50 INFECTIONS OF THE UPPER RESPIRATORY TRACT
Harrison’s Manual of Medicine
INFECTIONS OF THE UPPER RESPIRATORY TRACT
Nose and Face
Ear Pinna and Lobule
External and Middle Ear
Deep Neck Spaces
Most upper respiratory tract infections (URIs) can be treated on an outpatient basis. However, the potential complications of such infections that go untreated or are inadequately treated must be recognized.
NOSE AND FACE
Although the microbiologic etiologies of nasal mucosal infections are diverse, most acute infections at this site manifest as the common cold and are due to rhinovirus, coronavirus, parainfluenza virus, respiratory syncytial virus (RSV), influenza virus, or adenovirus. Treatment is symptom-based and is limited to antihistamines, decongestants, and ipratropium bromide nasal spray. Zinc gluconate lozenges may reduce the duration of symptoms.
Chronic infections of the nasal mucosa include congenital syphilis and infection with Mycobacterium leprae, both of which may present as chronic nasal congestion and saddle-nose deformity. Rhinosporidium seeberi causes obstructing nasal masses requiring surgery. Blastomyces dermatitidis can cause chronic ulcerations. Mucormycosis, a life-threatening infection in pts with neutropenia or diabetic ketoacidosis, presents as black crusts overlying necrotic tissue within the nasal cavity and may extend through to the palate or intracerebral compartment. Microbiologic diagnosis of chronic nasal infections from a tissue sample is usually indicated, and a serologic workup is done if congenital syphilis is suspected. Mucormycosis requires urgent surgical debridement, IV antifungal therapy, and correction of the underlying immunologic or metabolic predisposition.
ETIOLOGY AND PATHOGENESIS Obstruction of ostia in the anterior ethmoid and middle meatal complex by retained secretions, mucosal edema (often caused by an antecedent viral respiratory infection), or polyps promotes sinusitis. Barotrauma and ciliary transport defects also can predispose to infection. Nasal cannulation beyond 48 h is the chief risk factor for nosocomial sinusitis.
Acute bacterial sinusitis occurs in the setting of a viral URI. Only 0.5% of viral URIs are complicated by bacterial superinfection of the sinuses. Acute bacterial sinusitis in children and adults is caused most often by Streptococcus pneumoniae or Haemophilus influenzae (not type b); in children, Moraxella catarrhalis is also an important cause. Staphylococcus aureus and gram-negative organisms are most often involved in hospital-acquired sinusitis. Respiratory viruses are isolated alone or with bacteria in one-fifth of adult cases. In chronic sinusitis, S. aureus or Pseudomonas aeruginosa is often cultured from sinus fluid; however, it is unclear whether these organisms represent colonization or true infection. Pathogens of chronic sinusitis can also include anaerobes. Fungal sinusitis can be noninvasive due to Aspergillus spp. or invasive secondary to Aspergillus spp. or other fungi, including those causing mucormycosis.
CLINICAL MANIFESTATIONS Sinus pain can be dental, retroorbital, supraorbital, or occipital. Facial pain or pressure, nasal congestion, and purulent nasal or postnasal drainage are frequent manifestations of acute bacterial sinusitis. Pain often worsens if the pt bends forward or lies supine. Fever is an insensitive indicator of sinusitis, although it is present in about half of pts with acute maxillary sinusitis. In acute infection, tenderness over the involved sinus may be elicited.
Chronic sinusitis features congestion and postnasal drip but rarely fever, and there is usually a paucity of physical signs. Serious complications include orbital cellulitis, frontal subperiosteal abscess (Pott’s puffy tumor), and intracranial processes such as epidural abscess, subdural empyema, meningitis, cerebral abscess, and septic dural-vein (including cavernous sinus) thrombophlebitis.
DIAGNOSIS Nasal cultures are not useful. Acute sinusitis is usually diagnosed on the basis of a history of prolonged cold symptoms. Plain radiographs of the sinuses may show opacification, air-fluid levels, or mucosal thickening of ³4 mm, although CT is much more sensitive, especially for diagnosis of ethmoid and sphenoid disease. MRI or magnetic resonance angiography (MRA) is usually indicated in the evaluation of intracranial or vascular complications.
Reestablishment of ostial patency and bacterial eradication are the goals of therapy for acute bacterial sinusitis. Humidification, hydration, and use of vasoconstricting drugs (but not antihistamines) are indicated. Amoxicillin (500 mg tid) or trimethoprim-sulfamethoxazole (TMP-SMZ, 160/800 mg bid) may be effective for first-time cases; more expensive alternative agents include amoxicillin/clavulanate (40 mg/kg PO qd divided tid, up to 500 mg per dose) or a second-generation cephalosporin (e.g., cefuroxime axetil, 250 mg bid for pts >2 years old and 125 mg bid for pts <2 years old). Treatment should be administered for 1 to 2 weeks. Empirical therapy for nosocomial sinusitis should focus on S. aureus and gram-negative rods with nafcillin (2 g IV q4h) plus ceftriaxone (2 g IV qd) and should be tailored on the basis of sinus-fluid culture results. Therapy for chronic sinusitis is best guided by intraoperative culture results, with careful attention paid to adequate sinus drainage. Fungal sinusitis is best treated with surgical debridement and IV antifungal therapy.
Treatment of the complications of sinusitis (e.g., orbital cellulitis and orbital abscess, Pott’s puffy tumor, and intracranial suppurative complications) includes adequate drainage if indicated and at least 2 weeks of antibiotic treatment based on the organisms recovered. Treatment for osteomyelitis (6 weeks of IV antibiotic therapy after adequate surgical debridement) is indicated for Pott’s puffy tumor.
Outpatient and Home Care Considerations Most persons with bacterial sinusitis may be treated as outpatients with oral antibiotics. Severe disease (i.e., sinusitis with complications or systemic toxicity) should be treated with IV antibiotics. Adjunctive surgery to widen ostia and drain thick secretions may be necessary in severe cases or when disease fails to respond to initial IV therapy.
EAR PINNA AND LOBULE
Auricular cellulitis presents as a tender swollen pinna and lobule, most commonly due to S. aureus or Streptococcus spp., and is treated with nafcillin (1–2 g IV q6h) or cefazolin (1 g IV q8h). Perichondritis is associated with tenderness of the pinna, spares the lobule, is usually due to P. aeruginosa or S. aureus, and should be treated with IV ticarcillin/clavulanate (3.1 g q4–6h) or IV nafcillin (plus oral ciprofloxacin) for at least 4 weeks. These infections must be distinguished from relapsing polychondritis.
EXTERNAL AND MIDDLE EAR
ETIOLOGY AND PATHOGENESIS A viral URI, which can cause edema of the eustachian tube mucosa, often precedes or accompanies episodes of acute otitis media (AOM). Mastoid air cells are connected with the middle- ear cavity and thus are involved in otitis media. The incidence of AOM declines with age; the prevalence in adults is only 0.25%. Recurrent episodes of AOM in adults should prompt an evaluation for an anatomic abnormality that impedes eustachian tube drainage, such as a nasopharyngeal or skull base neoplasm. S. pneumoniae, H. influenzae (usually nontypable), and M. catarrhalis are the most common bacterial pathogens in AOM. Early recurrences in children are likely to be reinfections with different organisms or with organisms resistant to previously administered antibiotics. Serous otitis media is characterized by culture- negative middle-ear effusion that typically causes conductive hearing loss.
Untreated acute or recurrent otitis media may lead to chronic otitis with otorrhea from tympanic membrane perforation. Chronic otitis most often yields P. aeruginosa, S. aureus, Klebsiella spp., and aerobic gram-negative rods. Anaerobes, often mixed with aerobes, are implicated in half of cases of chronic otitis media. Tympanic membrane perforation and cholesteatoma are associated with chronic infection.
Otitis externa (OE), or swimmer’s ear, often follows water exposure and is thought to be due to alkalinization of the external canal and consequent bacterial overgrowth. OE is usually due to P. aeruginosa, S. aureus, or Streptococcus spp. In diabetic patients, Pseudomonas causes invasive (“malignant”) OE, which may invade the adjacent skull base.
CLINICAL MANIFESTATIONS AOM causes pain in the affected ear, conductive hearing loss, fever, and a red, bulging, or perforated eardrum. Diagnostic tympanocentesis is indicated for pts who appear toxic or are immunosuppressed. Associated mastoiditis presents as pain, tenderness, and swelling behind the affected ear and, if a subperiosteal abscess is present, can cause inferolateral displacement of the pinna and the development of a red fluctuant mass behind it. Serous otitis media features a dull retracted membrane with fluid. Chronic suppurative otitis media causes painless conductive hearing loss and intermittent purulent ear drainage. OE causes severe pain, typically exacerbated by manipulation of the external ear. Malignant OE usually causes a “deep” pain in the affected ear that is associated with swelling of the external auditory canal and may be associated with a paralysis of cranial nerve VII, IX, X, or XI.
DIAGNOSIS In all suspected ear infections, direct examination of the external ear canal and tympanic membrane is required. In cases of suspected accompanying mastoiditis or bony necrosis from malignant OE, CT is helpful.
The agents used to treat AOM include amoxicillin (500 mg PO tid or 875 mg PO bid); although 25–35% of H. influenzae and M. catarrhalis strains produce b-lactamase, empirical amoxicillin is still successful in routine cases. Amoxicillin/clavulanate (875/125 mg PO bid) and cefuroxime axetil (500 mg PO bid), each given for 10 days, are also commonly used. If penicillin-resistant pneumococci are not detected, TMP-SMZ (160/800 mg PO bid) or clarithromycin (500 mg PO bid) may be used, and levofloxacin (500 mg PO qd) may also be effective in adults. Drainage is indicated for unresolved or recurrent infection. Surgical drainage and placement of tympanostomy tubes have been the mainstay of treatment for chronic otitis media. Uncomplicated OE is treated with topical antibiotics such as polymyxin-neomycin (4 drops qid for 5 days). Complicated or refractory OE requires debridement of the canal. Irrigation is contraindicated. Malignant OE is treated with surgical debridement, antibacterial ear drops, control of coexisting metabolic abnormalities, and a 6- to 8-week course of IV antipseudomonal antibiotics: imipenem/ cilastatin, 500 mg IV q6h; meropenem, 0.5–1 g IV q8h; ciprofloxacin, 500–750 mg PO bid; ceftazidime, 1–2 g IV q8–12h; or cefepime, 1–2 g IV q12h) plus an aminoglycoside. If the recovered Pseudomonas strain is sensitive to quinolones, treatment may be changed to ciprofloxacin (750 mg PO bid for 6 weeks) after an initial 2 weeks of IV combination therapy.
Outpatient and Home Care Considerations Most persons with AOM can be treated as outpatients with oral antibiotics. Severe disease (i.e., with systemic toxicity) should be treated with IV antibiotics; both therapeutic and diagnostic drainage should be undertaken by a surgeon.
Oral anaerobes, especially Prevotella spp., cause gingivitis. Vincent’s angina (acute necrotizing ulcerative gingivitis, trench mouth) is characterized by halitosis and ulcerations of the gingiva. Treatment includes penicillin V (500 mg PO qid) plus metronidazole (500 mg PO q8h) or clindamycin alone (300 mg PO q6h). Streptococci and anaerobes are usually involved in Ludwig’s angina, or cellulitis of the submandibular and sublingual spaces. Surgical debridement may be indicated and airway obstruction can occur. Therapy with IV antibiotics is indicated—e.g., ampicillin/sulbactam (3 g q6h) or penicillin (24 million units per day by continuous infusion or divided q4–6h) plus metronidazole (7.5 mg/ kg q8h)—and should be followed by oral antibiotic treatment once improvement is documented, with a total course of 14 days. Fulminant gangrene of the facial tissues (noma, cancrum oris) commonly involves Fusobacterium nucleatum, classically occurs in malnourished children, and is treated with surgical debridement and IV penicillin (24 million units per day by continuous infusion or divided q4–6h). Cold sores—vesicular lesions affecting the lip, buccal mucosa, or tongue—are commonly due to herpes simplex virus (HSV). Primary HSV infection of the oral cavity can be severe; antiviral treatment decreases symptom severity and time to healing (acyclovir, 400 mg PO tid; famciclovir, 250 mg PO tid; or valacyclovir, 500–1000 mg PO bid, each for 7 to 10 days). Recurrent orolabial HSV infection in an immunocompetent pt does not require antiviral therapy; in immunocompromised pts antiviral therapy for 7–10 days is indicated. A burning tongue or sore throat in an immunocompromised person should raise suspicion of thrush due to Candida spp. (most commonly C. albicans), which should be treated with topical antifungals (clotrimazole troches or nystatin liquid) four times daily, fluconazole (200 mg PO the first day, then 100 mg PO qd for 14 days), or itraconazole (200 mg PO qd for 14 days).
ETIOLOGY AND PATHOGENESIS Most cases of acute pharyngitis are nonexudative and secondary to infection with respiratory viruses such as EBV, RSV, parainfluenza virus, influenza virus, and adenovirus; EBV- and adenovirus-associated pharyngitis can mimic streptococcal pharyngitis. Group A coxsackievirus causes herpangina. Exudative bacterial pharyngitis is most often caused by group A b-hemolytic streptococci, which are responsible for 15% of all cases of pharyngitis. Other bacterial causes of pharyngitis include group C and group G streptococci, Neisseria gonorrhoeae, Corynebacterium diphtheriae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Arcanobacterium haemolyticum, and Yersinia enterocolitica.
CLINICAL MANIFESTATIONS Acute pharyngitis features sore throat with erythema, exudate, and edema. Classic findings in streptococcal pharyngitis include fever, sore throat, cervical lymphadenopathy, and tonsillar exudate. Associated peritonsillar abscess (quinsy) causes fever, pain, dysphagia and odynophagia, palatal fullness, tonsillar asymmetry, trismus, and a “hot-potato” voice.
DIAGNOSIS In exudative pharyngitis, the “rapid strep” test is specific for group A Streptococcus. However, since this test is not sufficiently sensitive, a throat swab should be inoculated for confirmatory culture if the rapid test is negative. Herpes simplex is confirmed by culture or immunofluorescence staining. Neisseriae must be isolated on selective medium.
Penicillin or erythromycin (500 mg qid for 10 days) treats streptococcal pharyngitis and helps prevent rheumatic fever but not poststreptococcal glomerulonephritis. Peritonsillar abscess requires incision and drainage. Resistance of streptococci to erythromycin has been reported. Data on prevention of rheumatic fever are available only for penicillin.
ETIOLOGY AND PATHOGENESIS Acute laryngitis manifests with hoarseness; it is usually viral in etiology (due to rhinovirus, influenza virus, parainfluenza virus, coxsackievirus, adenovirus, or RSV) but may also be caused by group A Streptococcus or M. catarrhalis. Etiologies of chronic laryngitis include Mycobacterium tuberculosis, Histoplasma capsulatum, B. dermatitidis, and Candida spp. Croup (laryngotracheobronchitis) occurs as subglottic edema almost exclusively in children 2–3 years old, manifesting as a “seal’s bark” cough. Croup is largely attributable to parainfluenza virus, influenza virus, RSV, and M. pneumoniae. Epiglottitis is a rapidly progressive cellulitis of the supraglottic area presenting with fever, dysphonia, and drooling. In children it may rapidly progress to airway obstruction; such airway emergencies are less common in adults. Organisms responsible for acute epiglottitis in adults include H. influenzae, H. parainfluenzae, S. pneumoniae, group A Streptococcus, and S. aureus. Use of the H. influenzae type b (Hib) vaccine has decreased epiglottitis due to this organism by >95% in children, but its incidence has not changed in adults.
DIAGNOSIS Subglottic narrowing on lateral neck film (“hourglass sign”) indicates croup. A “thumb sign” on lateral neck film indicates epiglottitis, but negative films do not reliably exclude the diagnosis. Direct fiberoptic examination should be performed only in the operating room, with preparations made for securing the airway via tracheostomy if needed.
Rapid antigen testing and throat culture for group A Streptococcus should be performed if this organism is suspected in laryngitis; if tests are positive, the pt should be treated with penicillin VK (250 mg qid for 10 days) or IM benzathine penicillin (a single injection of 1.2 million units). Other cases should be managed in light of symptoms. Laryngoscopy should be considered for any pt with hoarseness that lasts over 4 weeks.
Croup must be differentiated from epiglottitis. Children with severe symptoms should be hospitalized and monitored. Systemic antibiotics are not indicated. Nebulized racemic epinephrine gives temporary relief, and both systemic and nebulized steroids have been shown to decrease the rate of hospitalization in affected pts.
A child in whom epiglottitis is suspected should be treated as having an impending airway emergency. Epiglottitis must be managed in the ICU with intubation and administration of empirical antibiotics effective against H. influenzae, such as cefuroxime (1.5 g IV q8h), cefotaxime (2 g IV q8h), or ceftriaxone (2 g IV q24h) for 7–10 days. The pediatric doses of cefuroxime and cefotaxime are 50 mg/kg IV q8h; the pediatric dose of ceftriaxone is 50 mg/kg IV q24h. If the pt has unvaccinated household contacts <4 years old, they and all other members of the household should receive prophylaxis with rifampin (20 mg/kg PO qd, up to 600 mg for 4 days) to eliminate carriage.
DEEP NECK SPACES
ETIOLOGY AND PATHOGENESIS Infection in the deep neck spaces may be fatal as a result of airway compromise, septic thrombophlebitis, or extension of infection into the mediastinum. Group A streptococci, Peptostreptococcus spp., Prevotella spp., Porphyromonas spp., and Fusobacterium spp. are the common isolates from these infections. The infections originate in dental abscesses, sites of oral infection, sites of oropharyngeal trauma, sinuses, and infected retropharyngeal lymph nodes that track into the submandibular, lateral pharyngeal, or retropharyngeal spaces.
CLINICAL MANIFESTATIONS Pts with lateral pharyngeal space infections appear toxic, with fever, sore throat, odynophagia, trismus, and leukocytosis. On examination, medial pharyngeal wall displacement may be evident. Associated septic thrombosis of the internal jugular vein by Fusobacterium necrophorum causes a septic picture associated with mandibular angle tenderness and septic pulmonary emboli (Lemierre’s syndrome). Carotid artery rupture occurs rarely. Infection of the retropharyngeal space can produce marked dysphagia and odynophagia, drooling, a “hot-potato” voice, and—in severe cases—dyspnea and inspiratory stridor. Examination may show nuchal rigidity or bulging of the posterior pharyngeal wall.
DIAGNOSIS Diagnosis of deep neck space infection involves contrast CT and, for vascular involvement, MRI or MRA.
Treatment requires establishment of a stable airway, drainage of the abscess, and antibiotic therapy effective against streptococci, anaerobes, S. aureus, and H. influenzae. Antibiotic treatment consists of ampicillin/sulbactam alone (3.1 g IV q6h) or clindamycin (900 mg IV q8h) plus ceftriaxone (2 g IV q24h). Infections due to F. necrophorum are treated with penicillin G (24 million units per day by continuous infusion or divided q4–6h) or clindamycin (900 mg IV q8h). Antibiotic therapy is recommended for at least 4 weeks.
For a more detailed discussion, see Durand M,Joseph M: Infections of the Upper Respiratory Tract, Chap. 30, p. 187, in HPIM-15.