SHEA NICU white paper series: Practical approaches for the prevention of viral respiratory infections.

This white paper provides clinicians and hospital leaders with practical guidance on the prevention and control of viral respiratory infections in the neonatal intensive care unit (NICU). This document serves as a companion to Centers for Disease Control and Prevention Healthcare Infection Control Practices Advisory Committee (HICPAC)'s "Prophylaxis and Screening for Prevention of Viral Respiratory Infections in Neonatal Intensive Care Unit Patients: A Systematic Review." It provides practical, expert opinion and/or evidence-based answers to frequently asked questions about viral respiratory detection and prevention in the NICU. It was developed by a writing panel of pediatric and pathogen-specific experts who collaborated with members of the HICPAC systematic review writing panel and the SHEA Pediatric Leadership Council to identify questions that should be addressed. The document has been endorsed by SHEA, the American Hospital Association (AHA), The Joint Commission, the Pediatric Infectious Diseases Society (PIDS), the Association for Professionals in Infection Control and Epidemiology (APIC), the Infectious Diseases Society of America (IDSA), and the National Association of Neonatal Nurses (NANN).

Monitoring health disparities in healthcare-associated infection surveillance: A Society for Healthcare Epidemiology of America (SHEA) Research Network (SRN) Survey.

We investigated whether and how infection prevention programs monitor for health disparities as part of healthcare-associated infection (HAI) surveillance through a survey of healthcare epidemiology leaders. Most facilities are not assessing for disparities in HAI rates. Professional society and national guidance should focus on addressing this gap.

Absolute Monocyte Count as Early and Safe Marker for Antibiotic Cessation in Febrile Neutropenia Without Etiology in Pediatric Oncology Patients.

BACKGROUND: There is no practice standard regarding antibiotic duration in children with cancer and unexplained febrile neutropenia (FN). We hypothesized that absolute monocyte count (AMC) and absolute phagocyte count (APC= ANC + AMC + bands) are more sensitive, earlier, and safe markers of antibiotic cessation compared with absolute neutrophil count (ANC). METHODS: A retrospective review of FN episodes (FNEs) in pediatric oncology patients was conducted between 2009 and 2016. Included patients were afebrile for 24 hours and without an identified infectious source at antibiotic cessation. Primary endpoints, including recurrent fever, readmission, bloodstream infection, microbiologically documented infection, and adverse outcomes, were assessed 10 days after antibiotic cessation and compared among different bone marrow recovery parameters (ANC, AMC, APC). Secondary endpoints included length of FN stay, antibiotic-free days, and cost. RESULTS: Three hundred ninety-one FNEs in 235 patients were included. Three groups were compared based on ANC (cells/µL) at the time of antibiotic cessation: < 200 in 102 (26%), 200 to 500 in 111 (28%), and >500 in 178 (46%). No statistically significant differences in primary endpoints were identified among the 3 ANC groups; however, a trend toward unfavorable outcomes in the ANC ≤200 cells/µL group compared with the ANC >200 cells/µL was observed. Primary endpoints based on AMC >100 cells/µL at the time of antibiotic cessation showed statistically significant favorable outcomes compared AMC ≤100 cells/µL (80%, 88%, 90%, 89%, and 93% risk reduction in recurrent fever, readmission, new bloodstream infection, new microbiologically documented infection, and adverse events, respectively). Similar favorable results were seen when APC >300 cells/µL was used as a threshold for antibiotic cessation. The median length of stay for FN if discharged when AMC >100 cells/µL was 3 days shorter and associated with fewer unfavorable outcomes, thus resulting in fewer hospital days, fewer antibiotic days, and decreased cost. CONCLUSION: Our results suggest that AMC >100 cells/µL (regardless of ANC) or APC >300 cells/µL may be safe thresholds for empiric antibiotic cessation and result in reduced unfavorable clinical outcomes within 10 days postdischarge, reduced antibiotic days of therapy and reduced health care costs. Further prospective studies are needed to validate AMC as an accurate surrogate marker for antibiotic cessation in FNEs in children with cancer.

Clostridioides difficile colonization and the frequency of subsequent treatment for C. difficile infection in critically ill patients.

OBJECTIVE: To determine risk factors for Clostridioides difficile colonization and C. difficile infection (CDI) among patients admitted to the intensive care unit (ICU). DESIGN: Retrospective observational cohort study. SETTING: Tertiary-care facility. PATIENTS: All adult patients admitted to an ICU from July 1, 2015, to November 6, 2019, who were tested for C. difficile colonization. Patients with CDI were excluded. METHODS: Information was collected on patient demographics, comorbidities, laboratory results, and prescriptions. We defined C. difficile colonization as a positive nucleic acid amplification test for C. difficile up to 48 hours before or 24 hours after intensive care unit (ICU) admission without evidence of active infection. We defined active infection as the receipt of an antibiotic whose only indication is the treatment of CDI. The primary outcome measure was the development of CDI up to 30 days after ICU admission. Logistic regression was used to model associations between clinical variables and the development of CDI. RESULTS: The overall C. difficile colonization rate was 4% and the overall CDI rate was 2%. Risk factors for the development of CDI included C. difficile colonization (aOR, 13.3; 95% CI, 8.3-21.3; P < .0001), increased ICU length of stay (aOR, 1.04; 95% CI, 1.03-1.05; P < .0001), and a history of inflammatory bowel disease (aOR, 3.8; 95% CI, 1.3-11.1; P = .02). Receipt of any antibiotic during the ICU stay was associated with a borderline increased odds of CDI (aOR, 1.9; 95% CI, 1.0-3.4; P = .05). CONCLUSION: C. difficile colonization is associated with the development of CDI among ICU patients.

Use of clinical pathways integrated into the electronic health record to address the coronavirus disease 2019 (COVID-19) pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has required healthcare systems to meet new demands for rapid information dissemination, resource allocation, and data reporting. To help address these challenges, our institution leveraged electronic health record (EHR)-integrated clinical pathways (E-ICPs), which are easily understood care algorithms accessible at the point of care. OBJECTIVE: To describe our institution's creation of E-ICPs to address the COVID-19 pandemic, and to assess the use and impact of these tools. SETTING: Urban academic medical center with adult and pediatric hospitals, emergency departments, and ambulatory practices. METHODS: Using the E-ICP processes and infrastructure established at our institution as a foundation, we developed a suite of COVID-19-specific E-ICPs along with a process for frequent reassessment and updating. We examined the development and use of our COVID-19-specific pathways for a 6-month period (March 1-September 1, 2020), and we have described their impact using case studies. RESULTS: In total, 45 COVID-19-specific pathways were developed, pertaining to triage, diagnosis, and management of COVID-19 in diverse patient settings. Orders available in E-ICPs included those for isolation precautions, testing, treatments, admissions, and transfers. Pathways were accessed 86,400 times, with 99,081 individual orders were placed. Case studies demonstrate the impact of COVID-19 E-ICPs on stewardship of resources, testing optimization, and data reporting. CONCLUSIONS: E-ICPs provide a flexible and unified mechanism to meet the evolving demands of the COVID-19 pandemic, and they continue to be a critical tool leveraged by clinicians and hospital administrators alike for the management of COVID-19. Lessons learned may be generalizable to other urgent and nonurgent clinical conditions.

Staphylococcal Toxic Shock Syndrome in a Burned Child Treated with an Antimicrobial Foam Dressing: A Case Report.

Staphylococcal toxic shock syndrome (TSS) is a severe systemic disease characterized by fever, hypotension, desquamating rash, and multiorgan dysfunction. Attributed to bacterial exotoxins, TSS has been a known, though rare, complication in the field of pediatric burns for decades. The adoption of new antimicrobial burn dressings has allowed for the management of small to medium sized burns with minimal discomfort or inconvenience to the patient. In this report, we discuss a 3-year-old male with burns wounds dressed using a silver-impregnated foam who went on to develop TSS.

A Preliminary, Single-Center Retrospective Chart Review of Infusion Times of Intravenous Immune Globulin in Kawasaki Disease and Clinical Outcomes.

OBJECTIVE: Patients diagnosed with Kawasaki disease (KD) are at a high risk of developing coronary artery aneurysms. Intravenous immune globulin (IVIG) given in combination with aspirin is the standard of treatment for the prevention of coronary aneurysm. IVIG is recommended to be administered as a dose of 2 g/kg infused during 10 to 12 hours for the prevention of coronary aneurysms in KD; however, this does not always occur in practice. We aimed to investigate if an infusion time of <10 hours is associated with more coronary artery aneurysms than the recommended infusion time of 10 to 12 hours. METHODS: Patients with a diagnosis of and treated for KD with IVIG at the University of Chicago Medicine Comer Children's Hospital were identified by drug use reports that included patients who received IVIG between September 2008 and August 2018. Data were collected though chart review and patients were divided into 2 groups based on duration of infusion (<10 hours and 10-12 hours). The primary outcome was the incidence of coronary artery aneurysm. The secondary outcome was the time to defervescence. The safety outcome was the development of renal dysfunction. RESULTS: A total of 70 patients were screened and 44 were included in the analysis. Coronary aneurysm occurred in 2 of 33 patients (6.0%) in the <10-hour group and no patients in the 10- to 12-hour group (p = 0.558). The median time to defervescence was 0.5 hours in the <10-hour group and 0.95 hours in the 10- to 12-hour group (p = 0.166). The incidence of acute kidney injury was 6% (2 of 33 patients) in the 10-hour group and 9.1% (1 of 11 patients) in the 10- to 12-hour group (p = 0.588). CONCLUSIONS: All incidences of coronary artery aneurysm occurred in the patients who received IVIG with an infusion time of <10 hours. The incidence of acute kidney injury was numerically higher in the 10- to 12-hour group. Based on the recommendations in the American Heart Association KD guideline, our internal hospital policy, and our results, we recommend the infusion of IVIG be administered at a rate of 10 to 12 hours.

A prediction model for bacteremia and transfer to intensive care in pediatric and adolescent cancer patients with febrile neutropenia.

Febrile neutropenia (FN) is a common condition in children receiving chemotherapy. Our goal in this study was to develop a model for predicting blood stream infection (BSI) and transfer to intensive care (TIC) at time of presentation in pediatric cancer patients with FN. We conducted an observational cohort analysis of pediatric and adolescent cancer patients younger than 24 years admitted for fever and chemotherapy-induced neutropenia over a 7-year period. We excluded stem cell transplant recipients who developed FN after transplant and febrile non-neutropenic episodes. The primary outcome was onset of BSI, as determined by positive blood culture within 7 days of onset of FN. The secondary outcome was transfer to intensive care (TIC) within 14 days of FN onset. Predictor variables include demographics, clinical, and laboratory measures on initial presentation for FN. Data were divided into independent derivation (2009-2014) and prospective validation (2015-2016) cohorts. Prediction models were built for both outcomes using logistic regression and random forest and compared with Hakim model. Performance was assessed using area under the receiver operating characteristic curve (AUC) metrics. A total of 505 FN episodes (FNEs) were identified in 230 patients. BSI was diagnosed in 106 (21%) and TIC occurred in 56 (10.6%) episodes. The most common oncologic diagnosis with FN was acute lymphoblastic leukemia (ALL), and the highest rate of BSI was in patients with AML. Patients who had BSI had higher maximum temperature, higher rates of prior BSI and higher incidence of hypotension at time of presentation compared with patients who did not have BSI. FN patients who were transferred to the intensive care (TIC) had higher temperature and higher incidence of hypotension at presentation compared to FN patients who didn't have TIC. We compared 3 models: (1) random forest (2) logistic regression and (3) Hakim model. The areas under the curve for BSI prediction were (0.79, 0.65, and 0.64, P < 0.05) for models 1, 2, and 3, respectively. And for TIC prediction were (0.88, 0.76, and 0.65, P < 0.05) respectively. The random forest model demonstrated higher accuracy in predicting BSI and TIC and showed a negative predictive value (NPV) of 0.91 and 0.97 for BSI and TIC respectively at the best cutoff point as determined by Youden's Index. Likelihood ratios (LRs) (post-test probability) for RF model have potential utility of identifying low risk for BSI and TIC (0.24 and 0.12) and high-risk patients (3.5 and 6.8) respectively. Our prediction model has a very good diagnostic performance in clinical practices for both BSI and TIC in FN patients at the time of presentation. The model can be used to identify a group of individuals at low risk for BSI who may benefit from early discharge and reduced length of stay, also it can identify FN patients at high risk of complications who might benefit from more intensive therapies at presentation.

Pediatric Febrile Neutropenia: Change in Etiology of Bacteremia, Empiric Choice of Therapy and Clinical Outcomes.

BACKGROUND: The optimal choice of initial antibiotic therapy for patients with high-risk febrile neutropenia (FN) in children is unclear and varies by the institution on the basis of local antibiograms and epidemiology of specific pathogens. The authors evaluated the appropriateness of antibiotics for the empiric treatment of FN in pediatric patients with cancer in our institution on the basis of changes in the epidemiology of organisms isolated from blood cultures (BCx). METHODS: The authors conducted a retrospective medical record review of pediatric patients who received any oncology care (including patients with cancer and patients who had stem cell transplant) at University of Chicago Medicine Comer Children's Hospitals (March 2009 to December 2016) with a diagnosis of FN who had at least 1 BCx obtained. They reviewed pathogens isolated from BCx and determined whether they were pathogens or contaminants using the Infectious Diseases Society of America (IDSA) guidelines and the team's decision to treat. They investigated the microbiologic spectrum and susceptibility patterns of pathogens causing bacteremia in pediatric FN and whether the empiric therapy chosen may have affected clinical outcomes. RESULTS: A total of 667 FN episodes were identified in 268 patients. BCx were negative in 497 (74.5%) and were determined to be contaminants in 27 (4%). In 143 episodes (21.5%), the BCx were positive for a pathogenic species. Polymicrobial bacteremia was identified in 25 episodes; a total of 176 pathogens were isolated. The majority of pathogens (95/176, 54%) were Gram-positive (GP), whereas 64 of 162 (36%) were Gram-negative (GN), 5 were fungal, and 4 were mycobacterial. The most common GP pathogens were viridans group streptococci (VGS) (n=34, 19.3%), coagulase-negative staphylococci (n=25, 14%), and methicillin-susceptible Staphylococcus aureus (n=12, 6.8%). Of aerobic GN bacilli, 15 (8.5%) were AmpC producers and 3 (1.7%) carried extended-spectrum beta-lactamases. There was no increase in the prevalence of multidrug-resistant GN isolates during the study period. Patients with VGS and multidrug-resistant GN bacteremia were more likely to be admitted to the pediatric intensive care unit [odds ratio (OR), 3.24; P=0.017; and OR, 2.8; P=0.07, respectively]. There were trends toward a higher prevalence of GP pathogens causing bacteremia and the emergence of VGS with decreased penicillin sensitivity. The prevalence of bacteremia with VGS was higher in acute myelogenous leukemia and neuroblastoma (OR, 2.3; P<0.01) than in patients with other solid tumors. CONCLUSIONS: Empiric antibiotic treatment should be tailored to patients' risk for VGS and multidrug-resistant organisms. Individual hospitals should monitor the pathogens causing FN among patients with cancer to guide choice of empiric therapy.

Association Between Depth of Neutropenia and Clinical Outcomes in Febrile Pediatric Cancer and/or Patients Undergoing Hematopoietic Stem-cell Transplantation.

BACKGROUND: Infectious Diseases Society of America guidelines defines febrile neutropenia (FN) patients as high risk, if they have an absolute neutrophil count (ANC) ≤100 cells/µL anticipated to last >7 days. However, data evaluating the clinical significance of the depth and duration of neutropenia are limited. METHODS: We conducted a retrospective cohort study of pediatric oncology patients presenting with FN to examine whether the effects of the depth and duration of neutropenia prior to presentation were predictive of blood stream infection (BSI), invasive fungal disease (IFD), pediatric intensive care unit (PICU) admission or length of stay. RESULTS: A total of 585 FN episodes (FNEs) were identified in 265 patients. ANC at the time of presentation was <100 in 411 (70%), 100-500 in 119 (20%), and >500 cells/µL with subsequent decline to <500 cells/µL in the next 48 hours in 55 (10%) of FNEs. In the group with ANC > 500 with subsequent decline in 48 hours, rates of IFD and BSI were higher when compared with ANC < 100 cells/µL [odds ratio (OR) = 5.9, 95% confidence interval (CI): 0.7-29.6] and (OR = 2.35, 95% CI: 01.02-5.4), and patients in this group were more likely to be admitted to the PICU (OR= 5.1, 95% CI: 1.134-19.46). No difference in outcomes was identified when the groups of ANC < 100 and ANC of 100-500 cells/µL were compared. Neutropenia >7 days prior to FNE was an independent risk factor for BSI (OR = 2.88, 95% CI: 1.55-5.35 and increased length of stay. CONCLUSIONS: Clinicians should not be reassured when patients present with FN and initial ANC >500 cells/mL after recent chemotherapy if continued decline is expected as patients in this group are at high risk of IFD, BSI and PICU admission.

Comparison of Neonatal Outcomes With the Use Cefotaxime Versus Ceftazidime in a Neonatal Intensive Care Unit.

OBJECTIVES: There is a national drug shortage of cefotaxime, and ceftazidime is recommended as an alternative to cefotaxime for neonates. This study evaluated culture-positive late-onset sepsis (LOS), multidrug resistant organisms (MDROs), and other neonatal outcomes with the use of ceftazidime compared with cefotaxime in neonates. METHODS: This was a single-center, retrospective cohort study of neonatal subjects who received at least 24 hours of ceftazidime or cefotaxime between April 1, 2015, and August 1, 2017. Subjects were excluded if they received the alternate antibiotic for more than 24 hours. RESULTS: A total of 101 subjects were included (ceftazidime, n = 58; cefotaxime, n = 43). Median gestational ages were significantly different between groups (28.1 [IQR, 25.0-36.6] weeks versus 32.3 [IQR, 26.9-37.4] in the ceftazidime and cefotaxime groups, respectively, p < 0.05). Results showed a non-statistically significant increased incidence of culture-positive LOS (17.2% versus 2.3%, respectively, adjusted OR 6.51 [95% CI, 0.78-55.23], p = 0.09) and MDRO infections (5.2% versus 0%, respectively, p = 0.26) with the use of ceftazidime compared with cefotaxime. There was a statistically significant increased risk of stage II to III necrotizing enterocolitis (NEC) with the use of ceftazidime (22.4% versus 2.3%, respectively, adjusted OR 9.68 [95% CI, 1.18-79.45], p = 0.04). CONCLUSIONS: This study found a statistically significant increase in stage II to III NEC with the use of ceftazidime compared with cefotaxime. There was a higher rate of culture-positive LOS and MDRO infections with ceftazidime, but this was not significant. Further research is warranted to assess the implications ceftazidime use in neonates.

A Multi-Centered Case-Case-Control Study of Factors Associated With Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae Infections in Children and Young Adults.

BACKGROUND: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae (KPC-CRE) are multidrug-resistant organisms causing morbidity and mortality worldwide. KPC-CRE prevalence is increasing in pediatric populations, though multi-centered data are lacking. Identifying risk factors for KPC-CRE infection in children and classifying genotypes is a priority in this vulnerable population. METHODS: A case-case-control study of patients (0-22 years) at 3 tertiary-care Chicago-area medical centers, 2008-2015, was conducted. Case group 1 children possessed KPC-CRE infections; case group 2 harbored carbapenem-susceptible Enterobacteriaceae (CSE) infections; controls had negative cultures. Case-control matching was 1:1:3 by age, infection site and hospital. Statistical and molecular analyses were performed. RESULTS: Eighteen KPC-CRE infections were identified; median patient age was 16.5 years. Of 4 available KPC-CRE, 2 were unrelated, non-ST258 KP strains harboring blaKPC-2, one was a ST258 KP harboring blaKPC-3, and the last was an E. coli containing blaKPC-2. KPC-CRE and CSE-infected patients had more multidrug-resistant organisms infections, long-term care facility admissions and lengths of stay (LOS) > 7 days before culture. KPC-CRE and CSE patients had more gastrointestinal comorbidities (odds ratios [Ors], 28.0 and 6.4) and ≥ 3 comorbidities (Or 15.4 and 3.5) compared with controls; KPC-CRE patients had significantly more pulmonary and neurologic comorbidities (both ORs 4.4) or GI and pulmonary devices (ORs, 11.4 and 6.1). Compared with controls, CSE patients had more prior fluoroquinolone use (OR, 7.4); KPC-CRE patients had more carbapenem or aminoglycoside use (ORs, 10.0 and 8.0). Race, gender, LOS and mortality differences were insignificant. CONCLUSIONS: Pediatric patients with KPC-CRE infection suffer from high multi-system disease/device burdens and exposures to carbapenems and aminoglycosides. Different from adult reports, non-ST258 KP strains were more common, and LOS and mortality rates were similar in all groups. Pediatric CRE control in should focus on modifiable risk factors including antibiotic and device utilization.

Improved rates of antimicrobial stewardship interventions following implementation of the Epic antimicrobial stewardship module.

We evaluated the impact of the Epic antimicrobial stewardship module (EAM) on the number of interventions, antimicrobial usage, and clinical outcomes. Use of the EAM allowed us to significantly increase the number of ASP antimicrobial reviews and interventions while maintaining a sustained impact on antimicrobial utilization.

Physician Knowledge, Attitudes, and Practices Related to Chagas Disease in Tabasco, Mexico.

We designed and implemented a survey of physician knowledge, attitudes, and practices with respect to Chagas disease in the state of Tabasco, Mexico. Seventy-eight public sector physicians from across the state responded via Research Electronic Data Capture, an online survey capture tool. Improved performance on knowledge-based questions (P < 0.01) and an increase in decisions to screen (P = 0.04) were associated with previous training specific to this disease. Our results provide important descriptive information regarding knowledge, attitudes, and practices among a group of public sector Mexican doctors and highlight the importance of Chagas disease-specific physician training for identification and, ultimately, treatment of patients affected by this disease.