Assessment of Aspergillus-specific PCR as a screening method for invasive aspergillosis in paediatric cancer patients and allogeneic haematopoietic stem cell recipients with suspected infections.

Invasive aspergillosis (IA) remains difficult to diagnose in immunocompromised patients, because diagnostic EORTC/MSG criteria are often not met. As biomarkers might elucidate the pathogen, we analysed the performance of an Aspergillus PCR assay in blood for diagnosis of IA in immunocompromised paediatric patients with suspected infections. Ninety-five haemato-oncological paediatric patients were included over a period of 3 years, the underlying diseases consisting of acute leukaemia, solid tumours, non-malignant immunocompromising disorders and haematopoietic stem cell transplantation recipients. We retrospectively analysed 253 consecutive episodes of suspected infections. Thirty-eight patients had possible IA, none of the patients fulfilled EORTC/MSG criteria of probable/proven IA. PCR positivity was observed in 97/967 analyses. Sensitivity, specificity, positive and negative predictive value of the PCR per episode were 34%, 78%, 31% and 81% using possible IA as endpoint. Taken together, an undirected blood screening by Aspergillus-specific PCR is of little diagnostic value in a heterogenous paediatric patient cohort. Harnessing PCR for diagnosis of IA should thus be focused on blood analyses of more homogenous high-risk patients and/or analyses of bronchoalveolar lavage, tissue or cerebrospinal fluid specimens.

[Drug interactions of antimicrobial agents in children with cancer]. / Arzneimittelinteraktionen antimikrobieller Substanzen bei Kindern und Jugendlichen.

Antimicrobial agents are among the most common therapeutics prescribed to children and adolescents with hematologic/oncologic disorders. Because of the polymorbid state of most patients, they are frequently administered concomitantly with other drugs, resulting in a considerable potential for drug interactions. While many of these interactions are of marginal clinical significance, others are associated with substantial risks of decreased therapeutic efficacy or increased drug toxicity. Prevention and recognition of drug interactions are therefore of vital importance to optimizing effective use of antimicrobials and enhancing patient outcome. Key to minimize drug interactions are a thorough understanding of the pharmacology of frequently used antimicrobial agents and a careful evaluation of risks and benefits of potentially interacting drugs. This article reviews mechanisms and clinical relevance of drug interactions of antimicrobial agents in the supportive care of children and adolescents with hematologic/oncologic disorders and provides strategies for their prevention.

Liposomal amphotericin B for prophylaxis of invasive fungal infections in high-risk paediatric patients with chemotherapy-related neutropenia: interim analysis of a prospective study.

Invasive fungal infections (IFI) are a major cause of morbidity and mortality in patients with cancer. A retrospective analysis of children with cancer at high risk for IFI treated at Münster University Hospital showed that the incidence (7.4% vs. 1.8%) and lethality (28.1% vs. 0) of documented IFI were lower in patients receiving systemic antifungal prophylaxis with liposomal amphotericin B (l-AmB) in comparison to a historical control group. To determine whether this decline in incidence and lethality was due to antifungal prophylaxis or was produced by advances in diagnostic procedures and early empirical antifungal therapy, a prospective study was initiated. Patients in the prophylaxis arm received thrice-weekly 1 mg kg(-1) body weight l-AmB, whilst patients in the early intervention arm received no prophylaxis. Diagnostic procedures and antifungal therapy for suspected or proven IFI were initiated as clinically indicated for all patients. The primary endpoint of the study was the incidence of IFI. Secondary endpoints were the use of therapeutic doses of l-AmB, the safety of prophylactic l-AmB, and the total consumption of l-AmB for antifungal therapy. The interim analysis after 1 year showed no differences between the two approaches with respect to the incidence of IFI and to safety issues.