Next-generation Diagnostics for Melioidosis: Evaluation of a Prototype i-STAT Cartridge to Detect Burkholderia pseudomallei Biomarkers

2018 ◽  
Vol 69 (3) ◽  
pp. 421-427 ◽  
Author(s):  
Kevin L Schully ◽  
Charles C Young ◽  
Mark Mayo ◽  
Amy L Connolly ◽  
Vanessa Rigas ◽  
...  
Keyword(s):  
Blood Culture ◽  
Burkholderia Pseudomallei ◽  
High Sensitivity ◽  
Diagnostic Tools ◽  
Next Generation ◽  
Blood Samples ◽  
Life Threatening ◽  
Low Sensitivity ◽  
Culture Positive ◽  
Culture Negative

AbstractBackgroundInfection with the gram-negative bacterium Burkholderia pseudomallei can result in melioidosis, a life-threatening disease that can be difficult to diagnose. Culture remains the gold standard for diagnosis but requires laboratory resources not available in many endemic regions. A lateral flow immunoassay has shown promise for POC diagnostics but suffers from low sensitivity when used on blood samples. PCR also has low sensitivity on blood, attributed to the low bacterial numbers in blood observed in melioidosis patients, even when bacteraemic.MethodsA prototype i-STAT cartridge was developed to utilize the monoclonal antibody specific for the capsule of pathogenic Burkholderia species employed on the LFI. The resulting POC assay was evaluated on 414 clinical specimens from Darwin, Australia and Cambodia.ResultsThe i-STAT assay accurately distinguished Australian blood culture positive melioidosis patients from Australian patients hospitalized with other infections (AUC = 0.91, 95% CI 0.817 - 1.0). We derived an assay cutoff with 76% sensitivity and 94% specificity that correctly classified 88% (n = 74) of the Australian patients. Interestingly, only 46% (6/13) of the culture-positive melioidosis patients in Cambodia were classified correctly. Of great importance however, the assay detected capsule from blood samples for 32% of blood culture negative melioidosis patients in both cohorts and previously undiagnosed melioidosis patients in Cambodia. In addition the assay showed high sensitivity and specificity for urine, pus and sputum.ConclusionsDiagnostic tools that are not dependent upon the growth kinetics or the levels of bacteremia of B. pseudomallei represent the next-generation of diagnostics and must be pursued further.

scholarly journals Diagnosing Sepsis in the Intensive Care Unit: A Retrospective Cohort Study

2020 ◽  
Author(s):  
Kerina Denny ◽  
Ross Lindell-Innes ◽  
Aaron Heffernan ◽  
David L. Paterson ◽  
John F Mcnamara ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Blood Culture ◽  
Organ Dysfunction ◽  
Point Of Care ◽  
Clinical History ◽  
Diagnostic Tools ◽  
Retrospective Diagnosis ◽  
Life Threatening ◽  
Culture Negative

Abstract Background: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In the intensive care unit (ICU), organ dysfunction is common. The challenge lies in determining when organ dysfunction can be attributed to infection. We aimed to retrospectively determine what proportion of patients commenced on antibiotics for presumed sepsis in a mixed ICU had blood-culture positive sepsis, blood-culture negative sepsis, or an aseptic mimic.Methods: One hundred antibiotic naïve ICU patients who were clinically deemed to have an infection were enrolled. Retrospective interpretation of clinical history, biochemical, and microbiological data was performed by three clinicians from the fields of intensive care and infectious disease who aimed to differentiate infective from non-infective insults.Results: There was good interrater reliability amongst clinician assessors using this approach (Krippendorf’s alpha 0.868) for the retrospective diagnosis of infection. In the examined cohort, 35 percent of patients met the criteria of blood culture positivity and an additional 41 percent of patients were assessed as having probable blood culture negative sepsis. Twenty-four percent of patients were retrospectively determined to not have had sepsis.Conclusions: Misdiagnosis of infection as a cause for organ dysfunction in the ICU is common. The false attribution of organ dysfunction to infection in the ICU has significant clinical and research implications, and highlights the need for accurate point-of-care sepsis diagnostic tools.

scholarly journals Comparison of Typhidot IgM test and blood culture in children with clinically compatible enteric fever

2018 ◽  
Vol 5 (6) ◽  
pp. 2129
Author(s):  
Sandeep Garg ◽  
Ajay Sankhe ◽  
Anuradha Joshi ◽  
Samrat Mehta
Keyword(s):  
Blood Culture ◽  
Observational Study ◽  
Enteric Fever ◽  
Early Stage ◽  
Antibiotic Administration ◽  
Highly Sensitive ◽  
Culture Sensitivity ◽  
Low Sensitivity ◽  
Culture Positive ◽  
Culture Negative

Background: The often-non-specific presentation of typhoid fever makes clinical diagnosis difficult. The blood culture is time consuming, affected by often given prior antibiotics and has low sensitivity (60%). Typhidot IgM gives quick results in early stage of disease. Pediatric data are scarce. So, we studied and compare Typhidot IgM test and blood culture in children with clinically compatible enteric fever.Methods: This was retrospective observational study done in Department of Pediatrics from the 1st October, 2017 to 30 September, 2018. 42 children with clinically compatible enteric fever (aged 6 months to 18 years); with either typhidot IgM or blood culture positive for Salmonella species were sampled and analyzed.Results: Typhidot IgM test had sensitivity of 92.7% (N = 39/42) compared to blood culture with sensitivity of 79.4% (N = 27/34). 2 out of 3 typhidot negative cases were S. Paratyphi positive in blood culture. Typhidot IgM had positive predictive value = 97.4% due to 1 false positive case. 19 (79.2%) out of 24 blood culture positive patients had not received any antibiotic prior test, 3 (60 %) out of 5 blood culture negative patients had received antibiotics.Conclusions: Typhidot IgM is a highly sensitive quick diagnostic tool for diagnosing enteric fever in children with sensitivity of 92.3% and PPV of 97.4% compared to blood culture (sensitivity= 79.4%). It is more sensitive to diagnose S. typhi enteric fever (sensitivity= 97.3%) then S. paratyphi (sensitivity= 50%). Antibiotic administration prior to blood culture testing reduces its positivity rate but not significantly statistically. Larger studies are needed to change the current recommendations on typhidot IgM.

scholarly journals Predictive and prognostic factors in patients with blood-culture-positive community-acquired pneumococcal pneumonia

2016 ◽  
Vol 48 (3) ◽  
pp. 797-807 ◽  
Author(s):  
Rosanel Amaro ◽  
Adamantia Liapikou ◽  
Catia Cilloniz ◽  
Albert Gabarrus ◽  
Francesc Marco ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Blood Culture ◽  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Pneumococcal Pneumonia ◽  
Protective Factor ◽  
Severe Pneumonia ◽  
Increased Risk ◽  
Culture Positive ◽  
Culture Negative

In patients with pneumococcal community-acquired pneumonia (CAP), the risk factors for bacteraemia and its impact on outcomes are not fully elucidated. We aimed to compare characteristics of patients with blood-culture-positiveversusblood-culture-negative pneumococcal CAP, and to characterise bacteraemic serotypes.We describe a prospective, observational study on nonimmunocompromised patients with pneumococcal CAP, from 1996 to 2013. We define severe pneumonia according to American Thoracic Society/Infectious Diseases Society of America guidelines.Of a total of 917 patients with pneumococcal CAP, 362 had blood-culture-positive pneumococcal pneumonia (BCPPP; 39%). High C-reactive protein (CRP) (≥20 mg·dL−1) (odds ratio (OR) 2.36, 95% CI 1.45–3.85), pleural effusion (OR 2.03, 95% CI 1.13–3.65) and multilobar involvement (OR 1.69, 95% CI 1.02–2.79) were independently associated with bacteraemic CAP, while nursing home resident (OR 0.12, 95% CI 0.01–1.00) was found as a protective factor. Despite the clinical differences, BCPPP showed similar outcomes to blood-culture-negative pneumococcal pneumonia (BCNPP). 14% of the serotypes (period 2006–2013) causing bacteraemia are included in pneumococcal conjugate vaccine PVC7, 74% in pneumococcal conjugate vaccine PVC13 and 83% in pneumococcal polysaccharide vaccine PPSV23.Pleural effusion, a high level of CRP and multilobar involvement predicted an increased risk of BCPPP. Although BCPPP patients were more severely ill at admission, mortality was not significantly greater than in BCNPP patients.

Diagnosis of blood culture-negative endocarditis and clinical comparison between blood culture-negative and blood culture-positive cases

Infection ◽  
2015 ◽  
Vol 44 (4) ◽  
pp. 459-466 ◽  
Author(s):  
Cristiane C. Lamas ◽  
Pierre-Edouard Fournier ◽  
Monica Zappa ◽  
Tatiana J. D. Brandão ◽  
Carolina A. Januário-da-Silva ◽  
...  
Keyword(s):  
Blood Culture ◽  
Clinical Comparison ◽  
Culture Positive ◽  
Culture Negative

scholarly journals Rapid Diagnosis of Bacteremia in Adults Using Acridine Orange Stained Buffy Coat Smears

1990 ◽  
Vol 1 (1) ◽  
pp. 7-10
Author(s):  
Mark Miller ◽  
Jack Mendelson
Keyword(s):  
Blood Culture ◽  
Acridine Orange ◽  
Buffy Coat ◽  
Blood Cultures ◽  
Rapid Screening ◽  
Blood Culture System ◽  
Blood Samples ◽  
Significant Difference ◽  
Rapid Screening Test ◽  
Low Sensitivity

The use of acridine orange stained buffy coat smears was assessed as a rapid screening test for bacteremia in adults. A total of 356 consecutive blood cultures were submitted with simultaneous anticoagulated blood samples, from which a buffy coat smear was prepared and stained with acridine orange (100 mg/L; pH 3.0). Forty-one of 356 blood samples (12%) yielded organisms in the blood culture system. Compared to blood culture, the overall sensitivity of acridine orange stained buffy coat smears was 16%, specificity 88%, and positive predictive value 13%. There was no statistically significant difference in performance of the test among patients who had fever greater than 39°C and/or shock. The low sensitivity and specificity of the test makes it unsuitable as a means of rapid screening for adults with suspected bacteremia.

Reassessment of Blood Culture-Negative Endocarditis: Its Profile Is Similar to That of Blood Culture-Positive Endocarditis

2012 ◽  
Vol 65 (10) ◽  
pp. 891-900 ◽  
Author(s):  
Carlos Ferrera ◽  
Isidre Vilacosta ◽  
Cristina Fernández ◽  
Javier López ◽  
Carmen Olmos ◽  
...  
Keyword(s):  
Blood Culture ◽  
Culture Positive ◽  
Culture Negative

scholarly journals Serial Detection of Circulating Mucorales DNA in Invasive Mucormycosis: A Retrospective Multicenter Evaluation

2019 ◽  
Vol 5 (4) ◽  
pp. 113 ◽  
Author(s):  
Toine Mercier ◽  
Marijke Reynders ◽  
Kurt Beuselinck ◽  
Ellen Guldentops ◽  
Johan Maertens ◽  
...  
Keyword(s):  
Positive Culture ◽  
Final Diagnosis ◽  
Diagnostic Tools ◽  
Kinetic Properties ◽  
Appropriate Treatment ◽  
Positive Culture Result ◽  
Appropriate Therapy ◽  
Low Sensitivity ◽  
Culture Positive ◽  
Missed Diagnoses

Invasive mucormycosis is a fungal infection with high mortality. Early diagnosis and initiation of appropriate treatment is essential to improve survival. However, current diagnostic tools suffer from low sensitivity, leading to delayed or missed diagnoses. Recently, several PCR assays for the detection of Mucorales DNA have been developed. We retrospectively assessed the diagnostic and kinetic properties of a commercial Mucorales PCR assay (MucorGenius®, PathoNostics) on serial blood samples from patients with culture-positive invasive mucormycosis and found an overall sensitivity of 75%. Importantly, a positive test preceded a positive culture result by up to 81 days (median eight days, inter-quartile range 1.75–16.25). After initiation of appropriate therapy, the average levels of circulating DNA decreased after one week and stabilized after two weeks. In conclusion, detection of circulating Mucorales DNA appears to be a good, fast diagnostic test that often precedes the final diagnosis by several days to weeks. This test could be especially useful in cases in which sampling for culture or histopathology is not feasible.

scholarly journals Comparing mortality between positive and negative blood culture results: an inverse probability of treatment weighting analysis of a multicenter cohort

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Aibo Liu ◽  
Chia-Hung Yo ◽  
Lu Nie ◽  
Hua Yu ◽  
Kuihai Wu ◽  
...  
Keyword(s):  
Propensity Score ◽  
Blood Culture ◽  
Early Mortality ◽  
Negative Blood Culture ◽  
Late Mortality ◽  
Inverse Probability ◽  
Propensity Score Model ◽  
Significant Difference ◽  
Culture Positive ◽  
Culture Negative

Abstract Background The association between blood culture status and mortality among sepsis patients remains controversial hence we conducted a tri-center retrospective cohort study to compare the early and late mortality of culture-negative versus culture-positive sepsis using the inverse probability of treatment weighting (IPTW) method. Methods Adult patients with suspected sepsis who completed the blood culture and procalcitonin tests in the emergency department or hospital floor were eligible for inclusion. Early mortality was defined as 30-day mortality, and late mortality was defined as 30- to 90-day mortality. IPTW was calculated from propensity score and was employed to create two equal-sized hypothetical cohorts with similar covariates for outcome comparison. Results A total of 1405 patients met the inclusion criteria, of which 216 (15.4%) yielded positive culture results and 46 (21.3%) died before hospital discharge. The propensity score model showed that diabetes mellitus, urinary tract infection, and hepatobiliary infection were independently associated with positive blood culture results. There was no significant difference in early mortality between patients with positive or negative blood culture results. However, culture-positive patients had increased late mortality as compared with culture-negative patients in the full cohort (IPTW-OR, 1.95, 95%CI: 1.14–3.32) and in patients with severe sepsis or septic shock (IPTW-OR, 1.92, 95%CI: 1.10–3.33). After excluding Staphylococcal bacteremia patients, late mortality difference became nonsignificant (IPTW-OR, 1.78, 95%CI: 0.87–3.62). Conclusions Culture-positive sepsis patients had comparable early mortality but worse late mortality than culture-negative sepsis patients in this cohort. Persistent Staphylococcal bacteremia may have contributed to the increased late mortality.

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