Hostname: page-component-848d4c4894-75dct Total loading time: 0 Render date: 2024-06-12T02:26:22.090Z Has data issue: false hasContentIssue false

New Insights on the Genetic Basis for Resistance

Published online by Cambridge University Press:  21 June 2016

Charles W. Stratton*
Affiliation:
Vanderbilt University School of Medicine, Nashville, Tennessee
*
Vanderbilt University School of Medicine, Nashville, TN 37232-2561

Extract

One of the more important aspects of nosocomial infections is that they often are caused by bacterial strains resistant to many antimicrobial agents. Despite over 50 years in the development and use of a wide variety of antibiotics, bacterial resistance mechanisms have not been defeated and are playing an increasingly important role in the therapy of infections.

The mechanisms of bacterial resistance, moreover, are constantly changing, but our understanding of these resistance mechanisms at a molecular level is rapidly increasing.” Yet importantly, a detailed knowledge and understanding of the genetic basis for bacterial resistance is of great importance for the proper evaluation and control of nosocomial infections caused by resistant pathogens. The purpose of this discussion is to provide insights into the genetic basis for bacterial resistance and to describe some newer mechanisms of bacterial resistance that influence the therapeutic approach to nosocomial infections.

Type
Special Sections
Copyright
Copyright © The Society for Healthcare Epidemiology of America 1989

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Lyon, BR, Skurray, R: Antimicrobial resistance of Staphylococcus aureus . Microbiol Rev 1987; 51:83134.10.1128/mr.51.1.88-134.1987Google Scholar
2. Speller, DCE: Hospital infection by multi-resistant gram-negative bacilli. J Antimicrob Chemother 1980; 6: 16X170.10.1093/jac/6.2.168Google Scholar
3. Neu, HC: The emergence of bacterial resistance and irs influence on empiric therapy. Rev Infect Dis 1983; 5(suppl):S9S20.10.1093/clinids/5.Supplement_1.S9Google Scholar
4. Neu, HC: Changing mechanisms of bacterial resistance. Am J Med 1984; 77:1123.10.1016/S0002-9343(84)80091-1Google Scholar
5. Young, HK: Recent advances in the evolution of drug resistance. J Antimicrob Chemother 3985; 16:679680.10.1093/jac/16.6.679CrossRefGoogle Scholar
6. Greenwood, D: Phenotypic resistance to antimicrobial agents. J Antimicrob Chemother 15:653658.10.1093/jac/15.6.653Google Scholar
7. Gunnison, JB, Fraher, MA. Jawetz, E: Persistence of Staphylococcus aureus in penicillin in-vitro. J Gen Microbiol 1963; 34:335349.Google Scholar
8. Greenwood, D, O'Grady, F: Trimodal response of Escherichia coli and Proteus mirabilis to penicillins. Nature 1970; 228:457458.10.1038/228457a0Google Scholar
9. Tuomanen, E, Cozens, R. Tosch, W, et at: The rate of killing of Escherichia coli by β-Iactam antibiotics is strictly proportional to the rate of bacterial growth. J Gen Microbiol tY86; 132:12971304.Google Scholar
10. Richmond, MH. Sykes, RB: The β-lactamases of gram-negative bacteria and their possible physiologic role. Adv Microb Physiol 1973; 9:3188.10.1016/S0065-2911(08)60376-8Google Scholar
11. Sanders, CC. Sanders, WE Jr: Emergence of resistance to cefamandole: Possible role of cefoxitin-inducible β-lactamases. Antimicrob Agents Chum-other 1979; 15:792797.10.1128/AAC.15.6.792Google Scholar
12. Sanders, CC, Sanders, WE Jr: Emergence of resistance during therapy with the newer β-lactam antibiotics: Rote of inducible β-lactamases and implications for the future. Rev Infect Dis 1983; 5:639648.10.1093/clinids/5.4.639Google Scholar
13. Bush, K, Freudenberger, JS, Sykes, RB: Interaction of aztreonam and related monobactams with β-lactamases from gram-negative bacteria. Antimicrob Agents Chemother 1982; 22:414420.10.1128/AAC.22.3.414Google Scholar
14. Parr, TR. Bayer, AS: Mechanisms of aminoglycoside resistance in variants of Pseudomonas aeruginosa isolated during treatment of experimentat endocarditis in rabbits. J Infect Dis 1988; 158: 10031010.10.1093/infdis/158.5.1003Google Scholar
15. Bryan, LE: Aminoglycoside resistance, in Bryan, LE (ed): Antimicrobial Drug Resistance, Orlando, Fla, Academic Press, 1984.Google Scholar
16. Bryan, LE, Kwan, S: Roles of ribosomal binding, membrane potential and electron transport in bacterial uptake of streptomycin and gentamicin. Antimkrob Agents Chemother 1983; 23:835845.10.1128/AAC.23.6.835Google Scholar
17. Mawer, SL. Greenwood, D: Specific and non-specific resistance to aminoglycosides in Escherichia coli . J Clin Pathol 1978; 31:1215.10.1136/jcp.31.1.12Google Scholar
18. Mawer, SL, Greenwood, D: Aminoglycoside resistance emerging during therapy. Lancet 1977; 1:749750.10.1016/S0140-6736(77)92192-4Google Scholar
19. Sanders, CC, Sanders, WE Jr: Type I β-lactamases of gram-negative bacteria: Interactions with β-lactam antibiotics. J Inject Dis 1986; 154:792800.10.1093/infdis/154.5.792Google Scholar
20. Livermore, DM, Yang, YJ: β-lactamase liability and Inducer power of newer β-lactams in relation to their activity against β-lactamase inducibility mutants of Pseudomonas aeruginosa . J Infect Dis 1987; 155:775782.10.1093/infdis/155.4.775Google Scholar
21. Vu, H. Nikaido, H: Role of β-lactam hydrolysis in mechanism of resistance of a β-lactamase-constitutive Enterobacter cloacae strain to expanded spectrum β-lactams. Antimicrob Agents Chemother tY85: 27:393398.10.1128/AAC.27.3.393Google Scholar
22. Stratton, CW, Tausk, F: Synergistic resistance mechanisms in Pseudomonas aeruginosa . J Antimicrob Chemother 1987; 19:413–410.10.1093/jac/19.4.413Google Scholar
23. Qtinn, JP. Di Vincenzo, CA, Foster, J: Emergence of resistance to ceftazidime during therapy tor Enterobacter cloacae infections. J Infect Dis 1987: 155:942947.Google Scholar
24. Nikaido, H: Role of permeability barriers in resistance to β-lactam antibiotics. Pharmacol Titer 1985; 27:197231.Google ScholarPubMed
25. Hancock, REW: Role of porins in outer membrane permeability. J Bacteriol 1987: 169:929933.10.1128/jb.169.3.929-933.1987Google Scholar
26. Quinn, JP, Studemeister, AE. DiVincenzo, CA, et al: Resistance to imipenem in Pseudomonas aeruginosa: Clinical experience and biochemical mechanisms. Rev Infect Dis 1988; 10:892898.10.1093/clinids/10.4.892Google Scholar
27. Legakis, NJ, Tzouvelekm, LS, Makris, A, et al: Outer membrane alterations in multiresistant mutants of Pseudomonas aeruginosa selected by ciprofloxacin. Antimicrob Agents Chemother 1989; 33:124127.10.1128/AAC.33.1.124Google Scholar
28. Robillard, NJ. Scarpa, AL: Genetic: and physiological characterization of ciprofloxacin resistance in Pseudomonas aeruginosa PAO. Antimicrob Agents Chemother 1988; 32:535539.10.1128/AAC.32.4.535Google Scholar
29. Neu, HC: Bacterial resistance to fluoroquinolones. Rev Infect Dis 1988: 10(suppl 1):S27S63.10.1093/clinids/10.Supplement_1.S57Google Scholar
30. Stratton, CW, Franke, JJ, Weeks, LS. et al: Comparison of the bactericidal activity of ciprofloxacin alone and in combination with selected anti-pseudomonal β-lactam agents against clinical isolates of Pseudomonas aeruginosa . Diagn Microbiol Infect Dis 1989; 11:4152.10.1016/0732-8893(88)90072-7Google Scholar
31. Sanders, CC, Sanders, WF Jr., Goering, RV. et al: Selection of multiple-antibiotic resistance by quinolones, β-lactams, and aminoglycosides with special reference to cross-resistance between unrelated drug classes. Antimicrob Agents Chemother 1984; 26:797801.10.1128/AAC.26.6.797Google Scholar
32. Lupski, JR: Molecular mechanisms for transposition of drug-resistance genes and other movable genetic elements. Rev Infect Dis 1987; 9:357368.10.1093/clinids/9.2.357Google Scholar
33. Engel, HWB, Soedirman, N. Rost, JA, et al: Transterability of macrolide lincomycin and Streptogramiu resistances between group A. B and D streptococci, Streptococcus pneumoniae and Staphylococcus aureus . J Bacteriol 1980; 142:407413.10.1128/jb.142.2.407-413.1980Google Scholar
34. Guiney, DG Jr: Promiscuous transfer of drug resistance in gram-negative bacteria. J Infect Dis, 1984; 149:320328.10.1093/infdis/149.3.320Google Scholar
35. Wiedemann, B, Meyer, JF, Nies, BA, et al: Transposable multiresistance. J Antimicrob Chemother 1985; 16:416417.10.1093/jac/16.4.416Google Scholar
36. Shaberg, DR. Rubens, CE, Alford, RH, et al: Evolution of antimicrobial resistance and nosocomial infection. Am J Med 1981; 70:445448.10.1016/0002-9343(81)90786-5Google Scholar
37. Kliebe, C, Nies, BA, Meyer, JE, et al: Evolution of plasmid-coded resistance to broad-spectrum cephalosporins. Antimicrob Agents Chemother 1985; 28:302307.10.1128/AAC.28.2.302Google Scholar
38. Sougakoff, W, Goussard, S, Gerbaud, G, et al: Plasmid-niediated resistance to third-generation cephalosporins caused by point mutations in TEM-type penicillinase genes. Rev Infect Dis 1988:10:879884.10.1093/clinids/10.4.879Google Scholar
39. Sirot, D, Sirot, J, Labia, R. et al: Transferable resistance to third-generation cephalosporins in clinical isolates of Klebsiella pneumoniae: Identification of CTX-1, a novel β-lactamase. J Antimicrob Chemother 1987; 20:323334.10.1093/jac/20.3.323Google Scholar
40. Petit, A. Sirot, DL, Chanal, M, et al: Novel plasmid-mediated β-lactamase in clinical isolates of Klebsiella pneumoniae more resistant to ceftazidime than to other broad-spectrum cephalosporins. Antimicrob Agents Chemother 1988; 32:626630.10.1128/AAC.32.5.626Google Scholar
41. Lacey, RW: Evolution of microorganisms and antibiotic resistance. Lancet 1984; ii: 10221025.10.1016/S0140-6736(84)91117-6Google Scholar
42. Hawkey, PM: The molecular evolution of antibiotic resistance genes in gram-negative bacteria. J Antimicrob Chemother 1986; 18:147151.10.1093/jac/18.2.147Google Scholar
43. Datta, N. Kontomichalou, P: Penicillinase synthesis controlled by infectious R-factors in Enterobactenaceae . Nature (London) 1965; 208:239241.10.1038/208239a0Google Scholar
44. Matthew, M: Plasmid-mediated β-lactamases of gram-negative bacteria: Properties and distribution. J Antimicrob Chemother 1979; 5:349358.10.1093/jac/5.4.349Google Scholar
45. Hedges, RW. Jacob, AE: Transposition of ampieillin resistance from RP4 to other replicons. Mol Gen Genet 1974: 132:3140.10.1007/BF00268228Google Scholar
46. Archer, GL. Johnston, JL: Self-transmissible plasmids in staphylococci that encode resistance to aminoglycosides. Antimicrob Agents Chemother 1983; 24:7077.10.1128/AAC.24.1.70Google Scholar
47. Ikeda, DP. Barry, AL. Anderson, SG: Emergence of Streptococcus faecalis isolates with high-level resistance to multiple aminocyclitol aminoglycosides. Diag Microbiol Infect Dis 1984; 2:171177.10.1016/0732-8893(84)90027-0Google Scholar
48. Murray, BE, Mederski-Samoraj, BD: Transferable β-lactamase: A new mechanism for in-vitro penicillin resistance in Streptococcus faecalis . J Clin Invest 1983; 72:11681171.10.1172/JCI111042Google Scholar
49. Williamson, R, Al-Obeid, S, Shlaes, JH. et al: Inducible resistance to Vancomycin in Enterococcus faecium D366. J Infect Dis 1989; 159: 10951104.10.1093/infdis/159.6.1095Google Scholar
50. Uttley, AHC, Collins, CH, Naidodo, J, et al: Vancomvcin-resistaiit enterococci. Lancet 1988; i:5758.10.1016/S0140-6736(88)91037-9Google Scholar