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. 1996 Apr;40(4):874–878. doi: 10.1128/aac.40.4.874

Activities of the glycylcyclines N,N-dimethylglycylamido-minocycline and N,N-dimethylglycylamido-6-demethyl-6-deoxytetracycline against Nocardia spp. and tetracycline-resistant isolates of rapidly growing mycobacteria.

B A Brown 1, R J Wallace Jr 1, G Onyi 1
PMCID: PMC163222  PMID: 8849243

Abstract

Susceptibilities to the new semisynthetic tetracycline (Tet) compounds N,N-dimethylglycylamido-minocycline (DMG-MINO) and N,N-dimethylglycylamido-6-demethyl-6-deoxytetracycline (DMG-DMDOT) were compared with those to doxycycline, minocycline, and Tet for 198 Tet-resistant (Tetr) and 33 Tet-susceptible (Tets) clinical isolates of rapidly growing mycobacteria (RGM) including the Mycobacterium fortuitum group, Mycobacterium abscessus, Mycobacterium chelonae, and Mycobacterium mucogenicum and 68 isolates belonging to six taxa of Nocardia spp. All Tetr RGM were highly susceptible to the glycylcyclines. The MICs at which 50 and 90% of isolates are inhibited were < or = 0.125 and < or = 0.25 microgram/ml, respectively, for DMG-DMDOT and < or = 0.25 and 1 microgram/ml, respectively, for DMG-MINO. The MIC of DMG-DMDOT at which 50% of Tetr strains are inhibited was the same as that for Tets strains for each of the four taxa of RGM. The new agents were less active against Nocardia spp. MICs of DMG-DMDOT were comparable to those of minocycline except for the MICs for Nocardia brasiliensis sensu stricto, the new taxon Nocardia pseudobrasiliensis, and some isolates of Nocardia nova, against which they were four- to eightfold more active. The MICs of DMG-DMDOT were consistently lower than those of DMG-MINO for RGM. This class of drugs offers exciting therapeutic potential for RGM and for selected species of Nocardia.

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Selected References

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  1. Band J. D., Ward J. I., Fraser D. W., Peterson N. J., Silcox V. A., Good R. C., Ostroy P. R., Kennedy J. Peritonitis due to a mycobacterium chelonei-like organism associated with intermittent chronic peritoneal dialysis. J Infect Dis. 1982 Jan;145(1):9–17. doi: 10.1093/infdis/145.1.9. [DOI] [PubMed] [Google Scholar]
  2. Brown B. A., Wallace R. J., Jr, Flanagan C. W., Wilson R. W., Luman J. I., Redditt S. D. Tetracycline and erythromycin resistance among clinical isolates of Branhamella catarrhalis. Antimicrob Agents Chemother. 1989 Sep;33(9):1631–1633. doi: 10.1128/aac.33.9.1631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brown B. A., Wallace R. J., Jr, Onyi G. O., De Rosas V., Wallace R. J., 3rd Activities of four macrolides, including clarithromycin, against Mycobacterium fortuitum, Mycobacterium chelonae, and M. chelonae-like organisms. Antimicrob Agents Chemother. 1992 Jan;36(1):180–184. doi: 10.1128/aac.36.1.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chopra I., Hawkey P. M., Hinton M. Tetracyclines, molecular and clinical aspects. J Antimicrob Chemother. 1992 Mar;29(3):245–277. doi: 10.1093/jac/29.3.245. [DOI] [PubMed] [Google Scholar]
  5. Dalovisio J. R., Pankey G. A., Wallace R. J., Jones D. B. Clinical usefulness of amikacin and doxycycline in the treatment of infection due to Mycobacterium fortuitum and Mycobacterium chelonei. Rev Infect Dis. 1981 Sep-Oct;3(5):1068–1074. doi: 10.1093/clinids/3.5.1068. [DOI] [PubMed] [Google Scholar]
  6. Dore N., Collins J. P., Mankiewicz E. A sporotrichoid-like Mycobacterium kansasii infection of the skin treated with minocycline hydrochloride. Br J Dermatol. 1979 Jul;101(1):75–79. doi: 10.1111/j.1365-2133.1979.tb15296.x. [DOI] [PubMed] [Google Scholar]
  7. Hironaga M., Mochizuki T., Watanabe S. Acute primary cutaneous nocardiosis. J Am Acad Dermatol. 1990 Aug;23(2 Pt 2):399–400. doi: 10.1016/0190-9622(90)70232-7. [DOI] [PubMed] [Google Scholar]
  8. Ji B., Jamet P., Perani E. G., Bobin P., Grosset J. H. Powerful bactericidal activities of clarithromycin and minocycline against Mycobacterium leprae in lepromatous leprosy. J Infect Dis. 1993 Jul;168(1):188–190. doi: 10.1093/infdis/168.1.188. [DOI] [PubMed] [Google Scholar]
  9. Manavathu E. K., Fernandez C. L., Cooperman B. S., Taylor D. E. Molecular studies on the mechanism of tetracycline resistance mediated by Tet(O). Antimicrob Agents Chemother. 1990 Jan;34(1):71–77. doi: 10.1128/aac.34.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Pang Y., Brown B. A., Steingrube V. A., Wallace R. J., Jr, Roberts M. C. Tetracycline resistance determinants in Mycobacterium and Streptomyces species. Antimicrob Agents Chemother. 1994 Jun;38(6):1408–1412. doi: 10.1128/aac.38.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rasmussen B. A., Gluzman Y., Tally F. P. Inhibition of protein synthesis occurring on tetracycline-resistant, TetM-protected ribosomes by a novel class of tetracyclines, the glycylcyclines. Antimicrob Agents Chemother. 1994 Jul;38(7):1658–1660. doi: 10.1128/aac.38.7.1658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ruimy R., Riegel P., Carlotti A., Boiron P., Bernardin G., Monteil H., Wallace R. J., Jr, Christen R. Nocardia pseudobrasiliensis sp. nov., a new species of Nocardia which groups bacterial strains previously identified as Nocardia brasiliensis and associated with invasive diseases. Int J Syst Bacteriol. 1996 Jan;46(1):259–264. doi: 10.1099/00207713-46-1-259. [DOI] [PubMed] [Google Scholar]
  13. Silcox V. A., Good R. C., Floyd M. M. Identification of clinically significant Mycobacterium fortuitum complex isolates. J Clin Microbiol. 1981 Dec;14(6):686–691. doi: 10.1128/jcm.14.6.686-691.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Speer B. S., Shoemaker N. B., Salyers A. A. Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance. Clin Microbiol Rev. 1992 Oct;5(4):387–399. doi: 10.1128/cmr.5.4.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Springer B., Böttger E. C., Kirschner P., Wallace R. J., Jr Phylogeny of the Mycobacterium chelonae-like organism based on partial sequencing of the 16S rRNA gene and proposal of Mycobacterium mucogenicum sp. nov. Int J Syst Bacteriol. 1995 Apr;45(2):262–267. doi: 10.1099/00207713-45-2-262. [DOI] [PubMed] [Google Scholar]
  16. Steingrube V. A., Brown B. A., Gibson J. L., Wilson R. W., Brown J., Blacklock Z., Jost K., Locke S., Ulrich R. F., Wallace R. J., Jr DNA amplification and restriction endonuclease analysis for differentiation of 12 species and taxa of Nocardia, including recognition of four new taxa within the Nocardia asteroides complex. J Clin Microbiol. 1995 Dec;33(12):3096–3101. doi: 10.1128/jcm.33.12.3096-3101.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Swenson J. M., Wallace R. J., Jr, Silcox V. A., Thornsberry C. Antimicrobial susceptibility of five subgroups of Mycobacterium fortuitum and Mycobacterium chelonae. Antimicrob Agents Chemother. 1985 Dec;28(6):807–811. doi: 10.1128/aac.28.6.807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Tally F. T., Ellestad G. A., Testa R. T. Glycylcyclines: a new generation of tetracyclines. J Antimicrob Chemother. 1995 Apr;35(4):449–452. doi: 10.1093/jac/35.4.449. [DOI] [PubMed] [Google Scholar]
  19. Testa R. T., Petersen P. J., Jacobus N. V., Sum P. E., Lee V. J., Tally F. P. In vitro and in vivo antibacterial activities of the glycylcyclines, a new class of semisynthetic tetracyclines. Antimicrob Agents Chemother. 1993 Nov;37(11):2270–2277. doi: 10.1128/aac.37.11.2270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wallace R. J., Jr, Brown B. A., Blacklock Z., Ulrich R., Jost K., Brown J. M., McNeil M. M., Onyi G., Steingrube V. A., Gibson J. New Nocardia taxon among isolates of Nocardia brasiliensis associated with invasive disease. J Clin Microbiol. 1995 Jun;33(6):1528–1533. doi: 10.1128/jcm.33.6.1528-1533.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wallace R. J., Jr, Brown B. A., Onyi G. O. Skin, soft tissue, and bone infections due to Mycobacterium chelonae chelonae: importance of prior corticosteroid therapy, frequency of disseminated infections, and resistance to oral antimicrobials other than clarithromycin. J Infect Dis. 1992 Aug;166(2):405–412. doi: 10.1093/infdis/166.2.405. [DOI] [PubMed] [Google Scholar]
  22. Wallace R. J., Jr, Brown B. A., Silcox V. A., Tsukamura M., Nash D. R., Steele L. C., Steingrube V. A., Smith J., Sumter G., Zhang Y. S. Clinical disease, drug susceptibility, and biochemical patterns of the unnamed third biovariant complex of Mycobacterium fortuitum. J Infect Dis. 1991 Mar;163(3):598–603. doi: 10.1093/infdis/163.3.598. [DOI] [PubMed] [Google Scholar]
  23. Wallace R. J., Jr, Brown B. A., Tsukamura M., Brown J. M., Onyi G. O. Clinical and laboratory features of Nocardia nova. J Clin Microbiol. 1991 Nov;29(11):2407–2411. doi: 10.1128/jcm.29.11.2407-2411.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wallace R. J., Jr, Silcox V. A., Tsukamura M., Brown B. A., Kilburn J. O., Butler W. R., Onyi G. Clinical significance, biochemical features, and susceptibility patterns of sporadic isolates of the Mycobacterium chelonae-like organism. J Clin Microbiol. 1993 Dec;31(12):3231–3239. doi: 10.1128/jcm.31.12.3231-3239.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wallace R. J., Jr, Steele L. C., Sumter G., Smith J. M. Antimicrobial susceptibility patterns of Nocardia asteroides. Antimicrob Agents Chemother. 1988 Dec;32(12):1776–1779. doi: 10.1128/aac.32.12.1776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wallace R. J., Jr, Swenson J. M., Silcox V. A., Good R. C. Disk diffusion testing with polymyxin and amikacin for differentiation of Mycobacterium fortuitum and Mycobacterium chelonei. J Clin Microbiol. 1982 Dec;16(6):1003–1006. doi: 10.1128/jcm.16.6.1003-1006.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wallace R. J., Jr, Tanner D., Brennan P. J., Brown B. A. Clinical trial of clarithromycin for cutaneous (disseminated) infection due to Mycobacterium chelonae. Ann Intern Med. 1993 Sep 15;119(6):482–486. doi: 10.7326/0003-4819-119-6-199309150-00006. [DOI] [PubMed] [Google Scholar]
  28. Wallace R. J., Jr, Tsukamura M., Brown B. A., Brown J., Steingrube V. A., Zhang Y. S., Nash D. R. Cefotaxime-resistant Nocardia asteroides strains are isolates of the controversial species Nocardia farcinica. J Clin Microbiol. 1990 Dec;28(12):2726–2732. doi: 10.1128/jcm.28.12.2726-2732.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wallace R. J., Jr, Wiss K. Susceptibility of Mycobacterium marinum to tetracyclines and aminoglycosides. Antimicrob Agents Chemother. 1981 Nov;20(5):610–612. doi: 10.1128/aac.20.5.610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wise R., Andrews J. M. In vitro activities of two glycylcyclines. Antimicrob Agents Chemother. 1994 May;38(5):1096–1102. doi: 10.1128/aac.38.5.1096. [DOI] [PMC free article] [PubMed] [Google Scholar]

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