AB1319 Drug resistance in bacteria isolated from urine of rheumatoid arthritispatients and induction of resistance by chloroquine
Authors: I. Konieczna, L. Lechowicz, M. Chrzanowska, M. Chyb, S. Cholewa, D. Grzegorczyk, J. Ciura, J. Gaweda
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) was connected with bacterial infections.<sup>1</sup> Usage of antibiotics generate resistance in pathogens as well as natural microflora.<sup>2</sup> Some anti-rheumatic drug (chloroquine) probably is associated with selection of quinolone resistant bacteria.<sup>3</sup> <h3>Objectives</h3> To isolate bacteria from urine of rheumatoid arthritis patients, determinate antibiotic resistance profiles for isolated bacteria and induce ciprofloxacin resistance by exposition to chloroquine. <h3>Methods</h3> Two consecutive samples of morning urine was obtained from 26 RA patients without urinary infection tract symptoms. Patients were treatment-naïve or treated with different anti-rheumatic drugs. Bacteriuria was determinate on UTI chromogenic medium (HIMEDIA). Resistance against 38 commonly used drugs (MAST) was determined according EUCAST standards. For OXA-48 carbapenemase detection, a temocillin disc was used. Isolated bacterial strains were cultivated on LB broth supplemented with chloroquine (625 and 1875 µg/ml) for 2 weeks, than incubated on medium with ciprofloxacin (32, 15, 8, 4, 2, 1, 0.5 µg/ml). Growth was measured with spectrophotometer (λ=600 nm) against non-inoculeted medium. <h3>Results</h3> Bacteria were cultivated from almost 88% of patients, but only in 26% of them in titer higher than 10<sup>5</sup> cfu/ml of urine. Bacteriuria were more often in treated individuals. Isolated bacteria belonged to <i>Escherichia coli</i>, <i>Klebsiella pneumoniae</i>, <i>Enterobacter cloacae</i>, <i>Proteus mirabilis</i>, <i>Morganella morganii</i>, <i>Staphylococcus</i> sp. Among tested bacteria 23% were determined as MDRs and one strain were XDR. Screening test detecting OXA-48 revealed that 35% of strains probably possess this resistance mechanism. Selected 10 ciprofloxacin sensitive strains (<i>E. coli</i>, <i>P. mirabilis</i>, <i>E. cloacae</i>, <i>M. morganii</i>) were exposed to increasing concentration of chloroquine. After 2 weeks of passing, 80% of bacteria become resistant to antibiotic (with ciprofloxacin MIC up to 8 µg/ml). <h3>Conclusions</h3> Asymptomatic bacteriuria is general phenomenon in RA patients. This research showed that many of Polish RA patients may be carriers of drug resistant bacteria, including MDR. This phenomenon may be connected with poor comply of antibiotic policy by patients as well as health service in Poland. Exposition on chloroquine induce bacterial resistance against ciprofloxacin. In RA treatment procedure, a risk of induction of quinolone resistance in bacterial flora should be considered. <h3>References</h3> [1] Li S. et al. Microbial Infection and Rheumatoid Arthritis. J Clin Cell Immunol. 2014; 4(6). doi:10.4172/2155-9899.1000174 [2] Ventola C.L. The Antibiotic Resistance Crisis: Part 1: Causes and Threats. P&amp;T. 2015; 40(4): 277–283. [3] Davidson R.J. et al. Antimalarial Therapy Selection for Quinolone Resistance among Escherichia coli in the Absence of Quinolone Exposure, in Tropical South America. PLoS ONE2008; 3(7). doi:10.1371/journal.pone.0002727 <h3>Acknowledgements</h3> This work was supported by grant No. UMO-2011/03/D/NZ6/03316 from the National Science Centre, Poland <h3>Disclosure of Interest</h3> None declared