, Volume 61, Issue 5, pp 553–564 | Cite as

Emerging Strategies in Infectious Diseases

New Carbapenem and Trinem Antibacterial Agents
  • Hélio S. Sader
  • Ana C. Gales
Leading Article


β-Lactam antibiotics represent the most commonly prescribed antibacterial agents. New β-lactams have been introduced continuously as many bacteria have developed resistance to older agents. In the late 1970s, a new class of exceptionally broad spectrum β-lactams, the carbapenems, was identified. Despite being a very potent compound, the antibacterial activity of the first carbapenem, imipenem, was compromised because of hydrolysis by the renal dehydropeptidase enzyme (DHP-1), and it is now coadministered with a potent competitive inhibitor of the DHP-1 enzyme, cilastin. Molecular modifications in the carbapenem nucleus were able to increase stability to DHP-1 and retain the antibacterial activity. However, some important pathogenic bacteria were found to be resistant to this new class of agents. In addition, other clinically important Gram-negative species, such as Pseudomonas aeruginosa, developed resistance mainly by the production of potent β-lactamases and reduced permeability of the outer membrane. Since the discovery of imipenem/cilastatin, a great number of carbapenems have been developed, and a few of them have been marketed. Stability to hydrolysis by DHP-1 and decrease in toxicity were achieved by meropenem and biapenem. However, only a slight increase in the antibacterial potency and spectrum has been accomplished with either the new marketed or experimental parenteral compounds. In addition, compounds that can be administered orally, such as the carbapenens faropenem, CS-834 and MK-826, and the trinem sanfetrinem, have been developed. However, when compared with the parenterally administered compounds, the oral agents seem to lose some in vitro antibacterial activity, especially against P. aeruginosa.


Minimum Inhibitory Concentration Imipenem Meropenem Carbapenems Cefpodoxime 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We would like to thank Dr Ronald N. Jones for critically reviewing the manuscript.


  1. 1.
    Livermore DM, Williams DJ. β-lactams: mode of action and mechanism of bacterial resistance. In: Lorian V, editor. Antibiotics in laboratory medicine. Baltimore: Williams & Wilkins, 1996: 502–78Google Scholar
  2. 2.
    Jacoby GA, Archer GL. New mechanisms of bacterial resistance to antimcrobial agents. N Engl J Med 1991; 324: 601–12PubMedCrossRefGoogle Scholar
  3. 3.
    Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for β-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother 1995; 39: 1211–33PubMedCrossRefGoogle Scholar
  4. 4.
    Philippon A, Labia R, Jacoby GA. Extended-spectrum β-lactamases. Antimicrob Agents Chemother 1989; 33: 1131–6PubMedCrossRefGoogle Scholar
  5. 5.
    Jones RN. Important and emerging beta-lactamase-mediated resistances in hospital-based pathogens: the Amp C enzymes. Diagn Microbiol Infect Dis 1998 Jul; 31: 461–6PubMedCrossRefGoogle Scholar
  6. 6.
    Kahan FM, Kropp H, Sundelof JG, et al. Thienamycin: development of imipenem-cilastatin. Antimicrob Agents Chemother 1983; 12D Suppl.: 1S–35SGoogle Scholar
  7. 7.
    Hikida M, Kawashima K, Yoshida M, et al. Inactivation of new carbapenem antibiotics by dehydropeptidase-I from porcine and human renal cortex. J Antimicrob Chemother 1992 Aug; 30: 129–34PubMedCrossRefGoogle Scholar
  8. 8.
    Fink MP, Snydman DR, Niederman MS, et al. Treatment of severe pneumonia in hospitalized patients: results of a multi-center, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. Antimicrob Agents Chemother 1994 Mar; 38: 547–57PubMedCrossRefGoogle Scholar
  9. 9.
    Bradley JS, Garau J, Lode H, et al. Carbapenems in clinical practice: a guide to their use in serious infection. Int J Antimicrob Agents 1999; 11: 93–100PubMedCrossRefGoogle Scholar
  10. 10.
    Coulton S, Hunt E. Recent Advances in the chemistry and biology of carbapenems antibiotics. In: Ellis GP, Lumskobe DK, editors. Progress in medicinal chemistry. Amsterdam, Elsevier Science BV, 1996: 99–145Google Scholar
  11. 11.
    Andrus A, Baker FA, Bouffard FA, et al. Structure-activity relationships among some totally synthetic carbapenems. In: Brown AG, Roberts SM, editors. Recent advances in the chemistry of β-lactams. London: The Royal Society of Chemistry, 1984: 86–99Google Scholar
  12. 12.
    Christensen BG. Structure activity relationships in beta-lactam antibiotics. In: Salton MEJ, Schockman GD, editors. Betalactam antibiotics. Mode of action, new development, and future prospects. London: Academic Press, 1981: 101–25Google Scholar
  13. 13.
    Miyadera T, Sugimura Y, Hashimoto T, et al. Synthesis and in vitro activity of a new carbapenem, RS-533. J Antibiot 1983 Aug; 36: 1034–9PubMedCrossRefGoogle Scholar
  14. 14.
    Edwards JR, Betts MJ. Carbapenems: the pinnacle of the β-lactam antibiotics or room for improvement. J Antimicrob Chemother 2000 Jan; 45: 1–4PubMedCrossRefGoogle Scholar
  15. 15.
    Tanimura H, Ochiai M, Sugimoto Y, et al. Tissue concentration and clinical efficacy of panipenem/betamipron in surgical infections. Chemotherapy Tokyo 1991; 39: 585–95Google Scholar
  16. 16.
    Edwards JR, Turner PJ, Wannop C, et al. In vitro antibacterial activity of SM-7338, a carbapenem antibiotic with stability to dehydropeptidase. I. Antimicrob Agents Chemother 1989 Feb; 33: 215–22CrossRefGoogle Scholar
  17. 17.
    Ubukata K, Hikida M, Yoshida M, et al. In vitro activity of LJC10,627, a new carbapenem antibiotic with high stability to dehydropeptidase. I. Antimicrob Agents Chemother 1990 June; 34: 994–1000CrossRefGoogle Scholar
  18. 18.
    Petersen PJ, Jacobous NV, Weiss WJ, et al. In vitro and in vivo activity of LJC10,627, a new carbapenem antibiotic with stability to dehydropeptidase. I. Antimicrob Agents Chemother 1991 Jan; 35: 203–7CrossRefGoogle Scholar
  19. 19.
    Neu HC, Gu JW, Fang W, et al. In vitro activity and β-lactamase stability of LJC 10, 627. Antimicrob Agents Chemother 1992 Jul; 36: 1418–23PubMedCrossRefGoogle Scholar
  20. 20.
    Malanoski GJ, Collins L, Wennersten C, et al. In vitro activity of biapenem against clinical isolates of Gram-positive and Gram-negative bacteria. Antimicrob Agents Chemother 1993 Sep; 37: 2009–16PubMedCrossRefGoogle Scholar
  21. 21.
    Clarke AM, Zemcov SJV. Comparative in vitro activity of biapenem, a new carbapenem antibiotic. Eur J Clin Microbiol Infect Dis 1993; 12: 377–84PubMedCrossRefGoogle Scholar
  22. 22.
    Catchopole CR, Wise R, Thornber D, et al. In vitro activity of L-627, a new carbapenem. Antimicrob Agents Chemother 1992 Sep; 36: 1928–34CrossRefGoogle Scholar
  23. 23.
    Sader HS, Jones RN. Antimicrobial activity of the new carbapenem biapenem compared to imipenem, meropenem, and other broad-spectrum beta-lactam drugs. Eur J Clin Microbiol Infect Dis 1993; 12: 384–91PubMedCrossRefGoogle Scholar
  24. 24.
    Nord CE, Lahnborg G. Biapenem versus imipenem in the treatment of experimental intra-abdominal infections. J Chemother 1995 Feb; 7: 42–4PubMedGoogle Scholar
  25. 25.
    Hikida M, Masukawa Y, Nishiki K, et al. Low neurotoxicity of LJC 10,627, a novel 1β-methyl carbapenem antibiotic: inhibition of γ-aminobutyric acidA, benzodiazepine, and glycine receptor binding in relation to lack of central nervous system toxicity in rats. Antimicrob Agents Chemother 1993 Feb; 37: 199–202PubMedCrossRefGoogle Scholar
  26. 26.
    Hikida M, Kawashima K, Nishiki K, et al. Renal dehydropeptidase-I stability of LJC 10,627, a new carbapenem antibiotic. Antimicrob Agents Chemother 1992 Feb; 36: 481–3PubMedCrossRefGoogle Scholar
  27. 27.
    Kozawa O, Uematsu T, Matsuno H, et al. Pharmacokinetics and safety of a new parenteral carbapenem antibiotic, biapenem (L-627), in elderly subjects. Antimicrob Agents Chemother 1998 Jun; 42: 1433–6PubMedGoogle Scholar
  28. 28.
    Toynaga Y, Ishihara T, Tezuka T, et al. Pharmacokinetic and clinical studies on biapenem (L-627) in the pediatric field [in Japanese]. Jpn J Antibiot 1994 Dec; 47: 1691–705PubMedGoogle Scholar
  29. 29.
    Brismar Bo, Åkerlund JE, Sjöstedt S, et al. Biapenem versus imipenem/cilastatin in the treatment of complicated intra-abdominal infections: report from a Swedish Study Group. Scand J Infect Dis 1996; 28: 507–12PubMedCrossRefGoogle Scholar
  30. 30.
    Ohtake N, Okamoto O, Mitomo R, et al. lβ-methyl-2-(5-sustituted pyrrolidin-3-ylthio)carbapenems; 3. Synthesis and antibacterial activity of BO-2727 and its related compounds. J Antibiot 1997 Jul; 50: 598–613Google Scholar
  31. 31.
    Mori M, Hikida M, Nishihara T, et al. Comparative stability of carbapenem and penem antibiotics to human recombinant dehydropeptidase-I. J Antimicrob Chemother 1996; 37: 1034–6PubMedCrossRefGoogle Scholar
  32. 32.
    Hashizume T, Nakamura K, Nakagawa S. Affinities of BO-2727 for bactericidal penicillin-binding proteins and morphological change of Gram-negative rods. J Antibiot 1997 Feb; 50: 139–42PubMedCrossRefGoogle Scholar
  33. 33.
    Kato Y, Otsuki M, Nishino T. Antibacterial properties of BO-2727, a new carbapenem antibiotic. J Antimicrob Chemother 1997; 40: 195–203PubMedCrossRefGoogle Scholar
  34. 34.
    Shibata K, Adachi Y, Kato E, et al. In vitro and in vivo evaluation of BO-2727 against imipenem- and/or meropenem-resistant Pseudomonas aeruginosa. J Antibiot 1997 Feb; 50: 135–8PubMedCrossRefGoogle Scholar
  35. 35.
    Mikamo H, Kawazoe K, Izumi K, et al. In vitro and in vivo antibacterial of a new carbapenem BO-2727 for use in obstetrics and gynecology. Chemother 1998; 44: 12–6CrossRefGoogle Scholar
  36. 36.
    Miyauchi M, Endo R, Hisaoka M, et al. Synthesis and structure-activity relantionships of a novel oral carbapenem, CS-834. J Antibiot 1997 May; 50: 429–39PubMedCrossRefGoogle Scholar
  37. 37.
    Miyauchi M, Kanno M, Kawamoto I. A novel oral carbapenem CS-834: chemical stability of pivaloyloxymethyl esters of carbapenems and cephalosporins in phosphate buffer solution. J Antibiot 1997 Sep; 50: 794–5PubMedCrossRefGoogle Scholar
  38. 38.
    Holme E, Greter J, Jacobson CE, et al. Carnitine deficiency induced by pivampicillin and pivamecillinam therapy. Lancet 1989 Aug; 2: 469–73PubMedCrossRefGoogle Scholar
  39. 39.
    Umemura K, Ikeda Y, Kondo K, et al. Safety and pharmacokinetics of CS-834, a new oral carbapenem antibiotic, in healthy volunteers. Antimicrob Agents Chemother 1997 Dec; 41: 2664–9PubMedGoogle Scholar
  40. 40.
    Sakagawa E, Otsuki M, Ou T, et al. In-vitro and in-vivo antibacterial activities of CS-834, a new oral carbapenem. J Antimicrob Chemother 1998; 42: 427–37PubMedCrossRefGoogle Scholar
  41. 41.
    Fukuoka T, Ohya S, Utsui Y, et al. In vitro and in vivo antibacterial activities of CS-834, a novel oral carbapenem. Antimicrob Agents Chemother 1997 Dec; 41: 2652–63PubMedGoogle Scholar
  42. 42.
    Yamaguchi K, Domon H, Miyazaki S, et al. In vitro and in vivo antibacterial activities of CS-834, a new oral carbapenem. Antimicrob Agents Chemother 1998 Mar; 42: 555–63PubMedCrossRefGoogle Scholar
  43. 43.
    Fukuoka T, Kawada H, Kitayama A, et al. Efficacy of CS-834 against experimental pneumonia caused by penicillin-susceptible and -resistant Streptococcus pneumoniae in mice. Antimicrob Agents Chemother 1998 Jan; 42: 23–7PubMedGoogle Scholar
  44. 44.
    Gill CJ, Jackson JJ, Gerckens LS, et al. In vitro activity and pharmacokinetic evaluation of a novel long-acting carbapenem antibiotic, MK-826 (L-749, 345). Antimicrob Agents Chemother 1998 Aug; 42: 1996–2001PubMedGoogle Scholar
  45. 45.
    Fuchs PC, Barry AL, Brown SD. In-vitro antimicrobial activity of a carbapenem, MK-0826 (L-749,345) and a provisional interpretative criteria for disc tests. J Antimicrob Chemother 1999; 43: 703–6PubMedCrossRefGoogle Scholar
  46. 46.
    Odenholt I, Löwdin E, Cars O. In vitro pharmacodynamic studies of L-749,345 in comparison with imipenem and ceftriaxone against Gram-positive and Gram-negative bacteria. Antimicrob Agents Chemother 1998 Sep; 42: 2365–70PubMedGoogle Scholar
  47. 47.
    Jacoby G, Han P, Tran J. Comparative in vitro activities of carbapenem L-749,345 and other antimicrobials against multiresistant Gram-negative clinical pathogens. Antimicrob Agents Chemother 1997 Aug; 41: 1830–1PubMedGoogle Scholar
  48. 48.
    Kohler J, Dorso KL, Young K, et al. In vitro activities of the potent, broad-spectrum carbapenem MK-0826 (L-749,345) against broad-spectrum and extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Escherichia coli clinical isolates. Antimicrob Agents Chemother 1999 May; 43: 1170–6PubMedGoogle Scholar
  49. 49.
    Sundelof JG, Hajdu R, Gill CJ, et al. Pharmacokinetics of L-749,345, a long-acting carbapenem antibiotic, in primates. Antimicrob Agents Chemother 1997 Aug; 41: 1743–8PubMedGoogle Scholar
  50. 50.
    Majumdar A, Birk K, Blum RA, et al. Pharmacokinetics of L-749,345, a carbapenem antibiotic, in healthy male and female volunteers [abstract F130]. In: Abstracts of the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington (DC): American Society for Microbiology, 1996: 122Google Scholar
  51. 51.
    Sturm A, Pachon-Diaz J, Bach M, et al. Phase IIA randomized, double-blind, multicenter study of MK-826 versus ceftriaxone sodium in the treatment of serious lower respiratory tract infections: a preliminary analysis [abstract]. Clin Infect Dis 1998 Oct; 27: 952Google Scholar
  52. 52.
    Kim SH, Kim WB, Lee MG. Stability, tissue metabolism, tissue distribution, and blood partition of DA-1131, a new carbapenem. Res Commun Mol Pathol Pharmacol Dec 1995; 90: 347–62Google Scholar
  53. 53.
    Kim SH, Kwon JW, Lee MG. Pharmacokinetics and tissue distribution of a new carbapenem, DA-1131, after intravenous administration to mice, rats, rabbits, and dogs. Biopharm Drug Dispos 1998; 19: 219–29PubMedCrossRefGoogle Scholar
  54. 54.
    Kim SH, Kim WB, Lee MG. Effect of probenecid on the renal excretion mechanism of a new carbapenem, DA-1131, in rats and rabbits. Antimicrob Agents Chemother 1999 Jan; 43: 96–9PubMedGoogle Scholar
  55. 55.
    Kim SH, Kim WB, Lee MG. Interspecies pharmacokinetic scaling of a new carbapenem, DA-1131, in mice, rats, rabbits, and dogs, and prediction of human pharmacokinetics. Biopharm Drug Dispos 1998; 19: 231–5PubMedCrossRefGoogle Scholar
  56. 56.
    Tsuji M, Ishii Y, Ohno A, et al. In vitro and in vivo antibacterial activities of S-4661, a new carbapenm. Antimicrob Agents Chemother 1998 Jan; 42: 94–9PubMedGoogle Scholar
  57. 57.
    Tanaka M, Hohmura M, Nishi T, et al. Antimicrobial activity of DU-6681a, a parent compound of novel oral carbapenem DZ-2640. Antimicrob Agents Chemother 1997 Jun; 41: 1260–8PubMedGoogle Scholar
  58. 58.
    Ohba F, Nakamura-Kamijo M, Watanabe N, et al. In vitro and in vivo antibacterial activities of ER-35786, a new antipseudomonal carbapenem. Antimicrob Agents Chemother 1997 Feb; 41: 298–307PubMedGoogle Scholar
  59. 59.
    Kohler T, Michea-Hamzehpour M, Epp SF, et al. Carbapenem activities against Pseudomonas aeruginosa: respective contributions of OprD and efflux systems. Antimicrob Agents Chemother 1999 Feb; 43: 424–7PubMedGoogle Scholar
  60. 60.
    Yang Y, Testa RT, Bhachech N, et al. Biochemical characterization of novel tetrahydrofuranyl 1beta-methylcarbapenems: stability to hydrolysis by renal dehydropeptidases and bacterial beta-lactamases, binding to penicillin binding proteins, and permeability properties. Antimicrob Agents Chemother. 1999 Dec; 43: 2904–9PubMedGoogle Scholar
  61. 61.
    Weiss WJ, Mikels SM, Petersen PJ, et al. In vivo activities of peptidic prodrugs of novel aminomethyl tetrahydrofuranyl-1 beta-methylcarbapenems. Antimicrob Agents Chemother 1999 Mar; 43: 460–4PubMedGoogle Scholar
  62. 62.
    Matsumara N, Minami S, Mitsuhashi S. Antibacterial activity of T-5575, a novel 2-carboxypenam, and its stability to β-lactamase. J Antimicrob Chemother 1997; 39: 31–4CrossRefGoogle Scholar
  63. 63.
    Modugno ED, Erbetti I, Ferrari L, et al. In vitro activity of the tribactam GV129606 against Gram-positive, Gram-negative, and anaerobic bacteria. Antimicrob Agents Chemother 1994 Oct; 38: 2362–8PubMedCrossRefGoogle Scholar
  64. 64.
    Johnson AP, Warner M, Speller DC. In-vitro activity of sanfetrinem against isolates of Streptococcus pneumoniae and Staphylococcus aureus. J Antimicrob Chemother 1998 Nov; 42: 643–6PubMedCrossRefGoogle Scholar
  65. 65.
    Sifaoui F, Varon E, Kitzis MD, et al. In vitro activity of sanfetrinem and affinity for the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother 1998 Jan; 42: 173–5PubMedGoogle Scholar
  66. 66.
    Modugno ED, Broggio R, Erbetti I, et al. In vitro and in vivo antibacterial activities of GV 129606, a new broad-spectrum trinem. Antimicrob Agents Chemother 1997 Dec; 41: 2742–8PubMedGoogle Scholar
  67. 67.
    Wise R, Andrews JM, Brenwald N. In vitro activity of the tricyclic β-lactam GV 104326. Antimicrob Agents Chemother 1996 May; 40: 1248–53PubMedGoogle Scholar
  68. 68.
    Singh KV, Coque TM, Murray BE. In vitro activity of the trinem sanfetrinem (GV 104326) against gram-positive organisms. Antimicrob Agents Chemother 1996 Sep; 40: 2142–6PubMedGoogle Scholar
  69. 69.
    Doern GV, Pierce G, Brueggemann AB. In vitro activity of sanfetrinem (GV104326), a new trinem antimicrobial agent, versus Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Diagn Microbiol Infect Dis 1996 Sep; 26: 39–42PubMedCrossRefGoogle Scholar
  70. 70.
    Andrews JM, Hadley N, Brenwald NP, et al. Susceptibility testing of fastidious organisms. J Antimicrob Chemother 1997 Mar; 39: 436–7PubMedCrossRefGoogle Scholar
  71. 71.
    Spangler SK, Lin G, Jacobs MR, et al. Postantibiotic effect of sanfetrinem compared with those of six other agents against 12 penicillin-susceptible and -resistant pneumococci. Antimicrob Agents Chemother 1997 Oct; 41: 2173–6PubMedGoogle Scholar
  72. 72.
    Spangler SK, Jacobs MR, Appelbaum PC. MIC and time-kill studies of antipneumococcal activity of GV 118819X (sanfetrinem) compared with those of other agents. Antimicrob Agents Chemother 1997 Jan; 41: 148–55PubMedGoogle Scholar
  73. 73.
    Betriu C, Gomez M, Palau ML, et al. Activities of new antimicrobial agents (trovafloxacin, moxifloxacin, sanfetrinem, and quinupristin-dalfopristin) against Bacteroides fragilis group: comparison with the activities of 14 other agents. Antimicrob Agents Chemother 1999 Sep; 43: 2320–2PubMedGoogle Scholar
  74. 74.
    Babini GS, Yuan M, Livermore DM. Interactions of beta-lactamases with sanfetrinem (GV 104326) compared to those with imipenem and with oral beta-lactams. Antimicrob Agents Chemother 1998 May; 42: 1168–75PubMedGoogle Scholar
  75. 75.
    Chen HY, Livermore DM. Comparative activity of cefepime against chromosomal β-lactamase inducibility mutants of gram-negative bacteria. J Antimicrob Chemother 1993; 32 Suppl. B: 63–74PubMedCrossRefGoogle Scholar
  76. 76.
    Tullio V, Palarchio AI, Bonino A, et al. Sub-MICs of sanfetrinem promote the interaction of human polymorphonuclear granulocytes with a multiply resistant strain of Klebsiella pneumoniae. J Antimicrob Chemother 1998 Aug; 42: 249–52PubMedCrossRefGoogle Scholar
  77. 77.
    Cuffini AM, Tullio V, Bonino A, et al. Entry of sanfetrinem into human polymorphonuclear granulocytes and its cell-associated activity against intracellular, penicillin-resistant Streptococcus pneumoniae. Antimicrob Agents Chemother 1998 Jul; 42: 1745–50PubMedGoogle Scholar
  78. 78.
    Tamura S, Miyazaki S, Tateda K, et al. In vivo antibacterial activities of sanfetrinem cilexetil, a new oral tricyclic antibiotic. Antimicrob Agents Chemother 1998 Jul; 42: 1858–61PubMedGoogle Scholar
  79. 79.
    Efthymiopoulos CA, Capriati A, Barrington P, et al. Pharmacokinetics of GV 104326, a novel tribactam antibiotic, following single intravenous and oral (as its prodrug GV118819X) administration in man [abstract F82]. In: Abstracts of the 34th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washinton, DC: American Society for Microbiology, 1994: 129Google Scholar
  80. 80.
    Wise R, Andrews JM, Da Ros L, et al. A study to determine the pharmacokinetics and inflammatory fluid penetration of two doses of a solid formulation of the hexetil prodrug of a trinem, sanfetrinem (GV 104326). Antimicrob Agents Chemother 1997 Aug; 41: 1761–4PubMedGoogle Scholar
  81. 81.
    Sader HS, Pfaller MA, Tenover FC, et al. Evaluation and characterization of multiresistant Enterococcus faecium from twelve U.S. medical centers. J Clin Microbiol 1994 Nov; 32: 2840–2PubMedGoogle Scholar
  82. 82.
    Jones RN, Pfaller MA. Bacterial resistance: a worldwide problem. Diagn Microbiol Infect Dis 1998 Jun; 31: 379–88PubMedCrossRefGoogle Scholar
  83. 83.
    Sader HS, Mendes CF, Pignatari AC, et al. Use of macrorestriction analysis to demonstration interhospital spread of multi-resistant Acinetobacter baumannii in São Paulo, Brazil. Clin Infect Dis 1996 Sep; 23: 631–4PubMedCrossRefGoogle Scholar
  84. 84.
    Sader HS, Jones RN, Gales AC, et al. Antimicrobial susceptibility of patterns for pathogens isolated from patients in Latin American medical centers with a diagnosis of pneumonia: results from the SENTRY Antimicrobial Surveillance Program (1997). Diagn Microbiol Infect Dis 1998 Dec; 32: 289–301PubMedCrossRefGoogle Scholar
  85. 85.
    Carmeli Y, Troillet N, Eliopoulos GM, et al. Emergence of antibiotic-resistant Pseudomonas aeruginosa: comparison of risks associated with different antipseudomonal agents. Antimicrob Agents Chemother 1999 Jun; 43: 1379–82PubMedGoogle Scholar

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© Adis International Limited 2001

Authors and Affiliations

  1. 1.Division of Infectious DiseasesUniversidade Federal de São Paulo - Escola Paulista de MedicinaSão PauloBrazil
  2. 2.Medical Microbiology Division, Department of PathologyUniversity of Iowa College of MedicineIowa CityUSA

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