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http://dx.doi.org/10.7845/kjm.2016.6072

Characteristics of Klebsiella pneumoniae exposed to serial antibiotic treatments  

Jung, Lae-Seung (Department of Medical Biomaterials Engineering, Kangwon National University)
Jo, Ara (Department of Medical Biomaterials Engineering, Kangwon National University)
Kim, Jeongjin (Department of Medical Biomaterials Engineering, Kangwon National University)
Ahn, Juhee (Department of Medical Biomaterials Engineering, Kangwon National University)
Publication Information
Korean Journal of Microbiology / v.52, no.4, 2016 , pp. 428-436 More about this Journal
Abstract
The emergence of antibiotic-resistant bacteria has been increased and become a public health concern worldwide. Many bacterial infections can be sequentially treated with different types of antibiotics. Thus, this study was designed to evaluate the changes in survival, antibiotic susceptibility, mutant frequency, ${\beta}$-lactamase activity, biofilm formation, and gene expression in Klebsiella pneumoniae after exposure to sequential antibiotic treatments of ciprofloxacin and meropenem. Treatments include control (CON; no addition), 1/2 MIC ciprofloxacin addition (1/2CIP), 2 MIC ciprofloxacin addition (2CIP), initial 1/2 MIC ciprofloxacin addition followed by 1/2 MIC meropenem (8 h-incubation) and 2 MIC ciprofloxacin (16 h-incubation) (1/2CIP-1/2MER-2CIP), initial 1/2 MIC ciprofloxacin addition followed by 1/2 MIC meropenem (8 h-incubation) and 2 MIC meropenem (16 h-incubation) (1/2CIP-1/2MER-2MER), and initial 1/2 MIC ciprofloxacin addition followed by 2 MIC ciprofloxacin(8 h-incubation) and 2 MIC meropenem(16 h-incubation) (1/2CIP-2CIP-2MER). No growth of K. pneumoniae was observed for the 2CIP throughout the incubation period. The numbers of planktonic cells varied with the treatments (7~10 log CFU/ml), while those of biofilm cells were not significantly different among treatments after 24-h incubation, showing approximately 7 log CFU/ml. Among the sequential treatments, the least mutant frequency was observed at the 1/2CIP-1/2MER-2CIP (14%). Compared to the CON, 1/2CIP-2CIP-2MER decreased the sensitivity of K. pneumoniae to piperacillin, cefotaxime, and nalidixic acid. The highest ${\beta}$-lactamase activity was 22 nmol/min/ml for 1/2CIP-1/2MER-2CIP, while the least ${\beta}$-lactamase activity was 6 nmol/min/ml for 1/2CIP-2CIP-2MER. The relative expression levels of multidrug efflux pump-related genes (acrA, acrB, and ramA) were increased more than 2-fold in K. pneumoniae exposed to 1/2CIP-1/2MER-2MER and 1/2CIP-2CIP-2MER. The results suggest that the sequential antibiotic treatments could change the antibiotic resistance profiles in K. pneumoniae.
Keywords
Klebsiella pneumoniae; antibiotic resistance; ${\beta}$-lactamase; biofilm;
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1 Du, J., Li, P., Liu, H., Lu, D., Liang, H., and Dou, Y. 2014. Phenotypic and molecular characterization of multidrug resistant Klebsiella pneumoniae isolated from a University teaching hospital, China. PLoS ONE 9, e95181.   DOI
2 George, A.M., Hall, R.M., and Stokes, H.W. 1995. Multidrug resistance in Klebsiella pneumoniae: a novel gene, ramA, confers a multidrug resistance phenotype in Escherichia coli. Microbiology 141, 1909-1920.   DOI
3 Gutierrez, A., Laureti, L., Crussard, S., Abida, H., Rodriguez-Rojas, A., Blazquez, J., Baharoglu, Z., Mazel, D., Darfeuille, F., Vogel, J., et al. 2013. ${\beta}$-Lactam antibiotics promote bacterial mutagenesis via an RpoS-mediated reduction in replication fidelity. Nat. Commun. 4, 1610.   DOI
4 Jacobs, M.R. 2001. Optimisation of antimicrobial therapy using pharmacokinetic and pharmacodynamic parameters. Clin. Microbiol. Infect. 7, 589-596.   DOI
5 Latifpour, M., Gholipour, A., and Damavandi, M.S. 2016. Prevalence of extended-spectrum ${\beta}$-lactamase-producing Klebsiella pneumoniae isolates in nosocomial and community-acquired urinary tract infections. Jundishapur J. Microbiol. 9, e31179.
6 Lopez, E. and Blazquez, J. 2009. Effect of subinhibitory concentrations of antibiotics on intrachromosomal homologous recombination in Escherichia coli. Antimicrob. Agent. Chemother. 53, 3411-3415.   DOI
7 Mulcahy, H., Charron-Mazenod, L., and Lewenza, S. 2008. Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms. PLoS Pathog. 4, e1000213.   DOI
8 Nichol, D., Jeavons, P., Fletcher, A.G., Bonomo, R.A., Maini, P.K., Paul, J.L., Gatenby, R.A., Anderson, A.R.A., and Scott, J.G. 2015. Steering evolution with sequential therapy to prevent the emergence of bacterial antibiotic resistance. PLoS Comput. Biol. 11, e1004493.   DOI
9 Pages, J.M., Lavigne, J.P., Leflon-Guibout, V., Marcon, E., Bert, F., Noussair, L., and Nicolas-Chanoine, M.H. 2009. Efflux pump, the masked side of ${\ss}$-lactam resistance in Klebsiella pneumoniae clinical isolates. PLoS ONE 4, e4817.   DOI
10 Pakzad, I., Karin, M.Z., Taherikalani, M., Boustanshenas, M., and Lari, A.R. 2013. Contribution of AcrAB efflux pump to ciprofloxacin resistance in Klebsiella pneumoniae isolated from burn patients. GMS Hyg. Infect. Control 8, 1-6.
11 Penesyan, A., Gillings, M., and Paulsen, I. 2015. Antibiotic discovery: Combatting bacterial resistance in cells and in biofilm communities. Molecules 20, 5286-5298.   DOI
12 Perron, G.G., Kryazhimskiy, S., Rice, D.P., and Buckling, A. 2012. Multidrug therapy and evolution of antibiotic resistance: When order matters. Appl. Environ. Microbiol. 78, 6137-6142.   DOI
13 Poole, K. 2004. Resistance to ${\beta}$-lactam antibiotics. Cell. Mol. Life Sci. 61, 2200-2223.
14 Rice, L.B., Yao, J.D.C., Klimm, K., Eliopoulos, G.M., and Moellering, R.C. 1991. Efficacy of different ${\beta}$-lactams against an extendedspectrum ${\beta}$-lactamase-producing Klebsiella pneumoniae strain in the rat intra-abdominal abscess model. Antimicrob. Agent. Chemother. 35, 1243-1244.   DOI
15 Warren, D.K., Hill, H.A., Merz, L.R., Kollef, M.H., Hayden, M.K., Fraser, V.J., and Fridkin, S.K. 2004. Cycling empirical antimicrobial agents to prevent emergence of antimicrobial-resistant Gramnegative bacteria among intensive care unit patients. Crit. Care Med. 32, 2450-2456.   DOI
16 Shaikh, S., Fatima, J., Shakil, S., Rizvi, S.M.D., and Kamal, M.A. 2015. Antibiotic resistance and extended spectrum ${\beta}$-lactamases: Types, epidemiology and treatment. Saudi J. Biol. Sci. 22, 90-101.   DOI
17 Shannon, K. and Phillips, I. 1986. The effects on ${\beta}$-lactam susceptibility of phenotypic induction and genotypic derepression of ${\beta}$-lactamase synthesis. J. Antimicrob. Chemother. 18, 15-22.   DOI
18 Tolun, V., Kucukbasmaci, O., Torumkuney-Akbulut, D., Catal, C., Ang-Kucuker, M., and Aug, O. 2004. Relationship between ciprofloxacin resistance and extended-spectrum ${\beta}$-lactamase production in Escherichia coli and Klebsiella pneumoniae strains. Clin. Microbiol. Infect. 10, 72-75.   DOI
19 Tuomanen, E., Durack, D.T., and Tomasz, A. 1986. Antibiotic tolerance among clinical isolates of bacteria. Antimicrob. Agent. Chemother. 30, 521-527.   DOI
20 Vestergaard, M., Paulander, W., Marvig, R.L., Clasen, J., Jochumsen, N., Molin, S., Jelsbak, L., Ingmer, H., and Folkesson, A. 2016. Antibiotic combination therapy can select for broad-spectrum multidrug resistance in Pseudomonas aeruginosa. Int. J. Antimicrob. Agent 47, 48-55.   DOI
21 Williamson, R. and Tomasz, A. 1985. Inhibition of cell wall synthesis and acylation of the penicillin binding proteins during prolonged exposure of growing Streptococcus pneumoniae to benzylpenicillin. Eur. J. Biochem. 151, 475-483.   DOI
22 Zhong, H.Q., Zhang, S., Pan, H., and Cai, T. 2013. Influence of induced ciprofloxacin resistance on efflux pump activity of Klebsiella pneumoniae. J. Zhejiang Univ. Sci. B 14, 837.   DOI
23 Drago, L., Nicola, L., Mattina, R., and De Vecchi, E. 2010. In vitro selection of resistance in Escherichia coli and Klebsiella spp. at in vivo fluoroquinolone concentrations. BMC Microbiol. 10, 119.   DOI
24 Baran, I. and Aksu, N. 2016. Phenotypic and genotypic characteristics of carbapenem-resistant Enterobacteriaceae in a tertiary-level reference hospital in Turkey. Ann. Clin. Microbiol. Antimicrob. 15, 20.   DOI
25 Chen, L.X., He, S., Li, C., and Ryu, J. 2009. Sublethal kanamycin induced cross resistance to functionally and structurally unrelated antibiotics. J. Exp. Microbiol. Immunol. 13, 53-57.