scholarly journals Evaluation of an Oral Suspension of VP20621, Spores of Nontoxigenic Clostridium difficile Strain M3, in Healthy Subjects

2012 ◽  
Vol 56 (10) ◽  
pp. 5224-5229 ◽  
Author(s):  
Stephen A. Villano ◽  
Michael Seiberling ◽  
Walter Tatarowicz ◽  
Elizabeth Monnot-Chase ◽  
Dale N. Gerding
Keyword(s):  
Clostridium Difficile ◽  
Healthy Adult ◽  
Oral Suspension ◽  
Oral Vancomycin ◽  
Serious Adverse Events ◽  
Content Type ◽  
Group 4 ◽  
Positive Stool ◽  
Toxigenic Strains ◽  
Stool Cultures

ABSTRACTVP20621, spores of nontoxigenicClostridium difficile(NTCD) strain M3, is protective against challenge with toxigenic strains in hamsters. Human administration and colonization may prevent primaryC. difficileinfection (CDI) or recurrent CDI. Healthy adult subjects 18 to 45 years old or ≥60 years old received single or multiple doses of an oral suspension of VP20621 (104, 106, or 108spores) or placebo. Group 4 (≥60 years old) received oral vancomycin for 5 days, followed by 14 days of VP20621 or placebo. Subjects were monitored for safety and followed through day 28. Stool was cultured forC. difficilebefore, during, and after VP20621 administration. Isolates were tested for toxin by enzyme immunoassay, and VP20621 was confirmed by molecular typing. After single escalating doses, no subjects hadC. difficile-positive stool cultures. VP20621 was found in the stool of all subjects given 108spores twice a day. Following vancomycin administration, VP20621 was detected in the stool of all subjects given 104, 106, or 108spores daily beginning on day 2 to 6. Recovered isolates were toxin negative and confirmed to be VP20621. There were no serious adverse events, and no subjects prematurely discontinued study drugs. Following vancomycin administration, 2 placebo subjects became colonized with toxigenicC. difficileand 3 placebo subjects became colonized with VP20621. Persistent colonization with VP20621 was detected in stools on days 21 to 28 in 44% of subjects. VP20621 was well tolerated and able to colonize the gastrointestinal tracts of subjects pretreated with vancomycin. Further study of VP20621 to prevent CDI in patients is warranted.

scholarly journals Clinical and Economic Benefits of Fidaxomicin Compared to Vancomycin for Clostridium difficile Infection

2015 ◽  
Vol 59 (11) ◽  
pp. 7007-7010 ◽  
Author(s):  
Jason C. Gallagher ◽  
Joseph P. Reilly ◽  
Bhagyashri Navalkele ◽  
Gemma Downham ◽  
Kevin Haynes ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Treated Patient ◽  
Hospital Costs ◽  
Antibiotic Use ◽  
Economic Benefits ◽  
Drug Costs ◽  
Hospital Charges ◽  
Oral Vancomycin ◽  
Content Type ◽  
Lengths Of Stay

ABSTRACTWe studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment ofClostridium difficileinfection (CDI) in patients hospitalized during a 2-year period. This study evaluated patients who received oral vancomycin or fidaxomicin for the treatment of CDI during a 2-year period. All included patients were eligible for administration of fidaxomicin via a protocol that encouraged its use for selected patients. The primary clinical endpoint was 90-day readmission with a diagnosis of CDI. Hospital charges and insurance reimbursements for readmissions were calculated along with the cost of CDI therapy to estimate the financial impact of the choice of therapy. Recurrences were seen in 10/49 (20.4%) fidaxomicin patients and 19/46 (41.3%) vancomycin patients (P= 0.027). In a multivariate analysis that included determinations of severity of CDI, serum creatinine increases, and concomitant antibiotic use, only fidaxomicin was significantly associated with decreased recurrence (adjusted odds ratio [aOR], 0.33; 95% confidence interval [CI], 0.12 to 0.93). The total lengths of stay of readmitted patients were 183 days for vancomycin and 87 days for fidaxomicin, with costs of $454,800 and $196,200, respectively. Readmissions for CDI were reimbursed on the basis of the severity of CDI, totaling $151,136 for vancomycin and $107,176 for fidaxomicin. Fidaxomicin drug costs totaled $62,112, and vancomycin drug costs were $6,646. We calculated that the hospital lost an average of $3,286 per fidaxomicin-treated patient and $6,333 per vancomycin-treated patient, thus saving $3,047 per patient with fidaxomicin. Fidaxomicin use for CDI treatment prevented readmission and decreased hospital costs compared to use of oral vancomycin.

Trimethoprim/Sulfamethoxazole-Associated Pseudomembranous Colitis

1982 ◽  
Vol 16 (3) ◽  
pp. 244-247 ◽  
Author(s):  
Steven A. Scott
Keyword(s):  
Urinary Tract Infection ◽  
Adverse Reaction ◽  
Urinary Tract ◽  
Clostridium Difficile ◽  
Tract Infection ◽  
Pseudomembranous Colitis ◽  
Causative Organism ◽  
Oral Vancomycin ◽  
Stool Cultures

A case of TMP/SMX-associated pseudomembranous colitis is described in a patient being treated for a urinary tract infection. Pseudomembranes are visualized on proctosigmoidoscopy, and stool cultures identified Clostridium difficile as the causative organism. The patient was treated successfully with oral vancomycin. A review of this infrequently reported adverse reaction to TMP/SMX is presented, emphasizing etiology and treatment.

scholarly journals A Novel Agent Effective against Clostridium difficile Infection

2011 ◽  
Vol 56 (3) ◽  
pp. 1624-1626 ◽  
Author(s):  
Sofya Dvoskin ◽  
Wei-Chu Xu ◽  
Neal C. Brown ◽  
Ivan B. Yanachkov ◽  
Milka Yanachkova ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Dna Polymerase ◽  
Clostridium Difficile Infection ◽  
Human Disease ◽  
Oral Vancomycin ◽  
Hamster Model ◽  
Content Type ◽  
Novel Agent

ABSTRACTN2-(3,4-Dichlorobenzyl)-7-(2-[1-morpholinyl]ethyl)guanine (MorE-DCBG, 362E) is a synthetic purine that selectively inhibits the replication-specific DNA polymerase ofClostridium difficile. MorE-DCBG and its analogs strongly inhibited the growth of a wide variety ofC. difficilestrains. When administered orally in a hamster model ofC. difficile-specific colitis, 362E was as effective as oral vancomycin, the current agent of choice for treating severe forms of the human disease.

scholarly journals Clostridium difficile PCR Cycle Threshold Predicts Free Toxin

2017 ◽  
Vol 55 (9) ◽  
pp. 2651-2660 ◽  
Author(s):  
Fiona Senchyna ◽  
Rajiv L. Gaur ◽  
Saurabh Gombar ◽  
Cynthia Y. Truong ◽  
Lee F. Schroeder ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Predictive Value ◽  
Reference Method ◽  
Neutralization Assay ◽  
Enzyme Linked Immunosorbent Assay ◽  
Content Type ◽  
Cycle Threshold ◽  
Positive Stool ◽  
Stool Samples ◽  
Sensitivity Specificity

ABSTRACTThere is no stand-aloneClostridium difficilediagnostic that can sensitively and rapidly detect fecal free toxins. We investigated the performance of theC. difficilePCR cycle threshold (CT) for predicting free toxin status. Consecutive stool samples (n= 312) positive for toxigenicC. difficileby the GeneXpertC. difficile/EpitcdBPCR assay were tested with the rapid membrane C. Diff Quik Chek Complete immunoassay (RMEIA). RMEIA toxin-negative samples were tested with the cell cytotoxicity neutralization assay (CCNA) and tgcBIOMICS enzyme-linked immunosorbent assay (ELISA). Using RMEIA alone or in combination with CCNA and/or ELISA as the reference method, the accuracy ofCTwas measured at differentCTcutoffs. Using RMEIA as the reference method, aCTcutoff of 26.35 detected toxin-positive samples with a sensitivity, specificity, positive predictive value, and negative predictive value of 96.0% (95% confidence interval [CI], 90.2% to 98.9%), 65.9% (95% CI, 59.0% to 72.2%), 57.4% (95% CI, 52.7% to 62%), and 97.1% (95% CI, 92.8% to 98.9), respectively. Inclusion of CCNA in the reference method improvedCTspecificity to 78.0% (95% CI, 70.7% to 84.2%). Intercartridge lotCTvariability measured as the average coefficient of variation was 2.8% (95% CI, 1.2% to 3.2%). Standardizing the input stool volume did not improveCTtoxin specificity. The medianCTvalues were not significantly different between stool samples with Bristol scores of 5, 6, and 7, between pediatric and adult samples, or between presumptive 027 and non-027 strains. In addition to sensitively detecting toxigenicC. difficilein stool, on-demand PCR may also be used to accurately predict toxin-negative stool samples, thus providing additional results in PCR-positive stool samples to guide therapy.

scholarly journals Strategies for Optimizing the Diagnostic Predictive Value of Clostridium difficile Molecular Diagnostics

2017 ◽  
Vol 55 (5) ◽  
pp. 1244-1248 ◽  
Author(s):  
Larry K. Kociolek
Keyword(s):  
Clostridium Difficile ◽  
Predictive Value ◽  
Clinical Microbiology ◽  
Nucleic Acid Amplification ◽  
Oral Vancomycin ◽  
Content Type ◽  
Clinical Bioinformatics ◽  
Laxative Use ◽  
Low Probability ◽  
Clinically Significant

ABSTRACT Because nucleic acid amplification tests (NAATs) do not distinguish Clostridium difficile infection (CDI) and asymptomatic C. difficile carriage, the diagnostic predictive value of NAATs is limited when used in patients with a low probability of CDI. In this issue of the Journal of Clinical Microbiology , Truong et al. (J. Clin. Microbiol., 55:1276–1284, 2017, https://doi.org/10.1128/JCM.02319-16 ) report significant reductions in hospital-onset CDI and oral vancomycin utilization at their institution following implementation of a novel intervention that leveraged their clinical bioinformatics resources to prevent C. difficile testing of stools from patients without clinically significant diarrhea and in patients with recent laxative use.

scholarly journals Real-Time Electronic Tracking of Diarrheal Episodes and Laxative Therapy Enables Verification of Clostridium difficile Clinical Testing Criteria and Reduction of Clostridium difficile Infection Rates

2017 ◽  
Vol 55 (5) ◽  
pp. 1276-1284 ◽  
Author(s):  
Cynthia Y. Truong ◽  
Saurabh Gombar ◽  
Richard Wilson ◽  
Gopalakrishnan Sundararajan ◽  
Natasa Tekic ◽  
...  
Keyword(s):  
Health Care ◽  
Clostridium Difficile ◽  
Real Time ◽  
Complication Rates ◽  
Clinical Testing ◽  
Oral Vancomycin ◽  
Content Type ◽  
Days Of Therapy ◽  
Data Tracking ◽  
Testing Criteria

ABSTRACT Health care-onset health care facility-associated Clostridium difficile infection (HO-CDI) is overdiagnosed for several reasons, including the high prevalence of C. difficile colonization and the inability of hospitals to limit testing to patients with clinically significant diarrhea. We conducted a quasiexperimental study from 22 June 2015 to 30 June 2016 on consecutive inpatients with C. difficile test orders at an academic hospital. Real-time electronic patient data tracking was used by the laboratory to enforce testing criteria (defined as the presence of diarrhea [≥3 unformed stools in 24 h] and absence of laxative intake in the prior 48 h). Outcome measures included C. difficile test utilization, HO-CDI incidence, oral vancomycin utilization, and clinical complications. During the intervention, 7.1% (164) and 9.1% (211) of 2,321 C. difficile test orders were canceled due to absence of diarrhea and receipt of laxative therapy, respectively. C. difficile test utilization decreased upon implementation from an average of 208.8 tests to 143.0 tests per 10,000 patient-days ( P < 0.001). HO-CDI incidence rate decreased from an average of 13.0 cases to 9.7 cases per 10,000 patient-days ( P = 0.008). Oral vancomycin days of therapy decreased from an average of 13.8 days to 9.4 days per 1,000 patient-days ( P = 0.009). Clinical complication rates were not significantly different in patients with 375 canceled orders compared with 869 episodes with diarrhea but negative C. difficile results. Real-time electronic clinical data tracking is an effective tool for verification of C. difficile clinical testing criteria and safe reduction of inflated HO-CDI rates.

scholarly journals High Prevalence of Toxigenic and NontoxigenicClostridium difficileStrains in Malaysia

2018 ◽  
Vol 56 (6) ◽  
Author(s):  
Thomas V. Riley ◽  
Deirdre A. Collins ◽  
Rina Karunakaran ◽  
Maria Abdul Kahar ◽  
Ariza Adnan ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Southeast Asia ◽  
Kuala Lumpur ◽  
Content Type ◽  
Clinical Presentations ◽  
High Prevalence ◽  
Pcr Ribotyping ◽  
Severe Infections ◽  
Stool Specimens ◽  
Toxigenic Strains

ABSTRACTAccumulating evidence shows a high prevalence ofClostridium difficilein Southeast Asia associated with a range of clinical presentations. However, severe infections are rarely reported. We investigatedC. difficileinfection (CDI) across four hospitals in Kuala Lumpur and Kota Bharu, Malaysia. Enzyme immunoassays for glutamate dehydrogenase (GDH) and toxin A or B were performed on diarrheal stool specimens collected from patients in 2015 and 2016. Specimens were also cultured and isolates ofC. difficilecharacterized by PCR ribotyping and detection of toxin genes. In total, 437 specimens were collected and fecal toxin was detected in 3.0%. A further 16.2% of specimens were GDH positive and toxin negative. After culture, toxigenic strains were isolated from 10.3% and nontoxigenic strains from 12.4% of specimens. The most prevalent PCR ribotypes (RTs) were RT 017 (20.0%) and RT 043 (10.0%). The high prevalence of RT 017 and nontoxigenic strains in Malaysia and in neighboring Thailand and Indonesia suggests that they localize to the region of Southeast Asia, with an implication that they may mediate the burden of CDI in the region.

scholarly journals Clinical Significance of Toxigenic Clostridioides difficile Growth in Stool Cultures during the Era of Nonculture Methods for the Diagnosis of C. difficile Infection

2021 ◽  
Author(s):  
Ching-Chi Lee ◽  
Jen-Chieh Lee ◽  
Chun-Wei Chiu ◽  
Pei-Jane Tsai ◽  
Wen-Chien Ko ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Fecal Samples ◽  
Content Type ◽  
Toxin Genes ◽  
Clostridioides Difficile ◽  
Positive Stool ◽  
Stool Cultures

The importance of detecting toxins or toxin genes when diagnosing Clostridioides difficile infections (CDIs) or predicting the severity and outcomes of CDI has been emphasized in recent years. Although the yielding of C. difficile from stool cultures might implicate higher bacterial loads in fecal samples, in an era of nonculture methods for the standard diagnosis of CDIs, clinical significance of positive stool cultures of toxigenic C. difficile was analyzed in this study.

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.

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