Prospective Audit of Gentamicin Drug Monitoring Practice in a Pediatric Cancer Center

Sarah Herberger; Nadine Oberkircher; Gentiana I. Wenzel; Dietmar Hecker; Gudrun Wagenpfeil; Rhoikos Furtwängler; Sören L. Becker; Cihan Papan; Norbert Graf; Arne Simon

doi:10.1055/a-1352-5053

Klinische Pädiatrie, Inhaltsverzeichnis

Klin Padiatr 2021; 233(03): 123-126
DOI: 10.1055/a-1352-5053

Original Article

Prospective Audit of Gentamicin Drug Monitoring Practice in a Pediatric Cancer Center

Prospektives Audit des Gentamicin Drug Monitorings in einem Kinderkrebszentrum

Sarah Herberger

¹Pediatric Oncology and Hematology, Saarland University Hospital and Saarland University Faculty of Medicine, Homburg, Germany

,

Nadine Oberkircher

¹Pediatric Oncology and Hematology, Saarland University Hospital and Saarland University Faculty of Medicine, Homburg, Germany

,

Gentiana I. Wenzel

²Otorhinolaryngology, Saarland University Hospital and Saarland University Faculty of Medicine, Homburg, Germany

,

Dietmar Hecker

²Otorhinolaryngology, Saarland University Hospital and Saarland University Faculty of Medicine, Homburg, Germany

,

Gudrun Wagenpfeil

³Institute for Medical Biometry, Epidemiology and Medical Informatics, Saarland University Hospital and Saarland University Faculty of Medicine, Homburg, Germany

,

Rhoikos Furtwängler

¹Pediatric Oncology and Hematology, Saarland University Hospital and Saarland University Faculty of Medicine, Homburg, Germany

,

Sören L. Becker

⁴Center for Infectious Diseases, Institute of Medical Microbiology and Hygiene, Saarland University, Homburg, Germany

,

Cihan Papan

⁴Center for Infectious Diseases, Institute of Medical Microbiology and Hygiene, Saarland University, Homburg, Germany

,

Norbert Graf

¹Pediatric Oncology and Hematology, Saarland University Hospital and Saarland University Faculty of Medicine, Homburg, Germany

,

Arne Simon

¹Pediatric Oncology and Hematology, Saarland University Hospital and Saarland University Faculty of Medicine, Homburg, Germany

› Institutsangaben

Abstract

Zusammenfassung

Hintergrund Gentamicin kommt in vielen pädiatrisch onkologischen Behandlungszentren in der Erstlinien-Kombinationstherapie bei Fieber und Granulozytopenie zum Einsatz. Seit 2011 verwenden wir hierzu eine Dosierung von 250 mg/m² KOF (max. 10 mg/kg, max. 400 mg) als tgl. Einmalgabe nach der deutschen Leitlinie.

Patienten und Methoden In diesem prospektiven Audit (Februar 2011 – Dezember 2019) wurden bei 66 kinderonkologischen Patienten 105 Gentamicin-Zyklen in Hinblick auf die Adhärenz zum Dosierungsstandard und auf die Ergebnisse des Drug Monitorings analysiert.

Ergebnisse Die Adhärenz mit dem neuen Dosierungsschema war hoch (89%). In 64% der Zyklen wurde ein Spitzenspiegel (1 h nach der 2. Gabe) im Zielbereich (C_max; 10–20 µg/ml) erreicht. C_max korrelierte signifikant mit der Dosis in mg/m² KOF (p=0,007), jedoch nicht mit der Dosis in mg/kg (p=0,366). Ein Lebensalter unter 6 Jahre beeinflusste dieses Ergebnis nicht. Der Gentamicin C_trough (8–10 h nach der zweiten Gabe) lag in 93% der Zyklen unter 2 µg/ml und korrelierte nicht mit der Dosis. Kein Patient in diesem Audit erfüllte die Kriterien für eine Gentamicin-assoziierte Nephrotoxizität.

Diskussion und Schlussfolgerung Dieses prospektive Audit der tgl. Einmalgabe von Gentamicin bei nierengesunden pädiatrisch-onkologischen Patienten bestätigt die praktische Anwendbarkeit und Sicherheit der Dosierung in mg/m² nach der deutschen Leitlinie. Aufgrund der eingeschränkten Indikationen für Gentamicin in der Erstlinientherapie ist eine prospektive multizentrische Studie zur Bestätigung dieser Beobachtungen wünschenswert.

Abstract

Background Many pediatric cancer centers still use Gentamicin as first line combination treatment in patients with fever and neutropenia. Since 2011, our center has implemented a dosing regimen with 250 mg/m² BSA (max. 10 mg/kg, max. 400 mg) as a single daily infusion according to the German guideline.

Patients and Methods In this prospective audit (February 2011 to December 2019), 105 Gentamicin treatment cycles were analyzed in 66 pediatric cancer patients, focusing on adherence to the dosing regimen and the drug monitoring results.

Results Adherence to the dosing regimen was high (89%). In 64% of all cycles, the C_max (drawn 1 h after the 2^nd dose) reached the target of 10–20 µg/ml. C_max significantly correlated with dosing in mg/m² BSA (p=0,007), but not with dosing in mg/kg (p=0,366). Age below 6 years did not influence these results. The Gentamicin C_trough (drawn 8–10 h after the second dose) was < 2 µg/ml in 93% of all cycles without any dose correlation. None of the patients experienced Gentamicin-associated nephrotoxicity.

Discussion and Conclusion This prospective audit of single daily infusion Gentamicin in pediatric cancer patients without impaired renal function elicits the feasibility and safety of the dosing regimen in mg/m² BSA according to the German guideline. Since indications for first-line gentamicin are limited, a multicenter prospective study would be advantageous to confirm these observations.

Key words

children with cancer - febrile neutropenia - empiric antibiotic treatment - gentamicin - therapeutic drug monitoring

Schlüsselwörter

Kinder mit Krebserkrankung - febrile Granulozytopenie - empirische Antibiotikatherapie - Gentamicin - therapeutisches Drug Monitoring

Volltext

Referenzen

References
1 Bass KD, Larkin SE, Paap C. et al. Pharmacokinetics of once-daily gentamicin dosing in pediatric patients. J Pediatr Surg 1998; 33: 1104-1107
2 Bate J, Gibson F, Selwood K. et al. A reaudit of current febrile neutropenia practice in UK paediatric oncology centres prior to implementation of NICE guidance. Arch Dis Child 2013; 98: 315-316
3 Best EJ, Gazarian M, Cohn R. et al. Once-daily gentamicin in infants and children: a prospective cohort study evaluating safety and the role of therapeutic drug monitoring in minimizing toxicity. Pediatr Infect Dis J 2011; 30: 827-832
4 Best EJ, Palasanthiran P, Gazarian M. Extended-interval aminoglycosides in children: more guidance is needed. Pediatrics 2005; 115: 827-828 author reply 828
5 Brock PR, Knight KR, Freyer DR. et al. Platinum-induced ototoxicity in children: a consensus review on mechanisms, predisposition, and protection, including a new International Society of Pediatric Oncology Boston ototoxicity scale. J Clin Oncol 2012; 30: 2408-2417
6 Deutsche Gesellschaft für pädiatrische Infektiologie (DGPI), Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH). Diagnostik und Therapie bei Kindern mit onkologischer Grunderkrankung, Fieber und Granulozytopenie (mit febriler Neutropenie) außerhalb der allogenen Stammzelltransplantation. Arbeitsgemeinschaft Wissenschaftlicher Fachgesellschaften (AWMF) 2016; Registernummer 048/ 14
7 Fisher BT, Gerber JS, Leckerman KH. et al. Variation in hospital antibiotic prescribing practices for children with acute lymphoblastic leukemia. Leuk Lymphoma 2013; 54: 1633-1639
8 Germovsek E, Barker CI, Sharland M. What do I need to know about aminoglycoside antibiotics?. Arch Dis Child Educ Pract Ed 2017; 102: 89-93
9 Ho KK, Bryson SM, Thiessen JJ. et al. The effects of age and chemotherapy on gentamicin pharmacokinetics and dosing in pediatric oncology patients. Pharmacotherapy 1995; 15: 754-764
10 Houot M, Pilmis B, Thepot-Seegers V. et al. Aminoglycoside use in a pediatric hospital: there is room for improvement-a before/after study. Eur J Pediatr 2016; 175: 659-665
11 Inparajah M, Wong C, Sibbald C. et al. Once-daily gentamicin dosing in children with febrile neutropenia resulting from antineoplastic therapy. Pharmacotherapy 2010; 30: 43-51
12 Lehrnbecher T, Phillips R, Alexander S. et al. Guideline for the Management of Fever and Neutropenia in Children With Cancer and/or Undergoing Hematopoietic Stem-Cell Transplantation. J Clin Oncol 2012; 30: 4427-4438
13 Lehrnbecher T, Robinson P, Fisher B. et al. Guideline for the Management of Fever and Neutropenia in Children With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update. J Clin Oncol 2017; 35: 2082-2094
14 Lynn J, Baily MA, Bottrell M. et al. The ethics of using quality improvement methods in health care. Ann Intern Med 2007; 146: 666-673
15 Manji A, Lehrnbecher T, Dupuis LL. et al. A meta-analysis of antipseudomonal penicillins and cephalosporins in pediatric patients with fever and neutropenia. Pediatr Infect Dis J 2012; 31: 353-358
16 Manji A, Lehrnbecher T, Dupuis LL. et al. A systematic review and meta-analysis of anti-pseudomonal penicillins and carbapenems in pediatric febrile neutropenia. Support Care Cancer 2012; 20: 2295-2304
17 McMullan BJ, Haeusler GM, Hall L. et al. Aminoglycoside use in paediatric febrile neutropenia - Outcomes from a nationwide prospective cohort study. PLoS One 2020; 15: e0238787
18 Newby B, Prevost D, Lotocka-Reysner H. Assessment of gentamicin 7 mg/kg once daily for pediatric patients with febrile neutropenia: a pilot project. J Oncol Pharm Pract 2009; 15: 211-216
19 Robinson PD, Lehrnbecher T, Phillips R. et al. Strategies for Empiric Management of Pediatric Fever and Neutropenia in Patients With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: A Systematic Review of Randomized Trials. J Clin Oncol 2016; 34: 2054-2060
20 Saban JA, Pizzi M, Caldwell J. et al. Previous aminoglycoside use and acute kidney injury risk in non-critically ill children. Pediatr Nephrol 2017; 32: 173-179
21 Scheler M, Lehrnbecher T, Groll A. et al. Management of children with fever and neutropenia: results of a survey in 51 pediatric cancer centers in Germany, Austria, and Switzerland. Infection. 2020; online first: https://link.springer.com/article/10.1007/s15010-020-01462-z
22 Schwartz GJ, Haycock GB, Edelmann CM. et al. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976; 58: 259-263
23 Taylor HA, Pronovost PJ, Faden RR. et al. The ethical review of health care quality improvement initiatives: findings from the field. Issue Brief (Commonw Fund) 2010; 95: 1-12
24 Wolf J, Sun Y, Tang L. et al. Antimicrobial Stewardship Barriers and Goals in Pediatric Oncology and Bone Marrow Transplantation: A Survey of Antimicrobial Stewardship Practitioners. Infect Control Hosp Epidemiol 2016; 37: 343-347

Zusatzmaterial

Supplementary Material