Skip to main content Accessibility help
×
Home

The Microbial Genetics of Antibiotic Cycling

  • Joseph F. John (a1) and Louis B. Rice (a2)

Abstract

Cycling of currently available antibiotics to reduce resistance is an attractive concept. For cycling strategies to be successful, their implementation must have a demonstrable impact on the prevalence of resistance determinants already dispersed throughout the hospital and associated healthcare facilities. While antibiotic use in hospitals clearly constitutes a stimulus for the emergence of resistance, it is by no means the only important factor. The incorporation of resistance determinants into potentially stable genetic structures, including bacteriophages, plasmids, transposons, and the more newly discovered movable elements termed integrons and gene cassettes, forces some degree of skepticism about the potential for such strategies in institutions where resistance determinants are already prevalent. In particular, the expanding role of integrons may pose an ultimate threat to formulary manipulations such as cycling. Despite these concerns, the crisis posed by antimicrobial resistance warrants investigation of any strategy with the potential for reducing the prevalence of resistance. Over the next decade, new studies with carefully designed outcomes should determine the utility of antibiotic cycling as one control measure for nosocomial resistance.

Copyright

Corresponding author

1 RWJPl, 356 MEB, UMDNJ/RWJMS, New Brunswick, NJ 08903-0019

References

Hide All
1.Davies, J, Webb, V. Antibiotic resistance in bacteria. In: Krause, RM, ed. Emerging Infections. San Diego, CA: Academic Press; 1998:239273.
2.Shlaes, DM, Gerding, DN, John, JF Jr, Craig, WA, Bornstein, DL, Duncan, RA, et al. Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals. Infect Control Hosp Epidemiol 1997;18:275291.
3.McGowan, JE Jr, Gerding, DN. Does antibiotic restriction prevent resistance? New Horiz 1996;4:370376.
4.Quintilliani, R, Sahm, DF, Courvalin, P. Antimicrobial resistance. In: Murray, R, Baron, MJ, Pfaller, MA, Tenover, FC, Yolken, RH, eds. Manual of Clinical Microbiology. Washington, DC: ASM Press; 1999:15051524.
5.Dyke, KG, Gregory, PResistance to β-lactam antibiotics. In: Crossley, KB, Archer, GL, eds. The Staphylococci in Human Disease. New York, NY: Livingstone Churchill; 1998:139157.
6.Bennett, PM. Integrons and gene cassettes: a genetic construction kit for bacteria. J Antimkrob Chemother 1999;43:14.
7.Lyon, BR, Skurray, R. Antimicrobial resistance of Staphylococcus aureus: genetic basis. Microbiol Rev 1987;51:88134.
8.Rice, LB, Carias, LL, Donskey, CL, Rudin, SD. Transferable, plasmid mediated vanB-type glycopeptide resistance in Enterococcus faecium. Antimkrob Agents Chemother 1998;42:963964.
9.Dowson, CG, Hutchison, A, Brannigan, JA, George, RC, Hansman, D, Linares, J, et al. Horizontal transfer of penicillin-binding protein genes in penicillin-resistant clinical isolates of Streptococcus pneumoniae. Proc Natl Acad Sci USA 1989;86:88428846.
10.Dowson, CG, Coffey, TJ, Spratt, BG. Origin and molecular epidemiology of penicillin-binding-protein-mediated resistance to beta-lactam antibiotics. Trends Microbiol 1994;2:361366.
11.Pradier, C, Dunais, B, Carsenti-Etesse, H, Dellamonica, P. Pneumococcal resistance patterns in Europe. Eur J Clin Microbiol Infect Dis 1997;16:644647.
12.Medeiros, AA, Cohenford, M, Jacoby, GA. Five novel plasmid-determined beta-lactamases. Antimkrob Agents Chemother 1985;27:715719.
13.Bush, K, Jacoby, GA, Medeiros, AA. A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimkrob Agents Chemother 1995;39:12111233.
14.Chambers, HEMethicillin resistance in staphylococci: molecular and biochemical basis and clinical implications. Clin Microbiol Rev 1997;10:781791.
15.Lowy, FD. Staphylococcus aureus infections. NEngl J Med 1998;339:520532.
16.Grayson, ML, Eliopoulos, GM, Wennersten, CB, Ruoff, KL, DeGirolami, PC, Ferrara, MJ, et al. Increasing resistance to beta-lactam antibiotics among clinical isolates of Enterococcus faecium: a 22-year review at one institution. Antimkrob Agents Chemother 1991;35:21802184.
17.Chow, JW, Fine, MJ, Shlaes, DM, Quinn, JP, Hooper, DC, Johnson, MP, et al. Enterobacter bacteremia: clinical features and emergence of antibiotic resistance during therapy. Ann Intern Med 1991;115:585590.
18.Livermore, DM. Interplay of impermeability and chromosomal beta-lactamase activity in imipenem-resistant Pseudomonas aeruginosa. Antimkrob Agents Chemother 1992;36:20462048.
19.Bradford, PA, Urban, C, Mariano, N, Projan, SJ, Ranal, JJ, Bush, K. Imipenem resistance in Klebsiella pneumoniae is associated with the combination of ACT-1, a plasmid-mediated AmpC beta-lactamase, and the foss of an outer membrane protein. Antimkrob Agents Chemother 1997;41:563569.
20.Papanicolaou, GA, Medeiros, AA, Jacoby, GANovel plasmid-mediated beta-lactamase (MIR-1) conferring resistance to oxyimino- and alpha-methoxy beta-lactams in clinical isolates of Klebsiella pneumoniae. Antimkrob Agents Chemother 1990;34:22002209.
21.Hooper, DC. Bacterial topoisomerases, antitopoisomerases, and anti-topoisomerase resistance. Clin Infect Dis 1998;27(suppl 1):S54S63.
22.Dubin, DT, Fitzgibbon, JE, Nahvi, MD, John, JF. Topoisomerase sequences of coagulase-negative staphylococcal isolates resistant to ciprofloxacin or trovafloxacin. Antimkrob Agents Chemother 1999;43:16311637.
23.Huovinen, P, Sundstrom, L, Swedberg, G, Skold, O. Trimethoprim and sulfonamide resistance. Antimkrob Agents Chemother 1995;39:279289.
24.Amyes, SG. Genes and spectrum: the theoretical limits. Clin Infect Dis 1998;27:S21S28.
25.Hall, RM, Collis, CM. Antibiotic resistance in gram-negative bacteria: the role of gene cassettes and integrons. Drug Resistance Updates 1999;1:109119.
26.John, JF Jr, McNeill, WF. Characteristics of Serratia marcescens containing a plasmid coding for gentamicin resistance in nosocomial infections. J Infect Dis 1981;143:810818.
27.Gerding, DN, Larson, TA. Aminoglycoside resistance in gram-negative bacilli during increased amikacin use. Comparison of experience in 14 United States hospitals with experience in the Minneapolis Veterans' Administration Medical Center. Am J Med 1985;79:17.
28.Gerding, DN, Larson, TA, Hughes, RA, Weiler, M, Shanholtzer, C, Peterson, LR. Aminoglycoside resistance and aminoglycoside usage: ten years of experience in one hospital. Antimkrob Agents Chemother 1991;35:12841290.
29.Zervos, MJ, Kauffman, CA, Therasse, PM, Bergman, AG, Mikesell, TS, Schaberg, DR. Nosocomial infection by gentamicin-resistant Streptococcus faecalis. An epidemiologic study. Ann Intern Med 1987;106:687691.
30.Paul, SM, Gursky, EAA statewide surveillance system for antibiotic-resistant bacteria: the New Jersey Department of Health. Infect Control Hosp Epidemiol 1996;17:345.
31.Hospital Infections Program, Centers for Disease Control and Prevention. NNIS Antimicrobial Resistance Surveillance Report. Updated October 22, 1999. Atlanta, GA: CDC. http://www.cdc.gov/ncidod/hip/NNIS/AR_Survll98.htm.
32.Bartiett, JG, Chang, TW, Gurwith, M, Gorbach, SL, Onderdonk, AB. Antibiotic-associated pseudomembranous colitis due to toxin-producing Clostridia. N Engl J Med 1978;298:531534.
33.Arthur, M, Reynolds, P, Courvalin, PGlycopeptide resistance in entero-cocci. Trends Microbiol 1996;4:401407.
34.Pugliese, G, Weinstein, RA, eds. Issues and Controversies in Prevention and Control of VRE, Vancomycin-Resistant Enterococci. Chicago, IL: ETNA Communications; 1998.
35.Hall, RM, Brown, HJ, Brookes, DE, Stokes, HW. Integrons found in different locations have identical 5′ ends but variable 3′ ends. J Bacterid 1994;176:62866294.
36.Martinez-Freijo, P, Fluit, AC, Schmitz, FJ, Verhoef, J, Jones, ME. Many class I integrons comprise distinct stable structures occurring in different species of Enterobacteriaceae isolated from widespread geographic regions in Europe. Antimkrob Agents Chemother 1999;43:686689.
37.Foster, TJ, Hook, M. Surface protein adhesins of Staphylococcus aureus. Trends Microbiol 1998;6:484488.
38.Manning, PAClark, CA, Focareta, T. Gene capture in Vibrio cholerae. Trends Microbiol 1999;7:9395.
39.Clark, NC, Olsvik, O, Swenson, JM, Spiegel, CATenover, FC. Detection of a streptomycin/spectinomycin adenylyltransferase gene (aadA) in Enterococcus faecalis. Antimkrob Agents Chemother 1999;43:157160.
40.Archer, GL, Niemeyer, DM. Origin and evolution of DNA associated with resistance to methicillin in staphylococci. Trends Microbiol 1994;2:343347.
41.Clewell, DB. Movable genetic elements and antibiotic resistance in enterococci. Eur J Clin Microbiol Infect Dis 1990;9:90102.
42.Rice, LB, Carias, LL. Transfer of Tn5385, a composite, multiresistance chromosomal element from Enterococcus faecalis. J Bacterial 1998;180:714721.
43.Firth, N, Skurray, RThe staphylococci in human. Drug Resistance Updates 1997;1:4958.
44.Nahvi, MD. Structure of the mec Region of Staphylococcal Chromosome: Diversity, Evolution, and Instability. Piscataway, NJ: University of Medicine and Dentistry of New Jersey; 1997. Thesis.
45.Bonhoeffer, S, Lipsitch, M, Levin, BR. Evaluating treatment protocols to prevent antibiotic resistance. Proc Natl Acad Sci USA 1997;94:1210612111.
46.Donskey, CJ, Hanrahan, JAHutton, RARice, LB. Effect of parenteral antibiotic administration on persistence of vancomycin-resistant Enterococcus faecium in the mouse gastrointestinal tract. J Infect Dis 1999;180:384390.
47.Trick, WE, Kuehnert, MJ, Quirk, SB, Arduino, MJ, Aguero, SM, Carson, LAet al. Regional dissemination of vancomycin-resistant enterococci resulting from interfacility transfer of colonized patients. J Infect Dis 1999;180:391396.
48.Go, ES, Urban, C, Burns, J, Kreiswirth, B, Eisner, W, Mariano, N, et al. Clinical and molecular epidemiology of Acinetobacter infections sensitive only to polymyxin B and sulbactam. Lancet 1994;344:13291332.
49.Livermore, DM, Yuan, M. Antibiotic resistance and production of extended-spectrum beta-lactamases amongst Klebsiella species from intensive care units in Europe. J Antimkrob Chemother 1996;38:409424.
50.Spencer, RC. The emergence of epidemic, multiple-antibiotic-resistant Stenotrophomonas (Xanthomonas) maltophilia and Burkholderia (Pseudomonas) cepacia. J Hosp Infect 1995;30(suppl):453464.
51.Pallares, R, Pujol, M, Pena, C, Ariza, J, Martin, R, Gudiol, F. Cephalosporins as risk factor for nosocomial Enterococcus faecalis bacteremia. A matched case-control study. Arch Intern Med 1993;153:15811586.
52.Rice, LB, Carias, LL, Bonomo, RAShlaes, DM. Molecular genetics of resistance to both ceftazidime and beta-lactam-beta-lactamase inhibitor combinations in Klebsiella pneumoniae and in vivo response to beta-lactam therapy. J Infect Dis 1996;173:151158.
53.Burwen, DR, Banerjee, SN, Gaynes, RE Ceftazidime resistance among selected nosocomial gram-negative bacilli in the United States. National Nosocomial Infections Surveillance System. J Infect Dis 1994;170:16221625.
54.Carmeli, Y, Troillet, N, Eliopoulos, GM, Samore, MH. Emergence of antibiotic-resistant Pseudomonas aeruginosa: comparison of risks associated with different antipseudomonal agents. Antimkrob Agents Chemother 1999;43:13791382.
55.Levy, SB. Multidrug resistance: a sign of the times. N Engl J Med 1998;338:13761378.
56.Stapleton, PD, Shannon, KP, French, GL. Carbapenem resistance in Escherichia coli associated with plasmid-determined CMY-4 beta-lactamase production and loss of an outer membrane protein. Antimkrob Agents Chemother 1999;43:12061210.
57.Meyer, KS, Urban, C, Eagan, JABerger, BJ, Rahal, JJ. Nosocomial outbreak of Klebsiella infection resistant to late-generation cephalosporins. Ann Intern Med 1993;119:353358.
58.Pena, C, Pujol, M, Ardanuy, C, Ricart A Pallares, R, Linares, J, et al. Epidemiology and successful control of a large outbreak due to Klebsiella pneumoniae producing extended-spectrum beta-lactamases. Antimkrob Agents Chemother 1998;42:5358.
59.Rice, LB, Eckstein, EC, DeVente, J, Shlaes, DM. Ceftazidime-resistant Klebsiella pneumoniae isolates recovered at the Cleveland Department of Veterans' Affairs Medical Center. Clin Infect Dis 1996;23:118124.
60.Rahal, JJ, Urban, C, Horn, D, Freeman, K, Segal-Maurer, S, Maurer, J, et al. Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella. JAMA 1998;280:12331237.
61.Wiener, J, Quinn, JP, Bradford, PAGoering, RV, Nathan, C, Bush, K, et al. Multiple antibiotic-resistant Klebsiella and Escherichia coli in nursing homes. JAMA 1999;281:517523.
62.Fierer, J, Guiney, D. Extended-spectrum beta-lactamases: a plague of Plasmids. JAMA 1999;281:563564.
63.Shaw, WV. Chloramphenicol resistance in meningococci. N Engl J Med 1998;339:917918.
64.Kobayashi, N, Urasawa, S, Uehara, N, Watanabe, N. Distribution of insertion sequence-like element IS1272 and its position relative to methicillin resistance genes in clinically important staphylococci. Antimkrob Agents Chemother 1999;43:27802782.
65.Arthur, M, Molinas, C, Courvalin, P. The vanS-vanR two-component regulatory system controls synthesis of depsipeptide peptidoglycan precursors in Enterococcus faecium BM4147. J Bacterial 1992;174:25822591.
66.Evers, S, Courvalin, P. Regulation of vanB-type vancomycin resistance gene expression by the vanS(B)-vanR (B) two-component regulatory system in Enterococcus faecalis V583. J Bacterial 1996;178:13021309.
67.Hackbarth, CJ, Chambers, HF. Wal and WaRl regulate beta-lactamase and PBP 2a production in methicillin-resistant Staphylococcus aureus. Antimkrob Agents Chemother 1993;37:11441149.
68.Low, DE, Kellner, JD, Wright, GD. Superbugs: how they evolve and minimize the cost of resistance. In: Mandeli, LA, ed. Current Infectious Disease Reports. Philadelphia, PACurrent Science. In press.
69.Berger-Bachi, B. Resistance not mediated by β-lactamase (methicillin resistance). In: Crossley, KB, Archer, GL, eds. The Staphylococci in Human Disease. New York, NY: Livingstone Churchill; 1998:159174.
70.Jacoby, GAMedeiros, AAMore extended-spectrum beta-lactamases. Antimkrob Agents Chemother 1991;35:16971704.
71.Schiappa, DAHayden, MK, Matushek, MG, Hashemi, FN, Sullivan, J, Smith, KY, et al. Ceftazidime-resistant Klebsiella pneumoniae and Escherichia coli bloodstream infection: a case-control and molecular epidemiologic investigation. J Infect Dis 1996;174:529536.
72.Gerding, DN. Is there a relationship between vancomycin-resistant ente-rococcal infection and Clostridium difficile infection? Clin Infect Dis 1997;25(suppl 2):S206S210.
73.Morris, JG Jr, Shay, DK, Hebden, JN, McCarter, RJ Jr, Perdue, BE, Jarvis, W, et al. Enterococci resistant to multiple antimicrobial agents, including vancomycin. Establishment of endemicity in a university medical center. Ann Intern Med 1995;123:250259.
74.Moreno, F, Grota, P, Crisp, C, Magnon, K, Melcher, GP, Jorgensen, JH, et al. Clinical and molecular epidemiology of vancomycin-resistant Enterococcus faecium during its emergence in a city in southern Texas. Clin Infect Dis 1995;21:12341237.
75.Quale, J, Landman, D, Saurina, G, Atwood, E, DiTore, V, Patel, K. Manipulation of a hospital antimicrobial formulary to control an outbreak of vancomycin-resistant enterococci. Clin Infect Dis 1996;23:10201025.
76.Carias, LL, Rudin, SD, Donskey, CJ, Rice, LB. Genetic linkage and cotrans-fer of a novel, vanB-containing transposon (Tn5382) and a low-affinity penicillin-binding protein 5 gene in a clinical vancomycin-resistant Enterococcus faecium isolate. J Bacterial 1998;180:44264434.
77.Chirurgi, VA, Oster, SE, Goldberg, AA, McCabe, RE. Nosocomial acquisition of beta-lactamase—negative, ampicillin-resistant Enterococcus. Arch Intern Med 1992;152:14571461.
78.Smith, KE, Besser, JM, Hedberg, CW, Leano, FT, Bender, JB, Wicklund, JH, et al. Quinolone-resistant Campylobacter jejuni infections in Minnesota, 1992-1998. N Engl J Med 1999;340:15241532.
79.Low, DE, Wright, GD. Persistence of resistance genes. In: Ghanassia, JP, ed. Antibiotic Therapy and Control of Antimicrobials. Paris, France: Elsevier. In press.
80.Bisognano, C, Vaudaux, PE, Lew, DP, Ng, EY, Hooper, DC. Increased expression of fibronectm-binding proteins by fluoroquinolone-resistant Staphylococcus aureus exposed to subinhibitory levels of ciprofloxacin. Antimkrob Agents Chemother 1997;41:906913.
81.Roghmann, MC, Qaiyumi, S, Johnson, JA, Schwalbe, R, Morris, JG Jr. Recurrent vancomycin-resistant Enterococcus faecium bacteremia in a leukemia patient who was persistently colonized with vancomycin-resistant enterococci for two years. Clin Infect Dis 1997;24:514515.
82.Berchieri, A. Intestinal colonization of a human subject by vancomycin-resistant Enterococcus faecium. Clin Microbiol Infect 1999;5:97100.
83.Bradly, SJ, Wilson, ALT, Allen, MC, Sher, HA, Goldstone, AH, Scott, GM. The control of hyperendemic glycopeptide-resistant Enterococcus spp. on a haematolgy unit by changing antibiotic usage. J Antimkrob Chemother 1999;43:261266.
84.Martinez, E, de la Cruz, F. Genetic elements involved in Tn21 site-specific integration, a novel mechanism for the dissemination of antibiotic resistance genes. EMBO J 1990;9:12751281.
85.Dominguez, EA, Smith, TL, Reed, E, Sanders, CC, Sanders, WE Jr. A pilot study of antibiotic cycling in a hematology-oncology unit. Infect Control Hosp Epidemiol 1999;21(suppl):S4S8.
86.Gerding, DE. Antimicrobial cycling: lessons learned from the aminoglycoside experience. Infect Control Hosp Epidemiol 1999;21(suppl):S12S17.
87.Baquero, F, Negri, MC, Morosini, MI, Blazquez, J. Antibiotic-selective environments. Clin Infect Dis 1998;27(suppl 1):S5S11.
88.Johnson, AP, Livermore, DM. Quinupristin/dalfopristin, a new addition to the antibiotic arsenal. Lancet 1999;354:212213.
89.Cockerill, FR III. Genetic methods for assessing antimicrobial resistance. Antimkrob Agents Chemother 1999;43:199212.

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed