Microbiology of Sinusitis

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Microbiology of Sinusitis
Itzhak Brook1
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ABSTRACT


Most sinus infections are viral, and only a small proportion develops a secondary bacterial infection. Rhinoviruses, influenza viruses, and parainfluenza viruses are the most common causes of sinusitis. The most common bacteria isolated from pediatric and adult patients with community-acquired acute purulent sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes. Staphylococcus aureus and anaerobic bacteria (Prevotella and Porphyromonas, Fusobacterium and Peptostreptococcus spp.) are the main isolates in chronic sinusitis. Pseudomonas aeruginosa and other aerobic and facultative gram-negative rods are commonly isolated from patients with nosocomial sinusitis, the immunocompromised host, those with HIV infection, and in cystic fibrosis. Fungi and Pseudomonas aeruginosa are the most common isolates in neutropenic patients. The microbiology of sinusitis is influenced by the previous antimicrobial therapy, vaccinations, and the presence of normal flora capable of interfering with the growth of pathogens.

KEYWORDS: sinusitis, bacteria, Streptococcus pneumoniae , Staphylococcus aureus , anaerobes

The upper respiratory tract, including the nasopharynx, serves as the reservoir for pathogens capable of causing respiratory tract infections, including sinusitis (1). Potential pathogens can relocate during a viral respiratory infection from the nasopharynx into the sinus cavity, causing sinusitis (2). Establishment of the microbiology of all forms of sinusitis is of primary importance as it can serve as a guide for choosing the adequate antimicrobial therapy. This review presents the microbiology of all forms of sinusitis.

NASAL FLORA


The origin of organisms that are introduced into the sinuses and may eventually cause sinusitis is the nasal cavity. The normal flora of that site includes Staphylococcus aureus, Staphylococcus epidermidis, α- and γ-streptococci, Propionibacterium acnes, and aerobic diphtheroid (3–5). Potential sinus pathogens have been infrequently isolated from healthy nasal cavities. These included Streptococcus pneumoniae (0.5–15%), Haemophilus influenzae (0–6%), Moraxella catarrhalis (0–4%), Streptococcus pyogenes (0–1%), and anaerobic bacteria (Peptostreptococcus spp. [7–16%] and Prevotella spp. [6–8%]) (3–5).

The nasal cavity flora of patients with sinusitis is different from healthy flora. Although the recovery of Staphylococcus spp. and diphtheroids is reduced, the isolation of pathogens increases: S. pneumoniae was found in 36% of patients, H. influenzae in more than 50%, S. pyogenes in 6%, and M. catarrhalis in 4% (6–10).

In many studies of the nasal bacterial flora in sinusitis a simultaneous sinus aspirate was not taken (8, 9). Some studies found the correlation between the floras to be poor (8, 11), whereas others illustrated good correlation (9, 6, 11). In one study (6) in which the sinus aspirate culture yielded a presumed sinus pathogen, the same organism was found in the nasal cavity sample in 91% of the 185 patients. The predictive value of a pathogen-positive nasal finding was high for S. pyogenes (94%), H. influenzae (78%), and S. pneumoniae (69%), but was low for M. catarrhalis (20%).

Hsin and colleagues (12) demonstrated that when performed in pediatric patients, the correlation between endoscopic middle meatal culture and maxillary sinus puncture was only in 78%. The authors concluded that endoscopic sampling is not as favorable in children as in the case of adult patients.

Despite these encouraging data, nasopharyngeal culture is not an acceptable alternative to culture through aspiration.

NORMAL SINUS FLORA


The question of whether normal bacterial flora in the sinuses exists is controversial. The communication of the sinuses with the nasal cavity through the ostia could enable organisms that reside in the nasopharynx to spread into the sinus. After closure of the ostium, these bacteria can become involved in the inflammation. Organisms have been isolated from uninflamed sinuses in several studies (13–16). The bacterial flora of noninflamed sinuses were studied for aerobic and anaerobic bacteria in 12 adults who underwent corrective surgery for septal deviation (13). Organisms were found in all aspirates with an average of four isolates per sinus aspirate. The predominant anaerobic isolates were Prevotella, Porphyromonas, Fusobacterium, and Peptostreptococcus spp. The most common aerobic bacteria were S. pyogenes, S. aureus, S. pneumoniae, and H. influenzae.

In another study, specimens were processed for aerobic bacteria only, and Staphylococcus spp. and α-hemolytic streptococci were isolated (14). Organisms were isolated in 20% of maxillary sinuses of patients who underwent surgical repositioning of the maxilla (15). In contrast, another report of aspirates of 12 volunteers with no sinus disease showed no bacterial growth (16).

Jiang and colleagues (17) evaluated endoscopically the bacteriology of normal maxillary sinuses. Organisms were recovered from 14 of 30 (47%) swab specimens and 7 of 17 (41%) mucosal specimens.

Gordts and colleagues (18) reported the microbiology of the middle meatus in healthy adults and children. Fifty-two (75%) adults had bacterial isolates present, mostly S. epidermidis (35%), Corynebacterium spp. (23%), and S. aureus (8%). In children, the most common organisms were H. influenzae (40%), M. catarrhalis (34%), and S. pneumoniae (50%).

INTERFERING FLORA


The nasopharynx of healthy individuals is generally colonized by relatively nonpathogenic aerobic and anaerobic organisms (19, 20), some of which are able to interfere with the growth of potential pathogens (21). This phenomenon is called bacterial interference. These organisms include the aerobic α-hemolytic streptococci (mostly Streptococcus mitis and Streptococcus sanguis) (22) and anaerobic bacteria (Prevotella melaninogenica and Peptostreptococcus anaerobius) (23). Many interfering bacteria produce bacteriocins, which are bactericidal proteins.

Nasopharyngeal carriage of upper respiratory tract pathogens, such as S. pneumoniae, H. influenzae, and M. catarrhalis, can, however, occur in healthy individuals and increases significantly in young children during respiratory illness (23, 24) and in those prone to sinusitis (25). The absence of interfering organisms can explain the higher recovery of pathogens in these children. Colonization with interfering organisms may play a role in preventing colonization by pathogens and the development of upper respiratory infections, including sinusitis.

Exposure to direct and indirect smoking can increase oral colonization with pathogenic bacteria and decrease the number of organisms that interfere with their growth. The flora of smokers contained fewer aerobic and anaerobic organisms with interfering capability and more potential pathogens as compared with nonsmokers (26). The high number of pathogens and the low number of interfering organisms found in the nasopharynx of smokers reverts to normal levels after complete cessation of smoking (27). The oral flora of smoking parents contains more potential pathogens that are similar to the one recovered from their otitis media–prone children and fewer interfering organisms as compared with nonsmoking parents (28). Because smoking parents harbor more potential pathogens and fewer interfering organisms, they may serve as a source of pathogens that can colonize and/or infect their children. These colonization patterns may place smokers and their children at greater risk of acquiring respiratory infections, including sinusitis.

Administration of antimicrobials can influence the composition of nasopharyngeal flora (29, 30). Therapy with oral second- or third-generation cephalosporins does not eliminate organisms with interfering capabilities, as does amoxicillin (31) or amoxicillin–clavulanate.

MICROBIOLOGY OF SINUSITIS


The pattern of many upper respiratory infections, including sinusitis, evolves in several phases (Figure 1). The early stage often is a viral infection that generally lasts up to 10 days, and complete recovery occurs in most individuals (7). However, in a small number of patients with viral sinusitis (estimated at 0.5%) a secondary acute bacterial infection may develop. This is generally caused by facultative aerobic bacteria (i.e., S. pneumoniae, H. influenzae, and M. catarrhalis). If resolution does not occur, anaerobic bacteria of oral flora origin become predominant over time. The dynamic of these bacterial changes were recently demonstrated by performing serial culture in patients with maxillary sinusitis (32).


Figure 1. The dynamics and changes over time in the microbiology of bacterial sinusitis.
Viral Infections
Viral illness is the most common cause for upper respiratory tract infections, including sinusitis (33). Rhinovirus, influenza virus, and parainfluenza virus are the most common causes of sinusitis (34, 35). It is not known for certain whether the viral infection only precedes or is also concurrent with the bacterial infection. The actual mechanisms by which a virus causes sinus disease are unknown. The proposed mechanism by which viruses predispose to sinusitis involve microbial synergy, induction of local inflammation that blocks the sinus ostia, increase of bacterial attachment to the epithelial cells, and disruption of the local immune defense (Figure 1).

Epithelial cells are often infected with the common respiratory viruses, which can induce the production of several cytokines (33, 36, 37). In the case of rhinoviruses, after deposition in the nose the virus is transported to the posterior nasopharynx (36, 38) and attaches to a specific rhinovirus receptor (39). After initiation of the infection, several inflammatory pathways are induced, as well as the sympathetic nervous system, which generate the classic symptoms of a cold (40). The common cold involves not only the nasal passages but also the paranasal sinuses. Sinus computed tomography (CT) scans of 31 young adults with early common colds showed frequent abnormalities in the sinus cavity (41). Mucosal thickening is observed in radiographs of 87% of patients with colds (42), probably because of excess amounts of mucus discharge from goblet cells. These were seen in the maxillary sinus in 87% of the cases, the ethmoid in 65%, the frontal in 32%, and the sphenoid in 39%. Similar sinus abnormalities during colds were observed in adults and children (43, 44).

CT scans showed occlusion of the infundibulum in 77% of patients with viral rhinosinusitis (41). A malfunction in the ability of the cilia to move material deposits toward the ostia was also found (44). This adverse effect is compounded by infundibular and ostiomeatal obstruction from mucosal swelling. Some viral infections, such as influenza, can cause epithelial damage, which enhances bacterial adherence.

During a cold, nasal fluid containing viruses, bacteria, and inflammatory mediators is suctioned into the sinuses cavities where it produces inflammation and/or infection that is thickened by exocytosis of mucin from the sinus goblet cells. The CT abnormalities present in viral sinusitis could, therefore, represent inflammation alone or a viral infection. In sinus puncture studies in patients with acute community-acquired sinusitis, 15% of the sinus aspirates yielded rhinovirus, 5% influenza virus, 3% parainfluenza virus, and 2% adenovirus (45). Some of the sinus aspirates yielded both viruses and bacteria.

Bacteria in Acute Sinusitis
Bacteria can be recovered from two-thirds of patients with acute infection of the maxillary, ethmoid, frontal, and sphenoid sinuses (46). The bacteria recovered from pediatric and adult patients with community-acquired acute purulent sinusitis are the common respiratory pathogens (S. pneumoniae, M. catarrhalis, H. influenzae, and S. pyogenes) and those considered as part of the normal flora of the nose (S. aureus) (Table 1) (47–49). The vaccination of children with the 7-valent pneumococcal vaccine introduced in 2000 in the United States brought about the decline in the recovery rate of S. pneumoniae and an increase in H. influenzae (50).


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TABLE 1. MICROBIOLOGY OF ACUTE AND CHRONIC SINUSITIS (% OF PATIENTS)

Hsin and colleagues (51) evaluated acute rhinosinusitis in 20 patients with nasopharyngeal carcinoma who receive radiotherapy. The predominant isolates were α-hemolytic streptococcus (8 isolates), S. aureus (5 isolates), and P. aeruginosa (3 isolates). S. pneumoniae, H. influenzae, and M. catarrhalis, however, are far less common, thus illustrating the unique microbiology of acute infection in these patients.

S. aureus is a common pathogen in sphenoid sinusitis (49). A significant increased occurred recently in the recovery rate of methicillin-resistant S. aureus (MRSA) in patients with upper respiratory tract infections, including acute and chronic maxillary sinusitis (52).

We found an increase in the recovery of MRSA in 2004 to 2006 as compared with 2001 to 2003 in acute and chronic maxillary sinusitis (53). S. aureus was isolated from 10 (8%) of 118 patients with acute sinusitis between 2001 and 2003, and 3 (30%) were MRSA. S. aureus was recovered from 13 (10%) of 126 patients with acute sinusitis between 2004 and 2006, and 9 (69%) were MRSA (P < 0.01). S. aureus was found in 15 (16%) of 97 patients with chronic sinusitis between 2001 and 2003, and 4 (27%) were MRSA. S. aureus was recovered from 23 (20%) of 117 patients with chronic sinusitis between 2004 and 2006, and 14 (61%) were MRSA (P < 0.05).

The infection is polymicrobial in about one-third of the cases. Enteric bacteria were isolated less often, and anaerobes were recovered only from a few cases with acute sinusitis. However, appropriate methods for their recovery were rarely used in most studies of acute sinusitis. Anaerobic bacteria are commonly recovered from acute sinusitis associated with dental disease, mostly as an extension of the infection from the roots of the premolar or molar teeth (54, 55).

P. aeruginosa and other gram-negative rods were recovered in sinusitis of nosocomial origin (especially in patients who have nasal tubes or catheters), the immunocompromised, patients with HIV infection, and those with cystic fibrosis (56).

Bacteria in Chronic Sinusitis
Although the exact cause of the inflammation associated with this chronic sinusitis is uncertain, the presence of bacteria within the sinuses has been well documented (57, 58). Most clinicians believe that microorganisms play a major role in the cause and pathogenesis of most cases of chronic sinusitis, and prescribe antimicrobial therapy. In contrast to the agreement regarding the microbiology of acute sinusitis, there is disagreement regarding the microbiology of chronic sinusitis. Unfortunately, there are several issues that confound the reliability of many microbiological studies and therefore contribute to the disparity of their results. These issues include: various methods used to sample the sinus cavity, failure to sterilize the area through which the trocar or endoscope is passed, different sinuses or areas that are sampled (i.e., ethmoid bulla or maxillary antrum or middle meatus), lack of assessment of the inflammatory response, lack of quantitation of bacteria, previous or current use of antibiotics, variable patient selection (i.e., age, duration, extent of disease, surgical or nonsurgical subjects), presence of nasal polyps, and time of culture transport and method of culture.

Numerous studies examined the bacterial pathogens associated with chronic sinusitis. However, most of these did not use methods that are adequate for the recovery of anaerobic bacteria. Studies have described significant differences in the microbial pathogens present in chronic sinusitis as compared with acute sinusitis. S. aureus, S. epidermidis, and anaerobic gram-negative bacteria predominate in chronic sinusitis. The pathogenicity of some of the low-virulence organisms, such S. epidermidis, a colonizer of the nasal cavity, is questionable (18, 59). The absence of quantitation or performance of Gram stains in most studies prevents an assessment of both the density of organisms and the accompaniment of an inflammatory response. The common resistance of S. epidermidis to antimicrobials does not prove its pathogenicity. Although S. epidermidis is discounted as a pathogen in sinusitis, its role as a pathogen in other body sites has been well documented (i.e., neutropenic sepsis, infections of indwelling catheters, and in burn patients) (60). The frequent isolation of S. epidermidis from swabs obtained from the middle meatus of normal subjects marks it as a commensal and likely contaminant. In the unusual situation in which a large number of white blood cells and organisms are present on Gram stain and there is heavy growth of S. epidermidis, and proper anaerobic cultures shows no growth of these and other organisms, the possibility of a true infection by S. epidermidis should be entertained (60–63).

Isolation of gram-negative enteric rods, including P. aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter spp., and Escherichia coli were also reported in some studies (61). Because these bacteria are rarely isolated from middle meatus cultures obtained from normal individuals, their recovery from these symptomatic patients suggests their pathogenic role. These organisms may have been selected out following administration of antimicrobial therapy in patients with chronic sinusitis.

The exact events leading to chronic sinusitis have been difficult to identify or prove (64). It has been proposed that chronic sinusitis is an extension of unresolved acute infection. As mentioned previously, the etiology of acute sinusitis frequently is viral, which can establish an environment that is synergistic with the growth of other organisms, both aerobic and anaerobic. If the infection is not properly treated, the inflammatory process can persist, which, over time, fosters the growth of anaerobes. Thus, the pathogens in sinusitis appear to evolve over the course of infection—from viruses to aerobic to anaerobic bacterial growth—as the symptoms and pathology persist over a period of weeks to months.

The microbiology of chronic sinusitis differs from that of acute sinusitis (Table 1) (65–68). The transition from acute to chronic sinusitis was studied by repeated endoscopic sinus aspirations in five patients (32). Most bacteria isolated from the first culture were aerobic or facultatives: S. pneumoniae, H. influenzae, and M. catarrhalis. Failure to respond to therapy was associated with the emergence of resistant aerobic and anaerobic bacteria in subsequent aspirates. These included Fusobacterium nucleatum, pigmented Prevotella, Porphyromonas spp., and Peptostreptococcus spp. (Figure 2). Eradication of the infection was finally achieved after administration of effective antimicrobial agents and in three cases also by surgical drainage.


Figure 2. Dynamics of sinusitis. Amox = amoxicillin; Cipro = ciprofloxacin; clinda = clindamycin; NG = no growth. Reprinted by permission from Reference 87.
This study illustrates that over time the aerobic and facultative species are gradually replaced by anaerobes (32). This may result from the selective pressure of antimicrobial agents that enable resistant organisms to survive and from the development of conditions appropriate for anaerobic growth, which include the reduction in oxygen tension and an increase in acidity within the sinus. These are caused by persistent edema and swelling, which reduces blood supply, and by the consumption of oxygen by the aerobic bacteria (69). Other factors include the emergence over time or selection of anaerobes that possess virulence factors, such as a capsule (70).

In chronic infections, when adequate methods are used, anaerobes can be recovered in more than half of all cases, whereas the pathogens in acute sinusitis (e.g., S. pneumoniae, H. influenzae, M. catarrhalis) are found with lower frequency (65–68, 71). A recent study using sequencing the species-specific 16S ribosomal DNA fragment for genetic identification of bacteria illustrated the recovery of anaerobes in half of the 18 patients with chronic sinusitis (72).

Polymicrobial infection is common in chronic sinusitis, which is a synergistic infection (70) and may therefore be more difficult to eradicate with narrow-spectrum antimicrobial agents. Chronic sinusitis caused by anaerobes is a particular concern clinically because many of the complications associated with this condition (e.g., mucocele formation, osteomyelitis, local and intracranial abscess) are caused by these bacteria (55).

The role of anaerobes in chronic sinusitis is supported by their ability to induce chronic sinusitis in a rabbit by intrasinus inoculation of Bacteroides fragilis and the rapid production of serum IgG antibodies against this organism in the infected animals (73). The pathogenic role of these organisms is also supported by the detection of antibodies (IgG) to two anaerobic organisms commonly recovered from sinus aspirates (F. nucleatum and Prevotella intermedia) (74). Antibody levels to these organisms declined in the individuals who responded to therapy and were cured, but did not decline in those who failed treatment (Figure 3).


Figure 3. Serum antibodies to Fusobacterium nucleatum and Prevotella intermedia in 23 patients with chronic sinusitis.
Studies in Children.
There have been 11 studies of the microbiology of chronic sinusitis in children between 1981 and 2010 (67, 75–85). Four of these studies were prospective (75, 76, 80, 82) and six were retrospective (Table 2). In all but three studies, the maxillary sinus was sampled by transnasal aspiration. The most common criteria for evaluation were symptoms that lasted more than 90 days. An attempt was made to sterilize the nose before obtaining the culture only in five studies and bacterial quantitation was rarely done. In two of the studies, normal nasal flora were the most common organisms recovered. It is difficult to know what pathologic significance to ascribe to these organisms. In the remaining studies, the pathogens common in acute infection were recovered in about 60% of cases (i.e., H. influenzae, S. pneumoniae, and M. catarrhalis). This was especially true when the criteria for entry included purulent secretions. In the remaining 30 to 40% of children, contaminants were recovered. Anaerobes were recovered in four studies, the only ones that used methods for their recovery (67, 75, 82, 83).


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TABLE 2. SUMMARY OF 18 STUDIES THAT EVALUATED THE ROLE OF ANAEROBES IN CHRONIC BACTERIAL SINUSITIS

S. aureus (19%) and α-hemolytic streptococci (23%) predominated in ethmoid sinusitis in one study (84), and S. epidermidis and α-hemolytic streptococci in the another (76). M. catarrhalis was the most common isolate in a study of children with allergies, although 25% of them had polymicrobial flora (85). S. pneumoniae and H. influenzae predominated in children with acute exacerbations (86).

Brook and Yocum (87) studied 40 children with chronic sinusitis. The sinuses infected were the maxillary (15 cases), ethmoid (13 cases), and frontal (7 cases). Pansinusitis was present in five patients. A total of 121 isolates (97 anaerobic and 24 aerobic) were recovered. Anaerobes were recovered from all 37 culture-positive specimens, and in 14 cases (38%) they were mixed with aerobes. The predominant anaerobic organisms were gram-negative bacilli (36), anaerobic gram-positive cocci (28), and Fusobacterium spp. (13). The predominant aerobes were α-hemolytic streptococci (7), S. aureus (7), and Haemophilus spp. (4).

Brook and colleagues (75) correlated the microbiology of concurrent chronic otitis media with effusion and chronic maxillary sinusitis in 32 children. Two-thirds of the children had a bacterial etiology. The most common isolates were H. influenzae (9 isolates), S. pneumoniae (7 isolates), Prevotella spp. (8 isolates), and Peptostreptococcus spp. (6 isolates). Microbiological concordance between the ear and sinus was found in 22 (69%) of culture-positive children.

Erkan and colleagues (82) studied 93 chronically inflamed maxillary sinuses. Anaerobes were isolated in 81 of 87 (93%) culture-positive specimens and were recovered alone in 61 (70%) and mixed with aerobic or facultative bacteria in 20 (23%). Aerobic or facultative bacteria were found alone in six cases (7%). A total of 261 isolates, 19 anaerobes, and 69 aerobes or facultatives were isolated. The predominant anaerobes were Bacteroides spp. and anaerobic cocci; the predominant aerobes or facultatives were Streptococcus spp. and S. aureus.

Hsin and colleagues (83) obtained cultures from 165 children with chronic rhinosinusitis. Of the 399 isolates, 21% were α-hemolytic Streptococcus, 19% H. influenzae (19.5%), 14% S. pneumoniae, 9% S. aureus, and 8% anaerobes. Antimicrobial susceptibility rates of all aerobic isolates had shown a significant increase over the six years of the study.

Studies in Adults.
The presence of anaerobes in chronic sinusitis in adults is often clinically significant (88, 89). Finegold and colleagues (68) found recurrence of signs and symptoms twice as frequent when cultures showed anaerobic bacterial counts greater than 103 colony-forming units per milliliter.

Anaerobes were frequently identified whenever techniques for their cultivation were used (Table 2). The predominant isolates were pigmented Prevotella, Fusobacterium, and Peptostreptococcus spp. The predominant aerobes were S. aureus, M. catarrhalis, and Haemophilus spp. Aerobic and anaerobic β-lactamase–producing bacteria (BLPB) were isolated from more than one-third of these patients (61, 65, 66, 71, 89, 90). These BLPB were S. aureus, Haemophilus, Prevotella, Porphyromonas, and Fusobacterium spp.

A summary of 18 studies of chronic sinusitis done since 1974, including 1,923 patients (298 were children) is shown in Table 2 (66–68, 82, 83, 90–102). Anaerobes were recovered in 8 to 93%. The variability in recovery may be due to differences in the methodologies used for transportation and cultivation, patient population, geography, and previous antimicrobial therapy.

Brook and Frazier (103) correlated the microbiology with the history of sinus surgery in 108 patients with chronic maxillary sinusitis and found a higher rate of isolation of P. aeruginosa and other gram-negative bacilli in patients with previous sinus surgery. Anaerobes were, however, isolated significantly more frequently in patients who had not had prior surgery.

Brook evaluated the microbiology of 13 chronically infected frontal (104), seven sphenoid (105), and 17 ethmoid sinuses (106) (Table 1). Anaerobic bacteria were recovered in more than two-thirds of the patients. The predominant anaerobes included Prevotella, Peptostreptococcus, and Fusobacterium spp. The main aerobic organisms were gram-negative bacilli (H. influenzae, K. pneumoniae, E. coli, and P. aeruginosa).

Nadel and colleagues (61) also isolated gram-negative rods more commonly in previous surgery patients or those who had sinus irrigation. P. aeruginosa was also more frequent in patients who received systemic steroids. Other studies have also noted this shift toward gram-negative organisms in patients who have been extensively and repeatedly treated (60, 62, 63). The bacterial flora includes Pseudomonas spp., Enterobacter spp., MRSA, H. influenzae, and M. catarrhalis.

Bacteria in Chronic Maxillary Sinusitis Associated with Nasal Polyposis
Nasal polyps can impair paranasal sinus ventilation and drainage by blockage of the ostiomeatal complex. Several studies have shown that in the majority of cases of chronic sinusitis in which nasal polyps are present, bacterial cultures are negative. Even polymerase chain reaction techniques failed to demonstrate bacterial infection in most cases (107). Hamilos and colleagues (108) obtained antral culture in 12 subjects with chronic maxillary sinusitis with nasal polyps and isolated organisms in only 3 cases. However, none of these studies used methods that were adequate for the recovery of anaerobes.

We evaluated aspirates of 48 chronically inflamed maxillary sinuses from patients who had nasal polyposis that were cultured for aerobic and anaerobic bacteria (109). Bacterial growth was present in 46 (96%) specimens. Aerobic or facultative bacteria were present in 6 (13%) specimens, anaerobic bacteria alone in 18 (39%), and mixed aerobic and anaerobic bacteria in 22 (48%). There were 110 bacterial isolates (2.4 per specimen). Thirty-nine of the isolates were aerobic or facultative organisms (0.85 per specimen). The predominant aerobic or facultative organisms were: S. aureus, microaerophilic streptococci, H. influenzae, and M. catarrhalis. There were 71 anaerobes isolated (1.5 per specimen). The predominant anaerobes were Peptostreptococcus spp., Prevotella spp., P. asaccharolytica, Fusobacterium spp., and P. acnes.

Kim and colleagues (110) studied the bacteriology and antimicrobial susceptibility of maxillary sinus aspirates in chronic sinusitis with nasal polyps in 81 patients. Aerobes were isolated from 48% of the aspirates and included S. aureus, H. influenzae, and S. pneumoniae. Anaerobes were isolated from 18.5%, and the predominant ones were Prevotella and Peptostreptococcus.

These findings suggest that the microbiology of the maxillary sinus of those with chronic sinusitis with polyposis is not different than those who develop chronic sinusitis without this condition, as the major isolates are polymicrobial aerobic-anaerobic flora.

Bacteria in Acute Exacerbation of Chronic Sinusitis
Acute exacerbation of chronic sinusitis (AECS) represents a sudden worsening of the baseline chronic sinusitis with either worsening or new symptoms. Typically, the acute (not chronic) symptoms resolve completely between occurrences (111). We evaluated the microbiology of acute AECS (112) by performing repeated endoscopic sinus aspirations in seven patients over a period of 125 to 242 days. Bacteria were recovered from all 22 aspirates and the number of isolates varied between two and four. A total of 54 isolates were isolated, 16 aerobic and facultatives and 38 anaerobic bacteria. The aerobic bacteria were seven H. influenzae, three S. pneumoniae, three M. catarrhalis, two S. aureus, and one K. pneumoniae. The anaerobic bacteria included pigmented Prevotella and Porphyromonas spp. (19), Peptostreptococcus spp. (9), Fusobacterium spp. (8) and P. acnes (2). A change in the types of isolates was noted in all consecutive cultures obtained from the same patients, as different organisms emerged and previously isolated bacteria were no longer recovered. An increase in antimicrobial resistance was noted in six instances. These findings illustrate the microbial dynamics of AECS where anaerobic and aerobic bacteria prevail and highlight the importance of obtaining cultures from patients with this infection for guidance in selection of proper antimicrobial therapy.

Brook (113) compared the aerobic and anaerobic microbiology of maxillary AECS with the microbiology of chronic maxillary sinusitis. Included in the study were 32 with chronic sinusitis and 30 with AECS. A total of 81 isolates were recovered from the 32 cases (2.5 per specimen) with chronic sinusitis, 33 aerobic and 48 anaerobic. Aerobes alone were recovered in 8 specimens (25%), anaerobes only were isolated in 11 (34%), and mixed aerobes and anaerobes were recovered in 13 (41%). The predominant aerobic and facultatives were Enterobacteriaceae and S. aureus. The predominant anaerobes were Peptostreptococcus spp., Fusobacterium spp., anaerobic gram-negative bacilli, and P. acnes. A total of 89 isolates were recovered from the 30 cases (3.0 per specimen) with AECS, 40 aerobic and facultatives, and 49 anaerobic. Aerobes were recovered in 8 instance (27%), anaerobes only in 11 (37%), and mixed aerobes and anaerobes were recovered in 11 (37%). The predominant aerobes were S. pneumoniae, Enterobacteriaceae, and S. aureus. The most common anaerobes were Peptostreptococcus spp., Fusobacterium spp., anaerobic gram-negative bacilli, and P. acnes. This study illustrates that the organisms isolated from patients with AECS were predominantly anaerobic and were similar to those generally recovered in chronic sinusitis. However, aerobic bacteria that are usually found in acute infections (e.g., S. pneumoniae, H. influenzae, and M. catarrhalis) can also emerge in some of the episodes of AECS.

Nosocomial Rhinosinusitis
Patients with nosocomial sinusitis are generally those who require extended periods of intensive care (postoperative patients, burn victims, patients with severe trauma) involving prolonged endotracheal or nasogastric intubation (114). Nasotracheal intubation places the patient at a substantially higher risk for nosocomial sinusitis than orotracheal intubation (116). Approximately 25% of patients requiring nasotracheal intubation for more than 5 days develop nosocomial sinusitis (117). In contrast to community-acquired sinusitis, the usual pathogens are gram-negative enterics (e.g., P. aeruginosa, K. pneumoniae, Enterobacter spp., P. mirabilis, Serratia marcescens) and gram-positive cocci (occasionally streptococci and staphylococci) (115–119). Whether these organisms are actually pathogenic is unclear, and they usually represent colonization of an environment with impaired mucociliary transport and foreign body presence in the nasal cavity.

Souweine and colleagues (120) studied the microbiology of ventilator-associated maxillary sinusitis in 24 patients. Nine cultures were monomicrobial and 15 were polymicrobial. An average of 2 organisms per sinus was recovered and included 21 gram-positive bacteria, 22 gram-negative bacteria, and 5 yeasts. P. aeruginosa and enterococci were the most commonly identified organisms.

Evaluation of the microbiology of nosocomial sinusitis in nine children with neurologic impairment illustrated the presence of anaerobic bacteria, always mixed with aerobic and facultative bacteria, in six (67%) sinus aspirates and aerobic bacteria only in three (33%) (121). There were 24 bacterial isolates, 12 aerobic or facultative and 12 anaerobic. The predominant aerobic isolates were K. pneumoniae, E. coli, and S. aureus (two each) and P. mirabilis, P. aeruginosa, H. influenzae, M. catarrhalis, and S. pneumoniae (one each). The predominant anaerobes were Prevotella spp. (five), Peptostreptococcus spp. (four), F. nucleatum (two), and B. fragilis (one). Organisms similar to those recovered from the sinuses were also isolated from tracheostomy site and gastrostomy wound aspirates in five of seven instances. This study demonstrates the uniqueness of the microbiologic features of sinusitis in neurologically impaired children, in whom, in addition to the organisms known to cause infection in normal children, facultative and anaerobic gram-negative organisms that can colonize other body sites are predominant.

Discrepancies in the Recovery of Bacteria from Multiple Sinuses
There are differences in the distribution of organisms in a single patient who suffers from infections in several sinuses that emphasize the importance of obtaining cultures from all infected sinuses. A recent study evaluated the discrepancies between infected sinuses by studying the aerobic and anaerobic microbiology of acute and chronic sinusitis in patients with involvement of multiple sinuses (122). The 155 evaluated patients had sinusitis of either the maxillary, ethmoid, or frontal sinuses (any combination) and had organisms recovered from two to four concomitantly infected sinuses. Similar aerobic, facultative, and anaerobic organisms were recovered from all the groups of patients. In patients who had organisms isolated from two sinuses and had acute sinusitis, 31 (56%) of the 55 isolates were found only in a single sinus, and 24 (44%) were recovered concomitantly from two sinuses. In those with chronic infection, 31 (34%) of the 91 isolates were recovered only from a single sinus, and 60 (66%) were found concomitantly from two sinuses. Anaerobic bacteria were more often concomitantly isolated from two sinuses (50 of 70) than aerobic and facultative (10 of 21; P < 0.05). Similar findings were observed in patients who had organisms isolated from three or four sinuses. BLPB were more often isolated from patients with chronic infection (58–83%) as compared with those with acute infections (32–43%). These observations illustrate that there are differences in the distribution of organisms in a single patients who suffers from infections in multiple sinuses and emphasizes the importance of obtaining cultures from all infected sinuses.

Beta Lactamase Producing Bacteria
S. aureus, H. influenzae, and M. catarrhalis, pigmented Prevotella, Porphyromonas, and Fusobacterium species can produce the enzyme β-lactamase (123). The recovery rate of aerobic and anaerobic BLPB in the oropharynx has increased in recent years, and these organisms were isolated in more than half of the patients with head and neck infections, including sinusitis (123). BLPB can be involved directly in the infection, protecting not only themselves from the activity of penicillins but also penicillin-susceptible organisms. This can occur when the enzyme β-lactamase is secreted into the infected tissue or abscess fluid in sufficient quantities to break the penicillin's β-lactam ring before it can kill the susceptible bacteria (124).

The high incidence of recovery of BLPB in upper respiratory tract infections may be due to the selection of these organisms after antimicrobial therapy with β-lactam antibiotics. Emergence of penicillin-resistant flora can occur after only a short course of penicillin (125, 126).

The actual activity of the enzyme β-lactamase and the phenomenon of shielding were demonstrated in acutely and chronically inflamed sinuses fluids (127). BLPB were isolated in 4 of 10 acute sinusitis (Table 3) aspirates, and in 10 of 13 chronic sinusitis aspirates. The predominant BLPB isolated in acute sinusitis were H. influenzae and M. catarrhalis, and those found in chronic sinusitis were Prevotella and Fusobacterium spp. The recovery of BLPB is not surprising, because more than two-thirds of the patients with acute and all of the patients with chronic sinusitis received antimicrobial agents that might have selected for BLPB.


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TABLE 3. β-LACTAMASE DETECTED IN CHRONIC SINUSITIS ASPIRATES

Atypical Organisms
Chlamydia pneumoniae was isolated from patients with respiratory infection that also included clinical features of sinusitis (128), and serological evidence of its presence in patients with sinusitis was found in only 2% of 103 patients (129). However, because it was only recovered in one case from sinus aspirate (130), its exact role is uncertain.

Mycoplasma pneumoniae has been suspect as a cause of acute sinusitis, but no attempts have been made so far to isolate it from infected sinuses. However, the increase in antibody titers to it suggests a link between sinusitis and M. pneumoniae infection (131) in purulent bacterial and nonpurulent nonbacterial infections.

M. pneumoniae–specific DNA was identified in a small group of patients with sinusitis and/or nasal polyposis (132). However, another study did not confirm the presence of bacterial-specific DNA sequences for 16S ribosomal RNA (107).

Lee and colleagues (133) were unable to identify any atypical bacteria in 11 patients with chronic sinusitis by using polymerase chain reaction.

THE ROLE OF FUNGI IN SINUSITIS


Fungal “colonization” of the nose and paranasal sinuses is common in the normal and inflamed sinuses (134–138). The role of fungi in the pathogenesis of chronic sinusitis is controversial. Although fungi can be detected in the nose and paranasal sinuses of nearly all patients with chronic sinusitis and are present in almost all healthy controls, some studies suggest that there may be mechanisms by which fungi exert an effect on sinus mucosa in susceptible individuals only (139). Presently, in the absence of convincing immunological data and evidence for clinical improvement of chronic sinusitis after therapy with antifungal agents, the role of the fungi remains unproven.

Under certain conditions, however, clinically significant growth of fungus balls (also called mycetomas) or saprophytic growth of fungus can occur. This can cause the formation and accumulation of fungal mycelia within the nose and paranasal sinuses without significant mucosal inflammation. However, in other forms the inflammatory response to the fungi can result in clinically significant disease.

Fungal sinusitis can be either noninvasive or invasive. Invasiveness is generally considered as an acute and fulminant disease. In immunologically deficient individuals, however, the invasive fungal sinusitis is mild or not apparent and can have a long and chronic course. Diagnosis is confirmed histologically in the presence of nasal or sinus invasive fungal involvement lasting longer than 12 weeks.

Fungi can occasionally cause commonly acquired sinusitis (140). They are especially common in patients with uncontrolled diabetes, HIV disease, and those on prolonged immunosuppressive therapy (especially transplant recipients) and those on prolonged courses of antimicrobials. Aspergillus fumigatus is the most common fungus associated with sinusitis (141, 142) and can cause disease in the normal as well as the immunocompromised hosts. It can cause an invasive and noninvasive illness. Sinusitis due to Aspergillus has been associated with the smoking of marijuana, because it contaminates the leaves. The organism can cause noninvasive, invasive, and disseminated forms. The noninvasive form presents as chronic rhinitis and nasal obstruction, and if untreated can spread through the bloodstream, seeding numerous sites.

Other Aspergillus species able to cause sinusitis in normal hosts include Aspergillus flavus and Aspergillus niger (142).

Chronic invasive fungal sinusitis is divided into granulomatous and nongranulomatous subtypes based on histopathology. Chronic invasive rhinosinusitis has been associated with Mucor, Alternaria, Curvularia, Bipolaris, Candida, Sporothrix schenckii, and Pseudallescheria boydii (138). Other fungi able to cause sinus infection include Schizophyllum commune (143), Emericella nidulans (144), Pseudoallescheria boydii (145), Paecilomyces spp., Cryptococcus neoformans, Penicillium melinii, Scedosporium (Monosporium), Apiospermum, and Blastomycosis dermatitides (146). Saprophytic fungi causing infections are Drechslera spp., Alternaria spp., Curvularia lunata, and Exserohilum spp. (147). Mucormycosis is caused by fungi of the Mucorales order. The sinusitis induced occurs mainly in patients with diabetes and in the immunocompromised.

Allergic sinusitis has been associated with Alternaria, Aspergillus, Bipolaris, Chrysosporium, Drechslera, and Exserohilum (148). Allergic fungal sinusitis from Aspergillus spp. is similar to allergic bronchopulmonary aspergillus, with secretions containing eosinophils, Charcot-Leyden crystals, and fungal hyphae (149). Patients usually have evidence of atopy or asthma. The sinusitis is protracted, and generally involves multiple sinuses. Myriodontium keratinophilum also produces allergic-like fungal sinusitis (150). The patients generally suffer from chronic sinusitis, nasal polyps, and proptosis due to orbital and ethmoid cell invasion. Allergic fungal sinusitis was also described to be associated with Drechslera (151), Alternaria, and Curvularia (152).

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Correspondence and requests for reprints should be addressed to Itzhak Brook, M.D., M.Sc., 4431 Albemarle Street, NW, Washington DC 20016. E-mail: ***@georgetown.edu
Accepted August 6, 2010
Received June 15, 2010
© 2011 The American Thoracic Society
Author Disclosure: I.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.




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