Meropenem Use in Pediatric Oncology – Audit on Indication, Appropriateness and Consumption Comparing Patient Derived and Pharmacy Dispensing Data

Svenja Ockfen; Leonie Egle; Katharina Sauter; Manfred Haber; Sören L. Becker; Gudrun Wagenpfeil; Norbert Graf; Arne Simon

doi:10.1055/a-1481-8905

Klin Padiatr 2021; 233(06): 278-285
DOI: 10.1055/a-1481-8905

Original Article

Meropenem Use in Pediatric Oncology – Audit on Indication, Appropriateness and Consumption Comparing Patient Derived and Pharmacy Dispensing Data

Meropenem in der Kinderonkologie – Audit zum angemessenen Einsatz sowie zum tatsächlichen Verbrauch im Vergleich mit Apothekenlieferdaten

Svenja Ockfen

¹Pediatric Hematology and Oncology, Children’s Hospital Medical Center, Children’s Hospital Medical Center, Saarland University Hospital, Homburg, Germany

,

Leonie Egle

¹Pediatric Hematology and Oncology, Children’s Hospital Medical Center, Children’s Hospital Medical Center, Saarland University Hospital, Homburg, Germany

,

Katharina Sauter

²Paediatric Hematology and Oncology, Children's Hospital Medical Center, Homburg, Germany

,

Manfred Haber

³Director Hospital Pharmacy, Saarland University Hospital, Homburg/Saar, Homburg, Germany

,

Sören L. Becker

⁴Medical Microbiology and Hygiene, Saarland University Medical Center, Homburg, Germany

,

Gudrun Wagenpfeil

⁵Saarland University, Campus Homburg, Institutes for Medical Biometry, Epidemiology and Medical Informatics (IMBEI), Homburg, Germany

,

Norbert Graf

⁶Paediatric Hematology and Oncology, Children's Hospital Medical Center, Homburg, Germany

,

Arne Simon

⁶Paediatric Hematology and Oncology, Children's Hospital Medical Center, Homburg, Germany

› Author Affiliations

Abstract

ABSTRACT

Background Meropenem is an important second- or third-line antibiotic in pediatric cancer patients with febrile neutropenia (FN). Concise utilization data of meropenem in this setting is limited. It remains unclear how drug dispensing data from the hospital pharmacy correlate with data derived from patients’ files.

Methods Retrospective audit of meropenem-consumption in a University-affiliated pediatric oncology center in days of therapy (DOT)/100 inpatient days. The individual indication for meropenem was critically reviewed. The real consumption (in g/100 inpatient days) was compared with the drug amounts dispensed by the hospital pharmacy (in gram and in defined daily doses (DDD)/100 inpatient days). All patients receiving at least one dose of meropenem from 1st of April 2016 until the 30th of June 2018 were included.

Result Of 235 consecutive patients, 45 (19%) received meropenem, comprising 57 FN events. The probability of receiving at least one dose of meropenem was significantly higher in patients with ALL, AML, NHL and certain CNS tumors. Preceding the use of meropenem, only 5% of patients were known to be colonized with multidrug-resistant Gram-negative pathogens. Meropenem was administered as first-line treatment in 26% of all meropenem cycles, in 74% of all FN events with meropenem, Piperacillin-Tazobactam was used for initial treatment. In 5 of 57 FN events (8.8%), initial blood cultures yielded a Gram-negative pathogen. Concerning definite treatment, appropriate alternatives to meropenem with a smaller spectrum of activity would have been available in 4 cases, but a de-escalation was not performed. The median length of therapy in the meropenem group was 6 days, the corresponding median for days of therapy (DOT) was 12 days. This corresponds with combination therapy in 56% of all meropenem treatments, mostly with teicoplanin. On average, drug dispensing data from the hospital pharmacy were 1.53 times higher than real use (relying on patients’ data) without a significant correlation. A higher Case-mix Index positively correlated with meropenem-consumption.

Conclusion The use of meropenem should become a target of antibiotic stewardship programs in order to restrict its use to certain indications and preserve its outstanding role as second- or third-line antibiotic in this vulnerable population. Irrespective of the metrics used (g or DDD/100 inpatient days), pharmacy dispensing data do not accurately depict real patient-derived data concerning meropenem use in pediatric cancer patients.

ZUSAMMENFASSUNG

Hintergrund Meropenem ist ein wichtiges Reserveantibiotikum bei pädiatrisch-onkologischen Patienten mit Fieber bei Granulozytopenie (FN). Präzise Daten zur klinischen Anwendung sind rar. Es ist unklar, wie Liefermengen aus der Apotheke mit dem tatsächlichen Patienten-bezogenen Verbrauch korrelieren.

Methoden Retrospektives Audit des Meropenem Einsatzes in einer universitären Klinik für pädiatrische Onkologie und Hämatologie in days of therapy (DOT)/100 stat. Patiententage). Die Indikation wurde kritisch überprüft. Der tatsächliche Verbrauch (in g/100 Patiententage) wurde mit den Apothekenlieferdaten (in g und in DDD/100 Patiententage) verglichen. Alle Patienten mit mind. einer Meropenem-Gabe zwischen dem 1. April 2016 und dem 30. Juni 2018 wurden eingeschlossen.

Ergebnisse Von 235 konsekutiven Patienten erhielten 45 (19%) Meropenem während 57 FN Episoden. Die Wahrscheinlichkeit mind. Einer Meropenem-Gabe war signifikant erhöht bei Patienten mit ALL, AML, NHL und bestimmten Hirntumoren. Vor der Meropenem-Gabe war lediglich bei 5% der Patienten eine Vorbesiedlung mit multiresistenten Gram-negativen Erregern bekannt. Meropenem wurde in 26% aller Zyklen als Erstlinientherapie verwendet, bei 74% nach Erstlinientherapie mit Piperacillin-Tazobactam. Bei 5 FN (8,8%) wurde in der Blutkultur ein gramnegativer Erreger nachgewiesen. Bei vier von 5 hätte es in Hinblick auf die gezielte Therapie eine weniger breit wirksame Alternative gegeben, eine Deeskalation blieb jedoch aus. Die mediane Therapiedauer in der Meropenem-Gruppe betrug 6 Tage, die mediane DOT 12 Tage. Dieser Unterscheid wurde dadurch verursacht, dass in 56% eine Kombinationstherapie (meist mit Teicoplanin) verabreicht wurde. Die Apotheken-Liefermengen lagen um den Faktor 1,53 über dem tatsächlichen Verbrauch. Eine höherer mittlerer Case Mix Index korrelierte mit dem Meropenem Verbrauich.

Schlussfolgerung Der Einsatz von Meropenem sollte durch ein ABS Programm geprüft werden, um seinen Einsatz auf definierte Indikationen zu begrenzen und das Potential dieses Reservetherapeutikums in der Kinderonkologie zu erhalten. Unabhängig von der Messgröße (g oder DDD/100 Patiententage) geben die Apotheken-Lieferdaten nicht den tatsächlichen Meropenem-Verbrauch wieder.

Keywords

Meropenem - Febrile Neutropenia - Children with Cancer - Antibiotic Stewardship

Schlüsselwörter

Meropenem - Fieber bei Neutropenie - Kinder mit Krebserkrankung - Antibiotic Stewardship

Full Text

References

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