Advertisement

Drugs

, Volume 67, Issue 16, pp 2355–2382 | Cite as

Multidrug-Resistant Streptococcus pneumoniae Infections

Current and Future Therapeutic Options
  • Françoise Van Bambeke
  • René R. Reinert
  • Peter C. Appelbaum
  • Paul M. Tulkens
  • Willy E. Peetermans
Review Article

Abstract

Antibacterial resistance in Streptococcus pneumoniae is increasing worldwide, affecting principally β-lactams and macrolides (prevalence ranging between ≈1% and 90% depending on the geographical area). Fluoroquinolone resistance has also started to emerge in countries with high level of antibacterial resistance and consumption. Of more concern, 40% of pneumococci display multi-drug resistant phenotypes, again with highly variable prevalence among countries.

Infections caused by resistant pneumococci can still be treated using first-line antibacterials (β-lactams), provided the dosage is optimised to cover less susceptible strains. Macrolides can no longer be used as monotherapy, but are combined with β-lactams to cover intracellular bacteria. Ketolides could be an alternative, but toxicity issues have recently restricted the use of telithromycin in the US. The so-called respiratory fluoroquinolones offer the advantages of easy administration and a spectrum covering extracellular and intracellular pathogens. However, their broad spectrum raises questions regarding the global risk of resistance selection and their safety profile is far from optimal for wide use in the community. For multi-drug resistant pneumococci, ketolides and fluoroquinolones could be considered. A large number of drugs with activity against these multi-drug resistant strains (cephalosporins, carbapenems, glycopeptides, lipopeptides, ketolides, lincosamides, oxazolidinones, glycylcyclines, quinolones, deformylase inhibitors) are currently in development. Most of them are only new derivatives in existing classes, with improved intrinsic activity or lower susceptibility to resistance mechanisms. Except for the new fluoroquinolones, these agents are also primarily targeted towards methicillin-resistant Staphylococcus aureus infections; therefore, demonstration of their clinical efficacy in the management of pneumococcal infections is still awaited.

Keywords

Minimum Inhibitory Concentration Pneumococcal Disease Pneumococcal Pneumonia Telithromycin Ceftaroline 
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.

Notes

Acknowledgements

Dr Van Bambeke is Maître de Recherches of the Belgian Fonds de la Recherche Scientifique - Fonds National de la Recherche Scientifique. Dr Van Bambeke has acted as a consultant to Targanta, Dr Reinert has received honoraria for consultancies from Wyeth and GSK, and a research grant from Wyeth. Drs Appelbaum, Tulkens and Peetermans have no conflicts of interest that are directly relevant to the content of this review. No sources of funding were used to assist in the preparation of this review.

Supplementary material

40265_2012_67162355_MOESM1_ESM.pdf (145 kb)
Supplementary material, approximately 149 KB.

References

  1. 1.
    Musher DM. Infections caused by Streptococcus pneumoniae: clinical spectrum, pathogenesis, immunity, and treatment. Clin Infect Dis 1992 Apr; 14(4): 801–7PubMedGoogle Scholar
  2. 2.
    Ortqvist A, Hedlund J, Kalin M. Streptococcus pneumoniae: epidemiology, risk factors, and clinical features. Semin Respir Crit Care Med 2005 Dec; 26(6): 563–74PubMedGoogle Scholar
  3. 3.
    Appelbaum PC. Resistance among Streptococcus pneumoniae: implications for drug selection. Clin Infect Dis 2002 Jun 15; 34(12): 1613–20PubMedGoogle Scholar
  4. 4.
    Lynch III JP, Zhanel GG. Escalation of antimicrobial resistance among Streptococcus pneumoniae: implications for therapy. Semin Respir Crit Care Med 2005 Dec; 26(6): 575–616PubMedGoogle Scholar
  5. 5.
    Hakenbeck R, Briese T, Chalkley L, et al. Antigenic variation of penicillin-binding proteins from penicillin-resistant clinical strains of Streptococcus pneumoniae. J Infect Dis 1991 Aug; 164(2): 313–9PubMedGoogle Scholar
  6. 6.
    Reinert RR. Clinical efficacy of ketolides in the treatment of respiratory tract infections. J Antimicrob Chemother 2004 Jun; 53(6): 918–27PubMedGoogle Scholar
  7. 7.
    Sutcliffe J, Tait-Kamradt A, Wondrack L. Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by an efflux system. Antimicrob Agents Chemother 1996 Aug; 40(8): 1817–24PubMedGoogle Scholar
  8. 8.
    Canu A, Malbruny B, Coquemont M, et al. Diversity of ribosomal mutations conferring resistance to macrolides, clindamycin, streptogramin, and telithromycin in Streptococcus pneumoniae. Antimicrob Agents Chemother 2002 Jan; 46(1): 125–31PubMedGoogle Scholar
  9. 9.
    Depardieu F, Courvalin P. Mutation in 23S rRNA responsible for resistance to 16-membered macrolides and streptogramins in Streptococcus pneumoniae. Antimicrob Agents Chemother 2001 Jan; 45(1): 319–23PubMedGoogle Scholar
  10. 10.
    Reinert RR, Wild A, Appelbaum P, et al. Ribosomal mutations conferring resistance to macrolides in Streptococcus pneumoniae clinical strains isolated in Germany. Antimicrob Agents Chemother 2003 Jul; 47(7): 2319–22PubMedGoogle Scholar
  11. 11.
    Tait-Kamradt A, Davies T, Cronan M, et al. Mutations in 23S rRNA and ribosomal protein L4 account for resistance in pneumococcal strains selected in vitro by macrolide passage. Antimicrob Agents Chemother 2000 Aug; 44(8): 2118–25PubMedGoogle Scholar
  12. 12.
    Pan XS, Ambler J, Mehtar S, et al. Involvement of topoisomerase IV and DNA gyrase as ciprofloxacin targets in Streptococcus pneumoniae. Antimicrob Agents Chemother 1996 Oct; 40(10): 2321–6PubMedGoogle Scholar
  13. 13.
    Jones ME, Critchley IA, Karlowsky JA, et al. In vitro activities of novel nonfluorinated quinolones PGE 9262932 and PGE 9509924 against clinical isolates of Staphylococcus aureus and Streptococcus pneumoniae with defined mutations in DNA gyrase and topoisomerase IV. Antimicrob Agents Chemother 2002 Jun; 46(6): 1651–7PubMedGoogle Scholar
  14. 14.
    Van Bambeke F, Michot JM, Van Eldere J, et al. Quinolones in 2005: an update. Clin Microbiol Infect 2005 Apr; 11(4): 256–80PubMedGoogle Scholar
  15. 15.
    Gill MJ, Brenwald NP, Wise R. Identification of an efflux pump gene, pmrA, associated with fluoroquinolone resistance in Streptococcus pneumoniae. Antimicrob Agents Chemother 1999 Jan; 43(1): 187–9PubMedGoogle Scholar
  16. 16.
    Marrer E, Schad K, Satoh AT, et al. Involvement of the putative ATP-dependent efflux proteins PatA and PatB in fluoroquinolone resistance of a multidrug-resistant mutant of Streptococcus pneumoniae. Antimicrob Agents Chemother 2006 Feb; 50(2): 685–93PubMedGoogle Scholar
  17. 17.
    Coffey TJ, Dowson CG, Daniels M, et al. Horizontal transfer of multiple penicillin-binding protein genes, and capsular biosynthetic genes, in natural populations of Streptococcus pneumoniae. Mol Microbiol 1991 Sep; 5(9): 2255–60PubMedGoogle Scholar
  18. 18.
    Widdowson CA, Klugman KP. Molecular mechanisms of resistance to commonly used non-betalactam drugs in Streptococcus pneumoniae. Semin Respir Infect 1999 Sep; 14(3): 255–68PubMedGoogle Scholar
  19. 19.
    Syrogiannopoulos GA, Grivea IN, Tait-Kamradt A, et al. Identification of an erm(A) erythromycin resistance methylase gene in Streptococcus pneumoniae isolated in Greece. Antimicrob Agents Chemother 2001 Jan; 45(1): 342–4PubMedGoogle Scholar
  20. 20.
    Meka VG, Gold HS. Antimicrobial resistance to linezolid. Clin Infect Dis 2004 Oct 1; 39(7): 1010–5PubMedGoogle Scholar
  21. 21.
    Clinical and Laboratory Standards Institute. CLSI guidelines [online]. Available from URL: http://www.clsi.org/source/orders/index.cfm?section=Shop&task=3&CATEGORY=MI&-PRODUCT_TYPE=SALES&SKU=M100S17E [Accessed 2007 Sep 11]
  22. 22.
    European Committee on Antimicrobial Susceptibility Testing [online]. Available from URL: http://www.escmid.org [Accessed 2007 Sep 11]
  23. 23.
    Schurek KN, Adam HJ, Hoban DJ, et al. Call for the international adoption of microbiological breakpoints for fluoroquinolones and Streptococcus pneumoniae. Int J Antimicrob Agents 2006 Sep; 28(3): 266–9PubMedGoogle Scholar
  24. 24.
    Kariuki S, Muyodi J, Mirza B, et al. Antimicrobial susceptibility in community-acquired bacterial pneumonia in adults. East Afr Med J 2003 Apr; 80(4): 213–7PubMedGoogle Scholar
  25. 25.
    Valles X, Flannery B, Roca A, et al. Serotype distribution and antibiotic susceptibility of invasive and nasopharyngeal isolates of Streptococcus pneumoniae among children in rural Mozambique. Trop Med Int Health 2006 Mar; 11(3): 358–66PubMedGoogle Scholar
  26. 26.
    Liebowitz LD, Slabbert M, Huisamen A. National surveillance programme on susceptibility patterns of respiratory pathogens in South Africa: moxifloxacin compared with eight other antimicrobial agents. J Clin Pathol 2003 May; 56(5): 344–7PubMedGoogle Scholar
  27. 27.
    Schito GC, Felmingham D. Susceptibility of Streptococcus pneumoniae to penicillin, azithromycin and telithromycin (PROTEKT 1999–2003). Int J Antimicrob Agents 2005 Dec; 26(6): 479–85PubMedGoogle Scholar
  28. 28.
    Mendes C, Marin ME, Quinones F, et al. Antibacterial resistance of community-acquired respiratory tract pathogens recovered from patients in Latin America: results from the PROTEKT surveillance study (1999–2000). Braz J Infect Dis 2003 Feb; 7(1): 44–61PubMedGoogle Scholar
  29. 29.
    Canton R, Morosini M, Enright MC, et al. Worldwide incidence, molecular epidemiology and mutations implicated in fluoroquinolone-resistant Streptococcus pneumoniae: data from the global PROTEKT surveillance programme. J Antimicrob Chemother 2003 Dec; 52(6): 944–52PubMedGoogle Scholar
  30. 30.
    Bonofiglio L, Ojeda MI, de Mier C, et al. Phenotypic and genotypic characterization of macrolide resistant Streptococcus pneumoniae recovered from adult patients with community-acquired pneumonia in an Argentinian teaching hospital. Int J Antimicrob Agents 2005 Mar; 25(3): 260–3PubMedGoogle Scholar
  31. 31.
    Koeth LM, Felmingham D, Jacobs MR, et al. Antimicrobial resistance of Streptococcus pneumoniae and Haemophilus influenzae in Sao Paulo, Brazil from 1996 to 2000. Int J Antimicrob Agents 2004 Apr; 23(4): 356–61PubMedGoogle Scholar
  32. 32.
    Ochoa TJ, Rupa R, Guerra H, et al. Penicillin resistance and serotypes/serogroups of Streptococcus pneumoniae in nasopharyngeal carrier children younger than 2 years in Lima, Peru. Diagn Microbiol Infect Dis 2005 May; 52(1): 59–64PubMedGoogle Scholar
  33. 33.
    Zhanel GG, Palatnick L, Nichol KA, et al. Antimicrobial resistance in respiratory tract Streptococcus pneumoniae isolates: results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002. Antimicrob Agents Chemother 2003 Jun; 47(6): 1867–74PubMedGoogle Scholar
  34. 34.
    Powis J, McGeer A, Green K, et al. In vitro antimicrobial susceptibilities of Streptococcus pneumoniae clinical isolates obtained in Canada in 2002. Antimicrob Agents Chemother 2004 Sep; 48(9): 3305–11PubMedGoogle Scholar
  35. 35.
    Jenkins SG, Farrell DJ, Patel M, et al. Trends in anti-bacterial resistance among Streptococcus pneumoniae isolated in the USA, 2000–2003: PROTEKT US years 1–3. J Infect 2005 Dec; 51(5): 355–63PubMedGoogle Scholar
  36. 36.
    Doern GV, Richter SS, Miller A, et al. Antimicrobial resistance among Streptococcus pneumoniae in the United States: have we begun to turn the corner on resistance to certain antimicrobial classes? Clin Infect Dis 2005 Jul 15; 41(2): 139–48PubMedGoogle Scholar
  37. 37.
    Draghi DC, Jones ME, Sahm DF, et al. Geographically-based evaluation of multidrug resistance trends among Streptococcus pneumoniae in the USA: findings of the FAST surveillance initiative (2003–2004). Int J Antimicrob Agents 2006 Dec; 28(6): 525–31PubMedGoogle Scholar
  38. 38.
    Ho PL, Que TL, Chiu SS, et al. Fluoroquinolone and other antimicrobial resistance in invasive pneumococci, Hong Kong, 1995–2001. Emerg Infect Dis 2004 Jul; 10(7): 1250–7PubMedGoogle Scholar
  39. 39.
    Yamaguchi K, Ohno A. Investigation of the susceptibility trends in Japan to fluoroquinolones and other antimicrobial agents in a nationwide collection of clinical isolates: a longitudinal analysis from 1994 to 2002. Diagn Microbiol Infect Dis 2005 Jun; 52(2): 135–43PubMedGoogle Scholar
  40. 40.
    Inoue M, Kaneko K, Akizawa K, et al. Antimicrobial susceptibility of respiratory tract pathogens in Japan during PROTEKT years 1–3 (1999–2002). J Infect Chemother 2006 Feb; 12(1): 9–21PubMedGoogle Scholar
  41. 41.
    Oishi K, Yoshimine H, Watanabe H, et al. Drug-resistant genes and serotypes of pneumococcal strains of community-acquired pneumonia among adults in Japan. Respirology 2006 Jul; 11(4): 429–36PubMedGoogle Scholar
  42. 42.
    Chiba N, Kobayashi R, Hasegawa K, et al. Antibiotic susceptibility according to genotype of penicillin-binding protein and macrolide resistance genes, and serotype of Streptococcus pneumoniae isolates from community-acquired pneumonia in children. J Antimicrob Chemother 2005 Oct; 56(4): 756–60PubMedGoogle Scholar
  43. 43.
    Stratchounski LS, Kozlov RS, Appelbaum PC, et al. Antimicrobial resistance of nasopharyngeal pneumococci from children from day-care centres and orphanages in Russia: results of a unique prospective multicentre study. Clin Microbiol Infect 2006 Sep; 12(9): 853–66PubMedGoogle Scholar
  44. 44.
    Lin WJ, Lo WT, Chou CY, et al. Antimicrobial resistance patterns and serotype distribution of invasive Streptococcus pneumoniae isolates from children in Taiwan from 1999 to 2004. Diagn Microbiol Infect Dis 2006 Oct; 56(2): 189–96PubMedGoogle Scholar
  45. 45.
    Greenberg D, Dagan R, Muallem M, et al. Antibiotic-resistant invasive pediatric Streptococcus pneumoniae clones in Israel. J Clin Microbiol 2003 Dec; 41(12): 5541–5PubMedGoogle Scholar
  46. 46.
    Memish ZA, Balkhy HH, Shibl AM, et al. Streptococcus pneumoniae in Saudi Arabia: antibiotic resistance and serotypes of recent clinical isolates. Int J Antimicrob Agents 2004 Jan; 23(1): 32–8PubMedGoogle Scholar
  47. 47.
    Buxbaum A, Forsthuber S, Sauermann R, et al. Development of macrolide-resistance and comparative activity of telithromycin in streptococci in Austria, 1996–2002. Int J Antimicrob Agents 2004 Oct; 24(4): 397–400PubMedGoogle Scholar
  48. 48.
    Rendi-Wagner P, Georgopoulos A, Kundi M, et al. Prospective surveillance of incidence, serotypes and antimicrobial susceptibility of invasive Streptococcus pneumoniae among hospitalized children in Austria. J Antimicrob Chemother 2004 May; 53(5): 826–31PubMedGoogle Scholar
  49. 49.
    Reinert RR, Reinert S, van der LM, et al. Antimicrobial susceptibility of Streptococcus pneumoniae in eight European countries from 2001 to 2003. Antimicrob Agents Chemother 2005 Jul; 49(7): 2903–13PubMedGoogle Scholar
  50. 50.
    Van Eldere J, Meekers E, Lagrou K, et al. Macrolide-resistance mechanisms in Streptococcus pneumoniae isolates from Belgium. Clin Microbiol Infect 2005 Apr; 11(4): 332–4PubMedGoogle Scholar
  51. 51.
    Vanhoof R, Carpentier M, Cartuyvels R, et al. Surveillance of antibiotic resistance in non invasive clinical isolates of Streptococcus pneumoniae collected in Belgium during winters 2003 and 2004. Acta Clin Belg 2006 Mar; 61(2): 49–57PubMedGoogle Scholar
  52. 52.
    Altraja A, Naaber P, Tamm E, et al. Antimicrobial susceptibility of common pathogens from community-acquired lower respiratory tract infections in Estonia. J Chemother 2006 Dec; 18(6): 603–9PubMedGoogle Scholar
  53. 53.
    Pihlajamaki M, Jalava J, Huovinen P, et al. Antimicrobial resistance of invasive pneumococci in Finland in 1999–2000. Antimicrob Agents Chemother 2003 Jun; 47(6): 1832–5PubMedGoogle Scholar
  54. 54.
    Bergman M, Huikko S, Huovinen P, et al. Macrolide and azithromycin use are linked to increased macrolide resistance in Streptococcus pneumoniae. Antimicrob Agents Chemother 2006 Nov; 50(11): 3646–50PubMedGoogle Scholar
  55. 55.
    Rantala M, Huikko S, Huovinen P, et al. Prevalence and molecular genetics of macrolide resistance among Streptococcus pneumoniae isolates collected in Finland in 2002. Antimicrob Agents Chemother 2005 Oct; 49(10): 4180–4PubMedGoogle Scholar
  56. 56.
    Decousser JW, Pina P, Viguier F, et al. Invasive Streptococcus pneumoniae in France: antimicrobial resistance, serotype, and molecular epidemiology findings from a monthly national study in 2000 to 2002. Antimicrob Agents Chemother 2004 Sep; 48(9): 3636–9PubMedGoogle Scholar
  57. 57.
    Reinert RR, Simic S, Al Lahham A, et al. Antimicrobial resistance of Streptococcus pneumoniae recovered from outpatients with respiratory tract infections in Germany from 1998 to 1999: results of a national surveillance study. J Clin Microbiol 2001 Mar; 39(3): 1187–9PubMedGoogle Scholar
  58. 58.
    Reinert RR, van der Linden M, Al-Lahham A, et al. Molecular epidemiology of penicillin-resistant Streptococcus pneumoniae isolated from children with invasive pneumococcal disease in Germany. Clin Microbiol Infect 2007 Apr; 13(4): 363–8PubMedGoogle Scholar
  59. 59.
    Ioannidou S, Tassios PT, Zachariadou L, et al. In vitro activity of telithromycin (HMR 3647) against Greek Streptococcus pyogenes and Streptococcus pneumoniae clinical isolates with different macrolide susceptibilities. Clin Microbiol Infect 2003 Jul; 9(7): 704–7PubMedGoogle Scholar
  60. 60.
    Dobay O, Rozgonyi F, Hajdu E, et al. Antibiotic susceptibility and serotypes of Streptococcus pneumoniae isolates from Hungary. J Antimicrob Chemother 2003 Apr; 51(4): 887–93PubMedGoogle Scholar
  61. 61.
    Busetti M, Longo B, Campello C. Low rates of antimicrobial resistance in respiratory pathogens from a pediatric population in north-eastern Italy. Pediatr Med Chir 2003 Mar; 25(2): 131–4PubMedGoogle Scholar
  62. 62.
    Boccia D, D’Ancona F, Salmaso S, et al. Antibiotic-resistance in Italy: activity of the first year of the surveillance project ARISS [in Italian]. Ann Ig 2005 Mar; 17(2): 95–110PubMedGoogle Scholar
  63. 63.
    Marchese A, Gualco L, Cochetti I, et al. Antibiotic susceptibility and serotype distribution in Streptococcus pneumoniae circulating in Italy: results of the SEMPRE surveillance study (2000–2002). Int J Antimicrob Agents 2005 Aug; 26(2): 138–45PubMedGoogle Scholar
  64. 64.
    Deshpande LM, Sader HS, Debbia E, et al. Emergence and epidemiology of fluoroquinolone-resistant Streptococcus pneumoniae strains from Italy: report from the SENTRY Antimicrobial Surveillance Program (2001–2004). Diagn Microbiol Infect Dis 2006 Mar; 54(3): 157–64PubMedGoogle Scholar
  65. 65.
    Littauer P, Sangvik M, Caugant DA, et al. Molecular epidemiology of macrolide-resistant isolates of Streptococcus pneumoniae collected from blood and respiratory specimens in Norway. J Clin Microbiol 2005 May; 43(5): 2125–32PubMedGoogle Scholar
  66. 66.
    Sadowy E, Izdebski R, Skoczynska A, et al. Phenotypic and molecular analysis of penicillin-nonsusceptible Streptococcus pneumoniae isolates in Poland. Antimicrob Agents Chemother 2007 Jan; 51(1): 40–7PubMedGoogle Scholar
  67. 67.
    Melo-Cristino J, Ramirez M, Serrano N, et al. Macrolide resistance in Streptococcus pneumoniae isolated from patients with community-acquired lower respiratory tract infections in Portugal: results of a 3-year (1999–2001) multicenter surveillance study. Microb Drug Resist 2003; 9(1): 73–80PubMedGoogle Scholar
  68. 68.
    Dias R, Louro D, Canica M. Antimicrobial susceptibility of invasive Streptococcus pneumoniae isolates in Portugal over an 11-year period. Antimicrob Agents Chemother 2006 Jun; 50(6): 2098–105PubMedGoogle Scholar
  69. 69.
    Cizman M, Beovic B, Seme K, et al. Macrolide resistance rates in respiratory pathogens in Slovenia following reduced macrolide use. Int J Antimicrob Agents 2006 Dec; 28(6): 537–42PubMedGoogle Scholar
  70. 70.
    Valles X, Marcos A, Pinart M, et al. Hospitalized community-acquired pneumonia due to Streptococcus pneumoniae: has resistance to antibiotics decreased? Chest 2006 Sep; 130(3): 800–6PubMedGoogle Scholar
  71. 71.
    Perez-Trallero E, Garcia-de-la-Fuente C, Garcia-Rey C, et al. Geographical and ecological analysis of resistance, coresistance, and coupled resistance to antimicrobials in respiratory pathogenic bacteria in Spain. Antimicrob Agents Chemother 2005 May; 49(5): 1965–72PubMedGoogle Scholar
  72. 72.
    Neeleman C, De Valk JA, Klaassen CH, et al. In-vitro susceptibility and molecular characterisation of macrolide resistance mechanisms among Streptococcus pneumonia isolates in The Netherlands: the DUEL 2 study. Clin Microbiol Infect 2005 Apr; 11(4): 312–8PubMedGoogle Scholar
  73. 73.
    Sener B, Koseoglu O, Fisenk I, et al. Streptococcus pneumoniae strains resistance to macrolide, lincosamide, streptogramin, oxazolidinone and ketolide [in Turkish]. Mikrobiyol Bul 2002 Apr; 36(2): 125–31PubMedGoogle Scholar
  74. 74.
    Sener B, Koseoglu O, Gur D, et al. Mechanisms of macrolide resistance in clinical pneumococcal isolates in a university hospital, Ankara, Turkey. J Chemother 2005 Feb; 17(1): 31–5PubMedGoogle Scholar
  75. 75.
    Gazi H, Kurutepe S, Surucuoglu S, et al. Antimicrobial susceptibility of bacterial pathogens in the oropharynx of healthy school children in Turkey. Indian J Med Res 2004 Nov; 120(5): 489–94PubMedGoogle Scholar
  76. 76.
    Shackcloth J, Williams L, Farrell DJ. Streptococcus pneumoniae and Streptococcus pyogenes isolated from a paediatric population in Great Britain and Ireland: the in vitro activity of telithromcycin versus comparators. J Infect 2004 Apr; 48(3): 229–35PubMedGoogle Scholar
  77. 77.
    Gosbell IB, Fernandes LA, Fernandes CJ. In vitro antibacterial activity of beta-lactams and non-beta-lactams against Streptococcus pneumoniae isolates from Sydney, Australia. Pathology 2006 Aug; 38(4): 343–8PubMedGoogle Scholar
  78. 78.
    Felmingham D, Reinert RR, Hirakata Y, et al. Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and compatative in vitro activity of the ketolide, telithromycin. J Antimicrob Chemother 2002 Sep; 50 Suppl. S1: 25–37Google Scholar
  79. 79.
    Jacobs MR, Felmingham D, Appelbaum PC, et al. The Alexander Project 1998–2000: susceptibility of pathogens isolated from community-acquired respiratory tract infection to commonly used antimicrobial agents. J Antimicrob Chemother 2003 Aug; 52(2): 229–46PubMedGoogle Scholar
  80. 80.
    Schito GC, Debbia EA, Marchese A. The evolving threat of antibiotic resistance in Europe: new data from the Alexander Project. J Antimicrob Chemother 2000 Jul; 46 Suppl. T1: 3–9Google Scholar
  81. 81.
    Fluit AC, Jones ME, Schmitz FJ, et al. Antimicrobial susceptibility and frequency of occurrence of clinical blood isolates in Europe from the SENTRY antimicrobial surveillance program, 1997 and 1998. Clin Infect Dis 2000 Mar; 30(3): 454–60PubMedGoogle Scholar
  82. 82.
    Gordon KA, Biedenbach DJ, Jones RN. Comparison of Streptococcus pneumoniae and Haemophilus influenzae susceptibilities from community-acquired respiratory tract infections and hospitalized patients with pneumonia: five-year results for the SENTRY Antimicrobial Surveillance Program. Diagn Microbiol Infect Dis 2003 Aug; 46(4): 285–9PubMedGoogle Scholar
  83. 83.
    Whitney CG, Farley MM, Hadler J, et al. Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States. N Engl J Med 2000 Dec 28; 343(26): 1917–24PubMedGoogle Scholar
  84. 84.
    Bartlett JG, Breiman RF, Mandell LA, et al. Community-acquired pneumonia in adults: guidelines for management. The Infectious Diseases Society of America. Clin Infect Dis 1998 Apr; 26(4): 811–38Google Scholar
  85. 85.
    Kam KM, Luey KY, Fung SM, et al. Emergence of multiple-antibiotic-resistant Streptococcus pneumoniae in Hong Kong. Antimicrob Agents Chemother 1995 Dec; 39(12): 2667–70PubMedGoogle Scholar
  86. 86.
    Rahman M, Hossain S, Shoma S, et al. Emergence of a unique multiply-antibiotic-resistant Streptococcus pneumoniae serotype 7B clone in Dhaka, Bangladesh. J Clin Microbiol 2006 Dec; 44(12): 4625–7PubMedGoogle Scholar
  87. 87.
    Song JH, Yang JW, Jin JH, et al. Molecular characterization of multidrug-resistant Streptococcus pneumoniae isolates in Korea: the Asian Network for Surveillance of Resistant Pathogens (ANSORP) Study Group. J Clin Microbiol 2000 Apr; 38(4): 1641–4PubMedGoogle Scholar
  88. 88.
    Song JH, Yang JW, Peck KR, et al. Spread of multidrug-resistant Streptococcus pneumoniae in South Korea. Clin Infect Dis 1997 Sep; 25(3): 747–9PubMedGoogle Scholar
  89. 89.
    Time magazine. Menace from South Africa [online]. Available from URL: http://www.time.com/time/magazine/article/0,9171,915505,00.html [Accessed 2007 Mar 8]
  90. 90.
    Reinert RR. Resistance phenotypes and multi-drag resistance in Streptococcus pneumoniae (PROTEKT years 1–3 [1999–2001]). J Chemother 2004 Dec; 16 Suppl. 6: 35–48Google Scholar
  91. 91.
    Reinert RR, Jacobs MR, Appelbaum PC, et al. Relationship between the original multiply resistant South African isolates of Streptococcus pneumoniae from 1977 to 1978 and contemporary international resistant clones. J Clin Microbiol 2005 Dec; 43(12): 6035–41PubMedGoogle Scholar
  92. 92.
    Maiden MC, Bygraves JA, Feil E, et al. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci U S A 1998 Mar 17; 95(6): 3140–5PubMedGoogle Scholar
  93. 93.
    Enright MC, Spratt BG. A multilocus sequence typing scheme for Streptococcus pneumoniae: identification of clones associated with serious invasive disease. Microbiology 1998 Nov; 144 (Pt 11): 3049–60PubMedGoogle Scholar
  94. 94.
    Reinert RR. Pneumococcal conjugate vaccines: a European perspective. Int J Med Microbiol 2004 Oct; 294(5): 277–94PubMedGoogle Scholar
  95. 95.
    Kyaw MH, Lynfield R, Schaffner W, et al. Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant Streptococcus pneumoniae. N Engl J Med 2006 Apr 6; 354(14): 1455–63PubMedGoogle Scholar
  96. 96.
    Pai R, Moore MR, Pilishvili T, et al. Postvaccine genetic structure of Streptococcus pneumoniae serotype 19A from children in the United States. J Infect Dis 2005 Dec 1; 192(11): 1988–95PubMedGoogle Scholar
  97. 97.
    Singleton RJ, Hennessy TW, Bulkow LR, et al. Invasive pneumococcal disease caused by nonvaccine serotypes among alaska native children with high levels of 7-valent pneumococcal conjugate vaccine coverage. JAMA 2007 Apr 25; 297(16): 1784–92PubMedGoogle Scholar
  98. 98.
    Woodhead M, Blasi F, Ewig S, et al. Guidelines for the management of adult lower respiratory tract infections. Eur Respir J 2005 Dec; 26(6): 1138–80PubMedGoogle Scholar
  99. 99.
    Mandell LA, Wunderink RG, Anzueto A, et al. Infectious diseases society of america/american thoracic society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007 Mar 1; 44 Suppl. 2: S27–72PubMedGoogle Scholar
  100. 100.
    Arancibia F, Ewig S, Martinez JA, et al. Antimicrobial treatment failures in patients with community-acquired pneumonia: causes and prognostic implications. Am J Respir Crit Care Med 2000 Jul; 162(1): 154–60PubMedGoogle Scholar
  101. 101.
    Tleyjeh IM, Tlaygeh HM, Hejal R, et al. The impact of penicillin resistance on short-term mortality in hospitalized adults with pneumococcal pneumonia: a systematic review and meta-analysis. Clin Infect Dis 2006 Mar 15; 42(6): 788–97PubMedGoogle Scholar
  102. 102.
    Falco V, Almirante B, Jordano Q, et al. Influence of penicillin resistance on outcome in adult patients with invasive pneumococcal pneumonia: is penicillin useful against intermediately resistant strains? J Antimicrob Chemother 2004 Aug; 54(2): 481–8PubMedGoogle Scholar
  103. 103.
    Moroney JF, Fiore AE, Harrison LH, et al. Clinical outcomes of bacteremic pneumococcal pneumonia in the era of antibiotic resistance. Clin Infect Dis 2001 Sep 15; 33(6): 797–805PubMedGoogle Scholar
  104. 104.
    Song JH, Jung SI, Ki HK, et al. 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 2004 Jun 1; 38(11): 1570–8PubMedGoogle Scholar
  105. 105.
    Falagas ME, Siempos II, Bliziotis IA, et al. Impact of initial discordant treatment with beta-lactam antibiotics on clinical outcomes in adults with pneumococcal pneumonia: a systematic review. Mayo Clin Proc 2006 Dec; 81(12): 1567–74PubMedGoogle Scholar
  106. 106.
    Yu VL, Chiou CC, Feldman C, et al. An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome. Clin Infect Dis 2003 Jul 15; 37(2): 230–7PubMedGoogle Scholar
  107. 107.
    Garau J. Treatment of drug-resistant pneumococcal pneumonia. Lancet Infect Dis 2002 Jul; 2(7): 404–15PubMedGoogle Scholar
  108. 108.
    Klugman KP, Low DE, Metlay J, et al. Community-acquired pneumonia: new management strategies for evolving pathogens and antimicrobial susceptibilities. Int J Antimicrob Agents 2004 Nov; 24(5): 411–22PubMedGoogle Scholar
  109. 109.
    Chiou CC, Yu VL. Severe pneumococcal pneumonia: new strategies for management. Curr Opin Crit Care 2006 Oct; 12(5): 470–6PubMedGoogle Scholar
  110. 110.
    Kosowska K, Hoellman DB, Lin G, et al. Antipneumococcal activity of ceftobiprole, a novel broad-spectrum cephalosporin. Antimicrob Agents Chemother 2005 May; 49(5): 1932–42PubMedGoogle Scholar
  111. 111.
    Fenoll A, Gimenez MJ, Robledo O, et al. Activity of cefditoren against clinical isolates of Streptococcus pneumoniae showing non-susceptibility to penicillins, cephalosporins, macrolides, ketolides or quinolones. Int J Antimicrob Agents 2007 Feb; 29(2): 224–6PubMedGoogle Scholar
  112. 112.
    Hoffman-Roberts HL, Babcock C, Mitropoulos IF. Investigational new drugs for the treatment of resistant pneumococcal infections. Expert Opin Investig Drugs 2005 Aug; 14(8): 973–95PubMedGoogle Scholar
  113. 113.
    Tsuji M, Ishii Y, Ohno A, et al. In vitro and in vivo antibacterial activities of S-1090, a new oral cephalosporin. Antimicrob Agents Chemother 1995 Nov; 39(11): 2544–51PubMedGoogle Scholar
  114. 114.
    Sader HS, Deshpande LM, Jones RN. Antimicrobial activity and spectrum of PPI-0903 (TAK-599) a novel cephalosporin, tested against a worldwide collection of clinical strains [abstract no. F-325]. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2004 Oct 30–Nov 1; Washington, DCGoogle Scholar
  115. 115.
    Koga T, Abe T, Inoue H, et al. In vitro and in vivo antibacterial activities of CS-023 (RO4908463), a novel parenteral carbapenem. Antimicrob Agents Chemother 2005 Aug; 49(8): 3239–50PubMedGoogle Scholar
  116. 116.
    Candiani G, Abbondi M, Borgonovi M, et al. In-vitro and in-vivo antibacterial activity of BI 397, a new semi-synthetic glycopeptide antibiotic. J Antimicrob Chemother 1999 Aug; 44(2): 179–92PubMedGoogle Scholar
  117. 117.
    King A, Phillips I, Kaniga K. Comparative in vitro activity of telavancin (TD-6424), a rapidly bactericidal, concentration-dependent anti-infective with multiple mechanisms of action against Gram-positive bacteria. J Antimicrob Chemother 2004 May; 53(5): 797–803PubMedGoogle Scholar
  118. 118.
    Piper KE, Steckelberg JM, Patel R. In vitro activity of daptomycin against clinical isolates of Gram-positive bacteria. J Infect Chemother 2005 Aug; 11(4): 207–9PubMedGoogle Scholar
  119. 119.
    Dugourd D, Siu R, Fenn J, et al. In vitro characterization of MX-2401: a novel amphomycin derivative active against Gram-positive bacteria. [abstract no. F1-1879]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Fransisco (CA)Google Scholar
  120. 120.
    Mason Jr EO, Lamberth LB, Wald ER, et al. In vitro activities of cethromycin (ABT-773), a new ketolide, against Streptococcus pneumoniae strains that are not susceptible to penicillin or macrolides. Antimicrob Agents Chemother 2003 Jan; 47(1): 166–9PubMedGoogle Scholar
  121. 121.
    Shortridge VD, Zhong P, Cao Z, et al. Comparison of in vitro activities of ABT-773 and telithromycin against macrolide-susceptible and -resistant streptococci and staphylococci. Antimicrob Agents Chemother 2002 Mar; 46(3): 783–6PubMedGoogle Scholar
  122. 122.
    Food and Drag Administration. FDA announces label and indication changes for the antibiotic ketek [online]. Available from URL: http://www.fda.gov/cder/drµg/infopage/telithromycin/default.htm [Accessed 2007 Feb 28]
  123. 123.
    Phan LT, Polemeropoulos A, Wang G, et al. In vitro antibacterial activity of EDP-420, a new bridged bicyclic macrolide [abstract no. E-1858]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)Google Scholar
  124. 124.
    Sugiyama H, Suzuki K, Nanaumi K, et al. FMA-1485, a novel 2-fluoroketolide: in vitro and in vivo antibacterial activity against respiratory tract pathogens [abstract no. F1-1485]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)Google Scholar
  125. 125.
    Jones RN, Sader HS, Fritsche TR. Activity of VIC-105555 (VIC), a novel lincosamide, tested against Gram-positive bacteria and anaerobes [abstract no. F-2040]. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2005 Dec 16–19; Washington, DCGoogle Scholar
  126. 126.
    Reinert RR, Kresken M, Mechery V, et al. In vitro activity of quinupristin/dalfopristin against erythromycin-susceptible and erythromycin-resistant Streptococcus pneumoniae. Eur J Clin Microbiol Infect Dis 1998 Sep; 17(9): 662–5PubMedGoogle Scholar
  127. 127.
    Hoellman DB, Lin G, Ednie LM, et al. Antipneumococcal and antistaphylococcal activities of ranbezolid (RBX 7644), a new oxazolidinone, compared to those of other agents. Antimicrob Agents Chemother 2003 Mar; 47(3): 1148–50PubMedGoogle Scholar
  128. 128.
    Traczewski MM, Brown SD. Potency and spectrum of activity compared to ten other antimicrobial compounds [abstract no. F-753]. 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2003 Sep 14–17; Chicago (IL)Google Scholar
  129. 129.
    Weir S, Macone A, Donatelli J, et al. The activity of PTK 0796 against tetracycline resistance [abstract no. F-752]. 43rd Inter-science Conference on Antimicrobial Agents and Chemotherapy; 2003 Sep 14–17; Chicago (IL)Google Scholar
  130. 130.
    Kosowska-Shick K, Credito K, Pankuch GA, et al. Antipneumococcal activity of DW-224a, a new quinolone, compared to those of eight other agents. Antimicrob Agents Chemother 2006 Jun; 50(6): 2064–71PubMedGoogle Scholar
  131. 131.
    Pankuch GA, Nagai K, Davies TA, et al. Antipneumococcal activity of BMS 284756 compared to those of six other agents. Antimicrob Agents Chemother 2002 Jan; 46(1): 251–4PubMedGoogle Scholar
  132. 132.
    Al Lahham A, De Souza NJ, Patel M, et al. Activity of the new quinolones WCK 771, WCK 1152 and WCK 1153 against clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes. J Antimicrob Chemother 2005 Dec; 56(6): 1130–3Google Scholar
  133. 133.
    Wickman PA, Black JA, Moland ES, et al. In vitro activities of DX-619 and comparison quinolones against gram-positive cocci. Antimicrob Agents Chemother 2006 Jun; 50(6): 2255–7PubMedGoogle Scholar
  134. 134.
    Wickman PA, Moland ES, Black JA, et al. In vitro activity of DX-619, a novel des-fluoro(6) quinolone, against a panel of Streptococcus pneumoniae mutants with characterized resistance mechanisms. Antimicrob Agents Chemother 2006 Feb; 50(2): 796–8PubMedGoogle Scholar
  135. 135.
    Browne FA, Bozdogan B, Clark C, et al. Antipneumococcal activity of DK-507k, a new quinolone, compared with the activities of 10 other agents. Antimicrob Agents Chemother 2003 Dec; 47(12): 3815–24PubMedGoogle Scholar
  136. 136.
    Jones RN, Sader HS, Fritsche TR. DC-159a, a novel oral quinolone, activity tested against community-acquired respiratory tract (CA-RTI) pathogens [abstract no. F1-480]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)Google Scholar
  137. 137.
    Adam HJ, Schurek KN, Decorby MR, et al. Comparative in vitro activity of PGE 9262932 and fluoroquinolones against Canadian clinical Streptococcus pneumoniae isolates, including molecularly characterized ciprofloxacin-resistant isolates. J Antimicrob Chemother 2006 Jul; 58(1): 202–4PubMedGoogle Scholar
  138. 138.
    Watanabe A, Tokue Y, Takahashi H, et al. In vitro activity of HSR-903, a new oral quinolone, against bacteria causing respiratory infections. Antimicrob Agents Chemother 1999 Jul; 43(7): 1767–8PubMedGoogle Scholar
  139. 139.
    Schneider P, Hawser S, Islam K. Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria. Bioorg Med Chem Lett 2003 Dec 1; 13(23): 4217–21PubMedGoogle Scholar
  140. 140.
    Jacobs MR, Good CE, Windau A, et al. AR-709, A novel diaminopyrimidine compound: activity against Streptococcus pneumoniae [abstract no. F1-1956]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)Google Scholar
  141. 141.
    Ednie LM, Pankuch G, Appelbaum PC. Antipneumococcal activity of LBM415, a new peptide deformylase inhibitor, compared with those of other agents. Antimicrob Agents Chemother 2004 Oct; 48(10): 4027–32PubMedGoogle Scholar
  142. 142.
    Suarez-Kurtz G, Ribeiro FM, Vicente FL, et al. Development and validation of limited-sampling strategies for predicting amoxicillin pharmacokinetic and pharmacodynamic parameters. Antimicrob Agents Chemother 2001 Nov; 45(11): 3029–36PubMedGoogle Scholar
  143. 143.
    Andes D, Craig WA. Understanding pharmacokinetics and pharmacodynamics: application to the antimicrobial formulary decision process. In: Owens RC, Ambrose PG, Nightingale CH, editors. Antibiotic optimization: concepts and strategies in clinical practice. New York: Marcel Decker, 2005: 65–88Google Scholar
  144. 144.
    Spyker DA, Rugloski RJ, Vann RL, et al. Pharmacokinetics of amoxicillin: dose dependence after intravenous, oral, and intramuscular administration. Antimicrob Agents Chemother 1977 Jan; 11(1): 132–41PubMedGoogle Scholar
  145. 145.
    Chen RR, Lee TY, Hsieh WC. Effect of food on pharmacokinetics of cefuroxime axetil in Chinese subjects. J Formos Med Assoc 1992 Dec; 91(12): 1177–81PubMedGoogle Scholar
  146. 146.
    Patel IH, Chen S, Parsonnet M, et al. Pharmacokinetics of ceftriaxone in humans. Antimicrob Agents Chemother 1981 Nov; 20(5): 634–41PubMedGoogle Scholar
  147. 147.
    Kemmerich B, Lode H, Belmega G, et al. Comparative pharmacokinetics of cefoperazone, cefotaxime, and moxalactam. Antimicrob Agents Chemother 1983 Mar; 23(3): 429–34PubMedGoogle Scholar
  148. 148.
    Li JT, Hou F, Lu H, et al. Phase I clinical trial of cefditoren pivoxil (ME 1207): pharmacokinetics in healthy volunteers. Drugs Exp Clin Res 1997; 23(5-6): 145–50PubMedGoogle Scholar
  149. 149.
    Schmitt-Hoffmann A, Roos B, Schleimer M, et al. Single-dose pharmacokinetics and safety of a novel broad-spectrum cephalosporin (BAL5788) in healthy volunteers. Antimicrob Agents Chemother 2004 Jul; 48(7): 2570–5PubMedGoogle Scholar
  150. 150.
    Ge Y, Hubbel A. In vitro evaluation of plasma protein binding and metabolic stability of ceftaroline (PPP-0903) [abstract no. A-1935]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)Google Scholar
  151. 151.
    Ge Y, Redman R, FlorenL, et al. The pharmacokinetics and safety of ceftaroline (PPI-0903) in healty subjects receiving multiple-dose intravenous infusions [abstract no. A-1937]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)Google Scholar
  152. 152.
    Hadley JA, Tillotson GS, Tosiello R, et al. Faropenem medoxomil: a treatment option in acute bacterial rhinosinusitis. Expert Rev Anti Infect Ther 2006 Dec; 4(6): 923–37PubMedGoogle Scholar
  153. 153.
    Feketi R. Vancomycin, teicoplanin, and the streptogramins: quinupristin and dalfopristin. In: Mandell GL, Bennett JEDR, editors. Principles and practice of infectious diseases. Philadelphia (PA): Churchill Livingstone, 2000: 382–92Google Scholar
  154. 154.
    Shaw JP, Seroogy J, Kaniga K, et al. Pharmacokinetics, serum inhibitory and bactericidal activity, and safety of telavancin in healthy subjects. Antimicrob Agents Chemother 2005 Jan; 49(1): 195–201PubMedGoogle Scholar
  155. 155.
    Hegde SS, Reyes N, Wiens T, et al. Pharmacodynamics of telavancin (TD-6424), a novel bactericidal agent, against Gram-positive bacteria. Antimicrob Agents Chemother 2004 Aug; 48(8): 3043–50PubMedGoogle Scholar
  156. 156.
    Chu S, Wilson DS, Deaton RL, et al. Single- and multiple-dose pharmacokinetics of clarithromycin, a new macrolide antimicrobial. J Clin Pharmacol 1993 Aug; 33(8): 719–26PubMedGoogle Scholar
  157. 157.
    Foulds G, Shepard RM, Johnson RB. The pharmacokinetics of azithromycin in human serum and tissues. J Antimicrob Chemother 1990 Jan; 25 Suppl. A: 73–82PubMedGoogle Scholar
  158. 158.
    Craig WA. Does the dose matter? Clin Infect Dis 2001 Sep 15; 33 Suppl. 3: S233–237PubMedGoogle Scholar
  159. 159.
    Gattringer R, Urbauer E, Traunmuller F, et al. Pharmacokinetics of telithromycin in plasma and soft tissues after single-dose administration to healthy volunteers. Antimicrob Agents Chemother 2004 Dec; 48(12): 4650–3PubMedGoogle Scholar
  160. 160.
    Lodise TP, Preston S, Bhargava V, et al. Pharmacodynamics of an 800-mg dose of telithromycin in patients with community-acquired pneumonia caused by extracellular pathogens. Diagn Microbiol Infect Dis 2005 May; 52(1): 45–52PubMedGoogle Scholar
  161. 161.
    Conte Jr JE, Golden JA, Kipps J, et al. Steady-state plasma and intrapulmonary pharmacokinetics and pharmacodynamics of cethromycin. Antimicrob Agents Chemother 2004 Sep; 48(9): 3508–15PubMedGoogle Scholar
  162. 162.
    MacGowan AP. Pharmacokinetic and pharmacodynamic profile of linezolid in healthy volunteers and patients with Gram-positive infections. J Antimicrob Chemother 2003 May; 51 Suppl. 2: ii17–25PubMedGoogle Scholar
  163. 163.
    Andes D, van Ogtrop ML, Peng J, et al. In vivo pharmacodynamics of a new oxazolidinone (linezolid). Antimicrob Agents Chemother 2002 Nov; 46(11): 3484–9PubMedGoogle Scholar
  164. 164.
    Agwuh KN, MacGowan A. Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. J Antimicrob Chemother 2006 Aug; 58(2): 256–65PubMedGoogle Scholar
  165. 165.
    Zhanel GG, Fontaine S, Adam H, et al. A Review of new fluoroquinolones: focus on their use in respiratory tract infections. Treat Respir Med 2006; 5(6): 437–65PubMedGoogle Scholar
  166. 166.
    Arditi M, Mason Jr EO, Bradley JS, et al. Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use. Pediatrics 1998 Nov; 102(5): 1087–97PubMedGoogle Scholar
  167. 167.
    Flores-Cordero JM, Amaya-Villar R, Rincon-Ferrari MD, et al. Acute community-acquired bacterial meningitis in adults admitted to the intensive care unit: clinical manifestations, management and prognostic factors. Intensive Care Med 2003 Nov; 29(11): 1967–73PubMedGoogle Scholar
  168. 168.
    Friedland IR, Klugman KP. Failure of chloramphenicol therapy in penicillin-resistant pneumococcal meningitis. Lancet 1992 Feb 15; 339(8790): 405–8PubMedGoogle Scholar
  169. 169.
    Auburtin M, Wolff M, Charpentier J, et al. Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care unit patients with pneumococcal meningitis: the PNEUMOREA prospective multicenter study. Crit Care Med 2006 Nov; 34(11): 2758–65PubMedGoogle Scholar
  170. 170.
    Andes DR, Craig WA. Pharmacokinetics and pharmacodynamics of antibiotics in meningitis. Infect Dis Clin North Am 1999 Sep; 13(3): 595–618PubMedGoogle Scholar
  171. 171.
    Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004 Nov 1; 39(9): 1267–84PubMedGoogle Scholar
  172. 172.
    Lonks JR, Garau J, Gomez L, et al. Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae. Clin Infect Dis 2002 Sep 1; 35(5): 556–64PubMedGoogle Scholar
  173. 173.
    Van Kerkhoven D, Peetermans WE, Verbist L, et al. Breakthrough pneumococcal bacteraemia in patients treated with clarithromycin or oral beta-lactams. J Antimicrob Chemother 2003 Mar; 51(3): 691–6PubMedGoogle Scholar
  174. 174.
    Daneman N, McGeer A, Green K, et al. Macrolide resistance in bacteremic pneumococcal disease: implications for patient management. Clin Infect Dis 2006 Aug 15; 43(4): 432–8PubMedGoogle Scholar
  175. 175.
    Nuermberger E, Bishai WR. The clinical significance of macrolide-resistant Streptococcus pneumoniae: it’s all relative. Clin Infect Dis 2004 Jan 1; 38(1): 99–103PubMedGoogle Scholar
  176. 176.
    Peterson LR. Penicillins for treatment of pneumococcal pneumonia: does in vitro resistance really matter? Clin Infect Dis 2006 Jan 15; 42(2): 224–33PubMedGoogle Scholar
  177. 177.
    Fuller JD, Low DE. A review of Streptococcus pneumoniae infection treatment failures associated with fluoroquinolone resistance. Clin Infect Dis 2005 Jul 1; 41(1): 118–21PubMedGoogle Scholar
  178. 178.
    Martinez JA, Horcajada JP, Almela M, et al. 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 2003 Feb 15; 36(4): 389–95PubMedGoogle Scholar
  179. 179.
    Waterer GW, Somes GW, Wunderink RG. Monotherapy may be suboptimal for severe bacteremic pneumococcal pneumonia. Arch Intern Med 2001 Aug 13; 161(15): 1837–42PubMedGoogle Scholar
  180. 180.
    Gleason PP, Meehan TP, Fine JM, et al. Associations between initial antimicrobial therapy and medical outcomes for hospitalized elderly patients with pneumonia. Arch Intern Med 1999 Nov 22; 159(21): 2562–72PubMedGoogle Scholar
  181. 181.
    Frei CR, Koeller JM, Burgess DS, et al. Impact of atypical coverage for patients with community-acquired pneumonia managed on the medical ward: results from the United States Community-Acquired Pneumonia Project. Pharmacotherapy 2003 Sep; 23(9): 1167–74PubMedGoogle Scholar
  182. 182.
    Harbarth S, Garbino J, Pugin J, et al. Lack of effect of combination antibiotic therapy on mortality in patients with pneumococcal sepsis. Eur J Clin Microbiol Infect Dis 2005 Oct; 24(10): 688–90PubMedGoogle Scholar
  183. 183.
    Mills GD, Oehley MR, Arrol B. Effectiveness of beta lactam antibiotics compared with antibiotics active against atypical pathogens in non-severe community acquired pneumonia: meta-analysis. BMJ 2005 Feb 26; 330(7489): 456PubMedGoogle Scholar
  184. 184.
    Shefet D, Robenshtock E, Paul M, et al. Empiric antibiotic coverage of atypical pathogens for community acquired pneumonia in hospitalized adults. Cochrane Database Syst Rev 2005; (2): CD004418Google Scholar
  185. 185.
    Aspa J, Rajas O, Rodriguez DC, et al. Impact of initial antibiotic choice on mortality from pneumococcal pneumonia. Eur Respir J 2006 May; 27(5): 1010–9PubMedGoogle Scholar
  186. 186.
    Baddour LM, Yu VL, Klugman KP, et al. Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia. Am J Respir Crit Care Med 2004 Aug 15; 170(4): 440–4PubMedGoogle Scholar
  187. 187.
    Garcia VE, Mensa J, Martinez JA, et al. 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 2005 Mar; 24(3): 190–5Google Scholar
  188. 188.
    Arason VA, Sigurdsson JA, Erlendsdottir H, et al. The role of antimicrobial use in the epidemiology of resistant pneumococci: a 10-year follow up. Microb Drug Resist 2006; 12(3): 169–76PubMedGoogle Scholar
  189. 189.
    Dagan R, Barkai G, Leibovitz E, et al. Will reduction of antibiotic use reduce antibiotic resistance?: the pneumococcus paradigm. Pediatr Infect Dis J 2006 Oct; 25(10): 981–6PubMedGoogle Scholar
  190. 190.
    File Jr TM. Clinical implications and treatment of multiresistant Streptococcus pneumoniae pneumonia. Clin Microbiol Infect 2006 May; 12 Suppl. 3: 31–41Google Scholar
  191. 191.
    Cunha BA. Antimicrobial therapy of multidrug-resistant Streptococcus pneumoniae, vancomycin-resistant enterococci, and methicillin-resistant Staphylococcus aureus. Med Clin North Am 2006 Nov; 90(6): 1165–82PubMedGoogle Scholar
  192. 192.
    Varon E, Levy C, De La RF, et al. Impact of antimicrobial therapy on nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Branhamella catarrhalis in children with respiratory tract infections. Clin Infect Dis 2000 Aug; 31(2): 477–81PubMedGoogle Scholar
  193. 193.
    Ferrara AM. New fluoroquinolones in lower respiratory tract infections and emerging patterns of pneumococcal resistance. Infection 2005 Jun; 33(3): 106–14PubMedGoogle Scholar
  194. 194.
    Appelbaum PC, Jacobs MR. Recently approved and investigational antibiotics for treatment of severe infections caused by Gram-positive bacteria. Curr Opin Microbiol 2005 Oct; 8(5): 510–7PubMedGoogle Scholar
  195. 195.
    Van Bambeke F, Van Laethem Y, Courvalin P, et al. Glycopeptide antibiotics: from conventional molecules to new derivatives. Drugs 2004; 64(9): 913–36PubMedGoogle Scholar
  196. 196.
    Douthwaite S. Structure-activity relationships of ketolides vs. macrolides. Clin Microbiol Infect 2001; 7 Suppl. 3: 11–7Google Scholar
  197. 197.
    Van Bambeke F, Glupczynski Y, Plesiat P, et al. Antibiotic efflux pumps in prokaryotic cells: occurrence, impact on resistance and strategies for the future of antimicrobial therapy. J Antimicrob Chemother 2003 May; 51(5): 1055–65PubMedGoogle Scholar
  198. 198.
    Zhanel GG, Homenuik K, Nichol K, et al. The glycylcyclines: a comparative review with the tetracyclines. Drugs 2004; 64(1): 63–88PubMedGoogle Scholar
  199. 199.
    Pletz MW, Shergill AP, McGee L, et al. Prevalence of first-step mutants among levofloxacin-susceptible invasive isolates of Streptococcus pneumoniae in the United States. Antimicrob Agents Chemother 2006 Apr; 50(4): 1561–3PubMedGoogle Scholar
  200. 200.
    Schurek KN, Adam HJ, Siemens CG, et al. Are fluoroquinolone-susceptible isolates of Streptococcus pneumoniae really susceptible? A comparison of resistance mechanisms in Canadian isolates from 1997 and 2003. J Antimicrob Chemother 2005 Oct; 56(4): 769–72PubMedGoogle Scholar
  201. 201.
    Livermore DM. Can beta-lactams be re-engineered to beat MRSA? Clin Microbiol Infect 2006 Apr; 12 Suppl. 2: 11–6PubMedGoogle Scholar
  202. 202.
    Azoulay-Dupuis E, Bedos JP, Mohler J, et al. Efficacy of BAL5788, a prodrug of cephalosporin BAL9141, in a mouse model of acute pneumococcal pneumonia. Antimicrob Agents Chemother 2004 Apr; 48(4): 1105–11PubMedGoogle Scholar
  203. 203.
    Adis R8D profile. Ceftobiprole Medocaril: BAL5788, JNJ 30982081, JNJ30982081, RO 65-5788, RO 655788. Drugs R D 2006; 7 (5): 305–11Google Scholar
  204. 204.
    Wilcox MH. Efficacy of linezolid versus comparator therapies in Gram-positive infections. J Antimicrob Chemother 2003 May; 51 Suppl. 2: ii27–35PubMedGoogle Scholar
  205. 205.
    San Pedro GS, Cammarata SK, Oliphant TH, et al. Linezolid versus ceftriaxone/cefpodoxime in patients hospitalized for the treatment of Streptococcus pneumoniae pneumonia. Scand J Infect Dis 2002; 34(10): 720–8PubMedGoogle Scholar
  206. 206.
    Leclercq R. Overcoming antimicrobial resistance: profile of a new ketolide antibacterial, telithromycin. J Antimicrob Chemother 2001 Sep; 48 Suppl. T1: 9–23Google Scholar
  207. 207.
    Doern GV. Macrolide and ketolide resistance with Streptococcus pneumoniae. Med Clin North Am 2006 Nov; 90(6): 1109–24PubMedGoogle Scholar
  208. 208.
    Wolter N, Smith AM, Low DE, et al. High-level telithromycin resistance in a clinical isolate of Streptococcus pneumoniae. Antimicrob Agents Chemother 2007 Mar; 51(3): 1092–5PubMedGoogle Scholar
  209. 209.
    Hirakata Y, Mizuta Y, Wada A, et al. The first telithromycin-resistant Streptococcus pneumoniae isolate in Japan associated with erm(B) and mutations in 23S rRNA and riboprotein L 4. Jpn J Infect Dis 2007 Feb; 60(1): 48–50PubMedGoogle Scholar
  210. 210.
    Al Lahham A, Appelbaum PC, van der LM, et al. Telithromycin-nonsusceptible clinical isolates of Streptococcus pneumoniae from Europe. Antimicrob Agents Chemother 2006 Nov; 50(11): 3897–900Google Scholar
  211. 211.
    Paratek Pharmaceuticals. Technology platforms: the tetracycline program [online]. Available from URL: http://www.paratekpharm.com/pt_tet_inhib.html [Accessed 2007 Mar 5]
  212. 212.
    Owens Jr RC, Ambrose PG. Antimicrobial safety: focus on fluoroquinolones. Clin Infect Dis 2005 Jul 15; 41 Suppl. 2: S144–157PubMedGoogle Scholar
  213. 213.
    Food and Drug Administration. Raxar (grepafloxacin) [online]. Available from URL: http://www.fda.gov/medwatch/safety/1999/safety99.htm#raxar [Accessed 2007 Mar 6]
  214. 214.
    Gurwitz JH. Serious adverse drug effects: seeing the trees through the forest. N Engl J Med 2006 Mar 30; 354(13): 1413–5PubMedGoogle Scholar
  215. 215.
    Food and Drug Administration. Tequin (gatifloxacin) [online]. Available from URL: http://www.fda.gov/medwatch/safety/2006/safety06.htm#Tequin [Accessed 2007 Mar 6]
  216. 216.
    Schmid RE. Drug company taking tequin off market [online]. Available from URL: http://www.sfgate.com/cgi-bin/article.cgi?.file=/news/archive/2006/05/01/national/w120748D88.DTL&type=health [Accessed 2007 Mar 6]
  217. 217.
    Galan MV, Potts JA, Silverman AL, et al. The burden of acute nonfulminant drug-induced hepatitis in a United States tertiary referral center. J Clin Gastroenterol 2005 Jan; 39(1): 64–7PubMedGoogle Scholar
  218. 218.
    Food and Drug Administration. Trovan (travofloxacin) [online]. Available from URL: http://www.fda.gov/medwatch/safety/1999/safety99.htm#trovan2 [Accessed 2007 Mar 6]
  219. 219.
    Mera R. Predicting the future Streptococcus pneumoniae resistance landscape. Curr Opin Pharmacol 2005 Oct; 5(5): 459–64PubMedGoogle Scholar

Copyright information

© Adis Data Information 2007

Authors and Affiliations

  • Françoise Van Bambeke
    • 1
  • René R. Reinert
    • 2
  • Peter C. Appelbaum
    • 3
  • Paul M. Tulkens
    • 1
  • Willy E. Peetermans
    • 4
  1. 1.Unité de Pharmacologie Cellulaire et MoléculaireUniversité Catholique de LouvainBrusselsBelgium
  2. 2.Institute for Medical Microbiology, National Reference Center for StreptococciUniversity Hospital (RWTH)AachenGermany
  3. 3.Department of PathologyHershey Medical CenterHersheyUSA
  4. 4.Department of Internal Medicine-Infectious DiseasesKatholieke Universiteit Leuven, University Hospital GasthuisbergLeuvenBelgium

Personalised recommendations