Mupirocin inhibits bacterial isoleucyl-tRNA synthetase, leading to disruption of protein synthesis. Mupirocin has bacteriostatic and bactericidal effects against most aerobic gram-positive bacteria in both planktonic and biofilm form, with less activity against gram-negative and anaerobic bacteria. With regard to the common bacteria in recalcitrant CRS, mupirocin displays high levels of activity against S. aureus, including MRSA, with low activity against P. aeruginosa. The MIC of mupirocin for S. aureus has been found to be 0.12–1.0 μg/mL, and the minimal bactericidal concentration (MBC) has been found to be 4–32 μg/mL [37]. The MIC for MRSA is 0.5–2 μg/mL [38]. It has been suggested that topical antibiotic regimens be formulated with anti-biofilm intent, requiring antibiotic concentrations well above the MIC of a given bacterium’s planktonic form [33]. Ha et al. performed in vitro testing of mupirocin on S. aureus and showed that a concentration of 125 μg/mL was able to reduce the biofilm mass by over 90 % [13].

The pharmacokinetics and dynamics of mupirocin sinonasal irrigations have mostly been extrapolated from topical skin applications. Mupirocin undergoes rapid degradation to an inactive metabolite in serum, and studies using topical skin preparations of mupirocin have revealed no detectable levels of the drug in serum after standard therapeutic dosages for 3–5 days [39]. No studies have assessed mupirocin serum levels after sinonasal irrigations. Very few minor adverse effects have been reported with topical intranasal mupirocin use, such as local irritation [28]. There is a theoretical risk of mupirocin causing renal damage given its renal excretion and polyethylene glycol base. Patients with renal insufficiency could therefore be at higher theoretical risk. However, no studies to date have documented nephrotoxicity.

Antimicrobial resistance is another potential concern, and variable resistance rates have been reported with topical mupirocin use. A resistance rate of 2.4 % was shown after 1 month of topical mupirocin sinus irrigations [40], while higher resistance rates of 11–65 % have been reported in areas of widespread topical mupirocin use [41–44].

Topical mupirocin is available as either a 2 % ointment or cream, both being formulated with polyethylene glycol base. While the cream is more water soluble, the ointment will dissolve in saline if mixed vigorously (Fig. 14.1). Since the cream is significantly more expensive, the ointment is more commonly used. Mupirocin irrigations have been formulated most commonly as 0.05 % solutions. This can be achieved by dissolving 120 mg of mupirocin into 240 mL of saline, often in a positive-pressure squeeze bottle. It is usually administered twice daily, for about a month [28, 29]. The effective mupirocin concentration of 500 μg/mL is significantly greater than the MIC and MBC of both S. aureus and MRSA.

Mupirocin irrigations have shown promising results in several in vivo studies of CRS patients with S. aureus and MRSA-positive recalcitrant CRS. Solares et al. retrospectively reviewed their use of topical mupirocin irrigations to treat 42 MRSA-related CRS exacerbations in 24 patients. They used a 22 g/L (0.02 %) solution, administering 50 mL twice daily for 4–6 weeks, either alone or in combination with oral antibiotics. Although topical mupirocin resulted in symptomatic improvement for 67 % of cases, 50 % of patients experienced symptom recurrence during the mean follow-up period of 11.8 months. The authors concluded that while the benefit from topical mupirocin may be temporary, it may be a less morbid alternative than IV antibiotic therapy for MRSA-positive CRS exacerbations [32].

Uren et al. performed a small prospective, observational cohort pilot study of 16 recalcitrant CRS patients, evaluating the effects of 0.05 % mupirocin irrigations twice daily for 3 weeks in patients with S. aureus-positive refractory CRS. Fifteen patients demonstrated S. aureus culture negativity at the conclusion of treatment, implying mupirocin irrigations were effective at eradicating the planktonic forms of S. aureus. Patients also had improved endoscopic and overall symptom scores with minimal adverse effects. No long-term follow-up was performed [28].

Jervis-Bardy et al. recently performed a retrospective review of 57 recalcitrant CRS patients treated with 0.05 % mupirocin nasal irrigations for 1 month and followed them long term. These patients had a 73.7 % rate of S. aureus positivity on repeat culture, with a mean relapse time of 144 days. Sensitivities from the repeat cultures revealed only 1 patient developed mupirocin resistance, for an overall resistance rate of 2.4 % [40].

Jervis-Bardy et al. also conducted a double-blinded RCT utilizing mupirocin irrigations. Twenty-five S. aureus-positive recalcitrant CRS patients with persistent symptoms after ESS were administered either 0.05 % topical mupirocin or placebo saline irrigations for 1 month. The mupirocin treatment group showed a culture negativity rate of 89 %, compared with 0 % of controls. They also showed both symptomatic and endoscopic improvement compared to controls. At a 3-month follow-up visit, while cultures remained negative in 85 % of patients, prior symptomatic and endoscopic improvement had deteriorated to baseline [29].

An in vivo study in rabbits by Chiu et al. assessed the response of P. aeruginosa biofilms in rabbit maxillary sinuses to topical tobramycin irrigations through a maxillary sinus catheter. At standard therapeutic concentrations (80× MIC), topical tobramycin was effective against planktonic bacteria, but could not eradicate biofilms, even at significantly higher concentrations (400× MIC) [45].

Sykes et al. performed the first double-blinded RCT of intranasal topical antibiotics for CRS. Fifty CRS patients were randomized to receive one of three empiric treatment regimens by nasal spray delivery: dexamethasone and tramazoline with neomycin, dexamethasone and tramazoline without neomycin, or a placebo of propellant alone. Patients administered the medication as a metered-dose spray four times daily for 2 weeks. Both of the treatment groups showed improvement over placebo, but there was no significant difference in outcomes between the two treatment groups [25].

Moss and King performed a nonrandomized controlled trial with 51 cystic fibrosis patients with recalcitrant CRS and treated them with either a combination of surgery and postoperative tobramycin irrigations (n = 32) or surgery alone (n = 19). Through maxillary sinus catheters placed intraoperatively, patients with positive P. aeruginosa cultures were administered 1 mL (40 mg) of tobramycin per side three times daily for the first 7–10 postoperative days. Thereafter the catheters were removed, but the patients still received 1 mL of tobramycin irrigations directly into the maxillary sinus by way of a curved suction under endoscopic guidance at monthly follow-up visits. A statistically significant decrease in nasal polyposis and the need for revision surgery were reported in the tobramycin surgery group (22 %) versus controls (72 %) [30].

Desrosiers et al. performed an RCT with 20 recalcitrant CRS patients who had failed medical and surgical intervention. Patients were randomized into one of two treatment groups: nebulized tobramycin (4 mL, three times daily for 4 weeks) or nebulized saline-quinine placebo. No differences in postoperative symptom or quality of life scores were found between the tobramycin and placebo groups [26].

Wei et al. evaluated 40 pediatric CRS patients, only evaluating patients who had not undergone sinus surgery. Patients received either gentamicin/saline irrigation or saline placebo irrigation (40 mL daily × 6 weeks). While both groups of patients improved symptomatically, no differences were noted between the groups [34].

Minor side effects from topical nasal aminoglycoside use have been reported. Vaughan and Carvalho reported sore throat and cough after nebulized tobramycin in 7–10 % of patients [27]. Desrosiers et al. also reported a significantly higher rate of nasal congestion with nebulized tobramycin compared with placebo [26]. There have also been concerns raised with topical aminoglycoside use and the potential for nephrotoxicity and ototoxicity. Two small pilot studies demonstrated that gentamicin was detectable in serum after nasal irrigations, though no otologic or renal complications occurred [35, 46]. While the serum levels in those studies were considered nontoxic, there have been reports of nontoxic serum levels still leading to ototoxicity and, therefore, remains a potential concern with these antibiotics.

Ceftazidime is a third-generation cephalosporin with broad-spectrum activity against S. aureus and P. aeruginosa. Leonard et al. reported retrospectively on 50 recalcitrant CRS patients treated with 0.1 % ceftazidime irrigations (300 mL, three times daily). Both symptomatic and endoscopic improvements were noted [36].

Videler et al. treated 14 patients with S. aureus-positive recalcitrant CRS with either nebulized bacitracin-colimycin or saline for 8 weeks, following 2 weeks of oral levofloxacin. While both the nebulized antibiotic and saline groups improved in symptom and quality of life scores, no significant difference was demonstrated between the two treatment groups [47].

Other antibiotics have been formulated into topical solutions, although in vitro studies have shown that S. aureus is less susceptible to many of these agents. For example, the MICs for vancomycin and ciprofloxacin were found to be >1,000 μg/mL [13], and moxifloxacin was found to be effective at lowering S. aureus counts only when formulated as a concentration 1,000× the MIC [10].

Three systematic reviews have been conducted recently to assess the efficacy of topical antibiotics in the management of CRS. Lim et al. reviewed nine studies on topical antibiotic use, though only 1 RCT was available. Uncontrolled studies showed clinical improvements in CRS patients receiving topical antibiotics, with most benefit being noted for postsurgical patients, culture-directed therapy, and higher-volume delivery. The authors concluded that topical antibiotics should not be first-line management but may be attempted in patients refractory to oral antibiotics and traditional topical steroids [48].

Rudmik et al. reviewed 3 RCTs that assessed topical neomycin spray, nebulized tobramycin, or nebulized bacitracin-colimycin, and they also evaluated the review by Lim et al. [31]. Soler et al. reviewed nine studies on topical antibiotic use, of which three were RCTs. A wide variety of antibiotic classes were studied across the studies reviewed, as well as a wide variety of delivery methods [11]. This review was the only review that evaluated the study on mupirocin irrigations by Uren et al. [28], but did not review the mupirocin RCT by Jervis-Bardy et al. [29]. Both reviews by Rudmik et al. and Soler et al. reached similar conclusions that, based on current levels of evidence, topical antibiotics cannot be recommended for routine use in CRS. However, they may still play a role in certain subsets of recalcitrant CRS [11, 31].