Toward identification and intervention to address financial toxicity and unmet health-related social needs among adolescents and emerging adults with cancer and their caregivers: A cross-cultural perspective.

PURPOSE: We qualitatively explored the unique needs and preferences for financial toxicity screening and interventions to address financial toxicity among adolescents and emerging adults (younger AYAs: 15-25 years) with cancer and their caregivers. METHODS: We recruited English- or Spanish-speaking younger AYAs who were treated for cancer within the past 2 years and their caregivers. Semi-structured interviews were conducted to explore preferences for screening and interventional study development to address financial toxicity. The data were coded using conventional content analysis. Codes were reviewed with the study team, and interviews continued until saturation was reached; codes were consolidated into categories and themes during consensus discussions. RESULTS: We interviewed 17 participants; nine were younger AYAs. Seven of the 17 preferred to speak Spanish. We identified three cross-cutting themes: burden, support, and routine, consistent, and clear. The burden came in the form of unexpected costs such as transportation to appointments, as well as emotional burdens such as AYAs worrying about how much their family sacrificed for their care or caregivers worrying about the AYA's physical and financial future. Support, in the form of familial, community, healthcare institution, and insurance, was critical to mitigating the effects of financial toxicity in this population. Participants emphasized the importance of meeting individual financial needs by routinely and consistently asking about financial factors and providing clear guidance to navigate these needs. CONCLUSION: Younger AYAs and their caregivers experience significant financial challenges and unmet health-related social needs during cancer treatment and often rely on key supports to alleviate these unmet needs. When developing interventions to mitigate financial toxicity, clinicians and health systems should prioritize clear, consistent, and tailorable approaches to support younger AYA cancer survivors and their families.

Guideline for the management of Clostridioides difficile infection in pediatric patients with cancer and hematopoietic cell transplantation recipients: 2024 update.

Our objective was to update a clinical practice guideline for the prevention and treatment of Clostridioides difficile infection (CDI) in pediatric patients with cancer and hematopoietic cell transplantation recipients. We reconvened an international multi-disciplinary panel. A systematic review of randomized controlled trials (RCTs) for the prevention or treatment of CDI in any population was updated and identified 31 new RCTs. Strong recommendations were made to use either oral metronidazole or oral vancomycin for non-severe CDI treatment, and to use either oral vancomycin or oral fidaxomicin for severe CDI. A strong recommendation that fecal microbiota transplantation should not be routinely used to treat CDI was also made. The panel made two new good practice statements to follow infection control practices including isolation in patients experiencing CDI, and to minimize systemic antibacterial administration where feasible, especially in patients who have experienced CDI.

Defining Practice Capacity for Cancer Care Delivery to Adolescents and Young Adults in the Community Setting: 2022 Landscape Assessment Results.

Background: Adolescents and young adults (AYAs) commonly receive cancer care in the community setting, but the availability of treatment options, resources, and support services for this population is not well known. The National Cancer Institute Community Oncology Research Program (NCORP) funds a network of practices whose mission is to increase access to cancer care and clinical trials in the community setting. We describe our interdisciplinary methodological approach to identify and characterize NCORP practices where AYAs receive cancer care. Methods: NCORP practices completed a cross-sectional Landscape Assessment to describe resources and practice characteristics. We established an interdisciplinary team of stakeholders to analyze the Landscape Assessment data relating to AYAs. Through an iterative process, we assessed NCORP practice responses to questions assessing AYA cancer care capacity, determined a threshold to define practices treating AYAs, and characterized these practices. Results: We determined that practices provide cancer care to AYAs if the following criteria were met: (1) endorsed having an AYA program (n = 20), (2) AYAs comprised ≥5% of annual cancer cases (n = 55), or (3) the practice treated ≥50 AYA cancer cases annually (n = 70). Of 271 NCORP practices, 100 (37%) met any criteria, whereas 87 (32%) did not; 84 (31%) could not be classified due to missing or unknown data. Conclusion: Using an interdisciplinary process, we define practices that treat AYAs in the community. We posit a uniform approach to examine resources and practice capacity for AYAs receiving cancer care across the United States to guide future AYA-focused cancer care delivery research development.

Association Between Copayment Assistance, Insurance Type, Prior Authorization, and Time to Receipt of Oral Anticancer Drugs.

PURPOSE: Oral anticancer drugs (OACDs) have become increasingly prevalent over the past decade. OACD prescriptions require coordination between payers and providers, which can delay drug receipt. We examined the association between insurance type, pursuit of copayment assistance, pursuit of prior authorization (PA), and time to receipt (TTR) for new OACD prescriptions. METHODS: We prospectively collected data on new OACD prescriptions for adult oncology patients from January 1, 2018, to December 31, 2019, including demographic and clinical characteristics, insurance type, and pursuit of PA and copayment assistance. TTR was defined as the number of days from prescription to OACD receipt. We summarized TTR using cumulative incidence and compared TTR by insurance type, pursuit of copayment assistance, and PA activity using the log-rank test. RESULTS: Our cohort of 1,024 patients was 53% male, and 40% were younger than 65. Twenty-six percent had commercial insurance only, 16% had Medicaid only, and 59% had Medicare with or without additional insurance. Eighty-six percent of prescriptions were successfully received. Across all prescriptions, 69% involved PA activity, and 21% involved the copayment assistance process. In unadjusted analyses, prescriptions involving the copayment assistance process had longer TTR compared with those not involving assistance (log-rank P value = .005) and OACDs covered by Medicare/commercial insurance had a longer TTR compared with Medicaid (log-rank P value = .006). The PA process was not associated with TTR (log-rank P value = .124). CONCLUSION: The process for obtaining OACDs is complex. The copayment assistance process and Medicare/commercial insurance are associated with delayed TTR. New policies are needed to reduce time to OACD receipt.

Children's Oncology Group's 2023 blueprint for research: Diversity and health disparities.

The Children's Oncology Group (COG) Diversity and Health Disparities Committee's (DHDC's) mission is to guarantee the highest standard of care for children and adolescents and young adults (AYA) with cancer regardless of ethnic, racial, gender, or socioeconomic background. We strive to identify and address issues of disparity within the existing scientific structure of COG and to support research across COG to improve survival by ensuring equitable access to COG-sponsored clinical trials. We are committed to advance COG-led research identifying mechanistic drivers of disparities and, concurrently, evaluating interventions to alleviate disparities in the COG trial setting. As trials identify the most promising therapies, diverse representation is critical to ensure that findings are relevant to everyone. Factors impacting clinical trial participation among vulnerable populations are complex, consisting of barriers at societal, systems, and individual levels. Recent efforts by investigators within DHDC demonstrated that trial-embedded collection of family-reported sociodemographic data and social determinants of health (SDoH) is feasible and acceptable in the context of COG. Diversity in the pediatric oncology workforce is essential and one potential approach to improving representation on clinical trials. To support and retain diverse oncology providers and researchers, a Minority Young Investigator Award (MYIA) was created to facilitate opportunities for graduating trainees and YIs with an interest in childhood cancer disparities research within COG. Although there are challenges to achieve the DHDC's priorities, only through collaboration and support for this work we will be able to elucidate mechanisms underlying inferior survival outcomes for historically marginalized children and AYA, and more importantly, implement interventional investigation to improve outcomes.

Children's Oncology Group 2023 blueprint for research: Cancer care delivery research.

The National Cancer Institute (NCI) has a 40-year history of initiatives to encourage the participation of community oncology sites into clinical trials research and clinical care. In 2014, the NCI re-organized to form the NCI Community Oncology Research Program (NCORP) network across seven research bases, including the Children's Oncology Group (COG), and numerous community sites. The COG portfolio for Cancer Care Delivery Research (CCDR), mirroring the larger NCORP network, has included two studies addressing guideline congruence, as an important marker of quality cancer care, and another focusing on financial toxicity, addressing the pervasive problems of healthcare cost. CCDR is a cross-cutting field that frequently examines intersectional aspects of healthcare delivery. With that in mind, we explicitly define domains of CCDR to propel our research agenda into the next phase of the NCORP CCDR program while acknowledging the complex and dynamic fields of clinical care, policy level decisions, research findings, and needs of communities served by the NCORP network that will inform the subsequent research questions. To ensure programmatic success, we will engage a broad interdisciplinary group of investigators and clinicians with expertise and dedication to community oncology and the populations they serve.

Childhood Cancer Death When Life Transpires Where High Childhood Poverty Has Persisted for Decades.

It is increasingly clear that social determinants of health impact health, well-being, and quality of life. How these factors can impact cancer-related mortality has only recently included the impact on childhood cancer mortality. Hoppman and colleagues examined the impact of historically prevalent poverty on children with cancer in Alabama, a state with elevated pediatric poverty. Their findings provide a revised framework for understanding the contribution of neighborhood-level factors to pediatric cancer outcomes, identifying previously unrecognized gaps and directing us toward new study approaches to better inform interventions at the individual, institutional and policy levels to improve childhood cancer survival. We provide additional commentary on the implications of these findings, unanswered questions, and considerations for the next generation of interventions to improve childhood cancer survival. See related article by Hoppmann et al., p. 380.

Implementation of Systematic Financial Screening in an Outpatient Breast Oncology Setting.

PURPOSE: Implementation of routine financial screening is a critical step toward mitigating financial toxicity. We evaluated the feasibility, sustainability, and acceptability of systematic financial screening in the outpatient breast oncology clinic at a large, urban cancer center. METHODS: We developed and implemented a stakeholder-informed process to systematically screen for financial hardship and worry. A 2-item assessment in English or Spanish was administered to patients through the electronic medical record portal or using paper forms. We evaluated completion rates and mode of completion. Through feedback from patients, clinicians, and staff, we identified strategies to improve completion rates and acceptability. RESULTS: From March, 2021, to February, 2022, 3,500 patients were seen in the breast oncology clinic. Of them, 39% (n = 1,349) responded to the screening items, either by paper or portal, 12% (n = 437) preferred not to answer, and the remaining 49% (n = 1,714) did not have data in their electronic health record, meaning they were not offered screening or did not complete the paper forms. Young adults (18-39 years) were more likely to respond compared with patients 70 years or older (61% v 30%, P < .01). English-preferring patients were more likely to complete the screening compared with those who preferred Spanish (46% v 28%, P < .01). Non-Hispanic White patients were more likely to respond compared with Non-Hispanic Black patients and with Hispanic patients (46% v 39% v 32%, P < .01). Strategies to improve completion rates included partnering with staff to facilitate paper form administration, optimizing patient engagement with the portal, and clearly communicating the purpose of the screening. CONCLUSION: Systematic financial screening is feasible, and electronic data capture facilitates successful implementation. However, inclusive procedures that address language and technology preferences are needed to optimize screening.

Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update.

PURPOSE: To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell transplantation recipients. METHODS: The International Pediatric Fever and Neutropenia Guideline Panel reconvened to conduct the second update of this CPG. We updated the previous systematic review to identify new randomized controlled trials (RCTs) evaluating any strategy for the management of FN in pediatric patients. Using the Grading of Recommendations Assessment, Development and Evaluation framework, evidence quality was classified as high, moderate, low, or very low. The panel updated recommendations related to initial management, ongoing management, and empiric antifungal therapy. Changes from the 2017 CPG were articulated, and good practice statements were considered. RESULTS: We identified 10 new RCTs in addition to the 69 RCTs identified in previous FN CPGs to inform the 2023 FN CPG. Changes from the 2017 CPG included two conditional recommendations regarding (1) discontinuation of empiric antibacterial therapy in clinically well and afebrile patients with low-risk FN if blood cultures remain negative at 48 hours despite no evidence of marrow recovery and (2) pre-emptive antifungal therapy for invasive fungal disease in high-risk patients not receiving antimold prophylaxis. The panel created a good practice statement to initiate FN CPG-consistent empiric antibacterial therapy as soon as possible in clinically unstable febrile patients. CONCLUSION: The updated FN CPG incorporates important modifications on the basis of recently published trials. Future work should focus on addressing knowledge gaps, improving CPG implementation, and measuring the impact of CPG-consistent care.

Reducing Adolescent and Young Adult Cancer Outcome Disparities Through Optimized Care Delivery: A Blueprint from the Children's Oncology Group.

Achieving equitable, high-quality cancer care delivery across socioeconomically and biologically diverse populations requires multilevel interventions, including those at the patient, provider, institution, and policy levels that influence cost, quality, and access to care. For adolescent and young adults (AYAs), who experience suboptimal health outcomes compared with younger and older people with cancer, cancer care delivery is influenced by additional contextual factors unique to the patients' developmental stage, psychosocial and economic status, and cancer subtype. In this review, we highlight the most pressing research needs in AYA cancer care delivery and opportunities to improve outcomes for this population.

Impact of a Hospital-Based Specialty Pharmacy in Partnership With a Care Coordination Organization on Time to Delivery and Receipt of Oral Anticancer Drugs.

PURPOSE: Oral anticancer drug (OACD) prescriptions require extensive coordination between providers and payers, which can delay drug receipt. Specialty pharmacies facilitate communication between multiple entities. In 2018, our cancer center partnered with a freestanding organization to implement a hospital-based specialty pharmacy (HB-SP). We evaluated the time to drug receipt (TTR) before and after HB-SP implementation. METHODS: Data were prospectively collected on all new OACD prescriptions for adult oncology patients from January 1, 2018, to December 31, 2019. In fall 2018, a HB-SP was initiated. We collected patient sociodemographic, clinical, and prescription data. TTR was the number of days from OACD prescription to drug receipt. We used multivariable logistic regression to examine factors associated with TTR ≤ 7 days before and after HB-SP implementation. RESULTS: In total, 954 patients were included, representing 1,102 new OACDs. The majority of prescribed drugs were targeted OACDs (56%, n = 617), and 71% (n = 779) required prior authorization. Of all prescriptions, 84% (n = 960) were successfully received with an overall median TTR of 7 days. In unadjusted analysis, HB-SP implementation, drug class, race and ethnicity, and prior authorization requirement were significantly associated with TTR. Adjusted analyses found that patients were more likely to receive their drugs ≤ 7 days after HB-SP implementation (53% v 47%; adjusted odds ratio [aOR], 1.29; 95% CI, 1.00 to 1.68; P = .05). CONCLUSION: The implementation of a HB-SP in partnership with a collaborative care model contributed to a decrease in TTR for OACDs. This difference is in part attributable to improved care coordination and communication. A centralized approach may improve overall efficiency due to fewer practice disruptions.

Factors Associated With Patients Not Receiving Oral Anticancer Drugs.

Importance: Oral anticancer drugs (OACDs) are increasingly prescribed for cancer treatment and require significant coordination of care. Retrospective studies suggest that 10% to 20% of OACD prescriptions are never received by the patients, but the reasons behind this are poorly understood. Objectives: To estimate the rate of failure to receive OACD prescriptions among patients with cancer and to examine the underlying reasons for this failure. Design, Setting, and Participants: A prospective cohort study was conducted among patients with cancer who were prescribed a new OACD from January 1, 2018, to December 31, 2019, at an urban academic medical center. Data analysis was conducted between 2021 and 2022. Main Outcomes and Measures: Patient demographic, clinical, and insurance data and OACD delivery dates were collected. The reasons for a failure to receive a prescribed OACD within 3 months were confirmed by manual review of medical records and were classified into 7 categories: clinical deterioration, financial access, clinician-directed change in decision-making, patient-directed change in decision-making, transfer of care, loss to follow-up, and unknown or other. A multivariable random-effects model was developed to identify factors associated with failure to receive a prescribed OACD. Results: The cohort included 1024 patients (538 men [53%]; mean [SD] age, 66.2 [13.9] years; 463 non-Hispanic White patients [45%], 140 non-Hispanic Black patients [14%], and 300 Hispanic patients [29%]), representing 1197 new OACD prescriptions. Of the 1197 prescriptions, 158 (13%) were categorized as having not been received by the patient. The most common reason for the failure to receive a prescribed OACD was due to patient and clinician decision-making (73 of 158 [46%]), and 20 cases (13%) in which prescriptions were not received were associated with financial access issues. In multivariable analysis, patients with a nonmetastatic solid malignant neoplasm were significantly less likely to not receive their OACDs than those with a hematologic malignant neoplasm (odds ratio, 0.57 [95% CI, 0.33-1.00]; P = .048). Conclusions and Relevance: This cohort study of patients prescribed a new OACD found that 13% of prescriptions were not received. The failure to receive a prescribed OACD was most frequently due to a change in clinical decision-making or patient choice. Ultimately, the reasons for the failure to receive a prescribed OACD were multifactorial and may have been appropriate in some cases.

New and Persistent Sedative-Hypnotic Use After Adjuvant Chemotherapy for Breast Cancer.

BACKGROUND: Sedative-hypnotic medications are used to treat chemotherapy-related nausea, anxiety, and insomnia. However, prolonged sedative-hypnotic use can lead to dependence, misuse, and increased health-care use. We aimed to estimate the rates at which patients who receive adjuvant chemotherapy for breast cancer become new persistent users of sedative-hypnotic medications, specifically benzodiazepines and nonbenzodiazepine sedative-hypnotics (Z-drugs). METHODS: Using the MarketScan health-care claims database, we identified sedative-hypnotic-naïve patients who received adjuvant chemotherapy for breast cancer. Patients who filled 1 and more prescriptions during chemotherapy and 2 and more prescriptions up to 1 year after chemotherapy were classified as new persistent users. Univariate and multivariable logistic regression analyses were used to estimate odds of new persistent use and associated characteristics. RESULTS: We identified 22 039 benzodiazepine-naïve patients and 23 816 Z-drug-naïve patients who received adjuvant chemotherapy from 2008 to 2017. Among benzodiazepine-naïve patients, 6159 (27.9%) filled 1 and more benzodiazepine prescriptions during chemotherapy, and 963 of those (15.6%) went on to become new persistent users. Among Z-drug-naïve patients, 1769 (7.4%) filled 1 and more prescriptions during chemotherapy, and 483 (27.3%) became new persistent users. In both groups, shorter durations of chemotherapy and receipt of opioid prescriptions were associated with new persistent use. Medicaid insurance was associated with new persistent benzodiazepine use (odds ratio = 1.88, 95% confidence interval = 1.43 to 2.47) compared with commercial or Medicare insurance. CONCLUSIONS: Patients who receive sedative-hypnotic medications during adjuvant chemotherapy for breast cancer are at risk of becoming new persistent users of these medications after chemotherapy. Providers should ensure appropriate sedative-hypnotic use through tapering dosages and encouraging nonpharmacologic strategies when appropriate.

Efficacy of a password-protected, pill-dispensing device with mail return capacity to enhance disposal of unused opioids after cancer surgery.

BACKGROUND: Opioid misuse is a public health crisis, and unused postoperative opioids are an important source. Although 70% of pills prescribed go unused, only 9% are discarded. This study evaluated whether an inexpensive pill-dispensing device with mail return capacity could enhance disposal of unused opioids after cancer surgery. METHODS: A prospective pilot study was conducted among adult patients who underwent major cancer-related surgery. Patients received opioid prescriptions in a mechanical device (Addinex) linked to a smartphone application (app). The app provided passwords on a prescriber-defined schedule. Patients could enter a password into the device and receive a pill if the prescribed time had elapsed. Patients were instructed to return the device and any unused pills in a disposal mailer. The primary end point was feasibility of device return, defined as ≥50% of patients returning the device within 6 weeks of surgery. Also explored was total pill use and return as well as patient satisfaction. RESULTS: Among 30 patients enrolled, the majority (n = 24, 80%) returned the device, and 17 (57%) returned it within 6 weeks of surgery. In total, 567 opioid pills were prescribed and 170 (30%) were used. Of 397 excess pills, 332 (84% of unused pills, 59% of all pills prescribed) were disposed of by mail. Among 19 patients who obtained opioids from the device, most (n = 14, 74%) felt the benefits of the device justified the added steps involved. CONCLUSIONS: Use of an inexpensive pill-dispensing device with mail return capacity is a feasible strategy to enhance disposal of unused postoperative opioids.

New persistent opioid use among adolescents and young adults with sarcoma.

BACKGROUND: Adolescents and young adults (AYA) with sarcoma experience both acute and chronic pain related to their disease and treatment. Studies in older adults have reported a high risk of persistent opioid use after cancer therapy among previously opioid-naive patients; however, few studies have evaluated posttreatment opioid use among AYAs. This article describes patterns of new persistent opioid use among AYAs in the year after treatment for sarcoma. METHODS: Opioid-naive patients who were 10 to 26 years old and diagnosed with sarcoma (2008-2016) were identified with the IBM Marketscan Database. Included subjects had an International Classification of Diseases code for sarcoma (ninth or tenth revision), received anticancer therapy (chemotherapy, surgery, and/or radiation) within 30 days of the first diagnosis code, and had continuous insurance coverage (commercial or Medicaid) for more than 12 months both before the diagnosis and after the last therapy. The primary outcome was new persistent opioid use, which was defined as at least 2 opioid prescriptions in the 12 months following treatment completion. Covariates included age, sex, insurance, tumor type, surgical procedure, mental health (MH) or substance use diagnoses before or during therapy, and concomitant lorazepam use. RESULTS: In total, 938 patients met the inclusion criteria; 521 (56%) were male, and 578 (62%) were younger than 18 years. In total, 727 (78%) had commercial insurance, and 273 (29%) had an MH diagnosis either before or during the treatment period. Of the total group, 464 (49%) used opioids during treatment only. Of those who used opioids during treatment, 135 (23%) received at least 2 prescriptions in the year after therapy. In a multivariable analysis, Medicaid versus commercial insurance (odds ratio [OR], 1.74; 95% confidence interval [CI], 1.15-2.64) and non-soft tissue sarcoma (OR for Ewing sarcoma, 3.23; 95% CI, 1.81-5.78; OR for osteosarcoma, 2.05; 95% CI, 1.36-3.09) conferred a higher likelihood of new persistent use. CONCLUSIONS: In this cohort of AYAs treated for sarcoma, 64% of the patients received opioid prescriptions during treatment, and 23% of these patients became new persistent users. Because of the risks associated with persistent opioid use, studies of novel pain management strategies along with age-appropriate education and anticipatory guidance are urgently needed. LAY SUMMARY: Using an insurance claims database, we conducted a study to determine the rate of new persistent opioid use among adolescents and young adults treated for sarcoma. We found that 64% of adolescents and young adults treated for sarcoma received opioid prescriptions during treatment, and 23% of these patients met the criteria for new persistent opioid use. These findings support the need for age-appropriate education and novel pain management strategies in this vulnerable population.

New and persistent controlled substance use among patients undergoing mastectomy and reconstructive surgery.

PURPOSE: Prolonged use of controlled substances can place patients at increased risk of dependence and complications. Women who have mastectomy and reconstructive surgery (M + R) may be vulnerable to becoming new persistent users (NPUs) of opioid and sedative-hypnotic medications. METHODS: Using the MarketScan health-care claims database, we identified opioid- and sedative-hypnotic-naïve women who had M + R from 2008 to 2017. Women who filled ≥ 1 peri-operative prescription and ≥ 2 post-operative prescriptions within one year after surgery were classified as NPUs. Univariate and multivariable logistic regression analyses were used to estimate rates of new persistent use and predictive factors. Risk summary scores were created based on the sum of associated factors. RESULTS: We evaluated 23,025 opioid-naïve women and 25,046 sedative-hypnotic-naïve women. We found that 17,174 opioid-naïve women filled a peri-operative opioid prescription, and of those, 2962 (17.2%) became opioid NPUs post-operatively. Additionally, 9426 sedative-hypnotic-naïve women filled a peri-operative sedative-hypnotic prescription, and of those, 1612 (17.1%) became sedative-hypnotic NPUs. Development of new persistent sedative-hypnotic use was associated with age ≤ 49 [OR 1.77 (95% CI 1.40-2.24)] and age 50-64 [1.60 (1.27-2.03)] compared to age ≥ 65; Medicaid insurance [2.34 (1.40-3.90)]; southern residence [1.42 (1.22-1.64)]; breast cancer diagnosis [2.24 (1.28-3.91)]; and chemotherapy [2.17 (1.94-2.42)]. Risk of NPU increased with higher risk score. Women with ≥ 3 of these risk factors were three times more likely to become sedative-hypnotic NPUs than patients with 0 or 1 factors [2.94 (2.51-3.43)]. Comparable findings were seen regarding new persistent opioid use. CONCLUSION: Women who have M + R are at risk of developing both new persistent opioid and new persistent sedative-hypnotic use. A patient's risk of becoming an NPU increases as their number of risk factors increases. Non-pharmacologic strategies are needed to manage pain and anxiety following cancer-related surgery.

Prior antibiotic use and acquisition of multidrug-resistant organisms in hospitalized children: A systematic review.

OBJECTIVE: Multidrug-resistant organisms (MDROs) cause ~5%-10% of infections in hospitalized children, leading to an increased risk of death, prolonged hospitalization, and additional costs. Antibiotic exposure is considered a driving factor of MDRO acquisition; however, consensus regarding the impact of antibiotic factors, especially in children, is lacking. We conducted a systematic review to examine the relationship between antibiotic use and subsequent healthcare-associated infection or colonization with an MDRO in children. DESIGN: Systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline. METHODS: We searched PubMed and Embase for all English, peer-reviewed original research studies published before September 2018. Included studies evaluated hospitalized children, antibiotic use as an exposure, and bacterial MDRO as an outcome. RESULTS: Of the 535 studies initially identified, 29 met the inclusion criteria. Overall, a positive association was identified in most studies evaluating a specific antibiotic exposure (17 of 21, 81%), duration of antibiotics (9 of 12, 75%), and number of antibiotics received (2 of 3, 67%). Those studies that evaluated any antibiotic exposure had mixed results (5 of 10, 50%). Study sites, populations, and definitions of antibiotic use and MDROs varied widely. CONCLUSIONS: Published studies evaluating this relationship are limited and are of mixed quality. Limitations include observation bias in recall of antibiotic exposure, variations in case definitions, and lack of evaluation of antibiotic dosing and appropriateness. Additional studies exploring the impact of antibiotic use and MDRO acquisition may be needed to develop effective antibiotic stewardship programs for hospitalized children.