Diagnosis and empirical treatment of fever of unknown origin (FUO) in adult neutropenic patients: guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)

Abstract

Fever may be the only clinical symptom at the onset of infection in neutropenic cancer patients undergoing myelosuppressive chemotherapy. A prompt and evidence-based diagnostic and therapeutic approach is mandatory. A systematic search of current literature was conducted, including only full papers and excluding allogeneic hematopoietic stem cell transplant recipients. Recommendations for diagnosis and therapy were developed by an expert panel and approved after plenary discussion by the AGIHO. Randomized clinical trials were mainly available for therapeutic decisions, and new diagnostic procedures have been introduced into clinical practice in the past decade. Stratification into a high-risk versus low-risk patient population is recommended. In high-risk patients, initial empirical antimicrobial therapy should be active against pathogens most commonly involved in microbiologically documented and most threatening infections, including Pseudomonas aeruginosa, but excluding coagulase-negative staphylococci. In patients whose expected duration of neutropenia is more than 7 days and who do not respond to first-line antibacterial treatment, specifically in the absence of mold-active antifungal prophylaxis, further therapy should be directed also against fungi, in particular Aspergillus species. With regard to antimicrobial stewardship, treatment duration after defervescence in persistently neutropenic patients must be critically reconsidered and the choice of anti-infective agents adjusted to local epidemiology. This guideline updates recommendations for diagnosis and empirical therapy of fever of unknown origin in adult neutropenic cancer patients in light of the challenges of antimicrobial stewardship.Electronic supplementary materialThe online version of this article (doi:10.1007/s00277-017-3098-3) contains supplementary material, which is available to authorized users.

EQUAL Aspergillosis Score 2018: An ECMM score derived from current guidelines to measure QUALity of the clinical management of invasive pulmonary aspergillosis

“…In a population of patients with (expected) neutropenia >10 days or patients undergoing allogeneic stem cell transplantation use of mould active prophylaxis or galactomannan screening 2‐3x/week in those not receiving prophylaxis is indicated (three points). In patients with 72‐96 hours of persistent fever despite broad‐spectrum antibacterial treatment chest computed tomography (CT) is the imaging modality of choice (three points) . In case of pulmonary infiltrates a bronchoalveolar lavage is warranted .…”

“…In order to provide a simplified overview we extracted key recommendations from recent guidance documents of the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), European Confederation of Medical Mycology (ECMM), European Respiratory Society (ERS), Infectious Diseases Society of America (IDSA), and the Infectious Diseases Working Party of the German Society for Hematology and Medical Oncology . We broke down guidelines and grouped recommendations into three groups: diagnosis, treatment, follow‐up.…”

Challenges in Infectious Diseases for Haematologists

“…In brief, carbapenems as empirical antibiotic therapy for febrile neutropenia should be reserved for patients with a high risk of bacteraemia due to extended-spectrum β−lactamase producing Enterobacteriaceae, while patients without respective risk factors should be treated preferably with an anti-pseudomonal cephalosporin or piperacillin-tazobactam. Glycopeptides, aminoglycosides and fluoroquinolones should only be given to patients with defined indications as per current guideline [12]. In this context, it is essential to interpret microbiological results correctly.…”

“…ABS can be applied to all patients, including patients with HM, but needs to take specific risks into account. The European Conference on Infections in Leukemia (ECIL) has published an approach towards ABS in febrile neutropenic high-risk patients advocating a more rational use of MDR-inducing antibiotics [11] which has been adapted in the current guidelines on febrile neutropenia from the Infectious Diseases Working Party (AGIHO - Arbeitsgemeinschaft Infektionen in der Hämatologie und Onkologie) [12]. In brief, carbapenems as empirical antibiotic therapy for febrile neutropenia should be reserved for patients with a high risk of bacteraemia due to extended-spectrum β−lactamase producing Enterobacteriaceae, while patients without respective risk factors should be treated preferably with an anti-pseudomonal cephalosporin or piperacillin-tazobactam.…”

Hematopoietic Growth Factors in the Management of Anemia and Febrile Neutropenia

“…The first sign of infection in neutropenia is usually fever, as the only symptom (measured orally), with no identifiable cause, from ≥38.3 or ≥38.0 °C for at least 1 h, persisting or occurring twice within 12 h. Fever in neutropenia must always be regarded as a life-threatening infection, which must be treated within 1 h with antibiotics in a standardized way [5,6]. The necessary diagnostics must not delay the therapy.…”