Chronic Sinusitis

Chronic sinusitis is one of the more prevalent chronic illnesses in the United States, affecting persons of all age groups (see Epidemiology). It is an inflammatory process that involves the paranasal sinuses and persists for 12 weeks or longer (see Pathophysiology). The literature has supported that chronic sinusitis is almost always accompanied by concurrent nasal airway inflammation and is often preceded by rhinitis symptoms; thus, the term chronic rhinosinusitis (CRS) has evolved to more accurately describe this condition.

CRS may manifest as one of three major clinical syndromes: CRS without nasal polyps, CRS with nasal polyps, or allergic fungal rhinosinusitis. These classifications possess a great deal of therapeutic significance.

Most cases of chronic sinusitis are continuations of unresolved acute sinusitis; however, chronic sinusitis usually manifests differently from acute sinusitis. Symptoms of chronic sinusitis include nasal stuffiness, postnasal drip, facial fullness, and malaise. (See Clinical Presentation.)

Chronic sinusitis may be noninfectious and related to allergy, cystic fibrosis, gastroesophageal reflux, or exposure to environmental pollutants.[1, 2] Allergic rhinitis, nonallergic rhinitis, anatomic obstruction in the ostiomeatal complex, and immunologic disorders are known risk factors for chronic sinusitis. (See Etiology.)

Medical therapy is directed toward controlling predisposing factors, treating concomitant infections, reducing edema of sinus tissues, and facilitating the drainage of sinus secretions. The goal in surgical treatment is to reestablish sinus ventilation and to correct mucosal opposition in order to restore the mucociliary clearance system. Surgery strives to restore the functional integrity of the inflamed mucosal lining.(See Treatment and Management and Medication.)

Definition of chronic rhinosinusitis

In 1996, the American Academy of Otolaryngology-Head & Neck Surgery multidisciplinary Rhinosinusitis Task Force (RTF) defined adult rhinosinusitis diagnostic criteria.[3] Major factors included facial pain or pressure, nasal obstruction or blockage, nasal discharge or purulence or discolored postnasal discharge, hyposmia or anosmia, purulence in nasal cavity, and fever. In 2003, the RTF’s definition was amended to require confirmatory radiographic or nasal endoscopic or physical examination findings in addition to suggestive history.[4, 5] (See Clinical Presentation.)

Knowledge of the anatomy of paranasal sinuses is essential for understanding the pathophysiology and management of chronic sinusitis. The four 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. 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). Initially, the resulting acute sinusitis involves only one type of aerobic bacteria. With persistence of the infection, mixed flora, anaerobic organisms, and, occasionally, fungus[6] contribute to the pathogenesis, with anaerobic bacteria of oral flora origin often eventually predominating. In one study, these bacterial changes were demonstrated with repeated endoscopic aspiration in patients with maxillary sinusitis.[7] 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 being reassessed. Repeated and persistent sinus infections can develop in persons with severe acquired or congenital immunodeficiency states or cystic fibrosis.

Current thinking supports the concept that chronic rhinosinusitis (CRS) is predominantly a multifactorial inflammatory disease. Confounding factors that may contribute to inflammation include the following:

• Persistent infection (including biofilms and osteitis) ^{[8, 9]}
• Allergies and other immunologic disorders ^[10]
• Intrinsic factors of the upper airway
• Superantigens
• Colonizing fungi that induce and sustain eosinophilic inflammation
• Metabolic abnormalities such as aspirin sensitivity

All of these factors can play a role in disruption of the intrinsic mucociliary transport system. This is because an alteration in sinus ostia patency, ciliary function, or the quality of secretions leads to stagnation of secretions, decreased pH levels, and lowered oxygen tension within the sinus. These changes create a favorable environment for bacterial growth that, in turn, further contributes to increased mucosal inflammation.

The etiology of chronic sinusitis is multifactorial. The interaction between many systemic, local host, and environmental factors contribute to sinus inflammation and to the pathophysiology of the disease. Systemic factors include genetic diseases such as cystic fibrosis, conditions that cause immunodeficiency, autoimmune disease, idiopathic conditions such as Samter triad (aspirin-exacerbated respiratory disease), and acid reflux. Local host factors include sinonasal anatomic abnormalities, iatrogenic conditions such as scarring due to prior sinus surgery, neoplasm, or the presence of a foreign body, among others. Possible environmental factors that may contribute to the condition include the presence of biofilms and bacterial infection, as well as fungal infection, allergy, environmental pollutants, and smoking.

Increasing evidence shows that biofilms are critical to the pathophysiology of chronic infections including chronic sinusitis. Recent advances in methods for biofilm identification and molecular biology offer new insights into the role of biofilms in chronic sinusitis.[11]

Currently, etiologic studies of sinusitis are increasingly focusing on ostiomeatal obstruction, allergies, polyps, occult and subtle immunodeficiency states, and dental diseases. Microorganisms are more often recognized as secondary invaders. Any disease process or toxin that affects cilia has a negative effect on CRS.

Bacterial involvement

The bacteria presumed to be involved in CRS differ from those involved in acute rhinosinusitis. The following bacteria have been reported in samples obtained through endoscopy or sinus puncture in patients with chronic sinusitis.

• Staphylococcus aureus (both methicillin-susceptible S aureus [MSSA] and methicillin-resistant S aureus [MRSA] strains) ^[12]
• Coagulase-negative staphylococci
• Haemphillus  influenzae
• Moraxella catarrhalis
• Streptococcus pneumoniae
• Streptococcus intermedius
• Pseudomonas aeruginosa
• Nocardia species
• Anaerobic bacteria ( Peptostreptococcus, Prevotella, Porphyromonas, Bacteroides, Fusobacterium species ^{[13, 14]}
• Microaerophilic streptococci ^[15]

In contrast with the well-established roles of microbes in the etiology of acute sinusitis, the exact roles of all of these microbes in the etiology of chronic sinusitis are uncertain. 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, whereas those that did not use such methods have failed to recover them. When proper techniques are used, anaerobic bacteria can be recovered in 50% to 70% of specimens.[14] 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 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.[16] In addition, IgG antibodies to anaerobic organisms have been observed in patients with chronic sinusitis.[17] 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 one to six isolates per specimen.[13]  The microbial flora of chronic sinusitis is affected by previous antibiotic administration, past vaccinations, and the presence of normal flora that can suppress the emergence of pathogenic species.

In some cases, the baseline chronic sinusitis worsens suddenly or causes new symptoms. This acute exacerbation of chronic sinusitis is often polymicrobial as well, with anaerobic bacteria predominating. However, aerobic bacteria that are usually associated with acute sinusitis (eg, S pneumoniae, H influenzae,M catarrhalis) may emerge.[18]  A change of bacterial isolates during the course of recurrent exacerbation was observed in 68% (76/112) of patients studied by Yaniv et al,[19]  necessitating a change of treatment in 40% (45/112). The main risk factor for the subsequent change in cultures was polymicrobial growth. The authors recommended that repeated middle meatal cultures should be considered in patients with recurrent exacerbations of CRS, particularly in cases not responding to standard therapy.

S aureus including methicillin resistant[20]  is associated with the development of persistent severe inflammatory disease of the upper airway, including chronic sinusitis with nasal polyps.[21]

Gram-negative facultative and aerobic bacteria, including P aeruginosa, are more often isolated in patients with chronic sinusitis who have undergone endoscopic sinus surgery.[22]

Fungal involvement

The following fungi have been reported in samples obtained with endoscopy or sinus puncture in patients with chronic sinusitis[23] :

• Aspergillus species

• Cryptococcus neoformans

• Candida species

• Sporothrix schenckii

• Alternaria species

Polymicrobial aerobic-anaerobic flora is sinus cultures obtained from present with fungus ball.[24]  To see complete information on fungal sinusitis, please go to the main article by clicking here.

Risk factors

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 ^[25]
• Aspirin sensitivity
• Asthma
• Nasal polyps
• Nonallergic rhinitis (eg, vasomotor rhinitis, rhinitis medicamentosa, cocaine abuse)
• Defects in mucociliary clearance
• Nasotracheal intubation
• Nasogastric intubation
• Hormonal (eg, puberty, pregnancy, oral contraception)
• Obstruction by tumor
• Immunologic disorders (eg, common variable immunodeficiency, immunoglobulin A [IgA] deficiency, IgG subclass deficiency, AIDS)
• Cystic fibrosis
• Primary ciliary dyskinesia, Kartagener syndrome
• Wegener granulomatosis
• Repeated viral upper respiratory tract infections
• Smoking
• Environmental irritants and pollutants
• Gastroesophageal reflux disease (GERD). The reflux of gastric contents may play a contributing role in some cases of CRS; this relationship still needs to be better defined
• Periodontitis/significant dental disease
• Systemic diseases (ie, granulomatosis with polyangiitis (Wegener granulomatosis), Churg-Strauss vasculitis, sarcoidosis)
• Yellow nail syndrome

Chronic sinusitis is one of the more prevalent chronic illnesses in the United States, affecting persons of all age groups. The overall prevalence of CRS in the United States is 146 per 1000 population. For unknown reasons, the incidence of this disease appears to be increasing yearly. This results in a conservative estimate of 18-22 million physician visits in the United States each year and a direct treatment cost of $3.4-5 billion annually.[26] Chronic sinusitis is the fifth most common disease treated with antibiotics. Up to 64% of patients with AIDS develop chronic sinusitis.[27]

International prevalence

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.

Rhinosinusitis in children

Rhinosinusitis is more common in the pediatric population because this term includes both acute and chronic infection and both viral and bacterial disease. This is likely secondary to an increased frequency of exposure to upper respiratory tract infections in the pediatric population.

Because of its persistent nature, chronic sinusitis can become a significant cause of morbidity. If left 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.

Early and aggressive medical treatment for chronic sinusitis typically results in satisfactory outcomes. Functional endoscopic sinus surgery (FESS) restores sinus health with complete or moderate relief of symptoms in 80% to 90% of patients with recurrent or medically unresponsive chronic sinusitis.(See Treatment and Management.)

Chronic sinusitis rarely is life threatening, although serious complications can occur because of the proximity to the orbit and cranial cavity. Approximately 75% of all orbital infections are directly related to sinusitis. Intracranial complications remain comparatively rare, with 3.7% to 10% of intracranial infections related to sinusitis.[28] (See Complications.)

Patient history is extremely important in chronic rhinosinusitis (CRS) because of the broad overlap between sinus symptoms and other disease processes, as well as poor correlation between symptoms and endoscopic and radiographic findings.

Chronic sinusitis manifests more subtly than acute sinusitis. However, it may start suddenly, as an upper respiratory tract infection or acute sinusitis that does not resolve, or emerge slowly and insidiously over months or years. At times, the initial symptoms may be acute in nature. 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. Fever, when present, may be low grade.

Patients with chronic sinusitis may present with the following symptoms:

• Nasal obstruction, blockage, congestion, stuffiness

• Nasal discharge (of any character from thin to thick and from clear to purulent)

• Postnasal drip

• Facial fullness, discomfort, pain, and headache (more with nasal polyposis)

• Chronic unproductive cough (primarily in children)

• Hyposmia or anosmia (more with nasal polyposis)

• Sore throat

• Fetid breath

• Malaise

• Easy fatigability

• Anorexia

• Exacerbation of asthma

• Dental pain (upper teeth)

• Visual disturbances

• Sneezing

• Stuffy ears

• Unpleasant taste

• Fever of unknown origin

In pediatric settings, halitosis is more commonly reported by parents of younger children. Nasal obstruction with mouth breathing and associated sore throat may be present. In some individuals with chronic sinusitis, parents may note occasional and painless morning eye swelling. Older children may complain of loss of taste due to associated nasal obstruction and anosmia. Nocturnal symptoms may include snoring and coughing due to associated postnasal drip.

The patient history should focus on the following key factors, beginning with consideration of major and minor diagnostic criteria:

• The presence of major symptoms, including purulent anterior nasal drainage and/or purulent discolored posterior nasal drainage, nasal obstruction or blockage, facial congestion/fullness, facial pain/pressure, and hyposmia or anosmia (diagnosis of chronic sinusitis requires the presence of 2 of these symptom complexes of more than 3 months’ duration, 1 of which must be either obstruction or discharge[29] )

• Duration of symptoms

• Exacerbating and relieving factors

• Current medications

• Previous nasal or paranasal sinus surgery

• Previous treatments and their duration

• Previous imaging studies

• Other confounding health problems (including asthma, allergy, and immunocompromising disorders)

• Active or passive tobacco smoke

• Exposure to allergens

Physical examination in patients with chronic sinusitis may reveal various findings. It should include a complete head and neck examination (lymphadenopathy) to confirm the diagnosis and to rule out more serious disorders.

Sinus palpation is performed to evaluate tenderness or swelling. Pain or tenderness on palpation over frontal or maxillary sinuses may be noted. Transillumination of maxillary or frontal sinuses may be useful; it lacks sensitivity but may have value in experienced hands.

An oral cavity and oropharynx examination is used to evaluate the integrity of the palate and the condition of dentition and to look for evidence of postnasal drip. Oropharyngeal erythema and purulent secretions may be noted. Dental caries may be present.

Anterior rhinoscopy, with the use of a nasal speculum, is used to evaluate the condition of the nasal mucosa and to look for purulent drainage or evidence of polyps or other nasal masses. Other contributing factors to CRS that can be evaluated are nasal septal deviation and turbinate hypertrophy. The nasal examination should be carried out both before and after the use of a topical decongestant.

The nasal examination can be supplemented with the use of nasal endoscopy (if available) and CT scanning. Endoscopic (rhinoscopic) examination findings include the following:

• Nasal mucosal erythema, edema

• Purulent secretions within the middle meatus

• Nasal obstruction due to deviated nasal septum or hypertrophied turbinates

• Nasal polyps

An endoscopic view of the nasal cavity can be seen below.

Endoscopic view right nasal cavity; lacrimal bone (L), uncinate process (U), ethmoid bulla (B), middle turbinate (MT), nasal septum (S).

Ear examination for the presence of middle ear fluid that may be the sign of a mass in the nasopharynx is indicated.

Ocular examination for spread of disease to the orbit and function of ocular musculature is indicated. Ophthalmic manifestations include the following:

• Conjunctival congestion

• Lacrimation

• Proptosis, extraocular muscle palsies, and visual disturbances (when complicated by orbital extension)

Laryngeal examination is used to look for other confounding upper airway pathology including laryngeal-pharyngeal reflux (LPR). Lung examination is performed to determine if coexisting lower airway disease is present.

Cranial nerve examination is performed to look for underlying sinus malignancy or neurological disorder.

Manifestations of fungal sinusitis

Fungal sinusitis can manifest in different ways.[30] Unlike acute invasive fungal sinusitis, which is observed in patients who are immunosuppressed or who have diabetes, chronic fungal sinusitis is usually observed in immunocompetent patients. Mycetomas or fungus balls may be asymptomatic or may manifest as chronic sinusitis. Allergic fungal sinusitis usually manifests as nasal polyps and allergic sinusitis. Fungal elements in the sinuses are the inciting allergens.

In 1996, the American Academy of Otolaryngology-Head & Neck Surgery convened a multidisciplinary Rhinosinusitis Task Force (RTF). This group defined adult rhinosinusitis diagnostic criteria.[3] These 1996 diagnostic criteria required 2 or more major factors or 1 major factor and 2 minor factors for the diagnosis of rhinosinusitis.

Major factors included facial pain or pressure, nasal obstruction or blockage, nasal discharge or purulence or discolored postnasal discharge, hyposmia or anosmia, purulence in nasal cavity, and fever (for acute rhinosinusitis only).

Minor factors were defined as headache, fever (for CRS), halitosis, fatigue, dental pain, cough, and ear pain, pressure, or fullness. Of note, facial pain requires another major factor associated with it for diagnosis (facial pain plus 2 minor factors is not deemed sufficient for diagnosis of rhinosinusitis).

In 2003, the RTF’s definition was amended to require confirmatory radiographic or nasal endoscopic or physical examination findings in addition to suggestive history.[4] The 2003 diagnostic criteria for CRS require the above criteria for longer than 12 weeks or more than 12 weeks of physical findings. In addition, one of the following signs of inflammation must be present:

• Discolored nasal drainage from the nasal passages, nasal polyps, or polypoid swelling as identified on physical examination with anterior rhinoscopy after decongestion or nasal endoscopy

• Edema or erythema of the middle meatus or ethmoid bulla on nasal endoscopy

• Generalized or localized erythema, edema, or granulation tissue (If the middle meatus or ethmoid bulla is not involved, radiologic imaging is required to confirm a diagnosis.)

Imaging modalities confirming the diagnosis include the following:

• Computed tomography (CT) scanning demonstrating isolated or diffuse mucosal thickening, bone changes, or air-fluid levels

OR

• Plain sinus radiography revealing air-fluid levels or greater than 5 mm of opacification of one or more sinuses

• Magnetic resonance imaging (MRI) not recommended for routine diagnosis because of its excessive sensitivity and lack of specificity

In general, plain radiography has low sensitivity and specificity. CT scanning is considered the imaging standard for evaluation of chronic sinusitis.[31]

The latest executive summary on adult sinusitis has altered the definition for CRS to read 12 weeks or longer of 2 or more of the following symptoms[32] :

• Anterior or posterior mucopurulent drainage

• Nasal obstruction

• Facial pain-pressure-fullness

• Decreased sense of smell

In addition, inflammation must be documented by demonstrating one of the following:

• Purulent mucus or edema in the middle meatus or ethmoid region

• Polyps in the nasal cavity or middle meatus

• Imaging showing inflammation of the paranasal sinuses[29]

This is in contrast to recurrent acute sinusitis, which is present when 4 or more episodes per year of acute bacterial rhinosinusitis without signs and symptoms of rhinosinusitis between episodes.

The most serious complications of chronic sinusitis are neurological. Among these include subdural empyema, meningitis, venous sinus thrombosis, orbital cellulitis, and epidural abscess.[33]

Always consider serious underlying conditions, such as tumors and immunodeficiency states, in the workup of chronic sinusitis. In general, plain radiography has low sensitivity and specificity. CT scanning is considered the imaging standard for evaluation of chronic sinusitis. Routine blood cell counts and sedimentation rates are generally unhelpful; however, these may be elevated in patients with fever.

The cornerstone in the diagnostic workup of chronic sinusitis is the radiologic examination. Nasal endoscopy is recommended in most cases before obtaining imaging because it demonstrates the condition of the nasal mucosa and evaluates for purulent drainage.

Radiographic findings in individuals with chronic sinusitis may demonstrate osteoblastic response in the affected sinus walls, mucoperiosteal thickening, opacification of sinus cavity, and even reduction of cavity size. Younger children with persistent respiratory symptoms probably have significant abnormalities that are observable on sinus radiographs. These radiographs provide noninvasive and rapid evaluation of the lower third of the nasal cavity and of the maxillary, frontal, sphenoid, and posterior ethmoid sinuses. Unfortunately, these views provide only limited information about anterior ethmoid anatomy and may be misleading in soft-tissue inflammatory disease; hence, more physicians are using CT for preoperative evaluation and MRI for excluding orbital and intracranial extension.[31, 34]

Unilateral sinus disease usually represents chronic inflammation but may be a sign of underlying malignancy, especially in individuals with a unilateral polyp.[35]

For more information, see the Medscape Reference article Imaging in Sinusitis.

Lund-Mackay scale for evaluation of images

Various staging systems have been proposed; however, no one system is accepted as the standard for use in chronic rhinosinusitis (CRS). Many studies use the Lund-Mackay scale to evaluate radiographic images. This scale grades the right and left sides independently, looking at the maxillary, anterior ethmoids, posterior ethmoids, sphenoid, and frontal sinuses, as well as the ostiomeatal complex. Each sinus is scored a 0 (no abnormality), 1 (partial opacification), or 2 (total opacification), while the ostiomeatal complex is scored either a 0 or 2 (for presence or absence of disease). Scores range from 0 to 24.

Establishing the presence of sinus infection requires obtaining bacterial and fungal cultures. These can be obtained directly from the sinus cavity (by maxillary sinus tap or during surgery) or endoscopically from the ostia. Studies of chronic sinusitis have demonstrated no correlation between nasal flora and culture from the sinuses. Nasal swab cultures have therefore no diagnostic value. In severe cases, blood cultures, including fungal blood cultures, may be helpful. A change of bacterial isolates during the course of recurrent exacerbation was observed in 68% (76/112) of patients studied by Yniv et al.[19]  The authors recommended that repeated middle meatal cultures should be considered in those with recurrent exacerbation of CRS, particularly in cases not responding to antimicrobial therapy.

Maxillary sinus tap

Traditionally, maxillary sinus tap via inferior meatal puncture was performed for sinus culture. Many otolaryngologists have moved away from maxillary sinus tap because of the discomfort of the procedure and the understanding that a culture of an organism from the middle meatus may be more accurate to determine the bacteria involved in the disease process.

Endoscopically directed middle meatal culture

Recent literature has supported the use of endoscopically directed culture of the middle meatus (the primary drainage system of the anterior ethmoid, maxillary, and frontal sinuses) with the use of either a suction trap or a swab. Endoscopically directed middle meatal cultures had a sensitivity of 80.9% and a specificity of 90.5% in a recent meta-analysis.[36]

Plain radiography may show mucosal thickenings or sinus opacities. However, it is not adequate to diagnose CRS because abnormalities detected on plain films are not sensitive or specific for sinusitis. Air fluid levels are uncommon in chronic sinusitis. Ethmoid sinuses and the ostiomeatal complex are not visualized well on plain sinus radiography. For more information, see the Medscape Reference article Imaging in Sinusitis.[72]

Multiplanar sinus CT scan is the preferred imaging technique for evaluating CRS. Sinusitis is characterized by the presence of sinus mucosal thickening, sinus ostial obstruction, and sinus opacification. Other findings include polyps, mucoceles, and bony changes due to CRS (sclerosis, septations, erosions, and bowing).

Contrast-enhanced CT scanning 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. CT scan combined with endoscopic examination helps the surgeon to make operative decisions.[80]

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.

Most centers now offer limited sinus CT scans that consist of 5 to 12 coronal cuts. These limited or screening CT scans cost about the same as a plain radiography but provide more information.

Magnetic resonance imaging (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.

Biopsy samples from the maxillary sinus mucosa of patients with chronic sinusitis show basement membrane thickening, atypical gland formation, goblet cell hyperplasia, mononuclear cell infiltration, and subepithelial edema. The mononuclear cell infiltrate often predominantly demonstrates neutrophils in acute disease and eosinophils in chronic disease. Rarely, squamous cell metaplasia may be seen.

Brush biopsy or turbinate biopsy

Evaluation of cilia function with a brush biopsy or turbinate biopsy can be considered in cases of presumed cilia dysfunction.

Endoscopic biopsy

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.

Environmental allergen evaluation should be considered. Radioallergosorbent assay test (RAST) or skin testing for allergens may play an important role in treating patients with chronic rhinosinusitis (CRS) and confounding allergies. 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).[10]

A sweat test for cystic fibrosis should be considered in all children with nasal polyposis and CRS.

Total immunoglobulin E (IgE) levels, as well as the degree of staining of IgE in sinus epithelium and subepithelium, can be tested and may be helpful to evaluate for allergic fungal sinusitis.[37]

The American Academy of Otolaryngology-Head and Neck Surgery Foundation has updated its clinical practice guidelines for the treatment of adult sinusitis.[38] The recommendations to clinicians are as follows:

• Distinguish acute bacterial rhinosinusitis from acute rhinosinusitis caused by viral upper respiratory infections and noninfectious conditions
• Confirm the clinical diagnosis of CRS with objective documentation of sinonasal inflammation via anterior rhinoscopy, nasal endoscopy, or CT scan
• Offer either watchful waiting (without antibiotics) or initial antibiotic therapy for adults with uncomplicated acute bacterial rhinosinusitis
• If antibiotics are prescribed, the initial antibiotic therapy for adults with uncomplicated acute bacterial rhinosinusitis should be amoxicillin with or without clavulanate as first-line therapy for 5-10 days
• Reassess the patient to confirm the bacterial rhinosinusitis and exclude other causes of illness; assess for complications if the patient worsens or fails to improve with the initial management option by 7 days after diagnosis or worsens during the initial management
• Distinguish CRS and recurrent acute rhinosinusitis from isolated episodes of acute bacterial rhinosinusitis and other causes of sinonasal symptoms
• Assess patients with CRS or recurrent acute rhinosinusitis for multiple chronic conditions that would modify management (eg, asthma, cystic fibrosis, immunodeficiency, ciliary dyskinesia)
• Assess for nasal polyps in patients with CRS
• Recommend saline nasal irrigation, topical intranasal corticosteroids, or both for symptomatic relief of CRS
• Do not prescribe topical or systemic antifungal therapy in patients with CRS

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.[39] 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 and allergic factors

Environmental factors and/or allergic factors may predispose some individuals to chronic sinusitis. Reduce exposure to dust, molds, cigarette smoke, and other environmental chemical irritants. For patients with confounding nasal allergy, other antiallergy therapies, including either oral or topical antihistamines, cromolyn, topical steroids, and immunotherapy, may reduce recurrences and symptoms of allergic rhinitis.

Smoking cessation likely plays a large role in the success of both medical and surgical treatments because tobacco products act as an irritant to normal nasal mucosa and cilia function.

Gastroesophageal reflux disease

Patients with adult chronic sinusitis may benefit from control of gastroesophageal reflux disease (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

Appropriate control of various congenital and acquired immunodeficiency states is necessary to cure chronic sinusitis.

Asthma

Especially for patients with co-existing asthma, leukotriene inhibitors may play a role.[40]

Cystic fibrosis 

Guidelines fortreatment of  cystuc fibrosis induced sinusistis are not available. Treatment with intranasal dornase alfa, topical tobramycin and coiistin, and targeting the genetic defect, are promising.[40]

Symptoms may be relieved with topical decongestants, topical steroids, antibiotics, nasal saline, topical cromolyn, or mucolytics.

Steam inhalation and nasal saline irrigation may help by moistening dry secretions, reducing mucosal edema, and reducing mucous viscosity. A recent review concluded that low-volume (5 mL) nebulized saline spray was not more beneficial than intranasal steroids. Larger volume (150 mL) was marginally more efficacious than placebo.[41]

Initial oral steroid therapy followed by topical steroid therapy was found to be more effective than topical steroid therapy alone in decreasing polyp size and improving olfaction in patients with CRS with at least moderate nasal polyposis.[42] The severity of all symptoms was lessened.[43]

There was mo increased risk of acquiring COVID 19 infection in individuals with CRS treated with oral coritcosteroids compared with those who were not treated.[44]

In June 2019, the FDA approved dupilumab for the treatment of inadequately controlled severe chronic rhinosinusitis with nasal polyps (CRSwNP) in adults. Dupilumab is a humanized monoclonal antibody that inhibits interleukin-4 (IL-4) and IL-13 signaling by specifically binding to the IL-4R-alpha subunit shared by the IL-4 and IL-13 receptor complexes. Blocking the IL-4R-alpha subunit inhibits IL-4 and IL-13 cytokine-induced responses, including the release of proinflammatory cytokines, chemokines, and IgE. Approval was supported by phase 3 clinical trials (eg, SINUS-24, SINUS-52) demonstrating significant improvement nasal congestion/obstruction, nasal polyps score, sinus opacification, and improvement in smell when added to standard-of-care mometasone furoate nasal spray compared with placebo plus mometasone.[45, 46, 47]

In individuals with CRSwNP, the major intervention is to relieve the obstruction to sinus drainage by reducing or eliminating the polyp. This is achieved primarily with glucocorticosteroids, both systemically and intranasally. Antileukotriene agents can be adjunctive to the effect of the steroids, especially in patients with asthma or an allergy to aspirin.[48]  Biologics for CRSwNP modulate the type 2 inflammatory pathway.[49]  The efficacy and safety of biologicals  (dupilumab, omalizumab, mepolizumab, and reslizumab-) for CRS with nasal polyps compared with the standard of care was evaluated by Agache et al.[50]  Dupilumab and omalizumab reduce the need for surgery and oral corticosteroid use and improve smell and quality of life, and patients experienced fewer treatment-related adverse events. There was low certainty for mepolizumab or reslizumab in achieving these goals. A systematic review by Chong et al[51]  found that omalizumab probably improves disease-specific health-related quality of life compared with placebo. There was no evidence regarding the effect of omalizumab on disease severity.

Catalano et al evaluated balloon dilation for the treatment of chronic frontal sinusitis in 20 patients with advanced sinus disease in whom medical therapy had failed and who therefore required operative intervention. Preoperative and postoperative CT scans were compared. There were no significant complications from balloon dilation, and there was significant improvement in patients with certain subsets of CRS.[52]

To see complete information on Balloon Sinuplasty, please go to the main article by clicking here.

An adequate antibiotic trial in CRS usually consists of a minimum of 3 to 4 weeks of treatment, preferably culture directed. Oral antibiotic regimens are generally used to treat chronic sinusitis, since this condition is primarily treated in an outpatient setting. For resistant cases, there may be a role for intravenous antibiotic therapy.

Initial choice of the appropriate antimicrobial(s) is usually empiric. Sinus cultures generally are not obtained 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. The likelihood of involvement by beta-lactamase–producing organisms should be considered. If methicillin-resistant Staphylococcus aureus (MRSA) is a possible pathogen, coverage for this should be included. History of drug allergies (if any) and cost of therapy should be taken into account as well. In addition, if the patient has received antibiotics during the preceding 3 months, a different class of antibiotics should be used.

Therapeutic regimens include the combination of a penicillin (eg, amoxicillin) plus a beta-lactamase inhibitor (eg, clavulanic acid), 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, Pseudomonas 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.

Agents that provide coverage for MRSA should be administered. Some options include tetracyclines, trimethoprim-sulfamethoxazole or linezolid, which are added to other regimens that cover anaerobes. Parenteral antimicrobials effective against MRSA include vancomycin, linezolid, and daptomycin. Biologics have shown promise in the treatment of refractory sinusitis.[53]

Ferguson et al performed a prospective observational study of 125 adults with classic symptoms of CRS who underwent nasal endoscopy and sinus CT. Severe symptoms occurred more often in younger patients with normal CT scans of the sinus than in those with positive CT findings. Improvement in response to antibiotics was similar for patients with positive CT findings and those with normal CT scans. The authors concluded that most symptoms considered to be typical for CRS proved to be nonspecific, and they suggest that objective evidence of mucopurulence assessed by endoscopy or CT should be obtained if a prolonged course of antibiotics is being considered.[54] Overall, there is little concrete evidence that systemic antibiotic therapy offers much improvement in the quality of life among adults with chronic sinusitis without polyps.[55]

It is useful to tailor therapy to the clinical type of CRS.[56] CRS without nasal polyps is treated with prednisone 20-40 mg daily tapered over 10 days plus an intranasal steroid. Antibiotic therapy is often required for up to 6 weeks or longer and should not be discontinued until the patient is asymptomatic. Discontinuation of antimicrobial therapy prior to complete resolution increases the likelihood of relapse.

Nebulized antibiotics and antifungal agents be used in refractory cases, especially in patients who have undergone sinus surgery and as a means to avoid prolonged therapy with intravenous antibiotics. Further studies need to be done to establish their role in treating CRS.[57, 58]

There is a high rate of S aureus colonization of the sinus mucosa in CRS with nasal polyps. Three weeks of doxycycline therapy has been demonstrated to reduce polyp size, possibly because of the anti-inflammatory properties of the tetracyclines, as well as their anti-staphylococcal effects.[59]

Failure to relieve the polyposis obstruction with medical therapy is an indication for a surgical approach.

A 2015 study indicates that there is little difference in clinical outcomes between 3 weeks versus 6 weeks of antibiotic therapy for CRS.[60] This conclusion is contrary to the experience of many practitioners. At minimum, 3 weeks of antibiotic therapy could be used as a benchmark to reevaluate whether the patient has adequately responded. If not, a surgical approach may be considered.

The role of nebulized antibiotics and antifungal agents in treating refractory cases, especially in patients who have undergone sinus surgery, is very limited and generally should be avoided.[57] Fungal CRP is primarily treated with appropriate surgery.[38]

Difficult-to-treat chronic sinusitis is associated with nasal polyps, asthma, and aspirin-exacerbated respiratory disease.[61]

In summary, daily saline irrigation with topical cortical steroid therapy is to be considered prime therapy for chronic sinusitis. In patients with nasal polyposis, systemic corticosteroids (3 weeks), doxycycline (3 weeks), and/or a leukotriene antagonist should be considered. Omalizumab (anti-IgE antibody) is a biologic that may help patients with severe CR with polyps. Omalizumab made patients' symptom better and shrank their polyps in small-size randomised controlled trials.[62, 63, 64]  In patients without nasal polyps, 3 months of a macrolide antibiotic may be useful.[65]

Probiotic therapies may offer clinical benefit in CRS.[66]  Further investigation is warranted for evaluation of long-term outcomes and pathogenic deterrence.

Functional Endoscopic Sinus Surgery

Surgical care is used as an adjunct to medical treatment in some cases. Surgical care is usually reserved for cases that are refractory to medical treatment and for patients with anatomic obstruction. Preoperative CT findings prior to sinus surgery may be poor predictors of surgical outcomes.[67]

The goal in surgical treatment is to reestablish sinus ventilation and to correct mucosal opposition in order to restore the mucociliary clearance system. Surgery strives to restore the functional integrity of the inflamed mucosal lining.

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.[68]

FESS facilitates the removal of disease in key areas, restores adequate aeration and drainage of the sinuses by establishing patency of the ostiomeatal complex, debulks severe polyposis, 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% to 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.

Occupational exposure may affect FESS outcomes. Symptoms may persist with work-related exposure to inhaled agents, and revision surgery may be required.[69]

In patients who have undergone endoscopic sinus surgery, total and direct healthcare costs, antibiotic usage, and the total number of imaging studies performed decreased after surgery for at least 3 years. However, the use of oral corticosteroids did not change.[70]

For more information, see the Medscape Reference article Functional Endoscopic Sinus Surgery.

Balloon Sinuplasty

Balloon sinuplasty is an option in the treatment of sinusitis that has failed to respond to appropriate medical therapy. Evidence is best for limited disease in patients with chronic rhinosinusitis without nasal polyposis affecting the frontal, sphenoid, and maxillary sinuses. Because it can be performed in an office setting, it can be a viable therapeutic alternative in patients with comorbidities who are unable to tolerate general anesthesia.[71]

Management of Chronic Maxillary Sinusitis

Three main surgical options are available for chronic maxillary sinusitis:

• Endoscopic uncinectomy with or without maxillary antrostomy

• Caldwell-Luc procedure

• Inferior antrostomy (naso-antral window)

Management of Fungal Sinusitis

The preferred treatment for chronic fungal sinusitis is surgical debridement. Mycetomas or fungus balls are best treated by means of surgical removal. Allergic fungal sinusitis, which usually manifests as nasal polyps and allergic sinusitis, is treated by means of systemic steroids and surgical removal of polyps and mucinous secretions. Prolonged postoperative tapering doses of prednisone and anterior nasal glucocorticoid steroids are indicated to suppress the symptoms of fungal CRS.[72]

Some literature has suggested that topical antifungals may have a role in the treatment of CRS[73] ; however, this treatment remains controversial, and other studies have not supported this approach. A recent assessment that included 6 studies (N = 380) showed no statistically significant benefit of topical or systemic antifungals over placebo for the treatment of CRS.[74] Head et al concluded uncertainty regarding whether topical or systemic antifungals affect patient outcomes in adults with chronic rhinosinusitis compared with placebo or no treatment.[75]

Garlic has an active ingredient (allyl thiosulfinate) that provides a short-term decongestant effect. Eating foods highly seasoned with garlic has been considered therapeutic. Chewing horseradish root is another home remedy reported by some patients as effective for clearing the sinuses, but no scientific data support this belief.

The most common complication of chronic sinusitis is superimposed acute sinusitis. In children, the presence of pus in the nasopharynx may cause adenoiditis, and a high percentage of such patients develop secondary serous or purulent otitis media. Dacryocystitis and laryngitis may also occur as complications of chronic sinusitis in children.

Patients should be urgently referred to an otolaryngologist when they manifest any of these signs and/or symptoms: double or reduced vision, proptosis, rapidly developing periorbital edema, ophthalmoplegia, focal neurologic signs, high fever, severe headache, meningeal irritation, or significant or recurrent nose bleeding.[28]

Orbital complications include preseptal cellulitis, subperiosteal abscess, orbital cellulitis, orbital abscess, and cavernous sinus thrombosis. Intracranial complications include meningitis, epidural abscess, subdural abscess, and brain abscess.[28]

Other complications include osteomyelitis and mucocele formation.

Some studies have suggested a higher incidence of complications associated with fungal sinusitis.[76, 77] Untreated chronic sinusitis can lead to life-threatening complications, as in patients with cystic fibrosis.[78]

Individuals with medically resistant CRS exhibit a higher rate of asthma development. Those who have undergone endoscopic surgery early in their course appear to have a decreased risk of asthma.[79]

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.

A consult with an otolaryngologist should be considered when one of the following occurs:

• The disease is refractory to maximal medical therapy.

• The disease has progressed beyond the paranasal sinuses.

• The disease is unilateral (patient should be evaluated for potential neoplasm).

• Patients have coexisting morbidities that are exacerbated by the sinus disease.

• Urgent referral when a complication is suspected (see above)

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.

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

Nasal douching may improve symptoms, particularly following surgical treatment. Steam inhalation may have a role to liquefy and soften crusts while moisturizing dry inflamed mucosa.

Nasal cavity irrigation using buffered normal saline may have a role in decreasing mucosal edema. Irrigation should be performed at least twice daily.

Patients with presumed allergic rhinitis in conjunction with chronic sinusitis may benefit from an evaluation by an otolaryngologist trained in otolaryngic allergy or an allergist/immunologist. In most instances, prick/puncture tests are performed to clarify the role of allergies.

Canadian Rhinology Working Group consensus statement: biologic therapies for chronic rhinosinusitis.[80]

Consensus statements statement: biologic therapies for CRS with polyps.

1. Patients must have both subjective and objective findings consistent with the diagnosis of CRSwNP to qualify for biologic therapy. All endotypes of CRSwNP are considered eligible except for primary ciliary dyskinesia and cystic fibrosis.
2. Patients with CRSwNP do not need another Type 2 inflammatory condition such as asthma to be considered for biologic therapy
3. There is insufficient evidence to make a recommendation for providing biologics to patients with CRSsNP.
4. Biologics should not be provided to those suffering with recurrent acute bacterial sinusitis.
5. The severity of subjective CRS symptoms needs to be moderate to severe based on the clinicians choosing of a validated patient reported outcome measure for chronic sinus disease.
6. Biologics should only be considered for those who have undergone adequate sinus surgery and failed appropriate medical therapy following surgery. Patients unfit for surgery who have failed AMT may also be considered candidates for biologic therapy.
7. Option: A CT sinus scan performed prior to administration of biologics may determine if adequate sinus surgery was performed and to objectively confirm global mucosal inflammation.
8. Response to biologics is based on subjective and objective improvement. Patients should experience an improvement to some or all of their major symptoms which include sense of smell, nasal obstruction, nasal discharge and facial pain. By 16 weeks, there should also be objective improvement on endoscopy or CT scan and this should be re-evaluated at 1 year.
9. Providers have the option of providing another biologic therapy if patients fail to respond to one biologic agent but continue to fit the inclusion criteria for biologic therapy. At this time, there are no biological markers to determine the best biological agent to use.
10. Cost of biologics matters in the decision making of the use of biologics for CRS patients.
11. The short-term use of biologics (12 months) in CRSwNP is considered safe. In other Type 2 inflammatory conditions, biologics have been shown to be safe long term.

The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications. Agents used in the treatment of chronic sinusitis include antibiotics, decongestants, nasal saline sprays, mast cell stabilizers, and expectorants.[81]

In June 2019, the FDA approved dupilumab for treatment of inadequately controlled severe chronic rhinosinusitis with nasal polyps (CRSwNP) in adults. Approval was supported by phase 3 clinical trials (eg, SINUS-24, SINUS-52) demonstrating significant improvement nasal congestion/obstruction, nasal polyps score, sinus opacification, and improvement in smell when added to standard-of-care mometasone furoate nasal spray compared with placebo plus mometasone.[45, 46, 47]

Antibiotics Summary

Criteria of antibiotic selection for the treatment of chronic sinusitis include the following:

• Culture-directed when possible

• Knowledge of changing antimicrobial resistance in a community

• History of medication allergy, especially the sulfa drugs and penicillins

• Adverse effect profile of the medication

• Cost of the medication and the economic status of the patient

• Other factors that affect compliance, such as dosing and formulation

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.

Currently, first-line antibiotics for patients with chronic sinusitis include amoxicillin-clavulanate, second-generation cephalosporins, and erythromycin-sulfasoxazole. Beta-lactamase–mediated resistance to the early second-generation cephalosporins is high among strains of Haemophilus influenzae and Moraxella catarrhalis. Cefixime, a third-generation cephalosporin, may be selected for infections caused by H influenzae or M catarrhalis, but it has a poor spectrum of activity against Streptococcus pneumoniae. The newer-generation macrolides, clarithromycin and azithromycin, achieve excellent mucosal levels and should be considered in patients with penicillin allergies. Some recent studies suggest that macrolides may also have some anti-inflammatory effects. Clindamycin should be reserved for resistant S pneumoniae.

Antimicrobials effective against S aureus may also be needed. Whenever methicillin-resistant S aureus (MRSA) is present, vancomycin or linezolid should be administered.

Antibiotics can also be administered topically with or without a nebulizer. This mode of administration is used in patients who have had prior sinus surgery.[82] The antimicrobials used are mupirocin, gentamicin, or tobramycin.

Class Summary

The penicillins are bactericidal antibiotics that work against sensitive organisms at adequate concentrations and inhibit the biosynthesis of cell wall mucopeptide. Examples of penicillins include amoxicillin (Amoxil, Trimox, Moxatag) and combination products such as amoxicillin-clavulanate (Augmentin, Augmentin XR, Augmentin ES).

Amoxicillin (Amoxil, Trimox, Biomox)

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

Amoxicillin and clavulanate (Augmentin)

This drug combination treats bacteria resistant to beta-lactam antibiotics.

Class Summary

Cephalosporins are structurally and pharmacologically related to penicillins. They inhibit bacterial cell wall synthesis, resulting in bactericidal activity. Cephalosporins are divided into first, second, third and fourth generation. First generation-cephalosporins have greater activity against gram-positive bacteria, and succeeding generations have increased activity against gram-negative bacteria and decreased activity against gram-positive bacteria.

Cefuroxime (Ceftin)

Cefuroxime is a second-generation cephalosporin that maintains gram-positive activity of first-generation cephalosporins; it also adds activity against Proteus mirabilis, H influenzae, Escherichia coli, Klebsiella pneumoniae, and M catarrhalis. The condition of the patient, severity of infection, and susceptibility of the microorganism determine the proper dose and route of administration.

Cefixime (Suprax)

Cefixime is a third-generation cephalosporin that arrests bacterial cell wall synthesis and inhibits bacterial growth by binding to one or more of the penicillin-binding proteins.

Cefaclor (Ceclor)

Cefaclor is a second-generation cephalosporin indicated for the management of infections caused by susceptible mixed aerobic-anaerobic microorganisms.

Cefprozil

Cefprozil is a second-generation cephalosporin that binds to one or more of the penicillin-binding proteins, which, in turn, inhibits cell wall synthesis and results in bactericidal activity.

Cefpodoxime (Vantin)

Cefpodoxime is a third-generation cephalosporin indicated for the management of infections caused by susceptible mixed aerobic-anaerobic microorganisms.

Cefepime

Cefepime is a fourth-generation cephalosporin that has gram-negative coverage comparable to ceftazidime but has better gram-positive coverage (comparable to ceftriaxone). Cefepime is a zwitter ion; it rapidly penetrates gram-negative cells.

Class Summary

Macrolide antibiotics have bacteriostatic activity and exert their antibacterial action by binding to the 50S ribosomal subunit of susceptible organisms, resulting in inhibition of protein synthesis.

Clarithromycin (Biaxin)

Clarithromycin is a semisynthetic macrolide antibiotic that reversibly binds to the P site of 50S the ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition.

Azithromycin (Zithromax)

Azithromycin is an advanced-generation macrolide; it works similarly to clarithromycin but with a shorter dosage time.

Erythromycin base / sulfisoxazole

Erythromycin is a macrolide antibiotic with a large spectrum of activity. Erythromycin binds to the 50S ribosomal subunit of the bacteria, which inhibits protein synthesis. Sulfisoxazole expands erythromycin's coverage to include gram-negative bacteria. Sulfisoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid.

Class Summary

Fluoroquinolones have broad-spectrum activity against gram-positive and gram-negative aerobic organisms. They inhibit DNA synthesis and growth by inhibiting DNA gyrase and topoisomerase, which is required for replication, transcription, and translation of genetic material.

Levofloxacin (Levaquin)

Levofloxacin inhibits bacterial topoisomerase IV and DNA gyrase, which are required for bacterial DNA replication and transcription.

Moxifloxacin (Avelox)

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

Class Summary

Tetracyclines bind with the 30S and possibly 50S ribosomal subunits of susceptible bacteria to inhibit bacterial protein synthesis.

Minocycline (Minocin, Dynacin, Solodyn)

For the treatment of infections caused by susceptible gram-negative and gram-positive organisms.

Doxycycline (Adoxa, Alodox, Doxy 100, Doryx, Vibramycin)

Doxycycline is a broad-spectrum, synthetically derived, bacteriostatic antibiotic in the tetracycline class. It is almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations. The drug inhibits protein synthesis (and thus bacterial growth) by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Doxycycline may block dissociation of peptidyl transfer ribonucleic acid (t-RNA) from ribosomes, causing RNA-dependent protein synthesis to arrest.

Class Summary

Anti-infectives such as vancomycin, doxycycline/minocycline, metronidazole and sulfamethoxazole/trimethoprim are effective against some types of bacteria that have become resistant to other antibiotics.

Vancomycin (Lyphocin, Vancocin, Vancoled)

Vancomycin is indicated for patients who have infections with resistant staphylococci. To avoid toxicity, the current recommendation is to assay vancomycin trough levels after the third dose is drawn 0.5 hour prior to next dosing. Use CrCl to adjust the dose in patients diagnosed with renal impairment. It is used in conjunction with gentamicin for prophylaxis in patients with penicillin allergy who are undergoing gastrointestinal or genitourinary procedures.

Metronidazole (Flagyl)

Metronidazole is an imidazole ring-based antibiotic that is active against various anaerobic bacteria and protozoa. It is used in combination with other antimicrobial agents (except C difficile enterocolitis).

Trimethoprim/sulfamethoxazole (Bactrim DS, Septra DS)

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

Class Summary

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.[16]

Goals include reduction of tissue edema, facilitation of drainage, and maintenance of patency of sinus ostia. In short, decongestants are necessary to meet the management goals for chronic sinusitis. Decongestants are available in 2 forms, topical and oral. Each agent differs slightly in its method of action.

Topical agents are locally active vasoconstrictor agents such as phenylephrine HCl 0.5% and oxymetazoline HCl 0.5% that provide almost immediate symptomatic relief by shrinking the inflamed and swollen nasal mucosa. Topical nasal formulations should not be used for longer than 3-5 consecutive days because of the risk of development of tolerance, rhinitis medicamentosa, and rebound after drug withdrawal.

Oral systemic agents are used when decongestion is necessary for longer than 3 days. An oral systemic agent, such as phenylpropanolamine (recalled from US market) or pseudoephedrine, is preferred. Oral decongestants are alpha-adrenergic agonists that reduce nasal blood flow. Theoretically, these oral systemic agents have the potential to act on tissues deep in the ostiomeatal complex, where topical agents may not penetrate effectively.

Oxymetazoline (Afrin)

Oxymetazoline is 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.

Naphazoline (Privine)

Naphazoline's alpha-adrenergic effects on arterioles of conjunctiva and nasal mucosa produce vasoconstriction.

Tetrahydrozoline, ophthalmic (Tyzine, Visine)

The alpha-adrenergic effects of tetrahydrozoline on nasal mucosa produce vasoconstriction.

Xylometazoline (Otrivin)

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

Phenylephrine (Neo-Synephrine)

Phenylephrine HCl is a synthetic sympathomimetic amine. It is a strong postsynaptic alpha-receptor stimulant with little beta-adrenergic activity that produces vasoconstriction of arterioles in the body.

Pseudoephedrine (Sudafed)

Pseudoephedrine stimulates vasoconstriction by directly activating the alpha-adrenergic receptors of the respiratory mucosa; it induces bronchial relaxation and increases heart rate and contractility by stimulating beta-adrenergic receptors. The drug is available in tabs, chewables, solution, extended-release tabs, and infant drops.

Class Summary

These agents are particularly effective for chronic sinusitis associated with allergic rhinitis, nasal polyps, and rhinitis medicamentosa. Corticosteroids can be administered in the form of nasal sprays or solutions. Topical steroids along with systemic antibiotics are now the key components of the medical armamentarium in the management of chronic sinusitis. Oral glucocorticoids (eg, prednisone) may be prescribed to patients with chronic rhinosinusitis in allergic fungal rhinosinusitis, reducing the size of polyps, and refractory mucosal edema.

Fluticasone propionate (Flonase)

Fluticasone propionate is applied as a nasal spray. It is particularly effective in allergic and vasomotor rhinosinusitis and rhinosinusitis medicamentosa. It is also used as prophylaxis for nasal polyps. Plasma concentrations are very low following intranasal administration in recommended doses.

Beclomethasone dipropionate (Beconase AQ)

Beclomethasone dipropionate is a topical steroid nasal spray. It acts locally as an anti-inflammatory and vasoconstrictor. The drug is readily absorbed through the nasopharyngeal mucosa and GI tract. It is useful in allergic and vasomotor rhinosinusitis and sinusitis medicamentosa.

Class Summary

Nasal saline spray, nasal irrigation, 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. Nasal irrigation washes the nasal cavities, reduces postnasal drainage, removes secretions, and rinses allergens and irritants. The use of saline washes prior to administration of other intranasal medications enables the medication to affect the mucosa.

Saline nasal spray (Ayr, Ocean)

Saline nasal spray loosens mucous secretions to help remove mucus from the nose and sinuses.

Class Summary

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

Cromolyn sodium (Nasalcrom)

Cromolyn sodium inhibits degranulation of sensitized mast cells following their exposure to specific antigens.

Class Summary

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.

Class Summary

Leukotriene inhibitors may play a role especially in patients with coexisting asthma. Leukotrienes are products of arachidonic acid from mast cells and eosinophiles. They cause bronchial edema, smooth muscle contraction, and inflammation. A selective binding to the receptor occurs, preventing this reaction.

Montelukast (Singulair)

Montelukast selectively prevents the action of leukotrienes released by mast cells and eosinophils. Montelukast works to inhibit the effects of the leukotriene receptor that causes asthma, including airway edema, smooth muscle contraction, and cellular activity associated with the symptoms.

Zafirlukast (Accolate)

Zafirlukast selectively prevents the action of leukotrienes released by mast cells and eosinophils. It inhibits the effects by the leukotriene receptor, which has been associated with asthma, including airway edema, smooth muscle contraction, and cellular activity associated with the symptoms.

Class Summary

Inhibition of interleukins 4 and 13 with dupilumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) has shown to decrease polyp burden and improve symptoms.[45, 46, 47]

Dupilumab (Dupixent)

Monoclonal antibody that inhibits interleukin-4 (IL-4) and IL-13 signaling by specifically binding to the IL-4R-alpha subunit shared by the IL-4 and IL-13 receptor complexes. Blocking the IL-4R-alpha subunit inhibits IL-4 and IL-13 cytokine-induced responses, including the release of proinflammatory cytokines, chemokines, and IgE. It is indicated for adults with inadequately controlled severe CRSwNP.

Class Summary

Dupilumab Dupilumab, ( Dupixent), is a monoclonal antibody blocking interleukin 4 and interleukin 13, used for allergic diseases such as eczema, asthma and nasal polyps which result in chronic sinusitis.