Diagnostic Accuracy of a Rapid Antigen Detection Test for Group A Streptococcus in Children With Pleural Empyema

To the Editors: Pleural empyema is a severe complication of pediatric community-acquired pneumonia, with group A Streptococcus (GAS) being one of the leading causes, especially in the era of pneumococcal conjugate vaccines.1–3 Rapid identification of the pathogen responsible for pleural empyema is essential to provide an early appropriate antibiotic therapy and help reduce unnecessary diagnostic testing. Bacterial culture of pleural fluid has been the traditional reference standard for detecting pathogens in children with pleural empyema, but it requires a 24–48-hour turnaround and often yields negative results, notably when children have received antibiotics before pleural puncture.1 Hence, nonculture-based laboratory methods such as polymerase chain reaction (PCR) and rapid antigen detection tests (RADTs) have gained attention in recent years. Here, we evaluated the diagnostic accuracy of a GAS-RADT performed in pleural fluids from children with empyema-complicated pneumonia. We retrospectively analyzed a series of 24 frozen (−80°C) pleural fluids from children (median age: 1.7 years, interquartile range: 0.1–4.7) admitted to the Necker - Enfants Malades Hospital (Paris, France) between April 2016 and May 2024. All samples were tested for GAS using the Streptatest (Biosynex, Illkirch-Graffenstaden, France), a GAS-RADT widely used in France in children with pharyngitis. Briefly, the sterile swab provided in the kit was stirred in the thawed pleural fluid for 10 seconds, and the test was performed following the manufacturer’s instructions. GAS-RADT results were compared to those of a composite reference standard, which was considered positive if GAS was identified in the pleural fluid specimens (by culture, GAS-specific PCR, or 16S PCR) or in blood culture. The reference standard was considered negative in other cases. Our local algorithm begins with culture, followed by specific PCRs if culture is negative, and then 16S PCR if specific PCRs are also negative. The GAS-RADT showed a sensitivity of 92.9% (13/14; 95% confidence interval: 66.1−99.8) and a specificity of 100.0% (10/10; 95% confidence interval: 69.2−100.0). Results differed between the 2 tests only for 1 sample (#22). Of note, this false negative result occurred in a sample in which the GAS-specific PCR was positive with a high cycle threshold value (Ct: 32). No cross-reactions were observed between the GAS-RADT and other microorganisms present in the samples (Table 1). TABLE 1. - Diagnostic Accuracy of a Rapid Antigen Detection Test for Detecting Group A Streptococcus (GAS-RADT) in Children With Pleural Empyema Pleural Specimen Number GAS-RADT in Pleural Fluid Composite Reference Standard Culture From Pleural Fluid GAS-specific PCR From Pleural Fluid (Ct)* 16S PCR From Pleural Fluid* Blood Culture 1† + + − + (21) ND − 2 + + − + (29) ND − 3 + + + ND ND − 4 + + + ND ND − 5 + + + ND ND − 6 + + − + (26) + − 7 + + + + (19) ND ND 8 − − − − ND ND 9 + + + ND ND − 10 − − − − ND − 11‡ − − − ND ND − 12‡ − − − ND ND − 13 + + + ND ND − 14‡ − − − ND ND ND 15 + + + + (24) ND − 16 + + + ND ND ND 17 + + + ND ND ND 18 + + + ND ND − 19‡ − − − ND ND − 20 − − − − − ND 21 − − − − ND ND 22 − + − + (32) ND − 23‡ − − − ND ND − 24‡ − − − ND − − GAS-RADT sensitivity: 92.9% (13/14; 95% confidence interval: 66.1–99.8); GAS-RADT specificity: 100.0% (10/10; 95% confidence interval: 69.2–100.0).*GAS-specific PCR and 16S PCR were performed if the sample volume was sufficient.†The pleural fluid specimen contained pseudomembranes.‡The culture of these samples grew bacteria other than GAS: Staphylococcus aureus and bacteria from oropharyngeal flora (Neisseria spp., Streptococcus viridans) (sample 11); Parvimonas micra (sample 12); Staphylococcus capitis (sample 14); Staphylococcus epidermidis (samples 19 and 24); Haemophilus influenzae (sample 23).− indicates GAS not identified; +, GAS identified; Ct, cycle threshold; ND, not done. Our study highlights the high diagnostic accuracy of the GAS-RADT in children with pleural empyema. This test provides results within 5 minutes, is easy to perform and can be done by clinicians at the bedside. Our results are consistent with previous studies: Zheng et al4 reported a sensitivity of 90% (9/10) and a specificity of 100% (110/110), and De Schuyter et al5 found a sensitivity of 95% (20/21) and a specificity of 100% (42/42). However, the limitations of our study include its small sample size, retrospective design, single-center setting and the fact that tests were performed on frozen samples. In conclusion, GAS-RADT appears to be an accurate tool to improve the rapid identification of GAS in children with empyema-complicated pneumonia, thereby potentially contributing to diagnostic and antimicrobial stewardship. Large, prospective, multicenter studies are needed to confirm these findings before widespread clinical implementation.

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The Pediatric Infectious Disease Journal
Published
2024-11-04
DOI
https://doi.org/10.1097/inf.0000000000004610
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Pleural and Pulmonary Diseases
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article

Diagnostic Accuracy of a Rapid Antigen Detection Test for Group A Streptococcus in Children With Pleural Empyema

Hélène Faury, Jérémie F. Cohen, Alix Flamant, Agnès Ferroni
The Pediatric Infectious Disease Journal
Pleural and Pulmonary Diseases
article

Diagnostic Accuracy of a Rapid Antigen Detection Test for Group A Streptococcus in Children With Pleural Empyema

Hélène Faury, Jérémie F. Cohen, Alix Flamant, Agnès Ferroni
article en

Abstract

To the Editors: Pleural empyema is a severe complication of pediatric community-acquired pneumonia, with group A Streptococcus (GAS) being one of the leading causes, especially in the era of pneumococcal conjugate vaccines.1–3 Rapid identification of the pathogen responsible for pleural empyema is essential to provide an early appropriate antibiotic therapy and help reduce unnecessary diagnostic testing. Bacterial culture of pleural fluid has been the traditional reference standard for detecting pathogens in children with pleural empyema, but it requires a 24–48-hour turnaround and often yields negative results, notably when children have received antibiotics before pleural puncture.1 Hence, nonculture-based laboratory methods such as polymerase chain reaction (PCR) and rapid antigen detection tests (RADTs) have gained attention in recent years. Here, we evaluated the diagnostic accuracy of a GAS-RADT performed in pleural fluids from children with empyema-complicated pneumonia. We retrospectively analyzed a series of 24 frozen (−80°C) pleural fluids from children (median age: 1.7 years, interquartile range: 0.1–4.7) admitted to the Necker - Enfants Malades Hospital (Paris, France) between April 2016 and May 2024. All samples were tested for GAS using the Streptatest (Biosynex, Illkirch-Graffenstaden, France), a GAS-RADT widely used in France in children with pharyngitis. Briefly, the sterile swab provided in the kit was stirred in the thawed pleural fluid for 10 seconds, and the test was performed following the manufacturer’s instructions. GAS-RADT results were compared to those of a composite reference standard, which was considered positive if GAS was identified in the pleural fluid specimens (by culture, GAS-specific PCR, or 16S PCR) or in blood culture. The reference standard was considered negative in other cases. Our local algorithm begins with culture, followed by specific PCRs if culture is negative, and then 16S PCR if specific PCRs are also negative. The GAS-RADT showed a sensitivity of 92.9% (13/14; 95% confidence interval: 66.1−99.8) and a specificity of 100.0% (10/10; 95% confidence interval: 69.2−100.0). Results differed between the 2 tests only for 1 sample (#22). Of note, this false negative result occurred in a sample in which the GAS-specific PCR was positive with a high cycle threshold value (Ct: 32). No cross-reactions were observed between the GAS-RADT and other microorganisms present in the samples (Table 1). TABLE 1. - Diagnostic Accuracy of a Rapid Antigen Detection Test for Detecting Group A Streptococcus (GAS-RADT) in Children With Pleural Empyema Pleural Specimen Number GAS-RADT in Pleural Fluid Composite Reference Standard Culture From Pleural Fluid GAS-specific PCR From Pleural Fluid (Ct)* 16S PCR From Pleural Fluid* Blood Culture 1† + + − + (21) ND − 2 + + − + (29) ND − 3 + + + ND ND − 4 + + + ND ND − 5 + + + ND ND − 6 + + − + (26) + − 7 + + + + (19) ND ND 8 − − − − ND ND 9 + + + ND ND − 10 − − − − ND − 11‡ − − − ND ND − 12‡ − − − ND ND − 13 + + + ND ND − 14‡ − − − ND ND ND 15 + + + + (24) ND − 16 + + + ND ND ND 17 + + + ND ND ND 18 + + + ND ND − 19‡ − − − ND ND − 20 − − − − − ND 21 − − − − ND ND 22 − + − + (32) ND − 23‡ − − − ND ND − 24‡ − − − ND − − GAS-RADT sensitivity: 92.9% (13/14; 95% confidence interval: 66.1–99.8); GAS-RADT specificity: 100.0% (10/10; 95% confidence interval: 69.2–100.0).*GAS-specific PCR and 16S PCR were performed if the sample volume was sufficient.†The pleural fluid specimen contained pseudomembranes.‡The culture of these samples grew bacteria other than GAS: Staphylococcus aureus and bacteria from oropharyngeal flora (Neisseria spp., Streptococcus viridans) (sample 11); Parvimonas micra (sample 12); Staphylococcus capitis (sample 14); Staphylococcus epidermidis (samples 19 and 24); Haemophilus influenzae (sample 23).− indicates GAS not identified; +, GAS identified; Ct, cycle threshold; ND, not done. Our study highlights the high diagnostic accuracy of the GAS-RADT in children with pleural empyema. This test provides results within 5 minutes, is easy to perform and can be done by clinicians at the bedside. Our results are consistent with previous studies: Zheng et al4 reported a sensitivity of 90% (9/10) and a specificity of 100% (110/110), and De Schuyter et al5 found a sensitivity of 95% (20/21) and a specificity of 100% (42/42). However, the limitations of our study include its small sample size, retrospective design, single-center setting and the fact that tests were performed on frozen samples. In conclusion, GAS-RADT appears to be an accurate tool to improve the rapid identification of GAS in children with empyema-complicated pneumonia, thereby potentially contributing to diagnostic and antimicrobial stewardship. Large, prospective, multicenter studies are needed to confirm these findings before widespread clinical implementation.

The Pediatric Infectious Disease JournalVol. 44(3)
Hôpital Necker-Enfants Malades (FR), Centre National de la Recherche Scientifique (FR), Inserm (FR), Université Paris Cité (FR), Institut Necker Enfants Malades (FR), Assistance Publique – Hôpitaux de Paris (FR)
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