Circulating microRNAs differentiate Kawasaki Disease from infectious febrile illnesses in childhood.

BACKGROUND: Kawasaki Disease (KD) is an acute vasculitis of unknown etiology in children that can lead to coronary artery lesions (CAL) in 25% of untreated patients. There is currently no diagnostic test for KD, and the clinical presentation is often difficult to differentiate from other febrile childhood illnesses. Circulating microRNAs (miRNAs) are small noncoding RNA molecules that control gene expression by inducing transcript degradation or by blocking translation. We hypothesize that the expression of circulating miRNAs will differentiate KD from non-KD febrile illnesses in children. METHODS: Circulating miRNA profiles from 84 KD patients and 29 non-KD febrile controls (7 viral and 22 bacterial infections) were evaluated. 3 ul of serum from each subject was submitted to 3 freeze/heat cycles to ensure miRNA release from microvesicles or interaction with serum proteins. miRNAs were reverse transcribed using a pool of primers specific for each miRNA. Real-time PCR reactions were performed in a 384 well plate containing sequence-specific primers and TaqMan probes in the ABI7900. '. RESULTS: KD patients (3.6 ± 2.2 yrs., 58% male) were found to have a unique circulating miRNA profile, including upregulation of miRNA-210-3p, -184, and -19a-3p (p < .0001), compared to non-KD febrile controls (8.5 ± 6.1 yrs., 72% male). CONCLUSIONS: Circulating miRNAs can differentiate KD from infectious febrile childhood diseases, supporting their potential as a diagnostic biomarker for KD.

Phase I/IIa Trial of Atorvastatin in Patients with Acute Kawasaki Disease with Coronary Artery Aneurysm.

OBJECTIVES: To determine the safety, tolerability, pharmacokinetics, and immunomodulatory effects of a 6-week course of atorvastatin in patients with acute Kawasaki disease with coronary artery (CA) aneurysm (CAA). STUDY DESIGN: This was a Phase I/IIa 2-center dose-escalation study of atorvastatin (0.125-0.75 mg/kg/day) in 34 patients with Kawasaki disease (aged 2-17 years) with echocardiographic evidence of CAA. We measured levels of the brain metabolite 24(S)-hydroxycholesterol (24-OHC), serum lipids, acute-phase reactants, liver enzymes, and creatine phosphokinase; peripheral blood mononuclear cell populations; and CA internal diameter normalized for body surface area before atorvastatin treatment and at 2 and 6 weeks after initiation of atorvastatin treatment. RESULTS: A 6-week course of up to 0.75 mg/kg/day of atorvastatin was well tolerated by the 34 subjects (median age, 5.3 years; IQR, 2.6-6.4 years), with no serious adverse events attributable to the study drug. The areas under the curve for atorvastatin and its metabolite were larger in the study subjects compared with those reported in adults, suggesting a slower rate of metabolism in children. The 24-OHC levels were similar between the atorvastatin-treated subjects and matched controls. CONCLUSIONS: Atorvastatin was safe and well tolerated in our cohort of children with acute Kawasaki disease and CAA. A Phase III efficacy trial is warranted in this patient population, which may benefit from the known anti-inflammatory and immunomodulatory effects of this drug.

Diagnostic and Treatment Trends in Children With Kawasaki Disease in the United States, 2006-2015.

OBJECTIVE: To evaluate variations in treatment practice and compliance with national guidelines for the diagnostic evaluation of children with Kawasaki disease (KD). STUDY DESIGN: We used the Pediatric Hospital Information System database to analyze demographic, laboratory and treatment data from patients admitted with KD between January 1, 2006, and December 31, 2015. RESULTS: During the study period, 12,089 children with KD were diagnosed. Nearly all patients had a complete blood cell count, erythrocyte sedimentation rate, and C-reactive protein ordered. Fewer patients had alanine aminotransferase (48.6%) or a urinalysis (75.3%). A small percentage of children had abdominal imaging (11.5%), neck imaging (5.9%), and lumbar punctures (4.5%), and 36.0% of patients received antibiotic therapy. Obtaining echocardiograms pretreatment and the use of steroids and infliximab significantly increased over the study period (P < 0.001). For patients who failed initial intravenous immunoglobulin (IVIG) monotherapy, 82.0% received a second dose of IVIG, 7.7% received steroids, 6.5% received infliximab, and 3.9% received combination therapy. Patients receiving infliximab or steroids as second therapy had a higher response rate than those who received only a second IVIG dose (87.9% versus 83.0% versus 73.3%, P < 0.001). CONCLUSIONS: KD remains a challenging diagnosis. Opportunities exist for earlier use of echocardiograms in the evaluation of children with potential KD. Significant variations in practice exist surrounding second-line therapy. Our data suggest superiority of second-line therapy use of infliximab or steroids over IVIG in terms of reducing need for additional therapies. Prospective, controlled studies are needed to confirm this finding.

Diagnosis of Kawasaki Disease Using a Minimal Whole-Blood Gene Expression Signature.

Importance: To date, there is no diagnostic test for Kawasaki disease (KD). Diagnosis is based on clinical features shared with other febrile conditions, frequently resulting in delayed or missed treatment and an increased risk of coronary artery aneurysms. Objective: To identify a whole-blood gene expression signature that distinguishes children with KD in the first week of illness from other febrile conditions. Design, Setting, and Participants: The case-control study comprised a discovery group that included a training and test set and a validation group of children with KD or comparator febrile illness. The setting was pediatric centers in the United Kingdom, Spain, the Netherlands, and the United States. The training and test discovery group comprised 404 children with infectious and inflammatory conditions (78 KD, 84 other inflammatory diseases, and 242 bacterial or viral infections) and 55 healthy controls. The independent validation group comprised 102 patients with KD, including 72 in the first 7 days of illness, and 130 febrile controls. The study dates were March 1, 2009, to November 14, 2013, and data analysis took place from January 1, 2015, to December 31, 2017. Main Outcomes and Measures: Whole-blood gene expression was evaluated using microarrays, and minimal transcript sets distinguishing KD were identified using a novel variable selection method (parallel regularized regression model search). The ability of transcript signatures (implemented as disease risk scores) to discriminate KD cases from controls was assessed by area under the curve (AUC), sensitivity, and specificity at the optimal cut point according to the Youden index. Results: Among 404 patients in the discovery set, there were 78 with KD (median age, 27 months; 55.1% male) and 326 febrile controls (median age, 37 months; 56.4% male). Among 202 patients in the validation set, there were 72 with KD (median age, 34 months; 62.5% male) and 130 febrile controls (median age, 17 months; 56.9% male). A 13-transcript signature identified in the discovery training set distinguished KD from other infectious and inflammatory conditions in the discovery test set, with AUC of 96.2% (95% CI, 92.5%-99.9%), sensitivity of 81.7% (95% CI, 60.0%-94.8%), and specificity of 92.1% (95% CI, 84.0%-97.0%). In the validation set, the signature distinguished KD from febrile controls, with AUC of 94.6% (95% CI, 91.3%-98.0%), sensitivity of 85.9% (95% CI, 76.8%-92.6%), and specificity of 89.1% (95% CI, 83.0%-93.7%). The signature was applied to clinically defined categories of definite, highly probable, and possible KD, resulting in AUCs of 98.1% (95% CI, 94.5%-100%), 96.3% (95% CI, 93.3%-99.4%), and 70.0% (95% CI, 53.4%-86.6%), respectively, mirroring certainty of clinical diagnosis. Conclusions and Relevance: In this study, a 13-transcript blood gene expression signature distinguished KD from other febrile conditions. Diagnostic accuracy increased with certainty of clinical diagnosis. A test incorporating the 13-transcript disease risk score may enable earlier diagnosis and treatment of KD and reduce inappropriate treatment in those with other diagnoses.

Infliximab Plus Intravenous Immunoglobulin (IVIG) Versus IVIG Alone as Initial Therapy in Children With Kawasaki Disease Presenting With Coronary Artery Lesions: Is Dual Therapy More Effective?

BACKGROUND: We previously demonstrated that 80% of Kawasaki disease (KD) patients who develop coronary artery lesions (CALs) have them at diagnosis. We postulated that KD patients presenting with CALs represent a group that may benefit from more aggressive initial therapy. Infliximab has been shown to decrease inflammation in KD patients when added to standard therapy. We compared outcomes of KD patients with CALs initially treated with intravenous immunoglobulin (IVIG) alone versus IVIG plus infliximab. METHODS: Medical records of KD patients from January 2009 to July 2016 were retrospectively reviewed. CALs were defined as a left anterior descending or right coronary artery Z score ≥2.5. KD patients with CALs on initial echocardiogram treated with IVIG alone were compared with those treated with IVIG plus infliximab. Clinical characteristics were compared between groups using Wilcoxon rank-sum test, χ test and Fischer's exact tests; length of stay was analyzed using log-normal regression and need for additional therapy using logistic regression. Effect of treatment on CALs between groups was assessed using linear mixed models. RESULTS: Sixty-nine KD patients with CALs at presentation were included. Fifteen of 34 (44%) patients treated with IVIG alone required additional therapy compared with 4 of 35 (11%) patients treated with IVIG plus infliximab (P = 0.003). There were no significant differences between treatment groups for length of stay, CALs or C-reactive protein fall. CONCLUSIONS: IVIG plus infliximab as initial therapy reduces the need for additional therapy in KD patients presenting with CALs. Intensified initial therapy, consisting of infliximab plus IVIG, could be considered for this group of KD patients.

Epidemiology and Molecular Characteristics of Mycoplasma pneumoniae During an Outbreak of M. pneumoniae-associated Stevens-Johnson Syndrome.

BACKGROUND: An increase in Mycoplasma pneumoniae-associated Stevens-Johnson syndrome (SJS) cases at a Colorado pediatric hospital led to an outbreak investigation. We describe the epidemiologic and molecular characteristics of M. pneumoniae among SJS case-patients and surrounding community members during the outbreak. METHODS: M. pneumoniae polymerase chain reaction-positive respiratory specimens from 5 Colorado hospitals and 4 referral laboratories underwent confirmatory polymerase chain reaction testing; positive specimens then underwent multilocus variable-number tandem-repeat analysis (MLVA) and macrolide resistance testing. Three SJS-M. pneumoniae case-patient households were surveyed using a standardized questionnaire, and nasopharyngeal/oropharyngeal swabs were obtained from all consenting/assenting household contacts. International Classification of Diseases, 9th revision codes were used to identify pneumonia cases among Colorado patients 5-21 years of age from January 2009 to March 2014. RESULTS: Three different M. pneumoniae MLVA types were identified among the 5 SJS case-patients with confirmed infection; MLVA type 3-X-6-2 was seen more commonly in SJS case-patients (60%) than in 69 non-SJS community specimens (29%). Macrolide resistance was identified in 7% of community specimens but not among SJS case-patients. Of 15 household contacts, 5 (33%) were M. pneumoniae positive; all MLVA types were identical to those of the corresponding SJS case-patient, although the specimen from 1 contact was macrolide resistant. Overall pneumonia cases as well as those caused by M. pneumoniae specifically peaked in October 2013, coinciding with the SJS outbreak. CONCLUSIONS: The outbreak of M. pneumoniae-associated SJS may have been associated with a community outbreak of M. pneumoniae; clinicians should be aware of the M. pneumoniae-SJS relationship. Household transmission of M. pneumoniae was common within the households investigated.

Missed Opportunities for Influenza Vaccination Among Hospitalized Children With Influenza at a Tertiary Care Facility.

OBJECTIVES: To identify the extent and characteristics of missed opportunities for influenza vaccination among children hospitalized with influenza at a tertiary children's hospital. METHODS: We conducted a retrospective cohort study of hospitalized patients with polymerase chain reaction-confirmed influenza admitted to Children's Hospital Colorado from 2010 to 2014. We reviewed medical records for vaccination status and previous visits. The primary outcome was the proportion of underimmunized patients hospitalized with influenza with at least 1 missed opportunity visit (visit before influenza diagnosis in which an eligible patient did not receive the influenza vaccine). The relationship between sociodemographic characteristics and the primary outcome were examined using χ(2) tests and nonparametric tests, and variables with P < .2 were entered into a multivariate logistic regression model. RESULTS: Among 322 patients hospitalized with influenza, 199 (61%) were undervaccinated; 83 of 199 (42%) had at least 1 missed opportunity for influenza vaccination. Multivariate analysis demonstrated that high-risk status (adjusted odds ratio 6.9, 95% confidence interval 3.8-12.4) was associated with increased odds of having a missed opportunity visit. Most missed opportunity visits were to subspecialty clinics (42%), and most visits (71%) occurred from September to November. CONCLUSIONS: More than 40% of hospitalizations for influenza in children are associated with at least 1 missed opportunity visit at a tertiary center. Our findings highlight the potential role of tertiary care institutions in increasing influenza vaccination rates among children.

Myocardial Strain and Strain Rate in Kawasaki Disease: Range, Recovery, and Relationship to Systemic Inflammation/Coronary Artery Dilation.

BACKGROUND: Kawasaki Disease (KD), a systemic vasculitis of medium sized vessels, is the most common cause of acquired heart disease among children in the developed world. Some KD patients demonstrate echocardiographic evidence of depressed myocardial mechanics. However, the incidence, etiology, and reversibility of abnormal mechanics in KD patients remain undefined. METHODS AND RESULTS: We retrospectively studied 41 KD patients and measured myocardial strain and strain rate by velocity vector imaging from pre-treatment and convalescent echocardiograms. Pre-treatment procalcitonin, C-reactive protein (CRP), and coronary artery z-scores were obtained in all patients and compared between the groups with preserved versus depressed acute phase mechanics. The change in mechanics between the acute and convalescent phases was also assessed. Patients with initially low longitudinal strain improved by the convalescent period (mean difference - 4.0%; p<0.005) with the greatest improvement occurring in patients with the lowest initial strain (-7.3%; p<0.05). Patients with higher initial strain did not change significantly by the convalescent period. Patients with lower longitudinal and circumferential strain demonstrated higher median procalcitonin levels (1.2 vs. 0.3 ng/mL; p<0.05 and 1.8 vs. 0.4 ng/mL; p<0.05 respectively) and a trend towards higher CRP, but no difference in coronary artery z-scores. Strain rate was not associated with inflammatory markers or coronary artery z-scores. CONCLUSIONS: The range of strain found in our cohort was large. Improvement in mean strain was driven primarily by patients with lower initial strain. Lower strain was associated with increased markers of systemic inflammation, but not proximal coronary artery changes.

Procalcitonin (PCT) and Kawasaki Disease: Does PCT Correlate With IVIG-Resistant Disease, Admission to the Intensive Care Unit, or Development of Coronary Artery Lesions?

BACKGROUND: Kawasaki disease (KD) remains a clinical diagnosis due to the absence of a sensitive and specific diagnostic test. There are limited published data on the usefulness of procalcitonin (PCT) as a biomarker for the diagnosis or prognosis of children with KD. We hypothesized that PCT might be useful in predicting coronary artery lesions (CALs) and intravenous immunoglobulin (IVIG) resistance. METHODS: Eighty-five children with KD who were hospitalized within the first 10 days of illness were retrospectively reviewed. PCT was measured on stored serum or plasma samples obtained at the time of admission (pre-IVIG). Data were analyzed to determine whether there were statistically significant associations with PCT, erythrocyte sedimentation rate, and C-reactive protein levels and the incidence of CALs, pediatric intensive care unit admission, or IVIG-resistant disease in KD patients. RESULTS: PCT values in children hospitalized with acute KD ranged from 0.1 ng/mL to 143.9 ng/mL, with a median of 0.49 ng/mL (IQR 0.23-1.29 ng/mL). There was no correlation of PCT with patient age, race, or sex, but it was correlated with day of illness. KD patients with a PCT ≥ 0.5 ng/mL had a significantly higher incidence of IVIG-resistant disease (29% versus 7%, P = .02). There was no association between PCT and development of CALs in our sample. CONCLUSIONS: Additional research is needed to establish the sensitivity and specificity of PCT for the diagnosis of KD. PCT may be of value in predicting which children are at increased risk for IVIG-resistant disease.

Concurrent Respiratory Viruses and Kawasaki Disease.

BACKGROUND: The diagnosis of Kawasaki disease (KD) remains challenging without a definitive diagnostic test and currently is guided by using clinical patient characteristics and supported by laboratory data. The role of respiratory viruses in the pathogenesis of KD is not fully understood. METHODS: Charts of patients with KD admitted to Children's Hospital Colorado from January 2009 to May 2013 were retrospectively reviewed. Patients with KD who had a nasopharyngeal wash submitted for multiplex polymerase chain reaction (PCR) viral testing were included. Clinical characteristics, laboratory data, and outcomes of patients with and without positive respiratory viral PCR results were compared. RESULTS: Of 222 patients with KD admitted to the hospital, 192 (86%) had a respiratory viral PCR test performed on or shortly after admission. Ninety-three (41.9%) of the 192 patients with KD had a positive respiratory viral PCR, and the majority were positive for rhinovirus/enterovirus. No statistically significant differences were found in the clinical characteristics and laboratory values between the groups with and without positive respiratory viral PCR findings. Both groups had the same frequency of upper respiratory and gastrointestinal symptoms and had the same incidence of admission to the PICU, intravenous immunoglobulin-resistant disease, and coronary artery lesions. CONCLUSIONS: No differences in clinical presentations or outcomes in children with KD stratified according to positive or negative respiratory viral PCR testing were observed. A positive respiratory viral PCR or presence of respiratory symptoms at the time of presentation should not be used to exclude a diagnosis of KD.

Outbreak of Mycoplasma pneumoniae-Associated Stevens-Johnson Syndrome.

BACKGROUND: Stevens-Johnson syndrome (SJS) is an uncommon, sporadic disease and outbreaks are rare. In November 2013, an outbreak of SJS was identified at Children's Hospital Colorado. METHODS: Outbreak cases were children aged 5-21 with a discharge diagnosis of SJS admitted from September 1 to November 30, 2013. Medical charts were reviewed using standardized data collection forms. Respiratory specimens were tested for viruses and Mycoplasma pneumoniae (Mp) by polymerase chain reaction (PCR). We conducted a separate 4-year retrospective case-control study comparing hospitalized SJS cases with and without evidence of Mp infection. RESULTS: During the outbreak, 8 children met SJS criteria. Median age was 11.5 years (range 8-16 years); 5 (63%) were boys and 5 (63%) were Mp-PCR-positive. Of the 5 PCR-positive children, none had preceding medication exposure, and all had radiographic pneumonia. All outbreak Mp isolates were macrolide susceptible. The retrospective case-control analysis showed that Mp-associated SJS episodes (n = 17) were more likely to have pneumonia (odds ratio [OR] 7.5, confidence interval [CI] 1.6­35.1), preceding respiratory symptoms (OR 30.0, CI 3.3­269.4) [corrected] an erythrocyte sedimentation rate ≥35 mg/dL (OR 22.8, CI 2.1-244.9), and ≤3 affected skin sites (OR 4.5, CI 1.2-17.4) than non-Mp-associated SJS episodes (n = 23). CONCLUSIONS: We report the largest outbreak of SJS in children, which was also predominately associated with Mp infection. Mp-associated SJS was associated with a distinct clinical presentation that included less extensive skin disease, an elevated erythrocyte sedimentation rate, and evidence of a preceding respiratory infection.

Tissue Doppler Imaging as a Predictor of Immunoglobulin Resistance in Kawasaki Disease.

Kawasaki disease (KD) is characterized by myocarditis and left ventricular dysfunction during the acute phase of the illness. Despite treatment with intravenous immunoglobulin (IVIG), a significant number of patients are IVIG resistant. We evaluated KD patients in the acute phase of illness using tissue Doppler imaging (TDI) to assess whether myocardial dysfunction may predict IVIG resistance. All patients with acute KD presenting to Children's Hospital Colorado from February 2007 through March 2014 were included in this study and underwent echocardiograms with TDI evaluation at diagnosis. Patients were divided into two groups: IVIG resistant and IVIG responder. Group differences were assessed using Wilcoxon-Mann-Whitney and Chi-square testing. Receiver operating characteristic (ROC) curve analysis was utilized to determine threshold values of TDI measurements associated with IVIG resistance. Fifty-one age-matched IVIG resistant patients were compared to 51 IVIG responder patients [median age, IQR 44.57 (20.13-77.07) vs. 33.49 (17.30-62.89) months, p < 0.44]. There were significant differences in the septal and mitral early diastolic velocities (E') (p < 0.001 and p < 0.01), respectively. ROC analysis demonstrated that tricuspid E' <0.15 cm/s, septal E' <0.12 cm/s, and mitral E' <0.16 cm/s were good predictors of IVIG unresponsiveness (AUC = 0.66, 0.66, and 0.70, respectively). There were no differences between the systolic velocities and late diastolic velocities (A'). IVIG resistant KD patients present with significantly greater diastolic dysfunction compared to responders in patients with KD. TDI may be a useful tool to differentiate KD patients at higher risk of IVIG resistance.

A cluster of acute flaccid paralysis and cranial nerve dysfunction temporally associated with an outbreak of enterovirus D68 in children in Colorado, USA.

BACKGROUND: Clusters of acute flaccid paralysis or cranial nerve dysfunction in children are uncommon. We aimed to assess a cluster of children with acute flaccid paralysis and cranial nerve dysfunction geographically and temporally associated with an outbreak of enterovirus-D68 respiratory disease. METHODS: We defined a case of neurological disease as any child admitted to Children's Hospital Colorado (Aurora, CO, USA) with acute flaccid paralysis with spinal-cord lesions involving mainly grey matter on imaging, or acute cranial nerve dysfunction with brainstem lesions on imaging, who had onset of neurological symptoms between Aug 1, 2014, and Oct 31, 2014. We used Poisson regression to assess whether the numbers of cases during the outbreak period were significantly greater than baseline case numbers from a historical control period (July 31, 2010, to July 31, 2014). FINDINGS: 12 children met the case definition (median age 11·5 years [IQR 6·75-15]). All had a prodromal febrile illness preceding neurological symptoms by a median of 7 days (IQR 5·75-8). Neurological deficits included flaccid limb weakness (n=10; asymmetric n=7), bulbar weakness (n=6), and cranial nerve VI (n=3) and VII (n=2) dysfunction. Ten (83%) children had confluent, longitudinally extensive spinal-cord lesions of the central grey matter, with predominant anterior horn-cell involvement, and nine (75%) children had brainstem lesions. Ten (91%) of 11 children had cerebrospinal fluid pleocytosis. Nasopharyngeal specimens from eight (73%) of 11 children were positive for rhinovirus or enterovirus. Viruses from five (45%) of 11 children were typed as enterovirus D68. Enterovirus PCR of cerebrospinal fluid, blood, and rectal swabs, and tests for other causes, were negative. Improvement of cranial nerve dysfunction has been noted in three (30%) of ten children. All ten children with limb weakness have residual deficits. INTERPRETATION: We report the first geographically and temporally defined cluster of acute flaccid paralysis and cranial nerve dysfunction in children associated with an outbreak of enterovirus-D68 respiratory illness. Our findings suggest the possibility of an association between enterovirus D68 and neurological disease in children. If enterovirus-D68 infections continue to happen in an endemic or epidemic pattern, development of effective antiviral or immunomodulatory therapies and vaccines should become scientific priorities. FUNDING: National Center for Advancing Translational Sciences, National Institutes of Health.

Clinical practice guideline for the diagnosis and management of acute bacterial sinusitis in children aged 1 to 18 years.

OBJECTIVE: To update the American Academy of Pediatrics clinical practice guideline regarding the diagnosis and management of acute bacterial sinusitis in children and adolescents. METHODS: Analysis of the medical literature published since the last version of the guideline (2001). RESULTS: The diagnosis of acute bacterial sinusitis is made when a child with an acute upper respiratory tract infection (URI) presents with (1) persistent illness (nasal discharge [of any quality] or daytime cough or both lasting more than 10 days without improvement), (2) a worsening course (worsening or new onset of nasal discharge, daytime cough, or fever after initial improvement), or (3) severe onset (concurrent fever[temperature ≥39°C/102.2°F] and purulent nasal discharge for at least 3 consecutive days). Clinicians should not obtain imaging studies of any kind to distinguish acute bacterial sinusitis from viral URI, because they do not contribute to the diagnosis; however, a contrast-enhanced computed tomography scan of the paranasal sinuses should be obtained whenever a child is suspected of having orbital or central nervous system complications. The clinician should prescribe antibiotic therapy for acute bacterial sinusitis in children with severe onset or worsening course. The clinician should either prescribe antibiotic therapy or offer additional observation for 3 days to children with persistent illness. Amoxicillin with or without clavulanate is the firstline treatment of acute bacterial sinusitis. Clinicians should reassess initial management if there is either a caregiver report of worsening(progression of initial signs/symptoms or appearance of new signs/symptoms) or failure to improve within 72 hours of initial management.If the diagnosis of acute bacterial sinusitis is confirmed in a child with worsening symptoms or failure to improve, then clinicians may change the antibiotic therapy for the child initially managed with antibiotic or initiate antibiotic treatment of the child initially managed with observation. CONCLUSIONS: Changes in this revision include the addition of a clinical presentation designated as "worsening course," an option to treat immediately or observe children with persistent symptoms for 3 days before treating, and a review of evidence indicating that imaging is not necessary in children with uncomplicated acute bacterial sinusitis.

Rhino/enteroviruses in hospitalized children: a comparison to influenza viruses.

BACKGROUND: The relative impact of human rhino/enteroviruses (HRV/EV) compared to influenza viruses on hospitalized children is unknown. OBJECTIVES: This retrospective study compared the epidemiology and clinical characteristics of hospitalized patients with HRV/EV to patients hospitalized with influenza virus. STUDY DESIGN: Respiratory specimens from hospitalized children submitted between January 1, 2009 and December 31, 2009 to Children's Hospital Colorado Virology Laboratory in Aurora, CO were tested by a commercial multiplex PCR for 16 respiratory viruses and subtypes. Patients with specimens positive for HRV/EV or influenza virus without bacterial or viral co-infection were selected for retrospective chart review. RESULTS: Of the 2299 patients with specimens tested during the study period, 427 (18.6%) were singly positive for HRV/EV and 202 (8.8%) for influenza virus (p<0.01). Children with HRV/EV were more likely to present with increased work of breathing (67.9% vs. 52.5%, p<0.01) with crackles (36.3% vs. 23.3%, p<0.01) and wheezing (41.7% vs. 22.8%, p<0.01) noted on exam. Children hospitalized with HRV/EV had a shorter median length of stay (2 days vs. 3 days, p<0.01), duration of fever (1 days vs. 3 days, p<0.01), and duration of hypoxemia (2 days vs. 3 days, p<0.01) than children with influenza virus. Similar percentages of children with HRV/EV and influenza virus were admitted to the PICU and required positive pressure ventilation. There were no deaths in children hospitalized with HRV/EV, whereas 6 children with influenza virus expired. CONCLUSIONS: HRV/EVs are common pathogens in hospitalized children associated with serious lower respiratory tract disease and significant morbidity, similar to influenza viruses.

Kawasaki disease and the pediatric gastroenterologist: a diagnostic challenge.

BACKGROUND AND OBJECTIVES: Gastrointestinal symptoms and signs are rarely the main clinical presentation of Kawasaki disease (KD). In the present study, we report a series of patients with KD in whom a gastroenterology consult was obtained before consideration of the diagnosis of KD. METHODS: We retrospectively reviewed all patients with KD admitted to Children's Hospital Colorado from January 2009 through February 2011 with prominent gastrointestinal symptoms, resulting in gastrointestinal service consultation before their diagnosis of KD. RESULTS: We identified 7 of 118 (6%) patients with KD who met our criteria. All 7 patients were males, and the median age at admission was 9.7 years. All patients had abdominal pain and fever at presentation. Vomiting, diarrhea, and clinical jaundice were present in 70%, 50%, and 43% of patients, respectively. Aminotransferases and/or γ-glutamyl transpeptidase abnormalities were observed in 6 (89%) patients. All of the patients had fever and rash on admission, and 86% had nonexudative conjunctivitis and 71% had mucosal changes. Median duration of illness at gastroenterology consultation was 5 days, whereas median duration of illness at infectious disease consultation was 6 days. One patient developed coronary artery dilation and 2 patients had intravenous immunoglobulin-resistant KD. CONCLUSIONS: Gastroenterologists should be aware of gastrointestinal presentations of KD. Unexplained gastrointestinal symptoms in the presence of fever, and 1 or 2 of the major clinical signs of KD, should prompt consideration of KD in the differential diagnosis.

Variability in the Diagnosis of Encephalitis by Pediatric Subspecialists: The Need For a Uniform Definition.

Research definitions of encephalitis vary widely. When surveyed on the criteria used in clinical diagnosis, 88 pediatric specialists demonstrated diverse responses, with pediatric neurologists and pediatric infectious disease specialists differing significantly in their consideration of cerebrospinal fluid pleocytosis and abnormal neuroimaging. Results emphasize the need for a uniform definition.

Preventing coronary artery abnormalities: a need for earlier diagnosis and treatment of Kawasaki disease.

OBJECTIVES: The aim of this study was to explore the timing of coronary artery (CA) abnormalities in light of the expanding clinical spectrum of Kawasaki disease (KD). METHODS: We reviewed all cases of KD admitted to Children's Hospital Colorado from January 2007 through February 2011 who had CA abnormalities. A retrospective chart review was conducted to collect demographic, clinical, laboratory and echocardiogram (ECHO) data. CA abnormalities were defined as Z score ≥2.5 or presence of ectasia or aneurysms. RESULTS: A total of 210 patients with KD were identified. Fifty-seven (27.1%) of the 210 children with KD had CA abnormalities. Forty-six of the 57 (81%) children with CA abnormalities had CA abnormalities noted on their initial ECHO. Of the 46 children who had CA abnormalities detected on their initial ECHO, 37 (80%) had their ECHO on or before illness day 10. The median day of illness when abnormalities were detected on initial ECHO was day 7 (interquartile range: 5-8; range: 2-24 days). Only 25 of the 46 children (54%) were classified as complete KD, but 40 (87%) had the triad of conjunctivitis, rash and mucous membrane involvement. Thirteen (28%) had intravenous immunoglobulin-resistant disease. CONCLUSION: The majority of CA abnormalities in children with KD were identified in the initial ECHO, during the first week of illness. Earlier diagnosis and treatment is needed to impact the incidence of CA abnormalities in children with KD. Increased clinical suspicion and earlier use of ECHO in the initial workup of children with suspected KD may lead to more rapid diagnosis and treatment.

Association of Bacillus cereus infection with contaminated alcohol prep pads.

BACKGROUND: Bacillus species have caused healthcare-associated outbreaks of invasive disease as well as pseudo-outbreaks. We report an outbreak investigation of blood cultures positive for Bacillus cereus associated with alcohol prep pads (APPs) contaminated with B. cereus and Bacillus species resulting in a rapid internal product recall and subsequent international product recall. DESIGN: Epidemiologic and microbiologic outbreak investigation. SETTING: A 300-bed tertiary care children's hospital in Aurora, Colorado. PATIENTS: Patients with blood or cerebrospinal fluid cultures positive for B. cereus. METHODS: Three patients with blood cultures positive for B. cereus were identified in late 2010. Breaches in procedural and surgical techniques, common interventions, and products were explored. The following 3 common products were cultured: sterile saline syringes, chlorhexidine/alcohol skin preparation solution, and APPs. Repetitive sequence-based polymerase chain reaction (Rep-PCR) was used to compare isolates obtained from patients and from APPs and was confirmed by independent pulsed-field gel electrophoresis. RESULTS: There appeared to be a significant increase in blood cultures positive for B. cereus during 2009-2010. B. cereus and other Bacillus species were cultured from the internal contents of 63.3% of APPs not labeled as sterile, and 8 of the 10 positive lots were manufactured after 2007. None of the isolates obtained from the patients matched strains isolated from the APPs. However, some lots of APPs had strains that were indistinguishable from one another. CONCLUSIONS: APPs that were not labeled as sterile were contaminated with Bacillus species. The product was immediately recalled internally and replaced with APPs from another manufacturer that were labeled as sterile. On January 3, 2011, the manufacturer voluntarily recalled its APPs. Healthcare facilities, healthcare providers, and users of APPs should avoid the use of APPs not specifically labeled as sterile.