, a significant number are potentially preventable cases secondary to intravenous catheters.

Intravenous immunoglobulin in acute rheumatic fever: a randomized controlled trial.

BACKGROUND: Acute rheumatic fever (ARF) remains the leading cause of acquired heart disease in children worldwide. No therapeutic agent has been shown to alter the clinical outcome of the acute illness. Immunological mechanisms appear to be involved in the pathogenesis of ARF. Intravenous immunoglobulin (IVIG), a proven immunomodulator, may benefit cardiac conditions of an autoimmune nature. We investigated whether IVIG modified the natural history of ARF by reducing the extent and severity of carditis. METHODS AND RESULTS: This prospective, double-blind, randomized, placebo-controlled trial evaluated IVIG in patients with a first episode of rheumatic fever, stratifying patients by the presence and severity of carditis before randomization. Patients were randomly allocated to receive 1 g/kg IVIG on days 1 and 2 and 0.4 g/kg on days 14 and 28, or they received a placebo infusion. Clinical, laboratory, and echocardiographic evaluation was performed at 0, 2, 4, 6, 26, and 52 weeks. Fifty-nine patients were treated, of whom 39 had carditis (including 4 subclinical) and/or migratory polyarthritis (n=39). There was no difference between groups in the rate of normalization of the erythrocyte sedimentation rate or acute-phase proteins at the 6-week follow-up. On echocardiography, 59% in the IVIG group and 69% in the placebo group had carditis at baseline. There was no significant difference in the cardiac outcome, including the proportion of valves involved, or in the severity of valvar regurgitation at 1 year. At 1 year, 41% of the IVIG and 50% of the placebo group had carditis. CONCLUSIONS: IVIG did not alter the natural history of ARF, with no detectable difference in the clinical, laboratory, or echocardiographic parameters of the disease process during the subsequent 12 months.

Management of tuberculosis in children.

This paper provides specific guidelines on the management of tuberculosis infection and disease, covering general principles, recommended drug regimens and discuss the evidence to support these. It also covers use of corticosteroids, intermittent therapy, directly observed therapy and an approach to the management of a patient with drug-resistant tuberculosis.

Acute rheumatic fever in Auckland, New Zealand: spectrum of associated group A streptococci different from expected.

Annual specific rates for acute rheumatic fever (ARF) in Auckland children less than 15 years were 22/100,000 for the years 1980 to 1984. From 1984 to 1992 the rates remained relatively constant with an average of 45 (range, 30 to 70) children annually admitted with ARF to the Auckland Children's Hospital. This study examined retrospectively Group A streptococci identified from hospitalized pediatric patients during these 9 years. The total of 2410 isolates included 32 isolates from well-documented cases of ARF and an additional 6 from siblings of cases. Results of M typing indicated that streptococci associated with ARF are generally different from those described overseas and involved types which cause more skin than throat infections in the community.

Musculoskeletal and soft tissue Aeromonas infection: an environmental disease.

During a 4-year period from November 1985 to November 1989, Aeromonas was isolated from wounds and soft tissues with clinical evidence of infection in 28 patients at our institution. Of the 28 patients, 23 (82%) had sustained an acute open or penetrating injury, more than half of which (13 of the 23) were water-related trauma. One patient had Aeromonas osteomyelitis. Five patients had no history of trauma, and three of these five had an underlying chronic disease. Treatment included débridement and antimicrobial agents. Susceptibility testing on 25 isolates from 23 patients showed uniform resistance to ampicillin and considerable resistance to cefazolin sodium (68%), but all isolates were sensitive to gentamicin sulfate, cefuroxime sodium, and the third-generation cephalosporins.

Heteroconjugate antibodies enhance cell-mediated anti-herpes simplex virus immunity in vivo.

Heteroconjugate antibodies are generated by covalently linking two mAbs with different specificities. When anti-CD3 mAb, capable of activating effector T cells, is coupled to anti-herpes simplex virus (HSV) mAb, which binds HSV antigens on virally-infected target cells, the resulting heteroconjugate antibody can be used in vitro to enhance anti-HSV immunity. Specifically, these heteroconjugate antibodies can augment anti-HSV immunity among lymphocytes previously lacking cytotoxicity against HSV-infected target cells. However, the efficacy of these specialized reagents in enhancing anti-HSV immunity in vivo has not been determined. We report here that anti-HSV heteroconjugates used in an adoptive transfer murine model of HSV-1 infection inhibited HSV replication in vivo and improved long-term survival. These results demonstrate that heteroconjugate antibodies have a potential therapeutic role in enhancement of anti-HSV immunity.

Defective T-lymphocyte signal transduction and function in leukocyte adhesion deficiency.

The lymphocyte function-associated antigen-1 (LFA-1) molecule is a cell surface heterodimeric protein that directly mediates cellular adhesion. However, it remains unclear whether LFA-1 molecules are also involved in transmembrane signaling and in the subsequent regulation of cellular functions. Previous attempts to evaluate this issue have been hampered by (1) the ubiquitous expression of LFA-1 on normal lymphoid cells, (2) the limited availability of assays for cellular activation that are not affected by cellular adhesion, and (3) the difficulties in interpreting studies where anti-LFA-1 mAbs are used to alternatively block or stimulate this antigen. In order to avoid these pitfalls, we first isolated and cloned T lymphocytes from a patient with leukocyte adhesion deficiency (LAD), an inherited disorder in which the defective expression of leukocyte integrins results in the production of LFA-1- T lymphocytes. Different T-cell lines from this patient and from normal individuals were then stimulated through their T-cell antigen receptor complex and were then tested for three aspects of cellular activation: (1) transmembrane signaling (i.e., phosphoinositide turnover), (2) lymphokine secretion (i.e., release of lymphotoxin), and (3) their capacity to mediate cellular cytotoxicity (using murine anti-CD3-producing hybridoma cells as targets). Using assay systems that did not involve LFA-1-mediated adhesion to antigen-presenting cells or target cells, the T-cell lines from the LAD patient were found to be intrinsically defective in all three of these parameters of T cell activation.(ABSTRACT TRUNCATED AT 250 WORDS)

Neonatal ascites due to congenital jejunal obstruction.

Small bowel atresia may present with congenital ascites. A neonate with ascites was found to have jejunal atresia complicated by volvulus and perforation.