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A Prospective Multicenter Study of Microbiologically Defined Infections in Pediatric Cancer Patients With Fever and Neutropenia: Swiss Pediatric Oncology Group 2003 Fever and Neutropenia Study

Agyeman, Philipp MD*†; Kontny, Udo MD‡§; Nadal, David MD; Leibundgut, Kurt MD*; Niggli, Felix MD; Simon, Arne MD**; Kronenberg, Andreas MD† ††; Frei, Reno MD‡‡; Escobar, Hugo MD‡ §§; Kühne, Thomas MD¶¶; Beck-Popovic, Maja MD‖‖; Bodmer, Nicole MD; Ammann, Roland A. MD*

The Pediatric Infectious Disease Journal: September 2014 - Volume 33 - Issue 9 - p e219–e225
doi: 10.1097/INF.0000000000000326
Original Studies

Background: Fever and neutropenia (FN) often complicate anticancer treatment and can be caused by potentially fatal infections. Knowledge of pathogen distribution is paramount for optimal patient management.

Methods: Microbiologically defined infections (MDI) in pediatric cancer patients presenting with FN by nonmyeloablative chemotherapy enrolled in a prospective multicenter study were analyzed. Effectiveness of empiric antibiotic therapy in FN episodes with bacteremia was assessed taking into consideration recently published treatment guidelines for pediatric patients with FN.

Results: MDI were identified in a minority (22%) of pediatric cancer patients with FN. In patients with, compared with patients without MDI, fever [median, 5 (interquartile range: 3–8) vs. 2 (interquartile range: 1–3) days, P < 0.001] and hospitalization [10 (6–14) vs. 5 (3–8) days, P < 0.001] lasted longer, transfer to the intensive care unit was more likely [13 of 95 (14%) vs. 7 of 346 (2.0%), P < 0.001], and antibiotics were given longer [10 (7–14) vs. 5 (4–7) days, P < 0.001]. Empiric antibiotic therapy in FN episodes with bacteremia was highly effective if not only intrinsic and reported antimicrobial susceptibilities were considered but also the purposeful omission of coverage for coagulase-negative staphylococci and enterococci was taken into account [81% (95% confidence interval: 68–90) vs. 96.6% (95% confidence interval: 87–99.4), P = 0.004].

Conclusions: MDI were identified in a minority of FN episodes but they significantly affected management and the clinical course of pediatric cancer patients. Compliance with published guidelines was associated with effectiveness of empiric antibiotic therapy in FN episodes with bacteremia.

From the *Department of Pediatrics; Institute for Infectious Diseases, University of Bern, Bern, Switzerland; Division of Pediatric Oncology, University Children’s Hospital, Freiburg, Germany; §Division of Pediatric Oncology, Department of Pediatrics, University of Aachen, Aachen, Germany; Division of Infectious Diseases and Hospital Epidemiology; Division of Oncology, Department of Pediatrics, University of Zurich, Zurich, Switzerland; **Department of Pediatric Oncology and Hematology, Saarland University Hospital, Homburg, Saarland, Germany; ††Department of Infectious Diseases, University of Bern, Bern, Switzerland; ‡‡Division of Clinical Microbiology, University Hospital Basel, Basel, Switzerland; §§Rehabilitation Center Katharinenhoehe, Schoenwald, Germany; ¶¶Division of Oncology/Hematology, Department of Pediatrics, University Children’s Hospital, Basel, Switzerland; and ‖‖Department of Pediatrics, University of Lausanne, Lausanne, Switzerland.

Accepted for publication December 8, 2013.

This study was supported by unrestricted research grants from Oncosuisse/Swiss Cancer League (OCS-01466-02-2004), Bayer AG (Switzerland), and GSK AG (Switzerland). The Swiss Centre for Antibiotic Resistance (ANRESIS) is financially supported by the Swiss government and the University of Bern (Bern, Switzerland).

The authors have no conflicts of interest or funding to disclose.

Address for correspondence: Philipp Agyeman, MD, Department of Pediatrics, University of Bern, Inselspital, 3010 Bern, Switzerland. E-mail:

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© 2014 by Lippincott Williams & Wilkins, Inc.