eMedicine Specialties > Infectious Diseases > HEENT Infections

Sinusitis, Chronic

Itzhak Brook, MD, MSc, Professor, Department of Pediatrics, Georgetown University School of Medicine
Himal Bajracharya, MBBS, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases, Kansas University Medical Center; Daniel Hinthorn, MD, Director, Division of Infectious Diseases, Professor, Departments of Internal Medicine, Pediatrics and Family Medicine, University of Kansas

Updated: Jun 17, 2009

Introduction

Background

Chronic sinusitis is one of the more prevalent chronic illnesses in the United States, affecting persons of all age groups. Generally defined as a sinus infection that persists for more than 3 months, chronic sinusitis usually manifests differently than acute sinusitis. Symptoms of chronic sinusitis include nasal stuffiness, postnasal drip, facial fullness, and malaise. Most cases of chronic sinusitis are continuations of unresolved acute sinusitis.

Allergic rhinitis, nonallergic rhinitis, anatomic obstruction in the ostiomeatal complex, and immunologic disorders are known risk factors for chronic sinusitis.

Pathophysiology

Anatomic considerations

Knowledge of the anatomy of paranasal sinuses is essential for understanding the pathophysiology and management of chronic sinusitis.

The 4 pairs of paranasal sinuses are lined with ciliated, pseudostratified columnar epithelium. Goblet cells are interspersed among the columnar cells. The mucosa is attached directly to the bone. Involvement of the surrounding bone and further extension of the infection into the orbital and intracranial compartments can result from inadequate treatment of sinusitis and specific types of sinusitis (eg, fungal sinusitis).

The maxillary, frontal, and anterior ethmoid sinuses drain through their ostia located at the ostiomeatal complex lying lateral to the middle turbinate within the middle meatus. The posterior ethmoid and sphenoid sinuses open into the superior meatus and sphenoethmoid recess, respectively. The maxillary ostium is connected to the nasal cavity by a narrow tubular passage called the infundibulum, located at the highest part of the sinus; hence, drainage from the maxillary sinus flows against gravity via mucociliary clearance. Because the floor of the maxillary sinus is the tooth-bearing part of the maxilla, dental infections can easily extend to the maxillary sinus. Although the nasal cavity is usually colonized with bacteria, the sinuses are typically sterile.

Stasis of secretions inside the sinuses can be triggered by (1) mechanical obstruction at the ostiomeatal complex due to anatomic factors or (2) mucosal edema caused by various etiologies (eg, acute viral or allergic rhinitis). Mucous stagnation in the sinus forms a rich medium for the growth of various pathogens. Initially, resulting acute sinusitis involves only one type of aerobic bacteria. With persistence of the infection, mixed flora, anaerobic organisms, and, occasionally, fungus¹ contribute to the pathogenesis. Most cases of chronic sinusitis are due to acute sinusitis that either is untreated or does not respond to treatment.

The role of bacteria in the pathogenesis of chronic sinusitis is currently being questioned. Repeated and persistent sinus infections can develop in persons with severe acquired or congenital immunodeficiency states or cystic fibrosis.

Frequency

United States

• Chronic sinusitis affects approximately 32 million persons each year and accounts for 11.6 million visits to physicians' offices.
• Chronic sinusitis is the fifth most common disease treated with antibiotics.
• Up to 64% of patients with AIDS develop chronic sinusitis.

International

• Chronic sinusitis is a common disease worldwide, particularly in places with high levels of atmospheric pollution.
• In the northern hemisphere, damp temperate climates along with higher concentrations of pollens are associated with a higher prevalence of chronic sinusitis.

Mortality/Morbidity

• Because of its persistent nature, chronic sinusitis can become a significant cause of morbidity. Untreated, it can reduce the quality of life and the productivity of the affected person.
• Chronic sinusitis is associated with exacerbation of asthma and serious complications such as brain abscess and meningitis, which can produce significant morbidity and mortality.

Race

Chronic sinusitis is observed in all races.

Sex

Chronic sinusitis has no sexual predilection.

Age

Chronic sinusitis has no age predilection.

Clinical

History

Chronic sinusitis manifests more subtly than acute sinusitis. Unless an appropriate history is taken, the diagnosis may be missed. The typical symptoms of acute sinusitis—fever and facial pain—are usually absent in chronic sinusitis.

• Patients with chronic sinusitis usually present with the following symptoms:
  • Nasal stuffiness
  • Nasal discharge
  • Postnasal drip
  • Facial fullness, discomfort, and headache
  • Chronic unproductive cough
  • Hyposmia
  • Sore throat
  • Fetid breath
  • Malaise
  • Exacerbation of asthma
  • Dental pain
  • Visual disturbances
  • Sneezing
  • Stuffy ears
  • Unpleasant taste
  • Fever of unknown origin

Physical

Physical examination in patients with chronic sinusitis may reveal various findings.

• Pain or tenderness on palpation over frontal or maxillary sinuses: Transillumination of maxillary or frontal sinuses is useful.
• Oropharyngeal erythema, purulent secretions
• Dental caries
• Endoscopic (rhinoscopic) examination findings
  • Nasal mucosal erythema, edema
  • Purulent secretions
  • Nasal obstruction due to deviated nasal septum or hypertrophied turbinates
  • Nasal polyps
• Ophthalmic manifestations
  • Conjunctival congestion
  • Lacrimation
  • Proptosis, extraocular muscle palsies, and visual disturbances (when complicated by orbital extension)

Causes

Sinusitis has a pattern of several phases. The early stage of sinusitis is often a viral infection that generally lasts up to 10 days and that completely resolves in 99% of cases. However, a small number of patients may develop a secondary acute bacterial infection that is generally caused by aerobic bacteria (ie, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis). If the infection does not resolve, anaerobic bacteria of oral flora origin eventually predominate. In a 1996 study, these bacterial changes were demonstrated with repeated endoscopic aspiration in patients with maxillary sinusitis.²

Currently, etiologic studies of sinusitis are increasingly focussing on ostiomeatal obstruction, allergies, polyps, occult and subtle immunodeficiency states, and dental diseases, while the role of bacteria in the etiology of sinusitis has been reduced to that of an opportunistic colonizer.

While the microbiology of acute sinusitis has been well established, various researchers disagree on the microbial etiology of chronic sinusitis. Much of the disagreement may be explained by methodology. Studies that have used adequate methods for recovery of anaerobes have demonstrated their prominence in chronic sinusitis, while those that did not use such methods have failed to recover them. When proper techniques are used, anaerobic bacteria can be recovered in 50-70% of specimens. The variable growth of microbes in samples may also be due to prior exposure of various broad-spectrum antibiotics in patients involved in the studies.

Jyonouchi et al (1999) successfully induced chronic sinusitis in rabbits via intrasinus inoculation of Bacteroides fragilis. The authors subsequently identified immunoglobulin G (IgG) antibodies against this organism in the infected animals. In addition, IgG antibodies to anaerobic organisms have been observed in patients with chronic sinusitis. These findings further support a role for anaerobes in chronic sinusitis.

Microbiologic studies of chronic sinusitis often show that the infection is polymicrobial, with isolation of 1-6 isolates per specimen.

In some cases, the baseline chronic sinusitis worsens suddenly or causes new symptoms. This acute exacerbation of chronic sinusitis is often polymicrobial, with anaerobic bacteria predominating. However, aerobic bacteria that are usually associated with acute sinusitis (eg, S pneumoniae, H influenzae, M catarrhalis) may emerge.

Gram-negative facultative and aerobic bacteria, including Pseudomonas aeruginosa, are more often isolated in patients with chronic sinusitis who have undergone endoscopic sinus surgery.

• The following bacteria have been reported in samples obtained through endoscopy or sinus puncture in patients with chronic sinusitis. The exact role of all of these microbes in the pathogenesis of chronic sinusitis is uncertain.
  • Staphylococcus aureus (both methicillin-susceptible S aureus [MSSA] and methicillin-resistant S aureus [MRSA] strains)
  • Coagulase-negative staphylococci
  • H influenzae
  • M catarrhalis
  • S pneumoniae
  • Streptococcus intermedius
  • P aeruginosa
  • Nocardia species
  • Anaerobic bacteria (Peptostreptococcus, Prevotella, Porphyromonas, Bacteroides, Fusobacterium species³ )
• The following fungi have been reported in samples obtained with endoscopy or sinus puncture in patients with chronic sinusitis:
  • Aspergillus species
  • Cryptococcus neoformans
  • Candida species
  • Sporothrix schenckii
  • Alternaria species
• The following conditions and risk factors predispose patients to the development of chronic sinusitis:
  • Anatomic abnormalities of the ostiomeatal complex (eg, septal deviation, concha bullosa, deviation of uncinate process, Haller cells)
  • Allergic rhinitis
  • Nasal polyps
  • Nonallergic rhinitis (eg, vasomotor rhinitis, rhinitis medicamentosa, cocaine abuse)
  • Nasotracheal intubation
  • Nasogastric intubation
  • Hormonal (eg, puberty, pregnancy, oral contraception)
  • Tumoral obstruction
  • Immunologic disorders (eg, common variable immunodeficiency, immunoglobulin A [IgA] deficiency, IgG subclass deficiency, AIDS)
  • Cystic fibrosis
  • Primary ciliary dyskinesia, Kartagener syndrome
  • Wegener granulomatosis
  • Repeated upper respiratory tract infections
  • Smoking
  • Environmental pollution
  • Gastroesophageal reflux disease (GERD)
  • Periodontitis/significant dental disease

Differential Diagnoses

Fever of Unknown Origin
Gastroesophageal Reflux Disease
Rhinitis, Allergic
Rhinocerebral Mucormycosis
Sinusitis, Acute

Other Problems to Be Considered

Temporomandibular joint syndrome
Asthma
Other chronic rhinitis
Nasal and sinus cavity tumors
Facial pain attributable to other causes
Nasal polyp
Dental infection
Periodontal abscess

Workup

Laboratory Studies

• Studies of chronic sinusitis have demonstrated no correlation between nasal flora and culture from the sinuses.
• Nasal swab cultures have no diagnostic value.
• Occasionally, an abundance of eosinophils in the nasal smear suggests an allergic etiology.
• Specimens obtained from sinus openings via endoscopy correlate well with those obtained with endoscopic surgery or sinus puncture. These should be processed for cultivation of aerobic and anaerobic bacteria, as well as fungi. Specimens evaluated for anaerobic bacteria should be sent in proper transport media. Liquid specimens are preferred to swab specimens.
• Routine blood cell counts and sedimentation rates are generally unhelpful; however, these may be elevated in patients with fever.
• In severe cases, blood cultures, including fungal blood cultures, may be helpful.
• Perform allergy testing if allergy is thought to be the underlying cause.
• Associated immune deficiency is evaluated with serum immunoglobulin and IgG subclass determination, antibody response to specific antigens, and HIV antibody testing (when indicated).

Imaging Studies

The cornerstone in the diagnostic workup of chronic sinusitis is the radiologic examination.

• Plain radiography
  • Routine sinus radiography has limited value in the evaluation of chronic sinusitis.
  • Plain radiography may show mucosal thickenings or sinus opacities.
  • Air fluid levels are uncommon in chronic sinusitis.
  • Ethmoid sinuses and the ostiomeatal complex are not visualized well on plain sinus radiography.
• CT scan
  • Contrast-enhanced CT scan is the current radiologic criterion standard for the evaluation of sinus diseases, although performing CT scanning in all patients with chronic sinus disease may be prohibitively expensive or medically unnecessary.
  • CT scans are usually indicated after failure of maximal medical therapy, before surgical planning for evaluation of suspected complications, and when a neoplasm is a possibility.
  • Coronal CT scan of the sinus correlates best with the surgical approach, permitting visualization of the anatomy of the nasal cavity, ostiomeatal complex, sinus cavities, and surrounding structures such as the orbit, cribriform plate, and optic canal. Anatomic obstructions at the ostiomeatal complex and dental pathologies are visualized well. Specific entities in the sinus cavity, such as aspergilloma, are also visualized well.
  • CT scan combined with endoscopic examination helps the surgeon to make operative decisions.
  • Most centers now offer limited sinus CT scans that consist of 5-12 coronal cuts. These limited or screening CT scans cost about the same as a plain radiography but provide more information.
• MRI
  • MRI is generally reserved only for complex cases.
  • Soft-tissue contrast is better with MRI.
  • Neoplasms, orbital and intracranial complications, and fungal sinusitis can be better evaluated with MRI.

Procedures

• Cultures are most accurate if obtained with endoscopy.

Treatment

Medical Care

Medical therapy is often considered an adjunct to surgical treatment and is directed toward controlling predisposing factors, treating concomitant infections, reducing edema of sinus tissues, and facilitating the drainage of sinus secretions. The role of bacteria in the pathogenesis of chronic sinusitis remains debatable; however, an early diagnosis and intensive treatment with oral antibiotics, topical nasal steroids, decongestants, and saline nasal sprays results in symptom relief in a significant number of patients, many of whom can be cured. When medical therapy is unsuccessful, refer the patient for surgical evaluation.

• Control of predisposing factors: Because chronic sinusitis has many risk factors and potential etiologies, apply a combined approach to control or modify these factors in the management of chronic sinusitis.
  • Viral upper respiratory tract infections: Reduce viral exposures by improved personal hygiene. The roles of zinc and vitamin C in the prevention of viral upper respiratory tract infection are controversial. On June 16, 2009, the US Food and Drug Administration (FDA) issued a public health advisory and notified consumers and health care providers to discontinue the use of intranasal zinc products.⁴ The intranasal zinc products (Zicam Nasal Gel/Nasal Swab; Matrixx Initiatives) are herbal cold remedies that claim to reduce the duration and severity of cold symptoms and are sold without a prescription. The FDA received more than 130 reports of anosmia (ie, an inability to detect odors) associated with intranasal zinc. Many of the reports described the loss of smell with the first dose.
  • Environmental factors: Reduce exposure to dust, molds, cigarette smoke, and other environmental chemical irritants.
  • Allergic rhinitis: Environmental control, antihistamines, cromolyn, topical steroids, or immunotherapy may be necessary.
  • Patients with adult chronic sinusitis may benefit from control of GERD, which has increasingly been implicated in causing or exacerbating respiratory ailments such as asthma and chronic sinusitis. The exact relationships and mechanisms are presently a matter of speculation.
  • Immunodeficiency states: Appropriate control of various congenital and acquired immunodeficiency states is necessary to cure chronic sinusitis.
• Symptomatic measures
  • Symptoms may be relieved with topical decongestants, topical steroids, antibiotics, nasal saline, topical cromolyn, or mucolytics. See the Medication section for further discussion.
  • Steam inhalation and nasal saline irrigation may help by moistening dry secretions, reducing mucosal edema, and reducing mucous viscosity.[#antimicrobials]
•  The choice of antimicrobial therapy
  • Oral antibiotic regimens are generally used to treat chronic sinusitis, since this condition is primarily treated in an outpatient setting. Antibiotic selection depends on several factors, including history of drug allergies, cost of therapy, and the likelihood of involvement by beta-lactamase–producing organisms and MRSA. In addition, if the patient has received antibiotics during the preceding 3 months, a different class of antibiotics should be used.
  • Initial selection of the appropriate antimicrobial(s) is usually empiric. Sinus cultures are generally unnecessary for community-acquired infections unless empiric therapy fails to elicit a response. The agent(s) chosen should be effective against the most likely bacterial etiologies, including both aerobic and anaerobic pathogens. If MRSA is a possible pathogen, coverage for this should be included.
  • Therapeutic regimens include the combination of a penicillin (eg, amoxicillin) plus a beta-lactamase inhibitor (eg, clavulanic acid), clindamycin, a combination of metronidazole plus a macrolide or a second- or third-generation cephalosporin, and the newer quinolones (eg, moxifloxacin). All of these agents (or similar ones) are available in oral and parenteral forms. Other effective antimicrobials are available only in parenteral form (eg, cefoxitin, cefotetan). If aerobic gram-negative organisms (eg, P aeruginosa) are involved, parenteral therapy with an aminoglycoside, a fourth-generation cephalosporin (cefepime or ceftazidime), or oral or parenteral treatment with a fluoroquinolone (only in postpubertal patients) is added. Parenteral therapy with a carbapenem (ie, imipenem, meropenem) is more expensive but provides coverage for most potential pathogens, both anaerobes and aerobes.
  • Clindamycin as initial therapy provides coverage for MRSA and is effective against anaerobes. Alternatives include trimethoprim-sulfamethoxazole (TMP-SMX) or linezolid, which are added to other regimens that cover anaerobes. Parenteral antimicrobials effective against MRSA include vancomycin, linezolid, and daptomycin.

Surgical Care

Recent advances in endoscopic technology and a better understanding of the importance of the ostiomeatal complex in the pathophysiology of sinusitis have led to the establishment of functional endoscopic sinus surgery (FESS) as the surgical procedure of choice for the treatment of chronic sinusitis. FESS facilitates the removal of disease in key areas, restores adequate aeration and drainage of the sinuses by establishing patency of the ostiomeatal complex, and causes less damage to normal nasal functioning. FESS is successful in restoring sinus health, with complete or at least moderate relief of symptoms in 80-90% of patients. Supportive medical treatment is instituted preoperatively and postoperatively. In children, surgical management is not as well established and should be reserved for complicated cases.

• Fungal sinusitis: Fungal sinusitis can manifest in different ways.¹
  • Acute invasive fungal sinusitis is observed in patients who are immunosuppressed or who have diabetes and is usually caused by members of the genera Aspergillus, Mucor, and Rhizopus. This condition requires urgent workup and aggressive medical and surgical therapy. Mortality rates associated with acute invasive fungal sinusitis are very high.
  • Chronic fungal sinusitis is usually observed in immunocompetent patients. Surgical debridement is the preferred treatment.
  • Mycetomas or fungus balls may be asymptomatic or may manifest as chronic sinusitis. Surgical removal is the preferred treatment.
  • Allergic fungal sinusitis usually manifests as nasal polyps and allergic sinusitis. Fungal elements in the sinuses are the inciting allergens. Treatment consists of systemic steroids and surgical removal of polyps and mucinous secretions.

Consultations

• Persistent or recurrent episodes of sinusitis despite appropriate medical therapy necessitate referral to an otolaryngologist. Examination, including nasal endoscopy and CT scanning, is mandatory to exclude surgically amenable conditions.
• Seek consultation with an ophthalmologist at the earliest suggestion of orbital involvement.
• Seek consultation with a dentist when an odontogenic infection is present or suspected.

Medication

The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.

Antibiotics

Many antibiotics have been used in the treatment of chronic sinusitis; the most common ones are presented below. Ideally, direct antibiotics against the organism obtained from endoscopic sampling and based on microbial sensitivity testing. If the patient is ill, empiric antimicrobial therapy may be indicated, which should be comprehensive and cover all likely pathogens in the context of the clinical setting. Duration of antibiotics is not well established. An initial 2- to 4-week trial of antibiotics may be reasonable. A longer duration (up to 12 mo) may be needed in some cases. After surgical management for uncomplicated chronic sinusitis is completed, antibiotics are of unclear benefit. Invasion of bone or deep structures may require a prolonged antibiotic course.

Vancomycin (Lyphocin, Vancocin, Vancoled)

Indicated for patients 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 CrCl to adjust dose in patients diagnosed with renal impairment. Used in conjunction with gentamicin for prophylaxis in patients with penicillin allergy who are undergoing gastrointestinal or genitourinary procedures.

Dosing

Adult

1 g or 15 mg/kg IV q12h

Pediatric

30-40 mg/kg/d IV in 2 doses

Interactions

Erythema, histaminelike flushing, and anaphylactic reactions may occur following administration of anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal failure and neutropenia; red man syndrome is caused by too rapid IV infusion (dose given over a few minutes) but rarely happens when dose given IV over 2 h administration or as PO or IP administration; red man syndrome is not an allergic reaction

Moxifloxacin (Avelox)

Inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.

Dosing

Adult

400 mg PO/IV qd

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Interactions

Antacids and electrolyte supplements reduce absorption; loop diuretics, probenecid, and cimetidine increase serum levels; NSAIDs enhance CNS stimulating effect
May increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT); ferrous sulfate decreases bioavailability (administer moxifloxacin 4 h prior or 8 h following ferrous sulfate); coadministration with drugs that prolong QTc interval (quinidine, procainamide, amiodarone, sotalol, erythromycin, tricyclic antidepressants) increase risk of life-threatening arrhythmia

Contraindications

Documented hypersensitivity; known QT prolongation; concurrent administration of drugs that cause QT prolongation

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic); superinfections may occur with prolonged or repeated antibiotic therapy; fluoroquinolones have induced seizures in CNS disorders and caused tendinitis or tendon rupture

Clindamycin (Cleocin)

Semisynthetic antibiotic produced by 7(S)-chloro-substitution of 7(R)-hydroxyl group of parent compound lincomycin. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Widely distributes in the body without penetration of CNS. Protein bound and excreted by the liver and kidneys.

Dosing

Adult

150-450 mg PO q6h with full glass of water

Pediatric

Children <10 kg: 8-20 mg/kg/d PO; equally divided q6-8h; dosage administered depends on severity of the infection; oral dosage (clindamycin palmitate hydrochloride oral granules)
Children >10 kg: 37.5 mg PO tid should be considered the minimum dose

Interactions

Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin

Contraindications

Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis by allowing overgrowth of Clostridium difficile

Metronidazole (Flagyl)

Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents (except C difficile enterocolitis).

Dosing

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 IV or 500 mg for 70-kg adult over 1 h q6-8h; not to exceed 4 g/d

Pediatric

Administer as in adults based on body weight

Interactions

May increase toxicity of anticoagulants, cyclosporine, lithium, phenytoin, tacrolimus, and carbamazepine; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol; coadministration increases amiodarone toxicity (QT prolongation); increases disulfiram toxicity (psychotic symptoms) with concurrent use; phenobarbital and rifampin may increase metabolism of metronidazole

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution with liver impairment; blood dyscrasias; CNS disease; reduce dosage in severe hepatic disease; monitor for seizures and development of peripheral neuropathy

Amoxicillin (Amoxil, Trimox, Biomox)

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

Dosing

Adult

500 mg to 1 g PO q8h

Pediatric

40-45 mg/kg/d PO q8h divided

Interactions

Reduces efficacy of oral contraceptives; increased amoxicillin levels with disulfiram and probenecid

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Skin rash in patients with infectious mononucleosis; potential superinfections with mycotic and bacterial pathogens; adjust dose in renal impairment

Amoxicillin and clavulanate (Augmentin)

Drug combination treats bacteria resistant to beta-lactam antibiotics.

Dosing

Adult

500 mg PO q8h or 875 mg PO q12h

Pediatric

<3 months: 30 mg/kg/d PO q12h divided ; base dosing protocol on amoxicillin content
>3 months: 40-50 mg/kg/d PO divided q8-12h

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

Interactions

Coadministration with warfarin or heparin increases risk of bleeding

Contraindications

Documented hypersensitivity; history of amoxicillin/clavulanate-associated cholestatic jaundice/hepatic dysfunction

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Skin rash in patients with infectious mononucleosis; potential superinfections with mycotic and bacterial pathogens; adjust dose in renal impairment; periodically monitor renal, hepatic, and hemopoietic functions during prolonged therapy

Clarithromycin (Biaxin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Dosing

Adult

500 mg PO q12h

Pediatric

7.5 mg/kg PO q12h

Interactions

Toxicity increases with coadministration of fluconazole and pimozide; effects decrease and adverse GI effects may increase with coadministration of rifabutin or rifampin; may increase toxicity of anticoagulants, cyclosporine, tacrolimus, digoxin, omeprazole, carbamazepine, ergot alkaloids, triazolam, and HMG CoA-reductase inhibitors; plasma levels of certain benzodiazepines may increase, prolonging CNS depression; arrhythmias and increase in QTc intervals occur with disopyramide, cisapride, and pimozide; coadministration with omeprazole may increase plasma levels of both agents

Contraindications

Documented hypersensitivity; coadministration with cisapride or pimozide

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adjust dose in renal insufficiency; drug interactions and teratogenicity are important considerations; occasionally hepatotoxic; coadministration with ranitidine or bismuth citrate is not recommended with CrCl <25 mL/min; administer half dose or increase dosing interval if CrCl <30 mL/min; diarrhea may be sign of pseudomembranous colitis; superinfections may occur with prolonged or repeated antibiotic therapies

Cefuroxime (Ceftin)

Second-generation cephalosporin that maintains gram-positive activity of first-generation cephalosporins; adds activity against Proteus mirabilis, H influenzae, Escherichia coli, Klebsiella pneumoniae, and M catarrhalis. Condition of patient, severity of infection, and susceptibility of microorganism determine proper dose and route of administration.

Dosing

Adult

500 mg PO bid

Pediatric

125-250 mg PO (tab) bid; alternatively, 20-30 mg/kg/d PO (susp) divided bid

Interactions

Disulfiramlike reactions may occur when alcohol is consumed within 72 h after taking cefuroxime; may increase hypoprothrombinemic effects of anticoagulants; may increase nephrotoxicity in patients receiving potent diuretics (eg, loop diuretics); coadministration with aminoglycosides increases nephrotoxic potential; probenecid increases level of this group of drugs

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Administer one half dose if CrCl is 10-30 mL/min and one quarter dose if <10 mL/min; fungal and microorganism overgrowth may occur with prolonged therapy; 10% of patients who are allergic to penicillin may show cross-hypersensitivity

Cefixime (Suprax)

Arrests bacterial cell wall synthesis and inhibits bacterial growth by binding to one or more of the penicillin-binding proteins.

Dosing

Adult

400 mg/d PO or divided q12h

Pediatric

<12 years: 8 mg/kg/d PO or 4 mg/kg/d PO bid
>12 years or >50 kg: Administer as in adults

Interactions

Coadministration of aminoglycosides increases nephrotoxicity; probenecid may increase effects; carbamazepine levels may be increased

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Superinfections possible during prolonged therapy; adjust dose in renal insufficiency

Levofloxacin (Levaquin)

Inhibits bacterial topoisomeraseIV and DNA gyrase, which are required for bacterial DNA replication and transcription.

Dosing

Adult

500 mg PO qd

Pediatric

Not recommended for children <18 y

Interactions

Enhances effects of warfarin; increased levels of theophylline may occur; increased risk of CNS stimulation when used with NSAIDs

Contraindications

Documented hypersensitivity to fluoroquinolones

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid if allergic to other quinolones

Trimethoprim and sulfamethoxazole (Bactrim DS, Septra DS)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. One double-strength tab contains trimethoprim (TMP) 160 mg and sulfamethoxazole (SMX) 800 mg

Dosing

Adult

1 DS tab PO q12h

Pediatric

8 mg/kg/d TMP and 40 mg/kg/d SMX PO q12h divided

Interactions

May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of MTX in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine

Contraindications

Documented hypersensitivity; megaloblastic anemia due to folate deficiency; term pregnancy; breastfeeding women and infants <2 mo because of possibility of development of kernicterus

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, administer 5-15 mg/d leucovorin); caution in folate deficiency (eg, patients with chronic alcoholism, elderly patients, those receiving anticonvulsant therapy, or those with malabsorption syndrome); hemolysis may occur in individuals who are G-6-PD deficient; patients with AIDS may not tolerate or respond to TMP-SMX; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); administer fluids to prevent crystalluria and stone formation

Decongestants, topical

These agents are alpha-adrenergic agonists that act by constricting dilated mucosal vessels. Topical preparations of oxymetazoline, naphazoline, tetrahydrozoline, and xylometazoline are available. Use all adrenergic topical preparations with caution in young patients and the elderly population. Topical agents can produce rebound vasodilation on discontinuation and rhinitis medicamentosa on prolonged use. Both of these adverse effects respond well to topical steroids.

Oxymetazoline (Afrin)

Applied directly to mucous membranes, where it stimulates alpha-adrenergic receptors and causes vasoconstriction. Decongestion occurs without drastic changes in blood pressure, vascular redistribution, or cardiac stimulation.

Dosing

Adult

Available in 0.05% nasal solution; 2-3 gtt each nostril q12h; generally, use for no longer than 5 d

Pediatric

<6 years: Not recommended
>6 years: 1-2 gtt q12h for 3-5 d

Interactions

Hypotensive action of guanethidine may be reversed; concurrent administration with methyldopa may result in increased vasopressor response; concurrent use of MAOIs and ephedrine may result in hypertensive crisis; pressor sensitivity to mixed-acting agents such as ephedrine may be increased; guanethidine potentiates effects of epinephrine and inhibits effects of ephedrine; phenothiazines may reverse action of nasal decongestants such as oxymetazoline; TCAs potentiate vasopressor response and may result in dysrhythmias

Contraindications

Documented hypersensitivity; MAOIs

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with hyperthyroidism, coronary artery and ischemic heart disease, diabetes mellitus, increased intraocular pressure, or prostatic hypertrophy; because of increase in vasoconstriction, patients who are hypertensive may experience change in blood pressure; do not use topical decongestants for longer than 3-5 d

Naphazoline (Privine)

Alpha-adrenergic effects on arterioles of conjunctiva and nasal mucosa produce vasoconstriction.

Dosing

Adult

2 gtt of 0.05% nasal solution in each nostril q3-6h; generally, not to exceed 3-5 d

Pediatric

<6 years: Not recommended
6-12 years: Administer 1-2 gtt of 0.025% solution; do not use for more than 3-5 d
>12 years: Administer as in adults

Interactions

Risk of hypertensive reactions increases when used concurrently with TCAs or MAOIs; toxicity increases when used concurrently with anesthetics

Contraindications

Documented hypersensitivity; narrow-angle glaucoma; do not use before a peripheral iridectomy is performed

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prolonged use may cause rebound congestion; caution in patients with diabetes, hypertension, heart disease, cerebral arteriosclerosis, hyperthyroidism, and asthma

Tetrahydrozoline (Tyzine, Visine)

Alpha-adrenergic effects on nasal mucosa produce vasoconstriction.

Dosing

Adult

2-4 gtt of 0.1% nasal solution in each nostril q4-6h; do not use longer than 3-5 d

Pediatric

<2 years: Not recommended
2-6 years: May administer 2-3 gtt of 0.05% nasal solution in each nostril q4-6h, not to exceed 3-5 d
>6 years: Administer as in adults

Interactions

Risk of hypertensive reactions increases when used concurrently with TCAs or MAOIs

Contraindications

Documented hypersensitivity; narrow-angle glaucoma

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prolonged use may cause rebound congestion; caution in patients with diabetes, hypertension, heart disease, cerebral arteriosclerosis, hyperthyroidism, and asthma

Xylometazoline (Otrivin)

Applied directly to mucous membranes, where it stimulates alpha-adrenergic receptors and causes vasoconstriction.

Dosing

Adult

2-3 gtt of 0.1% nasal solution in each nostril q8-10h; generally, do not use for longer than 3-5 d

Pediatric

<2 years: Use only under direct supervision of physician
2-12 years: 2-3 gtt of 0.05% nasal solution q8-10h
>12 years: Administer as in adults; duration of treatment generally not to exceed 5 d

Interactions

Risk of hypertensive reactions increases when used concurrently with TCAs or MAOIs; toxicity increases when used concurrently with anesthetics

Contraindications

Documented hypersensitivity; narrow-angle glaucoma

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Prolonged use may cause rebound congestion; caution in patients with diabetes, hypertension, heart disease, cerebral arteriosclerosis, hyperthyroidism, and asthma

Corticosteroids, topical

These agents are particularly effective for chronic sinusitis associated with allergic rhinitis, nasal polyps, and rhinitis medicamentosa. Topical steroids along with systemic antibiotics are now the key components of the medical armamentarium in the management of chronic sinusitis.

Fluticasone propionate (Flonase)

Applied as nasal spray. Particularly effective in allergic and vasomotor rhinosinusitis and rhinosinusitis medicamentosa. Used as prophylaxis for nasal polyps. Plasma concentrations very low following intranasal administration in recommended doses.

Dosing

Adult

50 mcg/spray; 2 sprays in each nostril qd or 1 spray in each nostril bid; not to exceed total dose of 200 mcg/d

Pediatric

<12 years: Not recommended
>12 years: 1 spray (50 mcg) in each nostril qd

Interactions

None reported; concomitant use with other inhaled and/or systemically absorbed corticosteroids can increase risk of hypercorticism and/or suppression of HPA

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Epistaxis or sensations of nasal burnings may occur; local candidal infections of nasopharynx have been reported with topical steroid use; always consider potential risk of suppression of HPA when using large dose for prolonged periods; rare cases of cataract, glaucoma, and increased intraocular pressure have been reported following intranasal use of corticosteroids; concomitant use of intranasal corticosteroids and other inhaled and/or systemically absorbed corticosteroids may cause hypercorticism and/or HPA suppression; if exposed to measles or chickenpox, consider prophylactic therapy

Beclomethasone dipropionate (Beconase AQ)

Topical steroid nasal spray. Acts locally as anti-inflammatory and vasoconstrictor. Readily absorbed through nasopharyngeal mucosa and GI tract. Useful in allergic and vasomotor rhinosinusitis and sinusitis medicamentosa.

Dosing

Adult

42 mcg/spray; 1 spray in each nostril bid/tid/qid

Pediatric

<6 years: Not recommended
6-12 years: 1 spray in each nostril tid
>12 years: Administer as in adults

Interactions

None reported; concomitant use with other inhaled and/or systemically absorbed corticosteroids can increase risk of hypercorticism and/or suppression of HPA

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Always consider potential risk of suppression of HPA when using large dose for prolonged periods; rare cases of cataract, glaucoma, and increased intraocular pressure have been reported following intranasal use of corticosteroids; concomitant use of intranasal corticosteroids and other inhaled and/or systemically absorbed corticosteroids may cause hypercorticism and/or HPA suppression; if exposed to measles or chickenpox, consider prophylactic therapy

Nasal sprays

Nasal saline spray and steam inhalation help by moistening dry secretions, reducing mucosal edema, and reducing mucous viscosity. Symptomatic relief gained in some patients can be substantial; moreover, these are benign modalities of therapy.

Saline nasal spray (Ayr, Ocean)

Loosens mucous secretions to help remove mucus from nose and sinuses.

Dosing

Adult

0.65% buffered isotonic sodium chloride nasal solution, 1-2 sprays or gtt in each nostril

Pediatric

Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

None reported

Mast cell stabilizers

These agents may be helpful in chronic sinusitis associated with allergic rhinitis.

Cromolyn sodium (Nasalcrom)

Inhibits degranulation of sensitized mast cells following their exposure to specific antigens.

Dosing

Adult

5.2 mg/spray; 1 spray in each nostril q4-6h; begin 1-2 wk before exposure to known allergen

Pediatric

<6 years: Not recommended
>6 years: 1 spray of 5.2 mg q6h

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal or hepatic impairment; symptoms may reoccur when withdrawing drug

Expectorants

Although no controlled studies on the efficacy of mucolytics in chronic sinusitis are available, guaifenesin (mucolytic agent) may be helpful in ameliorating some symptoms.

Guaifenesin (Humibid-LA)

Increases respiratory tract fluid secretions and helps to loosen phlegm and bronchial secretions. Indicated for patients with bronchiectasis complicated by tenacious mucous and/or mucous plugs.

Dosing

Adult

600-mg sustained-release tab
1-2 tab PO q12h

Pediatric

<2 years: Not recommended
2-6 years: One-half tab PO q12h
6-12 years: 1 tab PO q12h

Interactions

May increase renal clearance of urate and lower serum uric acid levels; may interfere with urine laboratory tests for 5-hydroxyindoleacetic acid and urine testing for catecholamines

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

When prescribing medication that may suppress cough, important to identify cause of cough so that suppression does not increase risk of clinical or physiologic complications

Follow-up

Further Inpatient Care

• Inpatient treatment of chronic sinusitis is indicated for patients with orbital and intracranial complications (see Complications).
• Immunosuppressed patients and pediatric patients with chronic sinusitis may need inpatient care, depending on the severity of the disease.

Further Outpatient Care

• Continued outpatient medical treatment with nasal decongestants and topical steroids is important even after surgical treatment.

Deterrence/Prevention

• Certain conditions predispose to chronic sinusitis (see Causes). Environmental factors and/or allergic factors may predispose some individuals to chronic sinusitis. In these patients, the following preventive measures may be helpful:
  • Reduce exposure to dust, molds, cigarette smoke, and other environmental chemical irritants.
  • Environmental control, antihistamines, cromolyn, topical steroids, or immunotherapy may reduce recurrences and symptoms of allergic rhinitis.

Complications

• Orbital cellulitis
• Cavernous sinus thrombosis
• Intracranial extension (eg, brain abscess, meningitis)
• Mucocele formation

Prognosis

• Early and aggressive medical treatment for chronic sinusitis typically results in satisfactory outcomes.
• FESS restores sinus health with complete or moderate relief of symptoms in 80-90% of patients with recurrent or medically unresponsive chronic sinusitis.

Miscellaneous

Medicolegal Pitfalls

• Nasal swab culture does not correlate with sinus culture results. The role and type of microbes in the pathogenesis of chronic sinusitis is controversial.
• Always consider serious underlying conditions, such as tumors and immunodeficiency states, in the workup.
• Fungal sinusitis can be devastating in immunosuppressed patients and, rarely, in immunocompetent patients.

References

1. Gwaltney JM Jr, Phillips CD, Miller RD, et al. Computed tomographic study of the common cold. N Engl J Med. Jan 6 1994;330(1):25-30. [Medline].

2. Biel MA, Brown CA, Levinson RM, et al. Evaluation of the microbiology of chronic maxillary sinusitis. Ann Otol Rhinol Laryngol. Nov 1998;107(11 Pt 1):942-5. [Medline].

3. Brook I. Acute and chronic bacterial sinusitis. Infect Dis Clin North Am. Jun 2007;21(2):427-48, vii. [Medline].

4. United States Food and Drug Administration. Zicam cold remedy nasal products (Cold Remedy Nasal Gel, Cold Remedy Nasal Swabs, and Cold Remedy Saws, Kids Size). MedWatch Public Health Advisory. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm166996.htm. Accessed June 16, 2009.

5. Cunha BA. Antibiotic Essentials. 7th Ed. Royal Oak, MI: Physicans Press; 2008.

6. Brook I. Bacteriology of chronic sinusitis and acute exacerbation of chronic sinusitis. Arch Otolaryngol Head Neck Surg. Oct 2006;132(10):1099-101. [Medline].

7. Brook I. Sinusitis of odontogenic origin. Otolaryngol Head Neck Surg. Sep 2006;135(3):349-55. [Medline].

8. Brook I, Frazier EH, Foote PA. Microbiology of the transition from acute to chronic maxillary sinusitis. J Med Microbiol. Nov 1996;45(5):372-5. [Medline].

9. Brook I, Yocum P. Immune response to Fusobacterium nucleatum and Prevotella intermedia in patients with chronic maxillary sinusitis. Ann Otol Rhinol Laryngol. Mar 1999;108(3):293-5. [Medline].

10. Evans KL. Recognition and management of sinusitis. Drugs. Jul 1998;56(1):59-71. [Medline].

11. Finegold SM, Flynn MJ, Rose FV, et al. Bacteriologic findings associated with chronic bacterial maxillary sinusitis in adults. Clin Infect Dis. Aug 15 2002;35(4):428-33. [Medline].

12. Hafidh M, Harney M, Kane R, et al. The role of fungi in the etiology of chronic rhinosinusitis: a prospective study. Auris Nasus Larynx. Jun 2007;34(2):185-9. [Medline].

13. Hinthorn D, Schwartz J. Efficacy and safety of cefixime and cefaclor in adults with purulent maxillary sinusitis. Postgrad Med. May 1998;58-62.

14. Johnson JT, Ferguson BJ. Infection/paranasal sinus. Otolaryngol Head Neck Surg. 1998;2:1107-1134.

15. Jyonouchi H, Sun S, Kennedy CA, et al. Localized sinus inflammation in a rabbit sinusitis model induced by Bacteroides fragilis is accompanied by rigorous immune responses. Otolaryngol Head Neck Surg. Jun 1999;120(6):869-75. [Medline].

16. Lockey RF. Management of chronic sinusitis. Hosp Pract (Off Ed). Mar 15 1996;31(3):141-6,149-5. [Medline].

17. Lund VJ. Surgical outcomes in chronic rhinosinusitis and nasal polyposis. Rhinology. Jun 2006;44(2):97. [Medline].

18. Lusk R. Pediatric chronic rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg. Dec 2006;14(6):393-6. [Medline].

19. Nord CE. The role of anaerobic bacteria in recurrent episodes of sinusitis and tonsillitis. Clin Infect Dis. Jun 1995;20(6):1512-24. [Medline].

20. Slavin RG. Nasal polyps and sinusitis. JAMA. Dec 10 1997;278(22):1849-54. [Medline].

Keywords

chronic sinusitis, acute sinusitis, sinus infection, paranasal sinus, postnasal drip, facial pain, hyposmia, rhinitis, fungal sinusitis, cystic fibrosis, CF, asthma, nasal polyps, allergy, allergies, gastroesophageal reflux disease, GERD, brain abscess, meningitis, Streptococcus pneumoniae, S pneumoniae, Haemophilus influenzae, H influenzae, Moraxella catarrhalis, M catarrhalis, functional endoscopic sinus surgery, FESS

Contributor Information and Disclosures

Author

Itzhak Brook, MD, MSc, Professor, Department of Pediatrics, Georgetown University School of Medicine
Itzhak Brook, MD, MSc is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Armed Forces Infectious Diseases Society, Association of Military Surgeons of the US, Infectious Diseases Society of America, International Immunocompromised Host Society, International Society for Infectious Diseases, Medical Society of the District of Columbia, New York Academy of Sciences, Pediatric Infectious Diseases Society, Society for Ear, Nose and Throat Advances in Children, Society for Experimental Biology and Medicine, Society for Pediatric Research, Southern Medical Association, and Surgical Infection Society
Disclosure: Nothing to disclose.

Coauthor(s)

Himal Bajracharya, MBBS, Assistant Professor, Department of Internal Medicine, Division of Infectious Diseases, Kansas University Medical Center
Himal Bajracharya, MBBS is a member of the following medical societies: American College of Physicians, American Medical Association, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Daniel Hinthorn, MD, Director, Division of Infectious Diseases, Professor, Departments of Internal Medicine, Pediatrics and Family Medicine, University of Kansas
Daniel Hinthorn, MD is a member of the following medical societies: American Academy of Family Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Medical Editor

Kenneth C Earhart, MD, Deputy Head, Disease Surveillance Program, United States Naval Medical Research Unit #3
Kenneth C Earhart, MD is a member of the following medical societies: American College of Physicians, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and Undersea and Hyperbaric Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Gordon L Woods, MD, Consulting Staff, Department of Internal Medicine, University Medical Center
Gordon L Woods, MD is a member of the following medical societies: Society of General Internal Medicine
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Eleftherios Mylonakis, MD, to the development and writing of this article.

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