Normal Head and Neck Flora

Huge numbers of bacteria reside in the oral cavity in health, with the bacterial load exceeding 10¹¹/mL in the gingival crevices of patients with teeth.¹ The main bacterial species are anaerobes including Bacteroides, Fusobacterium, Prevotella, and Peptostreptococcus. Other common oral inhabitants include Streptococcus mutans, Staphylococcus aureus, Actinomyces spp., and Eikenella corrodens. Pharyngeal colonization and subsequent infection with organisms such as Streptococcus pneumoniae, Neisseria meningitidis, and Streptococcus pyogenes may also occur.

In acute illness, an additional modifying factor is the decreased production of oral mucosal fibronectin. This is of relevance to the clinician because fibronectin in normal physiologic amounts will preferentially bind gram-positive bacteria (such as S. mutans); however, when the production of fibronectin is decreased, there is rapid colonization of the oral cavity with gram-negative organisms, including species such as Pseudomonas aeruginosa.² These gram-negative organisms may then participate in head and neck infections of oral or odontogenic origin, necessitating broad nosocomial-type gram-negative antibiotic coverage when the patient has been recently hospitalized or acquired the infection in the intensive care unit (ICU).

Sites of Deep Head and Neck Infection

Serious infection of the head and neck can involve the following general anatomic areas:

Some of these anatomic areas are connected via actual or potential spaces. Thus infection beginning in one space may spread rapidly to involve others, with potential resultant damage or destruction of vital structures. Such connections are discussed in the following sections, and differentiating features are highlighted in Table 136-1.

TABLE 136-1 Differentiating Features of Deep Neck Infections

Space	Clinical Features*
Submandibular space (“Ludwig’s angina”)	Woody submental induration, protruding swollen/necrotic tongue, no trismus, rotted lower molars commonly present
Lateral pharyngeal space (anterior)	Fever, toxicity, trismus, neck swelling
Lateral pharyngeal space (posterior)	No trismus, no swelling (unless ipsilateral parotid is involved), cranial nerve IX-XII palsies, Horner’s syndrome, carotid artery erosion
Retropharyngeal space (retropharynx)	Neck stiffness, decreased neck range of motion, soft-tissue bulging of posterior pharyngeal wall, sore throat, dysphagia, dyspnea
Retropharyngeal space (“danger space”)	Mediastinal or pleural involvement
Retropharyngeal space (prevertebral)	Neck stiffness, decreased neck range of motion, cervical instability, possible spread along length of vertebral column
Jugular vein septic thrombophlebitis (Lemierre syndrome)	Sore throat, swollen tender neck, dyspnea, chest pain, septic arthritis

* Fever and signs of systemic toxicity are common to all.

Clinical Syndromes

Sinusitis (fungal) Aspergillus spp.
Mucorales spp. Pharyngitis Corynebacterium diphtheriae Epstein-Barr virus (with airway compromise) Epiglottitis H. influenzae type b
Streptococcus pyogenes (group A strep)

* Antibiotic choices listed are examples, since for most infections, multiple different antibiotics are effective, and individual choice will be influenced by patient factors (allergies, etc.), local hospital bacterial resistance rates, and microbiological culture results.

Complications of nosocomial sinusitis are related to the local anatomy. Spread via the diploic veins can result in meningitis, brain abscess, contiguous osteomyelitis, or cavernous sinus thrombosis. Spread from the ethmoid sinuses can result in frontal lobe brain abscesses, whereas sphenoid sinus infection can spread to involve the surrounding pituitary gland, optic chiasm, internal carotid artery, cavernous sinus, or temporal lobe of the brain.¹

In patients with diabetic ketoacidosis, high-dose steroid treatment, severe neutropenia, or history of desferrioxamine treatment, rhinocerebral mucormycosis or aspergillosis can develop. This infection can be rapidly fatal if the underlying problem cannot be corrected. The general teaching has been that high-dose antifungal therapy (see Table 136-2) plus extensive surgery is always required for any hope of survival. However, the need for major surgery in all cases has come into question recently.⁴ Close collaboration with appropriate surgeons and infectious disease colleagues is required in such cases.

Pharyngeal Infections

Life-threatening pharyngeal infections include acute anaerobic pharyngitis (Vincent’s angina) caused by a combination of oral anaerobes and spirochetes. The clinical manifestations of this entity in the critically ill host include acute ulcerations and necrosis of the oral mucosa and gums. Secondary bacteremia with sepsis syndrome can complicate matters. Treatment involves adequate oral débridement and administration of antibiotics with both aerobic and anaerobic activity (see Table 136-2).¹

Quinsy (peritonsillar abscess) can complicate prior tonsillitis and is most common among young adults. Presenting symptoms include fever, pharyngeal pain, and unilateral pharyngeal swelling. If not adequately drained, the infection can spread into the lateral pharyngeal space, which was the commonest cause of mortality due to quinsy in preantibiotic days. Infection with anaerobes can result in a higher rate of recurrence of quinsy.⁵ Fusobacterium necrophorum is currently the most commonly encountered organism in peritonsillar abscesses in Denmark.⁶

Diphtheria is now rare thanks to mass vaccination. It presents as a sharply demarcated adherent dark gray nasal or pharyngeal membrane. Clinical illness is due to release of a bacterial toxin that inhibits translocase (via inhibition of elongation factor 2). Myocardial dysfunction and central nervous system toxin-mediated injury may occur late, but fulminant infections can be complicated by death from acute respiratory obstruction or circulatory failure (bull-neck diphtheria).¹ Culture of the organism (Corynebacterium diphtheriae) requires the use of specific Loeffler medium.

Epiglottitis

Acute epiglottitis is primarily a disease of children who have not received the Haemophilus influenzae type b (Hib) vaccine and is thus rare at present.⁷ Acute epiglottitis presents as an acute febrile illness usually of less than 12 hours duration, with the child characteristically sitting forward, drooling saliva, and taking shallow and apprehensive breaths (deeper breathing draws the epiglottis over the airway and produces obstruction). The diagnosis is made clinically, although lateral neck radiography (if the child is stable enough to go for x-ray) characteristically shows enlargement of the epiglottis 30% to 57% of the time. Attempts to visualize the classically described edematous cherry red epiglottis directly may precipitate acute airway obstruction and should not be attempted unless the ability to secure an airway immediately is certain. Blood and epiglottis cultures usually grow H. influenzae type b. However, since the introduction of mass vaccination against H. influenzae type b, the incidence of infection with non–type b strains is increasing.⁷

Antibiotic options for epiglottitis are outlined in Table 136-2. There is no clear consensus on the role of exogenous corticosteroids to decrease epiglottic edema. Rifampin prophylaxis should be administered for 4 days to close household and hospital contacts of patients (especially those younger than 4 years) with invasive H. influenzae type b disease.

Retropharyngeal Infections

The area situated between the pharynx anteriorly and the vertebrae posteriorly constitutes the retropharyngeal space, which begins behind the pharynx and ends at the junction of the cervical and thoracic vertebrae (see Table 136-1). The space is subdivided into several distinct anatomic spaces (retropharyngeal, prevertebral, “danger space”), some of which may provide the means of spread of infection from the initial retropharyngeal area to distant sites.⁸

Located between the prevertebral space posteriorly and the retropharyngeal space anteriorly is a potential space called the danger space, which connects the base of the skull with the posterior mediastinum and diaphragm. Infection may spread unimpeded within in this space. In addition, infection occurring between the vertebrae and the prevertebral fascia may spread along the length of the vertebral column.

Infections of the retropharynx occur either as:

Clinically, retropharyngeal infections present with acute fever, systemic toxicity, sore throat, neck stiffness, dysphagia, and dyspnea. Airway obstruction may occur as a consequence of anterior bulging of the pharyngeal wall with supraglottic compression.

Prevertebral infections usually involve the cervical vertebrae and present with neck pain and stiffness and prevertebral soft-tissue swelling. Rarely, instability or destruction of the cervical vertebrae may develop, with death due to acute spinal cord compression.

Danger-space infection is suspected when pleural or mediastinal infection or pain complicates a retropharyngeal infection.⁸ Mediastinitis secondary to danger-space infection is generally fulminant with pleural extension and a high mortality rate. Rarely, mediastinal infections, such as may occur after coronary artery bypass graft surgery, may spread upwards through the danger space and present in the retropharynx.

The bacteriology of retropharyngeal infections is that of mixed aerobic/anaerobic oral bacteria. In the critically ill host with nosocomial infection, colonization of the oropharynx with resistant pathogens will necessitate modification of antimicrobial coverage. The imaging techniques needed include plain lateral neck x-rays that will show loss of normal cervical lordosis as well as thickening of the retrotracheal area (usually < 22 mm) or of the prevertebral fascia (usually < 7 mm). Bedside ultrasonography may provide information regarding the presence or absence of drainable collections, but if the patient is stable enough to go to the radiology suite, computed tomography (CT) or magnetic resonance imaging (MRI) scans provide the best definition studies. Close collaboration with appropriate surgical colleagues is necessary for successful management.⁸ Therapy is outlined in Table 136-3. On occasion, nonbacterial processes such as Kawasaki disease can mimic retropharyngeal abscesses.⁹

TABLE 136-3 Therapeutic Options for Deep Neck Infections

Syndrome	Likely Flora	Therapeutic Options*
Submandibular space infection (community-acquired)	Anaerobes, streptococci, Staphylococcus aureus	• Ampicillin-sulbactam (3 g IV q 6 h) • Ceftriaxone (1-2 g IV q 24 h) plus clindamycin (300-900 mg IV q 8 h) or metronidazole (500 mg IV q 6 h) • Ertapenem (1 g IV q day)

Submandibular space infection (hospital/ICU-acquired) Pseudomonas aeruginosa
Methicillin-resistant S. aureus (MRSA)
Anaerobes Retropharyngeal space infection Anaerobes, streptococci, S. aureus Lateral pharyngeal space infection Anaerobes, streptococci, S. aureus Internal jugular vein septic thrombophlebitis Fusobacterium necrophorum

* Antibiotic choices listed are examples, since for most infections, multiple different antibiotics are effective, and individual choice will be influenced by patient factors (allergies, concurrent medications, etc.), local hospital bacterial resistance rates, and microbiological culture results.

Submandibular Space Infection (Ludwig’s Angina)

The submandibular space is contained between the mucous membranes of the floor of the mouth superiorly and the muscle and fascia attachments of the hyoid bone inferiorly. The most common route of infection into this space is via infected lower molar teeth, and infection is more common in persons with underlying diabetes, neutropenia, or systemic lupus erythematosus.

Clinical presentation of submandibular space infection is that of an acutely ill patient with mouth pain, dysphagia, drooling of saliva, stiff neck, and fever. The submandibular tissues are “woody,” not fluctuant, and true drainable collections are uncommon. The tongue may be swollen and displaced upwards against the palate and also protrude out of the mouth. Trismus is not present; however if the infection spreads to the lateral pharyngeal space, trismus may occur. Unrecognized lateral pharyngeal space involvement may be complicated by subsequent spread to the retropharyngeal space. Late complications of Ludwig’s angina include death from airway obstruction, aspiration pneumonia, carotid artery erosion, and tongue necrosis.¹⁰

Lateral neck x-rays will demonstrate edema of the submandibular soft tissues. Pockets of gas may be seen if gas-forming organisms are involved. CT scanning is most helpful diagnostically. However, attention must be paid to having qualified staff accompany the patient to the CT scanner in case acute airway obstruction develops. Should airway protection be needed, tracheotomy or cricothyroidotomy is advocated because of the risk of inducing acute airway obstruction with routine “blind” nasal or oral intubation. The infection is commonly polymicrobial, and appropriate antibiotic therapy options are described in Table 136-3. In approximately 50% of cases, surgical drainage is required. In addition, causative rotted molar teeth (if present) should be removed.¹⁰

Lateral Pharyngeal Space Infections

Infection of the lateral pharyngeal space is one of the most common deep neck infections encountered. In a review of 110 deep neck infections in adults seen at an academic medical center over a 10-year period, infections of the lateral pharyngeal space accounted for 55%.¹⁰ In contrast, in children such infections are rare, with peritonsillar infection (quinsy) being the most common deep neck infection.

The lateral pharyngeal space is cone shaped, extending from the sphenoid bone down to the hyoid bone. Posteriorly it is bound by the prevertebral fascia (that separates it from the retropharyngeal space) and anteriorly by the buccinator and superior constrictor muscles. The parotid gland communicates with this space. The styloid process divides the space into an anterior compartment (containing fat, lymph nodes and muscle) and a posterior compartment (containing the carotid artery, cranial nerves IX-XII, and the cervical sympathetic trunk).

Common precipitating causes of lateral pharyngeal space infection include dental disease (33%), injection drug use (inserting needles directly into the space; 20%), local trauma (9%) and tonsillitis (4%). Patients frequently have underlying diabetes or human immunodeficiency virus (HIV) infection.

Clinically, anterior lateral pharyngeal space infections present with fever, pain, trismus, and systemic toxicity. Turning the head to the opposite side causes increased pain due to stretching of the ipsilateral sternocleidomastoid muscle.

Infection of the posterior lateral pharyngeal space presents differently from infections involving the anterior pharyngeal space. Common symptoms include fever, systemic toxicity, and parotid swelling. Trismus and external swelling do not occur. Involvement of local vital structures can occur, including carotid artery erosion or clot, septic thrombophlebitis of the internal jugular vein, cranial nerve IX-XII palsies, or Horner’s syndrome.

Therapy involves urgent surgical intervention to drain purulent material and prevent spread of infection to the retropharyngeal space or erosion of the carotid artery. The choice of antibiotics for this frequently polymicrobial infection is shown in Table 136-3.

Descending Necrotizing Mediastinitis

Rapid downward spread of deep neck infections can result in the development of necrotizing soft-tissue infections of the chest wall and mediastinum. A recent study of 45 such cases collected over a 12-year period demonstrated that they tended to develop as a complication of dental or deep neck polymicrobial infections, affecting persons aged 40 to 60 years most commonly. Mixed aerobic/anaerobic flora was the rule, and risk factors included alcoholism and diabetes mellitus. Mortality was around 15% to 20%.⁸

Internal Jugular Vein Septic Thrombophlebitis (Lemierre Syndrome)

Septic thrombophlebitis of the internal jugular vein is known as Lemierre syndrome. It is a relatively rare entity usually caused by infection with the anaerobe Fusobacterium necrophorum, a normal inhabitant of the human gingival crevice. Latest theories on the pathogenesis of this infection indicate that the first stage of infection is pharyngitis in approximately 87% of cases. Recent data suggest that F. necrophorum causes pharyngitis in young adults aged 15 to 24 years as frequently as Streptococcus pyogenes.⁶ This is then followed by invasion of the lateral pharyngeal space, with development of septic thrombophlebitis of the internal jugular vein.¹¹ Subsequently, bloodborne infection develops, with the classic findings of septic pulmonary emboli or cavitating pneumonia and septic arthritis. Other precipitating factors include mastoiditis, lateral pharyngeal space infection, or trauma to the internal jugular vein.

Clinically, Lemierre syndrome begins with fever and sore throat. When internal jugular vein involvement develops, patients complain of a swollen and/or tender neck, which is thus a warning sign of danger in a patient with recent pharyngitis. Dyspnea and pleuritic chest pain indicate pulmonary involvement.

Early diagnosis is critical to minimize the risk of infectious metastatic complications requiring surgical intervention or drainage. Blood cultures should be promptly obtained and empirical antianaerobic bacterial coverage begun. Radiologic diagnosis is made most reliably by CT scanning, although bedside ultrasound examination of the internal jugular vein can be useful in the critically ill patient who cannot leave the ICU. If the infection occurs secondary to mastoiditis, it is necessary to rule out intracerebral vein thrombosis by MRI scanning.

Antibiotic choices are outlined in Table 136-3. There are no firm data to support or refute the use of anticoagulants in Lemierre syndrome.¹² In addition, surgical ligation or excision of the internal jugular vein for uncontrollable sepsis was necessary in approximately 8% of cases in a recently published series of cases.¹² MRSA has recently been shown to cause Lemierre syndrome, especially in injection drug users or patients with the infection developing as a complication of venous cannulation.¹⁴

Conclusions

The intensivist will frequently be asked to assist in the care of patients with serious deep neck infections. Critical issues encountered include protection of the airway, sepsis management, and the potential for erosion of the infection into surrounding vital structures in the neck. Such infections are frequently polymicrobial in nature, and thus broad-spectrum antibiotics with both aerobic and anaerobic coverage should be chosen.

Common issues to be decided for each patient individually include: