Efficiency of combined action of antimicrobial preparations against poly-resistant strains of conditionally-pathogenic bacteria isolated from wounds of surgery patients

  • T. V. Sklyar Oles Honchar Dnipro National University
  • K. V. Lavrentievа Oles Honchar Dnipro National University
  • O. M. Rudas Oles Honchar Dnipro National University
  • О. V. Bilotserkivska Oles Honchar Dnipro National University
  • N. V. Kurahina Oles Honchar Dnipro National University
  • M. G. Papiashvili Independent laboratory Invitro LLC
  • O. A. Lykholat University of Customs and Finance
Keywords: antibiotics; antiseptics; multi-drug resistant strains; combinative effect.

Abstract

The strategy of use of combination therapy of antibacterial preparations is being broadly introduced to clinical practice to fight bacterial infections caused by poly-resistant strains of microorganisms. From the wounds of surgery patients, we isolated 67 clinical strains of conditionally-pathogenic bacteria identified as Staphylococcus aureus, S. epidermidis, Escherichia coli, Klebsiella pneumoniaе, Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa. Using disk diffusion method, the isolated bacterial strains were found to be most resistant to penicillin preparations: ampicillin, oxacillin, amoxicillin/clavulanat; tetracycline and cephalosporin of the II generation – cefoxitin. The percentage of strains insusceptible to these antibacterial preparations accounted for 65.0%. The division of antibiotic-resistant cultures regarding phenotype groups according to the level of their antibiotic resistance allowed determination of 4 PDR-, 8 XDR- and 14 MDR-strains. During the studies on experimental determining of MIC of antibiotic and antiseptics in the condition of applying them as monopreparations against isolated bacterial cultures, we saw significant exceess in the threshold values of MIC, and, first of all, regarding pandrug-resistant and extensive drug-resistant clinical microbial isolates. Use of combinations of antibacterial preparations was found to show the synergic effect of antibiotics (ceftriaxone, ofloxacin, gentamicin) and antiseptics (chlorhexidine, decasan), which is expressed in simultaneous decrease in MIC of each of the tested preparations by 2–8 times compared with their isolative application. Such combinatory approach regarding simultaneous application of antibacterial preparations may be considered as one of the most promising ways to combat poly-resistant clinical isolates of conditionally-pathogenic microorganisms and to offer a new strategic approach to prevention of spread of antibiotic resistance as a phenomenon in medical practice.

References

Agyekum, A., Fajardo-Lubián, A., Ai, X., Ginn, A., Zong, Z., Guo, X., Turnidge, J., Partridge, S., & Iredell, J. (2016). Predictability of phenotype in relation to common-lactam resistance mechanisms in Escherichia coli and Klebsiella pneumonia. Journal of Clinical Microbiology, 54(5), 1243–1250.

Al-Talib, H., Alkhateeb, A., Syahriza, A., Ruzuk, A., Zulkifli, F., Hamizi, S., Muhammad, N., & Karim, F. (2019). Effectiveness of commonly used antiseptics on bacteria causing nosocomial infections in tertiary hospital in Malaysia. African Journal of Microbiology Research, 13(10), 188–194.

Anesi, J., Lautenbach, E., Nachamkin, I., Garrigan, C., Bilker, W., Wheeler, M., Tolomeo, P., & Han, J. (2016). Clinical and molecular characterization of community-onset urinary tract infections due to extended-spectrum cephalosporin-resistant Enterobacteriaceae. Infection Control and Hospital Epidemiology, 37(12), 1433–1439.

Aslam, B., Wang, W., Arshad, M., Khurshid, M., Muzammil, S., Rasool, M., Nisar, M., Alvi, R., Aslam, M., Qamar, M., Salamat, M., & Baloch, Z. (2018). Antibiotic resistance: A rundown of a global crisis. Infection and Drug Resistance, 11, 1645–1658.

Barnes, M., Taracila, M, Rutter, J., Bethel, C., Galdadas, I., Hujer, A., Caselli, E., Prati, F., Dekker, P., Papp-Wallace, K., Haider, S., & Bonomo, R. (2018). Deciphering the evolution of cephalosporin resistance to ceftolozane-tazobactam in Pseudomonas aeruginosa. MBio, 9(6), e2085-18.

Bassetti, M., Vena, A., Croxatto, A., Righi, E., & Guery, B. (2018). How to manage Pseudomonas aeruginosa infections. Drugs in Context, 7, 1–18.

Botelho, J., Grosso, F., & Peixe L. (2019). Antibiotic resistance in Pseudomonas aeruginosa – mechanisms, epidemiology and evolution. Drug Resistance Updates, 44, 26–47.

Campbell, S., Goodnough, L., Bennett, C., & Giori, N. (2018). Antiseptics commonly used in total joint arthroplasty interact and may form toxic products. The Journal of Arthroplasty, 33(3), 844–846.

Campos, M., Jimenez, F., Sanchez, G., Juarez, J., Morales, A., Canovas-Segura, B., & Palacios, F. (2020). A methodology based on multiple criteria decision analysis for combining antibiotics in empirical therapy. Artificial Intelligence in Medicine, 102, 101751.

Chellat, M., Raguž, L., & Riedl, R. (2016). Targeting antibiotic resistance. Angewandte Chemie International Edition, 55(23), 6600–6626.

Cheng, G., Ning, J., Ahmed, S., Huang, J., Ullah, R., An, B., Hao, H., Dai, M., Huang, L., Wang, X., & Yuan, Z. (2019). Selection and dissemination of antimicrobial resistance in agri-food production. Antimicrobial Resistance and Infection Control, 158(8), 1–13.

Chervet, D., Lortholary, O., Zahar, J., Dufougeray, A., Pilmis, B., & Partouche, H. (2018). Antimicrobial resistance in community-acquired urinary tract infections in Paris in 2015. Medecine at Maladies Infectieuses, 48(3), 188–192.

Dalhoff, A. (2012). Global fluoroquinolone resistance epidemiology and implictions for clinical use. Interdisciplinary Perspectives on Infectious Diseases, 2012, 976273.

Djachenko, V., Marjushhenko, A., Chigirins'ka, N., & Kucaj, N. (2016). Efektivnіst’ dіji kombіnacіj preparatіv z grupy ftorhіnolonіv z іnshymy antibіotykamy na polіrezystentnі shtamy syn’ognіjnoji palychky ta enterobakterіj [Effectiveness of a combination of drugs from the group of fluoroquinolones with other antibiotics on multidrug-resistant strains of Pseudomonas aeruginosa and enterobacteria]. Biomedical and Biosocial Anthropology, 26, 71–73 (in Ukrainian).

Dopcea, N., Dopcea, I., Nanu, A., Diguta, C., & Matei, F. (2020). Resistance and cross-resistance in Staphyloccocus sp. after prolonged exposure to different antiseptics. Journal of Global Antimicrobial Resistance, 21, 399–404.

European Centre for Disease Prevention and Control (2018). Surveillance of antimicrobial resistance in Europe. Annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net) 2017. ECDC, Stockholm.

Fabry, W., & Kock, H.-J. (2014). In-vitro activity of polyhexanide alone and in combination with antibiotics against Staphylococcus aureus. Journal of Hospital Infection, 86(1), 68–72.

Garimella, N., Zere, T., Hartman, N., Gandhi, A., Bekele, A., Li, X., Stone, H., Sacks, L., & Weaver, J. (2020). Effect of drug combinations on the kinetics of antibiotic resistance emergence in E. coli CFT073 using an in vitro hollow-fiber infection model. International Journal of Antimicrobial Agents, 55(4), 105861.

Hansen, S., Schwab, F., Zingg, W., & Gastmeier, P. (2018). Process and outcome indicators for infection control and prevention in European acute care hospitals in 2011 to 2012 – Results of the Prohibit study. Eurosurveillance, 2(21), 1700513.

Jenull, S., Laggner, H., Hassl, I., Velimirov, B., Huettinger, B., & Zemann, N. (2017). Cooperativity between antibiotics and antiseptics: Testing the bactericidal effect. Journal of Wound Care, 26(12), 720–726.

Kramer, A., Assadian, O., & Koburger-Janssen, T. (2016). Antimicrobial efficacy of the combination of chlorhexidine digluconate and dexpanthenol. GMS Hygiene and Infection Control, 11, 1–6.

Magiorakos, A.-P., Srinivasan, A., Carey, R., Carmeli, Y., Falagas, M., Giske, C., Harbarth, S., Hindler, J., Kahlmeter, G., Olsson-Liljequist, B., Paterson, D., Rice, L., Stelling, J., Struelens, M., Vatopoulos, A., Weber, J., & Monnet, D. (2012). Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clinical Microbiology and Infection, 18(3), 268–281.

Marques, D., Machado, S., Ebinuma, V., Duarte, C., Converti, A., & Porto, A. (2018). Production of β-lactamase inhibitors by Streptomyces species. Antibiotics, 7(3), 1–26.

Matthew, E., Lucy, J., Laura, C., & Sutton, J. (2017). Mechanisms of increased resistance to chlorhexidine and cross-resistance to colistin following exposure of Klebsiella pneumoniae clinical isolates to chlorhexidine. Antimicrobial Agents and Chemotherapy, 61(1), 1–12.

Mobarki, N., Almerabі, B., & Hattan, A. (2019). Antibiotic resistance crisis. International Journal of Medicine in Developing Countries, 3(6), 561–564.

Noites, R., Pina-Vaz, C., Rocha, R., Carvalho, M., Gonçalves, A., & Pina-Vaz, I. (2014). Synergistic antimicrobial action of chlorhexidine and ozone in endodontic treatment. Journal of Biomedicine and Biotechnology, 2014, 1–6.

Pachori, P., Gothalwal, R., & Gandhi, P. (2019). Emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit; A critical review. Genes and Diseases, 6, 109–119.

Palchykov, V. A., Zazharskyi, V. V., Brygadyrenko, V. V., Davydenko, P. O., Kulishenko, O. M., & Borovik, I. V. (2020). Chemical composition and antibacterial effect of ethanolic extract of Buxus sempervirens on cryogenic strains of microorganisms in vitro. Chemical Data Collections, 25, 100323.

Pervical, S., Finnegan, S., Donelli, G., Vuotto, C., Rimmer, S., Benjamin, A., & Lipsky, B. (2016). Antiseptics for treating infected wounds: Efficacy on biofilms and effect of pH. Critical Reviews in Microbiology, 42(2), 293–309.

Potapov, V., Vakulenko, E., & Protasenko, Y. (2016). Vybor optimal’nyh antisepticheskih sredstv dlja obrabotki kostnoj polosti v processe hirurgicheskogo lechenija nagnoivshihsja radikuljarnyh kist [The choice of optimal antiseptic agents for the treatment of the bone cavity in the process of surgical treatment of festering radicular cysts]. Ukrajinskyj Stomatologichnyj Al’manakh, 4, 40–42 (in Russian).

Rather, I., Byung-Chun K., Bajpai, V., & Yong-HaPark (2017). Self-medication and antibiotic resistance: Crisis, current challenges, and prevention. Saudi Journal of Biological Sciences, 24(4), 808–812.

Rodríguez-Baño, J., Gutiérrez-Gutiérrez, B., Machuca, I., & Pascual, A. (2018). Treatment of infections caused by extended-spectrum-beta-lactamase-, AmpC-, and carbapenemase-producing Enterobacteriaceae. Clinical Microbiology Reviews, 31(2), e00079-17.

Schmid, A., Wolfensberger, A., Nemeth, J., Schreiber, P., Sax, H., & Kuster, S. (2019). Monotherapy versus combination therapy for multidrug-resistant Gram-negative infections: Systematic review and meta-analysis. Scientific Reports, 9, 1–11.

Sweeney, M., Lubbers, B., Schwarz, S., & Watts, J. (2018). Applying definitions for multidrug resistance, extensive drug resistance and pandrug resistance to clinically significant livestock and companion animal bacterial pathogens. The Journal of Antimicrobial Chemotherapy, 73(6), 1460–1463.

Tacconelli, E., Carrara, E., Savoldi, A., Harbarth, S., Mendelson, M., Monnet, D., Pulcini, С., Kahlmeter, G., Kluytmans, J., Carmeli, Y., Ouellette, M., Outterson, K., Patel, J., Cavaleri, M., Cox, E., Houchens, C., Grayson, M., Hansen, P., Singh, N., Theuretzbacher, U., & Magrini, N. (2018). Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. The Lancet Infectious Diseases, 18(3), 318–327.

Tängdén, T. (2014). Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria. Upsala Journal of Medical Sciences, 119(2), 149–153.

Thwaites, M., Hall, D., Stoneburner, A., Shinabarger, D., Serio, A., Krause, K., Marra, A., & Pillar, C. (2018). Activity of plazomicin in combination with other antibiotics against multidrug-resistant Enterobacteriaceae. Diagnostic Microbiology and Іnfectious Disease, 92(4), 338–345.

Velez, R., & Sloand, E. (2016). Combating antibiotic resistance, mitigating future threats and ongoing initiatives. Journal of Clinical Nursing, 25, 1886–1889.

Von Wintersdorff, C., Penders, J., van Niekerk, J., Mills, N., Majumder, S., van Alphen, L., Savelkoul, P., & Wolffs, P. (2016). Dissemination of antimicrobial resistance in microbial ecosystems through horizontal gene transfer. Frontiers in Microbiology, 7, 1–10.

Williamson, D., Carter, G., & Howden, B. (2017). Current and emerging topical antibacterials and antiseptics: Agents, action, and resistance patterns. Clinical Microbiology Reviews, 30(3), 827–860.

Zazharskyi, V. V., Davydenko, P. О., Kulishenko, O. М., Borovik, I. V., & Brygadyrenko, V. V. (2019). Antimicrobial activity of 50 plant extracts. Biosystems Diversity, 27(2), 163–169.

Published
2020-08-21
How to Cite
Sklyar, T. V., LavrentievаK. V., Rudas, O. M., BilotserkivskaО. V., Kurahina, N. V., Papiashvili, M. G., & Lykholat, O. A. (2020). Efficiency of combined action of antimicrobial preparations against poly-resistant strains of conditionally-pathogenic bacteria isolated from wounds of surgery patients. Regulatory Mechanisms in Biosystems, 11(3), 392–398. https://doi.org/10.15421/022060