Bench-to-bedside review: Bacterial pneumonia with influenza - pathogenesis and clinical implications

Critical Care

Volumn 14, Issue 2, 2010, Pages

  van der Sluijs, Koenraad F ^a   van der Poll, Tom ^a   Lutter, René ^a   Juffermans, Nicole P ^a   Schultz, Marcus J ^a  

^a ACADEMIC MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

AMANTADINE; AMPICILLIN; AZITHROMYCIN; CEFOTAXIME; CEFTRIAXONE; CLINDAMYCIN; CYTOKINE; INTERLEUKIN 10; LINEZOLID; OSELTAMIVIR; OUTER SURFACE PROTEIN A; PATTERN RECOGNITION RECEPTOR; QUINOLONE DERIVATIVE; RIMANTADINE; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 5; VANCOMYCIN; VIRUS SIALIDASE; ZANAMIVIR;

BACTERIAL INFECTION; BACTERIAL PNEUMONIA; CELL FUNCTION; COMMUNITY ACQUIRED PNEUMONIA; HUMAN; IMMUNOCOMPETENT CELL; INFLUENZA; INFLUENZA VACCINATION; MACROPHAGE; MIXED INFECTION; NEUTROPHIL; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; STREPTOCOCCUS PNEUMONIA; VIRUS INFECTION; COMORBIDITY; PATHOPHYSIOLOGY; VIROLOGY;

COMORBIDITY; HUMANS; INFLUENZA, HUMAN; PNEUMONIA, BACTERIAL;

EID: 78149273027     PISSN: 13648535     EISSN: 1466609X     Source Type: Journal    
DOI: 10.1186/cc8893     Document Type: Review

References (84)

1. Monto AS. Epidemiology of influenza. Vaccine 2008, 26:D45-48. 10.1016/j.vaccine.2008.07.066, 19230159.
2. Eccles R. Understanding the symptoms of the common cold and influenza. Lancet Infect Dis 2005, 5:718-725. 10.1016/S1473-3099(05)70270-X, 16253889.
3. Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ, Gubareva LV, Xu X, Bridges CB, Uyeki TM. Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009, 360:2605-2615. 10.1056/NEJMoa0903810, 19423869, Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team.
4. Scholtissek C. Molecular evolution of influenza viruses. Virus Genes 1995, 11:209-215. 10.1007/BF01728660, 8828147.
5. Hilleman MR. Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control. Vaccine 2002, 20:3068-3087. 10.1016/S0264-410X(02)00254-2, 12163258.
6. Glezen WP. Asthma, influenza, and vaccination. J Allergy Clin Immunol 2006, 118:1199-1206. 10.1016/j.jaci.2006.08.032, 17157648.
7. Mallia P, Johnston SL. Influenza infection and COPD. Int J Chron Obstruct Pulmon Dis 2007, 2:55-64. 2692119, 18044066.
8. Rajan S, Saiman L. Pulmonary infections in patients with cystic fibrosis. Semin Respir Infect 2002, 17:47-56. 10.1053/srin.2002.31690, 11891518.
9. Mamas MA, Fraser D, Neyses L. Cardiovascular manifestations associated with influenza virus infection. Int J Cardiol 2008, 130:304-309. 10.1016/j.ijcard.2008.04.044, 18625525.
10. Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med 2004, 351:2611-2618. 10.1056/NEJMoa041747, 15602021.
11. Keller TT, Sluijs KF, de Kruif MD, Gerdes VE, Meijers JC, Florquin S, Poll T, van Gorp EC, Brandjes DP, Büller HR, Levi M. Effects on coagulation and fibrinolysis induced by influenza in mice with a reduced capacity to generate activated protein C and a deficiency in plasminogen activator inhibitor type 1. Circ Res 2006, 99:1261-1269. 10.1161/01.RES.0000250834.29108.1a, 17068293.
12. Morens DM, Taubenberger JK, Fauci AS. Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness. J Infect Dis 2008, 198:962-970. 2599911, 18710327, 10.1086/591708.
13. Hers JF, Masurel N, Mulder J. Bacteriology and histopathology of the respiratory tract and lungs in fatal Asian influenza. Lancet 1958, 2:1141-1143. 10.1016/S0140-6736(58)92404-8, 13612141.
14. de Roux A, Ewig S, García E, Marcos MA, Mensa J, Lode H, Torres A. Mixed community-acquired pneumonia in hospitalised patients. Eur Respir J 2006, 27:795-800. 10.1183/09031936.06.00058605, 16585087.
15. Grabowska K, Höberg L, Penttinen P, Svensson A, Ekdahl K. Occurrence of invasive pneumococcal disease and number of excess cases due to influenza. BMC Infect Dis 2006, 6:58. 1534049, 16549029, 10.1186/1471-2334-6-58.
16. Centers for Disease Control and Prevention (CDC) Bacterial coinfections in lung tissue specimens from fatal cases of 2009 pandemic influenza A (H1N1) - United States, May-August 2009. MMWR Morb Mortal Wkly Rep 2009, 58:1071-1074. Centers for Disease Control and Prevention (CDC).
17. Louie JK, Acosta M, Winter K, Jean C, Gavali S, Schechter R, Vugia D, Harriman K, Matyas B, Glaser CA, Samuel MC, Rosenberg J, Talarico J, Hatch D, . California Pandemic (H1N1) Working Group Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California. JAMA 2009, 302:1896-1902. 10.1001/jama.2009.1583, 19887665, California Pandemic (H1N1) Working Group.
18. Rothberg MB, Haessler SD. Complications of seasonal and pandemic influenza. Crit Care Med 2010, 38:e91-7. 10.1097/CCM.0b013e3181c92eeb, 19935413.
19. Khater F, Moorman JP. Complications of influenza. South Med J 2003, 96:740-743. 10.1097/01.SMJ.0000084984.13843.C0, 14515911.
20. Oliveira EC, Marik PE, Colice G. Influenza pneumonia: a descriptive study. Chest 2001, 119:1717-1723. 10.1378/chest.119.6.1717, 11399696.
21. Talbot TR, Poehling KA, Hartert TV, Arbogast PG, Halasa NB, Edwards KM, Schaffner W, Craig AS, Griffin MR. Seasonality of invasive pneumococcal disease: temporal relation to documented influenza and respiratory syncytial viral circulation. Am J Med 2005, 118:285-291. 10.1016/j.amjmed.2004.09.016, 15745727.
22. Patel J, Faden H, Sharma S, Ogra PL. Effect of respiratory syncytial virus on adherence, colonization and immunity of non-typable Haemophilus influenzae: implications for otitis media. Int J Pediatr Otorhinolaryngol 1992, 23:15-23. 10.1016/0165-5876(92)90075-Z, 1592548.
23. Kumar A, Zarychanski R, Pinto R, Cook DJ, Marshall J, Lacroix J, Stelfox T, Bagshaw S, Choong K, Lamontagne F, Turgeon AF, Lapinsky S, Ahern SP, Smith O, Siddiqui F, Jouvet P, Khwaja K, McIntyre L, Menon K, Hutchison J, Hornstein D, Joffe A, Lauzier F, Singh J, Karachi T, Wiebe K, Olafson K, Ramsey C, Sharma S, Dodek P, Meade M, Hall R, Fowler RA, . Canadian Critical Care Trials Group H1N1 Collaborative Critically ill patients with 2009 influenza A(H1N1) infection in Canada. JAMA 2009, 302:1872-1879. 10.1001/jama.2009.1496, 19822627, Canadian Critical Care Trials Group H1N1 Collaborative.
24. Madhi SA, Klugman KP, . Vaccine Trialist Group A role for Streptococcus pneumoniae in virus-associated pneumonia. Nat Med 2004, 10:811-813. 10.1038/nm1077, 15247911, Vaccine Trialist Group.
25. Boyd M, Clezy K, Lindley R, Pearce R. Pandemic influenza: clinical issues. Med J Aust 2006, 185:S44-S47.
26. Jakab GJ. Mechanisms of bacterial superinfections in viral pneumonias. Schweiz Med Wschr 1985, 115:75-86.
27. Jones WT, Menna JH, Wennerstrom DE. Lethal synergism induced in mice by influenza type A virus and type Ia group B streptococci. Infect Immun 1983, 41:618-623. 264687, 6347892.
28. Sluijs KF, van Elden LJ, Nijhuis M, Schuurman R, Pater JM, Florquin S, Goldman M, Jansen HM, Lutter R, Poll T. IL-10 is an important mediator of the enhanced susceptibility to pneumococcal pneumonia after influenza infection. J Immunol 2004, 172:7603-7609.
29. Didierlaurent A, Goulding J, Patel S, Snelgrove R, Low L, Bebien M, Lawrence T, van Rijt LS, Lambrecht BN, Sirard JC, Hussell T. Sustained desensitization to bacterial Toll-like receptor ligands after resolution of respiratory influenza infection. J Exp Med 2008, 205:323-329. 2271005, 18227219, 10.1084/jem.20070891.
30. Plotkowski MC, Puchelle E, Beck G, Jacquot J, Hannoun C. Adherence of type I Streptococcus pneumoniae to tracheal epithelium of mice infected with influenza A/PR8 virus. Am Rev Respir Dis 1986, 134:1040-1044.
31. Brydon EW, Smith H, Sweet C. Influenza A virus-induced apoptosis in bronchiolar epithelial (NCI-H292) cells limits pro-inflammatory cytokine release. J Gen Virol 2003, 84:2389-2400. 10.1099/vir.0.18913-0, 12917460.
32. Fujimoto I, Pan J, Takizawa T, Nakanishi Y. Virus clearance through apoptosis-dependent phagocytosis of influenza A virus-infected cells by macrophages. J Virol 2000, 74:3399-3403. 111841, 10708457, 10.1128/JVI.74.7.3399-3403.2000.
33. Pittet LA, Hall-Stoodley L, Rutkowski MR, Harmsen AG. Influenza virus infection decreases tracheal mucociliary velocity and clearance of Streptococcus pneumoniae . Am J Respir Cell Mol Biol 2010, 42:450-460. 10.1165/rcmb.2007-0417OC, 19520922.
34. LeVine AM, Koeningsknecht V, Stark JM. Decreased pulmonary clearance of S. pneumoniae following influenza A infection in mice. J Virol Methods 2001, 94:173-186. 10.1016/S0166-0934(01)00287-7, 11337052.
35. McCullers JA, Rehg JE. Lethal synergism between influenza virus and Streptococcus pneumoniae characterization of a mouse model and the role of platelet-activating factor receptor. J Infect Dis 2002, 186:341-350. 10.1086/341462, 12134230.
36. McCullers JA, Bartmess KC. Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae . J Infect Dis 2003, 187:1000-1009. 10.1086/368163, 12660947.
37. Peltola VT, Murti KG, McCullers JA. Influenza virus neuraminidase contributes to secondary bacterial pneumonia. J Infect Dis 2005, 192:249-257. 2715995, 15962219, 10.1086/430954.
38. McCullers JA. Effect of antiviral treatment on the outcome of secondary bacterial pneumonia after influenza. J Infect Dis 2004, 190:519-526. 10.1086/421525, 15243927.
39. McAuley JL, Hornung F, Boyd KL, Smith AM, McKeon R, Bennink J, Yewdell JW, McCullers JA. Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host Microbe 2007, 2:240-249. 2083255, 18005742, 10.1016/j.chom.2007.09.001.
40. King QO, Lei B, Harmsen AG. Pneumococcal surface protein A contributes to secondary Streptococcus pneumoniae infection after influenza virus infection. J Infect Dis 2009, 200:537-545. 10.1086/600871, 19586418.
41. Berry AM, Paton JC. Additive attenuation of virulence of Streptococcus pneumoniae by mutation of the genes encoding pneumolysin and other putative pneumococcal virulence proteins. Infect Immun 2000, 68:133-140. 97112, 10603379, 10.1128/IAI.68.1.133-140.2000.
42. Cundell DR, Gerard NP, Gerard C, Idanpaan-Heikkila I, Tuomanen EI. Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 1995, 377:435-438. 10.1038/377435a0, 7566121.
43. McCullers JA, Iverson AR, McKeon R, Murray PJ. The platelet activating factor receptor is not required for exacerbation of bacterial pneumonia following influenza. Scand J Infect Dis 2008, 40:11-17. 2715993, 17852951, 10.1080/00365540701477568.
44. Sluijs KF, van Elden LJ, Nijhuis M, Schuurman R, Florquin S, Shimizu T, Ishii S, Jansen HM, Lutter R, Poll T. Involvement of the platelet-activating factor receptor in host defense against Streptococcus pneumoniae during postinfluenza pneumonia. Am J Physiol Lung Cell Mol Physiol 2006, 290:L194-L199. 10.1152/ajplung.00050.2005, 16100290.
45. Rijneveld AW, Weijer S, Florquin S, Speelman P, Shimizu T, Ishii S, Poll T. Improved host defense against pneumococcal pneumonia in platelet-activating factor receptor-deficient mice. J Infect Dis 2004, 189:711-716. 10.1086/381392, 14767826.
46. Tashiro M, Klenk HD, Rott R. Inhibitory effect of a protease inhibitor, leupeptin, on the development of influenza pneumonia, mediated by concomitant bacteria. J Gen Virol 1987, 68:2039-2041. 10.1099/0022-1317-68-7-2039, 3298542.
47. McNamee LA, Harmsen AG. Both influenza-induced neutrophil dysfunction and neutrophil-independent mechanisms contribute to increased susceptibility to a secondary Streptococcus pneumoniae infection. Infect Immun 2006, 74:6707-6721. 1698099, 16982840, 10.1128/IAI.00789-06.
48. Engelich G, White M, Hartshorn KL. Neutrophil survival is markedly reduced by incubation with influenza virus and Streptococcus pneumoniae role of respiratory burst. J Leukoc Biol 2001, 69:50-56.
49. Abramson JS, Hudnor HR. Effect of priming polymorphonuclear leukocytes with cytokines (granulocyte-macrophage colony-stimulating factor [GM-CSF] and G-CSF) on the host resistance to Streptococcus pneumoniae in chinchillas infected with influenza A virus. Blood 1994, 83:1929-1934.
50. Cassidy LF, Lyles DS, Abramson JS. Depression of polymorphonuclear leukocyte functions by purified influenza virus hemagglutinin and sialic acid-binding lectins. J Immunol 1989, 142:4401-4406.
51. Verhoef J, Mills EL, Debets-Ossenkopp Y, Verbrugh HA. The effect of influenza virus on oxygen-dependent metabolism of human neutrophils. Adv Exp Med Biol 1982, 141:647-654.
52. Larson HE, Parry RP, Tyrrell DA. Impaired polymorphonuclear leucocyte chemotaxis after influenza virus infection. Br J Dis Chest 1980, 74:56-62. 10.1016/0007-0971(80)90008-X, 7356914.
53. Shahangian A, Chow EK, Tian X, Kang JR, Ghaffari A, Liu SY, Belperio JA, Cheng G, Deng JC. Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice. J Clin Invest 2009, 119:1910-1920. 2701856, 19487810, 10.1172/JCI35412.
54. Colamussi ML, White MR, Crouch E, Hartshorn KL. Influenza A virus accelerates neutrophil apoptosis and markedly potentiates apoptotic effects of bacteria. Blood 1999, 93:2395-2403.
55. Ruutu P, Vaheri A, Kosunen TU. Depression of human neutrophil motility by influenza virus in vitro . Scand J Immunol 1977, 6:897-906.
56. Smith MW, Schmidt JE, Rehg JE, Orihuela CJ, McCullers JA. Induction of pro- and anti-inflammatory molecules in a mouse model of pneumococcal pneumonia after influenza. Comp Med 2007, 57:82-89. 2736785, 17348295.
57. Abramson JS, Mills EL, Giebink GS, Quie PG. Depression of monocyte and polymorphonuclear leukocyte oxidative metabolism and bactericidal capacity by influenza A virus. Infect Immun 1982, 35:350-355. 351036, 7054126.
58. Debets-Ossenkopp Y, Mills EL, van Dijk WC, Verbrugh HA, Verhoef J. Effect of influenza virus on phagocytic cells. Eur J Clin Microbiol 1982, 1:171-177. 10.1007/BF02019619, 7173182.
59. Sun K, Metzger DW. Inhibition of pulmonary antibacterial defense by interferon-gamma during recovery from influenza infection. Nat Med 2008, 14:558-564. 10.1038/nm1765, 18438414.
60. Sun J, Madan R, Karp CL, Braciale TJ. Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nat Med 2009, 15:277-284. 2693210, 19234462, 10.1038/nm.1929.
61. Sluijs KF, Nijhuis M, Levels JH, Florquin S, Mellor AL, Jansen HM, Poll T, Lutter R. Influenza-induced expression of indoleamine 2,3-dioxygenase enhances interleukin-10 production and bacterial outgrowth during secondary pneumococcal pneumonia. J Infect Dis 2006, 193:214-222. 10.1086/498911, 16362885.
62. Morita T, Saito K, Takemura M, Maekawa N, Fujigaki S, Fujii H, Wada H, Takeuchi S, Noma A, Seishima M. 3-Hydroxyanthranilic acid, an L-tryptophan metabolite, induces apoptosis in monocyte-derived cells stimulated by interferon-gamma. Ann Clin Biochem 2001, 38:242-251. 10.1258/0004563011900461, 11392499.
63. Fallarino F, Grohmann U, Vacca C, Bianchi R, Orabona C, Spreca A, Fioretti MC, Puccetti P. T cell apoptosis by tryptophan catabolism. Cell Death Differ 2002, 9:1069-1077. 10.1038/sj.cdd.4401073, 12232795.
64. Astry CL, Jakab GJ. Influenza virus-induced immune complexes suppress alveolar macrophage phagocytosis. J Virol 1984, 50:287-292. 255619, 6708169.
65. Arredouani M, Yang Z, Ning Y, Qin G, Soininen R, Tryggvason K, Kobzik L. The scavenger receptor MARCO is required for lung defense against pneumococcal pneumonia and inhaled particles. J Exp Med 2004, 200:267-272. 2212010, 15263032, 10.1084/jem.20040731.
66. Gordon SB, Irving GR, Lawson RA, Lee ME, Read RC. Intracellular trafficking and killing of Streptococcus pneumoniae by human alveolar macrophages are influenced by opsonins. Infect Immun 2000, 68:2286-2293. 97415, 10722631, 10.1128/IAI.68.4.2286-2293.2000.
67. Ali F, Lee ME, Iannelli F, Pozzi G, Mitchell TJ, Read RC, Dockrell DH. Streptococcus pneumoniae-associated human macrophage apoptosis after bacterial internalization via complement and Fcgamma receptors correlates with intracellular bacterial load. J Infect Dis 2003, 188:1119-1131. 10.1086/378675, 14551881.
68. LeVine AM, Whitsett JA, Gwozdz JA, Richardson TR, Fisher JH, Burhans MS, Korfhagen TR. Distinct effects of surfactant protein A or D deficiency during bacterial infection on the lung. J Immunol 2000, 165:3934-3940.
69. Dessing MC, Sluijs KF, Florquin S, Akira S, Poll T. Toll-like receptor 2 does not contribute to host response during postinfluenza pneumococcal pneumonia. Am J Respir Cell Mol Biol 2007, 36:609-614. 10.1165/rcmb.2006-0166OC, 17170383.
70. Dessing MC, Florquin S, Paton JC, Poll T. Toll-like receptor 2 contributes to antibacterial defence against pneumolysin-deficient pneumococci. Cell Microbiol 2008, 10:237-246. 2253695, 17711480.
71. Hussell T, Cavanagh MM. The innate immune rheostat: influence on lung inflammatory disease and secondary bacterial pneumonia. Biochem Soc Trans 2009, 37:811-813. 10.1042/BST0370811, 19614599.
72. Fallarino F, Asselin-Paturel C, Vacca C, Bianchi R, Gizzi S, Fioretti MC, Trinchieri G, Grohmann U, Puccetti P. Murine plasmacytoid dendritic cells initiate the immunosuppressive pathway of tryptophan catabolism in response to CD200 receptor engagement. J Immunol 2004, 173:3748-3754.
73. Rothberg MB, Haessler SD, Brown RB. Complications of viral influenza. Am J Med 2008, 121:258-264. 10.1016/j.amjmed.2007.10.040, 18374680.
74. Xia Z, Jin G, Zhu J, Zhou R. Using a mutual information-based site transition network to map the genetic evolution of influenza A/H3N2 virus. Bioinformatics 2009, 25:2309-2317. 10.1093/bioinformatics/btp423, 19706746.
75. Smith GJ, Vijaykrishna D, Bahl J, Lycett SJ, Worobey M, Pybus OG, Ma SK, Cheung CL, Raghwani J, Bhatt S, Peiris JS, Guan Y, Rambaut A. Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Nature 2009, 459:1122-1125. 10.1038/nature08182, 19516283.
76. von Itzstein M, Wu WY, Kok GB, Pegg MS, Dyason JC, Jin B, Van Phan T, Smythe ML, White HF, Oliver SW, Colman PM, Varghese JN, Ryan DM, Woods JM, Bethell RC, Hotham VJ, Cameron§ JM, Penn CR. Rational design of potent sialidase-based inhibitors of influenza virus replication. Nature 1993, 363:418-423. 10.1038/363418a0, 8502295.
77. Kim CU, Lew W, Williams MA, Liu H, Zhang L, Swaminathan S, Bischofberger N, Chen MS, Mendel DB, Tai CY, Laver WG, Stevens RC. Influenza neuraminidase inhibitors possessing a novel hydrophobic interaction in the enzyme active site: design, synthesis, and structural analysis of carbocyclic sialic acid analogues with potent anti-influenza activity. J Am Chem Soc 1997, 119:681-690. 10.1021/ja963036t, 16526129.
78. Davies WL, Grunert RR, Haff RF, Mcgahen JW, Neumayer EM, Paulshock M, Watts JC, Wood TR, Hermann EC, Hoffmann CE. Antiviral activity of 1-Adamantanamine (Amantadine). Science 1964, 144:862-863. 10.1126/science.144.3620.862, 14151624.
79. Ruf BR, Szucs T. Reducing the burden of influenza-associated complications with antiviral therapy. Infection 2009, 37:186-196.
80. Crusat M, de Jong MD. Neuraminidase inhibitors and their role in avian and pandemic influenza. Antivir Ther 2007, 12:593-602.
81. Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM, Musher DM, Niederman MS, Torres A, Whitney CG, . 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:S27-S72. 10.1086/511159, 17278083, Infectious Diseases Society of America; American Thoracic Society.
82. Karlström A, Boyd KL, English BK, McCullers JA. Treatment with protein synthesis inhibitors improves outcomes of secondary bacterial pneumonia after influenza. J Infect Dis 2009, 199:311-319. 2687083, 19113989, 10.1086/596051.
83. Yamaryo T, Oishi K, Yoshimine H, Tsuchihashi Y, Matsushima K, Nagatake T. Fourteen-member macrolides promote the phosphatidylserine receptor-dependent phagocytosis of apoptotic neutrophils by alveolar macrophages. Antimicrob Agents Chemother 2003, 47:48-53. 148990, 12499168, 10.1128/AAC.47.1.48-53.2003.
84. Laterre PF, Garber G, Levy H, Wunderink R, Kinasewitz GT, Sollet JP, Maki DG, Bates B, Yan SC, Dhainaut JF, . PROWESS Clinical Evaluation Committee Severe community-acquired pneumonia as a cause of severe sepsis: data from the PROWESS study. Crit Care Med 2005, 33:952-961. 10.1097/01.CCM.0000162381.24074.D7, 15891319, PROWESS Clinical Evaluation Committee.