Antimicrobial use in pediatric oncology and hematology in Germany and Austria, 2020/2021: a cross-sectional, multi-center point-prevalence study with a multi-step qualitative adjudication process

Cihan Papan; Katharina Reifenrath; Katharina Last; Andishe Attarbaschi; Norbert Graf; Andreas H Groll; Johannes Hübner; Hans-Jürgen Laws; Thomas Lehrnbecher; Johannes G Liese; Luise Martin; Tobias Tenenbaum; Simon Vieth; Ulrich von Both; Gudrun Wagenpfeil; Stefan Weichert; Markus Hufnagel; Arne Simon; AB-PPS PedOnc Study Group

doi:10.1016/j.lanepe.2023.100599

Antimicrobial use in pediatric oncology and hematology in Germany and Austria, 2020/2021: a cross-sectional, multi-center point-prevalence study with a multi-step qualitative adjudication process

Lancet Reg Health Eur. 2023 Mar 1:28:100599. doi: 10.1016/j.lanepe.2023.100599. eCollection 2023 May.

Authors

Cihan Papan^{1

2}, Katharina Reifenrath³, Katharina Last^{1

2}, Andishe Attarbaschi⁴, Norbert Graf³, Andreas H Groll⁵, Johannes Hübner⁶, Hans-Jürgen Laws⁷, Thomas Lehrnbecher⁸, Johannes G Liese⁹, Luise Martin¹⁰, Tobias Tenenbaum¹¹, Simon Vieth¹², Ulrich von Both⁶, Gudrun Wagenpfeil¹³, Stefan Weichert¹¹, Markus Hufnagel¹⁴, Arne Simon³; AB-PPS PedOnc Study Group

Collaborators

Affiliations

¹ Center for Infectious Diseases, Institute of Medical Microbiology and Hygiene, Saarland University, Homburg, Germany.
² Institute for Hygiene and Public Health, University Hospital Bonn, Bonn, Germany.
³ Pediatric Oncology and Hematology, Children's Hospital, Saarland University, Homburg, Germany.
⁴ Department of Pediatric Hematology and Oncology, St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria.
⁵ Infectious Disease Research Program, Department of Pediatric Hematology/Oncology and Center for Bone Marrow Transplantation, University Children's Hospital Münster, Münster, Germany.
⁶ Division of Pediatric Infectious Disease, Dr. V. Hauner Children's Hospital, University of Munich (LMU), Munich, Germany.
⁷ Department of Pediatric Oncology, Hematology and Clinical Immunology, University of Duesseldorf, Duesseldorf, Germany.
⁸ Division for Pediatric Hematology and Oncology, Hospital for Children and Adolescents, University Hospital, Goethe University Frankfurt Am Main, Frankfurt, Germany.
⁹ Pediatric Infectious Diseases and Immunology, University Children's Hospital, Würzburg, Germany.
¹⁰ Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt - Universität zu Berlin, and Berlin Institute of Health, Medical Directorate, Berlin, Germany.
¹¹ Pediatric Infectious Diseases, Department of Pediatrics, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, Mannheim, D-68167, Germany.
¹² Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany.
¹³ Institute of Medical Biometry, Epidemiology and Medical Informatics, Saarland University, Homburg, Germany.
¹⁴ Division of Pediatric Infectious Diseases and Rheumatology, Department of Pediatrics and Adolescent Medicine, University Medical Center, Medical Faculty, University of Freiburg, Freiburg, Germany.

Abstract

Background: Due to the high risk of severe infection among pediatric hematology and oncology patients, antimicrobial use is particularly high. With our study, we quantitatively and qualitatively evaluated, based on institutional standards and national guidelines, antimicrobial usage by employing a point-prevalence survey with a multi-step, expert panel approach. We analyzed reasons for inappropriate antimicrobial usage.

Methods: This cross-sectional study was conducted at 30 pediatric hematology and oncology centers in 2020 and 2021. Centers affiliated to the German Society for Pediatric Oncology and Hematology were invited to join, and an existing institutional standard was a prerequisite to participate. We included hematologic/oncologic inpatients under 19 years old, who had a systemic antimicrobial treatment on the day of the point prevalence survey. In addition to a one-day, point-prevalence survey, external experts individually assessed the appropriateness of each therapy. This step was followed by an expert panel adjudication based upon the participating centers' institutional standards, as well as upon national guidelines. We analyzed antimicrobial prevalence rate, along with the rate of appropriate, inappropriate, and indeterminate antimicrobial therapies with regard to institutional and national guidelines. We compared the results of academic and non-academic centers, and performed a multinomial logistic regression using center- and patient-related data to identify variables that predict inappropriate therapy.

Findings: At the time of the study, a total of 342 patients were hospitalized at 30 hospitals, of whom 320 were included for the calculation of the antimicrobial prevalence rate. The overall antimicrobial prevalence rate was 44.4% (142/320; range 11.1-78.6%) with a median antimicrobial prevalence rate per center of 44.5% (95% confidence interval [CI] 35.9-49.9). Antimicrobial prevalence rate was significantly higher (p < 0.001) at academic centers (median 50.0%; 95% CI 41.2-55.2) compared to non-academic centers (median 20.0%; 95% CI 11.0-32.4). After expert panel adjudication, 33.8% (48/142) of all therapies were labelled inappropriate based upon institutional standards, with a higher rate (47.9% [68/142]) when national guidelines were taken into consideration. The most frequent reasons for inappropriate therapy were incorrect dosage (26.2% [37/141]) and (de-)escalation/spectrum-related errors (20.6% [29/141]). Multinomial, logistic regression yielded the number of antimicrobial drugs (odds ratio, OR, 3.13, 95% CI 1.76-5.54, p < 0.001), the diagnosis febrile neutropenia (OR 0.18, 95% CI 0.06-0.51, p = 0.0015), and an existing pediatric antimicrobial stewardship program (OR 0.35, 95% CI 0.15-0.84, p = 0.019) as predictors of inappropriate therapy. Our analysis revealed no evidence of a difference between academic and non-academic centers regarding appropriate usage.

Interpretation: Our study revealed there to be high levels of antimicrobial usage at German and Austrian pediatric oncology and hematology centers with a significant higher number at academic centers. Incorrect dosing was shown to be the most frequent reason for inappropriate usage. Diagnosis of febrile neutropenia and antimicrobial stewardship programs were associated with a lower likelihood of inappropriate therapy. These findings suggest the importance of febrile neutropenia guidelines and guidelines compliance, as well as the need for regular antibiotic stewardship counselling at pediatric oncology and hematology centers.

Funding: European Society of Clinical Microbiology and Infectious Diseases, Deutsche Gesellschaft für Pädiatrische Infektiologie, Deutsche Gesellschaft für Krankenhaushygiene, Stiftung Kreissparkasse Saarbrücken.

Keywords: Antimicrobial resistance; Antimicrobial stewardship; Cancer; Expert panel; Pediatric hematology; Pediatric oncology; Point-prevalence survey.