New molecular and surrogate biomarker-based tests in the diagnosis of bacterial and fungal infection in febrile neutropenic patients.
OBJECTIVE
Prompt diagnosis of infection in febrile neutropenia hosts with hematological malignancy is essential in directing therapy. We highlight experience using modern molecular and biomarker-based methods to diagnose bacterial and fungal bloodstream infections and invasive aspergillosis in these patients.


RESULTS
Nucleic acid amplification-based strategies are used to detect and identify pathogens from blood cultures or from blood/clinical specimens; the latter are more likely to influence clinical management. Advances in DNA extraction include standardization of isolation of Aspergillus DNA from blood. Broad-range and/or multiplex PCR generally have greater clinical utility than pathogen-specific assays. However, Aspergillus-PCR assays are useful in confirming/excluding disease and monitoring high-risk patients for invasive aspergillosis. Commercial real-time PCR/peptide nucleic acid fluorescent in-situ hybridization systems, used as adjuncts to blood cultures, to detect bacteria and fungi in blood cultures (or blood), are as sensitive as culture and enable earlier institution of targeted therapy. Yet there are no data indicating that molecular detection of bacterial/fungal pathogens influences patient outcomes. Positive serum Aspergillus galactomannan and 1,3-β-D-glucan tests are useful biomarkers in the diagnosis/screening of fungal infection, and have potential as measures of response to antifungal therapy. Serum procalcitonin levels can help differentiate infectious, from noninfectious, fever. Combined molecular and nonmolecular testing likely offers optimal diagnostic accuracy.


CONCLUSIONS
Numerous PCR-based and biomarker tools are available for the diagnosis and screening of infection in febrile neutropenia hosts. The optimal approach remains to be resolved by prospective studies examining the impact of one or more of tests on patient outcomes.
Chen
Sharon C-A
SC
Centre for Infectious Diseases and Microbiology, Westmead Hospital and the University of Sydney, Westmead, NSW, Australia. sharon.chen@swahs.health.nsw.gov.au
Kontoyiannis
Dimitrios P
DP
D000946:Antigens, Fungal / Q000097:blood; D016470:Bacteremia / Q000150:complications / Q000175:diagnosis* / Q000382:microbiology; D015415:Biomarkers / Q000097:blood*; D004269:DNA, Bacterial / Q000302:isolation & purification; D004271:DNA, Fungal / Q000302:isolation & purification; D005334:Fever / Q000382:microbiology; D016469:Fungemia / Q000150:complications / Q000175:diagnosis* / Q000382:microbiology; D019337:Hematologic Neoplasms / Q000150:complications* / Q000382:microbiology; D006801:Humans; D009503:Neutropenia / Q000150:complications* / Q000382:microbiology; D057089:Pathology, Molecular / Q000379:methods*; D016133:Polymerase Chain Reaction / Q000379:methods
D000946:Antigens, Fungal; D015415:Biomarkers; D004269:DNA, Bacterial; D004271:DNA, Fungal