Modern approach to the therapy of infections caused by Clostridium difficile

Jaćović, Saša; Milisavljević, Slobodan; Milosavljević, Miloš; Janković, Slobodan; Stefanović, Srđan

doi:10.5937/racter10-18509

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Racionalna terapija

2018, vol. 10, br. 2, str. 25-31

Savremeni pristup u terapiji infekcija izazvanih sa Clostridium difficile

Jaćović Saša^a, Milisavljević Slobodan^b, Milosavljević Miloš^c

, Janković Slobodan^c

, Stefanović Srđan^c

^aAgencija za lekove i medicinska sredstva Srbije, Beograd
^bUniverzitet u Kragujevcu, Fakultet medicinskih nauka, Katedra za hirurgiju, Srbija
^cUniverzitet u Kragujevcu, Fakultet medicinskih nauka, Katedra za farmakologiju i toksikologiju, Srbija

e-adresa: milosavljevicmilos91@gmail.com

Projekat:

Farmakološka analiza efekata biološki aktivnih supstanci na izolovane glatke mišiće gastrointestinalnog i urogenitalnog trakta čoveka (MPNTR - 175007)

Ključne reči: Clostridium difficile; vankomicin; fidaksomicin; metronidazol; bezlotoksumab; fekalna transplantacija

Sažetak

Kolitis uzrokovan bakterijom Clostridium difficile (CDC) nastaje kao rezultat poremećaja ravnoteže bakterija u gastrointestinalnom traktu, uglavnom zbog prethodne sistemske primene antibiotika širokog spektra dejstva. U današnje vreme ova vrsta kolitisa predstavlja jednu od najučestalijih infekcija stečenih u bolničkoj sredini. Pri tome, danas se kliničari često suočavaju sa rastućom incidencijom fulminantnih i rekurentnih CDC, koji su praćeni brojnim kolektomijama, produženim boravakom u bolnici, fatalnim ishodom i povećanjem sveukupnih troškova zdravstvene zaštite. Tradicionalni antibiotici za lečenje CDC-a, poput metronidazola, vankomicina ili fidaksomicina, u prethodnim istraživanjima pokazali su određene terapijske nedostatke. Stoga je cilj ovog narativnog revijalnog rada bio da se kritički proceni efikasnost svakog od preporučenih lekova za CDC, kao i učestalost i ozbiljnost neželjenih događaja koji prate njihovu primenu. Na osnovu aktuelnih saznanja, dijapazon standardnih antibiotika odobrenih za lečenje inicijalne ili rekurentne CDC prilično je ograničen. Bez obzira na težinu CDC, oralni ili rektalni vankomicin danas se smatra terapijskom opcijom prve linije kod odraslih, dok fidaksomicin ili metronidazol predstavljaju odgovarajuće alternative. S druge strane, metronidazol je lek izbora za lečenje inicijalne i prve rekurentne epizode CDC u dečijoj populaciji. Drugi potencijalno efikasni antimikrobni lekovi za CDC, poput rifaksimina, nitazoksanida, fusidinske kiselina, tigeciklina, bacitracina, kao i upotreba probiotika, ne mogu se preporučiti kao terapija izbora s obzirom da u prethodnim istraživanjima u pogledu kliničkih efekata nisu pokazali nikakve prednosti u odnosu na vankomicin ili fidaksomicin. U pokušaju da se reši problem rekurentnih CDC događaja, što je jedan od najvažnijih izazova sa kojima se danas sreću zdravstveni radnici, dodatna upotreba humanog monoklonskog antitela protiv toksina B CD (bez lotoksumab) uz standardni način lečenja ili infuzija suspenzije fecesa zdravih donora u debelo crevo pacijenta (fekalna transplantacija), mogu biti efikasan i bezbedan terapijski pristup u situacijama gde su takve procedure dostupne. Do završetka kliničkog razvoja inovativne terapije za CDC, poput novih antibiotika i vakcina protiv Clostridium difficile, primarni fokus treba da bude na efikasnoj prevenciji ove infekcije, u smislu unapređenja racionalne upotrebe sistemskih antibiotika širokog spektra dejstva i inhibitora protonske pumpe.

Abstract

Infection caused by Clostridium difficile (CDI) occurs as a result of imbalance of bacteria in intestinal tract mainly due to previous exposure to wide-spectrum systemic antibiotics. Nowadays, it is recognized as one of the most frequent infections acquired in hospitals. Contemporary clinicians often face an increased incidence of fulminant and recurrent CDIs that are accompanied with a number of colectomies, prolonged stay in hospitals, fatal outcome, and rising healthcare costs. Traditional antibiotics for CDI, such as metronidazole, vancomycin or fidaxomicin, have been linked to certain treatment limitations in previous studies. Thus, the aim of this narrative mini literature review was to critically evaluate efficiency of each of the recommended modern therapy modalities for CDI, as well as the frequency and severity of adverse events associated with their use. Based on current knowledge, the range of standard antibiotics approved for treatment of initial or recurrent CDI remains quite limited. Regardless of severity of CDI, oral or rectal vancomycin should be considered as the first-line therapeutic option in adults and children, while fidaxomicin or metronidazole could be an appropriate alternative. The other potentially effective antimicrobials against CDI, such as rifaximin, nitazoxanide, fusidic acid, tigecyclin, bacitracin and use of probiotics cannot be advised as the therapy of choice, as they did not provide any advantage over vancomycin or fidaxomicin in prior investigations. In an attempt to solve the problem of recurrent CDI events, which is one of the most important challenges facing health professionals today, adjunct use of human monoclonal antibody against toxin B (bezlotoxumab) or instillation of normal colonic bacteria obtained from healthy donor into patient's intestine (Fecal Microbiota Transplantation), could be effective and safe approach where available. Besides clinical development of innovative therapy for CDI, such as new antibiotics and vaccines, primary focus should be on effective prevention of this infection, in terms of improving rational use of broad-spectrum systemic antibiotics and proton pump inhibitors.

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O članku

jezik rada: engleski
vrsta rada: pregledni članak
DOI: 10.5937/racter10-18509
objavljen u SCIndeksu: 28.02.2019.

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