1 3 DOI 10.1007/s10337-014-2839-x Chromatographia (2015) 78:379–389 REVIEW Mass Spectrometry in Clinical Microbiology and Infectious Diseases Frank Fleurbaaij · Hans C. van Leeuwen · Oleg I. Klychnikov · Ed J. Kuijper · Paul J. Hensbergen Received: 17 September 2014 / Revised: 10 December 2014 / Accepted: 12 December 2014 / Published online: 9 January 2015 © Springer-Verlag Berlin Heidelberg 2015 Abbreviations 2D-PAGE Two-dimensional polyacrylamide gel electrophoresis CDI Clostridium difficile infection ESI Electrospray ionization FDA Food and Drug Administration FESF Far-Eastern spotted fever FTICR Fourier transform ion cyclotron resonance GPL Glycopeptidolipids HPLC High-performance liquid chromatography HS-SPME-GC-MS Headspace solid-phase microex- traction gas chromatography mass spectrometry LC Liquid chromatography MALDI-ToF MS Matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry MDR-TB Multidrug-resistant tuberculosis MLST Multilocus sequence typing MRM Multiple reaction monitoring MS Mass spectrometry MS/MS Tandem mass spectrometry MTBC Mycobacterium tuberculosis complex NMR Nuclear magnetic resonance PCR Polymerase chain reaction PCR/ESI–MS Polymerase chain reaction/electro- spray ionization–mass spectrometry PTR-ToF-MS Proton transfer reaction time-of- flight mass spectrometry QTOF Quadrupole time-of-flight SEP Surface-exposed proteins SPME Solid-phase micro extraction Abstract Mass spectrometry (MS) has a long history in which it has undergone a transformation from an instru- ment used in elemental analysis to a flexible tool for bio- analysis. Recent years have seen the adoption of the mass spectrometer in the (clinical) microbiology laboratory, as a tool for both research and diagnostic purposes. Matrix- assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF MS) has been the frontrunner in routine identification, enabling pathogen identification through whole cell extract profiling. However, many more MS-based applications related to clinical microbiology and the study of infectious diseases exist. This review provides an overview of recently published studies using MS for, i.e., pathogen identification, exploration of potential diag- nostic makers and dosage studies, exemplifying the versa- tility of the technique and its potential applications in the study of microbes. Keywords Microbiology · Mass spectrometry · PCR · MALDI-ToF MS · Proteomics · Metabolomics · Clinical Published in the topical collection Recent Developments in Clinical Omics with guest editors Martin Giera and Manfred Wuhrer. F. Fleurbaaij · H. C. van Leeuwen · E. J. Kuijper (*) Section Experimental Microbiology, Department of Medical Microbiology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands e-mail: E.J.Kuijper@lumc.nl O. I. Klychnikov · P. J. Hensbergen (*) Center for Proteomics and Metabolomics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands e-mail: P.Hensbergen@lumc.nl