John A. Vanchiere

Oseltamivir Pharmacokinetics, Dosing, and Resistance Among Children Aged <2 Years With Influenza

BACKGROUND Children <2 years of age are at high risk of influenza-related mortality and morbidity. However, the appropriate dose of oseltamivir for children <2 years of age is unknown. METHODS The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group evaluated oseltamivir in infants aged <2 years in an age-de-escalation, adaptive design with a targeted systemic exposure. RESULTS From 2006 to 2010, 87 subjects enrolled. An oseltamivir dose of 3.0 mg/kg produced drug exposures within the target range in subjects 0-8 months of age, although there was a greater degree of variability in infants <3 months of age. In subjects 9-11 months of age, a dose of 3.5 mg/kg produced drug exposures within the target range. Six of 10 subjects aged 12-23 months receiving the Food and Drug Administration-approved unit dose for this age group (ie, 30 mg) had oseltamivir carboxylate exposures below the target range. Virus from 3 subjects developed oseltamivir resistance during antiviral treatment. CONCLUSIONS The appropriate twice-daily oral oseltamivir dose for infants ≤8 months of age is 3.0 mg/kg, while the dose for infants 9-11 months old is 3.5 mg/kg.

A system for the analysis of BKV non-coding control regions: application to clinical isolates from an HIV/AIDS patient.

The human polyomavirus BK virus (BKV) is an important opportunistic pathogen whose disease prevalence continues to increase with the growing immunocompromised population. To date, the major determinant of replication in cell culture has not been formally proven. BKV exists as archetype virus and rearranged variants, which are classified based on the DNA sequence of their non-coding control regions (NCCRs). The archetype BKV NCCR is divided into five blocks of sequence and rearranged variants contain deletions and duplications of these blocks. In this study, a genetic system was developed and used to identify the major determinant of replication ability in primary renal proximal tubule epithelial cells, the natural host cell of BKV. This system was also used to analyze NCCR variants isolated from an immunocompromised patient which contain assorted rearrangement patterns and functional differences. This study solidifies the NCCR as the major genetic determinant of BKV replication ability in vitro.

Treatment of BK virus-associated nephropathy with CMX001 after kidney transplantation in a young child

NC, with renal failure secondary to bilateral dysplastic kidneys, received an LRD renal transplant (tx) at 17 months of age. Her early post‐tx course was complicated by persistently elevated blood polyoma BK virus DNA loads. A protocol biopsy at six months post‐transplant revealed BKVAN. Blood viral loads did not respond to decreased immunosuppression or treatment with ciprofloxacin and leflunomide. Six months post‐tx, her serum creatinine began to rise and we sought experimental therapy to prevent the loss of her graft. At seven months post‐tx, with FDA approval under an eIND, the patient was started on a 36‐wk course of treatment with the investigational drug. The patient is now more than 24 months after stopping treatment with CMX. BKV viral DNA loads remain at low, but still detectable levels. Urine viral loads have declined, but remain elevated. EBV DNA loads become undetectable. The patients serum creatinine has declined back to a baseline of 0.5–0.7 mg/dL and has been stable for two yr. Renal function was preserved in association with the use of CMX001 to treat BKV nephropathy in a young pediatric kidney transplant recipient. There were no serious adverse events associated with the use of CMX001. This novel medication may be of value in the treatment of BKVAN in pediatric renal transplant recipients.

Adherence to CLSI Recommendations for Testing of Staphylococcus aureus Isolates in Louisiana Hospitals: Report of a Clinical Failure and Results of a Questionnaire Study

ABSTRACT We report a case of failure of clindamycin therapy due to inducible clindamycin resistance. We surveyed and found that only 52% of reporting hospitals in the state of Louisiana were performing the D test for inducible clindamycin resistance according to guidelines recommended by the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards).

Evolution of Alu Subfamily Structure in the Saimiri Lineage of New World Monkeys

Abstract Squirrel monkeys, Saimiri, are commonly found in zoological parks and used in biomedical research. S. boliviensis is the most common species for research; however, there is little information about genome evolution within this primate lineage. Here, we reconstruct the Alu element sequence amplification and evolution in the genus Saimiri at the time of divergence within the family Cebidae lineage. Alu elements are the most successful SINE (Short Interspersed Element) in primates. Here, we report 46 Saimiri lineage specific Alu subfamilies. Retrotransposition activity involved subfamilies related to AluS, AluTa10, and AluTa15. Many subfamilies are simultaneously active within the Saimiri lineage, a finding which supports the stealth model of Alu amplification. We also report a high resolution analysis of Alu subfamilies within the S. boliviensis genome [saiBol1].

A Novel Tool for Health Literacy: Using Comic Books to Combat Childhood Obesity

Childhood obesity remains a serious problem that requires health literacy projects to engage both parents and children in making healthy choices. This paper describes an award-funded project designed by LSU Health Shreveport (LSUHS) faculty from the Health Sciences Library and the Department of Pediatrics who created a comic book to help children and their parents learn practical ways children can make healthier lifestyle choices. LSUHS also collaborated with LSU-Shreveport to recruit a student artist, who illustrated the comic and designed promotional items used to promote the print and online versions of the book throughout the community.

A27: Polyomavirus Excretion in Children with Rheumatic Diseases on Immunosuppressive Therapy

Biologic therapies have revolutionized the care and outcome of children with rheumatic diseases. However, the long term risks associated with these therapies remain unclear. For example, the occurrence of Progressive Multifocal Leukoencephalopathy (PML), caused by reactivation of the JC poly‐omavirus (JCV), in patients treated with Rituximab is a major concern. PML has also been reported with Infliximab and other non‐biologic immunosuppressive therapies. Human BK polyomavirus (BKV) results in allograft loss in kidney transplant recipients. While primary infection with the polyoma viruses occurs in childhood and is usually asymptomatic, the factors associated with reactivation and clinical disease remain unclear. Given the devastating and frequently fatal nature of PML, identification of specific risk factors may be useful prior to initiating immunosuppressive therapy and in long term surveillance.

Oseltamivir pharmacokinetics, dosing, and resistance among children aged

BACKGROUND Children <2 years of age are at high risk of influenza-related mortality and morbidity. However, the appropriate dose of oseltamivir for children <2 years of age is unknown. METHODS The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group evaluated oseltamivir in infants aged <2 years in an age-de-escalation, adaptive design with a targeted systemic exposure. RESULTS From 2006 to 2010, 87 subjects enrolled. An oseltamivir dose of 3.0 mg/kg produced drug exposures within the target range in subjects 0-8 months of age, although there was a greater degree of variability in infants <3 months of age. In subjects 9-11 months of age, a dose of 3.5 mg/kg produced drug exposures within the target range. Six of 10 subjects aged 12-23 months receiving the Food and Drug Administration-approved unit dose for this age group (ie, 30 mg) had oseltamivir carboxylate exposures below the target range. Virus from 3 subjects developed oseltamivir resistance during antiviral treatment. CONCLUSIONS The appropriate twice-daily oral oseltamivir dose for infants ≤8 months of age is 3.0 mg/kg, while the dose for infants 9-11 months old is 3.5 mg/kg.

Oseltamivir Pharmacokinetics, Dosing, and Resistance in Children From Birth to Two Years of Age with Influenza

BACKGROUND Children <2 years of age are at high risk of influenza-related mortality and morbidity. However, the appropriate dose of oseltamivir for children <2 years of age is unknown. METHODS The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group evaluated oseltamivir in infants aged <2 years in an age-de-escalation, adaptive design with a targeted systemic exposure. RESULTS From 2006 to 2010, 87 subjects enrolled. An oseltamivir dose of 3.0 mg/kg produced drug exposures within the target range in subjects 0-8 months of age, although there was a greater degree of variability in infants <3 months of age. In subjects 9-11 months of age, a dose of 3.5 mg/kg produced drug exposures within the target range. Six of 10 subjects aged 12-23 months receiving the Food and Drug Administration-approved unit dose for this age group (ie, 30 mg) had oseltamivir carboxylate exposures below the target range. Virus from 3 subjects developed oseltamivir resistance during antiviral treatment. CONCLUSIONS The appropriate twice-daily oral oseltamivir dose for infants ≤8 months of age is 3.0 mg/kg, while the dose for infants 9-11 months old is 3.5 mg/kg.

Non tuberculous mycobacterial lesion of the parotid gland and facial skin in a 4year old girl: A proposed treatment strategy.

OBJECTIVE We report a case of a parotid-facial caseating granulomatous infection caused by atypical mycobacteria (Mycobacterium avium) in an immuno-competent child. The size and depth of the lesion and its proximity to the facial nerve present a challenge for a purely surgical treatment strategy. An alternative treatment strategy is developed to avoid severe disfigurement. STUDY DESIGN/SUBJECT Atypical mycobacterial infection of the parotid region in a 5 year old girl: timeline and definition of a planned combined treatment strategy with antibiotics and surgical excision. RESULTS/CONCLUSION Cervicofacial infections caused by non-tuberculous mycobacteria (NTM) may present surgical challenges due to the size and depth of the lesion and its proximity to the facial nerve and major vascular structures. Even minor scars are highly visible and poorly tolerated. Close clinical monitoring combined with judicious treatment strategies is necessary for successful treatment and good cosmesis. Recent literature provides insufficient guidance in formulating the best treatment strategy for the individual patient. Comparisons of antibiotic therapy with variations of surgical excision are abundant but poorly formulated. Our case presented with a lesion involving skin, superficial and deep lobe of the parotid gland. Lesion was in immediate proximity to the distribution of the facial nerve through the parotid gland. The risk of surgical damage to the facial nerve in the acute phase of the inflammation and the required extent of skin excision were significant. We decided to start treatment with combination antimycobacterial antibiotics in close cooperation with the pediatric infectious disease specialists. We observed and documented the regress and executed a delayed surgical excision when the lesion was reduced to skin only. In our opinion this was the best treatment strategy that helped us avoid extensive dissection in the vicinity of the facial nerve as well as a parotidectomy. Excision of the involved skin with the deep portion was performed 6.5 months after initial diagnosis.