Zakażenie clostridioides difficile
Diagnostyka i diagnoza

Zakażenie Clostridioides difficile (CDI) jest główną przyczyną biegunek związanych z opieką zdrowotną, z około 500 000 przypadków i 15 000 zgonów rocznie w USA. Diagnostyka powinna być prowadzona wyłącznie u pacjentów z objawami klinicznymi, tj. ≥3 luźne stolce w ciągu 24 godzin o konsystencji typów 5-7 w skali Bristol, bez innych przyczyn biegunki. Metody diagnostyczne obejmują testy przesiewowe na dehydrogenazę glutaminianową (GDH) o czułości 90-100%, testy immunoenzymatyczne (EIA) na toksyny A/B o swoistości 95-100% i czułości 53-94%, oraz testy amplifikacji kwasów nukleinowych (NAAT) z czułością 90-95% i swoistością 94-98%. Zalecane są algorytmy wieloetapowe łączące testy o wysokiej czułości (GDH lub NAAT) z testami o wysokiej swoistości (EIA), co pozwala na precyzyjne rozróżnienie zakażenia od nosicielstwa i ogranicza nadrozpoznawalność. Próbki kału powinny być transportowane do laboratorium natychmiast lub przechowywane w lodówce, aby uniknąć degradacji toksyn w ciągu 2 godzin od pobrania.

Diagnostyka zakażenia Clostridioides difficile

Zakażenie Clostridioides difficile (CDI) jest najczęstszą przyczyną biegunki związanej z opieką zdrowotną i stanowi istotny problem zdrowotny na całym świecie. W Stanach Zjednoczonych notuje się około 500 000 przypadków rocznie, powodujących 15 000 zgonów.1 Prawidłowa i szybka diagnostyka ma kluczowe znaczenie dla skutecznego leczenia pacjentów oraz wdrożenia odpowiednich środków kontroli zakażeń.2 Rozpoznanie CDI opiera się na obecności objawów klinicznych (najczęściej biegunki) oraz wynikach badań laboratoryjnych potwierdzających obecność toksyn lub szczepów toksynotwórczych C. difficile.3

Kryteria kliniczne kwalifikacji do diagnostyki

Według aktualnych wytycznych Infectious Diseases Society of America (IDSA) oraz Society for Healthcare Epidemiology of America (SHEA), badania w kierunku CDI powinny być wykonywane wyłącznie u pacjentów z objawami klinicznymi:45

  • Występowanie niewyjaśnionej, nowo powstałej biegunki (≥3 luźne stolce w ciągu 24 godzin)
  • Konsystencja stolca powinna być płynna lub nieuformowana (odpowiadająca typom 5-7 w skali Bristol)
  • Brak innych oczywistych przyczyn biegunki (np. stosowanie środków przeczyszczających)

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Nie należy przeprowadzać badań u pacjentów bezobjawowych lub z uformowanym stolcem, gdyż może to prowadzić do wykrycia nosicielstwa, a nie faktycznego zakażenia.8 Diagnostyka u pacjentów bez biegunki może być rozważona jedynie w przypadku podejrzenia niedrożności jelita grubego wywołanej przez C. difficile.9

Osoby z grupy wysokiego ryzyka CDI, u których diagnostyka powinna być rozważona w pierwszej kolejności, to:1011

  • Pacjenci, którzy otrzymywali antybiotyki w ciągu ostatnich 3 miesięcy
  • Osoby hospitalizowane lub przebywające w placówkach opieki długoterminowej
  • Pacjenci w wieku powyżej 65 lat
  • Osoby z obniżoną odpornością
  • Pacjenci po zabiegach chirurgicznych przewodu pokarmowego

Metody diagnostyczne

Dostępnych jest kilka metod diagnostycznych zakażenia C. difficile. Wybór odpowiedniej strategii diagnostycznej pozostaje przedmiotem dyskusji i zależy od czynników takich jak czułość, swoistość, dostępność, koszty oraz czas oczekiwania na wynik.12

Metody referencyjne

Historycznie za metody referencyjne („złoty standard”) uważano:1314

  • Hodowla toksynotwórcza (TC) – polega na wyhodowaniu C. difficile z próbki kału i potwierdzeniu zdolności wyizolowanych szczepów do produkcji toksyn. Jest to metoda najbardziej czuła, ale czasochłonna (wymaga 2-5 dni) i kosztowna.15
  • Test neutralizacji cytotoksyczności komórkowej (CCNA) – wykrywa toksynę B w kale. Metoda ta wymaga specjalistycznej wiedzy technicznej, jest kosztowna i wymaga 24-48 godzin na uzyskanie wyniku, ale zapewnia wysoką swoistość i czułość.13

Obecnie metody te rzadko są stosowane w rutynowej diagnostyce klinicznej ze względu na ich złożoność i czas oczekiwania na wynik.16

Testy diagnostyczne stosowane w praktyce klinicznej

W praktyce klinicznej najczęściej stosuje się:1718

  1. Test na obecność dehydrogenazy glutaminianowej (GDH):13
    • GDH jest antygenem wspólnym dla wszystkich szczepów C. difficile (zarówno toksynotwórczych, jak i nietoksynotwórczych)
    • Charakteryzuje się wysoką czułością (90-100%), ale niską swoistością, gdyż nie różnicuje szczepów toksynotwórczych od nietoksynotwórczych
    • Jest szybki (wynik w ciągu godziny) i stosunkowo tani
    • Często używany jako test przesiewowy w algorytmach wieloetapowych
  2. Testy immunoenzymatyczne (EIA) na toksyny A i B:19
    • Wykrywają bezpośrednio toksyny A i/lub B w kale
    • Charakteryzują się wysoką swoistością (95-100%), ale zmienną czułością (53-94%)
    • Są szybkie i łatwe w wykonaniu
    • Wyniki mogą być fałszywie ujemne, gdyż toksyna C. difficile jest niestabilna i ulega degradacji w temperaturze pokojowej (w ciągu 2 godzin od pobrania próbki)
  3. Testy amplifikacji kwasów nukleinowych (NAAT), w tym PCR:20
    • Wykrywają geny kodujące toksyny (najczęściej gen tcdB dla toksyny B)
    • Cechują się bardzo wysoką czułością (90-95%) i swoistością (94-98%)
    • Dostarczają wynik w ciągu kilku godzin
    • Ich wadą jest wykrywanie szczepów toksynotwórczych również u nosicieli bezobjawowych (nie różnicują między kolonizacją a aktywnym zakażeniem)

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Algorytmy diagnostyczne

Ze względu na ograniczenia poszczególnych testów, aktualne wytyczne zalecają stosowanie wieloetapowych algorytmów diagnostycznych, które zwiększają dokładność rozpoznania.422

Najczęściej stosowane algorytmy to:2324

  • Algorytm dwuetapowy:
    • Krok 1: Test przesiewowy o wysokiej czułości (GDH lub NAAT)
    • Krok 2: Jeśli wynik kroku 1 jest dodatni, wykonuje się test o wysokiej swoistości (EIA na toksyny A/B)
    • Interpretacja: Wynik ujemny w kroku 1 wyklucza CDI; wynik dodatni w obu krokach potwierdza CDI
  • Algorytm trzyetapowy:
    • Krok 1: Test GDH jako przesiewowy
    • Krok 2: Jeśli GDH dodatni, wykonuje się EIA na toksyny A/B
    • Krok 3: Jeśli GDH dodatni, ale EIA ujemny, wykonuje się NAAT jako test rozstrzygający
    • Interpretacja: GDH ujemny wyklucza CDI; GDH i EIA dodatnie potwierdzają CDI; GDH dodatni, EIA ujemny, ale NAAT dodatni sugeruje możliwe CDI

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Wybór algorytmu zależy od lokalnych protokołów instytucjonalnych:4

  • Jeśli w placówce istnieją ustalone kryteria kwalifikacji pacjentów do badań (np. badanie tylko pacjentów z ≥3 luźnymi stolcami w ciągu 24h, bez stosowania środków przeczyszczających), można stosować sam NAAT lub algorytm wieloetapowy
  • Jeśli takie kryteria nie są stosowane, zalecany jest algorytm wieloetapowy z użyciem testu na toksyny

Dodatkowe metody diagnostyczne

W niektórych przypadkach stosuje się dodatkowe metody diagnostyczne:2526

  1. Badania endoskopowe (kolonoskopia, sigmoidoskopia):
    • Umożliwiają bezpośrednią wizualizację zmian w jelicie grubym, w tym rzekomobłoniastego zapalenia jelita grubego
    • Pozwalają na pobranie wycinków do badań histopatologicznych
    • Stosowane rzadko, głównie w przypadkach diagnostyki różnicowej lub trudności diagnostycznych
    • Czułość metody jest ograniczona, gdyż pseudobłony nie zawsze są obecne, zwłaszcza w łagodniejszych przypadkach
  2. Badania obrazowe (RTG jamy brzusznej, tomografia komputerowa):
    • Mogą wykazać pogrubienie ściany jelita, poszerzenie okrężnicy, perforację
    • Stosowane głównie w przypadkach ciężkiego przebiegu zakażenia do oceny powikłań
    • Nie służą do potwierdzenia rozpoznania CDI, ale do oceny jego powikłań
  3. Badania krwi:
    • Podwyższony poziom leukocytów (>15 000/µl), hipoalbuminemia i kwasica mleczanowa mogą wskazywać na ciężki przebieg CDI
    • Nie służą do potwierdzenia rozpoznania, ale do oceny ciężkości zakażenia

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Wyzwania diagnostyczne

Diagnostyka CDI wiąże się z szeregiem wyzwań:228

  • Różnicowanie między nosicielstwem a aktywnym zakażeniem – badania laboratoryjne nie mogą samodzielnie rozstrzygnąć, czy obecność C. difficile jest przyczyną objawów klinicznych czy jedynie kolonizacją. Dlatego tak ważne jest badanie wyłącznie pacjentów z objawami biegunki.
  • Nadrozpoznawalność przy stosowaniu samych testów NAAT – ze względu na ich wysoką czułość mogą one wykrywać nosicielstwo, prowadząc do niepotrzebnego leczenia i raportowania zakażeń.
  • Stabilność próbek – toksyny C. difficile są niestabilne w temperaturze pokojowej i mogą ulec degradacji w ciągu 2 godzin od pobrania próbki, co może prowadzić do wyników fałszywie ujemnych. Próbki powinny być transportowane do laboratorium natychmiast lub przechowywane w lodówce.
  • Powtarzanie badań – nie zaleca się powtarzania badań w ciągu 7 dni od pierwszego badania w trakcie tego samego epizodu biegunki, gdyż nie zwiększa to dokładności diagnostycznej i może prowadzić do wyników fałszywie dodatnich.

4

Diagnostyka nawrotu zakażenia

Nawroty CDI występują u 20-40% pacjentów po pierwszym epizodzie zakażenia, a u osób z co najmniej jednym nawrotem ryzyko kolejnego nawrotu sięga 65%.28 Diagnostyka nawrotu CDI opiera się na tych samych zasadach co pierwotne zakażenie:29

  • Pojawienie się objawów biegunki po zakończonym leczeniu
  • Wykonanie badań diagnostycznych (najczęściej algorytmu wieloetapowego)
  • Nie zaleca się wykonywania badań kontrolnych po zakończeniu leczenia u pacjentów bez objawów (tzw. „test wyleczenia”), gdyż C. difficile lub jego toksyny mogą być wykrywane w kale do 30 dni po ustąpieniu objawów

Badania wskazujące na ciężki przebieg zakażenia

W celu oceny ciężkości zakażenia C. difficile, które ma wpływ na wybór metody leczenia, stosuje się następujące parametry:2330

  • Liczba leukocytów >15 000 komórek/μl
  • Stężenie kreatyniny w surowicy >1,5 mg/dl
  • Stężenie albuminy w surowicy <3 g/dl
  • Obecność kwasicy mleczanowej
  • Hipotensja lub wstrząs
  • Megacolon toxicum lub niedrożność przewodu pokarmowego w badaniach obrazowych

Podsumowanie

Prawidłowa diagnostyka zakażenia C. difficile pozostaje wyzwaniem klinicznym i laboratoryjnym. Wymaga ona zarówno oceny klinicznej pacjenta, jak i zastosowania odpowiednich testów laboratoryjnych. Obecnie zaleca się stosowanie algorytmów wieloetapowych, które łączą testy o wysokiej czułości (GDH, NAAT) z testami o wysokiej swoistości (EIA na toksyny), co pozwala na optymalizację diagnostyki.122

Kluczowymi elementami prawidłowej diagnostyki są:84

  • Badanie wyłącznie pacjentów z objawami biegunki (≥3 luźne stolce w ciągu 24h)
  • Stosowanie algorytmów wieloetapowych
  • Prawidłowe pobieranie i transport próbek
  • Unikanie powtarzania badań w trakcie tego samego epizodu choroby
  • Niestosowanie „testów wyleczenia” u pacjentów bezobjawowych

Przestrzeganie tych zasad pozwala na optymalizację diagnostyki, unikanie nadrozpoznawalności i niepotrzebnego leczenia, a także umożliwia wdrożenie odpowiednich środków kontroli zakażeń.831

Kolejne rozdziały

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  1. 11.04.2026
  2. www.leksykon.com.pl

Materiały źródłowe

  • #1 C. diff Infection: What It Is, Symptoms & Treatment
    https://my.clevelandclinic.org/health/diseases/15548-c-diff-infection
    C. diff infection (CDI) is a global health concern, although the exact rates of infection worldwide are unknown. In the U.S., 500,000 infections cause 15,000 deaths each year. […] If your healthcare provider suspects C. diff infection based on your symptoms, they’ll take a sample of your poop and send it to a lab. The lab will test it for C. diff toxins. […] If you test positive, your healthcare provider may conduct further tests to find out how severe the infection is. These may include blood tests and imaging tests that look inside your colon. […] Treatment for C. diff infection is based on how severe it is. If you developed a C. diff infection while taking antibiotics, your provider might begin by simply stopping those medications. […] For some people, this is enough. Their natural gut immunity returns and overcomes the infection. If this doesn’t happen, your provider will prescribe antibiotics that can stop C. diff.
  • #2
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7042017/
    Clostridium (reclassified as Clostridioides) difficile is an anaerobic, gram-positive bacterium that causes significant disease through elaboration of two potent toxins in patients whose normal gut microbiota has been altered through antimicrobial or chemotherapeutic agents (dysbiosis). The optimum method of laboratory diagnosis is still somewhat controversial. Recent practice guidelines published by professional societies recommend a two-step approach beginning with a test for glutamate dehydrogenase (GDH), followed by a toxin test and/or a nucleic acid test. Alternatively, in institutions where established clinical algorithms guide testing, a nucleic acid test alone is acceptable. Nucleic acid tests are the methods of choice in approximately 50% of laboratories in the United States. These tests are considered as the most sensitive methods for detection of C. difficile in stool and are the least specific. Because of the lower specificity with nucleic acid tests, some clinicians believe that toxin enzyme immunoassays are better predictors of disease, despite their known poor performance in certain patient populations. This review will discuss the advantages and disadvantages of the currently available test methods for the diagnosis of C. difficile with a brief mention of some novel assays that are currently in clinical trials.
  • #3 Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by SHEA/IDSA
    https://www.idsociety.org/practice-guideline/clostridium-difficile/
    A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. […] The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. […] CDI is defined by the presence of symptoms (usually diarrhea) and either a stool test positive for C. difficile toxins or detection of toxigenic C. difficile, or colonoscopic or histopathologic findings revealing pseudomembranous colitis. […] The panel followed a process used in the development of other Infectious Diseases Society of America (IDSA) guidelines, which included a systematic weighting of the strength of recommendation and quality of evidence using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system.
  • #4 Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by SHEA/IDSA
    https://www.idsociety.org/practice-guideline/clostridium-difficile/
    Patients with unexplained and new-onset 3 unformed stools in 24 hours are the preferred target population for testing for CDI. […] Use a stool toxin test as part of a multistep algorithm (ie, glutamate dehydrogenase [GDH] plus toxin; GDH plus toxin, arbitrated by nucleic acid amplification test [NAAT]; or NAAT plus toxin) rather than a NAAT alone for all specimens received in the clinical laboratory when there are no preagreed institutional criteria for patient stool submission. […] Use a NAAT alone or a multistep algorithm for testing (ie, GDH plus toxin; GDH plus toxin, arbitrated by NAAT; or NAAT plus toxin) rather than a toxin test alone when there are preagreed institutional criteria for patient stool submission. […] Do not perform repeat testing (within 7 days) during the same episode of diarrhea and do not test stool from asymptomatic patients, except for epidemiological studies.
  • #5 Clostridioides difficile Infection: Update on Management | AAFP
    https://www.aafp.org/pubs/afp/issues/2020/0201/p168.html
    Guidelines for the diagnosis and treatment of Clostridioides difficile infection have recently been updated. Testing in these patients should start with enzyme immunoassays for glutamate dehydrogenase and toxins A and B or nucleic acid amplification testing. The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America recommend limiting testing for C. difficile infection to patients with unexplained onset of three or more unformed stools in 24 hours while not taking laxatives. […] When the prevalence of C. difficile infection is low, no diagnostic test should be used alone because of low positive predictive values. […] The EIA for GDH has high sensitivity, which makes it a useful screening test because a negative result essentially rules out infection (negative predictive value = 94% to 100%). The EIA for toxins A and B has the highest specificity, whereas NAAT is both sensitive and specific.
  • #6 C. difficile Testing Clostridioides (Clostridium) difficile Toolkit for Long-term Care Facilities – MN Dept. of Health
    https://www.health.state.mn.us/diseases/cdiff/hcp/ltctoolkit/testing.html
    Only unformed stools should be tested (Bristol stool chart types 5-7). Testing asymptomatic residents (those with formed stools) is not recommended. Testing formed stools can lead to detecting colonized, not infected, cases. Since all positives must be reported to NHSN, this can lead to over-reporting CDI. […] In some cases, examination of the colon can be used to help confirm a diagnosis of CDI. If C. difficile colitis is not accompanied by pseudomembrane formation, endoscopic findings are relatively nonspecific, but a biopsy specimen may reveal changes typical of pseudomembranous colitis. […] Pseudomembranous colitis can only be diagnosed by direct visualization of pseudomembranes on lower gastrointestinal endoscopy. […] At least 90% of patients with pseudomembranous colitis demonstrate either C. difficile or its toxin in stool samples.
  • #7
    https://link.springer.com/article/10.1007/s40121-021-00417-7
    Strategies to optimize the clinical sensitivity and specificity of current laboratory tests are critical to differentiate the clinical CDI from colonization. To achieve high diagnostic yield, if preagreed institutional criteria for stool submission are not used, a multistep approach to CDI diagnosis is recommended, such as either GDH or NAAT followed by toxins A/B EIA in conjunction with laboratory stewardship by evaluating C. difficile test orders for appropriateness and providing feedback. Furthermore, antimicrobial stewardship, along with provider education on appropriate testing for C. difficile, is vital to differentiate CDI from colonization. […] The current IDSA Guidelines on C. difficile updated in 2018 recommend testing for CDI for patients with unexplained and new onset of 3 unformed stools in 24 h. The diagnostic methods are defined based on presence or absence of preagreed institutional criteria for patient stool submission such as to not submit stool specimens on patients receiving laxatives or other potential known causes of diarrhea and to submit stool specimens only from patients with unexplained and new onset 3 unformed stools in 24 h.
  • #8
    https://link.springer.com/article/10.1007/s40121-021-00417-7
    The increase in the incidence of CDI is likely multifactorial, stemming from decades of overuse of broad-spectrum antibacterial agents and the emergence of more virulent C. difficile strains. However, the challenges posed by testing methodologies incapable of accurately distinguishing clinical infection with C. difficile versus colonization have likely led to an overdiagnosis in an era of high-sensitivity molecular testing such as NAAT. […] One of the most concerning consequences of conflating CDI with colonization and subsequent overdiagnosis is the resultant unnecessary use of antibacterial agents for CDI treatment. […] Therefore, it would be prudent to avoid overdiagnosis of CDI to prevent incurrence of unnecessary expense to patients and healthcare systems. […] Several important strategies may be employed to improve appropriate testing of C. difficile and to differentiate colonization from clinical CDI. One of the most essential interventions includes the proper use and interpretation of diagnostic tests for CDI, or diagnostic stewardship. Patients should only be tested for C. difficile if they present with clinical signs and symptoms of actual infection, for example, unexplained and new-onset watery diarrhea (3 liquid stools within 24 h) without alternate explanations such as laxative use or antibacterial/chemotherapy-induced diarrhea.
  • #9 C Difficile Infection : Emergency Care BC
    https://emergencycarebc.ca/clinical_resource/clinical-summary/c-difficile-infection/
    Clostridioides difficile infection (CDI) is the most frequent cause of healthcare associated infectious diarrhea, and an emerging community pathogen causing significant morbidity and mortality. […] Diagnosis of CDI established via either a positive nucleic acid amplification test (NAAT) for C. difficile toxin B gene or a positive stool test for C. difficile toxins. […] Testing for C. difficile or its toxins should be performed only on diarrheal (unformed) stool, (Bristol Stool Chart type 6 or 7) unless ileus due to C. difficile is suspected. […] In British Columbia, the definition of a case of CDI is: Presence of diarrhea (e.g. three liquid or loose stools within a 24-hour period) or toxic megacolon (i.e. abnormal dilation of the large intestine documented radiologically) without other known etiology, AND laboratory confirmation of the presence of C. difficile toxin A and/or B (positive toxin, or culture with evidence of toxin production, or detection of toxin genes); OR Diagnosis of typical pseudo-membranes on sigmoidoscopy or colonoscopy; OR Histological/pathological diagnosis of CDI with or without diarrhea.
  • #10 Clostridioides difficile infection in adults: Clinical manifestations and diagnosis – UpToDate
    https://www.uptodate.com/contents/clostridioides-difficile-infection-in-adults-clinical-manifestations-and-diagnosis
    Clostridioides difficile infection in adults: Clinical manifestations and diagnosis […] The clinical manifestations and diagnosis of CDI will be reviewed here. […] Symptoms of CDI typically, but not always, occur in the setting of antibiotic therapy (table 1). Symptoms of CDI may begin during or after antibiotic therapy, and most cases occur within two weeks of antibiotic therapy. […] Additional risk factors for CDI include age >65, recent hospitalization, and use of proton-pump inhibitors. […]
  • #11 Diagnosing Clostridium Difficile Infections | NYU Langone Health
    https://nyulangone.org/conditions/clostridium-difficile-infections/diagnosis
    Infections with Clostridium difficile typically occur in people taking antibiotics or those who have recently taken them. […] To diagnose a C. difficile infection, your NYU Langone doctor takes a medical history and asks about any medications you are taking. He or she may also order one or several tests, depending on your symptoms, medical history, and whether you are currently in a hospital or healthcare facility or have recently been released from one. […] The simplest way to detect C. difficile is through a stool test, in which you provide a sample in a sterile container given to you at your doctors office or a lab. A pathologist, a doctor who studies diseases in a laboratory, determines whether the sample has signs of C. difficile. […] A blood test can reveal high levels of white blood cells, a sign of infection. Very high levels can signify a more severe C. difficile infection, in which a person may have watery diarrhea, intense stomach cramps, and dehydration.
  • #12 Diagnosis and Treatment of Clostridium difficile in Adults: A Systematic Review
    https://pmc.ncbi.nlm.nih.gov/articles/PMC6561347/
    Laboratory testing cannot distinguish between asymptomatic colonization and symptomatic infection with C. difficile. […] Diagnostic approaches are complex due to the availability of multiple testing strategies. […] Multistep algorithms using polymerase chain reaction (PCR) for the toxin gene(s) or single step PCR on liquid stool samples have the best test performance characteristics (multistep: sensitivity 0.68 to 1.00 / specificity 0.92 to 1.00; single step: sensitivity 0.860.92 / specificity 0.940.97). […] Diagnostic testing for CDI should be performed only in symptomatic patients. […] Treatment strategies should be based on disease severity, history of prior CDI, and the individual patients risk of recurrence. […] Vancomycin is the treatment of choice for severe or complicated CDI, with or without other adjunctive therapies.
  • #13 Clinical Testing and Diagnosis for CDI | C. diff | CDC
    https://www.cdc.gov/c-diff/hcp/diagnosis-testing/index.html
    There are four laboratory tests used to diagnose Clostridioides difficile infection or CDI. […] FDA-approved PCR assays are same-day tests that are highly sensitive and specific for the presence of a toxin-producing C. diff organism. […] Molecular assays can be positive for C. diff in asymptomatic individuals and those who do not have an infection. Patients with other causes of diarrhea might be positive, which leads to over-diagnosis and treatment. […] These rapid tests (1 hour) detect the presence of C. diff antigen glutamate dehydrogenase (GDH). […] Because results of antigen testing alone are nonspecific, antigen assays have been employed in combination with tests for toxin detection, PCR, or toxigenic culture in two-step testing algorithms. […] Tissue culture cytotoxicity assay only detects toxin B. This assay requires technical expertise to perform, is costly and requires 24 to 48 hours for a result. It does provide specific and sensitive results for CDI.
  • #14 Clinical Testing and Diagnosis for CDI | C. diff | CDC
    https://www.cdc.gov/c-diff/hcp/diagnosis-testing/index.html
    This is the most sensitive test available and is most often associated with false-positive results because of the presence of nontoxigenic C. diff strains. However, testing isolates for toxin production like so-called „toxigenic culture” helps to reduce false positive results. […] Results of toxigenic cultures serve as a gold standard compared to other test modalities in clinical trials of performance.
  • #15 Current knowledge on the laboratory diagnosis of Clostridium difficile infection
    https://www.wjgnet.com/1007-9327/full/v23/i9/1552.htm
    Neither the Clinical Practice Guidelines of the SHEA/IDSA nor the Guidelines of the ACG recommend retesting. […] The SHEA/IDSA guidelines recommend toxigenic culture (TC) as the standard to which other methods should be compared. […] The Cell Cytotoxic Neutralization Assay (CCNA) has been considered the gold standard for the diagnosis of CDI. […] Although GDH screening of stool specimens for the diagnosis of CDI diagnosis is common, its value is limited to being a preliminary test, since both toxigenic and non-toxigenic strains produce GDH. […] A two-step algorithm (step 1, GDH and toxin detection by EIA; step 2, loop-mediated isothermal amplification) yielded a sensitivity of 81%, a specificity and positive predictive value (PPV) of 100%, and a negative predictive value (NPV) of 96%.
  • #16 How to solve your C. Difficile diagnosis challenges
    https://lableaders.roche.com/global/en/articles/how-to-solve-your-c-difficile-diagnosis-challenges-2031.html
    It’s among the most challenging problems in modern healthcare: Clostridium difficile (C. difficile, C. diff), the spore-forming bacterium, infects thousands of patients in hospitals every year. […] In 2011, according to the U.S. Centers for Disease Control and Prevention (CDC), nearly 500,000 patients were infected with the diarrhea-causing bacterium, including 29,000 who died within 30 days of their C. diff diagnosis. […] The issue, as one recent study in the Journal of Clinical Microbiology (JCM) points out, involves the high prevalence of C. diff colonization. […] First of all, because of the potential for false-positive results, testing for C. diff is only recommended when patients have frequent diarrhea or watery stools. […] The gold standard tests for CDI diagnosis are Culture and Cell Culture Cytotoxicity Neutralization Assay (CCNA), however due to their need for highly trained staff and long turn around times, these tests are no longer used in regular clinical practice.
  • #17
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7042017/
    Therefore, accurate clinical and laboratory diagnosis is essential for prompt patient management and effective infection control measures. Recent practice guidelines emphasize that the targeted populations for C. difficile testing are patients with unexplained and new-onset unformed stools in 24 hours. However, the optimum laboratory based approach is still a matter of debate and controversy. A variety of methods exist for testing patients at risk for C. difficile. These can be broadly categorized into two groups: (1) those tests that detect the organism itself (or a component of the organism), such as anaerobic bacterial culture, glutamate dehydrogenase (GDH), the common antigen present in both toxigenic and nontoxigenic strains, and nucleic acid tests that detect the genes that encode toxins A and B; and (2) tests that detect free toxin, such as cell culture cytotoxicity neutralization assays (CCCNA) and enzyme immunoassays (EIAs). Bacterial culture with toxin testing of recovered isolates (toxigenic culture [TC]) and CCCNA are considered reference methods and the standards against which other methods are compared.
  • #18 Laboratory diagnosis of Clostridioides difficile infection: guidelines and status of practice in Korea – Annals of Clinical Microbiology
    https://www.acm.or.kr/2701-02/
    Clostridioides difficile infection (CDI) is a common healthcare-associated infection that is expected to increase with the increases in the elderly population, immunocompromised patients treated with chemotherapy and immunosuppressive drugs, antimicrobial-resistant bacteria, and invasive medical technologies. Accurate diagnosis is critical for proper treatment and management of CDI. Clinical laboratories typically use four methods to diagnose CDI: C. difficile culture, toxin detection using immunoassays, detection of glutamate dehydrogenase using immunoassays, and detection of toxin A/B gene. Each CDI diagnostic test has strengths and limitations, and varies in performance. […] Accurate diagnosis is critical for proper treatment and management of CDI. Various methods are used to diagnose CDI, and the large number of diagnostic tests reflect the difficulty of diagnosing CDI. Tests for the diagnosis of CDI detect C. difficile strains, toxins A and B, toxin genes (tcdA and tcdB), and glutamate dehydrogenase (GDH) secreted by C. difficile strains.
  • #19 Clinical Testing and Diagnosis for CDI | C. diff | CDC
    https://www.cdc.gov/c-diff/hcp/diagnosis-testing/index.html
    Although a historical gold standard for diagnosing disease caused by C. diff, this assay is less sensitive than PCR or toxigenic culture for patients with diarrhea. […] Enzyme immunoassay detects toxin A, toxin B, or both A and B. With concerns over toxin A-negative and B-positive strains causing disease, most laboratories employ a toxin B-only or A and B assay. Since these are same-day assays that are cheap and easy to perform, they are popular with clinical laboratories. However, there are increasing concerns about their relative insensitivity (less than tissue culture cytotoxicity and PCR or toxigenic culture). […] C. diff toxin is very unstable. The toxin degrades at room temperature and might be undetectable within two hours of stool specimen collection. False-negative results occur when specimens are not tested promptly or kept refrigerated until testing.
  • #20 Diagnosis, Prevention, and Treatment of C. difficile: Current State of the Evidence | Effective Health Care (EHC) Program
    https://effectivehealthcare.ahrq.gov/products/c-difficile-update/clinician
    Diagnosis of CDI: Nucleic acid amplification tests have high sensitivity and specificity for diagnosing CDI (high strength of evidence [SOE]). […] Diagnostic testing is recommended in patients in whom there is a suspicion of CDI based on symptoms and history. CDI is suspected in patients with symptoms of diarrhea (3 loose stools in 24 hours) or ileus who have additional risk factors (including use of antibiotics or antineoplastic agents in the previous 8 weeks, hospitalization, and older age). […] Nucleic Acid Amplification Test: loop-mediated isothermal amplification Sensitivity 12 Sensitive for CDI 0.95 (0.90 to 0.97) [evidence high] Specificity 12 Specific for CDI 0.98 (0.96 to 0.99) [evidence high] Nucleic Acid Amplification Test: polymerase chain reaction Sensitivity 31 Sensitive for CDI 0.95 (0.93 to 0.96) [evidence high] Specificity 31 Specific for CDI 0.97 (0.96 to 0.98) [evidence high] […] Testing for C. difficile or its toxins should be performed only on diarrheal (unformed) stool, unless ileus due to C. difficile is suspected.
  • #21 Laboratory diagnosis of Clostridioides difficile infection: guidelines and status of practice in Korea – Annals of Clinical Microbiology
    https://www.acm.or.kr/2701-02/
    Clinical laboratories typically use four methods to diagnose CDI: C. difficile culture, toxin detection using immunoassays, GDH detection using immunoassays, and toxin A/B gene detection. […] Guidelines for the diagnosis of CDI have been published by several organizations and countries, most by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of America (IDSA)/Society for Healthcare Epidemiology of America (SHEA), and the American College of Gastroenterology (ACG). […] Because each CDI diagnostic test has its strengths and limitations, varies in performance, and no single test is perfect, many guidelines recommend combining tests or using multistep algorithms. Guidelines for CDI diagnosis have been developed by organizations, such as ESCMID, IDSA/SHEA, and ACG, and other countries have guidelines. These guidelines are often revised as advances in diagnostic technology require revisions and changes in the diagnostic criteria. In Korea, there are no official CDI diagnostic criteria or guidelines. Each organization or medical staff will use international guidelines or synthesize several guidelines to develop their own guidelines. It is necessary to develop standardized diagnostic guidelines for CDI appropriate for the Korean context.
  • #22
    https://pmc.ncbi.nlm.nih.gov/articles/PMC7042017/
    In general, GDH negative specimens can be reported as negative and GDH positive/EIA positive specimens can be reported as positive (two-step algorithms). For GDH positive/EIA negative specimens, the third testing (NAT or TC) can be performed to rule out C. difficile with higher confidence (three-step algorithms). […] Regardless of the testing method or algorithm chosen, laboratories should have policies in place to ensure testing only on patients at risk for C. difficile infection. There should be clear specimen acceptance and rejection criteria. Specimens should be loose or take the shape of the container (Bristol stool chart 5 or 6), otherwise they should be rejected. […] Currently, there is no FDA-approved single rapid test that can be reliably used to diagnose C. difficile disease. Toxin EIAs provide good clinical specificity in symptomatic patients, but they are not sensitive enough to rule out C. difficile infection, and presence of toxins does not correlate with true C. difficile infection if asymptomatic carries or cured patients are tested. While NATs offer the excellent sensitivity to detect toxigenic C. difficile, they can detect patients colonized with C. difficile with no toxin production and may lead to overdiagnosis and overtreatment of C. difficile infection.
  • #23 Clostridioides difficile Infection: Update on Management | AAFP
    https://www.aafp.org/pubs/afp/issues/2020/0201/p168.html
    In facilities that limit C. difficile testing to patients with three or more unformed stools per 24 hours, testing can begin with NAAT or EIAs for GDH and toxins A and B. If the facility does not limit C. difficile testing and evaluates patients who do not meet testing criteria, EIAs for GDH and toxins A and B can be performed initially; if results are inconclusive, NAAT alone or in combination with an EIA for toxins A and B can be ordered. NAAT alone should not be performed in patients with a lower probability of C. difficile infection because a positive test could reflect asymptomatic colonization. […] The presence of peripheral leukocytosis, lactic acidosis, or hypoalbuminemia indicates more severe C. difficile infection. Adjuvant tests such as fecal hemoccult and lactoferrin are not recommended for assessment of disease severity. […] Repeat testing within seven days during the same episode of diarrhea is not recommended because the high sensitivity of the tests can lead to false-positive results.
  • #24 Consensus on the prevention, diagnosis, and treatment of Clostridium difficile infection | Revista de Gastroenterología de México
    https://www.revistagastroenterologiamexico.org/en-consensus-on-prevention-diagnosis-treatment-articulo-S2255534X19300295
    In recent decades, Clostridium difficile infection (CDI) has become a worldwide health problem. […] A 2-step diagnostic algorithm was proposed, in which a highly sensitive test, such as glutamate dehydrogenase (GDH), is first utilized, and if positive, confirmed by the detection of toxins through immunoassay or nucleic acid detection tests. […] CDI should be diagnosed only when there is clinical suspicion based on the 2-step algorithm. […] The most useful method for making the diagnosis when there is clinical suspicion of CDI is the 2-step algorithm. A first high-sensitivity test, such as glutamate dehydrogenase (GDH) or nucleic acid amplification tests (NAATs) through the polymerase chain reaction (PCR) technique should be performed. […] The GDH test is the first choice in 2 and 3-step algorithms that combine it with a toxin test and/or a molecular test for detecting the toxin’s gene.
  • #25 C. difficile infection – Diagnosis and treatment – Mayo Clinic
    https://www.mayoclinic.org/diseases-conditions/c-difficile/diagnosis-treatment/drc-20351697
    A diagnosis of C. difficile infection is based on having: […] C. difficile in a stool sample. […] People who have regular, formed stools should not be tested for C. difficile infection. Some people get C. difficile infection without having taken antibiotics. So recent use of antibiotics is not needed for making a diagnosis of C. difficile infection. […] If C. difficile infection is suspected, one or more tests of a stool sample can show either the toxins or strains of the bacteria that produce toxins. […] Rarely, to help confirm a diagnosis of C. difficile infection, a health care provider might check the inside of the colon. […] An X-ray of the stomach area or a CT scan can look for possible complications of C. difficile infection. These imaging tests can detect:
  • #26 Diagnosing Clostridium Difficile Infections | NYU Langone Health
    https://nyulangone.org/conditions/clostridium-difficile-infections/diagnosis
    If you have severe symptoms of C. difficile, a doctor may examine the colon using a colonoscopy or sigmoidoscopy. […] These tests can indicate whether inflammation is present, indicating a C. difficile infection. They also allow a doctor to take tissue samples, if necessary, to further test for infection. […] If a doctor suspects you have a complication of C. difficile infection, such as a hole in the intestines, he or she may order a CT scan.
  • #27 Clostridioides difficile-associated disease – Symptoms, diagnosis and treatment | BMJ Best Practice US
    https://bestpractice.bmj.com/topics/en-us/230
    Testing should be limited to patients with unexplained, new-onset diarrhea (defined as 3 or more unformed stools in 24 hours). Molecular testing alone or as part of a multistep algorithm is recommended depending on local institutional protocols. […] This topic focuses on the diagnosis and management of C difficile infection in adults only. […] Key diagnostic factors include diarrhea and abdominal pain. […] Other diagnostic factors include fever, abdominal tenderness, nausea and vomiting, abdominal distension, and symptoms of shock. […] 1st tests to order include CBC, stool guaiac (fecal occult blood test), stool polymerase chain reaction (PCR), stool immunoassay for glutamate dehydrogenase, stool immunoassay for toxins A and B, and abdominal x-ray. […] Tests to consider include cell culture cytotoxicity neutralization assay, CT abdomen, and sigmoidoscopy or colonoscopy. […] Emerging tests include stool lactoferrin or calprotectin.
  • #28 Clostridioides (Clostridium) Difficile Colitis: Background, Etiology, Pathophysiology
    https://emedicine.medscape.com/article/186458-overview
    Yet approximately 20-27% of patients treated for a first episode of C difficile colitis relapse after successfully completing therapy, typically 3 days to 3 weeks after treatment has ended. […] Patients who relapse once are at an even greater risk for further relapses; the relapse rate for patients with 2 or more relapses is 65%. […] The presence of all 3 factors resulted in a 57.1% mortality; in the absence of all 3, the mortality was 0%. […] Despite awareness and treatment of fulminant C difficile colitis, this condition remains highly lethal.
  • #29 C. diff Testing: MedlinePlus Medical TestLock
    https://medlineplus.gov/lab-tests/c-diff-testing/
    There is no known risk to having C. diff testing. […] A positive (abnormal) test result may mean that toxins from C. diff bacteria are causing your symptoms. You may be diagnosed with C. diff if your tests show that your sample contained: C. diff toxin genes. These are genes from the types of C. diff that can cause illness. C. diff toxins. These tests check for two types of toxins called A and B. […] A negative (normal) test result generally means that no signs of a C. diff infection were found in your sample. Your symptoms are probably caused by something else. […] After treatment for a C. diff infection, you won’t be tested again to see if you’re cured. That’s because it’s common to still have C. diff in your body after you get better. A test would only show that the bacteria is still there, but not whether you’re likely to get sick again.
  • #30 Clostridioides (Clostridium) Difficile Colitis: Background, Etiology, Pathophysiology
    https://emedicine.medscape.com/article/186458-overview
    The diagnosis of C difficile colitis should be suspected in any patient with diarrhea who has received antibiotics within the previous 3 months, has been recently hospitalized, and/or has an occurrence of diarrhea 48 hours or more after hospitalization. […] However, more recent studies have shown that C difficile can be the cause of diarrhea in community dwellers without previous hospitalization or antibiotic exposure; therefore, the diagnosis should be suspected in this population as well. […] Once infected with C difficile, the rate of disease recurrence is 20-40% when using metronidazole and vancomycin antibiotics as first-line therapy. […] Fidaxomicin is now recommended as first-line treatment due to a lower risk of CDI recurrence. […] The use of oral metronidazole or vancomycin produces response rates of greater than 95% in mild to moderate cases, with symptomatic improvement (diarrhea) in as little as 3-4 days and complete resolution in 7-10 days.
  • #31 Clostridioides difficile Infection: Diagnosis, Testing, Screening, and Treatment
    https://www.contagionlive.com/view/clostridioides-difficile-infection-diagnosis-testing-screening-and-treatment
    Feuerstadt said that in addition to the IDSA/SHEA guidelines that provide recommendations for selecting candidates for testing, factors such as WBC count, creatinine level, and recent history of antimicrobials are also helpful to consider. […] In general, tests for CDI detect the organism itself or its primary toxins (toxin A and/or B). Commonly available options include toxigenic culture, nucleic acid amplification test (NAAT), glutamate dehydrogenase (GDH) assay, cell culture cytotoxicity neutralization assay, and toxin A and B enzyme immunoassays. […] The IDSA/SHEA guidelines recommend using a stool toxin test as part of a multistep algorithm for diagnosis, which may involve GDH plus toxin test, GDH plus toxin test followed by NAAT as an arbitration test, or NAAT plus toxin test. […] According to Chopra, asymptomatic carriage is an important consideration because carriers can act as reservoirs of transmission and probable vehicles of transmission to other patients.