In acutely ill patients, particularly in intensive care units or in mixed infections, time to a microbe-specific diagnosis is critical to a successful outcome of therapy. We report the application of evolving technologies involving mass spectrometry to diagnose and monitor a patient's course. As proof of this concept, we studied five patients and used two rat models of mono-infection and coinfection. We report the noninvasive combined monitoring of Aspergillus fumigatus and Pseudomonas aeruginosa infection. The invasive coinfection was detected by monitoring the fungal triacetylfusarinine C and ferricrocin siderophore levels and the bacterial metabolites pyoverdin E, pyochelin, and 2-heptyl-4-quinolone, studied in the urine, endotracheal aspirate, or breath condensate. The coinfection was monitored by mass spectrometry followed by isotopic data filtering. In the rat infection model, detection indicated 100-fold more siderophores in urine compared to sera, indicating the diagnostic potential of urine sampling. The tools utilized in our studies can now be examined in large clinical series, where we could expect the accuracy and speed of diagnosis to be competitive with conventional methods and provide advantages in unraveling the complexities of mixed infections.

Clinical Department of Laboratory Medicine Proteomics Core Facility Medical University of Vienna A 1090 Wien Austria

Department of Analytical Chemistry Faculty of Science Palacký University 771 46 Olomouc Czech Republic

Department of Anesthesiology and Intensive Care Medicine University Hospital Ostrava 708 00 Ostrava Czech Republic

Department of Bacteriology and Mycology Public Health Institute in Ostrava 702 00 Ostrava Czech Republic

Department of Biomedical Sciences Faculty of Medicine University of Ostrava 703 00 Ostrava Czech Republic

Department of Intensive Medicine Emergency Medicine and Forensic Studies University of Ostrava 701 03 Ostrava Czech Republic

Department of Internal Medicine Ostrava City Hospital 728 80 Ostrava Czech Republic

Department of Medical Microbiology 2nd Faculty of Medicine Charles University and Motol University Hospital 150 06 Prague Czech Republic

Division of Infectious Diseases and Geographic Medicine Stanford University School of Medicine Stanford CA 95128 USA

Infectious Disease Research Laboratory California Institute for Medical Research San Jose CA 95128 USA

Institute of Microbiology of the Czech Academy of Sciences 142 20 Prague Czech Republic

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacky University 779 00 Olomouc Czech Republic

Institute of Physiology and Pathophysiology Faculty of Medicine University of Ostrava 701 03 Ostrava Czech Republic

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$a Noninvasive Combined Diagnosis and Monitoring of Aspergillus and Pseudomonas Infections: Proof of Concept / $c R. Dobiáš, A. Škríba, T. Pluháček, M. Petřík, A. Palyzová, M. Káňová, E. Čubová, J. Houšť, J. Novák, DA. Stevens, G. Mitulovič, E. Krejčí, P. Hubáček, V. Havlíček

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$a In acutely ill patients, particularly in intensive care units or in mixed infections, time to a microbe-specific diagnosis is critical to a successful outcome of therapy. We report the application of evolving technologies involving mass spectrometry to diagnose and monitor a patient's course. As proof of this concept, we studied five patients and used two rat models of mono-infection and coinfection. We report the noninvasive combined monitoring of Aspergillus fumigatus and Pseudomonas aeruginosa infection. The invasive coinfection was detected by monitoring the fungal triacetylfusarinine C and ferricrocin siderophore levels and the bacterial metabolites pyoverdin E, pyochelin, and 2-heptyl-4-quinolone, studied in the urine, endotracheal aspirate, or breath condensate. The coinfection was monitored by mass spectrometry followed by isotopic data filtering. In the rat infection model, detection indicated 100-fold more siderophores in urine compared to sera, indicating the diagnostic potential of urine sampling. The tools utilized in our studies can now be examined in large clinical series, where we could expect the accuracy and speed of diagnosis to be competitive with conventional methods and provide advantages in unraveling the complexities of mixed infections.

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