Examining the Evidence for Escalating Antimicrobial Regimens in Febrile Oncology and Hematopoietic Stem Cell Transplant Patients Admitted to the PICU: An Observational Study.

OBJECTIVES: To examine whether escalating antimicrobial treatment in pediatric oncology and hematopoietic cell transplantation (HSCT) patients admitted to the PICU is supported by culture data or affects patient outcomes. DESIGN: Retrospective cross-sectional study. SETTING: Quaternary care PICU. PATIENTS: Patients younger than 18 years old who were admitted to the PICU at Boston Children's Hospital from 2012 to 2017 with a diagnosis of cancer or who had received HSCT and who had suspected sepsis at the time of PICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 791 PICU admissions for 544 patients that met inclusion criteria, 71 (9%) had escalation of antimicrobial therapy. Median Pediatric Logistic Organ Dysfunction (PELOD) score was higher in the escalation group (4 vs 3; p = 0.01). There were 14 admissions (20%) with a positive culture in the escalation group and 110 (15%) in the no escalation group ( p = 0.31). In the escalation group, there were only 2 (3%) cultures with organisms resistant to the initial antimicrobial regimen, compared with 28 (4%) cultures with resistant organisms in the no escalation group ( p = 1). Mortality in the escalation group was higher (17%) compared with the nonescalation group (5%; p < 0.001). The escalation group had more acute kidney injury (AKI) (25%) during treatment compared with the no escalation group (15%; p = 0.04), although this difference was not statistically significant when controlling for age, neutropenia, and PELOD-2 score (odds ratio, 1.75; 95% CI, 0.95-3.08; p = 0.06). CONCLUSIONS: Few patients who had escalation of antimicrobials proved on culture data to have an organism resistant to the initial antimicrobials, and more patients developed AKI during escalated treatment. While the escalation group likely represents a sicker population, whether some of these patients would be safer without escalation of antimicrobial therapy warrants further study.

Rapid expansion and extinction of antibiotic resistance mutations during treatment of acute bacterial respiratory infections.

Acute bacterial infections are often treated empirically, with the choice of antibiotic therapy updated during treatment. The effects of such rapid antibiotic switching on the evolution of antibiotic resistance in individual patients are poorly understood. Here we find that low-frequency antibiotic resistance mutations emerge, contract, and even go to extinction within days of changes in therapy. We analyzed Pseudomonas aeruginosa populations in sputum samples collected serially from 7 mechanically ventilated patients at the onset of respiratory infection. Combining short- and long-read sequencing and resistance phenotyping of 420 isolates revealed that while new infections are near-clonal, reflecting a recent colonization bottleneck, resistance mutations could emerge at low frequencies within days of therapy. We then measured the in vivo frequencies of select resistance mutations in intact sputum samples with resistance-targeted deep amplicon sequencing (RETRA-Seq), which revealed that rare resistance mutations not detected by clinically used culture-based methods can increase by nearly 40-fold over 5-12 days in response to antibiotic changes. Conversely, mutations conferring resistance to antibiotics not administered diminish and even go to extinction. Our results underscore how therapy choice shapes the dynamics of low-frequency resistance mutations at short time scales, and the findings provide a possibility for driving resistance mutations to extinction during early stages of infection by designing patient-specific antibiotic cycling strategies informed by deep genomic surveillance.

Stewardship Intervention to Optimize Central Venous Catheter Utilization in Critically Ill Children.

We aimed to describe utilization and indication(s) for long-term central venous catheters (CVCs) in a pediatric intensive care unit (PICU) and identify potential strategies to decrease CVC utilization. METHODS: We conducted a single-center prospective quality improvement initiative at a 30-bed PICU in a large, freestanding, academic children's hospital. We created an electronic report to identify patients with an indwelling CVC for 7 days and older (defined as long term). We discussed the ongoing need for each long-term CVC with PICU clinicians at weekly interdisciplinary structured "CVC stewardship rounds." We then made recommendations around expedited removal of CVCs. We conducted multiple Plan-Do-Study-Act cycles to categorize CVC indications, identify modifiable factors, and educate PICU clinicians. We hypothesized that CVC stewardship rounds would decrease long-term CVC utilization in our PICU. RESULTS: From October 2016 to September 2017, 607 long-term CVCs were eligible for the stewardship intervention. Compared to the preintervention period, we recorded a significant increase in peripherally inserted central catheters and a decrease in nontunneled CVCs (P < 0.001). Most patients had single- or double-lumen CVCs in both the preintervention and intervention periods (86% and 91%, respectively). The utilization of overall long-term CVC devices, and those with modifiable indications, decreased during the intervention period. CONCLUSIONS: A single-center QI intervention focused on PICU CVC stewardship was associated with a decrease in CVC utilization.

Invasive and noninvasive ventilation strategies for acute respiratory failure in children with coronavirus disease 2019.

PURPOSE OF REVIEW: Severe Acute Respiratory Syndrome Coronavirus 2 presents as symptomatic coronavirus disease 2019 (COVID-19) disease in susceptible patients. Severe pediatric COVID-19 disease is rare, limiting potential data accumulation on associated respiratory failure in children. Pediatric intensivists and pulmonologists managing COVID-19 patients look to adult guidelines and pediatric-specific consensus statements to guide management. The purpose of this article is to review the current literature and recommended strategies for the escalation of noninvasive and invasive respiratory support for acute respiratory failure associated with COVID-19 disease in children. RECENT FINDINGS: There are no prospective studies comparing COVID-19 treatment strategies in children. Adult and pediatric ventilation management interim guidance is based on evidence-based guidelines in non-COVID acute respiratory distress syndrome, with considerations of (1) noninvasive positive pressure ventilation versus high-flow nasal cannula and (2) high versus lower positive end expiratory pressure strategies related to lung compliance and potential lung recruitability. SUMMARY: Management of acute respiratory failure from COVID-19 requires individualized titration of noninvasive and invasive ventilation modalities with consideration of preserved or compromised pulmonary compliance. Research regarding best practices in the management of pediatric severe COVID-19 with respiratory failure is lacking and is acutely needed as the pandemic surges and vaccination of the pediatric population will be delayed compared to adults.

Utilization of cumulative antibiograms for public health surveillance: Trends in Escherichia coli and Klebsiella pneumoniae susceptibility, Massachusetts, 2008-2018.

BACKGROUND: Antimicrobial resistance is an urgent public health threat. Identifying trends in antimicrobial susceptibility can inform public health policy at the state and local levels. OBJECTIVE: To determine the ability of statewide antibiogram aggregation for public health surveillance to identify changes in antimicrobial resistance trends. DESIGN: Facility-level trend analysis. METHODS: Crude and adjusted trend analyses of the susceptibility of Escherichia coli and Klebsiella pneumoniae to particular antibiotics, as reported by aggregated antibiograms, were examined from 2008 through 2018. Multivariable regression analyses via generalized linear mixed models were used to examine associations between hospital characteristics and trends of E. coli and K. pneumoniae susceptibility to ciprofloxacin and ceftriaxone. RESULTS: E. coli and K. pneumoniae showed inverse trends in drug susceptibility over time. K. pneumoniae susceptibility to fluoroquinolones increased by 5% between 2008 and 2018 (P < .05). In contrast, E. coli susceptibility declined during the same period to ceftriaxone (6%), gentamicin (4%), and fluoroquinolones (4%) (P < .05). When compared to Boston hospitals, E. coli isolates from hospitals in other regions had a >4% higher proportion of susceptibility to ciprofloxacin and a >3% higher proportion of susceptibility to ceftriaxone (P < .05). Isolates of K. pneumoniae had higher susceptibility to ciprofloxacin (>3%) and ceftriaxone (>1.5%) in all regions when compared to Boston hospitals (P < .05). CONCLUSIONS: Cumulative antibiograms can be used to monitor antimicrobial resistance, to discern regional and facility differences, and to detect changes in trends. Furthermore, because the number of years that hospitals contributed reports to the state-level aggregate had no significant influence on susceptibility trends, other states should not be discouraged by incomplete hospital compliance.

Whole-Genome Sequences of Staphylococcus aureus Isolates from Cystic Fibrosis Lung Infections.

Staphylococcus aureus is an early colonizer in the lungs of individuals with cystic fibrosis (CF), but surprisingly, only a limited number of genomes from CF-associated S. aureus isolates have been sequenced. Here, we present the whole-genome sequences of 65 S. aureus isolates obtained from 50 individuals with CF.

Acute Pancreatitis in a Patient with Maple Syrup Urine Disease: A Management Paradox.

Maple syrup urine disease (MSUD) is an inborn error of metabolism that causes elevated leucine in the setting of acute illnesses. We describe an 8-year-old boy with MSUD who developed acute pancreatitis and subsequent leucinosis. This case highlights the complexities of fluid management in patients with MSUD.