Impact of Respiratory Bacterial Codetection on Outcomes in Ventilated Infants With Bronchiolitis.

BACKGROUND: Viral bronchiolitis is a common cause of acute respiratory failure requiring intubation for infants. Bacterial respiratory tract infections can occur with bronchiolitis, although their prevalence and impact on outcomes are unclear, especially with increased use of noninvasive respiratory support. METHODS: This was a single-center retrospective cohort study of children <2 years old requiring intubation in the emergency department for bronchiolitis from 2012 to 2017 who had viral testing plus a lower respiratory culture obtained. We evaluated the impact of bacterial codetection (positive respiratory culture plus moderate or many polymorphonuclear neutrophils on Gram stain) on mechanical ventilation (MV) duration and intensive care unit length of stay using multivariable gamma regression. RESULTS: Of 149 patients enrolled, 52% had bacterial codetection. In adjusted analysis, patients with codetection had shorter MV duration [adjusted relative risk (aRR) 0.819, 95% confidence interval (CI): 0.69-0.98; marginal mean duration of 5.31 days (4.71-5.99) compared to 6.48 days (5.72-7.35) without codetection]. Patients with codetection had a shorter intensive care unit stay [aRR 0.806 (0.69-0.94); marginal mean length of stay 6.9 days (6.21-7.68) vs. 8.57 days (7.68-9.56) without codetection]. The association between codetection and duration of ventilation appears confined to those receiving earlier antibiotics (less than the median time) rather than later antibiotics [aRR 0.738 (0.56-0.95) for earlier vs. aRR 0.92 (0.70-1.18) for later]. CONCLUSIONS: Respiratory bacterial codetection is common and associated with shorter MV duration in infants requiring early intubation for bronchiolitis. Early antibiotics may contribute to these outcomes, but further multicenter studies are needed to understand the role of codetection and antibiotics on bronchiolitis outcomes.

Faculty Decision Making in Ad Hoc Entrustment of Pediatric Critical Care Fellows: A National Case-Based Survey.

Phenomenon: Ad hoc entrustment decisions reflect a clinical supervisor's estimation of the amount of supervision a trainee needs to successfully complete a task in the moment. These decisions have important consequences for patient safety, trainee learning, and preparation for independent practice. Determinants of these decisions have previously been described but have not been well described for acute care contexts such as critical care and emergency medicine. The ad hoc entrustment of trainees caring for vulnerable patient populations is a high-stakes decision that may differ from other contexts. Critically ill patients and children are vulnerable patient populations, making the ad hoc entrustment of a pediatric critical care medicine (PCCM) fellow a particularly high-stakes decision. This study sought to characterize how ad hoc entrustment decisions are made for PCCM fellows through faculty ratings of vignettes. The authors investigated how acuity, relationship, training level, and task interact to influence ad hoc entrustment decisions. Approach: A survey containing 16 vignettes that varied by four traits (acuity, relationship, training level, and task) was distributed to U.S. faculty of pediatric critical care fellowships in 2020. Respondents determined an entrustment level for each case and provided demographic data. Entrustment ratings were dichotomized by "high entrustment" versus "low entrustment" (direct supervision or observation only). The authors used logistic regression to evaluate the individual and interactive effects of the four traits on dichotomized entrustment ratings. Findings: One hundred seventy-eight respondents from 30 institutions completed the survey (44% institutional response rate). Acuity, relationship, and task all significantly influenced the entrustment level selected but did not interact. Faculty most frequently selected "direct supervision" as the entrustment level for vignettes, including for 24% of vignettes describing fellows in their final year of training. Faculty rated the majority of vignettes (61%) as "low entrustment." There was no relationship between faculty or institutional demographics and the entrustment level selected. Insights: As has been found in summative entrustment for pediatrics, internal medicine, and surgery trainees, PCCM fellows often rated at or below the "direct supervision" level of ad hoc entrustment. This may relate to declining opportunities to practice procedures, a culture of low trust propensity among the specialty, and/or variation in interpretation of entrustment scales.

A genome-wide association analysis of loss of ambulation in dystrophinopathy patients suggests multiple candidate modifiers of disease severity.

The major determinant of disease severity in Duchenne muscular dystrophy (DMD) or milder Becker muscular dystrophy (BMD) is whether the dystrophin gene (DMD) mutation truncates the mRNA reading frame or allows expression of a partially functional protein. However, even in the complete absence of dystrophin, variability in disease severity is observed, and candidate gene studies have implicated several genes as modifiers. Here we present the largest genome-wide search to date for loci influencing severity in N = 419 DMD patients. Availability of subjects for such studies is quite limited, leading to modest sample sizes, which present a challenge for GWAS design. We have therefore taken special steps to minimize heterogeneity within our dataset at the DMD locus itself, taking a novel approach to mutation classification to effectively exclude the possibility of residual dystrophin expression, and utilized statistical methods that are well adapted to smaller sample sizes, including the use of a novel linear regression-like residual for time to ambulatory loss and the application of evidential statistics for the GWAS approach. Finally, we applied an unbiased in silico pipeline, utilizing functional genomic datasets to explore the potential impact of the best supported SNPs. In all, we obtained eight SNPs (out of 1,385,356 total) with posterior probability of trait-marker association (PPLD) ≥ 0.4, representing six distinct loci. Our analysis prioritized likely non-coding SNP regulatory effects on six genes (ETAA1, PARD6G, GALNTL6, MAN1A1, ADAMTS19, and NCALD), each with plausibility as a DMD modifier. These results support both recurrent and potentially new pathways for intervention in the dystrophinopathies.

Reporting guidelines for allergy and immunology survey research.

Although survey reports are common, fewer than 10% of medical journals provide clear guidelines to investigators for survey research. In this special article, we provide guidance on minimum recommendations in the form of a CHecklist for Allergy and Immunology Reporting of Survey research (CHAIRS). Key components to consider include providing background information, such as a clear statement of the research hypothesis and question, and rationale for the study. When considering sample selection, a clear understanding of the relationship between the target population, sampling frame, sample scheme, representativeness, and sample size is needed. Review of the survey tool by content experts and assessment of threats to survey validity should occur early in questionnaire development with consideration of cognitive interviews and pretesting to facilitate accurate measurement. Last, a transparent description of data collection and qualitative and quantitative characteristics of response rate is needed to ensure that appropriate inferences and conclusions can be drawn from the survey research.

Type III Interferons, Viral Loads, Age, and Disease Severity in Young Children With Respiratory Syncytial Virus Infection.

BACKGROUND: The interplay among respiratory syncytial virus (RSV) loads, mucosal interferons (IFN), and disease severity in RSV-infected children is poorly understood. METHODS: Children <2 years of age with mild (outpatients) or severe (inpatients) RSV infection and healthy controls were enrolled, and nasopharyngeal samples obtained for RSV loads and innate cytokines quantification. Patients were stratified by age (0-6 and >6-24 months) and multivariable analyses performed to identify predictors of disease severity. RESULTS: In 2015-2019 we enrolled 219 RSV-infected children (78 outpatients; 141 inpatients) and 34 healthy controls. Type I, II, and III IFN concentrations were higher in children aged >6 versus 0-6 months and, like CXCL10, they were higher in outpatients than inpatients and correlated with RSV loads (P < .05). Higher IL6 concentrations increased the odds of hospitalization (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.07-5.36) only in children >6 months, while higher IFN-λ2/3 concentrations had the opposite effect irrespective of age (OR, 0.38; 95% CI, .15-.86). Likewise, higher CXCL10 concentrations decreased the odds of hospitalization (OR, 0.21; 95% CI, .08-.48), oxygen administration (OR, 0.42; 95% CI, .21-.80),PICU admission (OR, 0.39; 95% CI, .20-.73), and prolonged hospitalization (OR, 0.57; 95% CI, .32-.98) irrespective of age. CONCLUSIONS: Children with milder RSV infection and those aged >6 months had higher concentrations of mucosal IFNs, suggesting that maturation of mucosal IFN responses are associated with protection against severe RSV disease.

Novel Identification of Myeloid-Derived Suppressor Cells in Children With Septic Shock.

OBJECTIVES: Immunoparalysis in children with septic shock is associated with increased risk of nosocomial infections and death. Myeloid-derived suppressor cells (MDSCs) potently suppress T cell function and may perpetuate immunoparalysis. Our goal was to test the hypothesis that children with septic shock would demonstrate increased proportions of MDSCs and impaired immune function compared with healthy controls. DESIGN: Prospective observational study. SETTING: Fifty-four bed PICU in a quaternary-care children's hospital. PATIENTS: Eighteen children with septic shock and thirty age-matched healthy children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and stained for cell surface markers to identify MDSCs by flow cytometric analysis, including granulocytic and monocytic subsets. Adaptive and innate immune function was measured by ex vivo stimulation of whole blood with phytohemagglutinin-induced interferon (IFN) γ production and lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production, respectively. Prolonged organ dysfunction (OD) was defined as greater than 7 days. Children with septic shock had a higher percentage of circulating MDSCs, along with lower LPS-induced TNFα and phytohemagglutinin-induced IFNγ production capacities, compared with healthy controls. A cut-off of 25.2% MDSCs of total PBMCs in initial samples was optimal to discriminate children with septic shock who went on to have prolonged OD, area under the curve equal to 0.86. Children with prolonged OD also had decreased TNFα production capacity over time compared with those who recovered more quickly ( p = 0.02). CONCLUSIONS: This article is the first to describe increased MDSCs in children with septic shock, along with an association between early increase in MDSCs and adverse OD outcomes in this population. It remains unclear if MDSCs play a causative role in sepsis-induced immune suppression in children. Additional studies are warranted to establish MDSC as a potential therapeutic target.

Predictive value of the test of infant motor performance and the Hammersmith infant neurological examination for cerebral palsy in infants.

BACKGROUND: Current recommendations for early detection tools for cerebral palsy (CP) include assessments that vary in feasibility and resource requirements. The predictive value of less resource-intensive tools has not been fully explored. AIMS: To determine the predictive value of the Test of Infant Motor Performance (TIMP) at 3-4 months corrected age (CA) for CP, and whether administration of both the TIMP and the Hammersmith Infant Neurological Exam (HINE) improves early CP detection. STUDY DESIGN: Five-year retrospective observational study of infants who received the TIMP and the HINE at 3-4 months CA in a high-risk follow-up clinic. TIMP and HINE cut-off scores (alone and in combination) were compared for CP discriminatory ability. SUBJECTS: Of patients with HINE scores (n = 1389; 676 [48.7 %] female; median gestational age at birth 31 weeks [interquartile range 29-34 weeks]), 1343 had concurrent TIMP scores available. OUTCOME MEASURES: Clinical diagnosis of CP. RESULTS: HINE total score <57 had optimal CP predictive value (AUC = 0.815; 77 % sensitivity; 91 % specificity) compared to optimal TIMP cut-off (1 SD below the mean, AUC = 0.71; 52 % sensitivity; 94 % specificity) and all tested TIMP and HINE combinations (all p < 0.001). CONCLUSIONS: HINE total score <57 at 3-4 months CA had the best CP predictive value, confirming its value absent first-line detection tools. Concurrent administration of TIMP did not improve predictive value.

Impact of secukinumab on patient-reported outcomes in biologic-naive patients with psoriasis in a US real-world setting.

OBJECTIVE: To describe real-world baseline characteristics and patient-reported outcomes (PROs) at 6-month and 12-month follow-up visits among patients with psoriasis who initiated and maintained secukinumab, stratified by prior exposure to biologics. METHODS: This real-world study included patients enrolled in the CorEvitas (formerly Corrona) Psoriasis Registry who initiated and maintained secukinumab through 6-month and/or 12-month follow-up. Demographics, clinical characteristics, and PROs were collected. PROs included Dermatology Life Quality Index (DLQI); itch, skin pain, fatigue, and EuroQol visual analog scales; and Work Productivity and Activity Impairment. Mean (SD) differences between baseline and follow-up visits were calculated for all outcomes. RESULTS: Overall, 652 patients had a 6-month follow-up visit, 460 (70.6%) were biologic experienced and 192 (29.4%) were biologic naive. Biologic-experienced and biologic-naive patients reported mean (SD) improvements in all PROs measured at 6-month follow-up. Similar improvements were seen among patients with a 12-month follow-up visit (n = 390) and both 6-month and 12-month follow-up visits (n = 326). CONCLUSIONS: Biologic-experienced and biologic-naive patients with psoriasis who initiated and maintained secukinumab treatment reported improvements in PROs at 6-month and/or 12-month follow-up visits. These findings suggest that secukinumab is a potential biologic for psoriasis at any point along the patient treatment journey.

Myeloid-Derived Suppressor Cells and Clinical Outcomes in Children With COVID-19.

Background: Although children with COVID-19 account for fewer hospitalizations than adults, many develop severe disease requiring intensive care treatment. Critical illness due to COVID-19 has been associated with lymphopenia and functional immune suppression. Myeloid-derived suppressor cells (MDSCs) potently suppress T cells and are significantly increased in adults with severe COVID-19. The role of MDSCs in the immune response of children with COVID-19 is unknown. Aims: We hypothesized that children with severe COVID-19 will have expansion of MDSC populations compared to those with milder disease, and that higher proportions of MDSCs will correlate with clinical outcomes. Methods: We conducted a prospective, observational study on a convenience sample of children hospitalized with PCR-confirmed COVID-19 and pre-pandemic, uninfected healthy controls (HC). Blood samples were obtained within 48 h of admission and analyzed for MDSCs, T cells, and natural killer (NK) cells by flow cytometry. Demographic information and clinical outcomes were obtained from the electronic medical record and a dedicated survey built for this study. Results: Fifty children admitted to the hospital were enrolled; 28 diagnosed with symptomatic COVID-19 (10 requiring ICU admission) and 22 detected by universal screening (6 requiring ICU admission). We found that children with severe COVID-19 had a significantly higher percentage of MDSCs than those admitted to the ward and uninfected healthy controls. Increased percentages of MDSCs in peripheral blood mononuclear cells (PBMC) were associated with CD4+ T cell lymphopenia. MDSC expansion was associated with longer hospitalizations and need for respiratory support in children admitted with acute COVID-19. Conclusion: These findings suggest that MDSCs are part of the dysregulated immune responses observed in children with severe COVID-19 and may play a role in disease pathogenesis. Future mechanistic studies are required to further understand the function of MDSCs in the setting of SARS-CoV-2 infection in children.

Utilization Trends and Impact of Secukinumab Treatment on Clinical Outcomes in Biologic-Naive Patients with Psoriasis in a US Real-World Setting.

INTRODUCTION: Real-world evidence has demonstrated the effectiveness of secukinumab in the treatment of psoriasis; however, limited data are available on patient profiles of US secukinumab initiators over time and clinical outcomes in biologic-naive patients. This study describes clinical characteristics of secukinumab initiators by year, and the clinical outcomes in patients after 6- and/or 12-month follow-up visits, stratified by prior biologic use. METHODS: This observational study included patients enrolled in the CorEvitas (formerly Corrona) Psoriasis Registry. Analyses were conducted in two patient cohorts: (1) all secukinumab initiators, stratified by year, and (2) those who initiated and maintained secukinumab through a 6- and/or 12-month follow-up visit. For all secukinumab initiators, patient characteristics at initiation were described per calendar year; in initiators with follow-up visits, mean (SD) differences in percentage affected body surface area (BSA), five-point Investigator's Global Assessment (IGA), and Psoriasis Area and Severity Index (PASI) scores between baseline and follow-up visits were calculated. Analyses were conducted separately for biologic-naive and biologic-experienced patients. RESULTS: Between 2015 and 2020, the proportion of secukinumab initiators in the registry who were biologic-naive increased each year from 12.5% to 49.7%. Overall, 1518 patients initiated secukinumab at or after enrollment; 980 (64.6%) were biologic experienced, and 538 (35.4%) were biologic naive. At 6 months, biologic-experienced and biologic-naive patients reported mean (SD) decreases in BSA (-9.3 [14.5] versus -11.7 [16.6]), IGA (-1.4 [1.3] versus -1.7 [1.4]), and PASI (-5.2 [6.6] versus -6.7 [7.8]). The proportion of patients with an IGA score of clear/almost clear (0/1) increased over fivefold, irrespective of biologic experience. At 12 months, similar improvements were seen. CONCLUSIONS: The proportion of biologic-naive secukinumab initiators increased over time. Biologic-naive patients demonstrated similar improvements in clinical outcomes compared with biologic-experienced patients, suggesting that secukinumab may be considered as a first-line therapy for psoriasis.

Exceeding expectations after perinatal risks for poor development: associations in term- and preterm-born preschoolers.

OBJECTIVE: To define parenting/social characteristics associated with better-than-expected cognitive and motor outcomes in preschoolers at similar perinatal biological risk-level including various gestational ages at birth (GA) and perinatal complications. STUDY DESIGN: Prospective cohort study (n = 87) of children at four years, median GA 29 weeks (IQR 26, 38). Assessments included Differential Ability Scales, Movement Assessment Battery, parenting styles, and social risk scores. Perinatal risk factors were weighted based on regression models for each outcome; individual calculated risk scores became predictors to extract standardized residuals from the mean (>1 SD above mean = better-than-expected). Mixed-effect regressions examined associations between positive adaptation and parenting/social factors. RESULT: Perinatal risk scores explained 21-53% outcome variability. Children across all GA displayed positive adaptation. Children of parents with higher authoritarian scores had higher odds of better-than-expected outcomes (OR 1.17, p = 0.0002). CONCLUSION: Parental structure may promote positive adaptation at preschool age in children with perinatal risk factors for poor development, including extreme prematurity.

Healthcare Provider Characteristics and Cardiopulmonary Resuscitation Quality During Infant Resuscitation: A Simulation Study.

INTRODUCTION: Healthcare providers' anthropometric characteristics can adversely affect adult cardiopulmonary resuscitation (CPR) performance quality. However, their effects on infant CPR are unknown. We aimed to determine any relationships between healthcare provider characteristics (anthropomorphic, demographics, training, occupational data) and simulated infant CPR performance at multiple international sites. Our secondary aim was to examine provider's CPR performance degradation. METHODS: Providers from 4 international hospitals performed 2 minutes of single-rescuer simulated infant CPR using 2015 American Heart Association Basic Life Support criteria with guidance from a real-time visual performance feedback device. Providers' characteristics were collected, and the simulator collected compression and ventilation data. Multivariate analyses examined the entire 2 minutes and performance degradation. RESULTS: Data from 127 participants were analyzed. Although median values for all compression variables (depth, rate, lean) and ventilation volume were within guideline target ranges, when looking at individuals, only 52% chest compressions and 20% ventilations adhered to the American Heart Association guidelines. Age was found to be independently associated with ventilation volume (direct-relationship), and height was associated with chest compression lean (shorter participant-deeper lean). No significant differences were noted based on sex or body mass index. Neonatal intensive care unit participants were noted to perform shallower chest compressions (P < 0.001). Overall, there was minimal evidence of performance degradation over 2 minutes. CONCLUSIONS: Isolated provider characteristics were noted among a diverse cohort of healthcare providers that may affect the CPR quality on a simulated infant. Understanding the relationships between provider characteristics and CPR quality could inform future infant CPR guidelines customized for the provider and not just the patient.

Impaired T-Lymphocyte Responses During Childhood Staphylococcus aureus Infection.

BACKGROUND: Staphylococcus aureus infections are common throughout the lifespan, with recurrent infections occurring in nearly half of infected children. There is no licensed vaccine, underscoring the need to better understand how S. aureus evades protective immunity. Despite much study, the relative contributions of antibodies and T cells to protection against S. aureus infections in humans are not fully understood. METHODS: We prospectively quantified S. aureus-specific antibody levels by ELISA and T-cell responses by ELISpot in S. aureus-infected and healthy children. RESULTS: S. aureus-specific antibody levels and T-cell responses increased with age in healthy children, suggesting a coordinated development of anti-staphylococcal immunity. Antibody levels against leukotoxin E (LukE) and Panton-Valentine leukocidin (LukS-PV), but not α-hemolysin (Hla), were higher in younger infected children, compared with healthy children; these differences disappeared in older children. We observed a striking impairment of global and S. aureus-specific T-cell function in children with invasive and noninvasive infection, suggesting that S. aureus-specific immune responses are dysregulated during childhood infection regardless of the infection phenotype. CONCLUSIONS: These findings identify a potential mechanism by which S. aureus infection actively evades adaptive immune responses, thereby preventing the development of protective immunity and maintaining susceptibility to recurrent infection.

Brief Report: Evaluating the Effectiveness of Music to Obtain More Accurate Blood Pressure Readings in Children with Williams Syndrome.

This study examined if listening to music will improve the accuracy of blood pressure (BP) readings in children with Williams syndrome (WS). Fifty-two participants (7-12 years) were randomly assigned to a music or non-music group. BPs were obtained at two time points. There was a significant decrease in both systolic and diastolic BP from Time 1 to Time 2 for everyone. Participants from the music group had lower systolic BP readings at Time 2 than participants in the non-music group (Cohen's d = 0.33). Systolic BP readings were approximately 3.8 mmHg lower in the music group. Music may be beneficial in obtaining more accurate systolic BP readings in children with WS.

Phenotypic Spectrum of Dystrophinopathy Due to Duchenne Muscular Dystrophy Exon 2 Duplications.

BACKGROUND AND OBJECTIVES: To describe the phenotypic spectrum of dystrophinopathy in a large cohort of individuals with DMD exon 2 duplications (Dup2), who may be particularly amenable to therapies directed at restoring expression of either full-length dystrophin or nearly full-length dystrophin through utilization of the DMD exon 5 internal ribosome entry site (IRES). METHODS: In this retrospective observational study, we analyzed data from large genotype-phenotype databases (the United Dystrophinopathy Project [UDP] and the Italian DMD network) and classified participants into Duchenne muscular dystrophy (DMD), intermediate muscular dystrophy (IMD), or Becker muscular dystrophy (BMD) phenotypes. Log-rank tests for time-to-event variables were used to compare age at loss of ambulation (LOA) in participants with Dup2 vs controls without Dup2 in the UDP database and for comparisons between steroid-treated vs steroid-naive participants with Dup2. RESULTS: Among 66 participants with Dup2 (UDP = 40, Italy = 26), 61% were classified as DMD, 9% as IMD, and 30% as BMD. Median age at last observation was 15.4 years (interquartile range 8.79-26.0) and 75% had been on corticosteroids for at least 6 months. Age at LOA differed significantly between participants with Dup2 DMD and historical controls without Dup2 DMD (p < 0.001). Valid spirometry was limited but suggested a delay in the typical age-related decline in forced vital capacity and 24 of 55 participants with adequate cardiac data had cardiomyopathy. DISCUSSION: Some patients with Dup2 display a milder disease course than controls without Dup2 DMD, and prolonged ambulation with corticosteroids suggests the potential of IRES activation as a molecular mechanism. As Dup2-targeted therapies reach clinical applications, this information is critical to aid in the interpretation of the efficacy of new treatments.

Nasopharyngeal Codetection of Haemophilus influenzae and Streptococcus pneumoniae Shapes Respiratory Syncytial Virus Disease Outcomes in Children.

BACKGROUND: The role of nasopharyngeal bacteria in respiratory syncytial virus (RSV) disease has been underestimated. We measured the frequency and burden of respiratory bacteria in the upper respiratory tract of infants with RSV infection over 7 respiratory seasons, and their impact on clinical outcomes. METHODS: Children <2 years old with mild (outpatients, n=115) or severe (inpatients, n=566) RSV infection, and matched healthy controls (n=161) were enrolled. Nasopharyngeal samples were obtained for RSV, Streptococcus pneumoniae, Staphylococcus aureus, Moraxella catarrhalis, and Haemophilus influenzae detection and quantitation by PCR. Multivariable models were constructed to identify variables predictive of severe disease. RESULTS: S. pneumoniae, H. influenzae, and M. catarrhalis, but not S. aureus, were detected more frequently in RSV-infected children (84%) than healthy controls (46%; P<.001). Detection of S. pneumoniae and/or H. influenzae was associated with fever, more frequent antibiotic treatment, worse radiologic findings, and higher neutrophil counts (P<.01). In adjusted analyses, S. pneumoniae/H. influenzae codetection was independentlyassociated with greater odds of hospitalization, higher disease severity scores, need for supplemental oxygen, and longer hospitalization. CONCLUSIONS: Nasopharyngeal codetection of S. pneumoniae and H. influenzae in infants with RSV infection is associated with increased disease severity.

Creation of a Combination Antibiogram for Pseudomonas aeruginosa in a Pediatric Intensive Care Unit.

OBJECTIVE: This study describes the creation of a combination antibiogram directed toward Pseudomonas aeruginosa to determine the most appropriate empiric antimicrobial regimen(s). METHODS: P aeruginosa isolates were collected from all sites between January 2013 and December 2017 for patients admitted to the PICU. Patients with cystic fibrosis and isolates from the same site and susceptibility pattern obtained within 30 days were excluded. ß-Lactam susceptibilities were determined and compared with the addition of an aminoglycoside or fluroquinolone and summarized in a combination antibiogram. RESULTS: One hundred ninety-nine P aeruginosa isolates were included for analysis. The addition of a second agent to piperacillin-tazobactam was shown to have the most significant improvement among the ß-lactams, with 70% susceptibility as monotherapy and increases to above 90% with the addition of an aminoglycoside or fluroquinolone. The addition of an aminoglycoside or fluroquinolone to cefepime and meropenem increased coverage to above 95%. The addition of a second agent was likely to increase susceptibility of a monotherapy backbone; however, as the susceptibility of the first-line agent decreased, the susceptibility of the second agent needed to be higher to achieve a 95% coverage threshold. CONCLUSIONS: Our results support use of a second agent to significantly improve the likelihood of appropriate empiric coverage of P aeruginosa. Use of a combination antibiogram may be more beneficial than a simple antibiogram for units with increasing resistance rates, or for coverage of specific resistant organisms.