INFECTIONS OF THE UPPER RESPIRATORY TRACT

General Goal: To know the major cause(s) of these diseases, how they are transmitted, and the major manifestations of each disease.

Specific Educational Objectives: The student should be able to:

1. recite the common cause(s) of these disease.

2. describe the common means of transmission.

3. describe the major manifestations of this infection.

4. describe how you diagnose, treat and prevent this infection.

Reading: DL Kasper and AS Fauci, 2013. Harrison's Infectious Diseases, Chapter 17. 2nd Edition. Pg. 192-206 McGraw Hill Education, New York

Lecture: Dr. Neal R. Chamberlain

Acute Rhinosinusitis and Rhinocerebral Mucormycosis

Acute rhinosinusitis is defined as inflammation or infection of the mucosa of the nasal passages and at least one of the paranasal sinuses that lasts no longer than 4 weeks. Rhinosinusitis occurs in about 32 million people each year in the US. Rhinitis and sinusitis usually coexist and, therefore, the medical terminology has changed from sinusitis to rhinosinusitis.

Etiology

Most cases of acute rhinosinusitis are due to respiratory viruses (98-99.8%), which include rhinovirus, parainfluenza virus, respiratory syncytial virus, and adenovirus. However, acute rhinosinusitis can occasionally be complicated by a bacterial infection and is diagnosed as acute bacterial rhinosinusitis. The two most common causes of community-acquired acute bacterial rhinosinusitis are Streptococcus pneumoniae and nontypeable Haemophilus influenzae. The bacteria listed in Table URI-2 cause over 70% of the infections of the paranasal sinuses.

Rhinocerebral mucormycosis- Immunocompromised patients (e.g., diabetic patients with ketoacidosis, transplant recipients) can acquire an invasive, life-threatening fungal infection called rhinocerebral mucormycosis. The most common genera found in human infections are Rhizopus, Mucor, and Rhizomucor. Cunninghamella, Lichtheimia (formerly called Absidia), Saksenaea, and Apophysomyces are genera that less commonly cause this infection.

Manifestations

Acute rhinosinusitis- is characterized by mucosal inflammation of both the nose and the paranasal sinuses. Symptoms include sneezing, rhinorrhea, nasal congestion and postnasal drip, aural fullness, facial pressure and headache, sore throat, cough and fever, and myalgias. A viral upper respiratory tract infection usually precedes acute bacterial rhinosinusitis, and differentiating between a bacterial and a viral infection is difficult.

In rare cases, patients with advanced frontal rhinosinusitis may present with Pott’s puffy tumor. A soft tissue swelling and pitting edema over the frontal bone from a subperiostal abscess.

Rhinocerebral mucormycosis- Patients initially present with signs and symptoms of rhinosinusitis. However, in a few days the disease progression indicates a more serious infection. In addition to the manifestations of rhinosinusitis the patient may present with bloody nasal discharge, dusky or necrotic turbinates, and changes in mental state. The black eschar of the palate (necrotic hard-palate lesions that respect the midline) is a hallmark of this disease unfortunately; if no treatment begins before this the patient’s prognosis is poor. Earlier changes in the palate should be looked for: discolored or hyperemic areas of the palata. If the orbit is infected patient may have diplopia, decreased ocular motion, chemosis, and late in the disease proptosis and ptosis. The organism may also get into the brain producing abscess. The signs and symptoms vary depending on the part of the brain that is infected.

Epidemiology

Rhinosinusitis

• Results in millions of office visits each year.
• Respiratory viruses cause most cases of acute rhinosinusitis. Symptoms usually resolve within 5–7 days, and most people recover without medical treatment.
• Infection of the sinuses may follow the common cold, dental extractions, rhinitis due to allergies, and forcing water into the sinuses by jumping into water.
• Infections of the sinuses develop most often during winter months when the common cold occurs more frequently.
• In approximately 2% of adults and 10% of children, acute bacterial rhinosinusitis can follow acute viral rhinosinusitis, allergic rhinitis, or other upper respiratory tract infections.
• Table URI-3 contains many of the predisposing factors that cause individuals to be more likely to develop acute bacterial rhinosinusitis.
• Patients with hospital-acquired infections are more likely to be infected with gram-negative organisms when they develop acute bacterial rhinosinusitis.
• Anaerobic acute bacterial rhinosinusitis infections are usually associated with dental infections or procedures.

Rhinocerebral mucormycosis

• A very rare disease.
• Occurs in immunocompromised patients that include diabetic patient with ketoacidosis, transplant recipients, patients with hematologic malignancies, and patient on chronic glucocorticord or deferoxamine therapy.
• Until the 1950s, this disease almost always was a fatal disease. Permanent residual sequelae of the disease occur up to 70% of the time. Sequelae include blindness and cranial nerve defects.
• Mortality rates of are from 30-70%. The mortality rate in diabetic patients appears to be lower than in nondiabetic patients and in patients with intracerebral involvement. Patients who have been treated with amphotericin B and who have had surgery to debride the infected areas are more likely to survive.
• Survival rates are highest when the interval from diagnosis to treatment is less than 6 days.

Pathogenesis

Rhinosinusitis- The most common precursor to acute bacterial rhinosinusitis is a viral upper respiratory tract infection followed by sinus obstruction from the mucosal edema of inhalant allergies and by anatomic factors (e.g., nasal polyps). Obstruction of the paranasal sinusal ostia impedes drainage of mucus secretions. Bacteria then grow in these secretions, irritating the underlying mucosa and producing more secretions. Death and sloughing of the mucosal cells occurs. The cells will regenerate after the infection has cleared.

Rhinocerebral mucormycosis- The spores from these fungi are in the soil and air and enter through the mouth and the nose. The spores attach to the nasal or oral mucosa where massive spore germination occurs. Individuals who are immunocompetent produce phagocytes that will phagocytize these spores and they do not develop the disease. In immunocompromised patients their phagocytes aren't able to phagocytize the spores quick enough. This allows the spores the time they need to germinate and form hyphae. The hyphae then get into the blood vessels. The hyphae invade the nasal cavity and maxillary sinuses. Rhizopus organisms have an enzyme, ketone reductase, which allows them to thrive in high glucose, acidic conditions. Serum from patients with diabetic ketoacidosis stimulates growth. Deferoxamine is used to treat iron overload in patients receiving multiple blood transfusions. Deferoxamine chelates iron and deferoxamine-iron chelate, called feroxamine, is a siderophore for the species Rhizopus, increasing iron uptake by the fungus. This stimulates fungal growth and leads to tissue invasion. If the organisms get into the ethmoid sinuses the orbital regions can be affected. Intracranial spread can occur through the ophthalmic artery, superior fissure, or cribriform plate. The fungi invade the blood vessel lumina and cause thrombosis through inflammatory occlusion. Areas of ischemic infarction and necrosis will then appear in the infected tissue. Death may occur within 2 weeks if untreated or unsuccessfully treated.

 Diagnosis

Diagnosis of acute rhinosinusitis is based on the patient’s clinical signs and symptoms. Acute bacterial rhinosinusitis is correctly diagnosed about half the time based on clinical impressions. Acute bacterial rhinosinusitis and viral rhinosinusitis are difficult to differentiate because no single clinical finding can accurately distinguish between acute viral rhinosinusitis and acute bacterial rhinosinusitis. Acute bacterial rhinosinusitis, however, is more likely to become a chronic disease.

A diagnosis of acute bacterial rhinosinusitis is likely when an adult patient has moderate symptoms of rhinosinusitis that persists beyond 7 days or severe symptoms of any duration including unilateral/focal facial swelling or tooth pain. A diagnosis of acute bacterial rhinosinusitis is likely when a child has moderate symptoms of rhinosinusitis for longer than 10-14 days or severe symptoms of any duration that include fever (> 39°C or >102°F), unilateral/focal facial swelling or pain. Other signs and symptoms considered to be severe and more likely to be due to a bacterial pathogen include;

• persistent fever
• altered mental status
• diplopia
• infraorbital hypesthesia. 

Rhinocerebral mucormycosis- Clinical signs and symptoms are important in making the diagnosis. Culture and microscopic examination of biopsy samples are critical in making an accurate diagnosis. Significant amounts of tissue is needed therefore swabs are insufficient. Growth of the organisms is seen in 2 days and identified using microscopic techniques.

Therapy

Rhinosinusitis

Several different treatments can be employed to aid the patient in recovery. Symptomatic treatment is recommended for patients with acute viral rhinosinusitis; however, if a patient has acute bacterial rhinosinusitis, symptomatic and antibiotic treatment is recommended.

Symptomatic treatment

• Increase oral hydration with liberal use of nasal saline and steam to promote drainage.
• Antipyretics, analgesics (e.g., acetaminophen), and decongestants (e.g., oxymetazoline, phenylephrine, and naphazoline) may be needed for fever, headache, and facial pain.
• Mucolytics (e.g., guaifenesin) are helpful for thinning thick nasal secretions and especially for postnasal drip.

Antibiotic treatment

Recommendations for initial antibiotic therapy for patients with acute bacterial rhinosinusitis include amoxicillin or amoxicillin-clavulanate. If the patient is allergic to beta-lactam antibiotics, a second- or third-generation cephalosporin can be used, e.g. cefuroxime-axetil, cefdinir or cefpodoxime-proxetil, if the allergy is non-type 1. If it is type 1, then a respiratory fluoroquinolone, levofloxacin or moxifloxacin, or doxycycline can be used.

Cerebral Mucormycosis

Three factors are key to successful treatment:

• Reversal of underlying predisposition (e.g., reverse the diabetic ketoacidosis, minimize use of immunosuppressive mediations)
• Aggressive surgical debridement- removal of all dead tissue and of severely compromised tissue
• Aggressive antifungal therapy- high-dose amphotericin B. Continue treatment up to 3 months after all clinical abnormalities have stabilized. Amphotericin B is nephrotoxic in high doses. Lipid formulations of this drug can achieve higher concentrations in the infected tissue than traditional formulations with less damage occurring to the patients’ kidneys (less than 50% nephrotoxicity).

Prevention

No vaccines are available that prevent acute viral or bacterial rhinosinusitis; however, some patients can avoid future problems by

• Good management of their allergies
• Not getting Influenza (get the flu vaccine) or the common cold (avoid hand to hand contact with ill in winter)
• Avoiding jumping in water without plugging the nose.
• Have septal deviations and polyps or foreign bodies surgically removed.
• Practice proper dental management.

Rhinocerebral mucormycosis can be prevented by encouraging diabetic patients to maintain good control over their serum glucose levels.