Skip to main content
SpringerLink
Log in

Macrolides in Severe Community-Acquired Pneumonia and Sepsis

  • Chapter
Sepsis

  • 1193 Accesses

More than 750,000 cases of severe sepsis occur annually (Angus et al. 2001), making the incidence of severe sepsis higher than that of breast cancer, AIDS, or first myocardial infarction. The incidence of sepsis is increasing because of the aging population, the growing number of immunocompromised patients, and the increasing use of invasive procedures, and to a lesser extent, because of antibiotic resistance among pathogens. In the United States alone, almost $17 billion is spent each year treating patients with sepsis (Angus et al. 2001).

Despite advances in care, more than 210,000 patients with severe sepsis die annually (Angus et al. 2001). The mortality rate associated with severe sepsis remains between 20% and 80% (Zeni et al. 1997). Even dysfunction of a single organ places patients at a significant risk for dying (about 20%), with mortality rates increasing approximately 15–20% for each additional dysfunctional organ (Vincent et al. 1998). Mortality rates are highest (ranging from 50 to 80%) for patients with cardiovascular compromise (septic shock) (Rangel-Frausto et al. 1995). Respiratory infections, whether community- or hospital-acquired account for the most sepsis cases (Angus et al. 2001; Bernard et al. 2001; Martin et al. 2003). Community-acquired pneumonia (CAP) is one the most common reasons for sepsis and is itself, independent of sepsis, the seventh leading cause of death and the leading cause of infectious death in the United States (Hoyert et al. 2005).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  • Abdelghaffar H, Vazifeh D, and Labro MT (1997) Erythromycin A-derived macrolides modify the functional activities of human neutrophils by altering the phospholipase D-phosphatidate phosphohydrolase transduction pathway L-cladinose is involved both in alterations of neutrophil functions and modulation of this transductional pathway. J Immunol 159:3995–4005.

    PubMed  CAS  Google Scholar 

  • Abraham E, Wunderink R, Silverman H, Perl TM, Nasraway S, Levy H, et al. (1995) Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group. JAMA 273:934–941.

    Article  PubMed  CAS  Google Scholar 

  • Abraham E, Anzueto A, Gutierrez G, Tessler S, San Pedro G, Wunderink R, et al. (1998) Double-blind randomised controlled trial of monoclonal antibody to human tumour necrosis factor in treatment of septic shock. NORASEPT II Study Group. Lancet 351:929–933.

    PubMed  CAS  Google Scholar 

  • Abraham E, Glauser MP, Butler T, Garbino J, Gelmont D, Laterre PF, et al. (1997) p55 Tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock. A randomized controlled multicenter trial. Ro 45–2081 Study Group. JAMA 277:1531–1538.

    Article  PubMed  CAS  Google Scholar 

  • Abraham E, Laterre PF, Garbino J, Pingleton S, Butler T, Dugernier T, et al. (2001) Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients. Crit Care Med 29:503–510.

    Article  PubMed  CAS  Google Scholar 

  • Abraham E, Laterre PF, Garg R, Levy H, Talwar D, Trzaskoma BL, et al. (2005) Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med 353:1332–1341.

    Article  PubMed  CAS  Google Scholar 

  • Amayasu H, Yoshida S, Ebana S, Yamamoto Y, Nishikawa T, Shoji T, et al. (2000) Clarithromycin suppresses bronchial hyperresponsiveness associated with eosinophilic inflammation in patients with asthma. Ann Allergy Asthma Immunol 84:594–598.

    Article  PubMed  CAS  Google Scholar 

  • Amsden GW (2005) Anti-inflammatory effects of macrolides–an underappreciated benefit in the treatment of community-acquired respiratory tract infections and chronic inflammatory pulmonary conditions? J Antimicrob Chemother 55:10–21.

    Article  PubMed  CAS  Google Scholar 

  • Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, and Pinsky MR (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310.

    Article  PubMed  CAS  Google Scholar 

  • Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, et al. (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871.

    Article  PubMed  CAS  Google Scholar 

  • Annane D, Bellissant E, and Cavaillon JM (2005) Septic shock. Lancet 365:63–78.

    Article  PubMed  CAS  Google Scholar 

  • Austrian R and Gold J (1964) Pneumococcal bacteremia with special reference to bacteremic pneumococcal pneumonia. Ann Intern Med 60:759–776.

    PubMed  CAS  Google Scholar 

  • Baddour LM, Yu VL, Klugman KP, Feldman C, Ortqvist A, Rello J, et al. (2004) Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia. Am J Respir Crit Care Med 170:440–444.

    Article  PubMed  Google Scholar 

  • Basyigit I, Yildiz F, Ozkara SK, Yildirim E, Boyaci H, and Ilgazli A (2004) The effect of clarithromycin on inflammatory markers in chronic obstructive pulmonary disease: preliminary data. Ann Pharmacother 38:1400–1405.

    Article  PubMed  CAS  Google Scholar 

  • Beringer P, Huynh KM, Kriengkauykiat J, Bi L, Hoem N, Louie S, et al. (2005) Absolute bioavailability and intracellular pharmacokinetics of azithromycin in patients with cystic fibrosis. Antimicrob Agents Chemother 49:5013–5017.

    Article  PubMed  CAS  Google Scholar 

  • Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709.

    Article  PubMed  CAS  Google Scholar 

  • Beutler B (1993) Endotoxin, tumor necrosis factor, and related mediators: new approaches to shock. New Horiz 1:3–12.

    PubMed  CAS  Google Scholar 

  • Beutler B, Milsark IW, and Cerami AC (1985) Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 229:869–871.

    Article  PubMed  CAS  Google Scholar 

  • Bone RC (1996) Why sepsis trials fail. JAMA 276:565–566.

    Article  PubMed  CAS  Google Scholar 

  • Brown RB, Iannini P, Gross P, and 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.

    Article  PubMed  Google Scholar 

  • Carlson DL, Willis MS, White DJ, Horton JW, and Giroir BP (2005) Tumor necrosis factor-alpha-induced caspase activation mediates endotoxin-related cardiac dysfunction. Crit Care Med 33:1021–1028.

    Article  PubMed  CAS  Google Scholar 

  • Casey LC, Balk RA, and Bone RC (1993) Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome. Ann Intern Med 119:771–778.

    PubMed  CAS  Google Scholar 

  • Chow LW, Yuen KY, Woo PC, and Wei WI (2000) Clarithromycin attenuates mastectomy-induced acute inflammatory response. Clin Diagn Lab Immunol 7:925–931.

    PubMed  CAS  Google Scholar 

  • Clement A, Tamalet A, Leroux E, Ravilly S, Fauroux B, and Jais JP (2006) Long term effects of azithromycin in patients with cystic fibrosis: a double blind, placebo controlled trial. Thorax 61:895–902.

    Article  PubMed  CAS  Google Scholar 

  • Cohen J and Carlet J (1996) INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group. Crit Care Med 24:1431–1440.

    Article  PubMed  CAS  Google Scholar 

  • Creaven PJ, Brenner DE, Cowens JW, Huben RP, Wolf RM, Takita H, et al. (1989) A phase I clinical trial of recombinant human tumor necrosis factor given daily for five days. Cancer Chemother Pharmacol 23:186–191.

    PubMed  CAS  Google Scholar 

  • Culic O, Erakovic V, Cepelak I, Barisic K, Brajsa K, Ferencic Z, et al. (2002) Azithromycin modulates neutrophil function and circulating inflammatory mediators in healthy human subjects. Eur J Pharmacol 450:277–289.

    Article  PubMed  CAS  Google Scholar 

  • Dalhoff A and Shalit I (2003) Immunomodulatory effects of quinolones. Lancet Infect Dis 3:359–371.

    Article  PubMed  CAS  Google Scholar 

  • Deans KJ, Haley M, Natanson C, Eichacker PQ, and Minneci PC (2005) Novel therapies for sepsis: a review. J Trauma-Inj Infect Crit Care 58:867–874.

    Article  Google Scholar 

  • Debets JM, Kampmeijer R, van der Linden MP, Buurman WA, and van der Linden CJ (1989) Plasma tumor necrosis factor and mortality in critically ill septic patients. Crit Care Med 17:489–494.

    Article  PubMed  CAS  Google Scholar 

  • Desaki M, Takizawa H, Ohtoshi T, Kasama T, Kobayashi K, Sunazuka T, et al. (2000) Erythromycin suppresses nuclear factor-kappa B and activator protein-1 activation in human bronchial epithelial cells. Biochem Biophys Res Commun 267:124–128.

    Article  PubMed  CAS  Google Scholar 

  • Dofferhoff AS, Bom VJ, de Vries-Hospers HG, van Ingen J, vd Meer J, Hazenberg BP, et al. (1992) Patterns of cytokines, plasma endotoxin, plasminogen activator inhibitor, and acute-phase proteins during the treatment of severe sepsis in humans. Crit Care Med 20:185–192.

    Article  PubMed  CAS  Google Scholar 

  • Dudas V, Hopefl A, Jacobs R, and Guglielmo BJ (2000) Antimicrobial selection for hospitalized patients with presumed community-acquired pneumonia: a survey of nonteaching US community hospitals. Ann Pharmacother 34:446–452.

    Article  PubMed  CAS  Google Scholar 

  • Eichacker PQ, Parent C, Kalil A, Esposito C, Cui X, Banks SM, et al. (2002) Risk and the efficacy of antiinflammatory agents: retrospective and confirmatory studies of sepsis. Am J Respir Crit Care Med 166:1197–1205.

    Article  PubMed  Google Scholar 

  • Eichacker PQ, Danner RL, Suffredini AF, Cui X, and Natanson C (2005) Reassessing recombinant human activated protein C for sepsis: time for a new randomized controlled trial. Crit Care Med 33:2426–2428.

    Article  PubMed  Google Scholar 

  • Eichenholz PW, Eichacker PQ, Hoffman WD, Banks SM, Parrillo JE, Danner RL, et al. (1992) Tumor necrosis factor challenges in canines: patterns of cardiovascular dysfunction. Am J Physiol 263:H668–H675.

    PubMed  CAS  Google Scholar 

  • Equi A, Balfour-Lynn IM, Bush A, and Rosenthal M (2002) Long term azithromycin in children with cystic fibrosis: a randomised, placebo-controlled crossover trial. Lancet 360:978–984.

    Article  PubMed  CAS  Google Scholar 

  • Ferguson NR, Galley HF, and Webster NR (1999) T helper cell subset ratios in patients with severe sepsis. Intensive Care Med 25:106–109.

    Article  PubMed  CAS  Google Scholar 

  • Fisher CJ, Jr., Agosti JM, Opal SM, Lowry SF, Balk RA, Sadoff JC, et al. (1996) Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. The Soluble TNF Receptor Sepsis Study Group. N Engl J Med 334:1697–1702.

    Article  PubMed  CAS  Google Scholar 

  • Fumeaux T, Dufour J, Stern S, and Pugin J (2004) Immune monitoring of patients with septic shock by measurement of intraleukocyte cytokines. Intensive Care Med 30:2028–2037.

    Article  PubMed  Google Scholar 

  • Garcia Vazquez E, Mensa J, Martinez JA, Marcos MA, Puig J, Ortega M, et al. (2005) Lower mortality among patients with community-acquired pneumonia treated with a macrolide plus a beta-lactam agent versus a beta-lactam agent alone. Eur J Clin Microbiol Infect Dis 24:190–195.

    Article  PubMed  CAS  Google Scholar 

  • Gerhardt SG, McDyer JF, Girgis RE, Conte JV, Yang SC, and Orens JB (2003) Maintenance azithromycin therapy for bronchiolitis obliterans syndrome: results of a pilot study. Am J Respir Crit Care Med 168:121–125.

    Article  PubMed  Google Scholar 

  • Giamarellos-Bourboulis EJ, Adamis T, Laoutaris G, Sabracos L, Koussoulas V, Mouktaroudi M, et al. (2004) Immunomodulatory clarithromycin treatment of experimental sepsis and acute pyelonephritis caused by multidrug-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother 48:93–99.

    Article  PubMed  CAS  Google Scholar 

  • Giamarellos-Bourboulis E, Adamis T, Sabracos L, Raftogiannis M, Baziaka F, Tsaganos T, et al. (2005a) Clarithromycin: immunomodulatory therapy of experimental sepsis and acute pyelonephritis by Escherichia coli. Scand J Infect Dis 37:48–54.

    Article  PubMed  CAS  Google Scholar 

  • Giamarellos-Bourboulis EJ, Baziaka F, Antonopoulou A, Koutoukas P, Kousoulas V, Sabracos L, et al. (2005b) Clarithromycin co-administered with amikacin attenuates systemic inflammation in experimental sepsis with Escherichia coli. Int J Antimicrob Agents 25:168–172.

    Article  PubMed  CAS  Google Scholar 

  • Giamarellos-Bourboulis EJ, Pechère JC, Routsi C, Plachouras D, Kollias S, Raftogiannis M, et al. (2008) Effect of Clarithromycin in Patients with Sepsis and Ventilator-Associated Pneumonia. Clin Infect Dis 46:1157–1164.

    Article  PubMed  CAS  Google Scholar 

  • Gotfried MH (2004) Macrolides for the treatment of chronic sinusitis, asthma, and COPD. Chest 125:52S–60S; quiz 60S–61S.

    Google Scholar 

  • Hall IH, Schwab U, Ward ES, and Ives T (2004) In vitro anti-inflammatory effects and immunomodulation by gemifloxacin in stimulated human THP-1 monocytes. Pharmazie 59:713–719.

    PubMed  CAS  Google Scholar 

  • Hatipoglu U and Rubinstein I (2004) Low-dose, long-term macrolide therapy in asthma: an overview. Clin Mol Allergy 2:4.

    Article  PubMed  Google Scholar 

  • Hendeles L (1992) Erythromycin for the treatment of bronchial hyperresponsiveness in asthma. Chest 101:296.

    Article  PubMed  CAS  Google Scholar 

  • Hoiby N (2002) New antimicrobials in the management of cystic fibrosis. J Antimicrob Chemother 49:235–238.

    Article  PubMed  CAS  Google Scholar 

  • Houck PM, MacLehose RF, Niederman MS, and Lowery JK (2001) Empiric antibiotic therapy and mortality among medicare pneumonia inpatients in 10 western states: 1993, 1995, and 1997. Chest 119:1420–1426.

    Article  PubMed  CAS  Google Scholar 

  • Hoyert DL, Kung HC, and Smith BL (2005) Deaths: preliminary data for 2003. Natl Vital Stat Rep 53:1–48.

    Google Scholar 

  • Ishiguro M, Koga H, Kohno S, Hayashi T, Yamaguchi K, and Hirota M (1989) Penetration of macrolides into human polymorphonuclear leucocytes. J Antimicrob Chemother 24:719–729.

    Article  PubMed  CAS  Google Scholar 

  • Johnston SL, Blasi F, Black PN, Martin RJ, Farrell DJ, Nieman RB, et al. (2006) The effect of telithromycin in acute exacerbations of asthma. N Engl J Med 354:1589–1600.

    Article  PubMed  CAS  Google Scholar 

  • Kadota J, Mukae H, Ishii H, Nagata T, Kaida H, Tomono K, et al. (2003) Long-term efficacy and safety of clarithromycin treatment in patients with diffuse panbronchiolitis. Respir Med 97:844–850.

    Article  PubMed  CAS  Google Scholar 

  • Kawasaki S, Takizawa H, Ohtoshi T, Takeuchi N, Kohyama T, Nakamura H, et al. (1998) Roxithromycin inhibits cytokine production by and neutrophil attachment to human bronchial epithelial cells in vitro. Antimicrob Agents Chemother 42:1499–1502.

    PubMed  CAS  Google Scholar 

  • Khair OA, Devalia JL, Abdelaziz MM, Sapsford RJ, and Davies RJ (1995) Effect of erythromycin on Haemophilus influenzae endotoxin-induced release of IL-6, IL-8 and sICAM-1 by cultured human bronchial epithelial cells. Eur Respir J 8:1451–1457.

    PubMed  CAS  Google Scholar 

  • Khan AA, Slifer TR, Araujo FG, and Remington JS (1999) Effect of clarithromycin and azithromycin on production of cytokines by human monocytes. Int J Antimicrob Agents 11:121–132.

    Article  PubMed  CAS  Google Scholar 

  • Kikuchi T, Hagiwara K, Honda Y, Gomi K, Kobayashi T, Takahashi H, et al. (2002) Clarithromycin suppresses lipopolysaccharide-induced interleukin-8 production by human monocytes through AP-1 and NF-kappa B transcription factors. J Antimicrob Chemother 49:745–755.

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi M, Shimauchi T, Hino R, and Tokura Y (2004) Roxithromycin downmodulates Th2 chemokine production by keratinocytes and chemokine receptor expression on Th2 cells: its dual inhibitory effects on the ligands and the receptors. Cell Immunol 228:27–33.

    Article  PubMed  CAS  Google Scholar 

  • Koh YY, Lee MH, Sun YH, Sung KW, and Chae JH (1997) Effect of roxithromycin on airway responsiveness in children with bronchiectasis: a double-blind, placebo-controlled study. Eur Respir J 10:994–999.

    Article  PubMed  CAS  Google Scholar 

  • Kohri K, Tamaoki J, Kondo M, Aoshiba K, Tagaya E, and Nagai A (2000) Macrolide antibiotics inhibit nitric oxide generation by rat pulmonary alveolar macrophages. Eur Respir J 15:62–67.

    Article  PubMed  CAS  Google Scholar 

  • Kostadima E, Tsiodras S, Alexopoulos EI, Kaditis AG, Mavrou I, Georgatou N, et al. (2004) Clarithromycin reduces the severity of bronchial hyperresponsiveness in patients with asthma. Eur Respir J 23:714–717.

    Article  PubMed  CAS  Google Scholar 

  • Kraft M, Cassell GH, Pak J, and Martin RJ (2002) Mycoplasma pneumoniae and Chlamydia pneumoniae in asthma: effect of clarithromycin. Chest 121:1782–1788.

    Article  PubMed  CAS  Google Scholar 

  • Kudoh S, Azuma A, Yamamoto M, Izumi T, and Ando M (1998) Improvement of survival in patients with diffuse panbronchiolitis treated with low-dose erythromycin. Am J Respir Crit Care Med 157:1829–1832.

    PubMed  CAS  Google Scholar 

  • Kuno R, Wang J, Kawanokuchi J, Takeuchi H, Mizuno T, and Suzumura A (2005) Autocrine activation of microglia by tumor necrosis factor-alpha. J Neuroimmunol 162:89–96.

    Article  PubMed  CAS  Google Scholar 

  • Laterre PF, Garber G, Levy H, Wunderink R, Kinasewitz GT, Sollet JP, et al. (2005) Severe community-acquired pneumonia as a cause of severe sepsis: data from the PROWESS study. Crit Care Med 33:952–961.

    Article  PubMed  Google Scholar 

  • Lenk H, Tanneberger S, Muller U, Ebert J, and Shiga T (1989) Phase II clinical trial of high-dose recombinant human tumor necrosis factor. Cancer Chemother Pharmacol 24:391–392.

    Article  PubMed  CAS  Google Scholar 

  • Mandell LA, Bartlett JG, Dowell SF, File TM, Jr., Musher DM. and Whitney C (2003) Update of practice guidelines for the management of community-acquired pneumonia in immunocompetent adults. Clin Infect Dis 37:1405–1433.

    Article  PubMed  Google Scholar 

  • Martin GS, Mannino DM, Eaton S, and Moss M (2003) The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348:1546–1554.

    Article  PubMed  Google Scholar 

  • Martinez JA, Horcajada JP, Almela M, Marco F, Soriano A, Garcia E, et al. (2003) 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 36:389–395.

    Article  PubMed  CAS  Google Scholar 

  • Michie HR, Manogue KR, Spriggs DR, Revhaug A, O’Dwyer S, Dinarello CA, et al. (1988) Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med 318:1481–1486.

    PubMed  CAS  Google Scholar 

  • Mikamo H, Kawazoe K, Sato Y, and Tamaya T (1998) Effects of long-term/low-dose clarithromycin on neutrophil count and interleukin-8 level in pyometra. Chemotherapy 44:50–54.

    Article  PubMed  CAS  Google Scholar 

  • Mitsuyama T, Tanaka T, Hidaka K, Abe M, and Hara N (1995) Inhibition by erythromycin of superoxide anion production by human polymorphonuclear leukocytes through the action of cyclic AMP-dependent protein kinase. Respiration 62:269–273.

    Article  PubMed  CAS  Google Scholar 

  • Miyatake H, Suzuki K, Taki F, Takagi K, and Satake T (1991a) Effect of erythromycin on bronchial hyperresponsiveness in patients with bronchial asthma. Arzneimittelforschung 41:552–556.

    PubMed  CAS  Google Scholar 

  • Miyatake H, Taki F, Taniguchi H, Suzuki R, Takagi K, and Satake T (1991b) Erythromycin reduces the severity of bronchial hyperresponsiveness in asthma. Chest 99:670–673.

    Article  PubMed  CAS  Google Scholar 

  • Mortensen E, Restrepo M, Anzueto A, and Pugh J (2006a) The impact of empiric antimicrobial therapy with a beta-lactam and fluoroquinolone on mortality for patients hospitalized with severe pneumonia. Crit Care 10:R8.

    Article  Google Scholar 

  • Mortensen EM, Restrepo MI, Anzueto A, and Pugh JA (2006b) Antibiotic therapy and 48-hour mortality for patients with pneumonia. Am J Med 119:859–864.

    Article  PubMed  CAS  Google Scholar 

  • Mufson MA and Stanek RJ (1999) Bacteremic pneumococcal pneumonia in one American city: a 20-year longitudinal study, 1978–1997. Am J Med 107:34S–43S.

    Article  PubMed  CAS  Google Scholar 

  • Oishi K, Sonoda F, Kobayashi S, Iwagaki A, Nagatake T, Matsushima K, et al. (1994) Role of interleukin-8 (IL-8) and an inhibitory effect of erythromycin on IL-8 release in the airways of patients with chronic airway diseases. Infect Immun 62:4145–4152.

    PubMed  CAS  Google Scholar 

  • Panacek EA, Marshall JC, Albertson TE, Johnson DH, Johnson S, MacArthur RD, et al. (2004) Efficacy and safety of the monoclonal anti-tumor necrosis factor antibody F(ab’) 2 fragment afelimomab in patients with severe sepsis and elevated interleukin-6 levels. Crit Care Med 32:2173–2182.

    PubMed  CAS  Google Scholar 

  • Parnham MJ, Culic O, Erakovic V, Munic V, Popovic-Grle S, Barisic K, et al. (2005) Modulation of neutrophil and inflammation markers in chronic obstructive pulmonary disease by short-term azithromycin treatment. Eur J Pharmacol 517:132–143.

    Article  PubMed  CAS  Google Scholar 

  • Parrillo J.E, Parker MM, Natanson C, Suffredini AF, Danner RL, Cunnion RE, et al. (1990) Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med 113:227–242.

    PubMed  CAS  Google Scholar 

  • Piacentini GL, Peroni DG, Bodini A, Pigozzi R, Costella S, Loiacono A, et al. (2007) Azithromycin reduces bronchial hyperresponsiveness and neutrophilic airway inflammation in asthmatic children: a preliminary report. Allergy Asthma Proc 28:194–198.

    Article  PubMed  Google Scholar 

  • Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, and Wenzel RP (1995) The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA 273:117–123.

    Article  PubMed  CAS  Google Scholar 

  • Reinhart K, Wiegand-Lohnert C, Grimminger F, Kaul M, Withington S, Treacher D, et al. (1996) Assessment of the safety and efficacy of the monoclonal anti-tumor necrosis factor antibody-fragment, MAK 195F, in patients with sepsis and septic shock: a multicenter, randomized, placebo-controlled, dose-ranging study. Crit Care Med 24:733–742.

    Article  PubMed  CAS  Google Scholar 

  • Reinhart K and Karzai W (2001) Anti-tumor necrosis factor therapy in sepsis: update on clinical trials and lessons learned. Crit Care Med 29:S121–S125.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Rodvold KA (1999) Clinical pharmacokinetics of clarithromycin. Clin Pharmacokinet 37:385–398.

    Article  PubMed  CAS  Google Scholar 

  • Ruiz M, Ewig S, Torres A, Arancibia F, Marco F, Mensa J, et al. (1999) Severe community-acquired pneumonia. Risk factors and follow-up epidemiology. Am J Respir Crit Care Med 160:923–929.

    PubMed  CAS  Google Scholar 

  • Saiman L, Marshall BC, Mayer-Hamblett N, Burns JL, Quittner AL, Cibene DA, et al. (2003) Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA 290:1749–1756.

    Article  PubMed  CAS  Google Scholar 

  • Schultz MJ, Speelman P, Hack CE, Buurman WA, van Deventer SJH, and van der Poll T (2000) Intravenous infusion of erythromycin inhibits CXC chemokine production, but augments neutrophil degranulation in whole blood stimulated with Streptococcus pneumoniae. J Antimicrob Chemother 46:235–240.

    Article  PubMed  CAS  Google Scholar 

  • Schultz MJ (2004) Macrolide activities beyond their antimicrobial effects: macrolides in diffuse panbronchiolitis and cystic fibrosis. J Antimicrob Chemother 54:21–28.

    Article  PubMed  CAS  Google Scholar 

  • Southern KW and Barker PM (2004) Azithromycin for cystic fibrosis. Eur Respir J 24:834–838.

    Article  PubMed  CAS  Google Scholar 

  • Stover DE and Mangino D (2005) Macrolides: a treatment alternative for bronchiolitis obliterans organizing pneumonia? Chest 128:3611–3617.

    Article  PubMed  Google Scholar 

  • Tamaoki J (2004) The effects of macrolides on inflammatory cells. Chest 125:41S–50S; quiz 51S.

    Article  PubMed  CAS  Google Scholar 

  • Tamaoki J, Kadota J, and Takizawa H (2004) Clinical implications of the immunomodulatory effects of macrolides. Am J Med 117(Suppl 9A):5S–11S.

    PubMed  CAS  Google Scholar 

  • Tracey KJ, Fong Y, Hesse DG, Manogue KR, Lee AT, Kuo GC, et al. (1987) Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. Nature 330:662–664.

    Article  PubMed  CAS  Google Scholar 

  • Van Amersfoort ES, Van Berkel TJ, and Kuiper J (2003) Receptors, mediators, and mechanisms involved in bacterial sepsis and septic shock. Clin Microbiol Rev 16:379–414.

    Article  PubMed  CAS  Google Scholar 

  • van Leeuwen HJ, Van Der Tol M, Van Strijp JA, Verhoef J, and van Kessel KP (2005) The role of tumour necrosis factor in the kinetics of lipopolysaccharide-mediated neutrophil priming in whole blood. Clin Exp Immunol 140:65–72.

    Article  PubMed  CAS  Google Scholar 

  • Vazifeh D, Bryskier A, and Labro MT (2000) Effect of proinflammatory cytokines on the interplay between roxithromycin, HMR 3647, or HMR 3004 and human polymorphonuclear neutrophils. Antimicrob Agents Chemother 44:511–521.

    Article  PubMed  CAS  Google Scholar 

  • Verleden GM, Vanaudenaerde BM, Dupont LJ, and Van Raemdonck DE (2006) Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 174:566–570.

    Article  PubMed  CAS  Google Scholar 

  • Vila-del Sol V and Fresno M (2005) Involvement of TNF and NF-kappa B in the transcriptional control of cyclooxygenase-2 expression by IFN-gamma in macrophages. J Immunol 174:2825–2833.

    PubMed  CAS  Google Scholar 

  • Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, et al. (1998) Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med 26:1793–1800.

    PubMed  CAS  Google Scholar 

  • Waterer GW (2003) Combination antibiotic therapy with macrolides in community-acquired pneumonia: more smoke but is there any fire? Chest 123:1328–1329.

    Article  PubMed  Google Scholar 

  • Waterer GW (2005) Optimal antibiotic treatment in severe pneumococcal pneumonia - time for real answers. Eur J Clin Microbiol Infect Dis 24:691–692.

    Article  PubMed  CAS  Google Scholar 

  • Waterer GW, Somes GW, and Wunderink RG (2001) Monotherapy may be suboptimal for severe bacteremic pneumococcal pneumonia. Arch Intern Med 161:1837–1842.

    Article  PubMed  CAS  Google Scholar 

  • Weiss K, Low DE, Cortes L, Beaupre A, Gauthier R, Gregoire P, et al. (2004) Clinical characteristics at initial presentation and impact of dual therapy on the outcome of bacteremic Streptococcus pneumoniae pneumonia in adults. Can Respir J 11:589–593.

    PubMed  CAS  Google Scholar 

  • Williams AC, Galley HF, Watt AM, and Webster NR (2005) Differential effects of three antibiotics on T helper cell cytokine expression. J Antimicrob Chemother 56:502–506.

    Article  PubMed  CAS  Google Scholar 

  • Wolter J, Seeney S, Bell S, Bowler S, Masel P, and McCormack J (2002a) Effect of long term treatment with azithromycin on disease parameters in cystic fibrosis: a randomised trial. Thorax 57:212–216.

    Article  PubMed  CAS  Google Scholar 

  • Wolter JM, Seeney SL, and McCormack JG (2002b) Macrolides in cystic fibrosis: is there a role? Am J Respir Med 1:235–241.

    PubMed  CAS  Google Scholar 

  • Yalcin E, Kiper N, Ozcelik U, Dogru D, Firat P, Sahin A, et al. (2006) Effects of claritromycin on inflammatory parameters and clinical conditions in children with bronchiectasis. J Clin Pharm Ther 31:49–55.

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto M, Kondo A, Tamura M, Izumi T, Ina Y, and Noda M (1990) Long-term therapeutic effects of erythromycin and newquinolone antibacterial agents on diffuse panbronchiolitis. Nihon Kyobu Shikkan Gakkai Zasshi 28:1305–1313.

    PubMed  CAS  Google Scholar 

  • Yamanaka Y, Tamari M, Nakahata T, and Nakamura Y (2001) Gene expression profiles of human small airway epithelial cells treated with low doses of 14- and 16-membered macrolides. Biochem Biophys Res Commun 287:198–203.

    Article  PubMed  CAS  Google Scholar 

  • Zeni F, Freeman B, and Natanson C (1997) Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med 25:1095–1100.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division Pulmonary and Critical Care Medicine, San Antonio, TX, 78229-4404, USA

    Marcos I. Restrepo

  2. Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Marcos I. Restrepo & Eric M. Mortensen

  3. South Texas Veterans Health Care System, Audie L. Murphy Division, VERDICT, Ambulatory Care (11C6), 7400 Merton Minter Boulevard, San Antonio, TX, 78284, USA

    Marcos I. Restrepo & Eric M. Mortensen

  4. Australia Department of Respiratory Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Australia

    Grant W. Waterer

  5. Pulmonary and Critical Care Division, Northwestern University Feinberg School of Medicine, Chicago, Illinois, 60611, USA

    Richard G. Wunderink

  6. Department of Medicine, University of Texas Health Science Center, 7400 Merton Minter Blvd (111 East), San Antonio, TX, 78229-4404, USA

    Antonio Anzueto

Authors
  1. Marcos I. Restrepo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric M. Mortensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Grant W. Waterer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Richard G. Wunderink
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antonio Anzueto
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Critical Care Department – Joan XXIII University Hospital, Universidad Rovira & Virgili and Institut Pere Virgili CIBER Enfermedades Respiratorias, Doctor Mallafre Guasch, 4, 43007, Tarragona, Spain

    Jordi Rello MD, PhD

  2. Division Pulmonary and Critical Care Medicine, San Antonio, TX, 78229-4404, USA

    Marcos I. Restrepo MD, MSc

  3. Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Marcos I. Restrepo MD, MSc

  4. South Texas Veterans Health Care System Audie L. Murphy Division, Veterans Evidence-Based Research Dissemination Implementation Center (VERDICT), 7400 Merton Minter Blvd (11C6), San Antonio, TX, 78229-4404, USA

    Marcos I. Restrepo MD, MSc

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer-Verlag

About this chapter

Cite this chapter

Restrepo, M.I., Mortensen, E.M., Waterer, G.W., Wunderink, R.G., Anzueto, A. (2008). Macrolides in Severe Community-Acquired Pneumonia and Sepsis. In: Rello, J., Restrepo, M.I. (eds) Sepsis. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-79001-3_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-79001-3_1

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-79000-6

  • Online ISBN: 978-3-540-79001-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation