Cervical Fascial Space Infections
Deep fascial space infections of the head and neck are most frequently odontogenic in origin (Fig. 54-4).1,6,7 The potential pathways of extension of these infections from one space to another are illustrated in Fig. 54-5.8 Cervical fascial space infections considered to be life-threatening include those of the submandibular space, the lateral pharyngeal space, and the retropharyngeal, “danger,” and prevertebral spaces. Their salient clinical features are presented in Table 54-1.9 The approach to radiographic and microbiologic diagnoses is discussed toward the end of this chapter. Recommended antimicrobial regimens for initial empirical therapy are presented in Table 54-2.7
Table 54–1. Comparative Clinical Features of Deep Fascial Space Infections
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Table 54–1. Comparative Clinical Features of Deep Fascial Space Infections
|Submandibular||Present||Minimal||Mouth floor; submylohyoid||Present if bilateral involvement||Present if bilateral involvement|
| Anterior||Severe||Prominent||Anterior lateral pharynx; angle of jaw||Present||Occasional|
| Posterior||Minimal||Minimal||Posterior lateral pharynx (hidden)||Present||Severe|
|Retropharyngeal (and danger)||Present||Minimal||Posterior pharynx||Present||Present|
| Masseteric and pterygoid||Present||Prominent||May not be seen||Absent||Absent|
| Temporal||Present||None||Face, orbit||Absent||Absent|
|Parotid||Severe||None||Angle of jaw||Absent||Absent|
Table 54–2. Usual Causative Organisms and Initial Empirical Antimicrobial Regimens for Life-Threatening Infections of the Head, Neck, and Upper Respiratory Tract
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Table 54–2. Usual Causative Organisms and Initial Empirical Antimicrobial Regimens for Life-Threatening Infections of the Head, Neck, and Upper Respiratory Tract
|Infection||Usual Causative Organisms||Normal Host||Compromised Host|
|Cervical fascial space infections including Ludwig angina||Viridans and other streptococci, Peptostreptococcus spp., Bacteroides spp., and other oral anaerobes||
Penicillin G 2–4 MU IV q 4–6 h, plusmetronidazole 0.5 g IV q 6 h; orAmpicillin-sulbactam 2 g IV q 4 h; orClindamycin 600 mg IV q 6 h; orDoxycycline 200 mg IV q 12 h; orCefoxitin 1–2 g IV q 6 h; orCefotetan 2 g IV q 12 h||Cefotaxime 2 g IV q 6 h; orCeftizoxime 4 g IV q 8 h; orPiperacillin 3 g IV q 4 h; or Imipenem 500 mg IV q 6 h; orMeropenem 1 g IV q 8 h; orGatifloxacin 200 mg IV q 24 h|
|Lateral pharyngeal or retropharyngeal space infections|
|Odontogenic||Viridans and other streptococci, Staphylococcus spp., Peptostreptococcus spp., Bacteroides spp., and other oral anaerobes||
Penicillin G 2–4 MU IV q 4–6 h, plusmetronidazole 0.5 g IV q 6 h; orAmpicillin-sulbactam 2 g IV q 4 h; orClindamycin 600 mg IV q 6 h||Cefotaxime 2 g IV q 6 h; orCeftizoxime 4 g IV q 8 h; orPiperacillin 3 g IV q 4 h; or Imipenem 500 mg IV q 6 h; orGatifloxacin 400 mg IV q 24 h|
|Rhinogenic||Streptococcus pneumoniae, Haemophilus influenzae, viridans and other streptococci, Bacteroides spp., Peptostreptococcus spp., and other oral anacrobes||
Penicillin G 2–4 MU IV q 4–6 h; orCiprofloxacin 0.2 g q 12 h, plusmetronidazole 0.5 g IV q 6 h; orClindamycin 600 mg IV q 6 h; orGatifloxacin 400 mg IV q 24 h||Same as for odontogenic space infections|
|Otogenic||Same as for rhinogenic space infections||Same as for rhinogenic space infections||Same as for odontogenic space infections|
|Peritonsillar abscess (Quinsy)||Group A streptococcus (S. pyogenes), Fusobacterium spp., Peptostreptococcus spp., and other oral anaerobes||
Penicillin G 2–4 MU IV q 4–6 h, plusmetronidazole 0.5 g IV q 6 h; orAmpicillin-sulbactam 2 g IV q 4 h; orClindamycin 600 mg IV q 6 h; orCefoxitin 1–2 g IV q 6 h||Cefotaxime 2 g IV q 6 h; orCeftizoxime 3 g IV q 8 h; orPiperacillin 3 g IV q 4 h|
|Suppurative parotitis||Staphylococcus aureus, viridans and other streptococci, Bacteroides spp., Peptostreptococcus spp., and other oral anaerobes||Nafcillin 1.5 g IV q 4–6 h plusmetronidazole 0.5 g IV q 6 h; orClindamycin 600 mg IV q 6 h||Vancomycin 0.5 g IV q 6 h pluscefotaxime 2 g IV q 6 h; orCeftizoxime 3 g IV q 8 h; or Pipenacillin 3 g IV q 4 h|
|Extension of osteomyelitis from prevertebral space infection||Staphylococcus aureus, facultative gram-negative bacilli||Nafcillin 1.5 g IV q 4–6 h, plustobramycin 2 mg/kg q 8 h; orCiprofloxacin 0.2 g q 12 h||Vancomycin 0.5 g IV q 6 h, pluscefotaxime 2 g IV q 6 h; orCeftizoxime 4 g IV q 8 h; or Imipenim 500 mg IV q 6 h|
|Pott's puffy tumor (frontal osteitis)||Same as for rhinogenic space infections||Same as for rhinogenic space infections||Same as for odontogenic space infections|
|Malignant otitis media and petrous osteitis||Pseudomonas aeruginosa||Ciprofloxacin 200 mg IV q 12 h; or||Ciprofloxacin 200 mg IV q 12 h; or|
|Tobramycin 2 mg/kg q 8 h plusceftazidime 2 g IV q 6 h; or||Tobramycin 2 mg/kg q 8 h plusceftazidime 2 g IV q 6 h; or|
|Piperacillin 3 g IV q 4 h; or||Piperacillin 3 g IV q 4 h; or|
|Imipenem 1 g IV q 6 h||Imipenem 1 g IV q 6 h|
Routes of spread of odontogenic infections. A. Coronal section at first molar teeth: a, maxillary antrum; b, nasal cavity; c, palatal plate; d, sublingual space (above mylohyoid muscle); e, submylohyoid space; f, intraoral presentation with infection spreading through the buccal plates inside the attachment of the buccinator muscle; g, extraoral presentation to buccal space with infection spreading through the buccal plates outside the attachment of the buccinator muscle. B. Lingual aspect of the mandible: a, tooth apices above the mylohyoid muscle with spread of infection into sublingual space; b, tooth apices below the mylohyoid muscle with spread of infection into submylohyoid space. (Reproduced with permission from Chow.30)
Potential pathways of extension in deep fascial space infections. (Reproduced with permission from Blomquist and Bayer.8)
Submandibular Space Infections
The prototypical infection of this space is known as Ludwig angina. In 1836, von Ludwig described five patients with “gangrenous induration of the connective tissues of the neck which advances to involve the tissues that cover the small muscles between the larynx and the floor of the mouth.” The infection is characteristically an aggressive, rapidly spreading “woody” or brawny cellulitis involving the submandibular space. Although the submandibular space is divided by the mylohyoid muscle into the sublingual space above and the submylohyoid space below (Fig. 54-6), it can be considered a single unit owing to a direct communication around the posterior aspect of the mylohyoid muscle. Ludwig angina most commonly follows infection of the second or third mandibular molar teeth (70% to 85% of cases). The submylohyoid space is initially involved because the roots of these teeth are located below the attachments of the mylohyoid muscle to the mandible (see Fig. 54-4). Also, because the lingual aspects of periodontal bone around these teeth are thinner, medial spread of infection is facilitated. Infection extends contiguously (rather than by the lymphatics, which would limit the infection to one side) to involve the sublingual and thus the entire submandibular space in a symmetrical manner. Less commonly, an identical process initially involving the sublingual space arises from infection of the premolars and other teeth or from trauma to the floor of the mouth. Once established, infection can evolve rapidly. The tongue may enlarge to two or three times its normal size and distend posteriorly into the hypopharynx, superiorly against the palate, and anteriorly out of the mouth. Immediate posterior extension of the process directly involves the epiglottis (see Fig. 54-6). There exists a little-regarded dangerous connection between the submandibular and lateral pharyngeal spaces known as the buccopharyngeal gap. This gap is created by the styloglossus muscle as it leaves the tongue and passes between the middle and superior constrictor muscles to attach on the styloid process. Thus, cellulitis of the submandibular space may spread directly into the lateral pharyngeal space and thereby to the retropharyngeal space and mediastinum (see Fig. 54-6).
Anatomic relations in Ludwig angina. Sagittal (A) and oblique (B) sections of the head and neck: a, sublingual space; b, submylohyoid space; c, lateral pharyngeal space; d, parotid gland; f, masticator space; g, peritonsillar space; h, hyoid bone; 3, retropharyngeal space; 4, danger space; 5, prevertebral space. (Reproduced with permission from Blomquist and Bayer.8)
Clinically, the patient is febrile and complains of mouth pain, stiff neck, drooling, and dysphagia, leaning forward to maximize the airway diameter. A tender, symmetrical, and indurated swelling, sometimes with palpable crepitus, is present in the submandibular area. The mouth is held open by lingual swelling. Respirations are usually difficult, and stridor and cyanosis are considered ominous signs. Radiographic views of the teeth may indicate the source of infection, and lateral views of the neck will demonstrate the degree of soft tissue swelling around the airway and possibly submandibular gas. The development of significant asymmetry of the submandibular area should be viewed with great concern because it may be indicative of extension to the lateral pharyngeal space. Well-timed surgical drainage decreases the risk of spread to this space and subsequently to the superior mediastinum.10
The therapy of Ludwig angina has undergone a number of modifications since its initial description.11 Although maintenance of an adequate airway is the primary concern and may necessitate urgent tracheostomy, most cases can be managed initially by close observation and intravenous antibiotics. If cellulitis and swelling continue to advance rapidly or if dyspnea occurs, artificial airway control should be gained immediately, before stridor, cyanosis, and asphyxia require that it be done under emergency conditions. There is general agreement that blind oral or nasotracheal intubation is traumatic and unsafe in advanced Ludwig angina because of the potential for induction of severe laryngospasm. A recommended approach is to use a flexible fiberoptic scope to assess the airway and to aid in inserting an endotracheal tube. Tracheostomy is still the most widely recommended means of airway control, although cricothyroidotomy is advocated by some experts because of a lower complication rate.
Penicillin G with metronidazole or a similar regimen directed at the mixed aerobic and anaerobic flora of the mouth (see Table 54-2) is the antibiotic regimen of choice, but immunocompromised patients require a broader spectrum of antibiotic coverage to include organisms such as facultative gram-negative rods and S. aureus. Early surgical decompression, much advocated in the era before antibiotics, is unlikely to locate pus and at best may only moderately improve the airway. Pus collections develop relatively late (they are not usually present in the first 24 to 36 hours) and are sometimes difficult to detect clinically. If the patient is not responding adequately to antibiotics alone after this initial period or if fluctuance is detectable, needle aspiration or a more formal incision and drainage procedure under general anesthetic should be performed. Preferably, this should be done with a cuffed tracheostomy in place. In addition, the infected teeth implicated in the sepsis should be extracted.
With the combined use of systemic antibiotics and aggressive surgical intervention, the mortality rate for Ludwig angina has declined dramatically from more than 50% before the antibiotic era to 0% to 4% currently.
Lateral Pharyngeal Space Infections
Lateral pharyngeal space infections are potentially life-threatening because of involvement of vital structures within the carotid sheath and a tendency to bacteremic dissemination. Anatomically, the lateral pharyngeal space (also known as the pharyngomaxillary space) is shaped like an inverted cone in the lateral neck, with its base at the skull and its apex at the hyoid bone. Its medial wall is continuous with the carotid sheath, and anteriorly it lies between the superior pharyngeal constrictor muscle medially and the internal pterygoid muscle, mandibular ramus, and parotid gland laterally (Fig. 54-7). It is divided into an anterior (prestyloid or muscular) compartment and a posterior (retrostyloid or neurovascular) compartment by the styloid process and its attached muscles, the stylomandibular ligament, and the insertion of these structures into the hyoid bone. The anterior compartment contains no vital structures, but only fat, lymph nodes, connective tissue, and muscle. It is the compartment most closely related to the tonsillar fossa and the internal pterygoid muscle. The posterior compartment contains the ninth to twelfth cranial nerves, the carotid sheath and its contents, and the cervical sympathetic trunk. Infections of the lateral pharyngeal space may arise from sources throughout the neck. Dental infections are the most common source, followed by peritonsillar abscess (postanginal sepsis) and rarely parotitis, otitis, or mastoiditis (Bezold abscess).
Cross sections of the lateral pharyngeal space: P, parotid gland; T, tonsil; M, mandible; 3, retropharyngeal space; 4, danger space; 5, prevertebral space. Inset. Anterior and posterior compartments of the lateral pharyngeal space. (Reproduced with permission from Blomquist and Bayer.8)
Infection of the anterior compartment is often suppurative. Because most patients are already compromised by infection elsewhere, diagnosis of lateral pharyngeal involvement is often delayed. The cardinal clinical features, in order of importance, are (a) trismus, (b) induration and swelling below the angle of the mandible, (c) systemic toxicity with fever and rigors, and (d) medial bulging of the pharyngeal wall. Although not prominent, dyspnea can occur. Suppuration may advance quickly to other spaces, particularly to the retropharyngeal space and the mediastinum, or may spread to involve the posterior compartment of the lateral pharyngeal space. In these cases, timely surgical incision and drainage are of utmost importance.
Postanginal sepsis can involve the anterior or the posterior compartment, but because lymphatic drainage is the most important mechanism of spread, it most often involves the carotid sheath alone. A history of sore throat, although usually present on admission, is not invariable; it may only be mild or unilateral, and there may be a latent period of up to 3 weeks before manifestations of deep infection develop. The patient presents in a toxic condition or insidiously with a fever of undetermined origin. Trismus is absent, and signs of local suppuration may be subtle clinically because of the tight connective tissue around and within the carotid sheath. This barrier confines the infection and may limit it to only the internal jugular vein. Dyspnea may be prominent as edema and swelling may descend directly to involve the epiglottis and larynx. Swelling of the pharyngeal wall, if present, will be behind the palatopharyngeal arch and is easily missed.
Suppurative jugular thrombophlebitis (Lemierre syndrome) is the most common vascular complication of lateral pharyngeal space infection.12 An indurated swelling a few centimeters long may be palpable behind the sternocleidomastoid muscle or may be found more deeply behind the palatopharyngeal arch. Trismus is minimal and may be absent. Vocal cord paralysis or other neurologic signs representing lower cranial nerve involvement may be present. These signs are frequently missed unless specifically sought (they were detected in only 20% of cases antemortem in one series), and they may be transient. The patient may thus present as having an obscure septicemia (50% of cases). Metastatic abscesses are common, characteristically involving the lungs, bones, and joints or other sites. There may be retrograde spread of infection with cerebral abscess or meningitis. A diagnosis of right-side bacterial endocarditis may be considered. In common with other anaerobic septicemias, hepatic enlargement, tenderness, abnormal liver function tests, and even frank jaundice may be present, which may misdirect investigations and further delay diagnosis.13 Positive gallium or white-cell–labeled indium uptake in the neck is a useful diagnostic aid in these cases. Computed tomography (CT) of the neck visualizes edema within the lateral pharyngeal space and the presence of thrombus in the internal jugular vein (Fig. 54-8). Thrombosis of the jugular vein can also be demonstrated by magnetic resonance angiography. Rarely, the carotid artery is involved, leading to an arteritis and to the formation and eventual rupture of an aneurysm. This complication is usually heralded by several minor bleeds before a major hemorrhage occurs and signals the need for urgent surgical intervention. Such bleeding may involve the oral cavity, nose, or ear or appear as ecchymosis in the neck and surrounding tissues. An ipsilateral Horner syndrome and otherwise unexplained ninth to twelfth cranial nerve palsies are additional premonitory syndromes of carotid sheath involvement.
Computed tomographic scan of the neck in a patient with lateral pharyngeal space infection secondary to a peritonsillar infection. Arrow indicates a partial thrombus in the right internal jugular vein.
Treatment of lateral pharyngeal space infection initially depends on whether local suppuration is present, but often this is difficult to determine. CT, careful needle aspiration, or more definitive incision and drainage may be required. Most cases of postanginal sepsis with suppurative jugular thrombophlebitis can be managed medically without the need for ligation or surgical resection of the infected vein. Prolonged courses of intravenous antibiotics (3 to 6 weeks) will be required. Because anaerobic bacteremia caused by Bacteroides species or Fusobacteriumnecrophorum is frequently present14 and penicillin resistance among these organisms is increasingly recognized, therapy generally requires addition of metronidazole, clindamycin, or β-lactamase–stable cephalosporins. Fever may be slow to resolve, even in cases successfully treated, particularly if there is metastatic involvement. Anticoagulants have sometimes been used in this setting, but their efficacy is unconfirmed. Surgical ligation of the internal jugular vein, the only available therapeutic option before antibiotics, is currently required only in the rare patient who fails to respond to antibiotic therapy alone. When there is impending or frank rupture of the carotid artery, the artery must be ligated immediately, with special attention given to the airway and to restoration of blood volume. Predictably, morbidity (e.g., stroke) and mortality rates are high (20% to 40%). In all such cases, early surgical intervention is the key to a successful outcome.
Infections of the Retropharyngeal, “Danger,” and Prevertebral Spaces
The retropharyngeal, “danger,” and prevertebral spaces lie between the deep cervical fascia surrounding the pharynx and esophagus anteriorly and the vertebral spine posteriorly (see Fig. 54-1). The retropharyngeal space is bound anteriorly by the constrictor muscles of the neck and their fascia and posteriorly by the alar layer of the deep cervical fascia, extending from the base of the skull to the level of the superior mediastinum, where the two fascial layers fuse. The “danger” space is interposed between the retropharyngeal space anteriorly and the prevertebral space posteriorly. It extends from the base of the skull and descends freely through the entire posterior mediastinum to the diaphragm. The prevertebral space is bound by the prevertebral fascia, which originates posteriorly on the spinous processes and encircles the splenius, erector spinae, and semispinalis muscles. Before completing its circle anterior to the vertebral bodies, it fuses to the transverse processes. At this point it is split into two layers: the more anterior alar fascia and the prevertebral fascia. The prevertebral space extends from the base of the skull to the coccyx, thus allowing infectious spread as far down as the psoas muscle sheath.
Retropharyngeal abscesses are among the most serious of deep space infections because infection can extend directly into the anterior or posterior portions of the superior mediastinum or into the entire length of the posterior mediastinum through the danger space (see Fig. 54-1).
Retropharyngeal infections may occur in children and adults. In young children, infection usually reaches this space through lymphatic channels, most commonly as complications of suppurative adenitis after infections of the upper respiratory tract. The onset may be insidious, with little more than fever, irritability, drooling, or possibly nuchal rigidity. More acute symptoms include dysphagia and dyspnea. The latter may be due to a local mass effect or to laryngeal edema. In general, there is little pain, but the neck may be held rigidly and tilted to the unaffected side. Definite bulging of the posterior pharyngeal wall is usually seen but may need careful palpation to be appreciated. The main dangers are severe laryngeal edema with airway obstruction and abscess rupture with consequent aspiration pneumonia or asphyxia. Many cases will respond to antibiotic therapy alone if treatment precedes the development of frank suppuration.
In adults, infection may reach the retropharyngeal space from local or distant sites. The former usually results from penetrating trauma (e.g., from chicken bones or after instrumentation); in such cases, the presence of a sore throat or difficulty in swallowing or breathing may be the first indications of infection. More distant sources include odontogenic sepsis and peritonsillar abscess (now a rare cause). Infection from these sources often may obscure the diagnosis because of associated trismus, which makes direct examination of the posterior pharyngeal wall difficult. In this setting, CT and radiographic views of the lateral neck are especially helpful and may demonstrate cervical lordosis with swelling and gas collections in the retropharyngeal space, which causes anterior displacement of the larynx and trachea. Radiographs may also help to differentiate this infection from prevertebral space sepsis arising from cervical osteomyelitis. Once a diagnosis is made, surgical exploration and wide drainage should be carried out without delay.
Acute necrotizing mediastinitis is the most feared complication of retropharyngeal space infections.15 The onset is rapid and is characterized by (a) widespread necrotizing process extending the length of the posterior mediastinum and occasionally into the retroperitoneal space, (b) rupture of mediastinal abscess into the pleural cavity with empyema or development of loculations, and (c) pleural or pericardial effusions, frequently with tamponade. Aspiration pneumonia is also a significant problem (50% of cases) and may be secondary to impairment of swallowing or spontaneous rupture of the abscess into the airway. As might be expected, the mortality rate in adults is high (25%), even when appropriate antibiotics are administered. Early diagnosis and timely débridement are the mainstays of successful treatment. Mediastinal drainage may be attained by the cervical mediastinal or the transthoracic approach. Although the cervical approach may be effective in early mediastinitis, thoracotomy is generally indicated once the necrotizing process has entered the danger space. In patients who are recovering, it is important to restrict all oral intake until the swallowing impairment, which may have a prolonged course, has resolved completely.
Acute bacterial parotitis is a specific clinical entity primarily affecting the elderly, malnourished, dehydrated, or postoperative patient.16 Ductal (Stensen) obstruction secondary to sialolithiasis appears to be a major predisposing condition. Other predisposing factors include sialogogic drugs and trauma. Clinically, there is sudden onset of firm, erythematous swelling of the pre- and postauricular areas extending to the angle of the mandible. This is associated with exquisite local pain and tenderness but not trismus. Systemic findings of high fevers, chills, and marked toxicity are generally present. Septicemic spread may lead to osteomyelitis of the adjacent facial bones. Staphylococci have been the predominant isolates, and empirical antibiotic therapy should include an antistaphylococcal agent. Early surgical drainage and decompression of the gland are generally required because spontaneous drainage is uncommon. Because of its close relation to the posterior aspect of the lateral pharyngeal space, progression of infection into the parotid space may lead to massive swelling of the neck with respiratory obstruction and has the added potential risk of direct extension into the danger and visceral spaces and, hence, to the posterior mediastinum (see Fig. 54-1).
Peritonsillar Abscess and Pharyngeal Diphtheria
This condition, also known as quinsy, is a suppurative complication of acute tonsillitis involving the peritonsillar space. The latter consists of loose areolar tissue overlying the tonsil surrounded by the superior pharyngeal constrictor muscle and the anterior and posterior tonsillar pillars. Peritonsillar abscesses may affect patients of all ages but are most common among young adults 15 to 30 years old. The patient appears ill, with fever, sore throat, dysphagia, trismus, pooling of saliva, and a muffled voice. The abscess is usually unilateral, with associated cervical lymphadenitis. Examination of the pharynx in the majority of cases shows swelling of the anterior pillar and the soft palate and, less commonly, the middle portion or lower pole of the tonsil. Initially, needle drainage in the Trendelenburg position should be attempted, and the patient should be closely monitored and managed with intravenous antibiotics alone. Failure to obtain pus is an indication for surgical incision and more formal exploration. Delays increase the risk of spontaneous rupture. Aspiration of purulent material is the main hazard, particularly in the sleeping patient. More serious complications include (a) airway obstruction, especially with bilateral disease or when laryngeal edema develops; and (b) lateral dissection (usually from infections of the middle or lower portions of the tonsil) through the superior pharyngeal constrictor muscle to involve the lateral pharyngeal space (see Fig. 54-6B). Continued signs of sepsis after drainage of the peritonsillar space usually indicate coexisting, undrained lateral pharyngeal space infection. Fatalities associated with peritonsillar abscess (>50% before antibiotics) were due largely to this complication.
Ideally, antibiotics should be tailored according to the results of cultures of aspirated pus, but these are infrequently performed. Also, results are unlikely to be helpful unless specimens are collected without oropharyngeal contamination and are transported in appropriate media. Group A β-hemolytic streptococci (often as part of a mixed flora containing anaerobes) are most commonly isolated. Occasionally other β-hemolytic streptococci, Haemophilus influenzae, S. aureus, or anaerobes alone are cultured. Penicillin G is effective therapy in most cases. Bilateral tonsillectomy should be performed once the patient has recovered to avoid recurrences. Interim antibiotic prophylaxis should be considered in high-risk cases.
Widespread immunization has substantially reduced infections caused by toxigenic strains of Corynebacterium diphtheriae. Nevertheless, local outbreaks of infection continue to occur sporadically, where reservoirs of infections (e.g., nasopharyngeal carriage) and suboptimal levels of immunization exist. All age groups, irrespective of immunization status, may develop diphtheria, but most cases usually occur in children and young adolescents. Those previously immunized are more likely to have milder or asymptomatic infections. Tonsillitis is the commonest manifestation, but any site in the upper airway can be infected. Nasopharyngeal involvement usually occurs by contiguous spread from the tonsils. In these patients, local symptoms of sore throat and dysphagia frequently follow a prodrome of fever, malaise, headache, nausea, and vomiting. Even though infection is limited to the mucosal epithelium (toxin absorption is responsible for systemic complications), the tonsils, uvula, and pharynx may swell considerably, sometimes sufficiently to suggest the presence of a peritonsillar or retropharyngeal collection. Further, a brawny nonpitting edema or “bull neck” may develop secondary to reactive cervical lymphadenopathy. With nasopharyngeal infection, cervical lymphadenopathy may be marked. Diphtheria is known for the formation of a tenacious membrane, but this is not an invariable finding and may be confined to the tonsillar mucosa. It may be produced by other infections, but the typical membrane of diphtheria quickly becomes discolored and necrotic (Fig. 54-9).17 Bleeding may occur after attempts to remove it and is sometimes severe. Airway obstruction by membrane and local swelling may complicate severe tonsillar and nasopharyngeal infection but is more likely when the larynx is primarily involved. Urgent tracheostomy may then be required; if this measure fails to bypass the obstruction, bronchoscopy to remove any membrane present in the lower airways should be considered.
Tonsillar diphtheria with characteristic grayish green membrane overlying the right tonsil. (Reproduced with permission from Whiting and Chow.17)
Circulating toxin is responsible for the neurologic and cardiac manifestations of diphtheria (peripheral neuropathy and myocarditis). These manifestations develop after a latent period of 1 to 2 weeks or longer and are influenced by the rate of toxin production (increased by more available iron) and absorption (greater in the nasopharynx). Gravis, intermedius, and mitis variants of C. diphtheriae are similarly toxigenic, and their distinction is of primarily epidemiologic importance. Of the neurologic complications, palatal, ocular, and ciliary paralysis are the earliest to develop and may be followed by motor or sensory changes in the limbs; but these symptoms are reversible. Myocarditis may develop acutely or insidiously, with a gradually rising serum aspartic transaminase level. Manifestations include shock, heart failure, arrhythmias, and various conduction disturbances. The prognosis for cardiac disease is guarded, but complete recovery is the rule for those who survive.
For immediate treatment, equine diphtheria antitoxin should be given whenever clinical evidence of diphtheria exists because early administration decreases the risk of myocarditis. The dose depends on the site and severity of the infection. Testing for hypersensitivity to horse protein (and desensitization, if necessary) of all patients is mandatory. Diagnostic confirmation requires culturing C. diphtheriae, which must then be shown to be toxigenic. Although uncommon, toxigenic strains of C. ulcerans can also cause classic symptoms of laryngeal and cutaneous diphtheria.18 These organisms are sensitive to several antibiotics, including penicillin G and erythromycin, which are equally effective and are used for treating clinical cases, carriers, and contacts.
Acute Epiglottitis and Laryngotracheobronchitis
Acute epiglottitis is an infection that produces predominantly nonsuppurative inflammatory edema involving the supraglottic structures and the epiglottis. Once caused mainly by H. influenzae, widespread use of vaccination against this organism in children has greatly reduced its prevalence, so that other bacteria, such as Streptococcus pneumoniae, S. aureus, Haemophilus parainfluenzae, and oral anaerobes, are increasingly implicated. In addition, because of vaccination, the occurrence of the disease in children has fallen dramatically; in most centers, most current cases seen are in adults.19
In older children and adults, the chief initial complaint is a sore throat and later odynophagia, but in younger children the physician has to rely on clinical findings alone. Typically, the triad of fever, stridor, and drooling is present. The patient tends to sit up and remain quiet, often leaning forward to facilitate breathing. The voice is muffled rather than hoarse. Inspiration tends to draw down the epiglottis and further obstruct the airway, so respirations are deliberately slow rather than rapid. Cyanosis, pallor, and bradycardia are late signs of severe airway obstruction that signal the urgent need to establish an artificial airway.
Once the diagnosis is suspected, confirmation depends on the condition of the patient, with the knowledge that this can change rapidly and unexpectedly, particularly in younger children in whom, because of the relatively small size of the supraglottic larynx, even small degrees of swelling can rapidly lead to complete airway obstruction. Particularly in adults who appear not to be in great distress, frequently only antimicrobial therapy and close observation in an intensive care unit without endotracheal intubation are required.19 However, in a significant minority of adults (20%) and in most children (70%), respiratory distress, worsening stridor, or inability to easily clear secretions will mandate placement of an artificial airway.20 Whether the patient is managed expectantly or by intubation, it is worth emphasizing that the personnel involved should be highly experienced with all aspects of difficult airway management because even with close monitoring there can be abrupt changes in the clinical course. If intubation is indicated, it should be done by direct visualization and in the operating room, preferably by a skilled anesthetist. Equipment and personnel necessary for emergency tracheostomy and a bronchoscope should be immediately available. Attempts to visualize the cherry-red epiglottis by direct laryngoscopy in an awake patient in the absence of these precautions for immediate intubation are discouraged because acute airway obstruction can be precipitated by dislodging a mucus plug or causing the patient to gag. Radiographic views of the lateral neck usually show an enlarged epiglottis with edematous supraglottic structures and ballooning of the hypopharynx (Fig. 54-10).21 However, when the clinical signs point toward the diagnosis of epiglottitis with a significant compromise of the airway, radiologic investigation should not precede airway management.
Lateral view of the neck in an adult with acute epiglottitis, showing soft tissue swelling of the epiglottis (A) and aryepiglottic folds (B). (Reproduced with permission from Chow et al.21)
Additional laboratory data may indicate a moderate leukocytosis with a left shift and positive cultures of blood and epiglottis. A concurrent pneumonia is demonstrated on chest radiographs in about 25% of cases. Antibiotic treatment may be initiated with ampicillin-sulbactam or a β-lactamase–resistant cephalosporin such as cefuroxime, cefotaxime, or ceftriaxone. Culture and sensitivity results will dictate the ultimate choice of antibiotic, which should be continued for 7 to 10 days. When H. influenzae infection is demonstrated, rifampin prophylaxis should be provided for all household contacts when the household contains contacts younger than 4 years.
Laryngotracheobronchitis primarily affects young children after a viral upper respiratory infection caused by influenza, parainfluenza, respiratory syncytial virus, adenovirus, and occasionally Mycoplasma pneumoniae.22 Inflammation results in edematous swelling of the conus elasticus with narrowing of the infraglottic structures. Laryngotracheobronchitis follows a more gradual course than does bacterial epiglottitis and may be self-limiting or progress to respiratory obstruction. Clinical findings include a “brassy” or “barking” nonproductive cough associated with different degrees of inspiratory stridor, hoarseness, and respiratory distress. Respirations are noisy, often accompanied by chest wall retractions and inspiratory and expiratory wheezing. Nasal discharge and pharyngeal injection are common, but the epiglottis and supraglottic structures appear normal. Fever and malaise are present as part of the upper respiratory viral syndrome. A lateral radiograph of the neck can be helpful by showing the characteristic infraglottic narrowing. Management is similar to that for supraglottic laryngitis, including humidification, hydration, oxygen administration, and antibiotic therapy for secondary bacterial infection. Use of sedatives and narcotics, which suppress the cough reflex, is to be avoided. The role of steroids remains unclear.23 Occasionally, an artificial airway is required for 2 to 5 days or longer. Extubation is sometimes difficult because of additional edema secondary to the endotracheal tube. It seems reasonable that a tracheostomy rather than reintubation should then be considered when the patient fails extubation.
Pericranial Infections and Intracranial Suppuration
Sinusitis, Otitis, and Mastoiditis
Fortunately, suppurative and life-threatening complications of acute and chronic sinusitis have become relatively infrequent in the postantibiotic era. However, because of the unique pericranial location of these airspaces and the rich vascular supply in this region, contiguous spread of infection may extend intracranially through the diploic veins and result in serious complications such as meningitis, brain abscess, subdural or epidural empyema, osteomyelitis of the skull, and cavernous and other cortical venous sinus thrombosis.24 The clinical spectrum of such complications may be quite varied (Table 54-3). Because the roof of the frontal and ethmoidal sinuses forms the anterior cranial fossa, infection in either sinus may produce a frontal epidural abscess, subdural empyema, or a frontal lobe brain abscess (see Fig. 54-2). Frontal sinusitis may also result in thrombosis of the superior sagittal sinus, which arises in the roof of the frontal air sinuses. Extension of infection anteriorly into bone can lead to “Pott's puffy tumor of the forehead,” whereas an orbital extension may lead to periorbital cellulitis. The ethmoidal sinuses are separated from the orbital cavity by a paper-thin orbital plate. Perforation of the plate allows direct spread of infection into the retro-orbital space. Ethmoidal sinusitis can also spread to the superior sagittal vein or the cavernous venous sinus (see Fig. 54-2). The sphenoid sinus occupies the body of the sphenoid bone in close proximity to the pituitary gland above, the optic nerve and optic chiasma in front, and the internal carotids, the cavernous sinuses, and the temporal lobes of the brain on each side (see Fig. 54-2). Thus, sphenoid sinusitis can spread locally to cause cavernous sinus thrombosis, meningitis, temporal lobe abscess, and orbital fissure syndromes.7,25 The superior orbital fissure syndrome, characterized by orbital pain, exophthalmos, and ophthalmoplegia, is due to involvement of the abducens, oculomotor, and trochlear nerves and the ophthalmic division of the trigeminal nerve as they pass through the orbital fissure.24 Extension of infection from the maxillary sinus into the adjacent structures may result in osteomyelitis of the facial bones, including prolapse of the orbital antral wall with retro-orbital cellulitis, proptosis, and ophthalmoplegia. Direct intracranial extension from the maxillary sinus is rare, except in rhinocerebral mucormycosis and other types of invasive fungal sinusitis. Infections of the middle ear or mastoid within the petrous bone may extend into the middle fossa to involve the temporal lobe or into the posterior fossa to involve the cerebellum or brain stem. The skull overlying the dura of the cerebrum is covered extracranially by the galea aponeurotica. Pericranial infections due to head trauma or to a craniotomy may result in a subgaleal abscess and cranial osteomyelitis, with possible retrograde spread through the emissary veins to the epidural, subdural, and subarachnoid spaces.
Table 54–3. The Clinical Spectrum and Investigation of Intracranial Complications
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Table 54–3. The Clinical Spectrum and Investigation of Intracranial Complications
|Complication||Clinical Signs||Cerebrospinal Fluid||Plain||With Contrast|
|Meningitis||Headache, fever (++), stiff neck, lethargy (++), rapid course||High PMN and protein levels; low glucose level||Normal||Diffusely enhanced|
|Osteomyelitis||Pott's puffy tumor (±)||Normal||Bony defect||Bony defect|
|Epidural abscess or mucocele||Headache (±), fever (±)||Normal||Lucent area||Biconvex capsule|
|Subdural empyema||Headache (±), convulsions (±), hemiplegia (±), rapid course (±)||High PMN and protein levels; normal glucose level||Lucent area||Crescent-shaped enhancement|
|Cerebral abscess||Convulsions (+), headache (+), personality change (+)||Lymphocytosis; normal glucose level||Lucency with mass effect||Capsule|
|Venous sinus thrombosis (cavernous)||“Picket-fence" fever (++), rapid course (++), orbital edema (++), ocular palsies (++)||Normal or high PMN count||Nonspecific||Enhancing lesion|
Sinusitis occurring after prolonged endotracheal intubation is a recognized complication among critically ill patients. The incidence of this infection likely exceeds 15% in patients intubated longer than 5 days and is probably more frequent with nasal than with endotracheal and gastric tubes.26,27 One study pointed to the difficulties in assessing sinusitis associated with intubation.26 In this evaluation of 162 adult patients with intubation longer than 7 days, only 25% exhibited entirely normal maxillary sinuses at the time of an initial CT scan within 48 hours of admission. Some degree of mucosal thickening or an air–fluid level was present in most patients, suggesting that subsequent imaging studies must be interpreted in light of a high incidence of baseline abnormalities in patients admitted with respiratory failure. Nonetheless, when culture-positive sinusitis did develop, aggressive diagnosis and treatment appeared beneficial, and there was an association between sinusitis and bronchopneumonia. Interestingly, use of oral intubation was associated with a lower incidence of maxillary sinusitis than of nasal intubation.
Whether the use of soft feeding tubes or the Sengstaken-Blakemore tube carries a similar risk is currently unknown. This event is probably secondary to local trauma and edema within the intubated nasal cavity and is further promoted by limited head mobility, resulting in impaired drainage of the sinuses through the natural ostia. In contrast to community-acquired sinusitis, nosocomial sinusitis in the critically ill is often clinically silent, except for unexplained fever and leukocytosis. Purulent rhinorrhea and opacification or air–fluid levels on sinus roentgenograms or CT scans may suggest the diagnosis. The sequelae of unrecognized infection can be catastrophic, with intracranial extension and fulminant sepsis. A large percentage of cases of nosocomial sinusitis is polymicrobial (42% in one series), and most patients may be receiving broad-spectrum antibiotics at the time of diagnosis. The use of antral puncture for drainage and specimen collection for Gram stain and culture is strongly recommended. Antimicrobial therapy should be guided by Gram stain of the aspirate and culture results. Broad-spectrum coverage of S. aureus and enteric gram-negative bacilli is generally required.
Rhinocerebral Mucormycosis and Malignant Otitis Externa
Rhinocerebral mucormycosis is a progressive and destructive infection of the paranasal sinuses caused by fungi of the family Mucoraceae: Absidia, Mucor, Rhizomucor, and Rhizopus.28,29 It occurs primarily in debilitated patients with uncontrolled diabetes and ketoacidosis, in profoundly dehydrated children, and in neutropenic patients receiving cytotoxic therapy. The infection begins in the nose or nasopharynx and spreads through the sinuses into the orbit or central nervous system. It may extend through the cribriform plate to involve the meninges and the adjacent frontal lobe and cranial nerves, or it may extend through the nasolacrimal duct to involve the orbit, producing panophthalmitis. These fungi have a predilection for the walls of arteries, and infection spreads by this route, causing thrombosis and tissue infarction. The internal carotid artery or its major branches may be involved, as may the cavernous sinus. Clinically, black necrotic lesions may be found on the nasal mucous membranes or the soft palate. When orbital involvement is seen, there is proptosis, ophthalmoplegia, blindness, chemosis, and corneal anesthesia. Extension into the cranial cavity is manifested by headache, meningismus, trigeminal or facial cranial nerve palsy, seizures, and other focal neurologic signs. Progressive obtundation is seen, culminating in coma. The diagnosis is confirmed by the presence of broad, nonseptate hyphae in biopsy specimens and a positive culture. Treatment requires aggressive surgical débridement and systemic amphotericin B. With early diagnosis, control of the underlying condition, and appropriate antimicrobial therapy, long-term survival has been reported in 85% of cases.
Malignant otitis externa is a progressive and necrotizing infection of the external ear caused by P. aeruginosa, with spread through the cartilaginous and bony canal to the base of the skull. Affected patients are usually debilitated and often have poorly controlled diabetes mellitus. The infection is associated with severe otalgia, hearing loss, purulent discharge, edema, and granulation tissue or “polyp” in the cartilaginous portion of the external ear canal. Three stages of progression are recognized clinically: (a) locally invasive disease, (b) disease associated with facial palsy, and (c) disease associated with multiple cranial nerve palsies. In the latter stages, infection may involve the infratemporal fossa by extension into the temporal or occipital bone. Prolonged medical therapy in conjunction with local débridement of granulation tissue and infected cartilage is effective in the majority of patients. In patients with more extensive disease involving the base of the skull and multiple cranial nerve palsies, therapy is not as successful, and up to 20 months of antimicrobial treatment may be required to achieve eradication of infection without relapse.
These dreaded complications, which most commonly arise from chronic sinusitis, mastoiditis, or deep fascial space infections,30 are only briefly reviewed here. Readers are referred to Chap. 52 for a more comprehensive description of these entities.
Most brain abscesses occur in association with three identifiable clinical settings (a) a contiguous focus of infection, particularly sinusitis, otitis, or mastoiditis; (b) cranial trauma or trauma after craniotomy; and (c) hematogenous spread from an extracranial focus of infection, especially the lung and heart valves. Otogenic (e.g., temporal lobe or cerebellum) and sinusitis-related (e.g., frontal lobe) brain abscesses account for approximately 50% of all pericranial sources of infection.31 Hematogenous brain abscesses are frequently multiple and located in the distribution of the middle cerebral artery (i.e., in the posterior frontal or parietal lobes). The clinical presentations of brain abscesses are quite variable and appear to be influenced primarily by the anatomic location of the abscesses; their proximity to the ventricles, cisterns, or dural sinuses; and major alterations in the intracranial pressure dynamics secondary to the mass effect. Thus, a pontine abscess may bulge posteriorly and block the aqueduct of Sylvius acutely to cause obstructive hydrocephalus. An occipital lobe abscess could rupture or leak into the ventricular system, causing ventriculitis, or it could involve the transverse sinus and cause septic thrombophlebitis or a subdural empyema. Four distinctive clinical presentations of a brain abscess can be recognized, based on the unique pathophysiologic events implicated: (a) rapid focal mass expansion, (b) intracranial hypertension, (c) diffuse brain destruction, and (d) focal neurologic deficit. In the last category, the temporal progression of infection is so slow that it is often misdiagnosed as a neoplasm. Fever is present in only 45% to 50% of patients; therefore, absence of fever should not be used to exclude the diagnosis of brain abscess.
Subdural Empyema and Cranial Epidural Abscess
Intracranial subdural empyema in the adult usually results from a suppurative infection of the paranasal sinuses, mastoid, or middle ear. An acute flare-up with local pain and increase in purulent nasal or aural discharge and onset of generalized headache and high fevers are the first indications of intracranial spread. They are followed within days by focal neurologic findings such as unilateral motor seizures, hemiplegia, hemianesthesia, or aphasia, and signs of increased intracranial pressure with progressive lethargy and coma. The neck is stiff, but cerebrospinal fluid examination is more consistent with an aseptic meningitis syndrome. In infants and young children, however, an intracranial subdural empyema is almost invariably a complication of bacterial meningitis. Early signs such as irritability, poor feeding, or increased head size are nonspecific, but hemiparesis, convulsions, stupor, and coma may rapidly ensue. Streptococcus pneumoniae, Streptococcus agalactiae, and H. influenzae are the most common causes.
Cranial epidural abscess is usually associated with an infection after craniotomy or a cranial osteomyelitis secondary to chronic sinusitis or middle ear infection. The onset of symptoms may be insidious and overshadowed by the localized inflammatory process. Focal neurologic findings are less common than in subdural empyema. Rarely, a fifth and sixth cranial nerve palsy may develop in association with infections of the petrous portion of the temporal bone (Gradenigo syndrome).
Septic Intracranial Thrombophlebitis and Mycotic Aneurysm
Septic intracranial thrombophlebitis most frequently follows infection of the paranasal sinuses, middle ear, mastoid, or oropharynx. If collateral venous drainage is adequate, septic venous thrombosis may produce only transient neurologic findings or may be silent. If the thrombus outstrips collateral flow, progressive neurologic deficits will result, with impairment of consciousness, focal or generalized seizures, and increased intracranial pressure. The clinical findings differ with the location of cortical veins or dural sinuses involved. Cavernous sinus thrombosis is characterized by abrupt onset with diplopia, photophobia, orbital edema, and progressive exophthalmos. Involvement of cranial nerves III, IV, V, and VI produces ophthalmoplegia, a midposition fixed pupil, loss of the corneal reflex, and diminished sensation over the upper face. Obstruction of venous return from the retina results in papilledema, retinal hemorrhage, and visual loss. Contrast-enhanced CT (Fig. 54-11) and magnetic resonance imaging (MRI) are the imaging modalities of choice. Treatment requires early recognition, high-dose intravenous antibiotics, and surgical decompression of the underlying predisposing infection. Anticoagulation and steroids are not indicated. Mortality remains high, approximately 15% to 30%. Thrombosis of the superior sagittal sinus produces bilateral leg weakness and may cause communicating hydrocephalus. Occlusion of the lateral sinus produces pain over the ear and mastoid and may cause edema over the mastoid (Griesinger sign). Involvement of cranial nerves V and VI produces ipsilateral facial pain and lateral rectus weakness (Gradenigo syndrome). Intracranial mycotic aneurysm usually results from septic embolization as a complication of bacterial endocarditis. This produces infection and necrosis in the arterial wall, which leads to dilation and possible rupture. Mycotic aneurysms can be multiple and are usually found on distal branches of the middle or anterior cerebral arteries. The early clinical manifestations are similar to those of cerebral emboli and infarction. The weakened vessel may be seen to progressively grow on serial angiograms. Because the clinical course of a mycotic aneurysm is quite variable and the risk of rupture with catastrophic cerebral hemorrhage cannot be predicted even after successful therapy of the underlying endocarditis, early surgical intervention is advised.
Computed tomographic scan of the head in a patient with cavernous sinus thrombosis secondary to sphenoid sinusitis. Arrow indicates thrombus in the right cavernous sinus.