Clinical Reviews in Allergy and Immunology © Copyright 2006 by Humana Press Inc. All rights of any nature whatsoever reserved. 1080–0549/06/143–152/$30.00 ISSN (Online) 1559–0267

Antibiotics and Acute Rhinosinusitis

143

Beginning Antibiotics for Acute Rhinosinusitis and Choosing the Right Treatment Ellen R. Wald

Abstract

Department of Pediatrics, University of Wisconsin Medical School, Madison, WI. E-mail: [email protected].

Acute bacterial sinusitis (ABS) is an extremely common problem in both children and adults. There are three clinical presentations of acute sinusitis: (1) onset with persistent symptoms (nasal symptoms or cough or both for >10 but <30 d without evidence of improvement); (2) onset with severe symptoms (high fever and purulent nasal discharge for 3–4 consecutive days); and (3) onset with worsening symptoms (respiratory symptoms, with or without fever, which worsen after several days of improvement). Images to confirm the presence of acute sinusitis are necessary in older children (>6 years) and adults to enhance the certainty of diagnosis. The predominant bacterial species that are implicated in acute sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in children. In the last decade, there has been an increasing prevalence of penicillin-resistant S. pneumoniae, and β-lactamase-producing H. influenzae and M. catarrhalis. Although there has been some controversy in the literature regarding the effectiveness of antibiotics in the treatment of ABS, most studies in which the diagnosis of acute bacterial sinusitis is confirmed with images and appropriate anti-biotics are prescribed show superior outcomes in recipients of antibiotics. Therapy may be initiated with high-dose amoxicillin or amoxicillin–clavulanate. In penicillin-allergic patients or those who are unresponsive to amoxicillin, amoxicillin–clavulanate is appropriate. Alternatives include cefuroxime, cefpodoxime, or cefdinir. In cases of serious drug allergy, clarithromycin or azithromycin may be prescribed. The optimal duration of therapy is unknown. Some recommend treatment until the patient becomes free of symptoms and then for an additional 7 d.

Index Entries: Acute bacterial sinusitis; antimicrobials; images; treatment; rhinosinusitis.

Clinical Reviews in Allergy & Immunology

143_152_01_Wald_3P

143

Volume 30, 2006

143

5/1/06, 12:11 PM

144

Wald

Introduction Acute bacterial sinusitis (ABS) is an extremely common problem in both children and adults. The single most important risk factor for the development of ABS is a pre-existing viral rhinosinusitis (i.e., a community-acquired viral upper respiratory infection [URI]). Less commonly, allergic rhinitis is a predisposing problem. It is estimated that 0.5 to 2% of viral URIs in adults and 6 to 13% of viral URIs in children are complicated by the development of a secondary bacterial sinusitis (1–3). These proportions translate into a very large number of infected individuals and substantial medical expenditures.

Diagnosis

Fig. 1. A schematic showing the clinical course of an uncomplicated viral upper respiratory tract infection with respect to fever (if present) and severity of respiratory symptoms.

Difficulties With Diagnosis When considering a diagnosis of ABS, the major problem is to distinguish between, on the one hand, a viral URI or allergic inflammation from, on the other hand, a secondary bacterial infection of the paranasal sinuses, which may benefit from specific antimicrobial therapy. The problem is created because the membranes that line the nose are continuous with the membranes that line the sinus cavities. In a sense, every time you get a “cold” you not only have rhinitis, but also an element of sinusitis. However, this is not what is meant by clinically significant ABS, and most children and adults recover from viral URIs without the benefit of antimicrobial agents. The key question is, when, if ever, during the course of a viral URI are antibiotics indicated to shorten the course of the clinical illness or prevent the development of suppurative complications?

Uncomplicated Viral Upper Respiratory Tract Infection To develop criteria to be used in distinguishing episodes of ABS from other common respiratory infections, it is helpful to describe an uncomplicated viral URI (depicted sche-

matically in Fig. 1). The course of most uncomplicated viral URIs is 5 to 10 d (4). Although the patient may not be free from symptoms on day 10, the respiratory symptoms have almost always peaked in severity on days 3 to 6 and started to improve. Most patients with uncomplicated viral URIs do not have fever. However, if fever is present, it tends to be present early in the illness, often in concert with other constitutional symptoms such as headache and myalgias. Typically, the fever and constitutional symptoms disappear in the first 24 to 48 h and the respiratory symptoms become more prominent. Viral URIs are usually characterized by nasal symptoms (discharge and congestion/obstruction), cough, or both. Patients may also complain of a scratchy throat. Usually the nasal discharge begins as clear and watery. Often, however, the quality of nasal discharge changes during the course of the illness. Most typically, the nasal discharge becomes thicker and more mucoid and may become purulent (thick, colored, and opaque) for several days. The situation then reverses, with the purulent discharge becoming mucoid and then clear again or sim-

Clinical Reviews in Allergy & Immunology

143_152_01_Wald_3P

144

Volume 30, 2006

5/1/06, 12:11 PM

Antibiotics and Acute Rhinosinusitis

ply drying. The transition from clear to purulent to clear again occurs in uncomplicated viral URIs without the benefit of antimicrobial therapy.

Clinical Presentations of ABS With the clinical picture of an uncomplicated viral URI, we can outline the three clinical presentations of ABS (5). The most common clinical presentation is onset with persistent symptoms (6,7). The cardinal clinical features are nasal symptoms (anterior or posterior nasal discharge/nasal obstruction/congestion), cough, or both for more than 10 but less than 30 d that does not improve. This last qualifier is extremely important. Some individuals with uncomplicated viral URIs still have residual respiratory symptoms at the 10-d mark. To be considered a sign of ABS, these respiratory symptoms must be persistent without improvement. The nasal discharge in patients with persistent symptoms may be of any quality—thick or thin, serous, mucoid or purulent—and the cough, which may be wet or dry and must be present during the daytime, although it is often described as worse at night. The second presentation is described as onset with severe symptoms. Severity in children is described as a combination of high fever, a temperature of at least 38.5°C, and a particular quality of nasal discharge (a purulent nasal discharge) concurrently for at least 3 to 4 d consecutively (7). The presence of persistent fever for at least 3 to 4 d distinguishes this presentation from an uncomplicated viral URI (in which fever is present for less than 48 h). The analogous presentation in adults is the triad of fever, facial pain, and purulent nasal discharge. The third presentation is described as worsening symptoms or presentation with a biphasic illness (in the Scandinavian literature, this is referred to as “double sickening” [5,8]). This illness begins similarly to an uncomplicated viral URI from which the patient appears to be recovering. Suddenly, on the sixth or seventh day of

145

illness, the patient becomes substantially worse. The worsening symptoms may be manifest as an increase in respiratory symptoms (exacerbation of nasal discharge or nasal congestion or day time cough) or a new onset of fever or a recurrence of fever if it had been present at the outset.

Imaging in Patients With Suspected ABS Are Images Necessary in Adults With Suspected ABS? One of the controversial issues in the literature is the role of imaging in the diagnosis of ABS. The issue is whether treatment should be undertaken based on clinical criteria alone (one of the three presentations described previously) or if a confirmatory image should be obtained. Several studies performed in adults have shown that the clinical diagnosis of sinusitis is often inaccurate—that is, if you perform plain sinus radiographs or sinus CT scans on patients suspected of having acute sinusitis based on conventional clinical criteria, then the radiographs or scans will be normal or inconsistent with a diagnosis of acute sinusitis in approx 40 to 50% of cases (9,10). Recognizing that even complete opacification or an air–fluid level on a sinus CT does not necessarily implicate bacterial infection as the etiological agent (11), it is absolutely clear that a completely normal CT scan provides certainty that sinusitis is not the explanation for the respiratory symptoms. Accordingly, it is likely that no more than 50% of adult patients diagnosed to have acute sinusitis in clinical practice actually have a bacterial infection. The reluctance to routinely perform either sinus CT scans or radiographs to improve the certainty of diagnosis (and therefore avoid the unnecessary use of antibiotics) in patients suspected to have ABS is based on the inconvenience and expense associated with the performance of these diagnostic tests.

Clinical Reviews in Allergy & Immunology

143_152_01_Wald_3P

145

Volume 30, 2006

5/1/06, 12:11 PM

146

Wald

Despite the inaccuracy of the clinical diagnosis of acute sinusitis in adults with respiratory symptoms, current recommendations are that imaging studies are neither recommended nor required in the routine diagnosis of community-acquired ABS (12,13).

Are Images Necessary in Children With Suspected ABS? The evidence to answer the necessity of images in children with suspected ABS dates back to 1981. In that year, a study was undertaken to correlate the clinical, radiographic, and bacteriological findings in 30 children with upper respiratory symptoms (14). Children were eligible if they were between the ages of 2 and 16 yr and presented with either persistent or severe respiratory symptoms. Plain sinus radiographs were performed on all children and were considered abnormal if they showed complete opacification, mucosal thickening of at least 4 mm, or an air–fluid level. An aspiration of the maxillary sinus was performed on all children with clinical symptoms and abnormal radiographs and yielded bacteria in high density (ⱖ104 cfu/mL) in 75% of the children. In 1986, Wald et al. performed a study to compare the effectiveness of two antibiotics in treating acute paranasal sinus infections in children (15). In the course of this study, they determined that a history of persistent respiratory symptoms (respiratory symptoms for more than 10 but less than 30 d that were not improving) predicted significantly abnormal radiographs (complete opacification, mucosal thickening of at least 4 mm, or an air–fluid level) in 88% of children age 6 yr or younger. For children older than age 6 yr, the history of persistent symptoms predicted abnormal sinus radiographs in 70% of children. Accordingly, for children age 6 yr or younger, because a positive history so frequently predicts the finding of abnormal sinus radiographs (nearly 90% of the time), and because history plus abnormal radiographs results in a positive sinus aspirate

in 75% of cases, radiographs can be safely omitted and a diagnosis of ABS can be based on clinical criteria alone (7). Conversely to the general agreement that radiographs are not necessary in children younger than age 6 yr who have persistent symptoms, the need for radiographs as a confirmatory test of acute sinusitis in children older than age 6 yr with persistent symptoms and for all children (regardless of age) with severe or worsening symptoms has not been settled. The American College of Radiology has taken the position that the diagnosis of acute uncomplicated sinusitis should be made on clinical grounds alone (16). They support this position by noting that plain radiographs of the paranasal sinuses are technically difficult to perform—particularly in very young children. Correct positioning may be difficult to achieve, and, therefore, the radiographic images may both over- and underestimate the presence of abnormalities within the paranasal sinuses. Similarly, a recent set of guidelines generated by the Sinus and Allergy Health partnership (representing numerous constituencies from within otolaryngology) does not recommend either radiographs or CT or MRI scans to diagnose uncomplicated cases of ABS (2). However, they do not provide evidence to support their position. To summarize, images appear to be unnecessary in children younger than age 6 yr who have persistent symptoms; however, despite their inconvenience and cost, images may be necessary (to enhance accuracy of diagnosis) with all other presentations and all other age groups.

Microbiology of ABS To determine which antimicrobial is best prescribed to treat patients with ABS, it is necessary to review the microbiology of this disorder. The gold standard, or best measure, of a case of bacterial sinusitis is provided when a patient with typical symptoms of ABS undergoes sinus aspiration and the aspirate yields a

Clinical Reviews in Allergy & Immunology

143_152_01_Wald_3P

146

Volume 30, 2006

5/1/06, 12:11 PM

Antibiotics and Acute Rhinosinusitis

significant pathogen in high colony count (i.e., at least 10 4 colony-forming units/mL). The predominant bacterial species that have been involved include Streptococcus pneumoniae, Haemophilus influenzae (non-typeable), and Moraxella catarrhalis (17,18). In the last decade, there has been an increasing prevalence of penicillin-resistant S. pneumoniae, and many of the H. influenzae (35–50%) and M. catarrhalis (55–100%) are β-lactamase-producing and are thereby resistant to penicillin (19,20). Unfortunately, since 1986, no data have been generated regarding the microbiology of acute sinusitis in children (15). However, because of the similarity of the pathogenesis and microbiology of acute otitis media and ABS, it is acceptable to regard recent data generated from cultures of middle ear fluid (obtained by tympanocentesis) from children with acute otitis media as a surrogate for cultures of the paranasal sinuses (21). Perhaps partly attributable to the near universal use of pneumococcal conjugate vaccine in the United States, several recent reports have highlighted a slight decrease in isolates of S. pneumoniae and an increase in isolates of H. influenzae recovered from middle ear aspirates (22,23). Presumably, these changes are also occurring in the paranasal sinuses. Although sinus aspiration is the gold standard of ABS, it is an invasive technique that cannot be performed regularly in the context of usual patient care. Recently, there has been interest in obtaining cultures of the middle meatus endoscopically as a surrogate for cultures from a sinus aspirate. Several studies in adults have shown a good correlation between cultures of the middle meatus and sinus aspirate in patients with acute sinusitis—especially when purulence is seen in the middle meatus (24–26), but other studies have not (27,28). Importantly, middle meatal cultures are not useful in children suspected to have ABS because the meatus is colonized with S. pneumoniae, H. influenzae, and M. catarrhalis even when children are asymptomatic (29).

147

Treatment of ABS Are Antibiotics Effective in the Treatment of ABS? There has been a lot of controversy in the literature regarding the effectiveness of antibiotics in the treatment of ABS. Some have argued that it is difficult to distinguish viral rhinosinusitis from ABS and that the spontaneous cure rate in ABS is very high, thus obviating the need for antibiotics. Others believe that antimicrobial therapy is the cornerstone of management. Evidence that antimicrobials are beneficial can be derived from several studies in which sinus aspiration was performed on patients with typical clinical symptoms of ABS before and after they were treated with specific antimicrobials. Several of these investigations provide data that shows superior bacterial eradication when appropriate antimicrobials are used in an appropriate dose compared with results when inappropriate drugs are prescribed or appropriate drugs are prescribed in inappropriate doses (17,30). Several placebo-controlled studies have been performed in which patients with suspected sinusitis have been randomized to receive antibiotic or placebo. On the basis of the presumed accuracy of diagnosis, the expected prevalence of various pathogens, and the anticipated spontaneous recovery rate according to pathogen, it is estimated that the differences in the proportion of patients who improve or are cured, between treated and untreated patients, is about 25 to 30%. Furthermore, the most dramatic differences observed in treated vs untreated patients should occur during the first 72 to 96 h of treatment. If we were to design a study to test the hypothesis that antibiotics are beneficial in patients with ABS, we would propose the following: 1. Patients would be eligible if they presented with one of the clinical presenta-

Clinical Reviews in Allergy & Immunology

143_152_01_Wald_3P

147

Volume 30, 2006

5/1/06, 12:11 PM

148

2. 3. 4. 5. 6.

7.

Wald tions described previously (persistent, severe, or worsening symptoms). Stringent criteria would be applied to all groups. In patients with persistent symptoms, respiratory symptoms would need to be present for at least 10 d without evidence of improvement. Patients would not be eligible if they received antibiotic therapy in the last 15 d. Patients would not be eligible if they had an underlying disease or pre-existent condition that would alter response to therapy. Confirmatory images of sinus disease would be desirable. Patients would be stratified by age and clinical severity to ensure even distribution between treatment groups. It would be very important to use an antimicrobial with a comprehensive spectrum at an appropriate dose because the margin of difference that we are expecting is in the range of 20 to 30%. If our antibiotic selection does not have activity against nearly all bacterial pathogens, differences between treated and untreated patients may be obscured. (This does not necessarily imply that this antimicrobial would be recommended under all circumstances as treatment but that for a “proof of principle” study, it is important to select an antimicrobial with a very comprehensive spectrum.) Outcome assessments would be made almost daily during the first 5 d for two reasons: (1) some patients are on placebo and may need a rescue medication, and (2) differences in outcome are likely to be magnified during the first few days of therapy. If outcome assessments are only made at 10 to 14 d, then differences may be obscured.

Unfortunately, few published studies have fulfilled all of these criteria. Table 1 shows a summary of selected trials of antibiotic vs placebo in patients with suspected ABS performed since 1986. Study 1 was a small study of children age 2 to 16 yr that fulfilled virtually all criteria (15). Children with signs and symptoms and abnormal radiographs were enrolled.

Multiple outcome observations showed that children who received antibiotics recovered earlier and more often than children who received placebo. Study 2 was performed in children age 1 to 18 yr (31). In the absence of confirmatory radiographs and using low-dose amoxicillin in an era of potentially resistant S. pneumoniae, no difference in outcome was observed between treatment groups. Study 3, in which confirmatory radiographs were performed in adults with suspected acute sinusitis, showed significant differences in the time to and frequency of cure (32). In Study 4, confirmatory images were performed and the outcome on day 14 showed cure in 65% of antibiotic recipients compared with 52% of placebo recipients (p < 0.06) (9). In Study 5, radiographs were performed, but abnormal findings were not criteria for enrollment. Only 30% of images showed an air–fluid level or complete opacification. Analysis did not account for radiographic findings. A low dose of anti-biotics was prescribed for a short treatment interval, and not surprisingly, no differences in outcome were observed at day 7 or beyond (10). Study 6 did not perform confirmatory images but did demonstrate an earlier clinical improvement for antibiotic recipients (p = 0.039) (33). When images are performed and an appropriate dose of antibiotic is prescribed, most studies show superiority of outcome in recipients of antibiotics.

Treatment Recommendations Planning therapy for patients suspected to have ABS entails the need to provide antibacterial coverage for S. pneumoniae and H. influenzae in adults and for those agents plus M. catarrhalis in children. At least 50% of paranasal sinus aspirates are likely to produce β-lactamase. However, amoxicillin has been considered as first-line therapy in both children and adults, partly because of its general effectiveness, safety, low cost, and narrow spectrum. Because of a lack of adequately powered studies and a reluctance to perform sinus aspiration in the current era in which multidrug-resistant organ-

Clinical Reviews in Allergy & Immunology

143_152_01_Wald_3P

148

Volume 30, 2006

5/1/06, 12:11 PM

Antibiotics and Acute Rhinosinusitis

149

Clinical Reviews in Allergy & Immunology

143_152_01_Wald_3P

Table 1 Selected Clinical Trials of Antibiotic vs Placebo in Patients With Suspected Acute Bacterial Sinusitis No. of patients

Age (yr)

Strength of clinical criteria for entry

Confirmatory images

Wald et al. (15) (1986)

93

2–16

++++

Garbutt et al. (31) (2001)

214

1–18

Lindbaek et al. (32) (1996)

127

>18

Van Buchem et al. (9) (1997)

214

>18

++

252

>18

135

>18

Author (yr)

Outcome

Yes

Amoxicillin or amoxicillin/clavulanate, 45 mg/kg/d × 10 d

Day 3, 45 vs 11% (p < 0.05)a Day 10, 79 vs 60%a

Yes

++++

No

Amoxicillin or amoxicillin/clavulanate, 40–45 mg/kg/d × 10 d

No difference

No

++

Yes

1320 mg Penicillin tid or 500 mg amoxicillin tid ×10 d

Day 3, 20 vs 2% for much better (p ⱕ 0.001)a Day 3, 80 vs 38% for much better and somewhat bettera Day 10, 85 vs 56% for improved or cured (p < 0.001)a

Yes

Amoxicillin/Clavulanate, 875 mg bid × 7 d

Day 14, 65 vs 52% (p < 0.06) for curea

??

++

No

Amoxicillin/Clavulanate, 875 mg bid × 6 d

Day 3, no evaluation Day 7, no difference Day 14, no difference Day 21, no difference

No

++

No

1000 mg Amoxicillin bid × 10 d

Day 3, earlier clinical improvement in amoxicillin group (p = 0.039) Day 14, 48 vs 37% (p = 0.26)a

Yes

149

5/1/06, 12:11 PM

Bucher et al. (10) (2003)

Merenstein et al. (33) (2005)

Yes

First number always refers to antibiotic-treated patients and second number refers to placebo-treated recipients.

149

Volume 30, 2006

a

Benefit of antibiotics

Antibiotic dose

150

Wald

isms may be predominant, guidelines published by the Sinus and Allergy Health Partnership use a mathematical model based on the best available evidence for pathogen distribution in ABS, pharmacokinetic and pharmacodynamic data, mechanisms of antimicrobial resistance, and antimicrobial resistance surveillance data (2,34,35). Similarly, recent guidelines published by the American Academy of Pediatrics also developed suggestions for antimicrobial therapy based on theoretical calculations rather than on existing evidence (7). Several recent reviews have endorsed the use of amoxicillin as first-line therapy for adults with community-acquired ABS (36,37). It is acknowledged that higher daily doses of amoxicillin (3–4 g/d) may be necessary in areas with a high prevalence of penicillin-resistant S. pneumoniae (36). If the patient is allergic to penicillin, then cefuroxime, cefpodoxime, or cefdinir may be prescribed. If the patient has moderate-to-severe disease, has been exposed to antibiotics recently, or fails to respond to amoxicillin, a broader spectrum antimicrobial is necessary. Amoxicillin/clavulanate and fluoroquinolones (gatifloxacin, levofloxacin and moxifloxacin) currently have the best coverage for H. influenzae and S. pneumoniae and should be initiated (36,37). For children with uncomplicated ABS that is mild to moderate in degree of severity, who do not attend daycare, and have not recently been treated with an antimicrobial, amoxicillin, or amoxicillin/clavulanate are recommended at any dose between 45 and 90 mg/kg/d in two divided doses. The range of dosing is permissive to allow for some individual judgment (7,38). For example, if you are treating a 3-yrold child with his or her first sinus infection in October (when the rate of antibiotic resistance is low) (39), then you can comfortably use amoxicillin at 45 to 60 mg/kg/d. A higher dose may be more appropriate later in the season. If the patient is allergic to amoxicillin, either cefdinir (14 mg/kg/d in one or two doses),

cefuroxime (30 mg/kg/d), or cefpodoxime (10 mg/kg/d once daily) can be used (only if the allergic reaction was not a type 1 hypersensitivity reaction). In cases of serious allergic reactions, clarithromycin or azithromycin is preferred in an effort to select an antimicrobial of an entirely different class. Most patients with ABS who are treated with an appropriate antimicrobial agent respond promptly (within 48–72 h) with a diminution of respiratory symptoms (reduction of nasal discharge and cough) and an improvement in general well being. If a child fails to improve, then either the antimicrobial is ineffective or the diagnosis of sinusitis is not correct (7). If children do not improve while receiving the usual dose of amoxicillin, have recently been treated with an antimicrobial, have an illness that is moderate or more severe, or attend day care, therapy should be initiated with high-dose amoxicillin/clavulanate (80–90 mg/ kg/d of amoxicillin component, with 6.4 mg/ kg/d of clavulanate in two divided doses). Alternative therapies include cefdinir, cefuroxime, or cefpodoxime. A single dose of ceftriaxone (at 50 mg/kg/d), administered either intravenously or intramuscularly, can be used in children with vomiting that precludes administration of oral antibiotics (7). The optimal duration of therapy for patients with ABS has not been systematically studied. Often, empiric recommendations are made for 10, 14, 21, or 28 d of therapy. An alternative suggestion has been made that antibiotic therapy be continued until the patient becomes free of symptoms, and then for an additional 7 d (7). This strategy, which individualizes treatment for each patient, guarantees a minimum duration of 10 d for all and prolongs therapy in situations in which the response to antibiotics has been more sluggish.

Conclusion To answer the question that was posed in the title of this article: antimicrobials to treat

Clinical Reviews in Allergy & Immunology

143_152_01_Wald_3P

150

Volume 30, 2006

5/1/06, 12:11 PM

Antibiotics and Acute Rhinosinusitis

ABS should be prescribed when the diagnosis is suspected on the basis of the clinical history in children younger than age 6 yr who present with persistent respiratory symptoms. Antimicrobials should be initiated in all other patients when the diagnosis of ABS is suspected on clinical grounds and confirmed by a significantly abnormal plain sinus radiograph or sinus CT scan. Antibiotic selections should be based on degree of severity of the clinical illness, recent exposure to antibiotics, and other factors that increase the likelihood of infection with a resistant bacterial species.

151

17. 18. 19. 20. 21. 22. 23. 24.

References 1. Fendrick, A.M., Saint, S., Brook, I., et al. (2001), Clin Ther 23, 1683–1706. 2. Sinus and Allergy Health Partnership. (2000), Otolaryngol Head Neck Surg 123, 5–31. 3. Wald, E.R., Guerra, N., and Byers C. (1991), Pediatrics 87, 129–133. 4. Gwaltney, J.M., Hendley, J.O., Simon, G., and Jordan, W.S., Jr. JAMA 202, 158–164. 5. Meltzer, E.O., Hamilos, D.L., Hadley, J.A., et al. (2004), J Allergy Clin Immunol 114, S156–S204. 6. Wald, E.R. (1998), Pediatr Ann 27, 811-818. 7. American Academy of Pediatrics, Subcommittee on Management of Sinusitis. (2001), Pediatrics 108, 798–808. 8. Lindbaek, M., Hjortdahl, P., and Johnsen, U.L. (1996), Fam Med 28, 183–188. 9. Van Buchem, F.L., Knottnerus, J.A., Schrijnemaekers, V.J.J., and Peeters, M.F. (1997), Lancet 349, 683–687. 10. Bucher, H.C., Tschudi, P., Young, J., et al. (2003), Arch Int Med 163, 1793–1798. 11. Gwaltney, J.M. Jr., Phillips, C.D., Miller, R.D., and Riker, D.K. (1994), N Engl J Med 330, 25–30. 12. Hickner, J.M., Bartlett, J.G., Besser, R.E., Gonzales, R., Hoffman, J.R., and Sande, M.A. (2001), Ann Intern Med 134, 498–505. 13. Sande, M.A., and Gwaltney, J.M., Jr. (2004), Clin Infect Dis 39, S151–S158. 14. Wald, E.R., Milmoe, G.J., Bowen, A., LedesmaMedina, J., Salamon, N., and Bluestone, C.D. (1981), N Engl J Med 304, 749–754. 15. Wald, E.R., Chiponis, D., and Ledesma-Medina, J. (1986), Pediatrics 77, 795–800. 16. McAlister, W.H., Parker, B.R., Kushner, D.C., et al. (2000), in ACR Appropriateness Criteria. Reston,

25. 26. 27. 28. 29.

30. 31. 32. 33.

34. 35. 36. 37. 38. 39.

VA: American College of Radiology. Available at: http://www.acr.org/departments/appropriate ness_criteia/toc.html. Accessed February 23, 2001. Gwaltney, J.M. Jr, Scheld, W.M., Sande, M.A., et al. (1992) J Allergy Clin Immunol 90, S142–S150. Wald, E.R. (1998), Am J Med Sci 316, 13–20. Doern, G.V., Jones, R.N., Pfaller, M.A., and Kugler, K. (1999), Antimicrob Agents Chemother 43, 385–389. Gordon, K.A., Biedenbach, D.J., and Jones, R.N. (2003), Diagn Microbiol Infect Dis 46, 285–289. Parsons, D.S. and Wald, E.R. (1996), Otolaryngol Clin North Am 29, 11–25. Casey, J.R. and Pichichero, M.E. (2004), Pediatr Infect Dis J 23, 824–828. Leibovitz, E., Jacobs, M.R., and Dagan, R. (2004), Pediatr Infect Dis J 23, 1142–1152. Malekzadeh, S., Hamburger, M.D., Whelan, P.J., Biedlingmaier, J.F., and Baraniuk, J.N. (2002), Otolaryngol Head Neck Surg 127, 190–205. Talbot, G.H., Kennedy, D.W., Scheld, W.M., and Granito, K. (2001), Clin Infect Dis 33, 1668–1675. Gold, S.M. and Tami, T.A. (1997) Laryngoscope 107, 1586–1589. Winther, B., Vicery, C., Gross, C., and Hendley, O. (1996), Am J Rhinol 10, 347–350. Kountakis, S.E. and Skoulas, I.G. (2002), Otolaryngol Head Neck Surg 126, 377–381. Gordts, F., Abu Nasser, I., Clement, P.A., Pierard, D., and Kaufman, L. (1999), Int J Pediatr Otorhinolaryngol 48, 163–167. Gwaltney, J.M. Jr. (1996), Clin Infect Dis 23, 1209– 1223. Garbutt, J.M., Goldstein, M., Gellman, E., Shannon, W., and Littenberg, B. (2001), Pediatrics 107, 619–625. Lindbaek, M., Hjortdahl, P., and Johnsen, U.L. (1996), BMJ 313, 325–329. Merenstein, D., Whittaker, C., Chadwell, T., Wengner, B., and D’Amico, F. (2005), J Fam Pract 54, 144– 151. Anon, J.B., Jacobs, M.R., Poole, M.D., et al. (2004), Otolaryngol Head Neck Surg 130(Suppl), 1–45. Poole, M.D. (2004), Otolaryngol Head Neck Surg 130 (Suppl), 46–50. Scheid, D.C. and Hamm, R.M. (2204), Amer Fam Phys 70, 1697–1704. Piccirillo, J.F. (2004), N Engl J Med 351, 902–910. Contopoulos-Ioannidis, D.G. and Ioannidis, J.P. (2004), Curr Allergy Asthma Rep 4, 471–477. Hoberman, A., Paradise, J.L., Greenberg, D.P., Wald, E. R., Kearney, D.H., and Colborn D.K. (2005), Pediatr Infect Dis J 24, 115–120.

Clinical Reviews in Allergy & Immunology

143_152_01_Wald_3P

151

Volume 30, 2006

5/1/06, 12:11 PM