Regístrese
Buscar en
Enfermedades Infecciosas y Microbiología Clínica
Toda la web
Inicio Enfermedades Infecciosas y Microbiología Clínica Epidemiology and risk factors for Clostridium difficile infection in critically ...
Información de la revista
Vol. 36. Núm. 4.
Páginas 218-221 (Abril 2018)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Visitas
1029
Vol. 36. Núm. 4.
Páginas 218-221 (Abril 2018)
Brief report
DOI: 10.1016/j.eimc.2017.01.007
Acceso a texto completo
Epidemiology and risk factors for Clostridium difficile infection in critically ill patients in Spain: The PROCRID study
Epidemiología y factores de riesgo para la infección por Clostridium difficile en pacientes críticos en España: Estudio PROCRID
Visitas
1029
Antonio Gutiérrez-Pizarrayaa,
Autor para correspondencia
boticariors@gmail.com

Corresponding author.
, Luis Martín-Villénb, Luis Alcalá-Hernándezc,d, Mercedes Marín Arriazac,d, Bárbara Balandín-Morenoe, César Aragón-Gonzálezf, José Ferreres-Francog, Miguel Ángel Chiveli Monleónh, Paloma Anguita-Alonsoi, Emilio Bouza-Santiagoc,d, José Garnacho-Monteroj,k
a Instituto de Biomedicina de Sevilla, IBIS/Hospitales Universitarios Virgen Macarena – Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain
b Unidad Clínica de Cuidados Intensivos, Hospital Virgen del Rocío, Sevilla, Spain
c Microbiology Department, H. Universitario Gregorio Marañón, Madrid, Spain
d Department of Medicine, Universidad Complutense, IISGM and CIBERES, Spain
e Intensive Medicine Department, H. Puerta de Hierro, Madrid, Spain
f Unidad Clínica de Cuidados Intensivos, H. General Carlos Haya, Málaga, Spain
g Intensive Medicine Department, H. Clínico Universitario, Valencia, Spain
h Anaesthesia and Reanimation Department, H. Universitario La Fe, Valencia, Spain
i Astellas Pharma S.A., Spain
j Unidad Clínica de Cuidados Intensivos, Hospital Universitario Virgen Macarena, Sevilla, Spain
k Instituto Biomedicina, Sevilla, Spain
Este artículo ha recibido
1029
Visitas
Información del artículo
Resumen
Texto completo
Bibliografía
Descargar PDF
Estadísticas
Tablas (2)
Table 1. Baseline characteristics of patients with and without Clostridium difficile infection.
Table 2. Prescription of empiric antimicrobial therapy prior to onset of diarrheaa
Mostrar másMostrar menos
Abstract
Introduction

Our objectives were to describe the incidence, clinical characteristics, and risk factors for Clostridium difficile infection (CDI) in critically ill patients and to determine C. difficile PCR-ribotypes.

Methods

Prospective, observational study in 26 Spanish ICUs. Patients with diarrhea meeting ESCMID criteria for CDI were included. Molecular characterization of isolates was performed using PCR ribotyping.

Results

Of 4258 patients admitted to the ICUs, 190 (4.5%) developed diarrhea. Only 16 patients (8.4%) were diagnosed with CDI. Ribotype 078/126 (25.0%) was the most frequently identified. The mortality rate was similar in patients with ICD compared to patients with diarrhea not caused by C. difficile (p=0.115). Chronic renal insufficiency was identified as the only factor independently associated with the development of CDI (OR 5.87, 95% CI 1.24–27.83; p=0.026).

Conclusions

The incidence of CDI in Spanish ICUs is low. Only chronic renal insufficiency was observed to be a risk factor for CDI development.

Keywords:
Clostridium difficile
ICU
Incidence
Mortality
Resumen
Introducción

Pretendemos describir la incidencia, las características clínicas y los factores de riesgo de la infección por Clostridium difficile (ICD) en pacientes ingresados en unidades de cuidados intensivos, así como los ribotipos identificados.

Métodos

Estudio observacional, prospectivo, realizado en 26 unidades de cuidados intensivos de España. Se incluyeron pacientes con diarrea y criterios clínicos de la ESCMID por sospecha de ICD. La caracterización molecular se realizó mediante PCR.

Resultados

De 4.258 pacientes ingresados, 190 (4,5%) presentaron diarrea; en 16 causada por ICD. El ribotipo más frecuentemente aislado fue 078/126 (25%). La tasa de mortalidad cruda fue similar en pacientes con ICD y en pacientes con diarrea no causada por Clostridium difficile (p=0,115). La insuficiencia renal crónica fue identificada como factor independientemente asociado a desarrollo de ICD (OR: 5,87; IC 95%: 1,24-27,83; p=0,026).

Conclusiones

La incidencia de ICD en las unidades de cuidados intensivos españolas es baja. La insuficiencia renal crónica es el único factor identificado para desarrollo de ICD.

Palabras clave:
Clostridium difficile
UCI
Incidencia
Mortalidad
Texto completo
Introduction

Clostridium difficile is a Gram-positive, spore-forming anaerobic bacillus and, the leading cause of healthcare-associated diarrhea.1Clostridium difficile infection (CDI) is a major public health concern in developed countries.1 Some patients remain asymptomatic after exposure to C. difficile, while in others, disease symptoms can vary from mild diarrhea to fulminant colitis.2 Clinicians sometimes fail to suspect CDI in patients with diarrhea, and many microbiology laboratories apply suboptimal diagnostic techniques.3

Another problem is the emergence of the “hypervirulent” 027 ribotype strain of C. difficile that may cause fulminant cases with high mortality rates.4 To date, C. difficile 027 ribotype has only been identified in a limited number of episodes in Spain.5 The vast majority of our knowledge about CDI in the critical care setting is derived from retrospective studies without a predefined diagnostic workup or from studies carried out during outbreaks.6 The main objective of the study was to assess the incidence of CDI in critically ill patients with diarrhea fulfilling European Society of Clinical Microbiology and Infectious Diseases (ESCMID) clinical criteria for CDI suspicion.7 Secondary objectives were to describe clinical presentation, risk factors for development of CDI and the most prevalent C. difficile ribotypes in Spanish intensive care units (ICUs).

Methods

This multicenter, prospective, observational, non-interventional admitted to 26 ICUs in Spain between February 3 and April 3, 2014. The Institutional Review Board of the Virgen del Rocío Hospital (Seville, Spain) approved the protocol and each patient's informed consent (or the next of kin) was mandatory before enrolment.

Patients who subsequently developed diarrhea (defined as ≥3 unformed stools within 24h7) during their ICU stay were included. For every patient different clinical and analytical variables were recorded. Information was also collected on CDI recurrence, the prevalence of complications, and mortality either in hospital or within 60 days from CDI diagnosis for all patients analyzed.

Definitions

Immunosuppression was considered in those who had undergone organ transplantation, active malignancy, immunodeficiency due to any primary disease, HIV or treatment with radiation or cytotoxic or corticosteroid drugs use or haematologic disease. The rest of factors were defined as currently accepted. The severity of diarrhea was defined as: mild disease, 4–5 unformed stools per day or white blood cell (WBC) count ≤12,000/μL; moderate disease, 6–9 unformed stools per day or WBC count of 12,000–15,000/μL; severe disease, ≥10 unformed stools per day or WBC count ≥15,000/μL.8 Recurrence was defined as the return of symptoms and a positive stool sample separated from the former by between 15 and 60 days after recovery from a previous episode (at least 3 days without diarrhea and clinical improvement).9

Microbiological diagnosis

Participating ICUs provided cases and incidence data, and local laboratories sent all unformed stool specimens received on a single day to a central reference laboratory regardless with patient age/origin (inpatients and outpatients), the diagnosis requested by the clinician, or the transport medium (except when this contained sporicides, e.g. formaldehyde).

A microbiological diagnosis of CDI was made initially at the local laboratory. At weekly intervals, samples were sent to the reference laboratory located in the Microbiology Department of Hospital General Universitario Gregorio Marañón (Madrid, Spain) and the results were reported 2–5 days later.

Statistical analysis

Discrete variables were expressed as counts (percentage) and continuous variables as means±standard deviation. The chi-squared test or Fisher exact test was used for categorical variables, and the Mann–Whitney U test or Kruskal–Wallis test was used for continuous variables. To identify independent variables associated with CDI development, we performed a multivariate analysis using a binomial logistic regression.

Results

During the study period, 4258 patients were admitted to the participant ICUs. One-hundred and ninety patients (4.5%) developed diarrhea and met the study inclusion criteria. Only 11 out of the 26 participant centers provided positive CDI cases. Sixteen patients were diagnosed with CDI, representing an accumulated incidence of 0.37%. The baseline characteristics are described in Table 1.

Table 1.

Baseline characteristics of patients with and without Clostridium difficile infection.

Variable  Total cohort
N=190 
CDI
N=16 
No CDI
N=174 
p-value 
Age (years), median (IQR)  64 (52–74)  65 (56–73)  63 (52–74)  0.530 
Gender (female), n (%)  65 (34.2)  7 (43.8)  58 (33.3)  0.440 
APACHE II at admission to ICU, median (IQR)  19 (15–25)  17 (13–19)  20 (16–25)  0.723 
SOFA score, median (IQR)  5 (3–7)  5 (4–7)  5 (2–7)  0.739 
Patients with underlying disease, n (%)
Diabetes mellitus  41 (21.6)  4 (25.0)  37 (21.3)  0.765 
Heart failure  25 (13.2)  –  25 (14.4)  0.135 
COPD  45 (23.7)  6 (37.5)  39 (22.4)  0.223 
Chronic renal failure  17 (8.9)  5 (31.3)  12 (6.9)  0.008 
Chronic liver failure  18 (9.5)  2 (12.5)  16 (9.2)  0.657 
Immunosuppression  13 (6.8)  –  13 (7.5)  0.608 
Corticosteroids  15 (7.9)  1 (6.3)  14 (8.0) 
HIV infection  1 (0.5)  –  1 (0.6) 
Solid cancer  22 (11.6)  4 (25.0)  18 (10.3)  0.102 
Hematological neoplasia  7 (3.7)  –  7 (4.0) 
Others  104 (54.7)  7 (43.8)  97 (55.7)  0.305 
Prior infection with Clostridium difficile  2 (1.1)  1 (6.3)  1 (0.6)  0.156 
Characteristics of primary episode of diarrhea
Hospitalization >48h, n (%)  179 (94.2)  15 (93.8)  164 (94.3)  0.473 
Number of unformed stools/day  4 (3–6)  5 (3–6)  4 (3–5)  0.394 
Bloody diarrhea, n (%)  7 (3.7)  7 (4.0) 
Median (IQR) duration of diarrhea (days)  2 (2–3)  2 (2–3)  2 (2–3)  0.322 
SOFA score  6 (3–8)  5 (3–9)  6 (4–8)  0.797 
Temperature (°C)  36.8 (36–37.6)  36.5 (36.1–37.6)  36.9 (36–37.5)  0.922 
Leukocytes (×103cells/mm311 (7–19)  3 (2–18)  11 (8–19)  0.211 
Creatinine (mg/dL), median (IQR)  0.80 (0.51–1.70)  1.71 (0.73–5.60)  1.07 (0.71–1.69)  0.306 
Days from hospital admission to diarrhea  15 (8–25)  27 (12–44)  15 (8–24)  0.061 
Days from ICU admission to diarrhea  9 (4–19)  6 (1–28)  10 (5–27)  0.208 
Risk factors, n (%)
MV 48h before infection  141(74.2)  9 (56.3)  132 (75.9)  0.069 
Proton pump inhibitor  171 (90.0)  16 (100)  155 (89.1)  0.608 
Histamine-2-receptor antagonist  15 (7.9)  15 (8.6)  0.367 
Opiates (i.v.)  125 (65.8)  8 (50.0)  117 (67.2)  0.091 
Enteral nutrition  125 (65.8)  7 (43.8)  118 (67.8)  0.077 
Parenteral nutrition  56 (29.5)  8 (50.0)  48 (27.6)  0.101 
Antimicrobials 30 days prior to diarrhea  178 (93.7)  13 (81.3)  165 (94.8)  0.019 
Outcome
Death, n (%)  44(23.2)  6 (37.5)  38 (21.8)  0.155 

APACHE II=Acute Physiology and Chronic Health Evaluation II; COPD=chronic obstructive pulmonary disease; ICU=intensive care unit; IQR=inter-quartile range; SOFA=Sequential Organ Failure Assessment.

When patients with confirmed CDI were compared with those without CDI 1only chronic renal failure had higher prevalence in those with CDI compared with those without CDI (31.3% vs. 6.9%). The median number of unformed stools in patients diagnosed with a CDI per day was 5 (3–6) with a median duration of diarrhea of 2 days (range 2–3). Three patients with CDI (18.8%) presented with paralytic ileus. In addition, two cases of pseudomembranous colitis were reported. The infection was considered severe in seven cases (43.7%). The median length of stay in the ICU, measured in infected survivor patients, was 5 days (3–38). Only two patients (12.5%) suffered a recurrence of CDI, one infected by ribotype 027 and the other one by 014/020. The crude in-ICU mortality was 37.5% (6/16) in patients with CDI compared to 21.8% (38/174) in patients without CDI (p=0.155). One death was reported to be attributable to CDI.

The antibiotics prescribed before the episode of diarrhea are shown in Table 2. Following multivariate statistical analysis, adjusting by age, gender, APACHE II score, and previous antimicrobial therapy, only chronic renal insufficiency was identified in the final model as a factor independently associated with development of CDI (adjusted odds ratio [OR] 5.45 [95% confidence interval {CI} 1.72–25.42]; p=0.035) in this patient cohort. In a second model adjusting by the same variables and as well as prior carbapenem usage, the factors independently associated with development of CDI were the same as in the first regression model.

Table 2.

Prescription of empiric antimicrobial therapy prior to onset of diarrheaa

Antimicrobial class  No CDI
N=165
CDI
N=13
p-value 
  N  N   
Carbapenem  43  26.1  69.2  0.001 
Piperacillin-tazobactam  33  20.0  46.2  0.831 
Cephalosporins  24  14.5  7.7  0.493 
Quinolones  21  12.7  0.0  0.170 
Linezolid  17  10.3  23.1  0.160 
Penicillins  16  9.7  7.7  0.812 
Glycopeptides  10  6.1  15.4  0.196 
Antifungals  3.0  0.0  0.524 
Aminoglycosides  2.4  0.0  0.570 
Daptomycin  1.2  7.7  0.080 
Tetracyclines  1.8  0.0  0.168 
Metronidazole  1.2  0.0  0.689 
Macrolides  0.6  0.0  0.335 
Colistin  1.2  0.0  0.689 
Others  5.5  0.0  0.387 
a

Sixty-nine patients received more than one antimicrobial agent.

The most frequently isolated C. difficile ribotypes were 078/126 (n=4; 25.0%), 001 (n=3; 18.7%), 014/020 (n=2; 12.5%), and 027 (n=2; 12.5%) The rest f them (070, 157, 106, R156 and R64) we identified in one case. The two patients with ribotype 027 were both women with a similar APACHE II score at ICU admission.

Discussion

This is the first multicenter, prospective study describing the incidence, general characteristics, risk factors and complications of patients infected with C. difficile in Spanish ICUs. The present study demonstrates that real incidence of CDI appears to be low in Spain. Chronic renal failure was the only factor independently associated with CDI development which is similar to previously reported by a recent Mayo Clinic findings.10

Accurate diagnosis of CDI is a prerequisite for obtaining consistent epidemiologic data. To avoid this potential limitation, we centralized all sample analyses to a reference laboratory. Our accumulated incidence of CDI was 0.37%, lower than reported in a retrospective study carried out in a tertiary referral hospital in Barcelona, with 3.6% in 2 years.11 A retrospective analysis of patients included in the Spanish nosocomial infection surveillance registry in 2012 revealed an accumulated incidence of CDI of 0.35%.12 In our cohort, only three patients with CDI presented with some form of associated complication, all with paralytic ileus. Regarding mortality among the patients with diarrhea, we found no differences when comparing patients with and without CDI, which was perhaps related to the low severity of the majority of these infections, with 64.3% classified as mild or moderate. These findings are consistent with previous studies.6

Some limitations of our study should be acknowledged. First, we evaluated follow-up of all patients only until day 60 from CDI diagnosis, so CDI may have occurred beyond this timeframe. Secondly, the small number of cases of infection precluded certain statistical comparisons, and may have led to a type II error. Thirdly, we recognize that incidence density is the most accurate indicator. However, in our multicenter study the number of patients with ICU stays was not available for every participating hospital.

Conclusions

In summary, the key finding of our study was that CDI incidence was lower than expected. There were no clinical or analytical data that distinguished between CDI and other types of diarrhea. Our study highlighted the potential importance of chronic renal insufficiency as a risk factor for the development of CDI in these patients.

Conflict of interests

The authors declare that they have no conflicts of interest.

Acknowledgments

The authors acknowledge the investigators at the following centers:

Andalucía

Mª Carmen Lozano Domínguez (Hospital Universitario Virgen del Rocío), Rafael Rodríguez Jiménez y Enrique Muñoz (Hospital Universitario Virgen Macarena), Ana Loza Vázquez y Ana Isabel Aller García (Hospital Universitario Virgen de Valme), Cesar Aragón y Concepción Mediavilla Gradolph (Hospital General Carlos Haya), Mª Victoria de la Torre Prados, Francisco Cota Delgado, Estefania Cámara y Laura Mora Navas (Hospital Universitario Virgen de la Victoria), Rafael Guerrero Pavón y Francisco Solís Cuesta (Hospital Universitario Reina Sofía)

Madrid

Esther Diaz Rodríguez, Alfredo Bardal Ruiz y Alicia García Blanco (Hospital de la Princesa), Eva Herrero de Lucas, Belén Estébanez Montiel, Silvia García Bujalance y Emilio Maseda (Hospital La Paz), Mercedes Catalán González, Mª Ángeles Orellana Miguel y Concepción Camús Sánchez (Hospital 12 de Octubre), Mercedes Nieto Cabrera y Paloma Merino Amador (Hospital Clínico San Carlos), Sara Alcántara Carmona, Rocío Martínez Ruiz y Margarita Sánchez Castilla (Hospital Puerta de Hierro), Alexis Jaspe Codecido y Ana Mª Lajara Montell (Hospital Gregorio Marañón), Josefa Aurora Liétor Villanos y José Romero Vivas (Hospital Ramón y Cajal), Montserrat Rodríguez Aguirregabiria, Domingo Díaz Díaz y Carolina Campelo (Hospital Infanta Leonor).

Valencia

Concepción Gimeno y Juan Carlos Valía (Hospital General de Valencia), Juan Bonastre, Jose Luis López Hontangas, Mª Dolores Gómez Ruiz, Mª José Giménez Martí, Ignacio Moreno Puigdolers (Hospital La Fe de Valencia), Javier Buesa Gómez, Gerardo Aguilar y Nieves Carbonell Monleón (Hospital Clínico de Valencia), José Canovas Robles, Adelina Gimeno Gascón y Silverio Salvador (Hospital General de Alicante), Rafael Zaragoza Crespo, José Miguel Nogueira y Benedicta Sánchez Casado (Hospital Peset).

Cataluña

Jordi Rello Condomines, Jaume Valdría, Jesús Caballero, Rosa Alcaraz y Virginia Rodríguez Garrido (Hospital Vall D’Hebron), Javier Fernández Gómez y Miriam Álvarez (Hospital Clinic), Francisco Alvarez Lerma, Andrés Villasboa Vargas y Virginia Plasencia Miguel (Hospital del Mar), Rosa Granada Vicente y Jordi Niubó (Hospital de Bellvitge), Ricard Ferrer, Ana Parera y Josefa Pérez Jove (Hospital Mutua Terrassa), Jordi Vallés Dafnis y Isabel Sanfeliu Sala (Hospital Parc Taulí), Ignacio Javier Catalán Gómez y Montserrat Morta Pili (ALTHAIA Xarxa Assistencial Universitària de Manresa).

Euskadi

Ramón Cisterna y Unai Bengoetxea Uriarte (Hospital de Basurto), Iratxe Seijas Betolaza, Ildefonso Perales Palacios y Alberto Martinez Ruiz (Hospital de Cruces), Pedro María Olaechea Astigarraga y Patricia Martinez de la Fuente (Hospital Galdakao).

Cantabria

Camilo González Fernández, José Luis Teja Barbero y Mª Pia Roiz Mesones (Hospital Marqués de Valdecilla).

References
[1]
L.D. Bobo, E.R. Dubberke, M. Kollef.
Clostridium difficile in the ICU: the struggle continues.
Chest, 140 (2011), pp. 1643-1653
[2]
C. Kenneally, J.M. Rosini, L.P. Skrupky, J.A. Doherty, J.M. Hollands, E. Martinez, et al.
Analysis of 30-day mortality for Clostridium difficile-associated disease in the ICU setting.
Chest, 132 (2007), pp. 418-424
[3]
L. Alcalá, A. Martín, M. Marín, M. Sánchez-Somolinos, P. Catalán, T. Peláez, et al.
The undiagnosed cases of Clostridium difficile infection in a whole nation: where is the problem?.
Clin Microbiol Infect, 18 (2012), pp. E204-E213
[4]
K. Rao, D. Micic, M. Natarajan, S. Winters, M.J. Kiel, S.T. Walk, et al.
Clostridium difficile ribotype 027: relationship to age, detectability of toxins A or B in stool with rapid testing, severe infection, and mortality.
Clin Infect Dis, 61 (2015), pp. 233-241
[5]
M. Marín, A. Martín, A. Alcolea, C. Iglesias, L. Alcalá, T. Peláez, et al.
First case of autochthonous Clostridium difficile PCR ribotype 027 detected in Spain.
Enferm Infecc Microbiol Clin, 32 (2014), pp. 355-358
[6]
J.-R. Zahar, C. Schwebel, C. Adrie, M. Garrouste-Orgeas, A. Français, A. Vesin, et al.
Outcome of ICU patients with Clostridium difficile infection.
Crit Care, 16 (2012), pp. R215
[7]
S.B. Debast, M.P. Bauer, E.J. Kuijper.
European Society of Clinical Microbiology and Infectious Diseases. European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection.
Clin Microbiol Infect, 20 (2014), pp. 1-26
[8]
N. Bagdasarian, K. Rao, P.N. Malani.
Diagnosis and treatment of Clostridium difficile in adults: a systematic review.
JAMA, 313 (2015), pp. 398-408
[9]
J.L. Leslie, S.H. Cohen, J.V. Solnick, C.R. Polage.
Role of fecal Clostridium difficile load in discrepancies between toxin tests and PCR: is quantitation the next step in C. difficile testing?.
Eur J Clin Microbiol Infect Dis, 31 (2012), pp. 3295-3299
[10]
M.T. Keddis, S. Khanna, A. Noheria, L.M. Baddour, D.S. Pardi, Q. Qian.
Clostridium difficile infection in patients with chronic kidney disease.
Mayo Clin Proc, 87 (2012), pp. 1046-1053
[11]
S. Salva, N. Duran, V. Rodriguez, L. Nieto, J. Serra, J. Rello, et al.
Clostridium difficile in the ICU: study of the incidence, recurrence, clinical characteristics and complications in a university hospital.
Med Intensiva, 38 (2014), pp. 140-145
[12]
F. Alvarez-Lerma, M. Palomar, A. Villasboa, J. Amador, J. Almirall, M.P. Posada, et al.
Epidemiological study of Clostridium difficile infection in critical patients admitted to the Intensive Care Unit.
Med Intensiva, 38 (2014), pp. 558-566
Copyright © 2017. Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica
Opciones de artículo
Herramientas
es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos

es en pt
Política de cookies Cookies policy Política de cookies
Utilizamos cookies propias y de terceros para mejorar nuestros servicios y mostrarle publicidad relacionada con sus preferencias mediante el análisis de sus hábitos de navegación. Si continua navegando, consideramos que acepta su uso. Puede cambiar la configuración u obtener más información aquí. To improve our services and products, we use "cookies" (own or third parties authorized) to show advertising related to client preferences through the analyses of navigation customer behavior. Continuing navigation will be considered as acceptance of this use. You can change the settings or obtain more information by clicking here. Utilizamos cookies próprios e de terceiros para melhorar nossos serviços e mostrar publicidade relacionada às suas preferências, analisando seus hábitos de navegação. Se continuar a navegar, consideramos que aceita o seu uso. Você pode alterar a configuração ou obter mais informações aqui.