The pathogenicity of any member of the oral microbial community is challenged by the local and systemic defense mechanisms the host possesses. The most basic of these defenses is intact oral mucosa. The integrity of the mucosal surface can be breached by trauma or due to ulcerations related to chemotherapy for systemic cancer or radiation therapy used in the treatment of head and neck malignancies. The long-term use of certain medications, such as methotrexate, can cause ulcerative stomatitis or mucositis, allowing for invasion of pathogens. Ulcerative lesions caused by prostheses (e.g., partial or complete dentures) disrupt the continuity of the mucosal surface, as can accidental trauma during tooth brushing, retraction, or tissue manipulation during dental procedures. Regardless of the cause, an ulcerated mucosal surface provides the oral microbial community with access for local, regional, and even systemic dissemination.

Bacterial infections in the oral and maxillofacial complex are usually polymicrobial in nature. Odontogenic infections composed solely of anaerobic bacteria comprise about 50% of all odontogenic infections, while mixed infections (both aerobic and anaerobic bacteria) account for 44%, and 6% feature only aerobic bacteria [9]. The most common bacterial species involved in odontogenic infections are anaerobic gram-positive cocci such as Peptostreptococcus and Streptococcus milleri. Gram-negative anaerobic rods such as Bacteroides (Prevotella) are also associated with odontogenic infections [10].

Bacterial odontogenic infections progress through several stages of development [9]. The first stage, inoculation, involves bacterial access to the facial spaces from the periapical region of necrotic teeth or from deep periodontal pockets. Aerobic bacteria predominate during this stage. The patient experiences minimal discomfort, and the overlying oral mucosa have a soft, doughy consistency on palpation.

There are many viral infections that can affect the oral cavity and adjacent structures. The virulence of these pathogens varies widely and can be particularly severe in the immunosuppressed patient. Unlike bacterial or fungal pathogens, viruses cannot replicate on their own and most do so within the living cells of a host organism. The entire virus particle is called a virion, which is protected by an outer protein shell called a capsid. The inner core of ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) is generally the means by which host cells are infected. The type of cell the virion will infect is encoded by the capsid.

Dental caries are not the only means by which pathogenic bacteria have access to pulpal tissues. Dentinal tubules that are exposed due to gingival recession, cracks and fractures of enamel that extend into the dentin, micro-leakage around existing restorations, and traumatic injuries to teeth all provide pathogenic bacteria access to pulpal tissues. Accessory or lateral canals of the root canal system can be contaminated with bacteria when a periodontal pocket with its own pathogenic bacteria extends to their level. This can lead to pulpal necrosis of a tooth that is without caries or any prior restorations.

Pulpal infections vary in their bacterial composition, but some species have been more frequently associated with their development. Within the oral cavity, anaerobic bacteria predominate over aerobic bacteria, and this proportion is usually maintained in odontogenic infections involving the pulpal tissues. Although the metabolic needs for oxygen vary among the bacteria of the oral cavity, aerobic bacteria consume the available oxygen supply and creates an environment conducive to the growth of facultative or strict anaerobes, respectively. As such, the most common micro-organisms associated with endodontic infections are polymicrobial in composition and feature strict or facultative anaerobic bacteria as the majority component and aerobic bacteria in the minority. The most common gram-negative, strictly anaerobic bacteria isolated from endodontic infections are Prevotella intermedia, Fusobacterium nucleatum, Porphyromonas endodontalis, P. gingivalis, and Selenomonas sputigena; common facultative anaerobes include the gram-positive Streptococcus viridans and S. anginosus groups [27,28]. Individual variances in the bacterial composition of the microflora of the oral cavity, differences in the proportions of the bacteria among pulpal infections, and the degree of immunocompetence of the host further complicate the ability to determine the specific role of isolated bacterial species in the progression of pulpal pathology. Pulpal infections should be treated promptly, as pathogenic bacteria that exit the apical foramen can then perforate the bone and extend locally, regionally, and even systemically to cause sepsis.

The most common acute periodontal infection is periodontal abscess. An abscess is an abrupt exacerbation and pathogenic expression of the bacteria that cause chronic periodontal disease. Periodontal abscesses are the third most common dental emergency, accounting for approximately 7% to 14% of all emergency visits [29]. These infections present as acute local inflammation with swelling in the marginal and attached gingiva that can extend into the alveolar and buccal mucosa. Examination of these lesions reveals bleeding upon probing and suppuration. The affected tissues are intensely erythematous, often with lymphadenopathy and an elevated temperature. Pain can range from mild to severe (though significant pain is rare), and the inflammation and subsequent pressure exerted upon the periodontal ligament can produce the sensation that the tooth is mobile or that is the only tooth to be in occlusion. The affected gingival tissue is indurated (firm) in the initial stages and fluctuant in the latter stages. Spontaneous drainage can occur, after which an asymptomatic draining chronic fistula may develop. Drainage is often through the pocket. If a sinus tract is present, it should be explored.

The mandibular anterior teeth are most commonly involved in a periodontal abscess, followed by the maxillary anterior teeth and the mandibular molars [30]. A decrease in host defense or an increase in the number of pathogenic bacteria in the gingival sulcus and periodontal pocket can precipitate the development of an abscess. Other possible causes of periodontal abscess include occlusion of the gingival sulcus (preventing drainage) and root planing and scaling procedures that cause calculus to become dislodged and forced into the tissue. Periodontal abscesses that develop in patients without periodontal disease are usually the result of trauma. The introduction of a foreign body such as a popcorn kernel, a piece of a toothpick, a detached bristle of a toothbrush, or a detached piece of floss into the depth of the gingival sulcus can stimulate an inflammatory response that culminates in the formation of a periodontal abscess. Foreign materials introduced into the gingival sulcus and not removed after dental procedures, including excess dental cement, impression material, or small pieces of restorative material (e.g., amalgam or composite resin), may cause an iatrogenic periodontal abscess.

The clinical presentation of pericoronitis is characterized by a highly inflamed and erythematous operculum and contiguous mucosa. This can be exacerbated if the opposing tooth has drifted and traumatized the operculum. Bacterial species that have been isolated from pericoronitis include viridans streptococci, spirochetes, Fusobacterium, Prevotella intermedia, and Peptostreptococcus micros [33]. Pain can radiate toward the ear and the angle of the mandible. Pus may accumulate beneath the operculum and may drain spontaneously or after gentle pressure is applied. Fistulous tracts usually do not develop due to the acute nature and rapid development of the infection. Patients often have halitosis due to the presence of stagnated debris and pus. Edema in the contiguous tissues can interfere with the functional excursions of the mandible, and a soft diet may be required if the ability to masticate is compromised. Most occurrences of pericoronitis remain localized, but extension of the edema into adjacent fascial spaces, such as the masticator space or toward the pharynx, may cause a compromised airway. As such, these infections should be monitored carefully until they resolve.

There are no significant differences in the pathogens responsible for periodontal disease in patients with immunocompromising conditions compared to those without [35]. It is only the progressive immunosuppression of the host that permits a greater degree of virulence and acceleration of the involvement of the gingival tissues and of the alveolar bone.

Linear gingival erythema (LGE) is the most common periodontal disease in patients with HIV, but it can occur in any person with a compromised immune system [36]. LGE features a distinct erythematous band that involves the marginal gingiva, and it can develop without the presence of plaque or calculus and can be localized or generalized.

Unlike gingivitis in healthy patients, LGE does not respond to conventional periodontal treatment and does not improve with a meticulous at-home oral hygiene regimen. Gingival tissues affected by LGE may bleed easily and can be tender during brushing and flossing, but significant symptoms are usually absent. An increasing amount of evidence supports a fungal origin for LGE (specifically Candida spp.), and it has been classified as a disease of fungal etiology by the American Academy of Periodontology [37]. Treatments such as root planing and curettage do not eradicate the inflammation and erythema of LGE. Instead, treatment usually consists of the use of an antimicrobial mouth rinse (e.g., one-half ounce of 0.12% chlorhexidine for two weeks) or vacuum-formed trays loaded with antifungal medication placed against the affected gingival tissues. Increasing the dose or frequency of administration may be necessary [38]. A systemic antifungal medication, such as ketoconazole, fluconazole, or itraconazole, may be used in recalcitrant cases, but it should be used with caution, as they have many potential interactions with other medications.

Like LGE, acute necrotizing ulcerative periodontitis (NUP) primarily affects patients who are immunosuppressed, although it is also associated with heavy tobacco use and poor hygiene. In severely immunocompromised patients, such as those with AIDS, the development of NUP is associated with a 73% cumulative probability of death within two years of the diagnosis [38]. Compared with the slow progression of periodontal disease in immunocompetent patients, NUP features a rapid onset accompanied by severe pain. The gingival tissues necrose, followed by a rapid loss of the periodontal attachment and resorption of the alveolar bone. The destruction of the gingival tissues can lead to the exposure of the alveolar bone, which undergoes necrosis and subsequent sequestration. The formation of deep periodontal pockets characteristic of periodontal disease in healthy patients is not present in cases of NUP, as the junctional epithelium itself becomes necrotic. The necrotic tissues cause severe halitosis, and patients complain of deep, radiating jaw pain [38].

All patients with NUP should be prescribed an analgesic that is appropriate for their degree of pain. In addition, they may require liquid nutritional supplements, as the pressure generated on the teeth, the attached gingival tissues, and the mucosa can cause pain that interferes with the ability to chew and to eat properly [38]. The use of an antimicrobial mouth rinse can topically reduce the pathogenic microbial population. Chlorhexidine gluconate has substantivity, which promotes its retention on the teeth and soft tissues and prolongs its antimicrobial action for an extended period. Alcohol-free preparations (e.g., Paroex) are available from most manufacturers and should be used to avoid desiccation and irritation of the tissues [38]. When antibiotic treatment is used, metronidazole is the drug of choice and can be given at a dose of 250 mg four times a day or 500 mg twice daily for 7 to 10 days. Patients who cannot tolerate metronidazole may be prescribed clindamycin 150 mg four times per day or amoxicillin-clavulanate 875 mg twice daily for 7 to 10 days, if these medications are compatible with their medical history [40]. The selection and administration of any of these medications will depend on the severity of the disease and the patient's medical history. Debridement of the necrotic soft tissue and any sequestrations of bone is accomplished under local anesthesia [38].

There are several points to consider when prescribing penicillin. First, approximately 5% to 7% of the population is allergic to penicillin and must rely on different antibiotics for the treatment of odontogenic infections [41]. In addition, drug-drug interactions are a concern. The anticoagulant effect of warfarin can be enhanced when penicillin V is used concurrently, so an alternate antibiotic or adjustment of the warfarin dose should be considered. The effectiveness of oral contraceptives can be decreased when penicillin V is used simultaneously, and another means of contraception should be used for the duration of treatment [42]. Finally, the use of penicillin V should be modified or avoided in patients with renal impairment, as all beta-lactam antibiotics are actively secreted by the renal tubules and the majority is eliminated in an unchanged form in the urine [43].

The most serious adverse effects of clindamycin use are Clostridioides difficile-associated diarrhea and pseudomembranous colitis, caused by the overgrowth of C. difficile in the gastrointestinal tract [47]. Therefore, patients with a history of colitis should not use clindamycin.

The clinical presentation of oral candidiasis can vary. Acute pseudomembranous candidiasis appears as white to yellow-white plaques that are easily removed from the involved area and that leave an erythematous or bleeding surface. Acute erythematous candidiasis features painful red lesions, most frequently on the buccal mucosa, the palate, or the dorsum of the tongue that cannot be removed [49,50]. Chronic hyperplastic candidiasis is characterized by white lesions that cannot be removed by gentle scraping. Angular cheilitis is a fungal infection localized to the radiating fissures at the corner of the mouth. Oral candidiasis is more virulent and has a higher degree of morbidity when it occurs in patients who are immunosuppressed.

Although candidiasis is the most common oral fungal infection, the risk of other fungal infections appears to be growing, likely the result of a larger immunocompromised population and increased international travel and globalization [54]. Fungi that may cause disease in humans with oral manifestations include Aspergillus spp., Blastomycesdermatitidis, Coccidioides immitis, Cryptococcus neoformans, and Histoplasma capsulatum. In the United States, the most common sources of these mycoses are contaminated soil and decomposing plants. However, there have been reported cases of introduction of Aspergillus into the sinuses following perforation of the dental root cavity during a molar root canal [55].

The classic presentation of recurrent herpes labialis is of small, fluid-filled blisters that coalesce to form larger vesicles at the junction of the skin and the lip. Patients may experience fever, anorexia, listlessness, and gingivitis, which is the most striking feature with markedly swollen, erythematous, friable gums [57]. Most patients have a prodromal sensation of burning, itching, or tingling before the emergence of the actual lesions [56]. The lesions form scabs and heal without scarring in one to two weeks in the healthy patient, but healing time can extend for several weeks in patients who are immunocompromised.

The human herpesvirus 4, or Epstein-Barr virus, is the causative agent of infectious mononucleosis. In the years since the emergence of HIV/AIDS, EBV has also been associated with the development of the opportunistic oral lesion oral hairy leukoplakia. Oral hairy leukoplakia is a marker of any generalized immunosuppression, but it is most closely associated with HIV/AIDS [61]. These lesions feature bilateral, nonremovable hyperplastic tissue with a corrugated texture that appears on the lateral surface of the tongue. Replication of EBV in the epithelial cells causes hyperplasia along the lateral surface of the tongue, assuming a "hair-like" appearance. These lesions are asymptomatic and usually discovered during a routine oral examination [61]. Antiviral agents such as acyclovir can cause the lesions to regress, but cessation of the antiviral therapy prompts their return. In patients with HIV/AIDS, the appearance of oral hairy leukoplakia marks a point of progressive immunosuppression and poor prognosis for the patient's long-term survival [61].