Risk factors and outcomes of ventilator-associated pneumonia in COVID-19 patients: a propensity score matched analysis
Critical Care volume 25, Article number: 235 (2021)
Mechanically ventilated patients with coronavirus disease (COVID-19) may be at an increased risk of developing ventilator-associated pneumonia (VAP). Our aim was to describe the clinical characteristics, risk factors, and outcomes associated with VAP in critically ill COVID-19 patients.
In this single-center cohort study, all adult patients with laboratory-confirmed COVID-19, based on the detection of viral sequences by real-time reverse-transcription polymerase chain reaction, who needed mechanical ventilation (MV) between March 1, and April 30, 2020 were included. The local ethics committee approved this study and waived the need for informed consent due to the observational nature of the study. VAP was defined according to the current American Thoracic Society/Infectious Diseases Society of America guidelines criteria . Differences between quantitative variables were assessed by Student t-test or Mann–Whitney U-test. Chi-square or Fisher´s exact tests were used to analyze categorical data. To determine which variables were independently associated with VAP, a logistic regression analysis was performed, including the variables with p < 0.1 in the univariate analysis. To assess the influence of VAP in outcomes and account for inter-group imbalances of baseline characteristics, we conducted a propensity score matching including those variables with p < 0.1 in the univariate analysis. In all cases, 1:1 matching without replacement was used with a caliper 0.2 standard deviation of logit of the propensity score and with the nearest neighbor method. In the matched cohorts, differences in the categorical variables were analyzed using McNemar’s test, and differences in continuous variables were determined using paired t-test or Wilcoxon signed-rank test, as appropriate. All statistical analyses were performed using the Stata Statistical Software 14 (StataCorp 15. College Station, TX: StataCorp LP) and R, version 3.6.3 (R project for Statistical Computing, http://www.R-project.org).
Of the 353 patients admitted to the intensive care unit (ICU) during the study period, 250 (70.8%) required invasive MV (Table 1). VAP occurred in 100 (40%) of the mechanically ventilated patients. Of these, 78 were confirmed by a positive quantitative culture and 22 were defined by clinical criteria and a purulent respiratory sample. Median time to the diagnosis of VAP was 13 (8–20) days, with only 11 developing VAP within the first 96 h of admission. Antibiotic treatment was adequate in 89% of the cases. Admission to an open ICU (contingency unit without physical barriers between patients) (odds ratio [OR], 1.85; 95% confidence interval [CI], [1.04–3.33]; p = 0.037), higher Sequential Organ Failure Assessment score (OR 1.55; 95% CI [1.21–2.00]; p = 0.001), corticosteroid treatment (OR 3.26; 95% CI [1.78–5.97]; p < 0.001) and treatment with tocilizumab (OR 1.85; 95% CI [1.02–3.38]; p = 0.044) before VAP were independently associated with VAP development. After propensity score matching, VAP was associated with a longer duration of MV and ICU stay and higher ICU mortality (Table 2).
According to the results reported, VAP is a frequent complication among mechanically ventilated COVID-19 patients [2, 3] and strongly impacts outcomes. It has been reported that COVID-19 makes patients more prone to VAP, not entirely due to the increased duration of the MV . Despite the 28-day mortality benefit observed with corticosteroid use [4, 5] and controversies regarding tocilizumab use , both treatments were initiated prior to VAP occurrence, and often prior to ICU admission, and are independently associated with a higher risk of VAP. Limitations of the present study include its observational nature, single-center setting, and the fact that the total dose of administered steroids was not recorded. However, our findings suggest that excessive immunosuppression associated with the use of immunomodulatory drugs may facilitate VAP development in COVID-19 patients.
Availability of data and materials
The datasets used and analysed during the current study are available from the corresponding author on reasonable request.
Coronavirus disease 2019
Intensive care unit
Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, Napolitano LM, O’Grady NP, Bartlett JG, Carratalà J, 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.
Clinical characteristics and day-90 outcomes of 4244 critically ill adults with COVID-19: a prospective cohort study. Intensive Care Med. 2020;1–14.
Maes M, Higginson E, Pereira-Dias J, Curran MD, Parmar S, Khokhar F, Cuchet-Lourenço D, Lux J, Sharma-Hajela S, Ravenhill B, et al. Ventilator-associated pneumonia in critically ill patients with COVID-19. Crit Care. 2021;25(1):25.
RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693–704.
Sterne JAC, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, Annane D, Azevedo LCP, Berwanger O, Cavalcanti AB, et al. Association between administration of systemic corticosteroids and mortality among critically Ill patients with COVID-19: a meta-analysis. JAMA. 2020;324(13):1330–41.
Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, Harvey L, Foulkes AS, Horick NK, Healy BC, Shah R, Bensaci AM, Woolley AE, Nikiforow S, Lin N, Sagar M, Schrager H, Huckins DS, Axelrod M, Pincus MD, Fleisher J, Sacks CA, Dougan M, North CM, Halvorsen YD, Thurber TK, Dagher Z, Scherer A, Wallwork RS, Kim AY, Schoenfeld S, Sen P, Neilan TG, Perugino CA, Unizony SH, Collier DS, Matza MA, Yinh JM, Bowman KA, Meyerowitz E, Zafar A, Drobni ZD, Bolster MB, Kohler M, D'Silva KM, Dau J, Lockwood MM, Cubbison C, Weber BN, Mansour MK; BACC Bay Tocilizumab Trial Investigators. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med. 2020;383(24):2333–2344.
Ethics approval and consent to participate
The local ethics committee (CEIm [Comitè d’Ètica d’Investigació amb medicaments], Vall d’Hebron Institut de Recerca, Barcelona, Spain) approved this study and waived the need for informed consent due to the observational nature of the study.
Consent for publication
MMM declares that she has no competing interests. EPM declares that she has no competing interests. FXNC has received speaker fees from MSD, Pfizer, Shionogi, and Gilead outside the submitted work. OR has received research grants and speaker fees from Hamilton Medical outside the submitted work. RF has received speaker fees from MSD, Pfizer, Shionogi, and Gilead outside the submitted work.
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Martínez-Martínez, M., Plata-Menchaca, E.P., Nuvials, F.X. et al. Risk factors and outcomes of ventilator-associated pneumonia in COVID-19 patients: a propensity score matched analysis. Crit Care 25, 235 (2021). https://doi.org/10.1186/s13054-021-03654-x