Karbapenem dirençli Klebsiella pneumonia’nın neden olduğu idrar yolu enfeksiyonları: monoterapi ya da kombineterapi?

Yıl 2023, Cilt: 16 Sayı: 2, 290 - 297, 05.04.2023

Fatih TEMOÇİN Şeyma Betül KAYHAN Levent ŞENSOY Tuba KURUOĞLU Aynur ATİLLA Esra TANYEL

https://doi.org/10.31362/patd.1244480

Öz

Amaç: Bu çalışmada karbapenem dirençli Klebsiella pneumoniae'nın neden olduğu sağlık hizmeti ilişkili üriner sistem enfeksiyonlarını değerlendirildi.
Gereç yöntem: Çalışmaya karbapenem dirençli Klebsiella pneumoniae'nın (CR-Kp)neden olduğu sağlık hizmeti ilişkili idrar yolu enfeksiyonu tanısı almış 134 hasta dahil edildi. Hastaların demografik özellikleri, başlangıç klinik durumları, komorbiditeleri ve Charlson komorbidite indeksi kaydedildi. Ayrıca meropenemin CR-Kp izolatları üzerindeki MİK değerleri, tedavi rejimleri, tedaviye klinik ve mikrobiyolojik yanıtları ile hastaların 14 ve 28 günlük mortalite oranları incelendi.
Bulgular: 14 günlük mortalite oranı %34,3, 28 günlük mortalite oranı ise %42,5 bulundu. Ölen hastaların yaş ortalaması anlamlı olarak daha yüksekti (p=0,03). Benzer şekilde ölen hastalarda Charlson komorbidite indeksi (p=0,03) ve qSOFA değerleri (p=0,00) anlamlı olarak yüksekti. Yaşayan hastalarda mikrobiyolojik yanıt oranı daha yüksekti (p=0,01) ve bakteriyemi açısından gruplar arasında fark yoktu (p=0,29). Sepsisli hasta grubunda kombine antibiyoterapinin 14 ve 28 günlük mortalite oranlarını monoterapiye göre anlamlı olarak daha üstün olduğu saptandı (sırasıyla p=0,00 ve p=0,04). Ancak sepsis olmayan hasta gruplarında monoterapi ve kombinasyon tedavisi arasında anlamlı fark yoktu (sırasıyla p=0,72 ve p=0,36).
Sonuç: Çalışmamız, CR-Kp'nin neden olduğu üriner sistem enfeksiyonlarının tedavisinde sepsisli hastalarda kombinasyon tedavisinin, sepsis olmayan hastalarda ise in vitro aktif bir ajanla monoterapinin kullanılabileceğini desteklemektedir.

Anahtar Kelimeler

Klebsiella pneumonia, karbapenem dirençli, sağlık hizmetiyle ilişkili enfeksiyon, idrar yolu enfeksiyonu

Urinary tract infections caused by carbapenem-resistant Klebsiella pneumonia: monotherapy or combined therapy?

Öz

Purpose: In this study, we evaluated healthcare-associated urinary tract infections caused by carbapenem-resistant Klebsiella pneumoniae.
Materials and methods: The study included 134 patients, diagnosed with healthcare-associated urinary tract infection caused by carbapenem-resistant Klebsiella pneumoniae. Demographic features, initial clinical conditions, comorbidities, and Charlson’s comorbidity index of the patients were recorded. In addition, the MIC values of meropenem on the CR-Kp isolates, treatment regimens, clinical and microbiological responses to the treatment, as well as 14- and 28-day mortality rates of the patients, were reviewed.
Results: The 14-day mortality rate was 34.3%, and the 28-day mortality rate was 42.5%. The mean age of the patients who died was significantly higher (p=0.03). Similarly, Charlson’s comorbidity index (p=0.03) and the qSOFA values (p=0.00) were significantly higher in the patients who died. The microbiological response rate was higher in the patients who survived (p=0.01) with no difference in bacteremia between the groups (p=0.29). It was found that combined antibiotherapy provided significantly better 14- and 28-day mortality rates compared to monotherapy in the group of patients with sepsis (p=0.00 and p=0.04, respectively). However, monotherapy and combination therapy in groups of patients without sepsis were insignificant (p=0.72 and p=0.36, respectively).
Conclusion: Our study supports the use of combination therapy in patients with sepsis, and monotherapy with an in-vitro active agent may be used for patients without sepsis in the treatment of urinary tract infections caused by CR-KP.

Anahtar Kelimeler

Klebsiella pneumoniae, carbapenem-resistant, healthcare-associated infection;, urinary tract infection

Kaynakça

• 1. Munoz Price LS, Poirel L, Bonomo RA, et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis 2013;13:785-796. https://doi.org/10.1016/S1473-3099(13)70190-7
• 2. Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 2009;9:228-236. https://doi.org/10.1016/S1473-3099(09)70054-4
• 3. Logan LK, Weinstein RA. The Epidemiology of carbapenem-resistant Enterobacteriaceae: the impact and evolution of a global menace. J Infect Dis 2017;215:28-36. https://doi.org/10.1093/infdis/jiw282
• 4. Saeed NK, Alkhawaja S, Azam N, Alaradi K, Al Biltagi M. Epidemiology of carbapenem-resistant Enterobacteriaceae in a tertiary care center in the Kingdom of Bahrain. J Lab Physicians 2019;11:111-117. https://doi.org/10.4103/JLP.JLP_101_18
• 5. Eser F, Yılmaz GR, Güner R, Koçak Tufan Z. Carbapenem-resistant Enterobacteriaceae infections: risk factors. Akdeniz Medical Journal 2018;2:144-151. https://doi.org/10.17954/amj.2018.133
• 6. World Health Organization (WHO). List of bacteria for which new antibiotics are urgently needed. WHO 2017 Available at: https://www.who.int/en/news-room/detail/27-02-2017-who-publishes-list-of-bacteria-for-which-new-antibiotics-are-urgently-needed. Accessed February 17, 2020
• 7. Xu L, Sun X, Ma X. Systematic review and meta-analysis of mortality of patients infected with carbapenem-resistant Klebsiella pneumoniae. Ann Clin Microbiol Antimicrob 2017;16:18-19. https://doi.org/10.1186/s12941-017-0191-3
• 8. Monaco M, Giani T, Raffone M, et al. Colistin resistance superimposed to endemic carbapenem-resistant Klebsiella pneumoniae: a rapidly evolving problem in Italy, November 2013 to April 2014. Euro Surveill 2014;19:20939. https://doi.org/10.2807/1560-7917.es2014.19.42.20939
• 9. Falagas ME, Vouloumanou EK, Samonis G, Vardakas KZ. Fosfomycin. Clin Microbiol Rev 2016;29:321-347. https://doi.org/10.1128/CMR.00068-15
• 10. Grabein B, Graninger W, Rodriguez Bano J, Dinh A, Liesenfeld DB. Intravenous fosfomycin-back to the future. systematic review and meta-analysis of the clinical literature. Clin Microbiol Infect 2017;23:363-372. https://doi.org/10.1016/j.cmi.2016.12.005
• 11. Livermore DM, Warner M, Jamrozy D, et al. In vitro selection of ceftazidime-avibactam resistance in Enterobacteriaceae with KPC-3 carbapenemase. Antimicrob Agents Chemother 2015;59:5324-5330. https://doi.org/10.1128/AAC.00678-15
• 12. Alm RA, Johnstone MR, Lahiri SD. Characterization of Escherichia coli NDM isolates with decreased susceptibility to aztreonam/avibactam: role of a novel insertion in PBP3. J Antimicrob Chemother 2015;70:1420-1428. https://doi.org/10.1093/jac/dku568
• 13. Kontopidou F, Giamarellou H, Katerelos P, et al. Infections caused by carbapenem-resistant Klebsiella pneumoniae among patients in intensive care units in Greece: a multi-centre study on clinical outcome and therapeutic options. Clin Microbiol Infect 2014;20:117-123. https://doi.org/10.1111/1469-0691.12341
• 14. Zusman O, Altunin S, Koppel F, Dishon Benattar Y, Gedik H, Paul M. Polymyxin monotherapy or in combination against carbapenem-resistant bacteria: systematic review and meta-analysis. J Antimicrob Chemother 2017;72:29-39. https://doi.org/10.1093/jac/dkw377
• 15. Paul M, Daikos GL, Durante Mangoni E, et al. Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial. Lancet Infect Dis 2018;18:391-400. https://doi.org/10.1016/S1473-3099(18)30099-9
• 16. Tumbarello M, Trecarichi EM, De Rosa FG, et al. Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study. J Antimicrob Chemother 2015;70:2133-2143. https://doi.org/10.1093/jac/dkv086
• 17. Peri AM, Doi Y, Potoski BA, Harris PNA, Paterson DL, Righi E. Antimicrobial treatment challenges in the era of carbapenem resistance. Diagn Microbiol Infect Dis 2019;94:413-425. https://doi.org/10.1016/j.diagmicrobio.2019.01.020
• 18. Papst L, Beovic B, Pulcini C, et al. Antibiotic treatment of infections caused by carbapenem-resistant Gram-negative bacilli: an international ESCMID cross-sectional survey among infectious diseases specialists practicing in large hospitals. Clin Microbiol Infect 2018;24:1070-1076. https://doi.org/10.1016/j.cmi.2018.01.015
• 19. Balkan II, Aygun G, Aydin S, et al. Blood stream infections due to OXA-48-like carbapenemase-producing Enterobacteriaceae: treatment and survival. Int J Infect Dis 2014;26:51-56. https://doi.org/10.1016/j.ijid.2014.05.012
• 20. Falcone M, Russo A, Lacovelli A, et al. Predictors of outcome in ICU patients with septic shock caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. Clin Microbiol Infect 2016;22:444-450. https://doi.org/10.1016/j.cmi.2016.01.016
• 21. Giannella M, Trecarichi EM, Giacobbe DR, et al. Effect of combination therapy containing a high-dose carbapenem on mortality in patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection. Int J Antimicrob Agents 2018;51:244-248. https://doi.org/10.1016/j.ijantimicag.2017.08.019
• 22. Akova M, Daikos GL, Tzouvelekis L, Carmeli Y. Interventional strategies and current clinical experience with carbapenemase-producing Gram-negative bacteria. Clin Microbiol Infect 2012;18:439-448. https://doi.org/10.1111/j.1469-0691.2012.03823.x
• 23. Clinical Laboratory Standards Institute (CLSI). Performance standards for antimicrobial susceptibility testing, 27th ed. Wayne, PA. CLSI 2017;100:27-28.
• 24. The European Committee on Antimicrobial Susceptibility Testing (EUCAST). Recommendations for MIC determination of colistin (polymyxin E) as recommended by the joint CLSI-EUCAST Polymyxin Breakpoints Working Group. EUCAST 2016 Available at: http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/General_documents/Recommendations_ for_MIC_determination_of_colistin_March_2016.pdf. Accessed June 5, 2020
• 25. Tansarli GS, Papaparaskevas J, Balaska M, et al. Colistin resistance in carbapenemase-producing Klebsiella pneumoniae bloodstream isolates: evolution over 15 years and temporal association with colistin use by time series analysis. Int J Antimicrob Agents 2018;52:397-403. https://doi.org/10.1016/j.ijantimicag.2018.06.012