Medication Summary
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:
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Culture-directed when possible
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Knowledge of changing antimicrobial resistance in a community
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History of medication allergy, especially the sulfa drugs and penicillins
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Adverse effect profile of the medication
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Cost of the medication and the economic status of the patient
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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.
Penicillins
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.
Cephalosporins
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.
Macrolides
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.
Fluoroquinolones
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.
Tetracyclines
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.
Anti-Infectives
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
Decongestants
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.
Corticosteroids
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.
Nasal sprays
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.
Mast cell stabilizers
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.
Expectorants
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.
Leukotriene Receptor Antagonist
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.
Interleukin Inhibitors
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.
Biologics
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.
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Endoscopic view right nasal cavity; lacrimal bone (L), uncinate process (U), ethmoid bulla (B), middle turbinate (MT), nasal septum (S).
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Air-fluid level (arrow) in the maxillary sinus suggests sinusitis.
