Restricted accessResearch articleFirst published online 2016-07
Colistin Increases the Cidal Activity of Antibiotic Combinations Against Multidrug-Resistant Klebsiella pneumoniae : An In Vitro Model Comparing Multiple Combination Bactericidal Testing at One Peak Serum Concentration and Time–Kill Method
The lack of treatment for multidrug-resistant (MDR) Enterobacteriaceae often leads to the use of double or triple antibiotic combinations to increase the option of clinical success. This study analyzes multiple combination bactericidal testing (MCBT) to screen double and triple antibiotic combinations, at standard peak serum concentration, for bactericidal activity against 21 MDR Klebsiella pneumoniae isolates. This method was compared with time–killing curves. The full bactericidal activity against all strains was obtained only by adding colistin. MCBT has a potential to become a rapid method for testing multiple antibiotic combinations for MDR microorganisms when colistin is used, providing clinicians with in vitro cidal data within 48 hr of strain isolation.
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References
1.
AaronS.D., FerrisW., HenryD.A., et al.2000. Multiple combination bactericidal antibiotic testing for patients with cystic fibrosis infected with Burkholderia cepacia. Am. J. Respir. Crit. Care Med., 161:1206–1212.
2.
AaronS.D., VandemheenK.L., FerrisW., et al.2005. Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomized, double-blind, controlled clinical trial. Lancet, 366:463–471.
3.
BonapaceC.R., WhiteR.L., FriedrichL.V., et al.2000. Evaluation of antibiotic synergy against Acinetobacter baumannii: a comparison with Etest, time-kill, and checkerboard methods. Diagn. Microbiol. Infect. Dis., 38:43–50.
4.
BulikC.C., and NicolauD.P.2011. Double-carbapenem therapy for carbapenemase-producing Klebsiella pneumoniae. Antimicrob. Agents Chemother., 55:3002–3004.
5.
CeccarelliG., FalconeM., GiordanoA., et al.2013. Successful ertapenem-doripenem combination treatment of bacteremic ventilator-associated pneumonia due to colistin-resistant KPC-producing Klebsiella pneumoniae. Antimicrob. Agents Chemother., 57:2900–2901.
6.
Clinical and Laboratory Standards Institute. 2012. Methods for dilution of antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard—ninth edition. CLSI document M07-A9. Clinical and Laboratory Standards Institute, Wayne, PA.
7.
DalfinoL., PuntilloF., MoscaA., et al.2012. High-dose, extended-interval colistin administration in critically ill patients: is this the right dosing strategy?. A preliminary study. Clin. Infect. Dis., 54:1720–1726.
8.
European Committee on Antimicrobial Susceptibility Testing. Breakpoint tables for interpretation of MICs and zone diameters, version 4.0. EUCAST 2014, Växjö, Sweden.
9.
GalesA.C., ReisA.O., and JonesR.N.2001. Contemporary assessment of antimicrobial susceptibility testing methods for polymyxin B and colistin: review of available interpretative criteria and quality control guidelines. J. Clin. Microbiol., 39:183–190.
10.
GiamarellouH., GalaniL., BaziakaF., et al.2013. Effectiveness of a double-carbapenem regimen for infections in humans due to carbapenemase-producing pandrug-resistant Klebsiella pneumoniae. Antimicrob. Agents Chemother., 57:2388–2390.
11.
GomezE., SanchezM., GulZ., et al.2011. Polymyxin combination therapy and the use of serum bactericidal titers in the management of KPC-producing Klebsiella pneumoniae infections: a report of 3 cases. Case Rep. Med., 2011:659769.
12.
GonaF., BarberaF., PasquarielloA.C., et al.2014. In vivo multiclonal transfer of blaKPC-3 from Klebsiella pneumoniae to Escherichia coli in surgery patients. Clin. Microbiol. Infect., 20:633–635.
13.
HindlerJ.A., and HumphriesR.M.2013. Colistin MIC variability by method for contemporary clinical isolates of multidrug-resistant Gram-negative bacilli. J. Clin. Microbiol., 51:1678–1684.
14.
HirschE.B., GuoB., ChangK.T., et al.2013. Assessment of antimicrobial combinations for Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. J. Infect. Dis., 207:786–793.
15.
HumphriesR.M., KelesidisT., BardJ.D., et al.2010. Successful treatment of panresistant Klebsiella pneumoniae pneumonia and bacteraemia with a combination of high-dose tigecycline and colistin. J. Med. Microbiol., 59:1383–1386.
16.
Lo-Ten-FoeJ.R., de SmetA., DiederenB.M.W., et al.2007. Comparative evaluation of the VITEK 2, disk diffusion, Etest, broth microdilution, and agar dilution susceptibility testing methods for colistin in clinical isolates, including heteroresistant Enterobacter cloacae and Acinetobacter baumannii strains. Antimicrob. Agents Chemother., 51:3726–3730.
17.
MeredithG.J., PressE.G., NguyenM.H., et al.2012. The combination of doripenem and colistin is bactericidal and synergistic against colistin-resistant, carbapenemase-producing Klebsiella pneumoniae. Antimicrob. Agents Chemother., 56:3395–3398.
18.
MezzatestaM.L., CaioC., GonaF., et al.2014. Carbapenem and multidrug resistance in Gram-negative bacteria in a single centre in Italy: considerations on in vitro assay of active drugs. Int. J. Antimicrob. Agents, 44:112–116.
19.
MezzatestaM.L., GonaF., CaioC., et al.2013. Emergence of an extensively drug-resistant ArmA- and KPC-2-producing ST101 Klebsiella pneumoniae clone in Italy. J. Antimicrob. Chemother., 68:1932–1934.
20.
MichailG., LabrouM., PitirigaV., et al.2013. Activity of tigecycline in combination with colistin, meropenem, rifampin, or gentamicin against KPC-producing Enterobacteriaceae in a murine thigh infection model. Antimicrob. Agents Chemother., 57:6028–6033.
21.
Munoz-PriceL.S., PoirelL., BonomoR.A., et al.2013. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect. Dis., 13:785–796.
22.
NovelliA., AdembriC., LiviP., et al.2005. Pharmacokinetic evaluation of meropenem and imipenem in critically ill patients with sepsis. Clin. Pharmacokinet., 44:539–549.
23.
PournarasS., VrioniG., NeouE., et al.2011. Activity of tigecycline alone and in combination with colistin and meropenem against Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae strains by time-kill assay. Int. J. Antimicrob. Agents, 37:244–247.
24.
SopiralaM.M., ManginoJ.E., GebreyesW.A., et al.2010. Synergy testing by Etest, microdilution checkerboard, and time-kill methods for pan-drug-resistant Acinetobacter baumannii. Antimicrob. Agents Chemother., 54:4678–4683.
25.
TasciniC., TagliaferriE., GianiT., et al.2013. Synergistic activity of colistin plus rifampin against colistin-resistant KPC-producing Klebsiella pneumoniae. Antimicrob. Agents Chemother., 57:3990–3993.
26.
van BelkumA., HalimiD., BonettiE.J., et al.2015. Meropenem/colistin synergy testing for multidrug-resistant Acinetobacter baumannii strains by a two-dimensional gradient technique applicable in routine microbiology. J. Antimicrob. Chemother., 70:167–172.
27.
YzermanE.P., BoelensH.A., VogelM., et al.1998. Efficacy and safety of teicoplanin plus rifampicin in the treatment of bacteraemic infections caused by Staphylococcus aureus. J. Antimicrob. Chemother., 42:233–239.
28.
ZhanelG.G., BaudryP.J., TailorF., et al.2009. Determination of the pharmacodynamic activity of clinically achievable tigecycline serum concentrations against clinical isolates of Escherichia coli with extended-spectrum beta-lactamases, AmpC beta-lactamases and reduced susceptibility to carbapenems using an in vitro model. J. Antimicrob. Chemother., 64:824–828.
