Michael W. Simon

Pharmacokinetics and Safety of Valaciclovir in Children with Epstein-Barr Virus Illness

AbstractObjective: Valaciclovir has in vitro activity against Epstein-Barr virus (EBV) and, because of improved absorption with higher achievable serum concentrations, may be more effective than aciclovir in the treatment of EBV. No studies to date have evaluated the efficacy, safety or proper dosing of valaciclovir in children for the treatment of EBV infection. The objectives of this study were to determine the pharmacokinetics and safety of valaciclovir tablets and suspension in children with EBV illness. Methods: 24 children with EBV illness were randomised to receive valaciclovir suspension 10 mg/kg or 20 mg/kg; eight children subsequently were crossed over and also received valaciclovir 500mg tablets. Doses of either suspension or tablets were administered every 8 hours for four doses, and pharmacokinetic studies were performed to determine aciclovir serum concentrations. Samples for drug assay were obtained at 0, 0.5, 1, 2, 4, 6, 8 and 24 hours. Samples were assayed by high performance liquid chromatography (HPLC) methods and aciclovir pharmacokinetics determined using non-compartmental analysis. Results: Valaciclovir pharmacokinetic parameters (mean ± SD) in children who received tablets and suspension (normalised to 500mg dose) were: maximum serum concentration (Cmax) 3.16 ± 1.30 and 2.42 ± 0.74 mg/L, time to maximum serum concentration (tmax) 1.88 ± 0.99 and 1.31 ± 0.53 hours, half-life (t1/2) 1.72 ± 0.41 and 1.94 ± 0.60 hours, apparent total systemic clearance (CL/F) 20.01 ± 6.61 and 15.58 ± 3.34 ml/min/kg, volume of distribution/bioavailability (Vd/F) 3.04 ± 1.26 and 2.58 ± 0.81 L/kg, and area under the concentration-time curve (AUC) 10.13 ± 3.47 and 8.59 ± 2.52 mg • h/L, respectively. There were no statistically significant differences in the pharmacokinetics of valaciclovir tablets versus suspension. The relative bioavailability of the valaciclovir tablets compared with the suspension was 115 ± 32%. Valaciclovir was well tolerated, with gastrointestinal disturbances and headache being the most common adverse effects in a small number of subjects. Conclusions: Valaciclovir is absorbed and achieves concentrations in children that appear to be effective for the treatment of herpes lesions. The pharmacokinetics of valaciclovir suspension and tablets are similar, and the pharmacokinetics of aciclovir after administration of valaciclovir to children are similar to historical observations of aciclovir pharmacokinetics in adults. Valaciclovir has a good safety profile and was well tolerated after oral administration in this group of children.

Changes in Newborn Bathing Practices May Increase the Risk for Omphalitis

Aseptic cord care, in conjunction with antibacterial skin care, has reduced the incidence of omphalitis specifically caused by Staphylococcus aureus. However, this practice has resulted in the emergence of resistant organisms that may pose a greater risk for newborn infections. Subsequently, many institutions have changed to dry cord care and nonantiseptic whole-body baths, a practice that has not been adequately studied to determine potential infectious risks. Three cases of omphalitis occurring after an institutional change to nonantiseptic whole-body baths are presented. Clinical diagnosis and treatment of omphalitis are reviewed. Recommendations for surveillance of omphalitis are offered.

Occurrence of Epstein-Barr Virus Illness in Children Diagnosed with Group A Streptococcal Pharyngitis

Epstein-Barr virus mononucleosis and group A streptococcal pharyngitis are acute infectious processes similar in both their clinical manifestations. Coinfections may occur and be a direct result of a synergistic effect on inflamed pharyngeal and tonsillar tissue. It was our observation that a population of children diagnosed with group A streptococcal pharyngitis and not responding to appropriate antimicrobial therapy had Epstein-Barr virus illness.

Treatment of Acute Sinusitis in Childhood with Ceftibuten

Acute sinusitis is a common childhood illness. If it is overlooked or undertreated, suppurative and intracranial complications may develop. Amoxicillin has traditionally been the antibiotic of choice for treatment of acute sinusitis. However, the efficacy of amoxicillin has been reduced because of the emergence of bacteria producing b-lactamase and altered penicillin-binding proteins. This study compares the effectiveness of 10, 15, and 20 days of ceftibuten therapy with 14 days of erythromycin-sulfisoxazole therapy in treating acute sinusitis. The results indicate that both treatment regimens are effective in treating acute sinusitis (96% clinical response for erythromycin-sulfisoxazole vs 92% for a 10-or 15-day course of ceftibuten vs 100% for a 20-day course of ceftibuten). Longer treatment periods may be more effective in resolving the acute illness.

FluMist Reconsidering the Contraindications

To the Editor, In a recent article that appears in Pediatric News, the Advisory Committee of Immunization Practices recommends the use of the live attenuated flu vaccine (LAIV) as the vaccination of choice for healthy children aged 2 to 8 years. Despite a large body of emerging evidence, the vaccine, due to guidelines, remains contraindicated in children younger than 2 years, children younger than 5 years with a history of prior wheezing, and children of any age with asthma. In a culture that emphasizes the importance of evidence-based medicine, it seems time to reconsider the contraindications. Warnings are based largely on 2 separate studies. One study conducted among healthy children aged 1 to 17 years demonstrated a significant increase in reactive airway disease in those 18 to 35 months of age who received the LAIV as compared with the inactivated influenza vaccine (IIV). The second study revealed a small, but statistically significant increase in wheezing (3.8% LAIV vs 2.1% IIV) and hospitalization (6.1% LAIV vs 2.6% IIV) among children 6 to 11 months old. Of particular note, the majority of these hospitalizations occurred more than 6 weeks following vaccination, making causation unlikely. In 2012, Ambrose et al reviewed safety and efficacy data from 2 large, multinational comparative studies. These studies were conducted among children aged 24 to 71 months and included those with a history of prior wheezing, recurrent respiratory tract infections, and mild to moderate asthma. When stratified according to medical history, results revealed no significant difference in the rates of wheezing or hospitalization in the LAIV versus IIV groups. Regarding adverse events, LAIV was associated with a higher instance of stuffy nose and cough; however, these symptoms diminished with subsequent doses. Furthermore, a study assessing shedding of the vaccination virus in a daycare setting among children younger than 3 years showed the probability of transmission to nonvaccinated contacts to be 0.58% for type B virus and 2.4% for type A virus. Immunocompromised children and adults may have a greater risk of contracting community-acquired illness than illness derived from LAIV-vaccinated contacts. The superior efficacy of LAIV to IIV has been established in children as young as 6 months old. Certainly, to small children, as well as those with underlying pulmonary and immune compromise, the flu poses a serious risk. While we are in need of further data to validate its use in the latter, it indeed seems warranted to reconsider these contraindications and expand administration of the LAIV.

Prophylactic Antibiotics Ineffective or Inefficacious

Children with various congenital and acquired heart diseases benefit from improved care measures. These include surgical measures and outcomes as well as effective antibiotic prophylaxis. The recommendations have changed over the years, and the American Heart Association now recommends antimicrobial prophylaxis before dental procedures for patients with prosthetic heart valves, uncorrected congenital heart disease, valve repair with prosthetic material, leaflet pathology, a history of infectious endocarditis, and during the first 6 months after repair of a congenital heart defect. The rates of prosthetic valve endocarditis are 1% to 3% 1 year after valve replacement and are due to Staphylococcus aureus, coagulase negative staphylococci, gram negative bacilli, and fungal organisms within the first 2 postoperative months and streptococci, Staphylococcus aureus, coagulase-negative staphylococci, and enterococci after 2 months. The rate of endocarditis increases to 3% to 6% by 5 years after valve replacement. The mouth contains more than 700 species of bacteria. The most common is Viridans streptococci, comprising 30% of the microflora. Various β-lactamproducing bacteria, Staphylococcus aureus, and streptococci also inhabit the oral cavity. These bacteria may contribute to penicillin and cephalosporin resistance. The current recommendation for adult patients at risk for endocarditis is to receive 2 g of amoxicillin, whereas children at risk should receive 50 mg/kg of amoxicillin orally 30 to 60 minutes before a dental procedure. Despite these recommendations, amoxicillin resistance among the microflora of the oral cavity is reported as 43%. Considering the current rate of endocarditis and the antibiotic resistance of the microflora in the oral cavity, it may be time to change the recommendations to use a β-lactam-resistant antibiotic in situations where antibiotic prophylaxis is indicated in children.

Orbital Cellulitis A Presentation of Two Cases with Unusual Features

a layer of’ fascia separating the orbit from the eyelids. Orbital cellulitis is less common than periorbital cellulitis and is characterized clinically by varying degrees of proptosis, linritation of extraocuiar movements. chemosis, and diminished visual acuity.’ Serious systetrrie and ocrrlar complications may develop as a consequence of infection. These include orbital, subperiostea) or brain abscesses, meningitis, cavernous sinus thrombosis, optic neuritis, and loss of vision. 1.2 2