© Borgis - Postępy Nauk Medycznych 11/2014, s. 753-757
*Błażej Rozpłochowski1, 2, Olga Słyńko-Medoń1, 2, Michał Chojnicki1, 3, Agnieszka Seraszek-Jaros4, Arleta Kowala-Piaskowska1, 2, Iwona Mozer-Lisewska1, 2
Analiza deficytów białkowych u osób hospitalizowanych z powodu biegunki związanej z Clostridium difficile
The analysis of protein deficiency in patients hospitalized due to Clostridium difficile infection
1Department of Infectious Diseases, J. Struś Multispecialist City Hospital, Poznań
Head of Department: prof. Iwona Mozer-Lisewska, MD, PhD
2Department and Clinic of Infectious Diseases, Poznań University of Medical Sciences
Head of Department: prof. Iwona Mozer-Lisewska, MD, PhD
3Department of Biology and Environmental Protection, Poznań University of Medical Sciences
Head of Department: prof. Krzysztof Wiktorowicz, PhD
4Department of Bioinformatics and Computational Biology, Chair of Clinical Pathomorphology, Poznań University of Medical Sciences
Head of Department: prof. Elżbieta Kaczmarek, PhD
Streszczenie
Wstęp. Zakażenia Clostridium difficile są jedną z dominujących przyczyn biegunki bakteryjnej, zwłaszcza wśród osób po 65. roku życia. Czas trwania hospitalizacji zależy nie tylko od nasilenia biegunki, ale zwłaszcza od dekompensacji stanu ogólnego osób z towarzyszącymi chorobami przewlekłymi. Z powodu enteropatii wysiękowej, będącej powikłaniem ekspozycji jelit na toksyny C. difficile, dochodzi do znacznego ubytku białka, a zwłaszcza frakcji albumin, co wiąże się z pogorszeniem stanu ogólnego chorujących osób.
Cel pracy. Celem badania była ocena deficytów białkowych u pacjentów leczonych z powodu biegunki związanej z Clostridium difficile oraz wyznaczenie czynników ryzyka takich zaburzeń wśród parametrów demograficznych oraz jatrogennych.
Materiał i metody. Retrospektywna analiza zachorowań na biegunkę związaną z C. difficile CDI wśród pacjentów Oddziału Zakaźnego (Wielospecjalistyczny Szpital Miejski im. J. Strusia, Poznań) hospitalizowanych w 2013 roku.
Epizod CDI rozpoznawano w oparciu o rekomendacje ekspertów. Etiologię biegunki Clostridium difficile potwierdzono testami immunoenzymatycznymi TECHLAB, tj. szybkim testem membranowym na obecność antygenu dehydrogenazy glutaminowej (GDH) oraz szybkim testem do detekcji toksyny A i B C. difficile.
Ocenę gospodarki białkowej prowadzono w oparciu o oznaczenie stężenia białka całkowitego lub albumin w surowicy krwi.
Zaburzenia białkowe analizowane były w zależności od wieku i płci pacjentów, czasu trwania i nasilenia biegunki oraz wykładników stanu zapalnego takich jak stężenia białka C-reaktywnego oraz leukocytozy. Sprawdzono również korelację pomiędzy stężeniem kreatyniny oraz uznawanych za czynnik ryzyka wystąpienia CDI.
Zgodność z rozkładem normalnym sprawdzono za pomocą testu Shapir-Wilka. Porównanie miedzy grupami kobiet i mężczyzn wykonano za pomocą testu Manna-Whitney’a.
Wyniki. W badanej populacji potwierdzone niedobory stężenia białka całkowitego oraz albumin wystąpiły u 28 (71,8%) chorych. Niedobór białka całkowitego korelował z niedoborem frakcji albumin, zaś głębokość niedoboru była zależna nie od dobowej liczby stolców, ale od czasu trwania biegunki. Nie potwierdzono również przypuszczenia, że niedobór białka jest zależny od wieku pacjenta, czynności nerek lub wysokości wskaźników stanu zapalnego (białka C-reaktywnego oraz leukocytozy).
Wnioski. Biegunka związana z C. difficile jest chorobą ogólnoustrojową, która łączy się z utratą białka. Z uwagi na wiek pacjentów oraz liczne choroby współistniejące, biegunka związana z C. difficile jest poważnym zagrożeniem dla życia pacjentów i w każdym przypadku wymaga diagnostyki gospodarki białkowej.
Summary
Introduction. Clostridium difficile infections are one of the major causes of bacterial diarrhoea, particularly in patients aged over 65 years. Hospitalization time depends not only on the severity of the diarrhoea, but mainly on the decompensation of the general status of patients with concurrent chronic diseases. Protein-losing enteropathy, a complication resulting from the exposure of the intestines to toxins released by C. difficile, leads to a considerable loss of protein, particularly the albumin fraction, and deterioration of the patient’s general health.
Aim. The aim of this study was to evaluate protein deficiency in patients with CDI and to identify the risk factors for such disorders related to demographic and iatrogenic parameters.
Material and methods. The retrospective analysis of C. difficile-associated diarrhoea (CDAD) among patients hospitalized at the Department of Infectious Diseases (J. Struś Multispecialist City Hospital, Poznań) in 2013.
An episode of CDI was diagnosed based on the recommendations of the experts.
The aetiology of Clostridium difficile-associated diarrhoea was confirmed using TECHLAB immunoenzymatic tests, i.e. a rapid membrane-based assay detecting the glutamate dehydrogenase (GDH) antigen and a rapid assay detecting toxins A and B from C. difficile. Protein metabolism was evaluated based on the measured total protein or albumin levels in blood plasma.
Protein disorders were analysed depending on the age and sex of patients, the duration and severity of the diarrhoea, and inflammatory markers, i.e. levels of C-reactive protein and leukocytosis. The correlation between the creatinine levels and risk factors for CDI was also tested.
Test results were analysed using the Shapiro-Wilk and Mann-Whitney tests.
Results. Deficiency in total protein and albumin levels was found in 28 (71,8%) of patients from the studied population. Total protein deficiency correlated with deficiency of the albumin fraction, while the severity of the deficiency depended on the duration of the diarrhoea, and not on the daily number of passed stools. No evidence supporting the assumed correlation between the protein deficiency and the patient’s age, renal function or the levels of inflammatory markers (C-reactive protein and leukocytosis) was found.
Conclusions. CDI is a systemic disease correlated with protein loss. Because of the patient’s age and numerous concomitant diseases, CDI poses a serious threat to the patient’s life, and in each case requires the evaluation of protein metabolism.
Introduction
Clostridium difficile is a Gram-positive anaerobic, toxigenic and spore-forming bacterium. It was described for the first time in the 1940s as a nonpathogenic component of the intestinal microbial flora in healthy new-born infants (1). After broad-spectrum antibiotics were introduced in medical practice, attention was drawn to the pathogenic nature of this bacterium due to the growing number of patients suffering from pseudomembranous colitis (2). Currently, it is known that the spectrum of clinical manifestations for Clostridium difficile includes asymptomatic colonization, but also cases of colitis of various severity, including watery diarrhoea, pseudomembranous inflammation and toxic megacolon (2). The clinical picture is largely determined by the immune system function in individual patients, but disorders in the composition of intestinal microbial flora are the key factor for the development of Clostridium difficile infections (CDI) (3). For this reason, the inducing factors, e.g. the use of antibiotics, proton pump inhibitors, immunosuppressants, as well as hospitalizations or concomitant diseases are the major risk factors for this disease (3).
The worldwide incidence of CDI has been increasing for several decades, particularly in the developed countries (4). This process is attributed to the increased incidence of the above-mentioned risk factors, but also to the emergence of hypervirulent strains, and the ageing of the population (3, 4).
In 2013 in Poland 4716 cases of the disease were reported, which makes Clostridium difficile second to Salmonella spp. as the most frequent bacterial cause of intestinal infections. The prevalence of CDI is 12.24 per 100 000 people, and is currently lower than in other developed countries (5).
The rate of increase and scale of the problems associated with Clostridium difficile stimulate the need for the development and updating of guidelines on the classification, diagnostics, treatment and prevention of CDI. Despite the growing number of community-acquired CDI cases (CA-CDI), the disease is usually contracted through contact with health care and is one of the major iatrogenic types of infection (Health Care-Associated Infection – HCAI) (4). According to reports from the United States, including the analysis of the 5 most frequent HCAIs, these diseases generate annual costs of USD 9.8 bn, of which CDI is responsible for 15.4% (6).
In everyday medical practice, protein disorders seem to be frequent among patients hospitalized due to CDI. Proteins are involved in all processes at the cellular level and the entire body. Proteins take part in the coordination of life functions at multiple levels: the generation and transmission of information, buffering changes in the levels of other biologically active substances, the control of growth and differentiation, and cell-cell interactions. Albumins are mainly responsible for the maintenance of the oncotic pressure of plasma and its correct volume. They are also the carrier proteins transporting free fatty acids, bilirubin, certain drugs, metal ions and hormones. Albumins also form the protein reserve in the body and are used as a source of amino acids for the synthesis of proteins in cells of organs other than the liver (7). For this reason protein deficiency frequently results in peripheral oedema, ascites and hypotension. The mechanisms responsible for protein deficiency in patients with CDI and caused by protein-losing enteropathy were described more than twenty years ago (8). However, the results of studies analysing the incidence of protein disorders among patients with CDI were not conclusive and indicated the need for further research (9). Currently available reports contain the analysis of hypoproteinaemia in the context of evaluation of the severity of CDI recurrence (9). We have retrieved only one report evaluating protein deficiency in patients treated for CDI (10). Therefore, our study may set new trends in research and contribute to updating currently available guidelines.
Aim
The aim of this study was to evaluate protein deficiency in patients with CDI and to identify the risk factors for such disorders related to demographic and iatrogenic parameters.
Material and methods
We carried out a retrospective analysis of CDI among patients hospitalized at the Department of Infectious Diseases in 2013.
An episode of CDI was diagnosed based on the recommendations of the Polish National Programme of Antibiotic Protection, released in 2011, which are in line with the guidelines of the European Society for Clinical Microbiology and Infectious Diseases. According to the guidelines, the diagnosis of CDI was based on bacterial culture to confirm the presence of C. difficile in faeces, or detecting bacterial antigens or metabolites (11, 12).
The etiology of CDI was confirmed using TECHLAB immunoenzymatic tests, i.e. a rapid membrane-based assay detecting the glutamate dehydrogenase (GDH) antigen (sensitivity: 92.8%, specificity: 92.6%, positive predictive value: 78.6%, negative predictive value: 98.7%, correlation: 92.6%) and a rapid assay detecting toxins A and B from C. difficile (sensitivity: 90.2%, specificity: 99.7%, positive predictive value: 98.6%, negative predictive value: 97.9%, correlation: 98.0%).
Protein metabolism was evaluated based on the measured total protein and/or albumin levels in blood plasma.
Total protein levels were determined using a colorimetric method (burette reaction) by measuring the increase in absorbance at wavelength 540 nm. The sensitivity and range of the test was 1.0-15.0 mg/dl. The range for biological reference values was 6.2-8.5 g/dl.
Albumin levels were determined using a colorimetric method by measuring the increase in colour intensity at the wavelength of 630 nm. The sensitivity and range of the test was 0.5-8.0 g/dl. The range for biological reference values was 3.5-5.3 g/dl.
CRP levels were measured using the latex particle enhanced immunoturbidimetric method. The sensitivity and range of the test was 0-220 mg/l. The range for biological reference values was 0-10 mg/l.
Test results were analysed using the Shapiro-Wilk and Mann-Whitney tests.
Protein disorders were analysed depending on the age and sex of patients, the duration and severity of the diarrhoea, and inflammatory markers, i.e. levels of C-reactive protein and leukocytosis. We also tested the correlation between the creatinine levels and risk factors for CDI.
Results
CDI was diagnosed in 77 hospitalized patients. Protein metabolism was evaluated in 39 patients from the study group. Women were in the majority 22 vs. 17 (56 vs. 44%).
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Piśmiennictwo
1. Hall I, O’Toole E: Intestinal flora in new-born infants with a description of a new pathogenic anaerobe, bacillus difficilis. Am J Dis Child 1935; 49: 390-402.
2. Viscidi R, Willey S, Bartlett JG: Isolation rates and toxigenic potential of Clostridium difficile isolates from various patient populations. Gastroenterology 1981; 81: 5-9.
3. Loo VG, Bourgault AM, Poirier L et al.: Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med 2011; 365: 1693-1703.
4. Kuntz JL, Chrischilles EA, Pendergast JF et al.: Incidence of and risk factors for community-associated Clostridium difficile infection: a nested case-control study. BMC Infect Dis 2011; 11: 194.
5. Państwowy Zakład Higieny: Meldunki Epidemiologiczne 2013. Dostępne na stronie: www.pzh.gov.pl.
6. Kelly CP: Can we identify patients at high risk of recurrent Clostridium difficile infection? Clin Microbiol Infect 2012; 18 (suppl. 6): 21-27.
7. Pikuła S: Białka – struktura, synteza, funkcje. 2003. Dostępne na stronie: http://fundacjarozwojunauki.pl.
8. Dansinger ML, Johnson S, Jansen PC et al.: Protein-losing enteropathy is associated with Clostridium difficile diarrhea but not with asymptomatic colonization: a prospective, case-control study. Clin Infect Dis 1996; 22: 932-937.
9. Abou Chakra CN, Pepin J, Valiquette L: Prediction tools for unfavourable outcomes in Clostridium difficile infection: a systematic review. PLoS One 2012; 7: e30258.
10. Salazar-Kagunye R, Shah A, Loshkajian G et al.: Association of decreased serum protein fractions with Clostridium difficile infection in the acute care setting: a case – control study. Biomark Med 2012; 6(5): 663-669.
11. Hryniewicz W, Matirosian G, Ozorowski T: Zakażenie Clostridium difficile. Diagnostyka, terapia, profilaktyka. 2011. Dostępne na stronie: http://www.antybiotyki.edu.pl.
12. Barbut F, Delmèe M, Brazier JS et al.: A European survey of diagnostic methods and testing protocols for Clostridium difficile. Clin Microbiol Infect 2003; 9(10): 989-996.
13. Lessa FC, Gould CV, McDonald LC: Current status of Clostridium difficile infection epidemiology. Clin Infect Dis 2012; 55 (suppl. 2): S65-70.
14. Wistrom J, Norrby SR, Myhre EB et al.: Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients: a prospective study. J Antimicrob Chemother 2001; 47: 43-50.
15. Henrich TJ, Krakower D, Bitton A et al.: Clinical risk factors for severe Clostridium difficile-associated disease. Emerg Infect Dis 2009; 15(3): 415-422.
16. Narodowy Program Zdrowia na lata 2007-2015. 2007. Dostępne na stronie: http://www.mz.gov.pl.
