Antibiotic Resistance of Non-Pneumococcal Streptococci and Its Clinical Impact

  • Jari Jalava
  • Helena Seppälä
Part of the Infectious Disease book series (ID)

Viridans streptococci (VGS) form a phylogenetically heterogeneous group of species belonging to the genus Streptococcus (1). However, they have some common phenotypic properties. They are alfa- or non-haemolytic. They can be differentiated from S. pneumoniae by resistance to optochin and the lack of bile solubility (2). They can be differentiated from the Enterococcus species by their inability to grow in a medium containing 6.5% sodium chloride (2). Earlier, so-called nutritionally variant streptococci were included in the VGS but based on the molecular data they have now been removed to a new genus Abiotrophia (3) and are not included in the discussion below. VGS belong to the normal microbiota of the oral cavities and upper respiratory tracts of humans and animals. They can also be isolated from the female genital tract and all regions of the gastrointestinal tract (2, 3). Several species are included in VGS and are listed elsewhere (2, 3). Clinically the most important species belonging to the VGS are S. mitis, S. sanguis and S. oralis.


Infective Endocarditis Neutropenic Patient Macrolide Resistance Erythromycin Resistance Streptococcus Agalactiae 
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.


  1. 1.
    Kawamura, Y., Hou, X. G., Sultana, F., Miura, H. & Ezaki, T. (1995) Determination of 16S rRNA sequences of Streptococcus mitis and Streptococcus gordonii and phylogenetic relationships among members of the genus Streptococcus. Int. J. Syst. Bacteriol. 45, 406–408PubMedGoogle Scholar
  2. 2.
    Johnson, C. C. & Tunkel, A. R. (2000) Viridans streptococci and groups C and G streptococci. In: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (Mandell, G. L., Bennett, J. E. & Dolin, R., eds.), Chapter 191, pp. 2167–2173, 2 vols. Churchill Livingstone, PhiladelphiaGoogle Scholar
  3. 3.
    Whiley, R. A. & Beighton, D. (1998) Current classification of the oral streptococci. Oral Microbiol. Immunol. 13, 195–216PubMedCrossRefGoogle Scholar
  4. 4.
    Lancefield, R. C. (1933) A serological differentiation of human and other groups of hemolytic streptococci. J. Exp. Med. 57, 571–595CrossRefPubMedGoogle Scholar
  5. 5.
    Bisno, A. L. & van de Rijn, I. (1995) Classification of streptococci. In: Principles and Practice of Infectious Diseases Fourth edition (Mandell, G. L., Bennett, J. E. & Dolin, R., eds.), pp. 1784–1785. Churchill Livingstone Inc., New YorkGoogle Scholar
  6. 6.
    Farley, T. A., Wilson, S. A., Mahoney, F., Kelso, K. Y., Johnson, D. R. & Kaplan, E. L. (1993) Direct inoculation of food as the cause of an outbreak of group A streptococcal pharyngitis. J. Infect. Dis. 167, 1232–1235PubMedGoogle Scholar
  7. 7.
    Donald, F. E., Slack, R. C. B. & Colman, G. (1991) Streptococcus pyogenes vulvovaginitis in children in Nottingham. Epidemiol. Infect. 106, 459–465PubMedCrossRefGoogle Scholar
  8. 8.
    Bisno, A. L. & Stevens, D. L. (1996) Streptococcal infections of skin and soft tissues. N. Engl. J. Med. 334, 240–245PubMedCrossRefGoogle Scholar
  9. 9.
    Orden, B., Martin, R., Franco, A., Ibañez, G. & Mendez, E. (1996) Balanitis caused by group A beta-hemolytic streptococci. Pediatr. Infect. Dis. J. 15, 920–921PubMedCrossRefGoogle Scholar
  10. 10.
    Bisno, A. L. (1995) Streptococcus pyogenes. In: Principles and Practice of Infectious Diseases, Fourth edition (Mandell, G. L., Bennett, J. E. & Dolin, R., eds.), pp. 1786–1799. Churchill Livingstone Inc., New YorkGoogle Scholar
  11. 11.
    Stollerman, G. H. (1993) Variation in group A streptococci and the prevalence of rheumatic fever: a half-century vigil. Ann. Intern. Med. 118, 467–469PubMedGoogle Scholar
  12. 12.
    Weinstein, L. & Le Frock, J. (1971) Does antimicrobial therapy of streptococcal pharyngitis or pyoderma alter the risk of glomeru-lonephritis? J. Infect. Dis. 124, 229–231PubMedGoogle Scholar
  13. 13.
    Lancefield, R. C. (1962) Current knowledge of type-specific M antigens of group A streptococci. J. Immunol. 89, 307–313PubMedGoogle Scholar
  14. 14.
    Griffith, M. B. (1934) The serological classification of Streptococcus pyogenes. J. Hyg. 34, 542–584CrossRefGoogle Scholar
  15. 15.
    Maxted, W. R., Widdowson, J. P., Fraser, C. A. M., Ball, L. C. & Bassett, D. C. J. (1973) The use of the serum opacity reaction in the typing of group-A streptococci. J. Med. Microbiol. 6, 83–90PubMedCrossRefGoogle Scholar
  16. 16.
    Poyart, C., Quesne, G., Couloun, S., Berche, P. & Trieu-Cuot, P. (1998) Identification of streptococci to species level by sequencing the gene encoding the manganese-dependent superoxide dismutate. J. Clin. Microbiol. 36, 41–47PubMedGoogle Scholar
  17. 17.
    Edwards, M. S. & Baker, C. J. (1995) Streptococcus agalactiae (group B streptococcus). In: Principles and Practice of Infectious Diseases, Fourth edition (Mandell, G. L., Bennett, J. E. & Dolin, R., eds.), pp. 1835–1845. Churchill Livingstone, New YorkGoogle Scholar
  18. 18.
    Walsh, C. (2003) Antibiotics: Actions, Origins, Resistance. ASM Press, Washington, DCGoogle Scholar
  19. 19.
    Chambers, H. F. (1999) Penicillin-binding protein-mediated resistance in pneumococci and staphylococci. J. Infect. Dis. 179, S353–S359PubMedCrossRefGoogle Scholar
  20. 20.
    Ajdic, D., McShan, W. M., McLaughlin, R. E., Saviæ, G., Chang, J., Carson, M. B., Primeaux, C., Tian, R., Kenton, S., Jia, H., Lin, S., Qian, Y., Li, S., Zhu, H., Najar, F., Lai, H., White, J., Roe, B. A. & Ferretti, J. J. (2002) Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen. Proc. Natl. Acad. Sci. U.S.A. 99, 14434–14439PubMedCrossRefGoogle Scholar
  21. 21.
    Hoskins J., Alborn, W. E. J., Arnold, J., Blaszczak, L. B., Burgett, S., DeHoff, B. S., Estrem, S. T., Fritz, L., Fu, D. J., Fuller, W., Geringer, C., Gilmour, R., Glass, J. S., Khoja, H., Kraft, A. R., Lagace, R. E., LeBlanc, D. J., Lee, L. N., Lefkowitz, E. J., Lu, J., Matsushima, P., McAhren, S. M., McHenney, M., McLeaster, K., Mundy, C. W., Nicas, T. I., Norris, F. H., O'Gara, M., Peery, R. B., Robertson, G. T., Rockey, P., Sun, P. M., Winkler, M. E., Yang, Y., Young-Bellido, M., Zhao, G., Zook, C. A., Baltz, R. H., Jaskunas, S. R. & Rosteck, P. R., Jr. (2001) Genome of the bacterium Streptococcus pneumoniae Strain R6. J. Bacteriol 183, 5709–5717PubMedCrossRefGoogle Scholar
  22. 22.
    Dowson, C. G., Hutchison, A., Woodford, N., Johnson, A. P., George, R. C. & Spratt, B. G. (1990) Penicillin-resistant viridans streptococci have obtained altered penicillin-binding protein genes from penicillin-resistant strains of Streptococcus pneumoniae. Proc. Natl. Acad. Sci. U.S.A. 87, 5858–5862PubMedCrossRefGoogle Scholar
  23. 23.
    Ergin, A., Ercis, S. & Hascelik, G. (2003) In vitro susceptibility, tolerance and MLS resistance phenotypes of Group C and Group G streptococci isolated in Turkey between 1995 and 2002. Int. J. Antimicrob. Agents 22, 160–163PubMedCrossRefGoogle Scholar
  24. 24.
    Alcaide, F., Liñares, J., Pallares, R., Carratalà, J., Benitez, M. A., Gudiol, F. & Martin, R. (1995) In vitro activities of 22 β—lactam antibiotics against penicillin-resistant and penicillin-susceptible viridans group streptococci isolated from blood. Antimicrob. Agents Chemother. 39, 2243–2247PubMedGoogle Scholar
  25. 25.
    Renneberg, J., Niemann, L. L. & Gutschik, E. (1997) Antimicrobial susceptibility of 278 streptococcal blood isolates to seven antimicrobial agents. J. Antimicrob. Chemother. 39, 135–140PubMedGoogle Scholar
  26. 26.
    Doern, G. V., Ferraro, M. J., Brueggemann, A. B. & Ruoff, K. L. (1996) Emergence of high rates of antimicrobial resistance among viridans group streptococci in the United States. Antimicrob. Agents Chemother. 40, 891–894PubMedGoogle Scholar
  27. 27.
    Pfaller, M. A., Jones, R. N., Marshall, S. A., Edmond, M. B., Wenzel, R. P. & SCOPE Hospital Study Group (1997) Nosocomial streptococcal blood stream infections in the SCOPE program: species occurrence and antimicrobial resistance. Diagn. Microbiol. Infect. Dis. 29, 259–263PubMedCrossRefGoogle Scholar
  28. 28.
    Diekema, D. J., Beach, M. L., Pfaller, M. A., Jones, R. N. & Group, T. S. P. (2001) Antimicrobial resistance in viridans group streptococci among patients with and without the diagnosis of cancer in the USA, Canada and Latin America. Clin. Microbiol. Infect. 7, 152–157PubMedCrossRefGoogle Scholar
  29. 29.
    Diekema, D. J., Coffman, S. L., Marshall, S. A., Beach, M. L., Rolston, K. V. & Jones, R. N. (1999) Comparison of activities of broad-spectrum beta-lactam compounds against 1,128 gram-positive cocci recently isolated in cancer treatment centers. Antimicrob. Agents Chemother. 43, 940–943PubMedGoogle Scholar
  30. 30.
    Marron, A., Carratalà, J., Alcaide, F., Fernández-Sevilla, A. & Gudiol, F. (2001) High rates of resistance to cephalosporins among viridans-group streptococci causing bacteraemia in neutropenic cancer patients. J. Antimicrob. Chemother. 47, 87–91PubMedCrossRefGoogle Scholar
  31. 31.
    Marron, A., Carratalà, J., González-Barca, E., Fernández-Sevilla, A., Alcaide, F. & Gudiol, F. (2000) Serious complications of bacter-emia caused by viridans streptococci in neutropenic patients with cancer. Clin. Infect. Dis. 31, 1126–1130PubMedCrossRefGoogle Scholar
  32. 32.
    Teng, L. J., Hsueh, P. R., Chen, Y. C., Ho, S. W. & Luh, K. T. (1998) Antimicrobial susceptibility of viridans group streptococci in Taiwan with an emphasis on the high rates of resistance to penicillin and macrolides in Streptococcus oralis. J. Antimicrob. Chemother. 41, 621–627PubMedCrossRefGoogle Scholar
  33. 33.
    Seppälä, H., Haanperä, M., Al-Juhaish, M., Järvinen, H., Jalava, J. & Huovinen, P. (2003) Antimicrobial susceptibility patterns and macrolide resistance genes of viridans group streptococci from normal flora. J. Antimicrob. Chemother. 52, 636–644PubMedCrossRefGoogle Scholar
  34. 34.
    Lyytikainen, O., Rautio, M., Carlson, P., Anttila, V. J., Vuento, R., Sarkkinen, H., Kostiala, A., Vaisanen, M. L., Kanervo, A. & Ruutu, P. (2004) Nosocomial bloodstream infections due to viridans streptococci in haematological and non-haematological patients: species distribution and antimicrobial resistance. J. Antimicrob. Chemother. 53, 631–634PubMedCrossRefGoogle Scholar
  35. 35.
    Ioannidou, S., Tassios, P. T., Kotsovili-Tseleni, A., Foustoukou, M., Legakis, N. J. & Vatopoulos, A. (2001) Antibiotic resistance rates and macrolide resistance phenotypes of viridans group streptococci from the oropharynx of healthy Greek children. Int. J. Antimicrob. Agents 17, 195–201PubMedCrossRefGoogle Scholar
  36. 36.
    Alcaide, F., Benítez, M. A., Carratalà, J., Gudiol, F., Liñares, J. & Martín, R. (2001) In vitro activities of the New Ketolide HMR 3647 (Telithromycin) in comparison with those of eight other antibiotics against viridans group streptococci isolated from blood of neutropenic patients with cancer. Antimicrob. Agents Chemother. 45, 624–626PubMedCrossRefGoogle Scholar
  37. 37.
    Alcaide, F., Carratala, J., Linares, J., Gudiol, F. & Martin, R. (1996) In vitro activities of eight macrolide antibiotics and RP-59500 (quinupristin—dalfopristin) against viridans group streptococci isolated from blood of neutropenic cancer patients. Antimicrob. Agents Chemother. 40, 2117–2120PubMedGoogle Scholar
  38. 38.
    Gershon, A. S., de Azavedo, J. C., McGeer, A., Ostrowska, K. I., Church, D., Hoban, D. J., Harding, G. K., Weiss, K., Abbott, L., Smaill, F., Gourdeau, M., Murray, G. & Low, D. E. (2002) Activities of new fluoroquinolones, ketolides, and other antimicrobials against blood culture isolates of viridans group streptococci from across Canada, 2000. Antimicrob. Agents Chemother. 46, 1553–1556PubMedCrossRefGoogle Scholar
  39. 39.
    Pihlajamaki, M., Kataja, J., Seppälä, H., Elliot, J., Leinonen, M., Huovinen, P. & Jalava, J. (2002) Ribosomal mutations in Streptococcus pneumoniae clinical isolates. Antimicrob Agents Chemother 46, 654–658PubMedCrossRefGoogle Scholar
  40. 40.
    Johnson, A. P., Warner, M., Broughton, K., James, D., Efsratiou, A., George, R. C. & Livermore, D. M. (2001) Antibiotic susceptibility of streptococci and related genera causing endocarditis: analysis of UK reference laboratory referrals, January 1996 to March 2000. Br. Med. J. 322, 395–396CrossRefGoogle Scholar
  41. 41.
    de Azavedo, J. C., Trpeski, L., Pong-Porter, S., Matsumura, S. & Low, D. E. (1999) In vitro activities of fluoroquinolones against antibiotic-resistant blood culture isolates of viridans group streptococci from across Canada. Antimicrob. Agents Chemother. 43, 2299–2301PubMedGoogle Scholar
  42. 42.
    Wisplinghoff, H., Reinert, R. R., Cornely, O. & Seifert, H. (1999) Molecular relationships and antimicrobial susceptibilities of viri-dans group streptococci isolated from blood of neutropenic cancer patients. J. Clin. Microbiol. 37, 1876–1880PubMedGoogle Scholar
  43. 43.
    NCCLS. (1999) Performance Standards for Antimicrobial Susceptibility Testing; Ninth Informational Supplement, M100-S9, 19 Google Scholar
  44. 44.
    NCCLS. (2004) Performance Standards for Antimicrobial Susceptibility Testing; Fourteenth Informational Supplement, M100-S14 Google Scholar
  45. 45.
    Potgieter, E., Carmichael, M., Koornhof, H. J. & Chalkey, L. J. (1992) In vitro antimicrobial susceptibility of viridans streptococci isolated from blood cultures. Eur. J. Clin. Microbiol. Infect. Dis 11, 543–546PubMedCrossRefGoogle Scholar
  46. 46.
    Pfaller, M. A. & Jones, R. N. (2000) MYSTIC (meropenem yearly susceptibility test information collection) results from the Americas: resistance implications in the treatment of serious infections. J. Antimicrob. Chemother. 46(Suppl B), 25–37CrossRefGoogle Scholar
  47. 47.
    Weisblum, B. (1995) Erythromycin resistance by ribosome modification. Antimicrob. Agents Chemother. 39, 577–585PubMedGoogle Scholar
  48. 48.
    Sutcliffe, J., Tait-Kamradt, A. & Wondrack, L. (1996) Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by an efflux system. Antimicrob. Agents Chemother. 40, 1817–1824PubMedGoogle Scholar
  49. 49.
    Arpin, C., Canron, M. H., Maugein, J. & Quentin, C. (1999) Incidence of mefA and mefE genes in viridans group streptococci. Antimicrob. Agents Chemother. 43, 2335–2336PubMedGoogle Scholar
  50. 50.
    Ono, T., Shiota, S., Hirota, K., Nemoto, K., Tsuchiya, T. & Miyake, Y. (2000) Susceptibilities of oral and nasal isolates of Streptococcus mitis and Streptococcus oralis to macrolides and PCR detection of resistance genes. Antimicrob. Agents Chemother. 44, 1078–1080PubMedCrossRefGoogle Scholar
  51. 51.
    Reinert, R. R., von Eiff, C., Kresken, M., Brauers, J., Hafner, D., Al-Lahham, A., Schorn, H., Lutticken, R., Peters, G. & The Multicenter Study on Antibiotic Resistance in Staphylococci and Other Gram-Positive Cocci (Mars) Study Group (2001) Nationwide German multicenter study on the prevalence of antibiotic resistance in streptococcal blood isolates from neutropenic patients and comparative in vitro activities of quinupristin—dalfopristin and eight other antibiotics. J. Clin. Microbiol. 39, 1928–1931PubMedCrossRefGoogle Scholar
  52. 52.
    Fluit, A. C., Schmitz, F. J., Verhoef, J. & Milatovic, D. (2004) Daptomycin in vitro susceptibility in European Gram-positive clinical isolates. Int. J. Antimicrob. Agents 24, 59–66PubMedCrossRefGoogle Scholar
  53. 53.
    Ioannidou, S., Papaparaskevas, J., Tassios, P. T., Foustoukou, M., Legakis, N. J. & Vatopoulos, A. C. (2003) Prevalence and characterization of the mechanisms of macrolide, lincosamide and streptogramin resistance in viridans group streptococci. Int. J. Antimicrob. Agents 22, 626–629PubMedCrossRefGoogle Scholar
  54. 54.
    Leclercq, R. (2002) Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical implications. Clin. Infect. Dis. 34, 482–492PubMedCrossRefGoogle Scholar
  55. 55.
    Jalava, J., Kataja, J., Seppälä, H. & Huovinen, P. (2001) In vitro activities of the novel ketolide telithromycin (HMR 3647) against erythromycin-resistant Streptococcus species. Antimicrob. Agents Chemother. 45, 789–793PubMedCrossRefGoogle Scholar
  56. 56.
    Liu, M. & Douthwaite, S. (2002) Activity of the ketolide telithromycin is refractory to Erm monomethylation of bacterial rRNA. Antimicrob. Agents Chemother. 46, 1629–1633PubMedCrossRefGoogle Scholar
  57. 57.
    Thal, L. A. & Zervos, M. J. (1999) Occurrence and epidemiology of resistance to virginiamycin and streptogramins. J. Antimicrob. Chemother. 43, 171–176PubMedCrossRefGoogle Scholar
  58. 58.
    Malbruny, B., Canu, A., Bozdogan, B., Fantin, B., Zarrouk, V., Dutka-Malen, S., Feger, C. & Leclercq, R. (2002) Resistance to quinupristin–dalfopristin due to mutation of L22 ribosomal protein in Staphylococcus aureus. Antimicrob. Agents Chemother. 46, 2200–2207CrossRefGoogle Scholar
  59. 59.
    Aracil, B., Minambres, M., Oteo, J., Torresb, C., Gómez-Garcésa, J. L. & Alósa, J. I. (2001) High prevalence of erythromycin-resistant and clindamycin-susceptible (M phenotype) viridans group streptococci from pharyngeal samples: a reservoir of mef genes in commensal bacteria. J. Antimicrob. Chemother. 48, 592–594PubMedCrossRefGoogle Scholar
  60. 60.
    Kern, W. & Kurrle, E. (1991) Ofloxacin versus trimethoprim— sulfamethoxazole for prevention of infection in patients with acute leukemia and granulocytopenia. Infection 19, 73–80PubMedCrossRefGoogle Scholar
  61. 61.
    Ferrándiz, M. J., Oteo, J., Aracil, B., Gómez-Garcés, J. L. & De La Campa, A. G. (1999) Drug efflux and parC mutations are involved in fuoroquinolone resistance in viridans group streptococci. Antimicrob. Agents Chemother. 43, 2520–2523PubMedGoogle Scholar
  62. 62.
    González, I., Georgiou, M., Alcaide, F., Balas, D., Liñares, J. & de la Campa, A. G. (1998) Fluoroquinolone resistance mutations in the parC, parE, and gyrA genes of clinical isolates of viridans group streptococci. Antimicrob. Agents Chemother. 42, 2792–2798PubMedGoogle Scholar
  63. 63.
    Guerin, F., Varon, E., Hoï, A. B., Gutmann, L. & Podglajen, I. (2000) Fluoroquinolone resistance associated with target mutations and active efflux in oropharyngeal colonizing isolates of viridans group streptococci. Antimicrob. Agents Chemother. 44, 2197–2200PubMedCrossRefGoogle Scholar
  64. 64.
    Ferrándiz, M. J., Fenoll, A., Liñares, J. & De La Campa, A. G. (2000) Horizontal transfer of parC and gyrA in fluoroquinolone-resistant clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 44, 840–847PubMedCrossRefGoogle Scholar
  65. 65.
    Balsalobre, L., Ferrándiz, M. J., Liñares, J., Tubau, F. & de la Campa, A. G. (2003) Viridans group streptococci are donors in horizontal transfer of topoisomerase IV genes to Streptococcus pneumoniae. Antimicrob. Agents Chemother. 47, 2072–2081PubMedCrossRefGoogle Scholar
  66. 66.
    Janoir, C., Podglajen, I., Kitzis, M. D., Poyart, C. & Gutmann, L. (1999) In vitro exchange of fluoroquinolone resistance determinants between Streptococcus pneumoniae and viridans streptococci and genomic organization of the parE-parC region in S. mitis. J. Infect. Dis. 180, 555–558CrossRefGoogle Scholar
  67. 67.
    Phillips, I. & Shannon, K. P. (1997) Aminoglycosides and aminocy-clitols. In: Antibiotic and Chemotherapy: Anti-infective Agents and Their Use in Therapy, Seventh edition. (O'Grady, F., Lambert, H. P., Finch, R. G. & Greenwood, D., eds.), pp. 164–201. Churchill Livingstone Inc., New YorkGoogle Scholar
  68. 68.
    Horstkotte, D., Follath, F., Gutschik, E., Lengyel, M., Oto, A., Pavie, A., Soler-Soler, J., Thiene, G., von Graevenitz, A., Priori, S. G., Garcia, M. A., Blanc, J. J., Budaj, A., Cowie, M., Dean, V., Deckers, J., Fernandez Burgos, E., Lekakis, J., Lindahl, B., Mazzotta, G., Morais, J., Smiseth, O. A., Vahanian, A., Delahaye, F., Parkhomenko, A., Filipatos, G., Aldershvile, J. & Vardas, P. (2004) Guidelines on prevention, diagnosis and treatment of infective endocarditis executive summary; The task force on infective endocarditis of the European society of cardiology. Eur. Heart J. 25, 267–276PubMedCrossRefGoogle Scholar
  69. 69.
    Cometta, A., Zinner, S., de Bock, R., Calandra, T., Gaya, H., Klastersky, J., Langenaeken, J., Paesmans, M., Viscoli, C. & Glauser, M. P. (1995) Piperacillin–tazobactam plus amikacin versus ceftazidime plus amikacin as empiric therapy for fever in granulocytopenic patients with cancer. Antimicrob. Agents Chemother. 39, 445–452PubMedGoogle Scholar
  70. 70.
    Eliopoulos, G. M. (2003) Quinupristin—dalfopristin and linezolid: evidence and opinion. Clin. Infect. Dis. 36, 473–481PubMedCrossRefGoogle Scholar
  71. 71.
    Birmingham, M. C., Rayner, C. R., Meagher, A. K., Flavin, S. M., Batts, D. H. & Schentag, J. J. (2003) Linezolid for the treatment of multidrug-resistant, gram-positive infections: experience from a compassionate-use program. Clin. Infect. Dis. 36, 159–168PubMedCrossRefGoogle Scholar
  72. 72.
    Lowbury, E. J. & Hurst, L. (1959) The sensitivity of staphylococci and other wound bacteria to erythromycin, oleandomycin, and spiramycin. J. Clin. Pathol. 12, 163–169PubMedCrossRefGoogle Scholar
  73. 73.
    Kohn, J. & Evans, A. J. (1970) Group A streptococci resistant to clindamycin. Br. Med. J. 2, 423PubMedCrossRefGoogle Scholar
  74. 74.
    Betriu, C., Sanchez, A., Gomez, M., Cruceyra, A. & Picazo, J. J. (1993) Antibiotic susceptibility of group A streptococci: a 6-year follow-up study. Antimicrob. Agents Chemother. 37, 1717–1719PubMedGoogle Scholar
  75. 75.
    Seppälä, H., Nissinen, A., Järvinen, H., Huovinen, S., Henriksson, T., Herva, E., Holm, S. E., Jahkola, M., Katila, M. L., Klaukka, T. & et al. (1992) Resistance to erythromycin in group A streptococci. N. Engl. J. Med. 326, 292–297PubMedGoogle Scholar
  76. 76.
    Seppälä, H., Nissinen, A., Yu, Q. & Huovinen, P. (1993) Three different phenotypes of erythromycin-resistant Streptococcus pyo-genes in Finland. J. Antimicrob. Chemother. 32, 885–891PubMedCrossRefGoogle Scholar
  77. 77.
    Seppälä, H. (1994) Streptococcus pyogenes; erythromycin resistance and molecular typing, Turku UniversityGoogle Scholar
  78. 78.
    Dixon, J. M. & Lipinski, A. E. (1972) Resistance of group A beta-hemolytic streptococci to lincomycin and erythromycin. Antimicrob. Agents Chemother. 1, 333–339PubMedGoogle Scholar
  79. 79.
    Istre, G. R., Welch, D. F., Marks, M. I. & Moyer, N. (1981) Susceptibility of group A beta-hemolytic Streptococcus isolates to penicillin and erythromycin. Antimicrob. Agents Chemother. 20, 244–246PubMedGoogle Scholar
  80. 80.
    Arthur, J. D., Keiser, J. F., Brown, S. L., Higbee, J. & Butler, C. E.(1984) Erythromycin-resistant group A beta-hemolytic streptococci: prevalence at four medical centers. Pediatr. Infect. Dis. 3, 489PubMedGoogle Scholar
  81. 81.
    Gentry, J. L. & Burns, W. W. (1980) Antibiotic-resistant streptococci. Am. J. Dis. Child. 134, 801Google Scholar
  82. 82.
    Mitsuhashi, S., Inoue, M., Saito, K. & Nakae, M. (1982) Drug resistance in Streptococcus pyogenes strains isolated in Japan. In: Microbiology (Schlessinger, D., ed.), pp. 151–154. American Society of Microbiolgy, Washington DCGoogle Scholar
  83. 83.
    Stingemore, N., Francis, G. R. J., Toohey, M. & McGechie, D. B. (1989) The emergence of erythromycin resistance in Streptococcus pyogenes in Fremantle, Western Australia. Med. J. Aust. 150, 626–627, 630–621PubMedGoogle Scholar
  84. 84.
    Phillips, G., Parratt, D., Orange, G. V., Harper, I., McEwan, H. & Young, N. (1990) Erythromycin-resistant Streptococcus pyogenes. J. Antimicrob. Chemother. 25, 723–724PubMedCrossRefGoogle Scholar
  85. 85.
    Perez-Trallero, E., Fernandez-Mazarrasa, C., Garcia-Rey, C., Bouza, E., Aguilar, L., Garcia-de-Lomas, J. & Baquero, F. (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, 3334–3340PubMedCrossRefGoogle Scholar
  86. 86.
    Portillo, A., Lantero, M., Gastanares, M. J., Ruiz-Larrea, F. & Torres, C. (1999) Macrolide resistance phenotypes and mechanisms of resistance in Streptococcus pyogenes in La Rioja, Spain. Int. J. Antimicrob. Agents 13, 137–140PubMedCrossRefGoogle Scholar
  87. 87.
    Alos, J. I., Aracil, B., Oteo, J. & Gomez-Garces, J. L. (2003) Significant increase in the prevalence of erythromycin-resistant, clindamycin- and miocamycin-susceptible (M phenotype) Streptococcus pyogenes in Spain. J. Antimicrob. Chemother. 51, 333–337PubMedCrossRefGoogle Scholar
  88. 88.
    Ioannidou, S., Tassios, P. T., Kotsovili-Tseleni, A., Foustoukou, M., Legakis, N. J. & Vatopoulos, A. (2001) Antibiotic resistance rates and macrolide resistance phenotypes of viridans group streptococci from the oropharynx of healthy Greek children. Int. J. Antimicrob. Agents 17, 195–201PubMedCrossRefGoogle Scholar
  89. 89.
    Stamos, G., Bedevis, K., Paraskaki, I., Chronopoulou, A., Tsirepa, M. & Foustoukou, M. (2001) Emergence of group A beta-hemolytic streptococci resistant to erythromycin in Athens, Greece. Eur. J. Clin. Microbiol. Infect. Dis. 20, 70–71PubMedCrossRefGoogle Scholar
  90. 90.
    Tzelepi, E., Kouppari, G., Mavroidi, A., Zaphiropoulou, A. & Tzouvelekis, L. S. (1999) Erythromycin resistance amongst group A beta-haemolytic streptococci isolated in a paediatric hospital in Athens, Greece. J. Antimicrob. Chemother. 43, 745–746PubMedCrossRefGoogle Scholar
  91. 91.
    Syrogiannopoulos, G. A., Grivea, I. N., Fitoussi, F., Doit, C., Katopodis, G. D., Bingen, E. & Beratis, N. G. (2001) High prevalence of erythromycin resistance of Streptococcus pyogenes in Greek children. Pediatr. Infect. Dis. J. 20, 863–868PubMedCrossRefGoogle Scholar
  92. 92.
    Ioannidou, S., Tassios, P. T., Zachariadou, L., Salem, Z., Kanelopoulou, M., Kanavaki, S., Chronopoulou, G., Petropoulou, N., Foustoukou, M., Pangalis, A., Trikka-Graphakos, E., Papafraggas, E. & Vatopoulos, A. C. (2003) In vitro activity of telithromycin (HMR 3647) against Greek Streptococcus pyogenes and Streptococcus pneumoniae clinical isolates with different macrolide susceptibilities. Clin. Microbiol. Infect. 9, 704–707PubMedCrossRefGoogle Scholar
  93. 93.
    Petinaki, E., Kontos, F., Pratti, A., Skulakis, C. & Maniatis, A. N. (2003) Clinical isolates of macrolide-resistant Streptococcus pyo-genes in Central Greece. Int. J. Antimicrob. Agents 21, 67–70PubMedCrossRefGoogle Scholar
  94. 94.
    Arvand, M., Hoeck, M., Hahn, H. & Wagner, J. (2000) Antimicrobial resistance in Streptococcus pyogenes isolates in Berlin. J. Antimicrob. Chemother. 46, 621–624PubMedCrossRefGoogle Scholar
  95. 95.
    Brandt, C. M., Honscha, M., Truong, N. D., Holland, R., Hovener, B., Bryskier, A., Lutticken, R. & Reinert, R. R. (2001) Macrolide resistance in Streptococcus pyogenes isolates from throat infections in the region of Aachen, Germany. Microb. Drug Resist. 7, 165–170PubMedCrossRefGoogle Scholar
  96. 96.
    Reinert, R. R., Lutticken, R., Bryskier, A. & Al-Lahham, A. (2003) Macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes in the pediatric population in Germany during 2000–2001. Antimicrob. Agents Chemother. 47, 489–493PubMedCrossRefGoogle Scholar
  97. 97.
    Sauermann, R., Gattringer, R., Graninger, W., Buxbaum, A. & Georgopoulos, A. (2003) Phenotypes of macrolide resistance of group A streptococci isolated from outpatients in Bavaria and susceptibility to 16 antibiotics. J. Antimicrob. Chemother. 51, 53–57PubMedCrossRefGoogle Scholar
  98. 98.
    Savoia, D., Avanzini, C., Bosio, K., Volpe, G., Carpi, D., Dotti, G. & Zucca, M. (2000) Macrolide resistance in group A streptococci. J. Antimicrob. Chemother. 45, 41–47PubMedCrossRefGoogle Scholar
  99. 99.
    Varaldo, P. E., Debbia, E. A., Nicoletti, G., Pavesio, D., Ripa, S., Schito, G. C. & Tempera, G. (1999) Nationwide survey in Italy of treatment of Streptococcus pyogenes pharyngitis in children: influence of macrolide resistance on clinical and microbiological outcomes. Artemis-Italy Study Group. Clin. Infect. Dis. 29, 869–873PubMedCrossRefGoogle Scholar
  100. 100.
    Bingen, E., Fitoussi, F., Doit, C., Cohen, R., Tanna, A., George, R., Loukil, C., Brahimi, N., Le Thomas, I. & Deforche, D. (2000) Resistance to macrolides in Streptococcus pyogenes in France in pediatric patients. Antimicrob. Agents Chemother. 44, 1453–1457PubMedCrossRefGoogle Scholar
  101. 101.
    Weber, P., Filipecki, J., Bingen, E., Fitoussi, F., Goldfarb, G., Chauvin, J. P., Reitz, C. & Portier, H. (2001) Genetic and pheno-typic characterization of macrolide resistance in group A strep-tococci isolated from adults with pharyngo-tonsillitis in France. J. Antimicrob. Chemother. 48, 291–294PubMedCrossRefGoogle Scholar
  102. 102.
    Bozdogan, B., Appelbaum, P. C., Ednie, L., Grivea, I. N. & Syrogiannopoulos, G. A. (2003) Development of macrolide resistance by ribosomal protein L4 mutation in Streptococcus pyogenes during miocamycin treatment of an eight-year-old Greek child with tonsillopharyngitis. Clin. Microbiol. Infect. 9, 966–969PubMedCrossRefGoogle Scholar
  103. 103.
    Kozlov, R. S., Bogdanovitch, T. M., Appelbaum, P. C., Ednie, L., Stratchounski, L. S., Jacobs, M. R. & Bozdogan, B. (2002) Antistreptococcal activity of telithromycin compared with seven other drugs in relation to macrolide resistance mechanisms in Russia. Antimicrob. Agents Chemother. 46, 2963–2968PubMedCrossRefGoogle Scholar
  104. 104.
    Hsueh, P. R., Teng, L. J., Lee, L. N., Yang, P. C., Ho, S. W., Lue, H. C. & Luh, K. T. (2002) Increased prevalence of erythromycin resistance in streptococci: substantial upsurge in erythromycin-resistant M phenotype in Streptococcus pyogenes (1979–1998) but not in Streptococcus pneumoniae (1985–1999) in Taiwan. Microb. Drug Resist. 8, 27–33PubMedCrossRefGoogle Scholar
  105. 105.
    Yan, J. J., Wu, H. M., Huang, A. H., Fu, H. M., Lee, C. T. & Wu, J. J. (2000) Prevalence of polyclonal mefA-containing isolates among erythromycin-resistant group A streptococci in Southern Taiwan. J. Clin. Microbiol. 38, 2475–2479PubMedGoogle Scholar
  106. 106.
    Cha, S., Lee, H., Lee, K., Hwang, K., Bae, S. & Lee, Y. (2001) The emergence of erythromycin-resistant Streptococcus pyogenes in Seoul, Korea. J Infect Chemother 7, 81–86PubMedCrossRefGoogle Scholar
  107. 107.
    Ip, M., Lyon, D. J., Leung, T. & Cheng, A. F. (2002) Macrolide resistance and distribution of erm and mef genes among beta-haemolytic streptococci in Hong Kong. Eur. J. Clin. Microbiol. Infect. Dis. 21, 238–240PubMedCrossRefGoogle Scholar
  108. 108.
    Katz, K. C., McGeer, A. J., Duncan, C. L., Ashi-Sulaiman, A., Willey, B. M., Sarabia, A., McCann, J., Pong-Porter, S., Rzayev, Y., de Azavedo, J. S. & Low, D. E. (2003) Emergence of macrolide resistance in throat culture isolates of group a streptococci in Ontario, Canada, in 2001. Antimicrob. Agents Chemother. 47, 2370–2372PubMedCrossRefGoogle Scholar
  109. 109.
    Martin, J. M., Green, M., Barbadora, K. A. & Wald, E. R. (2002) Erythromycin-resistant group S streptococci in schoolchildren in Pittsburgh. N. Engl. J. Med. 346, 1200–1206PubMedCrossRefGoogle Scholar
  110. 110.
    Palavecino, E. L., Riedel, I., Berrios, X., Bajaksouzian, S., Johnson, D., Kaplan, E. & Jacobs, M. R. (2001) Prevalence and mechanisms of macrolide resistance in Streptococcus pyogenes in Santiago, Chile. Antimicrob. Agents Chemother. 45, 339–341PubMedCrossRefGoogle Scholar
  111. 111.
    Martinez, S., Amoroso, A. M., Famiglietti, A., de Mier, C., Vay, C. & Gutkind, G. O. (2004) Genetic and phenotypic characterization of resistance to macrolides in Streptococcus pyogenes from Argentina. Int J. Antimicrob. Agents 23, 95–98PubMedCrossRefGoogle Scholar
  112. 112.
    Eickhoff, T. C., Klein, J. O., Daly, A. K., Ingall, D. & Finland, M. (1964) Neonatal sepsis and other infections due to group B beta-hemolytic streptococci. N. Engl. J. Med. 271, 1221–1228PubMedGoogle Scholar
  113. 113.
    Morales, W. J., Dickey, S. S., Bornick, P. & Lim, D. V. (1999) Change in antibiotic resistance of group B streptococcus: impact on intrapartum management. Am. J. Obstet. Gynecol. 181, 310–314PubMedCrossRefGoogle Scholar
  114. 114.
    Betriu, C., Culebras, E., Gomez, M., Rodriguez-Avial, I., Sanchez, B. A., Agreda, M. C. & Picazo, J. J. (2003) Erythromycin and clindamycin resistance and telithromycin susceptibility in Streptococcus agalac-tiae. Antimicrob. Agents Chemother. 47, 1112–1114CrossRefGoogle Scholar
  115. 115.
    Hsueh, P. R., Teng, L. J., Lee, L. N., Ho, S. W., Yang, P. C. & Luh, K. T. (2001) High incidence of erythromycin resistance among clinical isolates of Streptococcus agalactiae in Taiwan. Antimicrob. Agents Chemother. 45, 3205–3208PubMedCrossRefGoogle Scholar
  116. 116.
    De Mouy, D., Cavallo, J. D., Leclercq, R. & Fabre, R. (2001) Antibiotic susceptibility and mechanisms of erythromy-cin resistance in clinical isolates of Streptococcus agalactiae: French multicenter study. Antimicrob. Agents Chemother. 45, 2400–2402PubMedCrossRefGoogle Scholar
  117. 117.
    Fitoussi, F., Loukil, C., Gros, I., Clermont, O., Mariani, P., Bonacorsi, S., Le Thomas, I., Deforche, D. & Bingen, E. (2001) Mechanisms of macrolide resistance in clinical group B streptococci isolated in France. Antimicrob. Agents Chemother. 45, 1889–1891PubMedCrossRefGoogle Scholar
  118. 118.
    Poyart, C., Jardy, L., Quesne, G., Berche, P. & Trieu-Cuot, P. (2003) Genetic basis of antibiotic resistance in Streptococcus agalactiae strains isolated in a French hospital. Antimicrob. Agents Chemother. 47, 794–797PubMedCrossRefGoogle Scholar
  119. 119.
    Andrews, J. I., Diekema, D. J., Hunter, S. K., Rhomberg, P. R., Pfaller, M. A., Jones, R. N. & Doern, G. V. (2000) Group B streptococci causing neonatal bloodstream infection: antimicrobial susceptibility and serotyping results from SENTRY centers in the Western Hemisphere. Am. J. Obstet. Gynecol. 183, 859–862PubMedCrossRefGoogle Scholar
  120. 120.
    de Azavedo, J. C., McGavin, M., Duncan, C., Low, D. E. & McGeer, A. (2001) Prevalence and mechanisms of macrolide resistance in invasive and noninvasive group B streptococcus isolates from Ontario, Canada. Antimicrob. Agents Chemother. 45, 3504–3508PubMedCrossRefGoogle Scholar
  121. 121.
    Uh, Y., Jang, I. H., Hwang, G. Y., Yoon, K. J. & Song, W. (2001) Emerging erythromycin resistance among group B streptococci in Korea. Eur. J. Clin. Microbiol. Infect. Dis. 20, 52–54PubMedCrossRefGoogle Scholar
  122. 122.
    Acikgoz, Z. C., Almayanlar, E., Gamberzade, S. & Gocer, S. (2004) Macrolide resistance determinants of invasive and non-invasive group B streptococci in a Turkish hospital. Antimicrob. Agents Chemother. 48, 1410–1412PubMedCrossRefGoogle Scholar
  123. 123.
    Kataja, J., Seppälä, H., Skurnik, M., Sarkkinen, H. & Huovinen, P. (1998) Different erythromycin resistance mechanisms in group C and group G streptococci. Antimicrob. Agents Chemother 42, 1493–1494PubMedGoogle Scholar
  124. 124.
    Wu, J. J., Lin, K. Y., Hsueh, P. R., Liu, J. W., Pan, H. I. & Sheu, S. M. (1997) High incidence of erythromycin-resistant streptococci in Taiwan. Antimicrob. Agents Chemother. 41, 844–846PubMedGoogle Scholar
  125. 125.
    Chabbert, Y. A. (1956) Antagonisme in vitro entre l'erythromycine et la spiramycine. Ann. Inst. Pasteur 90, 787–790Google Scholar
  126. 126.
    Hyder, S. L. & Streitfeld, M. M. (1973) Inducible and constitutive resistance to macrolide antibiotics and lincomycin in clinically isolated strains of Streptococcus pyogenes. Antimicrob. Agents Chemother. 4, 327–331PubMedGoogle Scholar
  127. 127.
    Dixon, J. M. & Lipinski, A. E. (1974) Infections with beta-hemo-lytic Streptococcus resistant to lincomycin and erythromycin and observations on zonal-pattern resistance to lincomycin. J. Infect. Dis. 130, 351–356PubMedGoogle Scholar
  128. 128.
    Horodniceanu, T., Bougueleret, L., El-Solh, N., Bouanchaud, D. H. & Chabbert, Y. A. (1979) Conjugative R plasmids in Streptococcus agalactiae (group B). Plasmid 2, 197–206PubMedCrossRefGoogle Scholar
  129. 129.
    Weisblum, B., Holder, S. B. & Halling, S. M. (1979) Deoxyribonucleic acid sequence common to staphylococcal and streptococcal plasmids which specify erythromycin resistance. J. Bacteriol. 138, 990–998PubMedGoogle Scholar
  130. 130.
    Horinouchi, S., Byeon, W. H. & Weisblum, B. (1983) A complex attenuator regulates inducible resistance to macrolides, lincosa-mides, and streptogramin type B antibiotics in Streptococcus sanguis. J. Bacteriol. 154, 1252–1262PubMedGoogle Scholar
  131. 131.
    Shaw, J. H. & Clewell, D. B. (1985) Complete nucleotide sequence of macrolide-lincosamide-streptogramin B- resistance transposon Tn917 in Streptococcus faecalis. J. Bacteriol. 164, 782–796PubMedGoogle Scholar
  132. 132.
    Seppälä, H., Skurnik, M., Soini, H., Roberts, M. C. & Huovinen, P. (1998) A novel erythromycin resistance methylase gene (ermTR) in Streptococcus pyogenes. Antimicrob. Agents Chemother. 42, 257–262PubMedGoogle Scholar
  133. 133.
    Roberts, M. C., Sutcliffe, J., Courvalin, P., Jensen, L. B., Rood, J. & Seppala, H. (1999) Nomenclature for macrolide and mac-rolide-lincosamide-streptogramin B resistance determinants. Antimicrob. Agents Chemother. 43, 2823–2830PubMedGoogle Scholar
  134. 134.
    Fines, M., Gueudin, M., Ramon, A. & Leclercq, R. (2001) In vitro selection of resistance to clindamycin related to alterations in the attenuator of the erm(TR) gene of Streptococcus pyo-genes UCN1 inducibly resistant to erythromycin. J. Antimicrob. Chemother. 48, 411–416PubMedCrossRefGoogle Scholar
  135. 135.
    Clancy, J., Petitpas, J., Dib-Hajj, F., Yuan, W., Cronan, M., Kamath, A. V., Bergeron, J. & Retsema, J. A. (1996) Molecular cloning and functional analysis of a novel macrolide-resistance determinant, mefA, from Streptococcus pyogenes. Mol. Microbiol. 22, 867–879PubMedCrossRefGoogle Scholar
  136. 136.
    Clancy, J., Petitpas, J., Dib-Hajj, F., Yuan, W., Cronan, M., Kamath, A. V., Bergeron, J. & Retsema, J. A. (1996) Molecular cloning and functional analysis of a novel macrolide-resistant determinant, mefA, from Streptococcus pyogenes. Mol. Microbiol. 22, 867–879PubMedCrossRefGoogle Scholar
  137. 137.
    Betriu, C., Redondo, M., Palau, M. L., Sanchez, A., Gomez, M., Culebras, E., Boloix, A. & Picazo, J. J. (2000) Comparative in vitro activities of linezolid, quinupristin-dalfopristin, moxifloxacin, and trovafloxacin against erythromycin-susceptible and -resistant streptococci. Antimicrob. Agents Chemother. 44, 1838–1841PubMedCrossRefGoogle Scholar
  138. 138.
    Kataja, J., Huovinen, P., Muotiala, A., Vuopio-Varkila, J., Efstratiou, A., Hallas, G. & Seppälä, H. (1998) Clonal spread of group A streptococcus with the new type of erythromycin resistance. Finnish Study Group for Antimicrobial Resistance. J. Infect. Dis. 177, 786–789PubMedCrossRefGoogle Scholar
  139. 139.
    Green, M., Martin, J. M., Barbadora, K. A., Beall, B. & Wald, E. R. (2004) Reemergence of macrolide resistance in pharyngeal isolates of group a streptococci in southwestern Pennsylvania. Antimicrob. Agents Chemother. 48, 473–476PubMedCrossRefGoogle Scholar
  140. 140.
    Bozdogan, B. & Appelbaum, P. C. (2004) Macrolide resistance in streptococci and Haemophilus influenzae. Clin. Lab. Med. 24, 455–475PubMedCrossRefGoogle Scholar
  141. 141.
    Diekema, D. J., Andrews, J. I., Huynh, H., Rhomberg, P. R., Doktor, S. R., Beyer, J., Shortridge, V. D., Flamm, R. K., Jones, R. N. & Pfaller, M. A. (2003) Molecular epidemiology of macrolide resistance in neonatal bloodstream isolates of group B streptococci. J. Clin. Microbiol. 41, 2659–2661PubMedCrossRefGoogle Scholar
  142. 142.
    Poyart, C., Quesne, G., Acar, P., Berche, P. & Trieu-Cuot, P. (2000) Characterization of the Tn916-like transposon Tn3872 in a strain of abiotrophia defectiva (Streptococcus defectivus) causing sequential episodes of endocarditis in a child. Antimicrob. Agents Chemother. 44, 790–793PubMedCrossRefGoogle Scholar
  143. 143.
    Culebras, E., Rodriguez-Avial, I., Betriu, C., Redondo, M. & Picazo, J. J. (2002) Macrolide and tetracycline resistance and molecular relationships of clinical strains of Streptococcus aga-lactiae. Antimicrob. Agents Chemother. 46, 1574–1576PubMedCrossRefGoogle Scholar
  144. 144.
    Betriu, C., Culebras, E., Rodriguez-Avial, I., Gomez, M., Sanchez, B. A. & Picazo, J. J. (2004) In vitro activities of tigecy-cline against erythromycin-resistant Streptococcus pyogenes and Streptococcus agalactiae: mechanisms of macrolide and tetracy-cline resistance. Antimicrob. Agents Chemother. 48, 323–325PubMedCrossRefGoogle Scholar
  145. 145.
    Wu, J. J., Lin, K. Y., Hsueh, P. R., Liu, J. W., Pan, H. I. & Sheu, S. M. (1997) High incidence of erythromycin-resistant streptococci in Taiwan. Antimicrob. Agents Chemother. 41, 844–846PubMedGoogle Scholar
  146. 146.
    Kataja, J., Seppälä, H., Skurnik, M., Sarkkinen, H. & Huovinen, P. (1998) Different erythromycin resistance mechanisms in group C and group G streptococci. Antimicrob. Agents Chemother. 42, 1493–1494PubMedGoogle Scholar
  147. 147.
    Bingen, E., Leclercq, R., Fitoussi, F., Brahimi, N., Malbruny, B., Deforche, D. & Cohen, R. (2002) Emergence of group A streptococcus strains with different mechanisms of macrolide resistance. Antimicrob. Agents Chemother. 46, 1199–1203PubMedCrossRefGoogle Scholar
  148. 148.
    Malbruny, B., Nagai, K., Coquemont, M., Bozdogan, B., Andrasevic, A. T., Hupkova, H., Leclercq, R. & Appelbaum, P. C. (2002) Resistance to macrolides in clinical isolates of Streptococcus pyogenes due to ribosomal mutations. J. Antimicrob. Chemother. 49, 935–939PubMedCrossRefGoogle Scholar
  149. 149.
    Jalava, J., Vaara, M. & Huovinen, P. (2004) Mutation at the position 2058 of the 23S rRNA as a cause of macrolide resistance in Streptococcus pyogenes. Ann. Clin. Microbiol. Antimicrob. 3, 5PubMedCrossRefGoogle Scholar
  150. 150.
    Giovanetti, E., Brenciani, A., Burioni, R. & Varaldo, P. E. (2002) A novel efflux system in inducibly erythromycin-resistant strains of Streptococcus pyogenes. Antimicrob. Agents Chemother. 46, 3750–3755PubMedCrossRefGoogle Scholar
  151. 151.
    Clancy, J., Petitpas, J., Dib-Hajj, F., Yuan, W., Cronan, M., Kamath, A. V., Bergeron, J. & Retsema, J. A. (1996) Molecular cloning and functional analysis of a novel macrolide- resistance determinant, mefA, from Streptococcus pyogenes. Mol. Microbiol. 22, 867–879PubMedCrossRefGoogle Scholar
  152. 152.
    Portillo, A., Lantero, M., Olarte, I., Ruiz-Larrea, F. & Torres, C. (2001) MLS resistance phenotypes and mechanisms in beta-haemolytic group B, C and G streptococcus isolates in La Rioja, Spain. J. Antimicrob. Chemother. 47, 115–116PubMedCrossRefGoogle Scholar
  153. 153.
    Giovanetti, E., Montanari, M. P., Mingoia, M. & Varaldo, P. E.(1999) Phenotypes and genotypes of erythromycin-resistant Streptococcus pyogenes strains in Italy and heterogeneity of inducibly resistant strains. Antimicrob. Agents Chemother. 43, 1935–1940PubMedGoogle Scholar
  154. 154.
    Buu-Hoi, A., Bieth, G. & Horaud, T. (1984) Broad host range of streptococcal macrolide resistance plasmids. Antimicrob. Agents Chemother. 25, 289–291PubMedGoogle Scholar
  155. 155.
    Malke, H. (1975) Transfer of a plasmid mediating antibiotic resistance between strains of Streptococcus pyogenes in mixed cultures. Z. Allg. Mikrobiol. 15, 645–649PubMedCrossRefGoogle Scholar
  156. 156.
    Malke, H., Starke, R., Kohler, W., Kolesnichenko, G. & Totolian, A. A. (1975) Bacteriophage P13234 mo-mediated intra- and inter-group transduction of antibiotic resistance among streptococci. Zentralbl. Bakteriol. [Orig A] 233, 24–34Google Scholar
  157. 157.
    Horaud, T., De Cespedes, G., Clermont, D., David, F. & Delbos, F. (1991) Variability of chromosomal genetic elements in streptococci. In: Genetics and Molecular Biology of Streptococci, Lactococci, and Enterococci (Dunny, G. M., Cleary, P. P. & McKay, L. L., eds.), pp. 16–20. American Society for Microbiology, Washington, DCGoogle Scholar
  158. 158.
    Kataja, J., Huovinen, P., Skurnik, M. & Seppälä, H. (1999) Erythromycin resistance genes in group A streptococci in Finland. The Finnish Study Group for antimicrobial resistance. Antimicrob. Agents Chemother. 43, 48–52PubMedGoogle Scholar
  159. 159.
    Giovanetti, E., Magi, G., Brenciani, A., Spinaci, C., Lupidi, R., Facinelli, B. & Varaldo, P. E. (2002) Conjugative transfer of the erm(A) gene from erythromycin-resistant Streptococcus pyogenes to macrolide-susceptible S. pyogenes, Enterococcus faecalis and Listeria innocua. J. Antimicrob. Chemother. 50, 249–252PubMedCrossRefGoogle Scholar
  160. 160.
    Le Bouguenec, C., de Cespedes, G. & Horaud, T. (1988) Molecular analysis of a composite chromosomal conjugative element (Tn3701) of Streptococcus pyogenes. J. Bacteriol. 170, 3930–3936PubMedGoogle Scholar
  161. 161.
    Giovanetti, E., Brenciani, A., Lupidi, R., Roberts, M. C. & Varaldo, P. E. (2003) Presence of the tet(O) gene in erythromycin-and tetracycline-resistant strains of Streptococcus pyogenes and linkage with either the mef(A) or the erm(A) gene. Antimicrob. Agents Chemother. 47, 2844–2849PubMedCrossRefGoogle Scholar
  162. 162.
    Cresti, S., Lattanzi, M., Zanchi, A., Montagnani, F., Pollini, S., Cellesi, C. & Rossolini, G. M. (2002) Resistance determinants and clonal diversity in group A streptococci collected during a period of increasing macrolide resistance. Antimicrob. Agents Chemother. 46, 1816–1822PubMedCrossRefGoogle Scholar
  163. 163.
    Banks, D. J., Porcella, S. F., Barbian, K. D., Martin, J. M. & Musser, J. M. (2003) Structure and distribution of an unusual chimeric genetic element encoding macrolide resistance in phy-logenetically diverse clones of group A streptococcus. J. Infect. Dis. 188, 1898–1908PubMedCrossRefGoogle Scholar
  164. 164.
    Kataja, J., Huovinen, P., Efstratiou, A., Perez-Trallero, E. & Seppälä, H. (2002) Clonal relationships among isolates of eryth-romycin-resistant Streptococcus pyogenes of different geographical origin. Eur. J. Clin. Microbiol. Infect. Dis. 21, 589–595PubMedCrossRefGoogle Scholar
  165. 165.
    Reinert, R. R., Lutticken, R., Sutcliffe, J. A., Tait-Kamradt, A., Cil, M. Y., Schorn, H. M., Bryskier, A. & Al-Lahham, A. (2004) Clonal relatedness of erythromycin-resistant Streptococcus pyogenes isolates in Germany. Antimicrob. Agents Chemother. 48, 1369–1373PubMedCrossRefGoogle Scholar
  166. 166.
    Perez-Trallero, E., Marimon, J. M., Montes, M., Orden, B. & de Pablos, M. (1999) Clonal differences among erythromycin-resistant Streptococcus pyogenes in Spain. Emerg. Infect. Dis. 5, 235–240PubMedGoogle Scholar
  167. 167.
    Reig, M., Galan, J., Baquero, F. & Perez-Diaz, J. C. (2001) Macrolide resistance in Peptostreptococcus spp. mediated by ermTR: possible source of macrolide-lincosamide- streptogramin B resistance in Streptococcus pyogenes. Antimicrob. Agents Chemother. 45, 630–632PubMedCrossRefGoogle Scholar
  168. 168.
    Granizo, J. J., Aguilar, L., Casal, J., Dal-Re, R. & Baquero, F. (2000) Streptococcus pyogenes resistance to erythromycin in relation to macrolide consumption in Spain (1986–1997). J. Antimicrob. Chemother. 46, 959–964PubMedCrossRefGoogle Scholar
  169. 169.
    Seppälä, H., Klaukka, T., Lehtonen, R., Nenonen, E. & Huovinen, P. (1995) Outpatient use of erythromycin: link to increased eryth-romycin resistance in group A streptococci. Clin. Infect. Dis. 21, 1378–1385PubMedGoogle Scholar
  170. 170.
    Bergman, M., Huikko, S., Pihlajamaki, M., Laippala, P., Palva, E., Huovinen, P. & Seppälä, H. (2004) Effect of macrolide consumption on erythromycin resistance in Streptococcus pyogenes in Finland in 1997–2001. Clin. Infect. Dis. 38, 1251–1256PubMedCrossRefGoogle Scholar
  171. 171.
    Ko, W. C., Lee, H. C., Wang, L. R., Lee, C. T., Liu, A. J. & Wu, J. J. (2001) Serotyping and antimicrobial susceptibility of group B streptococcus over an eight-year period in southern Taiwan. Eur. J. Clin. Microbiol. Infect. Dis. 20, 334–339PubMedCrossRefGoogle Scholar
  172. 172.
    De Azavedo, J. C., Yeung, R. H., Bast, D. J., Duncan, C. L., Borgia, S. B. & Low, D. E. (1999) Prevalence and mechanisms of mac-rolide resistance in clinical isolates of group A streptococci from Ontario, Canada. Antimicrob. Agents Chemother. 43, 2144–2147PubMedGoogle Scholar
  173. 173.
    Hogevik, H., Olaison, L., Andersson, R., Lindberg, J. & Alestig, K. (1995) Epidemiologic aspects of infective endocarditis in an urban population. A 5-year prospective study. Medicine (Baltimore) 74, 324–339CrossRefGoogle Scholar
  174. 174.
    Watanakunakorn, C. & Burkert, T. (1993) Infective endocarditis at a large community teaching hospital, 1980–1990. A review of 210 episodes. Medicine (Baltimore) 72, 90–102Google Scholar
  175. 175.
    Mylonakis, E. & Calderwood, S. B. (2001) Infective endocarditis in adults. N. Engl. J. Med. 345, 1318–1330PubMedCrossRefGoogle Scholar
  176. 176.
    Alestig, K., Hogevik, H. & Olaison, L. (2000) Infective endocarditis: a diagnostic and therapeutic challenge for the new millennium. Scand. J. Infect. Dis. 32, 343–356PubMedCrossRefGoogle Scholar
  177. 177.
    Eykyn, S. J. Bacteraemia, septicaemia and endocarditis, Vol. Chapter 16, pp. 277–298Google Scholar
  178. 178.
    Gutschik, E. (1999) New developments in the treatment of infective endocarditis infective cardiovasculitis. Int. J. Antimicrob. Agents 13, 79–92PubMedCrossRefGoogle Scholar
  179. 179.
    Shanson, D. C. (1998) New guidelines for the antibiotic treatment of streptococcal, enterococcal and staphylococcal endocarditis. J. Antimicrob. Chemother. 42, 292–296PubMedCrossRefGoogle Scholar
  180. 180.
    Levy, C. S., Kogulan, P., Gill, V. J., Croxton, M. B., Kane, J. G. & Lucey, D. R. (2001) Endocarditis caused by penicillin-resistant viridans streptococci: 2 cases and controversies in therapy. Clin. Infect. Dis. 33, 577–579PubMedCrossRefGoogle Scholar
  181. 181.
    Lonks, J. R., Dickinson, B. P. & Runarsdottir, V. (1999) Endocarditis due to Streptococcus mitis with high-level resistance to penicillin and cefotaxime. N. Engl. J. Med. 341, 1239PubMedCrossRefGoogle Scholar
  182. 182.
    Levitz, R. E. (1999) Prosthetic-valve endocarditis caused by penicillin-resistant Streptococcus mitis. N. Engl. J. Med. 340, 1843–1844PubMedCrossRefGoogle Scholar
  183. 183.
    Sabella, C., Murphy, D. & Drummond-Webb, J. (2001) Endocarditis due to Streptococcus mitis with high-level resistance to penicillin and ceftriaxone. JAMA 285, 2195PubMedCrossRefGoogle Scholar
  184. 184.
    Hamza, N., Ortiz, J. & Bonomo, R. A. (2004) Isolated pulmonic valve infective endocarditis: a persistent challenge. Infection 32, 170–175PubMedCrossRefGoogle Scholar
  185. 185.
    Klastersky, J. (1998) Science and pragmatism in the treatment and prevention of neutropenic infection. J. Antimicrob. Chemother. 41(Suppl D), 13–24PubMedCrossRefGoogle Scholar
  186. 186.
    Collin, B. A., Leather, H. L., Wingard, J. R. & Ramphal, R. (2001) Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients. Clin. Infect. Dis. 33, 947–953PubMedCrossRefGoogle Scholar
  187. 187.
    Ramphal, R. (2004) Changes in the etiology of bacteremia in febrile neutropenic patients and the susceptibilities of the currently isolated pathogens. Clin. Infect. Dis. 39, S25–S31PubMedCrossRefGoogle Scholar
  188. 188.
    Elting, L. S., Rubenstein, E. B., Rolston, K. V. & Bodey, G. P. (1997) Outcomes of bacteremia in patients with cancer and neu-tropenia: observations from two decades of epidemiological and clinical trials. Clin. Infect. Dis. 25, 247–259PubMedCrossRefGoogle Scholar
  189. 189.
    Elting, L. S., Bodey, G. P. & Keefe, B. H. (1992) Septicemia and shock syndrome due to viridans streptococci: a case-control study of predisposing factors. Clin. Infect. Dis. 14, 1201–1207PubMedGoogle Scholar
  190. 190.
    Picazo, J. (2004) Management of the febrile neutropenic patient: a consensus conference. Clin. Infect. Dis. 39, S1–S6PubMedCrossRefGoogle Scholar
  191. 191.
    Kanamaru, A. & Tatsumi, Y. (2004) Microbiological data for patients with febrile neutropenia. Clin. Infect. Dis. 39, S7–S10PubMedCrossRefGoogle Scholar
  192. 192.
    Gonzalez-Barca, E., Fernández-Sevilla, A., Carratalà, J., Grañena, A. & Gudiol, F. (1996) Prospective study of 288 episodes of bac-teremia in neutropenic cancer patients in a single institution. Eur. J. Clin. Microbiol. Infect. Dis 15, 291–296PubMedCrossRefGoogle Scholar
  193. 193.
    Bochud, P. Y., Calandra, T. & Francioli, P. (1994) Bacteremia due to viridans streptococci in neutropenic patients: a review. Am. J. Med. 97, 256–264PubMedCrossRefGoogle Scholar
  194. 194.
    Villablanca, J., Steiner, M., Kersey, J., Ramsay, N. K. C., Ferrieri, P., Haake, R. & Weisdorf, D. (1990) The clinical spectrum of infections with viridans streptococci in bone marrow transplant patients. Bone Marrow Transplant. 6, 387–393Google Scholar
  195. 195.
    Bochud, P. Y., Eggiman, P., Calandra, T., Van Melle, G., Saghafi, L. & Francioli, P. (1994) Bacteremia due to viridans streptococcus in neutropenic patients with cancer: clinical spectrum and risk factors. Clin. Infect. Dis. 18, 25–31PubMedGoogle Scholar
  196. 196.
    Richard, P., Amador Del Valle, G., Moreau, P., Milpied, N., Felice, M. P., Daeschler, T., Harousseau, J. L. & Richet, H. (1995) Viridans streptococcal bacteraemia in patients with neutropenia. Lancet 345, 1607–1609PubMedCrossRefGoogle Scholar
  197. 197.
    Kern, W., Kurrle, E. & Schmeiser, T. (1990) Streptococcal bacteremia in adult patients with leukemia undergoing aggressive chemotherapy. A review of 55 Cases. Infection 18, 138–145PubMedCrossRefGoogle Scholar
  198. 198.
    Steiner, M., Villablanca, J., Kersey, J., Ramsay, N., Haake, R., Ferrieri, P. & Weisdorf, D. (1993) Viridans streptococcal shock in bone marrow transplantation patients. Am. J Hematol. 42, 354–358PubMedCrossRefGoogle Scholar
  199. 199.
    Zinner, S., Calandra, T., Meunier, F., Gaya, H., Viscoli, C., Klastersky, J., Glauser, M. P., Langenaeken, J. & Paesmans, M. (1994) Reduction of fever and streptococcal bacteremia in granu-locytopenic patients with cancer. JAMA 272, 1183–1189CrossRefGoogle Scholar
  200. 200.
    Rolston, K. V. (2004) The infectious diseases society of America 2002 guidelines for the use of antimicrobial agents in patients with cancer and neutropenia: salient features and comments. Clin. Infect. Dis. 39, S44–S48PubMedCrossRefGoogle Scholar
  201. 201.
    Masaoka, T. (2004) Evidence-based recommendations for antimicrobial use in febrile neutropenia in Japan: executive summary. Clin. Infect. Dis. 39, S49–S52PubMedCrossRefGoogle Scholar
  202. 202.
    Tamura, K. (2004) Initial empirical antimicrobial therapy: duration and subsequent modifications. Clin. Infect. Dis. 39, S59–S64PubMedCrossRefGoogle Scholar
  203. 203.
    Cometta, A., Kern, W. V., De Bock, R., Paesmans, M., Vandenbergh, M., Crokaert, F., Engelhard, D., Marchetti, O., Akan, H., Skoutelis, A., Korten, V., Vandercam, M., Gaya, H., Padmos, A., Klastersky, J., Zinner, S., Glauser, M. P., Calandra, T. & Viscoli, C. (2003) Vancomycin versus placebo for treating persistent fever in patients with neutropenic cancer receiving piperacillin-tazobactam monotherapy. Clin. Infect. Dis. 37, 382–389PubMedCrossRefGoogle Scholar
  204. 204.
    Carratalà, J., Alcaide, F., Fernández-Sevilla, A., Corbella, X., Liñares, J. & Gudiol, F. (1995) Bacteremia due to viridans streptococci that are highly resistant to penicillin: increase among neu-tropenic patients with cancer. Clin. Infect. Dis. 20, 1169–1173PubMedGoogle Scholar
  205. 205.
    Cepeda, J. A., Whitehouse, T., Cooper, B., Hails, J., Jones, K., Kwaku, F., Taylor, L., Hayman, S., Shaw, S., Kibbler, C., Shulman, R., Singer, M. & Wilson, A. P. (2004) Linezolid versus teicoplanin in the treatment of Gram-positive infections in the critically ill: a randomized, double-blind, multicentre study. J. Antimicrob. Chemother. 53, 345–355PubMedCrossRefGoogle Scholar
  206. 206.
    Wilcox, M., Nathwani, D. & Dryden, M. (2004) Linezolid compared with teicoplanin for the treatment of suspected or proven Gram-positive infections. J. Antimicrob. Chemother. 53, 335–344PubMedCrossRefGoogle Scholar
  207. 207.
    Klastersky, J. (2003) Role of quinupristin/dalfopristin in the treatment of Gram-positive nosocomial infections in haematological or oncological patients. Cancer Treat. Rev. 29, 431–440PubMedCrossRefGoogle Scholar
  208. 208.
    Cruciani, M., Rampazzo, R., Malena, M., Lazzarini, L., Todeschini, G., Messori, A. & Concia, E. (1996) Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis. Clin. Infect. Dis. 23, 795–805PubMedGoogle Scholar
  209. 209.
    Guiot, H. F., Peters, W. G., van den Broek, P. J., van der Meer, J. W., Kramps, J. A., Willemze, R. & van Furth, R. (1990) Respiratory failure elicited by streptococcal septicaemia in patients treated with cytosine arabinoside, and its prevention by penicillin. Infection 18, 131–137PubMedCrossRefGoogle Scholar
  210. 210.
    Rondini, G., Cocuzza, C. E., Cianflone, M., Lanzafame, A., Santini, L. & Mattina, R. (2001) Bacteriological and clinical efficacy of various antibiotics used in the treatment of streptococcal pharyngitis in Italy. An epidemiological study. Int. J. Antimicrob. Agents 18, 9–17PubMedCrossRefGoogle Scholar
  211. 211.
    Bassetti, M., Manno, G., Collida, A., Ferrando, A., Gatti, G., Ugolotti, E., Cruciani, M. & Bassetti, D. (2000) Erythromycin resistance in Streptococcus pyogenes in Italy. Emerg. Infect. Dis. 6, 180–183PubMedCrossRefGoogle Scholar
  212. 212.
    Facinelli, B., Spinaci, C., Magi, G., Giovanetti, E. & Varaldo, E. P. (2001) Association between erythromycin resistance and ability to enter human respiratory cells in group A streptococci. Lancet 358, 30–33PubMedCrossRefGoogle Scholar
  213. 213.
    Seppälä, H., Klaukka, T., Vuopio-Varkila, J., Muotiala, A., Helenius, H., Lager, K., Huovinen, P. & Finnish Study Group for Antimicrobial Resistance (1997) The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. N. Engl. J. Med. 337, 441–446PubMedCrossRefGoogle Scholar
  214. 214.
    Fujita, K., Murono, K., Yoshikawa, M. & Murai, T. (1994) Decline of erythromycin resistance of group A streptococci in Japan. Pediatr. Infect. Dis. J. 13, 1075–1078PubMedCrossRefGoogle Scholar
  215. 215.
    Cizman, M., Pokorn, M., Seme, K., Orazem, A. & Paragi, M. (2001) The relationship between trends in macrolide use and resistance to macrolides of common respiratory pathogens. J. Antimicrob. Chemother. 47, 475–477PubMedCrossRefGoogle Scholar
  216. 216.
    Commitee. (1997) Revised guidelines for prevention of early-onset group B streptococcal (GBS) infection. American Academy of Pediatrics Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics 99, 489–496CrossRefGoogle Scholar
  217. 217.
    Horn, D. L., Zabriskie, J. B., Austrian, R., Cleary, P. P., Ferretti, J. J., Fischetti, V. A., Gotschlich, E., Kaplan, E. L., McCarty, M., Opal, S. M., Roberts, R. B., Tomasz, A. & Wachtfogel, Y. (1998) Why have group A streptococci remained susceptible to penicillin? Report on a symposium. Clin. Infect. Dis. 26, 1341–1345PubMedCrossRefGoogle Scholar
  218. 218.
    Bryskier, A. (2000) Ketolides-telithromycin, an example of a new class of antibacterial agents. Clin. Microbiol. Infect. 6, 661–669PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jari Jalava
    • 1
  • Helena Seppälä
    • 2
  1. 1.Department of Bacterial and Infectious DiseasesNational Public Health InstituteTurkuFinland
  2. 2.Ophthalmologist, Docent in Medical Bacteriology, Department of OphthalmologyTurku City HospitalTurkuFinland

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