Incidence of Antimicrobial-Associated Acute Kidney Injury in Children: A Structured Review.

Acute kidney injury (AKI) is a commonly reported adverse effect of administration of antimicrobials. While AKI can be associated with poorer outcomes, there is little information available to understand rates of AKI in children exposed to various antimicrobials. We performed a structured review using the PubMed and Embase databases. Articles were included if they provided an AKI definition in patients who were < 19 years of age receiving an antimicrobial and reported the frequency of AKI. Author-defined AKI rates were calculated for each study and mean pooled estimates for each antimicrobial were derived from among all study participants. Pooled estimates were also derived for those studies that reported AKI according to pRIFLE (pediatric risk, injury, failure, loss, end stage criteria), AKIN (acute kidney injury network), or KDIGO (kidney disease improving global outcomes) creatinine criteria. A total of 122 studies evaluating 28 antimicrobials met the inclusion criteria. Vancomycin was the most commonly studied drug: 11,514 courses across 44 included studies. Among the 27,285 antimicrobial exposures, the overall AKI rate was 13.2% (range 0-42.1% by drug), but the rate of AKI varied widely across studies (range 0-68.8%). Cidofovir (42.1%) and conventional amphotericin B (37.0%) had the highest pooled rates of author-defined AKI. Eighty-one studies used pRIFLE, AKIN, or KDIGO AKI criteria and the pooled rates of AKI were similar to author-defined AKI rates. In conclusion, antimicrobial-associated AKI is reported to occur frequently in children, but the rates of AKI varies widely across studies and drugs. Most published studies examined hospitalized patients and heterogeneity in study populations and in author definitions of AKI are barriers to a comparison of nephrotoxicity risk among antimicrobials in children.

The epidemiology of cephalosporin allergy labels in pediatric primary care.

Background: Recent studies have sought to understand the epidemiology and impact of beta-lactam allergy labels on children; however, most of these studies have focused on penicillin allergy labels. Fewer studies assess cephalosporin antibiotic allergy labels in children. The objective of this study was to determine the prevalence, factors associated with, and impact of cephalosporin allergy labels in children cared for in the primary care setting. Methods: Cephalosporin allergy labels were reviewed among children in a dual center, retrospective, birth cohort who were born between 2010 and 2020 and followed in 90 pediatric primary care practices. Antibiotic prescriptions for acute otitis media were compared in children with and without cephalosporin allergies. Results: 334,465 children comprised the birth cohort and 2,877 (0.9%) were labeled as cephalosporin allergic during the study period at a median age of 1.6 years. Third-generation cephalosporins were the most common class of cephalosporin allergy (83.0%). Cephalosporin allergy labels were more common in children with penicillin allergy labels than those without (5.8% vs. 0.6%). Other factors associated with a cephalosporin allergy label included white race, private insurance, presence of a chronic condition, and increased health care utilization. Children with third-generation cephalosporin allergy labels received more amoxicillin/clavulanate (28.8% vs. 10.2%) and macrolides (10.4% vs. 1.9%) and less amoxicillin (55.8% vs. 70.9%) for treatment of acute otitis media than non-allergic peers p < 0.001. Conclusions: One in 100 children is labeled as cephalosporin allergic, and these children receive different antibiotics for the treatment of acute otitis media compared to non-allergic peers.

Suboptimal antimicrobial discharge prescriptions at a tertiary referral children's hospital.

Objective: To determine the rate of and factors associated with suboptimal discharge antimicrobial prescribing at a tertiary referral children's hospital. Design: Retrospective cohort. Setting: Tertiary referral children's hospital. Population: All enteral antimicrobial discharge prescriptions at Lucile Packard Children's Hospital Stanford from January 1st, 2021 through December 31st, 2021. Method: All enteral discharge antimicrobials are routinely evaluated by our antimicrobial stewardship program within 48 hours of hospital discharge. Antimicrobials are determined to be optimal or suboptimal by an antimicrobial stewardship pharmacist after evaluating the prescribed choice of antimicrobial, dose, duration, dosing frequency, and formulation. The rate and factors associated with suboptimal antimicrobial discharge prescribing were evaluated. Results: Of 2,593 antimicrobial prescriptions ordered at discharge, 19.7% were suboptimal. Suboptimal prescriptions were due to incorrect duration (72.2%), dose (31.0%), dose frequency (23.3%), drug choice (6.5%), or formulation (5.7%). In total, 87.2% of antimicrobials for perioperative prophylaxis and 13.5% of treatment antimicrobials were suboptimal. Antimicrobials with the highest rate of suboptimal prescriptions were amoxicillin-clavulanate (40.7%), clindamycin (36.6%), and cephalexin (36.6%). Conclusion: Suboptimal antimicrobial discharge prescriptions are common and present an opportunity for antimicrobial stewardship programs during hospital transition of care. Factors associated with suboptimal prescriptions differ by antimicrobial and prescribed indication, indicating that multiple stewardship interventions may be needed to improve prescribing.

The Quality and Management of Penicillin Allergy Labels in Pediatric Primary Care.

BACKGROUND AND OBJECTIVES: Penicillin allergy labels are the most common drug allergy label. The objective of this study was to describe the quality and management of penicillin allergy labels in the pediatric primary care setting. METHODS: Retrospective chart review of 500 of 18 015 children with penicillin allergy labels born from January 1, 2010 to June 30, 2020 randomly selected from an outpatient birth cohort from Texas Children's Pediatrics and Children's Hospital of Philadelphia networks. Penicillin allergy risk classification ("not allergy," "low risk," "moderate or high risk," "severe risk," "unable to classify") was determined based on documentation within (1) the allergy tab and (2) electronic healthcare notes. Outcomes of allergy referrals and penicillin re-exposure were noted. RESULTS: Half of penicillin allergy labels were "unable to classify" based on allergy tab documentation. Risk classification agreement between allergy tabs and healthcare notes was fair (Cohen's ĸ = 0.35 ± 0.02). Primary care physicians referred 84 of 500 (16.8%) children to an allergist, but only 54 (10.8%) were seen in allergy clinic. All children who were challenged (25 of 25) passed skin testing. Removal of allergy labels was uncommon (69 of 500, 13.8%) but occurred more often following allergy appointments (26 of 54, 48%) than not (43 of 446, 9.6%, P < .001). Children delabeled by primary care physicians were as likely to tolerate subsequent penicillin-class antibiotics as those delabeled by an allergist (94% vs 93%, P = .87). CONCLUSIONS: Penicillin allergy documentation within the allergy tab was uninformative, and children were infrequently referred to allergists. Future quality improvement studies should improve penicillin allergy documentation and expand access to allergy services.

Impact of Penicillin Allergy Labels on Children Treated for Outpatient Respiratory Infections.

BACKGROUND: Penicillin allergy is the most common antibiotic allergy, yet most children labeled as allergic tolerate penicillin. The impact of inaccurate penicillin allergy labels (PALs) on pediatric outpatients is unknown. The objective of this study was to compare outcomes between children with and without a PAL after treatment for outpatient respiratory tract infections (RTI). METHODS: A retrospective, longitudinal birth cohort study was performed in children who received care in 90 pediatric primary care practices in Philadelphia and Houston metropolitan areas. Prescribing and clinical outcomes of children with a PAL at the time of an RTI were compared to non-allergic children, adjusting for potential confounders. RESULTS: Antibiotics were prescribed for 663,473 non-recurrent RTIs among 200,977 children. Children with a PAL (5% of cohort) were more likely than non-allergic children to receive broad-spectrum antibiotics (adjusted relative risk (aRR) 3.24, 95% CI 3.22-3.26) and second-line antibiotics (aRR 4.87, 95% CI 4.83, 4.89). Compared to non-allergic children receiving first-line antibiotics, children with a PAL were more likely to return with adverse drug events (aRR 1.28, 95% CI 1.18-1.39). There was no difference in treatment failure between groups (aRR 0.95, 95% CI 0.90-1.00). CONCLUSIONS: PALs lead to higher rates of broad-spectrum and second-line antibiotic prescribing in children treated for RTIs in primary care and contribute to unnecessary healthcare utilization through increased adverse events. Given the frequency of PALs, efforts to prevent inappropriate penicillin allergy labeling and promote de-labeling of existing inaccurate allergy labels may improve care of children treated for common bacterial infections.

Leveraging antimicrobial stewardship programs in response to the coronavirus disease 2019 (COVID-19) public health emergency.

The coronavirus disease 2019 (COVID-19) pandemic has strained antimicrobial stewardship programs (ASPs) but offered new opportunities. This review summarizes the impact of the COVID-19 pandemic on ASPs, review the contributions ASPs have made in the pandemic response, and highlight the potential role of ASPs in future pandemics.

Factors Associated With Penicillin Allergy Labels in Electronic Health Records of Children in 2 Large US Pediatric Primary Care Networks.

Importance: Penicillin allergy labels influence clinical decision-making, yet most children who are labeled do not have type 1 hypersensitivity allergic reactions and instead have a history of predictable adverse reactions or unspecified illness symptoms while receiving penicillin for viral infections. Studies describing penicillin allergy labeling in the pediatric outpatient setting are lacking. Objective: To describe the epidemiology and factors associated with penicillin allergy labels across 2 large US pediatric primary care networks. Design, Setting, and Participants: This retrospective, longitudinal birth cohort study was conducted in 90 primary care pediatric practices serving a diverse population of children across Houston, Texas, Austin, Texas, Philadelphia, Pennsylvania, and parts of New Jersey. Participants were children born between January 2010 and June 2020 who had a health care visit in the first 14 days of life and at least 2 additional visits in the first year of life at one of 90 primary care pediatric practices. Censoring criteria were additionally applied to exclude data from children no longer seeking health care in the 90 clinics over time. Statistical analysis was performed from February to May 2021. Exposures: Basic patient demographics, health care utilization, penicillin exposure, and primary clinic location. Main Outcomes and Measures: Addition of penicillin allergy label in the electronic medical record. Results: Among 334 465 children in the birth cohort, 164 173 (49.1%) were female; 72 831 (21.8%) were Hispanic, 59 598 (17.8%) were non-Hispanic Black, and 148 534 (44.4%) were non-Hispanic White; the median (IQR) age at censoring was 3.8 (1.7-6.6) years; 18 015 (5.4%) were labeled as penicillin allergic, but the prevalence of penicillin allergy labeling ranged from 0.9% to 10.2% across practices. Children were labeled at a median (IQR) age of 1.3 (0.9-2.3) years. Non-Hispanic White children were more likely to be labeled compared with non-Hispanic Black children after controlling for potential confounders (adjusted odds ratio, 1.7 [95% CI, 1.6-1.8]). There were 6797 allergic children (37.7%) labeled after receiving 1 penicillin prescription and 1423 (7.9%) labeled after receiving 0 penicillin prescriptions. Conclusions and Relevance: In this cohort study of more than 330 000 children, penicillin allergy labeling was common and varied widely across practices. Children were labeled early in life, and almost half were labeled after receiving 1 or 0 penicillin prescriptions. These findings raise questions regarding the validity of penicillin allergy labels. Future work exploring the fidelity of and outcomes associated with penicillin allergy-labeling in children is warranted.

Suppurative Intracranial Complications of Pediatric Sinusitis: A Single-Center Experience.

BACKGROUND: Suppurative intracranial complications of sinusitis are rare events in children and can lead to harmful neurologic sequelae and significant morbidity. We sought to review the presentation and management of patients admitted at our hospital with these conditions. METHODS: This was a retrospective study of pediatric patients admitted to a quaternary children's hospital from 2007 to 2019 for operative management of sinusitis with intracranial extension. Clinical characteristics, including surgical and microbiological data, were collected and analyzed. RESULTS: Fifty-four patients were included; the median age was 11.0 years, and there was a male predominance. Eighty-nine percent of patients had prior healthcare visits for the current episode of sinusitis; 46% of patients had an abnormal neurologic exam on admission. Epidural abscess and subdural empyema were the most common complications, and subdural empyema was associated with repeat surgical intervention. The dominant pathogens were Streptococcus anginosus group organisms (74%). The majority of patients completed treatment parenterally, with a median duration of therapy of 35 days. Neurological sequelae, including epilepsy or ongoing focal deficits, occurred in 22% of patients. History of seizure or an abnormal neurological exam at admission were associated with neurological sequelae. CONCLUSIONS: Clinicians should consider intracranial complications of sinusitis in patients with symptoms of sinusitis for >1 week. Patients should undergo urgent neuroimaging, as neurosurgical intervention is essential for these patients. Subdural empyema was associated with repeat neurosurgical intervention. Neurological sequelae occurred in 22% of patients, and new onset seizure or an abnormal neurological exam at admission were associated with neurological sequelae.

Murine macrophage inflammatory cytokine production and immune activation in response to Vibrio parahaemolyticus infection.

Vibrio parahaemolyticus is the most common cause of bacterial, seafood-related illness in the USA. Currently, there is a dearth of published reports regarding immunity to infection with this pathogen. Here, production of both pro- and anti-inflammatory cytokines by V. parahaemolyticus-infected RAW 264.7 murine macrophages was studied. It was determined that this infection results in increased concentrations of IL-1α, IL-6, TNF-α and IL-10. Additionally, decreases in cell surface TLR2 and TLR4 and increases in T-cell co-stimulatory molecules CD40 and CD86 were discovered. The data presented here begin to identify the immune variables required to eliminate V. parahaemolyticus from infected host tissues.

Disintegrins in health and disease.

Few of the proteins isolated and characterized from snake venom have proven to be more chemically diverse, exquisitely specific or promiscuously active than the family known as disintegrins. These small proteins have shown structural homology with hundreds of cell surface molecules from plants and animals other than snakes, and their precise mimicry of native receptor ligands speaks to evolutionary niches related to survival and geographic locale. Over 100 disintegrins have been named and studied, with the most recent efforts into molecular techniques providing significant clues to taxonomic relationships among four different snake families. Investigators have evaluated disintegrin applications in therapies for cancer, asthma, osteopenia and inappropriate angiogenesis. Crystal and NMR studies have confirmed hypotheses regarding ligand-receptor interactions while illuminating the complexities of structure-function evidence. Disintegrin chimeras with viruses, microbubbles and fluorescent labels have become useful tools in many investigations. While many disintegrin studies still involve platelets, previously unexplored interactions with glial cancer, T lymphocytes and the bacteria Yersinia have blazed new trails for this field. This review will summarize disintegrin investigations since 2003.