Antibiotic Therapies For The Treatment Of Sinus Infections.

Background
Sinusitis is usually defined as an acute bacterial infection involving the mucosal surfaces of the paranasal sinuses and nasal cavity.^1,3,9 It usually occurs secondary to an upper respiratory tract infection, but may develop from several other causes including swimming in contaminated water, the introduction of a nasal foreign body, or an ascending dental infection.⁹ Frequently what is seen is an increased colonization of some of the common respiratory pathogens such as S pneumoniae, H influenzae, or M catarrhalis. The presentation of sinusitis is highly variable, and is usually difficult to distinguish from simple rhinitis.^4,6 Allergy testing may be helpful, since perennial allergic rhinitis can mimic sinusitis symptoms.⁹ No single symptom or sign is diagnostic and it is important to look at the overall presentation of history and physical findings in order to make the diagnosis of uncomplicated sinusitis.^4,5,10When selecting an antibiotic regimen for sinusitis, one must consider the cost, safety, and local patterns of bacterial resistance in order to maximize therapy.^4,7 The recommended antibiotic regimens listed below under acute and chronic sinusitis are for uncomplicated cases and it is assumed that the patient does not have any intracranial or orbital complications and that the patient’s immune function is not compromised. Complicated cases usually require hospitalization and the use of broad-spectrum intravenous antibiotics in order to cover for MRSA, Pseudomonas, anaerobes, gram negative rods, and fungal pathogens. Patients who are diagnosed with uncomplicated sinusitis and do not respond to initial therapy should be referred to an infectious disease specialist or otorhinolaryngologist in order to guide continued therapy.^5,7

Acute Sinusitis

Organisms:
The principal bacterial pathogens in acute sinusitis are: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. These particular bacteria are frequently referred to as “respiratory pathogens.” Other potential organisms include: Streptococcus pyogenes, Staphylococcus aureus, as well as mixed anaerobic bacteria (Peptostreptococcus, Fusobacterium, Bacteroides, Prevotella). The infection is polymicrobial in about one third of the cases. Anaerobic bacteria are likely to be seen in dental disease from an extension of the infection from the roots of the premolar or molar teeth to the sinuses.^3,4Therapeutic Alternatives:
All dosages listed are for adult patients with normal renal function. The regimens are considered empiric and are based on the presence of the common organisms listed above. Cultures are rarely necessary and are often reserved for patients with suspected allergies, cystic fibrosis, immune deficiencies, mucociliary disorders and similar disease states.¹⁰ The antibiotic regimens listed below consist of first-line regimens such as amoxicillin or trimethoprim-sulfamethoxazole, and are followed by second-line choices. First-line regimens are less expensive and are recommended as initial therapy in the absence of drug allergies or the presence of resistant organisms, including beta-lactamase producing strains. Second-line agents such as the newer fluoroquinolones should be used when resistant pathogens are suspected or in patients who do not improve within 3 to 5 days after a first-line agent is started.^4,5,6 Azithromycin or clarithromycin are commonly prescribed for penicillin-allergic individuals.Though there is evidence of increasing beta-lactamase activity in bacterial pathogens, antibiotics that cover these organisms are generally used as second-line drugs due to their increased cost and potential side effects.^5,8

First-line agents:
1. Amoxicillin 500mg po tid or
2. trimethoprim-sulfamethoxazole (800mg/160mg) po bid or
3. Doxycycline 100mg po bid orSecond-line agents:4. Azithromycin 500mg po x 1 day, then 250mg po qd x 4 days or
5. Cefpodoxime proxetil 200 mg q12h or
6. Cefdinir 600 mg qd or
7. Amoxicillin/clavulanate 875/125 mg po bid or
8. Levofloxacin 500mg po qd or
9. Moxifloxacin 400mg po qd.
10. Gatifloxacin 400mg po qd.

General:
The usual effective treatment duration for acute uncomplicated sinusitis is 10 to 14 days. Some sources recommend that therapy should continue for at least 7 days beyond the resolution of symptoms.^4,8 It would seem prudent to treat the patient for 5 to 7 days after resolution of symptoms.⁹ In acute sinusitis, symptoms are present for less than 3-4 weeks and may include the following: facial tenderness or swelling, foul breath, nasal drainage and congestion, daytime and night-time cough (may be more severe at night).^2,4,5,8 Toothache may be a common complaint when the maxillary sinus is involved.^4,5 A low grade fever is usually seen in approximately 50% of adult patients.⁵

Adjunct therapies may include: 1. topical vasoconstrictor such as phenylephrine to treat sinus drainage (limit therapy to 72 hours or less). 2. Topical or oral decongestants to treat nasal congestion. 3. Nasal or oral corticosteroids, to reduce inflammation. 4. Normal Saline nasal irrigation – provides some local symptomatic relief. 5. Analgesics or antipyretics as needed.^1,2,4,5,10

Chronic Sinusitis

Organisms:
Typical organisms isolated in chronic sinusitis include the respiratory pathogens listed above, as well as Staphylococcus epidermidis, Staphylococcus aureus, anaerobes, and gram-negative rods. Pseudomonas aeruginosa may also be present.^1,2,4,5,7 To further complicate matters, chronic sinusitis is often a polymicrobial disease with cultures usually growing multiple pathogens.^4,5,9
Therapeutic Alternatives:
Antimicrobial agents used for chronic sinusitis therapy should be effective against both aerobic and anaerobic bacteria. This approach is based on several retrospective studies that have illustrated the superiority of regimens that include this particular spectrum of coverage.^4,10

Regimens:
1. Amoxicillin/clavulanate 875mg po bid or
2. cefpodoxime proxetil 200mg q12h + clindamycin 300mg po q6h or
3. Levofloxacin 500mg po qd or
4. Moxifloxacin 400mg po qd or
5. Gatifloxacin 400mg po qd.

General:
Chronic sinusitis is one of the most common chronic medical conditions in the US, and is characterized by symptoms greater than 3 to 4 weeks; however, many cases may last months or even years.^4,5,8 Patients are generally treated for at least 21 days. The duration of therapy is not clearly established and may be extended to 6 weeks or longer. The diagnosis of chronic sinusitis is made by the classic symptoms associated with radiographic findings of mucosal thickening on routine films or sinus CT scans.^5,9 Medication regimens should include broad-spectrum antibiotics that cover both aerobes and anaerobes. Treatment failures may require surgical intervention.^2,3,5 Many of the pathogens isolated from chronically inflamed sinuses are resistant to penicillins through the production of beta-lactamase.⁴ These resistant organisms include both aerobic (S aureus, H influenzae and M catarrhalis) and anaerobic isolates such as Bacteroides fragilis, Prevotella, and Fusobacterium spp.^4,5

Chronic sinusitis usually presents as a persistent low-grade infection involving the paranasal sinuses and a persistent mucosal thickening, nasal obstruction and drainage.⁹ Impaired drainage may be a major contribution to the development of chronic sinusitis, and correction of the obstruction helps alleviate the infection and prevent recurrence.^4,5,9,10 In contrast to acute uncomplicated sinusitis, chronic sinusitis that relies solely on the use of antimicrobial therapy without surgical drainage of collected pus may not result in clearance of the infection.^4,5,9 Many physicians believe that surgical drainage is the mainstay of therapy in chronic sinusitis.^4,5,9 When the patient does not respond to medical therapy, the physician should consider surgical drainage.⁹

References (Alphabetical order)

1. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Dis Mon - 2001 Nov; 47(11); 537.2. Brook I. Microbiology and antimicrobial management of sinusitis. Otolaryngol Clin North Am - 2004 Apr; 37(2); 253.3. Cohen J., Powderly W. Infectious Diseases, 2nd ed. Mosby 2003.

4. Dykewicz MS. Rhinitis and sinusitis. J Allergy Clin Immunol. 2003 Feb; 111(2 Suppl): S520-9.

5. Ferri, Fred F., Ferri's clinical advisor : instant diagnosis. Mosby 2002.

6. Gwaltney JM Jr. Acute community-acquired sinusitis. Clin Infect Dis 1996;23:1209-23.

7. Maccabee M. Medical therapy of acute and chronic frontal rhinosinusitis. Otolaryngol Clin North Am. 2001 Feb; 34(1): 41-7.

8. Mandell et al., eds., Principles and Practice of Infectious Diseases, 5th ed., vol. 2, pp. 676-683. New York: Churchill Livingston.

9. Noble J, ed. Textbook of Primary Care Medicine. Third ed. St. Louis: Mosby; 2001:1747-1753.

10. Osguthorpe JD. Adult rhinosinusitis: diagnosis and management. Am Fam Physician. Jan 2001; 63(1): 69-76.