Chronic Sinusitis in Children

Itzhak Brook, MD, MSc

hronic rhinosinusitis (CRS) is a complex inammatory condition of the paranasal sinuses and lining of the nasal passages that lasts 12 weeks or longer, despite medical management.1 Factors contributing to development of CRS include anatomical blockage, exposure to allergens and irritants, defects in mucociliary function, immunodeciency, and infections with bacteria, viruses, and fungi. The common result is local inammation and swelling of the sinonasal mucosa that leads to impairment of normal sinus drainage.2 CRS represents a multifactorial inammatory disorder rather than simply a persistent bacterial infection. The medical management of CRS is now focused upon controlling the inammation that predisposes patients to obstruction
Itzhak Brook, MD, MSc, is Professor at Georgetown University School of Medicine, Washington, DC. Address correspondence to: Itzhak Brook, MD, MSc, 4431 Albemarle St. NW, Washington, DC 20016; fax: 202-244-6809; e-mail: ib6@ georgetown.edu. Dr. Brook has disclosed no relevant nancial relationships. doi: 10.3928/00904481-20091222-05

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100 Percent of Patients 80 60 40 20 0

Viral Aerobes Anaerobes

8-10 Days

3 Months

Time

Figure. The microbiology of rhinosinusitis evolves through several phases.

and reducing the incidence of infections. However, all forms of CRS are associated with impaired sinus drainage and secondary bacterial infections. Most patients require initial antibiotics to clear infections and intermittently afterward to treat acute exacerbations of CRS.3 CRS can be divided into three distinct clinical syndromes, with different underlying causes, contributing factors, and medical or surgical management: CRS with nasal polyposis, CRS without nasal polyposis, and allergic fungal sinusitis. MICROBIOLOGY The microbiology of rhinosinusitis evolves through several phases (see Figure). The early stage (acute rhinosinusitis or ARS) is generally caused by a viral infection (rhinovirus, adenovirus, inuenza, or parainuenza), which persists up to 10 days.2 In some, a secondary acute bacterial sinusitis emerges. The most common bacterial causes are aerobes, such as Streptococcus pneumoniae, Haemophilus inuenzae, and Moraxella catarrhalis. If ARS does not resolve, colonizing anaerobic oropharyngeal ora and aerobes, such as Staphylococcus aureus, become predominant over time.2-19

Chronic otitis media with effusion and chronic maxillary sinusitis can occur simultaneously in children.11 The most common isolates are H. inuenzae, S. pneumoniae, Prevotella spp, and Peptostreptococcus spp. Microbiologic concordance between the ear and sinus was found in 22 (69%) of 32 culturepositive patients The prominence of anaerobes in CRS has been shown in children4.11,12 and adults.5-9 In a series of repeated endoscopic sinus aspirations from ve individuals with persistent symptoms who did not respond to antimicrobial therapy, growth of resistant anaerobes occurred over time, including pigmented Prevotella spp, Porphyromonas spp, Fusobacterium nucleatum, and Peptostreptococcus spp.13 The factors promoting the emergence of anaerobes include a) the selective pressure of antimicrobials enabling resistant organisms to survive, b) inammation and edema that reduces blood supply to the sinuses and leads to low oxygen tension,14 c) consumption of oxygen by aerobic bacteria, thereby decreasing the pH inside the sinuses,15 and d) expression of virulence factors (such as a capsule) by anaerobes.16

Although aerobes alone have been implicated in the pathogenesis of CRS in some studies, most of these investigations did not use techniques appropriate for the recovery of anaerobes. However, it is possible that some patients have a predominance of aerobes, or a mixture of aerobes and anaerobes. Aerobic gram-negative bacilli (AGNB), such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter spp, Proteus mirabilis, and Escherichia coli, have been implicated in CRS, mostly in patients with underlying conditions, such as cystic brosis (in the case of Pseudomonas) or diabetes, and in the immunocompromised (neutropenia, critical illness, diabetes mellitus, or HIV) patient.17-19 AGNB have been recovered most often in patients who have been extensively and repeatedly treated with antibiotics or have undergone sinus surgery.18,20 S. aureus, including MRSA, can also colonize the nasal mucosa and is recovered occasionally in acute and more often in CRS.21,22 Staphylococcus epidermidis is a colonizer of the nasal cavity, and its pathogenicity is questionable.18 Polymicrobial infection is common and may be synergistic in nature.16 Fungi can cause allergic fungal rhinosinusitis, fungal colonization, or invasive sinusitis. Invasive fungal sinusitis generally occurs in immunocompromised hosts and can be either rapidly progressive and potentially fatal or indolent. Odontogenic sinusitis is a wellrecognized entity in adult patients, accounts for approximately 10% to 12% of cases of maxillary sinusitis,23 and may be either acute or chronic. The etiology of odontogenic sinusitis is polymicrobial and reflects aerobic and anaerobic flora of the oral cavity.23 The association between periapical abscesses and rhinosinusitis was established in a study of purulent exudate from five periapical abscesses of

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the upper jaw and their corresponding maxillary sinuses.24 DIAGNOSIS Symptoms of CRS vary considerably. Fever may be absent or low grade. Frequently, symptoms are protracted and include malaise, easy fatigability, difculty in concentration, anorexia, irregular nasal or postnasal discharge, frequent headaches, and pain or tenderness to palpation over the affected sinus. Specimens obtained directly from the sinus cavity or via endoscopy, should be cultured in those who fail to show significant improvement within 5 to 7 days or who demonstrate signs of deterioration despite therapy. Culture results can ensure that antibiotic coverage is adequate. However, because anaerobes are difcult to isolate, coverage for them should be provided. Unfortunately, neither nasal nor nasopharyngeal cultures have predictive value in patients with CRS. Computed tomography (CT) scanning can assist in diagnosing chronic infection and its intracranial complications. ANTIMICROBIAL THERAPY The goal of medical therapy is to enhance sinus drainage, reduce chronic inammation, and eradicate pathogens. There are limited data showing that antibiotics alone are benecial in the treatment of CRS. An approach that combines antimicrobials and topical or systemic glucocorticoids, and sometimes other agents, is recommended. Studies examining the effects of comprehensive medical therapy are lacking, although most experts say antimicrobials are an important component of therapy for this disease. When these measures fail, the patient should be referred to an otolaryngologist for consideration of sinus surgery. Randomized trials in adults that compared different antibiotics found similar cure rates.25,26 However, observational studies suggested that antibiotics with anaerobic coverage might provide great-

er efcacy.9,27 One randomized trial of more than 200 adults with CRS showed a signicantly higher relapse in a cefuroxime group, compared with an amoxicillin-clavulanate group (7% versus 0%), suggesting that anaerobic coverage may be important.25 Antibiotic selection depends upon factors that include drug allergies, cost, and the incidence of and/or risk factors

CT scanning can assist in diagnosing chronic infection and its intracranial complications.
for beta-lactamase producing bacteria (BLPB) and MRSA. BLPB can not only survive beta-lactam therapy but may also protect other penicillin copathogens in CRS.28 The actual activity of the enzyme beta-lactamase and the phenomenon of shielding were demonstrated recently in aspirates obtained from acutely and chronically inamed sinuses.29 BLPB were isolated in 10 of 13 CRS aspirates. The predominant BLPBs isolated were S. aureus, Prevotella, and Fusobacterium spp. Recent receipt of antibiotics and attendance at daycare increases the risk of resistant organisms. Initial selection of antimicrobial therapy is usually empiric especially for community-acquired infections. Treat-

ment should be effective against the most likely bacterial etiologies, including aerobic (S. pneumoniae, H. inuenzae, and M catarrhalis) and anaerobic pathogens (Fusobacterium nucleatum, pigmented Prevotella, Porphyromonas, and Peptostreptococcus spp). Coverage for MRSA may be indicated. The following three regimens are effective against aerobic and anaerobic organisms: Amoxicillin-clavulanate (in children: 45 mg/kg per day divided every 12 hours; in adults: 500 mg three times daily or 875 mg twice daily or two 1,000 mg extended-release tablets twice daily). Amoxicillin-clavulanate is the rst-line regimen for most patients. Clindamycin (in children: 20 to 40 mg/kg per day orally divided every 68 hours; in adults: 300 mg four times daily or 450 mg three times daily). Clindamycin should be given to those with penicillin-allergy or when MRSA infection is suspected. Moxioxacin (400 mg once daily), generally for adults only. More cumbersome regimens reserved for refractory cases include metronidazole because it is highly effective against anaerobes: Metronidazole plus one of the following: cefuroxime axetil, cefdinir, cefpodoxime proxetil, levooxacin (generally for adults only), azithromycin, clarithromycin, or trimethoprim-sulfamethoxazole (TMP-SMX) is effective second-line therapy for patients with chronic sinusitis. Immunocompromised patients and those with cystic brosis or diabetes should be treated with agents that cover Pseudomonas spp. Cultures should be obtained when possible to guide the ultimate choice of therapy. Children with concurrent odontogenic infections should also be treated by a dentist, as antimicrobials are only an adjuvant to resolving the dental source of the infection.

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Treatment is usually given for at least 3 weeks and may be extended to up to 10 weeks in refractory cases. Patients who might benefit from the longer furation of treatment are those who failed previous courses, have severe symptoms, long duration of illness, or have had extensive surgery. Patients who are seriously ill, undergoing surgery, or in whom compliance is questionable, may require parenteral therapy. Parenteral antibiotics effective against anaerobes and aerobes include ampicillin-sulbactam, piperacillin-tazobactam, clindamycin, moxioxacin, a carbapenem (imipenem, meropenem), and a second-generation cephalosporin, cefoxitin or cefotetan. Parenteral antimicrobials effective against MRSA include vancomycin, linezolid, clindamycin, and daptomycin. For P. aeruginosa, antibiotics include a uoroquinolone in adults (eg, moxioxacin or levooxacin); a third- or fourth-generation cephalosporin with antipseudomonal activity (ceftazidime or cefepime); an aminoglycoside; or a carbapenem, imipenem or meropenem, for children. Metronidazole may also be given parenterally to cover anaerobes in combination with an agent with aerobic activity. In contrast to acute sinusitis, which generally is treated with antibiotics, many say surgical drainage and not antibiotics is the mainstay of therapy in CRS. The use of antimicrobials alone without surgical drainage may not result in clearance of the infection. The chronically inamed sinus membranes with diminished vascularity may be a poor means of achieving an adequate antibiotic level in the infected tissue, even though the blood level may be therapeutic. Furthermore, the reduction in pH and oxygen tension within the inamed sinus may interfere further with the activity of the antimicrobial agents, which can result in bacterial survival despite a high antibiotic concentration.

ANTI-INFLAMMATORY AGENTS When used in a topical form, nasal steroid sprays have been shown to be safe and effective in reducing the symptoms of allergic rhinitis.30 Their use in patients with CRS can decrease the size of nasal polyps and diminish allergic sinomucosal edema.31 There are no set

Patients who are seriously ill, undergoing surgery, or in whom compliance is questionable, may require parenteral therapy.
guidelines for duration of use, and side effects from long-term topical use are unknown. Experience in using oral steroids is only anecdotal. The extended use of oral steroid may result in serious side effects that include muscle wasting, osteoporosis, and delayed growth. Because of the side effects, steroids are tapered and given in short courses that span no more than 3 to 4 weeks. ADJUNCTIVE THERAPY Adjunctive therapy is intended to promote drainage of secretions and to improve oxygenation of the obstructed sinus ostia. Multiple agents with different mechanisms of action are often administered. These include decongestants

that are alpha-adrenergic agonists that constrict the capacitance vessels and decrease mucosal edema. Topical therapy, such as oxymetazoline or neosynephrine, may be used in an acute setting, but overuse can cause a rebound effect and rhinitis medicamentosa. Systemic decongestants can be used for longer periods of time but may cause insomnia and exacerbation of underlying systemic hypertension. Antihistamines are used in patients with underlying allergic rhinitis. They can relieve symptoms of itching, rhinorrhea, and sneezing in allergic patients, but, in nonallergic patients, they can cause thickening of secretions, which may interfere with needed drainage of the sinus ostia. Guaifenesin (glyceryl guaicolate) thins secretions, thereby facilitating drainage. Nasal saline irrigations are helpful in thinning secretions and may provide a mild benet in nasal congestion. Hypertonic saline irrigations improve patient comfort and quality of life, decrease medication use, and diminish the need for surgical therapy.32 Leukotriene inhibitors are systemic medications that block the receptor and/or production of leukotrienes, which are the potent lipid mediators that increase eosinophil recruitment, goblet cell production, mucosal edema, and airway remodeling. Their role in chronic sinusitis and nasal polyposis is not yet well established.33 COMPLICATIONS The most common complications of CRS are orbital cellulitis, subperiosteal abscess, orbital abscess, brain abscess, subdural empyema, and meningitis.8,3436 The predominant organisms recovered from these infections are anaerobic, aerobic, and microaerophilic bacteria originating from the oral ora. Establishing the microbiology by obtaining appropriate cultures for aerobic and anaerobic bacteria is essential for proper antimicrobial selection. Early recognition and

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appropriate surgical and medical therapy are essential to ensure recovery. REFERENCES
1. Clement PA, Bluestone CD, Gordts F, et al. Management of rhinosinusitis in children: consensus meeting, Brussels, Belgium, September 13, 1996. Arch Otolaryngol Head Neck Surg. 1998;124(1):31-34. 2. Brook I. Acute and chronic bacterial sinusitis. Infect Dis Clin North Am. 2007;21(2):427448, vii. 3. Bhattacharyya N. The role of infection in chronic rhinosinusitis. Curr Allergy Asthma Rep. 2002;2(6):500-506. 4. Brook I. Bacteriologic features of chronic sinusitis in children. JAMA. 1981;246(9):967-969. 5. Wald ER. Microbiology of acute and chronic sinusitis in children and adults. Am J Med Sci. 1998;316(1):13-20. 6. Brook I. Bacteriology of acute and chronic sphenoid sinusitis. Ann Otol Rhinol Laryngol. 2002;111(11):1002-4. 7. Brook I. Bacteriology of acute and chronic ethmoid sinusitis. J Clin Microbiol. 2005;43(7):3479-3480. 8. Nord CE. The role of anaerobic bacteria in recurrent episodes of sinusitis and tonsillitis. Clin Infect Dis. 1995;20(6):1512-1524. 9. Brook I, Thompson DH, Frazier EH. Microbiology and management of chronic maxillary sinusitis. Arch Otolaryngol Head Neck Surg. 1994;120(12):1317-1320. 10. Finegold SM, Flynn MJ, Rose FV, et al. Bacteriologic ndings associated with chronic bacterial maxillary sinusitis in adults. Clin Infect Dis. 2002 15;35(4):428-433. 11. Brook I, Yocum P, Shah K. Aerobic and anaerobic bacteriology of concurrent chronic otitis media with effusion and chronic sinusitis in children. Arch Otolaryngol Head Neck Surg. 2000;126(2):174-176. 12. Erkan M, Ozcan M, Arslan S, et al. Bacteriology of antrum in children with chronic maxillary sinusitis. Scand J Infect Dis. 1996;28(3):283-285.

13. Brook I, Frazier EH, Foote PA. Microbiology of the transition from acute to chronic maxillary sinusitis. J Med Microbiol. 1996;45(5):372-375. 14. Aust R, Drettner B. Oxygen tension in the human maxillary sinus under normal and pathological conditions. Acta Otolaryngol. 1974;78(3-4):264-269. 15. Carenfelt C, Lundberg C. Purulent and nonpurulent maxillary sinus secretions with respect to pO2, pCO2 and pH. Acta Otolaryngol. 1977;84(1-2):138-44. 16. Brook I. Role of encapsulated anaerobic bacteria in synergistic infections. Crit Rev Microbiol. 1987;14(3):171-193. 17. Shapiro ED, Milmoe GJ, Wald ER, Rodnan JB, Bowen AD. Bacteriology of the maxillary sinuses in patients with cystic brosis. J Infect Dis. 1982;146(5):589-593. 18. Nadel DM, Lanza DC, Kennedy DW. Endoscopically guided cultures in chronic sinusitis. Am J Rhinol. 1998;12(4):233-241. 19. Decker CF. Sinusitis in the Immunocompromised Host. Curr Infect Dis Rep. 1999;1(1):27-32. 20. Brook I, Frazier EH. Correlation between microbiology and previous sinus surgery in patients with chronic maxillary sinusitis. Ann Otol Rhinol Laryngol. 2001;110(2):148-151. 21. Manarey CR, Anand VK, Huang C. Incidence of methicillin-resistant Staphylococcus aureus causing chronic rhinosinusitis. Laryngoscope. 2004;114(5):939-941. 22. Brook I, Foote PA, Hausfeld JN. Increase in the frequency of recovery of meticillin-resistant Staphylococcus aureus in acute and chronic maxillary sinusitis. J Med Microbiol. 2008;57(Pt 8):1015-1017. 23. Brook I. Microbiology of acute and chronic maxillary sinusitis associated with an odontogenic origin. Laryngoscope. 2005;115(5):823-825. 24. Brook I, Frazier EH, Gher ME Jr. Microbiology of periapical abscesses and associated maxillary sinusitis. J Periodontol. 1996;67(6):608-610. 25. Namyslowski G, Misiolek M, Czecior E, et al. Comparison of the efcacy and tolerability of

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amoxycillin/clavulanic acid 875 mg b.i.d. with cefuroxime 500 mg b.i.d. in the treatment of chronic and acute exacerbation of chronic sinusitis in adults. J Chemother. 2002;14(5):508-517. Legent F, Bordure P, Beauvillain C, Berche P. A double-blind comparison of ciprofloxacin and amoxycillin/clavulanic acid in the treatment of chronic sinusitis. Chemotherapy. 1994;40 (Suppl 1):8-15. Brook I, Yocum P. Antimicrobial management of chronic sinusitis in children. J Laryngol Otol. 1995;109(12):1159-1162. Brook I, Yocum P, Frazier EH. Bacteriology and beta-lactamase activity in acute and chronic maxillary sinusitis. Arch Otolaryngol Head Neck Surg. 1996;122(4):418-422; discussion 423. Brook I. The role of beta-lactamase-producing bacteria in the persistence of streptococcal tonsillar infection. Rev Infect Dis. 1984;6(5):601-607. Nuutinen J, Ruoppi P, Suonp J. Onedose beclomethasone dipropionate aerosol in the treatment of seasonal allergic rhinitis. A preliminary report. Rhinology. 1987;25(2):121-127. Chalton R, Mackay I, Wilson R, Cole P. Double blind, placebo controlled trial of betamethasone nasal drops for nasal polyposis. Br Med J (Clin Res Ed). 1985;291(6498):788. Brown CL, Graham SM. Nasal irrigations: good or bad? Curr Opin Otolaryngol Head Neck Surg. 2004;12(1):9-13. Parnes SM, Chuma AV. Acute effects of antileukotrienes on sinonasal polyposis and sinusitis. Ear Nose Throat J. 2000;79(1):18-20, 24-25. Chandler JR, Langenbrunner DJ, Stevens ER. The pathogenesis of orbital complications in acute sinusitis. Laryngoscope. 1970;80(9):1414-1428. Finegold, SM. Anaerobic bacteria in human disease. Orlando, FL: Academic Press Inc; 1977. Brook I. Microbiology of intracranial abscesses and their associated sinusitis. Arch Otolaryngol Head Neck Surg. 2005;131(11):1017-1019.

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