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Review

Severe community-acquired pneumonia: current management and future therapeutic alternatives

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Pages 667-677 | Received 12 Apr 2018, Accepted 13 Aug 2018, Published online: 03 Sep 2018

References

  • Abubakar II, Tillmann T, Banerjee A. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the global burden of disease study 2013. Lancet. 2015;385(9963):117–171.
  • Jain S, Self WH, Wunderink RG, et al. CDC EPIC study team. Community-acquired pneumonia requiring hospitalization among U.S. Adults. N Engl J Med. 2015;373:415–427.
  • Lim WS, Eerden MM, van der, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax. 2003;58:377–382.
  • Angus DC, Marrie TJ, Obrosky DS, et al. Severe community-acquired pneumonia: use of intensive care services and evaluation of American and British thoracic society diagnostic criteria. Am J Respir Crit Care Med. 2002;166:717–723.
  • Charles PG, Wolfe R, Whitby M, et al. Australian community-acquired pneumonia study collaboration, Grayson ML. SMART-COP: a tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia. Clin Infect Dis. 2008;47:375–384.
  • Woodhead M, Welch CA, Harrison DA, et al. 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.
  • Arnold FW, Wiemken TL, Peyrani P, et al. CAPO authors. Mortality differences among hospitalized patients with community-acquired pneumonia in three world regions: results from the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study. Respir Med. 2013;107(7):1101–1111.
  • Ito A, Ishida T, Tokumasu H, et al. Prognostic factors in hospitalized community-acquired pneumonia: a retrospective study of a prospective observational cohort. BMC Pulm Med. 2017;17(1):78.
  • Walden AP, Clarke GM, McKechnie S, et al. ESICM/ECCRN GenOSept Investigators. Patients with community acquired pneumonia admitted to European intensive care units: an epidemiological survey of the GenOSept cohort. Crit Care. 2014 Apr 1;18(2):R58.
  • Vallés J, Diaz E, Martín-Loeches I, et al. Evolution over a 15-year period of the clinical characteristics and outcomes of critically ill patients with severe community-acquired pneumonia. Med Intensiva. 2016;40:238–245.
  • Antunes G, Evans SA, Lordan JL, et al. Systemic cytokine levels in community-acquired pneumonia and their association with disease severity. Eur Respir J. 2002;20:990–995.
  • Kellum JA, Kong L, Fink MP, et al. Understanding the inflammatory cytokine response in pneumonia and sepsis: results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Arch Intern Med. 2007;167:1655–1663.
  • Martínez R, Menéndez R, Reyes S, et al. Factors associated with inflammatory cytokine patterns in community-acquired pneumonia. Eur Respir J. 2011;37:393–399.
  • Ramírez P, Ferrer M, Martí V, et al. Inflammatory biomarkers and prediction for intensive care unit admission in severe community-acquired pneumonia. Crit Care Med. 2011;39:2211–2217.
  • Menendez R, Cavalcanti M, Reyes S, et al. Markers of treatment failure in hospitalised community acquired pneumonia. Thorax. 2008;63:447–452.
  • Sabatier C, Peredo R, Villagrá A, et al. Community-acquired pneumonia: a 7-years descriptive study. Usefulness of the IDSA/ATS 2007 in the assessment of ICU admission. Med Intensiva. 2010;34:237–245.
  • Garcia-Vidal C, Ardanuy C, Tubau F, et al. Pneumococcal pneumonia presenting with septic shock: host- and pathogen-related factors and outcomes. Thorax. 2010;65:77–81.
  • Mongardon N, Max A, Bouglé A, et al. Epidemiology and outcome of severe pneumococcal pneumonia admitted to intensive care unit: a multicenter study. Crit Care. 2012;16(4):R155.
  • Shorr AF, Bodi M, Rodriguez A, et al. CAPUCI Study Investigators. Impact of antibiotic guideline compliance on duration of mechanical ventilation in critically ill patients with community-acquired pneumonia. Chest. 2006;130(1):93–100.
  • Wiemkem T, Peyrani P, Bryant K, et al. Incidence of respiratory viruses in patients with community-acquired pneumonia admitted to the intensive care unit: results from the Severe Influenza Pneumonia Surveillance (SIPS) project. Eur J Clin Microbiol Infect Dis. 2013;32:705–710.
  • Choi SH, Hong SB, Ko GB, et al. Viral infection in patients with severe pneumonia requiring intensive care unit admission. Am J Respir Crit Care Med. 2012;186:325–332.
  • Arancibia F, Bauer TT, Ewig S, et al. Community-acquired pneumonia due to gram-negative bacteria and pseudomonas aeruginosa: incidence, risk, and prognosis. Arch Intern Med. 2002;162:1849–1858.
  • Falguera M, Carratalà J, Ruiz-Gonzalez A, et al. Risk factors and outcome of community-acquired pneumonia due to Gram-negative bacilli. Respirology. 2009;14:105–111.
  • Micek ST, Kollef KE, Reichley RM, et al. Health care-associated pneumonia and community-acquired pneumonia: a single-center experience. Antimicrob Agents Chemother. 2007;51:3568–3573.
  • Liapikou A, Polverino E, Cilloniz C, et al. Community-Acquired Pneumonia Organization (CAPO) Investigators. A worldwide perspective of nursing home-acquired pneumonia compared with community-acquired pneumonia. Respir Care. 2014;59:1078–1085.
  • Vallés J, Martin-Loeches I, Torres A, et al. Epidemiology, antibiotic therapy and clinical outcomes of healthcare-associated pneumonia in critically ill patients: a Spanish cohort study. Intensive Care Med. 2014;40:572–581.
  • Houck PM, Bratzler DW, Nsa W, et al. Timing of antibiotic administration and outcomes for Medicare patients hospitalized with community-acquired pneumonia. Arch Intern Med. 2004;164:637–644.
  • Berjohn CM, Fishman NO, Joffe MM, et al. Treatment and outcomes for patients with bacteremic pneumococcal pneumonia. Medicine (Baltimore). 2008;87:160–166.
  • Garnacho-Montero J, García-Cabrera E, Diaz-Martín A, et al. Determinants of outcome in patients with bacteraemic pneumococcal pneumonia: importance of early adequate treatment. Scand J Infect Dis. 2010;42:185–192.
  • Garnacho-Montero J, Gutiérrez-Pizarraya A, Escoresca-Ortega A, et al. Adequate antibiotic therapy prior to ICU admission in patients with severe sepsis and septic shock reduces hospital mortality. Crit Care. 2015;19:302.
  • García-Gigorro R, de la Cruz Vigo F, Andrés-Esteban EM, et al. Impact on patient outcome of emergency department length of stay prior to ICU admission. Med Intensiva. 2017;41:201–208.
  • Mandell LA, Wunderink RG, Anzueto A, et al. Infectious diseases society of America; American thoracic society. Infectious diseases society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44(Suppl 2):S27–72.
  • Lim WS, Baudouin SV, George RC, et al. Pneumonia Guidelines Committee of the BTS Standards of Care Committee. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009;64(Suppl 3):iii1–55.
  • Menéndez R, Torres A, Zalacaín R, et al. NEUMOFAIL Group. Guidelines for the treatment of community-acquired pneumonia: predictors of adherence and outcome. Am J Respir Crit Care Med. 2005;172(6):757–762.
  • Bodí M, Rodríguez A, Solé-Violán J, et al. Community-Acquired Pneumonia Intensive Care Units (CAPUCI) Study Investigators. Antibiotic prescription for community-acquired pneumonia in the intensive care unit: impact of adherence to Infectious Diseases Society of America guidelines on survival. Clin Infect Dis. 2005;41:1709–1716.
  • Rodríguez A, Mendia A, Sirvent JM, et al. CAPUCI Study Group. Combination antibiotic therapy improves survival in patients with community-acquired pneumonia and shock. Crit Care Med. 2007;35:1493–1498.
  • Waterer GW, Somes GW, Wunderink RG. Monotherapy may be suboptimal for severe bacteremic pneumococcal pneumonia. Arch Intern Med. 2001;161:1837–1842.
  • Martínez JA, Horcajada JP, Almela M, et al. Addition of a macrolide to a beta-lactam-based empirical antibiotic regimen is associated with lower in-hospital mortality for patients with bacteremic pneumococcal pneumonia. Clin Infect Dis. 2003;36:389–395.
  • Baddour LM, Yu VL, Klugman KP, et al. Combination antibiotic therapy lowers mortality among severely ill patients with Pneumococcal bacteraemia. Am J Respir Crit Care Med. 2004;170:440–444.
  • Gattarello S, Borgatta B, Solé-Violán J, et al. Decrease in mortality in severe community-acquired pneumococcal pneumonia: impact of improving antibiotic strategies (2000–2013). Chest. 2014;146:22–31.
  • De la Calle C, Hg T-DLV, Morata L, et al. Effectiveness of combination therapy versus monotherapy with a third-generation cephalosporin in bacteraemic pneumococcal pneumonia: a propensity score analysis. J Infection. 2018;76:342–347.
  • Gattarello S, Lagunes L, Vidaur L, et al. Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case-control study. Crit Care. 2015 Sep;10(19):335.
  • Asadi L, Sligl WI, Eurich DT, et al. Macrolide-based regimens and mortality in hospitalized patients with community-acquired pneumonia: a systematic review and meta-analysis. Clin Infect Dis. 2012;55:371–380.
  • Sligl WI, Asadi L, Eurich DT, et al. Macrolides and mortality in critically ill patients with community-acquired pneumonia: a systematic review and meta-analysis. Crit Care Med. 2014;42(2):420–432.
  • Martin-Loeches I, Lisboa T, Rodriguez A, et al. Combination antibiotic therapy with macrolides improves survival in intubated patients with community-acquired pneumonia. Intensive Care Med. 2010;36:612–620.
  • Restrepo MI, Mortensen EM, Waterer GW, et al. Impact of macrolide therapy on mortality for patients with severe sepsis due to pneumonia. Eur Respir J. 2009;33:153–159.
  • Tamaoki J. The effects of macrolides on inflammatory cells. Chest. 2004;125(2 Suppl):41S–50S.
  • Peyrani P, Wiemken TL, Metersky ML, et al. The order of administration of macrolides and beta-lactams may impact the outcomes of hospitalized patients with community-acquired pneumonia: results from the community-acquired pneumonia organization. Infect Dis (Lond). 2018;50:13–20.
  • Rosón B, Carratalà J, Fernández-Sabé N, et al. Causes and factors associated with early failure in hospitalized patients with community-acquired pneumonia. Arch Intern Med. 2004 Mar 8;164(5):502–508.
  • Pedro-Botet ML, Yu VL. Treatment strategies for Legionella infection. Expert Opin Pharmacother. 2009;10:1109–1121.
  • Garcia-Vidal C, Sanchez-Rodriguez I, Simonetti AF, et al. Levofloxacin versus azithromycin for treating legionella pneumonia: a propensity score analysis. Clin Microbiol Infect. 2017;23(9):653–658.
  • Gacouin A, Le Tulzo Y, Lavoue S, et al. Severe pneumonia due to Legionella pneumophila: prognostic factors, impact of delayed appropriate antimicrobial therapy. Intensive Care Med. 2002;28:686–691.
  • Rello J, Gattarello S, Souto J, et al. Community-acquired pneumonia in Unidad de Cuidados intensivos 2 CAPUCI 2 study investigators. Community-acquired Legionella Pneumonia in the intensive care unit: impact on survival of combined antibiotic therapy. Med Intensiva. 2013;37:320–326.
  • Bopp LH, Baltch AL, Ritz WJ, et al. Activities of tigecycline and comparators against Legionella pneumophila and Legionella micdadei extracellularly and in human monocyte-derived macrophages. Diagn Microbiol Infect Dis. 2011;69:86–93.
  • Giamarellos-Bourboulis EJ, Pechère JC, Routsi C, et al. Effect of clarithromycin in patients with sepsis and ventilator-associated pneumonia. Clin Infect Dis. 2008;46:1157–1164.
  • Flanders SA, Dudas V, Kerr K, et al. Effectiveness of ceftriaxone plus doxycycline in the treatment of patients hospitalized with community-acquired pneumonia. J Hosp Med. 2006;1:7–12.
  • Shoji H, Domenech A, Simonetti AF,Shoji H, Domenech A, Simonetti AF, et al. The Alere® BinaxNOW® pneumococcal urinary antigen test: diagnostic sensitivity for adult pneumococcal pneumonia and relationship to specific serotypes. J Clin Microbiol. 2018 Jan 24;56(2). pii: e00787-17. doi: 10.1128/JCM.00787-17.
  • Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43:304–377.
  • Zuckerman JM, Kaye KM. The newer macrolides. Azithromycin and clarithromycin. Infect Dis Clin North Am. 1995;9:731–745.
  • Ruiz J, Ramirez P, Gordon M, et al. mAntimicrobial stewardship programme in critical care medicine: a prospective interventional study. Med Intensiva. 2018;42:266–273.
  • Sader HS, Flamm RK, Streit JM, et al. Ceftaroline activity against bacterial pathogens frequently isolated in U.S. medical centers: results from five years of the AWARE surveillance program. Antimicrob Agents Chemother. 2015;59:2458–2461.
  • Biedenbach DJ, Iaconis JP, Sahm DF. Comparative in vitro activities of ceftaroline and ceftriaxone against bacterial pathogens associated with respiratory tract infections: results from the AWARE surveillance study. J Antimicrob Chemother. 2016;71:3459–3464.
  • Taboada M, Melnick D, Iaconis JP, et al. Ceftaroline fosamil versus ceftriaxone for the treatment of community-acquired pneumonia: individual patient data meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2016;71:862–870.
  • Nilius AM, Shen LL, Hensey-Rudloff D, et al. In vitro antibacterial potency and spectrum of ABT-492, a new fluoroquinolone. Antimicrob Agents Chemother. 2003;47:3260–3269.
  • Thabit AK, Crandon JL, Nicolau DP. Pharmacodynamic and pharmacokinetic profiling of delafloxacin in a murine lung model against community-acquired respiratory tract pathogens. Int J Antimicrob Agents. 2016;48:535–541.
  • https://clinicaltrials.gov/ct2/show/NCT02679573
  • Lee YM, Hong HL, Kim HS, et al. Fluoroquinolone resistance of Streptococcus pneumoniae isolates causing invasive disease: special focus on zabofloxacin. Diagn Microbiol Infect Dis. 2016;86: 181–183. Kim T, Park SJ, Chong YP, Park KH.
  • Kobayashi Y, Wada H, Rossios C, et al. A novel macrolide solithromycin exerts superior anti-inflammatory effect via NF-κB inhibition. J Pharmacol Exp Ther. 2013;345:76–84.
  • File TM Jr, Rewerska B, Vucinic-Mihailovic V, et al. SOLITAIRE-IV: a randomized, double-blind, multicenter study comparing the efficacy and safety of intravenous-to-oral solithromycin to intravenous-to-oral moxifloxacin for treatment of community-acquired bacterial pneumonia. Clin Infect Dis. 2016;63(8):1007–1016.
  • Pfaller MA, Rhomberg PR, Huband MD, et al. Activity of omadacycline tested against Streptococcus pneumoniae from a global surveillance program (2014). Diagn Microbiol Infect Dis Diagn Microbiol Infect Dis. 2018;90:143–147.
  • https://clinicaltrials.gov/ct2/show/NCT02531438?cond=Omadacycline&rank=3
  • Montón C, Ewig S, Torres A, et al. Role of glucocorticoids on inflammatory response in nonimmunosuppressed patients with pneumonia: a pilot study. Eur Respir J. 1999;14:2:18–20.
  • Salluh JIF, Bozza FA, Soares M, et al. Adrenal response in severe community-acquired pneumonia: impact on outcomes and disease severity. Chest. 2008;134:947–954.
  • Garcia-Vidal C, Calbo E, Pascual V, et al. Effects of systemic steroids in patients with severe community-acquired pneumonia. Eur Respir J. 2007 Nov;30(5):951–956.
  • Tagami T, Matsui H, Horiguchi H, et al. Low-dose corticosteroid use and mortality in severe community-acquired pneumonia patients. Eur Respir J. 2015;45:463–472.
  • Confalonieri M, Urbino R, Potena A, et al. Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Am J Respir Crit Care Med. 2005;171:242–248.
  • Mikami K, Suzuki M, Kitagawa H, et al. Efficacy of corticosteroids in the treatment of community-acquired pneumonia requiring hospitalization. Lung. 2007;185:249–255.
  • Snijders D, Daniels JM, De Graaff CS, et al. Efficacy of corticosteroids in community-acquired pneumonia: a randomized double-blinded clinical trial. Am J Respir Crit Care Med. 2010 May 1;181(9):975–982.
  • Meijvis SC, Hardeman H, Remmelts HH, et al. Dexamethasone and length of hospital stay in patients with community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial. Lancet. 2011;377(9782):2023–2030.
  • Fernández-Serrano S, Dorca J, Garcia-Vidal C, et al. Effect of corticosteroids on the clinical course of community-acquired pneumonia: a randomized controlled trial. Crit Care. 2011 Mar 15;15(2):R96.
  • Torres A, Sibila O, Ferrer M, 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;313:677–686.
  • Blum CA, Nigro N, Briel M, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015;385(9977):1511–1518.
  • Siempos II, Vardakas KZ, Kopterides P, et al. Adjunctive therapies for community-acquired pneumonia: a systematic review. J Antimicrob Chemother. 2008;62:661–668.
  • Nie W, Zhang Y, Cheng J, et al. Corticosteroids in the treatment of community-acquired pneumonia in adults: a meta-analysis. PLoS One. 2012;7(10):e47926.
  • Cheng M, Pan ZY, Yang J, et al. Corticosteroid therapy for severe community-acquired pneumonia: a meta-analysis. Respir Care. 2014;59:557–563.
  • Horita N, Otsuka T, Haranaga S, et al. Adjunctive systemic corticosteroids for hospitalized community-acquired pneumonia: systematic review and meta-analysis 2015 update. Sci Rep. 2015;5:14061.
  • Siemieniuk RA, Meade MO, Alonso-Coello P, et al. Corticosteroid therapy for patients hospitalized with community-acquired pneumonia: a systematic review and meta-analysis. Ann Intern Med. 2015;163:519–528.
  • Wan YD, Sun TW, Liu ZQ, et al. Efficacy and safety of corticosteroids for community-acquired pneumonia: a systematic review and meta-analysis. Chest. 2016;149:209–219.
  • Bi J, Yang J, Wang Y, et al. and safety of adjunctive corticosteroids therapy for severe community-acquired pneumonia in adults: an updated systematic review and meta-analysis. PLoS One. 2016 Nov 15;11(11):e0165942.
  • Wu WF, Fang Q, He GJ. Efficacy of corticosteroid treatment for severe community-acquired pneumonia: a meta-analysis. Am J Emerg Med. 2017 Jul 15:pii: S0735-6757(17)30577-6 Epub ahead of print. doi:10.1016/j.ajem.2017.07.050.
  • Marti C, Grosgurin O, Harbarth S, et al. Adjunctive corticotherapy for community acquired pneumonia: a systematic review and meta-analysis. PLoS One. 2015;10:e0144032.
  • Briel M, Spoorenberg SMC, Snijders D, et al. Ovidius study group; Capisce study group; STEP study group. Corticosteroids in patients hospitalized with community-acquired pneumonia: systematic review and individual patient data meta-analysis. Clin Infect Dis. 2018;66:346–354.
  • Wiersinga WJ, Bonten MJ, Boersma WG, et al. Management of community-acquired pneumonia in adults: 2016 guideline update from the Dutch Working Party on Antibiotic Policy (SWAB) and Dutch Association of Chest Physicians (NVALT). Neth J Med. 2018;76:4–13.
  • Shankar-Hari M, Spencer J, Sewell WA, et al. Bench-to-bedside review: immunoglobulin therapy for sepsis—biological plausibility from a critical care perspective. Crit Care. 2012;16:206.
  • Alejandria MM, Lansang MA, Dans LF, et al. Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database Syst Rev. 2013;9:CD001090.
  • Berlot G, Vassallo MC, Busetto N, et al. Relationship between the timing of administration of IgM and IgA enriched immunoglobulins in patients with severe sepsis and septic shock and the outcome: a retrospective analysis. J Crit Care. 2012;27:167–171.
  • de la Torre MC, Bolíbar I, Vendrell M, et al. Serum immunoglobulins in the infected and convalescent phases in community-acquired pneumonia. Respir Med. 2013;107:2038–2045.
  • de la Torre MC, Palomera E, Serra-Prat M, et al. IgG2 as an independent risk factor for mortality in patients with community-acquired pneumonia. J Crit Care. 2016;35:115–119.
  • Tagami T, Matsui H, Fushimi K, et al. Intravenous immunoglobulin and mortality in pneumonia patients with septic shock: an observational nationwide study. Clin Infect Dis. 2015;61:385–392.
  • Welte T, Dellinger RP, Ebelt H, et al. Concept for a study design in patients with severe community-acquired pneumonia: A randomised controlled trial with a novel IGM-enriched immunoglobulin preparation - The CIGMA study. Respir Med. 2015;109(6):758–767.
  • Welte T, Dellinger RP, Ebelt H, et al. Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patientswith severe community-acquired pneumonia: a randomized, placebo-controlled,double-blind, multicenter, phase II trial (CIGMA study). Intensive Care Med. 2018;44:438–448.
  • Schönbeck U, Libby P. Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents? Circulation. 2004;109(21 Suppl 1):II18–26.
  • Viasus D, Garcia-Vidal C, Simonetti AF, et al. The effect of simvastatin on inflammatory cytokines in community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial. BMJ Open. 2015 Jan 6;5(1):e006251.
  • Chopra V, Rogers MA, Buist M, et al. Is statin use associated with reduced mortality after pneumonia? A systematic review and meta-analysis. Am J Med. 2012;125:1111–1123.
  • Havers F, Bramley AM, Finelli L, et al. Statin use and hospital length of stay among adults hospitalized with community-acquired Pneumonia. Clin Infect Dis. 2016;62:1471–1478.
  • Gupta N, Krasnodembskaya A, Kapetanaki M, et al. Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia. Thorax. 2012;67:533–539.
  • Monsel A, Zhu YG, Gennai S, et al. Therapeutic effects of human mesenchymal stem cell-derived microvesicles in severe pneumonia in mice. Am J Respir Crit Care Med. 2015;192:324–336.
  • https://clinicaltrials.gov/ct2/show/NCT03158727

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