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Resistance in Streptococcus pneumoniae

  • Mathias W. R. Pletz
  • Tobias Welte
  • Lesley McGee
Part of the Birkhäuser Advances in Infectious Diseases book series (BAID)

Abstract

Streptococcus pneumoniae is a leading cause of community-acquired lower respiratory tract infections, sinusitis, meningitis, and bloodstream infections. Pneumococci are Gram positive, encapsulated bacteria and exhibit more than 90 different capsular serotypes.

Resistance to penicillin in clinical isolates was reported anecdotally as early as 1965, but was not considered a major concern until the mid-1990s. In the 1990s, there was a tremendous global increase in resistance to penicillins and this led to the increased use of macrolides and tetracyclines to treat infections. After several years, the resistance rates to these antibiotics began to increase as well. Currently, fluoroquinolones are used most frequently to treat community-acquired respiratory infections in adults and resistance rates globally are still low.

Pneumococci are naturally competent bacteria and frequently acquire resistance by intraspecies or interspecies gene transfer. Resistance to β-lactams is due to the acquisition of different mutations within the pencillin-binding proteins that have been demonstrated to originate from the less pathogenic viridans streptococci. Other mechanisms of antibiotic resistance include enzymes and efflux pumps on mobile genetic elements (e.g. erm and mef), or resistance arising through spontaneous mutations. Clinical studies show that resistance, particularly to penicillins, is not always related to clinical failure.

The global increase in resistance rates in pneumococci is in part due to the spread of a limited number of highly sucessful multiresistant pneumococcal clones. Isolates belonging to a specific clone, defined by sequence types according to multilocus sequencing, often exhibit the same serotype. However, capsular switching due to genetic rearrangements within the same clone has been observed. The recently introduced seven-valent conjugated pneumococcal vaccine has been shown to decrease disease and carrier rates of the included serotypes. Since some of the multiresistant clones exhibit vaccine serotypes, resistance rates to penicillin, macrolides and fluoroquinolones have been decreasing since the introduction of this vaccine.

Keywords

Streptococcus Pneumoniae Antimicrob Agent Pneumococcal Pneumonia Macrolide Resistance Fluoroquinolone Resistance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Hyde TB, Gay K, Stephens DS, Vugia DJ, Pass M, Johnson S et al (2001) Macrolide resistance among invasive Streptococcus pneumoniae isolates. JAMA 286(15): 1857–1862PubMedCrossRefGoogle Scholar
  2. 2.
    Seppala H, Klaukka T, Vuopio-Varkila J, Muotiala A, Helenius H, Lager K et al (1997) The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. Finnish Study Group for Antimicrobial Resistance. N Engl J Med 337(7): 441–446PubMedCrossRefGoogle Scholar
  3. 3.
    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(7): 2903–2913PubMedCrossRefGoogle Scholar
  4. 4.
    Ho PL, Yung RW, Tsang DN, Que TL, Ho M, Seto WH et al (2001) Increasing resistance of Streptococcus pneumoniae to fluoroquinolones: results of a Hong Kong multicentre study in 2000 J Antimicrob Chemother 48(5): 659–665PubMedCrossRefGoogle Scholar
  5. 5.
    Wolter N, Smith AM, Farrell DJ, Schaffner W, Moore M, Whitney CG et al (2005) Novel mechanism of resistance to oxazolidinones, macrolides, and chloramphenicol in ribosomal protein L4 of the pneumococcus. Antimicrob Agents Chemother 49(8): 3554–3557PubMedCrossRefGoogle Scholar
  6. 6.
    Reinert RR, van der Linden M, Al-Lahham A (2005) Molecular characterization of the first telithromycin-resistant Streptococcus pneumoniae isolate in Germany. Antimicrob Agents Chemother 49(8): 3520–3522PubMedCrossRefGoogle Scholar
  7. 7.
    Jones RN, Farrell DJ, Morrissey I (2003) Quinupristin-dalfopristin resistance in Streptococcus pneumoniae: novel L22 ribosomal protein mutation in two clinical isolates from the SENTRY antimicrobial surveillance program. Antimicrob Agents Chemother 47(8): 2696–2698PubMedCrossRefGoogle Scholar
  8. 8.
    Gillis LM, White HD, Whitehurst A, Sullivan DC (2005) Vancomycin-tolerance among clinical isolates of Streptococcus pneumoniae in Mississippi during 1999-2001 Am J Med Sci 330(2): 65–68PubMedCrossRefGoogle Scholar
  9. 9.
    Castanheira M, Gales AC, Mendes RE, Jones RN, Sader HS (2004) Antimicrobial susceptibility of Streptococcus pneumoniae in Latin America: results from five years of the SENTRY Antimicrobial Surveillance Program. Clin Microbiol Infect 10(7): 645–651PubMedCrossRefGoogle Scholar
  10. 10.
    Lefevre JC, Faucon G, Sicard AM, Gasc AM (1993) DNA fingerprinting of Streptococcus pneumoniae strains by pulsed-field gel electrophoresis. J Clin Microbiol 31(10): 2724–2728PubMedGoogle Scholar
  11. 11.
    Enright MC, Spratt BG (1998) A multilocus sequence typing scheme for Streptococcus pneumoniae: identification of clones associated with serious invasive disease. Microbiology 144 (Pt 11): 3049–3060PubMedCrossRefGoogle Scholar
  12. 12.
    McGee L, McDougal L, Zhou J, Spratt BG, Tenover FC, George R et al (2001) Nomenclature of major antimicrobial-resistant clones of Streptococcus pneumoniae defined by the pneumococcal molecular epidemiology network. J Clin Microbiol 39(7): 2565–2571PubMedCrossRefGoogle Scholar
  13. 13.
    Klugman KP (2002) The successful clone: the vector of dissemination of resistance in Streptococcus pneumoniae. J Antimicrob Chemother 50 (Suppl S2): 1–5PubMedCrossRefGoogle Scholar
  14. 14.
    Tomasz A (1979) From penicillin-binding proteins to the lysis and death of bacteria: a 1979 view. Rev Infect Dis 1(3): 434–467PubMedGoogle Scholar
  15. 15.
    Zighelboim S, Tomasz A (1980) Penicillin-binding proteins of multiply antibiotic-resistant South African strains of Streptococcus pneumoniae. Antimicrob Agents Chemother 17(3): 434–442PubMedGoogle Scholar
  16. 16.
    Coffey TJ, Dowson CG, Daniels M, Spratt BG (1995) Genetics and molecular biology of beta-lactam-resistant pneumococci. Microb Drug Resist 1(1): 29–34PubMedCrossRefGoogle Scholar
  17. 17.
    Hakenbeck R (1998) Mosaic genes and their role in penicillin-resistant Streptococcus pneumoniae. Electrophoresis 19(4): 597–601PubMedCrossRefGoogle Scholar
  18. 18.
    Schrag SJ, McGee L, Whitney CG, Beall B, Craig AS, Choate ME et al (2004) Emergence of Streptococcus pneumoniae with very-high-level resistance to penicillin. Antimicrob Agents Chemother 48(8): 3016–3023PubMedCrossRefGoogle Scholar
  19. 19.
    Dessen A, Mouz N, Gordon E, Hopkins J, Dideberg O (2001) Crystal structure of PBP2x from a highly penicillin-resistant Streptococcus pneumoniae clinical isolate: a mosaic framework containing 83 mutations. J Biol Chem 276(48): 45106–45112PubMedCrossRefGoogle Scholar
  20. 20.
    Filipe SR, Tomasz A (2000) Inhibition of the expression of penicillin resistance in Streptococcus pneumoniae by inactivation of cell wall muropeptide branching genes. Proc Natl Acad Sci USA 97(9): 4891–4896PubMedCrossRefGoogle Scholar
  21. 21.
    McGee L, Klugman KP, Wasas A, Capper T, Brink A (2001) Serotype 19f multiresistant pneumococcal clone harboring two erythromycin resistance deter minants (erm(B) and mef(A)) in South Africa. Antimicrob Agents Chemother 45(5): 1595–1598PubMedCrossRefGoogle Scholar
  22. 22.
    Edelstein PH (2004) Pneumococcal resistance to macrolides, lincosamides, ketolides, and streptogramin B agents: molecular mechanisms and resistance phenotypes. Clin Infect Dis 38 (Suppl 4): S322–327CrossRefGoogle Scholar
  23. 23.
    Pan XS, Ambler J, Mehtar S, Fisher LM (1996) Involvement of topoisomerase IV and DNA gyrase as ciprofloxacin targets in Streptococcus pneumoniae. Antimicrob Agents Chemother 40(10): 2321–2326PubMedGoogle Scholar
  24. 24.
    Balsalobre L, Ferrandiz MJ, Linares J, Tubau F, de la Campa AG (2003) Viridans group streptococci are donors in horizontal transfer of topoisomerase IV genes to Streptococcus pneumoniae. Antimicrob Agents Chemother 47(7): 2072–2081PubMedCrossRefGoogle Scholar
  25. 25.
    Bast DJ, de Azavedo JC, Tam TY, Kilburn L, Duncan C, Mandell LA et al (2001) Interspecies recombination contributes minimally to fluoroquinolone resistance in Streptococcus pneumoniae. Antimicrob Agents Chemother 45(9): 2631–2634PubMedCrossRefGoogle Scholar
  26. 26.
    Pletz MW, McGee L, Beall B, Whitney CG, Klugman KP (2005) Interspecies recombination in type II topoisomerase genes is not a major cause for fluoroquinolone resistance in invasive Streptococcus pneumoniae isolates in the United States. Antimicrob Agents Chemother 49: 779–780PubMedCrossRefGoogle Scholar
  27. 27.
    Gill M, Brenwald NP, Wise R (1999) Identification of an efflux pump gene, pmrA, associated with fluoroquinolone resistance in Streptococcus pneumoniae. Antimicrob Agents Chemother 43: 187–189PubMedCrossRefGoogle Scholar
  28. 28.
    Farrell DJ, Felmingham D (2005) The PROTEKT global study (year 4) demonstrates a continued lack of resistance development to telithromycin in Streptococcus pneumoniae. J Antimicrob Chemother 56(4): 795–797PubMedCrossRefGoogle Scholar
  29. 29.
    Canu A, Malbruny B, Coquemont M, Davies TA, Appelbaum PC, Leclercq R (2002) Diversity of ribosomal mutations conferring resistance to macrolides, clindamycin, streptogramin, and telithromycin in Streptococcus pneumoniae. Antimicrob Agents Chemother 46(1): 125–131PubMedCrossRefGoogle Scholar
  30. 30.
    Faccone D, Andres P, Galas M, Tokumoto M, Rosato A, Corso A (2005) Emergence of a Streptococcus pneumoniae clinical isolate highly resistant to telithromycin and fluoroquinolones. J Clin Microbiol 43(11): 5800–5803PubMedCrossRefGoogle Scholar
  31. 31.
    Hancock RE (1997) Peptide antibiotics. Lancet 349(9049): 418–422PubMedCrossRefGoogle Scholar
  32. 32.
    Feldman C (2004) Clinical relevance of antimicrobial resistance in the management of pneumococcal community-acquired pneumonia. J Lab Clin Med 143(5): 269–283PubMedCrossRefGoogle Scholar
  33. 33.
    Craig WA (1998) Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis 26(1): 1–10; quiz 11-12PubMedGoogle Scholar
  34. 34.
    Nuermberger E, Bishai WR (2004) The clinical significance of macrolide-resistant Streptococcus pneumoniae: it’s all relative. Clin Infect Dis 38(1): 99–103PubMedCrossRefGoogle Scholar
  35. 35.
    Perez-Trallero E, Marimon JM, Iglesias L, Larruskain J (2003) Fluoroquinolone and macrolide treatment failure in pneumococcal pneumonia and selection of multidrug-resistant isolates. Emerg Infect Dis 9(9): 1159–1162PubMedGoogle Scholar
  36. 36.
    Ewig S, Ruiz M, Torres A, Marco F, Martinez JA, Sanchez M et al (1999) Pneumonia acquired in the community through drug-resistant Streptococcus pneumoniae. Am J Respir Crit Care Med 159(6): 1835–1842PubMedGoogle Scholar
  37. 37.
    Goldstein EJ, Garabedian-Ruffalo SM (2002) Widespread use of fluoroquinolones versus emerging resistance in pneumococci. Clin Infect Dis 35(12): 1505–1511PubMedCrossRefGoogle Scholar
  38. 38.
    Davidson R, Cavalcanti R, Brunton JL, Bast DJ, de Azavedo JC, Kibsey P et al (2002) Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N Engl J Med 346(10): 747–750PubMedCrossRefGoogle Scholar
  39. 39.
    Fuller JD, Low DE (2005) A review of Streptococcus pneumoniae infection treatment failures associated with fluoroquinolone resistance. Clin Infect Dis 41(1): 118–121PubMedCrossRefGoogle Scholar
  40. 40.
    Lim S, Bast D, McGeer A, de Azavedo J, Low DE (2003) Antimicrobial susceptibility breakpoints and first-step parC mutations in Streptococcus pneumoniae: redefining fluoroquinolone resistance. Emerg Infect Dis 9(7): 833–837PubMedGoogle Scholar
  41. 41.
    Gillespie SH, Voelker LL, Ambler JE, Traini C, Dickens A (2003) Fluoroquinolone resistance in Streptococcus pneumoniae: evidence that gyrA mutations arise at a lower rate and that mutation in gyrA or parC predisposes to further mutation. Microb Drug Resist 9(1): 17–24PubMedCrossRefGoogle Scholar
  42. 42.
    Croisier D, Etienne M, Bergoin E, Charles PE, Lequeu C, Piroth L et al (2004) Mutant selection window in levofloxacin and moxifloxacin treatments of experimental pneumococcal pneumonia in a rabbit model of human therapy. Antimicrob Agents Chemother 48(5): 1699–1707PubMedCrossRefGoogle Scholar
  43. 43.
    Pletz MW, Shergill AP, McGee L, Beall B, Whitney C, Klugman KP (2006) Prevalence of first-step mutants among levofloxacin-susceptible invasive Streptococcus pneumoniae in the United States. Antimicrob Agents Chemother 50(4): 1561–1563PubMedCrossRefGoogle Scholar
  44. 44.
    Whitney CG, Farley MM, Hadler J, Harrison LH, Bennett NM, Lynfield R et al (2003) Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med 348(18): 1737–1746PubMedCrossRefGoogle Scholar
  45. 45.
    McEllistrem MC, Adams JM, Patel K, Mendelsohn AB, Kaplan SL, Bradley JS et al (2005) Acute otitis media due to penicillin-nonsusceptible Streptococcus pneumoniae before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis 40(12): 1738–1744PubMedCrossRefGoogle Scholar
  46. 46.
    Stephens DS, Zughaier SM, Whitney CG, Baughman WS, Barker L, Gay K et al (2005) Incidence of macrolide resistance in Streptococcus pneumoniae after introduction of the pneumococcal conjugate vaccine: population-based assessment. Lancet 365(9462): 855–863PubMedCrossRefGoogle Scholar
  47. 47.
    Pletz MW, McGee L, Jorgensen J, Beall B, Facklam RR, Whitney CG et al (2004) Levofloxacin-resistant invasive Streptococcus pneumoniae in the United States: evidence for clonal spread and the impact of conjugate pneumococcal vaccine. Antimicrob Agents Chemother 48(9): 3491–3497PubMedCrossRefGoogle Scholar
  48. 48.
    Porat N, Arguedas A, Spratt BG, Treffler R, Brilla E, Loaiza C (2004) Emergence of penicillin-nonsusceptible Streptococcus pneumoniae clones expressing serotypes not present in the antipneumococcal conjugate vaccine. J Infect Dis190: 2154–2161PubMedCrossRefGoogle Scholar
  49. 49.
    Pai R, Moore MR, Pilishvili T, Gertz RE, Whitney CG, Beall B and the Active Bacterial Core Surveillance Team (2005) Postvaccine genetic structure of Streptococcus pneumoniae serotype 19A from children in the United States. J Infect Dis 192: 1988–1995PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 2007

Authors and Affiliations

  • Mathias W. R. Pletz
    • 1
  • Tobias Welte
    • 1
  • Lesley McGee
    • 2
  1. 1.Department of Respiratory MedicineHannover Medical SchoolHannoverGermany
  2. 2.Hubert Department of Global HealthEmory UniversityAtlantaUSA

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