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Evaluation of Meropenem and Gentamicin Synergy on Klebsiella pneumonaie

Year 2024, Volume: 8 Issue: 3, 236 - 241, 31.12.2024
https://doi.org/10.34084/bshr.1590089

Abstract

Objective: Antimicrobial resistance is a severe global problem, causing both medical and economic results. Klebsiella pneumoniae (K. pneumoniae) is a gram-negative bacterium that plays a major role in these burdens due to its widespread resistance mechanisms. This study searchs for the synergy and antagonism between meropenem and gentamicin using the disk diffusion method and compares these findings with results from the checkerboard method. If the results are consistent, validating the reliability of the disk diffusion method, it could be a cost-effective alternative to other testing methods.
Methods: The checkerboard method is used to assess the interaction of two antimicrobial agents (synergistic, indifferent, or antagonistic) by preparing a grid of wells containing varying concentrations of the agents. The fractional inhibitory concentration index (FICI) is calculated to evaluate the combination's efficacy.
In the disc diffusion method, the antimicrobial activity of an agent is determined by placing discs soaked in the agent on an agar plate inoculated with bacteria. After incubation, the diameter of the inhibition zone is measured to assess susceptibility.
Results: No synergy or antagonism was detected in any of the 30 Klebsiella pneumaniae isolates by either method.
Conclusion: The disc diffusion method is a cost-effective and reliable alternative to other in vitro synergy tests, especially when facilities are limited.

Project Number

1919B012216444

References

  • Guoying W, Guo Z, Xiaoyu C, Longxiang X, Hongju W. The Characteristic of Virulence, Biofilm and Antibiotic Resistance of Klebsiella pneumoniae. Int J Environ Res Public Health. 2020; 17(17): 6278. DOI: 10.3390/ijerph17176278
  • Baykal A, Cöplü N, Simsek H, Esen B, Gür D. Kan İzolatı E. coli ve K.pneumoniae Suşlarında Genişlemiş Spektrumlu Beta-Laktamaz, KPC-Tip Karbapenemaz ve Plazmid Aracılı AmpC Beta-Laktamaz Varlığının Araştırılması. Mikrobiyol Bul. 2012; 46(2): 159-69. PMid: 22639305
  • Karampatakis, T.; Tsergouli, K.; Behzadi, P. Carbapenem-Resistant Klebsiella pneumoniae: Virulence Factors, Molecular Epidemiology and Latest Updates in Treatment Options. Antibiotics 2023, 12, 234. DOI: 10.3390/antibiotics12020234
  • Elemam, J. Rahimian, W. Mandell. Infection with panresistant Klebsiella pneumoniae: a report of 2 cases and a brief review of the literature. Clinical Infectious Diseases, Volume 49, Issue 2, 15 July 2009, Pages 271–274. DOI: 10.1086/600042
  • Dennis J. Doorduijn, Suzan H.M. Rooijakkers, Willem van Schaik, Bart W. Bardoel. Complement resistance mechanisms of Klebsiella pneumoniae. Immunobiology. Volume 221, Issue 10, October 2016, Pages 1102-1109. DOI: 10.1016/j.imbio.2016.06.014
  • Giske CG, Monnet DL, Cars O, Carmeli Y. Clinical and Economic Impact of Common Multidrug-resistant Gram-negative Bacilli. Antimicrob Agents Chemother. 2008;52(3):813–21. DOI: 10.1128/AAC.01169-07
  • Martin, R.M.; Bachman, M.A. Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae. Front. Cell. Infect. Microbiol. 2018, 8, 4. DOI: 10.3389/fcimb.2018.00004
  • Havan M, Kendirli T, Parlar ÖT, et al. Clinical Management of a Pandrug-Resistant OXA-48 Klebsiella pneumoniae Infection in the Pediatric Intensive Care Unit. Microb Drug Resist. 2023 Jun;29(6):256-262. DOI: 10.1089/mdr.2022.0247
  • Cojutti P, Sartor A, Bassetti M, Scarparo C, Pea F. Is meropenem MIC increase against KPC-producing Klebsiella pneumoniae correlated with increased resistance rates against other antimicrobials with Gram-negative activity? J Glob Antimicrob Resist. 2018 Sep;14:238-241. doi: 10.1016/j.jgar.2018.05.005. Epub 2018 Jul 9. DOI: 10.1016/j.jgar.2018.05.005
  • Firmo EF, Oliveira Júnior JB, Scavuzzi AML, et al. In vitro activity of polymyxin B in combination with meropenem, amikacin and gentamicin against Klebsiella pneumoniae clinical isolates co-harbouring aminoglycoside-modifying enzymes, blaNDM-1 and blaKPC-2. J Glob Antimicrob Resist. 2020 Sep;22:511-514. doi: 10.1016/j.jgar.2020.04.014.
  • Oliva A, Scorzolini L, Cipolla A, et al. In vitro evaluation of different antimicrobial combinations against carbapenemase-producing Klebsiella pneumoniae: the activity of the double-carbapenem regimen is related to meropenem MIC value. J Antimicrob Chemother. 2017 Jul 1;72(7):1981-1984. DOI: 10.1093/jac/dkx084
  • Chen Z, Xiang J. Preliminary study on resistance mechanism and virulence features in carbapenems-resistant Klebsiella pneumoniae from burn patients. Zhonghua Shao Shang Za Zhi. 2018 Nov 20;34(11):796-801. Chinese. doi: 10.3760/cma.j.issn.1009-2587.2018.11.015.
  • Yu L, Zhang J, Fu Y, et al. Synergetic Effects of Combined Treatment of Colistin With Meropenem or Amikacin on Carbapenem-Resistant Klebsiella pneumoniae in vitro. Front Cell Infect Microbiol. 2019 Dec 10;9:422. doi: 10.3389/fcimb.2019.00422.
  • Toledo PV, Tuon FF, Arend L, Aranha Junior AA. Efficacy of tigecycline, polymyxin, gentamicin, meropenem and associations in experimental Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae non- lethal sepsis. Braz J Infect Dis. 2014 Sep-Oct;18(5):574-5. DOI: 10.1016/j.bjid.2014.05.003
  • Gaudereto JJ, Neto LVP, Leite GC, Espinoza EPS, Martins RCR, Villas Boa Prado G, Rossi F, Guimarães T, Levin AS, Costa SF. Comparison of methods for the detection of in vitro synergy in multidrug-resistant gram-negative bacteria. BMC Microbiol. 2020 Apr 16;20(1):97. doi: 10.1186/s12866-020-01756-0.
  • Matuschek E, Copsey-Mawer S, Petersson S, Åhman J, Morris TE, Kahlmeter G. The European committee on antimicrobial susceptibility testing disc diffusion susceptibility testing method for frequently isolated anaerobic bacteria. Clin Microbiol Infect. 2023 Jun;29(6):795.e1-795.e7. DOI: 10.1016/j.cmi.2023.01.027
  • Erinmez M, Zer Y. In vitro effects of deferoxamine on antibiotic susceptibility in Gram-negative bacteria. Adv Clin Exp Med. 2024 May;33(5):491-497. doi: 10.17219/acem/169794.
  • Nordmann, P.; Naas, T.; Poirel, L. Global spread of Carbapenemase-producing Enterobacteriaceae. Emerg. Infect. Dis. 2011, 17, 1791–1798. DOI: 10.3201/eid1710.110655
  • Foudraine, D.E.; Strepis, N.; Klaassen, C.H.W. et al. Rapid and Accurate Detection of Aminoglycoside-Modifying Enzymes and 16S rRNA Methyltransferases by Targeted Liquid Chromatography-Tandem Mass Spectrometry. J. Clin Microbiol. 2021. DOI: 10.1128/JCM.00464-21
  • Doménech-Sánchez, A.; Martínez-Martínez, L.; Hernández-Allés, S., et al. Role of Klebsiella pneumoniae OmpK35 porin in antimicrobial resistance. Antimicrob. Agents Chemother. 2003, 47, 3332–3335. DOI: 10.1128/AAC.47.10.3332-3335.2003
  • Srinivasan, V.B.; Singh, B.B.; Priyadarshi, N.; Chauhan, N.K.; Rajamohan, G. Role of novel multidrug efflux pump involved in drug resistance in Klebsiella pneumoniae. PLoS ONE 2014, 9. DOI: 10.1371/journal.pone.0096288
  • Bhardwaj S, Mehra P, Dhanjal DS, et al. Antibiotics and Antibiotic Resistance Flipsides of the Same Coin. Curr Pharm Des. 2022;28(28):2312-2329. DOI: 10.2174/1381612828666220608120238
  • Jeannot K, Gaillot S, Triponney P, Portets S, Pourchet V, Fournier D, Potron A. Performance of the Disc Diffusion Method, MTS Gradient Tests and Two Commercially Available Microdilution Tests for the Determination of Cefiderocol Susceptibility in Acinetobacter spp. Microorganisms. 2023 Jul 31;11(8):1971. DOI: 10.3390/microorganisms11081971
  • Mansour-Ghanaei F, Poostizadeh G, Joukar F, Siavoshi F. Efficacy of Disc Diffusion and Agar Dilution Methods in Evaluating Helicobacter pylori Susceptibility to Antibiotics. Middle East J Dig Dis. 2022 Apr;14(2):207-213. DOI: 10.34172/mejdd.2022.274
  • Khaki P, Sharma A, Bhalla P. Comparison of two-disc diffusion methods with minimum inhibitory concentration for antimicrobial susceptibility testing of Neisseria gonorrhoea isolates. Ann Med Health Sci Res. 2014 May;4(3):453-6. DOI: 10.4103/2141-9248.133477
  • Rogers TM, Kline EG, Griffith MP, et al. Mutations in ompK36 differentially impact in vitro synergy of meropenem/vaborbactam and ceftazidime/avibactam in combination with other antibiotics against KPC-producing Klebsiella pneumoniae. JAC-Antimicrobial Resistance. 2023 Oct 26;5(5): dlad113. DOI: 10.1093/jacamr/dlad113
  • Dobreva E, Ivanov I, Donchev D, et al. In vitro Investigation of Antibiotic Combinations against Multi- and Extensively Drug-Resistant Klebsiella pneumoniae. Open Access Maced J Med Sci [Internet]. 2022 Apr. 5;10(B):1308-14.

Meropenem ve Gentamisin Sinerjisinin Klebsiella pneumoniae Üzerinde Değerlendirilmesi

Year 2024, Volume: 8 Issue: 3, 236 - 241, 31.12.2024
https://doi.org/10.34084/bshr.1590089

Abstract

Amaç: Antimikrobiyal direnç, hem tıbbi hem de ekonomik sonuçlara neden olan ciddi bir küresel sorundur. Klebsiella pneumoniae (K. pneumoniae), yaygın direnç mekanizmaları nedeniyle bu yüklerde önemli rol oynayan gram-negatif bir bakteridir. Bu çalışma, disk difüzyon yöntemini kullanarak meropenem ve gentamisin arasındaki sinerji ve antagonizmi araştırmakta ve bu bulguları dama tahtası yönteminden elde edilen sonuçlarla karşılaştırmaktadır. Sonuçlar tutarlıysa, disk difüzyon yönteminin güvenilirliğini doğrulayarak, diğer test yöntemlerine uygun maliyetli bir alternatif olabilir.
Yöntem: Dama tahtası yöntemi, iki antimikrobiyal ajanın etkileşimini (sinerjik, kayıtsız veya antagonistik) değerlendirmek için, ajanların değişen konsantrasyonlarını içeren kuyucuklardan oluşan bir ızgara hazırlayarak kullanılır. Kombinasyonun etkinliğini değerlendirmek için fraksiyonel inhibitör konsantrasyon indeksi (FICI) hesaplanır.
Disk difüzyon yönteminde, bir ajanın antimikrobiyal aktivitesi, ajana batırılmış disklerin bakterilerle aşılanmış bir agar plakasına yerleştirilmesiyle belirlenir. İnkübasyondan sonra, duyarlılığı değerlendirmek için inhibisyon bölgesinin çapı ölçülür.
Bulgular: Her iki yöntemle de 30 Klebsiella pneumaniae izolatının hiçbirinde sinerji veya antagonizm tespit edilmemiştir.
Sonuç: Disk difüzyon yöntemi, özellikle imkanların kısıtlı olduğu durumlarda, diğer in vitro sinerji testlerine uygun maliyetli ve güvenilir bir alternatiftir.

Project Number

1919B012216444

References

  • Guoying W, Guo Z, Xiaoyu C, Longxiang X, Hongju W. The Characteristic of Virulence, Biofilm and Antibiotic Resistance of Klebsiella pneumoniae. Int J Environ Res Public Health. 2020; 17(17): 6278. DOI: 10.3390/ijerph17176278
  • Baykal A, Cöplü N, Simsek H, Esen B, Gür D. Kan İzolatı E. coli ve K.pneumoniae Suşlarında Genişlemiş Spektrumlu Beta-Laktamaz, KPC-Tip Karbapenemaz ve Plazmid Aracılı AmpC Beta-Laktamaz Varlığının Araştırılması. Mikrobiyol Bul. 2012; 46(2): 159-69. PMid: 22639305
  • Karampatakis, T.; Tsergouli, K.; Behzadi, P. Carbapenem-Resistant Klebsiella pneumoniae: Virulence Factors, Molecular Epidemiology and Latest Updates in Treatment Options. Antibiotics 2023, 12, 234. DOI: 10.3390/antibiotics12020234
  • Elemam, J. Rahimian, W. Mandell. Infection with panresistant Klebsiella pneumoniae: a report of 2 cases and a brief review of the literature. Clinical Infectious Diseases, Volume 49, Issue 2, 15 July 2009, Pages 271–274. DOI: 10.1086/600042
  • Dennis J. Doorduijn, Suzan H.M. Rooijakkers, Willem van Schaik, Bart W. Bardoel. Complement resistance mechanisms of Klebsiella pneumoniae. Immunobiology. Volume 221, Issue 10, October 2016, Pages 1102-1109. DOI: 10.1016/j.imbio.2016.06.014
  • Giske CG, Monnet DL, Cars O, Carmeli Y. Clinical and Economic Impact of Common Multidrug-resistant Gram-negative Bacilli. Antimicrob Agents Chemother. 2008;52(3):813–21. DOI: 10.1128/AAC.01169-07
  • Martin, R.M.; Bachman, M.A. Colonization, Infection, and the Accessory Genome of Klebsiella pneumoniae. Front. Cell. Infect. Microbiol. 2018, 8, 4. DOI: 10.3389/fcimb.2018.00004
  • Havan M, Kendirli T, Parlar ÖT, et al. Clinical Management of a Pandrug-Resistant OXA-48 Klebsiella pneumoniae Infection in the Pediatric Intensive Care Unit. Microb Drug Resist. 2023 Jun;29(6):256-262. DOI: 10.1089/mdr.2022.0247
  • Cojutti P, Sartor A, Bassetti M, Scarparo C, Pea F. Is meropenem MIC increase against KPC-producing Klebsiella pneumoniae correlated with increased resistance rates against other antimicrobials with Gram-negative activity? J Glob Antimicrob Resist. 2018 Sep;14:238-241. doi: 10.1016/j.jgar.2018.05.005. Epub 2018 Jul 9. DOI: 10.1016/j.jgar.2018.05.005
  • Firmo EF, Oliveira Júnior JB, Scavuzzi AML, et al. In vitro activity of polymyxin B in combination with meropenem, amikacin and gentamicin against Klebsiella pneumoniae clinical isolates co-harbouring aminoglycoside-modifying enzymes, blaNDM-1 and blaKPC-2. J Glob Antimicrob Resist. 2020 Sep;22:511-514. doi: 10.1016/j.jgar.2020.04.014.
  • Oliva A, Scorzolini L, Cipolla A, et al. In vitro evaluation of different antimicrobial combinations against carbapenemase-producing Klebsiella pneumoniae: the activity of the double-carbapenem regimen is related to meropenem MIC value. J Antimicrob Chemother. 2017 Jul 1;72(7):1981-1984. DOI: 10.1093/jac/dkx084
  • Chen Z, Xiang J. Preliminary study on resistance mechanism and virulence features in carbapenems-resistant Klebsiella pneumoniae from burn patients. Zhonghua Shao Shang Za Zhi. 2018 Nov 20;34(11):796-801. Chinese. doi: 10.3760/cma.j.issn.1009-2587.2018.11.015.
  • Yu L, Zhang J, Fu Y, et al. Synergetic Effects of Combined Treatment of Colistin With Meropenem or Amikacin on Carbapenem-Resistant Klebsiella pneumoniae in vitro. Front Cell Infect Microbiol. 2019 Dec 10;9:422. doi: 10.3389/fcimb.2019.00422.
  • Toledo PV, Tuon FF, Arend L, Aranha Junior AA. Efficacy of tigecycline, polymyxin, gentamicin, meropenem and associations in experimental Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae non- lethal sepsis. Braz J Infect Dis. 2014 Sep-Oct;18(5):574-5. DOI: 10.1016/j.bjid.2014.05.003
  • Gaudereto JJ, Neto LVP, Leite GC, Espinoza EPS, Martins RCR, Villas Boa Prado G, Rossi F, Guimarães T, Levin AS, Costa SF. Comparison of methods for the detection of in vitro synergy in multidrug-resistant gram-negative bacteria. BMC Microbiol. 2020 Apr 16;20(1):97. doi: 10.1186/s12866-020-01756-0.
  • Matuschek E, Copsey-Mawer S, Petersson S, Åhman J, Morris TE, Kahlmeter G. The European committee on antimicrobial susceptibility testing disc diffusion susceptibility testing method for frequently isolated anaerobic bacteria. Clin Microbiol Infect. 2023 Jun;29(6):795.e1-795.e7. DOI: 10.1016/j.cmi.2023.01.027
  • Erinmez M, Zer Y. In vitro effects of deferoxamine on antibiotic susceptibility in Gram-negative bacteria. Adv Clin Exp Med. 2024 May;33(5):491-497. doi: 10.17219/acem/169794.
  • Nordmann, P.; Naas, T.; Poirel, L. Global spread of Carbapenemase-producing Enterobacteriaceae. Emerg. Infect. Dis. 2011, 17, 1791–1798. DOI: 10.3201/eid1710.110655
  • Foudraine, D.E.; Strepis, N.; Klaassen, C.H.W. et al. Rapid and Accurate Detection of Aminoglycoside-Modifying Enzymes and 16S rRNA Methyltransferases by Targeted Liquid Chromatography-Tandem Mass Spectrometry. J. Clin Microbiol. 2021. DOI: 10.1128/JCM.00464-21
  • Doménech-Sánchez, A.; Martínez-Martínez, L.; Hernández-Allés, S., et al. Role of Klebsiella pneumoniae OmpK35 porin in antimicrobial resistance. Antimicrob. Agents Chemother. 2003, 47, 3332–3335. DOI: 10.1128/AAC.47.10.3332-3335.2003
  • Srinivasan, V.B.; Singh, B.B.; Priyadarshi, N.; Chauhan, N.K.; Rajamohan, G. Role of novel multidrug efflux pump involved in drug resistance in Klebsiella pneumoniae. PLoS ONE 2014, 9. DOI: 10.1371/journal.pone.0096288
  • Bhardwaj S, Mehra P, Dhanjal DS, et al. Antibiotics and Antibiotic Resistance Flipsides of the Same Coin. Curr Pharm Des. 2022;28(28):2312-2329. DOI: 10.2174/1381612828666220608120238
  • Jeannot K, Gaillot S, Triponney P, Portets S, Pourchet V, Fournier D, Potron A. Performance of the Disc Diffusion Method, MTS Gradient Tests and Two Commercially Available Microdilution Tests for the Determination of Cefiderocol Susceptibility in Acinetobacter spp. Microorganisms. 2023 Jul 31;11(8):1971. DOI: 10.3390/microorganisms11081971
  • Mansour-Ghanaei F, Poostizadeh G, Joukar F, Siavoshi F. Efficacy of Disc Diffusion and Agar Dilution Methods in Evaluating Helicobacter pylori Susceptibility to Antibiotics. Middle East J Dig Dis. 2022 Apr;14(2):207-213. DOI: 10.34172/mejdd.2022.274
  • Khaki P, Sharma A, Bhalla P. Comparison of two-disc diffusion methods with minimum inhibitory concentration for antimicrobial susceptibility testing of Neisseria gonorrhoea isolates. Ann Med Health Sci Res. 2014 May;4(3):453-6. DOI: 10.4103/2141-9248.133477
  • Rogers TM, Kline EG, Griffith MP, et al. Mutations in ompK36 differentially impact in vitro synergy of meropenem/vaborbactam and ceftazidime/avibactam in combination with other antibiotics against KPC-producing Klebsiella pneumoniae. JAC-Antimicrobial Resistance. 2023 Oct 26;5(5): dlad113. DOI: 10.1093/jacamr/dlad113
  • Dobreva E, Ivanov I, Donchev D, et al. In vitro Investigation of Antibiotic Combinations against Multi- and Extensively Drug-Resistant Klebsiella pneumoniae. Open Access Maced J Med Sci [Internet]. 2022 Apr. 5;10(B):1308-14.
There are 27 citations in total.

Details

Primary Language English
Subjects Medical Microbiology (Other)
Journal Section Research Article
Authors

Ali Ünal 0009-0006-1014-4448

Yeliz Tanrıverdi Çaycı 0000-0002-9251-1953

İlknur Bıyık 0000-0002-3247-883X

Project Number 1919B012216444
Early Pub Date December 31, 2024
Publication Date December 31, 2024
Submission Date November 23, 2024
Acceptance Date November 27, 2024
Published in Issue Year 2024 Volume: 8 Issue: 3

Cite

AMA Ünal A, Tanrıverdi Çaycı Y, Bıyık İ. Evaluation of Meropenem and Gentamicin Synergy on Klebsiella pneumonaie. J Biotechnol and Strategic Health Res. December 2024;8(3):236-241. doi:10.34084/bshr.1590089

Journal of Biotechnology and Strategic Health Research