Clostridioides difficile’nin laboratuvar tanısında farklı algoritma şemalarının değerlendirilmesi

Yıl 2024, Cilt: 49 Sayı: 3, 801 - 806, 30.09.2024

Gülay Trak , Cihan Yeşiloğlu , Betigül Öngen

https://doi.org/10.17826/cumj.1531627

Öz

Amaç: Clostridioides difficile enfeksiyonu, başlıca hastanelerde olmak üzere, antibiyotiğe bağlı ishalin önemli bir nedenidir. Bu çalışmanın amacı, C. difficile enfeksiyonu için rutin klinik pratikte farklı laboratuvar algoritma şemalarının uygulanabilirliğini, hızını, maliyet etkinliğini ve tanısal doğruluğunu değerlendirmektir.
Gereç ve Yöntem: C. difficile enfeksiyonu şüphesi olan hastalardan alınan toplam 479 dışkı örneği, glutamat dehidrogenaz enzim immunoassay, toksin A/B immunoassay, toksijenik kültür ve gerçek zamanlı polimeraz zincir reaksiyonu kullanılarak incelenmiştir. Bu yöntemlerin farklı algoritmik dizilimlerde uygulandığında duyarlılıkları, maliyet etkinlikleri ve tanısal doğrulukları değerlendirilmiştir.
Bulgular: 479 örnekten 52'sinde glutamat dehidrogenaz antijeni pozitif bulunmuştur. Polimeraz zincir reaksiyonu, glutamat dehidrogenaz pozitif örneklerin %55,8'inde
C. difficile saptayarak en yüksek duyarlılığı göstermiştir; bunu %25 ile toksijenik kültür ve %23,1 ile toksin A/B enzim immunoassay izlemiştir. Glutamat dehidrogenaz antijeni taraması ve ardından yapılan polimeraz zincir reaksiyonundan oluşan algoritma hem yüksek duyarlılık hem de maliyet etkinliği sunan en etkin tanısal yaklaşım olmuştur.
Sonuç: Bu çalışma, C. difficile enfeksiyonu tanısında, başta glutamat dehidrogenaz antijen taraması ile başlayan ve ardından polimeraz zincir reaksiyonu uygulanan olmak üzere çok aşamalı algoritmaların tanısal doğruluğu ve maliyet etkinliği artırmadaki önemini vurgulamaktadır. Bu bulgular, laboratuvar kaynakları ve hasta popülasyonunun özelliklerine dayalı olarak uyarlanaan tanı stratejilerin gerekliliğini desteklemektedir.

Anahtar Kelimeler

Clostridioides difficile, tanı algoritması, glutamat dehidrogenaz taraması, PCR, toksijenik kültür, enzim immunassay

Etik Beyan

Ethical Approval: This study was approved by the Ethics Committee of Istanbul University, Istanbul Faculty of Medicine (Approval No: [1651/20.11.2012]).

Destekleyen Kurum

This study was supported by the Istanbul University Scientific Research Projects Coordination Unit (Project No: 29794).

Proje Numarası

This study was supported by the Istanbul University Scientific Research Projects Coordination Unit (Project No: 29794).

Teşekkür

This study was supported by the Istanbul University Scientific Research Projects Coordination Unit (Project No: 29794).

Evaluation of different algorithm schemes in the laboratory diagnosis of Clostridioides difficile

Öz

Purpose: Clostridioides difficile infection is a major cause of antibiotic-associated diarrhea, particularly in healthcare settings. This study aims to evaluate the applicability, speed, cost-effectiveness, and diagnostic accuracy of different laboratory algorithm schemes for C. difficile infection in a routine clinical setting.
Materials and Methods: A total of 479 stool samples from patients suspected of having C. difficile infection were analyzed using glutamate dehydrogenase enzyme immunoassay, toxin A/B enzyme immunoassay, toxigenic culture, and real-time polymerase chain reaction. The sensitivity, cost-effectiveness and overall diagnostic accuracy of these methods were assessed when applied in different algorithmic sequences.
Results: Of the 479 samples, 52 were positive for glutamate dehydrogenase antigen. Polymerase chain reaction exhibited the highest sensitivity, detecting
C. difficile in 55.8% of glutamate dehydrogenase -positive samples, followed by toxigenic culture at 25.0%, and toxin A/B enzyme immunoassay at 23.1%. The combination of glutamate dehydrogenase screening followed by polymerase chain reaction was the most effective diagnostic approach, offering both high sensitivity and cost-effectiveness.
Conclusion: The study emphasizes the importance of a multi-step diagnostic algorithm, particularly starting with glutamate dehydrogenase screening followed by PCR, to improve the accuracy and cost-effectiveness of C. difficile infection diagnosis. These findings support the need for tailored diagnostic strategies based on laboratory resources and patient population characteristics.

Anahtar Kelimeler

diagnostic algorithm, toxigenic culture, enzyme immunoassay, glutamate dehydrogenase screening, Clostridioides difficile, PCR

Proje Numarası

This study was supported by the Istanbul University Scientific Research Projects Coordination Unit (Project No: 29794).

Kaynakça

• Gerding DN, Young VB, Donskey CJ. Clostridioides difficile (Formerly Clostridium difficile) Infection. In Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 9th ed (Eds JE Bennett, R Dolin, MJ Blaser):2933-47. Philadelphia, Elsevier, 2020.
• Bartlett JG, Chang TW, Gurwith M, Gorbach SL, Onderdonk AB. Antibiotic-associated pseudomembranous colitis due to toxin-producing clostridia. N Engl J Med. 1978;298:531-4.
• Kelly CP, LaMont JT. Clostridium difficile more difficult than ever. N Engl J Med. 2008;359:1932-40.
• Rupnik M, Wilcox MH, Gerding DN. Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat Rev Microbiol. 2009;7:526-36.
• Martinez FJ, Leffler DA, Kelly CP. Clostridium difficile outbreaks: prevention and treatment strategies. Risk Manag Healthc Policy. 2012;5:55-64.
• McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018;66:e1-48.
• Öksüz Ş, Danış A, Öztürk E, Çalışkan E, Akar NK, Sungur MA. Uzun süre hastanede yatan hastalarda Clostridium difficile kolonizasyonunun araştırılması. Anadolu Kliniği Tıp Bilimleri Dergisi. 2017;22:177-82.
• İris NE, Demirel A, Koçulu S, Çevik E, Ordu A, Küçükkaya RD. The evaluation of Clostridium difficile toxin A ve B positivity rates and epidemiological characteristics in febrile neutropenic patients with diarrhea. Mediterr J Infect Microb Antimicrob. 2015;4:14.
• McDonald LC, Lessa F, Sievert D, Wise M, Herrera R, Gould C et al. Vital signs: preventing Clostridium difficile infections. MMWR Morb Mortal Wkly Rep. 2012;61:157-62.
• Altindiş M, Usluer S, Ciftci H, Tunç N, Cetinkaya Z, Aktepe OC. Investigation of the presence of Clostridium difficile in antibiotic associated diarrhea patients by culture and toxin detection methods. Mikrobiyol Bul. 2007;41:29-37.
• Rao K, Micic D, Chenoweth E, Deng L, Galecki AT, Ring C et al. Poor functional status as a risk factor for severe Clostridium difficile infection in hospitalized older adults. J Am Geriatr Soc. 2013;61:1738-42.
• Loo VG, Bourgault AM, Poirier L, Lamothe F, Michaud S, Turgeon N et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med. 2011;365:1693-703.
• Buchner AM, Sonnenberg A. Medical diagnoses and procedures associated with Clostridium difficile colitis. Am J Gastroenterol. 2001;96:766-72.
• Slimings C, Riley TV. Antibiotics and healthcare facility-associated Clostridioides difficile infection: systematic review and meta-analysis 2020 update. J Antimicrob Chemother. 2021;76:1676-88.
• Karp J, Edman-Wallér J, Jacobsson G. Duration from start of antibiotic exposure to onset of Clostridioides difficile infection for different antibiotics in a non-outbreak setting. Infect Dis (Lond). 2024; doi:10.1080/23744235.2024.2375602.
• Crobach MJT, Vernon JJ, Loo VG, Kong LYP, Péchiné S, Wilcox MH et al. Understanding Clostridium difficile colonization. Clin Microbiol Rev. 2018;31:e00021-17.
• Wilcox MH, Planche T, Fang FC, Gilligan P. What is the current role of algorithmic approaches for diagnosis of Clostridium difficile infection? J Clin Microbiol. 2010;48:4347-53.
• Goldenberg SD, Cliff PR, Smith S, Milner M, French GL. Two-step glutamate dehydrogenase antigen real-time polymerase chain reaction assay for detection of toxigenic Clostridium difficile. J Hosp Infect. 2010;74:48-54.
• Vasoo S, Stevens J, Portillo L, Barza R, Schejbal D, Wu MM et al. Cost-effectiveness of a modified two-step algorithm using a combined glutamate dehydrogenase/toxin enzyme immunoassay and real-time PCR for the diagnosis of Clostridium difficile infection. J Microbiol Immunol Infect. 2014;47:75-8.
• Cançado GGL, Abreu ES, Nardelli MJ, Serwa P, Brachmann M. A cost of illness comparison for toxigenic Clostridioides difficile diagnosis algorithms in developing countries. Anaerobe. 2021;70:102390
• Novak-Weekley SM, Marlowe EM, Miller JM, Cumpio J, Nomura JH, Vance PH, et al. Clostridium difficile testing in the clinical laboratory by use of multiple testing algorithms. J Clin Microbiol. 2010;48:889-93