Central-line-associated bloodstream infections and central-line-associated non-CLABSI complications among pediatric oncology patients.

OBJECTIVE: To assess central venous catheter (CVC) harm in pediatric oncology patients, we explored risks for central-line-associated bloodstream infections (CLABSIs) and central-line-associated non-CLABSI complications (CLANCs). DESIGN: Retrospective cohort study. SETTING: Midwestern US pediatric oncology program. PATIENTS: The study cohort comprised 592 pediatric oncology patients seen between 2006 and 2016. METHODS: CLABSIs were defined according to Centers for Disease Control and Prevention (CDC)/National Health Safety Network (NHSN) definitions. CLANCs were classified using a novel definition requiring CVC removal. Patient-level and central-line-level risks were calculated using a negative binomial model to adjust for correlations between total events and line numbers. RESULTS: CVCs were inserted in 62% of patients, with 175,937 total catheter days. The inpatient CLABSI and CLANC rates were 5.8 and 8.5 times higher than outpatient rates. At the patient level, shared risks included acute myeloid leukemia (AML) and age <1 year at diagnosis. At the line level, shared risks included age <1 year at diagnosis, non-mediports, and >1 lumen. AML was a CLABSI-specific risk. CLANC-specific risks included non-brain-tumor diagnosis, younger age at diagnosis or central-line placement, and age <1 year at diagnosis or line placement. Multivariable risks were for CLABSI >1 lumen and for CLANC age <1 year at placement. CONCLUSIONS: Among patients with CVCs, CLABSI and CLANC rates were similar, higher among inpatients than outpatients. For both CLABSIs and CLANCs, infants and patients with AML were at higher risk. In both univariate and multivariate models, lines with >1 lumen were associated with CLABSIs and placement during infancy with CLANCs.

Outcomes After Positive Syphilis Screening.

BACKGROUND: Syphilis screening during pregnancy helps prevent congenital syphilis. The harms associated with false positive (FP) screens and whether screening leads to correct treatments has not been well determined. METHODS: The population included mothers and infants from 75 056 pregnancies. Using laboratory-based criteria we classified initial positive syphilis screens as FP or true positive (TP) and calculated false discovery rates. For mothers and infants we determined treatments, clinical characteristics, and syphilis classifications. RESULTS: There were 221 positive screens: 183 FP and 38 TP. The false discovery rate was 0.83 (95% confidence interval [CI], 0.78-0.88). False discovery rates were similar for traditional 0.83 [95% CI, 0.72-0.94] and reverse algorithms 0.83 (95% CI, 0.77-0.88), and for syphilis Immunoglobin (Ig) G 0.79 (95% CI, 0.71-0.86) and total 0.90 (95% CI, 0.82-0.97) assays. FP screens led to treatment in 2 women and 1 infant. Two high-risk women were not rescreened at delivery and were diagnosed after hospital discharge; 1 infant developed congenital syphilis. Among 15 TP women with new syphilis, the diagnosis was before the late third trimester in 14 (93%). In one-half of these women, there was concern for reinfection, treatment failure, inadequate treatment or follow-up care, or late treatment, and their infants did not achieve an optimal syphilis classification. CONCLUSIONS: Syphilis screening identifies maternal syphilis, but limitations include FP screens, which occasionally lead to unnecessary treatment, inconsistent risk-based rescreening, and among TP mothers failure to optimize care to prevent birth of infants at higher risk for congenital syphilis.

Association of Diagnostic Stewardship for Blood Cultures in Critically Ill Children With Culture Rates, Antibiotic Use, and Patient Outcomes: Results of the Bright STAR Collaborative.

Importance: Blood culture overuse in the pediatric intensive care unit (PICU) can lead to unnecessary antibiotic use and contribute to antibiotic resistance. Optimizing blood culture practices through diagnostic stewardship may reduce unnecessary blood cultures and antibiotics. Objective: To evaluate the association of a 14-site multidisciplinary PICU blood culture collaborative with culture rates, antibiotic use, and patient outcomes. Design, Setting, and Participants: This prospective quality improvement (QI) collaborative involved 14 PICUs across the United States from 2017 to 2020 for the Bright STAR (Testing Stewardship for Antibiotic Reduction) collaborative. Data were collected from each participating PICU and from the Children's Hospital Association Pediatric Health Information System for prespecified primary and secondary outcomes. Exposures: A local QI program focusing on blood culture practices in the PICU (facilitated by a larger QI collaborative). Main Outcomes and Measures: The primary outcome was blood culture rates (per 1000 patient-days/mo). Secondary outcomes included broad-spectrum antibiotic use (total days of therapy and new initiations of broad-spectrum antibiotics ≥3 days after PICU admission) and PICU rates of central line-associated bloodstream infection (CLABSI), Clostridioides difficile infection, mortality, readmission, length of stay, sepsis, and severe sepsis/septic shock. Results: Across the 14 PICUs, the blood culture rate was 149.4 per 1000 patient-days/mo preimplementation and 100.5 per 1000 patient-days/mo postimplementation, for a 33% relative reduction (95% CI, 26%-39%). Comparing the periods before and after implementation, the rate of broad-spectrum antibiotic use decreased from 506 days to 440 days per 1000 patient-days/mo, respectively, a 13% relative reduction (95% CI, 7%-19%). The broad-spectrum antibiotic initiation rate decreased from 58.1 to 53.6 initiations/1000 patient-days/mo, an 8% relative reduction (95% CI, 4%-11%). Rates of CLABSI decreased from 1.8 to 1.1 per 1000 central venous line days/mo, a 36% relative reduction (95% CI, 20%-49%). Mortality, length of stay, readmission, sepsis, and severe sepsis/septic shock were similar before and after implementation. Conclusions and Relevance: Multidisciplinary diagnostic stewardship interventions can reduce blood culture and antibiotic use in the PICU. Future work will determine optimal strategies for wider-scale dissemination of diagnostic stewardship in this setting while monitoring patient safety and balancing measures.

Physician-to-Physician Electronic Consultation: A Tool for the Pediatric Infectious Diseases Specialist to Document Encounters and Quantify Effort.

E-consults replace "curbside" interactions, facilitate provider-specialist communication, document within the medical record, and track relative value units (RVUs). Pediatric infectious diseases (PID) E-consults commonly relate to vaccines, exposures, diagnoses, and treatments. The documented RVU effort of 197 consecutive PID E-consults was equivalent to 70 level 4 new outpatient consults.

Congenital syphilis: Missed opportunities and the case for rescreening during pregnancy and at delivery.

Two infants treated for syphilis born to at risk mothers who screened negative at their first prenatal visit but were not rescreened at delivery are described. The first presented with classic, but unrecognized, features of congenital syphilis. In the second case, possible early maternal syphilis was diagnosed soon after delivery using the treponemal first reverse-screening algorithm. Although the child's physical exam was normal and the maternal rapid plasma reagin (RPR) negative, the child was treated for syphilis because maternal confirmatory treponemal tests suggested recent seroconversion. Given the re-emergence of congenital syphilis, our report aims to demonstrate the importance of rescreening women at increased risk and improve awareness of common manifestations of the syphilis disease in the newborn. For women at increased risk, repeat syphilis testing early in the third trimester and again at delivery in communities and populations with a high prevalence of syphilis is recommended.

Catheter-Associated Urinary Tract Infection Reduction in a Pediatric Safety Engagement Network.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are a leading cause of health care-associated infection. Catheter insertion bundles (IBs) and maintenance bundles (MBs) have been developed to prevent CAUTIs but have not been extensively validated for use in pediatric populations. We report the CAUTI prevention efforts of a large network of children's hospitals. METHODS: Children's hospitals joined the Children's Hospitals' Solutions for Patient Safety engagement network from 2011 to 2017, using an open start time engagement approach, and elected to participate in CAUTI prevention efforts, with 26 submitting data initially and 128 at the end. CAUTI prevention recommendations were first released in May 2012, and IBs and MBs were released in May 2014. Hospitals reported on CAUTIs, patient-days, and urinary catheter-line days and tracked reliability to each bundle. For the network, run charts or control charts were used to plot CAUTI rates, urinary catheter use, and reliability to each bundle component. RESULTS: After the introduction of the pediatric CAUTI IBs and MBs, CAUTI rates across the network decreased 61.6%, from 2.55 to 0.98 infections per 1000 catheter-line days. Centerline shifts occurred both before and after the 2015 Centers for Disease Control and Prevention CAUTI definition change. Urinary catheter use rates did not decline during the intervention period. Network reliability to the IBs and MBs increased to 95.4% and 86.9%, respectively. CONCLUSIONS: IBs and MBs aimed at preventing CAUTIs were introduced across a large network of children's hospitals. Across the network, the rate of urinary tract infections among hospitalized children with indwelling urinary catheters decreased 61.6%.

Addressing the threat from within: Investigation of respiratory symptoms in a health care worker with untreated latent tuberculosis infection.

Tuberculosis (TB) in the health care worker demands orchestrated efforts from health care institutions to promptly identify cases and address community risk. We describe a pediatric intensive care unit nurse with latent TB infection who developed hemoptysis and a lung infiltrate concerning for active TB. Her evaluation and contact investigation were facilitated by our institution's command center. Although TB was ultimately ruled out, this case tested our team-based care in response to a suspected high-consequence pathogen.

Patient Satisfaction and Antibiotic Prescribing for Respiratory Infections by Telemedicine.

BACKGROUND AND OBJECTIVES: Respiratory tract infections (RTIs) are a common reason for direct-to-consumer (DTC) telemedicine consultation. Antibiotic prescribing during video-only DTC telemedicine encounters was explored for pediatric RTIs. METHODS: Encounter data were obtained from a nationwide DTC telemedicine platform. Mixed-effects regression was used to assess variation in antibiotic receipt by patient and physician factors as well as the association between antibiotic receipt and visit length or patient satisfaction. RESULTS: Of 12 842 RTI encounters with 560 physicians, antibiotics were prescribed in 55%. The provider was more likely to receive a 5-star rating from the parent when an antibiotic was prescribed (93.4% vs 80.8%). A 5-star rating was associated with a prescription for an antibiotic (odds ratio [OR] 3.38; 95% confidence interval [CI] 2.84 to 4.02), an antiviral (OR 2.56; 95% CI 1.81 to 3.64), or a nonantibiotic (OR 1.93; 95% CI 1.58 to 2.36). Visit length was associated with higher odds of a 5-star rating only when no antibiotic was prescribed (OR 1.03 per 6 seconds; 95% CI 1.01 to 1.06). Compared with nonpediatricians, pediatric providers were less likely to prescribe antibiotics (OR 0.44; 95% CI 0.29 to 0.68); however, pediatricians received higher encounter satisfaction ratings (OR 1.50; 95% CI 1.11 to 2.03). CONCLUSIONS: During DTC telemedicine consultations for RTIs, pediatric patients were frequently prescribed antibiotics, which correlated with visit satisfaction. Although pediatricians prescribed antibiotics at a lower rate than other physicians, their satisfaction scores were higher. Further work is required to ensure that antibiotic use during DTC telemedicine encounters is guideline concordant.

Risk factors for Clostridium difficile infection in pediatric inpatients: A meta-analysis and systematic review.

OBJECTIVE: To summarize risk factors for Clostridioides (formerly Clostridium) difficile infection (CDI) in hospitalized pediatric patients as determined by previous observational studies. DESIGN: Meta-analysis and systematic review. PATIENTS: Studies evaluating risk factors for CDI in pediatric inpatients were eligible for inclusion. METHOD: We systematically searched MEDLINE, Web of Science, Scopus, and EMBASE for subject headings and text words related to CDI and pediatrics from 1975 to 2017. Two of the investigators independently screened studies, extracted and compiled data, assessed study quality, and performed the meta-analysis. RESULTS: Of the 2,033 articles screened, 14 studies reporting 10,531,669 children met the inclusion criteria. Prior antibiotic exposure (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.31-3.52) and proton pump inhibitor (PPI) use (OR, 1.33; 95% CI, 1.07-1.64) were associated with an increased risk of CDI in children. Subgroup analyses using studies reporting only adjusted results suggested that prior antibiotic exposure is not a significant risk factor for CDI. H2 receptor antagonist (H2RA) use (OR, 1.36; 95% CI, 0.31-5.98) and that female gender (OR, 0.87; 95% CI, 0.74-1.03) did not play a significant role as a risk factor for developing CDI. CONCLUSION: Prior antibiotic exposure appears to be an important risk factor for CDI based on the combined analysis but not significant using adjusted studies. PPI use was associated with an increased risk of CDI. Judicious and appropriate use of antibiotics and PPIs may help reduce the risk of CDI in this vulnerable population.

A comparison of hospitalized children with enterovirus D68 to those with rhinovirus.

BACKGROUND: During the Fall of 2014, numerous children were hospitalized with asthma or respiratory distress related to Enterovirus D68 (EV-D68). A large proportion initially tested positive for rhinovirus. During this period our laboratory noted a cross-reactivity between EV-D68 and the rhinovirus component of the GenMark multiplex respiratory viral panel. Many other laboratories used assays not designed to distinguish these Picornoviridae. METHODS: To compare the presentation and outcomes of patients with rhinovirus and EV-D68, 103 GenMark rhinovirus positive nasopharyngeal swabs from hospitalized children were retested for EV-D68. RESULTS: EV-D68 positive patients versus EV-D68 negative patients were more likely to have a history of asthma (33.3% vs. 11.0%, P = 0.02) and to present with acute respiratory illness (66.7% vs. 40.2%, P = 0.048), especially status asthmaticus (47.6% vs. 2.4%, P < 0.001). On admission they had more wheezing, respiratory distress, and lower respiratory tract involvement, and were more likely to be treated with steroids and discharged home on asthma medications. Respiratory viral coinfection was less common in EV-D68 positive vs EV-D68 negative patients. In patients without a respiratory viral coinfection the overall findings were similar. CONCLUSION: Patients with EV-D68 versus rhinovirus were more likely to have a history of asthma, to present with status asthmaticus, to wheeze on admission, and to receive treatment with asthma medications in hospital and at discharge. The inability of common assays to distinguish EV-D68 from rhinoviruses raises the possibility that the role of EV-D68 as a viral trigger of asthma has been under appreciated. Pediatr Pulmonol. 2017;52:827-832. © 2017 Wiley Periodicals, Inc.

Piperacillin-Tazobactam-induced Adverse Drug Events in Pediatric Patients on Outpatient Parenteral Antimicrobial Therapy.

We report a significantly higher occurrence of adverse events associated with prolonged courses of piperacillin-tazobactam compared with other antibacterial agents used for pediatric outpatient parenteral antimicrobial therapy. These adverse events were characterized by a constellation of clinical findings including fever, hematologic abnormalities and transaminitis. Adverse events related to piperacillin-tazobactam should be considered in patients who develop a febrile illness associated with a prolonged course of therapy.

Selenoprotein P neutralizes lipopolysaccharide and participates in hepatic cell endoplasmic reticulum stress response.

Low serum selenium or selenoprotein P (SePP) levels have been repetitively observed in severe sepsis. The role of SePP in sepsis is incompletely characterized. To test the hypothesis that lipopolysaccharide (LPS) interacts with SePP, we investigated the interaction between LPS and the histidine-rich (His-rich) regions of SePP. We demonstrate that both purified SePP and synthetic peptides corresponding to the His-rich motifs neutralized LPS. In addition, we used a hepatocyte model to study the fate of SePP in response to LPS or endoplasmic reticulum (ER) stress. Our findings indicate that ER stress increases the cellular level of SePP and promotes its nuclear localization.

Characteristics of bacteremia in pediatric oncology patients based on pathogen classification as associated with the gastrointestinal mucosa or skin.

Factors favoring blood stream infections associated with gastrointestinal mucosa versus skin organisms were explored. An observed difference was attributable to bacteremia from oral flora in patients with acute myelogenous leukemia or mucositis. Our data do not support the conclusion that isolation of enteric Gram-negatives is unrelated to the central catheter.

Enterovirus D68: a clinically important respiratory enterovirus.

Seasonal peaks of viral respiratory illnesses are common during late summer and early fall and have often been attributed to human rhinovirus. In the fall of 2014, the number of children hospitalized with severe lower respiratory symptoms and asthma suddenly increased, and the children tested positive by sequencing for enterovirus D68 (EV-D68). As the outbreak unfolded, a possible association was also observed between EV-D68 infection, polio-like acute flaccid paralysis, and cranial neuropathy in children.

Severe neutropenia presenting with Candida albicans eyelid abscess in a 1-year-old child.

A previously healthy 1-year-old boy presented with a right lower eyelid abscess. Oral and topical antibiotics were initiated, and the lesion was drained and explored. Despite medical and surgical treatment, the abscess failed to resolve completely and formed again 1 month later. A second incision and drainage procedure was performed, and Candida albicans grew in cultures. Additional workup revealed severe neutropenia with an absolute neutrophil count of 0.18 k/µl (1.19-7.21 k/µl). The abscess resolved after 2 weeks of oral fluconazole. C. albicans eyelid abscess may be the presenting sign of systemic immunodeficiency.

Staphylococcus aureus colonization in children undergoing heart surgery.

BACKGROUND: Staphylococcus aureus is an important cause of cardiac surgical site infection. Based on studies in adults, nasal screening to detect S aureuscolonization is used to guide decolonization and selection of prophylactic antibiotics. In our Children's Hospital, a sensitive polymerase chain reaction (PCR)-based assay is used to screen patients undergoing cardiac surgery for nasal colonization with methicillin-sensitive S aureus (MSSA) and methicillin-resistant S aureus (MRSA). Additionally for patients in diapers, cultures are used to detect MRSA colonization of the groin. The purpose of this study was to determine whether screening two anatomic locations results in a higher MRSA detection rate among children undergoing cardiac surgery. METHODS: A retrospective chart review determined whether the frequency of bacterial colonization with MRSA differed by anatomic site. Records for 322 pediatric cardiac surgery procedures performed between January 2009 and June 2011 were reviewed. Both a nasal PCR and a second anatomic site culture were performed before 102 procedures. RESULTS: The overall rate of colonization with MRSA and MSSA was 4.2% and 29.1%, respectively. Of the seven dually screened patients who tested positive for MRSA, two were identified solely via a groin test, four by nasal screening alone, and one by both the tests. Screening of only the nose would have failed to detect 28.6% of the MRSA cases. CONCLUSION: Preoperative detection of MRSA colonization may be enhanced by screening both the nose and a second anatomic site. The clinical utility of the extranasal MRSA culture was limited due to the long assay turnaround time.

A luciferase reporter assay to investigate the differential selenium-dependent stability of selenoprotein mRNAs.

The mechanisms regulating the differential selenium (Se)-dependent stability of selenoprotein mRNAs are partially characterized. To further study the Se-dependent regulation of selenoproteins, we developed a novel chemiluminescent reporter to monitor the steady-state mRNA level of an artificial selenoprotein. Our reporter is a fusion of the Renilla luciferase gene and of the ß-globin gene, but contains features required for incorporation of selenocysteine (SEC), namely, a UGA-SEC codon and a 3' untranslated region RNA stem loop called a SEC incorporation sequence (SECIS). At various levels of Se, the activity of reporters containing GPX1 or GPX4 SECIS elements is proportional to the steady-state mRNA level of the reporter construct and reflects the level of the corresponding endogenous mRNA. In a reporter containing a UGA codon and a functional GPX1 SECIS, Se-dependent nonsense-mediated decay (NMD) occurred in the cytoplasm, as opposed to the more typical nuclear location. To validate the reporter system, we used genetic and pharmacologic approaches to inhibit or promote NMD. Modulation of UPF1 by siRNA, overexpression, or by inhibition of SMG1 altered NMD in this system. Our reporter is derived from a Renilla luciferase reporter gene fused to an intron containing B-globin gene and is subject to degradation by NMD when a stop codon is inserted before the second intron.

Serum selenium, genetic variation in selenoenzymes, and risk of colorectal cancer: primary analysis from the Women's Health Initiative Observational Study and meta-analysis.

BACKGROUND: Selenium may prevent colorectal cancer. However, several previous studies are small and few investigated the association between selenium and colorectal cancer among women whose selenium metabolism may differ from men. Furthermore, genetic variants in selenoenzymes may be associated with colorectal cancer risk. METHODS: This nested case-control study investigated whether serum selenium concentration and genetic variants in five selenoenzymes (glutathione peroxidase 1-4 and selenoprotein P) were associated with colorectal cancer risk in 804 colorectal cancer cases and 805 matched controls from the Women's Health Initiative (WHI) Observational Study. A meta-analysis was conducted to compare the WHI result with previous studies including 12 observational studies and two clinical trials on selenium. RESULTS: Within the WHI, selenium concentrations were relatively high (mean = 135.6 µg/L) and were not associated with colorectal cancer risk (P(trend) = 0.10); the adjusted OR comparing the fifth with first quintile was 1.26 (95% CI, 0.91-1.73). Moreover, genetic variants in selenoenzymes were not significantly associated with colorectal cancer risk. Consistent with the finding in WHI, our meta-analysis showed no association between selenium and colorectal tumor risk in women (OR = 0.97; 95% CI, 0.79-1.18) comparing the highest quantile with the lowest); however, in men, there was a significant inverse association (OR = 0.68; 95% CI, 0.57-0.82) (P = 0.01). CONCLUSION: Consistent with previous studies, we observed no protective effect of selenium on colorectal cancer among women. IMPACT: Our analyses suggest that a population with relatively high selenium concentrations, especially women, would not benefit from increasing selenium intake.