Skip to main content

Advertisement

Log in

Impact of antimicrobial resistance on the treatment of invasive pneumococcal infections

  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Infectious diseases, such as pneumococcal pneumonia, which were almost invariably lethal in the pre-antibiotic era, caused radically less mortality with the advent of antimicrobial chemotherapy. However, the use, misuse, and abuse of these agents have led to the emergence of antimicrobial resistance. In the past, pneumococci were all exquisitely sensitive to penicillin G. By the late 1960s, penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) was being described. Since then, this problem has achieved epidemic proportions in many areas of the world, including the United States. Many experts no longer consider penicillin an acceptable therapy for patients suspected of having invasive pneumococcal disease, especially if the central nervous system (CNS) is involved. Recommendations for therapy are based on theoretical concerns, in vitro susceptibility testing, animal data, and a few, scattered reports of penicillin failure in patients with invasive disease.

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.

Similar content being viewed by others

References and Recommended Reading

  1. Campbell GD, Silberman R: Drug-resistant Streptococcus pneumoniae. Clin Infect Dis 1998, 26:1188–1195. This paper provides an excellent review of the epidemiology, diagnosis, risk factors, preventive strategies and therapy of resistant pneumococcal infections.

    PubMed  Google Scholar 

  2. Bryan CS: Treatment of pneumococcal pneumonia: the case for penicillin G. Am J Med 1999, 107:63S-68S.

    Article  PubMed  CAS  Google Scholar 

  3. Ball P: Therapy for pneumococcal infections at the millennium: doubts and certainties. Am J Med 1999, 107:77S-85S.

    Article  PubMed  CAS  Google Scholar 

  4. Butler JC, Cetron MS: Pneumococcal drug resistance: the new “special enemy of old age”. Clin Infect Dis 1999, 28:730–735.

    PubMed  CAS  Google Scholar 

  5. National Committee for Clinical Laboratory Standards (NCCLS). Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically: approved standard. Document M7-A4 edn 3. NCCLS. Wayne, PA; 1997.

  6. Barry AL: Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in North America. Am J Med 1999, 107:28S-33S.

    Article  PubMed  CAS  Google Scholar 

  7. Tomasz A: New faces of an old pathogen: emergence and spread of multidrug-resistant Streptococcus pneumoniae. Am J Med 1999, 107:55S-62S. This outstanding paper reviews historical aspects of the global dissemination of penicillin-resistant strains of S. pneumoniae and the mechanisms of penicillin resistance.

    Article  PubMed  CAS  Google Scholar 

  8. Jacobs MR: Drug-resistant Streptococcus pneumoniae: rational antibiotic choices. Am J Med 1999, 106:19S-25S.

    Article  PubMed  CAS  Google Scholar 

  9. Thornsberry C, Hickey ML, Kahn J, et al.: Surveillance of antimicrobial resistance among respiratory tract pathogens in the United States, 1997 to 1998. Drugs 1999, 58(Suppl 2):361–363.

    Article  CAS  Google Scholar 

  10. Song J, Lee NY, Ichiyama S, et al.: Spread of Streptococcus pneumoniae in Asian Countries: Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study. Clin Infect Dis 1999, 28:1206–1211. This important epidemiologic study reveals areas with the highest incidence of PNSP in the world.

    PubMed  CAS  Google Scholar 

  11. Zhanel GG, Karlowsky JA, Palatnick L, et al.: Prevalence of antimicrobial resistance in respiratory tract isolates of Streptococcus pneumoniae: results of a Canadian national surveillance study. Antimicrob Agents Chemother 1999, 43:2504–2509.

    PubMed  CAS  Google Scholar 

  12. Winston LG, Perlman JL, Rose DA, Gerberding JL: Penicillinnonsusceptible Streptococcus pneumoniae at San Francisco General Hospital. Clin Infect Dis 1999, 29:580–585.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  14. CDC: Geographic variation in penicillin resistance in Streptococcus pneumoniae—selected sites, United States, 1997. MMWR 1997, 48(30):656–661.

    Google Scholar 

  15. Chen DK, McGeer A, De Azavedo JC, Low DE: Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. N Engl J Med 1999, 341:233–239. This large multicenter survey alerts clinicians to the increasing prevalence of fluoroquinolone resistance among pneumococci in Canada as a result of the increased use of this class of drugs.

    Article  PubMed  CAS  Google Scholar 

  16. Linares J, De La Campa AG, Pallares R: Fluoroquinolone resistance in Streptococcus pneumoniae [letter]. N Engl J Med 1999, 341:1546–1547.

    Article  PubMed  CAS  Google Scholar 

  17. Odland BA, Jones RN, Verhoef J, et al.: Antimicrobial activity of gatifloxacin (AM-1155, CG5501), and four other quinolones tested against 2,284 recent clinical strains of Streptococcus pneumoniae from Europe, Latin America, Canada and the United States. The SENTRY Antimicrobial Surveillance Group (Americas and Europe). Diag Microbiol Infect Dis 1999, 34:315–320.

    Article  CAS  Google Scholar 

  18. Invasive Bacterial Infection Surveillance (IBIS) Group, International Clinical Epidemiology Network (INCLEN): Prospective multicentre hospital surveillance of Streptococcus pneumoniae in India. Lancet 1999, 353:1216–1221. This four-year survey of six hospitals in India reveals a record low incidence of PNSP (penicillin-nonsusceptible S. pneumoniae) strains.

    Article  Google Scholar 

  19. Goldstein FW: Penicillin-resistant Streptococcus pneumoniae: selection by both β-lactam and non-β-lactam antibiotics. J Antimicrob Chemother 1999, 44:141–144.

    Article  PubMed  CAS  Google Scholar 

  20. Ko AI, Reis JN, Coppola SJ, et al.: Clonally related penicillinnonsusceptible Streptococcus pneumoniae serotype 14 from cases of meningitis in Salvador, Brazil. Clin Infect Dis 2000, 30:78–86.

    Article  PubMed  CAS  Google Scholar 

  21. Oster P, Zanchi A, Cresti S, et al.: Patterns of macrolide resistance determinants among community-acquired Streptococcus pneumoniae isolates over a 5-year period of decreased macrolide susceptibility rates. Antimicrob Agents Chemother 1999, 43:2510–2512.

    PubMed  CAS  Google Scholar 

  22. Padayachee T, Klugman KP: Molecular basis of rifampin resistance in Streptococcus pneumoniae. Antimicrob Agents Chemother 1999, 43:2361–2365.

    PubMed  CAS  Google Scholar 

  23. Morrisey I, George J: Activities of fluoroquinolones against Streptococcus pneumoniae type II topoisomerases purified as recombinant proteins. Antimicrob Agents Chemother 1999, 43:2579–2585.

    Google Scholar 

  24. Fine MJ, Smith MA, Carson CA, et al.: Prognosis and outcomes of patients with community-acquired pneumonia: a meta-analysis. JAMA 1996, 275:134–141. This article is a comprehensive review of etiology, prognosis and course of community-acquired pneumonia.

    Article  PubMed  CAS  Google Scholar 

  25. Friedland JR: Comparison of the response to antimicrobial therapy of penicillin-resistant and penicillin-susceptible pneumococcal disease. Pediatr Infect Dis J 1995, 14:885–890.

    Article  PubMed  CAS  Google Scholar 

  26. Pallares R, Linares J, Vadillo M, et al.: Resistance to penicillin and cephalosporin and mortality from severe pneumococcal pneumonia in Barcelona, Spain. N Engl J Med 1995, 333:474–480.

    Article  PubMed  CAS  Google Scholar 

  27. Plouffe JF, Breiman FR, Facklam RR: Bacteremia with Streptococcus pneumoniae. Implications for therapy and prevention. JAMA 1996, 275:194–198.

    Article  PubMed  CAS  Google Scholar 

  28. Mounedji A, Beilouny B, Cahen P, et al.: Penicillin resistance among 75 patients with pneumococcal pneumonia [abstract]. Am J Respir Crit Care Med 2000, 161:A650.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  30. Niederman MS, Bass JB Jr., Campbell GD Jr., et al.: Guidelines for the initial management of adults with community-acquired pneumonia: diagnosis, assessment of severity, and initial antimicrobial therapy. Am Rev Resp Dis 1993, 148:1418–1426. American Thoracic Society’s recommendations for diagnosis and treatment of community-acquired pneumonia.

    PubMed  CAS  Google Scholar 

  31. Bartlett JG, Breiman RF, Mandell LA, et al.: Communityacquired pneumonia in adults: guidelines for management. Clin Infect Dis 1998, 26:811–838. Infectious Diseases Society of America’s recommendations for diagnosis and treatment of community-acquired pneumonia.

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

  33. Friedland JR, McCracken GH Jr: Management of infections caused by antibiotic-resistant Streptococcus pneumoniae. N Engl J Med 1994, 331:377–382.

    Article  PubMed  CAS  Google Scholar 

  34. Mandell LA: Antibiotics for pneumonia therapy. Med Clin North Am 1994, 78:997–1014.

    PubMed  CAS  Google Scholar 

  35. Bryant RE, Salmon CJ: Pleural empyema. Clin Infect Dis 1996, 22:747–762.

    PubMed  CAS  Google Scholar 

  36. Aubier M, Lode H, Gialdroni-Grassi G, et al.: Sparfloxacin for the treatment of community-acquired pneumonia: a pooled data analysis of two studies. J Antimicrob Chemother 1996, 37(Suppl A) 73–82.

    PubMed  CAS  Google Scholar 

  37. Aubier M, Verster R, Regamcy C, et al.: Once-daily sparfloxacin versus high-dosage amoxicillin in the treatment of community-acquired, suspected pneumococcal pneumonia in adults. Sparfloxacin European Study Group. Clin Infect Dis 1998, 26:1312–1320.

    PubMed  CAS  Google Scholar 

  38. George J, Morrissey I: The bactericidal activity of levofloxacin compared with ofloxacin, D-ofloxacin, ciprofloxacin, sparfloxacin and cefotaxime against Streptococcus pneumoniae. J Antimicrob Chemother 1997, 39:719–723.

    Article  PubMed  CAS  Google Scholar 

  39. Tunkel AR, Scheld WM: Acute bacterial meningitis. Lancet 1995, 346:1675–1680.

    Article  PubMed  CAS  Google Scholar 

  40. Saez-Llorens X, McCracken GH Jr: Antimicrobial and anti-inflammatory treatment of bacterial meningitis. Infect Dis Clin North Am 1999, 13:619–636.

    Article  PubMed  CAS  Google Scholar 

  41. Kaplan SL, Mason EO: Management of infections due to antibiotic-resistant Streptococcus pneumoniae. Clin Microbiol Rev 1998, 11:628–644.

    PubMed  CAS  Google Scholar 

  42. Lutsar I, McCracken GH Jr., Friedland IR: Antibiotic pharmacodynamics in cerebrospinal fluid. Clin Infect Dis 1998, 27:1117–1129.

    PubMed  CAS  Google Scholar 

  43. Tunkel AR, Scheld WM: Acute meningitis. In Principles and Practice of Infectious Diseases edn 5. Edited by Mandell GL, Bennet JE, Dolin R. Philadelphia: Churchill-Livingstone; 1999:959–997. This state-of-the-art review of acute meningitis includes an excellent section on pathogenesis and pathophysiology. Epidemiology, diagnosis and treatment are discussed in detail for the different etiologies of acute meningitis.

    Google Scholar 

  44. Fitoussi F, Doit C, Benali K, et al.: Comparative in-vitro killing activities of meropenem, imipenem, ceftriaxone and ceftriaxone plus vancomycin at clinically achievable cerebrospinal fluid concentrations against penicillinresistant Streptococcus pneumoniae isolates from children with meningitis. Antimicrob Agents Chemother 1998, 42:942–944.

    PubMed  CAS  Google Scholar 

  45. Cabellos C, Martinez-Lacasa J, Tubau F, et al.: Evaluation of combined ceftriaxone and dexamethasone therapy in experimental cephalosporin-resistant pneumococcal meningitis. J Antimicrob Chemother 2000, 45:315–320.

    Article  PubMed  CAS  Google Scholar 

  46. Ahmed A, Jafri H, Lutsar I, et al.: Pharmacodynamics of vancomycin for the treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother 1999, 43:876–881.

    PubMed  CAS  Google Scholar 

  47. Ahmed A: A critical evaluation of vancomycin for treatment of bacterial meningitis. Pediatr Infect Dis J 1997, 16:895–903.

    Article  PubMed  CAS  Google Scholar 

  48. Nau R, Wellmer A, Soto A, et al.: Rifampin reduces early mortality in experimental Streptococcus pneumoniae meningitis. J Infect Dis 1999, 179:1557–1560.

    Article  PubMed  CAS  Google Scholar 

  49. Fitoussi F, Doit C, Geslin P, Bingen E: Killing activities of trovafloxacin alone and in combination with β-lactam agents, rifampin, or vancomycin against Streptococcus pneumoniae isolates with various susceptibilities to extended-spectrum cephalosporins at concentrations clinically achievable in cerebrospinal fluid. Antimicrob Agents Chemother 1999, 43:2372–2375.

    PubMed  CAS  Google Scholar 

  50. Schmidt H, Dalhoff A, Stuertz K, et al.: Moxifloxacin in the therapy of experimental pneumococcal meningitis. Antimicrob Agents Chemother 1999, 42:1397–1401.

    Google Scholar 

  51. Ostergaard C, Sorensen TK, Knudsen JD, Fridmot-Moller N: Evaluation of moxifloxacin, a new 8-methoxyquinolone, for treatment of meningitis caused by a penicillin-resistant pneumococcus in rabbits. Antimicrob Agents Chemother 1998, 42:1706–1712.

    PubMed  CAS  Google Scholar 

  52. Lutsar I, Friedland IR, Wubbel L, et al.: Pharmacodynamics of gatifloxacin in cerebrospinal fluid in experimental cephalosporin-resistant pneumococcal meningitis. Antimicrob Agents Chemother 1998, 42:2650–2655.

    PubMed  CAS  Google Scholar 

  53. Rodoni D, Hanni F, Gerber CM, et al.: Trovafloxacin in combination with vancomycin against penicillin-resistant pneumococci in the rabbit meningitis model. Antimicrob Agents Chemother 1999, 43:963–965.

    PubMed  CAS  Google Scholar 

  54. Tarasi A, Capone A, Tarasi D, et al.: Comparative in-vitro activity of moxifloxacin, penicillin, ceftriaxone and ciprofloxacin against pneumococci isolated from meningitis. J Antimicrob Chemother 1999, 43:833–835.

    Article  PubMed  CAS  Google Scholar 

  55. Lewandowski T, Berry V, Demarsh P, et al.: In-vivo activity of gemifloxacin (SB-265805) in an infant rat meningitis model with Streptococcus pneumoniae [abstract]. In Proceedings of the Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, 1999:82.

  56. Ortqvist A: Pneumococcal disease in Sweden: experiences and current situation. Am J Med 1999, 107:44S-49S.

    Article  PubMed  CAS  Google Scholar 

  57. Butler JC, Shapiro ED, Carlone GM: Pneumococcal vaccines: history, current status and future directions. Am J Med 1999, 107:69S-76S.

    Article  PubMed  CAS  Google Scholar 

  58. Food and Drug Administration: First pneumococcal vaccine approved for infants and toddlers [press release]. Rockville, MD: U.S. Department of Health and Human Services; February 17, 2000. Available on-line at

    Google Scholar 

  59. Black S, Shinefield H, Fireman B, et al.: Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J 2000, 19:187–195. This large study provides compelling data on the efficacy of the new heptavalent conjugate vaccine in preventing invasive pneumococcal disease in children.

    Article  PubMed  CAS  Google Scholar 

  60. Lieu TA, Ray GT, Black SB, et al.: Projected cost-effectiveness of pneumococcal conjugate vaccination of healthy infants and young children. JAMA 2000, 283:1460–1468. This is the first study to analyze the cost-effectiveness of the heptavalent pneumococcal conjugate vaccine, compared with other preventive health interventions.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rocha, P., Baleeiro, C. & Tunkel, A.R. Impact of antimicrobial resistance on the treatment of invasive pneumococcal infections. Curr Infect Dis Rep 2, 399–408 (2000). https://doi.org/10.1007/s11908-000-0066-0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11908-000-0066-0

Keywords

Navigation