| Background:A number of multiresistant pathogens including Acinetobacter baumannii(A.baumannii)place a heavy burden on ventilator-associated pneumonia(VAP)patients in the intensive care unit(ICU).It is critically important to differentiate between bacterial infection and colonization to avoid prescribing unnecessary antibiotics.Quantitative culture of lower respiratory tract(LRT)specimens,however,requires invasive procedures.Nowadays,volatile organic compounds(VOCs)have been studied in vitro and in vivo to identify pathogen-derived biomarkers.Therefore,an exploratory pilot study was conceived for proof of the concept that the appearance and level of A.baumannii-derived metabolites might be correlated with the presence of pathogen and its ecological niche(i.e.,the infection and colonization states)in ICU ventilated patients.Method:This diagnostic tool for VAP was recommended by the American Thoracic Society and the Infectious Diseases Society of America(ATS/ADSA)and the Chinese Society of Critical Care Medicine(CSCCM).Twenty patients with A.baumannii VAP(infection group),20 ventilated patients with LRT A.baumannii colonization(colonization group)and 20 ventilated patients with neurological disorders,but without pneumonia or A.baumannii colonization(control group)were enrolled in the in vivo pilot study.Patients with confirmed structural lung diseases,such as chronic obstructive pulmonary disease(COPD),respiratory tract neoplasms and asthma were excluded.A clinical isolate of A.baumannii strains was used for the in vitro culture experiment.Forty bottle cultures and another 40 corresponding controls were available for the following treatment.The adsorptive preconcentration(solid-phase microextraction fiber and Tenax(?)TA)and analysis technique of gas chromatography-mass spectrometry were applied in the studies.GC-MSSolution(LabSolutions,Shimadzu(?))and Automated Mass Spectral Deconvolution and Identification System(AMDIS,NIST)software were available for raw data preprocessing,including denoising,baseline correction(the drift and slope parameters were preset),resolution of overlapped chromatographic peaks and alignment.Results:Patients' baseline characteristics were statistically significant differences in the levels of liver and renal function,systemic inflammatory intensity and respiratory support,when comparing those from A.baumannii VAP patients to corresponding ones from ventilated patients of A.baumannii respiratory tract colonization,or to ones from ventilated patients without pneumonia or A.baumannii colonization.Breath profiles could be visually differentiated between A.baumannii cultivation in vitro and culture medium,and among in vivo groups.In the in vitro experiment,9 compounds of interest(2,5-dimethyl-pyrazine,1-undecene,isopentyl 3-methylbutanoate,decanal,1,3-naphthalenediol,longifolene,tetradecane,iminodibenzyl and 3-methyl-indene)in the headspace were found to be possible A.baumannii derivations.While there were 8 target VOCs(1-undecene,nonanal,decanal,2,6,10-trimethyl-dodecane,5-methyl-5-propyl-nonane,longifolene,tetradecane and 2-butyl-1-octanol)exhibiting characteristics of A.baumannii VAP derivations.The selected VOCs profile in vivo could be adopted to efficiently differentiate the presence of LRT A.baumannii from its absence,and LRT A.baumannii infection from its colonization(AUC = 0.89 and 0.88,respectively).Of these target VOCs,only 4 substances(1-Undecene,Decanal,Longifolene and Tetradecane)were found to be the same.By now there were no significant differences of breath profiles among different bacterial clones on the in vitro and in vivo studies.Conclusions:It is unfeasible to simply transfer the metabolic biomarkers from the in vitro condition to in vivo.The direct detection of exhaled A.baumannii-derived VOCs may be adopted for an early alert of the LRT bacterial presence in ventilated ICU patients,and even in different parasitic states of A.baumannii(i.e.,infection and colonization).However,further refinement and validation are required before its clinical use. |
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