Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae
Yıl: 2021 Cilt: 8 Sayı: 2 Sayfa Aralığı: 113 - 118 Metin Dili: İngilizce DOI: 10.14744/nci.2020.14238 İndeks Tarihi: 09-05-2021
Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae
Öz: OBJECTIVE: Klebsiella pneumoniae, a Gram-negative pathogen, especially which produces carbapenemase, is seen as a major threat to public health due to rapid plasmid-mediated spread of resistance and limited therapeutic options available for treatment. Although colistin has been recognized as a “last resort” antimicrobial for multidrug-resistant K. pneumoniaeinfections, these isolates have developed resistance to colistin as a result of its intensive use. The aim of this study was to evaluate the efficacy of double-carbapenem treatment of colistin-resistant K. pneumoniae experimental sepsis in mice.METHODS: In the study, 8–10-week-old Balb-c mice were divided as control groups (positive and negative) and treatment groups (colistin, ertapenem+meropenem, and ertapenem+meropenem+colistin). Sepsis was developed in mice by an intraperitoneal injection of colistin resistant K. pneumoniae. Antibiotics were given intraperitoneally 3 h after bacterial inoculation. Mice in each subgroup were sacrificed with overdose anesthetic at the end of 24–48 h and cultures were made from the heart, lung, liver, and spleen. Furthermore, homogenates of lung and liver were used to detect the number of colony-forming units per gram. Bacterial clearance was evaluated in lung and liver at different time points.RESULTS: When the quantitative bacterial loads in the lung and liver tissues are evaluated, no statistically significant difference was observed between different antibiotic treatments (p>0.05). All three treatment options were not effective, especially in 24 h. Only the decrease in bacterial load at the 48th h of the group treated with ertapenem + meropenem + colistin was found significant (p<0.05) compared to the 24 h.CONCLUSION: In the light of these data, it was understood that double-carbapenem application was not sufficient in the treatment of experimental sepsis in mice with colistin-resistant K. pneumoniae. Furthermore, ertapenem + meropenem + colistin combined therapy was not found to be superior to colistin monotherapy or double-carbapenem therapy.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
- 1. Cisneros JM, Reyes MJ, Pachón J, Becerril B, Caballero FJ, García-Garmendía JL, et al. Bacteremia due to Acinetobacter baumannii: epidemiology, clinical findings, and prognostic features. Clin Infect Dis 1996;22:1026–32.
- 2. Li B, Zhao Y, Liu C, Chen Z, Zhou D. Molecular pathogenesis of Klebsiella pneumoniae. Future Microbiol 2014;9:1071–81.
- 3. Jana B, Cain AK, Doerrler WT, Boinett CJ, Fookes MC, Parkhill J, et al. The secondary resistome of multidrug-resistant Klebsiella pneumoniae. Sci Rep 2017;7:42483.
- 4. Tumbarello M, Spanu T, Sanguinetti M, Citton R, Montuori E, Leone F, et al. Bloodstream infections caused by extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae: risk factors, molecular epidemiology, and clinical outcome. Antimicrob Agents Chemother 2006;50:498–504.
- 5. Queenan AM, Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev 2007;20:440–58.
- 6. La Bombardi VJ. The emergence of the KPC carbapenemases: clinical and laboratory issues. Rev Med Microbiol 2007;18:29–34.
- 7. Bratu S, Tolaney P, Karumudi U, Quale J, Mooty M, Nichani S, et al. Carbapenemase-producing Klebsiella pneumoniae in Brooklyn, NY: molecular epidemiology and in vitro activity of polymyxin B and other agents. J Antimicrob Chemother 2005;56:128–32.
- 8. DeLeo FR, Kobayashi SD, Porter AR, Freedman B, Dorward DW, Chen L, et al. Survival of Carbapenem-Resistant Klebsiella pneumoniae Sequence Type 258 in Human Blood. Antimicrob Agents Chemother 2017;61:e02533–16.
- 9. Li J, Ren J, Wang W, Wang G, Gu G, Wu X, et al. Risk factors and clinical outcomes of hypervirulent Klebsiella pneumoniae induced bloodstream infections. Eur J Clin Microbiol Infect Dis 2018;37:679–89.
- 10. Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 2009;9:228– 36.
- 11. Gaibani P, Lombardo D, Lewis RE, Mercuri M, Bonora S, Landini MP, et al. In vitro activity and post-antibiotic effects of colistin in combination with other antimicrobials against colistin-resistant KPC-producing Klebsiella pneumoniae bloodstream isolates. J Antimicrob Chemother 2014;69:1856–65.
- 12. Giamarellou H, Poulakou G. Multidrug-resistant Gram-negative infections: what are the treatment options? Drugs 2009;69:1879–901.
- 13. Sakoulas G, Olson J, Yim J, Singh NB, Kumaraswamy M, Quach DT, et al. Cefazolin and ertapenem, a synergistic combination used to clear persistent Staphylococcus aureus bacteremia. Antimicrob Agents Chemother 2016;60:6609–18.
- 14. Demiraslan H, Dinc G, Ahmed SS, Elmali F, Metan G, Alp E, et al. Carbapenem-resistant Klebsiella pneumoniae sepsis in corticosteroid receipt mice: tigecycline or colistin monotherapy versus tigecycline/colistin combination. J Chemother 2014;26:276–8
- 15. DeRyke CA, Banevicius MA, Fan HW, Nicolau DP. Bactericidal activities of meropenem and ertapenem against extended-spectrum-beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a neutropenic mouse thigh model. Antimicrob Agents Chemother 2007;51:1481–6.
- 16. Rowe TA, McKoy JM. Sepsis in older adults. Infect Dis Clin North Am 2017;31:731–42.
- 17. Tanır Basaranoglu S, Ozsurekci Y, Aykac K, Karadag Oncel E, Bıcakcigil A, Sancak B, et al. A comparison of blood stream infections with extended spectrum beta-lactamase-producing and non-producing Klebsiella pneumoniae in pediatric patients. Ital J Pediatr 2017;43:79.
- 18. Candan ED, Aksöz N. Klebsiella pneumoniae: characteristics of carbapenem resistance and virulence factors. Acta Biochim Pol 2015;62:867–74.
- 19. Chew KL, Lin RTP, Teo JWP. Klebsiella pneumoniae in Singapore: Hypervirulent Infections and the Carbapenemase Threat. Front Cell Infect Microbiol 2017;7:515.
- 20. Souli M, Karaiskos I, Masgala A, Galani L, Barmpouti E, Giamarellou H. Double-carbapenem combination as salvage therapy for untreatable infections by KPC-2-producing Klebsiella pneumoniae. Eur J Clin Microbiol Infect Dis 2017;36:1305–15.
- 21. Oliva A, Gizzi F, Mascellino MT, Cipolla A, D’Abramo A, D’Agostino C, et al. Bactericidal and synergistic activity of double-carbapenem regimen for infections caused by carbapenemase-producing Klebsiella pneumoniae. Clin Microbiol Infect 2016;22:147–53.
- 22. Oliva A, Scorzolini L, Cipolla A, Mascellino MT, Cancelli F, Castaldi D, 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;72:1981–4.
- 23. Evren E, Azap OK, Çolakoğlu Ş, Arslan H. In vitro activity of fosfomycin in combination with imipenem, meropenem, colistin and tigecycline against OXA 48-positive Klebsiella pneumoniae strains. Diagn Microbiol Infect Dis 2013;76:335–8.
- 24. Urban C, Mariano N, Rahal JJ. In vitro double and triple bactericidal activities of doripenem, polymyxin B, and rifampin against multidrug-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Antimicrob Agents Chemother 2010;54:2732–4.
- 25. Su J, Li D, Guo Q, Guo Y, Zheng Y, Xu X. In Vitro Bactericidal activity of trimethoprim-sulfamethoxazole/colistin combination against carbapenem-resistant Klebsiella pneumoniae clinical isolates. Microb Drug Resist 2019;25:152–6.
- 26. Dinc G, Eren E, Kontas O, Doganay M. The efficacy of mesenchymal stem cell therapy in experimental sepsis induced by carbapenem-resistant K. pneumoniae in neutropenic mice model. Eur J Clin Microbiol Infect Dis 2020;39:1739–44.
- 27. Petrosillo N, Taglietti F, Granata G. Treatment options for colistin resistant Klebsiella pneumoniae: present and future. J Clin Med 2019;8:934
| APA | Kosar I, Dinc G, Eryilmaz-Eren E, aykemat y, Kılıç H, Doganay M (2021). Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae. , 113 - 118. 10.14744/nci.2020.14238 |
| Chicago | Kosar Imran,Dinc Gokcen,Eryilmaz-Eren Esma,aykemat yusuf,Kılıç Hüseyin,Doganay Mehmet Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae. (2021): 113 - 118. 10.14744/nci.2020.14238 |
| MLA | Kosar Imran,Dinc Gokcen,Eryilmaz-Eren Esma,aykemat yusuf,Kılıç Hüseyin,Doganay Mehmet Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae. , 2021, ss.113 - 118. 10.14744/nci.2020.14238 |
| AMA | Kosar I,Dinc G,Eryilmaz-Eren E,aykemat y,Kılıç H,Doganay M Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae. . 2021; 113 - 118. 10.14744/nci.2020.14238 |
| Vancouver | Kosar I,Dinc G,Eryilmaz-Eren E,aykemat y,Kılıç H,Doganay M Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae. . 2021; 113 - 118. 10.14744/nci.2020.14238 |
| IEEE | Kosar I,Dinc G,Eryilmaz-Eren E,aykemat y,Kılıç H,Doganay M "Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae." , ss.113 - 118, 2021. 10.14744/nci.2020.14238 |
| ISNAD | Kosar, Imran vd. "Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae". (2021), 113-118. https://doi.org/10.14744/nci.2020.14238 |
| APA | Kosar I, Dinc G, Eryilmaz-Eren E, aykemat y, Kılıç H, Doganay M (2021). Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae. İstanbul Kuzey Klinikleri, 8(2), 113 - 118. 10.14744/nci.2020.14238 |
| Chicago | Kosar Imran,Dinc Gokcen,Eryilmaz-Eren Esma,aykemat yusuf,Kılıç Hüseyin,Doganay Mehmet Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae. İstanbul Kuzey Klinikleri 8, no.2 (2021): 113 - 118. 10.14744/nci.2020.14238 |
| MLA | Kosar Imran,Dinc Gokcen,Eryilmaz-Eren Esma,aykemat yusuf,Kılıç Hüseyin,Doganay Mehmet Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae. İstanbul Kuzey Klinikleri, vol.8, no.2, 2021, ss.113 - 118. 10.14744/nci.2020.14238 |
| AMA | Kosar I,Dinc G,Eryilmaz-Eren E,aykemat y,Kılıç H,Doganay M Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae. İstanbul Kuzey Klinikleri. 2021; 8(2): 113 - 118. 10.14744/nci.2020.14238 |
| Vancouver | Kosar I,Dinc G,Eryilmaz-Eren E,aykemat y,Kılıç H,Doganay M Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae. İstanbul Kuzey Klinikleri. 2021; 8(2): 113 - 118. 10.14744/nci.2020.14238 |
| IEEE | Kosar I,Dinc G,Eryilmaz-Eren E,aykemat y,Kılıç H,Doganay M "Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae." İstanbul Kuzey Klinikleri, 8, ss.113 - 118, 2021. 10.14744/nci.2020.14238 |
| ISNAD | Kosar, Imran vd. "Investigation of double-carbapenem efficiency in experimental sepsis of colistin-resistant Klebsiella pneumoniae". İstanbul Kuzey Klinikleri 8/2 (2021), 113-118. https://doi.org/10.14744/nci.2020.14238 |
