[Show abstract][Hide abstract] ABSTRACT: Background: Congenital CMV infection is a leading cause of sensorineural hearing loss (SNHL) and neurodevelopmental impairment in childhood. Information on CMV detection in cerebrospinal fluid (CSF) and its association with outcomes is limited. The objective of this study was to determine the significance of CMV detection in CSF of infants with congenital CMV infection.
Methods: Retrospective review of cases of congenital CMV infection diagnosed at Nationwide Children’s Hospital, Parkland Memorial Hospital/Children’s Medical Center Dallas, and the University of Oklahoma Health Sciences Center from 1996-2014. Diagnosis of congenital CMV was made by culture or PCR from urine or saliva within the first 3 weeks of age. Detection of CMV in CSF was performed by culture or PCR. Clinical, laboratory, radiographic, and audiologic data was reviewed. Infants in whom CMV was detected in CSF were compared to those whose CSF was negative for CMV.
Results: Twenty-two infants with congenital CMV infection who had a lumbar puncture performed and CSF tested for CMV were enrolled. All 22 infants had clinically apparent ("symptomatic") disease. 10 (45%) infants had CMV detected in CSF (CSF+) and were compared to the 12 infants whose CSF was CMV-negative (CSF-). The CSF+ infants did not differ from those whose CSF was CMV negative (CMV-) in age at diagnosis (median/range; 1.5 [1-8] vs.1 [1-17]; p>0.05), platelet count (p=0.47), alanine aminotransferase (p=0.11), direct bilirubin concentration (p=0.08), or CSF analyses including white blood cell count (p=0.98), protein content(p=0.39), or glucose concentration (p=0.31). Of the CSF+ infants, 6 (60%) had SNHL, while 10 (83%) CSF- infants had SNHL. Abnormalities on CNS imaging studies, either ultrasound/CT/MRI, were comparable between groups.
Conclusion: CMV was frequently detected in CSF of infants with clinically apparent congenital CMV infection. However, its detection was not associated with increased rate of SNHL or neuroimaging abnormalities. Larger studies that incorporate neurodevelopmental assessments are needed to determine the potential role of CSF evaluation in the management of infants with congenital CMV infection.
[Show abstract][Hide abstract] ABSTRACT: SCB34 is a sequence type 131, highly invasive, multidrug-resistant Escherichia coli isolate that produced neonatal bacteremia. Whole-genome sequencing was performed using a 250-bp library on the Illumina MiSeq
platform; 5,910,264 reads were assembled de novo using the A5 assembly pipeline. The total contig length was 5,227,742 bp; the RAST server was used for annotation.
Full-text · Article · May 2014 · Genome Announcements
[Show abstract][Hide abstract] ABSTRACT: Objectives:
The objective of this study was to describe the clinical characteristics of neonates with Escherichia coli bacteremia and the antibiotic resistance pattern of the bacterial isolates. We assessed the isolates' genetic relatedness and virulence phenotypic characteristics in vitro.
A total of 24 neonates with E. coli bacteremia were identified prospectively in a tertiary-care hospital. Clinical and antibiotic resistance data were investigated. The E. coli isolates were analyzed by multilocus sequence typing (MLST); the presence of the K1 capsule and their ability to invade intestinal epithelial cells were also assessed.
Most newborns were very low birth weight infants. Overall, 75% of the isolates were ampicillin resistant and 17% were gentamicin and tobramycin nonsusceptible. MLST determined sequence types 95 and 131 (ST95 and ST131) predominated, with ST131 becoming significantly more prevalent recently. The K1 capsule was present in 50% of the isolates. ST131 isolates and those producing bacteremia in newborns younger than 7 days showed a highly invasive phenotype.
Resistance to antibiotics currently used empirically to treat newborns is present in bacteremia-producing E. coli. Clonal spread among newborns of multidrug-resistant E. coli is possible; therefore, continued surveillance is needed. Identification of additional virulence factors associated with increased invasion in neonatal E. coli strains is important and further studies are warranted.
No preview · Article · Feb 2014 · American Journal of Perinatology
[Show abstract][Hide abstract] ABSTRACT: Background: Escherichia coli is the most common cause of Gram negative neonatal sepsis. E. coli invasion of intestinal epithelium is thought to be involved in the translocation process preceding bacteremia. The efficiency of E. coli neonatal isolates to invade intestinal epithelial cells is not known. Our objective was to assess the intestinal epithelial invasion in vitro ability of E. coli neonatal isolates causing early-onset sepsis (EOS) and late-onset sepsis (LOS).
Methods:Twenty E.coli clinical isolates were collected each from a newborn with bacteremia. The clinical isolates, the prototype E.coli K1 strain RS218, its non-capsulated mutant (K1 neg), and a non-pathogenic E. coli strain, DH5α, were studied for growth in vitro in both rich nutrient and cell tissue culture media. Epithelial invasion of each strain was assessed by infecting cultured intestinal T84 cells followed by a gentamicin protection assay to recover intracellular bacteria. Percent invasion (bacteria recovered /bacteria inoculated×100 =% invasion) was compared among isolates. The presence of K1 antigen was determined by a latex agglutination test. Multi-locus sequence typing (MLST) was done in 8 clinical isolates.
Results:N=8 isolates caused EOS, <72 hrs after birth. N=12 newborns ages 6-39 days old had LOS. A newborn in each group was born term, the other 18 were born at 24-35 weeks gestation age. N=3 neonates with EOS and n=5 with LOS died. In vitro growth analysis showed similar growth of EOS and LOS clinical isolates, RS218, K1 neg, and DH5α in both media. Mean percent invasion of EOS isolates was 0.46% (SD±0.25%), significantly greater than for LOS which had mean invasion of 0.24% (SD±0.16%), p=0.045. Mean percent invasion of RS218 and DH5α was 0.47% (SD±0.32%) and 0.11% (SD±0.02%), respectively; K1 neg invasion was similar than for RS218. 50% of the clinical isolates in each group were K1 antigen positive. MLST showed 7 different types, 2 strains shared the same type as RS218.
Conclusion:E. coli isolates causing bacteremia in newborns in both EOS and LOS have different invasive capabilities of intestinal epithelial cells. Specific genetic determinants associated with increased intestinal invasion and translocation in a larger sample of E. coli neonatal isolates need further study.
[Show abstract][Hide abstract] ABSTRACT: To measure systemic haptoglobin (HPT) concentrations from birth in preterm (PT) and T newborns. To compare HPT in newborns without hemolysis or infection with values in bacteremic newborns.
HPT was measured using enzyme-linked immunosorbent assay in 30 PT and 28 T newborns without hemolysis or infection at birth (cord blood), on days of life 2 to 4, and at 1 to 2 weeks of life. Concentrations were measured in eight additional newborns with bacteremia. Wilcoxon-Mann-Whitney test was used for comparisons.
HPT concentrations were consistently measurable from birth in PT and T neonates. Values were significantly greater in 2- to 4-day-old PT and T newborns than in newborns at birth (P<0.01). Bacteremic newborns had higher HPT concentrations than newborns without infection (P=0.033).
HPT is detectable from birth in PT and T newborns. HPT concentrations increase in bacteremic newborns. HPT levels may have clinical utility in the evaluation of neonatal sepsis.
No preview · Article · Jan 2011 · Journal of perinatology: official journal of the California Perinatal Association
[Show abstract][Hide abstract] ABSTRACT: Vaccines have saved the lives of millions of children and continue to be essential interventions to control infectious diseases among people of all ages. The list of recommended vaccines for children has expanded in recent years; however, many viral, bacterial and parasitic infections remain a major cause of morbidity and mortality in children. Improved vaccines to prevent Streptococcus pneumoniae and Neisseria meningitidis infections in children will soon be available. Recent scientific advances are being applied to design new childhood vaccines affording enhanced efficacy, safety and tolerability. Financial barriers and other obstacles to adequate vaccine access need to be eliminated to assure coverage for all children and adolescents.
No preview · Article · Sep 2010 · The American Journal of the Medical Sciences
[Show abstract][Hide abstract] ABSTRACT: Antibiotics are among the most frequently used drugs in children. Although antibacterials have been available for decades, many agents have not been studied to assess their safety and efficacy in the pediatric population. This article describes the pharmacologic characteristics and therapeutic use of the most commonly prescribed antibacterials for pediatric patients. Newer agents currently under clinical investigation are discussed as well.
Preview · Article · Dec 2009 · Infectious disease clinics of North America
[Show abstract][Hide abstract] ABSTRACT: Several studies have described a clear association between respiratory syncytial virus (RSV) lower respiratory tract infection in infancy and the subsequent development of persistent wheezing in children. Using the mouse model we demonstrated that RSV induces long-term airway disease characterized by chronic airway inflammation and airway hyperreactivity (AHR). The RSV murine model offers great advantages to study the immunopathogenesis of RSV-induced long-term airway disease. Mice can be challenged with aerosolized methylcholine to determine the presence of AHR. We can apply the reverse transcription-polymerase chain reaction assay (RT-PCR) to detect RSV RNA in the respiratory tract and we can perform lung gene expression analysis to further characterize the chronic changes induced by RSV infection. Compared with sham-inoculated controls, RSV-infected mice developed chronic airway disease characterized by AHR and persistent airway inflammation. Forty-two days after RSV infection, a time point when RSV could no longer be isolated, RT-PCR demonstrated, quite unexpectedly, the presence of RSV RNA in the lower respiratory tract of mice. The presence of genomic RNA persisted for months after inoculation. Furthermore, preliminary studies also demonstrated that on day 42 there were a number of genes differentially expressed in RSV-infected mice compared with controls. RSV-infected mice with persistent AHR exhibited presence of abnormal chronic inflammatory changes, altered gene expression profiles, and persistence of RSV RNA, which may contribute to long-term airway disease induced by RSV. Future studies are needed to define the significance of persistent RSV RNA in the mouse model, and its potential role in the pathogenesis of RSV-induced persistent wheezing in children.
Full-text · Article · Oct 2008 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: Risk factors for severe respiratory syncytial virus (RSV) disease include prematurity, congenital heart disease, chronic lung disease, and immunocompromised states. There is no consensus concerning the most effective therapy for severe RSV infection in high-risk patients. Palivizumab is approved for prevention of RSV disease, and ribavirin is approved for treatment of RSV infections but its efficacy in high-risk patients has not been conclusively established.
Retrospective chart review of RSV infected children treated with intravenous palivizumab and ribavirin in a pediatric hospital from 2001 to 2005.
: Twenty male and 11 female patients with a median age of 23.4 months, hospitalized for RSV infection were treated with intravenous palivizumab from October 2001 through July 2005. Mean dose was 14.93 (SD = 0.68) mg/kg. Twenty-five patients (80%) also received ribavirin, 22 of whom by aerosolization. Common baseline diagnoses were malignancy (n = 15), congenital heart disease (n = 5), and prematurity (n = 5). Included above are 1 cardiac and 6 hematopoietic stem cell transplant recipients. Eighteen (58%) patients had signs of lower respiratory tract infection, 17 were hypoxemic, 10 required intensive care unit (ICU) admission, and 5 were intubated. Twenty-nine (93.6%) patients survived and 2 died. No adverse events attributed to intravenous palivizumab or ribavirin administration were observed.
Treatment of RSV-infected high-risk children with intravenous palivizumab alone or in combination with ribavirin was well tolerated and associated with decreased mortality compared with previous reports.
Full-text · Article · Jan 2008 · The Pediatric Infectious Disease Journal
[Show abstract][Hide abstract] ABSTRACT: Prevalence of Panton-Valentine leukocidin (PVL) toxin, SCCmec, and accessory gene regulator (agr) types were studied in 197 community-acquired methicillin-resistant Staphylococcus aureus (MRSA) from children in Texas. The majority of pediatric macrolide-resistant clindamycin-susceptible community-associated MRSA belonged to PVL(+)/SCC type IV/agr type I group with msrA gene encoding for macrolide resistance. PVL(-)/SCC type II/agr type II strains, although rare, were consistently present in the community throughout the study period.
No preview · Article · Nov 2007 · Diagnostic Microbiology and Infectious Disease
[Show abstract][Hide abstract] ABSTRACT: Our aim was to obtain knowledge of how meteorological conditions affect community epidemics of respiratory syncytial virus (RSV) infection. To this end we recorded year-round RSV activity in nine cities that differ markedly in geographic location and climate. We correlated local weather conditions with weekly or monthly RSV cases. We reviewed similar reports from other areas varying in climate. Weekly RSV activity was related to temperature in a bimodal fashion, with peaks of activity at temperatures above 24-30 degrees C and at 2-6 degrees C. RSV activity was also greatest at 45-65% relative humidity. RSV activity was inversely related to UVB radiance at three sites where this could be tested. At sites with persistently warm temperatures and high humidity, RSV activity was continuous throughout the year, peaking in summer and early autumn. In temperate climates, RSV activity was maximal during winter, correlating with lower temperatures. In areas where temperatures remained colder throughout the year, RSV activity again became nearly continuous. Community activity of RSV is substantial when both ambient temperatures and absolute humidity are very high, perhaps reflecting greater stability of RSV in aerosols. Transmission of RSV in cooler climates is inversely related to temperature possibly as a result of increased stability of the virus in secretions in the colder environment. UVB radiation may inactivate virus in the environment, or influence susceptibility to RSV by altering host resistance.
Full-text · Article · Nov 2007 · Epidemiology and Infection
[Show abstract][Hide abstract] ABSTRACT: Motavizumab (MEDI-524) is a monoclonal antibody with enhanced neutralizing activity against RSV. In mice, motavizumab suppressed RSV replication which resulted in significant reduction of clinical parameters of disease severity. We evaluated the effect of motavizumab on the local and systemic immune response induced by RSV in the mouse model. Balb/c mice were intranasally inoculated with 106.5 PFU RSV A2 or medium. Motavizumab was given once intraperitoneally (1.25 mg/mouse) as prophylaxis, 24 h before virus inoculation. Bronchoalveolar lavage (BAL) and serum samples were obtained at days 1, 5 (acute) and 28 (long-term) post inoculation and analyzed with a multiplex assay (Beadlyte Upstate, NY) for simultaneous quantitation of 18 cytokines: IL-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, KC (similar to human IL-8), IL-10, IL-12p40, IL-12p70, IL-13, IL-17, TNF-alpha, MCP-1, RANTES, IFN-gamma and GM-CSF. Overall, cytokine concentrations were lower in serum than in BAL samples. By day 28, only KC was detected in BAL specimens at low concentrations in all groups. Administration of motavizumab significantly reduced (p < 0.05) BAL concentrations of IL-1alpha, IL-12p70 and TNF-alpha on day 1, and concentrations of IFN-gamma on days 1 and 5 compared with RSV-infected untreated controls. In the systemic compartment, the concentrations of IL-10, IFN-gamma and KC were significantly reduced in the motavizumab-treated mice compared with the untreated controls. In summary, prophylactic administration of motavizumab was associated with significant reductions on RSV replication and concentrations of cytokine and chemokines, which are likely related to the improvement observed in clinical markers of disease severity.
[Show abstract][Hide abstract] ABSTRACT: Publicación ISI Email : email@example.com Background. Respiratory syncytial virus (RSV) and influenza virus are common causes of infantile lower respiratory tract infection (LRTI). It is widely believed that both viral replication and inappropriately enhanced immune responses contribute to disease severity. In infants, RSV LRTI is known to be more severe than influenza virus LRTI. Methods. We compared cytokines and chemokines in secretions of infants surviving various forms of respiratory illness caused by RSV or influenza viruses, to determine which mediators were associated with more-severe illness. We analyzed lung tissue from infants with fatal cases of RSV and influenza virus LRTI to determine the types of inflammatory cells present. Autopsy tissues were studied for the lymphotoxin granzyme and the apoptosis marker caspase 3. Results. Quantities of lymphocyte-derived cytokines were minimal in secretions from infants with RSV infection. Concentrations of most cytokines were greater in influenza virus, rather than RSV, infection. Lung tissues from infants with fatal RSV and influenza virus LRTI demonstrated an extensive presence of viral antigen and a near absence of CD8-positive lymphocytes and natural killer cells, with marked expression of markers of apoptosis. Conclusions. Severe infantile RSV and influenza virus LRTI is characterized by inadequate (rather than excessive) adaptive immune responses, robust viral replication, and apoptotic crisis.
Full-text · Article · May 2007 · The Journal of Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Mycoplasma pneumoniae is a leading cause of pneumonia and is associated with asthma. Evidence links M. pneumoniae respiratory disease severity with interleukin-12 (IL-12) concentration in respiratory secretions. We evaluated the microbiologic, inflammatory, and pulmonary function indices of M. pneumoniae pneumonia in IL-12 (p35) knockout (KO) mice and wild-type (WT) mice to determine the role of IL-12 in M. pneumoniae respiratory disease. Eight-week-old wild-type BALB/c mice and 8-week-old IL-12 (p35) KO BALB/c mice were inoculated once intranasally with 10(7) CFU of M. pneumoniae. Mice were evaluated at days 2, 4, and 7 after inoculation. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic scores (HPS), BAL cytokine concentrations determined by enzyme-linked immunosorbent assay (tumor necrosis factor alpha [TNF-alpha], gamma interferon [IFN-gamma], IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor) and plethysmography, before and after methacholine, to assess airway obstruction (AO) and airway hyperreactivity (AHR). IL-12 (p35) KO mice infected with M. pneumoniae were found to have significantly lower BAL M. pneumoniae concentrations compared with M. pneumoniae-infected WT mice. Lung HPS and the parenchymal pneumonia subscores (neutrophilic alveolar infiltrate), as well as AO, were significantly lower in infected KO mice. No difference was found for AHR. Infected KO mice had significantly lower BAL concentrations of IFN-gamma than WT mice; a trend toward lower BAL concentrations was observed for IL-10 (P = 0.065) and TNF-alpha (P = 0.078). No differences were found for IL-1beta, IL-2, IL-4, IL-5, or IL-6. The lack of IL-12 in experimental M. pneumoniae pneumonia was associated with less severe pulmonary disease and more rapid microbiologic and histologic resolution.
Full-text · Article · Feb 2007 · Infection and Immunity
[Show abstract][Hide abstract] ABSTRACT: Clarithromycin is postulated to possess immunomodulatory properties in addition to its antimicrobial activity.
To evaluate the effect of clarithromycin on serum and nasopharyngeal cytokine and chemokine concentrations in children with an acute exacerbation of recurrent wheezing.
Children with a history of recurrent wheezing or asthma and who presented with an acute exacerbation of wheezing were enrolled in a double-blind, randomized trial of clarithromycin vs placebo. Concentrations of tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, RANTES, eotaxin, macrophage inflammatory protein 1alpha, macrophage inflammatory protein 1beta, and monocyte chemoattractant protein 1 were measured in serum and/or nasopharyngeal aspirates before, during, and after therapy. Mycoplasma pneumoniae and Chlamydophila pneumoniae infection were evaluated for by polymerase chain reaction and serologic testing.
Nasopharyngeal concentrations of TNF-alpha, IL-1beta, and IL-10 were significantly and persistently lower in children treated with clarithromycin compared with placebo. There tended to be a greater effect of clarithromycin on nasopharyngeal cytokine concentrations in patients with evidence of M. pneumoniae or C. pneumoniae infection. No significant differences were detected in serum cytokines for children treated with clarithromycin compared with placebo.
Clarithromycin therapy reduces mucosal TNF-alpha, IL-1beta, and IL-10 concentrations in children with an acute exacerbation of recurrent wheezing.
Full-text · Article · Nov 2006 · Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology
[Show abstract][Hide abstract] ABSTRACT: Mycoplasma pneumoniae infection has been associated with chronic lung disease. Treatment of chronic pulmonary mycoplasmosis has not been well investigated. BALB/c mice were intranasally inoculated once with M. pneumoniae or with sterile media (uninfected controls). Infected mice were treated with telithromycin or placebo daily for 10 days in the chronic phase of disease (18 months after inoculation). Mice (n=43) were evaluated before therapy and 1 day after completion of telithromycin. Treatment of infected mice with telithromycin at 18 months after infection significantly reduced chronic pulmonary histological inflammation compared with infected mice given placebo; however, this treatment did not improve airway obstruction or airway hyperresponsiveness. Therapy longer than 10 days may be necessary to improve pulmonary function.
Full-text · Article · Oct 2006 · International Journal of Antimicrobial Agents
[Show abstract][Hide abstract] ABSTRACT: Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness in infants and children worldwide and is responsible for over 120 000 annual hospitalizations in infants in the US alone. RSV is also recognized as a major respiratory viral pathogen in the elderly and other high-risk populations. Bronchiolitis, pneumonia, apnea, respiratory failure, and death are well known manifestations of severe acute RSV disease. RSV infection has also been associated with recurrent wheezing in children, but the mechanisms involved in this association are not completely understood. The host immune response plays a significant role in controlling the infection but is likely also involved in augmenting the disease through pathways that have not been completely identified. The treatment options for RSV infection are very limited. Ribavirin, corticosteroids, and bronchodilators are not used routinely because they have not proven to be sufficiently effective. Education of caregivers, strict handwashing, and avoidance of exposure to environmental factors associated with severe forms of RSV infection are among the most effective preventive means. Passive immunization with monoclonal antibodies provides protection against severe RSV disease in high-risk children. Clinical trials to evaluate the safety and efficacy of a second-generation monoclonal antibody are underway. Efforts to develop a safe and effective RSV vaccine have continued despite the poor outcomes observed following the administration of formalin-inactivated formulations in the 1960s. In the last decade, live attenuated vaccines (including those developed by recombinant techniques) and purified subunit vaccines have all been evaluated in humans. Results of clinical trials have been encouraging, but the availability of a safe and effective RSV vaccine is not a reality yet. Better prevention strategies will have an impact, not only on acute morbidity caused by RSV, but will also likely have an effect on ameliorating the chronic consequences of this disease.
Full-text · Article · Feb 2006 · Treatments in Respiratory Medicine
[Show abstract][Hide abstract] ABSTRACT: Respiratory syncytial virus (RSV) is the leading viral pathogen responsible for bronchiolitis and pneumonia in infants and young children worldwide. We have previously shown in the mouse model that treatment with an anti-RSV neutralizing monoclonal antibody (MAb) against the F glycoprotein of RSV, palivizumab, decreased lung inflammation, airway obstruction, and postmethacholine airway hyperresponsiveness. MEDI-524, or Numax, is a new MAb derived from palivizumab with enhanced neutralizing activity against RSV. We compared the effects of these two MAbs on different markers of disease severity using the murine model of RSV infection. BALB/c mice were intranasally inoculated with RSV A2. Palivizumab or MEDI-524 was administered once at either 24 h before or 48 h after RSV inoculation. Regardless of the time of administration, all treated mice showed significantly decreased RSV loads in bronchoalveolar lavage samples measured by plaque assay. Only MEDI-524 given at -24 h significantly decreased lung RSV RNA loads on days 5 and 28 after RSV inoculation. Pulmonary histopathologic scores, airway obstruction, and postmethacholine airway hyperresponsiveness were significantly reduced in mice treated with MEDI-524 at 24 h before inoculation, compared with untreated controls and the other regimens evaluated. MEDI-524 was superior to palivizumab on several outcome variables of RSV disease assessed in the mouse model: viral replication, inflammatory and clinical markers of acute disease severity, and long-term pulmonary abnormalities.
Full-text · Article · Dec 2005 · Antimicrobial Agents and Chemotherapy