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PMID: 8843287 Published · ppublish English Journal Article

Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by an efflux system.

Antimicrobial agents and chemotherapy ·Vol. 40 ·No. 8 ·1996-08-00 ·Pages 1817-24

Sutcliffe J, Tait-Kamradt A, Wondrack L

Abstract

Macrolide-resistant Streptococcus pyogenes isolates from Finland, Australia, and the United Kingdom and, more recently, Streptococcus pneumoniae and S. pyogenes strains from the United States were shown to have an unusual resistance pattern to macrolides, lincosamides, and streptogramin B antibiotics. This pattern, referred to as M resistance, consists of susceptibility to clindamycin and streptogramin B antibiotics but resistance to 14- and 15-membered macrolides. An evaluation of the macrolide-lincosamide-streptogramin B resistance phenotypes among our streptococcal strains collected from 1993 to 1995 suggested that this unusual resistance pattern is not rare. Eighty-five percent (n = 66) of the S. pneumoniae and 75% (n = 28) of the S. pyogenes strains in our collection had an M phenotype. The mechanism of M resistance was not mediated by target modification, as isolated ribosomes from a pneumococcal strain bearing the M phenotype were fully sensitive to erythromycin. Further, the presence of an erm methylase was excluded with primers specific for an erm consensus sequence. However, results of studies that determined the uptake and incorporation of radiolabeled erythromycin into cells were consistent with the presence of a macrolide efflux determinant. The putative efflux determinant in streptococci seems to be distinct from the multicomponent macrolide efflux system in coagulase-negative staphylococci. The recognition of the prevalence of the M phenotype in streptococci has implications for sensitivity testing and may have an impact on the choice of antibiotic therapy in clinical practice.

MeSH Terms
Anti-Bacterial Agents/metabolism,pharmacology Clindamycin/pharmacology Drug Resistance, Microbial Drug Resistance, Multiple Erythromycin/metabolism,pharmacology Methyltransferases/genetics,metabolism Microbial Sensitivity Tests Phenotype Streptococcus pneumoniae/drug effects,genetics,metabolism Streptococcus pyogenes/drug effects,genetics,metabolism Virginiamycin/pharmacology
Chemicals
Anti-Bacterial Agents Virginiamycin Clindamycin Erythromycin Methyltransferases rRNA (adenosine-O-2'-)methyltransferase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sutcliffe J
Department of Infectious Diseases, Pfizer, Inc., Groton, Connecticut 06340, USA.
Tait-Kamradt A
Wondrack L
References (67)
67 references, click to expand
  1. Erythromycin resistance by ribosome modification.
    Antimicrob Agents Chemother. 1995 Mar;39(3):577-85 PMID: 7793855
  2. Emergence of resistant Streptococcus pneumoniae: a problem in pediatrics.
    Pediatr Infect Dis J. 1995 May;14(5):424-8 PMID: 7638032
  3. In vivo efficacy of trovafloxacin (CP-99,219), a new quinolone with extended activities against gram-positive pathogens, Streptococcus pneumoniae, and Bacteroides fragilis.
    Antimicrob Agents Chemother. 1995 Oct;39(10):2210-6 PMID: 8619569
  4. Regulation of the permeability of the gonococcal cell envelope by the mtr system.
    Mol Microbiol. 1994 Feb;11(4):769-75 PMID: 8196548
  5. Multidrug resistance pumps in bacteria: variations on a theme.
    Trends Biochem Sci. 1994 Mar;19(3):119-23 PMID: 8203018
  6. Resistance to penicillin and non-beta-lactam antibiotics of Streptococcus pneumoniae at a children's hospital.
    Pediatr Infect Dis J. 1994 Apr;13(4):281-7 PMID: 8036044
  7. Extraction and isolation of individual ribosomal proteins from Escherichia coli.
    J Bacteriol. 1968 Aug;96(2):358-64 PMID: 4877123
  8. Altered methylation of ribosomal RNA in an erythromycin-resistant strain of Staphylococcus aureus.
    Proc Natl Acad Sci U S A. 1971 Apr;68(4):856-60 PMID: 5279527
  9. Substrate- and antibiotic-binding sites at the peptidyl-transferase centre of Escherichia coli ribosomes. Studies on the chloramphenicol. lincomycin and erythromycin sites.
    Eur J Biochem. 1971 Nov 11;23(1):185-93 PMID: 4942548
  10. Efficacy of clindamycin therapy for otitis media.
    Arch Otolaryngol. 1973 Jul;98(1):27-31 PMID: 4145912
  11. Characterization of a plasmid determining resistance to erythromycin, lincomycin, and vernamycin Balpha in a strain Streptococcus pyogenes.
    Antimicrob Agents Chemother. 1974 May;5(5):534-7 PMID: 4618462
  12. Humoral immunity to Streptococcus pneumoniae induced by a pneumococcal ribosomal protein fraction.
    Infect Immun. 1976 Aug;14(2):345-54 PMID: 9362
  13. Plasmid-mediated pristinamycin resistance. PAC IIA: a new enzyme which modifies pristinamycin IIA.
    J Antibiot (Tokyo). 1977 Aug;30(8):665-9 PMID: 908665
  14. Plasmid mediated pristinamycin resistance: PH 1A, a pristinamycin 1A hydrolase.
    Ann Microbiol (Paris). 1977 Nov-Dec;128B(4):471-4 PMID: 416739
  15. Two new types of resistance to lincomycin in pathogenic staphylococci from animals.
    Ann Microbiol (Paris). 1980 Nov-Dec;131B(3):261-6 PMID: 7469255
  16. The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage.
    Nature. 1983 Oct 20-26;305(5936):709-12 PMID: 6226876
  17. Erythromycin resistant Streptococcus pyogenes in Merseyside.
    J Infect. 1984 Jan;8(1):86-7 PMID: 6366071
  18. Translational attenuation: the regulation of bacterial resistance to the macrolide-lincosamide-streptogramin B antibiotics.
    CRC Crit Rev Biochem. 1984;16(2):103-32 PMID: 6203682
  19. Enzymic hydrolysis of erythromycin by a strain of Escherichia coli. A new mechanism of resistance.
    J Antibiot (Tokyo). 1984 Dec;37(12):1692-6 PMID: 6396291
  20. Nucleotide sequence of the gene ereA encoding the erythromycin esterase in Escherichia coli.
    Gene. 1985;35(3):271-8 PMID: 3899861
  21. Inducible resistance to macrolides, lincosamides and streptogramin type B antibiotics: the resistance phenotype, its biological diversity, and structural elements that regulate expression--a review.
    J Antimicrob Chemother. 1985 Jul;16 Suppl A:63-90 PMID: 3932311
  22. Plasmid-mediated high-level resistance to erythromycin in Escherichia coli.
    Antimicrob Agents Chemother. 1986 Mar;29(3):515-8 PMID: 3521489
  23. Analysis of the nucleotide sequence of the ereB gene encoding the erythromycin esterase type II.
    Nucleic Acids Res. 1986 Jun 25;14(12):4987-99 PMID: 3523438
  24. Clinical and nasopharyngeal isolates of unusual multiply resistant pneumococci.
    Am J Dis Child. 1986 Nov;140(11):1186-90 PMID: 3766492
  25. Novel mechanism for plasmid-mediated erythromycin resistance by pNE24 from Staphylococcus epidermidis.
    Antimicrob Agents Chemother. 1986 Nov;30(5):653-8 PMID: 3800341
  26. Distribution of erythromycin esterase and rRNA methylase genes in members of the family Enterobacteriaceae highly resistant to erythromycin.
    Antimicrob Agents Chemother. 1987 Mar;31(3):404-9 PMID: 3579257
  27. Phenotypic expression and genetic heterogeneity of lincosamide inactivation in Staphylococcus spp.
    Antimicrob Agents Chemother. 1987 Dec;31(12):1887-91 PMID: 3439797
  28. Resistance to macrolides, lincosamides and streptogramin type B antibiotics due to a mutation in an rRNA operon of Streptomyces ambofaciens.
    EMBO J. 1988 Jan;7(1):277-82 PMID: 2834204
  29. Inactivation of lincosaminide antibiotics in Staphylococcus. Identification of lincosaminide O-nucleotidyltransferases and comparison of the corresponding resistance genes.
    J Biol Chem. 1988 Nov 5;263(31):15880-7 PMID: 2846528
  30. Drug resistance patterns and serogroups or serotypes of pneumococcal isolates from cerebrospinal fluid or blood, 1979-1986.
    J Infect Dis. 1988 Nov;158(5):956-64 PMID: 3183429
  31. A community outbreak of group A beta haemolytic streptococci with transferable resistance to erythromycin.
    Epidemiol Infect. 1989 Feb;102(1):85-91 PMID: 2645155
  32. The emergence of erythromycin resistance in Streptococcus pyogenes in Fremantle, Western Australia.
    Med J Aust. 1989 Jun 5;150(11):626-7, 630-1 PMID: 2657347
  33. Purification and characterization of macrolide 2'-phosphotransferase from a strain of Escherichia coli that is highly resistant to erythromycin.
    Antimicrob Agents Chemother. 1989 Aug;33(8):1354-7 PMID: 2478074
  34. Characterisation and molecular cloning of the novel macrolide-streptogramin B resistance determinant from Staphylococcus epidermidis.
    J Antimicrob Chemother. 1989 Dec;24(6):851-62 PMID: 2559912
  35. Erythromycin-resistant Streptococcus pyogenes.
    J Antimicrob Chemother. 1990 Apr;25(4):723-4 PMID: 2190978
  36. Binding protein-dependent transport systems.
    J Bioenerg Biomembr. 1990 Aug;22(4):571-92 PMID: 2229036
  37. Inducible erythromycin resistance in staphylococci is encoded by a member of the ATP-binding transport super-gene family.
    Mol Microbiol. 1990 Jul;4(7):1207-14 PMID: 2233255
  38. Characterization of plasmids that confer inducible resistance to 14-membered macrolides and streptogramin type B antibiotics in Staphylococcus aureus.
    Microbiol Immunol. 1990;34(9):723-35 PMID: 2126591
  39. Triple post-transcriptional control.
    Mol Microbiol. 1990 Sep;4(9):1419-23 PMID: 1704997
  40. Detection of erythromycin resistance by the polymerase chain reaction using primers in conserved regions of erm rRNA methylase genes.
    Antimicrob Agents Chemother. 1990 Oct;34(10):2024-6 PMID: 2291670
  41. Antimicrobial resistance of Streptococcus pneumoniae in the United States, 1979-1987. The Pneumococcal Surveillance Working Group.
    J Infect Dis. 1991 Jun;163(6):1273-8 PMID: 2037792
  42. Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification.
    Antimicrob Agents Chemother. 1991 Jul;35(7):1267-72 PMID: 1929280
  43. Intrinsic and unusual resistance to macrolide, lincosamide, and streptogramin antibiotics in bacteria.
    Antimicrob Agents Chemother. 1991 Jul;35(7):1273-6 PMID: 1929281
  44. Resistance to erythromycin in group A streptococci.
    N Engl J Med. 1992 Jan 30;326(5):292-7 PMID: 1728733
  45. Antimicrobial resistance in Streptococcus pneumoniae: an overview.
    Clin Infect Dis. 1992 Jul;15(1):77-83 PMID: 1617076
  46. Cloning and sequencing of a plasmid-mediated erythromycin resistance determinant from Staphylococcus xylosus.
    FEMS Microbiol Lett. 1992 Oct 1;76(1-2):141-7 PMID: 1426997
  47. Purification and characterization of macrolide 2'-phosphotransferase type II from a strain of Escherichia coli highly resistant to macrolide antibiotics.
    FEMS Microbiol Lett. 1992 Oct 1;76(1-2):89-94 PMID: 1330822
  48. Nucleotide sequence and characterization of erythromycin resistance determinant that encodes macrolide 2'-phosphotransferase I in Escherichia coli.
    Antimicrob Agents Chemother. 1995 Oct;39(10):2359-63 PMID: 8619599
  49. A mechanism of resistance to partial macrolide and streptogramin B antibiotics in Staphylococcus aureus clinically isolated in Hungary.
    Biol Pharm Bull. 1995 Nov;18(11):1482-6 PMID: 8593463
  50. Clinical strain of Staphylococcus aureus inactivates and causes efflux of macrolides.
    Antimicrob Agents Chemother. 1996 Apr;40(4):992-8 PMID: 8849266
  51. Clindamycin therapy of experimental meningitis caused by penicillin- and cephalosporin-resistant Streptococcus pneumoniae.
    Antimicrob Agents Chemother. 1996 Jan;40(1):122-6 PMID: 8787892
  52. Recurrence of pneumococcal sepsis caused by an intermediately penicillin-resistant organism treated with loracarbef.
    Pediatr Infect Dis J. 1996 Apr;15(4):379-80 PMID: 8866813
  53. Distribution of genes encoding erythromycin ribosomal methylases and an erythromycin efflux pump in epidemiologically distinct groups of staphylococci.
    J Antimicrob Chemother. 1993 Feb;31(2):211-7 PMID: 8463168
  54. Penetration of lipophilic agents with multiple protonation sites into bacterial cells: tetracyclines and fluoroquinolones as examples.
    Antimicrob Agents Chemother. 1993 Jul;37(7):1393-9 PMID: 8363364
  55. An increase of 63 kDa-protein present in the cell membranes of Staphylococcus aureus that bears a plasmid mediating inducible resistance to partial macrolide and streptogramin B antibiotics.
    Biol Pharm Bull. 1993 Dec;16(12):1288-90 PMID: 8130780
  56. Three different phenotypes of erythromycin-resistant Streptococcus pyogenes in Finland.
    J Antimicrob Chemother. 1993 Dec;32(6):885-91 PMID: 8144429
  57. Prevention of drug access to bacterial targets: permeability barriers and active efflux.
    Science. 1994 Apr 15;264(5157):382-8 PMID: 8153625
  58. Identification of mutations in 23S rRNA gene of clarithromycin-resistant Mycobacterium intracellulare.
    Antimicrob Agents Chemother. 1994 Feb;38(2):381-4 PMID: 8192472
  59. Emergence of drug-resistant pneumococcal infections in the United States.
    JAMA. 1994 Jun 15;271(23):1831-5 PMID: 8196139
  60. Dilemmas in diagnosis and management of cephalosporin-resistant Streptococcus pneumoniae meningitis.
    Pediatr Infect Dis J. 1993 Mar;12(3):196-200 PMID: 8451095
  61. Activity of oral antibiotics in middle ear and sinus infections caused by penicillin-resistant Streptococcus pneumoniae: implications for treatment.
    Pediatr Infect Dis J. 1994 Jul;13(7):585-9 PMID: 7970944
  62. In vitro susceptibility of recent North American group A streptococcal isolates to eleven oral antibiotics.
    Pediatr Infect Dis J. 1994 Jul;13(7):630-5 PMID: 7970952
  63. Application of nuclear magnetic resonance spectrometry to measure the activity of bacterial macrolide esterase.
    Microbios. 1994;79(321):231-9 PMID: 7837995
  64. Identification of a chromosomally encoded ABC-transport system with which the staphylococcal erythromycin exporter MsrA may interact.
    Gene. 1995 Feb 3;153(1):93-8 PMID: 7883194
  65. Resistance of Neisseria gonorrhoeae to antimicrobial hydrophobic agents is modulated by the mtrRCDE efflux system.
    Microbiology. 1995 Mar;141 ( Pt 3):611-22 PMID: 7711899
  66. Antibiotic resistance in group A streptococci.
    Pediatr Clin North Am. 1995 Jun;42(3):539-51 PMID: 7761140
  67. Insights into erythromycin action from studies of its activity as inducer of resistance.
    Antimicrob Agents Chemother. 1995 Apr;39(4):797-805 PMID: 7785974
Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
Published
1996-08-00
Pages
1817-24
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC163423
Subset
IM
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