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 Table of Contents  
EDITORIAL
Year : 2016  |  Volume : 3  |  Issue : 1  |  Page : 1-3

Severe community-acquired pneumonia: Corticosteroids as adjunctive treatment to antibiotics


Department of Pneumology, Institut Clinic del Tórax, Hospital Clinic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona (UB), Ciber de Enfermedades Respiratorias (Ciberes), Barcelona, Spain

Date of Web Publication23-Mar-2016

Correspondence Address:
Antoni Torres
Department of Pneumology, Thorax Institute, Hospital Clínic, Villarroel 170 08036, Barcelona
Spain
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2225-6482.179225

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How to cite this article:
Torres A, Cilloniz C. Severe community-acquired pneumonia: Corticosteroids as adjunctive treatment to antibiotics . Community Acquir Infect 2016;3:1-3

How to cite this URL:
Torres A, Cilloniz C. Severe community-acquired pneumonia: Corticosteroids as adjunctive treatment to antibiotics . Community Acquir Infect [serial online] 2016 [cited 2021 Dec 1];3:1-3. Available from: http://www.caijournal.com/text.asp?2016/3/1/1/179225

Severe community-acquired pneumonia (SCAP) represents up to 18% of the hospitalized patients with CAP, and is a major cause of admission to the Intensive Care Unit (ICU), also is associated with high morbidity and mortality. [1],[2]

In a multicenter study carry out in French about severe pneumococcal CAP admitted to ICU, the overall mortality rate was 29% although antibiotherapy was adequate in 92% of the cases, septic shock (77%) and needing mechanical ventilation (84%) also was present in high proportion on this patients. [3]

SCAP is a progressive disease; patients might die despite an early and adequate antibiotic treatment. This is probably due, in part, to a misbalanced and disproportionate local and systemic inflammatory response that contributes to impairment of gas exchange, severe sepsis, and multiple organ dysfunctions. [4]

Systemic adjunctive corticosteroid therapy attenuates the local and systemic inflammatory response, [5] they inhibit expression of proinflammatory cytokines and accelerate expression of anti-inflammatory cytokines. [5] Downregulation of systemic inflammatory response in SCAP patients may improve the clinical course, and may potentially decrease the development of acute respiratory distress syndrome (ARDS), sepsis, and mortality in this population.

In an experimental model of Pseudomonas aeruginosa pneumonia in mechanically ventilated piglets, we observed a lower lung bacterial burden and less severe histological pneumonia in piglets treated with corticosteroids plus antibiotics. [6]

In humans, several trials have been performed mostly in hospitalized patients with non-SCAP. The meta-analysis of Nie et al. [7] showed that the use of corticosteroids was associated with improved mortality in severe CAP but not in the overall population. However, they not defined SCAP.

A recent meta-analysis by Siemieniuk et al. [8] showed that the use of systemic corticosteroids in CAP may reduce mortality, need for mechanical ventilation, development of ARDS, and with high certainty a reduction in time-to-clinical stability and duration of hospitalization. In a subgroup of SCAP patients, the study also showed a possible reduction in mortality.

The major problems with data about systemic corticoids therapy in these human trials are because they included many patients with low severity, therefore, these patients have a low mortality and consequently, it is very difficult to demonstrate differences in important clinical outcomes such as treatment failure and mortality. Another point is that some patients are included regardless the initial level of inflammation. We should remember that the rationale for use steroids in CAP is the presence of high inflammatory response of the patients. Up to now this variable has not been taken into account in the majority of human trials. Patients with a high inflammatory response have higher rates of treatment failure [9] and mortality. [10] Furthermore, the dosages, the type and the length of treatment are very different among trials, which makes very difficult to establish comparisons among them. Finally, the primary end-points are different between studies, and some of them, such as length of stay or even time-to-clinical stability are "soft."

We recently published a trial in SCAP patients [11] comparing methylprednisolone (0.5 mg/kg BID during 5 days) versus placebo, with important differential characteristics. Our definition of SCAP applied for patients with modified American Thoracic Society criteria, or with pneumonia severity index risk Class V. We included patients with a high systemic inflammatory response, (C-reactive protein [CRP] ≥15 mg/dL). Because treatment failure in, CAP is associated with higher mortality. [12] Our primary endpoint was treatment failure rather than mortality. We defined treatment failure as early (clinical deterioration indicated by the development of shock, need for invasive mechanical ventilation, not present at baseline, or death within 72 h), or late (radiographic progression or persistence of respiratory failure, development of shock, need for invasive mechanical ventilation not present at baseline or death between 72 h and 120 h after treatment initiation). In our trial, we monitored the systemic inflammatory response using different biomarkers such as CRP, procalcitonin, tumor necrosis factor-alpha, and interleukins 6, 8, and 10, until day 7 after the inclusion of patients in the trial.

Our results showed a decrease from 31% to 13% in the treatment failure rate (P = 0.02) of our population. This reflects that corticosteroids reduced the risk of treatment failure with an odds ratio of 0.34. Mortality did not differ significantly between groups (10% in the methylprednisolone arm vs. 15% in the placebo arm P = 0.37). This reduction in treatment failure was more evident in late treatment failure (3% vs. 25%; P = 0.001), and especially in radiographic progression, (2% vs. 15%; P = 0.007). The rates of side effects were not important and similar between arms.

The long-term recruitment period, 8 years, and the use of methylprednisolone for 5 days only with an abrupt interruption of the treatment were potential pitfalls of our study. However, we monitored proinflammatory biomarkers until day 7, and we did not find a rebound of the inflammatory response.

With this results, we believe that less treatment failure, particularly late, and less radiographic progression can be due to stopping a progression to ARDS or a potential blocking of the Jarisch-Herxheimer reaction, which is thought to be due to high concentrations of cytokines release after the initiation of antibiotics, possibly through the release of endotoxin, or other bacterial mediators in patients with high bacterial burden.

We believe that it is time to start introducing treatment with corticosteroids in the clinical practice in severe CAP. We recommend selecting SCAP patients with high inflammatory response measured by CRP. We need to exclude patients with influenza pneumonia as we did in our trial since there are increasing evidence that corticosteroids increase mortality in influenza pneumonia. [13] We do not have information on the possible effect of corticosteroids in other viral pneumonias. [14] However, a high serum level of CRP indicates that pure viral pneumonia is unlikely. A proposed algorithm for the use of corticosteroids as adjunctive treatment for CAP is shown in [Figure 1].
Figure 1: Proposed algorithm for the use of corticosteroids

Click here to view


In conclusion, after discussion these results, we believe that corticosteroids can help to decrease treatment failure and probably mortality in SCAP patients. A high systemic inflammatory response and to discard influenza pneumonia are the two important premises for their utilization.



 
  References Top

1.
Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009;302:2323-9.  Back to cited text no. 1
    
2.
Woodhead M, Welch CA, Harrison DA, Bellingan G, Ayres JG. Community-acquired pneumonia on the intensive care unit: Secondary analysis of 17,869 cases in the ICNARC Case Mix Programme Database. Crit Care 2006;10 Suppl 2:S1.  Back to cited text no. 2
    
3.
Mongardon N, Max A, Bouglé A, Pène F, Lemiale V, Charpentier J, et al. Epidemiology and outcome of severe pneumococcal pneumonia admitted to intensive care unit: A multicenter study. Crit Care 2012;16:R155.  Back to cited text no. 3
    
4.
Rittirsch D, Flierl MA, Ward PA. Harmful molecular mechanisms in sepsis. Nat Rev Immunol 2008;8:776-87.  Back to cited text no. 4
    
5.
Montón C, Ewig S, Torres A, El-Ebiary M, Filella X, Rañó A, et al. Role of glucocorticoids on inflammatory response in nonimmunosuppressed patients with pneumonia: A pilot study. Eur Respir J 1999;14:218-20.  Back to cited text no. 5
    
6.
Sibila O, Luna CM, Agustí C, Baquero S, Gando S, Patrón JR, et al. Effects of glucocorticoids in ventilated piglets with severe pneumonia. Eur Respir J 2008;32:1037-46.  Back to cited text no. 6
    
7.
Nie W, Zhang Y, Cheng J, Xiu Q. Corticosteroids in the treatment of community-acquired pneumonia in adults: A meta-analysis. PLoS One 2012;7:e47926.  Back to cited text no. 7
    
8.
Siemieniuk RA, Meade MO, Alonso-Coello P, Briel M, Evaniew N, Prasad M, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: A systematic review and meta-analysis. Ann Intern Med 2015;163:519-28.  Back to cited text no. 8
    
9.
Menéndez R, Martínez R, Reyes S, Mensa J, Filella X, Marcos MA, et al. Biomarkers improve mortality prediction by prognostic scales in community-acquired pneumonia. Thorax 2009;64:587-91.  Back to cited text no. 9
    
10.
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;186:657-65.  Back to cited text no. 10
    
11.
Torres A, Sibila O, Ferrer M, Polverino E, Menendez R, Mensa J, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: A randomized clinical trial. JAMA 2015;313:677-86.  Back to cited text no. 11
    
12.
Menéndez R, Torres A, Zalacaín R, Aspa J, Martín Villasclaras JJ, Borderías L, et al. Risk factors of treatment failure in community acquired pneumonia: Implications for disease outcome. Thora×2004;59:960-5.  Back to cited text no. 12
    
13.
Lee N, Leo YS, Cao B, Chan PK, Kyaw WM, Uyeki TM, et al. Neuraminidase inhibitors, superinfection and corticosteroids affect survival of influenza patients. Eur Respir J 2015;45:1642-52.  Back to cited text no. 13
    
14.
Timsit JF, Perner A, Bakker J, Bassetti M, Benoit D, Cecconi M, et al. Year in review in intensive care medicine 2014: III. Severe infections, septic shock, healthcare-associated infections, highly resistant bacteria, invasive fungal infections, severe viral infections, Ebola virus disease and paediatrics. Intensive Care Med 2015;41:575-88.  Back to cited text no. 14
    


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