Addressing antimicrobial resistance to treat children with atopic dermatitis in a tertiary pediatric allergy clinic.

BACKGROUND: Secondary skin infection with Staphylococcus aureus is a significant problem in atopic dermatitis (AD) patients. OBJECTIVE: This study evaluated antimicrobial resistance patterns of S aureus isolates from skin lesions in AD patients and empiric antimicrobial prescribing patterns. METHODS: Resistance patterns from positive skin cultures obtained from AD patients in the Allergy/Immunology clinic from May 1, 2006, to December 31, 2008, were compared with all outpatient wound cultures over the same period. RESULTS: Fifty-nine cultures were obtained from 38 AD patients. S aureus was the most common pathogen cultured from AD patients (53/59 cultures). S aureus resistance to clindamycin and methicillin differed significantly between the study group and the outpatient reference population (37.7% vs 9.4% and 45.3% vs 76.4%). Clindamycin was the most commonly prescribed antimicrobial (59%). Overall, 31.4% of organisms showed resistance to the antimicrobial prescribed. CONCLUSIONS: Susceptibility profiles of S aureus isolates from AD patients vary significantly from that of the general population.

Fungal infections and antifungal prophylaxis in pediatric cardiac extracorporeal life support.

OBJECTIVE: Infections acquired by children during extracorporeal membrane oxygenation (ECMO) increase mortality. Our aim was to evaluate the effectiveness of prophylactic fluconazole on the incidence of fungal infections and to assess whether hospital-acquired fungal infection is associated with increased in-hospital mortality in pediatric cardiac patients requiring ECMO. METHODS: We retrospectively reviewed a prospectively maintained database and collected data on all hospital-acquired infections in patients supported for cardiac indications at a tertiary children's hospital from 1989 to 2008. RESULTS: ECMO was deployed 801 times in 767 patients. After exclusion criteria were applied, 261 pediatric patients supported for cardiac indications were studied. Fungal infection (blood, urine, or surgical site) occurred in 12% (31/261) of patients, 9 (7%) of 127 patients receiving fluconazole prophylaxis versus 22 (16.4%) of 134 without antifungal prophylaxis (P = .02). Using a multivariable logistic regression model, the absence of fluconazole prophylaxis was associated with an increased risk of fungal infection (odds ratio [OR] = 2.8; 95% confidence intervals [CI], 1.2, 6.7; P = .016). In a multivariable logistic regression model for in-hospital mortality, the presence of fungal infection was associated with increased odds (OR = 3.8; 95% CI, 1.5, 9.6; P = .005) of in-hospital mortality among cardiac patients requiring ECMO, and the absence of antifungal prophylaxis showed a trend toward the same (OR = 1.6; 95% CI, 0.96, 2.8; P = .072). CONCLUSIONS: Children with cardiac disease supported with ECMO who acquire fungal infections have increased mortality. Routine fluconazole prophylaxis is associated with lower rates of fungal infections in these patients.

Reducing contamination of peripheral blood cultures in a pediatric emergency department.

OBJECTIVE: Blood culture contamination rates (CRs) in emergency departments (EDs) vary from 1% to 9% in previous studies. High CRs cause unnecessary admissions, antibiotics, and costs. Different measures have been tried to improve CR. This study sought to determine the ED CR at Arkansas Children's Hospital (ACH) and evaluate an educational intervention. DESIGN: A slide presentation of the ACH's blood culture collection procedure was made. The ED nursing staff viewed this individually and demonstrated the procedure on a mock extremity. Data before (from June 1 to November 30, 2007; PRE) and after (from February 1 to July 31, 2008; POST) intervention regarding blood cultures positive for organism submitted to the ED and any descriptive data were collected retrospectively. Descriptive statistics described the CR, positivity rate (PSR), and pathogen rate (PR). Frequent collectors were identified as those submitting more than 72 blood cultures during PRE and during POST. Contamination rate in frequent collectors was independently assessed for improvement. This study was approved by the institutional review board of the University of Arkansas for Medical Sciences. RESULTS: Positivity rate during PRE was 6.8% (n = 15; 95% confidence interval [CI], 2.9-10.7); 114 were contaminants (CR, 5.0%; 95% CI, 1.04-8.98) and 40 were pathogens (PR, 1.8%; 95% CI, ± 4.28). Positivity rate during POST was 6.3% (n = 157; 95% CI, 2.6-10.0); 124 were contaminants (CR, 4.9%; 95% CI, 1.14-8.66) and 33 were pathogens (PR, 1.4%; 95% CI, ± 4.22). For both PRE and POST, contaminants represented 74% or greater of all the positives and more than 75% of contaminants occurred in patients 0 to 36 months old.Contamination rates of individual practitioners ranged from 0% to 17% (PRE) and from 0% to 21% (POST). The CR was lower in POST for samples submitted from frequent collectors (practitioners submitting >72 blood cultures per study period, n = 6), was evaluated separately, and found to improve in POST (from 4.1% to 2.7%). A t test for matched samples for these samplers revealed a significant decrease in the POST period, P = 0.03. CONCLUSIONS: The CR in the ACH ED for peripherally drawn blood cultures is approximately 5% monthly with less than 2% PR. For each culture positive for organism, the chance of contamination is 75% or higher. An intervention emphasizing the appropriate technique, monitored training, and improved CR of a group of frequent collectors is warranted.

Increase in prevalence of Streptococcus pneumoniae serotype 6C at Eight Children's Hospitals in the United States from 1993 to 2009.

Streptococcus pneumoniae serotype 6C, which was described in 2007, causes invasive disease in adults and children. We investigated the prevalence of 6C among pediatric isolates obtained from eight children's hospitals in the United States. S. pneumoniae isolates were identified from a prospective multicenter study (1993 to 2009). Fifty-seven serotype 6C isolates were identified by multiplex PCR and/or Quellung reaction. Five were isolated before 2000, and the prevalence increased over time (P < 0.000001). The median patient age was 2.1 years (range, 0.2 to 22.5 years). Clinical presentations included bacteremia (n = 24), meningitis (n = 7), pneumonia (n = 4), abscess/wound (n = 3), mastoiditis (n = 2), cellulitis (n = 2), peritonitis (n = 1), septic arthritis (n = 1), otitis media (n = 10), and sinusitis (n = 3). By broth microdilution, 43/44 invasive serotype 6C isolates were susceptible to penicillin (median MIC, 0.015 µg/ml; range, 0.008 to 2 µg/ml); all were susceptible to ceftriaxone (median MIC, 0.015 µg/ml; range, 0.008 to 1 µg/ml). By disk diffusion, 16/44 invasive isolates (36%) were nonsusceptible to erythromycin, 19 isolates (43%) were nonsusceptible to trimethoprim-sulfamethoxazole (TMP-SMX), and all isolates were clindamycin susceptible. Multilocus sequence typing (MLST) revealed 24 sequence types (STs); 9 were new to the MLST database. The two main clonal clusters (CCs) were ST473 and single-locus variants (SLVs) (n = 13) and ST1292 and SLVs (n = 23). ST1292 and SLVs had decreased antibiotic susceptibility. Serotype 6C causes disease in children in the United States. Emerging CC1292 expressed TMP-SMX resistance and decreased susceptibility to penicillin and ceftriaxone. Continued surveillance is needed to monitor changes in serotype prevalence and possible emergence of antibiotic resistance in pediatric pneumococcal disease.

Nosocomial infection with Asaia lannensis in two paediatric patients with idiopathic dilated cardiomyopathy.

This is the first report, to our knowledge, of two temporally and geographically related nosocomial Asaia lannensis infections in a paediatric setting. Two patients with idiopathic dilated cardiomyopathy awaiting cardiac transplantation developed bacteraemia during their hospital stay. The physical location of both patients, the temporal association of infections, as well as the isolation of two identical pathogens suggested a nosocomial transmission. Commonly used identification methods and instruments failed to identify the isolated pathogens and only 16S rRNA gene sequencing provided definitive identification. These isolates of A. lannensis showed an unfavourable susceptibility pattern including resistance to carbapenems, all beta-lactam agents and fluoroquinolones.

Serotype 19A Is the most common serotype causing invasive pneumococcal infections in children.

OBJECTIVE: The purpose of this study was to monitor the clinical and microbiologic features of invasive infections caused by Streptococcus pneumoniae among children before and after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). DESIGN: We conducted a 15-year prospective surveillance study of all invasive pneumococcal infections in children. The sample included infants and children at 8 children's hospitals in the United States with culture-proven invasive S pneumoniae infections. RESULTS: Since the implementation of routine PCV7 immunization in 2000, invasive infections have decreased yearly from 2001 through 2004, to a nadir of 151 infections; the rate then increased from 2005 through 2008. Compared with the pre-PCV7 era, a greater proportion of children with invasive pneumococcal infection had an underlying condition in the post-PCV7 period. Compared with the total number of annual admissions, the number of 19A isolates increased significantly from 2001 to 2008 (P < .00001). In 2007 and 2008, only 16 isolates (4%) were vaccine serotypes; 19A accounted for 46% (168 of 369) of the non-PCV7 serotypes. Thirty percent of the 19A isolates were multidrug resistant. Serotypes 1, 3, and 7F accounted for 22% of the non-PCV7 serotypes. Among children with invasive pneumococcal infections, the likelihood of a 19A serotype increased with the number of preceding PCV7 doses. CONCLUSIONS: Since 2005, the number of invasive pneumococcal infections in children has increased at 8 children's hospitals, primarily as a result of serotype 19A isolates, one third of which were resistant to multiple antibiotics in 2007 and 2008. Continued surveillance is necessary to detect emerging serotypes after the planned introduction of 13-valent or other pneumococcal vaccines.

Role of vav1- and src-related tyrosine kinases in macrophage activation by CpG DNA.

Macrophage activation by CpG DNA requires toll-like receptor 9 and the adaptor protein MyD88. Gram-negative bacterial lipopolysaccharide also activates macrophages via a toll-like receptor pathway (TLR-4), but we and others have reported that lipopolysaccharide also stimulates tyrosine phosphorylation in macrophages. Herein we report that exposure of RAW 264.7 murine macrophages to CpG DNA (but not non-CpG DNA) provoked the rapid tyrosine phosphorylation of vav1. PP1, a selective inhibitor of src-related tyrosine kinases, blocked both the CpG DNA-mediated tyrosine phosphorylation of vav1 and the CpG DNA-mediated up-regulation of macrophage tumor necrosis factor secretion and inducible nitric-oxide synthase protein accumulation. Furthermore, we found that the inducible expression of any of three dominant interfering mutants of vav1 (a truncated protein, vavC; a form containing a point mutation in the regulatory tyrosine residue, vavYF174; and a form with an in-frame deletion of six amino acids required for the guanidine nucleotide exchange factor (GEF) activity of vav1 for rac family GTPases, vavGEFmt) consistently inhibited CpG DNA-mediated up-regulation of tumor necrosis factor secretion and inducible nitric-oxide synthase protein accumulation in RAW-TT10 macrophages. Finally, we determined that CpG DNA-mediated up-regulation of NF-kappaB activity (but not mitogen-activated protein kinase activation) was inhibited by preincubation with PP1 or by expression of the truncated vavC mutant. Taken together, our results indicate that the tyrosine phosphorylation of vav1 by a src-related tyrosine kinase or kinases plays an important role in the macrophage response to CpG DNA.

Meningococcal infections in children from Arkansas.

BACKGROUND: Infections with Neisseria meningitidis are an important cause of morbidity and mortality in children of all ages. With wide-spread use of the heptavalent pneumococcal conjugate vaccine, this organism might become the prominent pathogen for invasive disease in children. METHODS: Retrospective reviews of medical and microbiologic records from Arkansas Children's Hospital were done to identify patients with invasive N. meningitidis infections from January, 1988, through December, 2000. Basic demographic and clinical data were gathered and reviewed. Data on invasive meningococcal infections were obtained from the Arkansas Department of Health. RESULTS: Three hundred ninety-four cases of invasive meningococcal infection were reported to the Arkansas Department of Health during the study period. Two hundred ninety-six cases were in patients <21 years of age. The estimated annual incidence of meningococcal disease for the State of Arkansas was calculated to be 1.2-cases/100000 population during the study period. The annual incidence of meningococcal disease in patients <21 years of age was estimated at 2.9 and 21.7 cases/100000 population for children < 1 year of age. One hundred fifty patients (51%) <21 years of age with 151 episodes of invasive meningococcal infections were treated at our institution. Eighty percent of the patients were Caucasian, 55% were male, 31% live in a rural area and the median age at presentation was 30 months (range, 2 weeks to 21 years). The most common signs and symptoms at admission included fever (95%), petechial/purpuric rash (62%), nuchal rigidity (41%) and hypotension (41%). Thirty-eight patients (26%) required both inotropic support and mechanical ventilation during hospitalization, 15 patients died and 18 patients had long term sequelae. Eighty-three of the isolates were serogrouped and included the following: A (2); B (38); C (33); and Y (10). Eighty-four of the index cases were treated with parenteral cephalosporin therapy alone and did not receive additional chemoprophylaxis. CONCLUSIONS: Many infections in the general pediatric population are a result of N. meningitidis. Although most patients do well and recover without sequelae, there are a significant number who experience major morbidity and mortality as a result of this infection.