Abinash Virk MD
Nancy K. Henry PhD, MD
THE COMMON COLD
Essentials of Diagnosis
General Considerations
A “cold” is a self-limited viral infection of the upper respiratory tract presenting with a coryzal syndrome. It is the most common cause for physician visits and absenteeism in school and industry. Infection rates increase sharply during the fall through spring months with peak activity being in the winter. During these months, adults and children have an average of 2–4 and 6–8 colds per year, respectively.
Rhinoviruses are the most common cause of colds, accounting for one third of all colds (Box 9-1). Parainfluenza 1–4 viruses, coronaviruses, influenza types A and B, adenovirus, respiratory syncytial virus (RSV), and their numerous serotypes also are predominant viruses that induce colds. These viruses share a common property of frequent antigenic variation and evasion from the host humoral defense mechanisms, thereby permitting their persistent survival in the community. Other viruses can present with coldlike symptoms during the prodromal period, but their primary syndrome may be localized to another organ system(s).
Transmission is via aerosol, droplet, or direct contact with infected saliva or fomite from an infected person. The rate of infection increases in families with school-age children and in overcrowded and poorly ventilated living spaces. Cigarette smokers are more likely to develop severe disease as compared with nonsmokers.
Once the virus enters the cell, replication and subsequent shedding of the virus occur. The cytopathic effect of the virus on the epithelium varies depending on the virus, being relatively mild in rhinovirus and more marked with influenza virus infection. There is an acute inflammatory response, increased vascular permeability, tissue edema, mucus production, and serum transudation, resulting in the typical cold symptoms of rhinorrhea, nasal obstruction, and cough. After the initial neutrophilic response, there is immunoglobulin M (IgM), IgG antibody, and cytokine production such as interferon, tumor necrosis factor-α, interleukin 8, interleukin 6, and others. Cytolytic T-cell response is more marked and significant in the immune response against influenza viruses than rhinoviruses. Antibody neutralization is the predominant immune mechanism for the latter. Production of antibodies coincides with the cessation of viral replication and waning of the inflammatory response and symptoms. This period may vary depending on the infecting virus. Viral shedding may occur for a few days to weeks.
Clinical Findings
Associated clinical findings can suggest a specific viral diagnosis; for example, the presence of conjunctivitis suggests an adenoviral upper respiratory infection; myalgias and lower respiratory symptoms such as pneumonia or bronchiolitis may suggest an influenza or RSV infection. Mild disease suggests rhinovirus or coronaviruses. Symptoms of complications such as sinusitis, otitis media, or lower respiratory tract infection may be present. Patients with previous hyperactive airways or asthma can develop exacerbations.
The patient usually appears tired, with thin serous nasal discharge, mild tenderness over the sinuses, and mildly suffused conjunctiva without frank conjunctivitis, and the skin over the nostrils may be red from recurrent blowing of the nose. Pharyngeal erythema without any exudates or lymphadenopathy may be present. Lung examination may reveal evidence of bronchitis or bronchiolitis.
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BOX 9-1 Microbiology of the Common Cold |
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Differential Diagnosis
A common dilemma is clinically differentiating the common cold from GAS pharyngitis and prodromal symptoms related to systemic syndromes caused by other viruses such as measles, chickenpox, EBV, or CMV. The presence of high fever, chills, severe pharyngeal congestion with exudate, and tender lymphadenopathy is more likely to suggest GAS pharyngitis. An RADT and bacterial culture may be able to confirm this. An exposure history to chickenpox or other viral disease may be a helpful clue to the correct diagnosis. A diagnosis of allergies is evident with rapid resolution and no recurrences in the absence of exposure.
Complications
A complication of the common cold is viral or bacterial sinusitis. A common cold CT scan study by Gwaltney et al (1994) showed that sinus involvement occurs in >60% of patients with a cold, with 79% of these resolving spontaneously in 2 wk without antibiotics. However, bacterial superinfections of the sinuses, middle ear, or both are potential complications. Viral pneumonia or worsening of bronchospastic airway disease is seen, particularly in children or immunocompromised hosts.
Treatment
The old idiom of “prevention is better than cure” is certainly true for the treatment of the common cold. Multiple different viruses, their many serotypes, and rapid mutations pose a considerable challenge in the development of one vaccine or drug for cold prevention or treatment. Symptomatic support is the only therapy because no effective antiviral therapy is available.
Treatment is directed to rhinorrhea, nasal obstruction, sore throat, and cough. Sneezing, rhinorrhea, and nasal blockage improve markedly with topical or systemic decongestants that decrease edema by vasoconstriction. Topical decongestants such as phenylephrine (0.5% or 0.25%) or ephedrine (1%) nasal spray or drops should be used for a short period. Rebound congestion particularly with use of decongestant sprays beyond 3–4 d can occur. Systemic decongestants include pseudoephedrine hydrochloride, ephedrine, phenylephrine hydrochloride, propylhexedrine hydrochloride, phenylpropanolamine hydrochloride, xylometazoline hydrochloride, oxymetazoline hydrochloride, naphazoline hydrochloride, and tramazoline hydrochloride. Decongestant side effects include tachycardia, elevated blood pressure, fatigue, and dizziness. These should be used cautiously in patients with hypertension and dysrhythmias.
Nasal anticholinergics are effective in inhibiting the parasympathetic activation that contributes to rhinorrhea. Ipratropium bromide nasal spray reduces rhinorrhea and sneezing in the first 3 d of the cold.
Antitussives such as codeine, dextromethorphan, hydrocodone bitartrate, and diphenhydramine hydrochloride suppress the cough reflex in the medullary cough center. Analgesics can be used to improve the myalgias, headache, and sore throat that accompany the common cold. Antihistaminics have no role in the treatment of common cold. The majority of the above mentioned drugs are available over the counter in combination with antihistaminics, analgesics, or antitussives.
Nonspecific measures such as warm saline gargles are encouraged. The role of vitamin C in the common cold is controversial. Studies with dosages of 1–30 g/d demonstrate a 5–29% decrease in severity and duration of symptoms. However, these studies had significant variations for conclusive evidence. Similarly, despite numerous studies of the role of zinc in the management of cold, zinc's role is still controversial and needs further confirmation. Antibiotics have no role in colds unless patients have evidence of bacterial superinfection of the upper respiratory tract.
Prevention & Control
Handwashing is key in the prevention of common colds. Minimizing aerosol or droplet transmission with tissues or covering the mouth should be taught to children and adults. Experimental therapies with interferon-α2 and leukocyte A interferon show some role in the prevention of cold. Producing vaccines for these viruses is difficult because of their numerous serotypes. However, active vaccination can be used for influenza types A and B along with the prophylactic use of amantadine or rimantadine.
PHARYNGITIS
Essentials of Diagnosis
General Considerations
Pharyngitis is an acute infection of the pharyngeal mucosa caused by a variety of pathogenic microorganisms, the majority of which are viral (Box 9-2). A minority of pharyngitis episodes are bacterial and, of those, group A streptococcus is the most common cause. Viral pharyngitis is caused by respiratory viruses such as rhinoviruses, coronaviruses, adenoviruses, influenza, and EBV. Bacteria causing pharyngitis include group A and non-group A streptococci, Corynebacterium diphtheria, Corynebacterium pseudodiphtherium, Neisseria gonorrhoeae, Yersinia enterocolitica, Arcanobacterium hemolyticum, and anaerobic bacterial species. Persons infected with the human immunodeficiency virus (HIV) may present with an HIV-induced exudative pharyngitis during the acute retroviral syndrome or with Candida-induced pharyngitis. The etiology of pharyngitis remains obscure in 40% of cases. Most pharyngitis occurs as result of respiratory or contact transmission; few cases are foodborne. Outbreaks are common in winter or in crowded living situations, especially in families with children who serve as reservoirs by acquiring infections in daycare centers or school.
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BOX 9-2 Microbiology of Pharyngitis |
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Clinical Findings
An erythematous pharynx with or without exudates or cervical lymphadenopathy is the common finding on examination. Because it impacts therapeutic decision-making, it is important to attempt clinical differentiation between viral and bacterial pharyngitis. However, this may be difficult. Associated clinical signs and symptoms provide diagnostic clues to formulate a differential diagnosis. Mild pharyngeal symptoms with rhinorrhea usually suggest a viral etiology. Pharyngeal exudates suggest streptococcal pharyngitis, HIV, or EBV. Presence of vesicles and ulcers is seen with herpes simplex and coxsackievirus. Coxsackievirus-related vesicles often occur on the hard palate. Adenoviral pharyngitis is associated with conjunctival congestion. EBV, HIV, A hemolyticum, and streptococcal toxic shock can present with pharyngitis and a generalized rash. Pharyngitis with elevated transaminases, splenomegaly, and atypical lymphocytosis is the typical manifestation of EBV-induced infectious mononucleosis. Aseptic meningitis along with pharyngitis should suggest an acute HIV or enteroviral syndrome. Systemic viral infections with CMV, measles, and rubella, among others, can present with acute pharyngitis.
Sore throat with cough and signs of pneumonia may suggest influenza, Chlamydia pneumoniae or Mycoplasma pneumoniae. Diphtherial pharyngitis is associated with a grayish pseudomembrane.
GAS (Streptococcus pyogenes) pharyngitis frequently presents with fever of >38.3°C, chills, sudden-onset sore throat, painful and difficult swallowing, and tender cervical lymph nodes. Lymphadenopathy is more likely to be anterior and tender in GAS pharyngitis, unlike viral pharyngitis, which is more likely to be generalized and nontender. Exudate with intense pharyngeal and tonsillar pillars erythema is seen. Occasionally patients, especially children, present with systemic symptoms of nausea, vomiting, and headache. Symptoms of non-group A, such as group C or G, streptococcal pharyngitis are very similar to GAS and clinically indistinguishable. These symptoms and signs are nonspecific for GAS pharyngitis. However, absence of fever or presence of other symptoms such as rhinorrhea, cough, oral ulcers, and viral exanthema strongly suggests a viral rather than a GAS pharyngitis.
Special culture media for N gonorrhoeae or C diphtheria should be specifically requested when these bacteria are suspected. Serologic testing can establish the diagnosis of EBV, HIV, CMV, influenza, M pneumoniae, and C pneumoniae. During acute HIV retroviral syndrome, HIV RNA polymerase chain reaction, or HIV culture can help make a diagnosis because HIV serology may be negative.
Differential Diagnosis
In children, Kawasaki's syndrome can present with a clinical picture similar to an infectious pharyngitis. Noninfectious causes of pharyngitis include chemotherapy-induced mucositis, drug reactions, agranulocytosis, or connective-tissue disorders.
Complications
Local complications of bacterial pharyngitis include peritonsillar or retropharyngeal abscesses or Fusobacterium necrophorum jugular vein thrombophlebitis and its embolic complications (Lemeire's syndrome). In the United States, appropriate and timely antibiotics have decreased nonsuppurative complications of S pyogenes such as rheumatic heart disease or poststreptococcal glomerulonephritis. C diphtheria pharyngitis may become complicated by acute upper-airway obstruction, myocarditis, or neuritis. Viral pharyngitis may be complicated by secondary bacterial infection of the sinuses or lower respiratory tract.
Treatment
In patients with a clinical picture consistent with GAS pharyngitis, empirical therapy should be started to prevent suppurative and nonsuppurative complications, to decrease infectivity and transmissibility, and to induce clinical improvement of symptoms (Box 9-3). Patients with a high index of suspicion for GAS pharyngitis but negative or pending RADT/culture results can be given empirical antibiotics until the results are available. An alternative approach is to withhold antibiotics until the culture is positive for S pyogenes. Delaying therapy against GAS does not increase the incidence of rheumatic heart disease or recurrences with the same strain of S pyogenes. Following the latter course will decrease inappropriate antibiotic use and control the increase in antibiotic resistance.
Antibiotic selection is based on efficacy, ease of administration, cost, compliance, and spectrum of the antibiotic. The treatment of choice is penicillin V or amoxicillin for 10 d to treat and eradicate carriage. Intramuscular benzathine penicillin G may be given in patients unlikely to complete a 10-d course. Shorter courses are not recommended until more definitive studies are available. Erythromycin or other macrolides (such as clarithromycin or azithromycin), or oral cephalosporins are the recommended alternatives for bacterial pharyngitis in patients who are allergic to penicillin. Absence of penicillin-resistant GAS and limited (5%) resistance to erythromycin make it imperative to choose a cheaper alternative to the newer more expensive antibiotics. In some patients with recurrent GAS pharyngitis, penicillin is unable to eradicate nasopharyngeal carriage. In such patients, rifampin, clindamycin, or amoxicillin/clavulanate use may decrease colonization. Patients with negative throat RADT/cultures should have antibiotics discontinued.
Pharyngitis caused by anaerobic bacteria may respond to penicillins, amoxicillin/clavulanate, or clindamycin. A hemolyticum is susceptible to erythromycin. Yersinia pharyngitis requires treatment with a third-generation cephalosporin, an aminoglycoside or trimethoprim-sulfamethoxazole (TMP-SMX). Effective therapies for gonococcal pharyngitis include ceftriaxone, cefixime, or fluoroquinolones such as norfloxacin, ofloxacin, or ciprofloxacin. Treatment of choice for Mycoplasma pharyngitis is either doxycycline or macrolides. Doxycycline is contraindicated in children < 8 y old because it causes discoloration of teeth.
Symptomatic oropharyngeal herpes simplex ulcers, particularly in an immunocompromised host, should be treated with acyclovir for 7–10 d. Influenza type A pharyngitis can be treated with amantadine or rimantadine or the neuraminidase inhibitors if the patient presents within 48–72 h of onset of symptoms. HIV acute retroviral syndrome should be considered for treatment with combination antiretroviral therapy.
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BOX 9-3 Empiric Therapy of Acute Bacterial Pharyngitis |
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General measures for symptomatic relief include fluids, warm saline gargles, and nonsteroidal anti-inflammatory drugs. Aspirin should be avoided in children with viral infections, particularly varicella-zoster virus infection, to prevent Reye's syndrome. Patients that appear toxic or patients with suppurative complications should be hospitalized for parenteral or surgical management.
Prognosis
Uncomplicated pharyngitis results in no sequelae. Prognosis of GAS pharyngitis complicated by rheumatic heart disease or poststreptococcal glomerulonephritis is good with penicillin prophylaxis in rheumatic heart disease and spontaneous remission in poststreptococcal glomerulonephritis. Suppurative complications have minimal long-term adverse effects.
Prevention & Control
Active immunization plays a role in prevention with regard to diphtheria and influenza types A and B (Box 9-4). Tonsillectomy is recommended in selected patients. Penicillin prophylaxis is required in patients at risk for recurrent rheumatic fever.
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BOX 9-4 Control of Pharyngitis |
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ACUTE LARYNGITIS
Essentials of Diagnosis
General Considerations
Laryngitis is the infection of the larynx that results in an inflammatory reaction and consequential symptoms and signs. Common cold viruses such as rhinovirus, influenza virus, adenoviruses, RSV, or parainfluenza viruses may cause acute laryngitis. It usually presents in winter as part of an upper respiratory tract infectious syndrome. Bacterial laryngitis is less common and is caused mainly by S pyogenes or Moraxella catarrhalis. Rarely laryngitis may be caused by Mycobacterium tuberculosis, syphilis, or fungi such as Histoplasma capsulatum, Blastomyces dermatiditis, or Candida albicans.
Clinical Findings
Differential Diagnosis
Voice abuse is the most frequent noninfectious cause of hoarseness. Differential diagnosis includes tumors, paralysis of the vocal cords, chemical irritants, or gastroesophageal reflux. Patients with laryngitis must also be differentiated from those with acute epiglottitis or bacterial tracheitis, which usually present with more systemic symptoms.
Complications
Respiratory obstruction in children is the most serious complication.
Treatment
Because the majority of laryngeal infections are viral, therapy is mostly supportive with voice rest, warm saline gargles, and increased humidity. If specific microbiologic diagnosis is made with positive microbiologic cultures, then therapy should be directed at the organism isolated.
Prognosis
Long-term prognosis is excellent with no residual symptoms.
Prevention & Control
Preventive measures for laryngitis are similar to those for common cold and pharyngitis.
ACUTE LARYNGOTRACHEOBRONCHITIS (CROUP)
Essentials of Diagnosis
General Considerations
Acute laryngotracheobronchitis (LTB) or croup is subglottic inflammation and edema caused by a viral or bacterial infection of the larynx, trachea, and bronchi (Box 9-5). Croup is the most common cause of upper respiratory tract obstruction in children between the ages of 6 mo and 6 y, with the peak occurrence at 2 y old. It is caused mostly by viruses, primarily parainfluenza virus types I and II, although others, such as influenza type A or B, RSV, and adenovirus are also implicated. Occasionally M pneumoniae can cause LTB.
Clinical Findings
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BOX 9-5 Microbiology of Croup |
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Differential Diagnosis
Acute epiglottitis is a major differential diagnosis to be considered when a child presents with these symptoms. Radiographs of the neck can easily help differentiate the two conditions. Other causes of similar symptoms include foreign-body aspiration, which can be determined by history, x-rays, or endoscopic evaluation. Membranous croup or bacterial tracheitis should also be considered if the child presents with a clinical picture similar to croup but appears more toxic and has subglottic narrowing on radiographs of the neck.
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Figure 9-1. Lateral (A) and anterior-posterior (B) views of the neck of this 9-mo-old baby with 3 d of symptoms of upper respiratory infection show a normal appearing epiglottis and subglottic narrowing of the trachea consistent with LTB. |
Complications
Severe croup, as may occur with influenza type A, may require tracheotomy or intubation in ≤13% of patients and have an associated mortality of 0–2.7%. A small percentage of children with prolonged intubation or severe disease may develop subglottic stenosis. A few follow-up studies have shown an increase in hyperactive airways in children with a history of croup.
Treatment
Antibiotics are not routinely recommended for the treatment of croup unless the patient has symptoms or cultures suggestive of bacterial etiology (Box 9-6). Cool air humidification and supportive care are essential to keep the child calm, to prevent further tachypnea and distress. Respiratory rate is the best predictor of hypoxemia. Noninvasive pulse oximetry or arterial blood gas testing for PaO2 or PaCO2 should aid in assessment of the patient's condition and response to therapy. Noninvasive monitoring is preferred to prevent further anxiety in the child.
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Figure 9-2. Lateral chest x-ray views of a 2-mo-old infant with LTB show diffuse narrowing of the trachea and bronchi (A) and normal caliber trachea noted a few weeks later with resolution of infection (B). |
Nebulized racemic epinephrine is important in the therapy for croup because the α and β agonists decrease edema and relieve obstruction by vasoconstriction. Racemic epinephrine nebulization is well tolerated, even by the younger children, and may decrease the need for intubation. Children receiving racemic epinephrine should be observed for relapse because epinephrine has a short half-life and rebound vasodilatation and edema can occur. Racemic epinephrine nebulization should be used cautiously in children with left ventricular outflow tract obstruction such as tetralogy of Fallot or idiopathic hypertrophic subaortic stenosis. In severe croup, corticosteroids (eg, dexamethasone) decrease subglottic edema, the number of racemic epinephrine treatments, and intubations.
Some children will fail medical management and require intubation. Intubation should be done in fully equipped units and preferably via the nasotracheal route. Extubation is usually attempted in ~5–7 d if extubation criteria are met. Extubation criteria include decreased secretions, decreased leakage around the endotracheal tube (which indicates decreased edema), and an alert child. Failure to extubate should prompt further endoscopic evaluation.
Prognosis
Croup is mostly a self-limited disease with complete uncomplicated resolution. As mentioned above, some children may develop hyperactive airways or become predisposed to recurrent croup. A few may develop subglottic stenosis caused by severe disease or prolonged intubation.
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BOX 9-6 Empiric Therapy of Croup |
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Prevention & Control
Good handwashing and cleanliness can help decrease transmission from an infected patient, particularly at daycare centers or even in the home environment.
ACUTE EPIGLOTTITIS
Essentials of Diagnosis
General Considerations
Acute epiglottitis is a true respiratory emergency. An epiglottic infection leads to acute inflammation and edema of the epiglottis and can cause upper airway obstruction. Acute epiglottitis can occur at any age, however it is more common in children between 2–6 y and most often occurs in the winter and spring. Unlike croup, which is predominantly a viral disease, acute epiglottitis is a bacterial disease caused mainly by H influenzae type b, S aureus, or streptococcal species (Box 9-7). H influenzae type b was the most common organism isolated from children with acute epiglottitis, but widespread use of the H influenzae type b vaccine has dramatically decreased the incidence of H influenzae type b acute epiglottitis.
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BOX 9-7 Microbiology of Acute Epiglottitis |
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Clinical Findings
The patient looks anxious, appears toxic, and assumes a forward-leaning, neck-extended posture. Drooling of oral secretions and muffled voice are the sine qua non. The child has marked tachypnea and may have an inspiratory stridor from the supraglottic mucosa prolapsing into the glottis. Lung auscultation may reveal crepitations or bronchial breath sounds if there is associated pneumonia.
Differential Diagnosis
Croup or acute LTB presents with a clinical picture similar to that of acute epiglottitis. Croup has slower-onset, viral prodromal symptoms, a nontoxic appearing child, and absence of drooling. Anterior-posterior x-rays of the neck confirm the diagnosis. Other conditions that have a similar presentation include angioedema, foreign-body aspiration, and retropharyngeal or peritonsillar abscesses. Angioedema and foreign-body aspiration are suspected based on history and imaging or endoscopic evaluation. Radiographs or laryngoscopic evaluation identifies retropharyngeal or peritonsillar abscesses.
Complications
Mortality associated with untreated obstructive acute epiglottitis is ~80%. Respiratory failure from upper-airway obstruction is the most common complication. Occasionally patients will develop pulmonary edema along with the respiratory distress.
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Figure 9-3. Lateral (A) and anterior-posterior (B) views of the neck of this 3-y-old child reveal marked swelling of the epiglottis and the aryepiglottic folds characteristic of epiglottitis. Cultures of the epiglottis and blood grew H influenzae type B. |
Treatment
Acute epiglottitis is a medical emergency. Once acute epiglottitis is suspected, the child should be kept in an upright position and be accompanied at all times by personnel trained in advanced cardiopulmonary life support. Diagnosis should be expeditiously established clinically or radiographically. Laryngoscopic examination should be attempted only in a unit equipped for immediate intubation and only by experienced personnel. Maintenance of a patent airway is of foremost importance in the care of a patient with acute epiglottitis. Patients with impending respiratory failure who cannot be intubated may require an emergency subglottic tracheotomy. All pediatric patients with acute epiglottitis should be intubated preferably via a nasotracheal or an uncuffed endotracheal tube. Observation alone is not recommended in pediatric patients because of high associated mortality. Management of adult patients depends on the severity of clinical symptoms and signs of upper-airway obstruction.
Blood and epiglottic cultures should be obtained once the airway is secured. Patients should be started on parenteral antibiotics that are active against H influenzae type b, S aureus, and streptococci (Box 9-8). Because of the high degree of β-lactamase–mediated resistance in H influenzae type b, third-generation cephalosporins such as ceftriaxone or cefotaxime or a β-lactam/β-lactamase inhibitor combination antibiotic such as ampicillin/sulbactam should be started. Patients with acute epiglottitis usually improve within 12–48 h with appropriate antibiotics, and these should be continued orally or parenterally for 7–10 d. The average period of intubation is ~2 d, and direct visualization is the most effective way to determine time of extubation.
Prognosis
Expeditious diagnosis, immediate management of upper-airway obstruction, and institution of antibiotics decreases morbidity and mortality related to acute epiglottitis. Full recovery without sequelae is expected in such patients.
Prevention & Control
H influenzae type b polysaccharide vaccination can further decrease the incidence of acute epiglottitis (Box 9-9). However, patients can still be susceptible to non–type-b H influenzae and other bacterial etiologies of epiglottitis.
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BOX 9-8 Empiric Therapy of Acute Epiglottitis |
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BOX 9-9 Control of Acute Epiglottitis |
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The secondary attack rate of H influenzae type b among all household contacts, especially in children < 4 y old, can be decreased by a prophylactic 4-d course of rifampin (20 mg/kg/d in a single daily dose). Rifampin prophylaxis should be given to the patient and all household contacts regardless of previous immunization status, to prevent carriage state.
OTITIS MEDIA
Essentials of Diagnosis
General Considerations
Acute otitis media (AOM) is the middle ear inflammation that results in collection of fluid in the middle ear and associated local and systemic symptoms.
AOM is the most common reason for physician office visits for children under age 15 y. Children < 3 y and those at the age of school entry (5–6 y) are most vulnerable to AOM. Predisposing and recurrence factors for AOM include daycare attendance, particularly at large (>6 children per room) centers, a sibling with AOM, parental smoking, and drinking from a bottle while lying flat on the back. Boys, Native Americans, and Alaskans have a higher incidence of AOM. A small percentage of children have an identifiable risk factor for recurrences such as congenital orofacial deformities and congenital or acquired immunodeficiencies such as HIV/AIDS. Recurrences occur in normal children with no apparent anatomic defects. A large percentage of AOM is viral, which may explain recurrences.
The most common bacterial organism responsible for otitis media is Streptococcus pneumoniae, which accounts for ~30–40% (Box 9-10) of cases. Cultures from the middle ear in various studies have demonstrated S pneumoniae, nontypable strains of H influenzae (21%), M catarrhalis (12%), S aureus, GAS (2–6%), and other less common gram-negative organisms including Pseudomonas aeruginosa. Penicillin-resistant S pneumoniae (PRSP) is increasing in the community and contributes to recalcitrant cases of AOM. PRSP is common in children < 6 y old, children who have received recent antibiotics, children with previous AOM, and children attending group daycare. Gram-negative organisms should be considered in neonates with AOM. Rare causes include M pneumoniae, which has a classic bullous lesion on the tympanic membrane, and Chlamydia trachomatis may be seen in very young infants. Occasionally mycobacterial or diphtheria middle-ear infections can occur.
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BOX 9-10 Microbiology of Acute Otitis Media |
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Clinical Findings
Otoscopic examination reveals an erythematous tympanic membrane. The tympanic membrane may be bulging, retracted, or perforated and occasionally exuding purulent drainage from the perforation. Fluid in the middle ear is demonstrated by air-fluid levels, bulging, and decreased mobility of the tympanic membrane demonstrated by pneumatic otoscopy. Pneumatic otoscopy should be attempted in all children unless it is too painful. Other otologic techniques such as tympanometry and acoustic reflectometry can help assess the amount of fluid in the middle ear. Audiologic evaluation is necessary in children with hearing loss.
Differential Diagnosis
Noninfectious causes of AOM, such as Wegener's granulomatosis, must be considered in a patient with recurrent and nonresponding disease. A foreign body in the EAC can present with earache and minimal erythema of the tympanic membrane. History and otoscopic visualization should identify a foreign body. A viral infection, fever, or crying or earwax removal can also cause a red tympanic membrane.
Complications
Chronic otitis media, effusion, mastoiditis, and intracranial extension may result from recurrent otitis media and persistent middle ear effusion. In the preantibiotic era, mastoiditis and intracranial extension occurred in ~20% and 2.5%, respectively, of AOM patients. Now that the use of antibiotics is common, these rates have decreased to 2.8% and 0.13%, respectively. Contiguous spread to the cranial fossae, temporal or petrous bone, or sigmoid or lateral sinuses results in suppurative complications. Conductive hearing loss because of chronic otitis media and effusion can potentially impair language development and academic functioning of the child.
Treatment
A large number of AOM cases are viral in nature with or without bacterial superinfection. Approximately 30% of AOM cases are bacterial. Studies have also demonstrated spontaneous resolution in 16% of S pneumoniae infections, 50% of H influenzae infections, and ~80% of M catarrhalis AOM, particularly in children older than 2 y. Because of concerns regarding suppurative complications, parental expectation, and perhaps convenience, antibiotic therapy has become the norm for most AOM treatment (Box 9-11). Numerous studies have now demonstrated that antibiotics benefit defervescence and otalgia, decrease suppurative complications, and improve tympanic membrane healing, but they have no significant benefit in long-term outcomes such as recurrence rates or chronic middle ear effusion. These studies and the recent increase in multi–drug-resistant organisms that have no or minimally efficacious treatment have brought this practice of judicious antibiotics use for AOM into question.
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BOX 9-11 Empiric Therapy of Acute Otitis Media |
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The approach to patients with AOM should be individualized. A delayed antibiotic approach can be considered in children older than 2 y with no immunodeficiency, no craniofacial anatomic abnormalities, intact tympanic membrane, and no previous AOM. The child should be scheduled for a follow-up visit. If a follow-up visit is not possible, an antibiotic can be started at the initial evaluation. The initial empirical antibiotic regimen should be active against the common organisms. Despite the emergence of resistance in these bacteria, amoxicillin is still the preferred and effective initial antibiotic of choice. In children with a history of antibiotic use in the preceding month, the initial antibiotic is still amoxicillin but given at a higher dose.
Antibiotics effective in the treatment of AOM include amoxicillin/clavulanate, cephalosporins such as cefaclor, cefixime, cefprozil, cefuroxime, cefpodoxime, loracarbef, or macrolides such as erythromycin, azithromycin, or clarithromycin, TMP-SMX, and erythromycin/sulfisoxazole (Pediazole). The newer expensive antibiotics do not have a significant benefit as first-line agents when compared with their cheaper counterparts (eg, amoxicillin and TMP-SMX). In patients with penicillin allergy, cephalosporins, macrolides, or TMP-SMX can be prescribed. Cephalosporins should be avoided in patients with histories of anaphylactic reaction to penicillin. Studies report mean clinical cure rates of 85–94% with amoxicillin.
Most patients start responding in 48–72 h. Causes for slower response or recurrence with lower-dose amoxicillin therapy include resistant organisms such as intermediate- or high-grade PRSP or β-lactamase–producing H influenzae or M catarrhalis, suppurative complications, or noncompliance. Treatment failure is defined as lack of improvement in fever, ear pain, and persistent tympanic congestion, bulging, or otorrhea. It is important not to mistake a persistent middle ear effusion without signs of active infection as treatment failure. Treatment failure may be early (3 d) or late (10–25 d). If a child requires further treatment, high-dose (80 mg/kg/d) amoxicillin, a cephalosporin, amoxicillin/clavulanate, or a macrolide (either azithromycin or clarithromycin) may be prescribed. The choice of retreatment antibiotic depends on the risk of PRSP in the patient. Higher-dose amoxicillin or amoxicillin/clavulanate is still efficacious against intermediate-penicillin-susceptible S pneumoniae. Cefaclor and cefprozil are not good alternatives as second-line therapy because of their lower efficacy against nonsusceptible S pneumoniae and H influenzae. Because of the lack of activity against PRSP, clarithromycin, azithromycin, TMP/SMX, cefixime, ceftibuten, and loracarbef are recommended only as second-line antibiotics for patients at low risk for PRSP AOM.
Patients suspected of having PRSP AOM who fail high-dose amoxicillin should be considered for tympanocentesis for culture and susceptibilities. If empiric therapy is decided, the antimicrobial therapy should be effective against the β-lactamase–producing H influenza and M catarrhalis in addition to being active against PRSP. Options include oral cefuroxime axetil, cefpodoxime or clindamycin, or parenteral cefotaxime, ceftriaxone or vancomycin. In children receiving clindamycin for PRSP, the addition of a β-lactamase–stable cephalosporin may be required to cover for β-lactamase–producing H influenzae. One parenteral dose of ceftriaxone 50 mg/kg/d is approved for AOM caused by susceptible S pneumoniae. However, ceftriaxone given daily for 3 d is likely to be more efficacious for AOM failing the first-line antimicrobial-agent therapy. Parenteral therapy is usually needed only for patients with severe AOM or those failing their second regimen. Middle ear aspirates should be sent for culture and susceptibilities to guide therapy in children failing second-line therapy. These patients should be reevaluated in 2 wk to ascertain that no suppurative complications have developed. A severely ill child failing initial therapy should be considered for admission and treatment with parenteral vancomycin and a third-generation cephalosporin, such as cefotaxime or ceftriaxone. A thorough evaluation for complications should also be conducted.
Symptomatic treatment is primarily pain control with analgesics such as acetaminophen or nonsteroidal anti-inflammatory drugs. On occasion, myringotomy (incision of the tympanic membrane) may be required to relieve the middle ear pressure. In most studies, myringotomy did not improve outcome even when combined with antibiotics. Antihistaminics and decongestants have equal efficacy as a placebo in AOM, and they are not recommended.
Treatment of recurrent otitis media includes prevention of recurrent attacks, a second course of antibiotics with broader antibacterial spectrum as mentioned above or specific treatment depending on middle ear cultures. Secondary antibiotic prophylaxis, surgical drainage or adenoidectomy, and active immunization are some of the measures used to prevent AOM. Children with three new episodes in 6 mo or four episodes in 1 y should be considered for antibiotic prophylaxis with amoxicillin or erythromycin/sulfisoxazole. Antibiotic prophylaxis decreases recurrences ≤44%. The patient should be regularly evaluated for middle ear effusion. Middle ear effusion is seen in ~50% of children with AOM and usually resolves in 3 mo in the majority of patients. Persistent middle ear effusion or otitis media with effusion (OME) beyond 3–4 mo requires further management. Children with OME should have an audiologic test to detect any hearing loss. Patients with OME with normal hearing should be retreated with a 2- to 3-wk course of an antibiotic. If the effusion resolves, then a prophylactic antibiotic course of 3 mo may be of benefit to prevent recurrences. Children with OME and conductive hearing loss should be evaluated by an otorhinolaryngologist for surgical drainage procedures such as myringotomy and tympanostomy tubes (tubes placed in the tympanic membrane for permanent drainage).
Prognosis
Recurrent AOM or OME may impair hearing, language development, and learning capabilities of the patient. The prognosis is worsened in patients with intracranial extension of infection. Uncomplicated AOM resolves without significant sequelae.
Prevention & Control
Currently available 23 polyvalent pneumococcal polysaccharide vaccine produces poor immunologic responses in children < 2 y old but can be used for children >2 y. The Advisory Committee on Immunization Practices advises that this vaccine be given to children with higher likelihoods of pneumococcal infections such as HIV-positive, asplenic, or sickle cell anemia patients. Conjugated pneumococcal vaccine is available and is more efficacious in children < 2 y old and may contribute to lowering the incidence of pneumococcal otitis media.
OTITIS EXTERNA
Essentials of Diagnosis
General Considerations
Inflammation of the EAC is particularly symptomatic because of the limited space for expansion of edematous tissue in the narrow external auditory canal.
Clinical Findings
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BOX 9-12 Microbiology of Otitis Externa |
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Complications
Complications develop by local invasion such as temporal bone osteomyelitis, septic thrombophlebitis of the sigmoid or lateral sinus or jugular bulb, cranial nerve palsies, meningitis, or brain abscess.
Treatment
Gentle cleaning is recommended for most otitis externa. Local heat, topical antibiotic solutions such as neomycin, polymyxin, or ofloxacin, or systemic antibiotics, or some combination of these are effective in the treatment of acute otitis externa (Box 9-13). Irrigation with hypertonic (3%) saline and cleansing with alcohol and acetic acid mixed 1:1 are recommended for acute diffuse otitis externa, whether it is bacterial or fungal. Fungal otitis externa may also be amenable to treatment with m-cresyl acetate. Topical antibiotics combined with steroids are sometimes used for 1–2 d to decrease edema. Severe infections may require systemic antibiotics with activity against P aeruginosa. Malignant otitis externa may be treated with parenteral antipseudomonal antibiotics such as ceftazidime or penicillins with antipseudomonal activity such as piperacillin with aminoglycoside or oral antipseudomonal antibiotics such as the fluoroquinolones. Topical antipseudomonal antibiotics, such as neomycin, polymyxin, or ofloxacin, are used for 4–6 wk.
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BOX 9-13 Empiric Therapy of Otitis Externa |
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ACUTE & CHRONIC SINUSITIS
Essentials of Diagnosis
General Considerations
Inflammation of the pseudostratified epithelium of the sinuses may occur as a result of an infection, allergy, toxin, or an autoimmune disorder. The paranasal sinuses (maxillary, ethmoid, frontal, and sphenoid) are sterile under normal conditions. Any one or all of them may become infected resulting in inflammation and edema of the pseudostratified epithelium that leads to an increase in tenacious secretions and the symptoms of acute sinusitis. The maxillary sinus is most commonly involved because its ostium is located at the highest part of the medial wall of the sinus. This leads to inadequate drainage and pooling of excess secretions, increased tenacity of secretions, and a drop in oxygen tension creating a more favorable environment for bacterial growth. Acute sinusitis occurs in all ages.
Infectious sinusitis may be bacterial, fungal, or viral. A large percent of acute sinusitis results from viral infection of the sinuses with or without bacterial superinfection. The latter is more symptomatic and patients are more likely to present to the physician. Episodes of sinusitis that occur all year round may be associated with allergies, polyps, or swimming.
The microbiology of acute bacterial sinusitis is similar to that of otitis media (Box 9-14). S pneumoniae and H influenzae account for >50% of the sinusitis cases. Other pathogenic bacteria include M catarrhalis, α- and β-hemolytic streptococci, S aureus, C pneumoniae, anaerobic bacteria, and occasionally gram-negative bacteria such as the Enterobacteriaceae or P aeruginosa. The β-lactamase–producing H influenzae and M catarrhalis and intermediate or PRSP have proportionally increased in the microbiology of sinusitis and have important implications for management of sinusitis. Anaerobic bacteria, such as Peptostreptococcus, Fusobacterium, or Prevotella species, are implicated in ~8–10% of cases of acute sinusitis. These are usually polymicrobial and result from contiguous spread from the roots of the teeth.
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BOX 9-14 Microbiology of Sinusitis |
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Patients with craniofacial fractures have a higher incidence of sinusitis. P aeruginosa is a frequent cause of sinusitis in HIV-positive and in cystic fibrosis patients and must be considered in a patient who fails empirical antibiotic therapy that does not include antipseudomonal activity. S aureus is slightly more common in frontal or sphenoidal sinusitis. Fungi such as Aspergillus spp., Zygomycetes (Mucor spp.), and Pseudallescheria spp., among others, can occur in normal hosts or in immunocompromised hosts. Aspergillus sinusitis may occur in normal hosts or present as an allergic syndrome. Zygomycetes infection is more common in people with diabetes (particularly during acidosis), neutropenic patients, and patients on deferoxamine treatment. Viruses such as rhinovirus, influenza virus, adenovirus, coronavirus, and occasionally CMV, among others, account for sinusitis that presents with the primary rhinitis or upper respiratory tract infection syndrome. Coinfections of viruses and bacteria have a higher rate of prolonged duration of symptoms. Recurrent sinusitis may occur as a result of allergies, enlarged adenoids (especially in children), anatomic obstruction such as septal deviation, polyps, tumors, or craniofacial abnormalities, congenital primary or acquired immunodeficiency syndromes, or coexisting disease such as cystic fibrosis, asthma, or gastroesophageal reflux disease.
Chronic sinusitis, infection of the paranasal sinuses for 3 mo or more, may occur in patients with persistently impaired sinus drainage, immunodeficiency, or inadequately treated previous sinusitis episodes. The microbiology of chronic sinusitis is difficult to interpret with previous antibiotic use. However, chronic sinusitis is more often polymicrobial in etiology. There is a higher incidence of S aureus; anaerobes such as Peptostreptococcus, Fusobacterium, or Prevotella species (25–80%); gram-negative bacilli, such as P aeruginosa; and fungi in chronic sinusitis as compared with acute bacterial sinusitis.
Clinical Findings
The symptoms of sinusitis may last longer than a viral syndrome and ~60% of these patients will have positive sinus cultures. Headache is common and may be frontal, temporal, vertex, or retro-orbital depending on the sinus involved. Sphenoidal sinusitis predominantly causes a vertex headache. Eustachian tube blockage caused by local edema and nasopharyngeal secretions may cause the sensation of “blocked ears.” Patients may give a history of a predisposing condition such as sneezing or nasal itching with allergies. History of recurrent sinusitis or sinopulmonary disease, arthritis, and other organ disorders is important to identify immunodeficiencies and noninfectious etiologic diagnosis. Chronic sinusitis symptoms are occasional headaches, fatigue, irritability, low-grade temperature, facial pressure, and PND.
In acute uncomplicated bacterial sinusitis, there is severe tenderness overlying the affected sinuses. There may be swelling, erythema, and induration of the overlying area. Cloudy, yellow-to-green purulent drainage is noted. Intranasal examination should be conducted to attempt identifying the site of purulent discharge. Percussion examination of teeth should be done in patients with unilateral sinusitis or with a history of dental pain. Patients may have signs resulting from complications of sinusitis such as erythema, edema, and proptosis in orbital cellulitis. Purulent discharge and elevated temperature may be the only signs of acute sinusitis. Transillumination of the maxillary sinuses may demonstrate the presence of fluid.
Differential Diagnosis
Patients with noninfectious sinusitis such as that related to Wegener's granulomatosis, tumors, or allergic rhinitis may present with signs and symptoms similar to those of infectious sinusitis.
Complications
The proximity of the orbits to the sinuses accounts for orbital complications. Orbital complications include periocular edema, orbital cellulitis, abscess, and further extension into the cavernous sinus leading to cavernous sinus thrombosis. Infection of the bone by direct spread or septic thrombophlebitis may occur. Frontal bone osteomyelitis and subperiosteal abscess cause a swelling and doughy feeling of the frontal bone called Pott's puffy tumor. Intracranial extension results in meningitis or epidural, subdural, or brain abscess. The incidence of these complications has declined, but they present as medical emergencies and require immediate attention. Cough or bronchitis from aspiration of postnasal drainage into the respiratory tract may also occur.
Treatment
Therapy of acute bacterial sinusitis includes symptomatic care along with an appropriate antibiotic regimen (Box 9-15). It may be helpful to stratify patients by the severity of symptoms. Patients who present with complicated sinusitis with evidence of intracranial or orbital extension should be hospitalized, undergo immediate appropriate diagnostic tests, and start on a parenteral empirical antibiotic regimen. Therapy should be guided by diagnostic sinus fluid aspiration. The recommended empirical antibiotic regimen in complicated sinusitis should include vancomycin, which is active against intermediate and highly PRSP, and a high-dose, third-generation cephalosporin (ie, cefotaxime or ceftriaxone) with activity against other usual pathogens. Empirical therapy should continue until culture and susceptibility results from sinus aspiration are available. Surgical consultations should be sought for possible drainage procedures. The increasing incidence of intermediate and highly PRSP and β-lactamase–producing organisms has led to a decrease in the efficacy of amoxicillin for sinusitis.
Current recommendations for empirical antimicrobial therapy for acute uncomplicated bacterial sinusitis include amoxicillin/clavulanate or oral cephalosporins such as cefuroxime for 10 d. Other efficacious antibiotics include cefprozil, cefaclor, loracarbef, or cefpodoxime. TMP-SMX achieved 95% cure rates in older sinusitis studies; however, it is less effective against GAS and S pneumoniae.
Alternative antibiotics include macrolides such as clarithromycin (15 mg/kg/d for children, 500 mg every 12 h in adults) or azithromycin. Erythromycin has poor activity against H influenzae and is not recommended. Newer fluoroquinolones, such as levofloxacin or gatifloxacin (not approved for use in children and adolescents < 18 y old), have good activity against PRSP and are approved for use in adults with upper respiratory tract infections. TMP-SMX, cephalosporins or macrolides could be used for penicillin allergic patients. Odontogenic sinusitis treatment should include anaerobic coverage with either a β-lactam/β-lactamase inhibitor combination or the alternative regimen should include clindamycin or metronidazole. Fungal sinusitis requires aggressive surgical debridement along with parenteral or oral antifungal therapy.
Supportive measures for symptomatic relief may be considered. Decongestants provide symptomatic improvement by decreasing the nasal edema and obstruction. Oral decongestants are preferred over topical ones to avoid rebound vasodilatation. Steroid inhalers are not recommended unless the patient has significant allergy history and symptoms. Most symptoms will resolve in 7–10 d. Indiscriminate use of antibiotics is strongly discouraged to prevent the emergence of resistant strains of bacteria, particularly if the symptoms are consistent with a viral upper respiratory tract infection.
Persistent symptoms after an appropriate course of treatment may result from retained secretions, resistant or unusual organisms, presence of allergies, or possible immunodeficiency. Recurrent bacterial sinusitis should prompt further evaluation of the paranasal anatomy; immunoglobulin levels; neutrophil function analysis; HIV serology; sinus aspiration;
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and cultures for aerobic and anaerobic bacteria, fungi, and mycobacteria. Sinus aspiration and lavage or other drainage procedures may be more efficacious in relieving symptoms in these patients. Sinus aspirate should be sent for aerobic and anaerobic bacterial, mycobacterial and fungal culture, and susceptibilities. Patients with chronic sinusitis may require retreatment with a second course of broad-spectrum antibiotics to include antimicrobial activity against S aureusand anaerobes. This could be achieved with amoxicillin/clavulanate or combination therapy of a cephalosporin with clindamycin or metronidazole given for 4–6 wk. Occasionally antipseudomonal therapy may need to be added particularly in patients with cystic fibrosis, patients who are hospitalized, or patients who are HIV positive. Acute or chronic sinusitis exacerbations should be treated similarly to acute sinusitis.
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BOX 9-15 Empiric Therapy of Acute Bacterial Sinusitis |
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Prognosis
Most community-acquired bacterial sinusitis episodes respond well to antimicrobial therapy. Complicated sinusitis or sinusitis in an immunocompromised host may require aggressive treatment including surgery. Such patients may continue to have recurrences and the attendant morbidity. Mortality in sinusitis is related mostly to complications such as meningitis.
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BOX 9-16 Control of Acute Bacterial Sinusitis |
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Prevention & Control
Proper hygiene measures such as handwashing can reduce the incidence of acute sinusitis by decreasing transmission of infectious particles between persons (Box 9-16). Simple actions like covering the mouth with a handkerchief or tissue when sneezing or coughing can prevent aerosol or droplet transmission. Active immunization with pneumococcal polysaccharide vaccine or influenza vaccine may further decrease the incidence of these infections.
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