HIPNOSIS - DUERME y REPROGRAMA tu SUBCONSCIENCIA para Dejar de FUMAR u otra ADICCIÓN - ASMR
Clostridium difficile was first described as a cause of diarrhea in and is now among the leading 3 hospital-acquired infections in the United States, along with methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. In the past 2 decades, there has been an increase in the incidence, severity, and recurrence rates of C difficile infection, all of which are associated with poor outcomes.
In addition, several novel risk factors and newer treatment methods are emerging, including fidaxomicin therapy, treatment using monoclonal antibodies, and fecal microbiota transplantation, that have shown promise for the treatment of C difficile infection. This review focuses on the changing epidemiology, risk factors, and newer methods for alcool e drinkings difficili of C difficile infection. For more than 30 years, Clostridium difficile has been recognized as a toxin-producing anaerobic bacterium responsible for antibiotic-associated colitis, and it is now the most common infectious cause of nosocomial diarrhea.
Traditionally recognized risk factors for CDI include hospitalization, advanced age, gastrointestinal surgery or procedures, and antibiotic exposure, 7 and novel risk factors have been identified more recently.
Outcomes in patients with marked leukocytosis or acute kidney injury defined as severe CDI are worse than in those who do not have these laboratory abnormalities, and thus treatment recommendations are stratified according to disease severity. The review discusses the epidemiology, traditional and novel risk factors, and recent advancements in the management of CDI. The incidence of CDI was stable until the late s but has increased substantially in both hospital and community settings since the early s.
Most epidemiologic data for CDI are derived from hospital-based reports and administrative databases such as the US Nationwide Inpatient Alcool e drinkings difficili data and the national mortality data for CDI surveillance.
C difficile infection is defined as 1 community-acquired if symptom onset occurs in the community or within 48 hours of admission to a hospital, after no hospitalization in the past 12 weeks; 2 hospital-acquired if onset of symptoms occurs more than 48 hours after admission to or less than 4 weeks after discharge from a health care facility 12,13 ; or 3 indeterminate if symptom onset occurs in the community between 4 and 12 weeks after discharge from alcool e drinkings difficili hospital.
Theories that have been advanced to explain the increase in incidence of CDI include changes in the hospitalized patient population older and sicker patientschanges in antibiotic prescribing patterns in particular, increased use of newer-generation fluoroquinolonesa new more virulent strain of C difficilepotentially novel risk factors eg, treatment using proton pump inhibitors [PPIs]and changes in infection control practices eg, use of alcohol gel hand washes.
C difficile infection is more common in the elderly, who also are at higher risk of severe or severe-complicated infection. Some of alcool e drinkings difficili increase in incidence and severity found in recent reports likely reflects that our population is aging, a statistic that is particularly evident on inpatient wards. C difficile infection is now being described in populations who have traditionally been considered at low risk such as children and community dwellers, who lack the usual risk factors.
Patients with community-acquired CDI were younger, often had no history of recent hospitalization, and had fewer comorbid conditions. The increased incidence of CDI in the community may be due to an increased prevalence of asymptomatic colonizers.
An important consideration in the increasing incidence of CDI is the emergence of a hypervirulent strain of the bacterium, known as ribotypeNAP1 North American pulsed-field gel electrophoresis type 1or restriction endonuclease analysis group BI. This strain has been isolated from most states in the United States and in several countries in Europe.
The hypervirulent strain has a sequence variation in the tcdC repressor gene, which results in loss of function of the gene product, a protein that normally suppresses the transcription of toxin A and B genes. The traditional risk alcool e drinkings difficili for CDI include antibiotic exposure, hospitalization, and increasing age. It is well known that the normal human colonic flora offers protection against colonization by C difficile.
Exposure to systemic antibiotics leads to disruption of the normal colonic microbiome and increased susceptibility to colonization and toxin production by C difficile and increases the risk of symptomatic CDI by 2- to fold. The primary means of transmission of CDI are believed to be person-to-person via the fecal-oral route, through environmental contamination, and transmission via fomites and the hands of health care workers.
Additional potential risk factors for CDI that have been identified include a higher number of comorbid conditions, inflammatory bowel disease, immunodeficiency, hypoalbuminemia, malignant lesions, solid alcool e drinkings difficili transplant, chemotherapy, and the use of PPIs. Recent data have suggested that circumventing the potential protective effect of stomach acid, for example, through the use of postpyloric enteral feeding or the use of PPIs or histamine 2 receptor blockers, may lead to a 2- to 3-fold increased risk of acquisition of CDI.
A summary of risk factors for CDI is given in Table 1. The diagnosis of CDI is made on the basis of alcool e drinkings difficili combination of clinical features typically, abdominal pain and diarrhea and results of stool tests and, rarely, endoscopy or radiologic tests. Several stool tests are available for CDI including stool culture, stool cytotoxin alcool e drinkings difficili, polymerase chain reaction PCRenzyme immunoassay, and stool glutamate dehydrogenase assay.
Real-time PCR is considered an alternative criterion standard to stool culture because it has excellent sensitivity and specificity; however, it requires technical expertise and does not enable differentiation between asymptomatic carriage and symptomatic infection. Studies using PCR have found high sensitivity and specificity and test-retest reliability. Enzyme immunoassay has high specificity but is limited by moderate sensitivity. A detailed review of various strategies for stool tests for CDI is beyond the scope of this review and is available elsewhere.
Endoscopy is generally not used in making an initial diagnosis of CDI unless there is a high level of suspicion despite normal results of stool tests or if ileus secondary to CDI is suspected. Endoscopic findings of pseudomembranes are specific but not sensitive for a diagnosis of CDI, and if present, indicate severe infection.
Abdominal radiographs or computed tomographic scans are uncommonly used to make the initial diagnosis. Computed tomographic findings alcool e drinkings difficili of CDI include bowel wall thickening, pericolonic stranding, and fold thickening. Radiologic findings of a dilated colon may indicate severe-complicated CDI, and in the presence of severe abdominal pain, leukocytosis, fever, and hypotension alcool e drinkings difficili indicate toxic megacolon.
The spectrum of CDI ranges from mild to severe or severe-complicated. Patients who are asymptomatic carriers of C difficile should not receive treatment because there are no data to suggest that treating these individuals would prevent symptomatic infection or transmission. The use of antimotility agents such as narcotics and loperamide in active C difficile infection is discouraged because use of these agents may result in more severe colitis.
In patients with CDI, unnecessary antibiotic therapy should be discontinued, and if ongoing antibiotic therapy is needed, targeted narrow-spectrum agents should be used. In patients with severe diarrhea and risk factors for CDI such as increasing age, antibiotic alcool e drinkings difficili, or recent hospitalization, it may be reasonable to initiate empiric antibiotic therapy for CDI while stool test results are pending.
Measures for infection control include strict implementation of isolation precautions with the use of gloves and gowns, hand washing with soap and water, and use of hypochlorite-based agents for environmental disinfection. Metronidazole is an inexpensive, effective, off-label treatment recommended for mild to moderate CDI.
The usual dose is mg 3 times a day for 10 to 14 days. After adjusting for appropriate confounders, metronidazole may be associated with more complications than vancomycinz 6 and more adverse effects including nausea, disulfiram-like reaction when drinking alcoholic beverages, metallic taste, and peripheral neuropathy, and it is not recommended for use in children or in women during lactation or pregnancy.
Factors defining severity in that study included age older than 60 years, temperature higher than Of note, alcool e drinkings difficili relapse rate was not considerably different between the 2 treatment groups.
The recommended dose is mg 4 times a day for 10 to 14 days. If other diseases have been ruled out, treatment should be switched from metronidazole to vancomycin. In patients with severe disease, as defined by leukocytosis or renal failure, or who have a second or additional episodes of recurrence see subsequent discussionvancomycin should be the treatment of choice.
Fidaxomicin is a macrocyclic antibiotic with little or alcool e drinkings difficili systemic absorption after oral administration and a narrow spectrum of activity against gram-positive aerobic and anaerobic bacteria including C difficile. In alcool e drinkings difficili trial, fidaxomicin was not inferior to vancomycin in achieving clinical cure.
These data demonstrate that fidaxomicin is well tolerated, is not inferior to alcool e drinkings difficili vancomycin for clinical cure in mild to moderate CDI, and is associated with lower rates of recurrence than is vancomycin in patients infected with nonhypervirulent strains of C difficile.
Fidaxomicin might be favored over oral vancomycin in patients who require additional concomitant systemic antibiotics after a diagnosis of CDI. However, there are no randomized data comparing fidaxomicin with metronidazole for treatment of a alcool e drinkings difficili episode of mild to moderate CDI, for which metronidazole remains the initial treatment of choice. In addition, fidaxomicin has not been studied for efficacy in recurrent CDI and in special populations including children or individuals with inflammatory bowel diseases.
There are several pharmacoeconomic considerations for the use of fidaxomicin. To save on cost, some institutions administer oral vancomycin solution using the intravenous solution rather than capsules. With these cost considerations, fidaxomicin is often restricted to use in patients with an initial episode of CDI who are at high risk of recurrence eg, individuals of advanced age, alcool e drinkings difficili with severe CDI, and those receiving concomitant antibiotic therapy 75,76 and who are infected with the nonhypervirulent strain or in those who have had multiple episodes of recurrence.
However, currently there are no robust clinical models to predict recurrence in patients with Alcool e drinkings difficili. Furthermore, it should be noted that the efficacy of fidaxomicin compared with vancomycin or any other treatment has not been specifically studied in these patient groups. Fidaxomicin is also sometimes used in patients who have a severe intolerance of or allergic reaction to oral vancomycin.
A major risk factor for CDI is systemic antibiotic use, which disrupts normal gut flora and leads to increased predisposition to CDI. The pathophysiologic features of recurrent CDI are incompletely understood but likely involve ongoing disruption of alcool e drinkings difficili normal fecal flora and inadequate host immune response.
Standard treatment of CDI using antibiotics such as metronidazole and vancomycin further disrupts colonic microbial communities that normally keep expansion of C difficile populations in check.
Because C difficile spores are resistant to antibiotics, they can germinate to vegetative forms after antibiotic therapy has been discontinued.
These factors can perpetuate CDI recurrence after discontinuation of therapy. Therefore, a high percentage of patients experience multiple recurrences of CDI. Although it is hoped that the emerging narrow-spectrum antibiotics such as fidaxomicin will permit restoration of the gut microbiota in patients with the chronic relapsing form of CDI, this hypothesis has not been tested in these patients.
Fecal microbiota transplantation FMT is being studied as an alternative to standard antibiotic therapy to treat recurrent CDI, to restore colonic flora with the use of intestinal microorganisms from a healthy donor via infusion of a liquid suspension of stooland to restore the intestinal microbiota in patients with recurrent CDI.
A study from the University of Minnesota reported initial experience with FMT in 43 patients with recurrent CDI including patients with underlying inflammatory alcool e drinkings difficili disease. Another group reported their experience with FMT via enema and found a similar response rate and no adverse events. There are several considerations for FMT that include donor selection, including the use of a standard donor pool vs a related donor, the need to screen donors for transmissible infectious diseases, standardization of stool preparation techniques, insurance reimbursement for donor testing, and long-term safety and efficacy of FMT in this population.
Additional potential options for treatment of CDI alcool e drinkings difficili rifaximin, nitazoxanide, cholestyramine, intravenous immunoglobulin IVIGmonoclonal antibodies, vaccines, and probiotics. Rifaximin is a gastrointestinal-selective antibiotic characterized by a broad antimicrobial spectrum that has activity against most gram-negative and gram-positive bacteria and anaerobes and aerobes and has excellent in vitro activity against C difficile.
Nitazoxanide is an antiparasitic drug that is also active against C difficile and is as effective as vancomycin and metronidazole alcool e drinkings difficili treatment of CDI.
At present, nitazoxanide can be considered an alternate therapy in patients with multiple episodes of recurrence despite several courses of vancomycin and metronidazole and who are not candidates for FMT or other therapies. Anion exchange resins such as cholestyramine work by binding toxin and may help decrease symptoms in mild disease.
However, there is no evidence that adding cholestyramine to the treatment regimen decreases the risk of recurrence, and these alcool e drinkings difficili also bind vancomycin and alcool e drinkings difficili should not be used simultaneously. Intravenous immunoglobulin has been used to treat recurrent and severe CDI with variable success, and there are no randomized controlled trials reporting a benefit of IVIG therapy in CDI.
A phase 3 study is under way to further establish the safety and efficacy of monoclonal antitoxin antibody treatment of CDI. Preliminary trials of a parenteral vaccine containing toxoids A and B found excellent serum antibody responses in healthy adults.
No serious adverse effects were reported. Phase 2 trials are ongoing to further alcool e drinkings difficili the efficacy of this toxoid vaccine for prevention of CDI recurrence. Probiotics are preparations of live microorganisms that have been used to prevent and treat CDI, with a suggested objective to repopulate the colonic microflora. The various probiotics commonly used include species of Lactobacillus, Alcool e drinkings difficili, and Saccharomyces. There is currently no role for probiotics in the primary prevention of CDI because of limited data and the potential risk of bloodstream infection with these agents.
Surgery is indicated for treatment of refractory CDI not responding to medical therapy or for fulminant colitis, which is a relatively rare complication of CDI. Clinical features of fulminant CDI include systemic inflammatory response syndrome, severe abdominal pain and tenderness, and colonic distention observed on radiographs.
Diarrhea may be absent because of ileus. The timing of surgical consultation for CDI remains controversial, more so because alcool e drinkings difficili with fulminant CDI are generally poor surgical candidates because of age and comorbid conditions. It is therefore recommended that a surgical consultation be obtained early if a patient has worsening diarrhea despite optimal medical therapy, symptoms of megacolon, or sepsis.
Clinically, alcool e drinkings difficili CDI is defined as occurrence of symptomatic diarrhea or abdominal pain, with positive results of a stool test within 56 days of a previous episode after interim symptom resolution.
This definition is important because positive stool test results without diarrhea should not be considered a recurrence of CDI, and recurrent diarrhea with normal findings on a stool test should lead the clinician to consider a broader differential diagnosis including postinfectious irritable bowel syndrome, although false-negative stool test results in a patient with true recurrent CDI is a possibility. However, the practice of repeat stool testing for CDI is discouraged because the yield is low.
There are no randomized controlled trials of patients with multiple CDI recurrences, and treatment options and recommendations are often made on the basis of findings of small studies and case reports. In a patient with a confirmed first recurrence, initial therapy should consist of a 2-week course of oral metronidazole therapy for mild to moderate CDI if the first infection responded to this treatment or oral vancomycin for severe CDI.