Araştırma Makalesi
BibTex RIS Kaynak Göster

KARBAPENEMLERE DİRENÇLİ KLEBSİELLA PNEUMONİAE İZOLATLARININ APRAMİSİNE DUYARLILIKLARININ ARAŞTIRILMASI

Yıl 2022, Cilt: 5 Sayı: 1, 25 - 31, 10.02.2022

Öz

Amaç: Bu çalışmada, çeşitli klinik örneklerden izole edilen karbapenemlere dirençli Klebsiella pneumoniae izolatlarında blaOXA-48 benzeri, blaCTX-M-15, blaNDM-1 genlerinin varlığı ve apramisine duyarlılıklarının araştırılması amaçlanmıştır. Gereç ve Yöntem: Çalışmaya Haziran-Eylül 2020 tarihleri arasında İstanbul Tıp Fakültesi Hastanesinde yatan hastalara ait çeşitli klinik örneklerden izole edilen 12 çoğul dirençli K. pneumoniae izolatı dahil edilmiştir. Bu izolatlarda imipenem, meroperem, ertapenem ve apramisin için minimum inhbisyon konsantrasyon (MİK) değerleri, EUCAST önerilerine göre sıvı mikrodilüsyon yöntemiyle saptanmıştır. Antibiyotik konsantrasyonları EUCAST (imipenem, meropenem, ertapenem) ve NARMS (apramisin) klinik sınır değerlerini kapsayacak şekilde <0,016-256 μg/mL olarak belirlenmiştir. Klasik polimeraz zincir reaksiyonu (PCR) yöntemiyle K. pneumoniae izolatlarında blaOXA-48, blaNDM-1, blaCTX-M-15 genlerinin varlığı araştırılmıştır. Bulgular: Karpanenemlere dirençli K. pneumoniae izolatlarının tamamında (n=12) blaOXA-48 benzeri ve blaCTX-M-15 genleri, bir izolatta (%8,33) blaNDM-1 geni saptanmıştır. İzolatlarının tümü ertapeneme, %91,7’si meropeneme ve %58,3’ü imipeneme dirençli bulunmuştur. Tüm izolatların apramisine duyarlı olduğu belirlenmiştir. MİK aralığı ertapenem için 4-256 μg/mL, meropenem için 0,5-64 μg/mL, imipenem için 0,5-128 μg/mL, apramisin için <0,016-2 μg/mL aralığında saptanmıştır. Sonuç: K. pneumoniae izolatlarında apramisin için düşük MİK değerlerinin saptanması, karbapenemlere veya tüm antibiyotiklere dirençli izolatlarda, tedavide alternatif olarak kullanılabilecek bir ajan olabileceğini düşündürmektedir. Bu nedenle apramisinin klinikte kullanılabilmesiyle ilgili daha kapsamlı çalışmalara ihtiyaç duyulmaktadır.

Kaynakça

  • 1. Guh AY, Limbago BM, Kallen AJ. Epidemiology and prevention of carbapenem-resistant Enterobacteriaceae in the United States. Expert Rev Anti-Infe 2014;12(5):565-80.
  • 2. Gupta P, Bollam N, Mehta Y, Sengupta S, Gandra S. Risk factors associated with carbapenem-resistant Klebsiella pneumoniae bloodstream infections in a tertiary-care hospital in India. Infect Control Hosp Epidemiol 2020:1-3.
  • 3. van Duin D, Paterson DL. Multidrug-Resistant Bacteria in the Community Trends and Lessons Learned. Infect Dis Clin N Am 2016;30(2):377-90.
  • 4. Cui X, Zhang H, Du H. Carbapenemases in Enterobacteriaceae: Detection and Antimicrobial Therapy. Front Microbiol 2019;10:1823.
  • 5. Nordmann P, Naas T, Poirel L. Global Spread of Carbapenemaseproducing Enterobacteriaceae. Emerging Infectious Diseases 2011;17(10):1791-8.
  • 6. Nordmann P, Poirel L. The difficult-to-control spread of carbapenemase producers among Enterobacteriaceae worldwide. Clin Microbiol Infec 2014;20(9):821-30.
  • 7. Matt T, Ng CL, Lang K, Sha SH, Akbergenov R, Shcherbakov D, et al. Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apramycin. Proc Natl Acad Sci U S A 2012;109(27):10984-9.
  • 8. Ishikawa M, Garcia-Mateo N, Cusak A, Lopez-Hernandez I, Fernandez-Martinez M, Muller M, et al. Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use. Sci Rep-Uk 2019;9(1):2410.
  • 9. Juhas M, Widlake E, Teo J, Huseby DL, Tyrrell JM, Polikanov YS, et al. In vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii. J Antimicrob Chemother 2019;74(4):944-52.
  • 10. Krause KM, Serio AW, Kane TR, Connolly LE. Aminoglycosides: An Overview. Cold Spring Harb Perspect Med 2016;6(6):a027029.
  • 11. Kang AD, Smith KP, Eliopoulos GM, Berg AH, McCoy C, Kirby JE. Invitro Apramycin Activity against multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Diagn Microbiol Infect Dis 2017;88(2):188-91.
  • 12. Becker K, Cao S, Nilsson A, Erlandsson M, Hotop SK, Kuka J, et al. Antibacterial activity of apramycin at acidic pH warrants wide therapeutic window in the treatment of complicated urinary tract infections and acute pyelonephritis. EBioMedicine 2021;73:103652.
  • 13. 2000 National Antimicrobial Resistance Monitoring System (NARMS) For Enteric Bacteria Participants (Human Isolates) Available from: URL https://www.cdc.gov/narms/annual/2000/ NARMS_final_report_2000.pdf. Alıntılanma tarihi: 30.07.2021.
  • 14. EUCAST warnings concerning antimicrobial susceptibility testing products or procedures. Available from: URL: http://www.eucast. org/ast_of_bacteria/warnings/. Alıntılanma tarihi 19.08.2019.
  • 15. Aktas Z, Kayacan CB, Schneider I, Can B, Midilli K, Bauernfeind A. Carbapenem-hydrolyzing oxacillinase, OXA-48, persists in Klebsiella pneumoniae in Istanbul, Turkey. Chemotherapy 2008;54(2):101-6.
  • 16. Poirel L, Heritier C, Tolun V, Nordmann P. Emergence of oxacillinasemediated resistance to imipenem in Klebsiella pneumoniae. Antimicrob Agents Chemother 2004;48(1):15-22.
  • 17. Hidalgo L, Hopkins KL, Gutierrez B, Ovejero CM, Shukla S, Douthwaite S, et al. Association of the novel aminoglycoside resistance determinant RmtF with NDM carbapenemase in Enterobacteriaceae isolated in India and the UK. J Antimicrob Chemother 2013;68(7):1543-50.
  • 18. Poirel L, Naas T, Le Thomas I, Karim A, Bingen E, Nordmann P. CTX-M-type extended-spectrum beta-lactamase that hydrolyzes ceftazidime through a single amino acid substitution in the omega loop. Antimicrob Agents Ch 2001;45(12):3355-61.
  • 19. World Health Organization. WHO priority pathogens list for R&D of new antibiotics. http:// www.who.int/mediacentre/news/ releases/2017/bacteria-antibiotics-needed/en/.2017.
  • 20. van Duin D, Arias CA, Komarow L, Chen L, Hanson BM, Weston G, et al. Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study. Lancet Infect Dis 2020;20(6):731-41.
  • 21. Guh AY, Bulens SN, Mu Y, Jacob JT, Reno J, Scott J, et al. Epidemiology of Carbapenem-Resistant Enterobacteriaceae in 7 US Communities, 2012-2013. JAMA 2015;314(14):1479-87.
  • 22. Centers for Disease Control and Prevention. Facility Guidance for Control of Carbapenem-resistant Enterobacteriaceae (CRE). November 2015 Update - CRE Toolkit. https://www.cdc.gov/hai/ pdfs/cre/cre-guidance-508.pdf
  • 23. Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, et al. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 2009;53(12):5046- 54.
  • 24. Nordmann P, Poirel L, Toleman MA, Walsh TR. Does broadspectrum beta-lactam resistance due to NDM-1 herald the end of the antibiotic era for treatment of infections caused by Gramnegative bacteria? J Antimicrob Chemother 2011;66(4):689-92.
  • 25. Hawser SP, Bouchillon SK, Hoban DJ, Badal RE, Hsueh PR, Paterson DL. Emergence of high levels of extended-spectrumbeta- lactamase-producing gram-negative bacilli in the Asia- Pacific region: data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) program, 2007. Antimicrob Agents Chemother 2009;53(8):3280-4.
  • 26. Albiger B, Glasner C, Struelens MJ, Grundmann H, Monnet DL, European Survey of Carbapenemase-Producing Enterobacteriaceae working g. Carbapenemase-producing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015. Euro Surveill 2015;20(45):1-18.
  • 27. Hao M, Shi X, Lv J, Niu S, Cheng S, Du H, et al. In vitro Activity of Apramycin Against Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae Isolates. Front Microbiol 2020;11:425.
  • 28. Smith KP, Kirby JE. Evaluation of apramycin activity against carbapenem-resistant and -susceptible strains of Enterobacteriaceae. Diagn Microbiol Infect Dis 2016;86(4):439-41.
  • 29. Hu Y, Liu L, Zhang X, Feng Y, Zong Z. In Vitro Activity of Neomycin, Streptomycin, Paromomycin and Apramycin against Carbapenem Resistant Enterobacteriaceae Clinical Strains. Front Microbiol 2017;8:2275.
  • 30. Hao M, Schuyler J, Zhang H, Shashkina E, Du H, Fouts DE, et al. Apramycin resistance in epidemic carbapenem-resistant Klebsiella pneumoniae ST258 strains. J Antimicrob Chemother 2021;76(8):2017-23.
  • 31. Kilic U, Koroglu M, Olmez M, Altindis M. Investigation of the In Vitro Effectiveness of Aztreonam/Avibactam, Colistin/Apramycin, and Meropenem/Apramycin Combinations Against Carbapenemase- Producing, Extensively Drug-Resistant Klebsiella pneumoniae Strains. Microb Drug Resist 2020;26(11):1291-97.
  • 32. Livermore DM, Mushtaq S, Warner M, Zhang JC, Maharjan S, Doumith M, et al. Activity of aminoglycosides, including ACHN- 490, against carbapenem-resistant Enterobacteriaceae isolates. J Antimicrob Chemother 2011;66(1):48-53

INVESTIGATION OF THE SUSCEPTIBILITY OF CARBAPENEMRESISTANT KLEBSIELLA PNEUMONIAE ISOLATES TO APRAMYCIN

Yıl 2022, Cilt: 5 Sayı: 1, 25 - 31, 10.02.2022

Öz

Objective: In this study, it was aimed to investigate the presence of blaOXA-48- like, blaCTX-M-15, blaNDM-1 genes and susceptibility to apramycin of carbapenemresistant Klebsiella pneumoniae isolates isolated from various clinical samples. Material and Methods: Twelve multiple resistant K. pneumoniae isolates isolated from various clinical samples of hospitalized patients in Istanbul Faculty of Medicine Hospital between June and September 2020 were included in the study. The minimum inhibitory concentration (MIC) values for imipenem, meroperem, ertapenem and apramycin in these isolates were determined using the broth microdilution method according to EUCAST recommendations. The antibiotic concentrations were determined as <0.016-256 μg/mL, including the clinical breakpoints of EUCAST (imipenem, meropenem, ertapenem) and NARMS (apramycin). The presence of blaOXA-48, blaNDM-1, blaCTX-M-15 genes in K. pneumoniae isolates was investigated using the classical polymerase chain reaction (PCR) method. Results: The blaOXA-48-like and blaCTX-M-15 genes were detected in all isolates (n=12) of K. pneumoniae resistant to carbapenems, and the blaNDM-1 gene was found in one (8.33%). All isolates were found to be resistant to ertapenem, 91.7% of meropenem, 58.3% of imipenem. All isolates were determined as being susceptible to apramycin. The MIC values were detected between 4-256 μg/mL for ertapenem, 0.5-64 μg/mL for meropenem, 0.5-128 μg/mL for imipenem, and <0.016-2 μg/mL for apramycin. Conclusion: The detection of low MIC values for apramycin in K. pneumoniae isolates suggests that it may be an alternative treatment agent for isolates resistant to carbapenems or all antibiotics. Therefore, there is a need for more comprehensive studies on the clinical use of apramycin.

Kaynakça

  • 1. Guh AY, Limbago BM, Kallen AJ. Epidemiology and prevention of carbapenem-resistant Enterobacteriaceae in the United States. Expert Rev Anti-Infe 2014;12(5):565-80.
  • 2. Gupta P, Bollam N, Mehta Y, Sengupta S, Gandra S. Risk factors associated with carbapenem-resistant Klebsiella pneumoniae bloodstream infections in a tertiary-care hospital in India. Infect Control Hosp Epidemiol 2020:1-3.
  • 3. van Duin D, Paterson DL. Multidrug-Resistant Bacteria in the Community Trends and Lessons Learned. Infect Dis Clin N Am 2016;30(2):377-90.
  • 4. Cui X, Zhang H, Du H. Carbapenemases in Enterobacteriaceae: Detection and Antimicrobial Therapy. Front Microbiol 2019;10:1823.
  • 5. Nordmann P, Naas T, Poirel L. Global Spread of Carbapenemaseproducing Enterobacteriaceae. Emerging Infectious Diseases 2011;17(10):1791-8.
  • 6. Nordmann P, Poirel L. The difficult-to-control spread of carbapenemase producers among Enterobacteriaceae worldwide. Clin Microbiol Infec 2014;20(9):821-30.
  • 7. Matt T, Ng CL, Lang K, Sha SH, Akbergenov R, Shcherbakov D, et al. Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apramycin. Proc Natl Acad Sci U S A 2012;109(27):10984-9.
  • 8. Ishikawa M, Garcia-Mateo N, Cusak A, Lopez-Hernandez I, Fernandez-Martinez M, Muller M, et al. Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use. Sci Rep-Uk 2019;9(1):2410.
  • 9. Juhas M, Widlake E, Teo J, Huseby DL, Tyrrell JM, Polikanov YS, et al. In vitro activity of apramycin against multidrug-, carbapenem- and aminoglycoside-resistant Enterobacteriaceae and Acinetobacter baumannii. J Antimicrob Chemother 2019;74(4):944-52.
  • 10. Krause KM, Serio AW, Kane TR, Connolly LE. Aminoglycosides: An Overview. Cold Spring Harb Perspect Med 2016;6(6):a027029.
  • 11. Kang AD, Smith KP, Eliopoulos GM, Berg AH, McCoy C, Kirby JE. Invitro Apramycin Activity against multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa. Diagn Microbiol Infect Dis 2017;88(2):188-91.
  • 12. Becker K, Cao S, Nilsson A, Erlandsson M, Hotop SK, Kuka J, et al. Antibacterial activity of apramycin at acidic pH warrants wide therapeutic window in the treatment of complicated urinary tract infections and acute pyelonephritis. EBioMedicine 2021;73:103652.
  • 13. 2000 National Antimicrobial Resistance Monitoring System (NARMS) For Enteric Bacteria Participants (Human Isolates) Available from: URL https://www.cdc.gov/narms/annual/2000/ NARMS_final_report_2000.pdf. Alıntılanma tarihi: 30.07.2021.
  • 14. EUCAST warnings concerning antimicrobial susceptibility testing products or procedures. Available from: URL: http://www.eucast. org/ast_of_bacteria/warnings/. Alıntılanma tarihi 19.08.2019.
  • 15. Aktas Z, Kayacan CB, Schneider I, Can B, Midilli K, Bauernfeind A. Carbapenem-hydrolyzing oxacillinase, OXA-48, persists in Klebsiella pneumoniae in Istanbul, Turkey. Chemotherapy 2008;54(2):101-6.
  • 16. Poirel L, Heritier C, Tolun V, Nordmann P. Emergence of oxacillinasemediated resistance to imipenem in Klebsiella pneumoniae. Antimicrob Agents Chemother 2004;48(1):15-22.
  • 17. Hidalgo L, Hopkins KL, Gutierrez B, Ovejero CM, Shukla S, Douthwaite S, et al. Association of the novel aminoglycoside resistance determinant RmtF with NDM carbapenemase in Enterobacteriaceae isolated in India and the UK. J Antimicrob Chemother 2013;68(7):1543-50.
  • 18. Poirel L, Naas T, Le Thomas I, Karim A, Bingen E, Nordmann P. CTX-M-type extended-spectrum beta-lactamase that hydrolyzes ceftazidime through a single amino acid substitution in the omega loop. Antimicrob Agents Ch 2001;45(12):3355-61.
  • 19. World Health Organization. WHO priority pathogens list for R&D of new antibiotics. http:// www.who.int/mediacentre/news/ releases/2017/bacteria-antibiotics-needed/en/.2017.
  • 20. van Duin D, Arias CA, Komarow L, Chen L, Hanson BM, Weston G, et al. Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study. Lancet Infect Dis 2020;20(6):731-41.
  • 21. Guh AY, Bulens SN, Mu Y, Jacob JT, Reno J, Scott J, et al. Epidemiology of Carbapenem-Resistant Enterobacteriaceae in 7 US Communities, 2012-2013. JAMA 2015;314(14):1479-87.
  • 22. Centers for Disease Control and Prevention. Facility Guidance for Control of Carbapenem-resistant Enterobacteriaceae (CRE). November 2015 Update - CRE Toolkit. https://www.cdc.gov/hai/ pdfs/cre/cre-guidance-508.pdf
  • 23. Yong D, Toleman MA, Giske CG, Cho HS, Sundman K, Lee K, et al. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 2009;53(12):5046- 54.
  • 24. Nordmann P, Poirel L, Toleman MA, Walsh TR. Does broadspectrum beta-lactam resistance due to NDM-1 herald the end of the antibiotic era for treatment of infections caused by Gramnegative bacteria? J Antimicrob Chemother 2011;66(4):689-92.
  • 25. Hawser SP, Bouchillon SK, Hoban DJ, Badal RE, Hsueh PR, Paterson DL. Emergence of high levels of extended-spectrumbeta- lactamase-producing gram-negative bacilli in the Asia- Pacific region: data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) program, 2007. Antimicrob Agents Chemother 2009;53(8):3280-4.
  • 26. Albiger B, Glasner C, Struelens MJ, Grundmann H, Monnet DL, European Survey of Carbapenemase-Producing Enterobacteriaceae working g. Carbapenemase-producing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015. Euro Surveill 2015;20(45):1-18.
  • 27. Hao M, Shi X, Lv J, Niu S, Cheng S, Du H, et al. In vitro Activity of Apramycin Against Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae Isolates. Front Microbiol 2020;11:425.
  • 28. Smith KP, Kirby JE. Evaluation of apramycin activity against carbapenem-resistant and -susceptible strains of Enterobacteriaceae. Diagn Microbiol Infect Dis 2016;86(4):439-41.
  • 29. Hu Y, Liu L, Zhang X, Feng Y, Zong Z. In Vitro Activity of Neomycin, Streptomycin, Paromomycin and Apramycin against Carbapenem Resistant Enterobacteriaceae Clinical Strains. Front Microbiol 2017;8:2275.
  • 30. Hao M, Schuyler J, Zhang H, Shashkina E, Du H, Fouts DE, et al. Apramycin resistance in epidemic carbapenem-resistant Klebsiella pneumoniae ST258 strains. J Antimicrob Chemother 2021;76(8):2017-23.
  • 31. Kilic U, Koroglu M, Olmez M, Altindis M. Investigation of the In Vitro Effectiveness of Aztreonam/Avibactam, Colistin/Apramycin, and Meropenem/Apramycin Combinations Against Carbapenemase- Producing, Extensively Drug-Resistant Klebsiella pneumoniae Strains. Microb Drug Resist 2020;26(11):1291-97.
  • 32. Livermore DM, Mushtaq S, Warner M, Zhang JC, Maharjan S, Doumith M, et al. Activity of aminoglycosides, including ACHN- 490, against carbapenem-resistant Enterobacteriaceae isolates. J Antimicrob Chemother 2011;66(1):48-53
Toplam 32 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Klinik Tıp Bilimleri
Bölüm Araştırma Makaleleri
Yazarlar

Sevinç Baba 0000-0003-3625-155X

Zerrin Aktaş Bu kişi benim 0000-0002-5998-0440

Mustafa Oral Öncül Bu kişi benim 0000-0002-1681-1866

Erken Görünüm Tarihi 20 Ekim 2021
Yayımlanma Tarihi 10 Şubat 2022
Gönderilme Tarihi 16 Aralık 2021
Yayımlandığı Sayı Yıl 2022 Cilt: 5 Sayı: 1

Kaynak Göster

MLA Baba, Sevinç vd. “KARBAPENEMLERE DİRENÇLİ KLEBSİELLA PNEUMONİAE İZOLATLARININ APRAMİSİNE DUYARLILIKLARININ ARAŞTIRILMASI”. Sağlık Bilimlerinde İleri Araştırmalar Dergisi, c. 5, sy. 1, 2022, ss. 25-31.