fidaxomicin and Cross-Infection

Despite the large amount of scientific publications exploring the epidemiology and the clinical management of Clostridium difficile (CD) infection, some issues remain unsolved or need further studies. The aim of this review is to give an update on the hot topics on CD prevention, including stewardship programs, and on the non-microbiological treatment of CD infection. Areas covered: This article will review the importance of minimizing the CD spore shedding in the healthcare environment for potentially reducing CD transmission. Moreover, antimicrobial stewardship programs aimed to reduce CD incidence will be reviewed. Finally, new strategies for reducing CD infection recurrence will be described. Expert commentary: Besides the basic infection control and prevention practices, including hand hygiene, contact isolation and environmental cleaning, in the prevention of CD infection other issues should be addressed including minimizing the spread of CD in the healthcare setting, and implementing the best strategy for reducing CD infection occurrence, including tailored antimicrobial stewardship programs. Regarding new advancements in treatment and management of CDI episodes, non-antimicrobial approaches seem to be promising in reducing and managing recurrent CD infection.

Topics: Aminoglycosides; Anti-Bacterial Agents; Antimicrobial Stewardship; Clostridioides difficile; Clostridium Infections; Cross Infection; Fecal Microbiota Transplantation; Fidaxomicin; Hand Hygiene; Humans; Incidence; Infection Control; Probiotics; Spores, Bacterial

Clostridium difficile is the leading cause of antibiotic associated infectious nosocomial diarrhoea. Limited number of new pharmaceutical products have been developed and registered in the past decades for the treatment of Clostridium difficile infection. The available scientific evidence is limited and hardly comparable.. To analyse the clinical efficacy and safety of metronidazole, vancomycin and fidaxomicin in the therapy of Clostridium difficile infection.. Systematic review and meta-analysis of the literature data.. Meta-analysis of literature data showed no significant difference between these antibiotics in clinical cure endpoint (odss ratios: fidaxomicin vs. vancomycin 1.19; vancomycin vs. metronidazol 1.69 and fidaxomicin vs. metronidazol 2.00). However, fidaxomicin therapy was significantly more effective than vancomicin and metronidazol in endpoints of recurrence and global cure (odds ratios: fidaxomicin vs. vancomycin 0.47; vancomycin vs. metronidazol 0.91 és fidaxomicin vs. metronidazol 0.43). There was no significant difference between fidaxomicin, vancomycin and metronidazole in safety endpoints.. Each antibiotic similarly improved clinical cure. Fidaxomicin was the most effective therapeutic alternative in lowering the rate of recurrent Clostridium difficile infections.. Bevezetés: A Clostridium difficile az antibiotikum asszociálta hasmenések leggyakoribb kórokozója, aminek kezelésére az elmúlt évtizedekben kevés új szer került kifejlesztésre, és a tudományos bizonyítékok korlátozott mértékben és nehezen összehasonlítható módon állnak rendelkezésre. Célkitűzés: A Clostridium difficile okozta fertőzés terápiájának hatásossági és biztonságossági végpontjainak elemzése a metronidazol, vancomycin és a fidaxomicin alkalmazása esetén. Módszer: A szakirodalom áttekintése és az eredmények metaanalízise. Eredmények: A metaanalízis szerint a klinikai gyógyulás végpontban nincs szignifikáns különbség a három terápia között (esélyarányok: fidaxomicin vs. vancomycin 1,19, vancomycin vs. metronidazol 1,69 és fidaxomicin vs. metronidazol 2,00). A rekurrencia és a globális gyógyulás végpontokban a fidaxomicin szignifikánsan hatásosabbnak bizonyult, mint a vancomycin és a metronidazol (esélyarányok: fidaxomicin vs. vancomycin 0,47, vancomycin vs. metronidazol 0,91 és fidaxomicin vs. metronidazol 0,43). A biztonságossági végpontokat tekintve nem volt szignifikáns különbség az antibiotikumok között. Következtetések: A klinikai gyógyulás esetében a vizsgált antibiotikumok hatásossága hasonló. A rekurrens fertőzések megakadályozásában jelenleg a fidaxomicin a leghatásosabb terápiás alternatíva. Orv. Hetil., 2013, 154, 890–899.

Topics: Aminoglycosides; Anti-Bacterial Agents; Clostridioides difficile; Cross Infection; Diarrhea; Enterocolitis, Pseudomembranous; Fidaxomicin; Humans; Metronidazole; Treatment Outcome; Vancomycin

Clostridium difficile is an intestinal infection associated with antibiotic use, commonly seen in patients with chronic medical issues. The purpose of this review is to discuss the association of C. difficile-associated diarrhea with use of proton pump inhibitors.. Multiple medical factors predispose patients to C. difficile-associated diarrhea. Proton pump inhibitors, commonly used for gastric acid suppression, have been shown to have an association with C. difficile-associated diarrhea in both the outpatient and hospital setting. C. difficile-associated diarrhea also has been reported in the pediatric age range linked with proton pump inhibitor use.. An association exists between C. difficile infection and proton pump inhibitor use. Treatment options exist for C. difficile-associated diarrhea, although judicious use of proton pump inhibitors and antibiotics, emphasis on hand washing, and appropriate use of patient isolation should be implemented as well.

Topics: Adolescent; Aminoglycosides; Anti-Bacterial Agents; Child; Child, Preschool; Clostridioides difficile; Clostridium Infections; Cross Infection; Diarrhea; Female; Fidaxomicin; Hand Disinfection; Humans; Male; Patient Education as Topic; Proton Pump Inhibitors; Risk Factors

The incidence of Clostridium difficile has doubled over the past 15 years, and rising mortality rates associated with this infection have followed in its wake. C. difficile infection (CDI) has supplanted methicillin-resistant Staphylococcus aureus as the major cause of nosocomial infection. An insufficient response rate to currently available CDI therapies has prompted the search for new and alternative treatment modalities for this disease. The investigational pipeline includes evaluation of new antimicrobial agents that exhibit good activity against C. difficile without altering normal gut flora, C. difficile toxin-absorbing compounds, and preformed antibodies and vaccines against C. difficile toxin. In two robust clinical trials comparing fidaxomicin to vancomycin in the treatment of CDI, treatment with fidaxomicin demonstrated a superior global cure (cure without recurrence) rate compared with the current gold standard, vancomycin. Fidaxomicin, the first of a new class of macrocyclic antimicrobial agents, represents an advance in the management of CDI.

Topics: Actinomycetales; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; Clinical Trials, Phase III as Topic; Clostridioides difficile; Clostridium Infections; Cross Infection; DNA-Directed RNA Polymerases; Fidaxomicin; Gastrointestinal Tract; Humans; Microbial Sensitivity Tests; Nucleic Acid Synthesis Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome; Vancomycin

Clostridium difficile infection is now a major concern throughout the developed world and its occurrence is a consequence of broad-spectrum antibiotic therapy primarily in the elderly in-patient population and high spore loads in hospitals in these regions. With the emergence of a hypervirulent, endemic strain, more severe disease is being recognized and is occurring in previously considered unusual patient groups. Vancomycin and metronidazole are the current mainstays for therapy of severe and nonsevere disease, respectively. Relapse is a major concern, with treatment options for these cases often difficult. Any new drug must be better than vancomycin for severe disease with fewer relapses. Fidaxomicin, a macrocyclic RNA polymerase inhibitor, has a narrow spectrum of activity, which is almost C. difficile specific. This drug appears to have a higher clinical cure rate than vancomycin, and fewer patients relapse following initial treatment. From the results of a recent Phase III trial, fidaxomicin appears to be an extremely promising drug for treating C. difficile infection and preventing relapses.

Topics: Aged; Aminoglycosides; Anti-Bacterial Agents; Bacterial Proteins; Clinical Trials as Topic; Clostridioides difficile; Cross Infection; DNA-Directed RNA Polymerases; Enterocolitis, Pseudomembranous; Fidaxomicin; Humans; Secondary Prevention; Treatment Outcome; Vancomycin

Fidaxomicin is sporicidal and may be associated with a reduced time to resolution of diarrhoea when used to treat patients with Clostridium difficile infection (CDI). This study investigated whether fidaxomicin for treatment of all patients with CDI reduced C. difficile environmental contamination. Surfaces in the rooms of 66 hospitalized patients treated with metronidazole and/or vancomycin and 68 hospitalized patients treated with fidaxomicin were sampled. Patients treated with fidaxomicin were less likely to contaminate their environment (25/68, 36.8%) than patients treated with metronidazole and/or vancomycin (38/66 57.6%) (P = 0.02). Treatment with fidaxomicin was associated with reduced environmental contamination with C. difficile.

Topics: Adult; Aminoglycosides; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Cross Infection; Diarrhea; Environmental Microbiology; Female; Fidaxomicin; Hospitalization; Humans; Male; Metronidazole; Vancomycin

Clostridium difficile infections remain a problem especially for patients in the intensive care unit. The fact that C. difficile infections are strongly associated with antibiotic therapy calls for more caution in the use of antibiotics, especially in patients with a high risk of developing C. difficle infections. Severe infections and recurrent episodes are usually difficult to manage and therapeutic options are often limited. The method of stool transplantation, though not new, has received more attention in recent years, with studies showing stool transplantation to be a promising and easy method which has high clinical cure rates even for recurrent C. difficile infections. However, more randomised and controlled trials are needed to further study the efficacy of stool transplantation in patients with C. difficile infection.

Topics: Aminoglycosides; Biodiversity; Cause of Death; Colonoscopy; Cross Infection; Disinfection; Enterocolitis, Pseudomembranous; Feces; Fidaxomicin; Hospital Mortality; Humans; Metronidazole; Patient Readmission; Prognosis; Recurrence; Tomography, X-Ray Computed; Transplantation; Vancomycin

Clostridioides difficile is the leading cause of nosocomial infections and a worldwide urgent public health threat. Without doubt, there is an urgent need for new effective anticlostridial agents due to the increasing incidence and severity of C. difficile infection (CDI). The aim of the present study is to investigate the in vivo efficacy of auranofin (rheumatoid arthritis FDA-approved drug) in a CDI mouse model and establish an adequate dosage for treatment. The effects of increased C. difficile inoculum, and pre-exposure to simulated gastric intestinal fluid (SGF) and simulated intestinal fluid (SIF), on the antibacterial activity of auranofin were investigated. Auranofin's in vitro antibacterial activity was stable in the presence of high bacterial inoculum size compared to vancomycin and fidaxomicin. Moreover, it maintained its anti-C. difficile activity after being exposed to SGF and SIF. Upon testing in a CDI mouse model, auranofin at low clinically achievable doses (0.125 mg/kg and 0.25 mg/kg) significantly protected mice against CDI with 100% and 80% survival, respectively. Most importantly, auranofin (0.125 mg/kg and 0.25 mg/kg) significantly prevented CDI recurrence when compared with vancomycin. Collectively, these results indicate that auranofin could potentially provide an effective, safe and quick supplement to the current approaches for treating CDI.

Topics: Animals; Anti-Bacterial Agents; Arthritis, Rheumatoid; Auranofin; Clostridioides difficile; Clostridium Infections; Cross Infection; Drug Repositioning; Fidaxomicin; Gastrointestinal Tract; Humans; Mice; Microbial Sensitivity Tests; Recurrence; Vancomycin

Topics: Animals; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Cross Infection; Disease Models, Animal; Feces; Female; Fidaxomicin; Gastrointestinal Microbiome; Mice; Mice, Inbred C57BL; RNA, Ribosomal, 16S; Vancomycin

For surgeons the early identification of patients with clostridium difficile infections (CDI) is important, because the incidence and virulence of this potentially life-threatening disease are increasing.. The aim of this study was to describe the frequency of CDI among surgical patients, to analyze which treatment was successful and to define which factors were associated with mortality.. A retrospective analysis of patients with CDI was performed.. From January 2004 to June 2012 the overall incidence of CDI among all departments at the St. Josef Hospital, Ruhr University Bochum was 0.6 % (1669 out of 301,919 patients). In 2004 the number of surgical patients with CDI was 1 which increased to 41 in 2011. Before the diagnosis of CDI was made 84 % (151 out of 179) of patients had received an antibiotic treatment. Conservative management of CDI was performed with metronidazole in 75 % (134 out of 179), 60 % (107 out of 179) received vancomycin, while 44 % (79 out of 179) received a combination of metronidazole and vancomycin, tygecycline or fidaxomidin. The overall mortality was 7 % (12 out of 179). There was a significant association with mortality for patients with sepsis, readmission to the intensive care unit (ICU), requirement for vasopressor therapy and intubation with mechanical ventilation. In 4 % of patients (7 out of 179) colectomy was carried out. Despite maximum intensive care management, 86 % (6 out of 7) of patients who underwent colectomy ultimately died.. Although conservative management is successful for most patients with CDI, the mortality is high for patients who require intensive care management secondary to CDI. Mortality after colectomy for CDI is almost 100 %, mostly because the operation is usually only performed as a last resort in patients with sepsis. The most important risk factor for CDI is a prior antibiotic therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Clostridioides difficile; Cohort Studies; Cross Infection; Cross-Sectional Studies; Drug Therapy, Combination; Enterocolitis, Pseudomembranous; Female; Fidaxomicin; Germany; Hospital Mortality; Humans; Incidence; Intensive Care Units; Male; Metronidazole; Middle Aged; Minocycline; Patient Readmission; Retrospective Studies; Survival Rate; Tigecycline; Vancomycin; Young Adult

The objective of this study was to determine the activity of fidaxomicin and comparator antimicrobials against Clostridium difficile isolated from patients with C. difficile infection (CDI) in Australian hospitals and in the community.. One private and one public laboratory from five states in Australia submitted a total of 474 isolates/PCR-positive stool samples during three collection periods in August-September 2013 (n = 175), February-March 2014 (n = 134) and August-September 2014 (n = 165). Isolate identification was confirmed by selective culture for C. difficile and a proportion of isolates from each state were characterized by PCR for toxin genes and PCR ribotyping. MICs of fidaxomicin and eight comparator antimicrobials were determined for all isolates using agar methodology.. Site collection yielded 440 isolates of C. difficile and PCR revealed a heterogeneous strain population comprising 37 different PCR ribotypes (RTs), 95% of which were positive for tcdA and tcdB (A+B+). The most common RTs were 014 (29.8%) and 002 (15.9%). Epidemic RT 027 was not identified; however, small numbers of virulent RTs 078 and 244 were found. Resistance to vancomycin, metronidazole and fidaxomicin was not detected and resistance to moxifloxacin was very low (3.4%). Fidaxomicin showed potent in vitro activity against all 440 isolates (MIC50/MIC90 0.03/0.12 mg/L) and was superior to metronidazole (MIC50/MIC90 0.25/0.5 mg/L) and vancomycin (MIC50/MIC90 1/2 mg/L).. These data confirm the potent in vitro activity of fidaxomicin against C. difficile. Moreover, this study provides an important baseline for ongoing long-term surveillance of antimicrobial resistance and prospective tracking of prominent and emerging strain types.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Australia; Child; Child, Preschool; Clostridioides difficile; Clostridium Infections; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Epidemiological Monitoring; Female; Fidaxomicin; Humans; Infant; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction; Prospective Studies; Ribotyping; Young Adult

Clostridium difficile infection (CDI) and Klebsiella pneumoniae carbapenemase producing-Klebsiella pneumoniae (KPC-Kp) bloodstream infection (BSI) are emerging health-care associated (HCA) diseases of public health concern, in terms of morbidity, mortality, and insufficient response to antibiotic therapy. Both agents can be acquired in the hospital but clinical disease can develop in a community setting, after discharge. We report here a putative link between the above-mentioned healthcare associated infections that appeared as a dramatic community onset disease with a fulminant fatal outcome.. We describe the case of a 63 year old man affected by severe CDI. Even though the patient underwent 72 hours of standard CDI antibiotic treatment, the clinical course was complicated by toxic megacolon and KPC-Kp BSI. The patient died 24 hours after total colectomy.. The impact of HCA-BSIs in complicating CDI is still unknown. Intestinal inflammatory injury and disruption of intestinal flora by standard antibiotic treatment could be responsible for promoting difficult-to-treat infections in CDI. By preserving intestinal flora, Fidaxomicin could have a crucial role in preventing BSIs complicating severe CDI.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteremia; Bacterial Proteins; beta-Lactamases; Clostridioides difficile; Clostridium Infections; Coinfection; Cross Infection; Fatal Outcome; Fidaxomicin; Hospitals; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged

In November 2008, a study was performed with support from the European Centre for Disease Prevention and Control (ECDC) to obtain an overview of Clostridium difficile infections (CDIs) in European hospitals. A collection of 398 C. difficile isolates obtained from this hospital-based survey was utilized to identify antimicrobial susceptibility patterns of common C. difficile PCR ribotypes across Europe.. The MICs of three approved therapeutic agents (vancomycin, metronidazole and fidaxomicin) and LFF571 (a novel semi-synthetic thiopeptide antibiotic) were determined by the agar dilution method.. MICs of fidaxomicin and LFF571 were in general 2-4-fold lower than those of vancomycin and metronidazole. Isolates belonging to clade 2, including the hypervirulent ribotype 027, had one-dilution higher MIC50 and MIC90 values for fidaxomicin and metronidazole, whereas similar MIC values were observed for vancomycin and LFF571. Isolates belonging to C. difficile PCR ribotype 001 were more susceptible to fidaxomicin than other frequently found PCR ribotypes 014/020 and 078. Six isolates from three different countries had a metronidazole MIC of 2 mg/L. Four of the six isolates were characterized as PCR ribotype 001.. There was no evidence of in vitro resistance of C. difficile to any of the four agents tested. However, the results suggest type-specific differences in susceptibility for the treatment agents we investigated. Continuous surveillance of C. difficile isolates in Europe is needed to determine the possible clinical implications of ribotype-specific changes in susceptibility to therapeutic agents.

Topics: Aminoglycosides; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Cross Infection; Enterocolitis, Pseudomembranous; Europe; Fidaxomicin; Humans; Metronidazole; Microbial Sensitivity Tests; Multilocus Sequence Typing; Polymerase Chain Reaction; Ribotyping; Thiazoles; Treatment Outcome; Vancomycin

Topics: Aminoglycosides; Anti-Bacterial Agents; Clostridioides difficile; Colectomy; Combined Modality Therapy; Cross Infection; Disease Notification; Enterocolitis, Pseudomembranous; Fidaxomicin; Metronidazole; Probiotics; Vancomycin; Virulence

Topics: Aged; Aminoglycosides; Anti-Bacterial Agents; Carcinoma, Squamous Cell; Clostridioides difficile; Critical Care; Cross Infection; Enterocolitis, Pseudomembranous; Female; Fidaxomicin; Humans; Intubation, Gastrointestinal; Mandibular Neoplasms; Mouth Neoplasms; Necrosis; Shock, Septic

Topics: Aminoglycosides; Anti-Bacterial Agents; Cross Infection; Drug Approval; Drug Industry; Enterocolitis, Pseudomembranous; Fidaxomicin; United States; United States Food and Drug Administration

Agar dilution antimicrobial susceptibility testing (CLSI, M11-A7, 2007) performed for 208 toxin-producing clinical isolates of Clostridium difficile resulted in OPT-80 MICs ranging from 0.06 to 1 microg/ml, with 90% of the isolates inhibited by a concentration of 0.5 microg/ml. The in vitro activity of OPT-80 was independent of the susceptibilities of isolates to nine other antimicrobial agents.

Topics: Anti-Bacterial Agents; Bacterial Toxins; Clostridioides difficile; Cross Infection; Enterocolitis, Pseudomembranous; Glycosides; Humans; In Vitro Techniques; Microbial Sensitivity Tests