scholarly journals Microbiological Characterization and Clinical Outcomes After Extended-Pulsed Fidaxomicin Treatment for Clostridioides difficile Infection in the EXTEND Study

2019 ◽  
Vol 6 (11) ◽  
Author(s):  
Mark H Wilcox ◽  
Oliver A Cornely ◽  
Benoit Guery ◽  
Chris Longshaw ◽  
Areti Georgopali ◽  
...  

Abstract Background Clostridioides (Clostridium) difficile infection (CDI) is diagnosed using clinical signs and symptoms plus positive laboratory tests. Recurrence of CDI after treatment is common, and coinfection with other enteric pathogens may influence clinical outcomes. Methods We aimed to assess rates of C difficile positivity, by enzyme-linked immunosorbent assay (ELISA) toxin A/B and BioFire FilmArray, and the effect of enteric coinfection on clinical outcomes, using samples from the EXTEND study of extended-pulsed fidaxomicin (EPFX) versus standard vancomycin. Results All 356 randomized and treated patients tested positive for C difficile toxin A/B by local tests; a majority (225 of 356, 63.2%) also tested positive by both ELISA and BioFire. Most stool samples taken at screening tested positive for C difficile only using BioFire (EPFX: 112 of 165, 69.7%; vancomycin: 118 of 162, 72.8%). Of the 5 patients who failed treatment and had stool samples available, all (1) had tested negative for C difficile by BioFire at screening and (2) were negative by ELISA at time of treatment failure. When analyzed by BioFire results at screening, rates of sustained clinical cure at 30 days after end of treatment were numerically higher with EPFX than with vancomycin for almost all patients, except for those who tested negative for C difficile but positive for another pathogen. However, these outcome differences by presence of coinfection did not reach statistical significance. Whole-genome sequencing analysis determined that 20 of 26 paired samples from patients with recurrence were reinfections with the same C difficile strain. Conclusions Testing for presence of copathogens in clinical trials of antibiotics could help to explain clinical failures.

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Swarna Rajagopalan ◽  
Richard Ronca ◽  
Ausim Azizi

INTRODUCTION: Infection is a significant cause of mortality in patients with both ischemic and hemorrhagic stroke. This is thought to occur as a result of stroke-induced systemic immunosuppression (SIIS). The role of cerebral damage pre-disposing to sepsis has only been addressed in a few studies for ischemic stroke, and literature is sparse in Spontaneous Intracerebral Hemorrhage (SICH) patients who have higher mortality, greater disability and require more intensive medical care. We sought to determine identify predictors of SIIS and sepsis, so we may be able to recognize and intervene early. METHODOLOGY: We retrospectively analyzed 40 patients with SICH admitted to the NICU between January 2012 and January 30, 2014. We included patients with SICH. We excluded patients with multi-compartmental hemorrhage and patients lacking outcome data. Patient demographics including age, gender, location, volume of SICH, GCS, and total lymphocyte counts from days one to five of hospitalization was recorded. Data was divided into a non-infection group, where patients lacked any clinical or laboratory evidence of infections, and an infection group. Statistical analysis was performed to compare lymphocyte depletion over time between patients that developed an infection and those that did not. RESULTS: From the cohort of 40 patients with SICH, 20 developed an infection during their hospital course. Total lymphocyte counts were lower on all five days in the infection group compared to the non-infection group and became significant on day four of hospitalization (1 in the infection group vs. 2.1 in the non-infection group, p<0.01. Lymphopenia preceded clinical signs and symptoms of infection, which occurred in average on day 5.8 of hospitalization. Patients in the infection group had greater hemorrhage volume (32.5 ml vs. 15.5 ml) and poorer GCS scores on admission (12.7 vs. 11.8) although these differences did not reach statistical significance. CONCLUSION: The incidence of sepsis is high in SICH patients, and these patients have worse prognostic parameters. Our data suggests identification of lymphopenia may be a significant predictor of development of clinical infection in these patients. Future studies with larger sample sizes are warranted.


2016 ◽  
Vol 3 (4) ◽  
Author(s):  
Boushab Mohamed Boushab ◽  
Fatima Zahra Fall-Malick ◽  
Sidi El Wafi Ould Baba ◽  
Mohamed Lemine Ould Salem ◽  
Marie Roseline Darnycka Belizaire ◽  
...  

Abstract Background Rift Valley Fever epizootics are characterized by numerous abortions and mortality among young animals. In humans, the illness is usually characterized by a mild self-limited febrile illness, which could progress to more serious complications.Objectives. The aim of the present prospective study was to describe severe clinical signs and symptoms of Rift Valley Fever in southern Mauritania. Patients and methods Suspected cases were enrolled in Kiffa (Assaba) and Aleg (Brakna) Hospital Centers from September 1 to November 7, 2015, based on the presence of fever, hemorrhagic or meningoencephalitic syndromes, and probable contact with sick animals. Suspected cases were confirmed by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR). Results There were thirty-one confirmed cases. The sex ratio M/F and the average age were 2.9 and 25 years old [range, 4-70 years old], respectively. Mosquito bites, direct contact with aborted or dead animals, and frequent ingestion of milk from these animals were risk factors observed in all patients. Hemorrhagic and neurological manifestations were observed in 81% and 13% of cases, respectively. The results of laboratory analysis showed high levels of transaminases, creatinine, and urea associated with thrombocytopenia, anemia, and leukopenia. All patients who died (42%) had a hemorrhagic syndrome and 3 of them had a neurological complication. Among the cured patients, none had neurologic sequelae. Conclusion The hemorrhagic form was the most common clinical manifestation of RVF found in southern Mauritania and was responsible for a high mortality rate. Our results justify the implementation of a continuous epidemiological surveillance.


Author(s):  
Flywell Kawonga ◽  
Gerald Misinzo ◽  
Dylo Pemba ◽  
Leonard Mboera ◽  
Isaac Thom Shawa

Chikungunya is a mosquito-borne viral disease caused by Chikungunya virus (CHIKV. We conducted this study determine the seroprevalence and clinical presentation of Chikungunya infection among outpatients seeking healthcare in Mzuzu City, Malawi. Blood samples were collected from malaria negative and non-septic febrile outpatients with fevers &ge;38 &deg;C, for not more than 5 days. The enzyme- linked immunosorbent assay (ELISA) test was used to detect anti-CHIKV IgM antibodies and its results were used to determine seroprevalence of Chikungunya. A total of 119 serum samples were tested, of these, 73 (61.3%) tested positive for anti-CHIKV IgM antibodies by ELISA. Laboratory requisition forms were used to capture demographic information such as age, sex, clinical signs and symptoms presented by the enrolled patients. Age groups of 1-9, 10- 19, 20- 29, 30- 39, 40- 49, and &ge;50 years had 17.8% (n= 13), 12.3 %,( n=9), 15.1%) (n=11), 19.2%; (n=14), 17.8% (n=13) and 17.8% (n=13) proportion of seroprevalence respectively. Most of the CHIKV infected individuals presented with fever (52.05%), joint pain (45.21%) and abdominal pain (42.67%). The presence of anti- CHIKV IgM antibodies suggest the presence of recent CHIKV infection and therefore accurate laboratory assays are highly recommended for CHIKV diagnosis and appropriate management of febrile patients.


2016 ◽  
Vol 235 (2) ◽  
pp. 97-105 ◽  
Author(s):  
Yalu Liu ◽  
Qi Zhang ◽  
Jing Li ◽  
Xunda Ji ◽  
Yu Xu ◽  
...  

Objective: The aim of the study was to analyze the clinical characteristics of pediatric patients with ocular toxocariasis. Methods: Ocular toxocariasis was diagnosed and treated in 46 children from Shanghai and surrounding provinces. The diagnosis of ocular toxocariasis was confirmed immunologically by performing an enzyme-linked immunosorbent assay on serum and/or intraocular fluid. All pediatric patients and their guardians completed a questionnaire concerning their cases and living habits. Results: The mean age of onset was 6 ± 3 years. Most children (85%) resided in rural areas, and 91% of the children had contact with adult dogs or puppies. At the first visit, visual acuity (VA) was <20/200 in 36 cases, and we detected peripheral granuloma in 36 patients. In our study, the most common signs were vitritis, vitreous strands, and tractional retinal detachment. The Optomap 200Tx device detected granuloma with an 85% sensitivity, which is much higher than that of other techniques. We treated 40 cases (87%) with topical corticosteroids, while 28 patients (61%) were treated with systemic corticosteroids. Only 18 children (39%) required surgical intervention. All patients were examined and treated by the same ophthalmologists. Conclusions: Preschool children in China are more often affected by toxocariasis compared with other age groups. The most common signs included unilateral granuloma and ocular inflammation. In our study, clinical manifestations were severe and complicated. At the first visit, VA was <20/200 in most patients. Ocular toxocariasis was diagnosed on the basis of clinical signs and symptoms; the diagnosis was confirmed by immunological testing. Techniques using the Optomap 200Tx device can facilitate the early detection and lead to better visual prognosis.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S48-S49 ◽  
Author(s):  
Danielle Porter ◽  
Ying Guo ◽  
Jason Perry ◽  
David Gossage ◽  
Timothy Watkins ◽  
...  

Abstract Background Presatovir is an oral respiratory syncytial virus (RSV) fusion inhibitor in development for the treatment of RSV infection. Results from a healthy volunteer challenge study show that presatovir significantly reduced RSV viral load and clinical signs and symptoms. Here we present combined resistance analyses from 4 phase 2b studies in naturally RSV-infected adults. Methods RSV RNA was isolated from nasal swabs collected at baseline and postbaseline in studies GS-US-218-0108, GS-US-218–1502, GS-US-218–1227, and GS-US-218–1797. Full-length RSV fusion (F) gene was PCR amplified and population sequencing was performed. Results Of 233 presatovir-treated adults in the efficacy analyses, post-baseline resistance-associated substitutions were detected in 18 (7.7%) subjects. Frequencies of resistance development varied by study (Table 1). Resistance substitutions known to confer high-level (&gt;200 fold) reduced susceptibility to presatovir detected in &gt;1 subject were: T400I (n = 6), S398L (n = 3), L141F (n = 2), and F140I (n = 2) in F. Subjects with resistant virus had less viral load reduction than presatovir-treated subjects without resistant virus. Resistance development did not impact clinical outcomes. In study GS-US-218-0108, subjects with lymphopenia (&lt;200 cells/μL) at baseline were significantly more likely to develop resistance substitutions. Conclusion Presatovir treatment resulted in varying rates of resistance development across 4 phase 2b studies. Resistance development impacted virologic response without affecting clinical outcomes. Differences among study populations and dosing regimens may have influenced rates of resistance development. Disclosures D. Porter, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. Y. Guo, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. J. Perry, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. D. Gossage, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. T. Watkins, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. J. Chien, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. R. Jordan, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Asma Sadiq ◽  
Habib Bokhari ◽  
Zobia Noreen ◽  
Rai Muhammad Asghar ◽  
Nazish Bostan

Abstract Background Acute diarrhea is a leading cause of morbidity and mortality in children particularly in developing countries of Asia and Africa. The present study was conducted to detect the two most important pathogens, rotavirus and Campylobacter Jejuni in children suffering with diarrhea in Rawalpindi and Islamabad, Pakistan in 2014. The clinical and epidemiological aspects of the disease were also investigated. Methods A total of 500 stool samples were collected from children presented with clinical signs and symptoms of acute diarrhea. The samples were initially screened for the presence of rotavirus A (RVA) via ELISA (Enzyme-linked immunosorbent assay) and RT-PCR (Reverse Transcriptase PCR) and then were analysed for C. jejuni by using species specific PCR assay. Results The detection rate of RVA was 26.4% (132/500) while, Campylobacter was detected in 52% (260/500) of samples with C. jejuni accounted for 48.2% (241/500) of all study cases. Co-infection of C. jejuni with RVA was identified in 21.8% of all cases. Children with RVA and C. jejuni co-infection showed a higher probability (p = 0.01) to be dehydrated. A significant association (p = 0.02) was found between C. jejuni positive status and fever in children. The median age of children with both RVA and C. jejuni infection was 6–11 months. The RVA detection rate was high in winter months of the year while, C. jejuni infections were documented high in summer over 1 year study period. Conclusions The overall results have demonstrated the high prevalence of C. jejuni in Rawalpindi, Islamabad, Pakistan in 2014. The results of present study will not only help to calculate disease burden caused by C. jejuni and rotavirus but also will provide critical information to health authorities in planning public health care strategies against these pathogens.


2021 ◽  
Vol 23 (2) ◽  
pp. 212-216
Author(s):  
Maria G. Shvydkaya ◽  
A.M. Zatevalov ◽  
S.D. Mitrokhin ◽  
D.T. Dzhandarova

Objective. To improve stool sample culture and isolation of anaerobic flora, including Clostridioides difficile in the routine microbiological laboratory practice at the children’s oncology hospital. Materials and Methods. A total of 517 stool samples collected from patients in children’s oncology hospital from 2013 to 2015 were studied. All samples were analyzed by ELISA for C. difficile toxins and by culture according to dedicated 5 schemes for isolation of anaerobic bacteria, including C. difficile. Statistical significance of differences in isolation rates between the studied groups (culture schemes) was assessed by Pearson test. Results. Culture in liver broth and covering with technical agar followed by culture on anaerobic agar yielded 100% isolation rate of toxigenic C. difficile strains. This culture scheme is also suitable for isolating concomitant anaerobic flora: non-toxigenic C. difficile strains, Clostridium perfringens, other Clostridia spp. and Bacteroides spp. Conclusions. Use of the liquid accumulation medium and covering with technical agar make it possible to isolate anaerobic flora from stool samples and increase an isolation rate of toxigenic C. difficile strains to 100% of ELISA-positive samples.


2004 ◽  
Vol 4 (2) ◽  
pp. 22-24 ◽  
Author(s):  
Šukrija Zvizdić ◽  
Sađida Telalbašić ◽  
Edina Bešlagić ◽  
Semra Čavaljuga ◽  
Jasminka Maglajlić ◽  
...  

Rotaviruses are the major causes of viral gastroenteritis in infant and the young children. There are a wide spectrum of clinical signs and symptoms of rotavirosis. Rotavirus infection is fecal-oral infection. Rotaviruses prove with Latex agglutination test and electron microscopy. In a four year period 943 stool samples out of 527 hospitalized patients had been analyzed. A presence of rotavirus is proved with a LA and EM tests at 170 (32,2%) patients age 0-7 years, in their stool samples. Analyzing age groups of these patients, it was found that the rotavirusesinfection the most frequently occurred at age group from 7-24 months. From 170 positive patients, 122 or 71,8% were in this age group. At all patients was found diarrhea, vomiting in a 90,5% cases. Mild fever had 65,5% patients, signs of a respiratory infection appeared at 60,7% patients, abdominal pain at 13,3% patients. Severe dehydration had 49,9% patients and metabolic acidosis had 79,2% cases. Macroscopically blood in stool had 6,4% patients, slime in a stool 46,0% patients was found, and aholic stool had 8,4% patients. In all hospitalized patients disease lasted in average 12,6 days, and the hospitalization in average 10,2 days. None of the patient had any kind of complication, all of them very successfully cured. These results confirm that rotaviruses are important health problem among infant and the young children in Bosnia and Herzegovina.


2021 ◽  
Author(s):  
Mary K Young ◽  
Jhansi L Leslie ◽  
Gregory R Madden ◽  
David M Lyerly ◽  
Robert J Carman ◽  
...  

Background. The incidence of Clostridioides difficile infection (CDI) has increased over the past two decades and is considered an urgent threat by the Centers for Disease Control. Hypervirulent strains such as ribotype 027, that possess genes for an additional toxin C. difficile binary toxin (CDT) are contributing to increased morbidity and mortality. In the mouse model, CDT activates Toll-like receptor 2 resulting in suppression of a protective type 2 innate immune response mediated by eosinophils. Methods. We retrospectively tested stool from 215 CDI patients for CDT by enzyme-linked immunosorbent assay (ELISA). Stratifying patients by CDT status, we assessed if disease severity and clinical outcomes correlated with CDT positivity. Additionally, we performed 16 S rRNA gene sequencing to examine if CDT positive samples had an altered fecal microbiota. Results. We found that patients with CdtB, the pore forming component of CDT, detected in their stool were more likely to have severe disease and had higher 90-day mortality compared to CDT negative patients. CDT positive patients also had higher C. difficile bacterial burden and white blood cell counts. There was no significant difference in gut microbiome diversity between CDT positive and negative patients. Conclusions. Patients with fecal samples that were positive for CDT had increased disease severity and worse clinical outcomes. Utilization of PCR and C. difficile Toxins A and B testing may not reveal the entire picture when diagnosing CDI and the detection of CDT-expressing strains may be valuable during patient treatment.


2019 ◽  
Vol 70 (12) ◽  
pp. 2628-2633 ◽  
Author(s):  
Qianyun Lin ◽  
Nira R Pollock ◽  
Alice Banz ◽  
Aude Lantz ◽  
Hua Xu ◽  
...  

Abstract Background Most Clostridioides difficile toxinogenic strains produce both toxins A and B (A+B+), but toxin A–negative, toxin B–positive (A−B+) variants also cause disease. We report the identification of a series of pathogenic clinical C. difficile isolates that produce high amounts of toxin A with low or nondetectable toxin B. Methods An ultrasensitive, quantitative immunoassay was used to measure toxins A and B in stool samples from 187 C. difficile infection (CDI) patients and 44 carriers. Isolates were cultured and assessed for in vitro toxin production and in vivo phenotypes (mouse CDI model). Results There were 7 CDI patients and 6 carriers who had stools with detectable toxin A (TcdA, range 23–17 422 pg/mL; 5.6% of samples overall) but toxin B (TcdB) below the clinical detection limit (&lt;20 pg/mL; median TcdA:B ratio 17.93). Concentrations of toxin A far exceeded B in in vitro cultures of all 12 recovered isolates (median TcdA:B ratio 26). Of 8 toxin A&gt;&gt;B isolates tested in mice, 4 caused diarrhea, and 3 of those 4 caused lethal disease. Ribotyping demonstrated strain diversity. TcdA-predominant samples were also identified at 2 other centers, with similar frequencies (7.5% and 6.8%). Conclusions We report the discovery of clinical pathogenic C. difficile strains that produce high levels of toxin A but minimal or no toxin B. This pattern of toxin production is not rare (&gt;5% of isolates) and is consistently observed in vitro and in vivo in humans and mice. Our study highlights the significance of toxin A in human CDI pathogenesis and has important implications for CDI diagnosis, treatment, and vaccine development.


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