Unusual Case of Ludwig Angina Caused by in an Immunocompromised HIV-Positive Patient with Alcoholism and Dental Abscess

Background

Ludwig angina is a cellulitis of the submandibular, submental, and sublingual regions, which can progress quickly [1]. Rapid identification of the disease and accurate treatment of its underlying cause, therefore, become vital components of proper management and reduced morbidity and mortality [1]. Typical clinical presentation of Ludwig angina can include painful neck swelling, tooth pain, dysphagia, dyspnea, fever, tongue protrusion, tongue elevation, and malaise [1]. Prior to initiating antibiotic treatment or surgery, the patient’s airway must be secured, as airway compromise is the leading cause of death for this disease [1]. After securing the patient’s airway, the criterion standard of imaging for evaluation of disease severity is computed tomography (CT) [1]. Typical CT findings of Ludwig angina of the neck can include muscle edema, focal fluid collections, gas in the soft tissue space, thickening of the soft tissues, and increased attenuation of the subcutaneous fat [2]. Management consists of broad-spectrum antibiotic coverage, possible surgical drainage of the infection site for suppurative infection, and close airway monitoring [2,3].

Previously, the mortality rate of Ludwig angina was 50%, but modern advancements in antibiotics, imaging, and surgical techniques have reduced the mortality rate to 8% [1]. However, comorbidities associated with the development of further complications include diabetes mellitus and HIV infection [4]. One such complication is infection with rare pathogens, such as Clostridium sporogenes. There are previously reported cases of C. sporogenes leading to diseases such as gas gangrene, empyema, septic arthritis, pyogenic liver abscesses, bacteremia, and septicemia [5–16]. Here, we discuss the case of a 49-year-old HIV-positive man with a history significant for polysubstance abuse and poor dental hygiene leading to a lower molar tooth abscess presenting with Ludwig angina due to C. sporogenes.

Case Report

A 49-year-old man presented to the Emergency Department with concerns of severe left molar pain, fever, and worsening neck swelling for 5 days. At the time of presentation, the patient confirmed foul-tasting drainage in his mouth, congestion, sore throat, cough, shortness of breath, neck pain, intermittent fevers, and chills. His past medical history was significant for AIDS, which was not treated with antiretroviral therapy, poly-substance abuse, and depression. He tested HIV-positive 6 years prior to presentation and had remained compliant with his prescribed combined emtricitabine, rilpivirine, and tenofovir alafenamide (Odefsey) until he ran out 2 months prior to presentation and was unable to afford refills. His polysubstance abuse consisted of smoking 0.25 packs of cigarettes daily, frequent cocaine and marijuana use, and weekly intake of 60 cans of beer and 3 shots of liquor. No other significant comorbidities were noted in his past medical history. His family history was unremarkable.

Physical examination was positive for muffled voice quality, poor dentition, minimal ability to open his mouth, severe pain on palpation of left posterior molar, and severe swelling, in-duration, and tightness of the anterior neck. There was crepitus on palpation of the area. On initial presentation, the patient was febrile, with a temperature of 38°C, had tachycardia, with a heart rate of 93 beats per min, had tachypnea, with a respiratory rate of 23 breaths per min, and had a blood pressure of 107/67 mm Hg. His oxygen saturation was 95% on room air, and he was not in acute respiratory distress. His initial laboratory test results were significant for leukocytosis, with a white blood cell count of 14.7×103/uL (reference range: 4.4–10.5×103/uL), anemia, with hemoglobin level of 11.7 g/dL (reference range: 11.4–14.7 g/dL), hyponatremia, with sodium level of 125 mmol/L (reference range: 136–145 mmol/L), and an acute kidney injury, with a blood urea nitrogen level of 41 mg/dL (reference range: 7–25 mg/dL) and creatinine level of 1.59 mg/dL (reference range: 0.60–1.20 mg/dL). His lactate level was within normal limits, and his viral respiratory panel was negative. His absolute clusters of differentiation 4 (CD4 T cell) count was 260.56 cells/uL (reference range: 492.00–1656.00 cells/uL), and his HIV viral load was 109 000. Due to concern for infection, blood cultures were drawn on initial presentation.

Computed tomography (CT) of the neck was positive for extensive subcutaneous emphysema of the left sublingual space, extending inferiorly to the bilateral submental regions and diffusely along the fascial planes of the anterior neck down to the level of the anterior superior mediastinum. There was no evidence of a discrete walled-off fluid collection. A dental cavity with associated periapical lucency involving the posterior-most left mandibular molar with evidence of cortical breakthrough of the lingual cortex was also seen and noted as a possible source of infection (Figure 1).

Based on the above findings, a diagnosis of Ludwig angina with extensive bilateral deep soft tissue edema of the neck with emphysema secondary to a dental abscess was made. He was taken urgently by the Oral Maxillofacial Surgery Department for incision and drainage of the bilateral neck fascial space, extraction of the third molar on the lower left side (tooth #17), and excision of any abnormal appearing or inflamed mandibular bone surrounding tooth #17. Perioperatively, incision of the left submandibular region and subsequent blunt dissection revealed left submandibular and sublingual abscesses, which were cultured, and sublingual fluid loculations along the subperiosteal plane of the lateral and medial cortices of the mandibular bone. Additional incisions and blunt dissection toward the inferior border of the mandible and the anterior neck revealed abundant purulent drainage in the bilateral sub-mental, left submandibular, left sublingual, and anterior neck spaces. Abnormal-appearing bone surrounding tooth #17 was excised. Three drains were placed in the left sublingual space, anterior neck, and submental space. He was then started on vancomycin, ceftriaxone, and clindamycin but his treatment was later de-escalated to ampicillin/sulbactam and vancomycin per the recommendations of the Infectious Disease team. He was also started on antiretroviral therapy, with 200 mg of emtricitabine, 25 mg of rilpivirine, and 25 mg of tenofovir alafenamide (Odefsey). His acute kidney injury and hyponatremia resolved during his stay.

The blood cultures drawn during the patient’s initial presentation took 43 h to identify the causal organism, with 1 culture initially showing anaerobic gram-positive bacilli. On day 6 of hospitalization, 1 of 2 blood cultures grew pan-susceptible C. sporogenes. This result was identified using anaerobic phenylethyl alcohol agar. Further analysis of this positive culture with Filmarray polymerase chain reaction was negative for the 33 most common organisms recovered from blood cultures. The operating room cultures were finalized as normal flora; therefore, vancomycin was discontinued. He was taken back to the operating room on hospital day 7 for further debridement and irrigation, owing to continued purulent drainage and persistent fever with a maximum temperature of 39.4°C. He was found to have good granulating tissue, with no signs of necrosis. He continued ampicillin/sulbactam and tolerated it well until leaving against medical advice on hospital day 13. He was given a prescription for oral amoxicillin/clavulanic acid and Odefsey and instructed to follow up with the Oral Maxillofacial Surgery Department.

Six days later, the patient presented again to the Emergency Department due to continued wound drainage and skin burning in that area. He had not been compliant with his oral antibiotic treatment. CT of the neck revealed diffuse soft tissue edema and inflammatory changes, with an apparent open wound in the left anterior neck. There was also airway effacement, particularly in the region of the oropharynx. No focal walled-off collections were found (Figure 2).

He underwent elective endotracheal intubation due to severe airway compromise, was brought back to the operating room for surgical washout and complex repair of his anterior neck wound, and was found to have healthy granulation tissue in the bilateral neck wound bed with no purulent drainage found. He was then extubated and transferred to the Intensive Care Unit. Repeat blood cultures collected at the time of readmission had no growth. His course was further complicated by alcohol withdrawal seizures requiring emergent tracheostomy due to severe swelling in the posterior oropharynx, leading to the inability to visualize the vocal cords for re-intubation. He also developed severe dysphagia due to this severe oropharyngeal edema, requiring percutaneous endoscopic gastrostomy (PEG) placement. He was treated and cleared for discharge by the Pulmonology Department to a long-term care facility after a prolonged hospital stay.

Discussion

Ludwig angina can be rapidly fatal if not quickly identified and treated, particularly if it is caused by a rare pathogen in an immunocompromised patient. The infection of Ludwig an-gina is typically polymicrobial and is most commonly caused by Viridans streptococci species. Other common causal organisms include staphylococcus species, peptostreptococcus, fusobacterium, bacteroides, and actinomyces [2]. Streptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa were the most commonly isolated gram-positive organisms in patients with comorbid HIV, while Proteus mirabilis, Escherichia coli, and Klebsiella pneumoniae were the most commonly isolated gram-negative organisms [18]. Ludwig an-gina is most commonly odontogenic, but other sources, such as peritonsillar or parapharyngeal abscesses, mandibular fractures, oral lacerations or piercings, and submandibular sialadenitis, have been described [1]. In our patient’s case, the source of his infection was identified to be tooth #17, which was excised along with any abnormal or inflamed mandibular bone surrounding it during surgery. Recommended antibiotic treatment is therefore targeted toward anaerobic and gram-positive organisms with a penicillin and beta-lactase inhibitor plus clindamycin and the possible addition of an aminoglycoside [3].

Our patient did not grow any of the common causal organisms of Ludwig angina in his blood cultures. Instead, he grew C. sporogenes, an anaerobic gram-positive, spore-producing bacillus known to colonize the human gastrointestinal tract and which is very rarely considered pathogenic [5,19]. It was first described in 1908 by Metchnikoff after it was isolated from feces of normal patients and from diarrheal material of patients with chronic colitis [19]. Since then, there have been rare cases of infection caused by the bacterium, confirmed through growth on various cultures, such as blood, pleural fluid, and tissue [5–17]. Because only 1 of 2 blood cultures grew C. sporogenes, we cannot exclude the possibility that the organism grown represented a contaminant. However, the patient did not grow any other microorganism in his cultures, and his improvement after antibiotic treatment indicated that C. sporogenes was the causal organism.

There are very few reported cases of severe infection caused by C. sporogenes [5–17]. In a review of 114 cases of infection caused by Clostridium species, C. sporogenes was isolated in only 3 of them [5]. The cases associated with C. sporogenes included empyema, empyema with draining chest wall abscess, and frostbite [5]. A review of 130 cases of gas gangrene found that C. sporogenes was implicated in only 1 case [15]. An additional review of 136 cases of bacteremia caused by clostridium species found that only 12 were caused by C. sporogenes [16]. C. sporogenes has been implicated in the development of gas gangrene, empyema, septic arthritis, pyogenic liver abscesses, bacteremia, and septicemia [5–17]. To the best of our knowledge, C. sporogenes has not previously been shown to lead to deep neck infections, such as Ludwig angina. Our case is, therefore, the first case of Ludwig angina caused by C. sporogenes to be reported in the modern medical literature.

Several previous case reports of infection caused by C. sporogenes noted an initial presentation of fever, hypotension, or purulent skin wounds [6–9,13,16,17]. Six cases of C. sporogenes were associated with abdominal pain [9,14,16]. A further 4 cases were associated with pleuritic pain [5,10,12], with C. sporogenes having grown in the pleural fluid of these patients. In addition, for 1 patient presenting with septic arthritis, C. sporogenes grew in aspirated joint fluid [11]. Another patient presented with gas gangrene, and C. sporogenes was isolated from tissue culture [17]. After treatment of the infection, 6 of the patients died from complications of the disease, such as myonecrosis, renal failure, and worsening septicemia [6,8,13,14,16]. One patient died 4 weeks later from a likely unrelated cardiac arrest [10]. On the other hand, in 13 cases, the patients tolerated treatment well [7,9,11–13,16,17]. In comparison, our patient presented with typical alarming features of severe infection and was treated rapidly. Despite initially tolerating treatment well, he had a prolonged disease course after leaving our hospital.

Our patient’s course was complicated by his noncompliance with medication upon leaving against medical advice and later tracheostomy and PEG placement due to alcohol withdrawal seizures. It is well documented that alcohol withdrawal seizures are much more likely to lead to tracheostomy and PEG placement [20]. Our patient’s noncompliance with his antibiotics led to a situation in which re-intubation was not possible due to severe edema of the oropharynx, thus necessitating emergent tracheostomy placement. In addition, this same oropharyngeal edema caused our patient to have severe dysphagia, leading to PEG placement. Our patient’s course therefore highlights the extreme importance of the role the patient plays in managing their own care. When faced with an immunocompromised patient whose compliance is in question, it is of the utmost importance for the physician to educate the patient on the possible risks of leaving against medical advice, including but not limited to the possibility of a prolonged and complicated disease course.

It is not clear how C. sporogenes causes pathology [13]. The species has previously been shown to produce a hemorrhagic toxin that has been shown in vitro to primarily target endothelial cells, thus possibly leading to increased permeability or destruction of the capillary wall [19]. However, as previously discussed, C. sporogenes has been isolated from the gastrointestinal tract of healthy individuals and is rarely considered pathogenic [19]. Our patient’s comorbid AIDS contributed greatly to the severity of his presentation and his impressive CT imaging findings. As discussed previously, his disease course was further complicated by noncompliance and later alcohol withdrawal seizures. Patients infected with HIV, in general, have been found to have significantly greater risks for complications, such as sepsis, mediastinitis, jugular vein thrombosis, and pneumonia, than do patients without HIV (odds ratio [OR]=3.60, 95% CI [1.24,10.45]) [18]. HIV-positive patients have also been found to have a greater rate of death (OR=10.18, 95% CI [1.63, 63.06]) and a higher mean duration of hospital stay (OR=3.76, 95% CI [1.40, 6.11]) [18]. Our patient’s severe presentation combined with the extreme rarity of pathology caused by C. sporogenes therefore presents both a diagnostic and management challenge that must especially be considered in patients with comorbid immunocompromised states.

There is no current criterion standard of treatment for C. sporogenes. This makes starting optimal antibiotic treatment in a timely manner extremely difficult, placing patient lives at risk during this time. Previous studies have suggested that penicillins, clindamycin, and metronidazole were among the most effective antibiotics for treating C. sporogenes infection [16]. However, resistance of C. sporogenes to clindamycin has also been reported and should be taken into consideration when choosing antibiotic treatment [9]. Our patient’s excellent response to empiric vancomycin, clindamycin, and ceftriaxone and then subsequent de-escalation to ampicillin/sulbactam indicated that we were able to rapidly identify his underlying problem and optimize his medical care. Rapid identification of Ludwig angina, timely optimal treatment administration, and immediate surgical intervention all contributed to optimizing our patient’s medical outcome, even when his disease course was complicated by treatment noncompliance and a subsequent prolonged hospital stay. This case, therefore, illustrates the importance of broadening differential diagnoses for Ludwig angina in immunocompromised patients and the need for further investigation to develop a criterion standard of treatment addressing seemingly harmless microorganisms that can wreak havoc in such patients.

Conclusions

Most cases of Ludwig angina are caused by pathogenic bacteria, such as Viridans streptococcal species and occasionally staphylococcus and actinomyces. Less pathogenic bacteria have been reported in cases when there are comorbidities affecting the immune response, as in this case in which C. sporogenes was recovered from blood culture. To the best of our knowledge, this is the first reported case of Ludwig angina caused by C. sporogenes. This case highlights the need for rapid diagnosis and evaluation using criterion standard imaging, such as head and neck CT. Quickly choosing the proper target antibiotic regimen is also a mainstay of Ludwig angina treatment and will improve outcomes in all patients, particularly immunocompromised patients who may present with much rarer pathogens causing the disease. Completion of therapy and close follow-up are critical components in the treatment of this infectious disorder, especially in cases of immunocompromise.