scholarly journals Prospective Observational Study Comparing Three Different Treatment Regimes in Patients with Clostridium difficile Infection

2012 ◽  
Vol 56 (4) ◽  
pp. 1974-1978 ◽  
Author(s):  
Judith M. Wenisch ◽  
Daniela Schmid ◽  
Hung-Wei Kuo ◽  
Franz Allerberger ◽  
Verena Michl ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Prospective Observational Study ◽  
Standard Treatment ◽  
Fatal Outcome ◽  
Poisson Regression Model ◽  
Content Type ◽  
Treatment Groups ◽  
Treatment Regimens ◽  
Treatment Regimes ◽  
Comorbidity Index

ABSTRACTIn a hospital-based, prospective cohort study, the effects of the three standard treatment regimens for mildClostridium difficileinfection (CDI), oral (p.o.) metronidazole at 500 mg three times/day, intravenous (i.v.) metronidazole at 500 mg three times/day, and oral (p.o.) vancomycin at 250 mg four times/day, were compared with respect to the risk of occurrence of complications, sequelae, and all-cause death within 30 days after the date of starting treatment. Differences in the incidence of these outcomes were tested by χ2or Fisher's exact tests. A Poisson regression model was performed to control for possible confounding effects of sex, age, and severity of comorbidity categorized according to the Charlson comorbidity index. The highest mortality was observed in the metronidazole i.v. group, with a mortality rate 38.1% (16/42) compared to mortality rates of 7.4% (9/121) in the metronidazole p.o. group and 9.5% (4/42) in the vancomycin p.o. group (P< 0.001). After adjustment for possible effects of sex, age (>65 years), and severity of comorbidity, the relative risk of a 30-day fatal outcome for patients receiving metronidazole i.v. was 4.3 (95% confidence interval [CI] = 1.92 to 10;P< 0.0001) compared to patients treated with metronidazole p.o. and 4.0 (95% CI = 1.31 to 5.0;P< 0.015) compared to patients treated with vancomycin p.o. There were no significant differences in the risk of complications between the three treatment groups. This study generates the hypothesis that treatment with i.v. metronidazole is inferior to the oral alternatives metronidazole and vancomycin.

scholarly journals Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Ryan K. Shields ◽  
M. Hong Nguyen ◽  
Liang Chen ◽  
Ellen G. Press ◽  
Brian A. Potoski ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Success ◽  
Severity Of Illness ◽  
Content Type ◽  
Treatment Groups ◽  
Treatment Regimens ◽  
Carbapenem Resistant ◽  
Underlying Diseases

ABSTRACT There are no data comparing outcomes of patients treated with ceftazidime-avibactam versus comparators for carbapenem-resistant Enterobacteriaceae infections. At our center, ceftazidime-avibactam treatment of carbapenem-resistant Klebsiella pneumoniae bacteremia was associated with higher rates of clinical success (P = 0.006) and survival (P = 0.01) than other regimens. Across treatment groups, there were no differences in underlying diseases, severity of illness, source of bacteremia, or strain characteristics (97% produced K. pneumoniae carbapenemase). Aminoglycoside- and colistin-containing regimens were associated with increased rates of nephrotoxicity (P = 0.002).

scholarly journals Anlotinib Combined with Temozolomide Therapy for Recurrent Glioblastoma (IDH-wt and TERTp-mut) After Standard Treatment

2022 ◽  
Author(s):  
Tianwei Wang ◽  
Zhijun Liao ◽  
Ruizhi Wang ◽  
Ming Ye ◽  
Keman Liao ◽  
...  
Keyword(s):  
Management Strategy ◽  
Median Overall Survival ◽  
Standard Treatment ◽  
Group Versus ◽  
Supportive Therapy ◽  
Recurrent Glioblastoma ◽  
Effective Management ◽  
Treatment Groups ◽  
Treatment Regimens ◽  
Kaplan Meier

Abstract Purpose IDH1-wt glioblastoma patients with TERTp-mut had the worst prognosis, and no effective management strategy was established after tumor recurrence. The median overall survival (OS) of recurrent GBM patients who only received supportive therapy was approximately 1.0 month. We reported survival outcomes of recurrent glioblastoma (rGBM) treated with anlotinib combined with temozolomide therapy (ACTT), and to explore the management strategy of rGBM. Methods The clinical data of 14 rGBM patients treated with ACTT was collected. Therapeutic efficacy and adverse effects were evaluated in every 2 months of treatment. We also included 16 patients treated with bevacizumab (Bev), 22 with TMZ, 28 with re-operation, 21 with re-irradiation, and 75 with supportive care to make comparison. Kaplan-Meier analysis was used to compare the survival of ACTT group versus other treatment groups. Results Fourteen rGBM patients treated with ACTT were enrolled. After 2-month of ACTT, the overall response and disease control rate were 50.0% and 92.9%, respectively. The 6-months PFS rate was 78.6%, and the 1-year survival rate was 50.0%. The median PFS and OS in ACTT group were 11.0 and 13.0 months, respectively. The median PFS and OS in Bev-group was 4.0 and 8.0 months. The patients treated with ACTT had better PFS than that in Bev-group. And compared to all the others treatment groups, ACTT could prolong survival. Conclusion The treatment regimen of ACTT maybe reliable, safe, and effective for rGBM. The patients can gain survival benefits from ACTT, and prolonged survival were observed compared with other treatment regimens.

scholarly journals Comparative Susceptibilities to Fidaxomicin (OPT-80) of Isolates Collected at Baseline, Recurrence, and Failure from Patients in Two Phase III Trials of Fidaxomicin against Clostridium difficile Infection

2011 ◽  
Vol 55 (11) ◽  
pp. 5194-5199 ◽  
Author(s):  
Ellie J. C. Goldstein ◽  
Diane M. Citron ◽  
Pamela Sears ◽  
Farah Babakhani ◽  
Susan P. Sambol ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Restriction Endonuclease Analysis ◽  
Phase Iii ◽  
Two Phase ◽  
Double Blind ◽  
Single Strain ◽  
Content Type ◽  
Treatment Groups ◽  
Phase Iii Trials ◽  
Intent To Treat

ABSTRACTA 10-day course of oral fidaxomicin (200 mg twice a day [b.i.d.]), a potent new macrocyclic drug, was compared to vancomycin (125 mg four times a day [q.i.d.]) in 1,164 adults (1,105 in the modified intent-to-treat [mITT] population) withClostridium difficileinfection in two phase III randomized, double-blind trials at sites in North America and 7 European countries. Of 1,105 mITT patients, 792 (71.7%), including 719/999 (72.0%) in the per-protocol (PP) population, provided aC. difficilestrain at baseline, of whom 356 received fidaxomicin with 330 cures (92.7%) and 363 received vancomycin with 329 cures (90.6%). The susceptibilities (MIC90) of baseline isolates did not predict clinical cure, failure, or recurrence for fidaxomicin (MIC90, 0.25 μg/ml for both; range, ≤0.007 to 1 μg/ml), but there was a one-dilution difference in the MIC90(but not the MIC50) for vancomycin (MIC90, 2 μg/ml [range, 0.25 to 8 μg/ml] for cure and 4.0 μg/ml [range, 0.5 to 4 μg/ml] for failures). A total of 65 (7.9%) “rifaximin-resistant” (MIC > 256 μg/ml) strains were isolated in both treatment groups on enrollment, which increased to 25% for failures at the end of therapy. No resistance to either fidaxomicin or vancomycin developed during treatment in either of the phase III studies, although a single strain isolated from a cured patient had an elevated fidaxomicin MIC of 16 μg/ml at the time of recurrence. All isolates were susceptible to ≤4 μg/ml of metronidazole. When analyzed by restriction endonuclease analysis (REA) type, 247/719 (34.4%) isolates were BI group isolates, and the MICs were generally higher for all four drugs tested (MIC90s: fidaxomicin, 0.5; vancomycin, 2.0; metronidazole, 2.0; and rifaximin, >256 μg/ml) than for the other REA types. There was no correlation between the MIC of a baseline clinical isolate and clinical outcome. MIC90s were generally low for fidaxomicin and vancomycin, but BI isolates had higher MICs than other REA group isolates.

Synergistic action of propolis with levodopa in the management of Parkinsonism in Drosophila melanogaster

2020 ◽  
Vol 17 (3) ◽  
Author(s):  
Emmanuel Tiyo Ayikobua ◽  
Josephine Kasolo ◽  
Keneth Iceland Kasozi ◽  
Ejike Daniel Eze ◽  
Abass Safiriyu ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Drosophila Melanogaster ◽  
Side Effects ◽  
Motor Activity ◽  
Ethanolic Extract ◽  
Synergistic Action ◽  
Content Type ◽  
Treatment Groups ◽  
Ethanolic Extract Of Propolis ◽  
Different Doses

AbstractBackgroundThe Phosphatase and tensin-induced putative kinase 1 (PINK1B9) mutant for Drosophila melanogaster is a key tool that has been used in assessing the pathology of Parkinsonism and its possible remedy. This research was targeted toward determining the effects of ethanolic extract of propolis, with levodopa therapy in the management of Parkinsonism.MethodThe PINK1B9 flies were divided into groups and fed with the different treatment doses of ethanoic extract of propolis. The treatment groups were subjected to 21 days of administration of propolis and the levodopa at different doses after which percentage climbing index, antioxidant activity and lifespan studies were done.ResultsPropolis alone improved motor activity, antioxidant and lifespan in Drosophila melanogaster than in PINK1 flies. Propolis in combination with levodopa significantly (P<0.05) improved physiological parameters at higher than lower concentrations in Parkinsonism Drosophila melanogaster demonstrating its importance in managing side effects associated with levodopa.ConclusionPropolis is a novel candidate as an alternative and integrative medicinal option to use in the management of Parkinsonism in both animals and humans at higher concentrations.

scholarly journals Characterizations of Clinical Isolates of Clostridium difficile by Toxin Genotypes and by Susceptibility to 12 Antimicrobial Agents, Including Fidaxomicin (OPT-80) and Rifaximin: a Multicenter Study in Taiwan

2012 ◽  
Vol 56 (7) ◽  
pp. 3943-3949 ◽  
Author(s):  
Chun-Hsing Liao ◽  
Wen-Chien Ko ◽  
Jang-Jih Lu ◽  
Po-Ren Hsueh
Keyword(s):  
Clostridium Difficile ◽  
Care Setting ◽  
Antimicrobial Agents ◽  
Teaching Hospitals ◽  
Binary Toxin ◽  
Content Type ◽  
Vancomycin Mics ◽  
Major Teaching ◽  
Southern Taiwan

ABSTRACTA total of 403 nonduplicate isolates ofClostridium difficilewere collected at three major teaching hospitals representing northern, central, and southern Taiwan from January 2005 to December 2010. Of these 403 isolates, 170 (42.2%) were presumed to be nontoxigenic due to the absence of genes for toxins A or B or binary toxin. The remaining 233 (57.8%) isolates carried toxin A and B genes, and 39 (16.7%) of these also had binary toxin genes. The MIC90of all isolates for fidaxomicin and rifaximin was 0.5 μg/ml (range, ≤0.015 to 0.5 μg/ml) and >128 μg/ml (range, ≤0.015 to >128 μg/ml), respectively. All isolates were susceptible to metronidazole (MIC90of 0.5 μg/ml; range, ≤0.03 to 4 μg/ml). Two isolates had reduced susceptibility to vancomycin (MICs, 4 μg/ml). Only 13.6% of isolates were susceptible to clindamycin (MIC of ≤2 μg/ml). Nonsusceptibility to moxifloxacin (n= 81, 20.1%) was accompanied by single or multiple mutations ingyrAandgyrBgenes in all but eight moxifloxacin-nonsusceptible isolates. Two previously unreportedgyrBmutations might independently confer resistance (MIC, 16 μg/ml), Ser416 to Ala and Glu466 to Lys. Moxifloxacin-resistant isolates were cross-resistant to ciprofloxacin and levofloxacin, but some moxifloxacin-nonsusceptible isolates remained susceptible to gemifloxacin or nemonoxacin at 0.5 μg/ml. This study found the diversity of toxigenic and nontoxigenic strains ofC. difficilein the health care setting in Taiwan. All isolates tested were susceptible to metronidazole and vancomycin. Fidaxomicin exhibited potentin vitroactivity against all isolates tested, while the more than 10% of Taiwanese isolates with rifaximin MICs of ≥128 μg/ml raises concerns.

scholarly journals Impact of Variations in Test Method Parameters onIn VitroActivity of Surotomycin against Clostridium difficile and Surotomycin Quality Control Limits for Broth Microdilution and Agar Dilution Susceptibility Testing

2015 ◽  
Vol 54 (3) ◽  
pp. 749-753 ◽  
Author(s):  
Maria M. Traczewski ◽  
Jennifer Deane ◽  
Daniel Sahm ◽  
Steven D. Brown ◽  
Laurent Chesnel
Keyword(s):  
Quality Control ◽  
Clostridium Difficile ◽  
Calcium Concentration ◽  
Susceptibility Testing ◽  
Test Method ◽  
Test Parameter ◽  
Content Type ◽  
Parameter Variations ◽  
Agar Dilution ◽  
Control Limits

Test parameter variations were evaluated for their effects on surotomycin MICs. Calcium concentration was the only variable that influenced MICs; therefore, 50 μg/ml (standard for lipopeptide testing) is recommended. Quality control ranges forClostridium difficile(0.12 to 1 μg/ml) andEggerthella lenta(broth, 1 to 4 μg/ml; agar, 1 to 8 μg/ml) were approved by the Clinical and Laboratory Standards Institute based on these data.

scholarly journals Inflammasome Activation Contributes to Interleukin-23 Production in Response to Clostridium difficile

mBio ◽  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Carrie A. Cowardin ◽  
Sarah A. Kuehne ◽  
Erica L. Buonomo ◽  
Chelsea S. Marie ◽  
Nigel P. Minton ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Disease Severity ◽  
Tissue Damage ◽  
The United States ◽  
Host Cells ◽  
Inflammasome Activation ◽  
Content Type ◽  
Danger Signals ◽  
Interleukin 23 ◽  
Molecular Patterns

ABSTRACT  Clostridium difficileis the most common hospital-acquired pathogen, causing antibiotic-associated diarrhea in over 250,000 patients annually in the United States. Disease is primarily mediated by toxins A and B, which induce potent proinflammatory signaling in host cells and can activate an ASC-containing inflammasome. Recent findings suggest that the intensity of the host response to infection correlates with disease severity. Our lab has identified the proinflammatory cytokine interleukin-23 (IL-23) as a pathogenic mediator during C. difficile infection (CDI). The mechanisms by which C. difficile induces IL-23, however, are not well understood, and the role of toxins A and B in this process is unclear. Here, we show that toxins A and B alone are not sufficient for IL-23 production but synergistically increase the amount of IL-23 produced in response to MyD88-dependent danger signals, including pathogen-associated molecular patterns (PAMPs) and host-derived damage associated molecular patterns (DAMPs). Danger signals also enhanced the secretion of IL-1β in response to toxins A and B, and subsequent IL-1 receptor signaling accounted for the majority of the increase in IL-23 that occurred in the presence of the toxins. Inhibition of inflammasome activation in the presence of extracellular K+likewise decreased IL-23 production. Finally, we found that IL-1β was increased in the serum of patients with CDI, suggesting that this systemic response could influence downstream production of pathogenic IL-23. Identification of the synergy of danger signals with toxins A and B via inflammasome signaling represents a novel finding in the mechanistic understanding of C. difficile-induced inflammation.IMPORTANCEClostridium difficileis among the leading causes of death due to health care-associated infection, and factors determining disease severity are not well understood. C. difficile secretes toxins A and B, which cause inflammation and tissue damage, and recent findings suggest that some of this tissue damage may be due to an inappropriate host immune response. We have found that toxins A and B, in combination with both bacterium- and host-derived danger signals, can induce expression of the proinflammatory cytokines IL-1β and IL-23. Our results demonstrate that IL-1β signaling enhances IL-23 production and could lead to increased pathogenic inflammation during CDI.

scholarly journals Evaluation of the Cepheid Xpert C. difficile/Epiand Meridian Bioscienceillumigene C. difficile Assays for Detecting Clostridium difficile Ribotype 033 Strains

2014 ◽  
Vol 53 (3) ◽  
pp. 973-975 ◽  
Author(s):  
Grace O. Androga ◽  
Alan M. McGovern ◽  
Briony Elliott ◽  
Barbara J. Chang ◽  
Timothy T. Perkins ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Binary Toxin ◽  
Content Type ◽  
Toxin Genes ◽  
Production Animals

Clostridium difficilePCR ribotype 033 (RT033) is found in the gastrointestinal tracts of production animals and, occasionally, humans. TheillumigeneC. difficileassay (Meridian Bioscience, Inc.) failed to detect any of 52C. difficileRT033 isolates, while all strains signaled positive for the binary toxin genes but were reported as negative forC. difficileby the XpertC. difficile/Epiassay (Cepheid).

scholarly journals Infection with Toxin A-Negative, Toxin B-Negative, Binary Toxin-Positive Clostridium difficile in a Young Patient with Ulcerative Colitis

2015 ◽  
Vol 53 (11) ◽  
pp. 3702-3704 ◽  
Author(s):  
Grace O. Androga ◽  
Julie Hart ◽  
Niki F. Foster ◽  
Adrian Charles ◽  
David Forbes ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clostridium Difficile ◽  
Young Patient ◽  
Diagnostic Methods ◽  
Binary Toxin ◽  
Toxin A ◽  
Toxin B ◽  
Content Type ◽  
Severe Diarrhea ◽  
Clinically Significant

Large clostridial toxin-negative, binary toxin-positive (A−B−CDT+) strains ofClostridium difficileare almost never associated with clinically significantC. difficileinfection (CDI), possibly because such strains are not detected by most diagnostic methods. We report the isolation of an A−B−CDT+ribotype 033 (RT033) strain ofC. difficilefrom a young patient with ulcerative colitis and severe diarrhea.

scholarly journals Pharmacological Basis of CD101 Efficacy: Exposure Shape Matters

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Elizabeth A. Lakota ◽  
Justin C. Bader ◽  
Voon Ong ◽  
Ken Bartizal ◽  
Lynn Miesel ◽  
...  
Keyword(s):  
Time Course ◽  
Fungicidal Activity ◽  
Control Group ◽  
Time Curve ◽  
Content Type ◽  
Treatment Groups ◽  
Concentration Time ◽  
Treatment Control Group ◽  
Pharmacological Basis

ABSTRACT CD101 is a novel echinocandin with concentration-dependent fungicidal activity in vitro and a long half-life (∼133 h in humans, ∼70 to 80 h in mice). Given these characteristics, it is likely that the shape of the CD101 exposure (i.e., the time course of CD101 concentrations) influences efficacy. To test this hypothesis, doses which produce the same total area under the concentration-time curve (AUC) were administered to groups of neutropenic ICR mice infected with Candida albicans R303 using three different schedules. A total CD101 dose of 2 mg/kg was administered as a single intravenous (i.v.) dose or in equal divided doses of either 1 mg/kg twice weekly or 0.29 mg/kg/day over 7 days. The studies were performed using a murine disseminated candidiasis model. Animals were euthanized at 168 h following the start of treatment. Fungi grew well in the no-treatment control group and showed variable changes in fungal density in the treatment groups. When the CD101 AUC from 0 to 168 h (AUC0–168) was administered as a single dose, a >2 log10 CFU reduction from the baseline at 168 h was observed. When twice-weekly and daily regimens with similar AUC values were administered, net fungal stasis and a >1 log10 CFU increase from the baseline were observed, respectively. These data support the hypothesis that the shape of the CD101 AUC influences efficacy. Thus, CD101 administered once per week demonstrated a greater degree of fungal killing than the same dose divided into twice-weekly or daily regimens.

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