Pneumonia is a common and severe illness that requires prompt and effective management. Advanced, rapid, and accurate tools are needed to diagnose patients with severe bacterial pneumonia, and to rapidly select appropriate antimicrobial therapy, which must be initiated within the first few hours of care. Two multiplex molecular tests, Unyvero HPN and FilmArray Pneumonia+ Panel, have been developed using the multiplex polymerase chain reaction (mPCR) technique to rapidly identify pathogens and their main antibiotic resistance mechanisms from patient respiratory specimens. Performance evaluation of these tests showed strong correlations with reference techniques.
1. Introduction
Severe pneumonia remains a major cause of morbidity and mortality worldwide, and its therapeutic management is a public health issue. The severity of pneumonia is generally defined by clinical criteria leading to admission to an intensive care unit (ICU)
[1]. One of them is the need for mechanical ventilation (invasive or non-invasive), or severe hypoxemia defined by a PaO2/FiO2 ratio of less than 300 mmHg, requiring oxygen administration through a high-flow nasal cannula or a non-rebreathing mask. Among hospital-acquired pneumonia (HAP), the most severe and frequent is the ventilator-associated pneumonia (VAP). It is defined as an infection of the lung parenchyma in patients receiving invasive mechanical ventilation for at least 48 h. Conversely, community-acquired pneumonia (CAP) refers to episodes in patients with no recent healthcare exposure. In Europe, the estimated incidence of VAP is 18.3 episodes per 1000 ventilator-days
[2,3][2][3]. In-ICU mortality attributable to VAP is limited but significant (from 1 to 6% according to case mix and methods), suggesting that mortality in these patients is mainly driven by their underlying conditions, as well as the severity of the disease
[3,4,5][3][4][5]. However, VAP has been frequently associated with a longer duration of mechanical ventilation, ICU stay, prolonged hospitalization, and increased healthcare cost
[4].
2. Multiplex PCR: Available Tests
Two US Food and Drugs Administration-approved CE-marked tests are currently available for pneumonia diagnosis. The Unyvero HPN (Curetis, Unyvero TM) detects 21 bacteria and one parasite, semi quantitatively (from + to +++), and identifies 15 resistance genes in approximately 5 h. The FilmArray Pneumonia+ Panel (BioFire, bioMérieux) detects 18 bacteria, among which are three atypical ones, quantitatively (from 10
4 to ≥10
7 genomic copies/mL), and identifies seven resistance genes, and eight viruses in approximately 90 min. The main targets of both tests are shown in the
Table 1.
Table 1.
Unyvero HPN and FilmArray Pneumonia+ Panel main targets.
|
Unyvero HPN |
FilmArray Pneumonia+ Panel |
Number of targets |
36 |
33 |
Turnaround time |
5 h |
90 min |
Type of detection |
Semiquantitative (+ to +++) |
Quantitative (104 to ≥107) |
Included pathogens |
|
|
Bacteria |
|
|
Gram-positive cocci |
|
|
Staphylococcus aureus |
x |
x |
Streptococcus agalactiae |
|
x |
Streptococcus pneumoniae |
x |
x |
Streptococcus pyogenes |
|
x |
Gram-negative cocci |
|
|
Moraxella catarrhalis |
x |
x |
Gram-negative bacilli |
|
|
Haemophilus influenzae |
x |
x |
Group 1 Enterobacterales |
|
|
Escherichia coli |
x |
x |
Proteus spp. |
x |
x |
Group 2 Enterobacterales |
|
|
Klebsiella oxytoca |
x |
x |
Klebsiella pneumoniae |
x |
x |
Klebsiella variicola |
x |
|
Group 3 Enterobacterales |
|
|
Enterobacter cloacae complex |
x |
x |
Citrobacter freundii |
x |
|
Enterobacter cloacae complex |
x |
x |
Klebsiella aerogenes (Enterobacter aerogenes) |
x |
x |
Morganella morganii |
x |
|
Serratia marcescens |
x |
x |
Non-fermenting bacteria |
|
|
Acinetobacter baumannii complex * |
x |
x |
Pseudomonas aeruginosa |
x |
x |
Stenotrophomonas maltophilia |
x |
|
Atypical bacteria |
|
|
Chlamydia pneumoniae |
x |
x |
Legionella pneumophila |
x |
x |
Mycoplasma pneumoniae |
x |
x |
Others |
|
|
Pneumocystis jirovecii |
x |
|
Resistance genes |
x |
x |
Virus |
x |
x |