Volatile metabolites of pathogens: a systematic review

PLoS Pathog. 2013 May;9(5):e1003311. doi: 10.1371/journal.ppat.1003311. Epub 2013 May 9.


Ideally, invading bacteria are detected as early as possible in critically ill patients: the strain of morbific pathogens is identified rapidly, and antimicrobial sensitivity is known well before the start of new antimicrobial therapy. Bacteria have a distinct metabolism, part of which results in the production of bacteria-specific volatile organic compounds (VOCs), which might be used for diagnostic purposes. Volatile metabolites can be investigated directly in exhaled air, allowing for noninvasive monitoring. The aim of this review is to provide an overview of VOCs produced by the six most abundant and pathogenic bacteria in sepsis, including Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Such VOCs could be used as biological markers in the diagnostic approach of critically ill patients. A systematic review of existing literature revealed 31 articles. All six bacteria of interest produce isopentanol, formaldehyde, methyl mercaptan, and trimethylamine. Since humans do not produce these VOCs, they could serve as biological markers for presence of these pathogens. The following volatile biomarkers were found for identification of specific strains: isovaleric acid and 2-methyl-butanal for Staphylococcus aureus; 1-undecene, 2,4-dimethyl-1-heptane, 2-butanone, 4-methyl-quinazoline, hydrogen cyanide, and methyl thiocyanide for Pseudomonas aeruginosa; and methanol, pentanol, ethyl acetate, and indole for Escherichia coli. Notably, several factors that may effect VOC production were not controlled for, including used culture media, bacterial growth phase, and genomic variation within bacterial strains. In conclusion, VOCs produced by bacteria may serve as biological markers for their presence. Goal-targeted studies should be performed to identify potential sets of volatile biological markers and evaluate the diagnostic accuracy of these markers in critically ill patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Bacterial Infections / diagnosis*
  • Bacterial Infections / metabolism*
  • Biomarkers / analysis*
  • Biomarkers / metabolism
  • Humans
  • Volatile Organic Compounds / analysis*
  • Volatile Organic Compounds / metabolism*


  • Biomarkers
  • Volatile Organic Compounds

Grants and funding

LDJB is supported by a research grant (PhD Scholarship) of the Academic Medical Center (http://www.amc.nl/web/Onderwijs/PhD/AMC-Scholarships/AMC-Scholarschip-winners.htm) and by the ESICM Young Investigator Award (http://www.esicm.org/research/eccrn/awards-winners). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.