Clarification of adverse drug reactions by a pharmacovigilance team results in increased antibiotic re-prescribing at a freestanding United States children's hospital.

Documentation of adverse drug reactions (ADRs) is a key factor in guiding future prescribing. However, incomplete documentation is common and often fails to distinguish implicated drugs as true allergies. This in turn leads to unnecessary avoidance of implicated drug classes and may result in sub-optimal prescribing. Pharmacovigilance (PV) programs utilize a systematic approach to clarify ADR documentation and are known to improve patient safety. Yet it remains unclear if PV alters prescribing. Or, if the existence of the ADR documentation itself continues to prompt avoidance of implicated drugs. To address this, our work presents a retrospective cohort study assessing if clarification of antibiotic ADRs by a hospital-wide PV team was associated with future, safe, re-prescribing at a freestanding pediatric hospital in the midwestern United States. First, we compared the likelihood of future prescribing in an antibiotic class with an active ADR, as compared to alternative drug classes, between PV-clarified and non-clarified patients. Second, we assessed differences in adverse event rates 30-days after future prescribing based on PV clarification status. For robustness, analyses were performed on patients with ADRs in four antibiotic classes: penicillin-based beta-lactams (n = 45,642), sulfonamides/trimethoprim (n = 5,329), macrolides (n = 3,959), and glycopeptides (n = 622). Results illustrate that clarification of an ADR by PV was associated with an increased odds of future prescribing in the same drug class (Odds Ratio [95%-CI]): penicillin-based beta-lactams (1.59 [1.36-1.89]), sulfonamides/trimethoprim (2.29 [0.89-4.91]), macrolides (0.77 [0.33-1.61]), and glycopeptide (1.85 [1.12-3.20]). Notably, patients clarified by PV experienced no increase in the rate of adverse events within 30-days following the prescribing of antibiotics in the same class as an active ADR. Overall, this study provides strong evidence that PV reviews safely increase the rate of re-prescribing antibiotics even in the presence of an existing implicated drug ADR.

Multidisciplinary Approach to Deciphering Etoposide Infusion Reactions and Potential Role of Polyethersulfone Filter Membranes.

PURPOSE: Etoposide, a topoisomerase II inhibitor used clinically to treat cancer, has been associated with severe anaphylactic infusion related adverse drug reactions (ADRs). In a previous study we identified a hydrophilic polyethersulfone filter as a possible cause of increased rates of pediatric etoposide infusion reactions. In this multidisciplinary follow-up analytical study, we aimed to assess the chemical structure of etoposide after passing through the same hydrophilic polyethersulfone filter. METHODS: An etoposide 0.4 mg/mL infusion was prepared under aseptic conditions and then passed through a standard IV infusion set with an in-line filter in place. Samples were taken in triplicate using a needle-less access system to include sampling sites directly from the IV bag port and from the IV tubing both before and after the in-line filter. Samples were diluted into mobile phase, then an aliquot was injected into a high-performance liquid chromatography mass spectrometry HPLC-MS (Thermo TSQ Quantum Ultra) system coupled to a Diode Array Detector (DAD) (Thermo Dionex Ultimate 3000). Etoposide was monitored using a selected reaction monitoring scan (SRM) of 606.2/228.8 and wavelengths of 210, 220, 254, and 280 nm for 30 minutes. RESULTS: No detectable differences were observed upon comparing the three samples. Based on these results, a chemical change in etoposide resulting from an in-line filter is unlikely to be the primary cause of increased rates of infusion reactions. CONCLUSION: Pharmacists working in healthcare systems, observe many ADRs, but rarely have the resources necessary to investigate the potential etiology or causality. This report highlights importance of multi-disciplinary collaboration to investigate serious ADRs.

Increasing cefazolin use for surgical prophylaxis in penicillin-allergy-labeled patients.

Objective: Penicillin (PCN) allergy labels affect antimicrobial selection for surgical prophylaxis. We aimed to increase the percentage of cefazolin usage in patients with PCN allergy labels undergoing orthopedic surgery from 50% to 80%. Design: Quality improvement initiative. Setting: Children's Mercy Kansas City (CMKC), a freestanding children's hospital. Patients: Children scheduled for an orthopedic surgery (excluding spinal surgery) at CMKC who had a PCN allergy label and received a perioperative antibiotic. Methods: No standardized process existed to identify and clarify PCN-allergic-labeled patients preoperatively. We developed a process for patient identification combined with a pharmacist phone interview for PCN allergy clarification. In plan-do-study-act (PDSA) part 1, we implemented a computer-generated patient list. In PDSA part 2, we combined automated identification with a phone interview. In PDSA part 3, we enhanced the patient list, making it timely and concise. In PDSA part 4, we included a PCN allergy clarification electronic survey to caregivers via the electronic medical record. Results: Cefazolin use in PCN-allergic surgical patients increased from 50% to 74% following interventions. Patients who had their PCN allergy label clarified were 4 times more likely to receive cefazolin compared to those whose allergy labels were not clarified (OR, 4.21; 95% CI, 1.68-11.61; P = 0.003). Moreover, 90% of patients received cefazolin when their PCN allergy was clarified and cefazolin was recommended. When a PCN allergy label was not clarified, only 59% of patients received cefazolin. Conclusions: Appropriate clarification and documentation of PCN allergy labels increases the use of cefazolin for surgical prophylaxis.

Risks and mitigation strategies to prevent etoposide infusion-related reactions in children.

Etoposide is an antineoplastic agent widely used for treatment of many pediatric cancers. Etoposide has been associated with infusion-related reactions. In this brief report, we compare etoposide infusion-related reactions that occurred over a 10-year period at two freestanding pediatric hospitals. Infusion reactions occurred in 1% of patients at two hospitals across the study period. Rates of 4.8%, 3.4%, and 7.9% were observed at Children's Mercy Hospital during 2018, 2019, and 2020, respectively, after the implementation of in-line filters during etoposide infusions in late 2017. Of the 32 patients who experienced adverse reactions, 41% were rechallenged after the reaction and all were able to tolerate at least one future dose with either pre-treatment or extending infusion duration. This work highlights the importance of a multicenter approach to investigating adverse drug reactions (ADRs) as variation in practice can provide key information about ADRs and potential risk factors.

Methods for Detecting Pediatric Adverse Drug Reactions From the Electronic Medical Record.

Adverse drug reactions (ADRs) are common yet are often underreported, making them difficult to track and study. Prospective pharmacovigilance programs significantly increase detection and reporting of ADRs. The aim of this pilot study was to apply triggers used by a prospective pharmacovigilance program at a freestanding children's hospital to retrospectively detect ADRs at our institution, therefore determining if these methods could be replicated and provide the basis for implementation of a prospective pharmacovigilance program. In 2019, our institution had 22 000 inpatient admissions and 51 000 emergency room visits and had 21 ADRs voluntarily reported in an electronic medication safety tracking system. Additional ADRs were identified by methods including new or modified entries to a patient's allergy profile in the electronic medical record (EMR) and International Classification of Disease (ICD) codes. We identified 754 unique patients with changes to allergy profile and 5719 ICD codes in 3966 unique patients to evaluate. These triggers prompted screening of the EMR to validate the ADR, and we identified 280 ADRs occurring in 2019. Eight (2.8%) were identified solely by the electronic medication safety tracking system, 64 (23%) were identified by the allergy list, 110 (39%) were identified only by ICD coding, and the remaining 98 (35%) were identified by multiple methods. The use of triggers followed by review of the EMR identified 13-fold more ADRs than were voluntarily reported, illustrating the need for an active pharmacovigilance service and the successful use of multimodal methods to detect and track ADRs.

Utilization of the Naranjo scale to evaluate adverse drug reactions at a free-standing children's hospital.

The relationship between the Naranjo scaling system and pediatric adverse drug reactions (ADR) is poorly understood. We performed a retrospective review of 1,676 pediatric ADRs documented at our hospital from 2014-2018. We evaluated patient demographics, implicated medication, ADR severity, calculated Naranjo score, associated symptoms, and location within the hospital in which the ADR was documented. ADR severity was poorly correlated with Naranjo interpretation. Out of the 10 Naranjo scale questions, 4 had a response of "unknown" greater than 85% of the time. Cardiovascular and oncological/immunologic agents were more likely to have a probable or definite Naranjo interpretation compared to antimicrobials. Further strategies are needed to enhance the causality assessment of pediatric ADRs in clinical care.

Enhancing Pediatric Adverse Drug Reaction Documentation in the Electronic Medical Record.

Adverse drug reactions (ADRs) often go unreported or are inaccurately documented in the electronic medical recorded (EMR), even when they are severe and life-threatening. Incomplete reporting can lead to future prescribing challenges and ADR reoccurrence. The aim of this study was to evaluate the documentation of ADRs within the EMR and determine specific factors associated with appropriate and timely ADR documentation. Retrospective data were collected from a pediatric hospital system ADR reports from October 2010 to November 2018. Data included implicated medication, type, and severity of reaction, treatment location, the presence or absence of ADR documentation in the EMR alert profile within 24 hours of the ADR hospital or clinic encounter discharge, ADR identification method, and the presence or absence of pharmacovigilance oversight at the facility where the ADR was treated. A linear regression model was applied to identify factors contributing to optimal ADR documentation. A total of 3065 ADRs requiring medical care were identified. Of these, 961 ADRs (31%) did not have appropriate documentation added to the EMR alert profile prior to discharge. ADRs were documented in the EMR 87% of the time with the presence of pharmacovigilance oversight and only 61% without prospective pharmacovigilance (P < .01). Severity of ADR was not a predictor of ADR documentation in the EMR, yet the implicated medication and location of treatment did impact reporting. An active pharmacovigilance service significantly improved pediatric ADR documentation. Further work is needed to assure timely, accurate ADR documentation.

Cost and Potential Avoidability of Antibiotic-Associated Adverse Drug Reactions in Children.

We identified 375 children who visited the emergency department or urgent care clinic at Children's Mercy Hospitals & Clinics for antibiotic adverse drug reactions over a 1-year period, and the total cost for these visits was $170 893.20. Of these ADRs, 17% were likely avoidable. The potential negative consequences of antibiotics should be considered at the point of prescribing.