Septic patients in the intensive care unit present different nasal microbiotas

Xi-Lan Tan, Hai-Yue Liu, Jun Long, Zhaofang Jiang, Yuemei Luo, Xin Zhao, Shumin Cai, Xiaozhu Zhong, Zhongran Cen, Jin Su, Hongwei Zhou, Xi-Lan Tan, Hai-Yue Liu, Jun Long, Zhaofang Jiang, Yuemei Luo, Xin Zhao, Shumin Cai, Xiaozhu Zhong, Zhongran Cen, Jin Su, Hongwei Zhou

Abstract

Aim: The primary objective of this study was to evaluate correlations among mortality, intensive care unit (ICU) length of stay and airway microbiotas in septic patients.

Materials & methods: A deep-sequencing analysis of the 16S rRNA gene V4 region was performed.

Results: The nasal microbiota in septic patients was dominated by three nasal bacterial types (Corynebacterium, Staphylococcus and Acinetobacter). The Acinetobacter type was associated with the lowest diversity and longest length of stay (median: 9 days), and the Corynebacterium type was associated with the shortest length of stay. We found that the Acinetobacter type in the >9-day group was associated with the highest mortality (33%).

Conclusion: Septic patients have three nasal microbiota types, and the nasal microbiota is related to the length of stay and mortality.

Keywords: 16S rRNA; bacterial type; microbiome; nose; sepsis.

Conflict of interest statement

Financial & competing interests disclosure

This work was supported by the National Natural Science Foundation of China (NSFC313220143 and NSFC31270152). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1. . Comparison of nasal microbiota…
Figure 1.. Comparison of nasal microbiota between septic patients and healthy subjects.
(A) α diversity between the septic patients and healthy subjects. (B) Stacked bar chart of bacteria at the genus level between the septic patients and healthy controls.  (C) Principal coordinate analysis based on unweighted UniFrac distances. The red dots represent patients with sepsis, and the blue dots represent the controls. (D) significantly different taxa between the healthy participants and septic patients were determined using the linear discriminant analysis effect size (LEfSe). The data show increasing levels of Gammaproteobacteria, Pseudomonadales, Proteobacteria, Pseudomonas, Moraxellaceae, Acinetobacter, Enterobacteriaceae and Klebsiella in the patients. (E) Machine-learning classification based on nasal microbiota using random forest algorithms. LDA: Linear discriminant analysis.
Figure 1. . Comparison of nasal microbiota…
Figure 1.. Comparison of nasal microbiota between septic patients and healthy subjects.
(A) α diversity between the septic patients and healthy subjects. (B) Stacked bar chart of bacteria at the genus level between the septic patients and healthy controls.  (C) Principal coordinate analysis based on unweighted UniFrac distances. The red dots represent patients with sepsis, and the blue dots represent the controls. (D) significantly different taxa between the healthy participants and septic patients were determined using the linear discriminant analysis effect size (LEfSe). The data show increasing levels of Gammaproteobacteria, Pseudomonadales, Proteobacteria, Pseudomonas, Moraxellaceae, Acinetobacter, Enterobacteriaceae and Klebsiella in the patients. (E) Machine-learning classification based on nasal microbiota using random forest algorithms. LDA: Linear discriminant analysis.
Figure 2. . Differences in the results…
Figure 2.. Differences in the results of the principal coordinate analysis of nasal microbiota between healthy subjects and patients with sepsis.
(A) Principal coordinate analysis (PCoA) of septic patients and healthy subjects based on unweighted UniFrac distances. (B) PCoA of healthy subjects based on unweighted UniFrac distances. (C) PCoA of patients with sepsis based on unweighted UniFrac distances. The orange circles represent the samples (nasal microbiota) with the Acinetobacter type, the purple circles represent the samples with the Corynebacterium type and the green circles represent the samples with the Staphylococcus type.
Figure 3. . Relationship between the nasal…
Figure 3.. Relationship between the nasal bacterial type in the patients with sepsis and their length of stay in the intensive care unit.
(A) Comparison of the α diversity among the three nasal bacterial types in patients with sepsis. (B) Comparison of the length of intensive care unit stay among the three nasal bacterial types in patients with sepsis. (C) Comparison of the stacked bar charts of the genera in the three nasal bacterial types in patients with sepsis. ICU: Intensive care unit; PD: Phylogenetic diversity.
Figure 4. . Relationship between the nasal…
Figure 4.. Relationship between the nasal bacterial type of patients with sepsis and the number of antibiotic use days in the intensive care unit.
Figure 5. . Mortality rates of the…
Figure 5.. Mortality rates of the three nasal bacterial types based on different lengths of intensive care unit stay.
(A) Mortality of the Corynebacterium type based on different lengths of intensive care unit (ICU) stay. (B) Mortality of the Staphylococcus type based on different lengths of ICU stay. (C) Mortality of the Acinetobacter type based on different lengths of ICU stay.

References

    1. Labelle A, Juang P, Reichley R, et al. The determinants of hospital mortality among patients with septic shock receiving appropriate initial antibiotic treatment. Crit. Care Med. 2012;40(7):2016–2021.
    1. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N. Engl. J. Med. 2003;348(16):1546–1554.
    1. Zhou J, Tian H, Du X, et al. Population-based epidemiology of sepsis in a subdistrict of Beijing. Crit. Care Med. 2017;45(7):1168–1176.
    1. Tulloch LG, Chan JD, Carlbom DJ, Kelly MJ, Dellit TH, Lynch JB. Epidemiology and microbiology of sepsis syndromes in a university-affiliated urban teaching hospital and level-1 trauma and burn center. J. Intensive Care Med. 2017;32(4):264–272.
    1. Machado FR, Cavalcanti AB, Bozza FA, et al. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study. Lancet Infect. Dis. 2017;17(11):1180–1189.
    2. •• Sepsis is a serious public health problem with a reported mortality rate of 55.7%.

    1. Graspeuntner S, Waschina S, Kunzel S, et al. Gut dysbiosis with Bacilli dominance and accumulation of fermentation products precedes late-onset sepsis in preterm infants. Clin. Infect. Dis. 2018 Epub ahead of print.
    1. Stewart CJ, Embleton ND, Marrs ECL, et al. Longitudinal development of the gut microbiome and metabolome in preterm neonates with late onset sepsis and healthy controls. Microbiome. 2017;5(1):75.
    1. Alverdy JC, Krezalek MA. Collapse of the microbiome, emergence of the pathobiome, and the immunopathology of sepsis. Crit. Care Med. 2017;45(2):337–347.
    1. Dickson RP. The microbiome and critical illness. Lancet Respir. Med. 2016;4(1):59–72.
    1. Dickson RP, Singer BH, Newstead MW, et al. Enrichment of the lung microbiome with gut bacteria in sepsis and the acute respiratory distress syndrome. Nat. Microbiol. 2016;1(10):16113.
    1. Brown KA, Daneman N, Stevens VW, et al. Integrating time-varying and ecological exposures into multivariate analyses of hospital-acquired infection risk factors: a review and demonstration. Infect. Control Hosp. Epidemiol. 2016;37(4):411–419.
    1. Ochotorena E, Hernandez Morante JJ, Canavate R, Villegas RA, Viedma I. Methicillin-resistant Staphylococcus aureus and other multidrug-resistant colonizations/infections in an intensive care unit: predictive factors. Biol. Res. Nurs. 2018 Epub ahead of print.
    1. Wolkewitz M, Cooper BS, Palomar-Martinez M, et al. Multiple time scales in modeling the incidence of infections acquired in intensive care units. BMC Med. Res. Methodol. 2016;16(1):116.
    2. •• When patients are admitted to an intensive care unit, the risk of getting an infection is highly dependent on their length of stay in the intensive care unit.

    1. Kloepfer KM, Deschamp AR, Ross SE, et al. In children, the microbiota of the nasopharynx and bronchoalveolar lavage fluid are both similar and different. Pediatr. Pulmonol. 2018;53(4):475–482.
    1. Luna PN, Hasegawa K, Ajami NJ, et al. The association between anterior nares and nasopharyngeal microbiota in infants hospitalized for bronchiolitis. Microbiome. 2018;6(1):2.
    2. •• Microbiota severity associations from the nasopharynx are recapitulated in the anterior nares.

    1. Man WH, De Steenhuijsen Piters WA, Bogaert D. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat. Rev. Microbiol. 2017;15(5):259–270.
    1. Bessesen MT, Kotter CV, Wagner BD, et al. MRSA colonization and the nasal microbiome in adults at high risk of colonization and infection. J. Infect. 2015;71(6):649–657.
    1. Walsh AL, Fields AC, Dieterich JD, Chen DD, Bronson MJ, Moucha CS. Risk factors for Staphylococcus aureus nasal colonization in joint arthroplasty patients. J. Arthroplasty. 2018;33(5):1530–1533.
    1. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3) JAMA. 2016;315(8):801–810.
    1. Donnelly JP, Safford MM, Shapiro NI, Baddley JW, Wang HE. Application of the third international consensus definitions for sepsis (Sepsis-3) classification: a retrospective population-based cohort study. Lancet Infect. Dis. 2017;17(6):661–670.
    1. Huang YE, Wang Y, He Y, et al. Homogeneity of the vaginal microbiome at the cervix, posterior fornix, and vaginal canal in pregnant Chinese women. Microb. Ecol. 2015;69(2):407–414.
    1. Liu HY, Zhang SY, Yang WY, et al. Oropharyngeal and sputum microbiomes are similar following exacerbation of chronic obstructive pulmonary disease. Front. Microbiol. 2017;8:1163.
    1. He Y, Wu W, Zheng HM, et al. Regional variation limits applications of healthy gut microbiome reference ranges and disease models. Nat. Med. 2018;24(10):1532–1535.
    1. Lozupone C, Lladser ME, Knights D, Stombaugh J, Knight R. UniFrac: an effective distance metric for microbial community comparison. ISME J. 2011;5(2):169–172.
    1. Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature. 2011;473(7346):174–180.
    2. •• The tutorials of ‘enterotyping’ reported by Arumugam.

    1. Kuhn M. Building predictive models in R Using the caret Package. J. Stat Softw. 2008;28(5):1–26.
    2. • Random forest classification models were trained by the caret R package to classify samples from patients with sepsis and healthy controls.

    1. Svetnik V, Liaw A, Tong C, Culberson JC, Sheridan RP, Feuston BP. Random forest: a classification and regression tool for compound classification and QSAR modeling. J. Chem Inf. Comput. Sci. 2003;43(6):1947–1958.
    1. Fawcett T. An introduction to ROC analysis. Pattern Recognit. Lett. 2006;27(8):861–874.
    1. Costea PI, Hildebrand F, Arumugam M, et al. Enterotypes in the landscape of gut microbial community composition. Nat. Microbiol. 2018;3(1):8–16.
    1. Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334(6052):105–108.
    1. Bassis CM, Erb-Downward JR, Dickson RP, et al. Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals. mBio. 2015;6(2):e00037.
    2. •• Reports the nasal microbiota of healthy individuals.

    1. Wilson MT, Hamilos DL. The nasal and sinus microbiome in health and disease. Curr. Allergy Asthma Rep. 2014;14(12):485.
    2. •• Reports the nasal microbiota of healthy subjects.

    1. Pettigrew MM, Gent JF, Kong Y, et al. Association of sputum microbiota profiles with severity of community-acquired pneumonia in children. BMC Infect. Dis. 2016;16:317.
    1. Daniel MD, Gail A, Ludmila K. Extreme Dysbiosis of the microbiome in critical illness. Msphere. 2016;1(4):e00199–e00116.
    1. Jasani B, Kannan S, Nanavati R, Gogtay NJ, Thatte U. An audit of colistin use in neonatal sepsis from a tertiary care centre of a resource-limited country. Indian J. Med. Res. 2016;144(3):433–439.
    2. • Sepsis caused by drug-resistant Acinetobacter baumannii and other Gram-negative bacilli is a common challenge for clinicians and microbiologists.

    1. Raphael E, Riley LW. Infections caused by antimicrobial drug-resistant saprophytic Gram-negative bacteria in the environment. Front. Med. 2017;4:183.
    1. Everett BR, Sitton JT, Wilson M. Efficacy and cost-benefit analysis of a global environmental cleaning algorithm on hospital-acquired infection rates. J. Patient Saf. 2017;13(4):207–210.
    1. Liou ML, Chen KH, Yeh HL, Lai CY, Chen CH. Persistent nasal carriers of Acinetobacter baumannii in long-term-care facilities. Am. J. Infect. Control. 2017;45(7):723–727.
    2. •• Continuous colonization of the nasal cavity with Acinetobacter baumannii may be the source of Acinetobacter baumannii infection.

    1. Wang HL, Sui WJ, Wang JR, et al. [Risk factors for acquired multidrug-resistant Acinetobacter baumannii colonization in respiratory intensive care unit] Zhonghua Yi Xue Za Zhi. 2012;92(14):960–963.
    1. B R, B V, F A. Ventilator-associated pneumonia and its responsible germs: an epidemiological study. Emergency (Tehran) 2017;5(1):e26.
    1. Fodor AA, Klem ER, Gilpin DF, et al. The adult cystic fibrosis airway microbiota is stable over time and infection type, and highly resilient to antibiotic treatment of exacerbations. PLoS ONE. 2012;7(9):e45001.
    1. Slater M, Rivett DW, Williams L, et al. The impact of azithromycin therapy on the airway microbiota in asthma. Thorax. 2014;69(7):673–674.
    1. Frattari A, Parruti G, Erasmo R, et al. Recurring septic shock in a patient with blunt abdominal and pelvic trauma: how mandatory is source control surgery?: a case report. J. Med. Case Rep. 2017;11(1):49.
    1. Gajovic O, Todorovic Z, Mijalilovic Z, et al. [Incidence, risk factors and outcome of nosocomial pneumonia patients with central nervous system infections] Srp. Arh. Celok. Lek. 2011;139(7–8):476–480.
    1. Aktar F, Tekin R, Gunes A, et al. Determining the independent risk factors and mortality rate of nosocomial infections in pediatric patients. BioMed Res. Int. 2016:7240864. 2016.
    1. Kelly BJ, Imai I, Bittinger K, et al. Composition and dynamics of the respiratory tract microbiome in intubated patients. Microbiome. 2016;4:7.

Source: PubMed

Подписаться