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Macrolide-based regimens in absence of bacterial co-infection in critically ill H1N1 patients with primary viral pneumonia

I. Martín-Loeches| J. F. Bermejo-Martin| J. Vallés| R. Granada| L. Vidaur| J. C. Vergara-Serrano| M. Martín| J. C. Figueira| J. M. Sirvent| J. Blanquer| D. Suarez| A. Artigas| A. Torres| E. Diaz| A. Rodriguez
Original
Volume 39, Issue 4 / April , 2013

Pages 693 - 702

Abstract

Purpose

To determine whether macrolide-based treatment is associated with mortality in critically ill H1N1 patients with primary viral pneumonia.

Methods

Secondary analysis of a prospective, observational, multicenter study conducted across 148 Intensive Care Units (ICU) in Spain.

Results

Primary viral pneumonia was present in 733 ICU patients with pandemic influenza A (H1N1) virus infection with severe respiratory failure. Macrolide-based treatment was administered to 190 (25.9 %) patients. Patients who received macrolides had chronic obstructive pulmonary disease more often, lower severity on admission (APACHE II score on ICU admission (13.1 ± 6.8 vs. 14.4 ± 7.4 points, p < 0.05), and multiple organ dysfunction syndrome less often (23.4 vs. 30.1 %, p < 0.05). Length of ICU stay in survivors was not significantly different in patients who received macrolides compared to patients who did not (10 (IQR 4–20) vs. 10 (IQR 5–20), p = 0.9). ICU mortality was 24.1 % (n = 177). Patients with macrolide-based treatment had lower ICU mortality in the univariate analysis (19.2 vs. 28.1 %, p = 0.02); however, a propensity score analysis showed no effect of macrolide-based treatment on ICU mortality (OR = 0.87; 95 % CI 0.55–1.37, p = 0.5). Moreover, the sensitivity analysis revealed very similar results (OR = 0.91; 95 % CI 0.58–1.44, p = 0.7). A separate analysis of patients under mechanical ventilation yielded similar results (OR = 0.77; 95 % CI 0.44–1.35, p = 0.4).

Conclusion

Our results suggest that macrolide-based treatment was not associated with improved survival in critically ill H1N1 patients with primary viral pneumonia.

Keywords

References

  1. Pérez-Padilla R, de la Rosa-Zamboni D, Ponce de León S et al (2009) Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med 361:680–689
    • View reference on PubMed
    • View reference on publisher's website
  2. Louie JK, Acosta M, Winter K et al (2009) Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California. JAMA 302:1896–1902
    • View reference on PubMed
    • View reference on publisher's website
  3. The ANZIC Influenza Investigators (2009) Critical care services and 2009 H1N1 influenza in Australia and New Zealand. N Engl J Med 361:1925–1934
    • View reference on publisher's website
  4. Kumar A, Zarychanski R, Pinto R et al (2009) Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA 302:1872–1879
    • View reference on PubMed
    • View reference on publisher's website
  5. WHO (2010) Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med 362:1708–1719
    • View reference on publisher's website
  6. Rello J, Rodríguez A, Ibañez P, Socias L, Cebrian J, Marques A, Guerrero J, Ruiz-Santana S, Marquez E, Del Nogal-Saez F, Alvarez-Lerma F, Martínez S, Ferrer M, Avellanas M, Granada R, Maraví-Poma E, Albert P, Sierra R, Vidaur L, Ortiz P, Prieto del Portillo I, Galván B, León-Gil C, H1N1 SEMICYUC Working Group (2009) Intensive care adult patients with severe respiratory failure caused by influenza A (H1N1)v in Spain. Crit Care 13(5):R148
    • View reference on publisher's website
  7. Kumar A, Zarychanski R, Pinto R et al (2009) Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA 302:1872–1879
    • View reference on PubMed
    • View reference on publisher's website
  8. ANZIC Influenza Investigators, Webb SA, Pettilä V, Seppelt I et al (2009) Critical care services and 2009 H1N1 influenza in Australia and New Zealand. N Engl J Med 361(20):1925–1934
    • View reference on PubMed
    • View reference on publisher's website
  9. Martín-Loeches I, Sanchez-Corral A, Diaz E, Granada RM, Zaragoza R, Villavicencio C, Albaya A, Cerdá E, Catalán RM, Luque P, Paredes A, Navarrete I, Rello J, Rodríguez A, H1N1 SEMICYUC Working Group (2011) Community-acquired respiratory co-infection (CARC) in critically ill patients infected with pandemic 2009 influenza A (H1N1) virus infection. Chest 139:555–562
    • View reference on publisher's website
  10. Díaz E, Rodríguez A, Martin-Loeches I, Lorente L, del Mar Martín M, Pozo JC, Montejo JC, Estella A, Arenzana A, Rello J, H1N1 SEMICYUC Working Group (2011) Impact of obesity in patients infected with new influenza A (H1N1)v. Chest 139:382–386
    • View reference on publisher's website
  11. Martin-Loeches I, Lisboa T, Rhodes A, Moreno RP, Silva E, Sprung C, Chiche JD, Barahona D, Villabon M, Balasini C, Pearse RM, Matos R, Rello J, ESICM H1N1 Registry Contributors (2011) Use of early corticosteroid therapy on ICU admission in patients affected by severe pandemic (H1N1)v influenza A infection. Intensive Care Med 37:272–283
  12. Kim SH, Hong SB, Yun SC, Choi WI, Ahn JJ, Lee YJ, Lee HB, Lim CM, Koh Y, Korean Society of Critical Care Medicine H1N1 Collaborative (2011) Corticosteroid treatment in critically ill patients with pandemic influenza A/H1N1 2009 infection: analytic strategy using propensity scores. Am J Respir Crit Care Med 183:1207–1214
    • View reference on PubMed
    • View reference on publisher's website
  13. Rodríguez A, Díaz E, Martín-Loeches I, Sandiumenge A, Canadell L, Díaz JJ, Figueira JC, Marques A, Alvarez-Lerma F, Vallés J, Baladín B, García-López F, Suberviola B, Zaragoza R, Trefler S, Bonastre J, Blanquer J, Rello J, H1N1 SEMICYUC Working Group (2011) Impact of early oseltamivir treatment on outcome in critically ill patients with 2009 pandemic influenza A. J Antimicrob Chemother 66:1140–1149
    • View reference on publisher's website
  14. Hiba V, Chowers M, Levi-Vinograd I, Rubinovitch B, Leibovici L, Paul M (2011) Benefit of early treatment with oseltamivir in hospitalized patients with documented 2009 influenza A (H1N1): retrospective cohort study. J Antimicrob Chemother 66:1150–1155
    • View reference on PubMed
    • View reference on publisher's website
  15. Martin-Loeches I, Lisboa T, Rodriguez A, Putensen C, Annane D, Garnacho-Montero J, Restrepo MI, Rello J (2010) Combination antibiotic therapy with macrolides improves survival in intubated patients with community acquired pneumonia. Intensive Care Med 36:612–620
  16. Wunderink RG, Mandell L (2012) Adjunctive therapy in community-acquired pneumonia. Semin Respir Crit Care Med 33:311–318
    • View reference on PubMed
    • View reference on publisher's website
  17. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G, SCCM/ESICM/ACCP/ATS/SIS 2001 (2003) SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med 31:1250–1256
    • View reference on PubMed
    • View reference on publisher's website
  18. Alfageme I, Aspa J, Bello S et al (2005) Guidelines for the diagnosis and management of community-acquired pneumonia. Spanish Society of Pulmonology and Thoracic Surgery (SEPAR). Arch Bronconeumol 41:272–289
    • View reference on PubMed
  19. Mandell LA, Wunderink RG, Anzueto A et al (2007) Infectious diseases society of America/American thoracic society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 44(suppl 2):S27–S72
    • View reference on PubMed
    • View reference on publisher's website
  20. http://www.msc.es/profesionales/saludPublica/gripeA/guiasProtocolosInf/pdf/ProtocoloGripeAenUCI.pdf. Accessed 07 August 2009
  21. Woodhead MA, Arrowsmith J, Chamverlain-Webber R et al (1991) The value of routine microbial investigation in community-acquired pneumonia. Respir Med 85:313–317
    • View reference on PubMed
    • View reference on publisher's website
  22. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A, Acute Kidney Injury Network (2007) Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 11:R31
    • View reference on PubMed
    • View reference on publisher's website
  23. Suarez D, Faries DE, Propensity score regression and stratification (2010) In: Faries DE, Leon AC, Haro JM, Obenchain RL (eds) SAS Institute Inc Analysis of Observational Health Care Data Using SAS, Cary, NC, pp 23–50
  24. Waterer GW, Somes GW, Wunderink RG (2001) Monotherapy may be suboptimal for severe bacteremic pneumococcal pneumonia. Arch Intern Med 161:1837–1842
    • View reference on PubMed
    • View reference on publisher's website
  25. Baddour LM, Yu VL, Klugman KP, Feldman C, Ortkvist A, Rello J, Morris AJ, Luna CM, Snydman DR, Ko WC, Chedid BF, Hui DS, Andremont A, Chiou CCC, and the International Pneumococcal Study Group (2004) Combination antibiotic therapy may lower mortality in severely ill patients with Streptococcus pneumoniae bacteremia. Am J Respir Crit Care Med 170:400–404
    • View reference on publisher's website
  26. Rodríguez A, Mendia A, Sirvent JM, Barcenilla F, de la Torre-Prados MV, Solé-Violán J, Rello J; CAPUCI Study Group (2007) Combination antibiotic therapy improves survival in patients with community-acquired pneumonia and shock. Crit Care Med 35:1493–1498
    • View reference on publisher's website
  27. Brown RB, Iannini P, Gross P, Kunkel M (2003) Impact of initial antibiotic choice on clinical outcomes in community-acquired pneumonia: analysis of a hospital claims-made database. Chest 123:1503–1511
    • View reference on PubMed
    • View reference on publisher's website
  28. Gleason PP, Meehan TP, Fine JM, Galusha DH, Fine MJ (1999) Associations between initial antimicrobial therapy and medical outcomes for hospitalized elderly patients with pneumonia. Arch Intern Med 159:2562–2572
    • View reference on PubMed
    • View reference on publisher's website
  29. Metersky ML, Ma A, Houck PM, Bratzler DW (2007) Antibiotics for bacteremic pneumonia: improved outcomes with macrolides but not fluoroquinolones. Chest 131:466–473
    • View reference on PubMed
    • View reference on publisher's website
  30. Mortensen EM, Restrepo MI, Anzueto A, Pugh J (2006) The impact of empiric antimicrobial therapy with a β-lactam and fluoroquinolone on mortality for patients hospitalized with severe pneumonia. Crit Care 10:R8
    • View reference on publisher's website
  31. Restrepo MI, Mortensen EM, Waterer GW, Wunderink RG, Coalson JJ, Anzueto A (2009) Impact of macrolide therapy on mortality for patients with severe sepsis due to pneumonia. Eur Respir J 33:153–159
    • View reference on PubMed
    • View reference on publisher's website
  32. Tessmer A, Welte T, Martus P, Schnoor M, Marre R, Suttorp N (2009) Impact of intravenous β-lactam/macrolide versus β-lactam monotherapy on mortality in hospitalized patients with community-acquired pneumonia. J Antimicrob Chemother 63:1025–1033
    • View reference on PubMed
    • View reference on publisher's website
  33. Tamaoki J, Kadota J, Takizawa H (2004) Clinical implications of the immunomodulatory effects of macrolides. Am J Med 117(suppl 9A):5S–11S
  34. Healy DP (2007) Macrolide immunomodulation of chronic respiratory diseases. Curr Infect Dis Rep 9(1):7–13
    • View reference on PubMed
    • View reference on publisher's website
  35. Vanaudenaerde BM, Wuyts WA, Geudens N, Dupont LJ, Schoofs K, Smeets S, Van Raemdonck DE, Verleden GM (2007) Macrolides inhibit IL17-induced IL8 and 8-isoprostane release from human airway smooth muscle cells. Am J Transpl 7:76–82
    • View reference on publisher's website
  36. Bermejo-Martin JF, Ortiz de Lejarazu R, Pumarola T, Rello J, Almansa R, Ramírez P, Martin-Loeches I, Varillas D, Gallegos MC, Serón C, Micheloud D, Gomez JM, Tenorio-Abreu A, Ramos MJ, Molina ML, Huidobro S, Sanchez E, Gordón M, Fernández V, Del Castillo A, Marcos MA, Villanueva B, López CJ, Rodríguez-Domínguez M, Galan JC, Cantón R, Lietor A, Rojo S, Eiros JM, Hinojosa C, Gonzalez I, Torner N, Banner D, Leon A, Cuesta P, Rowe T, Kelvin DJ (2009) Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza. Crit Care 13(6):R201
    • View reference on PubMed
    • View reference on publisher's website
  37. To KK, Hung IF, Li IW et al (2010) Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection. Clin Infect Dis 50:850–859
    • View reference on PubMed
    • View reference on publisher's website
  38. Sato K, Suga M, Akaike T, Fujii S, Muranaka H, Doi T, Maeda H, Ando M (1998) Therapeutic effect of erythromycin on influenza virus-induced lung injury in mice. Am J Respir Crit Care Med 157:853–857
    • View reference on PubMed
  39. Tahan F, Ozcan A, Koc N (2007) Clarithromycin in the treatment of RSV bronchiolitis: a double-blind, randomised, placebo-controlled trial. Eur Respir J 29:91–97
    • View reference on PubMed
    • View reference on publisher's website
  40. Bermejo-Martin JF, Kelvin DJ, Eiros JM, Castrodeza J, Ortiz de Lejarazu R (2009) Macrolides for the treatment of severe respiratory illness caused by novel H1N1 swine influenza viral strains. J Infect Dev Ctries 30:159–161
  41. Viasus D, Paño-Pardo JR, Cordero E, Campins A, López-Medrano F, Villoslada A, Fariñas MC, Moreno A, Rodríguez-Baño J, Oteo JA, Martínez-Montauti J, Torre-Cisneros J, Segura F, Carratalà J, Novel Influenza A (H1N1) Study Group, Spanish Network for Research in Infectious Diseases (2011) Effect of immunomodulatory therapies in patients with pandemic influenza A (H1N1) 2009 complicated by pneumonia. J Infect 62:193–199
    • View reference on publisher's website

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