Epidemiological Aspects of Maternal and Congenital Toxoplasmosis in Panama.

In Panama, epidemiological data on congenital toxoplasmosis are limited, making it difficult to understand the scope of clinical manifestations in the population and factors that may increase the risk of infection. This study provides insight into the epidemiological situation of maternal and congenital toxoplasmosis in Panama and contributing information on the burden of this disease in Central America. Blood samples were collected from 2326 pregnant women and used for the detection of anti-T. gondii antibodies. A high seroprevalence (44.41%) was observed for T. gondii infection in pregnant women from different regions of Panama, with an estimated incidence rate of congenital toxoplasmosis of 3.8 cases per 1000 live births. The main risk factors associated with T. gondii infection using bivariate statistical analysis were an elementary level education and maternal age range of 34-45 years. Multivariate statistical analyses revealed that in some regions (San Miguelito, North and West regions), the number of positive cases correlated with the presence of pets, stray dogs and the consumption of poultry. In other regions (East and Metropolitan regions), the absence of pets was considered a protective factor associated with negative cases, while the presence of stray cats and the age range of 25-34 years did not represent any risk in these regions.

Enfermedad por Staphylococcus aureus resistente a meticilina en Panamá / Methicillin-resistant Staphylococcus aureus disease in Panama

Introducción: A nivel mundial se describe un incremento de las infecciones por Staphylococcus aureus (S. aureus) resistente a meticilina (SARM). El espectro clínico de la enfermedad incluye desde colonización nasal hasta infecciones superficiales e invasoras. Objetivo: Describir la frecuencia, características clínicas y factores de riesgo asociados a la enfermedad por SARM en menores de 15 años, establecer la prevalencia de colonización y la susceptibilidad a antimicrobianos de las cepas aisladas. Materiales y métodos: Estudio descriptivo. Se incluyó a sujetos con edades comprendidas entre 1 mes a 15 años de edad atendidos en el Hospital del Niño de Panamá con infección invasora o superficial por S. aureus entre el 1 de junio de 2009 al 30 de junio de 2010. El estado de portador fue evaluado a través de la realización de muestra nasal. Se analizaron variables epidemiológicas, clínicas, tratamiento de la enfermedad y patrones de resistencia antimicrobiana. Resultados: Cohorte constituida por 146 sujetos con infecciones por S. aureus, de los cuales el 8,9% (13/146) presentaron infección por SARM, 38,5% de los cuales fueron adquiridos en la comunidad. El 53,8% de los sujetos con SARM presentó infección invasora. No se identificaron factores de riesgo para el desarrollo de infecciones por SARM. La prevalencia de portador nasal fue del 8,3%. Las tasas de resistencia a eritromicina y clindamicina fueron de 15,4%. Conclusiones: La incidencia de infecciones por SARM fue baja comparada con otras regiones. Se recomienda la vigilancia epidemiológica activa a fin de establecer guías de tratamiento basadas en criterios epidemiológicos locales (AU)

Introduction: Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are increasing worldwide. The clinical spectrum of the disease ranges from nasal colonization to superficial and invasive infections. Objectives: To describe the frequency, clinical characteristics and risk factors associated with MRSA disease in children under 15years old. To establish the prevalence of colonization and antimicrobial susceptibility of isolates. Material and methods: Retrospective study. Included subjects; aged 1 month to 15years old treated in the Hospital del Niño in Panama with invasive or superficial infection by S. aureus in the period from June 1, 2009 to June 30, 2010. Carrier status was assessed by performing nasal swabs. Demographic, clinical features, treatment of disease and antimicrobial resistance patterns. Results: A total of 146 subjects were collected with S.aureus infections, of which 8.9% (13/146) were infected by MRSA. Community-acquired MRSA accounted for 38.5% of the isolates. We did not identify any risk factors for developing MRSA infections. The prevalence of nasal carriage was 8.3%. The resistance rates to erythromycin and clindamycin were 15.4%. Conclusions: The incidence of MRSA infections was low compared with other regions. We recommend active surveillance in order to establish measures to prevent nosocomial infections and treatment guidelines based on local epidemiological criteria (AU)

[Methicillin-resistant Staphylococcus aureus disease in Panama]. / Enfermedad por Staphylococcus aureus resistente a meticilina en Panamá

INTRODUCTION: Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are increasing worldwide. The clinical spectrum of the disease ranges from nasal colonization to superficial and invasive infections. OBJECTIVES: To describe the frequency, clinical characteristics and risk factors associated with MRSA disease in children under 15 years old. To establish the prevalence of colonization and antimicrobial susceptibility of isolates. MATERIAL AND METHODS: Retrospective study. Included subjects; aged 1 month to 15 years old treated in the Hospital del Niño in Panama with invasive or superficial infection by S. aureus in the period from June 1, 2009 to June 30, 2010. Carrier status was assessed by performing nasal swabs. Demographic, clinical features, treatment of disease and antimicrobial resistance patterns. RESULTS: A total of 146 subjects were collected with S.aureus infections, of which 8.9% (13/146) were infected by MRSA. Community-acquired MRSA accounted for 38.5% of the isolates. We did not identify any risk factors for developing MRSA infections. The prevalence of nasal carriage was 8.3%. The resistance rates to erythromycin and clindamycin were 15.4%. CONCLUSIONS: The incidence of MRSA infections was low compared with other regions. We recommend active surveillance in order to establish measures to prevent nosocomial infections and treatment guidelines based on local epidemiological criteria.

Pharmacokinetics and safety of famciclovir in children with herpes simplex or varicella-zoster virus infection.

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 (approximately 12.5 mg/kg of body weight [BW] for children weighing < 40 kg and 500 mg for children weighing > or = 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 BW(0.696). 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.

[Economic impact of rotavirus vaccination in Panama]. / Impacto económico de la vacuna antirrotavirus en Panamá

INTRODUCTION: Rotavirus (RV) gastroenteritis (GE) causes a significant health and economic burden in Panama. The main objective of this study is to estimate the healthcare costs and the cost-effectiveness of vaccination in Panama from the societal perspective. METHODS: An economic model was constructed, using published epidemiological data, country-specific cost estimates, and vaccine efficacy data. The main outcome measures were disease burden, economic burden and the incremental cost-effectiveness ratio (US$/DALY and US$/life saved) of vaccination. RESULTS: In Panama, among children during the first five years of life, it is estimated that due to RV GE, 283 per 1,000 have a clinic visit, 24 per 1,000 are hospitalized, and 0.53 per 1,000 die. For every 1,000 children born, RV infection results in US$16,463 in total costs during their first five years of life. An estimated US$862,388 may be spent annually on treatment of outpatient and hospitalized cases in Panama. Vaccination would prevent 65% of the associated deaths, 68% of hospitalizations, 69% of outpatient visits and 65% of associated DALY (Disability Adjusted Life Years). From the societal perspective, RV vaccination produces a cost-effectiveness ratio of US$487 per DALY when the price of the vaccine is US$7.50 per dose. CONCLUSIONS: Vaccination can effectively reduce the disease burden and healthcare costs of RV GE in Panama.

Impacto económico de la vacuna antirrotavirus en Panamá / Economic impact of rotavirus vaccination in Panama

Introducción: La gastroenteritis (GE) por rotavirus (RV) contribuye a una carga significativa de enfermedad y costes en Panamá. El objetivo principal de este estudio fue evaluar la relación coste-efectividad de la vacuna antirrotavirus (anti-RV) en la población panameña menor de 5 años de edad. Material y métodos: Se utilizó un modelo económico que plantea el seguimiento de esta población objeto de estudio, basado en información epidemiológica, de eficacia de la vacuna y de costes. Se estimó el número de casos evitados de hospitalizaciones, consultas médicas y muertes tras la aplicación de la vacuna, al igual que el coste promedio de atención de los casos de GE por RV desde la perspectiva de la sociedad. La relación coste-efectividad de la vacuna anti-RV se evaluó considerando la disminución de años de vida ajustados por discapacidad (AVAD) tras el uso programático de la vacuna. Resultados: Un programa de vacunación anti-RV evitaría anualmente en Panamá alrededor de 24 muertes, 1.140 hospitalizaciones y 13.685 visitas médicas ambulatorias causadas por RV durante los primeros 5 años de vida. En Panamá se estima un gasto total medio de alrededor de 16.463 dólares para cada 1.000 niños que nacen anualmente como consecuencia de esta enfermedad. Un programa de vacunación anti-RV evitaría alrededor del 69 % de estos gastos. Para un precio estimado de vacuna de 7,50 dólares por dosis, se genera una relación coste-efectividad de 487 dólares por AVAD. Conclusiones: Los resultados de este estudio demuestran que la vacuna anti-RV puede ser una estrategia coste-efectiva en la prevención de GE por RV en Panamá (AU)

Introduction: Rotavirus (RV) gastroenteritis (GE) causes a significant health and economic burden in Panama. The main objective of this study is to estimate the healthcare costs and the cost-effectiveness of vaccination in Panama from the societal perspective. Methods: An economic model was constructed, using published epidemiological data, country-specific cost estimates, and vaccine efficacy data. The main outcome measures were disease burden, economic burden and the incremental cost-effectiveness ratio (US$/DALY and US$/life saved) of vaccination. Results: In Panama, among children during the first five years of life, it is estimated that due to RV GE, 283 per 1,000 have a clinic visit, 24 per 1,000 are hospitalized, and 0.53 per 1,000 die. For every 1,000 children born, RV infection results in US$16,463 in total costs during their first five years of life. An estimated US$862,388 may be spent annually on treatment of outpatient and hospitalized cases in Panama. Vaccination would prevent 65 % of the associated deaths, 68 % of hospitalizations, 69 % of outpatient visits and 65 % of associated DALY (Disability Adjusted Life Years). From the societal perspective, RV vaccination produces a cost-effectiveness ratio of US$487 per DALY when the price of the vaccine is US$7.50 per dose. Conclusions: Vaccination can effectively reduce the disease burden and healthcare costs of RV GE in Panama (AU)

[Seroprevalence of cytomegalovirus infection in puerperal women and its impact on their newborns]. / Seroprevalencia de la infección por citomegalovirus en puérperas y su impacto neonatal.

INTRODUCTION: Cytomegalovirus (CMV) is the most frequent etiologic agent associated with perinatal infections. The incidence of this infection is higher in developing countries. The seroprevalence of CMV infection among pregnant women and its impact on newborns have not been studied in Panama and there are a few publications on this health problem in Latin America. OBJECTIVE: The purpose of this study was to determine the seroprevalence of CMV infection in puerperal women and CMV-related morbidity in the neonates of seropositive mothers. PATIENTS AND METHODS: A total of 316 blood samples from puerperal women and 317 urine samples from their newborns were obtained to determine CMV IgG and the polymerase chain reaction CMV test respectively. Risk factors such as parity, socioeconomic status and educational level were analyzed. RESULTS: The seroprevalence of CMV was 84 % and the incidence of congenital CMV infection in the newborns of seropositive women was 0.8 %. Two cases of congenital CMV infection were diagnosed, one of which showed clinical signs at birth, but neither of the newborns showed neurological or audiological sequels in the first 11 months of life. There were no correlations between positive serology and parity, socioeconomic status or educational level in the mothers studied. CONCLUSIONS: Although neither of the newborns diagnosed with congenital CMV infection showed clinical signs at the time of this report, we believe that the incidence of 0.8 % found in this study should be kept in mind with a view to evaluating the possibility of including CMV diagnostic tests in neonatal screening and introducing measures to prevent seronegative mothers from becoming infected.

Seroprevalencia de la infección por citomegalovirus en puérperas y su impacto neonatal / Seroprevalence of cytomegalovirus infection in puerperal women and its impact on their newborns

Introducción El citomegalovirus (CMV) es el agente etiológico más común asociado a infección perinatal. La incidencia de esta afección neonatal es más elevada en países con nivel socioeconómico bajo. La seroprevalencia del CMV en las embarazadas panameñas y la incidencia de la infección congénita son desconocidas, son también escasos los informes al respecto publicados en Latinoamérica. Objetivo El objetivo de este estudio es determinar la seroprevalencia de la infección por CMV en puérperas y la potencial morbilidad en los hijos de madres seropositivas. Pacientes y métodos Se tomaron 316 muestras de sangre a mujeres puérperas para determinación de inmunoglobulina G (IgG) para CMV y 317 muestras de orina a sus neonatos para prueba de reacción en cadena de la polimerasa (PCR) para CMV. Además se analizaron presuntos factores de riesgo tales como paridad, nivel socioeconómico y nivel educativo. Resultados Se encontró una seroprevalencia de CMV 84 % y una incidencia de 0,8 % de CMV congénito en mujeres seropositivas. Se diagnosticaron 2 casos de infección congénita por CMV, uno de los cuales presentó signos clínicos al nacimiento, pero ninguno de ellos presentó secuelas auditivas o en el neurodesarrollo en sus primeros 11 meses de vida. No se documentó asociación de serología positiva con la paridad, nivel socioeconómico ni educación de la madre. Conclusión Aunque ninguno de los niños diagnosticados con infección congénita por CMV en nuestro estudio presentó secuelas de la misma al momento de este informe, consideramos que la incidencia de infección congénita encontrada de 0,8 % debe ser tomada en cuenta para evaluar la posibilidad de incluir las pruebas diagnósticas para CMV dentro del tamizaje neonatal e implementar medidas educativas para evitar la exposición a posibles fuentes de este virus en madres seronegativas

Introduction Cytomegalovirus (CMV) is the most frequent etiologic agent associated with perinatal infections. The incidence of this infection is higher in developing countries. The seroprevalence of CMV infection among pregnant women and its impact on newborns have not been studied in Panama and there are a few publications on this health problem in Latin America. Objective The purpose of this study was to determine the seroprevalence of CMV infection in puerperal women and CMV-related morbidity in the neonates of seropositive mothers. Patients and methods A total of 316 blood samples from puerperal women and 317 urine samples from their newborns were obtained to determine CMV IgG and the polymerase chain reaction CMV test respectively. Risk factors such as parity, socioeconomic status and educational level were analyzed. Results The seroprevalence of CMV was 84 % and the incidence of congenital CMV infection in the newborns of seropositive women was 0.8 %. Two cases of congenital CMV infection were diagnosed, one of which showed clinical signs at birth, but neither of the newborns showed neurological or audiological sequels in the first 11 months of life. There were no correlations between positive serology and parity, socioeconomic status or educational level in the mothers studied. Conclusions Although neither of the newborns diagnosed with congenital CMV infection showed clinical signs at the time of this report, we believe that the incidence of 0.8 % found in this study should be kept in mind with a view to evaluating the possibility of including CMV diagnostic tests in neonatal screening and introducing measures to prevent seronegative mothers from becoming infected

[Dengue infection in children and adolescents in Panama]. / Dengue pediátrico en Panamá.

BACKGROUND: Dengue is a serious emerging infectious disease and constitutes a major international health concern. MATERIAL AND METHODS: All reports of confirmed dengue infection in patients aged less than 18 years old between 2000 and 2005 were included. A confirmed diagnosis was established by culture of the virus within the first 3 days of symptom onset or by serologic assays 5-30 days after symptom onset. Clinical and epidemiological features were analyzed. RESULTS: A total of 457 patients were included (57.6 % female). The median age was 13 years (IQR 5 6). A greater number of cases were detected in urban areas and during the rainy season (May-November). Two epidemics were reported in 2001 (33.9 %) and the first eight months of 2005 (23.1 %). The most prevalent symptoms were fever (95.2 %), severe headache (74.2 %), chills (65.9 %), rash (63.5 %), myalgias (51.9 %) and retro-orbital pain (51.6 %). No significant differences were found between male and female patients. Significant differences in clinical features were found when the patients were divided into 3 groups; < 5 years old, 6-10 years old and > 10 years old. Fifty-three percent of the patients had had previous contact with a dengue-infected individual. There were 7 patients with dengue hemorrhagic fever, 4 of whom died. CONCLUSIONS: Dengue virus infection is still a major health problem in Panama. To achieve effective control of dengue, further epidemiological studies, such as our own, are needed to design appropriate preventive measures.

Persistente presencia de dengue en el trópico / Persistente of Dengue in the tropics

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Dengue pediátrico en Panamá / Dengue infection in children and adolescents in Panama

Antecedentes El dengue es una enfermedad infecciosa emergente, considerada actualmente como un problema de salud pública mundial. Material y métodos Se incluyeron en el estudio todos los casos positivos de dengue confirmados de pacientes menores de 18 años, durante los años 2000-2005. En las muestras recibidas en los primeros 3 días de la enfermedad se aisló el virus mediante cultivo y en las recibidas entre los días 5-30 por serología. Se analizaron las características clínicas y epidemiológicas de los pacientes. Resultados Se incluyeron 457 pacientes (57,6 % niñas). La mediana de edad fue de 13 años (rango interquartílico 5 6). Se detectó un predominio de la infección en las zonas urbanas y en los meses de mayo-noviembre. Se registraron 2 epidemias en los años 2001 (33,9 %) y primeros 8 meses de 2005 (23,1 %). Las manifestaciones clínicas más frecuentes fueron: fiebre (95,2 %); cefalea (74,2 %); escalofríos (65,9 %); exantema (63,5 %); mialgias (51,9 %), y dolor retroorbitario (51,6 %). No se observaron diferencias significativas según el sexo pero sí al dividir a los pacientes en grupos de edad; menores de 5 años, 6-10 años y mayores de 10 años. En el 53,0 % de los pacientes se registró el antecedente de contacto con otro sujeto infectado en los 15 días previos. Se diagnosticaron 7 casos de dengue hemorrágico de los cuales cuatro murieron. Conclusiones En Panamá el dengue continúa siendo un importante problema de salud pública. Para conseguir un control efectivo de la infección es preciso realizar estudios epidemiológicos, que como el nuestro, contribuyan a diseñar estrategias preventivas adecuadas

Background Dengue is a serious emerging infectious disease and constitutes a major international health concern. Material and methods All reports of confirmed dengue infection in patients aged less than 18 years old between 2000 and 2005 were included. A confirmed diagnosis was established by culture of the virus within the first 3 days of symptom onset or by serologic assays 5-30 days after symptom onset. Clinical and epidemiological features were analyzed. Results A total of 457 patients were included (57.6 % female). The median age was 13 years (IQR 5 6). A greater number of cases were detected in urban areas and during the rainy season (May-November). Two epidemics were reported in 2001 (33.9 %) and the first eight months of 2005 (23.1 %). The most prevalent symptoms were fever (95.2 %), severe headache (74.2 %), chills (65.9 %), rash (63.5 %), myalgias (51.9 %) and retro-orbital pain (51.6 %). No significant differences were found between male and female patients. Significant differences in clinical features were found when the patients were divided into 3 groups; 10 years old. Fifty-three percent of the patients had had previous contact with a dengue-infected individual. There were 7 patients with dengue hemorrhagic fever, 4 of whom died. Conclusions Dengue virus infection is still a major health problem in Panama. To achieve effective control of dengue, further epidemiological studies, such as our own, are needed to design appropriate preventive measures

Impacto de la infección neumocócica invasora en niños / Impact of invasive pneumococcal infection in children

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Cefepime in the empiric treatment of meningitis in children.

BACKGROUND: Because the introduction of extended spectrum cephalosporins into pediatric practice offers a number of choices for treatment, we review efficacy studies of cefepime monotherapy in the treatment of bacterial meningitis in children. METHODS: Two open, randomized, comparative studies assessed the efficacy of cefepime empiric monotherapy in the treatment of bacterial meningitis in 345 pediatric patients. These studies were conducted in Latin America and compared cefepime (50 mg/kg/dose every 8 h) with either cefotaxime (50 mg/kg/dose every 6 h) or ceftriaxone (50 mg/kg/dose every 12 h). Patients 2 months to 14 years old who had clinical signs and symptoms consistent with a central nervous system infection were enrolled. Efficacy was based on clinical and bacteriologic response. RESULTS: Integrated results from the Latin American studies indicated a 75% cure rate with cefepime vs. a 78% cure rate with comparator, among evaluable patients. Overall the rate of treatment failure was 12%. Haemophilus influenzae had the highest bacterial eradication rate (97% overall), and rates were comparable in cefepime and comparator arms. Eradication rates for Neisseria meningitidis were equally high in both treatment arms (95% overall), and the eradication rate for Streptococcus pneumoniae was 92% overall. Of the patients with S. pneumoniae isolated during pretreatment (from either cerebrospinal fluid or blood), 11 (16 isolates in total) had their isolates tested against penicillin and all were susceptible. Presence or absence of seizures, level of consciousness, Glasgow Coma Score and duration of signs and symptoms were strong predictors of outcome. Collectively no specific safety concerns were identified. CONCLUSION: Cefepime represents an important therapeutic option for the empiric treatment of bacterial meningitis in children, based on the good clinical response and bacteriologic eradication rates observed in this review.

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. The CNAA3006 Study Team.

OBJECTIVES: Abacavir (ABC) is a potent inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase. We compared the efficacy, safety, and tolerability of combination therapy with ABC, lamivudine (3TC), and zidovudine (ZDV) versus 3TC and ZDV in antiretroviral experienced HIV-1-infected children over 48 weeks. METHODS: Two hundred five HIV-1-infected children who had received previous antiretroviral therapy and had CD4(+) cell counts >/=100 cells/mm(3) were stratified by age and by previous treatment. Participants were randomly assigned to receive ABC (8 mg/kg twice daily [BID]) plus 3TC (4 mg/kg BID) and ZDV (180 mg/m(2) BID; ABC/3TC/ZDV group) or ABC placebo plus 3TC (4 mg/kg BID) and ZDV (180 mg/m(2); 3TC/ZDV group). Participants who met a protocol-defined switch criteria (plasma HIV-1 RNA >0.5 log(10) copies/mL above baseline at week 8 or >10 000 copies/mL after week 16) had the option to switch to open-label ABC plus any antiretroviral combination or continue randomized therapy or withdraw from the study. RESULTS: The Kaplan-Meier estimates (95% confidence interval) of the proportion of participants who maintained HIV-1 RNA levels 10 000 copies/mL, a significantly higher proportion of participants in the ABC/3TC/ZDV group had HIV-1 RNA

[Clinical and virological correlation between the cerebrospinal fluid and blood of HIV-infected children]. / Correlación clinica y virológica entre el liquido cefalo-raquideo y la sangre de niños infectados por el HIV-1.

BACKGROUND: Although the neurological manifestations of HIV infection occur at any age, children with perinatal AIDS are affected earlier and with greater impact. There are no published data about a potential association between HIV encephalopathy and viral load in THE CSF OF the pediatric population. DESIGN: Twenty-three children, aged 7 months to 10 years, were studied as part of a multicenter international study that evaluated double versus triple antiretroviral therapy. Samples of CSF and plasma were collected for HIV RNA measurements on day 0 and on follow-up weeks 8, 16, and 48. Neurological assessments, psychological evaluations, and CT scans were done on admission and at study end. Viral isolates were processed for genotypic resistance. RESULTS: No correlation between viral load in CSF and plasma was detected at study onset. Eighty percent of children had >2 log HIV RNA in CSF at day 0 but only 30% at week 16. Eight subjects responded favorably to therapy and their CSF had undetectable viral load during follow-up determinations. On day 0, 72% of children had identical patterns of genotypic resistance in CSF and plasma samples. At week 48, however, only 11% of these subjects had identical patterns. On day 0, 83% of children had abnormal neurological findings but these alterations declined to 35% at week 48 (p = 0.004). Most children with neurological abnormalities had detectable CSF viral loads (65% vs 17%, p = 0.04). CONCLUSIONS: The data generated in this study suggest that CSF and plasma behave as two different body compartments in terms of HIV dynamics and resistance mutants. Presence of neurological abnormalities correlate with detection of HIV in CSF and these alterations improve as therapy decreases CSF viral load. These results underscore the importance of using ARV drugs with good CNS penetration for optimal management of HIV-infected young children.

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 $699,543 (US dollars) during 1995 and 1996 to $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.

Antimicrobial and anti-inflammatory treatment of bacterial meningitis.

Mortality and morbidity rates of bacterial meningitis are still unacceptably high, and thus, new, potent antimicrobial agents and adjuvant anti-inflammatory strategies are being evaluated to improve patient outcome. With the declining rates of Haemophilus influenzae type B infections, after the introduction of conjugated vaccines, research to find preventive measures for Streptococcus pneumoniae and Neisseria meningitidis infections is underway. In the meantime, scientific effort is being directed optimally to treat disease caused by multiresistant pneumococcal strains.

Safety and pharmacokinetics of an intramuscular humanized monoclonal antibody to respiratory syncytial virus in premature infants and infants with bronchopulmonary dysplasia. The MEDI-493 Study Group.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory disease in infants and children. MEDI-493 (palivizumab, Synagis) is a humanized monoclonal IgG1 antibody to the fusion protein of RSV, and it is highly active in vitro against RSV A and B strains. OBJECTIVE: To describe the safety, tolerance, immunogenicity and pharmacokinetics of monthly intramuscular injections of MEDI-493 among premature infants and children with bronchopulmonary dysplasia and to compare these data with information previously obtained with intravenous dosing. DESIGN: A Phase I/II multicenter, open label, escalating dose clinical trial. PATIENT POPULATION AND DOSING REGIMEN: Children (n=65) born prematurely at < or =35 weeks of gestation who were < or =6 months of age (n=41) and children with bronchopulmonary dysplasia who were < or =24 months of age (n=24) were enrolled. From 1 to 5 monthly injections were given at doses of 5 mg/kg (n=11), 10 mg/kg (n=6) and 15 mg/kg (n=48). Serum was collected before administration of each dose, 30 days after the last dose, and 2, 7 and 14 days after the first and second doses for measurement of MEDI-493 concentrations by enzyme-linked immunosorbent assay. RESULTS: The pharmacokinetics of MEDI-493 were similar to those of other human IgG1 antibodies. Mean serum MEDI-493 concentrations were 91.1 microg/ml (range, 52.3 to 174.0) 2 days after the initial dose of 15 mg/kg and 49.2 microg/ml (range, 13.5 to 132.0) at 30 days. Monthly dosing of 15 mg/kg maintained mean trough concentrations of approximately 70 microg/ml. These concentrations were similar to previously published trough concentrations after i.v. administration. MEDI-493 injections were well-tolerated. Only three children had adverse events judged to be possibly related to MEDI-493. Ten children had transient, low titer anti-MEDI-493 binding titers (1:10 to 1:40) which were not associated with a pattern of specific adverse events or alterations of MEDI-493 concentrations. Two patients in the 5-mg/kg dose group were hospitalized for RSV; no RSV hospitalizations were found in the higher dose groups. CONCLUSIONS: MEDI-493 was safe and well-tolerated. Monthly intramuscular doses of 15 mg/kg maintained mean trough serum concentrations that were above 40 microg/ml (the value associated with 99% reduction of pulmonary RSV in the cotton rat model). These concentrations were similar to those previously reported with i.v. administration of MEDI-493.