A infection model reveals double and triple antibiotic combination therapies with enhanced efficacy versus a multidrug-resistant strain of Free

Abstract

The aim of this study was to compare the inhibitory effect of antibiotic combinations with efficacy in larvae to identify efficacious combinations that target . NCTC 13437, a multidrug-resistant strain resistant to β-lactams and aminoglycosides, was used. Susceptibility to cefotaxime, piperacillin, meropenem, amikacin, levofloxacin and colistin alone, or in dual or triple combinations, was measured via a 24 h time-kill assay. results were then compared with the efficacy of the same dual or triple antibiotic combinations versus larvae infected with . haemolymph burden of was determined over 96 h post-infection and treatment with the most potent combination therapies. Many dual and triple combinations of antibiotics displayed synergistic inhibition of multidrug-resistant . There was little correlation between combinations that were synergistic and those that showed enhanced efficacy versus infected larvae. The most potent dual and triple combinations were cefotaxime plus piperacillin, and meropenem plus piperacillin and amikacin, respectively. Fewer combinations were found to offer enhanced therapeutic benefit compared with . The therapeutic benefit arising from treatment with antibiotic combinations correlated with reduced larval burden of . This study has identified antibiotic combinations that merit further investigation for their clinical potential and has demonstrated the utility of using to screen for novel antibiotic treatments that demonstrate efficacy .

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.074245-0
2014-07-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jmm/63/7/945.html?itemId=/content/journal/jmm/10.1099/jmm.0.074245-0&mimeType=html&fmt=ahah

References

  1. Al-Hasan M. N., Wilson J. W., Lahr B. D., Thomsen K. M., Eckel-Passow J. E., Vetter E. A., Tleyjeh I. M., Baddour L. M. 2009; β-lactam and fluoroquinolone combination antibiotic therapy for bacteremia caused by Gram-negative bacilli. Antimicrob Agents Chemother 53:1386–1394 [View Article][PubMed]
    [Google Scholar]
  2. Aloush V., Navon-Venezia S., Seigman-Igra Y., Cabili S., Carmeli Y. 2006; Multidrug-resistant Pseudomonas aeruginosa: risk factors and clinical impact. Antimicrob Agents Chemother 50:43–48 [View Article][PubMed]
    [Google Scholar]
  3. Bodey G. P., Jadeja L., Elting L. 1985; Pseudomonas Bacteremia. Retrospective analysis of 410 episodes. Arch Intern Med 145:1621–1629 [View Article][PubMed]
    [Google Scholar]
  4. Bowers D. R., Liew Y.-X., Lye D. C., Kwa A. L., Hsu L.-Y., Tam V. H. 2013; Outcomes of appropriate empiric combination versus monotherapy for Pseudomonas aeruginosa bacteremia. Antimicrob Agents Chemother 57:1270–1274 [View Article][PubMed]
    [Google Scholar]
  5. Chandrasekar P. H., Crane L. R., Bailey E. J. 1987; Comparison of the activity of antibiotic combinations in vitro with clinical outcome and resistance emergence in serious infection by Pseudomonas aeruginosa in non-neutropenic patients. J Antimicrob Chemother 19:321–329 [View Article][PubMed]
    [Google Scholar]
  6. Dales L., Ferris W., Vandemheen K., Aaron S. D. 2009; Combination antibiotic susceptibility of biofilm-grown Burkholderia cepacia and Pseudomonas aeruginosa isolated from patients with pulmonary exacerbations of cystic fibrosis. Eur J Clin Microbiol Infect Dis 28:1275–1279 [View Article][PubMed]
    [Google Scholar]
  7. He W., Kaniga K., Lynch A. S., Flamm R. K., Davies T. A. 2012; In vitro Etest synergy of doripenem with amikacin, colistin, and levofloxacin against Pseudomonas aeruginosa with defined carbapenem resistance mechanisms as determined by the Etest method. Diagn Microbiol Infect Dis 74:417–419 [View Article][PubMed]
    [Google Scholar]
  8. Hilf M., Yu V. L., Sharp J., Zuravleff J. J., Korvick J. A., Muder R. R. 1989; Antibiotic therapy for Pseudomonas aeruginosa bacteremia: outcome correlations in a prospective study of 200 patients. Am J Med 87:540–546 [View Article][PubMed]
    [Google Scholar]
  9. Hill L., Veli N., Coote P. J. 2013; Evaluation of Galleria mellonella larvae for measuring the efficacy and pharmacokinetics of antibiotic therapies against Pseudomonas aeruginosa infection. Int J Antimicrob Agents 43:254–261 [View Article][PubMed]
    [Google Scholar]
  10. Holm S. 1979; A simple sequentially rejective multiple test procedure. Scand J Stat 6:65–70
    [Google Scholar]
  11. Lister P. D., Wolter D. J., Hanson N. D. 2009; Antibacterial-resistant Pseudomonas aeruginosa: clinical impact and complex regulation of chromosomally encoded resistance mechanisms. Clin Microbiol Rev 22:582–610 [View Article][PubMed]
    [Google Scholar]
  12. Livermore D. M. 2002; Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare?. Clin Infect Dis 34:634–640 [View Article][PubMed]
    [Google Scholar]
  13. Micek S. T., Lloyd A. E., Ritchie D. J., Reichley R. M., Fraser V. J., Kollef M. H. 2005; Pseudomonas aeruginosa bloodstream infection: importance of appropriate initial antimicrobial treatment. Antimicrob Agents Chemother 49:1306–1311 [View Article][PubMed]
    [Google Scholar]
  14. Oie S., Uematsu T., Sawa A., Mizuno H., Tomita M., Ishida S., Okano Y., Kamiya A. 2003; In vitro effects of combinations of antipseudomonal agents against seven strains of multidrug-resistant Pseudomonas aeruginosa. J Antimicrob Chemother 52:911–914 [View Article][PubMed]
    [Google Scholar]
  15. Samonis G., Maraki S., Karageorgopoulos D. E., Vouloumanou E. K., Falagas M. E. 2012; Synergy of fosfomycin with carbapenems, colistin, netilmicin, and tigecycline against multidrug-resistant Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa clinical isolates. Eur J Clin Microbiol Infect Dis 31:695–701 [View Article][PubMed]
    [Google Scholar]
  16. Scribner R. K., Marks M. I., Weber A. H., Tarpay M. M., Welch D. F. 1982; Activities of various β-lactams and aminoglycosides, alone and in combination, against isolates of Pseudomonas aeruginosa from patients with cystic fibrosis. Antimicrob Agents Chemother 21:939–943 [View Article][PubMed]
    [Google Scholar]
  17. Spencer R. C. 1996; Predominant pathogens found in the European prevalence of infection in intensive care study. Eur J Clin Microbiol Infect Dis 15:281–285 [View Article][PubMed]
    [Google Scholar]
  18. Tamma P. D., Cosgrove S. E., Maragakis L. L. 2012; Combination therapy for treatment of infections with Gram-negative bacteria. Clin Microbiol Rev 25:450–470 [View Article][PubMed]
    [Google Scholar]
  19. Vardakas K. Z., Tansarli G. S., Bliziotis I. A., Falagas M. E. 2013; β-Lactam plus aminoglycoside or fluoroquinolone combination versus β-lactam monotherapy for Pseudomonas aeruginosa infections: a meta-analysis. Int J Antimicrob Agents 41:301–310 [View Article][PubMed]
    [Google Scholar]
  20. Vidaillac C., Benichou L., Duval R. E. 2012; In vitro synergy of colistin combinations against colistin-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae isolates. Antimicrob Agents Chemother 56:4856–4861 [View Article][PubMed]
    [Google Scholar]
  21. White R. L., Burgess D. S., Manduru M., Bosso J. A. 1996; Comparison of three different in vitro methods of detecting synergy: time-kill, checkerboard, and E test. Antimicrob Agents Chemother 40:1914–1918[PubMed]
    [Google Scholar]
  22. Winston D. J., Ho W. G., Bruckner D. A., Champlin R. E. 1991; Beta-lactam antibiotic therapy in febrile granulocytopenic patients. A randomized trial comparing cefoperazone plus piperacillin, ceftazidime plus piperacillin, and imipenem alone. Ann Intern Med 115:849–859 [View Article][PubMed]
    [Google Scholar]
  23. Woodford N., Zhang J., Kaufmann M. E., Yarde S., Tomas M. M., Faris C., Vardhan M. S., Dawson S., Cotterill S. L., Livermore D. M. 2008; Detection of Pseudomonas aeruginosa isolates producing VEB-type extended-spectrum β-lactamases in the United Kingdom. J Antimicrob Chemother 62:1265–1268 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.074245-0
Loading
/content/journal/jmm/10.1099/jmm.0.074245-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed