Reddy, Pavani MD*; Berggruen, Senta MD†; Noskin, Gary A. MD*
A 25-year-old man was admitted with a 6-day history of fevers, chills, and malaise. He noted that symptoms began with upper respiratory congestion and a sore throat. Two days later, he developed sharp pleuritic chest pain and nonproductive cough. The chest pain was left-sided and positional, exacerbated when supine, and relieved when sitting forward. When symptoms did not abate with ibuprofen, he visited the emergency room.
On arrival, he was febrile, with a temperature of 101.0°F, pulse of 114 beats per minute, respiratory rate of 20 breaths per minute, and blood pressure of 122/77 mm Hg. He appeared mildly uncomfortable. Physical examination revealed poor dentition, shotty cervical lymphadenopathy, a pericardial friction rub, and decreased breath sounds at both lung bases.
Peripheral white blood cell count was 16.3 × 109/L, 86% polymorphonuclear leukocytes. Hemoglobin was 13.5 g/dL, and platelet count was 348 × 109/L. Serum chemistry panel was notable for sodium (133 mEq/L) and potassium (2.8 mEq/L). Hepatic panel revealed an alkaline phosphatase level of 242 U/L (range, 30-115 U/L); alanine aminotransferase, 97 U/L (range, 0-48 U/L); aspartate aminotransferase, 27 U/L (range, 0-40 U/L); total bilirubin, 2.4 mg/dL (range, 0-1.3 mg/dL); and direct bilirubin, 1.4 mg/dL (range, 0-0.2 mg/dL).
A chest radiograph was performed in the emergency department (Fig. 1). Follow-up chest computed tomography (CT) with intravenous contrast is shown (Fig. 2A, B). The patient was given empiric intravenous metronidazole and cefotaxime.
The patient was admitted to the hospital where blood cultures from days 1, 2, and 3 grew group F β-hemolytic streptococcus, later identified as Streptococcus constellatus. On day 2, a cervical mediastinoscopy revealed descending necrotizing mediastinitis (DNM); tissue cultures grew S. constellatus and moderate Bacteroides, Eubacterium, and Peptostreptococcus species. Despite therapy, progressive symptoms necessitated a video-assisted thoracic surgery and chest-tube placement on day 10 (Fig. 3).
BACKGROUND AND PATHOPHYSIOLOGY
Descending necrotizing mediastinitis is a rare and severe form of acute mediastinitis, often (58%) due to the rapid spread of an oropharyngeal infection.1 Diagnostic criteria for DNM were created by Estrera et al and include (1) clinical manifestations of severe oropharyngeal infection, (2) characteristic radiographic features of mediastinitis, (3) operative or postmortem documentation of a necrotizing mediastinal infection, and (4) an established relationship between the oropharyngeal infection and the mediastinal process.2 Common primary etiologies include odontogenic infection, esophageal rupture, traumatic endotracheal intubation, cervical lymphadenitis, retropharyngeal or peritonsillar abscess, Ludwig angina, and suppurative parotitis.3,4
Layers of the deep cervical fascia allow for the formation of 3 deep neck spaces: pretracheal (superficial), perivascular, and prevertebral (or retrovisceral). The pretracheal space is anterior to the trachea, bound proximally by the thyroid cartilage and distally by the pericardium. The perivascular space is surrounded by the carotid sheath and is formed by the layers of the cervical fascia. The prevertebral space is anterior to the prevertebral fascia and posterior to the pharynx and esophagus. It is divided into the retropharyngeal and the "danger" spaces by the alar fascia. The "danger" space is patent from the skull base to the diaphragm, allowing rapid spread of infection to the mediastinum.3 An estimated 8% of DNM cases originate from the pretracheal space, whereas more than 70% spread through the prevertebral "danger" space.5 Spread through the fascial planes is enhanced by negative intrathoracic pressure.6
Descending necrotizing mediastinitis is usually the consequence of a polymicrobial infection. Brook and Frazier evaluated 17 cases of acute bacterial mediastinitis; only 18% of cases involved aerobic or facultative bacteria alone. An additional 41% of cases were due to anaerobic flora only, whereas the remaining cases were mixed. Among these cases, Prevotella, Porphyromonas, Peptostreptococcus, and Fusobacterium species were the most common anaerobes isolated.7
Streptococcus constellatus, S. anginosus, and S. intermedius comprise the Streptococcus milleri or anginosus group (SMG) and account for 24% to 57% of suppurative thoracic infections.8 Members of this group are commensals of the oral cavity, genitourinary, and gastrointestinal tracts, and tend to cause pyogenic infections. Deep abscesses are most often associated with the isolation of S. intermedius or S. constellatus.9 Of SMG members, S. constellatus is most commonly associated with the thoracic cavity and the upper respiratory tract.9,10
Most (33%-50%) SMG infections include anaerobic flora.8 In vitro studies demonstrated increased abscess formation in mice infected with S. constellatus and Prevotella species versus either organism alone, suggesting that a synergistic relationship between anaerobes and SMG members may exist. The authors propose that neutrophil inhibition by anaerobes and their metabolites may have allowed for increased S. constellatus activity.11 In a similar murine model, synergism between S. constellatus and Fusobacterium nucleatum was noted.12
Initial signs and symptoms of necrotizing mediastinitis depend on the primary infectious etiology. Patients with a history of esophageal trauma (ie, eating a chicken bone, undergoing bronchoscopy, or esophagogastroduodenoscopy) may initially complain of a sore throat, difficulty swallowing, or shortness of breath associated with local edema. When an odontogenic process is involved, patients may present with a variety of symptoms: unilateral throat pain, trismus, a muffled voice, and lymphadenopathy herald a peritonsillar abscess, whereas bilateral neck edema, mouth pain, stridor, and dysphagia may signal Ludwig angina. Subsequent symptoms of DNM include the acute onset of fever, respiratory distress, and localized chest pain. Systemic effects arise as the infection extends to the mediastinum, leading to increasing dyspnea, respiratory failure, and shock.
Serious complications secondary to DNM can occur. Suppurative mediastinitis rupture into adjoining cavities may cause empyema or acute pericarditis. Rarely, infection erosion into a perivascular space leads to hemorrhagic complications. For example, bacteria traversing the superior fascial planes and invading the carotid sheath may result in "false" aneurysm formation, hematoma development, or even artery rupture. Other symptoms of a spreading parapharyngeal process may include acute cranial nerve deficits, trismus, or stridor. Infection can spread rapidly, reaching the mediastinum within 5 to 15 days.4
Radiographic imaging plays an important role in the diagnosis and management of DNM. Initial evaluation with conventional chest radiography may be misleading in early diagnosis. As a result, cross-sectional radiographic techniques, such as CT or magnetic resonance imaging (MRI), are often required for diagnosis and evaluation of mediastinal involvement. Computed tomography may also guide optimal antibiotic and surgical management.
The mediastinum extends from the thoracic inlet to the diaphragm and lies between the right and left pleural cavities. It contains critical structures, such as the heart and great vessels, the trachea and bronchi, the vagus and recurrent laryngeal nerves, and the esophagus. These structures are surrounded by loose connective tissue and fat. The mediastinum may be divided into superior and inferior (anterior, middle, and posterior) parts.13 Although infection most often arises from the pretracheal and prevertebral "danger" spaces, spread through the carotid sheath into the upper mediastinum has also been noted. This path has been called "Lincoln's Highway," after the stretch of interstate that stretches from California to New York, the longest in the United States.14
Chest radiography is usually the first-line imaging modality in suspected cases of DNM. In the early phase of the disease, the chest radiograph may appear normal because findings are often subtle or nonspecific. However, as the disease progresses, characteristic features may become apparent. Roentgenogram abnormalities of DNM include widening of the mediastinum, associated pleural effusions, diffuse or focal ectopic gas bubbles within the mediastinum, and focal mediastinal soft tissue masses. In addition, the cardiac silhouette may be enlarged due to pericardial effusion. Mediastinal widening, suggestive of paratracheal pathology, is usually more evident superiorly; associated splaying of the carina is suggestive of subcarinal masses or fluid collections (Fig. 1). Air may be visible within the soft tissue planes of the neck as well.
Precise characterization of mediastinal infection may not be possible on the basis of chest radiography alone.14 Chest CT is considered the diagnostic modality of choice in DNM because it defines the location and extent of the infection, assists in clinical decision-making (ie, antibiotic, therapeutic, or surgical interventions), and allows for serial evaluation of treatment. Furthermore, CT is widely available and has the ability to exclude other etiologies in the differential diagnosis, such as pulmonary embolus, thoracic aortic dissection, or pneumonia.
In a recent retrospective study, Exarhos et al15 describe CT findings in 40 patients with acute mediastinitis. Characteristic DNM findings included increased attenuation of mediastinal fat (100%) and mediastinal lymph nodes (35%), demonstrated in Figure 2A. Free gas bubbles in the mediastinum (Fig. 2B) were noted in 23 patients (57.5%). Localized mediastinal fluid collections (55%) and pleural effusions (85%) are often seen (Fig. 3). Less commonly, pericardial effusions (27.5%) and pulmonary infiltrates (35%) may be noted. Computed tomography sensitivity for DNM was 100%, and therefore a valuable tool early in clinical presentation.15
Magnetic resonance imaging provides excellent soft tissue characterization and is the most sensitive imaging modality to evaluate for tissue water content (ie, inflammation). In addition, MRI is highly sensitive to fluid signal, allowing for the assessment of subtle mediastinal fluid collections. However, the current use of MRI in patients with DNM is limited because of its relative expense and imaging time constraints. As a result, CT has become the preferred imaging modality in the evaluation of DNM.
The preliminary diagnosis of DNM is often a clinical one, suspected on the basis of patient history and physical examination. Acute systemic signs (ie, fever, hypotension) in the presence of an antecedent upper airway infection or dental procedure should raise the possibility. As noted above, initial roentgenography may be useful, but further images of the mediastinum by CT are essential in initial assessment and serial evaluation. In addition, direct examination by laryngoscopy or exploration by mediastinoscopy may be warranted for diagnosis in certain instances. Careful examination of the mouth and teeth may reveal an etiologic infection. Finally, esophagus imaging with esophagram or CT may detect a primary mucosal breach.
A microbiologic etiology is not identified in most cases. Secondary bacteremia occurs in less than 11% of SMG thoracic infections.8 However, these estimates may reflect the difficulty in culturing these organisms; effective SMG growth requires higher (10%) carbon dioxide levels than routine bacterial cultures. Inevitably, initial antibiotic therapy is empiric.
TREATMENT AND OUTCOMES
Given the polymicrobial nature of infection, broad-spectrum antibiotic therapy is warranted in all cases of DNM. β-Lactams are the agents of choice in treating infection due to SMG; SMG isolates are generally susceptible to ampicillin or ceftriaxone, but 14-15% are resistant to clindamycin.16,17 In penicillin-allergic patients, vancomycin use may be warranted. Additional anaerobic coverage is indicated in all cases of DNM, accomplished by the addition of metronidazole or the use of a β-lactam/β-lactamase inhibitor combination, such as ampicillin-sulbactam. Of note,bacteremia with SMG has been associated with a mortality rate of 26%.10,18
Despite developments in critical care, broad-spectrum antibiotic therapy, and CT imaging, mortality rates from DNM remain high. Early studies reported a mortality rate of 40% to 49%2,5; recent reviews suggest little improvement, citing rates of 29% to 40%.1,19 Four standard surgical approaches to mediastinal drainage have been described: (1) transcervical, (2) standard posterolateral thoracotomy, (3) median sternotomy, and (4) transthoracic via the subxiphoid.20 Despite success with transcervical and subxiphoid drainage in cases involving the anterior mediastinum alone,1 most authors currently recommend the early use of standard thoracotomy in cases of DNM.19-22 Estrera et al recommend transthoracic surgery for any infection extending below the T4 plane (at the tracheal bifurcation); mediastinitis below this level tends to lead to pleural empyema.2
Finally, frequent reassessment of the patient is critical to success of surgical drainage in DNM. One author recommends repeat CT imaging of the neck and chest with any clinical deterioration or within 48-72 hours of initial surgical debridement. Nearly 60% of such surveillance CT imaging revealed unanticipated progression of the infection.19 Despite aggressive therapy and serial imaging, loculated infection may persist for weeks (Fig. 3).
After the CT shown in Figure 3, the case patient underwent additional anterior mediastinum and left-sided pleural fluid drain placement by interventional radiology. With broad-spectrum antibiotic therapy, continued drainage, and serial CT imaging, the patient improved slowly over the next 3 weeks. He was discharged in stable condition on hospital day 34.
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