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Drug-resistant pneumococcal pneumonia: clinical relevance and approach to management

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Abstract

Community-acquired pneumonia is the most common infectious disease that causes death, with Streptococcus pneumoniae remaining the leading causative pathogen. The worldwide incidence of infections caused by pneumococci resistant to penicillin, macrolides, and other antimicrobial agents has increased at an alarming rate during the past 2 decades. Yet, these agents are still used as first-line empirical therapy in the outpatient setting. There are several reasons for this, including the infrequency of making a pathogen-specific diagnosis, the failure of studies to demonstrate the relevance of resistance, and the infrequency with which clinicians recognize clinical failures. Despite this, there is mounting evidence that supports the practice of using high doses of some antimicrobial agents, a more active antimicrobial agent within a class, or switching to another class of antimicrobial agents when a patient is identified as being at an increased risk of infection with a resistant pneumococcus. There is now information that will allow the physician to identify not only the patient at risk for infection with a resistant pneumococcus but also the antimicrobial class and, in some cases, the agent within the class to which the organism is more likely to be resistant. This will allow clinicians to better define optimal therapy for patients with community-acquired pneumonia.

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References

  1. British Thoracic Society (1993) Guidelines for the management of community-acquired pneumonia in adults admitted to hospital. Br J Hosp Med 49:346–350

    Google Scholar 

  2. Ruiz-Gonzalez A, Falguera M, Nogues A et al (1999) Is Streptococcus pneumoniae the leading cause of pneumonia of unknown etiology? A microbiologic study of lung aspirates in consecutive patients with community-acquired pneumonia. Am J Med 106:385–390

    Article  PubMed  CAS  Google Scholar 

  3. Appelbaum PC (1992) Antimicrobial resistance in Streptococcus pneumoniae: an overview. Clin Infect Dis 15:77–83

    PubMed  CAS  Google Scholar 

  4. Sloas MM, Barrett FF, Chesney PJ et al (1992) Cephalosporin treatment failure in penicillin- and cephalosporin-resistant Streptococcus pneumoniae meningitis. Pediatr Infect Dis J 11:662–666

    PubMed  CAS  Google Scholar 

  5. Catalan MJ, Fernandez JM, Vazquez A et al (1994) Failure of cefotaxime in the treatment of meningitis due to relatively resistant Streptococcus pneumoniae. Clin Infect Dis 18:766–769

    PubMed  CAS  Google Scholar 

  6. Dagan R, Piglansky L, Fliss DM et al (1997) Bacteriologic response in acute otitis media: comparison between azithromycin, cefaclor and amoxicillin. Program and abstracts, 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, Canada, Abstract no. 346

  7. Friedland IR (1995) Comparison of the response to antimicrobial therapy of penicillin-resistant and penicillin-susceptible pneumococcal disease [see comments]. Pediatr Infect Dis J 14:885–890

    Article  PubMed  CAS  Google Scholar 

  8. Pallares R, Linares J, Vadillo M et al (1995) Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain [see comments] [published erratum appears in N Engl J Med (1995) 333:1655]. N Engl J Med 333:474–480

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  10. Ewig S, Ruiz M, Torres A et al (1999) Pneumonia acquired in the community through drug-resistant Streptococcus pneumoniae. Am J Respir Crit Care Med 159:1835–1842

    PubMed  CAS  Google Scholar 

  11. Jacobs MR, Koornhof HJ, Robins-Browne RM et al (1978) Emergence of multiply resistant pneumococci. N Engl J Med 299:735–740

    Article  PubMed  CAS  Google Scholar 

  12. Spika JS, Facklam RR, Plikaytis BD et al (1991) Antimicrobial resistance of Streptococcus pneumoniae in the United States, 1979–1987. The Pneumococcal Surveillance Working Group. J Infect Dis 163:1273–1278

    PubMed  CAS  Google Scholar 

  13. McGeer A, Low DE (2003) Is resistance futile? Nat Med 9:390–392

    Article  PubMed  CAS  Google Scholar 

  14. Powis J, McGeer A, Green K et al (2004) In vitro antimicrobial susceptibilities of Streptococcus pneumoniae clinical isolates obtained in Canada in 2002. Antimicrob Agents Chemother 48:3305–3311

    Article  PubMed  CAS  Google Scholar 

  15. Doern GV, Heilmann KP, Huynh HK et al (2001) Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in the United States during 1999–2000, including a comparison of resistance rates since 1994–1995. Antimicrob Agents Chemother 45:1721–1729

    Article  PubMed  CAS  Google Scholar 

  16. Low DE, de Azavedo J, Weiss K et al (2002) Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in Canada during 2000. Antimicrob Agents Chemother 46:1295–1301

    Article  PubMed  CAS  Google Scholar 

  17. Jacobs MR (2003) Worldwide trends in antimicrobial resistance among common respiratory tract pathogens in children. Pediatr Infect Dis J 22:S109–S119

    Article  PubMed  Google Scholar 

  18. Chen D, McGeer A, de Azavedo JC et al (1999) Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. N Eng J Med 341:233–239

    Article  CAS  Google Scholar 

  19. De La Campa AG, Balsalobre L, Ardanuy C et al (2004) Fluoroquinolone resistance in penicillin-resistant Streptococcus pneumoniae clones, Spain. Emerg Infect Dis 10:1751–1759

    PubMed  Google Scholar 

  20. Linares J, De La Campa AG, Pallares R (1999) Fluoroquinolone resistance in Streptococcus pneumoniae. N Engl J Med 341:1546–1547

    Article  PubMed  CAS  Google Scholar 

  21. Perez-Trallero E, Fernandez-Mazarrasa C, Garcia-Rey C et al (2001) Antimicrobial susceptibilities of 1,684 Streptococcus pneumoniae and 2,039 Streptococcus pyogenes isolates and their ecological relationships: results of a 1-year (1998–1999) multicenter surveillance study in Spain. Antimicrob Agents Chemother 45:3334–3340

    Article  PubMed  CAS  Google Scholar 

  22. Ho PL, Que TL, Tsang DN et al (1999) Emergence of fluoroquinolone resistance among multiply resistant strains of Streptococcus pneumoniae in Hong Kong. Antimicrob Agents Chemother 43:1310–1313

    PubMed  CAS  Google Scholar 

  23. Ho PL, Yung RW, Tsang DN et al (2001) Increasing resistance of Streptococcus pneumoniae to fluoroquinolones: results of a Hong Kong multicentre study in 2000. J Antimicrob Chemother 48:659–665

    Article  PubMed  CAS  Google Scholar 

  24. File TM Jr, Garau J, Blasi F et al (2004) Guidelines for empiric antimicrobial prescribing in community-acquired pneumonia. Chest 125:1888–1901

    Article  PubMed  Google Scholar 

  25. Metlay JP, Singer DE (2002) Outcomes in lower respiratory tract infections and the impact of antimicrobial drug resistance. Clin Microbiol Infect 8(Suppl 2):1–11

    Article  PubMed  Google Scholar 

  26. Jacobs MR, Bajaksouzian S, Zilles A et al (1999) Susceptibilities of Streptococcus pneumoniae and Haemophilus influenzae to 10 oral antimicrobial agents based on pharmacodynamic parameters: 1997 U.S. surveillance study. Antimicrob Agents Chemother 43:1901-1908

    PubMed  CAS  Google Scholar 

  27. Scott JA, Marston EL, Hall AJ et al (2003) Diagnosis of pneumococcal pneumonia by psaA PCR analysis of lung aspirates from adult patients in Kenya. J Clin Microbiol 41:2554–2559

    Article  PubMed  CAS  Google Scholar 

  28. Metlay JP, Fine MJ (2003) Testing strategies in the initial management of patients with community-acquired pneumonia. Ann Intern Med 138:109–118

    PubMed  Google Scholar 

  29. Musher DM (2005) The usefulness of sputum gram stain and culture. Arch Intern Med 165:470–471

    Article  PubMed  Google Scholar 

  30. Farr BM, Kaiser DL, Harrison BD et al (1989) Prediction of microbial aetiology at admission to hospital for pneumonia from the presenting clinical features. British Thoracic Society Pneumonia Research Subcommittee. Thorax 44:1031–1035

    PubMed  CAS  Google Scholar 

  31. Fang GD, Fine M, Orloff J et al (1990) New and emerging etiologies for community-acquired pneumonia with implications for therapy. A prospective multicenter study of 359 cases. Medicine (Baltimore) 69:307–316

    CAS  Google Scholar 

  32. Mandell LA, Bartlett JG, Dowell SF et al (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 

  33. Gutierrez F, Masia M, Rodriguez JC et al (2003) Evaluation of the immunochromatographic Binax NOW assay for detection of Streptococcus pneumoniae urinary antigen in a prospective study of community-acquired pneumonia in Spain. Clin Infect Dis 36:286–292

    Article  PubMed  CAS  Google Scholar 

  34. Navarro D, Garcia-Maset L, Gimeno C et al (2004) Performance of the Binax NOW Streptococcus pneumoniae urinary antigen assay for diagnosis of pneumonia in children with underlying pulmonary diseases in the absence of acute pneumococcal infection. J Clin Microbiol 42:4853–4855

    Article  PubMed  Google Scholar 

  35. Leclercq R (2002) Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical implications. Clin Infect Dis 34:482–492

    Article  PubMed  CAS  Google Scholar 

  36. Craig WA (1998) Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis 26:1–12

    Article  PubMed  CAS  Google Scholar 

  37. National Committee for Clinical Laboratory Standards (2004) Performance standards for antimicrobial susceptibility testing. Information supplement M100-S14. NCCLS, Wayne, PA

  38. Sacho H, Klugman KP, Koornhof HJ et al (1987) Community-acquired pneumonia in an adult due to a multiply-resistant pneumococcus. J Infect 14:188–189

    Article  PubMed  CAS  Google Scholar 

  39. Buckingham SC, Brown SP, Joaquin VH (1998) Breakthrough bacteremia and meningitis during treatment with cephalosporins parenterally for pneumococcal pneumonia. J Pediatr 132:174–176

    Article  PubMed  CAS  Google Scholar 

  40. Dowell SF, Smith T, Leversedge K et al (1999) Failure of treatment of pneumonia associated with highly resistant pneumococci in a child. Clin Infect Dis 29:462–463

    Article  PubMed  CAS  Google Scholar 

  41. Daum RS, Nachman JP, Leitch CD et al (1994) Nosocomial epiglottitis associated with penicillin- and cephalosporin-resistant Streptococcus pneumoniae bacteremia. J Clin Microbiol 32:246–248

    PubMed  CAS  Google Scholar 

  42. Chesney PJ, Wilimas JA, Presbury G et al (1995) Penicillin- and cephalosporin-resistant strains of Streptococcus pneumoniae causing sepsis and meningitis in children with sickle cell disease. J Pediatr 127:526–532

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  44. Deeks SL, Palacio R, Ruvinsky R et al (1999) Risk factors and course of illness among children with invasive penicillin-resistant Streptococcus pneumoniae. The Streptococcus pneumoniae Working Group. Pediatrics 103:409–413

    Article  PubMed  CAS  Google Scholar 

  45. Yu VL, Chiou CC, Feldman C et al (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 

  46. Turett GS, Blum S, Fazal BA et al (1999) Penicillin resistance and other predictors of mortality in pneumococcal bacteremia in a population with high human immunodeficiency virus seroprevalence. Clin Infect Dis 29:321–327

    Article  PubMed  CAS  Google Scholar 

  47. Feikin DR, Schuchat A, Kolczak M et al (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 

  48. Lujan M, Gallego M, Fontanals D et al (2004) Prospective observational study of bacteremic pneumococcal pneumonia: effect of discordant therapy on mortality. Crit Care Med 32:625–631

    Article  PubMed  CAS  Google Scholar 

  49. Kelley MA, Weber DJ, Gilligan P et al (2000) Breakthrough pneumococcal bacteremia in patients being treated with azithromycin and clarithromycin. Clin Infect Dis 31:1008–1011

    Article  PubMed  CAS  Google Scholar 

  50. Fogarty C, Goldschmidt R, Bush K (2000) Bacteremic pneumonia due to multidrug-resistant pneumococci in 3 patients treated unsuccessfully with azithromycin and successfully with levofloxacin. Clin Infect Dis 31:613–615

    Article  PubMed  CAS  Google Scholar 

  51. Musher DM, Dowell ME, Shortridge VD et al (2002) Emergence of macrolide resistance during treatment of pneumococcal pneumonia. N Engl J Med 346:630–631

    Article  PubMed  Google Scholar 

  52. Kays MB, Wack MF, Smith DW et al (2002) Azithromycin treatment failure in community-acquired pneumonia caused by Streptococcus pneumoniae resistant to macrolides by a 23S rRNA mutation. Diagn Microbiol Infect Dis 43:163–165

    Article  PubMed  CAS  Google Scholar 

  53. Lonks JR, Garau J, Gomez L et al (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 

  54. Perez-Trallero E, Marimon JM, Iglesias L et al (2003) Fluoroquinolone and macrolide treatment failure in pneumococcal pneumonia and selection of multidrug-resistant isolates. Emerg Infect Dis 9:1159–1162

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  56. Gonzalez BE, Martinez-Aguilar G, Mason EO Jr et al (2004) Azithromycin compared with beta-lactam antibiotic treatment failures in pneumococcal infections of children. Pediatr Infect Dis J 23:399–405

    Article  PubMed  Google Scholar 

  57. Butler JC, Lennox JL, McDougal LK et al (2003) Macrolide-resistant pneumococcal endocarditis and epidural abscess that develop during erythromycin therapy. Clin Infect Dis 36:e19–e25

    Article  PubMed  Google Scholar 

  58. Rodvold KA, Gotfried MH, Danziger LH et al (1997) Intrapulmonary steady-state concentrations of clarithromycin and azithromycin in healthy adult volunteers. Antimicrob Agents Chemother 41:1399–1402

    PubMed  CAS  Google Scholar 

  59. Ardanuy C, Tubau F, Linares J et al (2005) Distribution of subclasses mefA and mefE of the mefA gene among clinical isolates of macrolide-resistant (M-phenotype) Streptococcus pneumoniae, viridans group streptococci, and Streptococcus pyogenes. Antimicrob Agents Chemother 49:827–829

    Article  PubMed  CAS  Google Scholar 

  60. Noreddin AM, Roberts D, Nichol K et al (2002) Pharmacodynamic modeling of clarithromycin against macrolide-resistant [PCR-positive mef(A) or erm(B)] Streptococcus pneumoniae simulating clinically achievable serum and epithelial lining fluid free-drug concentrations. Antimicrob Agents Chemother 46:4029–4034

    Article  PubMed  CAS  Google Scholar 

  61. Hoffman HL, Klepser ME, Ernst EJ et al (2003) Influence of macrolide susceptibility on efficacies of clarithromycin and azithromycin against Streptococcus pneumoniae in a murine lung infection model. Antimicrob Agents Chemother 47:739–746

    Article  PubMed  CAS  Google Scholar 

  62. Maglio D, Capitano B, Banevicius MA et al (2004) Efficacy of clarithromycin against Streptococcus pneumoniae expressing mef(A)-mediated resistance. Int J Antimicrob Agents 23:498–501

    Article  PubMed  CAS  Google Scholar 

  63. Fuller JD, Low DE (2005) A review of Streptococcus pneumoniae treatment failures associated with fluoroquinolone resistance. Clin Infect Dis 41:118–121

    Article  PubMed  Google Scholar 

  64. Davidson R, Cavalcanti R, Brunton JL et al (2002) Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N Engl J Med 346:747–750

    Article  PubMed  Google Scholar 

  65. Ross JJ, Worthington MG, Gorbach SL et al (2002) Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. New Engl J Med 347:65–67

    Article  PubMed  Google Scholar 

  66. Kuehnert MJ, Nolte FS, Perlino CA (1999) Fluoroquinolone resistance in Streptococcus pneumoniae. Ann Intern Med 131:312–313

    PubMed  CAS  Google Scholar 

  67. Wortmann GW, Bennett SP (1999) Fatal meningitis due to levofloxacin-resistant Streptococcus pneumoniae. Clin Infect Dis 29:1599–1600

    Article  PubMed  CAS  Google Scholar 

  68. Anderson KB, Tan JS, File TM Jr et al (2003) Emergence of levofloxacin-resistant pneumococci in immunocompromised adults after therapy for community-acquired pneumonia. Clin Infect Dis 37:376–381

    Article  PubMed  Google Scholar 

  69. Kays MB, Smith DW, Wack ME et al (2002) Levofloxacin treatment failure in a patient with fluoroquinolone-resistant Streptococcus pneumoniae pneumonia. Pharmacotherapy 22:395–399

    Article  PubMed  Google Scholar 

  70. Urban C, Rahman N, Zhao X et al (2001) Fluoroquinolone-resistant Streptococcus pneumoniae associated with levofloxacin therapy. J Infect Dis 184:794–798

    Article  PubMed  CAS  Google Scholar 

  71. Empey PE, Jennings HR, Thornton AC et al (2001) Levofloxacin failure in a patient with pneumococcal pneumonia. Ann Pharmacother 35:687–690

    Article  PubMed  CAS  Google Scholar 

  72. Weiss K, Restieri C, Laverdiere M et al (2001) A nosocomial outbreak of fluoroquinolone-resistant Streptococcus pneumoniae. Clin Inf Dis 33:517–522

    Article  CAS  Google Scholar 

  73. Roson B, Carratala J, Fernandez-Sabe N et al (2004) Causes and factors associated with early failure in hospitalized patients with community-acquired pneumonia. Arch Intern Med 164:502–508

    Article  PubMed  Google Scholar 

  74. Pletz MW, McGee L, Burkhardt O et al (2005) Ciprofloxacin treatment failure in a patient with resistant Streptococcus pneumoniae infection following prior ciprofloxacin therapy. Eur J Clin Microbiol Infect Dis 24:58–60

    Article  PubMed  CAS  Google Scholar 

  75. Clavo-Sanchez AJ, Giron-Gonzalez JA, Lopez-Prieto D et al (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 

  76. Bedos JP, Chevret S, Chastang C et al (1996) Epidemiological features of and risk factors for infection by Streptococcus pneumoniae strains with diminished susceptibility to penicillin: findings of a French survey. Clin Infect Dis 22:63–72

    PubMed  CAS  Google Scholar 

  77. Samore MH, Magill MK, Alder SC et al (2001) High rates of multiple antibiotic resistance in Streptococcus pneumoniae from healthy children living in isolated rural communities: association with cephalosporin use and intrafamilial transmission. Pediatrics 108:856–865

    Article  PubMed  CAS  Google Scholar 

  78. Garcia-Leoni ME, Cercenado E, Rodeno P et al (1992) Susceptibility of Streptococcus pneumoniae to penicillin: a prospective microbiological and clinical study. Clin Infect Dis 14:427–435

    PubMed  CAS  Google Scholar 

  79. Niederman MS, Mandell LA, Anzueto A et al (2001) Guidelines for the management of adults with community-acquired pneumonia. Diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med 163:1730–1754

    PubMed  CAS  Google Scholar 

  80. Vanderkooi O, Low DE, Green K et al (2005) Predicting antimicrobial resistance in invasive pneumococcal infections. Clin Infect Dis 40:1288–1297

    Article  PubMed  CAS  Google Scholar 

  81. Albanese BA, Roche JC, Pass M et al (2002) Geographic, demographic, and seasonal differences in penicillin-resistant Streptococcus pneumoniae in Baltimore. Clin Infect Dis 34:15–21

    Article  PubMed  Google Scholar 

  82. Kupronis BA, Richards CL, Whitney CG (2003) Invasive pneumococcal disease in older adults residing in long-term care facilities and in the community. J Am Geriatr Soc 51:1520–1525

    Article  PubMed  Google Scholar 

  83. Ho PL, Tse WS, Tsang KW et al (2001) Risk factors for acquisition of levofloxacin-resistant Streptococcus pneumoniae: a case-control study. Clin Infect Dis 32:701–707

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Microbiology, Toronto Medical Laboratories and Mount Sinai Hospital, University of Toronto, 600 University Avenue, M5G 1X5, Toronto, Ontario, Canada

    J. D. Fuller, A. McGeer & D. E. Low

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  1. J. D. Fuller
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  2. A. McGeer
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  3. D. E. Low
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Fuller, J.D., McGeer, A. & Low, D.E. Drug-resistant pneumococcal pneumonia: clinical relevance and approach to management. Eur J Clin Microbiol Infect Dis 24, 780–788 (2005). https://doi.org/10.1007/s10096-005-0059-x

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