Although bacterial infection likely plays a role in the inflammatory process, it is no longer believed to be the principal causative factor. However, antibiotics remain important in the management of exacerbations and in overall management [1]. Interestingly, it has been shown that selective pressure from antimicrobial agents can alter the bacterial composition seen in CRS [2]. The most common bacteria occurring in acute rhinosinusitis (ARS) have been well characterized; however, bacteria involved in CRS have been less clearly identified making it difficult to treat chronic bacterial infections empirically.

Antibiotic resistance is an increasingly common issue in the management of CRS. One study showed that resistance from erythromycin is increasing at a higher rate than for other antibiotics [3]. Another retrospective review of culture results from 324 CRS patients obtained over a 5-year period showed that Pseudomonas was resistant to levofloxacin in 13 % percent of cultures and ciprofloxacin in 5 % of cultures [4]. Methicillin-resistant S. aureus was seen in 21 % of cultures. Most importantly, it was reported that 62 % of cultures were resistant to at least one antibiotic. This highlights the dramatic prevalence of antibiotic resistance that we are facing. Because of the aforementioned issues, when possible endoscopic-directed culture should be obtained to decrease the use of broad-spectrum antibiotics [5].

There is a surprising lack of high level evidence supporting the use of antibiotics in the treatment of CRS, in fact there have been no randomized placebo-controlled studies evaluating the treatment of CRS with oral antibiotics. Currently, no antibiotic agents are approved for the use in CRS by the US Food and Drug Administration [6].

Because of their inherent anti-inflammatory properties, macrolides often receive special mention when discussing antibiotic management of CRS. This immunomodulatory effect was first noted during the treatment of diffuse panbronchiolitis in which profound neutrophilic inflammation is seen [7]. Macrolides exert their anti-inflammatory effect in multiple ways, all of which lead to the protection of the mucosa from the negative effects of prolonged neutrophil activity. Macrolide immunomodulatory effects stem from their ability to alter cytokine profiles and decrease damaging free radical production [8, 9]. Another important characteristic of macrolides is their ability to prevent biofilm adherence [10]. Unfortunately, studies evaluating the clinical benefit of these properties in CRS patients are mixed. Of note, a placebo-controlled study by Wallwork et al. evaluating the use of macrolide therapy showed improved symptomatic control in a subgroup with normal or low IgE levels [11]. Further studies should be done, especially in this subset of patients in order to evaluate the effectiveness of oral macrolide therapy in the management of CRS.

There is very little in literature to support the use of intravenous antibiotics in the management of CRS. Indications for IV therapy include the presence of resistant organisms, intracranial or orbital complications, and intolerance to oral medications [12]. Although personal experience and several prior studies suggest that the underlying bone plays a significant part in making CRS resistant to therapy, there is currently no evidence for bacterial infection within the bone, and thus osteitis is not an indication for IV antibiotic therapy.

The goal of topical antibiotic therapy is to provide high concentrations of antimicrobials directly to the mucosa with the hope of eliminating the systemic absorption and side effects of traditional oral antibiotics. Although frequently utilized, currently little data exists to support efficacy in CRS. A recent meta-analysis of four randomized controlled clinical trials evaluated the use of topical antibacterial therapy [13]. Three of these studies showed no benefit of topical antibiotics; however, as pointed out by Cain and Lal [14], none of these studies utilized the high-volume low-pressure delivery technique that has been shown to be most beneficial in sinonasal topical delivery. Another study evaluated the use of topical mupirocin irrigation versus saline irrigation in post-endoscopic sinus surgery patients with positive S. aureus cultures [15]. At the 1-month time point, none of the patients treated with mupirocin irrigation had a positive culture, and endoscopic scores were improved, while 88.9 % of patients treated with saline irrigations had a positive culture. However, symptom scores were not statistically different. A 2007 review of the literature evaluated 14 studies with varying levels of evidence and suggested an overall low level of evidence for the use of topical antibacterials with the highest level of evidence existing in the postsurgical patients and in culture-directed therapy [16].

One hope is that topical delivery of antibiotic avoids systemic absorption; however, two studies utilizing gentamicin irrigation demonstrated mixed results [17, 18]. Taking these two studies into consideration, it appears that there may be a systemic accumulation of gentamicin over time. Further studies should be done in order to evaluate this topic and determine a safe duration of topical therapy especially in the case of gentamicin.

Fungi were originally proposed as the causative agent in CRS [19]. However, this has generally been discredited, and a placebo-controlled double-blind study using high-dose terbinafine showed no difference between active and placebo medication [20]. That said, personal clinical experience demonstrates that a small subset of patients with eosinophilic polypoid disease do appear to respond to oral itraconazole, although this may result from the antiangiogenesis effect of the medication rather than its antifungal effect. Given the hepatotoxic effects and potential cardiotoxic effects of the medication and its cost, as well as our inability to predict the small subset who will respond, itraconazole should be utilized sparingly and usually as a last resort. A review of the literature on oral antifungal therapy in the treatment of CRS was performed in 2011 and suggested some potential benefit from using itraconazole and ketoconazole, but the level of evidence was low [21].

A variety of studies have evaluated the use of topical antifungal agents, and although an initial randomized controlled trial evaluating the use of topical amphotericin B appeared promising, this was not replicated in subsequent studies, and the use of topical antifungals is not recommended [22–26]. However, it should be noted that there have been no studies evaluating the use of oral or topical antifungals specifically in patients with allergic fungal sinusitis (AFS).

The evidence supporting the use of systemic steroids varies among patients with CRSsNP, CRSwNP, and allergic fungal sinusitis (AFS). One literature review demonstrated that the level of evidence for the use of oral steroids in CRSsNP is low [27]. The use of systemic steroids in patients with CRSwNP is much more compelling both in clinical practice and in the literature, with evidence of improvement in nasal symptoms and airflow and reduction in polyp size [28–30]. Additionally, pretreatment with a short course of oral steroid followed by prolonged topical steroid therapy may be beneficial [31]. Similarly, the evidence is very strong for the use of oral steroids as an adjunct in the treatment of allergic fungal sinusitis (AFS) [31, 32]. However, since steroid use can occasionally induce fungal invasion in AFS, the prolonged use of steroids in the absence of surgical removal of bony partitions is not recommended.

It is important to keep in mind that side effects associated with systemic steroid use are common and include decrease in bone density, HPA axis suppression, hyperglycemia, weight gain, acne, cataract formation, mood alteration, insomnia, and gastric complications. The rare but devastating side effect of avascular necrosis should also be considered when weighing their use, and the use of oral steroids should be limited in patients with preexisting osteoporosis, diabetes, glaucoma, or a history of mental health issues. The risk to benefit ratio should be weighed on a patient to patient basis bearing in mind that the data are significantly more supportive of systemic steroid therapy in the setting of CRSwNP and AFS compared to CRSsNP.

Topical steroid preparations are the mainstay of treatment for allergic rhinitis, CRSwNP, and AFS but as with systemic steroids, their efficacy is less well documented in CRSsNP. FDA-approved, low-dose intranasal steroid sprays are known to be well tolerated with low bioavailability. An increased risk of epistaxis has been reported in patients who use steroid sprays improperly, live in dry climates, or use fluticasone propionate. Other side effects include nasal irritation and dryness, headache, and cough [33, 34].

For maximal effect, many rhinologists prefer the off-label use of topical steroids delivered in high-volume, high-dose method. It is believed that, in addition to the cleansing effect of the irrigation, this allows higher concentration of the topical steroid to be applied more diffusely throughout the sinonasal passages. However, at this point in time, there is little high-quality data to support the use of these medications and no long-term safety data. One 6-week study using 0.5 mg of budesonide mixed in 240 ml of saline over a 6-week period did not show any evidence of suppression of serum cortisol or urinary cortisol levels [35]. Similarly, a study of fluticasone propionate irrigation (3 mg in 240 ml of saline twice daily for 6 weeks) did not show evidence of suppression of salivary cortisol levels or ocular changes [36].

A recent retrospective review of prospectively collected data assessed the use of budesonide nasal irrigations (BNI) [37]. Subgroup analysis showed SNOT-20 scores were significantly improved with the use of BNI for patients with eosinophilic CRS (eCRS) and aspirin-exacerbated respiratory disease (AERD). Endoscopy scores were significantly improved only in the eCRS group. More prospective, randomized trials evaluating the efficacy and long-term safety of high-dose-high-volume steroid nasal irrigations are needed.

It has been shown that topical steroid delivered is useful in treating patients with CRS; however, delivery of a drug in such a manner is fraught with uncertainty including the amount of drug reaching the mucosa, duration of contact with the mucosa, difficulty reaching areas such as ethmoid and frontal sinuses, as well as patient compliance issues. Bioabsorbable steroid-eluting implants (SEIs) are now available. SEIs deliver a known dose of steroid to the mucosa over a known period of time. With SEIs, there is minimal systemic absorption of steroid, and there is no reliance on patient compliance.

The currently FDA-approved SEIs are the Propel and Mini-Propel Steroid-Releasing Implants (IntersectENT, Menlo Park, CA). The Propel implant contains 370 μg of mometasone furoate embedded in a spring-like polylactide-co-glycolide polymer matrix [38]. This implant is bioabsorbable and lasts approximately 30 days if left in place. A recent meta-analysis by Han et al. pooled data from two previous studies [39]. A total of 143 patients at 11 centers were evaluated. There was found to be a significant decrease in adhesions on the treatment side, reduction in middle turbinate lateralization, and decreased need for postoperative interventions (lysis of adhesions and postoperative oral steroids). Currently, a multicenter study is evaluating outpatient placement of a 90-day SEI placed in patients with recurrent ethmoid sinusitis who would otherwise be candidates for revision surgical intervention [40].

Allergic rhinitis and nonallergic rhinitis have been shown to be significant risk factors in the development of CRS [41]. In patients with refractory CRS, it was noted that the prevalence of allergy was approximately 60 %, while the prevalence was greater than 80 % in patients requiring endoscopic sinus surgery [42]. Nasal polyps are felt to be a result of a persistent inflammatory state. There is currently no data suggesting the benefit of immunotherapy in the treatment of patients with CRS, and the role of allergy in nasal polyp development is still unknown [43]. Because there is a theoretic benefit, low risk of severe side effects, and no negative long-term effects from the administration of immunotherapy, allergy testing and subsequent desensitization are often recommended for patients with eosinophilic chronic rhinosinusitis and allergic rhinitis [44].

Although the use of antihistamines provides symptomatic relief in allergic rhinitis, there is limited data to support the use of antihistamines in the treatment of CRS. One randomized double-blind placebo-controlled trial placed patients with acute exacerbations of sinusitis into two groups. Both groups were treated with 2 weeks of antibiotics and 10 days of oral corticosteroids, while one group was given a placebo and the other loratadine. The loratadine group reported a significant decrease in sneezing at 14 days and nasal obstruction at 28 days. Physicians also reported subjective improvement in patients in the loratadine group [45]. Despite the lack of data, nonsedating antihistamines are often prescribed as a component of the medical management of CRS.

Leukotrienes have also been proposed as having a beneficial role in treating patients with chronic rhinosinusitis when a significant allergic component is present or in patients with aspirin triad. However, again, support for their use in CRS from the literature is limited [46–49].