Efficacy of Fidaxomicin Versus Vancomycin as Therapy for Clostridium difficile Infection in Individuals Taking Concomitant Antibiotics for Other Concurrent Infections

Mullane, Kathleen M.; Miller, Mark A.; Weiss, Karl Heinz; Lentnek, Arnold; Golan, Yoav; Sears, P.S.; Shue, Youe‐Kong; Louie, Thomas; Gorbach, Sherwood L.

doi:10.1093/cid/cir404

Cited by 208 publications

(177 citation statements)

References 30 publications

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“…Higher rates of CDI treatment failures have been demonstrated in the past in patients given concomitant antibiotics (14), treated with fidaxomicin or vancomycin (15). As many hospitalized patients receive unnecessary antibiotics for an extended duration, antimicrobial stewardship efforts to decrease unnecessary concomitant use of non-CDI antibiotics may improve treatment outcomes of patients with CDI (16,17).…”

Section: Discussionmentioning

confidence: 99%

Age-Stratified Treatment Response Rates in Hospitalized Patients with Clostridium difficile Infection Treated with Metronidazole

Pham

Luce

Ruppelt

et al. 2015

Antimicrob Agents Chemother

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Consensus on the optimal treatment of Clostridium difficile infection (CDI) is rapidly changing. Treatment with metronidazole has been associated with increased clinical failure rates; however, the reasons for this are unclear. The purpose of this study was to assess age-related treatment response rates in hospitalized patients with CDI treated with metronidazole. This was a retrospective, multicenter cohort study of hospitalized patients with CDI. Patients were assessed for refractory CDI, defined as persistent diarrhea after 7 days of metronidazole therapy, and stratified by age and clinical characteristics. A total of 242 individuals, aged 60 ؎ 18 years (Charlson comorbidity index, 3.8 ؎ 2.4; Horn's index, 1.7 ؎ 1.0) were included. One hundred twenty-eight patients (53%) had severe CDI. Seventy patients (29%) had refractory CDI, a percentage that increased from 22% to 28% and to 37% for patients aged less than 50 years, for patients from 50 to 70 years, and for patients aged >70 years, respectively (P ‫؍‬ 0.05). In multivariate analysis, Horn's index (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.50 to 2.77; P < 0.001), severe CDI (OR, 2.25; 95% CI, 1.15 to 4.41; P ‫؍‬ 0.018), and continued use of antibiotics (OR, 2.65; 95% CI, 1.30 to 5.39; P ‫؍‬ 0.0072) were identified as significant predictors of refractory CDI. Age was not identified as an independent risk factor for refractory CDI. Therefore, hospitalized elderly patients with CDI treated with metronidazole had increased refractory CDI rates likely due to increased underlying severity of illness, severity of CDI, and concomitant antibiotic use. These results may help identify patients that may benefit from alternative C. difficile treatments other than metronidazole.I n the United States, Clostridium difficile is the most commonly reported pathogen for health setting-acquired infections, causing approximately 500,000 infections and 29,000 deaths (1, 2) annually. Oral metronidazole is a treatment option for C. difficile infection (CDI) and is recommended in the guidelines for the treatment of mild-to-moderate disease (3). However, observational (4) and randomized controlled (5, 6) studies have demonstrated high clinical failure rates in patients with CDI given metronidazole. Colonic concentrations of metronidazole are relatively low and not predictable, and this drug is not considered by many to be an optimal pharmacologic agent for CDI (7). However, the reason for increased clinical failure rates in patients treated with metronidazole is unknown. Mortality rates due to CDI increase in the elderly (8). We hypothesized that metronidazole response rates would also decrease in the elderly. The purpose of this study was to assess age-related treatment response rates in hospitalized patients with CDI treated with metronidazole. MATERIALS AND METHODSStudy design and study sites. This was a retrospective, multicenter cohort study of patients with CDI admitted to three large tertiary care academic institutions in Houston, TX, from January 2009 to August ...

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Section: Discussionmentioning

confidence: 99%

Age-Stratified Treatment Response Rates in Hospitalized Patients with Clostridium difficile Infection Treated with Metronidazole

Pham

Luce

Ruppelt

et al. 2015

Antimicrob Agents Chemother

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“…Daganatos betegeken végzett direkt összehasonlításban a fidaxomicin hatékonyabbnak bizonyult a vancomycinnél [23]. A fidaxomicin (200 mg per os, naponta 2-szer, 10 napig) jelenleg elsőként válasz-tandó rekurrens vagy a visszaesés vonatkozásában nagy kockázatú CD-fertőzés esetén [24], különösen azoknál, akik egyéb antibiotikumot kapnak [25], veseműködési zavarban [26] vagy daganatos betegségben [27] szenvednek, illetve idősek [28]. Kiemelendő, hogy az első CD-fertőzésből sikeresen felépülők egyharmada visszaesik [29].…”

Section: A Terápiaunclassified

A Clostridium difficile onkológiai vonatkozásai

Telekes

2016

Orvosi Hetilap

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A Clostridium difficile az egyik leggyakoribb fertőzés a daganatos betegek között. Diagnózisát nehezíti, hogy a fertőzés tünetei és az onkológiai kezelések mellékhatásai hasonlóak lehetnek. Maga a kemoterápia is elősegítheti a Clostridium difficile-infekció kialakulását. Bár számos kockázati faktor ismert, ezek hiányában is kialakulhat a fertő-zés. A fatális Clostridium difficile-infekció kockázati faktora a neutropenia, ami egyben a kemoterápia mellékhatása is. Ezért, ha daganatos betegek esetén a potenciális infekció tünetei megjelennek (például diarrhoea naponta több mint háromszor, 38,5 °C-ot meghaladó láz, colitis, szérumkreatinin-szint gyors emelkedése) a Clostridium difficile-fertő-zést ki kell zárni. Amennyiben a fertőzés igazolódik, azt a leghatékonyabb módon kezelni kell. Orv. Hetil., 2016, 157(28), 1110-1116. Kulcsszavak: Clostridium difficile, onkológia, fidaxomicin Oncologic aspects of Clostridium difficileClostridium difficile infection is one of the most frequent among cancer patients. Its diagnosis is complicated by the fact that the symptoms of the infection and the side effects of the anticancer treatments could be similar. Chemotherapy itself might facilitate Clostridium difficile infection. Several risk factors are known but Clostridium difficile infection can develop in the absence of these. Neutreopenia is a risk factor for fatal Clostridium difficile infection and also the side effect of chemotherapy. Therefore, if symptoms of the potential infection develop (eg. diarrhoea more than three times a day, fever above 38.5 o C, colitis, rapid increase of serum creatinin) Clostridium difficile infection should be excluded. If the infection is confirmed it should be managed in the most efficient way. Rövidítések CD = Clostridium difficile; CDAD = Clostridium difficile-aszszociált diarrhoea; EIA = enzimimmunoassay; PCR = polimeráz láncreakció; TcdA = Clostridium difficile toxin A; TcdB = Clostridium difficile toxin B Keywords: Clostridium difficile, oncology, fidaxomicin A Clostridium difficileA Clostridium difficile (CD) az ember normális bélflórá-jának része. Azonos családba tartozik, mint a patogén Clostridium tetani (ami a tetanust okozza) és a Clostridium botullinum (ami a botulizmust okozza). Mindenütt előfordul (levegő, víz, talaj, széklet, bármilyen felület), leggyakrabban WC-ülőkén, pelenkákon, padlón, telefonokon, körmökön, ékszereken, sztetoszkópon, háziálla-tokon, zöldségeken mutatták ki. A CD Gram-pozitív anaerob baktérium. A bélflórában lévő baktériumok egymás növekedését kordában tartják. Az aktív, infektív baktérium nem képes ellenállni a környezeti hatásoknak hosszú időn keresztül. Az inaktív forma, az úgynevezett spóra, azonban szabad levegőn, szennyeződésekben akár két évig is életképes. A spóra maga nem fertőző, de a bélbe jutva, belélegezve visszanyerheti infektív formáját. Antibiotikum-kezelést követően, amikor a bélflóra egyensúlya felborul, a CD-spórák a bélben aktív formává alakulnak és képesek gyorsan elszaporodni. Az aktív bak-

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“…Los resultados del análisis combinados de ambos estudios, por subgrupos de población, muestran que fidaxomicina fue significativamente mejor que vancomicina (19,7 vs 35,5%, p = 0,045) para el tratamiento de la segunda recurrencia de ICD 96 . Cuando se asoció tratamiento antimicrobiano para una infección concurrente durante la terapia frente a ICD o en el período de seguimiento, fidaxomicina obtuvo mejores tasas de curación (90 vs 79,4%, p = 0,04) y menores tasas de recurrencias (16,9 vs 29,2%, p = 0,048) comparado frente a vancomicina 97 . Fidaxomicina es segura y bien tolerada; los efectos adversos más frecuentes (< 3%) relacionados con el tratamiento son vómitos, náuseas y estreñimiento.…”

Section: Antimicrobianounclassified