Impact of FilmArray meningitis encephalitis panel on HSV testing and empiric acyclovir use in children beyond the neonatal period.

Following implementation of the FilmArray meningitis and encephalitis panel, which enables rapid syndromic cerebrospinal fluid testing, HSV testing doubled in children >60 days with suspected central nervous system infection at Children's Hospital Colorado. Acyclovir initiation was unchanged, but duration decreased. Diagnostic and antimicrobial stewardship is needed for MEP optimization.

Sustainability of Handshake Stewardship: Extending a Hand Is Effective Years Later.

BACKGROUND: Children's Hospital Colorado created a unique method of antimicrobial stewardship, called handshake stewardship, that effectively decreased hospital anti-infective use and costs in its pilot year (2013). Handshake stewardship is distinguished by: (1) the lack of prior authorization; (2) a review of all prescribed anti-infectives; (3) a shared review by the physician and the pharmacist; and (4) a daily, rounding-based, in-person approach to supporting providers. We sought to reevaluate the outcomes of the program after 5 years of experience, totaling 8 years of data. METHODS: We retrospectively measured anti-infective (antibiotic, antiviral, antifungal) use hospital-wide by unit and by drug for an 8-year period spanning October 2010 to October 2018. Aggregated monthly use was measured in days of therapy per thousand patient days (DOT/1000 PD). The percentage of children admitted ever receiving an anti-infective was also measured, as well as severity-adjusted mortality, readmissions, and lengths of stay. RESULTS: Hospital-wide mean anti-infective use significantly decreased, from 891 (95% confidence interval [CI] 859-923) in the pre-implementation phase to 655 (95% CI 637-694) DOT/1000 PD in post-implementation Year 5; in a segmented regression time series analysis, this was a rate of -2.6 DOT/1000 PD (95% CI -4.8 to -0.4). This is largely attributable to decreased antibacterial use, from 704 (95% CI 686-722) to 544 (95% CI 525 -562) DOT/1000 PD. The percentage of children ever receiving an anti-infective during admission likewise declined, from 65% to 52% (95% CI 49-54). There were no detrimental effects on severity adjusted mortality, readmissions, or lengths of stay. CONCLUSIONS: The handshake method is an effective and sustainable approach to stewardship.

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.

Epidemiology and Clinical Relevance of Toxic Shock Syndrome in US Children.

INTRODUCTION: It is important for clinicians to recognize the contribution of toxic shock syndrome (TSS) to the overall burden of pediatric septic shock because the clinical features, optimal therapy and prognosis differ from non-TSS septic shock. METHODS: We analyzed cases of pediatric septic shock reported to the Pediatric Health Information Systems database between 2009 and 2013 to define the clinical and demographic characteristics of pediatric TSS in the United States. Using a validated International Classification of Diseases, 9th revision, coding strategy, we identified patients with infectious shock among inpatients age 1-18 years and classified cases of staphylococcal and streptococcal TSS for comparison with non-TSS cases. RESULTS: Of 8,226 cases of pediatric septic shock, 909 (11.1%) were classified as TSS and 562 (6.8%) were possible TSS cases. Staphylococcal TSS represented the majority (83%) of TSS cases and occurred more commonly in females and at an older age. Compared with non-TSS septic shock, TSS had significantly lower fatality rates, disease severity and length of hospital stay and was present more often at the time of admission (P < 0.001 for each). Streptococcal TSS was associated with poorer outcomes than staphylococcal TSS. Treatment for TSS differed from non-TSS septic shock in use of more clindamycin, vancomycin and Intravenous Immunoglobulin and less need for vasopressors. CONCLUSIONS: Results demonstrate a significant contribution of TSS to the burden of pediatric septic shock in the United States. The findings emphasize the importance of inclusion of TSS diagnostic and therapeutic considerations in sepsis treatment protocols for children.

Implementation of Rapid Molecular Infectious Disease Diagnostics: the Role of Diagnostic and Antimicrobial Stewardship.

New rapid molecular diagnostic technologies for infectious diseases enable expedited accurate microbiological diagnoses. However, diagnostic stewardship and antimicrobial stewardship are necessary to ensure that these technologies conserve, rather than consume, additional health care resources and optimally affect patient care. Diagnostic stewardship is needed to implement appropriate tests for the clinical setting and to direct testing toward appropriate patients. Antimicrobial stewardship is needed to ensure prompt appropriate clinical action to translate faster diagnostic test results in the laboratory into improved outcomes at the bedside. This minireview outlines the roles of diagnostic stewardship and antimicrobial stewardship in the implementation of rapid molecular infectious disease diagnostics.

Handshake Stewardship: A Highly Effective Rounding-based Antimicrobial Optimization Service.

BACKGROUND: Implementation of an antimicrobial stewardship program is recommended as one solution to combat increasing antimicrobial resistance. Most antimicrobial stewardship programs use preauthorization or restrictive strategies recommended in national guidelines. We describe a unique, rounding-based strategy, handshake stewardship. Handshake stewardship is distinguished by: (1) lack of restriction and preauthorization, (2) review of all prescribed antimicrobials and (3) a rounding-based, in-person approach to feedback by a pharmacist-physician team. METHODS: We retrospectively measured antimicrobial use hospital-wide and by unit during preimplementation, planning, and postimplementation phases of the handshake stewardship approach to determine the efficacy of this strategy in decreasing use in a freestanding children's hospital. All antimicrobials prescribed on the inpatient services between October 2010 and September 2014 were included in the review. Monthly antimicrobial use (hospital-wide and by unit) was measured in days of therapy per 1000 patient days (DOT/1000 PD). RESULTS: Overall antimicrobial use decreased by 10.9% during the 4 years of the analysis (942 to 839 DOT/1000 PD, P < 0.01), with an impact of 10.3% on antibacterials (750 to 673 DOT/1000 PD, P < 0.01). Vancomycin use decreased by 25.7% (105 to 78 DOT/1000 PD, P < 0.01). Meropenem use decreased by 22.2% (45 to 35 DOT/1000 PD, P = 0.04) without a compensatory increase of other antipseudomonal agents. Decreased usage was observed both hospital-wide and on individual units for most agents. CONCLUSIONS: The handshake stewardship approach is an effective strategy for an antimicrobial stewardship program, as demonstrated by the widespread and significant decrease in antimicrobial use after implementation.

Comparison of Whole-Genome Sequencing and Molecular-Epidemiological Techniques for Clostridium difficile Strain Typing.

We analyzed in parallel 27 pediatric Clostridium difficile isolates by repetitive sequence-based polymerase chain reaction (RepPCR), pulsed-field gel electrophoresis (PFGE), and whole-genome next-generation sequencing. Next-generation sequencing distinguished 3 groups of isolates that were indistinguishable by RepPCR and 1 isolate that clustered in the same PFGE group as other isolates.

Risk Factors for Death and Major Morbidity in Guatemalan Children with Acute Bacterial Meningitis.

BACKGROUND: Acute bacterial meningitis (ABM) remains a significant cause of pediatric illness and death in low and middle income countries. Identifying severity risk factors and predictive scores may guide interventions to reduce poor outcomes. METHODS: Data from a prospective surveillance study for ABM in children aged 0-59 months admitted to 3 referral hospitals in Guatemala City from 2000 to 2007 were analyzed. ABM was defined as positive cerebrospinal fluid (CSF) culture, positive latex agglutination or CSF white blood cell greater than 100 cells/mL. Univariate and multivariate analyses of risk factors at hospital admission that predicted major morbidity or death during hospitalization were performed, along with validation of the predictive Herson-Todd score (HTS). RESULTS: Of 809 children with ABM episodes, 221 (27.3%) survived with major morbidity and 192 (23.7%) died. Among 383 children with nonmissing data, the most significant multivariate predictors for death or major morbidity were seizure [odds ratio (OR), 101.5; P < 0.001], CSF glucose less than 20 mg/dL (OR, 5.3; P = 0.0004), symptom duration more than 3 days (OR, 3.7; P = 0.003) and coma (OR, 6.3; P = 0.004). Of 221 children with a HTS greater than 5, 204 (92%) died or suffered major morbidity (OR, 10.3; P < 0.0001). CONCLUSION: ABM is a cause of considerable morbidity and mortality in Guatemala. Several clinical risk factors and the composite HTS predicted death or major morbidity. These predictors could help clinicians in low and middle income country guide medical care for ABM and could contribute to the public health impact assessment in preventing meningitis with vaccines.

Analysis of the pediatric health information system database as a surveillance tool for travel-associated infectious diseases.

The Pediatric Health Information System (PHIS) database collects admission, diagnostic, and treatment data among 44 children's hospitals across the United States (U.S.) and presents an opportunity for travel-associated infectious disease (TAID) surveillance. We calculated cumulative incidence rates among children admitted to 16 PHIS hospitals for dengue, malaria, and typhoid, and pooled TAID using discharge codes from 1999 to 2012. We compared incidence rates before, during, and after the 2007-2009 economic recession. Among 16 PHIS hospitals during the study period (1999-2012), incidence of dengue and pooled TAID (malaria, dengue, typhoid fever) increased significantly, and rates of malaria and typhoid trended upward. Admissions for dengue and pooled TAIDs increased significantly among 16 children's hospitals across the United States from 1999 to 2012. The PHIS database may provide a useful surveillance tool for TAIDs among children in the United States.

Herpes PCR testing and empiric acyclovir use beyond the neonatal period.

BACKGROUND: Diagnostic strategies based on empirical testing and treatment to identify herpes simplex virus (HSV) infection in neonates may not be appropriate for older children in whom the most common presentation of severe infection is encephalitis, a rare and clinically recognizable condition. METHODS: Use of acyclovir in infants and children in 6 common non-HSV infection-related diagnosis-related groups was characterized between 1999 and 2012 at 15 US pediatric hospitals by using the Pediatric Health Information System database. Characteristics of non-neonatal patients at 1 institution tested for HSV encephalitis over a 6.5-year period were then analyzed to identify factors associated with potentially unnecessary testing and treatment. RESULTS: Acyclovir use increased from 7.6% to 15.6% (P < .001) from 1999 to 2012. Much of this increase came in infants 30 to 60 days of age (82.7% increase, P < .001) and in patients with milder disease severity (44.8% increase, P < .001). Length of stay was increased by 2 days for children treated with acyclovir (P < .001). At our institution, 1394 HSV cerebrospinal fluid polymerase chain reactions were performed in children >30 days old, with only 3 positive results (0.22%). Comparison of the 3 subjects with positive testing and 55 with negative testing revealed that all cases, but only 4% (95% confidence interval 1.2%-14.0%) of noncases had clinical characteristics typical of HSV encephalitis. CONCLUSIONS: Strategies for diagnosis and empirical treatment of suspected HSV encephalitis beyond the neonatal period have trended toward the approach common for neonates without evidence of an increase in disease incidence. This may result in increased medical costs and risk to patients.

High colonization rate and prolonged shedding of Clostridium difficile in pediatric oncology patients.

Surveillance testing for Clostridium difficile among pediatric oncology patients identified stool colonization in 29% of patients without gastrointestinal symptoms and in 55% of patients with prior C. difficile infection (CDI). A high prevalence of C. difficile colonization and diarrhea complicates the diagnosis of CDI in this population.

Infectious shock and toxic shock syndrome diagnoses in hospitals, Colorado, USA.

In Colorado, USA, diagnoses coded as toxic shock syndrome (TSS) constituted 27.3% of infectious shock cases during 1993-2006. The incidence of staphylococcal TSS did not change significantly overall or in female patients 10-49 years of age but increased for streptococcal TSS. TSS may be underrecognized among all ages and both sexes.

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.

Influence of Culture Results on Management and Outcome of Pediatric Osteomyelitis and/or Septic Arthritis.

Children with uncomplicated osteomyelitis and/or septic arthritis were more likely (P < .01) to have positive focus than blood cultures. Those who grew a pathogen and/or started on a single antibiotic were more likely to be discharged on a single antibiotic, and those sent home on oral therapy had fewer adverse events.

Toxic shock syndrome and rhinosinusitis in children.

OBJECTIVE: To determine the association between toxic shock syndrome (TSS) and rhinosinusitis in children. DESIGN: Eighteen-year retrospective review of medical records. SETTING: Tertiary children's hospital. PATIENTS: A total of 76 patients were identified as having TSS. Twenty-three of them were also diagnosed as having either acute or chronic rhinosinusitis, with no other source of infection in 17 cases. INTERVENTIONS: Of the 23 patients with TSS and rhinosinusitis, 10 were admitted to the intensive care unit, 4 required pressors, and 6 received surgical intervention. Surgical intervention for sinus disease included bilateral antral lavage in 5 patients and bilateral maxillary antrostomy and ethmoidectomy in 1 patient. MAIN OUTCOME MEASURES: Patients with TSS and rhinosinusitis were identified using a rigorous set of definitions and detailed data pertaining to history, imaging studies, microbiologic studies, and hospital course. RESULTS: Correlation of the data revealed 4 patients who met the criteria for proven TSS and proven rhinosinusitis, 2 patients who met the criteria for probable TSS and proven rhinosinusitis, 7 patients who met the criteria for proven TSS and possible rhinosinusitis, and 3 patients who met the criteria for probable TSS and possible rhinosinusitis. CONCLUSIONS: Rhinosinusitis was found to be the primary cause of TSS 21% of the time in this series. Rhinosinusitis should be considered the primary cause of TSS when another site of infection has not been identified. Once the link is made, prompt otolaryngology consultation and sinus lavage should be considered.

Neonatal outcomes after elective cesarean delivery.

OBJECTIVE: To examine the outcomes of neonates born by elective repeat cesarean delivery compared with vaginal birth after cesarean (VBAC) in women with one prior cesarean delivery and to evaluate the cost differences between elective repeat cesarean and VBAC. METHODS: We conducted a retrospective cohort study of 672 women with one prior cesarean delivery and a singleton pregnancy at or after 37 weeks of gestation. Women were grouped according to their intention to have an elective repeat cesarean or a VBAC (successful or failed). The primary outcome was neonatal intensive care unit (NICU) admission and measures of respiratory morbidity. RESULTS: Neonates born by cesarean delivery had higher NICU admission rates compared with the VBAC group (9.3% compared with 4.9%, P=.025) and higher rates of oxygen supplementation for delivery room resuscitation (41.5% compared with 23.2%, P<.01) and after NICU admission (5.8% compared with 2.4%, P<.028). Neonates born by VBAC required the least delivery room resuscitation with oxygen, whereas neonates delivered after failed VBAC required the greatest degree of delivery room resuscitation. The costs of elective repeat cesarean were significantly greater than VBAC. However, failed VBAC accounted for the most expensive total birth experience (delivery and NICU use). CONCLUSION: In comparison with vaginal birth after cesarean, neonates born after elective repeat cesarean delivery have significantly higher rates of respiratory morbidity and NICU-admission and longer length of hospital stay. LEVEL OF EVIDENCE: II.

Effect of altitude on hospitalizations for respiratory syncytial virus infection.

OBJECTIVE: Respiratory syncytial virus (RSV) infection is the foremost cause of serious lower respiratory tract infection in young children and infants. Because higher rates of hospitalization for bronchiolitis and pneumonia have been noted in high-altitude regions, we hypothesized that physiologic responses to altitude would predispose children to more severe illness from RSV infection. This study examined the effect of residential altitude on hospitalizations for RSV infection in Colorado from 1998 through 2002. METHODS: A geographic information system was used to assemble data for altitude and demographic variables by zip code-tabulation areas. Data then were linked with hospital discharge data for RSV infections. Poisson regression models were developed to explore correlations between hospitalization rates and residential altitude, after adjustment for socioeconomic differences in the underlying population. RESULTS: RSV-associated hospitalizations averaged 15.9 per 1000 infants who were younger than 1 year and 1.8 per 1000 children who were 1 to 4 years of age per season. A multivariate analysis suggested that the rate of hospitalization for RSV-specific International Classification of Diseases, Ninth Revision, Clinical Modification codes increased 25% among infants who were younger than 1 year and 53% among children who were 1 to 4 years of age for every 1000-m increase in altitude. The risk for RSV-associated hospitalization was highest at elevations above 2500 m. CONCLUSIONS: High altitude above 2500 m is a modest predictor for RSV-associated hospitalization. Practitioners in these regions should consider additional efforts to educate parents about RSV infection and its prevention and the importance of early treatment.