INTRODUCTION — Chronic rhinosinusitis (CRS) is defined as a complex inflammatory condition involving the paranasal sinuses and linings of the nasal passages that lasts 12 weeks or longer despite attempts at medical management. The diagnostic criteria for CRS are discussed separately. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis", section on 'Diagnosis'.)
Factors that may contribute to the development of CRS include exposure to allergens and irritants, defects in mucociliary function, immunodeficiency, obstruction of sinus outflow (eg, polyps), and infections with bacteria, viruses, and fungi. The common endpoint is local inflammation and swelling of the sinonasal mucosa and impairment of normal sinus drainage. The recognition that CRS represents a multifactorial inflammatory disorder, rather than a persistent bacterial infection, has led to the reexamination of the role of antimicrobials in CRS. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis".)
The medical management of CRS is focused upon controlling the inflammation that predisposes patients to obstruction, thus minimizing the incidence of superinfections. Despite this, many forms of CRS are associated with poor sinus drainage and secondary bacterial infections. Most patients require antibiotics to clear infection at the outset of therapy and intermittently thereafter to treat acute exacerbations of CRS. However, the role of these agents beyond these two indications remains an area of investigation.
This topic will review the evolution of the upper respiratory flora in rhinosinusitis as well as the microbiology of and antibiotic selection for CRS. The overall approach to management of CRS is discussed in detail elsewhere. (See "Chronic rhinosinusitis without nasal polyposis: Management and prognosis" and "Chronic rhinosinusitis with nasal polyposis: Management and prognosis".)
Acute rhinosinusitis, allergic rhinitis, and fungal sinusitis are presented elsewhere. (See "Acute sinusitis and rhinosinusitis in adults: Clinical manifestations and diagnosis" and "Allergic rhinitis: Clinical manifestations, epidemiology, and diagnosis" and "Pathogenesis of allergic rhinitis (rhinosinusitis)" and "Fungal rhinosinusitis" and "Uncomplicated acute sinusitis and rhinosinusitis in adults: Treatment".)
MICROBIOLOGY
Bacterial flora of non-inflamed sinuses — The uninfected "normal" sinuses contain aerobic and anaerobic bacterial flora similar to those present in acute and chronic sinusitis [1].
Bacterial flora in the normal non-inflamed sinus has been delineated in studies utilizing bacterial cultures [1] and molecular methodologies [2]. In a study that evaluated the impact of the microbiota on predictors of disease outcomes, 26 control subjects had similar biodiversity as 56 patients with chronic rhinosinusitis (CRS) [3]. Among the CRS subtypes examined, only purulence and the comorbid condition of asthma were associated with alterations in microbial community composition. Among 27 patients with CRS who were followed postoperatively, better outcomes were associated with more diverse bacterial communities present at the time of surgery, along with higher relative abundances of Actinobacteria.
Other data suggest that the host response or lack of response to the normal sinus flora may be key to the development of sinus inflammation [4]. The number of organisms [4] and the likelihood of biofilm formation [5] are higher in chronic sinusitis than in uninfected sinuses. Microbial biofilms seem to play an active role in the pathogenesis of CRS. They represent an adaptive defense resource enabling resistance to antibiotics and host defense mechanisms. Biofilms are thought to be accountable for refractory cases of sinusitis by perpetuating local inflammation [6]. These observations may help to explain the chain of events that lead to inflammation in CRS.
Evolution of bacterial flora — The microbiology of rhinosinusitis evolves through several phases. The early phase (acute rhinosinusitis) is usually caused by a viral infection (most commonly rhinovirus, adenovirus, influenza, or parainfluenza) that generally lasts up to 10 days; complete recovery occurs in 99 percent of patients [7]. In occasional patients, a secondary acute bacterial infection develops. The most common bacterial causes of acute rhinosinusitis are aerobes such as Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. (See "Acute sinusitis and rhinosinusitis in adults: Clinical manifestations and diagnosis".)
If resolution from acute rhinosinusitis does not occur, colonizing anaerobic oropharyngeal flora and aerobes, such as Staphylococcus aureus, become predominant over time [8-17].
Anaerobes — Anaerobes are prominent in the sinuses of both children [10,18,19] and adults [11-14,16,17,20-26] with chronic rhinosinusitis. As an example, in one study, middle meatal specimens from patients with CRS without nasal polyps had anaerobic bacterial enrichment and lower microbiome diversity compared with healthy subjects, patients with acute rhinosinusitis, and patients with CRS with nasal polyps [27]. Similarly, in a series of five patients with acute maxillary rhinosinusitis who did not respond to therapy and underwent repeated endoscopic aspirations of sinus secretions, growth of resistant anaerobes occurred over time, including Fusobacterium nucleatum, pigmented Prevotella spp, Porphyromonas spp, and Peptostreptococcus spp [26]. Elevated immunoglobulin G (IgG) antibodies against Fusobacterium and Prevotella spp have also been described in patients with chronic sinusitis [28].
Several factors may contribute to the emergence of anaerobes:
●Selective pressure of antimicrobial agents that enable resistant organisms to survive.
●Mucosal inflammation and edema decrease the blood supply to the sinuses, which leads to reduced oxygen tension [29].
●Aerobic bacteria consume oxygen and decrease the pH of the sinuses, which promotes the growth of anaerobes [30].
●Expression of some anaerobic virulence factors, such as a capsule, is slow [31,32].
Aerobes — Aerobic gram-negative bacilli and S. aureus (including methicillin-resistant S. aureus [MRSA]) have also been implicated in CRS. Polymicrobial infection is common and may be synergistic [32].
Aerobes (in the absence of anaerobes) have been implicated in the pathogenesis of CRS. Most studies in which only aerobes were cultured from CRS patients did not use sufficiently careful techniques for the recovery of anaerobes; however, even carefully performed studies sometimes fail to identify anaerobes [33]. Thus, it is possible that some patients with CRS have a predominance of aerobes or a mixture of aerobes and anaerobes.
●Gram-negative bacilli – Aerobic gram-negative bacilli, such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter spp, and Escherichia coli, have been implicated as etiologic agents of CRS, especially in patients with underlying conditions such as cystic fibrosis (in the case of Pseudomonas) diabetes mellitus, and immunocompromising conditions (eg, stem cell transplant, neutropenia, or advanced human immunodeficiency virus [HIV]) [34-38].
Since these gram-negative bacilli are rarely found in cultures of the middle meatus obtained from normal individuals, their isolation from symptomatic patients suggests a pathogenic role. However, their presence could also be due to selection pressure following administration of antimicrobial therapy. In one study, aerobic gram-negative bacilli were recovered more often in patients who had had previous surgery or sinus irrigation [35]. P. aeruginosa was also more common in patients receiving systemic steroids. Other studies have also noted this shift toward gram-negative organisms in patients who have been extensively and repeatedly treated with antibiotics or have undergone sinus surgery [36,39,40].
●Staphylococcus aureus – S. aureus colonizes the nasal mucosa of 20 to 30 percent of normal individuals and is found more frequently in patients with rhinosinusitis, especially in those with CRS. In the United States, the incidence of MRSA specifically may be increasing as both a nasal colonizer and a cause of rhinosinusitis [41-44]. Some [45] but not all [46] studies suggest that patients with diabetes mellitus have a higher likelihood of nasal colonization with S. aureus.
Coagulase-negative staphylococci are normal nasal colonizers and are not thought to be pathogenic in sinusitis or other respiratory infections [47].
Specific clinical settings
Nasal polyposis — Studies of the microbiology of infections in patients with CRS with nasal polyposis suggest that the organisms involved are similar to those in CRS without nasal polyposis [48-50]. CRS with and without nasal polyposis are discussed in detail separately. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis" and "Chronic rhinosinusitis with nasal polyposis: Management and prognosis".)
Acute exacerbation of chronic rhinosinusitis — Acute exacerbation of CRS (AECRS) represents a sudden worsening of the baseline manifestations of CRS, which may involve new symptoms or an accentuation of existing symptoms. The acute, but not the chronic, symptoms typically resolve completely between occurrences. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis".)
The microbiology of AECRS includes H. influenzae, S. pneumoniae, and M. catarrhalis, in addition to the organisms potentially associated with CRS (ie, anaerobes, S. aureus, and gram-negative bacilli). (See 'Evolution of bacterial flora' above.)
This was demonstrated in a study in which serial endoscopic aspirations were performed in seven patients who had ≥3 episodes of maxillary AECRS per year, each lasting ≥10 days, with complete resolution of their acute symptoms between episodes [51]. The patients were followed over a period of 125 to 242 days.
Two to four bacterial isolates were recovered from each sample. The aerobes isolated were H. influenzae, S. pneumoniae, M. catarrhalis, S. aureus, and K. pneumoniae, while the anaerobes included pigmented Prevotella spp, Porphyromonas spp, Peptostreptococcus spp, Fusobacterium spp, and Cutibacterium acnes.
Sequential cultures over time noted changes in species isolated as well as increased antimicrobial resistance. A study of 112 patients experiencing recurrent acute exacerbations of CRS showed a change of bacterial isolates during recurrent exacerbations in 68 percent of patients, necessitating a change of treatment in 40 percent [52]. The main risk factor for the subsequent change in cultures was polymicrobial growth. Resistant strains developed in 11.6 percent of patients. Sinus surgery was not associated with subsequent change in cultured isolates.
Odontogenic sinusitis — Odontogenic sinusitis is a well-recognized entity and accounts for approximately 10 to 12 percent of cases of maxillary sinusitis [53] and may be either acute or chronic [54]. The microorganisms recovered from odontogenic infections generally reflect the oral flora (eg, anaerobes and streptococci). (See "Epidemiology, pathogenesis, and clinical manifestations of odontogenic infections".)
The association between periapical abscesses and rhinosinusitis was established in a study of pus aspirates from five periapical abscesses of the upper jaw and their corresponding maxillary sinuses [55]. A polymicrobial flora was found in all instances, and the number of isolates grown from each specimen ranged from two to five. Anaerobes were recovered from all specimens. The predominant anaerobes grown were Prevotella spp, Porphyromonas spp, Peptostreptococcus spp, and F. nucleatum. Concordance in the microbiologic findings between periapical abscess and the maxillary sinus flora was found in all instances, suggesting contiguous spread.
Another study evaluated the microbiology of 20 patients with acute rhinosinusitis and 28 patients with chronic maxillary sinusitis associated with odontogenic infection [37]. Polymicrobial infection was common, with an average of 3.4 isolates recovered per specimen. A total of 98 isolates were recovered from the 28 cases of CRS: 21 aerobic and facultative and 77 anaerobic. Aerobes alone were recovered in 3 (11 percent), anaerobes only in 11 (39 percent), and mixed aerobic and anaerobic bacteria in 14 (50 percent). The predominant anaerobes in both acute and chronic infection were Peptostreptococcus spp, Fusobacterium spp, and pigmented Prevotella and Porphyromonas spp, all members of the oropharyngeal flora that predominate in periodontal and endodontic infection. The most commonly isolated aerobes were alpha-hemolytic streptococci, microaerophilic streptococci, and S. aureus.
Concurrent chronic otitis media in children — One study correlated the microbiology of concurrent chronic otitis media with effusion and maxillary sinusitis in 32 children [18]. Two-thirds of the patients had a bacterial etiology. The most common isolates were H. influenzae (nine isolates), S. pneumoniae (seven isolates), Prevotella spp (eight isolates), and Peptostreptococcus spp (six isolates). Microbiologic concordance between the ear and sinus was found in 22 (69 percent) culture-positive patients.
Immunocompromised hosts — Rhinosinusitis occurs in a range of immunocompromised hosts including those with neutropenia, diabetes mellitus, critical illness, or HIV, and may be either acute or chronic [38].
●In patients with neutropenia, fungi and P. aeruginosa are the most common causes of rhinosinusitis [38,56]. When fungal rhinosinusitis is present, Aspergillus spp are frequently the causative organism, although Zygomycetes (eg, Mucor, Rhizopus), Alternaria, and other molds have been implicated [56]. Hematologic malignancy is another risk factor for invasive fungal rhinosinusitis. (See "Fungal rhinosinusitis".)
●In patients with diabetes mellitus, P. aeruginosa and other gram-negative bacilli have been isolated from intraoperative sinus cultures more frequently than in patients without diabetes mellitus, although data are limited [46]. Diabetes mellitus has also been associated with fungal rhinosinusitis. (See "Fungal rhinosinusitis".)
●In patients with cystic fibrosis, P. aeruginosa often causes rhinosinusitis [34].
●In patients with HIV, sinusitis often presents with non-specific symptoms and is refractory to treatment [57]. Causes of rhinosinusitis may include common and uncommon organisms, such as S. aureus, streptococci, anaerobes, P. aeruginosa, and fungi (Aspergillus, Cryptococcus, and Rhizopus) [38,58]. Most studies reporting on the microbiology of rhinosinusitis in patients with HIV, however, are from over 20 years ago and include mainly patients with low CD4 cell counts, so the findings may not be generalizable to patients with well-controlled HIV. Rare causes of rhinosinusitis in patients with acquired immunodeficiency syndrome (AIDS) include cytomegalovirus; nontuberculous mycobacteria, such as Mycobacterium kansasii; and parasites, such as Microsporidium, Cryptosporidium, and Acanthamoeba [38,59,60].
Complications — Complications of CRS, such as orbital cellulitis, brain abscess, subdural empyema, and epidural abscess are often polymicrobial and include both aerobes and anaerobes [15,61,62]. These infections are discussed separately. A significant proportion of people with CRS have symptoms of depression, anxiety, or a sleeping disorder [63,64]. (See "Orbital cellulitis" and "Pathogenesis, clinical manifestations, and diagnosis of brain abscess" and "Treatment and prognosis of bacterial brain abscess" and "Intracranial epidural abscess".)
Fungi — Fungi may cause allergic fungal rhinosinusitis, fungal colonization, or invasive fungal sinusitis. Allergic fungal rhinosinusitis refers to CRS that is accompanied by sinus opacification with "allergic mucin," or thick, inspissated mucus-containing degranulating eosinophils and fungal hyphae. Fungal colonization may also cause similar symptoms as those seen in CRS. In contrast, invasive fungal sinusitis typically occurs in immunocompromised hosts and can be rapidly progressive or indolent. (See "Allergic fungal rhinosinusitis" and "Fungal rhinosinusitis".)
ANTIMICROBIAL THERAPY
Uncertain role of systemic antibiotics — The primary focus of medical management of CRS is to control inflammation that predisposes to obstruction and thus promote sinus drainage. Antibiotics are not a routine component of CRS management; data informing the benefit of antibiotics in CRS are limited, and there is no high-quality evidence to support their use. The decision to use antibiotics in patients with CRS should thus weigh the uncertain benefit against their known adverse effects and the risk of selection for bacterial resistance [65]. We reserve antibiotics for situations when bacterial infection is suspected; however, infection complicating CRS can be difficult to establish, and so practice varies. Some experts, including an editor of this topic, only use antibiotic therapy for CRS in the setting of an acute flare (eg, sudden worsening of symptoms). Other experts, including the author of this topic, also use antibiotics in situations when infection is possible and cannot be excluded, such as CRS without nasal polyposis that does not respond to several months of topical glucocorticoids. Further discussion on use of antibiotic therapy for CRS is found elsewhere. (See "Chronic rhinosinusitis with nasal polyposis: Management and prognosis" and "Chronic rhinosinusitis without nasal polyposis: Management and prognosis".)
Limited data do not demonstrate an obvious effect of antibiotics in CRS. A 2016 systematic review identified only five randomized trials (totaling nearly 300 participants) that compared antibiotic therapy with placebo or other medical interventions, the quality of most of the evidence was deemed low, and there was not a clear benefit of antibiotics [66]. A 2015 systematic review identified one small randomized trial comparing a short course of antibiotics with placebo; in patients with CRS with polyps, doxycycline for three weeks was associated with decreased polyp size post-treatment compared with placebo, but the only symptom improvement measure associated with doxycycline was a temporary reduction in postnasal drip compared with placebo [67,68].
The evidence evaluating long-term, low-dose macrolide therapy as an anti-inflammatory strategy is discussed elsewhere. (See "Chronic rhinosinusitis without nasal polyposis: Management and prognosis", section on 'Extended course of a macrolide antibiotic'.)
Empiric regimen selection — When antibiotic therapy is used as a component of medical management of CRS, we favor obtaining sinus specimens for microbiology to inform the regimen choice (see 'Tailoring the regimen to culture results' below). However, the initial regimen can be selected empirically and subsequently adjusted once cultures and susceptibility testing are available. Regimens for CRS are generally oral, since it is primarily an outpatient disease. We suggest a regimen that provides coverage against anaerobic bacteria (F. nucleatum, pigmented Prevotella spp, Porphyromonas spp, and Peptostreptococcus spp) as well as streptococci and S. aureus. H. influenzae and M. catarrhalis are rarely isolated in CRS but can be seen in acute exacerbations, and so we favor coverage of these as well, if possible.
●For most patients, we suggest 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 1000 mg extended-release tablets twice daily) as the first-line regimen for most patients when antibiotic therapy is warranted for CRS.
Alternative regimens may be warranted in certain situations:
●For penicillin-allergic patients, we suggest monotherapy with clindamycin (in children 20 to 40 mg/kg per day orally divided every six to eight hours; in adults 300 mg four times daily or 450 mg three times daily). Although clindamycin does not cover H. influenzae, M. catarrhalis, or other gram-negative bacilli, we favor it as a simple single agent regimen for an initial empiric regimen with the understanding that it may need to be modified if the patient does not respond. Moxifloxacin is an alternative single-agent regimen that covers aerobic and anaerobic organisms, but it is used primarily in adults (400 mg once daily) as it has not been well studied in children.
●For patients with a history of nasal methicillin-resistant S. aureus (MRSA) colonization or MRSA infection, we also suggest monotherapy with clindamycin, as long as the prior MRSA isolate was not known to be clindamycin resistant.
●Patients with immunocompromising conditions, cystic fibrosis, or diabetes mellitus may also warrant coverage against P. aeruginosa, which can be achieved with levofloxacin (750 mg daily in adults) plus metronidazole.
Other regimens that provide aerobic and anaerobic coverage consist of two drugs. These regimens are more cumbersome and are usually reserved for patients who cannot take one of the single-drug regimens. These include:
●Metronidazole plus one of the following: cefuroxime axetil, cefdinir, cefpodoxime proxetil, azithromycin, clarithromycin. If MRSA coverage is needed, trimethoprim-sulfamethoxazole (TMP-SMX) or doxycycline could be used with metronidazole.
Among the options, antibiotic selection further depends upon other factors, including history of drug allergies and cost of therapy. In addition, if antibiotics have been given over the past three months, a different class of antibiotics should be used. Before choosing a fluoroquinolone (such as levofloxacin or moxifloxacin), clinicians and patients should be aware of the potential for adverse effects and the recommendations to avoid their use for uncomplicated infections when other alternatives are appropriate. (See "Fluoroquinolones", section on 'Restriction of use for uncomplicated infections'.)
Our approach to antibiotic selection is primarily based on the understanding of the microbiology of CRS. Data from trials have not suggested a higher likelihood of clinical cure with particular antimicrobial regimens over others [69-72], even though observational studies have suggested that antibiotics with anaerobic coverage might result in greater cure rates [16,73]. Nevertheless, in one randomized trial of more than 200 adults with CRS, the relapse rate was higher with cefuroxime compared with amoxicillin-clavulanate (7 versus 0 percent), suggesting that including anaerobic coverage may be important for preventing relapse [69].
Topical or systemic antifungal therapy should not be used as empiric therapy in patients with CRS, as it does not appear to be effective [74,75]. The role of antifungal therapy for patients with allergic fungal rhinosinusitis or invasive fungal rhinosinusitis is discussed separately. (See "Allergic fungal rhinosinusitis", section on 'Therapies of uncertain benefit' and "Fungal rhinosinusitis", section on 'Invasive fungal sinusitis'.)
Tailoring the regimen to culture results — We favor obtaining sinus specimens for microbiologic testing so that the empirically selected antibiotic regimen can be tailored accordingly. In particular, we favor obtaining sinus specimens for patients with severely immunocompromising conditions or persistent or worsening infection despite appropriate initial antibiotics (eg, no substantial improvement after five to seven days of treatment), as pathogens beyond the typical microbiology are more likely in these cases.
Middle meatus cultures provide inadequate information in about a quarter of patients with CRS, which may result in inadequate antibiotic therapy and contribute to increasing antibiotic resistance [76]. Additional sampling from the sinuses should be done whenever possible. Specimens should be obtained directly from the involved sinus cavity, usually by an otolaryngology specialist. An endoscopic approach to obtain culture specimens is a commonly used alternative to sinus puncture [77]. However, specimens obtained by endoscopy can become contaminated with nasal flora [78]. The sinus specimens should be submitted for culture for aerobic and anaerobic bacteria as well as fungi. Proper collection, transport, and plating are important for optimizing culture yield.
Once cultures are available, we tailor the regimen to ensure activity against isolated organisms that would be resistant to the empirically chosen regimen. We generally suggest not narrowing the empiric regimen to cover only the organism cultured because certain bacteria, such as anaerobes, may be difficult to isolate.
For patients who have a fungal organism isolated on sinus cultures, the approach is discussed elsewhere. (See "Fungal rhinosinusitis", section on 'Invasive fungal sinusitis'.)
Duration of therapy — The optimal duration of antimicrobial therapy is uncertain.
When antibiotics are used for acute exacerbations of CRS, seven days is a reasonable duration. In patients who are slow to respond, the author of this topic sometimes uses longer therapy (eg, up to 21 days).
If antibiotics are used for other situations when an infection is suspected and cannot be ruled out (eg, symptoms refractory to other anti-inflammatory measures), antibiotics are often given for two to four weeks. As above, use of antibiotics for this purpose is not universally endorsed. (See 'Uncertain role of systemic antibiotics' above.)
The evidence to support the duration recommendation is limited; only low-quality evidence supports the efficacy of antibiotics in the treatment of CRS, as above, and the duration of therapy has not been studied prospectively. Decisions on antibiotic duration in individual patients should weigh the uncertain benefit against the potential for adverse effects with prolonged therapy.
Limited role for other antibiotic routes
●Parenteral therapy – Even when antibiotics are warranted for CRS, parenteral therapy is rarely needed. Parenteral antibiotics may be indicated in patients who are seriously ill or perioperatively. Sinus cultures should be obtained from patients requiring parenteral therapy.
Parenteral antibiotics effective against both anaerobes and aerobes include ampicillin-sulbactam, piperacillin-tazobactam, clindamycin, and the second-generation cephalosporins (cefoxitin and cefotetan). A parenteral agent with aerobic activity (eg, a third-generation cephalosporin such as ceftriaxone) may also be given in combination with metronidazole to cover anaerobes. The absorption of oral metronidazole is excellent, so metronidazole should only be given parenterally if the patient is unable to take oral medications. The selection among parenteral options should be informed by available culture results.
If P. aeruginosa or MRSA is suspected, active parenteral options are discussed in detail elsewhere. (See "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections", section on 'Intravenous antibiotics' and "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment of bacteremia", section on 'Preferred agents'.)
●Topical antibiotic therapies – Data supporting the use of topic antibiotics are limited, and we do not routinely use them in patients with CRS. However, the author of this topic has used topical antibiotics (eg, mupirocin ointment in saline nasal irrigations) in select patients with refractory CRS with documented infection that has not responded to multiple courses of oral antibiotics. When used, the author suggests topical antibiotics once or twice daily for up to four weeks.
Topical antibiotic therapies are thought to deliver a high concentration of antibiotics to the diseased sinonasal mucosa. Studies do not demonstrate clear benefit of topical antibiotics, although there may be short-term benefit for select patients [67,77,79-82]. One review identified three randomized trials that showed no clinical effect compared with placebo and one randomized trial that demonstrated short-term symptom improvement with mupirocin in patients with S. aureus growth on sinus cultures [67]. In that trial, however, clinical and microbiologic effects were not maintained two months after therapy. Topical mupirocin has also been associated with a decline in the number of gram-positive bacteria and an increase in potential pathogenic gram-negative bacteria and Corynebacterium [83]. Another systematic review noted low-quality evidence of benefit for patients with refractory CRS who have undergone sinus surgery and receive culture-directed topical antibiotic therapy [82].
●Nebulized antimicrobials – Data supporting the use of nebulized antimicrobials are limited, and we do not routinely use them for patients with CRS. However, the author of this topic has used them in select patients with refractory CRS, such as those with cystic fibrosis, with documented infection that has not responded to multiple courses of oral antibiotics [84].
The use of nebulized antimicrobials is also generally reserved for postsurgical patients, in whom there are wider than usual openings into the sinus cavities [85]. Even in this population, data informing the effect of nebulized antimicrobials are limited to small observational studies. In a retrospective study of 42 patients with CRS, previous sinus surgery, and an acute infection, those who chose nebulized antibiotic therapy had a longer infection-free period than those who chose systemic antibiotics [86]. In another observational study, three to six weeks of nebulized antibiotics were safe and associated with improved symptoms in 34 of 41 (83 percent) of patients with CRS and recurrent acute infections after previous surgery [87]. Nebulized delivery may also offer potential benefits over nasal sprays in the management of CRS patients, as nebulization allows for small particles to be distributed over a wider area of sinonasal mucosa [88,89]. However, further studies are needed to define the role of nebulized antimicrobials in the management of CRS.
OTHER COMPONENTS OF THERAPY — The goal of medical therapy for CRS is to promote sinus drainage, reduce chronic inflammation, and eradicate infecting pathogens. Antimicrobial therapy is just one potential component of a comprehensive medical approach, which also includes topical or systemic glucocorticoids and nasal irrigation. These other components of therapy are discussed elsewhere. (See "Chronic rhinosinusitis with nasal polyposis: Management and prognosis" and "Chronic rhinosinusitis without nasal polyposis: Management and prognosis".)
When these measures fail, the patient should be referred to an otolaryngologist for consideration of sinus surgery. (See "Chronic rhinosinusitis with nasal polyposis: Management and prognosis", section on 'Surgical management' and "Chronic rhinosinusitis without nasal polyposis: Management and prognosis", section on 'Functional endoscopic sinus surgery'.)
Patients with concurrent odontogenic infections should be evaluated and treated by a multidisciplinary dental and otolaryngological team [90]. Antimicrobial therapy is only an adjuvant to dental management directed at resolving the odontogenic source. (See "Complications, diagnosis, and treatment of odontogenic infections", section on 'Therapeutic considerations'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic rhinosinusitis".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Chronic sinusitis (The Basics)")
●Beyond the Basics topic (see "Patient education: Chronic rhinosinusitis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Definition − Chronic rhinosinusitis (CRS) is defined as an inflammatory condition involving the paranasal sinuses and linings of the nasal passages that lasts 12 weeks or longer, despite attempts at medical management. The diagnostic criteria for CRS are discussed separately. (See 'Introduction' above and "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis", section on 'Diagnosis'.)
●Microbiology
•Evolution of bacterial flora − The microbiology evolves through several phases. The early phase (acute rhinosinusitis) is usually caused by a viral infection but may be followed by an aerobic bacterial infection in a minority of patients. With CRS, colonizing anaerobic oropharyngeal flora and aerobes such as Staphylococcus aureus become predominant over time. (See 'Evolution of bacterial flora' above.)
•Fungi − Fungi may cause allergic fungal rhinosinusitis, colonization of the sinuses, and invasive fungal sinusitis. (See 'Fungi' above and "Allergic fungal rhinosinusitis" and "Fungal rhinosinusitis".)
●Antimicrobial therapy
•Role of antibiotics − Antibiotics are not a routine component of CRS management, and there is no high-quality evidence to support their use. We reserve antibiotics for situations when bacterial infection is suspected; however, infection complicating CRS can be difficult to establish. Some experts, including an editor of this topic, only use antibiotic therapy for CRS in the setting of an acute flare (eg, sudden worsening of symptoms). Other experts, including the author of this topic, also use antibiotics in situations when infection is possible and cannot be excluded, such as CRS that does not respond to several months of topical glucocorticoids. (See 'Uncertain role of systemic antibiotics' above and "Chronic rhinosinusitis without nasal polyposis: Management and prognosis".)
•Empiric regimen selection − A number of antimicrobial regimens are available to treat CRS. Given that most of these infections are polymicrobial and many include anaerobes, we suggest amoxicillin-clavulanate as the first-line regimen for most patients (Grade 2C). Alternatives include clindamycin and combinations of metronidazole with a second- or third-generation cephalosporin, a macrolide, or trimethoprim-sulfamethoxazole. (See 'Empiric regimen selection' above.)
•Tailoring regimen to culture results − Sinus culture should be obtained in patients to inform the adequacy of the empiric regimen. We broaden therapy to include coverage for isolated pathogens that are resistant to the empiric regimen. We generally suggest not narrowing the regimen to cover only the organisms cultured because certain bacteria, such as anaerobes, may be difficult to isolate (Grade 2C). (See 'Tailoring the regimen to culture results' above.)
•Duration of therapy − Therapy is usually given for seven days for acute exacerbations of CRS, but may warrant a longer duration in some cases. (See 'Duration of therapy' above.)
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