M. von Lilienfeld-Toal

Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematological malignancies and solid tumors

Bacterial infections are the most common cause for treatment-related mortality in patients with neutropenia after chemotherapy. Here, we discuss the use of antibacterial prophylaxis against bacteria and Pneumocystis pneumonia (PCP) in neutropenic cancer patients and offer guidance towards the choice of drug. A literature search was performed to screen all articles published between September 2000 and January 2012 on antibiotic prophylaxis in neutropenic cancer patients. The authors assembled original reports and meta-analysis from the literature and drew conclusions, which were discussed and approved in a consensus conference of the Infectious Disease Working Party of the German Society of Hematology and Oncology (AGIHO). Antibacterial prophylaxis has led to a reduction of febrile events and infections. A significant reduction of overall mortality could only be shown in a meta-analysis. Fluoroquinolones are preferred for antibacterial and trimethoprim–sulfamethoxazole for PCP prophylaxis. Due to serious concerns about an increase of resistant pathogens, only patients at high risk of severe infections should be considered for antibiotic prophylaxis. Risk factors of individual patients and local resistance patterns must be taken into account. Risk factors, choice of drug for antibacterial and PCP prophylaxis and concerns regarding the use of prophylactic antibiotics are discussed in the review.

Management of sepsis in neutropenic patients: guidelines from the infectious diseases working party of the German Society of Hematology and Oncology

Sepsis is a leading cause of mortality in neutropenic cancer patients. Early initiation of effective causative therapy as well as intensive adjunctive therapy is mandatory to improve outcome. We give recommendations for the management of adults with neutropenia and sepsis. The guidelines are written for clinicians involved in care of cancer patients and focus on pathophysiology, diagnosis and treatment of sepsis during neutropenia.

False positivity of the Aspergillus galactomannan Platelia ELISA because of piperacillin/tazobactam treatment: does it represent a clinical problem?

OBJECTIVES False-positive results of the galactomannan (GM) ELISA caused by concurrent administration of piperacillin/tazobactam have been reported in patients with febrile neutropenia. PATIENTS AND METHODS This prospective study investigated different sampling times in 30 patients receiving piperacillin/tazobactam for febrile neutropenia. RESULTS Prior to the first piperacillin/tazobactam infusion, a median GM index of 0.2 [interquartile range (IQR) 0.1-0.3] was noted; in two patients (7%) the index was 0.5. Immediately after piperacillin/tazobactam infusion, the median index increased to 0.3 (IQR 0.2-0.4, P = 0.002) leading to 21% (7/30) false-positive results, if > or = 0.5 is assumed as the cut-off level. GM indices before the next piperacillin/tazobactam infusion were not increased (median 0.2, IQR 0.2-0.35, P > 0.05), but 10% (3/30) were still > or = 0.5. With a cut-off level of > 0.7, no false-positive results were noted at any sampling time point. CONCLUSIONS We conclude that the clinical relevance of false-positive GM results during piperacillin/tazobactam treatment is small if samples are collected prior to infusion and if a cut-off level of > 0.7 is used.

An Audit of Efficacy and Toxicity of Teicoplanin Versus Vancomycin in Febrile Neutropenia: Is the Different Toxicity Profile Clinically Relevant?

Background:Glycopeptides are often used for persistent fever in neutropenic patients. This study compares efficacy and toxicity of teicoplanin and vancomycin.Patients and Methods:Hundred consecutive neutropenic patients with hematological malignancies and persistent fever after 72 h of first-line antibiotic therapy (91% piperacillin/tazobactam) were treated with teicoplanin (800 mg on day 1, then 400 mg/day) + piperacillin/tazobactam + gentamicin from 08/96 to 09/00 (group T) or with vancomycin (2 g/day) + meropenem + levofloxacin from 10/00 to 04/02 (group V). Success was defervescence (≥ 7 days) in absence of any sign of continuing infection. Nephrotoxicity was monitored daily as increase in serum creatinine.Results:Fifty patients were analyzed in each group. Efficacy was evaluated in patients with piperacillin/tazobactam as first-line therapy only. Treatment was successful in 76% in group T (n = 42) and 59% in group V (n = 49), p = 0.118. Toxicity was evaluated in all patients. The median increase of creatinine was 11% (interquartile range 0%–30%) in group T and 17% (0%–74%) in group V, p = 0.062. In patients who received concomitant amphotericin B (given for 7 days and 6 days, respectively, p = 0.525), median creatinine increased from 0.9 mg/dl (0.8–1.1) to 1.2 mg/dl (0.9–1.5) in group T and from 0.9 mg/dl (0.8–1.08) to 1.55 mg/dl (1.33–2.23) in group V (p < 0.001). This led to a doubling of creatinine in 2/23 (9%) patients of group T and in 9/16 (56%) patients of group V (p = 0.003). A multivariate analysis revealed that concomitant use of amphotericin B (p < 0.001) and treatment with vancomycin (p = 0.002) were independently associated with nephrotoxicity.Conclusion:Teicoplanin and vancomycin were comparably effective in patients with neutropenia and persistent fever, but – if combined with amphotericin B – vancomycin was significantly more nephrotoxic than teicoplanin.

Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors—Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO)

Abstract Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline. The document was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) by reviewing currently available data and applying evidence-based medicine criteria.

Influenza virus infections in patients with malignancies: Characteristics and outcome of the spring season 2015-final analysis by the infectious diseases working party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO)

T cell stimulation with different cytokines results in distinct phenotypes and cytotoxic activity of CD19-specific CART cells