Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents.

BACKGROUND: The efficacy of the BNT162b2 vaccine in pediatrics was assessed by randomized trials before the Omicron variant's emergence. The long-term durability of vaccine protection in this population during the Omicron period remains limited. OBJECTIVE: To assess the effectiveness of BNT162b2 in preventing infection and severe diseases with various strains of the SARS-CoV-2 virus in previously uninfected children and adolescents. DESIGN: Comparative effectiveness research accounting for underreported vaccination in 3 study cohorts: adolescents (12 to 20 years) during the Delta phase and children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. SETTING: A national collaboration of pediatric health systems (PEDSnet). PARTICIPANTS: 77 392 adolescents (45 007 vaccinated) during the Delta phase and 111 539 children (50 398 vaccinated) and 56 080 adolescents (21 180 vaccinated) during the Omicron phase. INTERVENTION: First dose of the BNT162b2 vaccine versus no receipt of COVID-19 vaccine. MEASUREMENTS: Outcomes of interest include documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and cardiac complications. The effectiveness was reported as (1-relative risk)*100, with confounders balanced via propensity score stratification. RESULTS: During the Delta period, the estimated effectiveness of the BNT162b2 vaccine was 98.4% (95% CI, 98.1% to 98.7%) against documented infection among adolescents, with no statistically significant waning after receipt of the first dose. An analysis of cardiac complications did not suggest a statistically significant difference between vaccinated and unvaccinated groups. During the Omicron period, the effectiveness against documented infection among children was estimated to be 74.3% (CI, 72.2% to 76.2%). Higher levels of effectiveness were seen against moderate or severe COVID-19 (75.5% [CI, 69.0% to 81.0%]) and ICU admission with COVID-19 (84.9% [CI, 64.8% to 93.5%]). Among adolescents, the effectiveness against documented Omicron infection was 85.5% (CI, 83.8% to 87.1%), with 84.8% (CI, 77.3% to 89.9%) against moderate or severe COVID-19, and 91.5% (CI, 69.5% to 97.6%) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined 4 months after the first dose and then stabilized. The analysis showed a lower risk for cardiac complications in the vaccinated group during the Omicron variant period. LIMITATION: Observational study design and potentially undocumented infection. CONCLUSION: This study suggests that BNT162b2 was effective for various COVID-19-related outcomes in children and adolescents during the Delta and Omicron periods, and there is some evidence of waning effectiveness over time. PRIMARY FUNDING SOURCE: National Institutes of Health.

Dynamics and prognostic value of plasma cell-free DNA PCR in patients with invasive aspergillosis and mucormycosis.

Aspergillus species and Mucorales agents are the primary etiologies of invasive fungal disease (IFD). Biomarkers that predict outcomes are needed to improve care. Patients diagnosed with invasive aspergillosis and mucormycosis using plasma cell-free DNA (cfDNA) PCR were retested weekly for 4 weeks. The primary outcome included all-cause mortality at 6 weeks and 6 months based on baseline cycle threshold (CT) values and results of follow-up cfDNA PCR testing. Forty-five patients with Aspergillus and 30 with invasive Mucorales infection were retested weekly for a total of 197 tests. Using the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium (EORTC/MSG) criteria, 30.7% (23/75), 25.3% (19/75), and 38.7% (29/75) had proven, probable, and possible IFD, respectively. In addition, 97.3% (73/75) were immunocompromised. Baseline CT increased significantly starting at week 1 for Mucorales and week 2 for Aspergillus. Aspergillosis and mucormycosis patients with higher baseline CT (CT >40 and >35, respectively) had a nonsignificantly higher survival rate at 6 weeks, compared with patients with lower baseline CT. Mucormycosis patients with higher baseline CT had a significantly higher survival rate at 6 months. Mucormycosis, but not aspergillosis patients, with repeat positive cfDNA PCR results had a nonsignificantly lower survival rate at 6 weeks and 6 months compared with patients who reverted to negative. Aspergillosis patients with baseline serum Aspergillus galactomannan index <0.5 and <1.0 had significantly higher survival rates at 6 weeks when compared with those with index ≥0.5 and ≥1.0, respectively. Baseline plasma cfDNA PCR CT can potentially be used to prognosticate survival in patients with invasive Aspergillus and Mucorales infections. IMPORTANCE: We show that Aspergillus and Mucorales plasma cell-free DNA PCR can be used not only to noninvasively diagnose patients with invasive fungal disease but also to correlate the baseline cycle threshold with survival outcomes, thus potentially allowing the identification of patients at risk for poor outcomes, who may benefit from more targeted therapies.

Successful enteral administration of crushed posaconazole delayed-release tablets in children.

Erratic absorption of posaconazole oral suspension necessitates frequent dosing and administration with meals or supplements. Alternative enteral formulations are desirable for patients intolerant to enteral nutrition. Crushed posaconazole delayed-release tablets (POS-DRT) show promise in adults; limited evidence exists in children. We used crushed POS-DRT in 10 encounters with nine pediatric patients, achieving target POS concentrations in 90% of encounters. This highlights crushed POS-DRT as a potential enteral option for pediatric antifungal prophylaxis and treatment.

Application of cell-free DNA fungal polymerase chain reaction for invasive fungal disease evaluation in pediatric oncology and stem cell transplant patients.

BACKGROUND: Molecular diagnostics may enable early, noninvasive detection of invasive fungal disease (IFD) in immunocompromised patients. Cell-free deoxyribonucleic acid (cfDNA) fungal polymerase chain reaction (PCR) assays were recently incorporated into institutional prolonged febrile neutropenia pathways. We aimed to evaluate the performance of plasma cfDNA PCR panels (mold and Candida panels) in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients with clinical concern for IFD. METHODS: This single-center, observational study assessed plasma cfDNA fungal PCR performance for noninvasive IFD detection in hospitalized pediatric oncology and HSCT patients. The primary outcome was IFD diagnosis per published consensus definitions within 1 month. Positive and negative agreement between plasma cfDNA fungal PCR and consensus definitions were calculated. We also described test turnaround time and patient survival. RESULTS: From October 2021 to 2022, 54 patients underwent 60 evaluations with 11 proven/probable IFD cases. Comparing plasma cfDNA fungal PCRs to consensus definitions for proven/probable IFD, there was 73% positive agreement and 96% negative agreement. Two proven/probable cases with negative PCRs were caused by organisms not included on either panel. Median time to cfDNA fungal PCR result was 35 hours (interquartile range: 19-69) in eight proven/probable cases detected by cfDNA fungal PCR. There were 17 deaths among 54 patients, and IFD contributed to 45% of deaths in patients with proven/probable IFD. CONCLUSIONS: Plasma cfDNA fungal PCRs detected relevant molds or yeast in most cases classified as proven/probable IFD. However, this targeted approach missed some cases. More studies are required to determine optimal utilization of molecular diagnostics in pediatric patients.

Benefits of dermoscopy in primary care.

ABSTRACT: Skin cancer is the most common cancer in the United States, with an estimated 9,500 new diagnoses made each day. Dermoscopy (also called dermatoscopy) is an established clinical approach to improving skin cancer evaluation. However, only 8% to 9% of primary care physicians use it, and no data are available for physician associate/assistant or NP use. This article reports a dermoscopy algorithm that primary care providers can use to increase the detection of skin cancer and reduce unnecessary referrals and biopsies.

Closing the Shell: Gas-Phase Solvation of Halides by 1,3-Butadiene.

Gas-phase solvation of halides by 1,3-butadiene has been studied via a combination of photoelectron spectroscopy and density functional theory. Photoelectron spectra for X- ⋯(C4 H6 )n (X=Cl, Br, I where n=1-3, 1-3 and 1-7 respectively) are presented. For all complexes, the calculated structures indicate that butadiene is bound in a bidentate fashion through hydrogen-bonding, with the chloride complex showing the greatest degree of stabilisation of the internal C-C rotation of cis-butadiene. In both Cl- and Br- complexes, the first solvation shell is shown to be at least n = 4 ${n = 4}$ from the vertical detachment energies (VDEs), however for I- , increases in the VDE may suggest a metastable, partially filled, first solvation shell for n = 4 ${n = 4}$ and a complete shell at n = 6 ${n = 6}$ . These results have implications for gas-phase clustering in atmospheric and extraterrestrial environments.

Hydrogen Bonding versus Halogen Bonding: Spectroscopic Investigation of Gas-Phase Complexes Involving Bromide and Chloromethanes.

Hydrogen bonding and halogen bonding are important non-covalent interactions that are known to occur in large molecular systems, such as in proteins and crystal structures. Although these interactions are important on a large scale, studying hydrogen and halogen bonding in small, gas-phase chemical species allows for the binding strengths to be determined and compared at a fundamental level. In this study, anion photoelectron spectra are presented for the gas-phase complexes involving bromide and the four chloromethanes, CH3 Cl, CH2 Cl2 , CHCl3 , and CCl4 . The stabilisation energy and electron binding energy associated with each complex are determined experimentally, and the spectra are rationalised by high-level CCSD(T) calculations to determine the non-covalent interactions binding the complexes. These calculations involve nucleophilic bromide and electrophilic bromine interactions with chloromethanes, where the binding motifs, dissociation energies and vertical detachment energies are compared in terms of hydrogen bonding and halogen bonding.

Contribution of avoidable mortality to life expectancy inequalities in Wales: a decomposition by age and by cause between 2002 and 2020.

OBJECTIVES: To explore the contribution of avoidable mortality to life expectancy inequalities in Wales during 2002-2020. DESIGN: Observational study. SETTING: Wales, 2002-20, including early data from the COVID-19 pandemic. METHODS: We used routine statistics for 2002-2020 on population and deaths in Wales stratified by age, sex, deprivation quintile and cause of death. We estimated the contribution of avoidable causes of death and specific age-categories using the Arriaga decomposition method to highlight priorities for action. RESULTS: Life expectancy inequalities rose 2002-20 amongst both sexes, driven by serial decreases in life expectancy amongst the most deprived quintiles. The contributions of amenable and preventable mortality to life expectancy inequalities changed relatively little between 2002 and 2020, with larger rises in non-avoidable causes. Key avoidable mortality conditions driving the life expectancy gap in the most recent period of 2018-2020 for females were circulatory disease, cancers, respiratory disease and alcohol- and drug-related deaths, and also injuries for males. CONCLUSIONS: Life expectancy inequalities widened during 2002-20, driven by deteriorating life expectancy in the most deprived quintiles. Sustained investment in prevention post-COVID-19 is needed to address growing health inequity in Wales; there remains a role for the National Health Service in ensuring equitable healthcare access to alongside wider policies that promote equity.

Hydrogen sulfide dysregulates the immune response by suppressing central carbon metabolism to promote tuberculosis.

The ubiquitous gasotransmitter hydrogen sulfide (H2S) has been recognized to play a crucial role in human health. Using cystathionine γ-lyase (CSE)-deficient mice, we demonstrate an unexpected role of H2S in Mycobacterium tuberculosis (Mtb) pathogenesis. We showed that Mtb-infected CSE-/- mice survive longer than WT mice, and support reduced pathology and lower bacterial burdens in the lung, spleen, and liver. Similarly, in vitro Mtb infection of macrophages resulted in reduced colony forming units in CSE-/- cells. Chemical complementation of infected WT and CSE-/- macrophages using the slow H2S releaser GYY3147 and the CSE inhibitor DL-propargylglycine demonstrated that H2S is the effector molecule regulating Mtb survival in macrophages. Furthermore, we demonstrate that CSE promotes an excessive innate immune response, suppresses the adaptive immune response, and reduces circulating IL-1ß, IL-6, TNF-α, and IFN-γ levels in response to Mtb infection. Notably, Mtb infected CSE-/- macrophages show increased flux through glycolysis and the pentose phosphate pathway, thereby establishing a critical link between H2S and central metabolism. Our data suggest that excessive H2S produced by the infected WT mice reduce HIF-1α levels, thereby suppressing glycolysis and production of IL-1ß, IL-6, and IL-12, and increasing bacterial burden. Clinical relevance was demonstrated by the spatial distribution of H2S-producing enzymes in human necrotic, nonnecrotic, and cavitary pulmonary tuberculosis (TB) lesions. In summary, CSE exacerbates TB pathogenesis by altering immunometabolism in mice and inhibiting CSE or modulating glycolysis are potential targets for host-directed TB control.

Characterization of Glucokinases from Pathogenic Free-Living Amoebae.

Infection with pathogenic free-living amoebae, including Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris, can lead to life-threatening illnesses, primarily because of catastrophic central nervous system involvement. Efficacious treatment options for these infections are lacking, and the mortality rate due to infection is high. Previously, we evaluated the N. fowleri glucokinase (NfGlck) as a potential target for therapeutic intervention, as glucose metabolism is critical for in vitro viability. Here, we extended these studies to the glucokinases from two other pathogenic free-living amoebae, including Acanthamoeba castellanii (AcGlck) and B. mandrillaris (BmGlck). While these enzymes are similar (49.3% identical at the amino acid level), they have distinct kinetic properties that distinguish them from each other. For ATP, AcGlck and BmGlck have apparent Km values of 472.5 and 41.0 µM, while Homo sapiens Glck (HsGlck) has a value of 310 µM. Both parasite enzymes also have a higher apparent affinity for glucose than the human counterpart, with apparent Km values of 45.9 µM (AcGlck) and 124 µM (BmGlck) compared to ~8 mM for HsGlck. Additionally, AcGlck and BmGlck differ from each other and other Glcks in their sensitivity to small molecule inhibitors, suggesting that inhibitors with pan-amoebic activity could be challenging to generate.

Spectroscopic Study of the Br- +CH3 I→I- +CH3 Br SN 2 Reaction.

Mass spectrometry and anion photoelectron spectroscopy have been used to study the gas-phase S N 2 ${{{\rm S}}_{{\rm N}}2}$ reaction involving B r - ${{{\rm B}{\rm r}}^{-}}$ and C H 3 I ${{{\rm C}{\rm H}}_{3}{\rm I}}$ . The anion photoelectron spectra associated with the reaction intermediates of this S N 2 ${{{\rm S}}_{{\rm N}}2}$ reaction are presented. High-level CCSD(T) calculations have been utilised to investigate the reaction intermediates that may form as a result of the S N 2 ${{{\rm S}}_{{\rm N}}2}$ reaction along various different reaction pathways, including back-side attack and front-side attack. In addition, simulated vertical detachment energies of each reaction intermediate have been calculated to rationalise the photoelectron spectra.

A tale of two conformers: spectroscopic evidence for halide catalysed formic acid isomerisation.

Halide-formic acid complexes have been studied utilising a combined experimental and theoretical approach. Formic acid exists as two conformers, distinguished by the relative rotation about the C-OH bond. Computational investigation of the formic acid isomerisation reaction between the two conformers has revealed the ability of halide anions to catalyse the formation of, and preferentially stabilise, the higher energy conformer. Anion photoelectron spectroscopy has been used to study the halide-formic acid complexes, with the experimental vertical detachment energies compared with simulated photodetachment energies with respect to halide complexes with both formic acid conformers. The existence of experimental spectral features associated with halide complexes of the higher energy formic acid confomer confirms in situ generation, likely as a result of the halide mediated catalytic formation.

Clinical Accuracy and Impact of Plasma Cell-Free DNA Fungal Polymerase Chain Reaction Panel for Noninvasive Diagnosis of Fungal Infection.

BACKGROUND: Invasive fungal infection (IFI) is a growing cause of morbidity and mortality in oncology and transplant patients. Diagnosis of IFI is often delayed due to need for invasive biopsy and low sensitivity of conventional diagnostic methods. Fungal cell-free DNA (cfDNA) detection in plasma is a novel testing modality for the noninvasive diagnosis of IFI. METHODS: A novel bioinformatic pipeline was created to interrogate fungal genomes and identify multicopy sequences for cfDNA polymerase chain reaction (PCR) targeting. A real-time PCR panel was developed for 12 genera and species most commonly causing IFI. Sensitivity and specificity of the fungal PCR panel were determined using plasma samples from patients with IFI and non-IFI controls. Clinical impact of the fungal PCR panel was evaluated prospectively based on the treating team's interpretation of the results. RESULTS: Overall, the sensitivity and specificity were 56.5% (65/115; 95% confidence interval [CI], 47.4-65.2) and 99.5% (2064/2075; 95% CI, 99.0-99.7), respectively. In the subset of patients with an optimized plasma volume (2 mL), sensitivity was 69.6% (48/69; 95% CI, 57.9-79.2). Sensitivity was 91.7% (11/12; 95% CI, 62.5-100) for detection of Mucorales agents, 56.3% (9/16; 95% CI, 33.2-76.9) for Aspergillus species, and 84.6% (11/13; 95% CI, 56.5-96.9) for Candida albicans. In a prospective evaluation of 226 patients with suspected IFI, cfDNA testing was positive in 47 (20.8%) patients and resulted in a positive impact on clinical management in 20 of 47 (42.6%). CONCLUSIONS: The fungal cfDNA PCR panel offers a noninvasive approach to early diagnosis of IFI, providing actionable results for personalized care.

Recent advances in Clostridioides difficile infection epidemiology, diagnosis and treatment in children.

PURPOSE OF REVIEW: The US Centers for Disease Control and Prevention (CDC) classified Clostridioides difficile as an 'urgent' public health threat that requires 'urgent and aggressive action'. This call to action has led to new discoveries that have advanced C. difficile infection (CDI) epidemiology, diagnosis and treatment, albeit predominantly in adults. In 2017, the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America published clinical practice guidelines for both adults and children. At that time, recommendations in children were generally limited to relatively low-quality evidence. RECENT FINDINGS: Since publication of this guidance, there have been many advancements in the understanding of CDI in children. These include better understanding of healthcare settings as uncommon sources of C. difficile acquisition in children; risk factors for recurrent and community-associated CDI; performance of diagnostic tests in children and strategies for optimizing their use; and a more rigorous evidence base for CDI treatment in children, including the first-ever randomized controlled trial of CDI treatment in children and the largest study of fecal microbiota transplantation in children. SUMMARY: This review highlights the most recent salient advancements in paediatric CDI knowledge and practice that supplement published clinical guidance provided prior to these advancements.

Towards an Understanding of Halide Interactions with the Carbonyl-Containing Molecule CH3 CHO.

The anion photoelectron spectra of Cl- ⋅⋅⋅CD3 CDO, Cl- ⋅⋅⋅(CD3 CDO)2 , Br- ⋅⋅⋅CH3 CHO, and I- ⋅⋅⋅CH3 CHO are presented with electron stabilisation energies of 0.55, 0.93, 0.48, and 0.40 eV, respectively. Optimised geometries of the singly solvated species featured the halide appended to the CH3 CHO molecule in-line with the electropositive portion of the C=O bond and having binding energies between 45 and 52 kJ mol-1 . The doubly solvated Cl- ⋅⋅⋅(CH3 CHO)2 species features asymmetric solvation upon the addition of a second CH3 CHO molecule. Theoretical detachment energies were found to be in excellent agreement with experiment, with comparisons drawn between other halide complexes with simple carbonyl molecules.

Spectroscopic Investigation of Chalcogen Bonding: Halide-Carbon Disulfide Complexes.

A combined experimental and theoretical approach has been used to study intermolecular chalcogen bonding. Specifically, the chalcogen bonding occurring between halide anions and CS2 molecules has been investigated using both anion photoelectron spectroscopy and high-level CCSD(T) calculations. The relative strength of the chalcogen bond has been determined computationally using the complex dissociation energies as well as experimentally using the electron stabilisation energies. The anion complexes featured dissociation energies on the order of 47 kJ/mol to 37 kJ/mol, decreasing with increasing halide size. Additionally, the corresponding neutral complexes have been examined computationally, and show three loosely-bound structural motifs and a molecular radical.

Reducing Piperacillin and Tazobactam Use for Pediatric Perforated Appendicitis.

BACKGROUND: Although perforated appendicitis is associated with infectious complications, the choice of antibiotic therapy is controversial. We assess the effectiveness and safety of an intervention to reduce piperacillin and tazobactam (PT) use for pediatric acute perforated appendicitis. METHODS: This is a single-center, retrospective cohort study of children 18 y of age or younger who underwent primary appendectomy for perforated appendicitis between January 01, 2016 and June 30, 2019. An intervention to decrease PT use was implemented: the first phase was provider education (April 19, 2017) and the second phase was modification of electronic antibiotic orders to default to ceftriaxone and metronidazole (July 06, 2017). Preintervention and postintervention PT exposure, use of PT ≥ half of intravenous antibiotic days, and clinical outcomes were compared. RESULTS: Forty children before and 109 after intervention were included and had similar baseline characteristics. PT exposure was 31 of 40 (78%) and 20 of 109 (18%) (P < 0.001), and use ≥ half of intravenous antibiotic days was 31 of 40 (78%) and 14 of 109 (13%) (P < 0.001), in the preintervention and postintervention groups, respectively. There was no significant difference in mean duration of antibiotic therapy (10.8 versus 9.8 d), mean length of stay (6.2 versus 6.5 d), rate of surgical site infection (10% versus 11%), or rate of 30-d readmission and emergency department visit (20% versus 20%) between the preintervention and postintervention periods, respectively. CONCLUSIONS: Provider education and modification of electronic antibiotic orders safely reduced the use of PT for pediatric perforated appendicitis.

Standardization of post-operative antimicrobials reduced exposure while maintaining good outcomes in pediatric liver transplant recipients.

Infections following orthotopic liver transplant (OLT) result in significant morbidity and mortality, warranting careful consideration of risks associated with antibiotic overuse and benefits of infection prevention. In the absence of specific guidelines for antimicrobial prophylaxis in pediatric OLT, we developed a standardized approach to post-operative (post-op) antimicrobial therapy including 48 hours of antibiotics, no vancomycin for post-op fever within the first 48 hours, and caspofungin only for certain situations. The goal was to reduce antimicrobial utilization and adverse outcomes associated with longer duration of and broader treatment while maintaining good outcomes. The impact of this standardization on antimicrobial utilization and clinical outcomes at the largest pediatric liver transplant center in the United States is described. All individuals receiving an OLT from 1/1/17-9/30/17 (N = 38) and 3/14/18-12/13/18 (N = 27) were included in the pre-intervention (PreI) and post-intervention (PostI) groups, respectively. The intervention resulted in a significant reduction in individuals receiving post-op broad-spectrum gram-negative antibiotics for >48 hours (76% PreI vs 44% PostI OLT recipients, P = .01) and post-op vancomycin use (50% PreI, vs 7.4% PostI, P < .001). There were no statistically significant differences between groups for post-op fever, positive pre-/post-operative cultures, receipt of massive transfusion, or hospital length of stay. In conclusion, following the implementation of a standardized approach to post-op prophylaxis, antimicrobial exposure was significantly reduced without affecting OLT recipient outcomes.

Use of Prospective Audit and Feedback to Reduce Antibiotic Exposure in a Pediatric Cardiac ICU.

OBJECTIVES: We sought to determine whether a prospective audit and feedback intervention decreased antibiotic utilization in a pediatric cardiac ICU and to describe the characteristics of prospective audit and feedback audits and recommendations. DESIGN: Before-after study. SETTING: Pediatric cardiac ICU of a freestanding children's hospital. PATIENTS: All patients admitted to the cardiac ICU. INTERVENTIONS: A prospective audit and feedback program was established in our hospital's pediatric cardiac ICU on December 7, 2015. The antimicrobial stewardship program audited IV antibiotics, communicated prospective audit and feedback recommendations to the cardiac ICU, and regularly reviewed recommendation adherence. Mean monthly antibiotic utilization 18 months before ("preprospective audit and feedback"; from June 1, 2014 to November 30, 2015) and 24 months after ("prospective audit and feedback"; from January 1, 2016 to December 31, 2017) prospective audit and feedback implementation was compared. Antibiotic audit data during the prospective audit and feedback period were reviewed to capture the characteristics of prospective audit and feedback audits, recommendations, and adherence. MEASUREMENTS AND MAIN RESULTS: Mean cardiac ICU IV antibiotic use decreased 20% (701 vs 880 days of therapy per 1,000 patient days, p = 0.001) during the prospective audit and feedback period compared with the preprospective audit and feedback period. There was no difference in mean cardiac ICU length of stay (p = 0.573), mean hospital length of stay (p = 0.722), or the rate of discharge due to death (p = 0.541). There were 988 antibiotic audits and 370 prospective audit and feedback recommendations (37% recommendation rate) during the study period. The most commonly audited antibiotic category was broad-spectrum gram-negative agents and the most common indication for use was sepsis. Broad-spectrum gram-positive agents were more likely to be associated with a recommendation. CONCLUSIONS: There was a significant reduction in antibiotic use following implementation of a prospective audit and feedback program in our pediatric cardiac ICU. Over one-third of antibiotics audited in our cardiac ICU were associated with a prospective audit and feedback recommendation, revealing important targets for future antimicrobial stewardship efforts in this population.

A multifaceted quality improvement project improves intraoperative redosing of surgical antimicrobial prophylaxis during pediatric surgery.

BACKGROUND: Accurate intraoperative antibiotic redosing contributes to prevention of surgical site infections in pediatric patients. Ensuring compliance with evolving national guidelines of weight-based, intraoperative redosing of antibiotics is challenging to pediatric anesthesiologists. AIMS: Our primary aim was to increase compliance of antibiotic redoses at the appropriate time and appropriate weight-based dose to 70%. Secondary aims included a subset analysis of time compliance and dose compliance individually, and compliance based on order entry method of the first dose (verbal or electronic). METHODS: At a freestanding, academic pediatric hospital, we reviewed surgical cases between May 1, 2014, and October 31, 2017 requiring antibiotic redoses. After an institutional change in cefazolin dosing in May 2015, phased interventions to improve compliance included electronic countermeasures to display previous and next dose timing, an alert 5 minutes prior to next dose, and weight-based dose recommendation (September 2015). Physical countermeasures include badge cards, posting of guidelines, and updates to housestaff manual (September 2015). Statistical process control charts were used to assess overall antibiotic redose compliance, time compliance, and dose compliance. The chi-square test was used to analyze group differences. RESULTS: A total of 3015 antibiotic redoses were administered during 2341 operative cases between May 1, 2014, and October 31, 2017. Mean monthly compliance with redosing was 4.3% (May 2014-April 2015) and 73% (November 2015-October 2017) (P < 0.001). Dose-only compliance increased from 76% to 89% (P < 0.001), and time-only compliance increased from 4.9% to 82% (P < 0.001). After implementation of countermeasures, electronic order entry compared with verbal order was associated with higher dose compliance, 90% vs 86% (P = 0.015). CONCLUSION: This quality improvement project, utilizing electronic and physical interventions, was effective in improving overall prophylactic antibiotic redosing compliance in accordance with institutional redosing guidelines.