Xavier Sáez-Llorens

Impact of an antibiotic restriction policy on hospital expenditures and bacterial susceptibilities: a lesson from a pediatric institution in a developing country.

Background. In an era of growing concern about bacterial resistance and hospital costs, limiting the use of broad spectrum antibiotics is important. Objectives. To evaluate the effects of an antibiotic restriction policy on expenditures, antimicrobial resistance rates and clinical outcomes of hospitalized children. Design. Starting in January, 1997, a prior consultation with an infectious disease specialist for using restricted antibiotics was required in all hospital areas. A retrospective assessment of study objectives obtained 2 years before (1995, 1996) and 2 years after (1997, 1998) initiation of the restriction policy was performed. Setting. The present study was conducted in a 500‐bed university hospital serving children nationwide of a developing country, Panama. Results. Total expenditures for antimicrobial agents decreased by 50%, from

Pharmacokinetics and Safety of Famciclovir in Children with Herpes Simplex or Varicella-Zoster Virus Infection

699 543 (US dollars) during 1995 and 1996 to

Long-term safety and efficacy results of once-daily emtricitabine-based highly active antiretroviral therapy regimens in human immunodeficiency virus-infected pediatric subjects.

347 261 during 1997 and 1998. Susceptibility rates of many nosocomial isolates (especially staphylococci and Gram‐negative enteric bacilli) usually improved for restricted antibiotics with >35% reduction in utilization (notably for gentamicin, third generation cephalosporins, piperacillin and vancomycin). Major improvements in bacterial susceptibilities were observed in the nursery, a place harboring microorganisms exhibiting the higher initial resistance rates of the hospital. No differences in days of hospital stay and mortality rates of all patients and of children with nosocomial infections were detected during the study period. Conclusions. Requirement for prior approval of selected antimicrobial drugs in a pediatric institution decreases hospital expenditures and improves susceptibilities to antibiotics without compromising patient outcomes or length of hospital stays.

Complicaciones y costos asociados a la varicela en niños inmunocompetentes

ABSTRACT Two multicenter, open-label, single-arm, two-phase studies evaluated single-dose pharmacokinetics and single- and multiple-dose safety of a pediatric oral famciclovir formulation (prodrug of penciclovir) in children aged 1 to 12 years with suspicion or evidence of herpes simplex virus (HSV) or varicella-zoster virus (VZV) infection. Pooled pharmacokinetic data were generated after single doses in 51 participants (∼12.5 mg/kg of body weight [BW] for children weighing <40 kg and 500 mg for children weighing ≥40 kg). The average systemic exposure to penciclovir was similar (6- to 12-year-olds) or slightly lower (1- to <6-year-olds) than that in adults receiving a 500-mg dose of famciclovir (historical data). The apparent clearance of penciclovir increased with BW in a nonlinear manner, proportional to BW0.696. An eight-step weight-based dosing regimen was developed to optimize exposure in smaller children and was used in the 7-day multiple-dose safety phases of both studies, which enrolled 100 patients with confirmed/suspected viral infections. Twenty-six of 47 (55.3%) HSV-infected patients who received famciclovir twice a day and 24 of 53 (45.3%) VZV-infected patients who received famciclovir three times a day experienced at least one adverse event. Most adverse events were gastrointestinal in nature. Exploratory analysis following 7-day famciclovir dosing regimen showed resolution of symptoms in most children with active HSV (19/21 [90.5%]) or VZV disease (49/53 [92.5%]). Famciclovir formulation (sprinkle capsules in OraSweet) was acceptable to participants/caregivers. In summary, we present a weight-adjusted dosing schedule for children that achieves systemic exposures similar to those for adults given the 500-mg dose.

Effect of combination antiretroviral therapy on cerebrospinal fluid HIV RNA, HIV resistance, and clinical manifestations of encephalopathy

OBJECTIVES. The purpose of this work was to obtain long-term safety and efficacy data for antiretroviral regimens containing emtricitabine in HIV-infected pediatric subjects and confirm that a pediatric dose of 6 mg/kg once daily would provide steady-state emtricitabine concentrations comparable to those observed in adults given 200 mg of emtricitabine once daily. PATIENTS AND METHODS. HIV-infected subjects between 3 months and 16 years of age were enrolled, including 71 antiretroviral-naïve subjects and 45 antiretroviral-experienced subjects. Naive subjects received emtricitabine plus stavudine plus lopinavir or ritonavir. Experienced subjects replaced the lamivudine in their existing regimens with emtricitabine. Tolerance, safety, disease progression, and virologic and immunologic responses were evaluated. RESULTS. The Kaplan-Meier probability of persistent virologic response in the intent-to-treat population through week 164 at ≤400 copies per mL and ≤50 copies per mL was 74% and 62%, respectively. Three subjects (3%) discontinued the study for adverse events, 8 (7%) for virologic failure, and 1 died through a median follow-up of 164 weeks. The annualized incidence rate of grade 3 to 4 adverse events and grade 3 to 4 laboratory abnormalities was 6% and 3%, respectively. The annualized incidence rate of serious adverse events was 9%, with 1% attributed as related to emtricitabine. Genotypic analysis showed the emergence of the M184V mutation in 4 of the 15 subjects who experienced virologic failure through week 164. Pharmacokinetic evaluation demonstrated plasma drug exposures in these children comparable to adults receiving the approved dose of 200 mg once daily. CONCLUSIONS. These results demonstrate the safety and efficacy of emtricitabine in pediatric patients. They also support that the safety and efficacy profile of emtricitabine in children is similar to that demonstrated in adults.

A Randomized, Double-Blind Study of Triple Nucleoside Therapy of Abacavir, Lamivudine, and Zidovudine Versus Lamivudine and Zidovudine in Previously Treated Human Immunodeficiency Virus Type 1-Infected Children

Objetivos. La varicela es una infeccion comun de la infancia en paises que no han incorporado la vacunacion correspondiente en sus calendarios vacunales. Generalmente es benigna en ninos inmunocompetentes y no necesita tratamiento. Los objetivos de este estudio consistieron en investigar la frecuencia y caracteristicas de las complicaciones de la varicela que requieran tratamiento hospitalario en ninos inmunocompetentes y el curso clinico de los hijos de madres con varicela perinatal. Ademas, se calculo el gasto hospitalario asociado a la varicela en los ninos estudiados. Metodos. Estudio retrospectivo de los expedientes clinicos de ninos con varicela ingresados en el Hospital del Nino de Panama, de enero de 1991 a diciembre de 2000. Se analizaron el tipo de complicaciones, el curso clinico y los costos hospitalarios de los pacientes afectados por varicela. Resultados. De 5 203 ninos atendidos en consultas externas, 568 (11%) fueron hospitalizados. En el estudio se incluyeron 513 ninos: 381 (74%) con varicela adquirida en la comunidad, 92 (18%) hijos de madres con varicela y 40 (8%) con varicela nosocomial. Las complicaciones mas frecuentes fueron las infecciones cutaneas y subcutaneas (45%), las infecciones respiratorias (25%) y las alteraciones neurologicas (7%). Las complicaciones respiratorias y cutaneas ocurrieron a menor edad y en fases mas tempranas de la varicela que las alteraciones neurologicas. Trece ninos (2,5%) fallecieron, con una letalidad del 8% para la varicela con complicaciones respiratorias y neurologicas y nula para las complicaciones cutaneas. Sesenta de los 92 (65%) hijos de madres con varicela no desarrollaron la enfermedad y ninguno fallecio. En cambio, 2 de los 32 neonatos (6%) con varicela perinatal fallecieron. La duracion media de la hospitalizacion fue de 8,9 (1 a 27) dias. Se utilizo farmacoterapia parenteral en una gran proporcion de los ninos, especialmente antibioticos (54%), aciclovir (17%) e inmunoglobulinas intravenosas (14%). El costo medio por paciente hospitalizado fue de 1 209 dolares estadounidenses. Conclusiones. Los resultados obtenidos indican que la varicela es una infeccion que puede asociarse a un numero importante de complicaciones costosas y a una letalidad no despreciable en ninos inmunocompetentes. La vacunacion rutinaria contra la varicela podria reducir el impacto de esta enfermedad sobre la salud infantil en nuestro pais.