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Antimicrob Agents Chemother. Oct 1995; 39(10): 2282–2288.
PMCID: PMC162930

Identification of multiple clones of extended-spectrum cephalosporin-resistant Streptococcus pneumoniae isolates in the United States.


We characterized 12 isolates of Streptococcus pneumoniae with various levels of susceptibility of penicillin and extended-spectrum cephalosporins by antimicrobial susceptibility patterns, serotypes, ribotypes, chromosomal DNA restriction patterns by pulsed-field gel electrophoresis, multilocus enzyme electrophoresis patterns, penicillin-binding protein (PBP) profiles, and DNA restriction endonuclease cleavage profiles of pbp1a, pbp2x, and pbp2b. Seven cefotaxime-resistant (MIC, > or = 2 micrograms/ml) serotype 23F isolates were related on the basis of ribotyping, pulsed-field gel electrophoresis, and multilocus enzyme electrophoresis, but they had two slightly different PBP patterns: one unique to strains for which the MIC of penicillin is high (4.0 micrograms/ml) and one unique to strains for which the MIC of penicillin is low (0.12 to 1.0 micrograms/ml). The pbp1a and pbp2x fingerprints were identical for the seven isolates; however, the pbp2b fingerprints were different. An eighth serotype 23F isolate with high-level resistance to cephalosporins was not related to the other seven isolates by typing data but was a variant of the widespread, multiresistant serotype 23F Spanish clone. The PBP profiles and fingerprints of pbp1a, pbp2x, and pbp2b were identical to those of the Spanish clone isolate. An additional serotype 6B isolate with high-level resistance to cephalosporins had unique typing profiles and was unrelated to the serotype 23F cephalosporin-resistant isolates but was related on the basis of genetic typing methods to a second serotype 6B isolate that was cephalosporin susceptible. The serotype 6B isolates had different PBP profiles and fingerprints for pbp1a, but the fingerprints for pbp2x and pbp2b were the same.

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Selected References

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  • Appelbaum PC. Antimicrobial resistance in Streptococcus pneumoniae: an overview. Clin Infect Dis. 1992 Jul;15(1):77–83. [PubMed]
  • Bradley JS, Connor JD. Ceftriaxone failure in meningitis caused by Streptococcus pneumoniae with reduced susceptibility to beta-lactam antibiotics. Pediatr Infect Dis J. 1991 Nov;10(11):871–873. [PubMed]
  • Coffey TJ, Daniels M, McDougal LK, Dowson CG, Tenover FC, Spratt BG. Genetic analysis of clinical isolates of Streptococcus pneumoniae with high-level resistance to expanded-spectrum cephalosporins. Antimicrob Agents Chemother. 1995 Jun;39(6):1306–1313. [PMC free article] [PubMed]
  • Coffey TJ, Dowson CG, Daniels M, Zhou J, Martin C, Spratt BG, Musser JM. Horizontal transfer of multiple penicillin-binding protein genes, and capsular biosynthetic genes, in natural populations of Streptococcus pneumoniae. Mol Microbiol. 1991 Sep;5(9):2255–2260. [PubMed]
  • Dowson CG, Coffey TJ, Kell C, Whiley RA. Evolution of penicillin resistance in Streptococcus pneumoniae; the role of Streptococcus mitis in the formation of a low affinity PBP2B in S. pneumoniae. Mol Microbiol. 1993 Aug;9(3):635–643. [PubMed]
  • Dowson CG, Coffey TJ, Spratt BG. Origin and molecular epidemiology of penicillin-binding-protein-mediated resistance to beta-lactam antibiotics. Trends Microbiol. 1994 Oct;2(10):361–366. [PubMed]
  • Dowson CG, Hutchison A, Brannigan JA, George RC, Hansman D, Liñares J, Tomasz A, Smith JM, Spratt BG. Horizontal transfer of penicillin-binding protein genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8842–8846. [PMC free article] [PubMed]
  • Dowson CG, Hutchison A, Spratt BG. Extensive re-modelling of the transpeptidase domain of penicillin-binding protein 2B of a penicillin-resistant South African isolate of Streptococcus pneumoniae. Mol Microbiol. 1989 Jan;3(1):95–102. [PubMed]
  • Dowson CG, Johnson AP, Cercenado E, George RC. Genetics of oxacillin resistance in clinical isolates of Streptococcus pneumoniae that are oxacillin resistant and penicillin susceptible. Antimicrob Agents Chemother. 1994 Jan;38(1):49–53. [PMC free article] [PubMed]
  • Friedland IR, Shelton S, Paris M, Rinderknecht S, Ehrett S, Krisher K, McCracken GH., Jr Dilemmas in diagnosis and management of cephalosporin-resistant Streptococcus pneumoniae meningitis. Pediatr Infect Dis J. 1993 Mar;12(3):196–200. [PubMed]
  • Gasc AM, Kauc L, Barraillé P, Sicard M, Goodgal S. Gene localization, size, and physical map of the chromosome of Streptococcus pneumoniae. J Bacteriol. 1991 Nov;173(22):7361–7367. [PMC free article] [PubMed]
  • Haglund LA, Istre GR, Pickett DA, Welch DF, Fine DP. Invasive pneumococcal disease in central Oklahoma: emergence of high-level penicillin resistance and multiple antibiotic resistance. Pneumococcus Study Group. J Infect Dis. 1993 Dec;168(6):1532–1536. [PubMed]
  • Hakenbeck R, Martin C, Dowson C, Grebe T. Penicillin-binding protein 2b of Streptococcus pneumoniae in piperacillin-resistant laboratory mutants. J Bacteriol. 1994 Sep;176(17):5574–5577. [PMC free article] [PubMed]
  • Hakenbeck R, Tornette S, Adkinson NF. Interaction of non-lytic beta-lactams with penicillin-binding proteins in Streptococcus pneumoniae. J Gen Microbiol. 1987 Mar;133(3):755–760. [PubMed]
  • John CC. Treatment failure with use of a third-generation cephalosporin for penicillin-resistant pneumococcal meningitis: case report and review. Clin Infect Dis. 1994 Feb;18(2):188–193. [PubMed]
  • Jorgensen JH, Doern GV, Maher LA, Howell AW, Redding JS. Antimicrobial resistance among respiratory isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae in the United States. Antimicrob Agents Chemother. 1990 Nov;34(11):2075–2080. [PMC free article] [PubMed]
  • Kell CM, Jordens JZ, Daniels M, Coffey TJ, Bates J, Paul J, Gilks C, Spratt BG. Molecular epidemiology of penicillin-resistant pneumococci isolated in Nairobi, Kenya. Infect Immun. 1993 Oct;61(10):4382–4391. [PMC free article] [PubMed]
  • Klugman KP. Pneumococcal resistance to antibiotics. Clin Microbiol Rev. 1990 Apr;3(2):171–196. [PMC free article] [PubMed]
  • LACKS S, HOTCHKISS RD. A study of the genetic material determining an enzyme in Pneumococcus. Biochim Biophys Acta. 1960 Apr 22;39:508–518. [PubMed]
  • Laible G, Hakenbeck R. Five independent combinations of mutations can result in low-affinity penicillin-binding protein 2x of Streptococcus pneumoniae. J Bacteriol. 1991 Nov;173(21):6986–6990. [PMC free article] [PubMed]
  • Laible G, Hakenbeck R, Sicard MA, Joris B, Ghuysen JM. Nucleotide sequences of the pbpX genes encoding the penicillin-binding proteins 2x from Streptococcus pneumoniae R6 and a cefotaxime-resistant mutant, C506. Mol Microbiol. 1989 Oct;3(10):1337–1348. [PubMed]
  • Laible G, Spratt BG, Hakenbeck R. Interspecies recombinational events during the evolution of altered PBP 2x genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae. Mol Microbiol. 1991 Aug;5(8):1993–2002. [PubMed]
  • Lefevre JC, Faucon G, Sicard AM, Gasc AM. DNA fingerprinting of Streptococcus pneumoniae strains by pulsed-field gel electrophoresis. J Clin Microbiol. 1993 Oct;31(10):2724–2728. [PMC free article] [PubMed]
  • Levy J. Antibiotic resistance in Europe and the current use of antibiotics in severe pediatric infections. Scand J Infect Dis Suppl. 1990;73:23–29. [PubMed]
  • Martin C, Briese T, Hakenbeck R. Nucleotide sequences of genes encoding penicillin-binding proteins from Streptococcus pneumoniae and Streptococcus oralis with high homology to Escherichia coli penicillin-binding proteins 1a and 1b. J Bacteriol. 1992 Jul;174(13):4517–4523. [PMC free article] [PubMed]
  • Martin C, Sibold C, Hakenbeck R. Relatedness of penicillin-binding protein 1a genes from different clones of penicillin-resistant Streptococcus pneumoniae isolated in South Africa and Spain. EMBO J. 1992 Nov;11(11):3831–3836. [PMC free article] [PubMed]
  • McCaig LF, Hughes JM. Trends in antimicrobial drug prescribing among office-based physicians in the United States. JAMA. 1995 Jan 18;273(3):214–219. [PubMed]
  • McDougal LK, Facklam R, Reeves M, Hunter S, Swenson JM, Hill BC, Tenover FC. Analysis of multiply antimicrobial-resistant isolates of Streptococcus pneumoniae from the United States. Antimicrob Agents Chemother. 1992 Oct;36(10):2176–2184. [PMC free article] [PubMed]
  • Muñoz R, Coffey TJ, Daniels M, Dowson CG, Laible G, Casal J, Hakenbeck R, Jacobs M, Musser JM, Spratt BG, et al. Intercontinental spread of a multiresistant clone of serotype 23F Streptococcus pneumoniae. J Infect Dis. 1991 Aug;164(2):302–306. [PubMed]
  • Muñoz R, Dowson CG, Daniels M, Coffey TJ, Martin C, Hakenbeck R, Spratt BG. Genetics of resistance to third-generation cephalosporins in clinical isolates of Streptococcus pneumoniae. Mol Microbiol. 1992 Sep;6(17):2461–2465. [PubMed]
  • Munoz R, Musser JM, Crain M, Briles DE, Marton A, Parkinson AJ, Sorensen U, Tomasz A. Geographic distribution of penicillin-resistant clones of Streptococcus pneumoniae: characterization by penicillin-binding protein profile, surface protein A typing, and multilocus enzyme analysis. Clin Infect Dis. 1992 Jul;15(1):112–118. [PubMed]
  • Negri MC, Morosini MI, Loza E, Baquero F. In vitro selective antibiotic concentrations of beta-lactams for penicillin-resistant Streptococcus pneumoniae populations. Antimicrob Agents Chemother. 1994 Jan;38(1):122–125. [PMC free article] [PubMed]
  • Selander RK, Caugant DA, Ochman H, Musser JM, Gilmour MN, Whittam TS. Methods of multilocus enzyme electrophoresis for bacterial population genetics and systematics. Appl Environ Microbiol. 1986 May;51(5):873–884. [PMC free article] [PubMed]
  • Sibold C, Wang J, Henrichsen J, Hakenbeck R. Genetic relationships of penicillin-susceptible and -resistant Streptococcus pneumoniae strains isolated on different continents. Infect Immun. 1992 Oct;60(10):4119–4126. [PMC free article] [PubMed]
  • Sloas MM, Barrett FF, Chesney PJ, English BK, Hill BC, Tenover FC, Leggiadro RJ. Cephalosporin treatment failure in penicillin- and cephalosporin-resistant Streptococcus pneumoniae meningitis. Pediatr Infect Dis J. 1992 Aug;11(8):662–666. [PubMed]
  • Spika JS, Facklam RR, Plikaytis BD, Oxtoby MJ. Antimicrobial resistance of Streptococcus pneumoniae in the United States, 1979-1987. The Pneumococcal Surveillance Working Group. J Infect Dis. 1991 Jun;163(6):1273–1278. [PubMed]
  • Versalovic J, Kapur V, Mason EO, Jr, Shah U, Koeuth T, Lupski JR, Musser JM. Penicillin-resistant Streptococcus pneumoniae strains recovered in Houston: identification and molecular characterization of multiple clones. J Infect Dis. 1993 Apr;167(4):850–856. [PubMed]

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