Skip to main content

Advertisement

Log in

Optimal therapy for severe pneumococcal community-acquired pneumonia

  • Review
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Streptococcus pneumoniae is responsible for two-thirds of ICU admissions due to community-acquired pneumonia (CAP) and is the leading cause of CAP-related death. Early death is principally due to cardiovascular collapse, whereas late death is associated with hypoxemic respiratory failure. Outcome depends on interactions between non-modifiable factors of predisposition (age, comorbidities, host defences, genetic predisposition) or infection (toxins, virulence, bacterial burden) and modifiable factors (organ-failure support, surgical drainage for empyema, adjuvant therapies and antibiotics). Excess mortality has been reported when initial therapy is discordant, but more than 95% of isolates have minimum inhibitory concentration (MIC) < 4 μg/ml. Therefore, cefotaxime, ceftriaxone and high doses of amoxicillin remain successful for non-meningeal infections. Recent studies suggest that initial combination therapy improves survival in the subset of bacteremic episodes with highest severity, conceivably due to the immunomodulatory effects of macrolides. Prospective, randomized clinical trials of pneumonia patients with a pneumonia severity index score above 90 are warranted to define optimal antibiotic regimens.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Garibaldi RA (1985) Epidemiology of community-acquired respiratory tract infections in adults: incidence, aetiology and impact. Am J Med 78:32S–38S

    Article  PubMed  CAS  Google Scholar 

  2. Guest JF, Morris A (1997) Community-acquired pneumonia: the annual cost to the National Health Service in UK. Eur Resper J 10:1530–1534

    Article  CAS  Google Scholar 

  3. Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, Coley CM, Marrie TJ, Kapoor WN (1997) A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 336:243–250

    Article  PubMed  CAS  Google Scholar 

  4. Rello J, Bodi M, Mariscal D, Navarro M, Diaz E, Gallego M, Valles J (2003) Microbiological testing and outcome of patients with severe community-acquired pneumonia. Chest 123:174–180. DOI 10.1378/chest.123.1.174

    Article  PubMed  Google Scholar 

  5. Bodí M, Rodríguez A, Solé-Violán J, Gilavert MC, Garnacho J, Blanquer J, Jimenez J, de la Torre MV, Sirvent JM, Almirall J, Doblas A, Badía JR, García F, Mendia A, Jordá R, Bobillo F, Vallés J, Broch MJ, Carrasco N, Herranz MA, Rello J. for CAPUCI study investigators (2005) Antibiotic prescription for community-acquired pneumonia in the intensive care unit. Impact of adherence to IDSA guidelines on outcome. Clin Infect Dis 41:1709–171 DOI 10.1086/498119

    Article  PubMed  Google Scholar 

  6. Torres A, Serra-Batlles J, Ferrer A, Jimenez P, Celis R, Cobo E, Rodriguez-Roisin R (1991) Severe community-acquired pneumonia. Epidemiology and prognostic factors Am Rev Respir Dis 144:312–318

    CAS  Google Scholar 

  7. Musher D, Alexandraki I, Graviss E, Yanbeiy N, Eid A, Inderias L, Phan H, Solomon E (2000) Bacteremic and non-bacteremic pneumococcal pneumonia: a prospective study. Medicine 79:210–221

    Article  PubMed  CAS  Google Scholar 

  8. Whitney CG, Farley MM, Hadler J, Harrison LH, Bennett NM, Lynfield R, Reingold A, Cieslak PR, Pilishvili T, Jackson D, Facklam RR, Jorgensen JH, Schuchat A, Active Bacterial Core Surveillance of the Emerging Infections Program Network (2003) Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med 348:1737–1746

    Article  PubMed  Google Scholar 

  9. Waterer GW, Quasney MW, Cantor RM, Wunderink RG (2001) Septic shock and respiratory failure in community-acquired pneumonia have different TNF polymorphism associations. Am J Respir Crit Care Med 163:1599–1604

    PubMed  CAS  Google Scholar 

  10. Meehan TP, Fine MJ, Krumholz HM, Scinto JD, Galusha DH, Mockalis JT, Weber GF, Petrillo MK, Houck PM, Fine JM (1997) Quality of care, process, and outcomes in elderly patients with pneumonia. JAMA 278:2080–2084

    Article  PubMed  CAS  Google Scholar 

  11. Laterre PF, Garber G, Levy H, Wunderink R, Kinasewitz GT, Sollet JP, Maki DG, Bates B, Yan SC, Dhainaut JF, PROWESS Clinical Evaluation Committee (2005) Severe community-acquired pneumonia as a cause of severe sepsis: data from the PROWESS study. Crit Care Med 33:952–961. DOI 10.1097/01.CCM.0000162381.24074.D7

    Article  PubMed  Google Scholar 

  12. Lujan M, Gallego M, Fontanals D, Mariscal D, Rello J (2004) Prospective observational study of bacteremic pneumococcal pneumonia: Effect of discordant therapy on mortality. Crit Care Med 32:625–631. DOI: 10.1097/01.CCM.0000114817.58194.BF

    Article  PubMed  CAS  Google Scholar 

  13. Baddour LM, Yu VL, Klugman KP, Feldman C, Ortqvist A, Rello J, Morris AJ, Luna CM, Snydman DR, Ko WC, Chedid MB, Hui DS, Andremont A, Chiou CC, International Pneumococcal Study Group (2004) Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia. Am J Respir Crit Care Med 170:440–444. DOI 10.1164/rccm.200311–1578OC

    Article  PubMed  Google Scholar 

  14. Chow JW, Yu VL (1999) Combination antibiotic versus monotherapy for gram-negative bacteremia: a commentary. Int J Antimicrob Agents 11:7

    Article  PubMed  CAS  Google Scholar 

  15. American Thoracic Society (2001) Guidelines for the management of adults with community acquired pneumonia. Am J Respir Crit Care Med 163:1730–1754

    Google Scholar 

  16. Bartlett JG, Dowell SF, Mandell LA, File TM, Musher DM, Fine MJ (2000) Practice guidelines for the management of community-acquired pneumonia in adults. Infectious Diseases Society of America. Clin Infect Dis 31:347–382

    Article  PubMed  CAS  Google Scholar 

  17. British Thoracic Society (2001) BTS guidelines for the management of community-acquired pneumonia in adults. Thorax 56[Suppl 4]:1–64

  18. Lim WS, van der Eerden MM, Laing R, Boersma WG, Karalus N, Town GI, Lewis SA, Macfarlane JT (2003) Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 58:377–382. DOI 10.1136/thorax.58.5.377

    Article  PubMed  CAS  Google Scholar 

  19. Tighman RC, Finland M (1937) Clinical significance of bacteremia in pneumococcal pneumonia. Arch Intern Med 1937 59:602–619

    Google Scholar 

  20. Jacobs MR, Koornhof HJ, Robins-Browne RM, Stevenson CM, Vermaak ZA, Freiman I, Miller GB, Witcomb MA, Isaacson M, Ward JI, Austrian R (1978) Emergency of multiply resistant pneumococci. N Engl J Med 299:735–740

    Article  PubMed  CAS  Google Scholar 

  21. Magnusdottir AB, Hermansson A, Melhus A (2000) Experimental study of the virulence of Streptococcus pneumoniae with reduced susceptibility to penicillin. Int J Pediatr Otorhinolaryngol 55:1–9

    Article  PubMed  CAS  Google Scholar 

  22. Rieux V, Carbon C, Azoulay-Dupuis E (2001) Complex relationship between acquisition of beta-lactam resistance and loss of virulence in Streptococcus pneumoniae. J Infect Dis 184:66–72

    Article  PubMed  CAS  Google Scholar 

  23. Azoulay-Dupuis E, Rieux V, Muffat-Joly M, Bedos JP, Vallee E, Rivier C, Isturiz R, Carbon C, Moine P (2000) Relationship between capsular type, penicillin susceptibility, and virulence of human Streptococcus pneumoniae isolates in mice. Antimicrob Agents Chemother 44:1575–1577

    Article  PubMed  CAS  Google Scholar 

  24. Aspa J, Rajas O, Rodriguez de Castro F, Blanquer J, Zalacain R, Fenoll A, de Celis R, Vargas A, Rodriguez Salvanes F, Espana PP, Rello J, Torres A; Pneumococcal Pneumonia in Spain Study Group (2004) Drug-resistant pneumococcal pneumonia: clinical relevance and related factors. Clin Infect Dis 38:787–798

    Article  PubMed  CAS  Google Scholar 

  25. Clavo-Sanchez AJ, Giron-Gonzalez JA, Lopez-Prieto D (1997) Multivariate analysis of risk factors for infection due to penicillin-resistant and multidrug-resistant Streptococcus pneumoniae: a multicenter study. Clin Infect Dis 24:1052–1059

    Article  PubMed  CAS  Google Scholar 

  26. Winston LG, Perlman JL, Rose DA, Gerberding JL (1999) Penicillin-nonsusceptible Streptococcus pneumoniae at San Francisco General Hospital. Clin Infect Dis 29:580–585

    Article  PubMed  CAS  Google Scholar 

  27. Pallares R, Linares J, Vadillo M, Cabellos C, Manresa F, Viladrich PF, Martin R, Gudiol F (1995) Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain. N Engl J Med 333:474–480

    Article  PubMed  CAS  Google Scholar 

  28. Ewig S, Ruiz M, Torres A, Marco F, Martinez JA, Sanchez M, Mensa J (1999) Pneumonia acquired in the community through drug-resistant Streptococcus pneumoniae. Am J Respir Crit Care Med 159:1835–1842

    PubMed  CAS  Google Scholar 

  29. Martinez JA, Horcajada JP, Almela M, Marco F, Soriano A, Garcia E, Marco MA, Torres A, Mensa J (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 36:389–385

    Article  PubMed  CAS  Google Scholar 

  30. Metlay JP, Hoffman J, Cetron MS (2000) Impact of penicillin susceptibility on medical outcomes for adult patients with bacteremic pneumococcal pneumonia. Clin Infect Dis 90:520–528

    Article  Google Scholar 

  31. Musher DM, Bartlett JG, Doern GV (2001) A fresh look at the definition of susceptibility of Streptococcus pneumoniae to beta-lactam antibiotics. Arch Intern Med 161:2538–2544

    Article  PubMed  CAS  Google Scholar 

  32. Crnich CJ, Proctor RA (2004) Treatment of pneumococcal pneumonia: what's in an MIC? Crit Care Med 32:876–878. DOI 10.1097/01.CCM.0000114999.81252.B5

    Article  PubMed  Google Scholar 

  33. Lipman J, Wallis SC, Rickard CM, Fraenkel D (2001) Low cefpirome levels during twice-daily dosing in critically ill septic patients: pharmacokinetic modelling calls for more frequent dosing. Intensive Care Med 27:363–370

    Article  PubMed  CAS  Google Scholar 

  34. Craig WA (2004) Overview of newer antimicrobial formulations for overcoming pneumococcal resistance. Am J Med 117 [Suppl 3A]:16S–22S

  35. Castanheira M, Gales AC, Mendes RE, Jones RN, Sader HS (2004) Antimicrobial susceptibility of Streptococcus pneumoniae in Latin America: results from 5 years of the SENTRY Antimicrobial Surveillance Program. Clin Microbiol Infect 10:645–651

    Article  PubMed  CAS  Google Scholar 

  36. Yu, Campbell GD Jr, Siberman R (1998) Drug-resistant Streptococcus pneumoniae. Clin Infect Dis 26:1188–1195

    Article  Google Scholar 

  37. Reinert RR, Reinert S, van der Linden M, Cil MY, Al-Lahham A, Appelbaum P (2005) Antimicrobial susceptibility of Streptococcus pneumoniae in eight European countries from 2001 to 2003. Antimicrob Agents Chemother 49:2903–2913. DOI 10.1128/AAC.49.7.2903–2913.2005

    Article  PubMed  CAS  Google Scholar 

  38. Pihlajamaki M, Jalava J, Huovinen P, Kotilainen P, Finnish Study Group for Antimicrobial Resistance (2003) Antimicrobial resistance of invasive pneumococci in Finland in 1999–2000. Antimicrob Agents Chemother 47:1832–1835. DOI 10.1128/AAC.47.6.1832–1835.2003

    Article  PubMed  CAS  Google Scholar 

  39. Feikin DR, Schuchat A, Kolczak M, Barrett NL, Harrison LH, Lefkowitz L, McGeer A, Farley MM, Vugia DJ, Lexau C, Stefonek KR, Patterson JE, Jorgensen JH (2000) Mortality from invasive pneumococcal pneumonia in the era of antibiotic resistance, 1995–1997. Am J Public Health 90:223–229

    PubMed  CAS  Google Scholar 

  40. National Committee for Clinical Laboratory Standards (2002) Performance standards for antimicrobial susceptibility testing. Twelfth informational supplement. Document M100–S12. National Committee for Clinical Laboratory Standards, Wayne, PA, USA

    Google Scholar 

  41. Yu VL, Chiou CC, Feldman C, Ortqvist A, Rello J, Morris AJ, Baddour LM, Luna CM, Snydman DR, Ip M, Ko WC, Chedid MB, Andremont A, Klugman KP, International Pneumococcal Study Group (2003) An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome. Clin Infect Dis 37:230–237

    Article  PubMed  CAS  Google Scholar 

  42. Song JH, Jung SI, Ki HK (2004) Clinical outcomes of pneumococcal pneumonia caused by antibiotic-resistant strains in Asian countries: a study by the Asian Network for Surveillance of Resistant Pathogens. Clin Infect Dis 38:1570–1578

    Article  PubMed  Google Scholar 

  43. National Committee for Clinical Laboratory Standards (1999) Performance standards for antimicrobial susceptibility testing. Ninth informational supplement. Document M100–S9. National Committee for Clinical Laboratory Standards, Wayne, PA, USA

    Google Scholar 

  44. Tleyjeh IM, Tlaygeh HM, Hejal R, Montori VM, Baddour LM (2006) The impact of penicillin resistance on short-term mortality in hospitalized adults with pneumococcal pneumonia: a systematic review and meta-analysis. Clin Infect Dis 42:788–797. DOI 10.1086/500140

    Article  PubMed  Google Scholar 

  45. Lonks JR, Garau J, Gomez L, Xercavins M, Ochoa de Echaguen A, Gareen IF, Reiss PT, Medeiros AA (2002) Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae. Clin Infect Dis 35:556–564

    Article  PubMed  CAS  Google Scholar 

  46. Van Kerkhoven D, Peetermans WE, Verbist L, Verhaegen J (2003) Breakthrough pneumococcal bacteraemia in patients treated with clarithromycin or oral beta-lactams. J Antimicrob Chemother 51:691–696

    Article  PubMed  CAS  Google Scholar 

  47. 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. DOI 10.1186/cc3934

    Article  Google Scholar 

  48. Canton R, Morosini M, Enright MC, Morrissey I (2003) Worldwide incidence, molecular epidemiology and mutations implicated in fluoroquinolone resistant Streptococcus pneumoniae: data from the global PROTEKT surveillance programme. J Antimicrob Chemother 52:944–952. DOI 10.1093/jac/dkg465

    Article  PubMed  CAS  Google Scholar 

  49. Davidson R, Cavalcanti R, Brunton JL (2002) Resistance to levofloxacin and failure of treatment of Pneumococcal Pneumonia. N Engl J Med 346:747–750

    Article  PubMed  Google Scholar 

  50. Rello J, Catalán M, Díaz E, Bodí M, Alvarez B (2002) Associations between empirical antimicrobial therapy at the hospital and mortality in patients with severe community-acquired pneumonia. Intensive Care Med 28:1030–1035. DOI 10.1007/s00134-002-1325–3

    Article  PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  53. Harbarth S, Garbino J, Pugin J, Romand JA, Pittet D (2005) Lack of effect of combination antibiotic therapy on mortality in patients with pneumococcal sepsis. Eur J Clin Microbiol Infect Dis 24:688–690. DOI 10.1007/s10096-005-0018-6

    Article  PubMed  CAS  Google Scholar 

  54. Finch R, Schurmann D, Collins O, Kubin R, McGivern J, Bobbaers H, Izquierdo JL, Nikolaides P, Ogundare F, Raz R, Zuck P, Hoeffken G (2002) Randomized controlled trial of sequential intravenous (i.v.) and oral moxifloxacin compared with sequential i.v. and oral co-amoxiclav with or without clarithromycin in patients with community-acquired pneumonia requiring initial parenteral treatment. Antimicrob Agents Chemother 46:1746–1754. DOI 10.1128/AAC.46.6.1746–1754.2002

    Article  PubMed  CAS  Google Scholar 

  55. Frank E, Liu J, Kinasewitz G, Moran GJ, Oross MP, Olson WH, Reichl V, Freitag S, Bahal N, Wiesinger BA, Tennenberg A, Kahn JB (2002) A multicenter, open-label, randomized comparison of levofloxacin and azithromycin plus ceftriaxone in hospitalized adults with moderate to severe community-acquired pneumonia. Clin Ther 24:1292–1308

    Article  PubMed  CAS  Google Scholar 

  56. Sugiyama Y, Yanagisawa K, Tominaga SI, Kitamura S (1999) Effects of long-term administration of erythromycin on cytokine production in rat alveolar macrophages. Eur Respir J 14:1113–1116

    Article  PubMed  CAS  Google Scholar 

  57. Khan AA, Slifer TR, Araujo FG, 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 

  58. Lieberman D, Schlaeffer F, Boldur I et al (1996) Multiple pathogens in adult patients admitted with community-acquired pneumonia: a 1 year prospective study of 346 consecutive patients. Thorax 51:179–184

    Article  PubMed  CAS  Google Scholar 

  59. Almirall J, Bolibar I, Vidal J et al (2000) Epidemiology of community-acquired pneumonia in adults: a population-based study. Eur Respir J 15:757–763

    Article  PubMed  CAS  Google Scholar 

  60. Waterer RW, Rello J (2006) Choosing the right combination therapy in severe community-acquired pneumonia. Crit Care 10:115–116. DOI 10.1186/cc3976

    Article  PubMed  Google Scholar 

  61. Shorr AF, Bodi M, Rodriguez A, Sole-Violan J, Garnacho-Montero J, Rello J (2006) Impact of antibiotic guideline compliance on duration of mechanical ventilation in critically ill patients with community-acquired pneumonia. ATS Conference, San Diego, May 2006

  62. File TM jr, Tan JS, Boex JR (2006) The clinical relevance of penicillin-resistant Streptococcus pneumoniae: A new perspective. Clin Infect Dis 42:798–800. DOI 10.1086/500142

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jordi Rello.

Additional information

Supported in part by FISS PI 04/1500

Rights and permissions

Reprints and permissions

About this article

Cite this article

Luján, M., Gallego, M. & Rello, J. Optimal therapy for severe pneumococcal community-acquired pneumonia. Intensive Care Med 32, 971–980 (2006). https://doi.org/10.1007/s00134-006-0182-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-006-0182-x

Keywords

Navigation