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.

[Antimicrobial agents in pediatric cancer patients with hepatic or renal impairment]. / Antimikrobielle Therapie bei Kindern und Jugendlichen mit Nieren- und Leberinsuffizienz.

Antimicrobial agents are among the most frequently prescribed therapeutics in the supportive care of children and adolescents with cancer or following hematopoietic stem cell transplantation. Most of these agents are cleared from the body by elimination of unchanged drug by the kidney and/or metabolism by the liver. Impaired renal and hepatic function may have profound effects on the pharmacokinetics and pharmacodynamics of antimicrobial agents, necessitating modification of the dosage regimen in order to avoid toxicity through accumulation of the parent and/or its metabolites. Key to minimize such toxicities is a thorough understanding of the antimicrobial drug armamentarium and a careful evaluation of benefits and risks of antimicrobial interventions. This article reviews the mechanisms of renal and hepatic drug clearance in the normal state and in the state of functional impairment, their implications for antimicrobial therapy and dosage recommendations for pediatric cancer patients with impaired renal or hepatic function.

Antifungal agents: in vitro susceptibility testing, pharmacodynamics, and prospects for combination therapy.

As invasive fungal infections in immunocompromised patients become increasingly important, the field of antifungal chemotherapy continues to evolve rapidly. New agents have entered the clinical arena, providing physicians with a variety of choices for treatment of most infections. Standardized methods for testing the in vitro susceptibility of fungi have become available, and concentration-effect relationships are increasingly explored. Finally, the availability of an entirely new class of antifungal agents is opening new opportunities for combination therapy of infections that are notoriously difficult to treat and carry a dismal prognosis. However, the ongoing progress in these key areas has also made antifungal chemotherapy considerably more complex and susceptible to misconceptions. Continuing efforts in the laboratory and well designed collaborative clinical trials are needed more than ever to turn opportunities into lasting benefit for patients at risk for or suffering from life-threatening invasive mycoses.