Treatment Of Clostridium Difficile Infection Research Articles

Transcriptomic analysis indicates the mode of action of the novel antibiotic MGB-BP-3 against Staphylococcus aureus

MGB-BP-3 (MGB) is a novel synthetic antibiotic inspired by Distamycin – a natural product that is capable of binding to the minor groove of DNA. MGB has a high bactericidal activity against a broad range of Gram-positive bacteria without the toxicity associated with the natural products that it was inspired by. Its oral formulation, developedfor the treatment of Clostridium difficile infections, is currently progressing through a phase 2 clinical trial. This study investigatesthe mode of action of this novel antibiotic. To allow better understanding of MGB’s mode of action, RNA-Seq analysis was undertaken on S. aureus following challenge with 0.5 x MIC (0.1 µg ml−1) MGB-BP-3. Triplicate samples of RNA were extracted at 10 min after challenge. RNA-Seq analysis identified 698 transcripts showing significant changes in expression profile, which were confirmed by quantitative RT-PCR. Amongst these, 62 essential genes showed transcriptional arrest. Glycolysis, pentose phosphate pathway and the TCA cycle were affected. In addition, biosynthesis of nucleotides and certain amino acids were altered and Biolog phenotype arrays were performed in the presence of MGB to confirm this. DNA binding assays demonstrated MGB binding to intergenic regions upstream of strongly down-regulated essential genes (mraY and dnaD). Attempts to evolve resistance to MGB have so far been unsuccessful unlike with the rifampicin control. In conclusion our findings are consistent with a bactericidal mode of action of MGB at the transcriptional level of multiple essential genes.

Treatment and Prevention of Recurrent Clostridium difficile Infection with Functionalized Bovine Antibody-Enriched Whey in a Hamster Primary Infection Model.

Toxin-induced Clostridium difficile infection (CDI) is a major disease characterized by severe diarrhea and high morbidity rates. The aim with this study was to develop an alternative drug for the treatment of CDI. Cows were repeatedly immunized to establish specific immunoglobulin G and A titers against toxins A (TcdA) and B (TcdB) and against C. difficile cells in mature milk or colostrum. The effect of three different concentrations of anti-C. difficile whey protein isolates (anti-CD-WPI) and the standard of care antibiotic vancomycin were investigated in an animal model of CD infected hamsters (6 groups, with 10 hamsters each). WPI obtained from the milk of exactly the same cows pre-immunization and a vehicle group served as negative controls. The survival of hamsters receiving anti-CD-WPI was 50, 80 and 100% compared to 10 and 0% for the control groups, respectively. Vancomycin suppressed the growth of C. difficile and thus protected the hamsters at the time of administration, but 90% of these hamsters nevertheless died shortly after discontinuation of treatment. In contrast, the surviving hamsters of the anti-CD-WPI groups survived the entire study period, although they were treated for only 75 h. The specific antibodies not only inactivated the toxins for initial suppression of CDI, but also provoked the inhibition of C. difficile growth after discontinuation, thus preventing recurrence. Oral administration of anti-CD-WPI is a functional therapy of CDI in infected hamsters for both primary treatment and prevention of recurrence. Thus, anti-CD-WPI could address the urgent unmet medical need for treating and preventing recurrent CDI in humans.

Vancomycin Enema in the Treatment of Clostridium difficile Infection.

Background: Current guidelines for the treatment of Clostridium difficile infections (CDIs) recommend vancomycin enemas for patients with adynamic ileus. There is significant variability in guideline recommendations for vancomycin dose and enema volume and whether a retention enema should be used. The most recent (2017) guidelines from the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America recommend rectal instillation of 500 mg of vancomycin in 100 mL of physiologic saline every 6 hours as a retention enema. Methods: Published studies regarding vancomycin enema use in CDI (1990-present) were reviewed to compare drug dose, volume, and whether a retention enema was used in order to determine the efficacy and make recommendations for optimal dosing. Results: Case series with higher vancomycin dose, higher enema volume, and use of retention enema demonstrated greater efficacy. Use of smaller volumes and lower doses (100 mL; 125-250 mg q 6 hours) demonstrated no efficacy of intracolonic vancomycin. Conclusion: We recommend revision of the current CDI guideline recommendations for patients with adynamic ileus to the following: Vancomycin per rectum (500 mg in a volume of 500 mL q 6 hours) by retention enema (18F Foley catheter with 30-cc balloon inserted into the rectum, balloon inflated, solution instilled, and catheter clamped for 60 minutes) for optimal efficacy.

Clostridium difficile. A review on an emerging infection.

Clostridium difficile causes antibiotic-associated diarrhoea and pseudomembranous colitis. The main virulence factors of C. difficile are the toxins A (TcdA) and B (TcdB). A third toxin, binary toxin (CDT), which pathogenetic role had been remained largely overlooked until few years ago, nowadays have been detected in 5%-23% of strains. C. difficile has spread around world. Clostridium difficile infection (CDI) is one of the most common health-care associated infections and a significant cause of morbidity and mortality among older adult hospitalized patients. Diagnosis of CDI is often difficult and has a substantial impact on the management of patients with disease. It is usually based on a clinical history of recent antimicrobial usage and diarrhoea in combination with laboratory tests. Although the conventional methods are crucial for the diagnosis and the subsequent treatment of CDI, a timely laboratory diagnosis is essential for the detection of toxigenic strains providing either to an effective and immediately treatment or to the prevention of further disease transmission. In this review we provide general recommendations for testing of samples collected from patients with suspected CDI.

Cadazolid for the treatment of Clostridium difficile infection: results of two double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials

Cadazolid is a novel quinoxolidinone antibiotic developed for treating Clostridium difficile infection. We aimed to investigate the safety and efficacy of cadazolid compared with vancomycin in patients with C difficile infection. IMPACT 1 and IMPACT 2 were identically designed, multicentre, double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials. IMPACT 1 was done in Australia, Brazil, Canada, France, Germany, Italy, the Netherlands, Peru, Poland, Romania, Spain, and the USA, and IMPACT 2 was done in Argentina, Belgium, Brazil, Canada, Chile, Croatia, Czech Republic, Greece, Hungary, Israel, Romania, Slovakia, South Korea, the UK, and the USA. Patients (aged 18 years or older) with mild-to-moderate or severe C difficile infection (diarrhoea with positive glutamate dehydrogenase and toxin A or B enzyme immunoassays) were randomly assigned (1:1) with a randomisation list stratified by centre and C difficile infection episode type (block size of four), and allocation was masked to investigators and participants. Patients received either oral cadazolid 250 mg twice daily with vancomycin-matching placebo capsule four times daily or oral vancomycin 125 mg four times a day with cadazolid-matching placebo suspension twice daily for 10 days, with 30 days of follow-up. The primary efficacy outcome was non-inferiority (margin -10%) of cadazolid versus vancomycin for clinical cure in the modified intention-to-treat and per-protocol populations. Clinical cure was defined as resolution of diarrhoea with no additional treatment for C difficile infection. These trials are registered with ClinicalTrials.gov, numbers NCT01987895 (IMPACT 1) and NCT01983683 (IMPACT 2). Between March 28, 2014, and March 24, 2017, for IMPACT 1, and Dec 13, 2013, and May 2, 2017, for IMPACT 2, 1263 participants were randomly assigned to receive cadazolid (306 in IMPACT 1 and 298 in IMPACT 2) or vancomycin (326 in IMPACT 1 and 311 in IMPACT 2). In the modified intention-to-treat population in IMPACT 1, 253 (84%) of 302 had clinical cure in the cadazolid group versus 271 (85%) of 318 in the vancomycin group. In IMPACT 2, 235 (81%) of 290 versus 258 (86%) of 301 had clinical cure. In the per-protocol population, 247 (88%) of 282 versus 264 (92%) of 288 had clinical cure in IMPACT 1 and 214 (87%) of 247 versus 237 (92%) of 259 in IMPACT 2. Non-inferiority for clinical cure to vancomycin was shown in IMPACT 1 but not in IMPACT 2 (IMPACT 1 treatment difference: -1·4 [95% CI -7·2 to 4·3] for modified intention to treat and -4·1 [-9·2 to 1·0] for per protocol; IMPACT 2: -4·7 [-10·7 to 1·3] for modified intention to treat and -4·9 [-10·4 to 0·6] for per protocol). The safety and tolerability profiles of the two antibiotics were similar. Cadazolid was safe and well tolerated but did not achieve its primary endpoint of non-inferiority to vancomycin for clinical cure in one of two phase 3 C difficile infection trials. Therefore, further commercial development of cadazolid for C difficile infection is unlikely. Actelion Pharmaceuticals.

A 14-day repeat dose oral gavage range-finding study of a first-in-class CDI investigational antibiotic, in rats

Drug resistant bacteria are winning the fight over antibiotics with some bacteria not responding to any antibiotics, threatening modern medicine as we know it. The development of new, effective and safe antibiotics is critical for addressing this issue. Ramizol, a first-in-class styrylbenzene based antibiotic, is an investigational drug indicated for Clostridium difficile infections (CDI). The objective of this range-finding study was to evaluate the potential general toxicity (based on toxicological endpoints selected) and toxicokinetics of Ramizol in male and female rats that may arise from repeated exposure via oral gavage over a test period of at least 14 days at doses of 50 mg/kg, 500 mg/kg and 1500 mg/kg. There were no mortalities in this study and no Ramizol-related clinical observations. Additionally, there were no changes in mean body weight, body weight gain, food consumption or food efficiency for male and female rats attributable to Ramizol administration. The observed pharmacokinetic behavior showed the presence of Ramizol in plasma at 24 hours post-dosing combined with increasing AUC(0–24) values during the course of this study in groups administered 1500 mg/kg/day, which suggests that at least some dosing groups will show accumulation of compound during repeated dose studies. These toxicology results have shown Ramizol is well-tolerated at very high concentrations in rats and support the further drug development of Ramizol as a first-in-class antibiotic for the treatment of CDI.

Effect of using fidaxomicin on recurrent Clostridium difficile infection

Fidaxomicin is a macrocyclic antibiotic licensed for treating Clostridium difficile infection (CDI). In the UK, fidaxomicin is often reserved for severe CDI or recurrences. At Queen Elizabeth Hospital Birmingham, all courses of fidaxomicin during 2017/2018 were reviewed. Thirty-eight patients received fidaxomicin, of which 64% responded to treatment when fidaxomicin was given during the first episode of mild CDI. Conversely, all patients with recurrent CDI failed treatment with fidaxomicin. There were mixed results for the use of fidaxomicin for severe CDI, with only 42% of patients responding. These results suggest that fidaxomicin is best suited as a treatment for mild CDI during a patient's first episode.

Recurrent Clostridium difficile infection is associated with treatment failure and prolonged illness in cancer patients

Cancer patients are susceptible to recurrent Clostridium difficile infection (CDI) that is increasing globally, necessitating new approaches to prevent fatal consequences. We examined the clinical characteristics of cancer patients with recurrent CDI (RCDI). A retrospective review of cancer patients with C. difficile-positive test between January 2015 and May 2017 was carried out. CDI was defined as diarrhea and toxigenic C. difficile detection in the stool by nucleic acid amplification test and enzyme immunoassay. Patients having two CDI episodes were categorized as single recurrent CDI (SRCDI), and those having three or more CDI episodes were categorized as multiple recurrent CDI (MRCDI). Treatment failure was defined as the requirement of antimicrobial alteration or repetition. We included 170 patients having 270 CDI episodes; 85 patients had non-RCDI, and 85 had RCDI; 14 of them had MRCDI. Previous hospitalization and immunosuppressant use were more frequent in MRCDI group than in SRCDI group (P=0.009 and 0.002, respectively). Physicians treated more SRCDI episodes than MRCDI episodes with metronidazole alone (P=0.017), whereas, more MRCDI episodes needed combination antimicrobials (P=0.072). The mean duration of CDI treatment was longer in the MRCDI group than in the SRCDI group (P=0.030). MRCDI was associated with treatment failure more than SRCDI (P=0.021). The risk for a recurrent episode of CDI was increased in patients who had the following features of the first CDI episode: previous use of antibiotic, NSAID, immunosuppressant, chemotherapy, comorbidities, CDI treatment failure, and severe CDI (P<0.05). Risk factors for RCDI in cancer patients are similar to those without cancer, with the exception of chemotherapy that is only given to cancer patients. Long CDI treatment and CDI treatment failure are associated with MRCDI.

The impact of antimicrobial resistance on induction, transmission and treatment of Clostridium difficile infection

Clostridium difficile infection (CDI) of the gastrointestinal (GI) tract is a potentially life-threatening disease that has surpassed multi-drug-resistant Staphylococcus aureus as the commonest antimicrobial-resistant organism associated with healthcare1. This obligate anaerobic spore-forming Gram-positive bacillus colonises the GI tract and its numbers increase after disruption of the commensal GI microbiota often induced by exposure to antimicrobial agents2. Paradoxically, the disease that may follow its outgrowth necessitates further antimicrobial treatment. Already a major challenge to infection prevention and control strategies, there are indications that C. difficile is developing further resistance to currently used antimicrobial agents.

Analysis of Treatment Outcomes for Recurrent Clostridium difficile Infections and Fecal Microbiota Transplantation in a Pediatric Hospital

Clostridium difficile infection (CDI) is one of the most common nosocomial infections in the United States, with an increasing incidence in children. Approximately 20% of pediatric patients develop recurrent infections. It's imperative to further analyze the incidence of recurrent CDI in the pediatric population and determine the most effective treatments. The primary goal of this study is to characterize children with recurrent CDI at our institution, including both hospital-acquired CDI (HA-CDI) and community-acquired CDI (CA-CDI) cases, summarize the various treatments utilized, including fecal microbiota transplant (FMT) and compare their success rates. A retrospective cohort study of pediatric patients 1-21 years of age treated for CDI at a single institution from January 2010 to December 2014 was performed. There were 175 subjects with 215 separate episodes of CDI. Oral metronidazole was the most common initial treatment (145/207, 70%) followed by oral vancomycin (30/207, 15%), with recurrence rates of 30% (42/145) and 37% (11/30), respectively. Twenty-nine percent (63/215) of all initial CDI cases had at least 1 documented recurrence. Using multivariate analysis, subjects with HA-CDI were 2.6 times less likely to recur than those with CA-CDI (odds ratio: 0.39; 95% confidence interval: 0.18-0.85; P = 0.018). The overall success rate for FMT at our institution was 10/12 (83%). Our data show that cases of HA-CDI were less likely to recur compared with CA-CDI. Although currently reserved for multiply-recurrent cases, FMT was highly successful in our small cohort. More studies on FMT should be conducted to further evaluate its usefulness in the treatment of recurrent CDI in children.

The Microbiome and Its Potential for Pharmacology.

The human microbiota (the microscopic organisms that inhabit us) and microbiome (their genes) hold considerable potential for improving pharmacological practice. Recent advances in multi-"omics" techniques have dramatically improved our understanding of the constituents of the microbiome and their functions. The implications of this research for human health, including microbiome links to obesity, drug metabolism, neurological diseases, cancer, and many other health conditions, have sparked considerable interest in exploiting the microbiome for targeted therapeutics. Links between microbial pathways and disease states further highlight a rich potential for companion diagnostics and precision medicine approaches. For example, the success of fecal microbiota transplantation to treat Clostridium difficile infection has already started to redefine standard of care with a microbiome-directed therapy. In this review we briefly discuss the nature of human microbial ecosystems and with pathologies and biological processes linked to the microbiome. We then review emerging computational metagenomic, metabolomic, and wet lab techniques researchers are using today to learn about the roles host-microbial interactions have with respect to pharmacological purposes and vice versa. Finally, we describe how drugs affect the microbiome, how the microbiome can impact drug response in different people, and the potential of the microbiome itself as a source of new therapeutics.

Single centre clinical experience with fidaxomicin in the treatment of Clostridium difficile infection in Slovakia

Clostridium difficile infection (CDI) has become one of the most common causes of hospital-acquired infections. Fidaxomicin is one of the latest antibiotics used in the treatment of CDI, however, treatment cost affects recommendations for its use in several countries. We have analysed the treatment of our patients with CDI, treated by fidaxomicin since it was introduced to the market in 2018 and became available in the second biggest Slovak hospital, University Hospital of L. Pasteur. Our aim was to determine efficacy and safety of fidaxomicin in the treatment of CDI in Slovak patients. We reviewed all courses of fidaxomicin use in our hospital (n = 60). Fidaxomicin was used for first recurrence (12 times), second recurrence (4 times), third recurrence (2 times), and fifth recurrence (1 patient). 41 patients received fidaxomicin first-line. Success of fidaxomicin treatment was recorded at 86.7% within the whole cohort. In the recurrent Clostridium difficile infection (rCDI) subgroup, fidaxomicin was 63% effective with three patients dying (15.7%) and two patients developing subsequent rCDI. During the duration of the study, 6 patients in total died. Only one of three patients, with three or more recurrences of CDI, had no further presentations after eight weeks of completion of treatment. The biggest benefit from fidaxomicin treatment was shown in a cohort of patients with primary CDI infection demonstrating a low recurrence rate and significant reduction of fidaxomicin effectiveness in preventing a recurrence when treating patients with multiple rCDI.

Fecal microbiota transplantation in cancer management: Current status and perspectives.

The human gut is home to a large and diverse microbial community, comprising about 1,000 bacterial species. The gut microbiota exists in a symbiotic relationship with its host, playing a decisive role in the host's nutrition, immunity and metabolism. Accumulating studies have revealed the associations between gut dysbiosis or some special bacteria and various cancers. Emerging data suggest that gut microbiota can modulate the effectiveness of cancer therapies, especially immunotherapy. Manipulating the microbial populations with therapeutic intent has become a hot topic of cancer research, and the most dramatic manipulation of gut microbiota refers to fecal microbiota transplantation (FMT) from healthy individuals to patients. FMT has demonstrated remarkable clinical efficacy against Clostridium difficile infection (CDI) and it is highly recommended for the treatment of recurrent or refractory CDI. Lately, interest is growing in the therapeutic potential of FMT for other diseases, including cancers. We briefly reviewed the current researches about gut microbiota and its link to cancer, and then summarized the recent preclinical and clinical evidence to indicate the potential of FMT in cancer management as well as cancer‐treatment associated complications. We also presented the rationale of FMT for cancer management such as reconstruction of intestinal microbiota, amelioration of bile acid metabolism, and modulation of immunotherapy efficacy. This article would help to better understand this new therapeutic approach for cancer patients by targeting gut microbiota.

Five years of fecal microbiota transplantation - an update of the Israeli experience.

AIMTo evaluate and describe the efficacy of fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in a national Israeli cohort.METHODSAll patients who received FMT for recurrent (recurrence within 8 wk of the previous treatment) or refractory CDI from 2013 through 2017 in all the five medical centers in Israel currently performing FMT were included. Stool donors were screened according to the Israeli Ministry of Health guidelines. Clinical and laboratory data of patients were collected from patients’ medical files, and they included indications for FMT, risk factors for CDI and disease severity. Primary outcome was FMT success (at least 2 mo free of CDI-related diarrhea post-FMT). Secondary outcomes included initial response to FMT (cessation of diarrhea within 7 d) and recurrence at 6 mo.RESULTSThere were 111 FMTs for CDI, with a median age of 70 years [interquartile range (IQR): 53-82], and 42% (47) males. Fifty patients (45%) were treated via the lower gastrointestinal (LGI, represented only by colonoscopy) route, 37 (33%) via capsules, and 24 (22%) via the upper gastrointestinal (UGI) route. The overall success rate was 87.4% (97 patients), with no significant difference between routes of administration (P = 0.338). In the univariant analysis, FMT success correlated with milder disease (P = 0.01), ambulatory setting (P < 0.05) and lower Charlson comorbidity score (P < 0.05). In the multivariant analysis, only severe CDI [odd ratio (OR) = 0.14, P < 0.05] and inpatient FMT (OR = 0.19, P < 0.05) were each independently inversely related to FMT success. There were 35 (32%) patients younger than 60 years of age, and 14 (40%) of them had a background of inflammatory bowel disease.CONCLUSIONFMT is a safe and effective treatment for CDI, with capsules emerging as a successful and well-tolerated route. Severe CDI is less likely to respond to FMT.

What Is the Role for Metronidazole in the Treatment of Clostridium difficile Infection? Results From a National Cohort Study of Veterans With Initial Mild Disease

Metronidazole may still be an appropriate therapeutic option for mild Clostridium difficile infection (CDI) in select patients, but data are limited to guide clinicians in identifying these patients. Our 2-stage study included a national cohort of Veterans with a first episode of mild CDI (2010-2014). First, among those treated with metronidazole, we identified predictors of success, defined as absence of all-cause mortality or recurrence 30 days posttreatment, using multivariable unconditional logistic regression. Second, among a subgroup of patients with characteristics predictive of success identified in the first stage, we compared clinical outcomes among those treated with metronidazole compared with vancomycin, using Cox proportional hazards models for time to 30-day all-cause mortality, CDI recurrence, and failure. Among 3656 patients treated with metronidazole, we identified 3282 patients with success and 374 patients without success (failure). Younger age was the only independent predictor of success. Age ≤65 years was associated with an odds of success 1.63 times higher (95% confidence interval [CI], 1.29-2.06) than age >65 years. Among 115 propensity score-matched pairs ≤65 years of age, no significant differences were observed between metronidazole and vancomycin (reference) for all-cause mortality (hazard ratio [HR], 0.29 [95% CI, .06-1.38]), CDI recurrence (HR, 0.62 [95% CI, .26-1.49]), or failure (HR, 0.50 [95% CI, .23-1.07]). Among patients ≤65 years of age with initial mild CDI, clinical outcomes were similar with metronidazole and vancomycin. These data suggest that metronidazole may be considered for the treatment of initial mild CDI among patients 65 years of age or younger.

Efficacy and Safety of Fecal Microbiota Transplantation for the treatment of Clostridium difficile Infection in Patients with Liver Cirrhosis: a single center experience

Background and Hypothesis: Fecal microbiota transplant (FMT) is an effective therapy approaching a 90% success rate for recurrent and severe CDI. However, patients with liver cirrhosis are generally excluded from FMT trials due to concerns of infectious complications. We aimed to investigate the efficacy and safety of FMT in these patients. &#x0D; Project Methods: Electronic medical records (Cerner) and an institutional FMT database (REDCap) were utilized to gather data on patient demographics, medical history, and follow-up. Inclusion criteria were the diagnosis of liver cirrhosis and FMT to treat CDI. The primary outcomes were FMT success at 8 weeks and adverse events within 12 weeks post-FMT. &#x0D; Results: Among the 267 patients in the database, 15 had liver cirrhosis. Among these, 47% (N=7) were female. The average age was 61 years (range 28-83) and they received FMT between 2014 and 2017. There were 12 (80%) patients with recurrent CDI and 3 (20%) with severe CDI. Eleven patients had decompensated cirrhosis; Child-Pough scores were A: N=4, B: N=8, and C: N=3. Five (33%) failed before 8 weeks and needed 1-3 additional FMTs for cure. Fourteen (93.3%) patients experienced adverse events. Five patients experienced unrelated SAEs (Table). &#x0D; Conclusion: Patients with liver cirrhosis failed FMT more often than non-cirrhotic historical controls. While numerous AEs and SAEs were reported, few of the AEs were possibly related to the FMT and none of the SAEs were FMT-related. Importantly, no infectious complications were observed. Larger, multicenter studies are needed to establish efficacy and safety of FMT in cirrhotics before it can be recommended for widespread use.

Effect of Bifidobacterium breve in Combination With Different Antibiotics on Clostridium difficile.

While combinations of probiotics with antibiotics have exhibited beneficial and adverse effects in the treatment of Clostridium difficile infection (CDI), no substantive explanation has been provided for these effects. In this study, C. difficile ATCC 9689 (CD) was treated with Bifidobacterium breve (YH68) in combination with five different antibiotics to explore the effects of the different combinations on C. difficile. Cell-free culture supernatant (CFCS) of YH68 was combined with metronidazole (MTR), vancomycin (VAN), clindamycin (CLI), ceftazidime (CAZ) or ampicillin (AMP) to treat CD. The plate counting method was used to determine the growth and spore production of CD, and cell damage was assessed by the measurement of extracellular ATP levels with a luminescence-based kit. The production of toxin A/B was measured with an ELISA kit. The gene expression levels of tcdA and tcdB in CD were evaluated by real-time qPCR. The CFCS of YH68 (3 × 109 CFU/mL) at 0.25 times the minimal inhibitory concentration (MIC) (0.25YH68) in combination with the five antibiotics exerted stronger inhibitory effects on the growth and spore production of CD than the same antibiotics in the absence of 0.25YH68, except 0.25YH68&MTR&, 0.25YH68&MTR&CAZ, and 0.25YH68&VAN&CLI. However, treatment with 0.25YH68&VAN, 0.25YH68&, 0.25YH68&MTR&CAZ, 0.25YH68&VAN&CAZ, 0.25YH68&VAN&, and 0.25YH68&CAZ& resulted in increased cell damage. In addition, the different combinations, except 0.25YH68&CLI, 0.25YH68&MTR& and 0.25YH68&VAN&CLI, dramatically reduced the production of toxin A/B in comparison with the effects of the same antibiotics in the absence of 0.25YH68. The gene expression levels of tcdA and tcdB in CD were lowered upon treatment with 0.25YH68 in combination with MTR, CLI, CAZ, MTR&CAZ, MTR&, CLI&CAZ, and CLI&, whereas the levels were enhanced by 0.25YH68 in combination with VAN, AMP, MTR&CLI, VAN&CLI, VAN&, and CAZ&. In summary, YH68 in combination with specific antibiotics could enhance the inhibitory effects of antibiotics against CD. In addition, the antagonistic effects between some antibiotics could be weakened by YH68.

Опыт проведения трансплантации фекальной микробиоты у пациентки с клостридиальной инфекцией

In recent decades, against the background of widespread and, often, unfounded antibiotic therapy, an increase in Clostridium difficile infection (CDI) due to hypervirulent strains has been observed. According to international CDI treatment protocols, metronidazole and vancomycin are starting therapy for patients with newly diagnosed infections, even though the likelihood of a relapse is about 65%. In addition, the increased interest in CDI is associated with the need to develop and use alternative strategies aimed at preventing and increasing the effectiveness of treatment. In this regard, we first transplanted fecal microflora for this group of patients in Russia. This alternative method of treatment removes the spores of C. difficile, replenishes the normal intestinal flora, reduces the level of vegetative forms of C. difficile in the intestines, and supports the patient’s own immune response.

178. Impact of a Best Practice Alert Linking Clostridium difficile Infection Test Results to a Severity-Based Treatment Order Set

BackgroundAdherence to practice guidelines for the treatment of Clostridium difficile infection (CDI) has been associated with improved patient outcomes. In March 2014, the hospital’s Antimicrobial Stewardship Program (ASP) implemented a best practice alert (BPA) in the electronic medical record linking a positive test result to guideline-based CDI orders for those not on CDI therapy. We sought to assess provider adherence to practice guidelines before and after implementation of this clinical decision support tool.MethodsIn this quasi-experimental study, a retrospective chart review was conducted on inpatients diagnosed with CDI, defined using a tiered testing algorithm. Those diagnosed with CDI in 2013 served as controls before BPA implementation and patients from 2016 served as cases. Antibiotic prescribing was assessed and guideline compliance evaluated based on institutional guidelines for CDI treatment. Secondary endpoints were resolution of diarrhea, length of stay, in-hospital mortality, 30-day recurrence, and readmission rate. Continuous variables were analyzed using a two-tailed Student’s t-test, or for non-normally distributed data, Mann–Whitney U test. Categorical variables were analyzed using chi-square.ResultsBased on power analysis, 131 CDI cases were randomly selected, 66 in 2013 and 65 in 2016, which accounts for 23.7% (66/278) and 15.9% (65/409) of total inpatient CDI cases, respectively. Mean age was 55.0 ± 19.3 years pre-BPA/Order set and 58.5 ± 14.1 in the post-group. Immuncompormise was present in 53% of the pre-group when compared with 32.3% in the post-group. The majority of patients in both the pre-BPA/Order set group and post-group received metronidazole as initial therapy with 69.7% and 75.4%, respectively. The BPA was opened in 54% (28/57) of triggered encounters and led to signed orders in 82% (23/28) of those patients. Guideline-based prescribing increased from 39.4% in 2013 to 67.7% overall in 2016 (P = 0.014). Secondary endpoints were not significantly different between groups.ConclusionAfter implementation of the BPA linked to a severity-based treatment order set, there was an increase in guideline-compliant prescribing for CDI. Developing a better understanding of how to optimize guideline adherence using BPAs will aid ASPs in determining future improvement efforts.Disclosures S. Bergman, Merck: Grant Investigator, Grant recipient.

2367. Infection Incidence and Utilization of Antimicrobials in Physician Office Infusion Centers (POICs)

BackgroundPOICs offer a controlled setting for safe and effective outpatient treatment of moderate to severe infections with intravenous antimicrobial agents (IVAA) and agents used in treatment of Clostridium difficile infection (CDI). These therapies are provided via in-office or home administration. This study provides an overview of nationwide incidence of outpatient infections and utilization of IVAAs through POICs.MethodsA retrospective review of our centralized database was conducted of patient infections and therapy courses provided in POICs nationally that included complete data for 2017. All patients receiving IVAAs and drugs for CDI were included, along with dose, frequency, duration and method of administration. Descriptive measures were used to analyze data.ResultsA total of 12,930 infections were treated in 10,136 patients during 2017 among 77 POICs. Of those, 41% were treated directly from the community setting, avoiding hospitalization. Age distribution was <18 years <1%, 18–65 years 63% and >65 years 36%. Infections comprised 11 major diagnostic groups, with 47 subgroups. The most common diagnoses treated were bone and joint (37%), skin and skin structure (23%), genitourinary (14%) and bacteremia/septicemia (8%). 101 patients (1%) were treated for CDI. Geographical distribution occurred in the Midwest, Northeast, South, and West portion of the United States, where diagnoses were similar for all areas except the Northeast. This area had a significantly lower incidence of bone and joint infections (P < 0.0001) and a higher incidence of genitourinary infections (P < 0.0001). Overall utilization included 52 different agents, with 98.5% antimicrobials, 1% antifungals and 0.5% antivirals. Ceftriaxone was the most frequently used antimicrobial representing 16% of the total use, followed by vancomycin (14.5%), daptomycin (14.2%) and ertapenem (11%). The most prevalent infections and utilization of respective drug therapy is noted in the table. ConclusionThis study provides an annual overview of outpatient infection incidence with the utilization of IVAAs and therapy for CDI. A wide range of moderate to severe infections were treated, often avoiding hospitalization. Treatment regimens were broad, utilizing a wide variety of drugs and enabling extensive patient management in the POIC setting.Disclosures L. J. Van Anglen, Merck & Co.: Grant Investigator, Research grant.