Leaping Forward in the Treatment of Clostridium Difficile Infection: Update in 2015

Carmo, Joana; Marques, Susana; Chapim, Iolanda; Túlio, Maria Ana; Rodrigues, José; Bispo, Miguel; Chagas, Cristina

doi:10.1016/j.jpge.2015.07.006

Cited by 4 publications

(4 citation statements)

References 76 publications

(180 reference statements)

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“…Treating severe or complicated CDI: Prompt initiation of oral vancomycin, 125 mg q.i.d., for severely ill patients is critical. Some clinicians favor a higher dosing of vancomycin, 500 mg q.i.d., for severe disease [ 33 ]. Vancomycin may also be administered rectally as a retention enema in the setting of ileus, megacolon, and colonic diversion [ 34 ].…”

Section: Clinical Manifestations/diagnosis Of CDImentioning

confidence: 99%

Clostridium difficile infection: a review of current and emerging therapies

Ofosu¹

2016

aog

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Clostridium difficile (C. difficile) infection (CDI) is the most common cause of healthcare-associated infections in US hospitals. The epidemic strain NAP1/BI/ribotype 027 accounts for outbreaks worldwide, with increasing mortality and severity. CDI is acquired from an endogenous source or from spores in the environment, most easily acquired during the hospital stay. The use of antimicrobials disrupts the intestinal microflora enabling C. difficile to proliferate in the colon and produce toxins. Clinical diagnosis in symptomatic patients requires toxin detection from stool specimens and rarely in combination with stool culture to increase sensitivity. However, stool culture is essential for epidemiological studies. Oral metronidazole is the recommended therapy for milder cases of CDI and oral vancomycin or fidaxomicin for more severe cases. Treatment of first recurrence involves the use of the same therapy used in the initial CDI. In the event of a second recurrence oral vancomycin often given in a tapered dose or intermittently, or fidaxomicin may be used. Fecal transplantation is playing an immense role in therapy of recurrent CDI with remarkable results. Fulminant colitis and toxic megacolon warrant surgical intervention. Novel approaches including new antibiotics and immunotherapy against CDI or its toxins appear to be of potential value.

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Section: Clinical Manifestations/diagnosis Of CDImentioning

confidence: 99%

Clostridium difficile infection: a review of current and emerging therapies

Ofosu¹

2016

aog

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“…The introduction of intestinal microbiota from a healthy donor to restore the indigenous gut microbiota, commonly known as FMT, has been successfully used to treat recurrent C. difficile -associated diarrhea when standard therapy fails [29, 30]. Because FMT carries a potential risk of infectious disease transmission [21], the application of FMT has been used with caution in HSCT patients, who have a severely immunosuppressed status.…”

Section: Discussionmentioning

confidence: 99%

“…Given that FMT carries a potential risk of infection [20, 21], the application of FMT in patients with leukemia, especially in patients undergoing HSCT, has been greatly restricted until recently, when some studies evaluated the safety of FMT in patients with leukemia [22, 23]. In cases where diarrhea could not be mitigated with medicine, FMT has commonly been used to treat HSCT patients.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Fecal Donors with Different Feeding Patterns on Diarrhea in a Patient Undergoing Hematopoietic Stem Cell Transplantation

Zhang¹,

Ren²,

Li³

et al. 2019

Case Reports in Hematology

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Almost 90% of patients undergoing hematopoietic stem cell transplantation (HSCT) experience diarrheal episodes, which represent a severe, often life-threatening complication for these patients. Although fecal microbiota transplantation (FMT) represents an alternative treatment option for infection-related diarrhea, the application of FMT in HSCT patients is greatly restricted for safety reasons. Furthermore, the therapeutic outcomes of FMT as a diarrhea treatment are somewhat related to the choice of the FMT donor. Here, we comprehensively profiled the dynamic changes in the intestinal microbiota after FMT from two donors with different feeding patterns and the same severely diarrheal recipient undergoing HSCT via a 45-day clinical observation. Importantly, no adverse events attributed to FMT were observed. The stool volume and frequency of the patient were reduced when we used feces from donor #1 (mixed feeding), but these changes were not observed after FMT from donor #2 (exclusive breastfeeding). Interestingly, no obvious differences in overall diversity (Shannon) or richness (Chao1) between the two donors were observed. Additionally, Bifidobacterium accounted for 29.9% and 18.1% of OTUs in the stools of donors #1 and #2, respectively. Lactobacillus accounted for 16.3% and 2.9% of the stools of donors #1 and #2, respectively. Furthermore, through longitudinal monitoring of the patient, we identified 6 OTUs that were particularly sensitive to the different FMT complements. Together, we present a case report suggesting that the overall diversity of the intestinal microbiota may not be the only important element in the selection of an effective FMT donor.

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“…Interestingly, binding of the auxiliary alone by a fragment of these compounds “2-aminoquinolin-8-ol” could trap MetRS in the new conformation [ 85 ]. Because Clostridium difficile is one major toxic bacteria in human intestine to cause infectious diarrhea, this inhibitor class serves as a potential therapy for Clostridium difficile infection [ 142 ].…”

Section: Classification Of Aars Inhibitorsmentioning

confidence: 99%

Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification

Fang

Guo

2015

Life

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Aminoacyl-tRNA synthetases (aaRSs) are enzymes that catalyze the transfer of amino acids to their cognate tRNAs as building blocks for translation. Each of the aaRS families plays a pivotal role in protein biosynthesis and is indispensable for cell growth and survival. In addition, aaRSs in higher species have evolved important non-translational functions. These translational and non-translational functions of aaRS are attractive for developing antibacterial, antifungal, and antiparasitic agents and for treating other human diseases. The interplay between amino acids, tRNA, ATP, EF-Tu and non-canonical binding partners, had shaped each family with distinct pattern of key sites for regulation, with characters varying among species across the path of evolution. These sporadic variations in the aaRSs offer great opportunity to target these essential enzymes for therapy. Up to this day, growing numbers of aaRS inhibitors have been discovered and developed. Here, we summarize the latest developments and structural studies of aaRS inhibitors, and classify them with distinct binding modes into five categories.

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Leaping Forward in the Treatment of Clostridium Difficile Infection: Update in 2015

Cited by 4 publications

References 76 publications

Clostridium difficile infection: a review of current and emerging therapies

Clostridium difficile infection: a review of current and emerging therapies

The Effects of Fecal Donors with Different Feeding Patterns on Diarrhea in a Patient Undergoing Hematopoietic Stem Cell Transplantation

Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification

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