摘要:

Objective.To assess genotypic and phenotypic resistance testing in HIV-1-infected children failing a first protease inhibitor (PI) therapy.Methods.In a multicenter observational study 21 children, ages 3 to 16 years, were given two reverse transcriptase inhibitors and one PI (mainly ritonavir,n= 18). They were subsequently treated with single or dual PI-based therapy (predominantly nelfinavir,n= 10, or ritonavir-saquinavir,n= 7). Resistance testing was performed at the time of therapy switch via direct sequencing and a recombinant virus susceptibility assay.Results.A total of 21 genotypic and 15 phenotypic resistance profiles were obtained. Most viruses displayed several reverse transcriptase mutations; however, 7 isolates maintained a wild-type protease. Ritonavir targeted the well-known pathway containing 82, 54, 46 and other secondary (nonactive site) mutations includingT74A. Noin vitrocross-resistance, i.e. ≥8-fold resistance to saquinavir or amprenavir, was encountered. Secondary mutations enhanced the prediction of ritonavir resistance (i.e.L10I) andin vitronelfinavir cross-resistance (i.e.K20R/I) conferred by primary (active site) resistance mutations. Either the 82, 54, 46 mutational genotype or the phenotype showing ≥8-fold nelfinavir cross-resistance predicted a poorer virologic response to nelfinavir salvage therapy.Conclusion.In a small cohort of heavily pretreated pediatric patients, resistance testing appears to predict the response to nelfinavir as salvage for a ritonavir-based therapy. This is further supported by the correlation between ritonavir-selected mutations andin vitronelfinavir cross-resistance. Prospective studies should assess clinical outcome in children undergoing regimen changes based on resistance testing.

ISSN:0891-3668    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.Although rotaviruses (RVs) are the most common cause of severe gastroenteritis in children, there is a lack of information detailing the spectrum of clinical manifestations of RV disease resulting in hospitalization.Objective.To characterize the clinical spectrum of RV-associated hospitalizations, including short stay visits in children.Methods.Active RV disease surveillance was conducted at three children’s hospitals Sundays through Thursdays in children 15 days through 4 years of age admitted with diarrhea (D), vomiting (V) and/or unexplained fever (F) between November, 1997, and June, 1998. Stool specimens were collected and tested for RV by enzyme immunoassay.Results.Of the 862 children enrolled, 763 (88%) had a stool specimen tested for RV. Overall 31% of children excreted RV. RV excretion was highest when all 3 symptoms (D, V and F) occurred in the same child (56%), lower when 2 symptoms occurred together (38% DV; 19% DF; 13% VF) and lowest when each symptom occurred alone (3% D; 11% V; 6% F). Nine percent of the children without diarrhea excreted RV. Children admitted without diarrhea were more likely to have rotavirus if they developed diarrhea during their hospitalization.Conclusions.RV detection was greatest when diarrhea, vomiting and fever occurred together and lowest when each symptom occurred alone. The spectrum of symptoms of rotavirus disease in children at the time of admission to the hospital or short stay unit may be broader than previously recognized.

ISSN:0891-3668    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.Cumulative incidence of infections in the first year posttransplantation in adult patients has been well-described. Such description is less than complete for pediatric stem cell transplantation (SCT) patients. Further among those patients who have been infected, analysis of risk factors for infection has not been well-described for a large cohort of pediatric SCT patients.Methods.We conducted a retrospective cohort study of infections in the first year after SCT at Duke University Medical Center. We recorded all infections in the first year after transplantation. We determined incidences for 6 categories of infection: Gram-negative rods; Gram-positive cocci; yeast species;Aspergillussp.; adenovirus; and cytomegalovirus. We determined incidences based on type of transplant and days post transplantation. We also completed bivariable and multivariable analysis of risk factors [neutropenia, graftvs.host disease (GVHD) and GVHD treatment] for infection type among those children who were infected.Results.We evaluated 510 transplants in 485 children. There were 584 infections in the first year after transplantation. During the first 30 days posttransplantation, type of transplantation did not predict incidence of infection or type of infection. After 30 days children who received unrelated cord blood transplant and matched unrelated donor transplant were at much higher risk of infection than were patients who received autologous, matched sibling or haploidentical transplant (P< 0.001). Patients who received unrelated cord blood or matched unrelated donor transplantation were at higher risk of aspergillosis (P= 0.002), candidiasis (P= 0.005) and adenovirus (P< 0.0001) but not cytomegalovirus (P= 0.18). In analysis of risk factors among those infected, patients with aspergillosis were more likely to have severe GVHD: multivariable 1 year risk ratio, 7.5; 95% confidence interval, 3.0,18.4. Neutropenia was more strongly associated with Gram-negative rod infection than any other type of infection.Conclusions.The incidence of infection immediately after transplantation did not differ significantly by type of transplant in this pediatric population. Type of transplant predicted increased incidence of infection 30 days posttransplantation and increased incidence of infection with several organisms traditionally associated with a high mortality rate in the transplant population.

ISSN:0891-3668    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.Several dosing schedules for gentamicin have been recommended for very low birth weight infants during the early neonatal period. We conducted a prospective, randomized, controlled trial to compare efficacy and pharmacokinetics of two dosing schedules in preterm neonates.Methods.Fifty-eight very low birth weight infants (600 to 1500 g), prescribed gentamicin for treatment of suspected sepsis during the first week after birth, were randomized to receive either the new dosing schedule [every 48 h (q48h)] or the existing dosing schedule [every 24 h (q24h)]. Infants in the “q48h” group received gentamicin at 5.0 or 4.5 mg/kg/dose q48h depending on weight group and infants in the “q24h” group received 2.5 or 3.0 mg/kg/dose q24h. Peak and trough serum gentamicin concentrations were monitored.Results.Peak serum gentamicin concentrations after the first dose were significantly higher in the q48h infants than in q24h infants (8.19 ± 1.3vs.6.04 ± 2.2,P= 0.00001). Ninety percent of all peak serum gentamicin concentrations in the q48h group were in a higher therapeutic range of 6 to 12 &mgr;g/ml as compared with 55% of q24h (P= 0.0005). None of the q48h infants had subtherapeutic serum gentamicin concentrations immediately after administration of the first dose as compared with 36% of q24h infants (P< 0.005). Eighteen percent of q24h infants continued to have peak serum gentamicin concentrations in subtherapeutic range even after the third dose at 48 h. Trough serum gentamicin concentrations were significantly lower in q48h infants than in q24h infants. However, 9 of 30 (30%) q48h infants had trough serum gentamicin concentrations of ≤0.5 &mgr;g/ml before the dose at 48 h and 4 of the 9 had serum gentamicin concentrations of <1 &mgr;g/ml at 24 h after the first dose.Conclusions.The q48h dosing schedule of gentamicin given to very low birth weight infants during the first week after birth achieved therapeutic serum gentamicin concentrations and potentially higher peak to MIC ratios for microorganisms in all infants. However, nearly one-third of the infants had extremely low serum gentamicin concentrations before the next dose. A dosing interval of 36 h might be optimal for bactericidal activity and avoid bacterial growth during prolonged periods of extremely low serum gentamicin concentrations; this dosing interval warrants study.

ISSN:0891-3668    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Objective.To describe the safety and efficacy of voriconazole in children treated within the compassionate release program.Methods.Children received voriconazole on a compassionate basis for treatment of an invasive fungal infection if they were refractory to or intolerant of conventional antifungal therapy. Voriconazole was administered as a loading dose of 6 mg/kg every 12 h iv on Day 1 followed by 4 mg/kg every 12 h iv thereafter. When feasible the route of administration of voriconazole was changed from iv to oral (100 or 200 mg twice a day for patients weighing <40 or ≥40 kg, respectively). Outcome was assessed by investigators at the end of therapy or at the last visit as success (complete or partial response), stable infection, or failure, based on protocol-defined criteria.Results.Sixty-nine children (ages 9 months to 15 years; median, 7 years) received voriconazole; 58 had a proven or probable fungal infection. Among these 58 patients 27 had hematologic malignancies and 13 had chronic granulomatous disease as the most frequent underlying conditions. Forty-two patients had aspergillosis, 8 had scedosporiosis, 4 had invasive candidiasis and 4 had other invasive fungal infections. The median duration of voriconazole therapy was 93 days. At the end of therapy 26 patients (45%) had a complete or partial response. Four patients (7%) had a stable response, 25 (43%) failed therapy and 4 (7%) were discontinued from voriconazole because of intolerance. Success rates were highest in patients with chronic granulomatous disease (62%) and lowest in patients with hematologic malignancies (33%). Two patients experienced treatment-related serious adverse events (ulcerated lips with rash, elevated hepatic transaminases or bilirubin). A total of 23 patients had voriconazole-related adverse events, 3 (13%) of which caused discontinuation of voriconazole therapy. The most commonly reported adverse events included elevation in hepatic transaminases or bilirubin (n= 8), skin rash (n= 8), abnormal vision (n= 3) and a photosensitivity reaction (n= 3).Conclusion.These data support the use of voriconazole for treatment of invasive fungal infections in pediatric patients who are intolerant of or refractory to conventional antifungal therapy.

ISSN:0891-3668    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.The observation of an increased prevalence of allergic disorders coinciding with a decreasing frequency of infectious diseases in early childhood has led to the speculation that infections may prevent allergic sensitization. Information on the role of parasites in this context is limited. Bronchiolitis in infancy has been linked with asthmatic symptoms later in childhood, although the underlying cause of this association is unknown.Methods.To test the hypothesis that early parasitic infections in infancy might prevent the development of allergic manifestations later in life, the effect of malaria infections during the first year of life on the risk of bronchiolitis was studied in 675 Tanzanian children at 18 months of age. The study was conducted as part of an intervention trial of malaria chemoprophylaxis and/or iron supplementation for the prevention of malaria and anemia in infants.Results.The incidence of bronchiolitis up to 18 months of age in the 675 children was 0.58 episode per child per year. The risk factors analysis was based on 470 children with complete data. There was no difference in the incidence of bronchiolitis between those who had received malaria chemoprophylaxis during the first year of life and those who had not. However, the proportion of children who had bronchiolitis was lower among those who had had malaria episodes than among those who had not (48%vs.55%,P= 0.05).Conclusions.This study does not support the hypothesis that reduced exposure to parasites may modulate the development of bronchiolitis early in life.

ISSN:0891-3668    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0891-3668    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0891-3668    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0891-3668    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0891-3668    

出版商:OVID    

年代:2002

数据来源: OVID