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  • 1
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    Respiratory Syncytial Virus (RSV) Immune Globulin Intravenous Therapy for RSV Lower Respiratory Tract Infection in Infants and Young Children at High Risk for Severe RSV Infections
    American Academy of Pediatrics (AAP) ; 1997
    In:  Pediatrics Vol. 99, No. 3 ( 1997-03-01), p. 454-461
    Details
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 99, No. 3 ( 1997-03-01), p. 454-461
    Abstract: Objectives. To evaluate the efficacy of high-titer intravenous respiratory syncytial virus immune globulin (RSVIG) in the treatment of children at high risk for severe RSV infection who were hospitalized with proven RSV. Methods. Infants and young children younger than 2 years with bronchopulmonary dysplasia, chronic lung disease, congenital heart disease, or prematurity ( & lt;32 weeks' gestational age), hospitalized with a history of lower respiratory tract infection (LRI) of less than 4 days, were enrolled in this study. Patients were randomized in a blinded fashion to receive either 1500 mg/kg RSVIG or placebo in equal volumes. They were evaluated daily for safety and respiratory scores and for RSV nasal shedding. Results. One hundred seven high-risk children were randomized—54 in the RSVIG group and 53 in the placebo group. Of these children, 51 in each group were considered evaluable. Children with pulmonary disease, congenital heart disease, or prematurity were equally distributed between the two treatment groups. However, two important differences were found in baseline variables between the two groups: there were more patients in the placebo group who had histories of previous LRI and there was a trend toward more severe disease at study entry in the RSVIG group. This was manifested by a higher entry respiratory score in the RSVIG group than in the placebo group (3.4 ± 0.2 vs 3.1 ± .01). A higher proportion of children in the RSVIG group (47%) than in the placebo group (28%) required intensive care at entry and mechanical ventilation at study entry (31% RSVIG-treated vs 18% placebo-treated patients). No significant difference was found between groups in the mean unadjusted duration of hospitalization (RSVIG group, 9.10 ± 1.18 days; control group, 8.17 ± 1.08 days). When the mean was adjusted for entry respiratory score, likewise, no difference was observed between each group (8.41 ± 0.97 vs 8.89 ± .99 days). The lack of efficacy observed in the study primary endpoint was observed in all diagnostic groups. No differences between the RSVIG and placebo groups were observed in the following secondary endpoints: duration of intensive care unit stay, duration of intensive care unit stay for RSV, mechanical ventilation, or supplemental oxygen. No significant differences in adverse events were reported in the RSVIG group (16 children) when compared with the control group (10 children). Conclusion. RSVIG treatment was safe but not efficacious in the treatment of children with bronchopulmonary dysplasia, congenital heart disease, or premature gestation who were hospitalized with RSV LRI.
    Type of Medium: Online Resource
    ISSN: 1098-4275 , 0031-4005
    URL: Article
    DOI: 10.1542/peds.99.3.454
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 1997
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  • 2
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    Respiratory Syncytial Virus Immune Globulin Treatment of RSV Lower Respiratory Tract Infection in Previously Healthy Children
    American Academy of Pediatrics (AAP) ; 1997
    In:  Pediatrics Vol. 100, No. 6 ( 1997-12-01), p. 937-942
    Details
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 100, No. 6 ( 1997-12-01), p. 937-942
    Abstract: Objective. To evaluate the efficacy of high titer respiratory syncytial virus (RSV) immune globulin (RSVIG) in the treatment of previously healthy children hospitalized with proven RSV lower tract infection (LRI). Method. Infants and young children ≤2 years of age with RSV LRI of ≤4 days duration, and respiratory scores ≥2.5 were enrolled. Results. One hundred and one previously healthy children hospitalized with RSV LRI received either 1500 mg/kg of RSVIG (RespiGam, MedImmune Inc, Gaithersburg, MD) or albumin placebo in a randomized, double-blind, placebo-controlled trial. Forty-six RSVIG and 52 recipients of placebo met all eligibility criteria. Demographic characteristics of the two groups were similar. More RSVIG recipients (46% vs 29%) had an SaO2 ≤85% at entry than did placebo recipients, but a higher proportion of placebo recipients required intensive care unit (ICU) care and mechanical ventilation at study entry. The mean RSV hospital stay was 5.52 ± 0.69 days (SE) for placebo and 4.58 ± 0.40 days for RSVIG. Additionally, there was an interaction between treatment group and entry respiratory score, which led to subgroup analysis. Children with modest respiratory illness did not receive any benefit from RSVIG therapy. RSVIG recipients with more severe illness (entry respiratory scores ≥3.0) had 1.6 fewer hospital days and 2.7 days less ICU stays. Conclusion. RSVIG infusions seemed safe and generally well tolerated. Although some beneficial effect trends were seen for those with more severe disease who were treated there was no evidence that treatment with RSVIG resulted in reduced hospitalization and reduced ICU stays in all children with RSV disease.
    Type of Medium: Online Resource
    ISSN: 1098-4275 , 0031-4005
    URL: Article
    DOI: 10.1542/peds.100.6.937
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 1997
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  • 3
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    13-Valent Pneumococcal Conjugate Vaccine (PCV13) in Preterm Versus Term Infants
    American Academy of Pediatrics (AAP) ; 2015
    In:  Pediatrics Vol. 135, No. 4 ( 2015-04-01), p. e876-e886
    Details
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 135, No. 4 ( 2015-04-01), p. e876-e886
    Abstract: This study evaluated the immune response and safety profile of 13-valent pneumococcal conjugate vaccine (PCV13) in preterm infants compared with term infants. METHODS: This Phase IV, open-label, 2-arm, multicenter, parallel-group study enrolled 200 healthy infants (preterm, n = 100; term, n = 100) aged 42 to 98 days. All subjects received PCV13 at ages 2, 3, 4 (infant series), and 12 (toddler dose [TD]) months, together with routine vaccines (diphtheria-tetanus-acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b vaccine and meningococcal group C conjugate vaccine). RESULTS: Most subjects achieved an anticapsular immunoglobulin G (IgG) antibody concentration ≥0.35 μg/mL for all serotypes: & gt;85% after the infant series (except preterm infants for serotypes 5, 6A, and 6B) and & gt;97% after TD (except for serotype 3). Preterm infants had overall lower IgG geometric mean concentrations compared with term infants; however, geometric mean fold increases after TD were similar for all serotypes. Opsonophagocytic activity results were consistent with IgG results and titers increased after TD in both groups for all serotypes, including serotype 3. PCV13 was generally well tolerated, with similar safety profiles in all preterm subgroups. CONCLUSIONS: Immune responses were lower in preterm infants than in term infants. However, the majority of subjects in both groups achieved both pneumococcal serotype-specific IgG antibody levels after the infant series that exceeded the World Health Organization–established threshold of protection and functional antibody responses. Responses were uniformly higher after TD, reinforcing the importance of a timely booster dose. PCV13 was well tolerated regardless of gestational age.
    Type of Medium: Online Resource
    ISSN: 0031-4005 , 1098-4275
    URL: Article
    DOI: 10.1542/peds.2014-2941
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2015
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  • 4
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    Immunogenicity and Safety of 13-Valent Pneumococcal Conjugate Vaccine in Infants and Toddlers
    American Academy of Pediatrics (AAP) ; 2010
    In:  Pediatrics Vol. 126, No. 3 ( 2010-09-01), p. e493-e505
    Details
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 126, No. 3 ( 2010-09-01), p. e493-e505
    Abstract: 7-Valent pneumococcal conjugate vaccine (PCV7 [Prevnar, Wyeth Pharmaceuticals Inc, Philadelphia, PA], serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) is effective in preventing vaccine-serotype pneumococcal disease. 13-Valent pneumococcal conjugate vaccine (PCV13) (PCV7 serotypes plus 1, 3, 5, 6A, 7F, and 19A) was designed to provide broader pneumococcal disease coverage. We evaluated the immunogenicity and safety of PCV13 compared with PCV7. METHODS: Infants received PCV13 or PCV7 at ages 2, 4, 6, and 12 to 15 months with routine pediatric vaccinations. Pneumococcal anticapsular polysaccharide-binding immunoglobulin G responses and functional antipneumococcal opsonophagocytic activity were assessed 1 month after dose 3, before the toddler dose, and 1 month after the toddler dose. Safety and tolerability were also assessed. RESULTS: For the 7 common serotypes, PCV13-elicited immunoglobulin G titers were noninferior to those elicited by PCV7, although PCV13 responses were generally somewhat lower. PCV13 also elicited functional opsonophagocytic activity comparable with that elicited by PCV7. For the 6 additional serotypes in PCV13, PCV13 elicited binding and functional antibody levels notably greater than those in PCV7 recipients. After PCV13 immunization, concordance between antipolysaccharide and opsonophagocytic responses was noted for all 13 serotypes. The PCV13 toddler dose resulted in higher immune responses compared with infant-series doses. Safety and tolerability were comparable; reactogenicity was generally mild. CONCLUSIONS: PCV13 will be as effective as PCV7 in the prevention of pneumococcal disease caused by the 7 common serotypes and could provide expanded protection against the 6 additional serotypes. The PCV13 safety profile was comparable to that of PCV7.
    Type of Medium: Online Resource
    ISSN: 0031-4005 , 1098-4275
    URL: Article
    DOI: 10.1542/peds.2009-3027
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2010
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  • 5
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    Safety and Tolerability of Cold-Adapted Influenza Vaccine, Trivalent, in Infants Younger Than 6 Months of Age
    American Academy of Pediatrics (AAP) ; 2008
    In:  Pediatrics Vol. 121, No. 3 ( 2008-03-01), p. e568-e573
    Details
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 121, No. 3 ( 2008-03-01), p. e568-e573
    Abstract: OBJECTIVE. Young children are at high risk for influenza-related complications. Vaccination of close household contacts is recommended to provide indirect protection to children & lt;6 months of age. Studies have shown that live, cold-adapted influenza vaccine, trivalent, is efficacious in children. To assess the risks associated with inadvertent exposure of infants to vaccine viruses from vaccinated contacts, this study was designed to evaluate the safety and tolerability of cold-adapted influenza vaccine, trivalent, administered intranasally to healthy children 6 to & lt;24 weeks of age. METHODS. Healthy infants aged 6 to & lt;16 weeks and 16 to & lt;24 weeks, respectively, were randomly assigned to receive 2 doses of influenza vaccine, or placebo intranasally 35 ± 7 days apart. Reactogenicity events were monitored for 11 days after each dose. Other adverse events were monitored through 28 to 35 days after dose 2. RESULTS. Of the infants aged 6 to & lt;16 weeks, 31 received influenza vaccine and 28 received placebo, and of those aged 16 to & lt;24 weeks, 30 received influenza vaccine and 31 received placebo. In the 6- to & lt;16-week cohort, more influenza vaccine, recipients experienced irritability (66.7% vs 35.7%) and runny nose or nasal congestion (63.3% vs 33.3%) after dose 1 but not dose 2. There were no significant increases in any other reactogenicity events or adverse events in the vaccine recipients compared with the placebo group. CONCLUSIONS. Although there was an increase in mild reactogenicity events in children 6 to & lt;16 weeks of age, cold-adapted influenza vaccine, trivalent, was generally well tolerated in infants 6 to & lt;24 weeks of age. These findings support further evaluation of cold-adapted influenza vaccine, trivalent, in infants & lt;6 months of age.
    Type of Medium: Online Resource
    ISSN: 0031-4005 , 1098-4275
    URL: Article
    DOI: 10.1542/peds.2007-1405
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2008
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  • 6
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    Twenty Years of Outpatient Respiratory Syncytial Virus Infection: A Framework for Vaccine Efficacy Trials
    American Academy of Pediatrics (AAP) ; 1997
    In:  Pediatrics Vol. 99, No. 2 ( 1997-02-01), p. e7-e7
    Details
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 99, No. 2 ( 1997-02-01), p. e7-e7
    Abstract: Background. Respiratory syncytial virus (RSV) is the most important viral respiratory pathogen of infancy and childhood. Much has been written about inpatients with severe disease. Inpatients, however, represent only a minority of RSV-infected children. We studied the characteristics of symptomatic outpatient RSV infection in healthy children to gain a better understanding of RSV disease and to provide a background for the testing of intervention strategies in children without high-risk conditions. Methods. A total of 1113 children were followed during 20 consecutive RSV seasons. Signs and symptoms of respiratory infection were monitored. Cultures were obtained for febrile upper respiratory infection, acute otitis media, and lower respiratory infection (LRI). Rates of febrile upper respiratory infection, acute otitis media, LRI, and hospitalization were calculated. Given those rates, numbers of children needed to demonstrate efficacy of a vaccine product were calculated. Results. Mild disease from RSV infection lacked some of the classic features of RSV infection seen in hospitalized children. Involvement of the lower respiratory tract was, however, noted to be much higher in RSV infection than it was in infection with other viral respiratory pathogens. LRI was, therefore, considered the best candidate endpoint for vaccine trials. A product with 60% efficacy could be proven, with a power of 0.8, to be efficacious with as few as 1500 infants. Conclusions. RSV infection is common and often involves the lower respiratory tract, even in outpatients. Our 20-year study of RSV infection provides a basis for calculation of sample sizes to be used in trials of vaccine candidates. respiratory syncytial virus, outpatient, epidemiology, vaccine, bronchiolitis.
    Type of Medium: Online Resource
    ISSN: 1098-4275 , 0031-4005
    URL: Article
    DOI: 10.1542/peds.99.2.e7
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 1997
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  • 7
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    Natural History of Neonatal Herpes Simplex Virus Infections in the Acyclovir Era
    American Academy of Pediatrics (AAP) ; 2001
    In:  Pediatrics Vol. 108, No. 2 ( 2001-08-01), p. 223-229
    Details
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 108, No. 2 ( 2001-08-01), p. 223-229
    Abstract: During the 2 decades in which effective antiviral therapies have been available for neonatal herpes simplex virus (HSV) disease, changes have been documented not only in the outcomes of infected infants, but also in the natural history of the disease itself. Numerous studies previously have reported that early institution of antiviral therapy is beneficial to the outcome of the disease. The objective of this study was to provide an update of neonatal HSV disease to identify means by which future improvements in the management of HSV-infected neonates can be made. Design/Methods. Neonates enrolled in 2 studies of parenteral acyclovir for the treatment of neonatal HSV disease provided the data source. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted the studies between 1981 and 1997. A total of 186 patients are summarized, all of whom were treated with acyclovir. Demographic and clinical characteristics of these patients are reported. Results. Comparisons between patients treated in the periods between 1981–1988 and 1989–1997 according to extent of disease revealed that the mean time between the onset of disease symptoms and initiation of therapy has not changed significantly from the early 1980s to the late 1990s. Of all patients evaluated, 40% had fetal scalp monitors during the delivery process. A significant minority of patients did not have skin vesicles at the time of their presentation and did not develop them during the acute HSV disease (39% of patients with disseminated disease; 32% of patients with central nervous system [CNS] disease; and 17% of patients with skin, eye, and/or mouth disease). Among patients with CNS disease, mortality was associated with prematurity. Among patients with disseminated HSV disease treated with acyclovir at 30 mg/kg/d, mortality was associated with aspartate transaminase elevations of ≥10 times the upper limit of normal at the time of initiation of acyclovir therapy. Mortality was also associated with lethargy at initiation of antiviral therapy for patients with disseminated disease. Patients' morbidity status was associated with the extent of disease (skin, eye, and/or mouth disease vs CNS vs disseminated). For those patients with CNS disease, morbidity was also associated with seizures at initiation of antiviral therapy. Conclusion. Data presented in the current comparison of neonatal HSV disease over the 2 periods (1981–1988 vs 1989–1997) demonstrate that no progress has been made in decreasing the interval between onset of HSV symptoms and initiation of antiviral therapy. Additional strides in the improvement of disease outcome may occur only if the interval between onset of symptoms and initiation of therapy is shortened. The means by which this will be accomplished lie in increased consideration of neonatal HSV infections in acutely ill infants. Specific data and recommendations to facilitate this goal are contained within.
    Type of Medium: Online Resource
    ISSN: 1098-4275 , 0031-4005
    URL: Article
    DOI: 10.1542/peds.108.2.223
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2001
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  • 8
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    Safety and Immunogenicity of a 13-Valent Pneumococcal Conjugate Vaccine
    American Academy of Pediatrics (AAP) ; 2010
    In:  Pediatrics Vol. 125, No. 5 ( 2010-05-01), p. 866-875
    Details
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 125, No. 5 ( 2010-05-01), p. 866-875
    Abstract: Invasive pneumococcal disease rates have declined since immunization with 7-valent pneumococcal conjugate vaccine (PCV7) (Prevenar/Prevnar [Wyeth Pharmaceuticals, Philadelphia, PA] ) became routine. Certain nonvaccine Streptococcus pneumoniae serotypes (1, 3, 5, 6A, 7F, and 19A) still cause significant morbidity and mortality. The safety and immunogenicity of PCV7 were compared with those of 13-valent PCV (PCV13), which contains saccharides from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F conjugated to CRM197. PATIENTS AND METHODS: Infants were randomly assigned to receive PCV13 or PCV7 at ages 2, 4, and 6 months with other vaccines. Post–third-dose antibodies to each pneumococcal polysaccharide were measured by immunoglobulin G enzyme-linked immunosorbent assay. Antibacterial functional antibodies were measured by opsonophagocytic assay (OPA). RESULTS: Subjects received PCV13 (n = 122) or PCV7 (n = 127). All PCV13 serotypes were immunogenic, with 88% to 98% of infants achieving antibody concentrations of ≥0.35 μg/mL to shared PCV7 serotypes. For the 6 additional serotypes, 97% to 100% of PCV13-vaccinated infants achieved antibody concentrations of ≥0.35 μg/mL. Geometric mean antibody concentration for PCV13 recipients ranged from 1.32 μg/mL (serotype 23F) to 4.26 μg/mL (serotype 14). The ratio of OPA geometric mean titers for the 7 shared serotypes (PCV13:PCV7) ranged from 0.6 to 1.4, suggesting no clinically meaningful differences. For PCV13-only serotypes, OPA geometric mean titers were significantly higher in the PCV13 group than in the PCV7 group. Local reactions and systemic events were similar between groups. CONCLUSIONS: PCV13 was well tolerated and immunogenic, with most infants developing antipolysaccharide antibody concentrations of ≥0.35 μg/mL, as well as OPA responses, to each of the 13 serotypes.
    Type of Medium: Online Resource
    ISSN: 0031-4005 , 1098-4275
    URL: Article
    DOI: 10.1542/peds.2009-1405
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2010
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  • 9
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    Safety, Efficacy, and Effectiveness of Cold-Adapted Influenza Vaccine-Trivalent Against Community-Acquired, Culture-Confirmed Influenza in Young Children Attending Day Care
    American Academy of Pediatrics (AAP) ; 2006
    In:  Pediatrics Vol. 118, No. 6 ( 2006-12-01), p. 2298-2312
    Details
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 118, No. 6 ( 2006-12-01), p. 2298-2312
    Abstract: OBJECTIVE. The goal was to evaluate the safety, tolerability, and efficacy of an investigational, refrigerator-stable formulation of live attenuated influenza vaccine (cold-adapted influenza vaccine-trivalent) against culture-confirmed influenza, acute otitis media, and effectiveness outcomes in young children in day care over 2 consecutive influenza seasons. METHODS. Children 6 to & lt;36 months of age who were attending day care were assigned randomly in year 1 to receive 2 doses of vaccine or placebo intranasally, 35 ± 7 days apart. In year 2, subjects received 1 dose of the same treatment as in year 1. RESULTS. A total of 1616 subjects (vaccine: 951 subjects; placebo: 665 subjects) in year 1 and 1090 subjects (vaccine: 640 subjects; placebo: 450 subjects) in year 2 were able to be evaluated for efficacy. The mean age at first vaccination was 23.4 ± 7.9 months. In year 1, the overall efficacy of the vaccine against influenza subtypes similar to the vaccine was 85.4%; efficacy was 91.8% against A/H1N1 and 72.6% against B. In year 2, the overall efficacy was 88.7%; efficacy was 90.0% against H1N1, 90.3% against A/H3N2, and 81.7% against B. Efficacy against all episodes of acute otitis media associated with culture-confirmed influenza was 90.6% in year 1 and 97.0% in year 2. Runny nose or nasal discharge after dose 1 in year 1 was the only reactogenicity event that was significantly more frequent with cold-adapted influenza vaccine-trivalent (82.3%) than placebo (75.4%). CONCLUSIONS. Cold-adapted influenza vaccine-trivalent was well tolerated and effective in preventing culture-confirmed influenza illness in children as young as 6 months of age who attended day care.
    Type of Medium: Online Resource
    ISSN: 0031-4005 , 1098-4275
    URL: Article
    DOI: 10.1542/peds.2006-0725
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2006
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  • 10
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    Safety and Efficacy of High-Dose Intravenous Acyclovir in the Management of Neonatal Herpes Simplex Virus Infections
    American Academy of Pediatrics (AAP) ; 2001
    In:  Pediatrics Vol. 108, No. 2 ( 2001-08-01), p. 230-238
    Details
    In: Pediatrics, American Academy of Pediatrics (AAP), Vol. 108, No. 2 ( 2001-08-01), p. 230-238
    Abstract: The objective of this investigation was to establish the safety of high-dose (HD) acyclovir for the treatment of neonatal herpes simplex virus (HSV) disease. In addition, an estimate of therapeutic efficacy was sought, both with respect to mortality and to morbidity. Virologic efficacy of HD acyclovir was also assessed. Participants. Infants who were ≤28 days old and whose disease was considered to be caused by HSV were enrolled in this study. Patients with central nervous system (CNS; N = 28) or disseminated (N = 41) HSV infection were offered participation in the trial. A small number of patients with HSV disease limited to the skin, eyes, or mouth (SEM; N = 10) or whose disease was clinically consistent with HSV but who did not have virologic confirmation of infection (N = 9) also were enrolled on a compassionate basis. Only patients with virologically confirmed HSV disease were included in efficacy analyses. All enrolled patients were included in safety analyses. Methods. The study was an open-label evaluation of intravenous acyclovir at dosages higher than the 30 mg/kg/d standard dosage approved by the US Food and Drug Administration. The first 16 patients enrolled received intermediate-dose (ID) acyclovir (45 mg/kg/d), and the next 72 patients received HD acyclovir (60 mg/kg/d). Acyclovir was administered in 3 divided daily doses for 21 days. Neonates were assessed prospectively throughout treatment and at scheduled follow-up visits for the first 4 years of life. Data were compared with those of a previous National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial in which patients received standard-dose (SD) acyclovir for 10 days and in which identical methods (with the exception of acyclovir dosage and duration of therapy) were used. Results. Six (21%) of 29 HD acyclovir recipients whose HSV disease remained localized to the SEM or CNS experienced neutropenia. One of the 6 had an absolute neutrophil count & lt;500/mm3, and 5 patients had an absolute neutrophil count (ANC) between 500/mm3 and 1000/mm3. In all 6 cases, the ANC recovered during continuation of acyclovir at the same dosage or after completion of acyclovir therapy, and there were no apparent adverse sequelae of the transient neutropenia. No other drug-related adverse events were reported among ID or HD recipients, and no other laboratory aberrations could be correlated specifically with antiviral therapy. The survival rate for the patients with disseminated HSV disease treated with HD acyclovir was significantly higher than for those in the previous study treated with SD acyclovir, with an odds ratio (OR) of 3.3 (95% confidence interval [CI]: 1.4–7.9). For patients with CNS disease, however, survival rates were similar for the HD and SD groups. To assess the effect of HD acyclovir on survival for the entire population with neonatal HSV disease, the Cox proportional hazards regression analysis was performed with stratification for disease category (CNS versus disseminated). In performing this analysis, differences in mortality for each disease category were weighted to allow statistical comparison of the treatment dosage groups (HD, ID, and SD). This analysis indicated that the survival rate for patients treated with HD acyclovir was statistically significantly higher than for patients treated with SD acyclovir (OR: 3.3; 95% CI: 1.5–7.3). Recipients of HD acyclovir had a borderline significant decrease in morbidity compared with SD recipients, after stratification for the extent of disease (SEM vs CNS vs disseminated) and controlling for the potential confounding factors of HSV type (HSV-1 vs. HSV-2), prematurity, and disease severity (seizures). Patients treated with HD acyclovir were 6.6 times (adjusted OR; 95% CI: 0.8–113.6) as likely to be developmentally normal at 12 months of age as patients treated with SD therapy. Conclusion. These data support the use of a 21-day course of HD (60 mg/kg/d) intravenous acyclovir to treat neonatal CNS and disseminated HSV disease. Throughout the course of HD acyclovir therapy, serial ANC determination should be made at least twice weekly. Decreasing the acyclovir dosage or administering granulocyte colony-stimulating factor should be considered if the ANC remains below 500/mm3 for a prolonged period.
    Type of Medium: Online Resource
    ISSN: 1098-4275 , 0031-4005
    URL: Article
    DOI: 10.1542/peds.108.2.230
    Language: English
    Publisher: American Academy of Pediatrics (AAP)
    Publication Date: 2001
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