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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard care | No Intervention | 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. | |
| POC-PCR analysis supplied with a recommended action list developed by a microbiologist | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| POC-PCR | Diagnostic Test | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Antibiotic treatment at 4-hour plan | 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. | 4 hours after admission |
| Measure | Description | Time Frame |
|---|---|---|
| Intensive care unit (ICU) treatment | Transfer to the intensive care unit will be recorded during the current hospitalization as a binary variable (transferred/not-transferred) | within 60 days from admission to the emergency department |
| Length of hospital stay |
| Measure | Description | Time Frame |
|---|---|---|
| CURB-65 score for pneumonia severity | 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 | within 4 hours from admission |
| Pneumonia severity index (PSI) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christian Backer Mogensen, MD PhD | Esbjerg Hospital - University Hospital of Southern Denmark | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital of Southern Jutland | Aabenraa | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31253624 | Background | Skjot-Arkil H, Mogensen CB, Lassen AT, Johansen IS, Chen M, Petersen P, Andersen KV, Ellermann-Eriksen S, Moller 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. | |
| 24898129 |
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| ID | Term |
|---|---|
| D018410 | Pneumonia, Bacterial |
| D004630 | Emergencies |
| ID | Term |
|---|---|
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D011014 | Pneumonia |
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The patients will be blinded, and the investigator will be blinded to POC-PCR results, data management and analysis, but not allocation. Outcome assessors will not be blinded
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. |
| within 60 days from current admission to the emergency department |
| 30-days mortality | Mortality within 30 days from admission to the Emergency Department | 30 days from the admission to the emergency department |
| Readmission | 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. | within 30 days from the discharge to the hospital |
| In-hospital mortality | Patient mortality during the current hospitalization. Binary outcome - Died/ Not died | within 60 days from admission to the emergency department |
| Antibiotic treatment at 48 hour | The treatment will either be registered as targeted or non-targeted antibiotic treatment 48 hours after admission. This is a binary outcome. | 48 hours after admission |
| Antibiotic treatment at discharge from hospital | 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. | 24 hours after hospital discharge |
| Bacterial agents and viruses from the microbiological results | 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. | Within the first 7 days from specimen collection |
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) |
| within 4 hours from admission |
| Number of clostridium infections | Identify through patient records if the patient was infected with clostridium difficille, binary outcome yes/no | measured 40 days after discharge from the emergency department |
| Procalcitonin (PCT), Soluble Urokinase Plasminogen Activator Receptor (suPAR), YKL-40 and Krebs von den Lungen (KL-6) | Measurement of serum PCT and suPAR are collected in connection to routine blood tests within 1 hour from admission | results within 4 hour from admission |
| 90 days mortality | binary | Within 90 days from admission to emergency department |
| Background |
| Sogaard M, Nielsen RB, Schonheyder HC, Norgaard 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. |
| 20729232 | Background | 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. |
| 16061709 | Background | 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. doi: 10.1136/thx.2004.030411. |
| 26126606 | Background | 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. |
| 12006433 | Background | Ewig S, Schlochtermeier M, Goke 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. doi: 10.1378/chest.121.5.1486. |
| 11049763 | Background | Roson B, Carratala 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. doi: 10.1086/318151. Epub 2000 Oct 12. |
| 29150897 | Background | 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. |
| 38015833 | Derived | Cartuliares MB, Rosenvinge FS, Mogensen CB, Skovsted TA, Andersen SL, Ostergaard C, Pedersen AK, Skjot-Arkil H. Evaluation of point-of-care multiplex polymerase chain reaction in guiding antibiotic treatment of patients acutely admitted with suspected community-acquired pneumonia in Denmark: A multicentre randomised controlled trial. PLoS Med. 2023 Nov 28;20(11):e1004314. doi: 10.1371/journal.pmed.1004314. eCollection 2023 Nov. |
| 34593497 | Derived | Skjot-Arkil H, Heltborg A, Lorentzen MH, Cartuliares MB, Hertz MA, Graumann O, Rosenvinge FS, Petersen ERB, Ostergaard C, Laursen CB, Skovsted TA, Posth S, Chen M, Mogensen CB. Improved diagnostics of infectious diseases in emergency departments: a protocol of a multifaceted multicentre diagnostic study. BMJ Open. 2021 Sep 30;11(9):e049606. doi: 10.1136/bmjopen-2021-049606. |
| D012141 |
| Respiratory Tract Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |