scholarly journals Development and implementation of a customised rapid syndromic diagnostic test for severe pneumonia

2021 ◽  
Vol 6 ◽  
pp. 256
Author(s):  
Vilas Navapurkar ◽  
Josefin Bartholdson Scott ◽  
Mailis Maes ◽  
Thomas P Hellyer ◽  
Ellen Higginson ◽  
...  

Background: The diagnosis of pneumonia has been hampered by a reliance on bacterial cultures which take several days to return a result, and are frequently negative. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and compromises good antimicrobial stewardship. The objective of this study was to establish the performance of a syndromic molecular diagnostic approach, using a custom TaqMan array card (TAC) covering 52 respiratory pathogens, and assess its impact on antimicrobial prescribing. Methods: The TAC was validated against a retrospective multi-centre cohort of broncho-alveolar lavage samples. The TAC was assessed prospectively in patients undergoing investigation for suspected pneumonia, with a comparator cohort formed of patients investigated when the TAC laboratory team were unavailable. Co-primary outcomes were sensitivity compared to conventional microbiology and, for the prospective study, time to result. Metagenomic sequencing was performed to validate findings in prospective samples. Antibiotic free days (AFD) were compared between the study cohort and comparator group. Results: 128 stored samples were tested, with sensitivity of 97% (95% confidence interval (CI) 88-100%). Prospectively, 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (interquartile range 41-69 hours) faster than culture and with sensitivity of 92% (95% CI 83-98%) compared to conventional microbiology. 94% of organisms identified by sequencing were detected by TAC. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). TAC group were more likely to experience antimicrobial de-escalation (odds ratio 2.9 (95%1.5-5.5)). Conclusions: Implementation of a syndromic molecular diagnostic approach to pneumonia led to faster results, with high sensitivity and impact on antibiotic prescribing.

2020 ◽  
Author(s):  
Vilas Navapurkar ◽  
Josefin Bartholdson Scott ◽  
Mailis Maes ◽  
Ellen Higginson ◽  
Sally Forrest ◽  
...  

AbstractRationaleThe diagnosis of infectious diseases has been hampered by reliance on microbial culture. Cultures take several days to return a result and organisms frequently fail to grow. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and compromises effective stewardship.ObjectivesTo establish the performance and clinical utility of a syndromic diagnostic for severe pneumonia.MethodsSingle ICU observational cohort study with contemporaneous comparator group. We developed and implemented a TaqMan array card (TAC) covering 52 respiratory pathogens in ventilated patients with suspected pneumonia. The time to result was compared against conventional culture, and sensitivity compared to conventional microbiology and metagenomic sequencing. We observed the clinician decisions in response to array results, comparing antibiotic free days (AFD) between the study cohort and comparator group.Results95 patients were enrolled with 71 forming the comparator group. TAC returned results 61 hours (IQR 42-90) faster than culture. The test had an overall sensitivity of 93% (95% CI 88-97%) compared to a combined standard of conventional culture and metagenomic sequencing, with 100% sensitivity for most individual organisms. In 54% of cases the TAC results altered clinical management, with 62% of changes leading to deescalation, 30% to an increase in spectrum, and investigations for alternative diagnoses in 9%. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02).ConclusionsImplementation of a customised syndromic diagnostic for pneumonia led to faster results, with high sensitivity and measurable impact on clinical decision making.


2021 ◽  
Author(s):  
Alexander M Reyzelman ◽  
Chia-Ding Shih ◽  
Gregory Tovmassian ◽  
Mohan Nathan ◽  
Ran Ma ◽  
...  

BACKGROUND Diabetic foot ulcers represent major health care complications both in terms of cost and impact to quality of life for patients with diabetic peripheral neuropathy. Temperature monitoring has been shown in previous studies to provide a useful signal of inflammation that may indicate the early presence of a foot injury. OBJECTIVE In this study we evaluated the temperature data for patients that presented with a diabetic foot injury while utilizing a sock-based remote temperature monitoring device. METHODS The study abstracted data from patients enrolled in a remote temperature monitoring program in year 2020-2021 using a smart sock (Siren Care, San Francisco, California, USA). In the study cohort, a total of 5 participants with a diabetes-related lower extremity injury during study period were identified. In the second comparison cohort, a total of 26 patients met the criteria for monitoring by the same methods that did not present with a diabetes-related podiatric injury during the same period. The 15-day temperature differential between six defined locations on each foot was the primary outcome measure among subjects who presented a diagnosed foot injury. Paired t-tests were used to compare the differences between the two groups. RESULTS A significant difference in temperature differential was observed in the group that presented with a podiatric injury over the course of evaluation vs. the comparator group that did not present with a podiatric injury with temperature measured in °F. The average difference from all six measured points was 1.4°F between the injury group (mean 3.6 +/- 3.0) and the comparator group (mean 2.2 +/- 2.5, t=-71.4; P<.000). CONCLUSIONS The presented study demonstrated significant temperature difference for patients presenting with a foot injury in a 15-day period prior to the diagnosis of an injury compared with a similar period for patients without an injury. The findings suggest temperature monitoring may be a predictor of a developing foot injury. The continuous temperature monitoring system employed has implications for further algorithm development to enable early detection. The study was limited by a nonrandomized, observational design with limited injuries present in the study period.


2020 ◽  
Vol 41 (S1) ◽  
pp. s453-s454
Author(s):  
Hasti Mazdeyasna ◽  
Shaina Bernard ◽  
Le Kang ◽  
Emily Godbout ◽  
Kimberly Lee ◽  
...  

Background: Data regarding outpatient antibiotic prescribing for urinary tract infections (UTIs) are limited, and they have never been formally summarized in Virginia. Objective: We describe outpatient antibiotic prescribing trends for UTIs based on gender, age, geographic region, insurance payer and International Classification of Disease, Tenth Revision (ICD-10) codes in Virginia. Methods: We used the Virginia All-Payer Claims Database (APCD), administered by Virginia Health Information (VHI), which holds data for Medicare, Medicaid, and private insurance. The study cohort included Virginia residents who had a primary diagnosis of UTI, had an antibiotic claim 0–3 days after the date of the diagnosis and who were seen in an outpatient facility in Virginia between January 1, 2016, and December 31, 2016. A diagnosis of UTI was categorized as cystitis, urethritis or pyelonephritis and was defined using the following ICD-10 codes: N30.0, N30.00, N30.01, N30.9, N30.90, N30.91, N39.0, N34.1, N34.2, and N10. The following antibiotics were prescribed: aminoglycosides, sulfamethoxazole/trimethoprim (TMP-SMX), cephalosporins, fluoroquinolones, macrolides, penicillins, tetracyclines, or nitrofurantoin. Patients were categorized based on gender, age, location, insurance payer and UTI type. We used χ2 and Cochran-Mantel-Haenszel testing. Analyses were performed in SAS version 9.4 software (SAS Institute, Cary, NC). Results: In total, 15,580 patients were included in this study. Prescriptions for antibiotics by drug class differed significantly by gender (P < .0001), age (P < .0001), geographic region (P < .0001), insurance payer (P < .0001), and UTI type (P < .0001). Cephalosporins were prescribed more often to women (32.48%, 4,173 of 12,846) than to men (26.26%, 718 of 2,734), and fluoroquinolones were prescribed more often to men (53.88%, 1,473 of 2,734) than to women (47.91%, 6,155 of 12,846). Although cephalosporins were prescribed most frequently (42.58%, 557 of 1,308) in northern Virginia, fluoroquinolones were prescribed the most in eastern Virginia (50.76%, 1677 of 3,304). Patients with commercial health insurance, Medicaid, and Medicare were prescribed fluoroquinolones (39.31%, 1,149 of 2,923), cephalosporins (56.33%, 1,326 of 2,354), and fluoroquinolones (57.36%, 5,910 of 10,303) most frequently, respectively. Conclusions: Antibiotic prescribing trends for UTIs varied by gender, age, geographic region, payer status and UTI type in the state of Virginia. These data will inform future statewide antimicrobial stewardship efforts.Funding: NoneDisclosures: Michelle Doll reports a research grant from Molnlycke Healthcare.


2020 ◽  
Vol 41 (S1) ◽  
pp. s302-s302
Author(s):  
Amanda Barner ◽  
Lou Ann Bruno-Murtha

Background: The Infectious Diseases Society of America released updated community-acquired pneumonia (CAP) guidelines in October 2019. One of the recommendations, with a low quality of supporting evidence, is the standard administration of antibiotics in adult patients with influenza and radiographic evidence of pneumonia. Procalcitonin (PCT) is not endorsed as a strategy to withhold antibiotic therapy, but it could be used to de-escalate appropriate patients after 48–72 hours. Radiographic findings are not indicative of the etiology of pneumonia. Prescribing antibiotics for all influenza-positive patients with an infiltrate has significant implications for stewardship. Therefore, we reviewed hospitalized, influenza-positive patients at our institution during the 2018–2019 season, and we sought to assess the impact of an abnormal chest x-ray (CXR) and PCT on antibiotic prescribing and outcomes. Methods: We conducted a retrospective chart review of all influenza-positive admissions at 2 urban, community-based, teaching hospitals. Demographic data, vaccination status, PCT levels, CXR findings, and treatment regimens were reviewed. The primary outcome was the difference in receipt of antibiotics between patients with a negative (<0.25 ng/mL) and positive PCT. Secondary outcomes included the impact of CXR result on antibiotic prescribing, duration, 30-day readmission, and 90-day mortality. Results: We reviewed the medical records of 117 patients; 43 (36.7%) received antibiotics. The vaccination rate was 36.7%. Also, 11% of patients required intensive care unit (ICU) admission and 84% received antibiotics. Moreover, 109 patients had a CXR: 61 (55.9%) were negative, 29 (26.6%) indeterminate, and 19 (17.4%) positive per radiologist interpretation. Patients with a positive PCT (OR, 12.7; 95% CI, 3.43–60.98; P < .0007) and an abnormal CXR (OR, 7.4; 95% CI, 2.9–20.1; P = .000003) were more likely to receive antibiotics. There was no significant difference in 30-day readmission (11.6% vs 13.5%; OR, 0.89; 95% CI, 0.21–3.08; P = 1) and 90-day mortality (11.6% vs 5.4%; OR, 2.37; 95% CI, 0.48–12.75; P = .28) between those that received antibiotics and those that did not, respectively. Furthermore, 30 patients (62.5%) with an abnormal CXR received antibiotics and 21 (43.7%) had negative PCT. There was no difference in 30-day readmission or 90-day mortality between those that did and did not receive antibiotics. Conclusions: Utilization of PCT allowed selective prescribing of antibiotics without impacting readmission or mortality. Antibiotics should be initiated for critically ill patients and based on clinical judgement, rather than for all influenza-positive patients with CXR abnormalities.Funding: NoneDisclosures: None


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lu Xie ◽  
Jie Xu ◽  
Xiaowei Li ◽  
Zuli Zhou ◽  
Hongqing Zhuang ◽  
...  

Abstract Background Complete surgical remission (CSR) is the best predictor of overall survival (OS) for patients with metastatic osteosarcoma. However, metastasectomy has not been widely implemented in China in the last decade due to various factors, and instead, most physicians choose hypofractionated radiotherapy to treat pulmonary lesions. This study aimed to retrospectively evaluate the outcomes of different local treatments for pulmonary lesions and identify the best local therapy strategies for these patients. Methods We reviewed the clinical courses of osteosarcoma patients with pulmonary metastases who were initially treated in two sarcoma centres in Beijing, China, from June 1st, 2009, to March 26th, 2020. With a median follow-up of 32.4 (95% confidence interval (CI): 30.8, 36.1) months, a total of 127 patients with 605 pulmonary nodules, all of whom had received local therapy and firstly achieved CSR or complete radiated/metabolic remission (CRR), were included in the analysis. A total of 102 patients with 525 nodules were initially diagnosed with resectable lung metastases, while 25 patients had 80 indeterminate nodules at presentation and relapsed with pulmonary metastases within 6 months after the completion of adjuvant chemotherapy. Results Eighty-eight of 127 (69.3%) patients had fewer than 5 nodules at the time of local therapy, with 48 of 127 (37.8%) located in the unilateral pleura. No patient underwent thoracotomy, and 42 of 127 patients (85 nodules) received video-assisted thoracoscopic surgery (VATS). In addition, 79 of 127 patients (520 nodules) received hypofractionated stereotactic body radiotherapy (RT), such as Gamma Knife radiosurgery or CyberKnife radiosurgery. The twelve-month event-free survival (EFS) (from local therapy to progression) rate of this entire study cohort was 35.6% (95% CI: 26.8, 44.4%), without a significant difference between the two groups (44.7% for VATS vs. 28.4% for RT, P = 0.755). Radiation-induced pneumonitis was observed in 62 of 86 (72.1%) patients, with one patient (1/86, 1.2%) in grade 4. Conclusions Our past data showed a similar prognosis with the use of hypofractionated radiotherapy and VATS for the treatment of pulmonary metastasis and no inferiority to thoracotomy regarding historical outcomes. Currently, high-resolution chest computed tomography (CT) provides sufficient information on nodules, and less invasive modalities can thus be considered for treatment.


2020 ◽  
Vol 49 (6) ◽  
pp. 611-616
Author(s):  
Tarik Qassem ◽  
Mohamed S. Khater ◽  
Tamer Emara ◽  
Doha Rasheedy ◽  
Heba M. Tawfik ◽  
...  

<b><i>Background:</i></b> The mini-Addenbrooke’s Cognitive Examination (m-ACE) is a brief cognitive battery that assesses 5 subdomains of cognition (attention, memory, verbal fluency, visuospatial abilities, and memory recall). It is scored out of 30 and can be administered in under 5 min providing a quick screening tool for assessment of cognition. <b><i>Objectives:</i></b> We aimed to adapt the m-ACE in Arabic speakers in Egypt and to validate it in dementia patients to provide cutoff scores. <b><i>Methods:</i></b> We included 37 patients with dementia (Alzheimer’s disease [<i>n</i> = 25], vascular dementia [<i>n</i> = 8], and dementia with Lewy body [<i>n</i> = 4]) and 43 controls. <b><i>Results:</i></b> There was a statistically significant difference (<i>p</i> &#x3c; 0.001) on the total m-ACE score between dementia patients (mean 10.54 and standard deviation [SD] 5.83) and controls (mean 24.02 and SD 2.75). There was also a statistically significant difference between dementia patients and controls on all sub-score domains of the m-ACE (<i>p</i> &#x3c; 0.05). Performance on the m-ACE significantly correlated with both the Mini-Mental State Examination (MMSE) and the Addenbrooke’s Cognitive Examination-III (ACE-III). Using a receiver operator characteristic curve, the optimal cutoff score for dementia on the m-ACE total score was found to be 18 (92% sensitivity, 95% specificity, and 94% accuracy). <b><i>Conclusions:</i></b> We adapted the m-ACE in Arabic speakers in Egypt and provided objective validation of it as a screening tool for dementia, with high sensitivity, specificity, and accuracy.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Mostafa Abdelsalam ◽  
A. M. Wahab ◽  
Maysaa El Sayed Zaki ◽  
Mohamad Motawea

Background. Diabetes mellitus is the leading cause of end-stage renal disease worldwide. Microalbuminuria is the cornerstone for the diagnosis of diabetic nephropathy. However, it is an inadequate marker for early diagnosis. MicroRNAs are not only new and promising markers for early diagnosis but also, but they may also play a role in the prevention of disease progression. Methods. This study included ninety patients with type 2 DM in addition to 30 control subjects. MicroRNA-451 expression in blood and plasma using real-time PCR was evaluated in addition to the classic diabetic nephropathy markers (serum creatinine, urinary albumin, and eGFR). Results. There was a significant difference between the studied groups versus control regarding serum creatinine, eGFR, urinary, and plasma microRNA-451 with p=0.0001. Patients with eGFR 60 ml/min/1.73 m2 showed a significantly higher plasma microRNA-451 (29.6 ± 1.6) and significantly lower urinary microRNA-451 (21 ± 0.9) in comparison to patients with eGFR >60 ml/min/1.73 m2 and p=0.0001. eGFR showed a positive correlation with urinary microRNA-451 and negative correlation with both plasma microRNA-451 and urinary albumin. Both plasma and urinary microRNA-451 are highly sensitive and specific markers for chronicity in diabetic nephropathy patients with sensitivity of 90.9% and 95.5% and specificity of 67.6% and 95.6%, respectively. Conclusion. MicroRNA-451 is a promising early biomarker for chronic kidney disease in diabetic nephropathy with high sensitivity and specificity.


2016 ◽  
Vol 48 (6) ◽  
pp. 1764-1778 ◽  
Author(s):  
Antoni Torres ◽  
Nelson Lee ◽  
Catia Cilloniz ◽  
Jordi Vila ◽  
Menno Van der Eerden

Pneumonia remains a worldwide health problem with a high rate of morbidity and mortality. Identification of microbial pathogens which cause pneumonia is an important area for optimum clinical management of pneumonia patients and is a big challenge for conventional microbiological methods. The development and implementation of molecular diagnostic tests for pneumonia has been a major advance in the microbiological diagnosis of respiratory pathogens in recent years. However, with new knowledge regarding the microbiome, together with the recognition that the lungs are a dynamic microbiological ecosystem, our current concept of pneumonia is not totally realistic as this new concept of pneumonia involves a dysbiosis or alteration of the lung microbiome. A new challenge for microbiologists and clinicians has therefore arisen. There is much to learn regarding the information provided by this new diagnostic technology, which will lead to improvements in the time to antibiotic therapy, targeted antibiotic selection and more effective de-escalation and improved stewardship for pneumonia patients. This article provides an overview of current methods of laboratory diagnosis of pneumonia in the molecular age.


Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-216013
Author(s):  
Haopu Yang ◽  
Ghady Haidar ◽  
Nameer S Al-Yousif ◽  
Haris Zia ◽  
Daniel Kotok ◽  
...  

Host inflammatory responses predict worse outcome in severe pneumonia, yet little is known about what drives dysregulated inflammation. We performed metagenomic sequencing of microbial cell-free DNA (mcfDNA) in 83 mechanically ventilated patients (26 culture-positive, 41 culture-negative pneumonia, 16 uninfected controls). Culture-positive patients had higher levels of mcfDNA than those with culture-negative pneumonia and uninfected controls (p<0.005). Plasma levels of inflammatory biomarkers (fractalkine, procalcitonin, pentraxin-3 and suppression of tumorigenicity-2) were independently associated with mcfDNA levels (adjusted p<0.05) among all patients with pneumonia. Such host–microbe interactions in the systemic circulation of patients with severe pneumonia warrant further large-scale clinical and mechanistic investigations.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wei Song ◽  
Li-Ying Sun ◽  
Zhi-Jun Zhu ◽  
Lin Wei ◽  
Wei Qu ◽  
...  

Background and AimsBiliary atresia (BA) is an idiopathic neonatal cholestasis and is the most common indication in pediatric liver transplantation (LT). Previous studies have suggested that the gut microbiota (GM) in BA is disordered. However, the effect of LT on gut dysbiosis in patients with BA has not yet been elucidated.MethodsPatients with BA (n = 16) and healthy controls (n = 10) were recruited. In the early life of children with BA, Kasai surgery is a typical procedure for restoring bile flow. According to whether BA patients had previously undergone Kasai surgery, we divided the post-LT patients into the with-Kasai group (n = 8) and non-Kasai group (n = 8). Fecal samples were collected in both the BA and the control group; among BA patients, samples were obtained again 6 months after LT. A total of 40 fecal samples were collected, of which 16 were pre-LT, 14 were post-LT (8 were with-Kasai, 6 were non-Kasai), and 10 were from the control group. Metagenomic sequencing was performed to evaluate the GM.ResultsThe Kruskal-Wallis test showed a statistically significant difference in the number of genes between the pre-LT and the control group, the pre-LT and the post-LT group (P &lt; 0.05), but no statistical difference between the post-LT and the control group. Principal coordinate analysis also showed that the microbiome structure was similar between the post-LT and control group (P &gt; 0.05). Analysis of the GM composition showed a significant decrease in Serratia, Enterobacter, Morganella, Skunalikevirus, and Phifllikevirus while short chain fatty acid (SCFA)-producing bacteria such as Roseburia, Blautia, Clostridium, Akkermansia, and Ruminococcus were increased after LT (linear discriminant analysis &gt; 2, P &lt; 0.05). However, they still did not reach the normal control level. Concerning functional profiles, lipopolysaccharide metabolism, multidrug resistance, polyamine biosynthesis, GABA biosynthesis, and EHEC/EPEC pathogenicity signature were more enriched in the post-LT group compared with the control group. Prior Kasai surgery had a specific influence on the postoperative GM.ConclusionLT partly improved the GM in patients with BA, which provided new insight into understanding the role of LT in BA.


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