Ludwig angina

INTRODUCTION — Ludwig angina is a bilateral infection of the floor of the mouth that consists of three compartments: the submandibular, sublingual, and submental spaces (figure 1). It was first described by the German physician, Wilhelm Frederick von Ludwig in 1836. This infection most commonly arises from an infected second or third mandibular molar tooth. It is an aggressive, rapidly spreading cellulitis, often without marked lymphadenopathy, with potential for airway obstruction. The infection requires careful monitoring and rapid intervention for prevention of asphyxia and aspiration pneumonia.

The anatomy, microbiology, clinical manifestations, imaging, and treatment of Ludwig angina will be reviewed here. Other deep neck space infections are discussed separately. (See "Deep neck space infections in adults".)

DEFINITION — Ludwig angina is characteristically an aggressive, rapidly spreading "woody" or brawny cellulitis involving the bilateral submandibular, sublingual, and submental spaces. The infection most commonly arises from an infected second or third mandibular molar tooth. Ludwig angina is characterized by its lack of lymphadenopathy and abscess formation.

ANATOMIC CONSIDERATIONS — Mandibular anatomy is comprised of multiple potential spaces, including the submandibular, sublingual, and submental spaces [1]. The submandibular space is bordered anteriorly by the mandible, superiorly by the mylohyoid muscle, inferiorly by the hyoid bone, medially by the anterior belly of the digastric muscles, and laterally by the mandible as well. The sublingual space is superior to the submandibular space and separated by the mylohyoid muscle. However, the posterior portions of the spaces are in communication with each other, which allows for the contiguous spread of infection within the fascial spaces. The submental space is located antero-inferiorly to the submandibular space and is separated by the anterior digastric muscle (figure 1).

An overview of the anatomy of the deep neck spaces and anatomic considerations for other deep neck space infections are discussed separately. (See "Deep neck space infections in adults", section on 'Anatomic considerations'.)

MECHANISMS OF SPREAD — Over two-thirds of patients with Ludwig angina have a dental source of infection, usually involving the second or third mandibular molar teeth [2]. The submandibular space is initially involved, since the roots of these teeth are located below the attachments of the mylohyoid muscle to the mandible (figure 1) (see "Epidemiology, pathogenesis, and clinical manifestations of odontogenic infections"). Other sources of infection include contiguous spread from peritonsillar abscess or suppurative parotitis, trauma to the mandible or floor of the mouth, and sialolithiasis and infection of the submandibular or sublingual salivary glands [2-4].

Medial spread of infection is facilitated because the lingual aspects of periodontal bone around these teeth are thin. Infection extends contiguously to involve the sublingual and submental space in a bilateral manner. If infection were instead to spread via the lymphatics, involvement would be unilateral instead of bilateral as is observed. An identical process, initially involving the sublingual space, can arise less commonly from infection of the premolars and other teeth or from trauma to the floor of the mouth.

Once established, infection evolves 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 protruding out of the mouth, causing a “double-tongue” appearance [5]. Immediate posterior extension of the process will directly involve the epiglottis. There exists a little-known dangerous connection between the submandibular and parapharyngeal spaces known as the buccopharyngeal gap. This 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 along the styloglossus muscle into the parapharyngeal space and from there to the retropharyngeal space and the superior mediastinum [6]. (See "Deep neck space infections in adults".)

MICROBIOLOGY — Ludwig angina is typically a polymicrobial infection involving flora of the oral cavity [7]. (See "Epidemiology, pathogenesis, and clinical manifestations of odontogenic infections".)

The most common organisms isolated from deep neck space infections are viridans streptococci, reflecting their abundance in the mouth. The Streptococcus anginosus (Streptococcus milleri) group of viridans streptococci are particularly virulent, as evidenced by the case of a previously healthy woman who, several days after elective dental implants, developed rapidly progressive Ludwig angina due to Streptococcus constellatus (a member of this group) and oral anaerobes [8]. Most odontogenic infections originating from the teeth also harbor oral anaerobes, including Peptostreptococcus species, Fusobacterium nucleatum, pigmented Bacteroides (eg, Prevotella melaninogenica [formerly Bacteroides melaninogenicus] and Porphyromonas spp), and Actinomyces spp [9].

Gram-negative aerobes and Staphylococcus aureus, including methicillin-resistant S. aureus, may also contribute to deep neck space infections, especially in children, immunocompromised patients, or others with specific risk factors [2,10,11]. This is discussed in detail separately. (See "Deep neck space infections in adults", section on 'Microbiology'.)

CLINICAL FEATURES — Patients typically present with fever, chills, and malaise, as well as mouth pain, stiff neck, drooling, and dysphagia, and may lean forward to maximize the airway diameter [12]. They may have a muffled (“hot-potato”) voice or be unable to speak at all. Trismus is usually absent initially unless there is spread into the parapharyngeal space. As the illness progresses, breathing may become difficult; stridor and cyanosis are considered ominous signs. (See 'Airway management' below.)

On physical examination, patients have tender, symmetric, and "woody" induration, sometimes with palpable crepitus, in the submandibular area (“bull neck”) [12,13]. The mouth is held open by lingual swelling. There is typically no lymphadenopathy, although occasionally it may be present. The floor of the oral cavity is usually elevated and erythematous and is tender to palpation. Occasionally, the inflammation extends to the epiglottis.

Comorbidities in adults are common and include diabetes mellitus, hypertension, and human immunodeficiency virus (HIV) [14].

DIAGNOSIS — The diagnosis of Ludwig angina is established based on the presence of suggestive clinical findings (see 'Clinical features' above), usually with the support of imaging studies.

Diagnostic imaging — Computed tomography (CT) of the neck with intravenous contrast is the imaging modality of choice for the diagnosis of Ludwig angina and other deep neck space infections [15]. Suggestive findings include soft tissue thickening, increased attenuation of the subcutaneous fat, loss of fat planes in the submandibular space, gas bubbles within soft tissues (“bubble sign”) [16], focal fluid collections, and muscle edema. CT has a sensitivity of 95 percent and a specificity of 53 percent, but when combined with clinical examination, the specificity increases to 80 percent [3]. (See "Deep neck space infections in adults", section on 'Clinical suspicion and urgent imaging'.)

Although magnetic resonance imaging (MRI) of the neck is an alternative to CT, it should not be performed if there is any question of airway compromise and/or challenges with controlling respiratory sections, given the time it takes to obtain the scan. MRI is more accurate in soft-tissue discrimination and detection of an abscess, although abscesses are not typically seen in Ludwig angina. The positive predictive value for the detection of an abscess was 0.95 by MRI compared with 0.80 by CT [17]. However, emergency MRI is more time consuming, costly, and not as readily available [17].

For patients requiring urgent airway management, point-of-care-focused ultrasound is a valid and reliable tool for imaging the oral and oropharyngeal components of the airway and may be particularly useful in defining anatomy of the neck and the airway [18].

Microbiologic evaluation — Since Ludwig angina does not usually involve abscess formation, a microbiologic diagnosis from the site of infection is often not possible. Needle aspiration of the demonstrated fluid collections within the submandibular space may be attempted [19] and specimens should be obtained for Gram stain and culture of both facultative and anaerobic organisms [20]. (See 'Surgery' below.)

Aerobic and anaerobic blood cultures should be obtained from patients with Ludwig angina. (See "Detection of bacteremia: Blood cultures and other diagnostic tests".)

TREATMENT — The treatment of Ludwig angina involves timely assessment and management of the airway and empiric broad-spectrum antibiotics [12,21]. Surgical management of the airway may be required. Surgery directed to the infected region is not usually necessary since it is uncommon to have a drainable collection in the early stages of infection. Surgical drainage is important if abscesses are identified by imaging. Similarly, if infected teeth are identified as the cause, these should be addressed after appropriate consultation.

Airway management — While maintenance of an adequate airway is the primary concern and may necessitate urgent tracheostomy [22,23], most cases can be managed initially by close observation and intravenous antibiotics. If cellulitis and swelling continue to advance or if dyspnea occurs, artificial airway control should be gained immediately, before the onset of stridor, cyanosis, and asphyxia. Urgent consultation with otolaryngology and anesthesia is recommended as these patients can quickly deteriorate and are best managed in the operating room when possible. Tracheostomy under emergency conditions may be required in more severe cases.

If airway compromise is suspected, a recommended approach is to perform fiberoptic intubation via the nasal route. Fiberoptic laryngoscopy is carried out to assess the airway and to aid in nasal intubation of an endotracheal tube under direct observation [24]. A nasopharyngeal airway can be useful to bypass the airway obstruction. Blind oral or nasotracheal intubation is both traumatic and unsafe in advanced Ludwig angina because of the potential for inducing severe laryngospasm. If intubation is not possible, tracheostomy is the most widely recommended means of surgical airway control. (See "Emergency cricothyrotomy (cricothyroidotomy) in adults".)

We do not routinely use glucocorticoids in the management of airway edema in Ludwig angina, although many clinicians choose to administer glucocorticoids when the patient requires emergent surgical intervention for airway maintenance. Their use is controversial and evidence informing the potential benefits is limited mainly to case reports. One review identified 17 case series that included 31 patients with Ludwig angina who were treated with glucocorticoids, primarily dexamethasone, in addition to antimicrobial therapy [25]. All but four required surgical intervention, and three deaths were reported. Without comparative data, the benefits and harms of glucocorticoids in this setting are uncertain [4].

Antibiotics — The treatment of Ludwig angina has not been evaluated in clinical trials. Empiric antimicrobial regimens are based on the expected microbiology and should be tailored as microbiologic data become available. (See 'Microbiology' above.)

The antibiotic doses recommended below are intended for patients with normal renal function; dosing of some of these agents must be reduced in patients with renal dysfunction.

Immunocompetent patients — Empiric antibiotic treatment of immunocompetent patients entails broad-spectrum antibiotics with activity against beta-lactamase-producing aerobes and anaerobes, and Staphylococcus aureus, including, in some cases, methicillin-resistant S. aureus (MRSA).

For immunocompetent hosts who can take penicillins and/or cephalosporins, we suggest one of the following regimens:

●Ampicillin-sulbactam (In children: 100 to 200 mg ampicillin/kg/day intravenously [IV] divided every 6 six hours, maximum: 2000 mg ampicillin/dose; in adults: 3 g IV every six hours)

or

●Ceftriaxone (In children: 50 to 75 mg/kg/day IV in divided doses every 12 to 24 hours; maximum daily dose: 2000 mg/day; in adults: 2 g IV every 12 hours) PLUS metronidazole (in children: 30 to 40 mg/kg/day orally or IV in 3 divided doses, maximum: 500 mg/dose; in adults: 500 mg orally or IV every eight hours)

For patients who cannot take penicillins and cephalosporins, we prefer:

●Levofloxacin (In children 6 months to <5 years: 8 to 10 mg/kg/dose orally or IV twice daily; in children ≥5 years: 10 mg/kg/dose orally or IV once daily, maximum: 750 mg/day; in adults: 750 mg orally or IV once daily) PLUS metronidazole (in children: 30 to 40 mg/kg/day orally or IV in 3 divided doses, maximum: 500 mg/dose; in adults: 500 mg orally or IV every eight hours)

or

●Ertapenem (In children ≥3 months to 12 years: 15 mg/kg/dose IV every 12 hours, maximum: 500 mg/dose; in adolescents and adults: 1 g every 24 hours)

If the patient is <18 years of age, is known to be colonized with MRSA, and has risk factors for MRSA (eg, injection drug use, recent hospitalization, residence in a long-term care facility, hemodialysis, or is septic and/or at risk for rapid deterioration), we also add the following [12]:

●Vancomycin IV (table 1 and table 2) (see "Vancomycin: Parenteral dosing, monitoring, and adverse effects in adults", section on 'Approach to dosing and monitoring' and "Staphylococcus aureus in children: Overview of treatment of invasive infections")

or

●Linezolid (In children <12 years: 10 mg/kg/dose orally or IV every 8 hours, maximum: 600 mg/dose; in children and adolescents ≥12 years and adults: 600 mg orally or IV every 12 hours)

Certain factors increase the risk of MRSA (see "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Epidemiology" and "Methicillin-resistant Staphylococcus aureus infections in children: Epidemiology and clinical spectrum"). If MRSA is not isolated from the blood culture nor present on deep cultures (if available), empiric therapy against this organism can be discontinued.

If metronidazole cannot be used, clindamycin can be used as an alternative to metronidazole in conjunction with another antibiotic. Clindamycin alone does not provide adequate coverage due to the high rate of resistance (approximately 30 percent) in S. anginosus group and in other viridans streptococci and should not be used as monotherapy in the treatment of Ludwig angina.

Immunocompromised patients — Empiric antibiotic treatment of immunocompromised patients entails broad-spectrum antibiotics with activity against facultative gram-negative rods (including Pseudomonas aeruginosa), beta-lactamase-producing aerobes and anaerobes, and methicillin-resistant S. aureus.

For immunocompromised patients, we prefer one of the following regimens:

●Cefepime (In children: 50 mg/kg/dose IV every 8 hours, maximum dose: 2000 mg/dose; in adults: 2 g IV every eight hours) PLUS metronidazole (in children: 30 to 40 mg/kg/day orally or IV in 3 divided doses, maximum: 500 mg/dose; in adults: 500 mg orally or IV every eight hours)

or

●Meropenem (In children and adolescents: 20 mg/kg/dose IV every 8 hours, maximum dose: 1000 mg/dose; in adults: 2 g IV every eight hours)

or

●Piperacillin-tazobactam (In children and adolescents: 300 mg piperacillin/kg/day divided in 3 to 4 doses, maximum dose: 16 g/day; in adults: 4.5 g IV every six hours)

PLUS an agent with anti-MRSA activity, such as:

●Vancomycin IV (table 1 and table 2)  

or

●Linezolid (In children <12 years: 10 mg/kg/dose orally or IV every 8 hours, maximum: 600 mg/dose; in children ≥12 years and adults: 600 mg orally or IV every 12 hours)

Duration — In general, antimicrobial therapy should be continued for two to three weeks until clear evidence of clinical improvement is present, and fever and leucocytosis have subsided. Sequential C-reactive protein measurement [26] or procalcitonin levels [27,28] may be a useful tool for monitoring the progress of such patients. Longer courses are required when complications (eg, abscesses, Lemierre syndrome) are present. We favor IV antibiotics at least until the patient is clinically improved and is ready for discharge from the hospital; some contributors favor treating for the entire duration of treatment given the severity of the infection and risk for poor outcomes.

Surgery — Early surgical decompression is unlikely to locate pus and, at best, may only moderately improve the airway. Abscesses develop relatively late (not usually 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, we repeat computed tomography imaging to look for an abscess. If a collection is observed on imaging, needle aspiration or a more formal incision and drainage procedure under general anesthesia should be performed [19]. This should be done with a cuffed tracheostomy or endotracheal tube in place. Additionally, when a tooth is implicated as the source of infection, it should be extracted. (See "Complications, diagnosis, and treatment of odontogenic infections".)

When needle aspiration or incision and drainage is indicated, samples should be obtained for Gram stain and cultured for both aerobic and anaerobic microorganisms. (See 'Diagnosis' above.)

COMPLICATIONS — As noted above, airway compromise is a potential complication of Ludwig angina and requires careful monitoring and rapid intervention for prevention of asphyxia or aspiration pneumonia. (See 'Airway management' above.)

Mediastinitis is a rare complication resulting from spread into the parapharyngeal space and from there to the retropharyngeal space and the superior mediastinum [6]. Mortality associated with descending necrotizing mediastinitis can reach 40 percent [29]. Other complications include cervicofacial necrotizing cellulitis, pericarditis, carotid artery rupture, jugular vein thrombosis, pleural empyema, pneumonia, and acute respiratory distress syndrome [3,30,31]. (See 'Mechanisms of spread' above.)

PROGNOSIS — With the combined use of systemic antibiotics and aggressive surgical intervention in selected patients, the mortality rate for Ludwig angina has declined dramatically from over 50 percent in the preantibiotic era to 0 to 4 percent [6,32].

SUMMARY AND RECOMMENDATIONS

●General overview − Ludwig angina is a bilateral infection of the submandibular, sublingual, and submental spaces that begins in the floor of the mouth, most commonly due to an infection of the second or third mandibular molar teeth. It is an aggressive, rapidly spreading "woody" or brawny cellulitis without lymphadenopathy. Airway compromise is a potential complication and requires careful monitoring and rapid intervention for prevention of asphyxia and aspiration pneumonia. (See 'Definition' above and 'Mechanisms of spread' above and 'Complications' above.)

●Anatomic considerations − The submandibular space is bordered anteriorly by the mandible, superiorly by the mylohyoid muscle, inferiorly by the hyoid bone, medially by the anterior belly of the digastric muscles, and laterally by the mandible as well. The sublingual space is superior to the submandibular space and separated by the mylohyoid muscle. However, the posterior portions of the submandibular and sublingual spaces are in communication with each other, which allows for the contiguous spread of infection within the fascial spaces. The submental space is located antero-inferiorly to the submandibular space and is separated by the anterior digastric muscle (figure 1). (See 'Anatomic considerations' above and 'Mechanisms of spread' above.)

●Microbiology − Ludwig angina is typically a polymicrobial infection. The most common organisms implicated in deep neck space infections of odontogenic origin are viridans streptococci (including Streptococcus anginosus) and oral anaerobes. Gram-negative aerobes may also play a role in immunocompromised patients and in pediatric patients. Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), may also be involved in pediatric patients as well as immunocompromised patients and others with specific risk factors. (See 'Microbiology' above.)

●Clinical features  

•Patients typically present with fever, chills, and malaise, as well as mouth pain, stiff neck, drooling, and dysphagia, and may lean forward to maximize the airway diameter. They may have a muffled voice or be unable to speak at all. As the illness progresses, breathing may become difficult; stridor and cyanosis are considered ominous signs. (See 'Clinical features' above.)

•On physical examination, patients have tender, symmetric, and "woody" induration, sometimes with palpable crepitus, in the submandibular area. The mouth is held open by lingual swelling. The floor of the oral cavity is usually elevated, erythematous, and is tender to palpation. (See 'Clinical features' above.)

●Diagnosis − The diagnosis of Ludwig angina is established based on the presence of suggestive clinical findings, usually with the support of imaging studies. (See 'Diagnosis' above.)

•Diagnostic imaging − Computed tomography is the imaging modality of choice for the diagnosis of Ludwig angina. Magnetic resonance imaging is an alternative modality but should be avoided in emergencies and when airway compromise is of concern. (See 'Diagnostic imaging' above.)

•Microbiologic evaluation − Blood cultures should be obtained in patients with Ludwig angina. Needle aspiration may be attempted if a well-defined fluid collection is identified radiographically. When needle aspiration or incision and drainage are indicated, samples should be obtained for Gram stain and both aerobic and anaerobic culture. (See 'Microbiologic evaluation' above.)

●Treatment

•Airway management − While 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. (See 'Airway management' above.)

•Selection of antibiotic regimen − Patients with Ludwig angina should be treated empirically with intravenous antimicrobial agents that have broad-spectrum activity against oral flora aerobes and anaerobes. The appropriate regimen depends on the immune status of the patient and risk factors for MRSA (table 3).

-For immunocompetent patients, we prefer regimens with activity against streptococci and other oral aerobes and anaerobes. For adults with risk factors for MRSA and for pediatric patients, we prefer the addition of an agent with activity against MRSA (eg, vancomycin, linezolid). (See 'Immunocompetent patients' above.)

-For immunocompromised patients, empiric therapy should have additional activity against Pseudomonas aeruginosa and MRSA. (see 'Immunocompromised patients' above).

•Duration of antibiotic therapy − In general, antimicrobial therapy should be continued for two to three weeks until clear evidence of clinical improvement is present, and fever and leucocytosis have subsided. Longer courses are required when complications (eg, abscess, Lemierre syndrome) are present. (See 'Duration' above.)

•Surgical intervention − If the patient is not responding adequately to antibiotics alone after this initial period or if fluctuance is detectable, we repeat computed tomography imaging to look for an abscess. If a collection is observed on imaging, needle aspiration or a more formal incision and drainage procedure under general anesthesia should be performed. Likely sources, such as infected teeth, should be addressed concurrently. (See 'Surgery' above.)