Elsevier

Anaerobe

Volume 54, December 2018, Pages 65-71
Anaerobe

Clostridioides (Clostridium) difficile (including epidemiology)
Clinical epidemiology of Clostridium difficile infection among hospitalized patients with antibiotic-associated diarrhea in a university hospital of Brazil

https://doi.org/10.1016/j.anaerobe.2018.08.005Get rights and content

Highlights

  • Clinical characteristics of hospitalized patients with CDI in a Brazilian hospital were evaluated.

  • Comorbidity severity and the number of antibiotics used are strong predictors of CDI.

  • Diabetes was associated with a higher mortality among patients with antibiotic-associated diarrhea.

  • A high diversity of ribotypes was observed in absence of classical hypervirulent strains.

Abstract

A cohort of 110 adult individuals was analyzed to compare clinical characteristics of hospitalized patients who received antibiotics and developed Clostridium difficile infection (CDI) with those who received antibiotics and did not develop the disease in a university Hospital in Brazil. CDI was diagnosed by toxigenic culture and C. difficile isolates were characterized by PCR ribotyping. Stool samples were also screened for Clostridium perfringens, methicillin-resistant Staphylococcus aureus (MRSA) and Klebsiella oxytoca. The prevalence of CDI among patients with AAD was 31.8%. C. difficile diarrhea was significantly associated with the severity of underlying comorbidities at admission (OR = 1.21; 95% CI, 1.04–1.40) and with the number of antibiotics used during hospitalization (OR = 1.43; 95% CI, 1.07–1.92). Diabetes mellitus was markedly associated with a higher risk of death in patients with AAD (OR = 6.38; 95% CI, 1.33–30.7). PCR ribotypes 014/020 and 106 (20.6% each) were the most common among the isolates. Binary toxin-encoding gene (cdtB) was detected in six samples, but previously described hypervirulent ribotypes 027 and 078 were not found. K. oxytoca and enterotoxigenic C. perfringens were not detected, while only one patient (0.9%) was positive for MRSA. Our results indicate that comorbidity severity and the number of antibiotics used during hospitalization are strong independent predictors of nosocomial C. difficile diarrhea. Diabetes was associated with a higher mortality among patients with AAD. A huge diversity of C. difficile ribotypes was observed in our study, although classical hypervirulent strains were not observed.

Introduction

Antibiotic-associated diarrhea (AAD) is defined as an otherwise unexplained diarrhea that occurs in conjunction with the administration of antibiotics. Clostridium difficile infection (CDI) accounts for 10–33% of the cases of AAD and for the vast majority of cases of severe colitis associated with antibiotic therapy [1]. It is not only one of the most commonly diagnosed causes of nosocomial diarrhea in the developed world, but also closely related to increased morbidity, prolonged hospitalization, and rising health costs [2].

The risk factors for CDI include antimicrobial exposure, advanced age, prior hospitalization, use of feeding tubes, severe underlying disease, immunocompromising conditions, chemotherapeutic drugs, gastrointestinal surgery, and gastric acid suppression. Nearly all antimicrobials have been implicated in the development of CDI, particularly third-generation cephalosporins, clindamycin and fluoroquinolones [3]. It is believed that the disruption of the autochthonous intestinal microbiome by antibiotic use leads to the proliferation of C. difficile and potentially to the development of C. difficile–associated diarrhea [4].

Since the early 2000s, the incidence and severity of CDI have increased dramatically in North America and Europe, finding that has been attributed in part to the emergence of hypervirulent strains, such as ribotypes 027, 078 and 244 [5]. In contrast, little is known about the epidemiology of CDI in Latin American countries, where the majority of the hospitals lack personnel or structures for healthcare control of infection [6]. The potential worldwide spread of this infection calls for epidemiological studies to characterize currently circulating strains and also highlights the need for increased and permanent vigilance among public health professionals [7]. Furthermore, although previous studies found evidences that enterotoxin-producing Clostridium perfringens, methicillin-resistant Staphylococcus aureus (MRSA) and Klebisiella oxytoca could also be responsible for AAD, few studies have addressed these pathogens in patients with nosocomial diarrhea [8].

The aim of the current study is to compare clinical characteristics of hospitalized patients who received antibiotic therapy and developed CDI with those who received antibiotic therapy and developed diarrhea unrelated to C. difficile, as well as to identify other pathogens less frequently related to AAD. Furthermore, we assessed C. difficile ribotypes isolated from fecal samples of inpatients from a university hospital of Brazil, further contributing to clarify the epidemiology of CDI in Latin America.

Section snippets

Subjects and inclusion criteria

The study was carried out at the Clinical Hospital of the Federal University of Minas Gerais, a 500-bed quaternary care hospital of Belo Horizonte, Minas Gerais state, southeast Brazil. From January 2011, to December 2015, patients (18 years of age or older) who have received systemic antibiotics anytime in the last 3 months, presenting with acute diarrhea after 72 h or more of hospitalization, were invited to participate in the study. All patients were followed from the time of admission until

Clostridium difficile infection

A total of 154 stool samples provided by patients with AAD were submitted to the microbiologic laboratory for C. difficile diagnostics during the study period from 2011 to 2015 (Fig. 1). Since complete data sets were available for only 110 patients, 44 individuals were excluded from the final analysis. Among those 110 patients, thirty-five (31.8%) were diagnosed with CDI, 21 (60%) of whom were positive for A/B toxins by EIA. Seven subjects were colonized by non-toxigenic C. difficile strains

Discussion

Antibiotic-associated diarrhea is a significant cause of morbidity and mortality, particularly in the elderly. The most common known infective cause of AAD is C. difficile, which accounts for 10–33% of the cases, 50%–75% of antibiotic-associated colitis, and more than 90% of antibiotic-associated pseudomembranous colitis in hospitalized patients [1,18,19]. This is the first study to address different aspects of C. difficile clinical epidemiology in Brazil. A high prevalence of CDI among

Acknowledgements

The authors are grateful for the financial support from PRPQ-UFMG, Fapemig, Capes/Proex and CNPq.

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