S. aureus is a ubiquitous microorganism, occupying the nasal vestibule of nearly one-third of the human population at any given time. S. aureus has emerged as an important pathogen in community- and hospital-acquired infections, resulting in sepsis, bacteremia, endocarditis, and soft tissue infections. S. aureus is commonly assayed in cultures performed for CRS [10, 11, 13, 14]. Nadel et al. and Kingdom and Swain reported its presence in 23.1 and 25 % of sinus cultures, respectively [10, 11]. Though the exact role in pathogenesis is a matter of debate, the presence of S. aureus infection at the time of sinus surgery has been demonstrated to be a strong predictor of postoperative S. aureus infection and impaired mucosal healing.

A variety of novel mechanisms of pathogenicity have also been implicated, including biofilm formation and intracellular residency [15]. Foreman et al. characterized bacterial biofilm by fluorescence in situ hybridization in 50 CRS patients. Biofilms were detected in 36 of 50 patients, with S. aureus being the most common biofilm-forming organism [16]. The capacity to form biofilms may confer the ability to create a recalcitrant infectious state unresponsive to conventional antimicrobial therapies. An increase in the recovery of methicillin-resistant Staphylococcus aureus (MRSA) has recently been noted in acute and chronic rhinosinusitis and anterior nares of normal individuals [17]. Brook et al. compared MRSA rates in chronic maxillary sinusitis between two time periods. S. aureus was found in 15 (15 %) of the patients between 2001 and 2003, four (27 %) of which were MRSA. S. aureus was cultured in 23 (20 %) of the patients between 2004 and 2006, with 14 (61 %) being MRSA. Indeed, MRSA represents a treatment challenge in the setting of CRS, given paucity of optimal treatment options. Oral antibiotics that may be effective include doxycycline, trimethoprim/sulfamethoxazole, and clindamycin. Topical mupirocin irrigations may also serve as an important adjunct in the postoperative CRS patient [18].

The superantigen hypothesis proposes that S. aureus secretes high molecular weight proteins known as enterotoxins. These enterotoxins have significant stimulatory activity that can foster the characteristic tissue response seen in patients with nasal polyps. Approximately 50 % of CRSwNP patients show lymphocyte responses consistent with superantigen exposure [19]. In addition, staphylococcal toxin-specific IgE antibodies have been detected in 18 of 23 patients with nasal polyps [20]. It is unclear, however, whether S. aureus superantigens represent an etiologic agent or a disease modifier. The link between superantigens and CRSsNP has not yet been established.

The exact role of SCN in CRS remains to be determined, as its reported incidence varies widely [11]. It has been posited to be a contaminant, supported by previous work that found CNS in the middle meatus of 56 % of healthy patients and in only 20 % of patients with CRS [21]. Moreover, the microbe is ubiquitous on human skin; thus, contamination may occur readily without proper sterile precautions during culture technique. However, different strains of CNS may have differing abilities to cause disease. Recent studies evaluating CNS in indwelling devices have shown that bacterial pathogenicity is dependent on genes associated with biofilm formation, which are only found in certain strains [22]. The mere presence of SCN may not indicate infection, as a specific strain may be necessary for such an infection to develop. Nonetheless, endoscopically acquired cultures have consistently identified SCN in multiple studies in CRS. Bolger found SCN in 17 %, Hsu et al. in 42 %, and Nadel et al. in 35 % of cultures [10, 13, 14]. One possible method to ascertain significance of SCN culture is based on the quantitative growth on culture, along with presence of leukocytosis on the gram stain result. Scant or light growth, especially with a paucity of gram-positive rods or white blood cells (WBCs) on gram stain, likely represents contamination. In contrast, moderate to heavy growth, with large number of WBCs on gram stain, should alert the clinician of the possibility of a true infection.

Gram-negative rods are often identified in CRS cultures, more commonly in patients who have undergone endoscopic sinus surgery [10, 13, 14]. However, their role in patients with CRS without previous surgery should also not be underestimated. Kingdom and Swain found GNRs in 31 % of cultures in a group of patients at the time of primary sinus surgery [11]. Nadel et al. found GNRs in 9.5 % of cultures taken from patients without previous sinus surgery [10]. P. aeruginosa has long been recognized as an important pathogen in the upper and lower airway in cystic fibrosis patients. It also represents a common and problematic organism in CRS. Rates of assay in CRS cultures have been reported between 9 and 16 % [10, 11]. Nadel et al. noted that P. aeruginosa was most commonly cultured in patients with previous FESS and irrigation usage [10]. P. aeruginosa also has the capability of biofilm formation which may in part contribute to its refractory nature in CRS patients. Further, the presence of P. aeruginosa biofilm has been associated with poor evolution after FESS [23]. Fluoroquinolones are the only orally administered antibiotic group with efficacy against P. aeruginosa. Quinolone resistance has become more problematic, with limited alternate proven oral antimicrobial therapies for Pseudomonas rhinosinusitis.

Stenotrophomonas maltophilia is a multidrug-resistant gram-negative bacillus most often encountered as a nosocomial pathogen in immunocompromised and intensive care unit patients. Infection with S. maltophilia most frequently involves the respiratory tract, bloodstream, wounds, and genitourinary tract. S. maltophilia has also been cultured from the paranasal sinuses, often in the setting of prior antimicrobial treatment and sinus surgery. The exact implication of S. maltophilia cultures in the paranasal sinuses is unclear. Whether this represents a true infection by an atypical microorganism or colonization that surfaces after eradication of other microbes by antimicrobial therapy merits additional research. Despite its multidrug-resistant nature, trimethoprim/sulfamethoxazole and fluoroquinolone monotherapy has been employed with improvement of symptoms and endoscopic findings in CRS patients [24].

Patients with CRS frequently report that their symptoms initially started after an acute viral event [25]. Furthermore, viruses can cause multiple changes on a cellular level, facilitating an infectious and inflammatory milieu of CRS, such as increase in bacterial adhesion and production of inflammatory mediators by nasal epithelial cells [26, 27]. Multiple studies have evaluated the presence of respiratory viruses in samples taken from patients with CRS. Ramadan and colleagues found RSV present in 20 % of samples collected from patients with CRS [28]. However, this study did not report a control group or the timing of the specimen collection, as the presence of RSV is much greater in the winter months in the general population. Jang et al. reported a similar study with a control group and collected specimens during the summer months [29]. Rhinovirus was identified in 21 % of samples from CRS patients and 0 % in the control group. However, these samples were taken from the inferior turbinates and not the paranasal sinus mucosa. In contrast to the above studies, Wood et al. collected sinus mucosa samples from 13 CRS patients and 2 controls [25]. No respiratory viruses, including RSV and rhinovirus, were identified in any of the samples. While viruses may be implicated in the initial or ongoing stimulus of inflammation, their exact role in CRS is not clearly defined.

It is clear that fungus is responsible for some forms of sinusitis, in both invasive and noninvasive forms. Though a wide variety of fungi have been identified in the sinuses of CRS patients, the central etiologic role of fungus in CRS has not been clearly demonstrated. In 1999, positive fungal cultures from nasal mucus were used as the basis to posit that eosinophilic infiltration and fungal presence provided the main inciting event for CRS [30]. However, further studies found a similar percentage of positive cultures in normal control patients [31]. In addition, a double-blind, placebo-controlled randomized multicenter trial has failed to identify any benefit of topical antifungal therapy in objective and subjective outcome measures in patients with CRS [32]. A subset of CRS, allergic fungal rhinosinusitis (AFRS), is characterized by type I hypersensitivity to fungi, nasal polyposis, eosinophilic mucin, hyperdensities on CT imaging, and positive fungal stain or culture with the absence of diabetes, immunodeficiency, or an invasive fungal process [33]. Furthermore, patients with AFRS have been shown to have elevated levels of total serum IgE and IgG anti-Alternaria antibodies when compared to patients with CRS [34]. While fungus does play a role in specific subtypes of CRS, its role as a central pathophysiologic mechanism of CRS is not corroborated in the literature.

Osteitis is another possible etiologic factor for CRS. Patients with CRS often show areas of irregular bony thickening on CT imaging. It has been proposed that this irregular thickening and increased bone density may be a sign of inflammation in the bone, resulting in persistent inflammation of the overlying mucosa [35]. Osteitis is marked by varying degrees of osteoclast-osteoblast activity, leading to disruption of organized lamellar bone and formation of immature woven bone [36]. Entry of inflammatory infiltrate into the Haversian canal system may act as a potential pathway for spread of inflammation and, as such, mucosal disease. The prevalence of osteitis is estimated between 36 and 53 % in CRS patients, based on CT findings or pathologic evaluation [37]. This concept of osteitis, an inflammation of the bone, should be differentiated from osteomyelitis, as direct bacterial invasion of the bone in CRS has not yet been demonstrated in studies.