Activity of carbapenems combined with clavulanate against murine tuberculosis.

Nicolas Veziris, Chantal Truffot, Jean-Luc Mainardi, Vincent Jarlier
Author Information
  1. Nicolas Veziris: Laboratoire de Bactériologie, Faculté de Médecine Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634 Paris Cedex 13, France. nicolas.veziris@upmc.fr

Abstract

Although beta-lactam antibiotics are not considered as antituberculous drugs, it has been recently shown that the combination of carbapenems and clavulanate is bactericidal in vitro. We evaluated in a murine model of tuberculosis the activity of carbapenems alone and combined with clavulanate against Mycobacterium tuberculosis. Swiss mice infected intravenously with 3 x 10⁵ M. tuberculosis H37Rv were treated for 4 weeks with clavulanate alone or imipenem, meropenem, and ertapenem alone or combined with clavulanate, whereas a positive control group was treated with isoniazid, and a negative control group was held without treatment. The combination of imipenem or meropenem plus clavulanate significantly improved survival. Among groups of mice with 100% survival, only isoniazid reduced lung CFU counts; the carbapenem-clavulanate combinations did not prevent bacterial growth. Although less active than isoniazid, the combinations of imipenem or meropenem plus clavulanate improved the survival of mice infected with M. tuberculosis and should be further evaluated.

References

  1. MMWR Recomm Rep. 2009 Feb 13;58(RR-3):1-43 [PMID: 19214162]
  2. J Bacteriol. 1990 Mar;172(3):1418-23 [PMID: 2307653]
  3. Biochemistry. 2007 Oct 30;46(43):11998-2004 [PMID: 17915954]
  4. Antimicrob Agents Chemother. 1995 Dec;39(12):2620-4 [PMID: 8592990]
  5. Eur J Clin Microbiol Infect Dis. 2007 Jun;26(6):423-5 [PMID: 17458568]
  6. J Biol Chem. 2007 Oct 19;282(42):30414-22 [PMID: 17646161]
  7. J Antimicrob Chemother. 2004 Jun;53 Suppl 2:ii23-8 [PMID: 15150180]
  8. Antimicrob Agents Chemother. 2005 Oct;49(10):4015-9 [PMID: 16189074]
  9. Lancet. 2006 Nov 4;368(9547):1575-80 [PMID: 17084757]
  10. Antimicrob Agents Chemother. 2010 Nov;54(11):4765-71 [PMID: 20805388]
  11. J Bacteriol. 2008 Jun;190(12):4360-6 [PMID: 18408028]
  12. Int J Antimicrob Agents. 2005 Dec;26(6):449-56 [PMID: 16280244]
  13. MMWR Morb Mortal Wkly Rep. 2007 Mar 23;56(11):250-3 [PMID: 17380107]
  14. Antimicrob Agents Chemother. 1991 Sep;35(9):1937-9 [PMID: 1952873]
  15. Antimicrob Agents Chemother. 1997 Oct;41(10):2083-8 [PMID: 9333029]
  16. Antimicrob Agents Chemother. 2002 Sep;46(9):2990-5 [PMID: 12183258]
  17. Antimicrob Agents Chemother. 1982 Sep;22(3):369-75 [PMID: 7137980]
  18. Eur Respir J. 2009 May;33(5):1085-94 [PMID: 19164345]
  19. Antimicrob Agents Chemother. 2002 Dec;46(12):3712-8 [PMID: 12435666]
  20. Am Rev Respir Dis. 1989 Nov;140(5):1189-93 [PMID: 2817579]
  21. MMWR Morb Mortal Wkly Rep. 2006 Mar 24;55(11):301-5 [PMID: 16557213]
  22. Science. 2009 Feb 27;323(5918):1215-8 [PMID: 19251630]
  23. J Infect Dis. 2006 Aug 15;194(4):479-85 [PMID: 16845631]
  24. Antimicrob Agents Chemother. 2009 Oct;53(10):4298-304 [PMID: 19635957]
  25. Nat Med. 2010 Apr;16(4):466-9 [PMID: 20305661]
  26. J Antimicrob Chemother. 2005 Dec;56(6):1163-5 [PMID: 16234333]

MeSH Term

Animals
Anti-Bacterial Agents
Bacterial Load
Carbapenems
Clavulanic Acid
Drug Therapy, Combination
Female
Lung
Mice
Microbial Sensitivity Tests
Spleen
Tuberculosis

Chemicals

Anti-Bacterial Agents
Carbapenems
Clavulanic Acid

Word Cloud

Created with Highcharts 10.0.0clavulanatetuberculosiscarbapenemsalonecombinedmiceimipenemmeropenemisoniazidsurvivalAlthoughcombinationevaluatedmurineinfectedMtreatedcontrolgroupplusimprovedcombinationsbeta-lactamantibioticsconsideredantituberculousdrugsrecentlyshownbactericidalvitromodelactivityMycobacteriumSwissintravenously3x10⁵H37Rv4weeksertapenemwhereaspositivenegativeheldwithouttreatmentsignificantlyAmonggroups100%reducedlungCFUcountscarbapenem-clavulanatepreventbacterialgrowthlessactiveActivity

Similar Articles

Cited By