Descending necrotizing mediastinitis caused by Group A Streptococcus associated with influenza A infection

Abstract

Descending necrotizing mediastinitis (DNM), a severe complication arising from deep neck infection, developed in an obese 45-year-old Japanese male with diabetes. His condition was caused by a Group A Streptococcus (GAS) infection that arose following an earlier influenza A infection during a seasonal influenza outbreak. The patient had a good clinical course with surgical drainage and debridement with antibiotic treatment. Pre-existing medical conditions and co-infections such as influenza increase susceptibility to GAS infection, and invasive GAS infection leads to increased mortality. The patient initially presented with fever, sore throat, and cough following influenza A infection, symptoms that were difficult to distinguish from those of deep neck infection caused by GAS. As the GAS was detected in blood cultures, the initial diagnosis was primary bacteremia following influenza A. Subsequently, however, the appearance of erythema on the anterior neck and around the thyroid cartilage suggested a descending progression of the infection from the deep neck space. Contrast-enhanced CT led to a diagnosis of DNM. The reported cases of DNM associated with viral infections have so far been limited to those following varicella or Epstein-Barr virus (EBV) infection. To our knowledge, this is the first reported case of DNM caused by GAS associated with influenza A infection. DNM caused by GAS is a rare infection that requires prompt surgical intervention followed by thorough systemic management. Clinicians should carefully monitor patients with underlying medical conditions who manifest recurrent or new symptoms such as fever, sore throat, and dyspnea after influenza infection.

Highlights

• •DNM is a serious complication of deep neck infection.
• •DNM with viral infection has only been reported after varicella and Epstein-Barr virus infection.
• •First report of DNM caused by Group A Streptococcus following influenza A infection.

Introduction

Group A Streptococcus (GAS) infection has been recently attracting attention due to a sharp increase in invasive cases across Europe since 2022 [1], [2]. While the incidence of streptococcal toxic shock syndrome (STSS) in Japan remained low during the COVID-19 pandemic (2020 and 2022), cases have risen since 2023, primarily in people of less than 50 years of age [3]. The dominance of the M1_UK strain and reduced GAS immunity following the COVID-19 restrictions are likely to have contributed to the higher rates of invasive GAS infection [1]. As upper respiratory viral infections potentially facilitate invasive GAS infection, there is also a concern that respiratory virus epidemics could increase the incidence of the disease [2].

Descending necrotizing mediastinitis (DNM) is a serious complication of deep neck infections that spread in the cervical facial space and descend into the thoracic cavity. While DNM is typically caused by multiple organisms of normal oral flora, there have been sporadic reports of DNM caused by GAS [4], [5].

Seasonal influenza epidemics occur during winter months in temperate climates. In Japan, the influenza A epidemic begins in early January and peaks within a few weeks [6].

We present a case of DNM caused by GAS following influenza A infection during a seasonal influenza epidemic.

Case Presentation

An obese 45-year-old male with diabetes, hypothyroidism, gender identity disorder, and schizophrenia presented to our hospital with dyspnea, fever, chest pain, and a forceful cough. The patient visited a clinic with a 1-day history of fever and sore throat, was diagnosed with Influenza A based on a rapid influenza diagnostic test, was prescribed oseltamivir, and presented to our hospital three days later. The clinical course is shown in Fig. 1.

Fig. 1.

Clinical course.

The patient’s general appearance indicated acute illness. His body mass index (BMI) was 40.4 (height of 178 cm, body weight of 128 kg). He was conscious, with a respiratory rate of 30 breaths per minute, blood pressure of 169/90 mmHg, heart rate of 138 beats per minute, and a body temperature of 40.2 °C. His oxygen saturation was 97 % on supplemental oxygen (2 liters per minute via a nasal cannula). Wheezing was noted in the supine position, along with epigastric tenderness. No stridor, pharyngeal redness, trismus, or cervical lymphadenopathy was present. Laboratory tests revealed a white blood cell count of 22 × 10^3/L (with neutrophils constituting 86.2 %), a C-reactive protein level of 34.8 mg/dL (normal range: 0 – 0.14 mg/dL), a lactate dehydrogenase concentration of 390 U/L (normal range: 124–222 U/L), and a creatine kinase level of 571 U/L (normal range: 59–247 U/L). The highly elevated inflammatory markers indicated by these laboratory results were inconsistent with influenza. No obvious abscess was detected on an enhanced computed tomography (CT) scan. The patient was hospitalized (first admission) in the high care unit for respiratory failure and was immediately started on nasal high-flow oxygen therapy (day 1). Piperacillin-tazobactam was administered due to a suspected bacterial infection complicated with influenza. Blood cultures obtained on admission were positive on day 2 and later confirmed the presence of Group A Streptococcus (GAS). The patient was subsequently diagnosed with primary bacteremia caused by GAS, complicated with influenza A. Intravenous antibiotics were switched to penicillin G (24 million units per day). The fever subsided on day 4, and oxygen therapy was discontinued on day 6. Although the administration of penicillin G was initially planned for at least two weeks, the patient was discharged on day 7 at his strong request and the antibiotic therapy was stepped down to oral amoxicillin of 500 mg four times per day.

In his first outpatient consultation, on day 13, the patient complained of a recurrent fever starting from the day before (day 12). While the onset was not clearly defined, he experienced both hoarseness and a sore throat. Redness and tenderness were observed in the anterior neck and sub thyroid areas (Fig. 2). The physical examination raised a suspicion of downward progression of the deep neck infection. A contrast-enhanced CT scan revealed an abscess in the retropharyngeal space, around the thyroid cartilage, and in the right mediastinum (Fig. 3). The patient was hospitalized (second admission) for emergency surgical intervention and antibiotic therapy for DNM. Surgical drainage and debridement of the necrotic tissue in the mediastinum were performed via a thoracotomy on day 13. Tissue samples collected from the mediastinum were positive for a gram-positive chain organism on microscopic examination but negative on tissue culture. Ampicillin-sulbactam was administered in place of penicillin G to cover other microorganisms, including anaerobes, until the tissue culture result was confirmed. The patient’s fever subsided again on day 20. The antibiotic was switched to oral amoxicillin on day 25 and the patient was discharged on day 28. As residual mediastinal abscesses had been observed in a CT scan performed on day 18, long-term oral amoxicillin administration was planned and continued until day 61. No recurrence of DNM was observed during the first 4 months after discharge.

Fig. 2.

Redness in the anterior neck and sub thyroid areas (arrows).

Fig. 3.

Abscess in the retropharyngeal space, around the thyroid cartilage, and in the right mediastinum (Arrows).

Discussion

We successfully treated a case of DNM caused by GAS associated with influenza A infection. The clinical course of the patient was good with surgical drainage and debridement with antibiotic treatment. DNM is a serious complication of deep neck infections, with infections of the retropharyngeal, carotid and peritracheal spaces being the most likely to progress to this potentially life-threatening condition [7]. DNM is usually caused by polymicrobial infections involving aerobic and anaerobic organisms of the oral microflora, such as α-hemolytic Streptococcus, Peptostreptococcus species, Fusobacterium species, etc.[8], [9]. Though rare, DNM caused by GAS has been sporadically reported [4], [5], [10], [11]. The management of DNM requires a multidisciplinary approach, with early diagnosis by clinical and radiological examination, surgical debridement, antibiotic therapy, and aggressive monitoring in the intensive care unit [8], [12].

The abscess observed in the retropharyngeal space and around the thyroid cartilage on day 13 had not been clearly detected on the CT scan on day 1, suggesting that the deep neck infection caused by GAS had progressed downward into the mediastinum. The non-specific symptoms of DNM make it difficult to diagnose the condition early [8]. The upper respiratory symptoms associated with influenza, such as sore throat, fever, and cough, also made it difficult to detect when the deep neck infection caused by GAS developed and progressed to DNM.

Diabetes is associated with an elevated risk of GAS infection, and obesity (body mass index 30-<40) is associated with higher mortality [13]. Viral infections are also thought to contribute to the development of invasive GAS infection. To date, the only reported cases of DNM associated with viral infections have occurred after varicella or EBV infection [10], [14]. To the best of our knowledge, this is the first reported case of DNM caused by GAS associated with influenza A. GAS is the most common secondary bacterial pathogen of varicella infection and typically results in bacteremia, necrotizing fasciitis, and toxic shock syndrome. Skin lesion by varicella is considered to be a portal for GAS into the bloodstream [15]. Although cases of toxic shock syndrome and bacteremia caused by GAS have been reported following EBV infectious mononucleosis, the association between EBV and GAS infection remains unclear [15], [16]. Regarding influenza-associated GAS infections, microbiological and epidemiological studies from the Spanish influenza pandemic suggested that S. pneumoniae, S. aureus, and GAS were the most common pathogens associated with secondary bacterial infection and were responsible for many fatal cases [17], [18]. Pneumonia, bacteremia, and necrotizing fasciitis are common secondary GAS infections following influenza [19]. Influenza A infection promotes the binding and invasion of GAS into the host tissues through two mechanisms: viral hemagglutinin expression on the host cell surface, and the combined action of cyclophilin A and neuraminidase-induced TGF-β [19]. Our patient had underlying diabetes and obesity, known risk factors for GAS infection and progression to severe disease. The patient developed DNM as a result of a deep neck infection caused by GAS following influenza A infection.

Considering that influenza A infection increases the risk of GAS infection, and given the frequent reports of fatal GAS infections during the Spanish influenza pandemic, we conjecture that influenza A may elevate the risk of developing DNM, albeit rarely. Clinicians should be mindful of DNM when treating cases of invasive GAS with underlying risk factors, especially during seasonal influenza epidemics.

Ethical approval and Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.

CRediT authorship contribution statement

Nobuhiro Komiya: Supervision. Kenji Kubo: Supervision. Ken-ichiro Kobayashi: Writing – original draft.

Author agreement

The article is not under consideration for publication elsewhere.

• •The article's publication is approved by all authors and tacitly or explicitly by the responsible authorities where the work was carried out.
• •if accepted, the article will not be published elsewhere in the same form, in English or in any other language, including electronically, without the written consent of the copyright-holder.

Funding sources

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of Competing Interest

I have nothing to declare