scholarly journals Teicoplanin Suppresses Vegetative Clostridioides Difficile and Spore Outgrowth

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 984
Author(s):  
Suvash Chandra Ojha ◽  
Matthew Phanchana ◽  
Phurt Harnvoravongchai ◽  
Surang Chankhamhaengdecha ◽  
Sombat Singhakaew ◽  
...  

In recent decades, the incidence of Clostridioides difficile infection (CDI) has remained high in both community and health-care settings. With the increasing rate of treatment failures and its ability to form spores, an alternative treatment for CDI has become a global priority. We used the microdilution assay to determine minimal inhibitory concentrations (MICs) of vancomycin and teicoplanin against 30 distinct C. difficile strains isolated from various host origins. We also examined the effect of drugs on spore germination and outgrowth by following the development of OD600. Finally, we confirmed the spore germination and cell stages by microscopy. We showed that teicoplanin exhibited lower MICs compared to vancomycin in all tested isolates. MICs of teicoplanin ranged from 0.03–0.25 µg/mL, while vancomycin ranged from 0.5–4 µg/mL. Exposure of C. difficile spores to broth supplemented with various concentrations of antimicrobial agents did not affect the initiation of germination, but the outgrowth to vegetative cells was inhibited by all test compounds. This finding was concordant with aberrant vegetative cells after antibiotic treatment observed by light microscopy. This work highlights the efficiency of teicoplanin for treatment of C. difficile through prevention of vegetative cell outgrowth.

1993 ◽  
Vol 56 (9) ◽  
pp. 795-800 ◽  
Author(s):  
BOBBY L. BOWLES ◽  
ARTHUR J. MILLER

Several aromatic and aliphatic ketones were tested for inhibitory activity against Clostridium botulinum spores and cells. Six-tenths mM 3-heptanone, 3-hexanone, or benzophenone delayed spore germination in botulinal assay medium (BAM) broth at 32°C. Sporicidal activity was observed for 1,250 mM 2,3-pentanedione, while 2-octanone, 3-octanone, or benzophenone were effective at 2,500 mM. In general, higher concentrations were required to inhibit vegetative cells than to prevent spore germination. Maximum activity against vegetative cells was observed at 25 mM acetanisole (4′-methoxyacetophenone), 2,3-butanedione, 2,3-pentanedione, 2-pentanone, or benzophenone, and inhibition was independent of pH. Five-tenths mM acetanisole inhibited dipicolinic acid release, 100 mM reduced 20 min 80°C thermal resistance, and 5.0 mM delayed toxigenesis in BAM broth at 32°C. Furthermore, inhibitory activity of acetanisole was comparable to that observed in BAM broth when tested in commercially prepared chicken and beef broths. The spectrum of antibotulinal activity was dependent upon carbon chain length, carbonyl position, number of carbonyls, and aromaticity. The inhibitions observed suggest that aliphatic and aromatic ketones might have potential as novel antimicrobial agents.


2020 ◽  
Vol 9 (12) ◽  
pp. 4114
Author(s):  
Nicola Petrosillo ◽  
Maria Adriana Cataldo

Clostridioides difficile (CD) continues to be the number one health care-associated infectious pathogen in the United States [...]


2019 ◽  
Author(s):  
Bhagyashree Swarge ◽  
Martijs Jonker ◽  
Wishwas Abhyankar ◽  
Huub Hoefsloot ◽  
Chris G. de Koster ◽  
...  

AbstractBacillus subtilisforms highly resistant, metabolically inactive dormant spores upon nutrient limitation. These endospores pose challenges to the food and medical sectors. Spores reactivate their metabolism upon contact with germinants and develop into vegetative cells. The activation of the molecular machinery that triggers the progress of germination and spore outgrowth is still unsettled. To gain further insight in spore germination and outgrowth processes, the transcriptome and proteome changeover during spore germination and outgrowth to vegetative cells, was analysed.B. subtilistranscriptome analysis allow us to trace the different functional groups of genes expressed. For each time-point sample, the change in the spore proteome was quantitatively monitored relative to the reference proteome of15N metabolically labelled vegetative cells. We observed until the phase transition, i.e. completion of germination, no significant change in the proteome. We have identified 36 transcripts present abundantly in the dormant spores. This number is in close agreement with the previous findings. These transcripts mainly belong to the genes encoding small acid soluble proteins (sspE, sspO, sspI, sspK, sspF) and proteins with uncharacterized functions. We observed in total 3152 differentially expressed genes, but ‘only’ 323 differentially expressed proteins (total 451 proteins identified and quantified). Our data shows that 173 proteins from dormant spores, both spore unique proteins and protein shared with vegetative cells, are lost during the phase transitioning period. This loss is in addition to the active protein degradation, undertaken by the spore proteases such as Gpr, as germination and outgrowth proceeds. Further analysis is required to functionally interpret the observed protein loss. The observed diverse timing of the synthesis of different protein sets reveals a putative core-strategy of the revival of ‘life’ starting from theB. subtilisspore.


2016 ◽  
Vol 44 (2) ◽  
pp. 228-232 ◽  
Author(s):  
Evelyn Alvarez ◽  
Daniel Z. Uslan ◽  
Timothy Malloy ◽  
Peter Sinsheimer ◽  
Hilary Godwin

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S818-S818
Author(s):  
Cheon Hoo Jeon ◽  
Yu Mi Wi

Abstract Background Clostridioides difficile infection is a leading cause of healthcare-associated diarrhea. The epidemiology and characteristics of C. difficile vary geographically. We performed toxin enzyme immunoassay (EIA), toxigenic gene analysis, antimicrobial susceptibility tests (AST), and PCR ribotyping to elucidate the characteristics of C. difficile in Korea. Methods Between July 2017 and June 2018, C. difficile was prospectively isolated in 128 specimens from the culture of 1,182 unduplicated specimens. Seventy-five stool specimens with a positive toxin EIA between July 2016 and June 2017 were also included. We performed PCR for the tcdA and tcdB genes on these isolates, and AST and PCR ribotyping on the isolates with a positive toxin EIA. Results Older patients tended to have a higher rate of positive toxin EIA and positive cultures than did younger patients. Ribotype 018 was predominantly identified (48.6%), followed by ribotype 014/020 (9.9%), and ribotype 002 (8.3%). All of A-B+ isolates were either ribotype 017 or B-2. Ribotypes 017, 018, and B-2 showed high resistance to various antibiotics. In contrast, ribotypes 002, 014/020 and C-4 demonstrated low resistance rates, except that to moxifloxacin in ribotype 002. Clindamycin and erythromycin showed a positive correlation. Most of the isolates resistant to rifampicin or tetracycline showed a high MIC to both erythromycin and clindamycin. Conclusion Ribotype 018, which is highly transmissible and resistant to various antimicrobial agents, is predominant in Korea. Ribotype 002 has also been increasing in prevalence in Korea. Disclosures All authors: No reported disclosures.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S354-S355
Author(s):  
Lindsay Smith ◽  
John W Ahern

Abstract Background In 2017 The Joint Commission required all hospitals irrespective of size to implement antimicrobial stewardship programs (ASPs) using the CDC core elements (CE) for antimicrobial stewardship (AS). Critical access and rural community hospitals have struggled with developing effective ASPs. Many ASPs seek to reduce fluoroquinolone (FQ) prescribing due to its high risk for drug-drug interactions, risk of Clostridioides difficile infection, and numerous side effects, including five black box warnings from the FDA. Methods We contracted with the Vermont Department of Health to help rural VT hospitals develop ASPs that are compliant with the CDC CE for AS. Six of Vermont’s 13 hospitals were recruited between June – December 2017 (Table 1). Each hospital obtained antibiotic usage (AU) data in grams (g)/1000 (1k) patient-days (PD) from their electronic medical record (EMR), starting from January 2017. All identified FQ as frequently prescribed antimicrobials. Each hospital had unique interventions to decrease FQ prescribing (Table 1), including orderset changes and pharmacist intervention. Monthly combined FQ (ciprofloxacin + levofloxacin) administration data were collected in g/1K PD. AU data from each hospital were summed and expressed as total FQ g/1000 patient-days. The FQ prescribing trend was analyzed by linear regression. Results Prior to implementing ASP, there was a combined FQ rate of 69 g/1K PD. After 20 months of ASP interventions, combined FQ prescribing decreased to 26 g/1K PD (Figure 1, R= 0.9797, P < 0.001). This trend is also significant for each individual FQ: ciprofloxacin (R=0.8364, P < 0.05) and levofloxacin (R= 0.9801, P < 0.01). Conclusion Rural and critical access hospitals can have successful antimicrobial stewardship programs. We have shown that rural hospitals in Vermont (1) can extract AU data from their EMR, (2) develop interventions to decrease high use antimicrobial agents, and (3) be successful in decreasing FQ prescribing in less than 2 years. Disclosures All authors: No reported disclosures.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giovanny Herrera ◽  
Laura Vega ◽  
Manuel Alfonso Patarroyo ◽  
Juan David Ramírez ◽  
Marina Muñoz

AbstractThe role of gut microbiota in the establishment and development of Clostridioides difficile infection (CDI) has been widely discussed. Studies showed the impact of CDI on bacterial communities and the importance of some genera and species in recovering from and preventing infection. However, most studies have overlooked important components of the intestinal ecosystem, such as eukaryotes and archaea. We investigated the bacterial, archaea, and eukaryotic intestinal microbiota of patients with health-care-facility- or community-onset (HCFO and CO, respectively) diarrhea who were positive or negative for CDI. The CDI-positive groups (CO/+, HCFO/+) showed an increase in microorganisms belonging to Bacteroidetes, Firmicutes, Proteobacteria, Ascomycota, and Opalinata compared with the CDI-negative groups (CO/−, HCFO/−). Patients with intrahospital-acquired diarrhea (HCFO/+, HCFO/−) showed a marked decrease in bacteria beneficial to the intestine, and there was evidence of increased Archaea and Candida and Malassezia species compared with the CO groups (CO/+, CO/−). Characteristic microbiota biomarkers were established for each group. Finally, correlations between bacteria and eukaryotes indicated interactions among the different kingdoms making up the intestinal ecosystem. We showed the impact of CDI on microbiota and how it varies with where the infection is acquired, being intrahospital-acquired diarrhea one of the most influential factors in the modulation of bacterial, archaea, and eukaryotic populations. We also highlight interactions between the different kingdoms of the intestinal ecosystem, which need to be evaluated to improve our understanding of CDI pathophysiology.


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