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Critical Care
Published in: Critical Care 1/2021

01-12-2021 | Antibiotic | Research

Airway Pseudomonas aeruginosa density in mechanically ventilated patients: clinical impact and relation to therapeutic efficacy of antibiotics

Authors: Yohei Migiyama, Shinya Sakata, Shinji Iyama, Kentaro Tokunaga, Koichi Saruwatari, Yusuke Tomita, Sho Saeki, Shinichiro Okamoto, Hidenori Ichiyasu, Takuro Sakagami

Published in: Critical Care | Issue 1/2021

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Abstract

Background

The bacterial density of Pseudomonas aeruginosa is closely related to its pathogenicity. We evaluated the effect of airway P. aeruginosa density on the clinical course of mechanically ventilated patients and the therapeutic efficacy of antibiotics.

Methods

We retrospectively analyzed data of mechanically ventilated ICU patients with P. aeruginosa isolated from endotracheal aspirates. Patients were divided into three groups according to the peak P. aeruginosa density during ICU stay: low (≤ 104 cfu/mL), moderate (105‒106 cfu/mL), and high (≥ 107 cfu/mL) peak density groups. The relationship between peak P. aeruginosa density and weaning from mechanical ventilation, risk factors for isolation of high peak density of P. aeruginosa, and antibiotic efficacy were investigated using multivariate and propensity score-matched analyses.

Results

Four-hundred-and-sixty-one patients were enrolled. Patients with high peak density of P. aeruginosa had higher inflammation and developed more severe respiratory infections. High peak density of P. aeruginosa was independently associated with few ventilator-free days on day 28 (P < 0.01) and increased ICU mortality (P = 0.047). Risk factors for high peak density of P. aeruginosa were prolonged mechanical ventilation (odd ratio [OR] 3.07 95% confidence interval [CI] 1.35‒6.97), non-antipseudomonal cephalosporins (OR 2.17, 95% CI 1.35‒3.49), hyperglycemia (OR 2.01, 95% CI 1.26‒3.22) during ICU stay, and respiratory diseases (OR 1.9, 95% CI 1.12‒3.23). Isolation of commensal colonizer was associated with lower risks of high peak density of P. aeruginosa (OR 0.43, 95% CI 0.26‒0.73). Propensity score-matched analysis revealed that antibiotic therapy for patients with ventilator-associated tracheobronchitis improved weaning from mechanical ventilation only in the high peak P. aeruginosa group.

Conclusions

Patients with high peak density of P. aeruginosa had worse ventilator outcome and ICU mortality. In patients with ventilator-associated tracheobronchitis, antibiotic therapy was associated with favorable ventilator weaning only in the high peak P. aeruginosa density group, and bacterial density could be a good therapeutic indicator for ventilator-associated tracheobronchitis due to P. aeruginosa.
Literature
1.
Craven DE, Hjalmarson KI. Ventilator-associated tracheobronchitis and pneumonia: thinking outside the box. Clin Infect Dis. 2010;51(Suppl 1):S59-66.PubMedCrossRef
2.
Koulenti D, Arvaniti K, Judd M, Lalos N, Tjoeng I, Xu E, et al. Ventilator-associated tracheobronchitis: to treat or not to treat? Antibiotics (Basel). 2020;9(2):51.CrossRef
3.
Rello J, Lisboa T, Koulenti D. Respiratory infections in patients undergoing mechanical ventilation. Lancet Respir Med. 2014;2(9):764–74.PubMedCrossRef
4.
World Health Organization. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and the development of new antibiotics. Geneva: World Health Organization; 2017.
5.
6.
Köhler T, Guanella R, Carlet J, van Delden C. Quorum sensing-dependent virulence during Pseudomonas aeruginosa colonisation and pneumonia in mechanically ventilated patients. Thorax. 2010;65(8):703–10.PubMedCrossRef
7.
Welsh MA, Blackwell HE. Chemical genetics reveals environment-specific roles for quorum sensing circuits in Pseudomonas aeruginosa. Cell Chem Biol. 2016;23(3):361–9.PubMedPubMedCentralCrossRef
8.
O’Loughlin CT, Miller LC, Siryaporn A, Drescher K, Semmelhack MF, Bassler BL. A quorum-sensing inhibitor blocks Pseudomonas aeruginosa virulence and biofilm formation. Proc Natl Acad Sci USA. 2013;110(44):17981–6.PubMedCrossRefPubMedCentral
9.
Hraiech S, Hiblot J, Lafleur J, Lepidi H, Papazian L, Rolain JM, et al. Inhaled lactonase reduces Pseudomonas aeruginosa quorum sensing and mortality in rat pneumonia. PLoS ONE. 2014;9(10):e107125.PubMedPubMedCentralCrossRef
10.
Zhuo H, Yang K, Lynch SV, Dotson RH, Glidden DV, Singh G, et al. Increased mortality of ventilated patients with endotracheal Pseudomonas aeruginosa without clinical signs of infection. Crit Care Med. 2008;36(9):2495–503.PubMedCrossRef
11.
Ioanas M, Ferrer R, Angrill J, Ferrer M, Torres A. Microbial investigation in ventilator-associated pneumonia. Eur Respir J. 2001;17(4):791–801.PubMedCrossRef
12.
Pouly O, Lecailtel S, Six S, Préau S, Wallet F, Nseir S, et al. Accuracy of ventilator-associated events for the diagnosis of ventilator-associated lower respiratory tract infections. Ann Intensive Care. 2020;10(1):6.PubMedPubMedCentralCrossRef
13.
Craven DE, Chroneou A, Zias N, Hjalmarson KI. Ventilator-associated tracheobronchitis: the impact of targeted antibiotic therapy on patient outcomes. Chest. 2009;135(2):521–8.PubMedCrossRef
14.
Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818–29.CrossRefPubMed
15.
Vincent JL, De Mendonça A, Cantraine F, Moreno R, Takala J, Suter PM, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Crit Care Med. 1998;26(11):1793–800.PubMedCrossRef
16.
Luna CM, Blanzaco D, Niederman MS, Matarucco W, Baredes NC, Desmery P, et al. Resolution of ventilator-associated pneumonia: prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome. Crit Care Med. 2003;31(3):676–82.PubMedCrossRef
17.
Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011;173(6):676–82.PubMedCrossRef
18.
Clinical and Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing. In: 29th informational supplement. CLSI document M100S. Wayne, PA: CLSI; 2019.
19.
Charlson ES, Bittinger K, Haas AR, Fitzgerald AS, Frank I, Yadav A, et al. Topographical continuity of bacterial populations in the healthy human respiratory tract. Am J Respir Crit Care Med. 2011;184(8):957–63.PubMedPubMedCentralCrossRef
20.
21.
Pendleton KM, Huffnagle GB, Dickson RP. The significance of Candida in the human respiratory tract: our evolving understanding. Pathog Dis. 2017;75(3):029.CrossRef
22.
Snydman DR. Empiric antibiotic selection strategies for healthcare-associated pneumonia, intra-abdominal infections, and catheter-associated bacteremia. J Hosp Med. 2012;7(Suppl 1):S2-12.PubMedCrossRef
23.
Thuong M, Arvaniti K, Ruimy R, de la Salmonière P, Scanvic-Hameg A, Lucet JC, et al. Epidemiology of Pseudomonas aeruginosa and risk factors for carriage acquisition in an intensive care unit. J Hosp Infect. 2003;53(4):274–82.PubMedCrossRef
24.
Hoang S, Georget A, Asselineau J, Venier AG, Leroyer C, Rogues AM, et al. Risk factors for colonization and infection by Pseudomonas aeruginosa in patients hospitalized in intensive care units in France. PLoS ONE. 2018;13(3):e0193300.PubMedPubMedCentralCrossRef
25.
Venier AG, Leroyer C, Slekovec C, Talon D, Bertrand X, Parer S, et al. Risk factors for Pseudomonas aeruginosa acquisition in intensive care units: a prospective multicentre study. J Hosp Infect. 2014;88(2):103–8.PubMedCrossRef
26.
Apostolopoulou E, Bakakos P, Katostaras T, Gregorakos L. Incidence and risk factors for ventilator-associated pneumonia in 4 multidisciplinary intensive care units in Athens, Greece. Respir Care. 2003;48(7):681–8.PubMed
27.
Shin HJ, Chang JS, Ahn S, Kim TO, Park CK, Lim JH, et al. Clinical factors associated with weaning failure in patients requiring prolonged mechanical ventilation. J Thorac Dis. 2017;9(1):143–50.PubMedPubMedCentralCrossRef
28.
Wu YK, Tsai YH, Lan CC, Huang CY, Lee CH, Kao KC, et al. Prolonged mechanical ventilation in a respiratory-care setting: a comparison of outcome between tracheostomized and translaryngeal intubated patients. Crit Care. 2010;14(2):R26.PubMedPubMedCentralCrossRef
29.
Mason SE, Dieffenbach PB, Englert JA, Rogers AA, Massaro AF, Fredenburgh LE, et al. Semi-quantitative visual assessment of chest radiography is associated with clinical outcomes in critically ill patients. Respir Res. 2019;20(1):218.PubMedPubMedCentralCrossRef
30.
Chalmers JD, Smith MP, McHugh BJ, Doherty C, Govan JR, Hill AT. Short- and long-term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2012;186(7):657–65.PubMedCrossRef
31.
Dennis BM, Betzold RD, Patton D, Hopper HA, Jenkins J, Fonnesbeck C, et al. Bacterial burden in critically injured ventilated patients does not correlate with progression to pneumonia. Surg Infect (Larchmt). 2018;19(4):369–75.CrossRef
32.
Hill AT, Campbell EJ, Hill SL, Bayley DL, Stockley RA. Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis. Am J Med. 2000;109(4):288–95.PubMedCrossRef
33.
Zemanick ET, Wagner BD, Robertson CE, Ahrens RC, Chmiel JF, Clancy JP, et al. Airway microbiota across age and disease spectrum in cystic fibrosis. Eur Respir J. 2017;50(5):1700832.PubMedPubMedCentralCrossRef
34.
35.
van Oort PMP, de Bruin S, Weda H, Knobel HH, Schultz MJ, Bos LD, et al. Exhaled breath metabolomics for the diagnosis of pneumonia in intubated and mechanically-ventilated intensive care unit (ICU)-patients. Int J Mol Sci. 2017;18(2):449.PubMedCentralCrossRef
36.
Shi JX, Li JS, Hu R, Li CH, Wen Y, Zheng H, et al. Diagnostic value of sTREM-1 in bronchoalveolar lavage fluid in ICU patients with bacterial lung infections: a bivariate meta-analysis. PLoS ONE. 2013;8(5):e65436.PubMedPubMedCentralCrossRef
37.
Mauri T, Coppadoro A, Bombino M, Bellani G, Zambelli V, Fornari C, et al. Alveolar pentraxin 3 as an early marker of microbiologically confirmed pneumonia: a threshold-finding prospective observational study. Crit Care. 2014;18(5):562.PubMedPubMedCentralCrossRef
38.
Ewig S, Torres A, El-Ebiary M, Fábregas N, Hernández C, González J, et al. Bacterial colonization patterns in mechanically ventilated patients with traumatic and medical head injury Incidence, risk factors, and association with ventilator-associated pneumonia. Am J Respir Crit Care Med. 1999;159(1):188–98.PubMedCrossRef
39.
Kabak E, Hudcova J, Magyarics Z, Stulik L, Goggin M, Szijártó V, et al. The utility of endotracheal aspirate bacteriology in identifying mechanically ventilated patients at risk for ventilator associated pneumonia: a single-center prospective observational study. BMC Infect Dis. 2019;19(1):756.PubMedPubMedCentralCrossRef
40.
Nseir S, Favory R, Jozefowicz E, Decamps F, Dewavrin F, Brunin G, et al. Antimicrobial treatment for ventilator-associated tracheobronchitis: a randomized, controlled, multicenter study. Crit Care. 2008;12(3):R62.PubMedPubMedCentralCrossRef
41.
Palmer LB, Smaldone GC, Chen JJ, Baram D, Duan T, Monteforte M, et al. Aerosolized antibiotics and ventilator-associated tracheobronchitis in the intensive care unit. Crit Care Med. 2008;36(7):2008–13.PubMedCrossRef
42.
Nseir S, Martin-Loeches I, Makris D, Jaillette E, Karvouniaris M, Valles J, et al. Impact of appropriate antimicrobial treatment on transition from ventilator-associated tracheobronchitis to ventilator-associated pneumonia. Crit Care. 2014;18(3):R129.PubMedPubMedCentralCrossRef
43.
Martin-Loeches I, Povoa P, Rodríguez A, Curcio D, Suarez D, Mira JP, et al. Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre, prospective, observational study. Lancet Respir Med. 2015;3(11):859–68.PubMedCrossRef
44.
Nseir S, Di Pompeo C, Pronnier P, Beague S, Onimus T, Saulnier F, et al. Nosocomial tracheobronchitis in mechanically ventilated patients: incidence, aetiology and outcome. Eur Respir J. 2002;20(6):1483–9.PubMedCrossRef
45.
Nseir S, Di Pompeo C, Soubrier S, Lenci H, Delour P, Onimus T, et al. Effect of ventilator-associated tracheobronchitis on outcome in patients without chronic respiratory failure: a case–control study. Crit Care. 2005;9(3):R238–45.PubMedPubMedCentralCrossRef
46.
Gaudet A, Martin-Loeches I, Povoa P, Rodriguez A, Salluh J, Duhamel A, et al. Accuracy of the clinical pulmonary infection score to differentiate ventilator-associated tracheobronchitis from ventilator-associated pneumonia. Ann Intensive Care. 2020;10(1):101.PubMedPubMedCentralCrossRef
47.
Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 Clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61-111.PubMedPubMedCentralCrossRef
48.
Sibila O, Laserna E, Shoemark A, Keir HR, Finch S, Rodrigo-Troyano A, et al. Airway bacterial load and inhaled antibiotic response in bronchiectasis. Am J Respir Crit Care Med. 2019;200(1):33–41.PubMedCrossRef
49.
Åstrand A, Wingren C, Benjamin A, Tregoning JS, Garnett JP, Groves H, et al. Dapagliflozin-lowered blood glucose reduces respiratory Pseudomonas aeruginosa infection in diabetic mice. Br J Pharmacol. 2017;174(9):836–47.PubMedPubMedCentralCrossRef
50.
Gill SK, Hui K, Farne H, Garnett JP, Baines DL, Moore LSP, et al. Increased airway glucose increases airway bacterial load in hyperglycaemia. Sci Rep. 2016;6:27636.PubMedPubMedCentralCrossRef
51.
Philips BJ, Redman J, Brennan A, Wood D, Holliman R, Baines D, et al. Glucose in bronchial aspirates increases the risk of respiratory MRSA in intubated patients. Thorax. 2005;60(9):761–4.PubMedPubMedCentralCrossRef
52.
Cugini C, Calfee MW, Farrow JM 3rd, Morales DK, Pesci EC, Hogan DA. Farnesol, a common sesquiterpene, inhibits PQS production in Pseudomonas aeruginosa. Mol Microbiol. 2007;65(4):896–906.PubMedCrossRef
53.
Whiley RA, Fleming EV, Makhija R, Waite RD. Environment and colonisation sequence are key parameters driving cooperation and competition between Pseudomonas aeruginosa cystic fibrosis strains and oral commensal streptococci. PLoS ONE. 2015;10(2):e0115513.PubMedPubMedCentralCrossRef
Metadata
Title
Airway Pseudomonas aeruginosa density in mechanically ventilated patients: clinical impact and relation to therapeutic efficacy of antibiotics
Authors
Yohei Migiyama
Shinya Sakata
Shinji Iyama
Kentaro Tokunaga
Koichi Saruwatari
Yusuke Tomita
Sho Saeki
Shinichiro Okamoto
Hidenori Ichiyasu
Takuro Sakagami
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2021
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-021-03488-7

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