Primary objective: To determine the added diagnostic value of the lytA qPCR on samples of the upper respiratory tract on top of routine microbiological tests in detecting pneumococci as responsible pathogen in patients with CAP.Secondary objective (…
ID
Source
Brief title
Condition
- Bacterial infectious disorders
- Respiratory tract infections
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
A. Primary studyparameters (patients)
-Occurrence of qPCR proven pneumococcal pneumonia using the cut-off value in at
least one of the specimens;
-Occurrence of pneumococcal pneumonia proven by at least one of the routine
microbiological tests.
B. Primary studyparameters (controls)
Number of DNA copies of S. pneumoniae identified by lytA qPCR in samples of
different locations in patients with a positive qPCR test:
-Nasopharynx
-Oropharynx
-Saliva
-Sputum
Secondary outcome
A. Secondary study parameters (patients)
-Occurrence of positive lytA qPCR in the different samples: oropharynx,
nasopharynx, saliva and sputum;
-Occurrence of S. pneumoniae identified in the different samples by routine
microbiological tests;
-Number of DNA copies of S. pneumoniae in all lytA qPCR positive patients;
-Ct-values in all lytA qPCR positive study subjects;
-CURB-65 scores (or other pneumonia severity scores);
-CRP levels;
-PCT levels.
B. Secondary study parameters (controls)
-Occurrence of S. pneumoniae identified with lytA qPCR in at least one of the
specimens;
-Occurrence of S. pneumoniae identified in at least one of the specimens with
cultures (culture of oropharyngeal or nasopharyngeal swab or saliva);
-Ct-values in all lytA qPCR positive study subjects.
Background summary
Streptococcus pneumoniae (S. pneumoniae) is the leading cause of
community-acquired pneumonia (CAP) but is believed to be underdiagnosed due to
lack of sensitivity of used tests and inadequate specimen collection. The
current diagnostic standard (composite of blood culture, sputum culture and
urine antigen test (UAT)) detects S. pneumoniae as the responsible pathogen in
CAP in less than 30% of the cases. Assays with increased sensitivity applied on
easily obtainable specimens could improve the detection of S. pneumoniae and
treatment strategies.
Real-time quantitative polymerase chain reaction (qPCR) on samples of the upper
respiratory tract targeting the S. pneumoniae specific autolysin gene, lytA,
could be able to improve and fasten the diagnostic process of CAP. Rapid and
correct detection of pneumococcal pneumonia provides support for initial
narrow-spectrum antibiotic treatment. This targeted therapy might be able to
help in preventing antibiotic resistance.
At present, the qPCR targeting lytA (lytA qPCR) is not routinely performed in
the standard diagnostic process of a CAP. We recently set-up and validated a
home-made lytA qPCR and tested it in a pilot study in patients with a CAP.
Preliminary results were promising. Moreover, a recent study in South-Africa
(Albrich 2012) found an added diagnostic value of the lytA qPCR in mostly
HIV-positive patients with a CAP in nasopharyngeal specimens. The amount of
pneumococcal pneumonias increased from 27.1% to 52.5% after added the results
of the lytA qPCR.
In the present study we want to test this home-made qPCR prospectively in
patients with CAP and determine the added diagnostic value of the qPCR on
samples of the upper respiratory tract on top of the routine microbiologically
tests in diagnosing S. pneumoniae as the responsible pathogen in CAP. For the
differentiation between colonisation and CAP with S. pneumoniae we will
determine a cut-off value with the use of test results of CAP patients and
healthy subjects with colonisation. Patients with stable chronic obstructive
pulmonary disease (COPD) and those with an exacerbation will be tested as well
to determine the amount of copy numbers in stable and exacerbated disease. We
will perform the lytA qPCR in specimens of different sites of the upper
respiratory tract (oropharynx, nasopharynx, saliva and sputum) because of easy
access and availability and promising results in previous studies.
Study objective
Primary objective: To determine the added diagnostic value of the lytA qPCR on
samples of the upper respiratory tract on top of routine microbiological tests
in detecting pneumococci as responsible pathogen in patients with CAP.
Secondary objective (most important, the rest is described in the protocol): To
determine the cut-off value for the number of lytA DNA copies to differentiate
between colonisation and pneumonia with S. pneumoniae.
Study design
Multicenter cross-sectional case-control study with short follow-up period
(approximately 30 days) in the patient group and 4 different control groups.
Two centers: Noordwest Ziekenhuisgroep and Spaarne Gasthuis.
Study burden and risks
There are no risks associated with performing the lytA qPCR. Nasopharyngeal
swab collection causes a temporary unpleasant sensation. Extra blood sampling
is of negligible risk.
Wilhelminalaan 12
Alkmaar 1815JD
NL
Wilhelminalaan 12
Alkmaar 1815JD
NL
Listed location countries
Age
Inclusion criteria
Patients:
-Age 18 years or above;
-Presentation at the emergency department (ED);
-Working diagnosis of CAP at the ED with the presence of at least two of the
following criteria:
1. New or worsened coughing;
2. Production of purulent sputum or change in sputum colour;
3. Temperature >38.0 *C or <=36.0 *C (tympanic);
4. Auscultatory findings consistent with pneumonia, including rales, evidence
of pulmonary consolidation (dullness on percussion, bronchial breath sounds,
rales,
or egophony), or both;
5. White blood cell count of >10x10^9 cells/L or <4x10^9 cells/L or >15%
bands;
6. C-reactive protein level >=30mg/L;
7. Dyspnea, tachypnea, (>20 breaths per minute), or hypoxemia (arterial pO2
<60mmHg or peripheral O2 saturation <90%).
-New consolidation(s) on the chest radiograph or computed tomography (CT);
-No other explanation for the signs and symptoms;Control group 1 - Related
controls
-Being aged 18 years or above;
-Close relative of the patient: relative defined as living in the same house as
the CAP patient or daily contact;
-Is at the hospital at the moment of inclusion of the CAP patient or is willing
to come for testing within 7 days.Control group 2 - Unrelated healthy
individuals
-Being aged 18 years or above;
-Subject with a preoperative appointment with the anaesthiologist for a planned
surgical procedure;
-Age, gender and time matched to an included CAP patient.Control group 3 -
Patients with stable COPD
-Being aged 18 years or above;
-Diagnosis of COPD confirmed with spirometry (GOLD criteria 2017)(76).Control
group 4 - Patients with exacerbation of COPD
-Being aged 18 years or above;
-Diagnosis of COPD confirmed with spirometry (GOLD criteria 2017)(76);
-Diagnosis of exacerbation of COPD: defined as an acute event characterised by
a worsening of the patient*s respiratory symptoms that is beyond normal
day-to-day variations and leads to a change in medication (76);
Exclusion criteria
In general:
-Pneumonia in the last month or pneumococcal pneumonia (proven by usual
diagnostics) in the last three months;
-Not capable of understanding information needed to sign informed
consent;Patients:
-Was included in the present study group before;
-Aspiration pneumonia;
-Hospitalisation for two or more days in the last 14 days;
-History of cystic fibrosis.For all control groups:
-Fits inclusion criteria for patient group;
-Present or recent hospitalisation (14 days);
-Use of antibiotics in the last 14 days, including maintenance antibiotic
therapy.Control group 1 and 2 - Related healthy controls and unrelated healthy
individuals
-Active infectious respiratory complaints defined as defined as two or more
respiratory symptoms (cough, nasal congestion, runny nose, sore throat or
sneezes);
-Temperature >38.0 *C
-Chronic pulmonary disease: COPD, asthma, cystic fibrosis, bronchiectasis;
Control group 3 - Patients with stable COPD
-Temperature >38.0 *C;
-Stable disease;
-Recent exacerbation (<1 month) defined as increased respiratory symptoms with
need of antibiotic and/or corticosteroid therapy.Control group 4 - Patients
with exacerbation of COPD
-Current pneumonia;
-Recent exacerbation (<1 month) defined as increased respiratory symptoms with
need of antibiotic and/or corticosteroid therapy.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT03315403 |
| CCMO | NL63200.094.17 |