Laying the Groundwork for a Fulfilling Career in Pediatric Infectious Diseases: The Transition From Fellowship to Faculty.

There are limited resources for guidance on the transition from fellowship into a new faculty role in pediatric infectious diseases. This review aims to address this gap and provides a framework for a successful transition that is composed of four essential pillars-(1) stepping into your role, (2) finding your niche, (3) building your network, and (4) self-care-all of which are supported by strong mentorship/sponsorship and continual realignment with one's personal mission statement. In addition to providing general principles and guidance, this review also outlines specific steps that a junior faculty member can take to expand their influence and build a successful, fulfilling career in pediatric infectious diseases.

ACR Appropriateness Criteria® Central Venous Access Device and Site Selection.

The use of central venous access devices is ubiquitous in both inpatient and outpatient settings, whether for critical care, oncology, hemodialysis, parenteral nutrition, or diagnostic purposes. Radiology has a well-established role in the placement of these devices due to demonstrated benefits of radiologic placement in multiple clinical settings. A wide variety of devices are available for central venous access and optimal device selection is a common clinical challenge. Central venous access devices may be nontunneled, tunneled, or implantable. They may be centrally or peripherally inserted by way of veins in the neck, extremities, or elsewhere. Each device and access site presents specific risks that should be considered in each clinical scenario to minimize the risk of harm. The risk of infection and mechanical injury should be minimized in all patients. In hemodialysis patients, preservation of future access is an additional important consideration. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

A multi-disciplinary, comprehensive approach to management of children with heterotaxy.

Heterotaxy (HTX) is a rare condition of abnormal thoraco-abdominal organ arrangement across the left-right axis of the body. The pathogenesis of HTX includes a derangement of the complex signaling at the left-right organizer early in embryogenesis involving motile and non-motile cilia. It can be inherited as a single-gene disorder, a phenotypic feature of a known genetic syndrome or without any clear genetic etiology. Most patients with HTX have complex cardiovascular malformations requiring surgical intervention. Surgical risks are relatively high due to several serious comorbidities often seen in patients with HTX. Asplenia or functional hyposplenism significantly increase the risk for sepsis and therefore require antimicrobial prophylaxis and immediate medical attention with fever. Intestinal rotation abnormalities are common among patients with HTX, although volvulus is rare and surgical correction carries substantial risk. While routine screening for intestinal malrotation is not recommended, providers and families should promptly address symptoms concerning for volvulus and biliary atresia, another serious morbidity more common among patients with HTX. Many patients with HTX have chronic lung disease and should be screened for primary ciliary dyskinesia, a condition of respiratory cilia impairment leading to bronchiectasis. Mental health and neurodevelopmental conditions need to be carefully considered among this population of patients living with a substantial medical burden. Optimal care of children with HTX requires a cohesive team of primary care providers and experienced subspecialists collaborating to provide compassionate, standardized and evidence-based care. In this statement, subspecialty experts experienced in HTX care and research collaborated to provide expert- and evidence-based suggestions addressing the numerous medical issues affecting children living with HTX.

Not just vegetations: focal myocardial changes in patients with fungal infections.

BACKGROUND: Fungal endocarditis classically involves dense heterogenous vegetations. However, several patients with fungal infections were noted to have myocardial changes ranging from focal brightening to nodular thickening of chordae or papillary muscles. This study evaluates whether these findings are associated with fungal infections. METHODS: In a retrospective case-control study, paediatric inpatients with fungal infections (positive blood, urine, or catheter tip culture) in a 5-year period were matched 1:1 to inpatients without positive fungal cultures. Echocardiograms were scored on a 5-point scale by two independent readers for presence of myocardial brightenings, nodular thickenings, and vegetations. Clinical data were compared. RESULTS: Of 67 fungal cases, positive culture sites included blood (n = 44), vascular catheter tip (n = 7), and urine (n = 29); several had multiple positive sites. "Positive" echo findings (score ≥ 2+) were more frequent in the Fungal Group (33 versus 18%, p = 0.04). Fungal Group patients with "positive" versus "negative" echo findings had similar proportion of bacterial infections. Among fungal cases, those with "positive" echo findings had longer hospital length of stay than cases with "negative" echos (median 58 versus 40 days, p = 0.03) but no difference in intensive care unit admission, extracorporeal membranous oxygenation support, or mortality. CONCLUSIONS: Myocardial and papillary muscle brightening with nodular thickening on echocardiogram appear to be associated with fungal infections. There may be prognostic implications of these findings as patients with "positive" echo have longer length of stay. Further studies are needed to better understand the mechanism and temporal progression of these changes and determine the prognostic value of this scoring system.

In Vitro Activities of ß-Lactam-ß-Lactamase Inhibitor Antimicrobial Agents against Cystic Fibrosis Respiratory Pathogens.

We tested the in vitro activities of ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, piperacillin-tazobactam, and 11 other antimicrobial agents against 420 Burkholderia, Achromobacter, Stenotrophomonas, and Pandoraea strains, 89% of which were cultured from respiratory specimens from persons with cystic fibrosis. Among the ß-lactam-ß-lactamase inhibitor agents, meropenem-vaborbactam had the greatest activity against Burkholderia and Achromobacter, including multidrug-resistant and extensively-drug-resistant strains. None of the newer ß-lactam-ß-lactamase combination drugs showed increased activity compared to that of the older agents against Stenotrophomonas maltophilia or Pandoraea spp.

Enterovirus D68 infection induces IL-17-dependent neutrophilic airway inflammation and hyperresponsiveness.

Enterovirus D68 (EV-D68) shares biologic features with rhinovirus (RV). In 2014, a nationwide outbreak of EV-D68 was associated with severe asthma-like symptoms. We sought to develop a mouse model of EV-D68 infection and determine the mechanisms underlying airway disease. BALB/c mice were inoculated intranasally with EV-D68 (2014 isolate), RV-A1B, or sham, alone or in combination with anti-IL-17A or house dust mite (HDM) treatment. Like RV-A1B, lung EV-D68 viral RNA peaked 12 hours after infection. EV-D68 induced airway inflammation, expression of cytokines (TNF-α, IL-6, IL-12b, IL-17A, CXCL1, CXCL2, CXCL10, and CCL2), and airway hyperresponsiveness, which were suppressed by anti-IL-17A antibody. Neutrophilic inflammation and airway responsiveness were significantly higher after EV-D68 compared with RV-A1B infection. Flow cytometry showed increased lineage-, NKp46-, RORγt+ IL-17+ILC3s and γδ T cells in the lungs of EV-D68-treated mice compared with those in RV-treated mice. EV-D68 infection of HDM-exposed mice induced additive or synergistic increases in BAL neutrophils and eosinophils and expression of IL-17, CCL11, IL-5, and Muc5AC. Finally, patients from the 2014 epidemic period with EV-D68 showed significantly higher nasopharyngeal IL-17 mRNA levels compared with patients with RV-A infection. EV-D68 infection induces IL-17-dependent airway inflammation and hyperresponsiveness, which is greater than that generated by RV-A1B, consistent with the clinical picture of severe asthma-like symptoms.

Neonatal Adenovirus Infection Complicated by Hemophagocytic Lymphohistiocytosis Syndrome.

Two infants with disseminated adenoviral infections are described. Both these infants had a similar clinical course and were also diagnosed with secondary hemophagocytic lymphohistiocytosis (HLH). Previous reports of immunocompromised adults with adenovirus-associated HLH are in the literature; however, this is the first report that we are aware of with this pathology occurring in infants. These cases are used to demonstrate the importance of thinking about HLH in patients who are diagnosed with adenovirus and exhibit prolonged fevers that are unresponsive to antimicrobial agents with hepatosplenomegaly and cytopenias.

Infectious Risk after Allogeneic Hematopoietic Cell Transplantation Complicated by Acute Graft-versus-Host Disease.

The occurrence of infections after allogeneic hematopoietic stem cell transplantation (HCT) is nearly universal. However, the relationship between infections and graft-versus-host disease (GVHD) is complex and attribution of infectious-related mortality is highly inconsistent, making comparison of infectious complication rates across allogeneic HCT clinical studies difficult. We categorized infectious complications from diagnosis or 1 year before HCT (whichever occurred later) through 2 years after HCT according to timing, frequency, causative organism, severity, and contribution to mortality for 431 consecutive patients who underwent allogeneic HCT from 2008 to 2011. We then assessed the contribution of risk factors, such as the frequency of pre-HCT infections and post-HCT GVHD, on post-HCT infection frequency and severity. We found that each pre-HCT bacterial infection/year leads to an additional 2.15 post-HCT bacterial infection/year (P = .004). Pre-HCT viral and fungal infections were not predictors for post-HCT infections. Acute GVHD (aGVHD) significantly increased the risk of developing life-threatening (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.33 to 2.90) and fatal (HR, 2.8; 95% CI, 1.10 to 7.08) infections. Furthermore, patients who develop aGVHD experienced ~60% more infections than patients who never develop aGVHD. Quantification of infection frequency and severity for patients with and without GVHD may facilitate comparison of infectious outcomes across allogeneic HCT trials.

A Quality Assessment of a Collaborative Model of a Pediatric Antimicrobial Stewardship Program.

BACKGROUND: Infectious Diseases Society of America guidelines recommend that key antimicrobial stewardship program (ASP) personnel include an infectious disease (ID) physician leader and dedicated ID-trained clinical pharmacist. Limited resources prompted development of an alternative model by using ID physicians and service-based clinical pharmacists at a pediatric hospital. The aim of this study was to analyze the effectiveness and impact of this alternative ASP model. METHODS: The collaborative ASP model incorporated key strategies of education, antimicrobial restriction, day 3 audits, and practice guidelines. High-use and/or high-cost antimicrobial agents were chosen with audits targeting vancomycin, caspofungin, and meropenem. The electronic medical record was used to identify patients requiring day 3 audits and to communicate ASP recommendations. Segmented regression analyses were used to analyze quarterly antimicrobial agent prescription data for the institution and selected services over time. RESULTS: Initiation of ASP and day 3 auditing was associated with blunting of a preexisting increasing trend for caspofungin drug starts and use and a significant downward trend for vancomycin drug starts (relative change -12%) and use (-25%), with the largest reduction in critical care areas. Although meropenem use was already low due to preexisting requirements for preauthorization, a decline in drug use (-31%, P = .021) and a nonsignificant decline in drug starts (-21%, P = .067) were noted. A 3-month review of acceptance of ASP recommendations found rates of 90%, 93%, and 100% for vancomycin, caspofungin, and meropenem, respectively. CONCLUSIONS: This nontraditional ASP model significantly reduced targeted drug usage demonstrating acceptance of integration of service-based clinical pharmacists and ID consultants.

What Transmission Precautions Best Control Influenza Spread in a Hospital?

Influenza is a significant problem within hospitals, leading to extended hospital stays, excess morbidity and mortality, and economic loss. Prevention and control strategies are generally "bundled"; therefore, the individual effects of particular strategies and the value of combined strategies cannot be determined directly, making it difficult to discern the optimal strategy. To quantify the individual and joint effectiveness of several known influenza infection control measures used in general hospitals, we simulated influenza transmission at a hypothetical hospital in Ann Arbor, Michigan, during a 1-year seasonal epidemic (June 2012-June 2013), using a susceptible-exposed-infected-recovered (SEIR) compartmental model. The hospital population comprised patients and health-care workers, interacting with its larger community population. Parameter ranges and values were determined from the literature (both national and local to Ann Arbor) and took into account coverage levels and effects of vaccination. The most effective individual strategies, based on percent reduction of cases, were: hand-washing (11%-27%), health-care worker vaccination (6%-19%), prevaccination of patients (4%-17%), patient isolation (5%-16%), antiviral treatment (4%-14%), and use of face masks (3%-10%). Use of all strategies together with ideal levels of compliance could potentially halve the number of observed hospital cases of influenza; under a more realistic scenario, an almost 40% reduction could be achieved. A multifaceted approach is imperative to control and prevent nosocomial influenza in health-care settings.

Outbreak of KPC-3 Producing Carbapenem-Resistant Klebsiella pneumoniae in a US Pediatric Hospital.

BACKGROUND: The increase in carbapenem-resistant Enterobacteriaceae (CRE) infections is a critical public health issue. We recently experienced the largest single-center pediatric outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) at our hospital. The objective of this study was to describe the molecular epidemiology of this outbreak before and after infection-prevention interventions. METHODS: All positive cultures and associated clinical conditions were reviewed to determine whether health care-associated infections (HAIs) exist. HAIs were defined using Centers for Disease Control and Prevention guidelines. CRKP isolates were collected and screened for the presence of ß-lactamase genes. Strain relatedness of CRKP isolates was determined by field-inversion gel electrophoresis (FIGE) and multilocus sequence typing (MLST). Polymerase chain reaction (PCR) amplification and sequencing of blaTEM, blaSHV, and blaKPC genes were performed on representative isolates. RESULTS: During March-July 2010, 18 CRKP isolates were recovered from 15 unique patients. Six isolates were considered HAIs; all were central-line-associated bloodstream infections. All isolates testing positive by PCR for blaKPC were found to carry KPC-3 in transposon Tn4401 isotype "b." FIGE revealed 2 prevalent patterns (accounting for 10 and 3 CRKP isolates, respectively) that MLST demonstrated to consist entirely of strains from ST730; the remaining FIGE types corresponded to ST14, ST15, and ST1559 (a single-locus variant of ST730), with these alternate backgrounds appearing later in the outbreak. New CRKP cases decreased after the implementation of infection-control interventions. All isolates were ciprofloxacin sensitive. CONCLUSIONS: Molecular analyses document the introduction of a KPC-3-producing CRKP clone into our hospital setting, though some isolates appear to have other mechanisms of carbapenem resistance. The transition to a polyclonal epidemiology suggests that the initial outbreak was due to nosocomial spread of a single ST730 clone, while latter isolates may have been secondary to the introduction of a blaKPC-3/Tn4401 isotype "b"-containing plasmid into other K pneumoniae strain backgrounds versus new carbapenemase-producing bacteria.

Immune Abnormalities in Fontan Protein-Losing Enteropathy: A Case-Control Study.

OBJECTIVE: To comprehensively characterize the immunologic characteristics of patients with protein-losing enteropathy (PLE) post-Fontan and compare them with patients without PLE post-Fontan. STUDY DESIGN: Patients with PLE post-Fontan and age-matched controls post-Fontan were prospectively studied with laboratory markers of immune function. Infectious history was obtained by interview and chart review. The groups' demographics, cardiac history, immune characteristics, and infection history were compared using appropriate 2-group statistics. RESULTS: A total of 16 patients enrolled (8 patients with PLE and 8 controls). All patients with PLE had lymphopenia compared with 25% of controls (P = .01). All patients with PLE had markedly depressed CD4 T cell counts (median 58 cells/µL) compared with controls (median 450 cells/µL, P = .0002); CD4% was also low in the PLE group (12.3%) and normal in control (36.9%, P = .004). Both groups had mildly depressed CD8 T cells and normal to slightly elevated natural killer and B-cell subsets. A majority of patients with PLE (62.5%) had negative titers to measles, mumps, and rubella vaccination, compared with no control Fontan with a negative titer (P = .03). Despite profoundly low CD4 counts, the frequency of infection was not different between groups with no reported opportunistic infections. CONCLUSIONS: Patients with Fontan-associated PLE have extensive quantitative immune abnormalities, particularly CD4 deficiency. These immune abnormalities are similar to those found in non-Fontan patients with PLE caused by intestinal lymphangiectasia.

Accuracy of hospital administrative data in reporting central line-associated bloodstream infections in newborns.

OBJECTIVES: Central line-associated bloodstream infections (CLABSIs) are a significant source of morbidity and mortality in the NICU. In 2010, Medicaid was mandated not to pay hospitals for treatment of CLABSI; however, the source of CLABSI data for this policy was not specified. Our objective was to evaluate the accuracy of hospital administrative data compared with CLABSI confirmed by an infection control service. METHODS: We evaluated hospital administrative and infection control data for newborns admitted consecutively from January 1, 2008, to December 31, 2010. Clinical and demographic data were collected through chart review. We compared cases of CLABSI identified by administrative data (International Classification of Diseases, Ninth Revision, Clinical Modification 999.31) with infection control data that use national criteria from the Centers for Disease Control and Prevention as the gold standard. To ascertain the nature possible deficiencies in the administrative data, each patient's medical record was searched to determine if clinical phrases that commonly refer to CLABSI appeared. RESULTS: Of 2920 infants admitted to the NICU during our study period, 52 were identified as having a CLABSI: 42 by infection control data only, 7 through hospital administrative data only, and 3 appearing in both. Against the gold standard, hospital administrative data were 6.7% sensitive and 99.7% specific, with a positive predictive value of 30.0% and a negative predictive value of 98.6%. Only 48% of medical records indicated a CLABSI. CONCLUSIONS: Our findings from a major children's hospital NICU indicate that International Classification of Diseases, Ninth Revision, Clinical Modification code 993.31 is presently not accurate and cannot be used reliably to compare CLABSI rates in NICUs.