Epidemiology, Clinical and Microbiologic Profile and Risk Factors for Inpatient Mortality in Pediatric Severe Sepsis in the United States From 2003 to 2014: A Large Population Analysis.

OBJECTIVE: To evaluate the national trends in pediatric severe sepsis in the United States from 2003 to 2014. STUDY DESIGN: For this study, we included nonoverlapping years of Kids Inpatient database and National Inpatient Sample database while including hospitalizations of children between 1 and 20 years of age from more than 4200 hospitals across the United States. We identified patient hospitalizations with severe sepsis using specific ICD codes and modified Angus Criteria. Trend analysis of various factors associated with severe sepsis was calculated using the Cochrane-Armitage test. Associated foci of infection and comorbid conditions were identified using specific ICD codes, and a multivariate regression analysis with death as outcome variable was done to evaluate for in hospital predictors of mortality. RESULTS: Totally, 109,026 episodes of severe sepsis were identified during the study period between 2003 and 2014. Incidence of severe sepsis hospitalizations increased by 2.5 times (0.64-1.57 per 10,000 population) over the study period with notable concurrent significant decrease in mortality by more than 50%. Lower age, African American, Hispanic ethnicity, complex neurologic conditions, infective endocarditis, immunodeficient states including primary immunodeficiency disorder, HIV, burns, malignancy and transplant status are associated with mortality. There is a significant increase in use of healthcare resources (P < 0.001) with mean charges of 94,966$ despite a notable decrease in mean length of stay (22 vs. 16 days, P < 0.001) over the study period. CONCLUSION: Incidence of pediatric severe sepsis is high leading to a significant use of healthcare resources. This study provides a detailed analysis of associated inpatient factors and comorbidities associated with mortality.

Incidence Trends, Risk Factors, Mortality and Healthcare Utilization in Congenital Syphilis-related Hospitalizations in the United States: A Nationwide Population Analysis.

BACKGROUND: Congenital syphilis (CS) is a devastating yet preventable disease affecting the fetus. Recent increase in cases of CS in the United States has been reported by Centers for Disease Control and Prevention. There is a lack of data on hospitalization trends and healthcare utilization related to CS. We sought to describe CS hospitalization trends, morbidity and mortality during 2009 through 2016 and related healthcare expenditure. METHODS: National inpatient level data collected from Kid's Inpatient Database and National Inpatient Sample databases from 2009 to 2016 were analyzed. CS hospitalizations were identified using International Classification of Diseases codes in age less than 1 year. Related demographics, risk factors and outcomes were calculated. Infant mortality related to CS were calculated per number of hospitalizations. RESULTS: From 2009 to 2016, there were a total of 5912 CS-related hospitalizations. The overall trends in hospitalizations related to CS was up trending since 2009. African American ethnicity, public insurance/uninsured, low socioeconomic status, geographic location (South and West hospital regions), prematurity and low birth weight were significantly associated with CS and remained as independent risk factors. The mean length of stay (12.38 ± 0.10 d vs. 3.42 ± 0.1 d) and mean hospitalization charges were significantly higher in CS (P < 0.001) as compared with other hospitalized infants without CS. The total inflation-adjusted hospitalization charges have more than doubled over the years ($120,665,203 in 2016 vs. $54,290,310 in 2009). The rate of in-hospital deaths in CS hospitalization was 0.54% (32 deaths among 5912 hospitalizations). CONCLUSIONS: The incidence of CS hospitalization has been increasing since 2009. CS contributes to a significant healthcare utilization burden; its prevention can save a large amount of healthcare-related expenditure.

Chlamydia pneumoniae-induced tumour necrosis factor alpha responses are lower in children with asthma compared with non-asthma.

INTRODUCTION: Chlamydia pneumoniae respiratory tract infection has been implicated in the pathogenesis of reactive airway disease and asthma. Innate cytokine responses that are protective of infection with intracellular pathogens may be impaired in patients with asthma. Tumour necrosis factor alpha (TNF-α) is a cytokine related to functions of monocytes and may inhibit C. pneumoniae infection. We investigated TNF-α responses in C. pneumoniae-infected peripheral blood mononuclear cells (PBMCs) in patients with asthma and non-asthma, and whether ciprofloxacin, azithromycin or doxycycline affects TNF-α responses. METHODS: PBMC (1.5×106) from paediatric patients with asthma (n=19) and non-asthmatic controls (n=6) were infected or mock infected for 1 hour with or without C. pneumoniae AR-39 at a multiplicity of infection=0.1, and cultured+ciprofloxacin, azithromycin or doxycycline (0.1 ug/mL) for 48 hours. TNF-α levels were measured in supernatants by ELISA. RESULTS: When PBMC from patients with asthma were infected with C. pneumoniae, levels of TNF-α were significantly lower than in subjects without asthma (48 hours) (5.5±5.6, 38.4±53.7; p=0.0113). However, baseline responses (no infection with C. pneumoniae) were similar in asthma and non-asthma (1.0±1.7, 1.1±1.2; p=0.89). When PBMC frompatiens with asthma were infected with C. pneumoniae+ciprofloxacin, azithromycin or doxycycline, TNF-α levels increased (25%-45%); this affect was not observed in PBMC from patients without asthma. CONCLUSIONS: We identified differences in the quantity of TNF-α produced by C. pneumoniae-infected PBMC in asthma compared with non-asthma.

Seroprevalence of Chlamydia trachomatis in Inner-City Children and Adolescents-Implications for Vaccine Development.

BACKGROUND: Prevention of Chlamydia trachomatis infection is an ideal application for a vaccine program, which should optimally be administered before sexual debut. However, there are limited epidemiologic studies of C. trachomatis infection in an unselected pediatric population since routine screening and treatment of pregnant women was implemented in the United States in 1993. METHODS: Anonymized serum samples were obtained from children younger than 21 years in 2 medical centers in Brooklyn, New York, from 2013 to 2015. Anti-C. trachomatis IgG antibody was determined by a validated enzyme immunoassay. Infants younger than 1 year were excluded from the final analysis due to interference of maternal antibody. RESULTS: One thousand two sera were included in the final analysis. Fifty-seven percent were females. No antibody was detected at younger than 11 years. Anti-C. trachomatis IgG antibody was detected in 11.4% and 5.6% of female and male subjects, respectively, older than 11 years (P = 0.0027), and seropositivity increased with age. There was no significant difference in the distribution of age at infection between the centers (P = 0.432), but a difference was detected between genders (P = 0.012) with a higher percentage of female subjects testing positive. CONCLUSIONS: Antibody was first detected at 11 years of age, likely coinciding with sexual debut. The prevalence of antibody was higher and appeared earlier in females, mirroring national surveillance trends based on nucleic acid amplification testing. The delay in male antibody detection may be due to biological or behavioral differences between genders. These data are critical in informing potential C. trachomatis vaccine strategies.

Epigallocatechin gallate suppresses Chlamydia pneumoniae mediated IgE responses in peripheral blood mononuclear cells: a pilot study.

BACKGROUND: Chlamydia pneumoniae (C. pneumoniae) causes respiratory infection in children and adults and is associated with asthma and induction of immunoglobulin E (IgE) responses. Previous studies in our laboratory reported that green tea extract (GTE) and its catechin, epigallocatechin gallate (EGCG) have immunoregulatory effects on IgE responses. Whereas tea polyphenols have in vitro inhibitory effects on the proliferation of C. pneumoniae, the in vitro effects of EGCG on C. pneumoniae- mediated IgE responses haven't been studied. We sought to clarify the in vitro effect of EGCG on C. pneumoniae mediated IgE responses by peripheral blood mononuclear cells (PBMC) in asthma. METHODS: PBMC from subjects with asthma and non-asthmatic controls were incubated with C. pneumoniae and cultured for 10 days ±EGCG (0.5, 5.0, 50 ng/mL). IgE levels in supernatants were determined (ELISA). RESULTS: Elevated IgE levels were detected in supernatants of PBMC from an asthma patient (2.6 ng/mL), whereas IgE levels of PBMC from non-asthmatics were low (<2.0 ng/mL) at baseline. When EGCG (0.5-50 ng/mL) was added to PBMC from the asthma patient, IgE production was suppressed in a dose-dependent manner (10-30%), compared with no EGCG. When PBMC from the asthma patient were incubated with C. pneumoniae, IgE production was suppressed (70%); when PBMC from non-asthmatics were incubated with C. pneumoniae, IgE levels remained undetectable (<2.0 ng/mL). When EGCG (0.5-50 ng/mL) was added to PBMC from the asthma patient, C. pneumoniae-induced IgE production was suppressed moderately (35-48%). CONCLUSIONS: EGCG suppressed C. pneumoniae- mediated IgE responses in PBMC from a patient with asthma.

Chlamydia pneumoniae enhances the Th2 profile of stimulated peripheral blood mononuclear cells from asthmatic patients.

Chlamydia pneumoniae is a cause of respiratory infection in adults and children. There is evidence for an association between atypical bacterial respiratory pathogens and the pathogenesis of asthma. We compared T helper (Th) responses in C. pneumoniae - infected peripheral blood mononuclear cells (PBMC) in patients with or without asthma. PBMC (1×10(6)/mL) from asthmatic patients (N=11) and non-asthmatic controls (N=12) were infected or mock-infected for 1h +/- C. pneumoniae TW-183 at a multiplicity of infection (MOI)=1 and MOI=0.1, or cultured for 24h +/- Lactobacillus rhamnosus GG (LGG). Interleukin (IL)-4, IL-10, IL-12, Interferon (IFN)-gamma and total IgE levels were measured in supernatants (ELISA). C. pneumoniae infection led to an increase (>50%) of IgE levels in PBMC from asthmatics, compared with mock-infected on day 10; IgE wasn't detected in non-asthmatics. C. pneumoniae - infected PBMC from asthmatics increased levels of IL-4 and IFN-gamma after 24h, compared with PBMC alone; levels of IL-10 and IL-12 were low. When uninfected-PBMC from asthmatics were LGG-stimulated, after 24h, IL-4 was undetectable, but IL-10, IL-12, and IFN-gamma increased, compared with PBMC alone. Thus, C. pneumoniae infection has the ability to induce allergic responses in PBMC of asthmatics, as evidenced by production of Th2 responses and IgE.

Pediatric Fistula Initiative: Reducing Bloodstream Infections in an Outpatient Pediatric Hemodialysis Center.

Bloodstream infection is a major contributor to morbidity and mortality in children on hemodialysis (HD). From January 2009 through April 2011, the incidence of access-related bloodstream infections (ARBs) in pediatric patients on HD at our hospital was 3.45/1000 patient days. Almost all of these children were receiving HD via central line catheters, and none were receiving HD via arteriovenous fistulas (AVFs). In an effort to reduce the rate of infection in children receiving HD at our institution, we introduced the Pediatric Fistula Initiative, a program to increase creation and use of AVFs in children. Thirty-three children on HD were observed, 9 of whom received AVFs during the study period. The incidence of ARBs decreased to 1.30/1000 patient days (P < .001) during the 24-month intervention period from May 2011 through May 2013.

IgE anti Hepatitis B virus surface antigen antibodies detected in serum from inner city asthmatic and non asthmatic children.

Viral Hepatitis type B (HBV) is a public health concern, but has not been linked to asthma. Immunoglobulin (Ig) G is involved in HBV immune responses; less is known about IgE antibodies (Abs) against HBV in asthma. Given the importance of HBV, we sought to determine whether HBV vaccine contributes to asthma in children, by stimulating specific IgE production. Total IgE, IgE- or IgG-anti-HBVs Abs were studied in vaccinated pediatric asthmatics and non asthmatics. We found: (1) total IgE was higher in asthmatics; (2) total IgE did not correlate with IgE anti-HBVs; (3) IgE anti-HBVs did correlate with IgG-anti-HBVs in all subjects; (4)IgE- and IgG-HBVs Abs were similar in both groups; (5) IgE- or IgG anti-HBVs Abs did not correlate with age. Our findings indicate that HBV vaccination induces IgE responses in asthmatics and non asthmatics.

In vitro activity of nemonoxacin, a novel nonfluorinated quinolone antibiotic, against Chlamydia trachomatis and Chlamydia pneumoniae.

The in vitro activities of nemonoxacin, levofloxacin, azithromycin, and doxycycline were tested against 10 isolates each of Chlamydia trachomatis and Chlamydia pneumoniae. The MICs at which 90% of the isolates of both C. trachomatis and C. pneumoniae were inhibited (MIC90s) were 0.06 µg/ml (range, 0.03 to 0.13 µg/ml). The minimal bactericidal concentrations at which 90% of the isolates were killed by nemonoxacin (MBC90s) were 0.06 µg/ml for C. trachomatis (range, 0.03 to 0.125 µg/ml) and 0.25 for C. pneumoniae (range, 0.015 to 0.5 µg/ml).

Doxycycline suppresses Chlamydia pneumoniae-mediated increases in ongoing immunoglobulin E and interleukin-4 responses by peripheral blood mononuclear cells of patients with allergic asthma.

OBJECTIVES: Chlamydia pneumoniae, an obligate intracellular bacterium, has been associated with asthma and the induction of immunoglobulin E (IgE) responses. Whereas tetracyclines have anti-chlamydial activity, their effect on human IgE responses to C. pneumoniae has not been studied. METHODS: Peripheral blood mononuclear cells (PBMCs) from serum IgE+ allergic asthmatic subjects (n = 11) and healthy controls (n = 12) were infected with C. pneumoniae and cultured for 12 days with or without doxycycline (0.01-1.0 mg/L). IgE, interferon (IFN)-γ and interleukin (IL)-4 levels in supernatants were determined on days 1-12 post-infection, and C. pneumoniae DNA copy numbers in PBMC culture were measured on day 2 (quantitative PCR). RESULTS: C. pneumoniae-infected PBMCs from allergic asthmatic individuals had increased levels of IgE in supernatants compared with uninfected PBMCs (520% on day 10 post-infection, P = 0.008). IgE levels in PBMC cultures from controls were undetectable (<0.3 ng/mL). Increases in C. pneumoniae-induced IgE in asthmatics correlated with those of C. pneumoniae-induced IL-4 (r = 0.98; P < 0.001), but not with IFN-γ. The addition of doxycycline (1.0 mg/L) to the culture strongly suppressed the production of IgE (>70%, P = 0.04) and IL-4 (75%, P = 0.018), but not IFN-γ. The suppressive effect on IL-4 production remained significant even at concentrations of doxycycline that were subinhibitory (0.01 mg/L) for C. pneumoniae. In both asthmatic participants and controls, no significant effect of doxycycline on DNA copy numbers of C. pneumoniae was observed. CONCLUSIONS: Doxycycline suppressed the C. pneumoniae-induced production of IgE and IL-4, but not IFN-γ, in PBMCs from IgE+ allergic asthmatic subjects. These findings resulted from the immunomodulatory anti-allergic properties of tetracyclines.

Recurrent intravascular-catheter-related bacteremia caused by Delftia acidovorans in a hemodialysis patient.

We report the first case of recurrent intravascular-catheter-related bacteremia in a pediatric hemodialysis patient caused by Delftia acidovorans, previously called Comamonas acidovorans or Pseudomonas acidovorans. The patient had a history of multiple infections of central vascular catheters with other organisms, requiring courses of antibiotics and catheter replacements. Previously reported cases of D. acidovorans infections are reviewed. The isolate appeared to become resistant to cephalosporins after antibiotic treatment, but resistance could not be confirmed with additional testing. In vitro susceptibility testing for cephalosporins is not reliable for this organism.