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# Value of molecular biology tests in community-acquired acute pneumonia

V. Cattoir, A. Dinh, S. Jarraud, A. Le Monnier, P. Loubet

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V. Cattoir, A. Dinh, S. Jarraud, A. Le Monnier, P. Loubet. Value of molecular biology tests in community-acquired acute pneumonia. Infectious Diseases Now, 2025, 55 (6), pp.105128. 10.1016/j.idnow.2025.105128. hal-05228200

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# Value of molecular biology tests in community-acquired acute pneumonia

V. Cattoir<sup>a,b,c</sup><sup>ID</sup>, A. Dinh<sup>d,e,f</sup><sup>ID</sup>, S. Jarraud<sup>e,f</sup>, A.Le Monnier<sup>g,h</sup>, P. Loubet<sup>i</sup><sup>ID</sup>

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ARTICLE INFO

Keywords:

Community-acquired acute pneumonia

Molecular biology

Multiplex PCR

Syndromic panel

A B S T R A C T

For patients hospitalized with community-acquired acute pneumonia (CAP), molecular tools (especially multi-
plex PCR syndromic panels) are associated with a significant improvement of microbiological diagnosis yield,
compared with conventional methods. Two main families of tests are currently available: targeted viral PCR tests
(influenza, SARS-CoV-2, RSV) performed on nasopharyngeal swabs and adapted to epidemic situations; and
"upper respiratory tract" (nasopharyngeal) or "lower respiratory tract" (deep swabs) syndromic panels to detect a
broad spectrum of viral and bacterial agents, sometimes including resistance genes.

These tests are not recommended for routine use in CAP patients treated in ambulatory settings. In hospi-
talized CAP patients, their use must be guided by severity, epidemic context, and therapeutic implications.
"Upper respiratory tract" panels can be useful when an atypical agent or a virus undetected by targeted PCR tests
is suspected. "Lower respiratory tract" panels must only be used in case of severe forms or complex situations.

Clinical trials showed real diagnostic value but variable clinical impact, which is often limited in the absence
of an optimization strategy for the antibiotic therapy.

Multiplex PCR syndromic panels represent a promising step forward in the management of patients hospi-
talized with CAP, but their clinical value still depends on several factors: type of panel and swab, quick results,
presence of mobile teams of infectious diseases specialists, and capacity to correctly interpret results to guide
treatment decisions.

# 1. Introduction

Community-acquired acute pneumonia (CAP) remains a leading cause of morbidity and mortality worldwide, with an estimated incidence of 2 to 11 cases per 1,000 adults per year in developed countries, and a mortality ranging between 2 and 14 % depending on severity and patient's characteristics [1]. CAP management is usually based on empirical broad-spectrum antibiotic therapy, initiated at the emergency department, and followed by potential de-escalation when the infectious cause is identified. However, conventional microbiological tests – mainly based on microscopic examination and culture of respiratory swabs – only lead to etiological documentation in 30 to 40 % of cases; thus limiting the use of targeted antibiotic therapy [2–5].

2. Definition

Real-time PCR is the most widely used molecular biology technique. It has become the reference method for detecting respiratory viruses and atypical bacteria. Highly sensitive and specific, real-time PCR is also associated with rapid results (less than an hour to 4 h depending on the platforms and/or available equipment).

The PCR tests used differ in terms of the number of pathogens tested ("monoplex" = one pathogen, "biplex" = two pathogens, etc.).

Viral PCR testing for a single pathogen is no longer recommended in a context of co-circulation of several viruses, such as influenza A and B viruses, RSV, and SARS-CoV-2 [6].

Viral multiplex PCR testing for three to four viruses (influenza A and

<footnote><sup>a</sup> Service de Bactériologie-Hygienne Hospitalière, CHU de Rennes F-35033 Rennes, France</footnote>

<footnote><sup>b</sup> Centre National de Référence de la Résistance aux Antibiotiques (laboratoire associé 'Entérocoques'), CHU de Rennes F-35033 Rennes, France</footnote>

<footnote><sup>c</sup> Unité Inserm U1230 BRM, Université de Rennes F-35043 Rennes, France</footnote>

<footnote><sup>d</sup> Service des Maladies infectieuses Hôpital R. Poincaré, APHP, Garches, France</footnote>

<footnote><sup>e</sup> Laboratoire de microbiologie, Hospice civil de Lyon, Lyon, France</footnote>

<footnote><sup>f</sup> NR Légionelle, Lyon, France</footnote>

<footnote><sup>g</sup> Service de Microbiologie clinique, Hopitaux Paris Saint-Joseph & Marie Lannelongue, Paris, France</footnote>

<footnote><sup>h</sup> Institut Micalis, UMR 1319 Université Paris-Saclay, INRAE, AgroParisTech, Orsay, France</footnote>

<footnote><sup>i</sup> Virulence Bactérienne et Infections Chroniques, INSERM U1047, Univ Montpellier Department of Infectious and Tropical Disease, CHU Nîmes, Nîmes, France</footnote>

<footnote>* Corresponding author at: Department of Infectious and Tropical Disease, CHU R. Poincaré, 104 Bd R. Poincaré, 92380 Garches, France.
E-mail address: aurelien.dinh@aphp.fr (A. Dinh).</footnote>
B, SARS-CoV-2, and RSV) must therefore be distinguished from panel PCR testing known as “syndromic” panels. The latter, available only in recent years, have the advantage of detecting (from a single swab) a much higher number of agents, thus covering most viruses responsible for respiratory diseases as well as some bacteria (panel composition varies by manufacturers and platforms used).

Various syndromic panels are available:

- “Upper respiratory tract” panels: mainly performed on nasopharyngeal swabs (or oropharyngeal swabs, saliva samples, sputum samples), this type of panel can identify 10 to 15 viruses depending on the kit (among influenza A and B, RSV A and B, parainfluenza 1 to 4 viruses, adenovirus, rhinovirus/enterovirus, bocavirus, human metapneumovirus, seasonal human coronaviruses (HCoV-NL63, -229E, -OC43,- HKU1), MERS-CoV (Middle East respiratory syndrome coronavirus), SARS-CoV-2, and some atypical bacteria among *Mycoplasma pneumoniae*, *Chlamydophila pneumoniae* ± *Bordetella pertussis* and *B. parapertussis* ± *Legionella pneumophila*.

- “Lower respiratory tract” panels: mainly performed on lower respiratory tract samples (tracheal aspiration [TA], protected distal sampling [PDS], bronchoalveolar lavage [BAL]) in pneumonia patients (their use is also validated on sputum samples). The main panel currently available identifies 18 bacteria, 15 of which can be “cultured” (i.e., *Streptococcus pneumoniae*, *Staphylococcus aureus*, *Escherichia coli*, *Haemophilus influenzae*, *Pseudomonas aeruginosa*, *Klebsiella pneumoniae*) with semi-quantification (in DNA copies/mL) and three atypical bacteria with qualitative detection (*M. pneumoniae*, *C. pneumoniae*, *L. pneumophila*), nine viruses, and seven determinants of antibiotic resistance (*mecA*, CTX-M type extended-spectrum beta-lactamases, KPC, NDM, VIM, IMP and OXA-48-like type carbapenemases).

Considering their poor performance on nasopharyngeal swabs, syndromic PCR tests for *L. pneumophila* should only be used on sputum or deep respiratory tract samples [7–11].

### 3. Potential value

Respiratory syndromic panels can now rapidly detect a wide panel of bacterial and viral respiratory pathogens using a single sample. These tests have considerably improved **diagnostic yield**, especially when antibiotics have previously been prescribed, but their **clinical value** is still debated. A recent study [1] showed that adding a large panel to the respiratory tract sample analysis (sputum or tracheal aspiration) increased the rate of microbiological diagnoses from 39 % to 87 % in a cohort of patients hospitalized with CAP, including in those who had received antibiotics in the previous 72 h. Quantifying bacterial loads added a potential differentiator between colonization by oropharyngeal bacteria and true infection. This approach made it possible to consider **de-escalation** of antibiotic therapy in 77 % of cases – although this decision was evaluated retrospectively, without any direct impact on prescribing.

However, a recent study highlighted that the analytical performance of respiratory panels **does not always translate into clinical benefits** [12]. The low rate of antibiotic de-escalation observed in recent randomized controlled trials underlines the obstacles associated with their use: diagnostic uncertainty (especially in case of co-detection), absence of validated thresholds for bacterial loads, clinical reluctance to modify an effective empirical treatment, and lack of integration into a structured antibiotic stewardship strategy. Moreover, distinguishing between active infection and simple carriage is sometimes tricky, especially in non-sterile samples such as sputum samples.

### 4. Existing recommendations

The American Thoracic Society recommends against targeted

multiplex PCR testing for respiratory viruses in outpatients, but recommends testing for non-influenza viruses in hospitalized immunocompromised patients with severe CAP [13].

European guidelines on severe respiratory tract infection patients in intensive care units suggest performing a “lower respiratory tract” syndromic panel on a deep respiratory sample for severe CAP when broad-spectrum antibiotic treatment is discussed or initiated: conditional recommendation, very low level of scientific evidence [14].

In France, guidelines on indications for targeted multiplex tests (influenza A/B, RSV, and SARS-CoV-2) and syndromic panels for diagnosing respiratory viral diseases in hospitalized patients have been published by the ANRS-MIE (virology and medical pharmacology network/respiratory virus group) under the aegis of the French Microbiological Society (French acronym SFM) [6]. They recommend multiplex viral PCR testing for influenza A/B, RSV, and SARS-CoV-2 in patients with respiratory symptoms hospitalized in medical units, as well as performing right away an “upper respiratory tract” syndromic panel on nasopharyngeal swab (or a complete panel adapted to the local equipment available) in immunocompromised patients or in patients requiring intensive care unit admission [6].

### 5. Literature data

The impact of molecular biology tests on patient management is difficult to assess and depends on whether the test is performed in a medical biology laboratory or in a hospital ward (emergency department, medical ward, intensive care unit), as well as on the type of panel used (targeted multiplex PCR, “upper respiratory tract” or “lower respiratory tract” syndromic panel) and on the sampling site (nasopharyngeal versus deep respiratory sample).

#### 5.1. Viral targeted multiplex PCR tests and “upper respiratory tract” syndromic panels

Several studies suggest the positive impact of viral multiplex PCR tests and “upper respiratory tract” syndromic panels performed on nasopharyngeal swabs on the patient’s pathway in case of respiratory virus detection (i.e., by reducing waiting time in the emergency department, by reducing prescriptions of complementary examinations and imaging tests as well as hospital length of stay – even more so as time to results is short – and by implementing adequate complementary precaution measures for carriers of respiratory viruses) [1,15–25].

From a therapeutic standpoint, detection of SARS-CoV-2 or influenza virus by PCR test enables antiviral treatment to be introduced earlier and more frequently [26]. It should be noted that the lack of specific antiviral therapies, apart from those for these two viruses, limits the therapeutic value of detecting other respiratory viruses.

However, a *meta*-analysis [27] showed that “upper respiratory tract” syndromic panels performed on nasopharyngeal swabs had little or no impact on antibiotic consumption.

This lack of impact is probably due to the fact that these PCRs mainly test for viruses, and that the detection of a respiratory virus alone in a nasopharyngeal swab from a patient with CAP diagnosis does not always rule out the presence of an associated pulmonary bacterial co- or superinfection and therefore does not always allow for antibiotics discontinuation. In this situation, discontinuation of antibiotic treatment must be based on a combination of clinical, biological, and aging evidence, together with PCR test results.

It should be noted that some “upper respiratory tract” syndromic panels performed on nasopharyngeal swabs can detect *M. pneumoniae* and thus have a positive impact on antibiotic treatment initiation or early modification.

#### 5.2. “Lower respiratory tract” syndromic panels

The potential main advantage of “lower respiratory tract” syndromic
panels performed on sputum samples or deep respiratory samples is the ability to quickly adjust antibiotic therapy in case of resistant bacteria not covered by the empirical antibiotic treatment for severe pneumonia, or the possibility to de-escalate earlier a broad-spectrum antibiotic treatment [28,29]. A relation has indeed been demonstrated between time to appropriate antibiotic therapy and poor CAP prognosis, and conversely a negative impact for patients has been showed with the use of antibiotic therapy with too broad a spectrum [30,31]. Disadvantages of this technique are the possibility of inappropriate antibiotic escalation based on a false-positive PCR test result for a bacterium or resistance gene, and the fact that not all bacterial species responsible for pneumonia are included in this panel.

Finally, despite the high cost of “upper respiratory tract” and “lower respiratory tract” syndromic panels, no cost-effectiveness data are available.

Several studies assessing the potential impact of “lower respiratory tract” syndromic panels have been performed in other wards than the intensive care unit (Table 1):

- The randomized control study by Virk *et al.* [32] is one of the most comprehensive trials to date assessing the clinical impact of “lower respiratory tract” syndromic panels in the management of patients hospitalized for pneumonia, including CAP. Performed at the Mayo Clinic, United States, the study included 1,152 adult patients hospitalized for pneumonia suspicion and randomized to have “lower respiratory tract” syndromic panel (BioFire® FilmArray®, Pneumonia panel) on deep respiratory samples associated with standard cultures, or only conventional cultures alone with antimicrobial susceptibility testing.

The primary endpoint was the median time to first antibiotic modification (escalation or de-escalation) in the 96 h following randomization. The use of a “lower respiratory tract” syndromic panel did not significantly reduce this time in the global analysis (20.4 h versus 25.8 h; *p* = 0.076), but it was associated with a significant reduction in time to escalation of anti-Gram positive antibiotics (10.3 h versus 24.6 h; *p* = 0.044) and of anti-Gram negative antibiotics (17.3 h versus 27.2 h; *p* = 0.010), as well as with quicker de-escalation of treatments active against Gram-positive bacteria (20.7 h versus 27.8 h; *p* = 0.015). No significant benefit was observed in terms of de-escalation of anti-Gram-negative treatments, despite the diagnostic performance of the test.

In the subgroup of 514 patients with confirmed diagnosis of CAP (45.5 % of cases), results were similar overall. The syndromic panel was associated with quicker microbiological detection (2 h versus 31 h) and a more frequent detection of some pathogens such as *H. influenzae* or *Moraxella catarrhalis*. Recommendations from the antibiotic stewardship program were made earlier and more frequently in the syndromic panel group.

From a clinical impact standpoint, no significant difference was observed in terms of 30-day mortality or hospital length of stay. However, secondary admission to the intensive care unit was observed less frequently in the syndromic panel group (8.9 % versus 23.0 %; *p* = 0.014), suggesting a possible indirect benefit of the quicker therapeutic response.

These results confirm the potential value of “lower respiratory tract” syndromic panel to accelerate initial antibiotic therapy optimization, especially in patients with CAP. However, their efficacy highly depends on their integration into a structured and effective antibiotic stewardship program, as well as on physicians’ trust in the obtained results, especially in the absence of detection or to justify de-escalation targeted at Gram-negative bacteria [32].

- The Norwegian study CAPNOR [29] rigorously assessed the impact of an early use of “lower respiratory tract” syndromic panel (Bio-Fire® FilmArray®, Pneumonia plus) performed on induced sputum samples in patients hospitalized for CAP suspicion through the emergency department. The study included 374 adults (median age of 72 years), allocated to a “syndromic panel + standard of care” group and to a “standard of care alone” group, with a specific analysis performed in 200 patients with confirmed CAP.

The primary endpoint was measuring in the first 48 h the proportion

<table><caption>**Table 1**
Comparison of randomized trials assessing multiplex PCR testing in CAP patients.</caption><thead><tr><th>Study (year, country)</th><th>Population included (n)</th><th>Profile of patients (age, comorbidities)</th><th>Type of test &amp; sample</th><th>Primary endpoint</th><th>Key results</th><th>Impact on clinical course</th><th>Conclusion/ Limitations</th></tr></thead><tbody><tr><td>Virk et al. (2024, USA) [32]</td><td>1,152 hospitalized patients (514 CAP)</td><td>Median age: ~65 years; frequent comorbidities (cardio-pulmonary, diabetes)</td><td>FilmArray® Pneumonia Panel – sputum, BAL, aspirations</td><td>Time to first ATB modification (96 h)</td><td>↓ time to anti-Gram + and anti-Gram – escalation/de-escalation; no significant reduction in overall time to escalation/de-escalation</td><td>↓ ICU admissions; no difference in mortality or hospital length of stay</td><td>High-performance panel but benefits mainly on Gram + decisions; mobile ATB team dependence</td></tr><tr><td>Markussen et al. (2024, Norway) [29]</td><td>374 in the emergency department (200 confirmed CAP)</td><td>Median age: 72 years; frequent respiratory comorbidities</td><td>FilmArray® Pneumonia Panel – sputum</td><td>% of targeted treatments within 48 h</td><td>47 % (PCR) vs 15 % (standard); ↓ time to targeted treatment initiation of 12 h</td><td>No difference in mortality, hospital length of stay or readmission</td><td>Panel use increases targeted treatment prescriptions, but no effect on ATB duration or mortality</td></tr><tr><td>Cartulíares et al. (2023, Denmark) [33]</td><td>294 patients in the emergency department (59 % of CAP)</td><td>Median age: 73 years; 30 % of COPD, history of moderate cardiovascular events</td><td>FilmArray® Pneumonia Panel – sputum or aspirations</td><td>% of narrow-spectrum ATB at 4 h</td><td>No difference in ATB spectrum; ↑ in targeted and adequate treatments at 48 h and on Day 5</td><td>No significant clinical impact: mortality, readmission, hospital length of stay unchanged</td><td>Diagnostic impact but little behavior changes</td></tr><tr><td>Abelenda-Alonso et al. (2024, Spain) [34]</td><td>242 patients hospitalized for CAP</td><td>Median age: 76 years; >50 % >75 years, frequent pulmonary, cardiac, and renal diseases</td><td>FilmArray® Pneumonia Panel – sputum (65 %) or nasopharyngeal sample (35 %)</td><td>Number of days of antibiotic therapy</td><td>Days of treatment: 10.0 days (PCR) vs 11.3 days; *p* = 0.093; ↑ microbiological yield; ↓ time to diagnosis</td><td>↓ ICU admissions; no significant difference in clinical stability, mortality or hospital length of stay</td><td>No significant impact without mobile ATB team; study terminated for futility</td></tr></tbody></table>

ATB: antibiotics; CAP: community-acquired acute pneumonia; COPD: chronic obstructive pulmonary disease; PCR: Polymerase Chain Reaction; USA: United States of America.
of patients receiving antibiotic treatment based on microbiological results and time to treatment initiation. Results were clear:

- In the CAP cohort, **approximately 47 %** of patients of the “panel” group received adequate treatment within 48 h versus **15.5 %** in the control group (OR = 4.90; *p* < 0.001).

- **Median time** to adequate treatment initiation was associated with a reduction of **12.3 h** (29.9 h versus 42.3 h; HR = 3.45; *p* < 0.001).

- **Microbiological detection** (bacterial or viral) was significantly higher in the syndromic panel group.

- The study also reported a moderate but significant increase in **escalation to broader spectrum antibiotics** in the syndromic panel group, while de-escalation was not frequent in both groups. No benefits were observed in terms of hospital length of stay, 30-day or 90-day mortality, and re-admission rates.

This study highlights that “lower respiratory tract” syndromic panel used as soon as patient admission is associated with an increased rate of targeted treatment prescription and with quicker prescription of such treatment, even in a context of low antibiotic pressure. The study confirms real-time integration of such panels in emergency departments, but points to the **current limitations in terms of de-escalation and global clinical impact**, in the absence of antibiotic stewardship program/active mobile or transversal infectiology team.

- A randomized multicenter open-label study performed in three Danish emergency departments assessed the value of “lower respiratory tract” syndromic panel directly performed in the ward (through “Point of care” testing) to guide antibiotic prescription in 294 patients hospitalized for CAP suspicion. The intervention consisted in giving the test results to the clinician in less than 4 h (FilmArray®, Pneumonia Panel plus), alongside a decision guide based on national guidelines [33].

- The primary endpoint was to increase the proportion of patients receiving no treatment or a narrow-spectrum antibiotic within the first 4 h. This criterion was not met: the proportion was similar between the two groups (62.8 % in the syndromic panel group vs. 59.6 % in the standard group; *p* = 0.13). In contrast, prescriptions were significantly more targeted and appropriate in the syndromic panel group, particularly at 48 h and on Day 5 (targeted antibiotics: adjusted OR = 4.20 at 48 h; *p* < 0.001; appropriate treatments: OR = 2.11; *p* = 0.006). However, these results were based on a small number of positive cultures (19 %).

- No impact was observed on the following clinical criteria: mortality, readmissions, hospital length of stay (non-significant reduction of one day), or admission to the intensive care unit.

- The study, carried out in a context of very low prevalence of resistance and already restrictive empirical prescriptions (penicillin as first-line treatment), illustrates the value of the test in improving antibiotic treatment quality without necessarily changing its nature. It also points out that the test's ability to reduce antibiotic exposure depends closely on the epidemiological context (low viral circulation during the study) and active support for medical decision-making.

- The Spanish RADICAP trial evaluated the effect of systematically adding a “lower respiratory tract” syndromic panel performed on non-invasive respiratory samples (sputum or nasopharyngeal swabs) to the conventional microbiological strategy, in 242 adults hospitalized for CAP. Patients were randomized to have either “lower respiratory tract” syndromic panel (FilmArray®, Pneumonia Plus Panel) in addition to standard microbiological tests, or the latter tests alone. The primary endpoint was to reduce the duration of antibiotic treatment, measured in days of treatment [34].

Results showed a **significant increase in microbiological diagnostic yield** (63.9 % versus 26.0 %; *p* < 0.0001) and a reduced **time to etiological diagnosis** (0.17 versus 1.57 day; *p* < 0.0001) in the

syndromic panel group. **Antibiotic exposure duration** was slightly reduced in this group (10.04 versus 11.33 days), but the difference was **not statistically significant** (−1.04 day; 95 %CI: −2.42 to 0.17; *p* = 0.093). No benefit was observed on de-escalation rate, adverse events, clinical stability, or 30-day mortality. Switching from IV to oral antibiotic therapy was however quicker (1.2 days versus 2.7 days; *p* = 0.011), and the admission rate to the intensive care unit was lower in the syndromic panel group (1.7 % versus 8.9 %; *p* = 0.026).

The study, which was prematurely terminated for futility after interim analysis, did not include any structured intervention from a mobile antibiotic therapy team: clinicians were informed of the results of the syndromic panel but there was no formal protocol for therapeutic decision-making. These results show that the integration of a high-performance diagnostic tool alone is **not enough to optimize antibiotic use**, in the absence of active decision-making support. Nevertheless, the RADICAP study confirms the feasibility of early syndromic panel use in routine clinical practice on non-invasive samples, with good diagnostic yield.

## 6. Conclusion

The four recent randomized trials analyzed [29,32–34] confirm that syndromic panels allow, in heterogeneous contexts, a net improvement in **microbiological yield** and **accelerated access to etiological diagnosis** in hospitalized community-acquired pneumonia patients.

However, the clinical impact on **antibiotic prescription** remains uneven:

- **Two studies** showed a significant reduction in **time to antibiotic treatment modification** (escalation or de-escalation), but without any systematic reduction in the number of days of antibiotic therapy [29,32].

- **Two other studies** found **no significant reduction in the use of broad-spectrum antibiotics** or in the number of days of treatment, despite improved microbiological targeting [33,34].

In the absence of intervention from a **mobile antibiotic therapy team**, these tests seem above all to **reinforce the relevance** of antibiotic treatment, without necessarily reducing its duration or modifying its intensity. Their benefits are **greatest when the results are integrated into a controlled decision-making process**, in conjunction with a mobile antibiotic therapy team or formal prescribing assistance.

Finally, their **clinical acceptability** remains a limitation, particularly when PCR test identifies respiratory viruses or commensal bacteria: clinicians are still reluctant to de-escalate without confirmation by culture or in the event of clinical improvement on empirical treatment.

Respiratory multiplex panels therefore appear to be highly valuable **diagnostic tools** with a **potential impact on antibiotic use**, provided they are combined with an active decision-support strategy. Their isolated effects, without clinical support or interpretation systems, seem insufficient to significantly transform the management of hospitalized CAP patients.

## 7. 2025 recommendations

- **Ambulatory CAP**: testing for respiratory viruses and the use of syndromic PCR tests are not recommended (**Expert advice**).

- **Non-severe hospitalized CAP**:

It is recommended to perform targeted multiplex PCR test to detect influenza A/B, RSV, and SARS-CoV-2, depending on the epidemic context.

**“Upper respiratory tract” syndromic panel** or an extended test including *M. pneumoniae* (depending on the local equipment available) carried out on **nasopharyngeal swabs** may be proposed as a first or second-line option if the viral targeted multiplex PCR test is negative
(Grade C-2):

1. When detection of atypical bacteria (especially *M. pneumoniae*) is considered (depending on clinical presentation and/or epidemiology) and if specific PCR tests are not available.

2. If the detection of a virus other than influenza A and B/RSV/SARS-CoV-2 can influence the patient's management (de-escalation or discontinuation of antibiotics, isolation).

- Severe hospitalized CAP:

It is recommended to perform a targeted multiplex PCR test to detect influenza A/B, RSV, and SARS-CoV-2 viruses, depending on the epidemiological context (Grade C-2).

"Upper respiratory tract" syndromic panel or an extended test including *M. pneumoniae* (depending on the local equipment available) carried out on nasopharyngeal swabs may be proposed as a first or second-line option if the viral quadruplex PCR test is negative (Grade C-2):

1. When detection of atypical bacteria (especially *M. pneumoniae*) is considered (depending on clinical presentation and/or epidemiology) and if specific PCR tests are not available.

2. If the detection of a virus other than influenza A and B/RSV/SARS-CoV-2 can influence the patient's management (de-escalation or discontinuation of antibiotics, isolation).

"Lower respiratory tract" syndromic panel performed on deep respiratory samples (TA, PDS, or BAL; failing this, on good quality sputum samples) can be suggested (Grade C-2):

1. When unconventional antibiotic therapy is prescribed as empirical treatment (i.e., different from the third-generation cephalosporin + macrolide combination).

2. When testing for atypical bacteria (especially *L. pneumophila* when the antigen urinary test is negative) is considered (depending on the presentation and epidemiology, and if specific PCR tests are not available).

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

We would like to thank Marie Calus for editing.

Funding

None.

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