Short Report
Mediastinitis secondary to invasive infection by group A Streptococcus in Spain
https://doi.org/10.21203/rs.3.rs-3110549/v1
This work is licensed under a CC BY 4.0 License
published 27 Oct, 2023
Read the published version in European Journal of Pediatrics →
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This study describes 5 mediastinitis cases secondary to invasive group A Streptococcus (iGAS) disease in a recent outbreak in Spain. Among 398 iGAS cases between January 2019 - March 2023, 5 (1.3%) were mediastinitis, 4 occurring in December 2022, all secondary to pneumonia or deep neck infection. We outline the clinical outcome with a review of the scarce pediatric literature.
Mediastinitis
invasive infections
group A Streptococcus
pneumonia
deep neck infections
Mediastinitis is a rare complication of deep neck infection (DNI) in children, occurring in approximately 1%-2% of cases; group A Streptococcus (GAS) is one of the bacteria known to cause DNI1.
In December 2022, an alert reporting an unusual increase in non-invasive GAS and invasive GAS (iGAS) disease was published in the United Kingdom2,3. Other European countries have also reported a similar increase in GAS infections, including Spain4-5.
PedGAS-net is a Spanish multicenter network that studies iGAS in children, prospectively recruiting patients since January 1, 2019. In recent months, there has been a notable increase in mediastinitis associated with iGAS infection. The objective of our study is to provide a description of the mediastinitis cases observed in our cohort within the context of the overall increase in iGAS cases in Spain.
This study describes the frequency of mediastinitis identified as a complication of iGAS infection in patients <16 years old prospectively included in the PedGAS-net – which includes 24 hospitals in Spain. iGAS is defined as a clinical syndrome with Streptococcus pyogenes isolated from a normally sterile site, such as blood, cerebrospinal fluid or pleural fluid. iGAS was also considered if S. pyogenes was cultured from a wound in a child with necrotizing fasciitis or if a diagnosis of probable or definitive streptococcal toxic shock syndrome was made according to the definition from the Centers for Disease Control and Prevention (https://www.cdc.gov/abcs/methodology/case-def-ascertain.html. Accessed 17 January 2023).
This study was approved by the Ethics Committee of Gregorio Marañón Hospital, and the parents or guardians signed an informed consent prior to their inclusion in the study.
Between January 1, 2019, and March 30, 2023, a total of 398 patients with iGAS infection were included in the study. Among these cases, 103 (25.8%) occurred between January 2019 and March 2020 (pre-pandemic); 12 (3%) were reported from April 2020 to December 2021 (during the COVID-19 pandemic); and 283 (71.1%) occurred between January 2022 and March 2023 (post-pandemic).
Out of the 398 cases, 128 were diagnosed with pneumonia and 35 were deep cervical abscesses (19 retropharyngeal, 14 parapharyngeal and 2 laterocervical). Of the 398, 5 cases of mediastinitis were identified, accounting for 1.3% of the cases. One case occurred in 2019, whereas the remaining 4 were reported in the post-COVID pandemic period.
Among the mediastinitis cases: 2 had a pneumonia as their primary focus, 2 had DNI and 1 had both DNI and pneumonia. Consequently, mediastinitis was found to be a complication in 8.6% (3/35) of DNI cases and 2.3% (3/128) of pneumonia cases. The main clinical and analytical characteristics are shown in Table 1.
Table 1. Cases’ clinical and analytical characteristics.
|
Case |
1 |
2 |
3 |
4 |
5 |
|
Year |
2019 |
2022 |
2022 |
2023 |
2023 |
|
Period |
Pre-pandemic |
Post-pandemic |
|||
|
Age at diagnosis |
14 months |
4 years |
7 years |
8 years |
2 years |
|
Sex |
Male |
Male |
Male |
Male |
Female |
|
Comorbidities |
No |
No |
Personal history of epilepsy and CSF fistula (resolved) |
No |
No |
|
Vaccines |
Pneumococcal, varicella
|
Pneumococcal, varicella |
Pneumococcal, varicella, seasonal influenza. |
|
Pneumococcal |
|
Initial symptoms/ diagnosis |
Fever, neck pain |
Fever, respiratory distress |
Fever, respiratory distress, cough |
Fever, respiratory distress; epiglottitis-laryngitis |
Fever, respiratory distress, cough |
|
ICU stay (days) |
0 |
16 |
78 |
8 |
13 |
|
Inotropic drugs |
No |
Yes |
Yes |
No |
Yes |
|
Total antibiotic treatment (days) |
13 (7 i.v.) |
Ongoing (18 i.v.) |
140 (95 i.v.) |
40 (30 i.v.) |
75 (24 i.v.) |
|
Mediastinitis’ surgical drainage |
No |
No |
Yes |
Yes |
Yes |
|
Leukocytes at admission (maximum) /mm3 |
36,000 |
19,510 (40,970) |
20,600 |
|
15,450 (38,490) |
|
Neutrophils at admission (maximum) /mm3 |
30,100 |
17,360 (36,340) |
19,600 |
|
9780 (32,790) |
|
Platelets at admission (maximum) /mm3 |
756,000 |
408,000 |
329,000 |
|
316,000 (861,000) |
|
CRP at admission (maximum) mg/dL |
30.9 |
26.58 (33.66) |
39.24 |
|
17.22 (27.19) |
|
Procalcitonin at admission (maximum) ng/mL |
|
584.28 |
18.7 |
|
0.83 (14.92) |
|
iGAS |
DNI |
Sepsis, pneumonia |
Sepsis, pneumonia |
Sepsis, DNI |
Sepsis, DNI, and pneumonia |
|
Site of GAS isolation |
ENT abscess |
Blood, pleural fluid. |
Blood, pleural fluid. |
Blood |
Pleural fluid |
|
Viral coinfection |
No |
RSV |
No |
No |
rhinovirus, bocavirus |
|
Other relevant complications |
No. |
Acute kidney failure; Acute ischemic hepatitis; auricular thrombosis |
Cardiac tamponade; constrictive pericarditis |
Pyomyositis and fasciitis |
Acute kidney failure |
DNI = deep neck infection, RSV = respiratory syncytial virus, ICU = intensive care unit, i.v. = intravenous, CRP = C-reactive protein, CSF = cerebrospinal fluid.
In terms of age, all the patients in the post-pandemic period were older than 2 years, with a median age of 5.5 and an interquartile range (IQR) of 3-7.5 years. The patient in the pre-pandemic period was only 14 months old. The patients had no comorbidities. One patient had a personal history of epilepsy secondary to cerebral tuberculosis and a cerebrospinal fluid fistula – both issues resolved at the time of the GAS infection. The remaining 4 cases involved previously healthy children with no chronic treatments who had received adequate vaccinations. Among the patients: 3 presented with febrile syndrome accompanied by symptoms including tachypnea, cough and respiratory distress, all associated with pneumonia. One patient presented with epiglottitis and respiratory distress, while another presented with fever and neck pain. Four of the patients were diagnosed with sepsis in addition to pneumonia or DNI upon admission.
Mediastinitis was diagnosed upon admission in 2 of the cases with DNI; in the remaining cases, it was identified as a complication several days after admission. All the post-pandemic cases required intensive care support, with a median stay in the intensive care unit (ICU) of 14.5 days (IQR 10.5-47). Inotropic agents were required in 3/5 cases. The duration of antibiotic therapy varied among the cases, ranging from only 7 to 95 days of intravenous treatment. Surgical intervention for mediastinitis was required in 3/5 cases.
Leukocytosis with neutrophilia and elevated C-reactive protein were observed on admission but spiked several days later in 2 of the patients – in the context of a worsening clinical condition. GAS was isolated in 4/5 cases by culture in pleural fluid or abscess, whereas in 1 case it was only identified by polymerase chain reaction in pleural fluid. GAS also grew in blood culture in 3/5 (60%) cases. Two of the patients had a viral coinfection (2/3 pneumonia cases): respiratory syncytial virus was isolated in one patient and rhinovirus plus bocavirus in the other.
Other severe complications were present in the 4 post-pandemic patients, including acute kidney failure, acute ischemic hepatitis, auricular thrombosis, cardiac tamponade, constrictive pericarditis, pyomyositis, and fasciitis, as shown in in Table 1. The patient with constrictive pericarditis required surgery and prolonged antibiotic therapy. No patient died.
There has been an increase in iGAS infections during the post-pandemic period in Europe, including Spain4-6. Within the Spanish PedGas-net cohort, we have observed the emergence of mediastinitis as a complication of iGAS in 1.3% of cases, which is the largest series published as far as we know. This occurrence has primarily been observed in the post-pandemic stage and has been associated with 8.6% of DNI and 2.3% of pneumonia.
Mediastinitis has rarely been described with S. pyogenes infections7,8. It is an unusual complication of DNI, occurring in approximately 1%-2% of cases1. Therefore, the percentages observed in our series (8.6%) are unusually high. Although S. pyogenes is one of the most common agents causing/producing DNI, a study of 101 patients in Brazil did not detect any cases of mediastinitis in children; all had been diagnosed in adults9. Another small pediatric series from Taiwan reported that 4% of children with retropharyngeal abscess developed mediastinitis requiring drainage and prolonged antibiotic therapy, although the specific causative agent was not mentioned1.
On the other hand, mediastinitis is an exceptional complication in cases of severe pneumonia. Although mediastinitis has been described in certain resistant Streptococcus pneumoniae infections10 and empyema11, it is not a typical complication of pneumococcal infection.
In our cohort, the majority (4/5) of mediastinitis cases were detected in the post-pandemic period. Interestingly, the one pre-pandemic case was less severe, showing good progression and not requiring admission to the Pediatric ICU or any surgical intervention. Unfortunately, we have not been able to conduct a genotype analysis of the GAS strains in these cases, and therefore, we cannot confirm whether a more aggressive GAS serotype might be responsible. However, PedGAS-net is currently genotyping a significant number of strains from this epidemic outbreak, which will provide valuable information about the circulating strains in our country. The role of immune debt or compromised immune function in the severity of the complications observed is currently under discussion.
In conclusion, although it is a rare complication, mediastinitis should be investigated in the presence of worsening clinical condition or persistent fever in severe iGAS cases, especially with DNI or pneumonia. Furthermore, a high level of suspicion is appropriate in iGAS cases presenting with both DNI or pneumonia, and it is essential to continue epidemiological and clinical surveillance to assess the severity and trends of iGAS infections.
Author contributions: Isabel Mellado-Sola, Elvira Cobo-Vázquez, Jesús Saavedra-Lozano and Cristina Calvo wrote the main manuscript text and table and contributed equally. Amaia Calvo-Fernández, Belén Calderón-Llopis, Ana Coca and Eloisa Cervantes provided cases' clinical, analytical and microbiological details. All authors reviewed the manuscript.
Ethics approval statement: This study was approved by the Ethics Committee of Gregorio Marañón Hospital, and the parents or guardians signed an informed consent prior to their inclusion in the study.
Declaration of interests: The authors have no funding or conflicts of interest to disclose.
No competing interests reported.
published 27 Oct, 2023
Read the published version in European Journal of Pediatrics →
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You are reading this latest preprint version