Resistance to β-lactam antibiotics and erythromycin in bacteria of the Oral Cavity

Resistencia a antibióticos β-lactámicos y Eritromicina en bacterias de la Cavidad Oral

Introduction. The human microbiota as a source of bacteria and resistance genes is a public health problem. In this study was to investigate the prevalence of Gram-negative enteric bacilli resistant to β-lactams and erythomycin resistance in the oral cavity. Methods. A descriptive cross-sectional study was carried out with 193 isolates obtained from the healthy oral cavity of 178 adults who were treated at a Dental Clinic in the city of Cali during 2018. The evaluation of antimicrobial sensitivity was performed in 59 enteric bacilli and 134 EGV and the genes that confer resistance to β-lactam and erythromycin were identified by PCR. Statistical analysis was performed using the SPSS statistical package vs. 25.0. Results. 84.7% of the enteric bacilli presented the MDR phenotype and all presented the bla genes, blaTEM-1 (49.2%) and blaVIM-2 (30.5%) being the most prevalent. EGVs were resistant to erythromycin (38.8%) and clindamycin (28.4%). 18.7% presented the cMLSβ phenotype, 4.5% the iMLSβ and 14.9% were M. The ermB gene was detected more frequently in the cMLSβ, (13.4%) and the mef gene in the M (9.7%). Conclusion. This study demonstrated the presence of antibiotics and Gram-negative enteric bacilli resistant to antibiotics and carriers of erythromycin resistance genes and bla genes, respectively in the healthy oral cavity. The presence of these bacteria represents a risk to the health of carrier individuals and contributes to the growing epidemic of bacterial resistance

1. Nesme J, Cecillon S, Delmont TO, Monier JM, Vogel TM, Simonet P. Large-scale metagenomic-based study of antibiotic resistance in the environment. Curr Biol. 2014;24:1096-1100. http://dx.doi.org/10.1016/j.cub.2014.03.036
2. Sommer MOA, Church GM, Dantas G. The human microbiome harbors a diverse reservoir of antibiotic resistance genes. Virulence. 2010; 1(4): 299-303. https://www.researchgate.net/publication/49702544
3. Penders J, Stobberingh EE, Savelkoul PH, Wolffs PF. The human microbiome as a reservoir of antimicrobial resistance. Front Microbiol. 2013;4:87. Published 2013 Apr 17. doi:10.3389/fmicb.2013.00087
4. Khalil D, Hultin M, Rashid MU, Lund B. Oral microflora and selection of resistance after a single dose of amoxicillin. Clin. Microbiol. Infect. 2016;22:949.e1–949.e4. doi:10.1016/j.cmi.2016.08.008
5. Chaffanel F, Charron-Bourgoin F, Libante V, Leblond-Bourget N, Payot S. Resistance genes and genetic elements associated with antibiotic resistance in clinical and commensal isolates of Streptococcus salivarius. Appl. Environ. Microbiol. 2015;81:4155–4163. doi: 10.1128/AEM.00415-15. Epub 2015 Apr 10
6. Pasquantonio G, Condo S, Cerroni L, Bikiqu L, Nicoletti M, Prenna M, Ripa S. Antibacterial activity of various antibiotics against oral streptococci isolated oral cavity Int J Immunopathol Pharmacol. 2012;25:805-809. doi: 10.1177/039463201202500331
7. Dupin C, Tamanai-Shacoori Z, Ehrmann E, Dupont A, Barloy-Hubler F, Bousarghin L, et al. Oral Gram-negative anaerobic bacilli as a reservoir of β-lactam resistance genes facilitating infections with multiresistant bacteria. Int J Antimicrob Agents, 2015; 45(2): 99-105. doi: 10.1016/j.ijantimicag.2014.10.003
8. Brito-Aragão MG, Fernandes-Gomes FI, Ruliglesio-Rocha F, Teixeira-Pinto V. Prevalence and Susceptibility of Enterobacteriaceae Isolated from the Saliva of Students from the Northeast of Brazil. Glob J Med Res. 2016;16 (2):13-17. https://globaljournals.org/GJMR_Volume16/3-Prevalence-and-Susceptibility.pdf
9. Leão-Vasconcelos LS, Lima AB, Costa Dde M, Rocha-Vilefort, LO, Oliveira AC, Gonçalve NF, et al. Enterobacteriaceae isolates from the oral cavity of workers in a Brazilian oncology hospital. Rev Inst Med Trop Sao Paulo. 2015;57(2):121–127. doi:10.1590/S0036-46652015000200004
10. Bryskier A. Viridans group streptococci: a reservoir of resistant bacteria in oral cavities. Clin Microbiol Infect. 2002;8:65---9. doi: https://doi.org/10.1046/j.1198-743x.2001.00398.x
11. Handal T, Olsen I, Walker CB, Caugant DA. Beta-lactamase production and antimicrobial susceptibility of subgingival bacteria from refractory periodontitis. Oral Microbiol Immunol. 2004 ;19:303-8. doi: 10.1111/j.1399-302x.2004.00159.x
12. Sukumar S, Roberts AP, Martin FE, Adler CJ. Metagenomic insights into transferable antibiotic resistance in oral bacteria. J Dent Res 2016. https://doi.org/10.1177/0022034516648944.
13. Brolund A, Sandegren L. Characterization of ESBL disseminating plasmids. Infect Dis. 2016; 48:18-25. doi: 10.3109/23744235.2015.1062536. Epub 2015 Jul 1.
14. Sutcliffe J, Grebe T, Tait-Kamradt A, Wondrack Lillian. Detection of Erythromycin-Resistant Determinants by PCR. Antimicrob Agents Chemother. 1996; 40(11):2562–2566. PMID: 8913465; PMCID: PMC163576.
15. Villedieu A, Diaz-Torres ML, Roberts AP, Hunt N, McNab R,. Spratt DA, et al. Genetic Basis of Erythromycin Resistance in Oral Bacteria. Antimicrob Agents Chemoth. 2004; 48(6): 2298–2301. doi: 10.1128/AAC.48.6.2298–2301.2004.
16. Zhu L, Li Q, Li GC, Wu W, Pei N, He Y-x. Prevalence of erythromycin resistance genes among clinical isolates of viridians group Streptococci. Biomed Res. 2017; 28 (3): 1272-1275.
17. Clinical Laboratory Standards Institute. Performance standars for antimicrobial susceptibility testing, 27th informational supplement, 2017; M100-S27. Wayne, PA, USA.
18. Ying CM, Ling TK, Lee CC, Ling JM. Characterization of carbapenem-resistant Acinetobacter baumannii in Shanghai and Hong Kong. J. Med. Microbiol. 2006; 55:799-802. doi: 10.1099/jmm.0.46117-0
19. Mendes RE, Castanheira M, Garcia P, Guzman M, Toleman MA, Walsh TM, et al. First isolation of blaVIM-2 in Latin America: report from the SENTRY Antimicrobial Surveillance Program. Antimicrob Agents Chemother. 2004; 48:1433–34. doi: 10.1128/aac.48.4.1433-1434.2004
20. Mabilat C, Courvalin P. Development of oligotyping for characterization and molecular epidemiology of TEM β-lactamases in members of the family Enterobacteriaceae. Antimicrob Agents Chemother. 1990;34 (1): 2210-6. doi:10.1128/aac.34.11.2210
21. Herrera-León S, González-Sanz R, Rodríguez I, Rodicio MR, Echeita MA. Spread of a multiresistant CTX-M-9-producing Salmonella enterica serotype Virchow phage type 19 in Spain. Eur J Clin Microbiol Infect Dis. 2010;29:901–905. doi: 10.1007/s10096-010-0939-6
22. Kuo H, Yang C, Lin M, Cheng W, Tiene N, Liou M. Distribution of blaOXA-carrying imipenem-resistant Acinetobacter spp. in 3 hospitals in Taiwan. Diag. Microbiol. Infect. Dis. 2010; 66: 195–199. doi: 10.1128/AAC.00779-13
23. Coudron PE, Moland ES, Thomson KS. Occurrence and detection of AmpC beta- lactamases among Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis isolates at a veterans medical center”, J Clin Microbiol. 2000; 38(5):1791-6.
24. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infec. 2012; 18(3):268–281. doi: 10.1111/j.1469-0691.2011.03570.x. Epub 2011 Jul 27.
25. Ferreira PVA, Amêndola I, Dias de Oliveira L, Gonçalves e Ssilva CR, VPL Mariella, Ferreira dos Santo SS. Prevalence and Sensitivity of Bacilli and Pseudomonas in the Newborn’s Oral Cavity. Braz. Dent. J. 2017; 8 (4): 423-427. http://dx.doi.org/10.1590/0103-6440201601205
26. Zuanazzi D, Souto R, Mattos MB, Zuanazzi MR, Tura BR, Sansone C, et al. Prevalence of potential bacterial respiratory pathogens in the oral cavity of hospitalized individuals. Arch Oral Biol 2010;55(1):21–8.
27. Jones DJ, Munro CL. Oral care and the risk of bloodstream infections in mechanically ventilated adults: a review. Intensive Crit Care Nurs 2008;24(3):152–61.
28. Gaetti-Jardim EC, Marqueti AC, Faverani LP, Gaetti-Jardim Jr E. Antimicrobial resistance of aerobes and facultative anaerobes isolated from the oral cavity. J. Appl. Oral Sci. 2010; 18( 6 ): 551-559. doi: 10.1590/s1678-77572010000600004
29. Thomson KS. Extended-spectrum-lactamase, AmpC and carbapenemase issues. J Clin Microbiol. 2010;48:1019–1025. doi: 10.1128/JCM.00219-10. Epub 2010 Feb 24.
30. Coutinho V, Paiva RM, Reiter KC, de-Paris F, Barth AL, Machado AB, et al. Distribution of erm genes and low prevalence of inducible resistance to clindamycin among staphylococci isolates. Braz J Infect Dis. 2010; 14(6): 564-568. http://dx.doi.org/10.1590/S1413-86702010000600004.
31. Goudarzi G, Tahmasbi F, Anbari K, Ghafarzadeh M. Distribution of Genes Encoding Resistance to Macrolides Among Staphylococci Isolated From the Nasal Cavity of Hospital Employees in Khorramabad, Iran, Iran Red Crescent Med J. 2016; 18(2):e25701. doi: 10.5812/ircmj.25701.
32. Aracil B, Minambres M, Oteo J, Torres C, Gomez-Garces JL, Alos JI. High prevalence of erythromycin-resistant and clindamycin-susceptible (M phenotype) viridans group streptococci from pharyngeal samples: a reservoir of mef genes in commensal bacteria. J. Antimicrob. Chemother. 2001;48:592–594. https://doi.org/10.1093/jac/48.4.592
33. Luna VA, Heiken M, Judge K, Ulep C, Van Kirk N, Luis H, et al. Distribution of mef(A) in gram-positive bacteria from healthy Portuguese children. Antimicrob. Agents Chemother. 2002; 46:2513–2517. 86702010000600004&lng=en. http://dx.doi.org/10.1590/S1413-86702010000600004.
34. Sutcliffe J, Tait-Kamradt A, Wondrack L. Streptococcus pneumonia and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by efflux system. Antimicrob Agents Chemother. 1996;40:1817-24.
35. Liu N, Ando T, Ishiguro K, Maeda O, Watanabe, O, Funasaka K, et al. Characterization of bacterial biota in the distal esophagus of Japanese patients with reflux esophagitis and Barrett’s esophagus. BMC Infect. Dis. 2013;13:130. doi:10.1186/1471-2334-13-130
36. Mueller S, Saunier, K, Hanisch, C, Norin, E, Alm, L, Midtvedt, T, et al.. Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study. Appl. Environ. Microbiol. 2006; 72: 1027–1033. doi: 10.1128/AEM.72.2.1027-1033.