Danielle M. Zerr

Emergence of extended-spectrum β-lactam resistance among Escherichia coli at a US academic children's hospital is clonal at the sequence type level for CTX-M-15, but not for CMY-2

Resistance to extended-spectrum β-lactams is increasing worldwide among Escherichia coli and has been linked to a small number of emergent clones (e.g. ST38, ST131 and ST405) recovered from extraintestinal infections in community and hospital settings. There are, however, limited data about the relative contributions of bacterial strains, plasmids and β-lactamase genes to extended-spectrum β-lactam resistance in paediatric infections. We performed an extensive molecular analysis of phylogenetic, virulence and antibiotic resistance-related properties of 49 previously reported serial E. coli isolates recovered during 1999-2007 at Seattle Childrens Hospital (Seattle, WA). Class C enzyme CMY-2 and class A enzyme CTX-M-15 were the most prominent extended-spectrum β-lactam resistance enzymes in the collection, first appearing in this patient population in 2001 and 2003, respectively, and then steadily increasing in frequency over the remainder of the study period. Among 19 CMY-2-positive isolates, 16 distinct STs were detected (D = 98.25%, 95% CI 96-100.25%), indicating that CMY spread is non-clonal at the host strain level. In contrast, among ten CTX-M-15-positive isolates, three STs were detected (D = 37.78%, 95% CI 2.36-73.20%), of which eight represented the worldwide-disseminated ST131 lineage, consistent with clonal spread of CTX-M-15-associated resistance. fimHTR subtyping of ten ST131 isolates (including two CTX-M-negative isolates) revealed that, within ST131, carriage of allele fimHTR30 correlated with CTX-M-15 positivity, whilst carriage of non-fimHTR30 alleles correlated with carriage of non-CTX-M enzymes. Thus, spread of CMY-2 is non-clonal at the ST level, but clonal spread of CTX-M-15 may be associated with a specific fimHTR-defined sublineage of ST131.

Prevention of bacterial infection in pediatric oncology: what do we know, what can we learn?

Bacterial sepsis continues to be a leading cause of morbidity and toxic death in children receiving intensive therapy for cancer. Empiric therapy for suspected infections and treatment of documented infections are well‐established standards of care. The routine use of prophylactic strategies is much less common in pediatric oncology. This paper will review the current literature on the use and risks of antimicrobial prophylaxis as well as non‐pharmacological methods for infection prevention and will address areas in need of further research. Pediatr Blood Cancer 2012; 59: 16–20.

The cumulative burden of double-stranded DNA virus detection after allogeneic HCT is associated with increased mortality

Strategies to prevent active infection with certain double-stranded DNA (dsDNA) viruses after allogeneic hematopoietic cell transplantation (HCT) are limited by incomplete understanding of their epidemiology and clinical impact. We retrospectively tested weekly plasma samples from allogeneic HCT recipients at our center from 2007 to 2014. We used quantitative PCR to test for cytomegalovirus, BK polyomavirus, human herpesvirus 6B, HHV-6A, adenovirus, and Epstein-Barr virus between days 0 and 100 post-HCT. We evaluated risk factors for detection of multiple viruses and association of viruses with mortality through day 365 post-HCT with Cox models. Among 404 allogeneic HCT recipients, including 125 cord blood, 125 HLA-mismatched, and 154 HLA-matched HCTs, detection of multiple viruses was common through day 100: 90% had ≥1, 62% had ≥2, 28% had ≥3, and 5% had 4 or 5 viruses. Risk factors for detection of multiple viruses included cord blood or HLA-mismatched HCT, myeloablative conditioning, and acute graft-versus-host disease (P values < .01). Absolute lymphocyte count of <200 cells/mm3 was associated with greater virus exposure on the basis of the maximum cumulative viral load area under the curve (AUC) (P = .054). The maximum cumulative viral load AUC was the best predictor of early (days 0-100) and late (days 101-365) overall mortality (adjusted hazard ratio [aHR] = 1.36, 95% confidence interval [CI] [1.25, 1.49], and aHR = 1.04, 95% CI [1.0, 1.08], respectively) after accounting for immune reconstitution and graft-versus-host disease. In conclusion, detection of multiple dsDNA viruses was frequent after allogeneic HCT and had a dose-dependent association with increased mortality. These data suggest opportunities to improve outcomes with better antiviral strategies.

Clinical outcomes in outpatient respiratory syncytial virus infection in immunocompromised children

Immunocompromised patients are at high risk for morbidity and mortality due to respiratory syncytial virus (RSV) infection. Increasingly, pediatric patients with malignancy or undergoing transplantation are managed primarily as outpatients. Data regarding the clinical presentation and outcomes of RSV in the outpatient pediatric immunocompromised population are limited.

Parental vaccine hesitancy and acceptance of seasonal influenza vaccine in the pediatric emergency department

BACKGROUNDnProviding influenza vaccine to patients in the pediatric emergency department (PED) is one strategy to increase childhood influenza vaccine uptake. The Parent Attitudes about Childhood Vaccines (PACV) survey is a new tool to identify vaccine-hesitant parents that may facilitate influenza vaccine uptake in the PED.nnnOBJECTIVEnTo assess the feasibility of administering the PACV modified for influenza vaccination in the PED setting and to determine whether parental PACV scores are associated with patient receipt of influenza vaccine in the PED.nnnMETHODSnWe conducted a cross-sectional study in the PED of a tertiary pediatric hospital in Seattle, WA during the 2013-2014 influenza season. English-speaking parents of children aged 6 months to 7 years who were afebrile, medically stable to be discharged home from the PED, and had not already received an influenza vaccine this season were administered a modified version of the PACV. PACV scores (0-100, higher score=higher hesitancy) were dichotomized (<50 and ≥50) consistent with previous validation studies. Feasibility was assessed by determining time to complete the PACV. Our primary outcome was influenza vaccine refusal in the PED. We used multivariable logistic regression to estimate unadjusted and adjusted odds ratios for association between vaccine refusal and dichotomized PACV scores.nnnRESULTSn152 parent participants were included in the analysis. The median time for administering the PACV was 7 min. The median PACV score was 28, with 74% scoring <50. Parents who scored ≥50 on the PACV had increased odds of refusing the influenza vaccine compared to parents who scored <50 (adjusted OR [95% CI]: 6.58 [2.03-21.38]).nnnCONCLUSIONnAdministration of the PACV in the PED is feasible, and higher PACV scores in this setting are associated with increased influenza vaccine refusal.

A Comprehensive Intervention Associated With Reduced Surgical Site Infections Among Pediatric Cardiovascular Surgery Patients, Including Those With Delayed Closure

BACKGROUNDnSurgical site infections (SSIs) cause significant morbidity and mortality in patients undergoing cardiovascular (CV) surgery. Following an increase in SSIs in this population, driven by a high rate in those with delayed closure, we implemented an intervention to reduce these infections and assessed the intervention using both population- and patient-level analyses.nnnMETHODSnAn intervention drawing from existing guidelines and targeting preoperative preparation of the patient, prophylactic antibiotics, and postoperative incision care was implemented. Special attention was paid to standardizing the care of the incision of patients with delayed closure. National Healthcare Safety Network criteria were used to prospectively identify SSIs. Population-level intervention effect was assessed using interrupted time series. To assess intervention adherence and effect in our patient population, retrospective chart review was performed on a cohort of patients undergoing cardiac procedures pre- and postintervention. Multivariate analysis was used to assess risk of SSI at the patient level.nnnRESULTSnTimely preoperative prophylactic antibiotic dosing increased from 60% preintervention to 92% postintervention, and redosing during prolonged surgeries increased from 5% to 79% (both, Pxa0<xa0.001). At the population-level, a decrease of 6.7 infections per 100 surgeries per 6 months was observed directly following the intervention (Pxa0=xa0.002). The SSI rate decreased from 40% to 0.8% (Pxa0<xa0.001) in patients with delayed closure and from 4.3% to 1.8% (Pxa0=xa0.02) in patients with immediate closure. In multivariate analyses, surgery prior to the intervention was the strongest predictor for SSI (incidence rate ratio, 3.98; 95% confidence interval, 1.59 to 9.97).nnnCONCLUSIONSnOur intervention decreased SSIs in pediatric CV surgery patients, particularly those with delayed closures.

Shedding of pandemic (H1N1) 2009 virus among health care personnel, Seattle, Washington, USA.

The Centers for Disease Control and Prevention (CDC) recommends that health care personnel (HCP) infected with pandemic influenza (H1N1) 2009 virus not work until 24 hours after fever subsides without the use of antipyretics. During an influenza outbreak, we examined the association between viral shedding and fever among infected HCP. Participants recorded temperatures daily and provided nasal wash specimens for 2 weeks after symptom onset. Specimens were tested by using PCR and culture. When they met CDC criteria for returning to work, 12 of 16 HCP (75%) (95% confidence interval 48%–93%) had virus detected by PCR, and 9 (56%) (95% confidence interval 30%–80%) had virus detected by culture. Fever was not associated with shedding duration (p = 0.65). HCP might shed virus even when meeting CDC exclusion guidelines. Further research is needed to clarify the association between viral shedding, symptoms, and infectiousness.

Epidemiology and potential preventative measures for viral infections in children with malignancy and those undergoing hematopoietic cell transplantation

In pediatric patients with malignancy and those receiving hematopoietic stem cell transplants, bacterial and fungal infections have been the focus of fever and neutropenia episodes for decades. However, improved diagnostic capabilities have revealed viral pathogens as a significant cause of morbidity and mortality. Because of limited effective antiviral therapies, prevention of viral infections is paramount. Pre‐exposure and post‐exposure prophylaxis and antiviral suppressive therapeutic approaches are reviewed. Additionally, infection control practices specific to this patient population are discussed. A comprehensive approach utilizing each of these can be effective at reducing the negative impact of viral infections. Pediatr Blood Cancer 2012; 59: 11–15.

Identifying Antimicrobial Stewardship Targets for Pediatric Surgical Patients

BACKGROUNDnMore than 80% of surgical inpatients at US childrens hospitals receive antibiotics, accounting for >40% of all inpatient pediatric antibiotic use. We aimed to examine the collective pool of all systemic antibiotics prescribed to children hospitalized for surgical conditions and identify common surgical conditions with highly variable and potentially unnecessary antibiotic use, because these conditions may represent antimicrobial stewardship priorities.nnnMETHODSnWe conducted a retrospective cross-sectional study of surgical inpatients discharged in 2012 at 37 freestanding childrens hospitals. We captured all systemic antibiotic use as days of therapy (DOT), and we reported surgical conditions by frequency and contribution to overall antibiotic use. We used multivariable logistic and Poisson regression with marginal standardization to estimate (1) the standardized proportion and (2) DOT of condition-specific targeted antibiotic use among top surgical condition patients.nnnRESULTSnAmong 151 345 surgical inpatients, 82.9% received antimicrobials for a median 2 DOT per subject (interquartile range, 1-5; range, 1-958). The most commonly received antibiotics were cefazolin (16.7% of all DOT), vancomycin (12.5%), and piperacillin/tazobactam (6.9%). The top 10 conditions contributing most to antibiotic use accounted for 51.3% of all antibiotic use. Among these, adjusted use of postoperative and perioperative vancomycin varied across hospitals among craniotomy and cardiothoracic surgery subjects (all P < .001); adjusted use of broad-spectrum antipseudomonal agents varied across hospitals among gastrointestinal surgery subjects (all P < .001).nnnCONCLUSIONSnUse of (1) vancomycin for pediatric cardiothoracic and neurosurgical patients and (2) broad-spectrum antipseudomonal agents for gastrointestinal surgery patients represent potentially high-yield targets for stewardship efforts to reduce unnecessary antimicrobial use.

Molecular epidemiology of colonizing and disease-causing Klebsiella pneumoniae in paediatric patients

Klebsiella pneumoniae causes a range of clinical disease in paediatric patients and is of increasing concern due to growing antibiotic resistance, yet little is known about the relative distribution of commensal and pathogens throughout the population structure of K. pneumoniae. We conducted a prospective, observational study of 92 isolates from Seattle Childrens Hospital, including 49 disease isolates from blood and urine (13 and 36 isolates, respectively) and 43 colonization isolates from stool. Susceptibility to 20 antimicrobials was evaluated using disc diffusion, VITEK 2 and Etest. Strain relatedness was investigated using multilocus sequence typing (MLST). Demographic and clinical characteristics were largely similar between disease and colonization cohorts, with 85.7 and 74.4u200a% of disease and colonization cohort patients, respectively, having an underlying medical condition; the sole exception was a relative abundance of patients with urologic or renal abnormalities in the disease cohort, consistent with the predominance of urine specimens among the disease isolates. With regard to antibiotic susceptibility properties, no significant differences were noted between the disease and colonization cohorts. Using molecular analysis, 71 unique sequence types (STs) were distinguished, with novel MLST findings evident in both cohorts; 43 (46.7u200a%) isolates represented novel STs, including 22 with a novel allele sequence. Thirteen STs contained multiple isolates and all seven isolates with resistance to three or more antibiotic classes were within one of four multirepresentative STs. This study demonstrates that nearly half of paediatric Klebsiella isolates represent novel STs, with clustering of multidrug resistance within specific STs. These findings expand our understanding of the intersection of bacterial population structure, human colonization ecology and multidrug resistance in K. pneumoniae.