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A novel β-lactam-aminoglycoside combination in veterinary medicine: The couse of ceftiofur and gentamicin to combat resistant Escherichia coli

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The focus of this study was to evaluate the efficacy of ceftiofur+gentamicin combination to increase the success of antimicrobial inhibition against resistant Escherichia coli (E.coli) strains isolated from animals. Interaction between drugs was determined using checkerboard method and the fractional inhibitory concentration index was interpreted as synergism, antagonism and indifference. The combination was defined as bactericidal or bacteriostatic based on the minimum bactericidal test results. Mutant prevention concentration test was used to evaluate the resistance tendency suppression potential of the combination. The synergistic effect was detected for all E. coli strains by the checkerboard method; even the strains that were resistant to the individual compounds in the combination. Based on the results of minimum bactericidal concentration test, the combination exhibited bactericidal effect against all E. coli strains. In addition, the individual mutant prevention concentrations of ceftiofur and gentamicin decreased up to 125-fold by using the combination for the inhibition of resistant E. coli strains. The results indicated that killing potential of co-use of the compounds is much stronger than their individual use. The combination achieved to decrease the mutant prevention concentrations and this can reduce the risk of emergence of single mutations during treatment done with suggested doses.



Ceftiofur; gentamicin; resistant Escherichia coli; antimicrobial combination

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Blondeau JM, Zhao X, Hansen G, Drlica K (2001). Mutant prevention concentrations of fluoroquinolones for clinical isolates of Streptococcus pneumoniae. Antimicrob Agents Chemother 2 (45): 433-438.

Cengiz M, Sahinturk P, Sonal S, Buyukcangaz E, Sen A, Arslan E (2013). In vitro bactericidal activity of enrofloxacin against gyrA mutant and qnr-containing Escherichia coli isolates from animals. Vet Rec 172:474-479.

CLSI. Performance Standards for Antimicrobial Susceptibility Testing. 26th ed. CLSI supplement M100S. Wayne, PA: Clinical Laboratory Standards Institute; 2016.

Eliopoulos G and Moellering Jr RC (1996) Antimicrobial Combinations. In: Antibiotics in Laboratory Medicine. Lorian, V ed, The Williams & Wilkins Co., Baltimore: pp 330-396.

European Medicines Agency (2017). Reflection paper on use of aminoglycosides in animals in the European Union: development of resistance and impact on human and animal health. EMA/CVMP/AWP/721118/2014.

Hansen GT, Blondeau JM (2005). Comparison of the minimum inhibitory, mutant prevention and minimum bactericidal concentrations of ciprofloxacin, levofloxacin and garenoxacin against enteric Gram-negative urinary tract infection pathogens. J Chemother 17 (5): 484-492.

Hopkins K, Davies R, Therefall J (2005). Mechanisms of quinolone resistance in Escherichia coli and Salmonella: Recent developments. Int J

Antimicrob Agents 25: 358-373.

Ingerson-Mahar M, Reid A (2011). FAQ: E. coli: good, bad and deadly. A

Report From The American Academy of Microbiology. Kohanski MA, Dwyer DJ, Collins JJ (2010). How antibiotics kill bacteria: from targets to networks. Nat Rev Microbiol 8 (6): 423-435.

Maaland MG, Mo SS, Schwarz S Guardabassi L (2015). In vitro assessment of chloramphenicol and florfenicol as second-line antimicrobial agents in dogs. J Vet Pharmacol Ther 38: 443-450.

Meegan J (2013). Pharmacokinetics of ceftiofur crystalline-free acid (exceed sterile suspension®) administered via intramuscular injection in wild california sea lions (Zalophus californianus). J Zoo Wildl Med 44 (3): 714-720.

Noel AR, Bowker KE, Attwood M, MacGowan AP (2018). Antibacterial effect of ceftozolone/tazobactam in combination with amikacin against aerobic Gram-negative bacilli studied in an in vitro pharmacokinetic model of infection. J Antimicrob Chemother 73:2411-2417.

Prescott JF, Giguère S, Dowling PM, (editors) (2013). Antimicrobial Therapy in Veterinary Medicine. 5th ed. Blackwell Publishing.

Rafei AE (2018). Comparison of Dual β-Lactam therapy to penicillin-aminoglycoside combination in treatment of Enterococcus faecalis infective endocarditis. J Infect 77: 398-404.

Sahinturk P, Arslan E, Buyukcangaz E, Sonal S, Sen A, Ersoy F, Webber MA, Piddock LJV, Cengiz M (2016). High level fluoroquinolone resistance

in Escherichia coli isolated from animals in Turkey is due to multiple mechanisms. Turk J Vet Anim Sci 40:214-218.

Sun W, Sanderson P, Zheng W (2016). Drug combination therapy increases successful drug repositioning. Drug Discov Today 21 (7): 1189-1195.

Tamma PD, Cosgrove SE, Maragakis L (2012). Combination therapy for treatment of infections with Gram-negative bacteria. Clin Microbiol Rev 25 (3): 450-470.

Theelen MJP (2019). Initial antimicrobial treatment of foals with sepsis:

Do our choices make a difference? Vet J 243: 74-76.

Tschudin-Sutter S, Fosse N, Frei R, Widmer AF (2018). Combination therapy for treatment of Pseudomonas aeruginosa bloodstream infections. PLoS One 13(9):0203295.


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