LEGIONNAIRES’ DISEASE IN THE ERA OF
MOLECULAR DIAGNOSTICS: IMPACT OF
MULTIPLEX RESPIRATORY PANELS ON THE
EARLY DETECTION OF LEGIONELLA
PNEUMOPHILA MOLECULAR DIAGNOSIS OF
LEGIONELLA PNEUMONIA
ENFERMEDAD DEL LEGIONARIO EN LA ERA DEL
DIAGNÓSTICO MOLECULAR: IMPACTO DE LOS PANELES
RESPIRATORIOS MULTIPLEX EN LA DETECCIÓN
TEMPRANA DE LEGIONELLA PNEUMOPHILA /
DIAGNÓSTICO MOLECULAR DE LA NEUMONÍA POR
LEGIONELLA
Maria Guadalupe Martinez Alcaraz
Universidad Cuauhtémoc
Claudia Patricia Miramontes Gonzalez
Mexican Social Security Institute
Melissa Carrillo Hernandez
Hospital General ISSSTE Aguascalientes
Jaime Froylan Rojas Teran
Hospital General ISSSTE Aguascalientes
pág. 4131
DOI: https://doi.org/10.37811/cl_rcm.v10i2.23457
Legionnaires’ Disease in the Era of Molecular Diagnostics: Impact of
Multiplex Respiratory Panels on the Early Detection of Legionella
pneumophila Molecular Diagnosis of Legionella Pneumonia
Maria Guadalupe Martinez Alcaraz1
dra.melissa44carrillo@gmail.com
https://orcid.org/0009-0001-8652-0298
Department of Medicine, Universidad
Cuauhtémoc, Aguascalientes Campus,
Aguascalientes, Mexico
Claudia Patricia Miramontes Gonzalez
https://orcid.org/0009-0006-9810-030X
Department of Medicine, Mexican Social
Security Institute: Mexico City, Mexico
Melissa Carrillo Hernandez
https://orcid.org/0009-0002-5196-1269
Department of Internal Medicine, Hospital
General ISSSTE Aguascalientes,
Aguascalientes, Mexico
Jaime Froylan Rojas Teran
https://orcid.org/0000-0002-2536-560X
Department of Internal Medicine, Hospital
General ISSSTE Aguascalientes,
Aguascalientes, Mexico
ABSTRACT
Background: Legionnaires’ disease is a severe form of community-acquired pneumonia primarily
caused by Legionella pneumophila. Although relatively uncommon, delayed diagnosis is associated
with increased morbidity and mortality. Clinical suspicion is supported by extrapulmonary
manifestations such as gastrointestinal symptoms, hyponatremia, and failure to respond to beta-lactam
therapy. Case presentation: A 65-year-old male with hypertension and dyslipidemia developed fever,
progressive dyspnea, and dry cough after environmental exposure to bird droppings. Laboratory tests
showed leukocytosis, elevated C-reactive protein, and mild hyponatremia. After lack of response to
amoxicillin-clavulanate and negative viral testing, multiplex PCR respiratory panel (FilmArray®)
identified Legionella pneumophila. Targeted therapy with azithromycin led to rapid clinical
improvement. Discussion: Legionella infection may mimic viral or typical bacterial pneumonia.
Molecular multiplex diagnostic tools enable rapid pathogen identification. Early initiation of macrolides
or fluoroquinolones significantly improves outcomes. Conclusions: Legionnaires’ disease should be
suspected in atypical pneumonia with systemic features and poor response to beta-lactams. Early
molecular diagnosis and prompt intracellularly active antibiotic therapy are crucial determinants of
prognosis.
Keywords: Legionella pneumophila; community-acquired pneumonia; hyponatremia; multiplex PCR;
macrolides
1 Autor principal
Correspondencia: dra.melissa44carrillo@gmail.com
DOI: https://doi.org/10.37811/cl_rcm.v10i2.23457
Legionnaires’ Disease in the Era of Molecular Diagnostics: Impact of
Multiplex Respiratory Panels on the Early Detection of Legionella
pneumophila Molecular Diagnosis of Legionella Pneumonia
Maria Guadalupe Martinez Alcaraz1
dra.melissa44carrillo@gmail.com
https://orcid.org/0009-0001-8652-0298
Department of Medicine, Universidad
Cuauhtémoc, Aguascalientes Campus,
Aguascalientes, Mexico
Claudia Patricia Miramontes Gonzalez
https://orcid.org/0009-0006-9810-030X
Department of Medicine, Mexican Social
Security Institute: Mexico City, Mexico
Melissa Carrillo Hernandez
https://orcid.org/0009-0002-5196-1269
Department of Internal Medicine, Hospital
General ISSSTE Aguascalientes,
Aguascalientes, Mexico
Jaime Froylan Rojas Teran
https://orcid.org/0000-0002-2536-560X
Department of Internal Medicine, Hospital
General ISSSTE Aguascalientes,
Aguascalientes, Mexico
ABSTRACT
Background: Legionnaires’ disease is a severe form of community-acquired pneumonia primarily
caused by Legionella pneumophila. Although relatively uncommon, delayed diagnosis is associated
with increased morbidity and mortality. Clinical suspicion is supported by extrapulmonary
manifestations such as gastrointestinal symptoms, hyponatremia, and failure to respond to beta-lactam
therapy. Case presentation: A 65-year-old male with hypertension and dyslipidemia developed fever,
progressive dyspnea, and dry cough after environmental exposure to bird droppings. Laboratory tests
showed leukocytosis, elevated C-reactive protein, and mild hyponatremia. After lack of response to
amoxicillin-clavulanate and negative viral testing, multiplex PCR respiratory panel (FilmArray®)
identified Legionella pneumophila. Targeted therapy with azithromycin led to rapid clinical
improvement. Discussion: Legionella infection may mimic viral or typical bacterial pneumonia.
Molecular multiplex diagnostic tools enable rapid pathogen identification. Early initiation of macrolides
or fluoroquinolones significantly improves outcomes. Conclusions: Legionnaires’ disease should be
suspected in atypical pneumonia with systemic features and poor response to beta-lactams. Early
molecular diagnosis and prompt intracellularly active antibiotic therapy are crucial determinants of
prognosis.
Keywords: Legionella pneumophila; community-acquired pneumonia; hyponatremia; multiplex PCR;
macrolides
1 Autor principal
Correspondencia: dra.melissa44carrillo@gmail.com
pág. 4132
Enfermedad del Legionario en la Era del Diagnóstico Molecular: Impacto
de los Paneles Respiratorios Multiplex en la Detección Temprana de
Legionella pneumophila / Diagnóstico Molecular de la Neumonía por
Legionella
RESUMEN
Antecedentes: La enfermedad del legionario es una forma grave de neumonía adquirida en la
comunidad, causada principalmente por Legionella pneumophila. Aunque es relativamente poco
frecuente, el diagnóstico tardío se asocia con un aumento de la morbilidad y mortalidad. La sospecha
clínica se apoya en manifestaciones extrapulmonares como síntomas gastrointestinales, hiponatremia y
falta de respuesta a la terapia con betalactámicos. Presentación del caso: Un hombre de 65 años, con
antecedentes de hipertensión y dislipidemia, desarrolló fiebre, disnea progresiva y tos seca tras
exposición ambiental a excrementos de aves. Los estudios de laboratorio mostraron leucocitosis,
elevación de proteína C reactiva e hiponatremia leve. Tras la falta de respuesta a amoxicilina-
clavulánico y pruebas virales negativas, un panel respiratorio multiplex por PCR (FilmArray®)
identificó Legionella pneumophila. El tratamiento dirigido con azitromicina condujo a una rápida
mejoría clínica. Discusión: La infección por Legionella puede simular neumonía viral o bacteriana
típica. Las herramientas diagnósticas moleculares multiplex permiten una rápida identificación del
patógeno. El inicio temprano de macrólidos o fluoroquinolonas mejora significativamente los resultados
clínicos. Conclusiones: La enfermedad del legionario debe sospecharse en neumonías atípicas con
manifestaciones sistémicas y mala respuesta a betalactámicos. El diagnóstico molecular temprano y la
terapia antibiótica oportuna con fármacos activos intracelularmente son determinantes clave del
pronóstico.
Palabras clave: Legionella pneumophila; neumonía adquirida en la comunidad; hiponatremia; PCR
multiplex; macrólidos
Artículo recibido 28 febrero 2026
Aceptado para publicación: 28 marzo 2026
Enfermedad del Legionario en la Era del Diagnóstico Molecular: Impacto
de los Paneles Respiratorios Multiplex en la Detección Temprana de
Legionella pneumophila / Diagnóstico Molecular de la Neumonía por
Legionella
RESUMEN
Antecedentes: La enfermedad del legionario es una forma grave de neumonía adquirida en la
comunidad, causada principalmente por Legionella pneumophila. Aunque es relativamente poco
frecuente, el diagnóstico tardío se asocia con un aumento de la morbilidad y mortalidad. La sospecha
clínica se apoya en manifestaciones extrapulmonares como síntomas gastrointestinales, hiponatremia y
falta de respuesta a la terapia con betalactámicos. Presentación del caso: Un hombre de 65 años, con
antecedentes de hipertensión y dislipidemia, desarrolló fiebre, disnea progresiva y tos seca tras
exposición ambiental a excrementos de aves. Los estudios de laboratorio mostraron leucocitosis,
elevación de proteína C reactiva e hiponatremia leve. Tras la falta de respuesta a amoxicilina-
clavulánico y pruebas virales negativas, un panel respiratorio multiplex por PCR (FilmArray®)
identificó Legionella pneumophila. El tratamiento dirigido con azitromicina condujo a una rápida
mejoría clínica. Discusión: La infección por Legionella puede simular neumonía viral o bacteriana
típica. Las herramientas diagnósticas moleculares multiplex permiten una rápida identificación del
patógeno. El inicio temprano de macrólidos o fluoroquinolonas mejora significativamente los resultados
clínicos. Conclusiones: La enfermedad del legionario debe sospecharse en neumonías atípicas con
manifestaciones sistémicas y mala respuesta a betalactámicos. El diagnóstico molecular temprano y la
terapia antibiótica oportuna con fármacos activos intracelularmente son determinantes clave del
pronóstico.
Palabras clave: Legionella pneumophila; neumonía adquirida en la comunidad; hiponatremia; PCR
multiplex; macrólidos
Artículo recibido 28 febrero 2026
Aceptado para publicación: 28 marzo 2026
pág. 4133
INTRODUCTION
Legionnaires’ disease is a severe pneumonia predominantly caused by Legionella pneumophila, a
facultative intracellular gram-negative bacillus that proliferates in artificial aquatic environments such
as air-conditioning systems, cooling towers, and hospital water networks¹. Since its first description in
1976, it has remained a significant cause of community-acquired pneumonia (CAP), with increasing
incidence in several countries, partly attributed to improved diagnostic techniques and population
aging².
In Europe and North America, Legionella accounts for approximately 2–9% of hospitalized CAP cases;
however, its prevalence increases in severe presentations or among patients requiring intensive care³.
Reported mortality ranges from 4% to 18%, reaching higher rates in immunocompromised individuals
or when appropriate antimicrobial therapy is delayed⁴.
The pathophysiology is based on inhalation of contaminated aerosols. Once in the lower respiratory
tract, the bacterium invades alveolar macrophages using a type IV secretion system (Dot/Icm), which
allows it to evade phagolysosomal fusion and replicate intracellularly⁵. This intracellular localization
explains the limited efficacy of antibiotics that fail to achieve adequate intracellular concentrations.
Clinically, in addition to fever and respiratory symptoms, extrapulmonary manifestations are common
and may include diarrhea, mild hepatic abnormalities, marked elevation of acute-phase reactants, and
hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH)⁶. The
presence of these findings, together with lack of response to beta-lactam antibiotics, should increase
clinical suspicion.
Traditional diagnosis relies on urinary antigen detection for L. pneumophila serogroup 1; however, this
test does not identify other serogroups or species⁷. Currently, multiplex PCR techniques such as the
FilmArray® Respiratory Panel enable identification of multiple respiratory pathogens with high
sensitivity and specificity in approximately one hour⁸.
Recommended treatment according to international guidelines includes macrolides (azithromycin) or
fluoroquinolones (levofloxacin), with a minimum duration of five days, extended in severe cases⁹.
We present the case of a patient with Legionella pneumophila pneumonia confirmed by molecular
panel, highlighting the importance of early clinical recognition.
INTRODUCTION
Legionnaires’ disease is a severe pneumonia predominantly caused by Legionella pneumophila, a
facultative intracellular gram-negative bacillus that proliferates in artificial aquatic environments such
as air-conditioning systems, cooling towers, and hospital water networks¹. Since its first description in
1976, it has remained a significant cause of community-acquired pneumonia (CAP), with increasing
incidence in several countries, partly attributed to improved diagnostic techniques and population
aging².
In Europe and North America, Legionella accounts for approximately 2–9% of hospitalized CAP cases;
however, its prevalence increases in severe presentations or among patients requiring intensive care³.
Reported mortality ranges from 4% to 18%, reaching higher rates in immunocompromised individuals
or when appropriate antimicrobial therapy is delayed⁴.
The pathophysiology is based on inhalation of contaminated aerosols. Once in the lower respiratory
tract, the bacterium invades alveolar macrophages using a type IV secretion system (Dot/Icm), which
allows it to evade phagolysosomal fusion and replicate intracellularly⁵. This intracellular localization
explains the limited efficacy of antibiotics that fail to achieve adequate intracellular concentrations.
Clinically, in addition to fever and respiratory symptoms, extrapulmonary manifestations are common
and may include diarrhea, mild hepatic abnormalities, marked elevation of acute-phase reactants, and
hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion (SIADH)⁶. The
presence of these findings, together with lack of response to beta-lactam antibiotics, should increase
clinical suspicion.
Traditional diagnosis relies on urinary antigen detection for L. pneumophila serogroup 1; however, this
test does not identify other serogroups or species⁷. Currently, multiplex PCR techniques such as the
FilmArray® Respiratory Panel enable identification of multiple respiratory pathogens with high
sensitivity and specificity in approximately one hour⁸.
Recommended treatment according to international guidelines includes macrolides (azithromycin) or
fluoroquinolones (levofloxacin), with a minimum duration of five days, extended in severe cases⁹.
We present the case of a patient with Legionella pneumophila pneumonia confirmed by molecular
panel, highlighting the importance of early clinical recognition.
pág. 4134
CASE PRESENTATION
A 65-year-old male with a history of systemic arterial hypertension treated with
losartan/hydrochlorothiazide and dyslipidemia under pharmacologic management presented to the
hospital. He denied smoking and had no history of immunosuppression.
The patient developed unquantified fever, progressive dyspnea eventually occurring at rest, and
persistent dry cough. He also reported dyspepsia and a recent history of cleaning a roof contaminated
with bird droppings approximately five days prior to symptom onset.
At admission, respiratory rate was 24 breaths per minute, oxygen saturation was 90% on room air, and
body temperature was 38.3°C. Pulmonary auscultation revealed crackles over the right mid-lung field.
Initial laboratory tests demonstrated leukocytosis of 15,700/μL with neutrophilia (87%), C-reactive
protein of 96 mg/L, serum sodium of 133 mEq/L, preserved renal function, and mildly elevated
transaminases.
Chest radiography revealed ill-defined alveolar opacities, and empirical treatment with amoxicillin–
clavulanic acid was initiated.
Figure 1. Chest Computed Tomography
CASE PRESENTATION
A 65-year-old male with a history of systemic arterial hypertension treated with
losartan/hydrochlorothiazide and dyslipidemia under pharmacologic management presented to the
hospital. He denied smoking and had no history of immunosuppression.
The patient developed unquantified fever, progressive dyspnea eventually occurring at rest, and
persistent dry cough. He also reported dyspepsia and a recent history of cleaning a roof contaminated
with bird droppings approximately five days prior to symptom onset.
At admission, respiratory rate was 24 breaths per minute, oxygen saturation was 90% on room air, and
body temperature was 38.3°C. Pulmonary auscultation revealed crackles over the right mid-lung field.
Initial laboratory tests demonstrated leukocytosis of 15,700/μL with neutrophilia (87%), C-reactive
protein of 96 mg/L, serum sodium of 133 mEq/L, preserved renal function, and mildly elevated
transaminases.
Chest radiography revealed ill-defined alveolar opacities, and empirical treatment with amoxicillin–
clavulanic acid was initiated.
Figure 1. Chest Computed Tomography
pág. 4135
Non-contrast chest computed tomography performed in lung window with coronal and sagittal
reconstructions.
Coronal sections (upper row and lower left images) demonstrate areas of segmental parenchymal
consolidation in the right lung, predominantly involving the lateral segment of the middle lobe
(segment 5). The consolidation shows peripheral and subpleural distribution with visible air
bronchograms. Multiple adjacent ground-glass opacities are also observed, displaying a patchy and
poorly defined pattern.
Sagittal sections (central and right images) confirm focal alveolar consolidation in the right middle
lobe with extension toward the basal region, accompanied by mild interlobular septal thickening and
areas of mixed ground-glass and consolidative pattern.
No significant pleural effusion, cavitation, or evident mediastinal lymphadenopathy is identified.
These findings are compatible with an acute alveolar–interstitial infectious process in the clinical
context suggestive of atypical pneumonia caused by Legionella pneumophila.
Due to lack of clinical improvement and persistent fever, a chest computed tomography scan was
performed, demonstrating consolidation in the right segment 5, initially suggestive of viral etiology.
PCR tests for SARS-CoV-2, influenza, and respiratory syncytial virus were negative.
Non-contrast chest computed tomography performed in lung window with coronal and sagittal
reconstructions.
Coronal sections (upper row and lower left images) demonstrate areas of segmental parenchymal
consolidation in the right lung, predominantly involving the lateral segment of the middle lobe
(segment 5). The consolidation shows peripheral and subpleural distribution with visible air
bronchograms. Multiple adjacent ground-glass opacities are also observed, displaying a patchy and
poorly defined pattern.
Sagittal sections (central and right images) confirm focal alveolar consolidation in the right middle
lobe with extension toward the basal region, accompanied by mild interlobular septal thickening and
areas of mixed ground-glass and consolidative pattern.
No significant pleural effusion, cavitation, or evident mediastinal lymphadenopathy is identified.
These findings are compatible with an acute alveolar–interstitial infectious process in the clinical
context suggestive of atypical pneumonia caused by Legionella pneumophila.
Due to lack of clinical improvement and persistent fever, a chest computed tomography scan was
performed, demonstrating consolidation in the right segment 5, initially suggestive of viral etiology.
PCR tests for SARS-CoV-2, influenza, and respiratory syncytial virus were negative.
pág. 4136
Figure 2. Chest Computed Tomography
Non-contrast chest computed tomography in lung window, axial sections.
Segmental and subpleural areas of alveolar consolidation are observed in the right lung,
predominantly involving the middle lobe and the anterior basal segment of the right lower lobe. Air
bronchograms are visible within the lesions. The consolidations have poorly defined margins and are
associated with extensive perilesional ground-glass opacities, creating a mixed alveolar–interstitial
pattern.
Additional bilateral patchy opacities are identified, with right-sided predominance and mild adjacent
interlobular septal thickening. No cavitation, significant pleural effusion, or mediastinal
lymphadenopathy is observed in these sections.
These radiologic findings are consistent with acute pneumonia of probable atypical etiology,
concordant with Legionella pneumophila infection in the clinical context described.
Figure 2. Chest Computed Tomography
Non-contrast chest computed tomography in lung window, axial sections.
Segmental and subpleural areas of alveolar consolidation are observed in the right lung,
predominantly involving the middle lobe and the anterior basal segment of the right lower lobe. Air
bronchograms are visible within the lesions. The consolidations have poorly defined margins and are
associated with extensive perilesional ground-glass opacities, creating a mixed alveolar–interstitial
pattern.
Additional bilateral patchy opacities are identified, with right-sided predominance and mild adjacent
interlobular septal thickening. No cavitation, significant pleural effusion, or mediastinal
lymphadenopathy is observed in these sections.
These radiologic findings are consistent with acute pneumonia of probable atypical etiology,
concordant with Legionella pneumophila infection in the clinical context described.
pág. 4137
A molecular respiratory panel (FilmArray®) was requested and returned positive for Legionella
pneumophila. Treatment with azithromycin 500 mg orally every 24 hours for seven days was initiated,
with evident clinical improvement within 48 hours, resolution of fever, and progressive normalization
of inflammatory markers.
The patient was discharged without complications.
DISCUSSION
Legionnaires’ disease represents a diagnostic challenge due to its nonspecific clinical presentation¹⁰. In
this case, the combination of gastrointestinal symptoms, hyponatremia, and lack of response to beta-
lactam therapy suggested the presence of an atypical pathogen.
Hyponatremia is reported in up to 40% of cases and is attributed to inappropriate secretion of
antidiuretic hormone induced by inflammatory cytokines¹¹. Additionally, elevated C-reactive protein
levels (>100 mg/L) have been associated with a higher probability of Legionella etiology¹².
The FilmArray® respiratory panel demonstrated rapid diagnostic utility. Recent studies have shown
sensitivity exceeding 95% for the detection of bacterial and viral respiratory pathogens¹³. Its use in
severe pneumonia allows earlier adjustment of antimicrobial therapy and reduction of unnecessary
broad-spectrum antibiotic use¹⁴.
ATS/IDSA guidelines recommend empirical coverage against Legionella in moderate-to-severe CAP⁹.
Delayed initiation of macrolides or fluoroquinolones has been associated with increased hospital
mortality¹⁵.
Compared with recent reports, our case is consistent with the literature regarding patient age, clinical
presentation, and rapid response to macrolide therapy¹⁶–¹⁸.
Furthermore, in recent years an increase in the reported global incidence of legionellosis has been
described, a phenomenon attributed both to population aging and to the greater availability of highly
sensitive molecular diagnostic methods. Several epidemiological studies have indicated that the
increasing use of molecular respiratory tests has enabled the identification of cases that previously
remained underdiagnosed, particularly in patients hospitalized with community-acquired pneumonia
presenting with atypical clinical evolution¹⁹. This shift in the diagnostic approach has contributed to a
A molecular respiratory panel (FilmArray®) was requested and returned positive for Legionella
pneumophila. Treatment with azithromycin 500 mg orally every 24 hours for seven days was initiated,
with evident clinical improvement within 48 hours, resolution of fever, and progressive normalization
of inflammatory markers.
The patient was discharged without complications.
DISCUSSION
Legionnaires’ disease represents a diagnostic challenge due to its nonspecific clinical presentation¹⁰. In
this case, the combination of gastrointestinal symptoms, hyponatremia, and lack of response to beta-
lactam therapy suggested the presence of an atypical pathogen.
Hyponatremia is reported in up to 40% of cases and is attributed to inappropriate secretion of
antidiuretic hormone induced by inflammatory cytokines¹¹. Additionally, elevated C-reactive protein
levels (>100 mg/L) have been associated with a higher probability of Legionella etiology¹².
The FilmArray® respiratory panel demonstrated rapid diagnostic utility. Recent studies have shown
sensitivity exceeding 95% for the detection of bacterial and viral respiratory pathogens¹³. Its use in
severe pneumonia allows earlier adjustment of antimicrobial therapy and reduction of unnecessary
broad-spectrum antibiotic use¹⁴.
ATS/IDSA guidelines recommend empirical coverage against Legionella in moderate-to-severe CAP⁹.
Delayed initiation of macrolides or fluoroquinolones has been associated with increased hospital
mortality¹⁵.
Compared with recent reports, our case is consistent with the literature regarding patient age, clinical
presentation, and rapid response to macrolide therapy¹⁶–¹⁸.
Furthermore, in recent years an increase in the reported global incidence of legionellosis has been
described, a phenomenon attributed both to population aging and to the greater availability of highly
sensitive molecular diagnostic methods. Several epidemiological studies have indicated that the
increasing use of molecular respiratory tests has enabled the identification of cases that previously
remained underdiagnosed, particularly in patients hospitalized with community-acquired pneumonia
presenting with atypical clinical evolution¹⁹. This shift in the diagnostic approach has contributed to a
pág. 4138
better characterization of the true burden of the disease and has allowed optimization of targeted
therapeutic strategies.
On the other hand, the integration of rapid diagnostic tools into the clinical approach to severe
respiratory infections has become a key element of precision medicine in infectious diseases. Early
identification of the etiologic agent not only allows selection of the most appropriate antibiotic therapy
but also helps reduce the unnecessary use of broad-spectrum antimicrobials and supports antimicrobial
stewardship strategies²⁰. In this context, respiratory molecular panels represent a particularly useful
diagnostic tool in patients with atypical pneumonia or with poor response to initial empirical therapy.
CONCLUSION
Legionnaires’ disease should be considered in the differential diagnosis of community-acquired
pneumonia, particularly in patients presenting with atypical systemic manifestations such as
gastrointestinal symptoms, hyponatremia, marked elevation of acute-phase reactants, and lack of
clinical response to empirical regimens based exclusively on beta-lactam antibiotics. Recognition of
these clinical features may facilitate early suspicion of Legionella pneumophila infection and prevent
diagnostic delays associated with increased morbidity and mortality.
In recent years, multiplex molecular diagnostic tools have transformed the approach to respiratory
infections by enabling rapid and simultaneous detection of multiple pathogens with high sensitivity and
specificity. Their implementation in cases of moderate-to-severe pneumonia or in patients with atypical
clinical evolution facilitates early initiation of targeted antimicrobial therapy, optimizes antimicrobial
stewardship, and contributes to reduced hospital length of stay and complications.
Timely initiation of antimicrobials with adequate intracellular penetration, such as macrolides or
fluoroquinolones, remains a cornerstone of therapy due to the intracellular localization of the
microorganism within alveolar macrophages. The combination of clinical suspicion, radiological
support, and molecular confirmation significantly improves prognosis, reduces mortality, and
strengthens comprehensive management strategies for atypical pneumonia.
This case reinforces the importance of integrating clinical evaluation with advanced diagnostic tools in
contemporary medical practice. Early recognition of Legionnaires’ disease continues to be a challenge,
but it also represents an opportunity for timely, evidence-based intervention.
better characterization of the true burden of the disease and has allowed optimization of targeted
therapeutic strategies.
On the other hand, the integration of rapid diagnostic tools into the clinical approach to severe
respiratory infections has become a key element of precision medicine in infectious diseases. Early
identification of the etiologic agent not only allows selection of the most appropriate antibiotic therapy
but also helps reduce the unnecessary use of broad-spectrum antimicrobials and supports antimicrobial
stewardship strategies²⁰. In this context, respiratory molecular panels represent a particularly useful
diagnostic tool in patients with atypical pneumonia or with poor response to initial empirical therapy.
CONCLUSION
Legionnaires’ disease should be considered in the differential diagnosis of community-acquired
pneumonia, particularly in patients presenting with atypical systemic manifestations such as
gastrointestinal symptoms, hyponatremia, marked elevation of acute-phase reactants, and lack of
clinical response to empirical regimens based exclusively on beta-lactam antibiotics. Recognition of
these clinical features may facilitate early suspicion of Legionella pneumophila infection and prevent
diagnostic delays associated with increased morbidity and mortality.
In recent years, multiplex molecular diagnostic tools have transformed the approach to respiratory
infections by enabling rapid and simultaneous detection of multiple pathogens with high sensitivity and
specificity. Their implementation in cases of moderate-to-severe pneumonia or in patients with atypical
clinical evolution facilitates early initiation of targeted antimicrobial therapy, optimizes antimicrobial
stewardship, and contributes to reduced hospital length of stay and complications.
Timely initiation of antimicrobials with adequate intracellular penetration, such as macrolides or
fluoroquinolones, remains a cornerstone of therapy due to the intracellular localization of the
microorganism within alveolar macrophages. The combination of clinical suspicion, radiological
support, and molecular confirmation significantly improves prognosis, reduces mortality, and
strengthens comprehensive management strategies for atypical pneumonia.
This case reinforces the importance of integrating clinical evaluation with advanced diagnostic tools in
contemporary medical practice. Early recognition of Legionnaires’ disease continues to be a challenge,
but it also represents an opportunity for timely, evidence-based intervention.
pág. 4139
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BIBLIOGRÁPHIC REFERENCES
1. Cunha BA, Burillo A, Bouza E. Legionnaires’ disease. Lancet. 2016;387:376–85.¶
2. Beauté J, Sandin S, Uldum SA, et al. Legionnaires’ disease in Europe. Euro Surveill.
2020;25(7):1900581.¶
3. Phin N, Parry-Ford F, Harrison T, et al. Epidemiology and clinical management of Legionnaires’
disease. Lancet Infect Dis. 2014;14:1011–21.¶
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