Faringitis

History
Viral and bacterial causes of pharyngitis are similar, and the differentiation of the etiology is difficult based on history and physical examination alone. Despite this, classic presentations are described below. GAS infection is most common in children aged 4-7 years. Sudden onset is consistent with a GAS pharyngitis. Pharyngitis following several days of coughing or rhinorrhea is more consistent with a viral etiology. Person has been in contact with others diagnosed with GAS or rheumatic fever presenting with symptoms consistent with GAS are more likely to have GAS pharyngitis. Headache is consistent with GAS infection. Cough is not usually associated with GAS infection. Vomiting is associated with GAS infection but may be present in other types of pharyngitis. A history of recent orogenital contact suggests the possibility of gonococcal pharyngitis. A history of rheumatic fever is important when considering treatment.

The Centor criteria have been used in the past as a way to diagnose and treat GAS pharyngitis.6 These include the following: Fever Anterior cervical lymphadenopathy Tonsillar exudate Absence of cough

One point is awarded for each of the criteria met, with patients scoring 0-1 unlikely to have GAS infection and patients with a score of 4 more likely to have GAS. A clinical diagnosis of GAS infection using these criteria can result in an overestimation of the incidence of streptococcal pharyngitis, as many bacterial and viral cases of pharyngitis can be indistinguishable on clinical grounds. This can lead to an overtreatment of pharyngitis with antibiotics.7 In adults, the positive predictive value of the Centor criteria for predicting GAS pharyngitis is around 40% if 3 criteria are met, and about 50% if 4 criteria are met.8 These criteria along with other clinical features should be used to guide treatment for pharyngitis in adults.

Physical
Airway patency must be assessed and addressed first. Temperature: Fever is usually absent or low-grade in viral pharyngitis, but fever is not reliable to differentiate viral or bacterial etiologies. Hydration status: Oral intake usually is compromised because of odynophagia; therefore, various degrees of dehydration result. Head, ears, eyes, nose, and throat (HEENT) o Conjunctivitis may be seen in association with adenovirus. o Scleral icterus may be seen with infectious mononucleosis. o Rhinorrhea usually is associated with a viral cause. o Tonsillopharyngeal/palatal petechiae are seen in GAS infections and infectious mononucleosis. o A tonsillopharyngeal exudate may be seen in streptococcal infectious mononucleosis and occasionally in M pneumoniae, C pneumoniae, A haemolyticus, adenovirus, and herpesvirus infections. Therefore, exudate does not differentiate viral and bacterial causes.

Oropharyngeal vesicular lesions are seen in coxsackievirus and herpesvirus. Concomitant vesicles on the hands and feet are associated with coxsackievirus (hand-foot-and-mouth disease). Lymphadenopathy: Tender anterior cervical nodes are consistent with streptococcal infection, whereas generalized adenopathy is consistent with infectious mononucleosis or the acute lymphoglandular syndrome of HIV infection. Cardiovascular: Murmurs should be documented in an acute episode of pharyngitis to monitor for potential rheumatic fever. Pulmonary: Pharyngitis and lower respiratory tract infections are more consistent with M pneumoniae or C pneumoniae, particularly when a persistent nonproductive cough is present. Abdomen: Hepatosplenomegaly can be found in infectious mononucleosis infection. Skin o A sandpapery scarlatiniform rash is seen in GAS infection (see Scarlet Fever).9 o Maculopapular rashes are seen with various viral infections and with infectious mononucleosis empirically treated with penicillin.

Laboratory Studies
GABHS rapid antigen detection test

Rapid antigen detection test for group A beta-hemolytic streptococci.

This is the preferred method for diagnosing GAS infection in the emergency department because of difficulties with culture follow-up. o Only patients with a high clinical likelihood of GAS pharyngitis should be tested. Patients with a Centor score of 0-1 should be treated symptomatically without testing.11 o Antigens are specific, but sensitivities vary. Children with a negative antigen test should have a follow-up culture unless the antigen being used in the office has been shown to be as sensitive as a culture.9 o The use of a GABHS rapid antigen detection test can decrease the use of unnecessary antibiotics in pediatric patients when used properly.12 o Adults do not need follow-up culture after a negative antigen test because of the low incidence of GAS in this population.13 Throat culture o This is the criterion standard for diagnosis of GAS infection (90-99% sensitive). Although less expensive than the rapid antigen detection test, it is not be the best test to use in the emergency department because of difficulty with follow-up. The

guidelines that recommend cultures for GAS screening are aimed at office-based practices and not the emergency department. o Patients can be treated up to 9 days after onset of symptoms to prevent acute rheumatic fever, so immediate antibiotic therapy is not crucial if patients can be easily contacted for follow-up should a culture become positive.1 Mono spot is up to 95% sensitive in children (less than 60% sensitivity in infants). Peripheral smear may show atypical lymphocytes in infectious mononucleosis. 2 Perform gonococcal culture, as indicated by history. A complete blood count (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein have a low predictive value and usually are not indicated.

Imaging Studies
Imaging studies generally are not indicated for uncomplicated viral or streptococcal pharyngitis. Lateral neck film should be taken in patients with suspected epiglottitis or airway compromise. Soft tissue neck CT can be used if concern for abscess or deep-space infection exists; however, peritonsillar abscess is almost always a clinical diagnosis. Imaging is rarely needed for diagnosis.

Procedures
The procedure for a throat swab is to vigorously rub a dry swab over the posterior pharynx and both tonsils, obtaining a sample of exudate. If any exudate is obtained, then transport it dry (not in a liquid medium).

Prehospital Care
Prehospital care usually is not necessary for uncomplicated pharyngitis unless airway compromise is an issue. Intubation should not be attempted unless the patient stops breathing spontaneously.

Emergency Department Care

Assess and secure the airway, if necessary. Assess the patient for signs of toxicity, epiglottitis, or oropharyngeal abscess. 14 Evaluate the hydration status because severe pharyngitis limits oral intake. Appropriate measures to rehydrate should be initiated, including intravenous hydration. Assess for GAS infection if clinically suspected. A suggested algorithm as is follows. o In general, patients should not be treated without a positive culture or positive rapid antigen detection test result because of increasing antibiotic resistance. Guidelines from the Infectious Diseases Society of America (IDSA) and American Heart Association state that microbiologic confirmation (via a rapid antigen test or culture) is required for the diagnosis of GAS.7,5 New recommendations for pharyngitis therapy are due from the IDSA later in 2010. o Perform rapid antigen detection test if GAS is clinically suspected based on history and physical examination. If positive, begin antibiotic therapy. Testing does not usually need to be performed on patients with acute pharyngitis whose clinical and epidemiologic features do not suggest GAS as the etiology (Centor score 0-1).13 o Patients who are positive for all 4 Centor criteria can often be treated with antibiotics without antigen testing or cultures.

o o

Household contacts of patients with GAS infection or scarlet fever should be treated for a full 10 days without testing only if they have symptoms consistent with GAS. 5 If clinically doubtful or the above criteria are not met, it is best to await rapid antigen or culture results to initiate antibiotic therapy.

Consultations
With a few exceptions, uncomplicated cases of pharyngitis should not require a consultation. Infectious disease specialists should be consulted in the case of unusual presentation or in the case of a patient who is immunocompromised.

Medication
GAS pharyngitis is usually a self-limited disease, and most signs and symptoms resolve spontaneously in 3-4 days. If administered early, antibiotics can shorten the duration of the illness by up to 1 day, but the main reason they are given is for prevention of acute rheumatic fever. 15 This rationale is being questioned by many as the incidence of acute rheumatic fever in the United States is extremely low. Antibiotics do not prevent acute glomerulonephritis. Steroids may be used for airway compromise and symptomatic relief.16 Antifungals and antivirals are used in certain rare cases with specialist consultation.

Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Antibiotics are indicated for clinically suspected and culture or antigenverified GAS infection. They are effective in preventing rheumatic fever if given within 9 days of the onset of pharyngitis. Of note, some experts question the use of antibiotics for the treatment of GAS infection in the Western world because of the low prevalence of rheumatic fever. Some European guidelines for the treatment of pharyngitis only recommend antibiotics for patients with culture-positive GAS pharyngitis who are high-risk for acute rheumatic fever or very ill.17 One study suggested that observation alone was most cost-effective strategy for GAS pharyngitis in children, and this strategy also had lower morbidity and mortality than antibiotic treatment groups.18 For now, most experts in the United States still recommend treatment with antibiotics. Some support the use of cephalosporins instead of penicillin as first-line therapy for GAS.19,20 They cite literature that shows greater eradication of the bacteria in the pharynx after treatment with a cephalosporin. No evidence suggests that this is clinically significant, and most guidelines still advocate that penicillin is still the drug of choice for GAS in the United States. There has never been a clinical isolate of GAS documented to be resistant to penicillin anywhere in the world.7 In cases of clinical treatment failure of GAS pharyngitis after penicillin therapy, a cephalosporin or broaderspectrum penicillin (ampicillin-sulbactam) should be considered, but these instances are rare.14 Cephalosporins should be considered first-line therapy if the patient has a history of recent antibiotic usage, recurrent pharyngitis infection, or if a high failure rate of penicillin is documented in the community.21 Some controversy exists regarding the treatment of carriers of GAS. These are patients who have a positive rapid antigen or culture without symptoms of pharyngitis. It is believed that this carrier state does not lead to acute rheumatic fever or other complications of GAS pharyngitis. Most carriers should not be treated; however, treatment should be considered in carriers with the following characteristics:

Recurrent pharyngitis without cough or congestion Acute rheumatic fever (ARF) or poststreptococcal glomerulonephritis outbreaks GAS pharyngitis in closed community Family history of ARF Multiple documented GAS pharyngitis episodes within a family over several weeks despite therapy

If carriers are treated, clindamycin for 10 days or IM penicillin plus 4 days of rifampin are recommended treatment options.22 While some literature exists to support the use of a shorter course of antibiotic therapy for GAS pharyngitis, most international guidelines still recommend a 10-day course for most antibiotics.23 This may change shortly as new guidelines are due in 2010 from the Infectious Diseases Society of America (IDSA).

Penicillin G benzathine (Bicillin LA)

Inhibits biosynthesis of cell wall mucopeptide. Bactericidal against sensitive organisms when adequate concentrations reached, and most effective during stage of active multiplication. Inadequate concentrations may produce only bacteriostatic effects. Still is drug of choice in GAS pharyngitis because of its narrow spectrum of activity, low cost, and proven safety track record. IM penicillin is drug of choice in patients where compliance is an issue because of single dose.

Tonsillitis
History
The patient's history determines the type of tonsillitis (ie, acute, recurrent, chronic) that is present. Acute tonsillitis o Individuals with acute tonsillitis present with fever, sore throat, foul breath, dysphagia (difficulty swallowing), odynophagia (painful swallowing), and tender cervical lymph nodes. o Airway obstruction may manifest as mouth breathing, snoring, nocturnal breathing pauses, or sleep apnea. o Lethargy and malaise are common. o Symptoms usually resolve in 3-4 days but may last up to 2 weeks despite adequate therapy. Recurrent tonsillitis is diagnosed when an individual has 7 episodes in 1 year, 5 infections in 2 consecutive years, or 3 infections each year for 3 years consecutively. Individuals with chronic tonsillitis may present with chronic sore throat, halitosis, tonsillitis, and persistent tender cervical nodes. Children are most susceptible to infection by those in the carrier state. Individuals with peritonsillar abscess (PTA) present with severe throat pain, fever, drooling, foul breath, trismus (difficulty opening the mouth), and altered voice quality (the "hot potato" voice).

Physical

Physical examination should begin by determining the degree of distress regarding airway and swallowing function. Examination of the pharynx may be facilitated by opening the mouth without tongue protrusion, followed by gentle central depression of the tongue. Full assessment of oral mucosa, dentition, and salivary ducts may then be performed by gently "walking" a tongue depressor about the lateral oral cavity. Flexible fiberoptic nasopharyngoscopy may be useful in selected cases, particularly with severe trismus. The images below depict the oral examination.

Examination of the tonsils and pharynx.

Oral mucosal examination.

Physical examination in acute tonsillitis reveals fever and enlarged inflamed tonsils that may have exudates as seen in the image below.

Acute bacterial tonsillitis is shown. The tonsils are enlarged and inflamed with exudates. The uvula is midline.

Group A beta-hemolytic Streptococcus pyogenes and Epstein-Barr virus (EBV) can cause tonsillitis that may be associated with the presence of palatal petechiae. Group A betahemolytic Streptococcus (GABHS) pharyngitis usually occurs in children aged 5-15 years. Open-mouth breathing and voice change (ie, a thicker or deeper voice) result from obstructive tonsillar enlargement. The voice change with acute tonsillitis is usually not as severe as that associated with peritonsillar abscess (PTA). In peritonsillar abscess (PTA), the pharyngeal edema and trismus cause a hot potato voice.

Tender cervical lymph nodes and neck stiffness are observed in acute tonsillitis. Examine skin and mucosa for signs of dehydration. Consider infectious mononucleosis (MN) due to EBV in an adolescent or younger child with acute tonsillitis, particularly when tender cervical, axillary, and/or inguinal nodes; splenomegaly; severe lethargy and malaise; and low-grade fever accompany acute tonsillitis. A gray membrane may cover tonsils that are inflamed from an EBV infection as seen in the image below. This membrane can be removed without bleeding.

Tonsillitis caused by Epstein-Barr infection (infectious mononucleosis). The enlarged inflamed tonsils are covered with gray-white patches.

Palatal mucosal erosions and mucosal petechiae of the hard palate may be observed.

An individual with herpes simplex virus (HSV) pharyngitis presents with red, swollen tonsils that may have aphthous ulcers on their surfaces. Herpetic gingival stomatitis, herpes labialis, and hypopharyngeal and epiglottic lesions may be observed. Physical examination of a peritonsillar abscess (PTA) almost always reveals unilateral bulging above and lateral to one of the tonsils. Trismus is always present in varying severity. The abscess rarely is located adjacent to the inferior pole of the tonsil. Inferior pole peritonsillar abscess (PTA) is a difficult diagnosis to make, and radiologic imaging with a contrast-enhanced CT scan is helpful. Tender cervical adenopathy and torticollis (neck turned in the cock-robin position) may be present. Ipsilateral otalgia may be observed.

Workup
Laboratory Studies
Tonsillitis and peritonsillar abscess (PTA) are clinical diagnoses. Testing is indicated when GABHS infection is suspected. o Throat cultures are the criterion standard for detecting GABHS. GABHS is the principal organism for which antibiotic therapy (sensitivity 90-95%) is definitely indicated. Growing concerns over bacterial resistance make monitoring acute tonsillitis with throat swabs for culture and sensitivity an important endeavor. Relying only on clinical criteria, such as the presence of exudate, erythema, fever, and lymphadenopathy, is not an accurate method for distinguishing GABHS from viral tonsillitis. o Beta-lactamase resistance of streptococcal species may now be observed in up to a third of community-based streptococcal infections. This resistance is probably due to the presence of copathogens that are beta-lactamaseproducing organisms, such as H influenzae and Moraxella catarrhalis. These organisms are able to degrade the beta-lactam ring of penicillin and make an otherwise sensitive GABHS act resistant to beta-lactam antibiotics. In one study, erythromycin did not inhibit nearly half of S pyogenes isolates. The limited precision of many throat swabs may reduce the usefulness of these samples. o A rapid antigen detection test (RADT), also known as the rapid streptococcal test, detects the presence of GABHS cell wall carbohydrate from swabbed material and is considered less sensitive than throat cultures; however, the test has specificity of greater than or equal to 95% and produces a result in significantly less time than that required for throat cultures. A negative RADT requires that a throat culture be obtained before excluding GABHS infection. o A culture or RADT is not indicated in most cases following antibiotic therapy for acute GABHS pharyngitis. Routine testing of asymptomatic household contacts is similarly not usually warranted. A Monospot serum test, CBC count, and serum electrolyte level test may be indicated.

Serum may be examined for antistreptococcal antibodies, including antistreptolysin-O antibodies and antideoxyribonuclease (anti-DNAse) B antibodies. Titers are useful for documenting prior infection in persons diagnosed with acute rheumatic fever, glomerulonephritis, or other complications of GABHS pharyngitis. Laboratory evaluation in chronic tonsillitis relies upon documentation of results of pharyngeal swabs or cultures taken during prior episodes of tonsillitis. The usefulness and cost of throat swabs for pharyngitis are debated.

Imaging Studies
Routine radiologic imaging is not useful in cases of acute tonsillitis. For patients in whom acute tonsillitis is suspected to have spread to deep neck structures (ie, beyond the fascial planes of the oropharynx), radiologic imaging using plain films of the lateral neck or CT scans with contrast is warranted. In cases of peritonsillar abscess (PTA), CT scanning with contrast is indicated in general for the following situations:10 o Unusual presentations (eg, an inferior pole abscess) o For patients at high risk for drainage procedures (eg, patients with coagulopathy or anesthetic risk) CT scanning may be used to guide needle aspiration in the following situations: o Draining peritonsillar abscesses (PTAs) after an unsuccessful surgical attempt o Draining abscesses that are located in unusual locations and are anticipated to be difficult to reach with standard surgical approaches

Treatment
Medical Care
Treatment of acute tonsillitis is largely supportive and focuses on maintaining adequate hydration and caloric intake and controlling pain and fever. Inability to maintain adequate oral caloric and fluid intake may require IV hydration, antibiotics, and pain control. IV corticosteroids may be administered to reduce pharyngeal edema. Corticosteroids may shorten the duration of fever and pharyngitis in cases of infectious mononucleosis (MN). In severe cases of MN, corticosteroids or gammaglobulin may be helpful. Symptoms of MN may last for several months. Corticosteroids are also indicated for patients with airway obstruction, hemolytic anemia, and cardiac and neurologic disease. Inform patients of complications from steroid use. Antibiotics are reserved for secondary bacterial pharyngitis. Because of the risk of a generalized papular rash, avoid ampicillin and related compounds when MN is suspected. Similar reactions from oral penicillin-based antibiotics (eg, cephalexin) have been reported. Therefore, initiate therapy with another antistreptococcal antibiotic such as erythromycin. Administer antibiotics if conditions support bacterial etiology, such as the presence of tonsillar exudates, presence of a fever, leukocytosis, contacts who are ill, or contact with a person who has a documented GABHS infection. In many cases, bacterial and viral pharyngitis are clinically indistinguishable. Waiting 1-2 days for throat culture results has not been shown to diminish the usefulness of antibiotic therapy in preventing rheumatic fever. GABHS infection obligates antibiotic coverage. Bisno et al stated, in a practice guideline for the diagnosis and management of group A beta-hemolytic Streptococcus pyogenes (GABHS), the desired outcomes of therapy for GABHS pharyngitis are (1) prevention of acute rheumatic fever, (2) prevention of suppurative complications, (3) abatement of clinical symptoms and signs, (4) reduction in transmission of GABHS to close

contacts, and (5) minimization of potential adverse effects of inappropriate antimicrobial therapy.11 Administering oral penicillin for 10 days is the best treatment of acute GABHS pharyngitis. Intramuscular penicillin (ie, benzathine penicillin G) is required for persons who may not be compliant with a 10-day course of oral therapy. Penicillin is optimal for most patients (barring allergic reactions) because of its proven safety, efficacy, narrow spectrum, and low cost. Other antibiotics proven effective for GABHS pharyngitis are the penicillin congeners, many cephalosporins, macrolides, and clindamycin. Clindamycin may be of particular value because its tissue penetration is considered equivalent for both oral and IV administration. Clindamycin is effective even for organisms that are not rapidly dividing (Eagle effect), which explains its great efficacy for GABHS infection. Vancomycin and rifampin have also been useful. Reduced-frequency dosing is recommended to improve compliance with medication regimens. A consensus on the efficacy of such dosing has not yet been formulated. Airway obstruction may require management by placing a nasal airway device, using intravenous corticosteroids, and administering humidified oxygen. Observe the patient in a monitored setting until the airway obstruction is clearly resolving. Most acute pharyngitis is self-limited with clinical improvement observed in 3-4 days. Recent clinical practice guidelines state that avoiding antibiotic therapy for this time period is safe and that a delay of up to 9 days from symptom onset to antimicrobial treatment should still prevent the major complication of GABHS (ie, acute rheumatic fever). Recurrent tonsillitis may be managed with the same antibiotics as acute GABHS pharyngitis. If the infection recurs shortly after a course of an oral penicillin agent, then consider IM benzathine penicillin G. Clindamycin and amoxicillin/clavulanate have been shown to be effective in eradicating GABHS from the pharynx in persons experiencing repeated bouts of tonsillitis. A 3- to 6-week course of an antibiotic against beta-lactamaseproducing organisms (eg, amoxicillin/clavulanate) may allow tonsillectomy to be avoided. Carrier state should be treated when the family has a history of rheumatic fever, a history of glomerulonephritis in the carrier, a "ping pong" spread of infection between household contacts of the carrier, familial anxiety regarding the implications of GABHS carriage, infectious outbreak within a closed community such as a school, an outbreak of acute rheumatic fever, or when tonsillectomy may be under consideration to treat the chronic carriage of GABHS. Peritonsillar cellulitis may respond to oral antibiotics. Antibiotics, either orally or intravenously, are required to treat PTA medically, although most peritonsillar abscesses (PTAs) are refractory to antibiotic therapy alone. Penicillin, its congeners (eg, amoxicillin/clavulanic acid, cephalosporins), and clindamycin are appropriate antibiotics. Aetius of Amida, a sixth century Byzantine physician, managed spontaneously draining abscesses with gargles of honey, milk and herbs, or rose extract. In rare cases of spontaneous peritonsillar abscess (PTA) rupture, mouthwashes are still recommended for hygienic reasons. A 10-day course of an oral antibiotic is prescribed.

Surgical Care
Recurrent tonsillitis o Tonsillectomy is indicated for individuals who have experienced more than 6 episodes of streptococcal pharyngitis (confirmed by positive culture) in 1 year, 3 or more infections of tonsils and/or adenoids per year despite adequate medical therapy, or chronic or recurrent tonsillitis associated with the streptococcal carrier state that has not responded to beta-lactamaseresistant antibiotics.

Time missed from school or work and severity of illness (eg, whether hospitalization was required) are important considerations in recommending tonsillectomy. o Because adenoid tissue has similar bacteriology to the pharyngeal tonsils and minimal additional morbidity occurs with adenoidectomy if tonsillectomy is already being performed, most surgeons perform adenoidectomy if adenoids are present and inflamed at the time of tonsillectomy. However, this point remains controversial. o Recurrent tonsillitis after tonsillectomy is extremely rare. Tonsillectomy reduces the bacterial load of GABHS and may also allow an increase in alphaStreptococcus, which can be protective against GABHS infection. Recurrent tonsillitis is usually due to regrowth of tonsillar tissue, which is treated by excision. Chronic tonsillitis o Tonsillectomy with or without adenoidectomy is the treatment of chronic tonsillitis. The details of the technique are reviewed in the article on Tonsillectomy. o In cases of chronic tonsillitis, specific technical considerations for tonsillectomy include awareness of a higher intraoperative and perioperative bleeding risk and awareness that dissection may be more difficult because of fibrosis and scarring of the tonsillar capsule. Such considerations may affect instrument selection and discharge decisions. Lingual tonsillitis o Surgery is rarely required for acute lingual tonsillitis. o Surgery is indicated for frequent and disabling episodes of this uncommon malady. Tonsillitis in cases of MN: Tonsillar hypertrophy that persists after resolution of MN and causes obstructive airway symptoms may require tonsillectomy. Peritonsillar abscess o Treatment of peritonsillar abscesses (PTAs) includes aspiration and incision and drainage (I&D). o Aetius recommended incision if an abscess did not spontaneously drain. o When peritonsillar abscess (PTA) is suspected, aspiration with a needle may be attempted to confirm the diagnosis and to remove some of the purulence. The area of the peritonsillar abscess (PTA) is first anesthetized by infiltration with local anesthetic or by spray or sponge application of topical anesthesia (eg, Americaine, benzocaine). Sedation may be helpful; administer sedation only in a facility that is appropriately staffed and equipped. An 18-gauge needle on a 1 mL tuberculin syringe is placed into the pointing area, taking care not to penetrate the pharyngeal mucosa more than 1 inch in order to prevent injury to the vessels and nerves of the parapharyngeal space. If attempt at aspiration from 3 different peritonsillar sites does not locate the abscess, treat the patient with oral or IV antibiotics. If symptoms persist after 24-48 hours of therapy, CT scanning with contrast may be performed. o Once purulence is detected, complete aspiration may be attempted. In the author's experience, limited aspiration is best, provided that sufficient material is available for Gram stain and cultures with antibiotic sensitivities. Not all patients need microbiologic evaluation. For those who are immunosuppressed or who have developed a peritonsillar abscess (PTA) after several days of appropriate antibiotic therapy, send aspirated material for Gram stain, culture, and sensitivity tests. o After needle aspiration, incision and drainage may be performed using a knife. The handle of a knife with an attached No 15 blade is taped 1 inch from the tip to prevent deep penetration through the mucosa. A gentle curvilinear incision, not more than half an inch deep, is fashioned along the perimeter of the tonsillar capsule and through the point from which pus was evacuated. A

widely tipped blunt clamp (eg, Kelly clamp) is used to widely open the loculated pockets of purulence. A sponge-covered finger to break loculations is ideal. Rinsing with half-strength hydrogen peroxide solution aids hemostasis. When the patient is dehydrated and uncomfortable, this well-intentioned procedure is not greeted with enthusiasm from the patient. Sedation, hydration, analgesia, and anesthesia (at the least, topical or local) are important. Using the nondominant hand, the physician grasps the tongue with a sponge and observes the posterior oropharynx. In patients with severe trismus, a tongue blade may be used to depress the midportion of the tongue. Magnifying and illuminating loupes, such as the LumiView, are the best sources of light. A headlight or mirror is also effective. Arranging the instruments in order of use on a tray adjacent to the physician's dominant hand facilitates rapid accomplishment of this procedure. In experienced hands, this procedure should take fewer than 3 minutes from aspiration to rinsing with peroxide. Some adults and most children require deeper levels of sedation or general anesthesia for safe and adequate aspiration or drainage. An institution with a carefully designed policy for incision and drainage of peritonsillar abscess (PTA) with conscious sedation, including appropriate indications, staff, and criteria, may offer sedation to children. After the procedure, the patient is observed in accordance with sedation and anesthetic protocols. Hospitalization for adults and for older children is rarely required. The patient is discharged with a prescription for an oral antibiotic (10-d course of therapy), a prescription for an oral narcotic for pain control (taking care to avoid antiplatelet agents), and instructions to maintain hydration and control fever. Antibiotic therapy may be altered after cultures return. A follow-up office visit or telephone call is made in 2-4 weeks after the procedure to confirm symptomatic resolution. Tonsillectomy is indicated for peritonsillar abscess (PTA) associated with chronic or recurrent tonsillitis or for exposure of the abscess in unusual cases. Newer techniques and technologies offer improved recovery and reduced complications from surgery.12 Acute tonsillectomy is generally regarded as a safe and effective treatment of peritonsillar abscess (PTA). Some physicians advocate immediate tonsillectomy for younger patients with peritonsillar abscess (PTA). Removing hot tonsils (ie, those that are acutely infected) carries the expectation of higher intraoperative blood loss and a higher risk of immediate and delayed posttonsillectomy hemorrhage. The term quinsy tonsillectomy refers to tonsillectomy performed to treat peritonsillar abscess (PTA). Bilateral tonsillectomy is usually performed in these cases, and the abscessed tonsil is usually easier to remove during surgery than the inflamed contralateral tonsil. The abscessed tonsil is easier to remove because the abscess partially dissects the tonsil from the pharyngeal musculature. During surgery, if the abscess cannot be located in the usual superior lateral region of the tonsillar fossa, then careful exploration with needle aspiration may locate the collection, allowing for wide exposure and drainage. Tonsillectomy may be required for exposure in such cases. A CT scan with contrast may be indicated. Fleshy or pale, granular tonsillar tissue may indicate a neoplasm. Immunohistopathologic examination is indicated in such cases.

Consultations

Consultations with infectious-disease, hematologic, and pediatric subspecialists are valuable in selected cases.

Diet
Hydration is important, and the oral route is usually adequate. Intravenous fluids may be required for severe dehydration. Hyperalimentation is rarely necessary.

Activity
Adequate rest for adults and children with tonsillitis accelerates recovery. In order to reduce risk of splenic rupture in persons diagnosed with systemic mononucleosis (MN), patients must be cautioned against activities that may cause abdominal injury.

Medication
Medications used to manage tonsillitis include antibiotics, anti-inflammatory agents (eg, corticosteroids), antipyretics and analgesics (eg, acetaminophen, ibuprofen), and immunologic agents (eg, gammaglobulin).

Corticosteroids
The following agents reduce inflammation, which may impair swallowing and breathing.

Dexamethasone (Decadron, AK-Dex)

Short-acting, rapid-onset glucocorticoid.

Dosing Interactions Contraindications Precautions

Adult

Not established
Pediatric

0.5-1 mg/kg IV q8h; not to exceed 10 mg q8h; discontinue by tapering if prolonged use

Antibiotics
Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

Penicillin (Benzathine, Permapen)

Interferes with synthesis of cell wall mucopeptides during active multiplication, which results in bactericidal activity.
Dosing Interactions

Contraindications Precautions

Adult

1.2 million U IM, preferably into upper outer quadrant of buttock

Pediatric

<60 lb: 300,000-600,000 U IM; not to exceed 900,000 U IM; consulting hospital formulary at physician's institution recommended >60 lb: Administer as in adults

Clarithromycin (Biaxin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest. Semisynthetic macrolide with bid dosing.
Dosing Interactions Contraindications Precautions

Adult

250 mg PO q12h for 10 d

Pediatric

7.5 mg/kg PO q12h; not to exceed 250 mg/dose

Clindamycin (Cleocin)

Oral or parenteral antibiotic for anaerobic or susceptible streptococcal, pneumococcal, or staphylococcal species. Considered to have good absorption into bloodstream in both oral and parental forms.
Dosing Interactions Contraindications Precautions

Adult

150-450 mg PO q8h 1.2-2.7 g IV/IM q8h

Pediatric

Neonates: Consult hospital pharmacy Infants and children: 15-25 mg/kg/d PO q8h; 25-40 mg/kg/d IV/IM q8h

Vancomycin (Vancocin, Lyphocin)

Indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins, or who have infections with resistant staphylococci. To avoid toxicity, current recommendation is to

assay vancomycin trough levels after third dose drawn 0.5 h prior to next dosing. Use creatinine clearance (CrCl) to adjust dose in patients diagnosed with renal impairment. Used in conjunction with gentamicin for prophylaxis in penicillin allergic patients undergoing gastrointestinal or genitourinary procedures.
Dosing Interactions Contraindications Precautions

Adult

500 mg IV q6h or 1000 mg IV q12h

Pediatric

10 mg/kg IV q6h in neonates and infants; in first wk of life, 15 mg/kg IV first dose, followed by 10 mg/kg IV q12h, then q8h up to age 1 mo

Rifampin (Rifadin, Rimactane)

Inhibitor of bacterial DNA-dependent RNA polymerase activity.

Dosing Interactions Contraindications Precautions

Adult

Not used for this indication

Pediatric

<1 month: 5 mg/kg PO q12h for 2 d >1 month: 10 mg/kg PO q12h for 2 d; not to exceed 600 mg/dose

Amoxicillin (Trimox, Amoxil, Biomox)

Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.
Dosing Interactions Contraindications Precautions

Adult

500-875 mg PO q12h or 250-500 PO q8h

Pediatric

<12 weeks: 30 mg/kg PO q12h for 10 d; recommended for prevention of poststreptococcal rheumatic fever >3 months: 25 mg/kg/d PO q12h in 2 divided doses, 20 mg/kg/d q8h in 3 divided doses, or 45 mg/kg/d q12h in 2 divided doses

Amoxicillin-clavulanate (Augmentin)

Oral antibiotic with specific activity against penicillin-resistant organisms, due to beta-lactamase inhibitor, clavulanate potassium.
Dosing Interactions Contraindications Precautions

Adult

500 mg tab PO q12h or one 250 mg tab PO q8h

Pediatric

<12 weeks: 30 mg/kg/d PO q12h in 2 divided doses, based on reduced renal elimination of the amoxicillin component >3 months: 45 mg/kg/d PO q12h or 40 mg/kg/d q8h >40 kg: Administer as in adults

Metronidazole (Flagyl)

Effective in patients with tonsillitis and MN, shortening fever duration and reducing tonsillar size, and in management of acute episodes of nonstreptococcal tonsillitis.
Dosing Interactions Contraindications Precautions

Adult

Loading dose: 15 mg/kg or 1 g for 70-kg adult IV over 1 h Maintenance dose: 6 h following loading dose, infuse 7.5 mg/kg or 500 mg for 70-kg adult over 1 h q6-8h; not to exceed 4 g/d
Pediatric

Administer as in adults

Immune globulins
These agents are used to improve clinical aspects of the disease.

Immune globulin intravenous (Gamimune N, Gammagard, Sandoglobulin)

Pooled human Ig. Because of shortage of supply, reserved for use for severe infections. Use in accordance with institutional policies. Use in past was more common for various indications.
Dosing Interactions Contraindications Precautions

Adult

Consult hospital pharmacy and medical consultants if necessary

Pediatric

Consult hospital pharmacy and medical consultants if necessary

Otitis media
History
Suspect acute otitis media (AOM), with or without effusion, in children with a history of the following symptoms: o Head and neck Otalgia: Young children may exhibit signs of otalgia by pulling on the affected ear or ears or pulling on the hair. Otalgia apparently occurs more often when the child is lying down (eg, during the night, during nap time), which may be due to increased ETD when the child is in a recumbent position. Otorrhea: Discharge may come from the middle ear through a recently perforated TM, through a preexisting TT, or through another perforation. For trauma patients, excluding a basilar skull fracture with associated cerebrospinal fluid (CSF) otorrhea is important. Headache Concurrent or recent URI symptoms (eg, cough, rhinorrhea, sinus congestion) o General Two thirds of children with AOM have a history of fever, although fevers greater than 40C are uncommon and may represent bacteremia or other complications. Irritability may be the sole early symptom in a young infant or toddler. A history of lethargy, although nonspecific, is a sensitive marker for sick children and should not be dismissed. o GI tract: Symptoms include anorexia, nausea, vomiting, and diarrhea. OME often follows an episode of AOM. Consider OME in patients with recent AOM in whom the history includes any of the following symptoms: o Hearing loss: Most young children cannot provide an accurate history. Parents, caregivers, or teachers may suspect a hearing loss or describe the child as inattentive. o Tinnitus: This is possible, although it is an unusual complaint from a child. o Vertigo: Although true vertigo (ie, room-spinning dizziness) is a rare complaint in uncomplicated AOM or OME, parents may report some unsteadiness or clumsiness in a young child with AOM. o Otalgia: Intermittent otalgia tends to worsen at night. OM treatment widely varies based on the duration of symptoms, past therapeutic failures, and severity of current symptoms. Exposure to environmental risk factors is another important aspect of the history and includes the following: o Passive exposure (ie, secondhand) to tobacco smoke o Group daycare attendance

o o

Seasonality: AOM prevalence is much higher in winter and early spring than in summer and early fall. Supine bottle feeding (ie, bottle propping)

Physical
Pneumatic otoscopy remains the standard examination technique for patients with suspected OM. When performed correctly, this technique is 90% sensitive and 80% specific for diagnosis of AOM, and findings are more accurate than with myringotomy. Proper pneumatic otoscopy technique is crucial to distinguish AOM from OME because recommended therapies for these entities are significantly different. Studies show that most practitioners improperly perform otoscopic examinations. Almost one half of physicians never use pneumatic compression of the TM during routine otoscopic examination, and almost 30% use otoscopes with inadequate light sources. Tympanometry, acoustic reflectometry, and audiometry are important adjunctive techniques with which to evaluate patients with MEE. In addition to a carefully documented examination of the external ear and TM, examining the entire head and neck region of patients with suspected OM is important. Several congenital syndromes, craniofacial anomalies, and systemic diseases have increased incidence associated with OM, including cleft palate, Down syndrome, Treacher Collins syndrome (ie, mandibulofacial dysotosis), hemifacial microsomia, diabetes mellitus, human immunodeficiency virus (HIV) infection, and many types of mucopolysaccharidosis. Below are examination techniques used in the diagnosis of OM. Pneumatic otoscopy examination Under direct visualization, first remove any cerumen, which causes a limited and sometimes inaccurate view of the TM and inaccurate and confusing results on tympanometry and audiometry. To move the TM, the ear speculum must create an air seal against the external auditory canal (EAC), which is seldom possible with a standard disposable speculum. All otoscope manufacturers sell inexpensive cuffed ear speculums to perform insufflation. A rubber sleeve over the speculum may reduce patient discomfort during the examination. Usually, the TM is in the neutral position (ie, neither retracted nor bulging), pearly gray, translucent, and unperforated. It responds briskly to positive and negative pressure, indicating an air-filled space. Many older texts emphasize a TM "light reflex" in an otherwise normal ear. Because this reflex may be absent in entirely normal ears and present in ears with MEE, the light reflex does not help confirm or exclude an OM diagnosis. Every examination should include an evaluation and description of the following 4 TM characteristics: o Color A normal TM is a translucent pale gray. An opaque yellow or blue TM is consistent with MEE. Dark red indicates a recent trauma or blood behind the TM. A dark pink or lighter red TM is consistent with AOM or hyperemia of the TM caused by crying, coughing, or nose blowing. Color of the eardrum is less important diagnostically than its position and mobility. Redness of the TM alone does not necessarily suggest AOM because crying, removal of cerumen with associated irritation of the auditory canal, coughing, nose blowing, and fever can all cause redness of the

eardrum without a middle ear infection. Note that most children cry when their ears are examined. A study of 85 infants showed that the otoscopic finding most predictive of AOM was a poorly mobile, bulging, yellow, and opacified TM. However, this appearance was noted in only 19% of patients. In another analysis, a slightly red TM in a normal position and with normal mobility had a predictive value of only 7% for AOM. Position: The position of the TM (ie, bulging, retracted, neutral, full) is key to differentiating AOM from OME. In AOM, the TM is usually bulging. In OME, the TM is typically retracted or in the neutral position. Mobility: Abnormal movement of the TM during pneumatic otoscopy can suggest various conditions or disorders. Movement during negative pressure only suggests ETD. A TM that moves only slightly with both positive and negative pressure applied indicates the probable presence of middle ear fluid. No movement occurs with a TM perforation or a TT. Studies show that the most consistent physical finding in patients with OME is impaired mobility of the TM during pneumatic otoscopy. Pay special attention to movement of retracted segments of the TM because immobility of these sections may indicate middle ear cholesteatoma in the retraction pockets. Perforation Single perforations are most common, but some patients may have multiple perforations. Note the location and cause of the perforation. Perforations in the posterosuperior quadrant, which are the most difficult to detect, are important because they occasionally are associated with cholesteatoma. Pus or other fluid may drain through a perforation. Multiple perforations and otorrhea that does not yield pathogens on culture may indicate tuberculosis.

Adjunctive screening techniques for OM : Adjunctive techniques help identify patients with asymptomatic OME, which may comprise 10% of cases. Tympanometry (ie, impedance audiometry), the most commonly used adjunctive technique, measures changes in acoustic impedance of the TM/middle ear system with air pressure changes in the EAC. o Current recommendations call for screening tympanometry at the beginning of school and 1 year later to identify children aged 4-6 years with asymptomatic OME. o Tympanometry screening has a high degree of sensitivity (>90%) but is not specific for OME. o The test may yield false-positive results in children with a retracted TM or a thickened TM without effusion. Screening tests may also yield invalid results in children who have cerumen obstructing the external canal or who are crying during the examination. o Middle ear pressure more than 200 daPa or a flat tympanometric curve is classified as a failure. o Further physician evaluation is indicated in a child in whom tympanometry screening fails in both ears and who has at least a 20-dB hearing loss at 1, 2, or 4 kHz.

After 2 months, retest any child in whom tympanometry screening fails in one ear and hearing loss occurs (>20 dB). Also retest children in whom tympanometry screening fails in both ears, even without marked hearing loss (ie, <20 dB). A second screening failure should lead to physician evaluation. Assess the child's hearing, speech, and language and immediately start therapy to correct deficits. Acoustic reflectometry uses an acoustic otoscope to measure reflected sound from the TM; the louder the reflected sound, the greater the likelihood of an MEE. The breakpoint is defined as the level of sound reflectivity that correlates with the presence of MEE. o Acoustic reflectometry is rapid and easy to perform. Among its advantages over tympanometry is that an airtight seal of the EAC is unnecessary and that the test is unaffected by a crying patient or the presence of cerumen in the EAC. o Despite these advantages, acoustic reflectometry has not been widely accepted by otolaryngologists because of the difficulty in setting standards to interpret test results. o No accepted breakpoint standards have been established, so sensitivity and specificity vary according to the breakpoints set for each study. A low breakpoint leads to high sensitivity but low specificity. A high breakpoint leads to higher specificity but lower sensitivity.

Laboratory Studies
Laboratory evaluation is usually unnecessary, although many experts recommend a full sepsis workup in infants younger than 12 weeks who present with fever and associated acute otitis media (AOM). OM is associated with multiple systemic diseases and congenital syndromes. AOM may be the first presenting illness in some of these diseases; therefore, order appropriate laboratory studies to confirm or exclude possible systemic or congenital diseases.

Imaging Studies
Imaging studies are not indicated in patients with OM unless intratemporal or intracranial complications are suspected. In patients in whom an OM complication is suspected, the imaging study of choice is a contrast-enhanced CT scan of the temporal bones. CT findings help diagnose many complications (eg, mastoiditis, epidural abscess, sigmoid sinus thrombophlebitis, meningitis, brain abscess, subdural abscess). Finely cut CT sections through the temporal bone can reveal ossicular disease and cholesteatoma. MRI is more helpful in depicting fluid collections, especially small middle ear collections. MRI is usually performed following CT if further information is needed for definitive diagnosis.

Other Tests
Tympanometry may help with diagnosis in patients with OME. Some practitioners also use acoustic reflectometry to evaluate for MEE in patients with OM.

Procedures
In clinical trials, the criterion standard in the diagnosis of AOM is tympanocentesis to determine the presence of middle ear fluid, followed by culture of the fluid to identify causative pathogens. Because of the expense, effort, and lack of availability, no consensus guidelines call for routine use of tympanocentesis to manage AOM and OME.

Tympanocentesis can improve diagnostic accuracy, guide treatment, and help eliminate unnecessary medical or surgical interventions in selected patients with refractory or recurrent middle ear disease. Neonates, infants, and children with AOM who appear severely ill or toxic should undergo early tympanocentesis with culturing. Children with acquired immunodeficiency virus (AIDS) or those who are immunocompromised secondary to steroid therapy, chemotherapy, or immunosuppressive therapy following organ transplantation should undergo early tympanocentesis to exclude unusual organisms or nosocomial infection. A recent report from the Centers for Disease Control and Prevention (CDC) working group on drug-resistantS pneumoniae (DRSP) includes an option for tympanocentesis versus empiric second-line antibiotic therapy in patients in whom initial antibiotic therapy has failed. 13

Medical Care
Medical management of otitis media (OM) is actively debated in the medical literature, primarily because of a dramatic increase in acute OM (AOM) prevalence over the past 10 years caused by DRSP and beta-lactamaseproducing H influenzae or M catarrhalis. Beta-lactamases are enzymes that hydrolyze amoxicillin and some, but not all, oral cephalosporins, leading to in vitro resistance to these drugs. Currently, 90% of M catarrhalis isolates and 40-50% ofH influenzae isolates in the United States produce beta-lactamases. As a result, empiric antibiotic therapy for this disease has become more complex. Many opinions have been expressed regarding which drugs are best for first- and second-line therapy or whether antibiotics should be prescribed in all patients with AOM. Guidelines for medical management of AOM In 2004, the American Academy of Pediatrics and the American Academy of Family Practice published guidelines for the medical management of AOM based on expert opinion and a thorough, nonsystematic review of the literature.14 Their recommendations are summarized as follows: To diagnose AOM, the clinician should confirm a history of acute onset, identify signs of MEE, and evaluate for the presence of signs and symptoms of middle-ear inflammation. The management of AOM should include an assessment of pain. If pain is present, the clinician should recommend treatment to reduce pain. Acetaminophen and ibuprofen are firstline drugs for pain reduction. OM is one of the most common disorders in children, and concern regarding antimicrobial resistance due to aggressive antibiotic use is growing. Because of these concerns, treatment of OM has significantly changed over the last decade. A growing number of physicians do not recommend antibiotic prophylaxis or treatment in children with mild OM without a fever (or with minimal fever). More importance is now given to observation and close follow-up. Observation without use of antibacterial agents in a child with uncomplicated AOM is an option for selected children based on diagnostic certainty, age, illness severity, and assurance of follow-up. Many parents have concerns regarding this option, but education and involvement in medical decisions increases acceptability. Although instant access is available to clinical guidelines that recommend an expectant management for children with OM who are older than 1-2 years, the antibiotic prescription rate is still high in most emergency departments. If a decision is made to treat with an antibacterial agent, amoxicillin should be prescribed for most children. When amoxicillin is used, the dose should be 80-90 mg/kg/d. In vitro antibacterial activity of amoxicillin against penicillin-susceptible and nonsusceptible S pneumoniaestrains isolated from children with AOM has shown that penicillin resistance

cannot be extrapolated to amoxicillin. Therefore, minimal inhibitory concentrations of penicillin-nonsusceptible S pneumoniae for amoxicillin should be evaluated, and this antimicrobial agent still remains a first-line choice for children with AOM. If the patient fails to respond to the initial management option within 48-72 hours, the clinician must reassess the patient to confirm AOM and exclude other causes of illness. If AOM is confirmed in a patient initially treated with observation, the clinician should begin antibacterial therapy. If the patient was initially treated with one or more antibacterial agents, the clinician should change the antibacterial agent(s). New alternative treatments for OM are desirable because of the relatively high prevalence of recurrent and persistent AOM. The presence of the most prevalent etiologic agent, S pneumoniae, especially penicillin-nonsusceptible strains in children, also supports alternative treatment regimens. Large-dose cefdinir therapy can be used in combination with tympanocentesis and has high efficacy against penicillin-susceptible S pneumoniae.15 The effectiveness is low for nonsusceptible and H influenzae strains. Clinicians should encourage the prevention of AOM through reduction of risk factors. Evidence is insufficient to make a recommendation regarding the use of Complementary and Alternative Medicine (CAM) for AOM.

Earlier recommendations from the American Academy of Pediatrics and the CDC working group on AOM published in 1999 are summarized as follows: First, distinguishing AOM from OME is critical. Prompt antibiotic therapy has been the cornerstone of therapy for AOM for decades; however, antibiotics are not indicated for initial treatment of OME. Second, antimicrobials should not be prescribed in patients in whom AOM is only suspected or in response to parental pressure on providers for specific therapy. A diagnosis of AOM should be supported by a careful history and physical examination that document the presence of MEE and concurrent signs or symptoms of acute illness (see History and Physical). Third, patients with uncomplicated AOM who are younger than 2 years should be treated with a 10-day course of antimicrobials; children older than 2 years may be treated with a 5- to 7day course of antimicrobials. All patients with severe or recurrent AOM or with complications of AOM should be treated for a minimum of 10 days. Fourth, reserve antimicrobial prophylaxis for selected children with recurrent AOM. Recurrent AOM is defined as 3 or more documented episodes within the prior 6 months or 4 or more episodes in the preceding 12 months.

A meta-analysis of 6 randomized trials that studied the effects of antibiotic use in AOM showed that children older than 2 years with mild AOM can be observed without the need for antibiotic administration.16 Antibiotic administration seemed to have a beneficial effect in patients younger than 2 years with bilateral OM and in patients with AOM and otorrhea. A recent study determined the clinical practices related to the diagnosis of OM based on American Academy of Pediatrics guidelines.17 Authors reviewed 88 studies on OM diagnosis and treatment from 1994-2005. At least one American Academy of Pediatrics criteria were used in 81% of the studies, whereas 20% of the studies used all 3 criteria. Use of these criteria can help provide uniformity to the diagnosis and treatment of OM among various centers. The 2004 guidelines have also been shown to reduce the rate of antibiotic prescribing practices among primary care physicians. 18 Medical therapy for AOM

In 1999, the CDC therapeutic working group on DRSP published consensus recommendations for AOM management.19 The recommendations support the use of amoxicillin as the first-line antimicrobial agent of choice in patients with AOM. The group recommended increasing the dose used for empiric treatment from 40-45 mg/kg/d to 80-90 mg/kg/d because of concerns about increasingly resistant strains of S pneumoniae, which are theoretically susceptible to this higher dose. The recommendations for second-line therapy were more controversial, despite their reasonableness from a scientific viewpoint. Stressing the importance of documenting true clinical failure of therapy after at least 3 days of treatment with high-dose amoxicillin, the working group suggests tympanocentesis for identification and susceptibility testing of the etiologic bacteria to guide alternate antibiotic therapy. In cases in which second-line therapy is empirically chosen (a common occurrence, because few primary care physicians routinely perform tympanocentesis in the office), the recommendations suggest administering the following 3 preparations: High-dose oral amoxicillin/clavulanate (80-90 mg/kg/d of amoxicillin component, 6.4 mg/kg/d of clavulanate component) Oral cefuroxime axetil (suspension: 30 mg/mg/d; tablet 250 mg bid) Intramuscular (IM) ceftriaxone (administered as a single IM injection of 50 mg/kg on 3 consecutive days)

The choice of these 3 preparations from among the 16 antimicrobials currently approved by the US Food and Drug Administration (FDA) for OM therapy was based on studies that reported that these drugs achieve sufficient concentrations in middle ear fluid for bacteriocidal action against the common pathogens in AOM, including DRSP and beta-lactamaseproducing H influenzae. Similar studies for the other 13 approved agents either have not been completed or failed to show similar efficacy against resistant bacteria. These recommendations rely heavily on the pharmacodynamics model of drug efficacy. In this model, clinical cure is believed to correlate with demonstrated penetrance of the antibiotic into the middle ear at a level believed to be sufficient to kill the bacterial pathogens that cause AOM. Nevertheless, this model has the following shortcomings: Although bacteriologic eradication correlates with a successful clinical outcome, clinical success occurs in more than 60% of patients, even when bacteriologic eradication is not achieved. Eventually, almost all patients improve. Validation of the pharmacodynamic model relies on tympanocentesis to identify the causative bacteria and to measure antibiotic levels in middle ear fluid. Some antibiotics (eg, azithromycin [Zithromax], clarithromycin [Biaxin]) concentrate intracellularly, not in middle ear fluid, and are bacteriostatic, not bactericidal. A model predicated on certain drug levels and bacterial eradication may underestimate the efficacy of these agents. The drug levels used by the CDC to define bacterial killing were based on standards that changed 6 months after the CDC publication.

The following crucial issues in AOM treatment were not clearly addressed by the CDC recommendations: Patient compliance and the associated factors of dosing frequency, duration of therapy, palatability, and drug cost Guidance for special situations (eg, allergy to penicillins, beta-lactam drugs, or both) Discussion of the option of withholding antibiotic therapy for 2-3 days in a subset of patients with AOM who are likely to experience spontaneous resolution of disease with only supportive

care and analgesic therapy (a widespread practice in the Netherlands and Scandinavia but a practice with few proponents in the United States) Compliance, duration of therapy, and cost are important issues in treating children with AOM. The primary determinants of compliance appear to be frequency of dosing, palatability of the agent, and duration of therapy. Less frequent doses (ie, qd or bid) are more desirable than more frequent doses, which interfere with daily routines. Shorter duration of therapy (ie, 5-7 d vs 10-14 d) increases compliance but should be used only when equal clinical efficacy can be assured. In many instances, palatability ultimately determines compliance in children. For children who are allergic to penicillin or beta-lactam, the only currently available products are cephalosporins, trimethoprim-sulfamethoxazole, or macrolides. Patients who are allergic to penicillin show 10-15% cross-reactivity when treated with cephalosporins. Levofloxacin has demonstrated higher efficacy in the treatment of AOM when compared with amoxicillin/clavulanate and can be used in patients who are allergic to penicillin.20 Pneumococcal resistance to trimethoprim/sulfamethoxazole is increasing and has become more common than penicillin resistance in some areas. Use this drug to treat AOM only in regions where it remains effective. Of the macrolides, erythromycin/sulfisoxazole is a good choice, but many children refuse this agent because of taste; a 5-day course of azithromycin or 10-day course of clarithromycin may be preferred. If DRSP is the suspected etiologic bacterium, do not use macrolides because pneumococcal resistance is absolute with macrolides and, unlike the use of some beta-lactam antibiotics, resistance cannot be overcome by increasing the dose.

Many children with AOM do not benefit from antimicrobial therapy, either because the etiology of the illness is not bacterial or because their immune system clears the infection without use of a drug. No clinical criteria currently distinguish which children do not require antibiotic therapy for AOM. Until such criteria are available, many practitioners are unlikely to withhold initial antimicrobial therapy for proven cases of AOM. Increasing awareness of the pathophysiology of the disease among parents and healthcare providers has resulted in an increase in an observation-only approach in emergency departments with less parental anxiety.21 Medical therapy for OME Most cases of OME occur after an episode of AOM, and 67% of patients develop an MEE. The mean duration of the effusions is 23 days, but many persist much longer. Most cases of OME spontaneously resolve. Studies of the natural history of this disease report the following: An MEE is harbored in 50% of ears 1 month after an episode of acute OME. An MEE is harbored in 20% of ears after 2 months. An MEE continues to be harbored in 10-15% of ears after 3 months. OMEs that persist longer than 3 months have spontaneous resolution rates of only 20-30%, even after years of observation.

Most cases of chronic OME are associated with conductive hearing loss, averaging approximately 25 dB. Complications of hearing loss (eg, language delay, behavioral problems, poor academic performance) have led to investigations of multiple medical and surgical treatments for OME. The following are among the many strategies advocated for medical treatment in patients with OME:

Antimicrobials Antihistamine-decongestants Intranasal and systemic steroids Nonsteroidal anti-inflammatory drugs (NSAIDs) Mucolytics Aggressive management of allergic symptoms

Of these options, only antimicrobial therapy has provided measurable benefits. Steroid therapy (when administered in combination with a beta-lactam antimicrobial) has shown benefit in some studies and no benefit in others. All other medical therapies (ie, decongestants, antihistamines, mucolytics, NSAIDs) have not provided measurable short- or long-term improvements in patients with OME. Patients in whom OME is unresponsive to medical therapy and with an MEE that persists more than 12 weeks should be referred to an otolaryngologist to discuss surgical options in conjunction with further medical therapies. Antimicrobial therapy o No clinical guidelines or consensus recommendations suggest which antimicrobials to use as first-line agents for OME. In this era of increasing antibiotic resistance, selection of an antibiotic agent should be individualized to the patient. o In each patient, consider prior experience with antibiotics, age, sex, and daycare attendance. o If penicillin allergy is not a concern and if the patient has no recent exposure to antibiotics, a reasonable choice for initial therapy is amoxicillin, administered at the same high dose recommended by the CDC for AOM (ie, 80-90 mg/kg/d). o A reasonable first choice in a patient with antibiotic exposure during the prior month is trial administration of a beta-lactamasestable agent (eg, amoxicillin/clavulanate) or a second- or third-generation cephalosporin. o As with antimicrobial selection, no recommendations have been made regarding duration of therapy; 10 days is reasonable for amoxicillin, amoxicillin/clavulanate, and cephalosporins. Studies of prolonged treatment in patients with OME show no advantage in therapies that last longer than 10 days. Steroid therapy o The literature on steroid treatment is inconclusive. In 1994, the Agency for Health Care Policy and Research (AHCPR) reviewed more than 5000 articles concerning the management of OME and published a clinical practice guideline on the topic.22 The review reported that a combination of steroids plus antibiotics improved clearance of MEE in 25.1% of patients. This difference did not meet statistical significance standards, and the panel felt the risks of steroid administration outweighed potential benefits. The final guideline states, "steroid medications are not recommended for treatment of OME in a child of any age." o Since publication of the AHCPR guideline, another investigation of steroids plus antibiotics to treat OME has been published by Rosenfeld.23 Rosenfeld reported that surgery was avoided or postponed for 6 months in 1 of 4 children treated with steroids. Therefore, steroid administration may have a role in patients who are not good surgical candidates. o The steroid regimen should be oral prednisone or prednisolone at a dose of 1 mg/kg/d for 5-7 days, administered in combination with a beta-lactam antibiotic. o Steroids are contraindicated in patients with exposure to varicella who have not received the varicella vaccine because of the possibility of life-threatening disseminated disease.

Controversy continues over the optimal management of OME. The AHCPR guideline, although criticized for having a narrow scope, for favoring medical rather than surgical management of OME, and for minimizing the problem of drug-resistant bacteria, provides a framework with which to consider management options.

Surgical Care
From the beginning, integrate surgical management of AOM and OME with medical treatment for these diseases. Early surgical interventions (eg, tympanocentesis) may be performed by primary care providers, but more invasive procedures (eg, myringotomy, TT insertion, adenoidectomy) require an otolaryngologist. In patients with intratemporal or intracranial complications of OM, surgical consultation is critical. Certain special patient populations, such as those with cleft palate, Down syndrome, or other craniofacial abnormalities, may require early surgical intervention to prevent OM. Indications for tympanocentesis o OM in patients who have severe otalgia, who are seriously ill, or who appear toxic o Unsatisfactory response to antimicrobial therapy o Onset of AOM in a patient receiving antimicrobial therapy o OM associated with a confirmed or potential suppurative complication o OM in a newborn, sick neonate, or patient who is immunologically deficient, any of whom may harbor an unusual organism Recommendations for TT insertion in children o Chronic OME: TT insertion is recommended in children in whom OME is unresponsive to a trial of antibiotic therapy and has persisted for at least 3 months, when bilateral, or at least 6 months, when unilateral. In patients with unilateral OM, 6 months of persistent OME is not an absolute indication for TT placement. If the patient has evidence of TM structural abnormality secondary to OME or if the patient has recurrent infections, TT placement is indicated. If these criteria are not met and hearing is normal in the affected ear, careful observation is probably sufficient. o Recurrent AOM: TT insertion is recommended in children with recurrent AOM, especially when antimicrobial prophylaxis fails. A minimum frequency of 3 or more episodes of AOM during the previous 6 months or 4 or more episodes (one of which is recent) during the previous year indicates tube insertion. o Recurrent OME: TT insertion is recommended in children with recurrent OME in whom the duration of each episode does not meet criteria for chronic disease but cumulative duration is considered excessive (eg, 6 of previous 12 mo). o ETD: TT insertion is recommended in children with ETD (even in the absence of MEE) if the child has persistent or recurrent signs and symptoms of ETD not relieved by medical treatment options or if the child has ETD at the time of reconstructive middle ear surgery. Signs and symptoms include hearing loss (usually fluctuating), disequilibrium/vertigo, tinnitus, autophony, and severe retraction pocket. o Barotrauma: TT insertion is recommended in children with barotrauma, especially for prevention of recurrent episodes (eg, after air travel, hypobaric chamber treatment). Adenoidectomy and/or tonsillectomy procedures performed to treat patients with OM (in addition to myringotomy and TT placement) have generated extensive discussion and recent research, although potential benefits are controversial. Current literature supports the following recommendations from Bluestone:24 o Initial surgery: Myringotomy and TT placement are the initial surgical techniques (withhold adenoidectomy unless the patient has a nasal obstruction). Some experts advocate simultaneous adenoidectomy in patients older than 3 years because this has been shown to improve ET function.

Repeat surgery (following extrusion of tubes and recurrence of chronic MEE unresponsive to antimicrobial therapy): Myringotomy, with or without tube placement, and adenoidectomy, irrespective of adenoid size, are the techniques used. o Tonsillectomy: Although it is not indicated for treatment of OM because it has not been shown to benefit ET function, tonsillectomy may be performed concurrently with surgery for OM if indications are present (eg, frequently recurrent tonsillitis, pharyngeal obstruction). Recommendations for surgery in patients with cleft palate, Down syndrome, and other craniofacial abnormalities include the following: o Myringotomy and TT placement are warranted in most children with cleft palate because of inherent ETD and increased risk of OM. In patients who also have a cleft lip, the TT may be placed at the time of initial lip repair, many months prior to palate repair. Consider performing TT placement or replacement at the time of palate repair. o Children with Down syndrome often exhibit ETD, conductive and sensorineural hearing loss, EAC stenosis, and subtle immunologic deficiencies. These conditions create a high risk for OM, make diagnosis of MEE difficult, and can lead to profound language and learning difficulties. The essential elements of care in these patients include close monitoring, appropriate surgical interventions for EAC enlargement, and repetitive TT placements. Tube selection is a critical issue. These patients may require prolonged external ventilation with TTs because of prolonged ETD. Unfortunately, TTs labeled as long acting or permanent cause the greatest damage to the TM. These patients often require repeated TT insertions, even when long-acting or permanent TTs are used. The best procedure may be to anticipate early extrusion and reinsertion and to avoid these tubes in favor of ultrasmall TTs to prevent long-term TM damage.

Consultations
Otolaryngologist: Refer all patients who may require surgical interventions for complicated OM or who have recurrent AOM or chronic OME to an otolaryngologist. Primary care physicians who are uncomfortable performing tympanocentesis should refer patients who need this procedure to an otolaryngologist. Otologist: Children who present with subjective evidence of hearing loss should receive a formal hearing test (ie, audiogram). Subjective evidence of hearing loss is often provided by a parent or caregiver in younger children or, possibly, by a school teacher in older children. Speech therapist: Speech therapy is indicated for patients in whom COM has caused speech and language delays because of hearing loss.

Medication
The FDA has approved more than a dozen antibiotics to treat otitis media (OM). Some clinicians advocate administering corticosteroids in combination with a beta-lactamstable antibiotic. Before prescribing such therapy, obtain a history of varicella, vaccination against varicella, and recent exposure to a patient with varicella to avoid the risk of disseminated varicella.

Studies of other adjunctive therapy for acute OM (AOM) and OME have shown that NSAIDs, decongestants, and antihistamines provide no obvious benefits.

Antimicrobial agents
These agents remove pathogenic bacteria from middle ear fluid.

Amoxicillin (Biomox, Amoxil, Trimox)

Mainly bactericidal. As with penicillins, inhibits third and final stage of bacterial cell wall synthesis by preferentially binding to specific PBPs located inside the bacterial cell wall. PO semisynthetic aminopenicillin similar to ampicillin. Aminopenicillins are not stable in betalactamases of either gram-positive or gram-negative bacteria; more stable in gastric acid than penicillin and more bioavailable than PO ampicillin. Amoxicillin is associated with a lower prevalence of diarrhea than is ampicillin administered PO because of the greater bioavailability of amoxicillin. Commonly used to treat infections (eg, OM, bronchitis, sinusitis, bacterial cystitis) caused by susceptible organisms. To increase efficacy against PRSP in OM or respiratory infections, higher dosing regimens have been recommended.
Dosing Interactions Contraindications Precautions

Adult

Mild-to-moderate infections caused by highly susceptible organisms: 500 mg PO q12h or 250 mg PO q8h Severe infections or infections caused by less susceptible organisms: 875 mg PO q12h or 500 mg PO q8h
Pediatric

<3 months: 20-30 mg/kg/d PO q12h >3 months: <40 kg: 80-90 mg/kg/d PO divided q8-12h for 10 d in children with AOM who have received antibiotics during prior month or in whom OM is suspected to be caused by penicillin-intermediate PRSP; 25-45 mg/kg/d PO divided q12h or 20-40 mg/kg/d PO q8h for patients with no recent exposure to antibiotics and in whom PRSP is not suspected >40 kg: Administer as in adults

Amoxicillin and clavulanate (Augmentin)

As a beta-lactam antibiotic, amoxicillin is mainly bactericidal. Inhibits third and final stage of bacterial cell wall synthesis by preferentially binding to specific PBPs located inside the bacterial cell wall. As with all beta-lactam antibiotics, ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Clavulanic acid is a beta-lactamase inhibitor that possesses weak antibacterial activity and acts as a competitive "suicide" inhibitor of many plasmid-mediated and chromosome-mediated bacterial betalactamases. Excellent choice for second-line therapy in AOM or initial therapy in OME. Drug combination treats bacteria resistant to beta-lactam antibiotics. Combination with clavulanic acid reestablishes

amoxicillin's activity against beta-lactamase-producing bacteria. Excellent for treating infections due to beta-lactamase-producing H influenzaeand penicillinase-producing anaerobes. Commonly used to treat infections (eg, AOM, acute sinusitis, acute bacterial cystitis, uncomplicated gonorrhea, chancroid) caused by susceptible organisms. For children >3 mo, base dosing protocol on amoxicillin content. Because of different amoxicillin/clavulanic acid ratios in 250-mg tab (250/125) vs 250-mg chewable tab (250/62.5), do not use 250-mg tab until child weighs >40 kg. Use the 7:1 formulation (ie, bid formulation) in higher doses to minimize GI tract effects.
Dosing Interactions Contraindications Precautions

Adult

875 mg PO q12h or 500 mg PO q8h for 10 d

Pediatric

<3 months: 20-30 mg/kg/d (based on amoxicillin component) PO divided q12h for 10 d (use 125 mg/5 mL susp) >3 months: <40 kg: 40-45 mg/kg/d PO divided q8h for 10 d in patients with no recent exposure to antibiotics and patients in whom PRSP is not suspected; 80-90 mg/kg/d PO divided q8-12h for 10 d in patients with AOM caused by penicillin-intermediate PRSP or for empiric treatment of patients who have received antibiotic therapy during prior month or in whom amoxicillin therapy has failed >40 kg: Administer as in adults

Cefaclor (Ceclor)

Second-generation PO cephalosporin indicated for infections caused by susceptible gram-positive cocci and gram-negative rods. Has slightly improved activity against H influenzae compared to cephalexin. Although marketed after first-generation agents, causing some clinicians to consider it a second-generation agent, its spectrum more closely resembles first-generation cephalosporins. Clinically, used primarily to treat OM, sinusitis, and URIs caused by H influenzae that are resistant to ampicillin or amoxicillin. Use higher doses for severe infections (eg, pneumonia, OM), less susceptible strains of pathogens, and in patients who are obese.
Dosing Interactions Contraindications Precautions

Adult

IR: 250-500 mg PO q8h; not to exceed 4 g/d SR: 375-500 mg PO q12h for 7-10 d
Pediatric

>1 month: 20-40 mg/kg/d PO q8h; may be divided bid to treat OM or pharyngitis; not to exceed 2 g/d

Cefprozil (Cefzil)

PO, semisynthetic, second-generation cephalosporin. Binds to one or more PBPs, which, in turn, inhibit cell wall synthesis and result in bactericidal activity. Possible second-line therapy for AOM or initial therapy for OME. Therapeutic uses include OM, soft tissue infections, and respiratory tract infections.
Dosing Interactions Contraindications Precautions

Adult

250-500 mg PO q12h for 10 d

Pediatric

>6 months: 15 mg/kg PO q12h for 10 d; not to exceed 1 g/d

Cefuroxime (Ceftin)

Second-generation cephalosporin maintains the gram-positive activity of first-generation cephalosporins and adds activity against Proteus mirabilis, H influenzae, E coli, K pneumoniae, and M catarrhalis. Common clinical uses include severe upper and lower respiratory tract infections, skin infections, OM, and surgical prophylaxis. Condition of patient, severity of infection, and susceptibility of microorganism determine proper dose and route of administration. Susp is less bioavailable than tab. Bioavailability is enhanced when administered with food or infant formula.
Dosing Interactions Contraindications Precautions

Adult

OM: 250-500 mg PO bid Sinusitis: 250 mg PO bid for 10 d

Pediatric

Susp: 3 months to 12 years: 30 mg/kg/d PO divided bid pc; not to exceed 1000 mg/d Tab: 250 mg PO bid pc in children able to swallow tabs

Cefixime (Suprax)

Third-generation cephalosporin available in an PO formulation. As with ceftriaxone, has enhanced antibacterial activity and increased stability against many beta-lactamases. By binding to one or more PBPs, it arrests bacterial cell wall synthesis and inhibits bacterial growth. Commonly used to treat OM, respiratory tract infections, and URIs caused by susceptible organisms. When treating OM, susp is preferred due to higher serum concentrations achieved with this dosage form compared with tabs.

Dosing Interactions Contraindications Precautions

Adult

>50 kg: 400 mg/d PO qd or divided bid

Pediatric

6 months to 12 years: 8 mg/kg/d PO qd or divided bid; not to exceed 400 mg/d >12 years or >50 kg: Administer as in adults

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more PBPs. Has longest half-life of all cephalosporins, allowing once-daily dosing and making it a useful antibiotic for outpatient therapy. In Dec 1997, the FDA approved IM ceftriaxone to treat bacterial AOM caused by H influenzae (betalactamase negative), H influenzae (beta-lactamase positive), M catarrhalis (including beta-lactamase producing strains), and S pneumoniae. Approval was based on the following data in children aged 5 months to 5 years: A prospective, randomized, double-blind, clinical trial compared the effectiveness of a 50 mg/kg single dose of IM ceftriaxone (n=116) with a 10-d course of PO amoxicillin (n=117). The authors concluded that a single IM injection of ceftriaxone is as effective as PO amoxicillin to treat uncomplicated OM in children. The CDC's DRSP therapeutic working group suggests this dose for 3 consecutive days in cases of suspected resistant bacteria.
Dosing Interactions Contraindications Precautions

Adult

Not recommended
Pediatric

50 mg/kg IM once; not to exceed 1 g/dose

Cefpodoxime (Vantin)

Cefpodoxime proxetil is an PO prodrug for the extended-spectrum, semisynthetic, cephalosporin antibiotic cefpodoxime. Spectrum is similar to third-generation cephalosporins and primarily has gramnegative coverage but also covers some gram-positive organisms. Highly stable in the presence of beta-lactamase enzymes; as a result, many organisms resistant to penicillins and some cephalosporins (due to beta-lactamases) may be susceptible to cefpodoxime. Indicated for treatment of upper and lower respiratory tract infections, UTIs, STDs, and skin and skin structure infections. Has long half-life, allowing twice-daily administration. Approved by the FDA in 1984.

Dosing Interactions Contraindications Precautions

Adult

200 mg PO bid
Pediatric

10 mg/kg/d PO divided bid; not to exceed 400 mg/d

Clarithromycin (Biaxin)

PO macrolide antibiotic similar to erythromycin and azithromycin. Commonly used in infections of the respiratory tract, STDs, OM, and infections in patients with AIDS. As with other macrolides, binds to 50S subunit of the 70S ribosome, thereby blocking RNA-mediated bacterial protein synthesis. Can be bacteriostatic or bactericidal in action, depending on concentration and the particular organism and its inoculum. Also penetrates phagocytes and macrophages efficiently, and, as a result, is effective against a wide variety of organisms in respiratory infections. Generally active against organisms that are usually susceptible to erythromycin, including most staphylococcal and streptococcal strains. In addition, clarithromycin is active against M catarrhalis, Mycoplasma pneumoniae, Legionella species, and Chlamydia pneumoniae. Beta-lactamase production should have no effect on activity. Most strains of methicillin-resistant and oxacillin-resistant staphylococci are resistant to clarithromycin. Originally approved by the FDA in Oct 1991.
Dosing Interactions Contraindications Precautions

Adult

IR: 500 mg PO q12h for 7-14 d

Pediatric

>6 months: 7.5 mg/kg PO q12h for 10 d; not to exceed 1 g/d

Azithromycin (Zithromax)

Semisynthetic antibiotic belonging to the macrolide subgroup of azalides. Similar in structure to erythromycin. Inhibits protein synthesis in bacterial cells by binding to the 50S subunit of bacterial ribosomes. Action is generally bacteriostatic but can be bactericidal in high concentrations or against susceptible organisms. Although significantly more expensive, it can be administered as a once-daily dose and produces less GI tract intolerance than erythromycin. Apparent advantage over erythromycin is that it reaches higher intracellular concentrations, thus increasing efficacy and duration of action. These advantages are demonstrated in studies that show that single doses are effective for the treatment of STDs caused by chlamydial and gonorrheal organisms. Approved by FDA in Nov 1991. PO susp was introduced in Apr 1995. In late 1995, was approved for treatment of pediatric OM and pharyngitis and, in mid 1996, was approved for MAC prophylaxis in

patients with advanced HIV disease. IV form is also available for initial treatment of community-acquired pneumonia and pelvic inflammatory disease.
Dosing Interactions Contraindications Precautions

Adult

1 g PO as single dose Alternative: Day 1: 500 mg PO as single dose Days 2-5: 250 mg/d PO
Pediatric

<6 months: Not established >6 months: Day 1: 10 mg/kg PO as single dose; not to exceed 500 mg/d Days 2-5: 5 mg/kg/d PO; not to exceed 250 mg/d Administer susp on empty stomach (ie, 1 hr ac or 2 hr pc)

Trimethoprim and sulfamethoxazole (Bactrim DS, Septra DS)

Also known as co-trimoxazole. Combination product of TMP and SMZ in a fixed 1:5 ratio. Ratio produces serum concentrations of 1:20, which optimize antibacterial activity against some organisms. Both TMP and SMZ are synthetic folate antagonists that are effective antimicrobials as individual agents. TMP is usually bactericidal and acts by inhibiting sequential enzymes of the folic acid synthesis pathway. SMZ is a structural analog of PABA and competitively inhibits formation of dihydrofolic acid from PABA. TMP binds to and reversibly inhibits the enzyme dihydrofolate reductase, which prevents formation of THF from dihydrofolic acid. THF is a metabolically active form of folic acid. Without THF, bacteria cannot synthesize thymidine, which leads to interference with bacterial nucleic acid and protein formation. Combination of TMP with SMZ is synergistic against some bacteria. Usually active against Staphylococcus epidermidis, S aureus, S pneumoniae, Streptococcus viridans, most Enterobacteriaceae, Salmonella and Shigellaspecies, H influenzae, M catarrhalis, and Stenotrophomonas maltophilia. Enterococcus species, Neisseria gonorrhoeae, P aeruginosa, and anaerobes are usually resistant or less susceptible. Also effective againstPneumocystis carinii, Listeria monocytogenes, many Nocardia species, Yersinia enterocolitica, and Legionella pneumophila. Initially used in the treatment of UTIs but has since proved to be a versatile agent and is now widely used in the prevention and treatment of P carinii pneumonia. Approved by FDA in 1973.
Dosing Interactions Contraindications Precautions

Adult

160 mg (TMP component)/800 mg (SMZ component) PO q12h

Pediatric

<2 months: Contraindicated >2 months: 7.5-8 mg (based on TMP component)/kg/d PO divided bid

Erythromycin (E-Mycin, Eryc, Ery-Tab, Erythrocin)

Macrolide antibiotic produced by Streptomyces erythraeus; first of several macrolide antibiotics now on the market. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections. Effective against wide range of microorganisms and, as with other antibiotics that inhibit protein synthesis, is mainly bacteriostatic. Activity against gram-positive organisms is usually greater than against gram-negative organisms because of superior penetration into gram-positive organisms. Gram-positive organisms susceptible to erythromycin include S aureus, Streptococcus agalactiae, Streptococcus pyogenes, S pneumoniae, S viridans, and Corynebacterium diphtheriae. Gramnegative coverage is limited. In general, should not be used against H influenzae, although, in some cases, organism may be susceptible. Although erythromycin is active against many microbes, its clinical applications are relatively few. In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, half of the total daily dose may be taken q12h. For more severe infections, double the dose.
Dosing Interactions Contraindications Precautions

Adult

250 mg (erythromycin stearate/base) or 400 mg (ethylsuccinate) q6h PO 1 h ac, or 500 mg q12h Alternative: 333 mg q8h; increase to 4 g/d depending on severity of infection
Pediatric

Neonates: <7 days: 20 mg/kg/d PO divided q12h >7 days and <1200 g: 20 mg/kg/d PO divided q12h >7 days and >1200 g: 30 mg/kg/d PO divided q8h