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Two Important Risk Factors in Imipenem Resistant Acinetobacter spp. Infection: Hemodialysis and Hypoalbuminemia

Year 2020, Volume: 2 Issue: 1, 25 - 34, 01.03.2020
https://doi.org/10.38175/phnx.632622

Abstract

Objectives: İt is aimed to evaluated factors affecting the development of resistance to imipenem resistant Acinetobacter spp. infections with this study.
Materials and methods: This study was conducted retrospectively on outpatients treated in the main intensive units of the Diseases and Clinical Microbiology Department of Yıldırım Bayezit Education and Research Hospital between January 1st, 2008 and December 31st, 2011. The data of the patients, infection control committee follow-up forms, laboratory data in the hospital follow-up system and epicrisis were used in the analysis.
Results: 248 patients were included in this study (mean age: 65.1±17.8, 60.9% males). 80.4% of the patients had a comorbid factor (diabetes mellitus, chronic obstructive pulmonary disease, congestive heart failure, malignancy, neurological disorder). Investigating the effects of other antimicrobials, strains with aminoglycoside resistance were statistically significant [p: 0.005]. Dialysis and albumin value <3 g/dl were found to be risk factors [p <0.05]. We also found that the rate of imipenem resistance increased by 3.8 fold and by 2.3 fold when albumin level was below 3.
Conclusion: The factors of imipenem resistance were investigated in patients with Acinetobacter species in the intensive care unit and in those who developed the infection at the hospital, and early diagnosis of those at risk was found to have great importance in terms of prognosis and mortality. Besides central venous catheter, dialysis and the presence of hypoalbuminemia were found to affect the development of imipenem resistance. 

References

  • 1) Gaynes R, Edwards JR. Overview of Nosocomial Infections Caused by Gram-Negative Bacilli. Clin Infect Dis. 2005;41(6):848-54.
  • 2) Lee SO, Kim NJ, Choi SH, Kim TH, Chung JW, Woo JH et al. Risk factors for acquisition of imipenem-resistant Acinetobacter baumannii: a case-control study. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 2004;48 (1): 224–28.
  • 3) Bergogne-Berezın E, Towner KJ. Acinetobacter spp. As Nosocomial Pathogens: Microbiological, Clinical and Epidemiological Features. Clin Microbiol Rev. 1996;9(2):148-65.
  • 4) Özdem B, Gürelik FÇ, Çelikbilek N, Balıkçı H, Açıkgöz ZC. Çeşitli Klinik Örneklerden 2007-2010 Yıllarında İzole Edilen Acinetobacter Türlerinin Antibiyotik Direnç Profilleri. Mikrobiyol Bul 2011; 45(3): 526-534.
  • 5) Martin-Aspas A, Guerrero-Sanchez FM, Garcia-Colchero F, Rodriguez- Roca S, Antonio J, Gonzalez G. Differantial characteristics of Acinetobacter baumannii colonization and infection: risk factors, clinical picture and mortality. Infection and Drug Resistance 2018:11 861–872.
  • 6) Akalın H. Yoğun Bakım Ünitesinde Dirençli Acinetobacter spp. İnfeksiyonlarına Yaklaşım. In: Arman D, Vahaboğlu H (ed). Dirençli Mikroorganizma İnfeksiyonlarına Yaklaşım. 1.Baskı. Ankara: Bilimsel Tıp Yayınevi. 2009:133-147.
  • 7) Higgins PG, Dammhayn C, Hackel M, Seifert H. Global spread of carbapenem-resistant Acinetobacter baumannii. J Antimicrob Chemother. 2010,65(2):233-8.
  • 8) Başustaoğlu A, Özyurt M. Nozokomiyal patojen olarak Acinetobacter’lerin mikrobiyolojik, klinik ve epidemiyolojik özellikleri, Hastane İnfeksiyon Derg 1998,2(2):88-93.
  • 9) Wu HG, Liu WS, Zhu M, Li XX. Research and analysis of 74 blood stream infection cases of Acinetobacter baumannii and drug resistance. European Review for Medical and Pharmacological Sciences. 2018;22:1782-86.
  • 10) Yildiz A, Yigit A, Benli AR. The impact of nutritional status and complete blood count parameters on clinical outcome in geriatric critically III patients. J Clin Med Res. 2018;10(7):588-592.
  • 11) Romanelli RMC, Jesus LA, Clemente WT, Lima SSS, Rezende EM, Coutinho RL et al. Outbreak of resistant Acinetobacter baumannii – Measures and proposal for prevention and control. The Brazilian Journal of Infectious Diseases. 2009;13(5):341-347.
  • 12) Rello J, Diaz E. Acinetobacter baumannii: a threat for the ICU? Intensive Care Med. 2003;29(3):350-1.
  • 13) Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302(21):2323-9.
  • 14) Meric M, Willke A, Caglayan C, Toker K. Intensive Care Unit-Acquired Infections: Incidence, Risk Factors and Associated Mortality in a Turkish University Hospital. Jpn J Infect Dis.2005;58(5):297-302.
  • 15) Fishbain J, Peleg AY. Treatment of Acinetobacter Infections. Clin Infect Dis. 2010;51(1):79-84.
  • 16) Mera RM, Miller LA, Amrine-Madsen H, Sahm DF. Acinetobacter baumannii 2002-2008: Increase of Carbapenem-associated Multiclass resistance in the United States, Microb Drug Resist. 2010;16(3):209-15.
  • 17) İskender S, Çaylan R, Sucu N, Aktoz Boz G, Köksal İ, Aydın K. Acinetobacter Suşlarının Antibiyotik Duyarlılıklarının Dört Yıllık Analizi. Hastane İnfeksiyonları Dergisi. 2006;10:161-65.
  • 18) Balcı M, Bitirgen M, Kandemir B, Türk Arıbaş E, Erayman İ. Nozokomiyal Acinetobacter Baumannii Suşlarının Antibiyotik Duyarlılığı. ANKEM Derg. 2010;24(1):28-33.
  • 19) Hekimoğlu CH, Batır E. Ulusal Sağlık Hizmeti İlişkili Enfeksiyonlar Sürveyans Ağı Etken Dağılımı ve Antibiyotik Direnç Raporu 2017.
  • 20) Kollef MH. In adequate Antimicrobial Treatment: An Important Determinant of Outcome for Hospitalized Patients. Clin Infect Dis. 2000;31:131-8. PMID: 11017862.
  • 21) Baran G, Erbay A, Bodur H, Ongürü P, Akinci E, Balaban N et al. Risk factors for nosocomial imipenem-resistant Acinetobacter baumannii infections. Int J of Infect Dis. 2008;12(1):16-21.
  • 22) Fukuta Y, Muder RR, Agha ME, Clarke LG, Wagener MM, Hensler AM et al. Risk factors for acquisition of multi drug-resistant Acinetobacter baumannii among cancer patients. American Journal of Infection Control.2013;41:1249-52.
  • 23) Magnussen B, Gradel KO, Jensen TG, Kolmos HJ, Pedersen C, Vinholt PJ et al. Association between Hypoalbuminaemia and Mortality in Patients with Community-Acquired Bacteraemia Is Primarily Related to Acute Disorders. Plosone. 2016.11(9):1-14.
  • 24) Soeters PB, Wolfe RR, Shenkin A. Hypoalbuminemia: Pathogenesis and Clinical Significance. JPEN J Parenter Enteral Nutr. 2019;43(2):181-193.
  • 25) Viasus D, Garcia-Vidal C, Simonetti A, Manresa F, Dorca J, Gudiol F et al. Prognostic value of serum albumin levels in hospitalized adults with community-acquired pneumonia. Journal of Infection.2013;66:415-423.
  • 26) Yin M, Si L, Qin W, Li C, Zhang J, Yang H, et al. Predictive Value of Serum Albumin Level for the Prognosis of Severe Sepsis Without Exogenous Human Albumin Administration: A Prospective Cohort Study. Journal of Intensive Care Medicine. 2016;33(12):687-694.
  • 27) Artero A, Zaragoza R, Camarena JJ, Sancho S, Gonzalez R, Nogueira JM. Prognostic factors of mortality in patients with community-acquired blood stream infection with severe sepsis and septic shock. Journal of Critical Care.2010;25: 276–81. PMID:20149587.
  • 28) Sullivan SA, Le LV, Liberty AL, Soper JT, Barber EL. Association between hypoalbuminemia and surgical site infection in vulvar cancers. Gynecologic Oncology.2016;142(3):435–9.
  • 29) Barnes S, Permanente K, Concepcion D, Felizardo G, Moran J, Peters V et al. Guide to the Elimination of Infections in Hemodialysis, 2010. https://apic.org/Resource_/EliminationGuideForm/7966d850-0c5a-48ae-9090-a1da00bcf988/File/APIC-Hemodialysis.pdf. ErişimTarihi: 09.01.2018.
  • 30) Calfee DP. Multidrug-Resistant Organisms With in the Dialysis Population: A Potentially Preventable Perfect Storm. Am J Kidney Dis. 2015;65(1):3-5.
  • 31) Pop-Vicas A, Strom J, Stanley K, D’Agata EMC. Multidrug-Resistant Gram-Negative Bacteria among Patients Who Require Chronic Hemodialysis. Clin J Am Soc Nephrol. 2008; 3(3): 752–8.
  • 32) Su G, Xu H, Riggi E, He Z, Lu L, Lindholm B et al. Association of Kidney Function with Infections by Multidrug-Resistant Organisms: An Electronic Medical Record Analysis. SCIENTIFIC REPORTS. 2018;8(1):13372.
  • 33) Vasudevan A, Mukhopadhyay A,Li J, Yuen EG, Tambyah A. A prediction tool for nosocomial multi-drug resistant gram-negative bacilli infections in critically ill patients-prospective observational study. BMC Infectious Diseases 2014, 14:615.
  • 34) Seyman D, Cengiz M, Özen N, Turhan Ö, Ramazanoğlu A, Yalçın AN. Çok ilaca Dirençli Acinetobacter infeksiyonlarında Kolistin Deneyimi. Hastane İnfeksiyonları Dergisi. 2010;14(3):367-72.
  • 35) Xia J, Zhang D, Xu Y, Gong M, Zhou Y, Fang X. A retrospective analysis of carbapenem-resistant Acinetobacter baumannii-mediated nosocomial pneumonia and the in vitro therapeutic benefit of cefoperazone/sulbactam. Int J Infect Dis. 2014; Jun;23C:90-3. PMID:24726664.
  • 36) Lee CR, Lee JH, Park M, Park KS, Bae K, Kim YB et al. Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment options. Front Cell Infect Microbiol. 2017;7(55):1-35.
  • 37) Wong D, Nielsen TB, Bonomo RA, Pantapalangkoor P, Luna B, Spellberg B. Clinical and Pathophysiological overwiev of Acinetobacter infections: a century of challenges. Clinical Microbiology Reviews. 2017;30 (1): 409-447.
  • 38) Tsioutis C, Kritsotakis EI, Karageorgos SA, Stratakou S, Psarologakis C, Kokkini S et al. Clinical epidemiology, treatment and prognostic factors of extensively drug-resistant Acinetobacter baumannii ventilator –associated pneumonia in critically ill patients. International Journal of Antimicrobial Agents.2016;48(5):492–7.

İmipenem Dirençli Acinetobacter spp. Enfeksiyonunda İki Önemli Risk Faktörü: Hemodiyaliz ve Hipoalbüminemi

Year 2020, Volume: 2 Issue: 1, 25 - 34, 01.03.2020
https://doi.org/10.38175/phnx.632622

Abstract

Amaç: Bu çalışmada, imipenem dirençli Acinetobacter spp. enfeksiyonlarında direnç gelişimini etkileyen faktörlerin değerlendirilmesi amaçlanmıştır.
Gereç ve Yöntem: Çalışmamızda 1 Ocak 2008 ve 31 Aralık 2011 tarihleri arasında hastanemiz ana yoğun bakım ünitelerinde yatarak takip edilen hastaların dosyaları restrospektif olarak incelenmiştir. Bu incelemede, Acinetobacter spp.’ne bağlı hastane enfeksiyonu gelişen hastaların bilgileri, enfeksiyon kontrol komitesi takip formları, hastane takip sistemindeki laboratuvar verileri ve epikriz bilgilerinden yararlanılmıştır.
Bulgular: Çalışmaya 248 hasta dahil edilmiştir. Hastaların yaş ortalaması 65.1±17.8 (n:248) ve % 61’i erkek olarak saptanmıştır. Hastaların %80,4’ünde eşlik eden komorbid bir faktör (Diyabetes Mellitus, Kronik Obstruktif Akciğer Hastalığı, Konjestif Kalp Yetmezliği, Malignite, Nörolojik bozukluk) bulunmaktadır. İmipenem direncinin gelişiminde diğer antimikrobiyallerin etkisi incelendiğinde; aminoglikozid direncinin varlığının risk faktörü olduğu görülmüştür [p:0,005]. Diyalize giren ve albümin değeri <3 g/dl olan hastaların imipenem direncinde bu faktörlerin birer risk faktörü olduğu bulgusuna ulaşılmıştır [p<0,05]. İmipenem direnci gelişimindeki risk faktörlerine yapılan çok değişkenli analizlerde diğer faktörler kontrol edildiğinde; diyalize girmiş olmanın imipenem direnci tahmini rölatif riskini 3.8 kat artırdığı ve albümin düzeyinin 3’ün altında olmasının ise imipenem direnci tahmini rölatif riskini 2.3 kat artırmakta olduğu ortaya konulmuştur.
Sonuç: Yoğun bakım ünitelerinde Acinetobacter spp. ile hastane enfeksiyonu gelişmiş hastalarda, imipenem direnci varlığını etkileyen faktörlerin bilinmesinin ve imipenem direnci gelişimi açısından riskli hastaların erken tanınmasının prognoz ve mortalite açısından büyük önem taşıdığı görülmüştür. Hastalardaki santral venöz kateter varlığı, öncesinde antibiyotik kullanımı gibi durumların varlığının yanı sıra; diyaliz uygulanmış olması ve hipoalbüminemi direnç gelişiminde etkili olan faktörler olarak tespit edilmiştir.

References

  • 1) Gaynes R, Edwards JR. Overview of Nosocomial Infections Caused by Gram-Negative Bacilli. Clin Infect Dis. 2005;41(6):848-54.
  • 2) Lee SO, Kim NJ, Choi SH, Kim TH, Chung JW, Woo JH et al. Risk factors for acquisition of imipenem-resistant Acinetobacter baumannii: a case-control study. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 2004;48 (1): 224–28.
  • 3) Bergogne-Berezın E, Towner KJ. Acinetobacter spp. As Nosocomial Pathogens: Microbiological, Clinical and Epidemiological Features. Clin Microbiol Rev. 1996;9(2):148-65.
  • 4) Özdem B, Gürelik FÇ, Çelikbilek N, Balıkçı H, Açıkgöz ZC. Çeşitli Klinik Örneklerden 2007-2010 Yıllarında İzole Edilen Acinetobacter Türlerinin Antibiyotik Direnç Profilleri. Mikrobiyol Bul 2011; 45(3): 526-534.
  • 5) Martin-Aspas A, Guerrero-Sanchez FM, Garcia-Colchero F, Rodriguez- Roca S, Antonio J, Gonzalez G. Differantial characteristics of Acinetobacter baumannii colonization and infection: risk factors, clinical picture and mortality. Infection and Drug Resistance 2018:11 861–872.
  • 6) Akalın H. Yoğun Bakım Ünitesinde Dirençli Acinetobacter spp. İnfeksiyonlarına Yaklaşım. In: Arman D, Vahaboğlu H (ed). Dirençli Mikroorganizma İnfeksiyonlarına Yaklaşım. 1.Baskı. Ankara: Bilimsel Tıp Yayınevi. 2009:133-147.
  • 7) Higgins PG, Dammhayn C, Hackel M, Seifert H. Global spread of carbapenem-resistant Acinetobacter baumannii. J Antimicrob Chemother. 2010,65(2):233-8.
  • 8) Başustaoğlu A, Özyurt M. Nozokomiyal patojen olarak Acinetobacter’lerin mikrobiyolojik, klinik ve epidemiyolojik özellikleri, Hastane İnfeksiyon Derg 1998,2(2):88-93.
  • 9) Wu HG, Liu WS, Zhu M, Li XX. Research and analysis of 74 blood stream infection cases of Acinetobacter baumannii and drug resistance. European Review for Medical and Pharmacological Sciences. 2018;22:1782-86.
  • 10) Yildiz A, Yigit A, Benli AR. The impact of nutritional status and complete blood count parameters on clinical outcome in geriatric critically III patients. J Clin Med Res. 2018;10(7):588-592.
  • 11) Romanelli RMC, Jesus LA, Clemente WT, Lima SSS, Rezende EM, Coutinho RL et al. Outbreak of resistant Acinetobacter baumannii – Measures and proposal for prevention and control. The Brazilian Journal of Infectious Diseases. 2009;13(5):341-347.
  • 12) Rello J, Diaz E. Acinetobacter baumannii: a threat for the ICU? Intensive Care Med. 2003;29(3):350-1.
  • 13) Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302(21):2323-9.
  • 14) Meric M, Willke A, Caglayan C, Toker K. Intensive Care Unit-Acquired Infections: Incidence, Risk Factors and Associated Mortality in a Turkish University Hospital. Jpn J Infect Dis.2005;58(5):297-302.
  • 15) Fishbain J, Peleg AY. Treatment of Acinetobacter Infections. Clin Infect Dis. 2010;51(1):79-84.
  • 16) Mera RM, Miller LA, Amrine-Madsen H, Sahm DF. Acinetobacter baumannii 2002-2008: Increase of Carbapenem-associated Multiclass resistance in the United States, Microb Drug Resist. 2010;16(3):209-15.
  • 17) İskender S, Çaylan R, Sucu N, Aktoz Boz G, Köksal İ, Aydın K. Acinetobacter Suşlarının Antibiyotik Duyarlılıklarının Dört Yıllık Analizi. Hastane İnfeksiyonları Dergisi. 2006;10:161-65.
  • 18) Balcı M, Bitirgen M, Kandemir B, Türk Arıbaş E, Erayman İ. Nozokomiyal Acinetobacter Baumannii Suşlarının Antibiyotik Duyarlılığı. ANKEM Derg. 2010;24(1):28-33.
  • 19) Hekimoğlu CH, Batır E. Ulusal Sağlık Hizmeti İlişkili Enfeksiyonlar Sürveyans Ağı Etken Dağılımı ve Antibiyotik Direnç Raporu 2017.
  • 20) Kollef MH. In adequate Antimicrobial Treatment: An Important Determinant of Outcome for Hospitalized Patients. Clin Infect Dis. 2000;31:131-8. PMID: 11017862.
  • 21) Baran G, Erbay A, Bodur H, Ongürü P, Akinci E, Balaban N et al. Risk factors for nosocomial imipenem-resistant Acinetobacter baumannii infections. Int J of Infect Dis. 2008;12(1):16-21.
  • 22) Fukuta Y, Muder RR, Agha ME, Clarke LG, Wagener MM, Hensler AM et al. Risk factors for acquisition of multi drug-resistant Acinetobacter baumannii among cancer patients. American Journal of Infection Control.2013;41:1249-52.
  • 23) Magnussen B, Gradel KO, Jensen TG, Kolmos HJ, Pedersen C, Vinholt PJ et al. Association between Hypoalbuminaemia and Mortality in Patients with Community-Acquired Bacteraemia Is Primarily Related to Acute Disorders. Plosone. 2016.11(9):1-14.
  • 24) Soeters PB, Wolfe RR, Shenkin A. Hypoalbuminemia: Pathogenesis and Clinical Significance. JPEN J Parenter Enteral Nutr. 2019;43(2):181-193.
  • 25) Viasus D, Garcia-Vidal C, Simonetti A, Manresa F, Dorca J, Gudiol F et al. Prognostic value of serum albumin levels in hospitalized adults with community-acquired pneumonia. Journal of Infection.2013;66:415-423.
  • 26) Yin M, Si L, Qin W, Li C, Zhang J, Yang H, et al. Predictive Value of Serum Albumin Level for the Prognosis of Severe Sepsis Without Exogenous Human Albumin Administration: A Prospective Cohort Study. Journal of Intensive Care Medicine. 2016;33(12):687-694.
  • 27) Artero A, Zaragoza R, Camarena JJ, Sancho S, Gonzalez R, Nogueira JM. Prognostic factors of mortality in patients with community-acquired blood stream infection with severe sepsis and septic shock. Journal of Critical Care.2010;25: 276–81. PMID:20149587.
  • 28) Sullivan SA, Le LV, Liberty AL, Soper JT, Barber EL. Association between hypoalbuminemia and surgical site infection in vulvar cancers. Gynecologic Oncology.2016;142(3):435–9.
  • 29) Barnes S, Permanente K, Concepcion D, Felizardo G, Moran J, Peters V et al. Guide to the Elimination of Infections in Hemodialysis, 2010. https://apic.org/Resource_/EliminationGuideForm/7966d850-0c5a-48ae-9090-a1da00bcf988/File/APIC-Hemodialysis.pdf. ErişimTarihi: 09.01.2018.
  • 30) Calfee DP. Multidrug-Resistant Organisms With in the Dialysis Population: A Potentially Preventable Perfect Storm. Am J Kidney Dis. 2015;65(1):3-5.
  • 31) Pop-Vicas A, Strom J, Stanley K, D’Agata EMC. Multidrug-Resistant Gram-Negative Bacteria among Patients Who Require Chronic Hemodialysis. Clin J Am Soc Nephrol. 2008; 3(3): 752–8.
  • 32) Su G, Xu H, Riggi E, He Z, Lu L, Lindholm B et al. Association of Kidney Function with Infections by Multidrug-Resistant Organisms: An Electronic Medical Record Analysis. SCIENTIFIC REPORTS. 2018;8(1):13372.
  • 33) Vasudevan A, Mukhopadhyay A,Li J, Yuen EG, Tambyah A. A prediction tool for nosocomial multi-drug resistant gram-negative bacilli infections in critically ill patients-prospective observational study. BMC Infectious Diseases 2014, 14:615.
  • 34) Seyman D, Cengiz M, Özen N, Turhan Ö, Ramazanoğlu A, Yalçın AN. Çok ilaca Dirençli Acinetobacter infeksiyonlarında Kolistin Deneyimi. Hastane İnfeksiyonları Dergisi. 2010;14(3):367-72.
  • 35) Xia J, Zhang D, Xu Y, Gong M, Zhou Y, Fang X. A retrospective analysis of carbapenem-resistant Acinetobacter baumannii-mediated nosocomial pneumonia and the in vitro therapeutic benefit of cefoperazone/sulbactam. Int J Infect Dis. 2014; Jun;23C:90-3. PMID:24726664.
  • 36) Lee CR, Lee JH, Park M, Park KS, Bae K, Kim YB et al. Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment options. Front Cell Infect Microbiol. 2017;7(55):1-35.
  • 37) Wong D, Nielsen TB, Bonomo RA, Pantapalangkoor P, Luna B, Spellberg B. Clinical and Pathophysiological overwiev of Acinetobacter infections: a century of challenges. Clinical Microbiology Reviews. 2017;30 (1): 409-447.
  • 38) Tsioutis C, Kritsotakis EI, Karageorgos SA, Stratakou S, Psarologakis C, Kokkini S et al. Clinical epidemiology, treatment and prognostic factors of extensively drug-resistant Acinetobacter baumannii ventilator –associated pneumonia in critically ill patients. International Journal of Antimicrobial Agents.2016;48(5):492–7.
There are 38 citations in total.

Details

Primary Language Turkish
Subjects Infectious Diseases
Journal Section Research Articles
Authors

Merve Sefa Sayar 0000-0002-0436-4122

Fatma Aybala Altay 0000-0002-7149-2968

İrfan Şencan This is me 0000-0003-0465-5090

Publication Date March 1, 2020
Submission Date October 13, 2019
Acceptance Date November 8, 2019
Published in Issue Year 2020 Volume: 2 Issue: 1

Cite

Vancouver Sayar MS, Altay FA, Şencan İ. İmipenem Dirençli Acinetobacter spp. Enfeksiyonunda İki Önemli Risk Faktörü: Hemodiyaliz ve Hipoalbüminemi. Phnx Med J. 2020;2(1):25-34.

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