Materiały źródłowe

• #1 Antibiotic-associated diarrhea: epidemiology, trends and treatment – PubMed

  https://pubmed.ncbi.nlm.nih.gov/18811240/

  A common complication of antibiotic use is the development of gastrointestinal disease. This complication ranges from mild diarrhea to pseudomembranous colitis. Outbreaks of antibiotic-associated diarrhea (AAD) may also occur in healthcare settings, usually caused by Clostridium difficile. AAD typically occurs in 5-35% of patients taking antibiotics and varies depending upon the specific type of antibiotic, the health of the host and exposure to pathogens. […] The key to addressing AAD is prompt diagnosis followed by effective treatment and institution of control measures. Areas of active research include the search for other etiologies and more effective treatments.

• #2 Epidemiology, risk factors and treatments for antibiotic-associated diarrhea – PubMed

  https://pubmed.ncbi.nlm.nih.gov/9892789/

  Antibiotic-associated diarrhea (AAD) is a common complication of antibiotics and recent findings on the epidemiology, etiologies and treatment strategies are reviewed. Rates of AAD vary from 5 to 39% depending upon the specific type of antibiotic. […] The impact of AAD is reflected by increased hospital stays, higher medical costs and increased rates of comorbidity. The key to decreasing these consequences is prompt diagnosis followed by effective treatment and institution of control measures.

• #3 Prevalence and management of antibiotic associated diarrhea in general hospitals | BMC Infectious Diseases | Full Text

  https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-015-0869-0

  Antibiotic-associated diarrhea (AAD) is a common adverse effect of antibiotic (AB) treatment. This study aimed to measure the overall prevalence of AAD (including mild to moderate diarrhea) in hospitalized AB treated patients, to investigate associated risk factors and to document AAD associated diagnostic investigations, contamination control and treatment. […] AAD was observed in 9.6% of AB users including 4 with confirmed C. difficile infection. […] In this observational study, with one third of hospitalized patients receiving AB, an AAD period prevalence of 9.6% in AB users was found. AAD caused extra investigations and treatment and an estimated extra nursing care of almost one hour per day. […] The global prevalence of AAD, with inclusion of the mild to moderate attacks without further clinical diagnostic evaluation, is not well established.

• #4 Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections

  https://www.wjgnet.com/1007-9327/full/v22/i11/3078.htm

  Pediatric CDI incidence: Incidence of pediatric CDI is dependent upon two main factors: age and hospitalization status. […] The incidence of pediatric asymptomatic colonization with C. difficile decreases with the increase in age from 6 mo-1 year. […] The incidence of pediatric CDI declines from ages 6-18 years old to rates typically seen in adult CDI cases. […] The overall median incidence of pediatric AAD averages 27/100 compared to 15/100 for adult AAD, but the range in both populations is wide (1%-80%). […] The overall median incidence from Table 1 of pediatric CDI (31/10000) may be higher than adult CDI (10/10000), these rates are highly influenced by method in which the data was collected, differences in age distribution, setting (inpatient or outpatient) and underlying risk factor distribution.

• #5 Antibiotics and antibiotic-associated diarrhea: a real-world disproportionality study of the FDA adverse event reporting system from 2004 to 2022 | BMC Pharmacology and Toxicology | Full Text

  https://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-023-00710-w

  Our study aimed to assess the risk signals of antibiotic-associated diarrhea (AAD) caused by various antibiotics using real-world data and provide references for safe clinical applications. […] The incidence rate of AAD shows an upward trend due to the widespread use of antibiotics. AAD is frequently caused by various pathogenic bacteria, with Clostridium difficile (CD) being responsible for almost one-third of AAD cases. […] The excessive and inappropriate use of antibiotics and the emergence of novel antibiotics in recent years has resulted in an increase in the global incidence rate and severity of AAD. […] Our findings showed that patients aged 65 years or older had a higher ROR value, indicating that their probability of developing AAD was higher. […] Our comprehensive and systematic retrospective analysis of the FAERS database revealed a significant correlation between most post-marketing antibiotics and AAD and a different correlation within the same class, which has wider implications for antibiotic stewardship.

• #6 Prevalence and management of antibiotic associated diarrhea in general hospitals | BMC Infectious Diseases | Full Text

  https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-015-0869-0

  Reported prevalence ranges from 3.2 to 29.0%. […] Among all AAD cases, 10 to 20% are associated with C. difficile infection resulting in a mean estimated incidence in Belgian hospitals of 0.91 per 1000 hospital admissions in 2011. […] AAD prevalence varied also considerably between different age categories ranging from 5.9% in patients younger than 65 to 12.8% in patients over 85. […] In the univariate analysis, several demographic and clinical patients characteristics as well as previously reported risk factors and a particular type of ward were associated with the development of AAD. […] In the multivariate analysis the following characteristics were identified as independent risk factors for AAD: increased age, using more than one AB, increased ADL and disorientation scores, use of proton pump inhibitors, presence of decubitus and being hospitalized at a ward of nephrology. […] Our study showed that probiotics were very rarely used for the prevention of AAD with only 4 out of 743 AB users (0.5%) receiving a probiotic treatment before the occurrence of diarrhea.

• #7 Antibiotic-associated diarrhea – sboulardii – CNCM i-745

  https://www.saccharomycesboulardii.com/therapeutic-area/antibiotic-associated-diarrhea/

  The major consequence of antibiotic-induced changes to gut microbiota diversity is antibiotic-associated diarrhea (AAD).1 Diarrhea is the signal that there is an imbalance in the diversity of the microbiota in the gut.1 AAD generally occurs during antibiotic treatment, however diarrhea can occur 2 to 8 weeks after treatment has finished.4 […] Up to 35% of adults receiving antibiotics experience antibiotic-associated diarrhea (AAD).4 However, AAD occurs in a wide variety of populations including outpatients and residents of long-term care facilities4, with risk-associated factors such as a history of AAD, young or elderly age4 and co-morbidities.4 […] Factors associated with an increased risk of developing antibiotic-associated diarrhea: History of AAD, Age (elderly, young), Continuous tube-feeding, Antibiotics: oral administration; broad spectrum (cephalosporin, penicillin); biliary elimination; continuous antibiotic therapy; multiple antibiotics use.

• #8 Antibiotic Associated Colitis | Pediatric Surgery NaT

  https://www.pedsurglibrary.com/apsa/view/Pediatric-Surgery-NaT/829028/all/Antibiotic_Associated_Colitis

  C. difficile colitis (CDC) is increasing in the United States with rates of hospitalizations for treatment of CDC doubling between the years 2000 to 2010. […] In the United States, almost half a million patients were diagnosed with C. difficile infection by 2011 which accounts for approximately 30,000 deaths. […] In children, the incidence of infection has risen from 4.4 to 6.5 per 10,000 patient days from 2001 to 2006. […] Antibiotic use remains the key risk factor for CDC, but use of underlying bowel disease, gastrointestinal surgery, renal insufficiency and impaired humoral immunity have all been identified as risk factors. […] The epidemiologic studies in children are somewhat confounded by a high rate of colonization with C. difficile which is present in up to 70% of neonates compared to 3% of adults in the community and 20% in hospitalized patients.

• #9

  https://journals.lww.com/md-journal/fulltext/2019/03290/clostridium_difficile_associated_diarrhea.44.aspx

  More recently, PPIs have been implicated as a novel potential contributor to CDI. […] A recent meta-analysis of 50 studies involving 342,532 individuals showed a significant association between PPIs therapy and increased risk of CDI as compared with nonusers. […] The incidence of CDI is projected to increase, partly caused by greater spread of hypervirulent strains resistant to commonly used antibiotics. […] In addition to the broad-spectrum antimicrobial therapy and PPIs, the patient presented other risk factors leading to the development of CDAD, such as advanced age, previous hospitalization, underlying medical conditions, renal insufficiency, hypoalbuminemia, the presence of comorbidities. […] The case presented here concerned the impact of antibiotic and PPIs therapy on CDAD, indicating the importance of appropriate prescribing of acid-suppression therapy and high-risk antibiotics.

• #10 Risk factors, incidence, and morbidity associated with antibiotic-associated diarrhea in intensive care unit patients receiving antibiotic monotherapy

  https://www.wjgnet.com/2307-8960/full/v8/i10/1908.htm

  Older age, longer ICU stay time, proton pump inhibitor usage time, and duration of antibiotic increase the incidence of AAD in ICU patients receiving antibiotic monotherapy. […] The incidence of AAD in the intensive care unit (ICU) is growing, and it is becoming a serious condition. Therefore, prevention of AAD is essential for critically ill patients. […] Studies have shown that many factors, such as length of time of antibiotic use, combined use of antibiotics, older age, and serum albumin levels, are associated with the occurrence of AAD. […] Our study found that ICU stay time was a risk factor for AAD patients receiving antibiotic monotherapy. Previous studies have also shown that the longer the hospital stay, the higher the risk of AAD, and stays in a hospital for 2 wk are correlated with incidence of AAD. […] In conclusion, the incidence of AAD was high in ICU patients receiving antibiotic monotherapy, especially the use of the beta-lactam plus enzyme inhibitor antibiotics. Longer ICU stay time, duration of antibiotic, and duration of use of proton pump inhibitors increase the risk of AAD.

• #11 Case-Control Study of Antibiotic Use and Subsequent Clostridium difficile–Associated Diarrhea in Hospitalized Patients | Infection Control & Hospital Epidemiology | Cambridge Core

  https://www.cambridge.org/core/journals/infection-control-and-hospital-epidemiology/article/casecontrol-study-of-antibiotic-use-and-subsequent-clostridium-difficileassociated-diarrhea-in-hospitalized-patients/A79960BD1B7BA786B4A22CB5424B067D

  Objective. To determine which antibiotics increase or decrease the risk of Clostridium difficile-associated diarrhea (CDAD). […] The following antibiotics were associated with a significantly increased risk of acquiring CDAD: imipenem-cilastin (odds ratio [OR], 2.77), clindamycin (OR, 2.31), cefuroxime (OR, 2.16), moxifloxacin (OR, 1.88), ceftazidime (OR, 1.82), cefpodoxime (OR, 1.58), ceftizoxime (OR, 1.57), and ceftriaxone (OR, 1.49). Metronidazole and doxycycline were associated with a significantly reduced risk of CDAD (OR for metronidazole, 0.67; OR for doxycycline, 0.41). […] Some antibiotics appear to increase the risk of acquiring CDAD, notably clindamycin, third-generation cephalosporins, and carbapenems, whereas metronidazole and doxycycline appear to be protective, compared with other antibiotics.

• #12 Antibiotic-Associated Diarrhea – Gastrointestinal Infections – Intestinal Diseases – Gastrointestinal Diseases – Gastroenterology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.4.24.1.7.

  Antibiotic-associated diarrhea develops in the course of antimicrobial treatment or within 2 months of its discontinuation. […] The disease occurs in up to 30% of patients receiving antibiotics. […] The risk of antibiotic-associated diarrhea is higher in patients treated with cephalosporins, amoxicillin/clavulanic acid, ampicillin and other semisynthetic broad-spectrum penicillins, clindamycin, fluoroquinolones, patients receiving long-term treatment (4 weeks), and patients with multiple comorbidities.

• #13 Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections

  https://www.wjgnet.com/1007-9327/full/v22/i11/3078.htm

  The literature presents different results for proton-pump inhibitors, some showing significant risk, while others do not. […] The consequences of pediatric AAD for inpatients may include increased length of hospitalization and, for outpatients, parents may discontinue the inciting antibiotics due to the diarrhea, without fully treating the child for the inciting infection. […] Pediatric CDI consequences may include increased length-of-stays for inpatients, increased mortality, rates of surgery (colectomies), higher healthcare costs, and re-admissions to healthcare systems. […] The prevention of CDI is typically targeted at a common source of infection (healthcare facilities) and relies upon a multi-pronged approach of infection control programs, antibiotic stewardship and measures to support the hosts defenses.

• #14 Antibiotic-Associated Clostridium difficile Diarrhoea in Tertiary Care Hospital – A Study from Western India – Journal of Pure and Applied Microbiology

  https://microbiologyjournal.org/antibiotic-associated-clostridium-difficile-diarrhoea-in-tertiary-care-hospital-a-study-from-western-india/

  In our study, 18 out of 32 patients were on PPI. This could also have promoted the development of CDI in these patients. […] In countries with limited resources like India, besides the costly anaerobic culture techniques, lack of routine testing in patients with diarrhoea, usage of suboptimal testing methods creates more challenges the detection of CDI. […] In developing countries like India, knowledge of epidemiological patterns of CDI will help to develop useful strategies for the prevention and control of CDI.

• #15 Clostridium difficile–Associated Diarrhea | AAFP

  https://www.aafp.org/pubs/afp/issues/2005/0301/p921.html/1000

  Clostridium difficile infection is responsible for approximately 3 million cases of diarrhea and colitis annually in the United States. The mortality rate is 1 to 2.5 percent. […] Each year, C. difficile infection results in approximately 3 million cases of diarrhea and colitis in the United States. The case mortality rate is approximately 1 to 2.5 percent. […] The rate of C. difficile acquisition is estimated to be 13 percent in patients with hospital stays of up to two weeks and 50 percent in those with hospital stays longer than four weeks. […] The precipitating event for C. difficile colitis is disruption of the normal colonic microflora. This disruption usually is caused by broad-spectrum antibiotics. […] The risk of developing antibiotic-associated diarrhea more than doubles with longer than three days of antibiotic therapy (risk ratio: 2.28).

• #16 Clostridium difficile–Associated Diarrhea | AAFP

  https://www.aafp.org/pubs/afp/issues/2005/0301/p921.html/1000

  Most cases of C. difficile infection occur on days 4 through 9 of antibiotic therapy. […] The major host factors predisposing patients to the development of symptomatic C.difficile associated diarrhea include antibiotic therapy, advanced age, number and severity of underlying diseases, and faulty immune response to C. difficile toxins. […] Approximately 3 percent of patients develop severe C. difficile associated diarrhea. The mortality rate in these patients ranges from 30 to 85 percent. […] A multidiscipline antibiotic management program to restrict the inappropriate use of antibiotics (e.g., third-generation cephalosporins) can lead to a significant decrease in nosocomial infections caused by C. difficile. […] In particular, restriction of clindamycin use has been shown to decrease the incidence of C. difficile associated diarrhea.

• #17 C. diff: Facts for Clinicians | C. diff | CDC

  https://www.cdc.gov/c-diff/hcp/clinical-overview/index.html

  Clostridioides difficile (C. diff) is a common cause of antibiotic-associated diarrhea (AAD). It accounts for 15 to 25% of all events of AAD. […] EPA-registered disinfectants with a sporicidal claim have been successful in environmental surface disinfection of patient-care areas where surveillance and epidemiology indicate ongoing transmission of C. diff.

• #18 Predicting Clostridium difficile Toxin in Hospitalized Patients With Antibiotic-Associated Diarrhea | Infection Control & Hospital Epidemiology | Cambridge Core

  https://www.cambridge.org/core/journals/infection-control-and-hospital-epidemiology/article/predicting-clostridium-difficile-toxin-in-hospitalized-patients-with-antibioticassociated-diarrhea/AE548E382CFBD252054F1E52D1CE5946

  Clostridium difficile infection is implicated in 20%-30% of cases of antibiotic-associated diarrhea. […] Our results may help clinicians to predict the risk of CDAD in hospitalized patients with antibiotic-associated diarrhea, to guide careful, specific empirical therapy, and to direct early attention to infection control issues.

• #19 Antibiotic-Associated Diarrhea Beyond C. Difficile: A Scoping Review | Published in Journal of Brown Hospital Medicine

  https://bhm.scholasticahq.com/article/39745-antibiotic-associated-diarrhea-beyond-c-difficile-a-scoping-review

  Currently, studies estimate that there may be up to nearly half a million CDI cases every year, making it the most common bacterial cause of diarrhea in the United States. In spite of this number, a large proportion of AAD cases seem to be due to other causes. […] The likely pathogenesis of AAD includes alteration of intestinal microbiota, direct drug toxicity on the gut and development of a superinfection by a pathogenic microbe. […] Identifying the etiology and understanding the pathogenesis of AAD will help in improving healthcare and in reducing the economic burden. […] The review will also focus on the alteration of intestinal microflora and will provide a stronger basis for the use of non-pharmacologic therapies such as synbiotics as an effective therapeutic and preventive strategy.

• #20 Patient education: Antibiotic-associated diarrhea caused by Clostridioides difficile (Beyond the Basics) – UpToDate

  https://www.uptodate.com/contents/antibiotic-associated-diarrhea-caused-by-clostridioides-difficile-beyond-the-basics/print

  Antibiotic-associated diarrhea refers to diarrhea that develops in a person who is taking or recently took antibiotics. One of the most serious causes of antibiotic-associated diarrhea is infection with a bacterium called Clostridioides difficile. C. difficile infections are common, with approximately 500,000 cases per year in the United States. Infection is most common in people who are hospitalized, producing disease in more than 8 hospitalized patients per 1000 (0.9 percent) in 2008 in the United States. […] C. difficile infections have become more frequent, more severe, more difficult to treat, and more likely to recur after initial treatment. Although most people become infected with C. difficile in the hospital, community-acquired infection in patients who have not been hospitalized has also become more common. Community-acquired C. difficile infection can develop in the absence of any recent antibiotic use.

• #21 Clostridioides difficile infection – Wikipedia

  https://en.wikipedia.org/wiki/Clostridioides_difficile_infection

  C. difficile infection is estimated to occur in eight of 100,000 people each year. […] Among those who are admitted to hospital, it occurs in between four and eight people per 1,000. […] In 2011, it resulted in about half a million infections and 29,000 deaths in the United States. […] Due in part to the emergence of a fluoroquinolone-resistant strain, C. difficile-related deaths increased 400% between 2000 and 2007 in the United States. […] According to the CDC, „C. difficile has become the most common microbial cause of healthcare-associated infections in U.S. hospitals and costs up to $4.8 billion each year in excess health care costs for acute care facilities alone.”

• #22 Clostridioides difficile infection in adults: Epidemiology, microbiology, and pathophysiology – UpToDate

  https://www.uptodate.com/contents/clostridioides-difficile-infection-in-adults-epidemiology-microbiology-and-pathophysiology

  Antibiotic-associated diarrhea and colitis were well established soon after widespread use of antibiotics. In 1978, C. difficile was identified as the causative pathogen in the majority of cases of antibiotic-associated colitis; many early cases were attributed to clindamycin. Increasing use of penicillins and cephalosporins led to the implication of these antibiotic classes as precipitants as well. […] From 2003 to 2006, CDI was observed to be more frequent, severe, refractory to standard therapy, and more likely to relapse than previously described. These observations have been reported throughout North America and Europe and have been attributed, in part, to the emergence of a strain designated as BI, NAP1, or ribotype 027. This strain appears to be more virulent than other strains, which may be attributable to increased toxin production compared with previous strains.

• #23 Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by SHEA/IDSA

  https://www.idsociety.org/practice-guideline/clostridium-difficile/

  Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. […] Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. […] At a minimum, conduct surveillance for HO-CDI in all inpatient healthcare facilities to detect elevated rates or outbreaks of CDI within the facility (weak recommendation, low quality of evidence). […] Express the rate of HO-CDI as the number of cases per 10000 patient-days. Express the CO-HCFA prevalence rate as the number of cases per 1000 patient admissions (good practice recommendation).

• #24

  https://link.springer.com/article/10.1007/s10151-013-1081-0

  The occurrence of diarrhea and pseudomembranous colitis significantly increased, immediately following the introduction of widely available antibiotic treatments. […] The simple way in which the bacteria spread resulted in a significant increase in the number of infections, especially among hospitalized patients. […] The occurrence of more and more resistant strains resulted in the rapid spread of the bacteria to different departments, particularly the surgical wards and intensive care units but also many other medical wards. […] In a retrospective Canadian study, diarrhea and pseudomembranous colitis were identified as occurring 4 times more frequently in the general population in 2003 than in 1991 and 10 times more frequently than in 1938. […] Nosocomial infections are characterized by a much more severe form of the disease than in the general population, and a higher incidence of C. difficile infection has been noted, especially since 2000.

• #25 Antibiotic-Associated Diarrhea Beyond C. Difficile: A Scoping Review | Published in Journal of Brown Hospital Medicine

  https://bhm.scholasticahq.com/article/39745-antibiotic-associated-diarrhea-beyond-c-difficile-a-scoping-review

  C. difficile has been proven to cause AAD. C. difficile AAD is reported to be 4 and 60 times more common than C. perfringens or S. aureus, respectively. […] Although C. difficile is implicated in most AAD cases, other causes of Non-C. difficile Pathogen-specific AAD should also be considered. […] The role of Candida spp. in AAD has been debated since the 1950s and continues to be controversial. […] Only 40% of AAD can be accounted for by the above causes leaving a majority of AAD cases without an etiology. […] Non-microbial-causes of AAD tend to occur within 48-72 hours of starting antibiotics, tend to be less severe and usually are self-limiting. […] For better treatment options to be developed and the trend of increasing prevalence to be reversed, significant gains must be made in our understanding of the etiology and pathophysiology of AAD.

• #26 A worldwide systematic review and meta-analysis of bacteria related to antibiotic-associated diarrhea in hospitalized patients | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0260667

  Antibiotic-associated diarrhea (AAD) is a major hospital problem and a common adverse effect of antibiotic treatment. The aim of this study was to investigate the prevalence of the most important bacteria that cause AAD in hospitalized patients. […] The results of this study emphasize the need for a surveillance program, as well as timely public and hospital health measures in order to control and treat AAD infections. […] The prevalence of all four bacteria was higher in Europe compared to other continents. […] The highest resistance of C. difficile was estimated to ciprofloxacin and the lowest resistances were reported to chloramphenicol, vancomycin, and metronidazole. […] Limited studies have been reported on the most important bacteria related to AAD in different countries of the world, which may be due to lack of proper laboratory diagnostic tests. The analysis of the studies indicated that K. oxytoca, C. difficile and C. perfringens are the most prevalent among hospitalized patients with AAD in the world.

• #27 Antibiotic-Associated Clostridium difficile Diarrhoea in Tertiary Care Hospital – A Study from Western India – Journal of Pure and Applied Microbiology

  https://microbiologyjournal.org/antibiotic-associated-clostridium-difficile-diarrhoea-in-tertiary-care-hospital-a-study-from-western-india/

  Antibiotic-associated Clostridium difficile (CD) diarrhoea is one of the common causes of healthcare-acquired infection. […] In India, the prevalence of CDI is highly underestimated. This study aims to understand the prevalence, risk factors and comorbidities associated with CD diarrhoea in a tertiary care hospital from western India. […] The prevalence rate of CDI in our hospital was 5%. […] In developing countries, there is a lacuna in data on CDI. This could be due to the lack of awareness about the infection, poor capacity of the laboratory and insufficient mechanisms for surveillance. […] In spite of being a major agent responsible for AAD in the Europe and US, CD is majorly neglected in India. […] The prevalence rate in our study was found to be 5%. […] The reason for the lower prevalence could be due to the adhesion to the antibiotic policy adopted in our hospital and strict implementation of infection control practices.

• #28 Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by SHEA/IDSA

  https://www.idsociety.org/practice-guideline/clostridium-difficile/

  Stratify data by patient location to target control measures when CDI incidence is above national and/or facility reduction goals or if an outbreak is noted (weak recommendation, low quality of evidence). […] Use the same standardized case definitions (HO, CO-HCFA, CA) and rate expression (cases per 10000 patient-days for HO, cases per 1000 patient admissions for CO-HCFA) in pediatric patients as for adults (good practice recommendation). […] Conduct surveillance for HO-CDI for inpatient pediatric facilities but do not include cases 2 years of age (weak recommendation, low quality of evidence). […] Consider surveillance for CA-CDI to detect trends in the community (weak recommendation, low quality of evidence). […] The minimum surveillance that should be performed by all healthcare facilities is tracking of healthcare facility-onset (HO) cases, which will allow for detection of elevated rates or an outbreak within the facility.

• #29 Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by SHEA/IDSA

  https://www.idsociety.org/practice-guideline/clostridium-difficile/

  In the United States, CDI surveillance in healthcare facilities is conducted via the CDCs NHSN Multidrug-Resistant Organism and C. difficile Infection Module LabID Event Reporting. […] The prevalence of CO cases not associated with the facility (ie, defined in NHSN as present-on-admission with no discharge from the same facility within the previous 4 weeks) is also associated with HO-CDI. […] The incidence of CDI has increased overall, including increases in CDI among children in community and outpatient settings. […] The majority of pediatric studies have evaluated the incidence of CDI-related hospitalizations among multicenter cohorts of hospitalized children. […] The incidence of CDI has increased overall, including increases in CDI among children in community and outpatient settings.

• #30 Clostridioides difficile (C. diff) | Texas DSHS

  https://www.dshs.texas.gov/antibiotic-resistance-multidrug-resistant-organisms/clostridium-difficile-c-diff-infection

  Clostridioides difficile (C. diff) is a common cause of antibiotic-associated diarrhea (AAD). It accounts for 15-25% of all episodes of AAD. […] The risk for C. diff infections increases in patients with antibiotic exposure. […] In 2013, the Texas legislature funded C. difficile prevention activities. The goal is to improve identification in the laboratory, the use of antibiotics, and ways to prevent infection.

• #31 Probiotics for the prevention of antibiotic-associated adverse events in children – a systematic review to inform development of a core outcome set | bioRxiv

  https://www.biorxiv.org/content/10.1101/2020.01.27.920892v1.full-text

  Introduction Routine use of probiotics during antibiotic therapy in children remains a subject of discussion. […] Typical adverse events associated with antibiotic use include various gastrointestinal symptoms such as diarrhea, nausea, vomiting, and abdominal pain. Among them, antibiotic-associated diarrhea (AAD), often defined as ‘diarrhea that occurs in relation to antibiotic treatment with the exclusion of other etiologies’, is the best documented. […] In the largest observational study of 650 children published in 2003, the estimated AAD incidence in the pediatric outpatient population was 11%. […] In addition to estimates sometimes being derived from very small underpowered studies, one of the factors responsible for this heterogeneity in reported incidences could be the definition of AAD adopted by authors of different RCTs and the methods used for measurement of this outcome.

• #32 Probiotics for the prevention of antibiotic-associated adverse events in children – a systematic review to inform development of a core outcome set | bioRxiv

  https://www.biorxiv.org/content/10.1101/2020.01.27.920892v1.full-text

  According to the 2016 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines, some probiotic strains may be effective in AAD prevention. […] Results from this review suggest the need for a new core outcome set consisting of outcomes important for decision-making. […] The occurrence/incidence of diarrhea was reported as an outcome in 32 (89%) of the included studies and 20 (63%) of these studies reported it as a primary outcome. […] Surprisingly, among the 32 studies that reported data on diarrhea occurrence, the authors referred to their outcome as ‘antibiotic-associated diarrhea’ or ‘treatment-associated diarrhea’ in only 13 articles (39%). […] The most commonly assessed outcome from the ‘diarrhea’ domain was incidence data. […] Outcomes reported in studies on probiotic use in children receiving antibiotic therapy are characterized by substantial heterogeneity.

• #33 Clostridioides difficile infection in adults: Epidemiology, microbiology, and pathophysiology – UpToDate

  https://www.uptodate.com/contents/clostridioides-difficile-infection-in-adults-epidemiology-microbiology-and-pathophysiology

  Since 2005, CDI due to ribotype 078 has emerged in the Netherlands; the severity is similar to CDI caused by ribotype 027. Ribotype 078 appears to affect a younger patient population, is more frequently community associated, and is genetically similar to porcine isolates. Among 1366 Dutch patients hospitalized between 2006 and 2009, CDI was associated with a 2.5-fold increase in 30-day mortality.

• #34 Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by SHEA/IDSA

  https://www.idsociety.org/practice-guideline/clostridium-difficile/

  The potential role of asymptomatically colonized patients in transmission has recently been highlighted. […] The most important modifiable risk factor for the development of CDI is exposure to antibiotic agents. […] The disruption of the intestinal microbiota by antibiotics is long-lasting, and risk of CDI increases both during therapy and in the 3-month period following cessation of therapy. […] The attributable excess costs of CDI suggest a substantial burden on the healthcare system. […] The incidence of CDI increased significantly after the introduction of a sporicidal agent in a bone marrow transplant unit where there was a relatively high incidence of CDI. […] Daily sporicidal disinfection can be effective at reducing C. difficile environmental contamination and has been associated with reductions in CDI in outbreak settings in conjunction with other interventions to prevent CDI. […] The expert panel expresses its gratitude for thoughtful reviews of an earlier version by Curtis Collins, PharmD of the ASHP, Christopher Ohl, MD, and Ellie Goldstein, MD.

• #35 Antibiotic Associated Colitis | Pediatric Surgery NaT

  https://www.pedsurglibrary.com/apsa/view/Pediatric-Surgery-NaT/829028/all/Antibiotic_Associated_Colitis

  The NAP1 strain produces more toxin with a longer duration of effect than previous strains, leading to increasing morbidity and mortality. […] Community acquired infections have also increased during this millennium – particularly among children. […] Rates of antibiotic associated and C. difficile colitis (CDC) continue to rise in the era of modern medicine. […] The emergence of more virulent strains and an increase in community acquired infections have made previous low risk groups, including healthy children, more susceptible to serious disease.

• #36 Clostridioides (Clostridium) Difficile Colitis: Background, Etiology, Pathophysiology

  https://emedicine.medscape.com/article/186458-overview

  However, more recent studies have shown that C difficile can be the cause of diarrhea in community dwellers without previous hospitalization or antibiotic exposure; therefore, the diagnosis should be suspected in this population as well. […] The incidence of reported CDI infection continues to increase. In the 1980s, McFarland et al reported that 7% of patients admitted to a hospital and 28% of patients who were hospitalized had positive cultures for the organism. By the 1990s, the incidence of C difficile in hospitalized patients had risen to 30-40 per 100,000 population, and by 2005, to 84 per 100,000 population. […] New CDI populations have emerged, and studies have challenged the notion that C difficile is primarily a hospital infection, as more cases are being seen in the community.

• #37 Clostridioides (Clostridium) Difficile Colitis: Background, Etiology, Pathophysiology

  https://emedicine.medscape.com/article/186458-overview

  A population-based study from Olmsted County, Minnesota, demonstrated that 41% of the cases of CDI were community acquired and that the incidence of both community- and hospital-acquired C difficile increased significantly from 1991 to 2005. […] The worldwide increased incidence of CDI has been attributed to a variety of risk factors, including more elderly patients in the population, treatment resistance to fluoroquinolones, and the emergence of a newly discovered, more virulent strain of C difficile (BI/NAP1/027).

• #38 Probiotics for the Prevention of Antibiotic-Associated Diarrhea

  https://www.mdpi.com/2227-9032/10/8/1450

  Probiotics have been tested for a number of clinical uses. […] Probiotic research for the treatment of AAD is growing due to the increasing prevalence of AAD and the subsequent strain on the healthcare system. […] Studies have shown that a significant bulk of antibiotic use, especially in outpatient settings, may be inappropriate. […] Probiotics can be found in the form of yogurt, kefir, kombucha, tablets, capsules, etc. […] Probiotics have become quite accessible to the public, as one can find a source in most supermarkets, pharmacies, and supplement stores. […] The Canadian Agency for Drugs and Technologies in Health (CADTH) carried out an evaluation of probiotics for AAD in the pediatric population. […] A strong recommendation was made for the use of L rhamnosus GG and S. boulardii for preventing AAD in children.

• #39 Probiotics for the prevention of antibiotic-associated diarrhoea: a systematic review and meta-analysis | BMJ Open

  https://bmjopen.bmj.com/content/11/8/e043054

  Antibiotic-associated diarrhoea (AAD) has been reported in 5%35% of patients receiving antibiotics, varying with the type of antibiotics, the general health of the patient and their exposure to pathogens. […] The pooled analysis suggests that co-administration of probiotics with antibiotics reduces the risk of AAD in adults by 37% (risk ratio (RR)=0.63 (95% CI 0.54 to 0.73), p0.00001). […] Probiotics are effective for preventing AAD. […] Our results may not be applicable in clinical scenarios of lower baseline AAD risk. […] The principal finding of this review is that probiotics significantly reduce the risk of AAD in adults, with an NNT of 20 patients. […] This review found evidence supporting a moderate protective effect for probiotics in preventing AAD.

• #40

  https://journals.lww.com/jcge/fulltext/2021/07000/probiotics_for_the_prevention_of.4.aspx

  This updated meta-analysis suggested that using probiotics as early as possible during antibiotic therapy has a positive and safe effect on preventing AAD in adults. Further studies should focus on the optimal dosage and duration of probiotics to develop a specific recommendation. […] Probiotics reduced the incidence of AAD by 38% (pooled relative risk, 0.62; 95% confidence interval, 0.51-0.74). The protective effect of probiotics was still significant when grouped by reasons for antibiotics treatment, probiotic duration, probiotic dosage, and time from antibiotic to probiotic. However, there were no statistically significant increased adverse events in the probiotics group (relative risk, 1.00; 95% confidence interval, 0.87-1.14). […] Our meta-analysis indicated a reduction of AAD from 16% in placebo to 13% in probiotic-treated groups (RR, 0.62; 95% CI, 0.51-0.74; random-effects). Further subgroup analyses suggested that the protective effect was still significant when grouped by reasons for antibiotics treatment, probiotic duration, probiotic dosage, and time from antibiotic to probiotic. […] Our study suggests that using probiotics within 2 days during antibiotic treatment significantly reduces the incidence of AAD in adults and is safe.

• #41 Probiotics for the Prevention of Antibiotic-Associated Diarrhea in Outpatients—A Systematic Review and Meta-Analysis

  https://www.mdpi.com/2079-6382/6/4/21

  The results of this review point towards a protective effect of the use of probiotics as adjunct therapy to prevent antibiotic-associated diarrhea in outpatients of all ages. Data from 17 studies with a total of 3631 patients found that the use of a probiotic may reduce the risk of AAD by 51% (RR 0.49; 95% CI 0.36 to 0.66).

• #42 Clinical Study Designs for Antibiotic-Associated Diarrhea: Moving Forward – International Probiotics Association

  https://internationalprobiotics.org/home/clinical-study-designs-antibiotic-associated-diarrhea-moving-forward/

  AAD is a common side effect of many antibiotics, especially those that affect anaerobic bacteria. AAD occurs in about 5-39% of patients taking antibiotics. Incidence varies based on the vulnerability of patients. […] Clostridium difficile is reported to cause 10-20% of all cases of AAD and perhaps as high as 30%. […] In the case of AAD clinical research, probiotics are studied as an adjunct supplement or food product to prevent AAD. […] Difficulties in interpreting results of AAD studies have occurred due to several confounding factors, including the definition of diarrhea, course of antibiotic treatment, duration of treatment, concomitant medications, illness being treated or other concurrent illnesses, dietary changes (especially in hospital setting) and susceptibility of the probiotic to the antibiotics used in treatment, among many other variables.

• #43 Pathogenesis of antibiotic-associated diarrhea (AAD)—a systematic review

  https://digitalcommons.library.tmc.edu/dissertations/AAI1515607/

  A common complication of antibiotic use is the development of diarrheal illness. Currently less than 33% of AAD cases can be attributable to Clostridium difficile leaving a large number of cases undiagnosed and poorly treated. Although the pathogenesis of Clostridium difficile infection (CDI) has been well documented, the role of other putative microbial etiologies (Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida species) and their pathogenic mechanisms in AAD has been unclear. […] This review provides a comprehensive and systematic approach to the existing data on AAD and includes concise descriptions of the pathogenesis of CDI and non-CDI AAD in the form of figures.

• #44 Probiotics for the Prevention of Antibiotic-Associated Diarrhea

  https://www.mdpi.com/2227-9032/10/8/1450

  The guidelines for the use of probiotics for the treatment of AAD, including that associated with a C. difficile infection, are varied across the world. […] The potential to alter these microbial ecosystems offers great hope for new preventative treatment options for antibiotic-associated diarrhea and other gastrointestinal disorders.

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