The Effect of a Point-of-care Sputum Specimen Assay at the Emergency Department for Patients Suspected of Pneumonia
Study Details
Study Description
Brief Summary
Antibiotic resistance has been identified by the WHO as one of the biggest threats to the health of the world population. In Denmark, there has been an increasing focus on optimizing antibiotic consumption in recent years, but despite significant efforts, total consumption has increased in the hospital sector, especially regarding consumption and in the use of broad-spectrum antibiotics. Currently, a pneumonia diagnosis is primarily based on clinical symptoms such as cough, shortness of breath, chest pain, fever and sputum production, combined with X-ray of the lungs, relevant blood tests and microbiological analysis of sputum samples. X-ray is however an imprecise diagnostic tool, and sputum assays responses are available after 2 days. Sputum can be cultivated to determine the bacterial agent. However, the sputum samples are often of poor quality and many patients cannot deliver a sample. A recently published Danish study shows, that only half of the patients at the ED have sputum samples collected for culturing and none of them had the antibiotic treatment adjusted based on the microbiological results of the sputum.
This study's hypothesis is that point-of-care-polymerase chain reaction (POC-PCR) is superior to standard care on the prescription of targeted pneumonia treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
The diagnosis of pneumonia is challenged by nonspecific symptoms, uncertain diagnostic methods, poor prognostic tools and waiting time for test results up to several days. A patient's length of stay in a Danish Emergency Department rarely exceeds 48 hours. Within this period the patient is examined, treated and discharged either home or to another department. Therefore, rapid molecular detection of respiratory pathogens is needed to add value to the management of the diagnostics of pneumonia and could reduce the initial use of antibiotics. Molecular diagnostic tests based on polymerase chain reaction (PCR) assays generate high sensitive analyses in one hour from specimen collection. The Biofire® FilmArray® Pneumonia Panel plus (Biomérieux) can identify 18 bacterial agents including 3 atypical pathogens 9 viruses and 7 antimicrobial resistance genes. This point-of-care (POC) test is promising, as bacterial pathogens often coexist with viruses or are identified with mixed infections. However, the high specificity of molecular diagnostics can challenge the interpretation of clinically significant agents and demands interpretation by highly qualified specialists. Therefore, the POC-PCR combined with advice from a microbiologist has the potential to optimize therapeutic regimens and reduce prescriptions of inappropriate broad-spectrum antibiotics in the initial management of pneumonia.
This study aims to
-
investigate how effective the addition of POC-PCR analysis of sputum is to the diagnostic set-up for community-acquired pneumonia on antibiotic prescription at 4 hours after admission without consequent adverse advents
-
to identify the effect of POC-PCR on prescribed antibiotic treatment 48 hours after admission and 24 hours after discharge
-
to investigate the agreement between POC-PCR and sputum culture on microbiological analysis
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: Standard care A treating physician must perform a clinical assessment within half an hour of patient arrival. This assessment includes the decision whether the patient is suspected of having pneumonia and if this is the case, a sputum specimen and chest x-ray will be ordered. Patients with suspected pneumonia who can deliver a sputum specimen will be randomly allocated with a 1:1 computer-generated randomization schedule with permuting blocks in relation to optimal therapeutical intervention strategy. All standard care sputum samples will be cultured and analysed according to the sites' standard procedures. Under standard care, the treating physician alone decides on the optimal therapeutical intervention. |
|
| Active Comparator: POC-PCR analysis supplied with a recommended action list developed by a microbiologist Along with standard analyses, the specimens will be analysed with POC-PCR and the treating physician will receive an action-list with the results from POC-PCR. |
Diagnostic Test: POC-PCR
The result of the POC-PCR will be presented by the study assistant to the treating physician within four hours upon admission. The treating physician will along with the result receive a recommended action list, developed by microbiologists.
|
Outcome Measures
Primary Outcome Measures
- Antibiotic treatment at 4-hour plan [4 hours after admission]
The primary outcome is to determine the effectiveness of POC-PCR sputum analysis on antibiotic prescription, the treatment will either be registered as targeted or non-targeted antibiotic treatment at four hours after admission. This is a binary outcome.
Secondary Outcome Measures
- Intensive care unit (ICU) treatment [within 60 days from admission to the emergency department]
Transfer to the intensive care unit will be recorded during the current hospitalization as a binary variable (transferred/not-transferred)
- Length of hospital stay [within 60 days from current admission to the emergency department]
Defined as the time (in days) spent in hospital during the current admission. Measured in days from admission to hospital discharge. Discharge date minus admission date.
- 30-days mortality [30 days from the admission to the emergency department]
Mortality within 30 days from admission to the Emergency Department
- Readmission [within 30 days from the discharge to the hospital]
If a subject is admitted over a 30 day period after the current hospitalization discharge measured as a binary outcome Re-admissions/not re-admissions.
- In-hospital mortality [within 60 days from admission to the emergency department]
Patient mortality during the current hospitalization. Binary outcome - Died/ Not died
- Antibiotic treatment at 48 hour [48 hours after admission]
The treatment will either be registered as targeted or non-targeted antibiotic treatment 48 hours after admission. This is a binary outcome.
- Antibiotic treatment at discharge from hospital [24 hours after hospital discharge]
The treatment will either be registered as a targeted or non-targeted antibiotic treatment after the patient is discharged from the hospital. This is a binary outcome.
- Bacterial agents and viruses from the microbiological results [Within the first 7 days from specimen collection]
The bacterial agents and viruses from the Biofire® FilmArray® Pneumonia Panel plus (Biomérieux) and standard sputum culture for the two microbiological analysis will be presented as descriptive statistics.
Other Outcome Measures
- CURB-65 score for pneumonia severity [within 4 hours from admission]
Confusion of new onset, Blood Urea nitrogen greater than 7 mmol/L (19 mg/dL), respiratory rate of 30 breaths per minute or greater, blood pressure less than 90 mmHg systolic or diastolic blood pressure 60 mmHg or less and age 65 or older
- Pneumonia severity index (PSI) [within 4 hours from admission]
Risk classes to predict the severity of pneumonia. Scores are given based on demographics, comorbidity, clinical measurements and physical Exam Findings (<70 = Risk Class II, 71-90 = Risk Class III, 91-130 = Risk Class IV, >130 = Risk Class V)
- Number of clostridium infections [measured 40 days after discharge from the emergency department]
Identify through patient records if the patient was infected with clostridium difficille, binary outcome yes/no
- Procalcitonin (PCT), Soluble Urokinase Plasminogen Activator Receptor (suPAR), YKL-40 and Krebs von den Lungen (KL-6) [results within 4 hour from admission]
Measurement of serum PCT and suPAR are collected in connection to routine blood tests within 1 hour from admission
- 90 days mortality [Within 90 days from admission to emergency department]
binary
Eligibility Criteria
Criteria
Inclusion Criteria:
- Emergency department patients suspected of pneumonia by the attending physician and with at least one of the following symptoms: dyspnea, cough, expectoration, chest tightness or fever and indication for chest x-ray
Exclusion Criteria:
-
If the attending physician considers that participation will delay a life-saving treatment or patient needs direct transfer to the intensive care unit.
-
Admission within the last 14 days
-
Verified COVID-19 disease within 14 days before admission
-
Pregnant women
-
Severe immunodeficiencies: Primary immunodeficiencies and secondary immunodeficiencies (HIV positive CD4 <200, Patients receiving immunosuppressive treatment (ATC L04A), Corticosteroid treatment (>20 mg/day prednisone or equivalent for >14 days within the last 30 days), Chemotherapy within 30 days)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hospital of Southern Jutland | Aabenraa | Denmark |
Sponsors and Collaborators
- University of Southern Denmark
Investigators
- Study Chair: Christian Backer Mogensen, MD PhD, University Hospital of Southern Denmark
Study Documents (Full-Text)
None provided.More Information
Publications
- Becerra MB, Becerra BJ, Banta JE, Safdar N. Impact of Clostridium difficile infection among pneumonia and urinary tract infection hospitalizations: an analysis of the Nationwide Inpatient Sample. BMC Infect Dis. 2015 Jul 1;15:254. doi: 10.1186/s12879-015-0925-9.
- Ewig S, Schlochtermeier M, Göke N, Niederman MS. Applying sputum as a diagnostic tool in pneumonia: limited yield, minimal impact on treatment decisions. Chest. 2002 May;121(5):1486-92.
- Hadfield J, Bennett L. Determining best outcomes from community-acquired pneumonia and how to achieve them. Respirology. 2018 Feb;23(2):138-147. doi: 10.1111/resp.13218. Epub 2017 Nov 17. Review.
- Rosón B, Carratalà J, Verdaguer R, Dorca J, Manresa F, Gudiol F. Prospective study of the usefulness of sputum Gram stain in the initial approach to community-acquired pneumonia requiring hospitalization. Clin Infect Dis. 2000 Oct;31(4):869-74. Epub 2000 Oct 12.
- Skjøt-Arkil H, Mogensen CB, Lassen AT, Johansen IS, Chen M, Petersen P, Andersen KV, Ellermann-Eriksen S, Møller JM, Ludwig M, Fuglsang-Damgaard D, Nielsen FE, Petersen DB, Jensen US, Rosenvinge FS. Carrier prevalence and risk factors for colonisation of multiresistant bacteria in Danish emergency departments: a cross-sectional survey. BMJ Open. 2019 Jun 27;9(6):e029000. doi: 10.1136/bmjopen-2019-029000.
- Søgaard M, Nielsen RB, Schønheyder HC, Nørgaard M, Thomsen RW. Nationwide trends in pneumonia hospitalization rates and mortality, Denmark 1997-2011. Respir Med. 2014 Aug;108(8):1214-22. doi: 10.1016/j.rmed.2014.05.004. Epub 2014 May 20.
- van der Eerden MM, Vlaspolder F, de Graaff CS, Groot T, Bronsveld W, Jansen HM, Boersma WG. Comparison between pathogen directed antibiotic treatment and empirical broad spectrum antibiotic treatment in patients with community acquired pneumonia: a prospective randomised study. Thorax. 2005 Aug;60(8):672-8.
- Welte T, Torres A, Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax. 2012 Jan;67(1):71-9. doi: 10.1136/thx.2009.129502. Epub 2010 Aug 20. Review.
- SHS-ED-11c-2020