Comparison of outcomes following culture directed vs non culture directed antibiotics in treatment of acute exacerbations of chronic rhinosinusitis

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(1)ORIGINAL ARTICLE. Comparison of outcomes following culture-directed vs non–culture-directed antibiotics in treatment of acute exacerbations of chronic rhinosinusitis Carol H. Yan, MD1 , Navarat Tangbumrungtham, MD1,2 , Ximena A. Maul, MD1,3 , Yifei Ma, MS1 , Jayakar V. Nayak, MD, PhD1 , Peter H. Hwang, MD1 and Zara M. Patel, MD1. Background: Acute exacerbations in patients with chronic rhinosinusitis (CRS) are oen treated with courses of systemic antibiotics. Poor correlation between microbiologic culture results and the sinus microbiome in CRS has caused increased debate as to the relevance of culturedirected antibiotics. There is currently sparse data comparing outcomes of culture-directed antibiotics vs non-culturedirected antibiotics for treatment of CRS. Methods: This work reports a retrospective review. A total of 946 CRS patients treated with antibiotics were examined; 122 CRS patients with acute exacerbations were treated with culture-directed (n = 61) vs empiric (n = 61) antibiotics. Lund-Kennedy (LK) and 22-item Sino-Nasal Outcome Test (SNOT-22) scores were compared pretreatment and posreatment, with short-term (<1 month) and longterm (1-6 months) follow-up. Patient demographics, comorbidities, and prior surgical history were collected. Results: Both groups had similar pretreatment SNOT22 scores (p = 0.25) while the culture group had higher baseline LK endoscopy scores (p < 0.01). All data were adjusted for pertinent comorbidities, surgical history, cotherapeutics, and baseline scores. There was no difference in improvement in culture-directed and empirically treated groups in the short-term (p = 0.77) and long-term. (p = 0.58) for minimal clinically important difference (MCID) of SNOT-22 and no difference in the short-term for LK scores (p = 0.11), but there was significantly more improvement in long-term LK scores in the culture-directed group (p = 0.01). Conclusion: Culture-directed therapy improves long-term endoscopy scores but does not yield an advantage in improving short-term endoscopy scores, nor in improving short-term and long-term quality of life scores in CRS patients. A prospective study is necessary to examine the relevance of routine microbiologic cultures in CRS C 2018 ARS-AAOA, LLC. patients. . Key Words: chronic rhinosinusitis; exacerbation; culture; infection; antibiotic; SNOT-22; quality of life; Lund-Kennedy; therapeutics How to Cite this Article: Yan CH, Tangbumrungtham N, Maul X, et al. Comparison of outcomes following culture-directed vs non-culturedirected antibiotics in treatment of acute exacerbations of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2018;8:1028–1033.. C 1 Department. of Otolaryngology–Head and Neck Surgery, Stanford University, Stanford, CA; 2 Department of Otorhinolaryngology, Ramathibodi Hospital, Bangkok, Thailand; 3 Department of Otolaryngology, Pontificia Universidad Católica de Chile, Santiago, Chile. Correspondence to: Zara M. Patel, MD, Department of Otolaryngology–Head and Neck Surgery, 801 Welch Road Stanford, CA 94305; e-mail: C.H.Y. and N.T. contributed equally to this work. Potential conflict of interest: None. Presented at the ARS Meeting at the annual Combined Otolaryngology Spring Meetings (COSM) on April 18-22, 2018, National Harbor, MD. Received: 3 March 2018; Revised: 23 April 2018; Accepted: 3 May 2018 DOI: 10.1002/alr.22147. 1028. hronic rhinosinusitis (CRS) is a prevalent and debilitating condition that has a significant quality of life (QOL) impact and a large economic burden. It affects approximately 11% of the general U.S. population based on a national 2015 survey.1 Despite its widespread prevalence, the multifactorial nature of CRS pathophysiology has limited our ability to target therapy effectively. There is evidence that microorganisms play a critical role in the persistent inflammation and exacerbation of CRS.2 Although their indications are debated, antibiotics are often prescribed as a first-line medication for CRS treatment.. View this article online at International Forum of Allergy & Rhinology, Vol. 8, No. 9, September 2018.

(2) Utility of routine culture in sinusitis treatment. In fact, CRS is the most common diagnosis for antibiotic prescriptions at outpatient visits, accounting for 7% of all antibiotic visits.3 In the treatment of CRS exacerbations, sinus cultures are often obtained to guide treatment with antibiotics. Although it has been suggested that antibiotics may not change the clinical course of disease, expert opinion and consensus guidelines have favored the use of short-term antibiotics for acute CRS exacerbations in the setting of a positive culture.4–6 Endoscopic-guided cultures and use of culture-directed antibiotics result in improved sinonasal symptoms and QOL outcome scores, although this has not been directly compared to empiric antibiotics.7 In previous studies, patients treated with culture-inappropriate antibiotics (eg, those not covered by culture sensitivity profiles) have decreased QOL improvement compared to those treated with culture-appropriate antibiotics, but this difference was no longer apparent at 6-month follow-up.8 The implications of a positive sinus culture remain unclear as single-organism growth may not represent disease causality. Emerging research in the sinus microbiome has shown a predominance of Staphylococcus aureus and Pseudomonas bacteria in CRS patients but also the presence of a wide polymicrobial variety.7, 9 Treatment with culture-directed antibiotics decreases the abundance of the sinus microbiome, but its effect on species diversity is also debated.10, 11 A sinus culture does not capture the complete microbiome involved in an infected sinus.11 The nonculturable portion of the microbial community has been shown to range between 25% and 99% as certain bacteria taxa require alternative growth conditions to those available in vitro.12, 13 Studies have shown that a standard sinus culture may be a poor representation of the microbiota in chronic sinusitis.9, 14 Miller and Davis15 demonstrated that when multiple cultures were obtained from the same patient intraoperatively, 39% of them grew different pathogens. Despite these different culture results, only 5% prompted a change in antibiotics based on sensitivities.15 The utility of obtaining a routine sinus culture for CRS exacerbations is debatable given its potential limited portrayal of the microbiome and the additional healthcare cost. The benefit of treatment based off a sinus culture vs treatment with empirically prescribed, non-culture-directed antibiotics has not been studied in standard CRS. In this study, we aimed to evaluate QOL outcomes and nasal endoscopy scores in CRS patients treated with antibiotics either guided by a culture or empirically selected.. Patients and methods This was a retrospective study evaluating CRS patients seen at Stanford Sinus Center between 2014 and 2017. Approval was obtained from the Stanford University Institutional Review Board. CRS and acute exacerbation of CRS were diagnosed according to the International Consensus. Statement on Allergy and Rhinology: Rhinosinusitis 2016.16. Study population A total of 946 adult CRS patients with and without nasal polyposis presented to Stanford Sinus Center with an acute exacerbation and were treated with oral antibiotics. Patients who received oral antibiotics in the prior 30 days were excluded as well as those who were not evaluated pretreatment or did not return for follow-up in the allotted time period. A total of 122 patients who were treated with oral antibiotics, underwent pre- and post-treatment endoscopy and completed QOL surveys were included in this study; 61 patients were treated with antibiotics based off an endoscopic-directed sinus culture swab performed at the pretreatment visit and 61 patients were treated with antibiotics without any cultures performed.. Sinus cultures All cultures were obtained using endoscopic-directed swabs from frank purulence found in either the middle or superior meatus. Cultures were collected by attending rhinologists using standard Opti-Tranz culture swabs (Puritan, Guilford, ME). Only aerobic cultures were routinely obtained in this study.. Outcomes QOL outcomes using the 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Kennedy (LK) nasal endoscopy scores were prospectively collected during the initial pretreatment visit and 2 follow-up visits at <1 month (shortterm) and 1 to 6 months (long-term) posttreatment. Changes in SNOT-22 and LK scores along with the achievement of a minimal clinically important difference (MCID)17 in SNOT-22 score, defined as an 8.9-point improvement in SNOT-22, were calculated for each group at short-term and long-term follow-up. Patient age, gender, prior sinus surgery, presence of nasal polyps, aspirin-exacerbated respiratory disease (AERD), eosinophilia, asthma, cystic fibrosis (CF), diabetes mellitus (DM), immunodeficiency, and other comorbidities as defined according to the Charlson criteria18 were retrospectively collected. Concurrent treatments including topical and systemic steroids and topical antibiotics were also recorded.. Statistical analysis Fisher’s exact tests and 2-tailed t tests were used to calculate univariate analyses for categorical and continuous variables, respectively. An adjusted repeated measures model was used to evaluate the difference in LK score change postantibiotic treatment between the non-culture-directed and culture-directed groups. The LK score was log-transformed in order to approximate normal distribution and achieve constant variance. A fully adjusted logistic regression model was used to calculate the predicted probability and odds ratio (OR) of achieving the SNOT-22 MCID following. International Forum of Allergy & Rhinology, Vol. 8, No. 9, September 2018. 1029.

(3) Yan et al.. TABLE 1. Patient demographics*. TABLE 2. Pathogens found on 61 endoscopic-directed. sinus cultures*. Non–culturedirected (n = 61). Culturedirected (n = 61). p. 49.9 ± 15.6. 47 ± 15. 0.61. Male. 30 (49.2). 31 (50.8). Female. 31 (50.8). 30 (49.2). 0.86. 14 (23.0). 21 (34.4). 0.23. Age (years), mean ± SD. Pathogen. Gender, n (%). Nasal polyposis, n (%) AERD, n (%). 0 (0). 3 (4.9). 0.24. Eosinophilia, n (%). 4 (4.6). 4 (4.6). 1.00. 13 (21.3). 1.00. Asthma, n (%). 14 (23). Cystic fibrosis, n (%). 3 (4.9). 1 (1.6). 0.62. DM, n (%). 6 (9.8). 3 (4.9). 0.49. Immunodeficiency, n (%). 5 (8.2). 10 (16.4). 0.27. Charlson index, mean ± SD. 1.3 ± 1.6. 1.1 ± 1.3. 0.60. Prior sinus surgery, n (%). 39 (63.9). 53 (86.9). 0.01. SNOT-22 (pretreatment), mean ± SD. 45 ± 20.6. 40.7 ± 20.2. 0.25. LK score (pretreatment), mean ± SD. 3.4 ± 3.2. 6.6 ± 2.8. <0.01. Baseline topical steroid irrigation, n (%). 57 (93.4). 52 (85.2). 0.24. 8 (13.1). 18 (29.5). 0.05. Baseline topical antibiotic irrigation, n (%). *Bold values are significant at p < 0.05. AERD = aspirin-exacerbated respiratory disease; DM = diabetes mellitus; LK = Lund-Kennedy; SD = standard deviation; SNOT-22 = 22-item Sino-Nasal Outcome Test.. antibiotic treatment between non-culture-directed and culture-directed groups. In this model, patients with pretreatment SNOT-22 scores <9 were excluded. A value of p <0.05 was considered a statistically significant difference for all analyses. SAS version 9.4 (SAS Institute, Inc., Cary, NC) was used for all statistical analyses.. Results A total of 946 CRS patients with acute exacerbations requiring antibiotics were evaluated; 122 patients with pretreatment and posttreatment endoscopy and QOL surveys were included in the study; 61 patients were treated with antibiotics based off an endoscopic-guided sinus culture result while 61 patients were treated without culture guidance. Patient demographics are shown in Table 1. Both groups were similar in age, gender, and comorbidities. A higher percentage of the culture-directed group had undergone prior sinus surgery compared to the non-culturedirected group (86.9% vs 63.5%, p = 0.01). Pretreatment. 1030. Frequency (%). MSSA. 35 (57.3). MRSA. 8 (13.1). Pseudomonas aeruginosa. 7 (11.5). Haemophilus influenza. 6 (9.8). Corynebacterium sp.. 5 (8.2). Streptococcus sp.. 4 (6.6). Enterobacter sp.. 4 (6.6). Escherichia coli. 2 (3.3). Stenotrophomonas sp.. 2 (3.3). Klebsiella sp.. 2 (3.3). Citrobacter sp.. 2 (3.3). Other. 5 (8.2). *Some cultures had multiple pathogens. MRSA = methicillin-resistant Staphylococcus aureus; MSSA = methicillin-sensitive Staphylococcus aureus.. SNOT-22 scores were similar between the 2 groups, but the culture-directed group had higher pretreatment LK scores. The majority of patients in both groups were using topical steroid irrigations, but the culture-directed patients were more likely to be on topical antibiotic irrigations at baseline. Microorganisms identified from culture results in the culture-directed antibiotic group are shown in Table 2. There was a diverse variety of species obtained from the cultures, the most common being Staphylococcus aureus (methicillin-sensitive [MSSA] 46% and methicillin-resistant [MRSA] 10%) followed by Pseudomonas aeruginosa (9%) and Haemophilus influenzae (8%). The choice of antibiotics and concurrent therapies are highlighted in Table 3. In both groups, amoxicillin clavulanate was the most common antibiotic prescribed to treat acute CRS exacerbations. The culture-directed group was more likely to treat patients with trimethoprim/sulfamethoxazole while the non-culture-directed group used clarithromycin more frequently. Only a few patients required additional therapies such as topical irrigations or a second course of oral antibiotics within 6 months of the initial treatment. There was no statistical difference between the 2 groups in receiving additional therapies. Overall, the probability of achieving a SNOT-22 MCID change after antibiotic treatment for CRS exacerbation was 60.9% in the short-term and 56.7% in the longterm. A multivariable logistic regression model was used to compare the predicted probability of achieving a SNOT-22 MCID level between the non-culture-directed and culturedirected groups (Table 4). This model was adjusted for patient demographics including comorbidities, prior sinus. International Forum of Allergy & Rhinology, Vol. 8, No. 9, September 2018.

(4) Utility of routine culture in sinusitis treatment. TABLE 3. Non-culture-directed and culture-directed. TABLE 4. Logistic regression model evaluating predicted. treatments prescribed for CRS exacerbations*. probability of achieving the MCID level of 8.9 SNOT-22 points, following antibiotic treatment in non–culture-directed and culture-directed groups at short-term (<1 month) and long-term (1-6 months) follow-up*. Treatments. Non–culturedirected. Culturedirected. (n = 61). (n = 61). p. Oral antibiotics prescribed, n (%) Amoxicillin/clavulanic acid. Time (months). Odds ratio (95% CI). p. SNOT-22 (MCID). 1. 1.3 (0.2–8.3). 0.77. SNOT-22 (MCID). 6. 1.4 (0.5–4.1). 0.58. Outcome. 25 (41.7). 22 (36). 0.53. 3 (5). 13 (21.3). 0.01. 10 (16.7). 6 (9.8). 0.27. Clarithromycin. 12 (20). 4 (6.6). 0.03. Ciprofloxacin. 5 (8.3). 8 (13.1). 0.40. Levofloxacin. 2 (3.3). 4 (6.6). 0.68. Clindamycin. 2 (3.3). 1 (1.6). 0.62. TABLE 5. An adjusted repeated measure model was used. Moxifloxacin. 1 (1.7). 1 (1.6). 1.00. Amoxicillin. 0 (0). 1 (1.6). 1.00. Ceftriaxone. 1 (1.7). 0 (0). 0.50. to evaluate the change in LK scores in the non–culture-directed and culture-directed groups at short-term (<1 month) and long-term (1-6 months) follow-up post-antibiotic treatment*. Cephalexin. 0 (0). 1 (1.6). 1.00. Duration of antibiotics (days), mean ± SD. 18.5 ± 10. 15.4 ± 4.1. 0.21. Topical steroid irrigation, n (%). 1 (1.7). 0 (0). 0.68. Topical antibiotic irrigation, n (%). 2 (3.3). 4 (6.6). 1.00. Second course of oral antibiotic, n (%). 2 (3.3). Trimethoprim/ sulfamethoxazole Doxycycline. 3 (4.9). 1.00. *Bold values are significant at p < 0.05. CRS = chronic rhinosinusitis; SD = standard deviation.. surgery, and concurrent topical antibiotic and steroids usage. There was statistically no significant difference in their odds of achieving MCID at short-term (OR 1.3; 95% confidence interval [CI], 0.2 to 8.3; p = 0.77) or long-term (OR 1.4; 95% CI, 0.5 to 4.1; p = 0.58) follow-up. In this study, 70.8% patients demonstrated an improvement in LK nasal endoscopy score following antibiotic treatment in the short-term and 60.4% in the long-term. A repeated measure model was used to compare the change in LK scores post-antibiotic treatment between the non– culture-directed and culture-directed groups (Table 5). The effect size represents the difference between the 2 groups as a percentage in LK score reduction. This model was also fully adjusted for all covariates. There was no significant difference in improvement in the short-term following antibiotic treatment between the 2 groups. However, in our long-term follow up, the culture-directed antibiotics group had significant improvement in their LK scores compared to the non-culture-directed group (effect size −49.3%; 95% CI, −68.2 to −19.2; p = 0.01).. *The model was adjusted for covariates including patient age, gender, prior sinus surgery, AERD status, nasal polyposis, eosinophilia, asthma, cystic fibrosis, diabetes mellitus, immunodeficiency, Charlson index, concurrent steroid treatment, and topical antibiotic treatment. AERD = aspirin-exacerbated respiratory disease; CI = confidence interval; MCID = minimal clinically important difference; SNOT-22 = 22-item Sino-Nasal Outcome Test.. Time (months). Effect size (95% CI). p. LK. 1. −38.6 (−66.3 to 12.2). 0.11. LK. 6. −49.3 (−68.2 to −19.2). 0.01. Outcome. *The calculated effect size depicts the difference between the culture-directed and non-culture directed groups as a percentage in LK score reduction. The model was adjusted for all covariates as described in Table 4. CI = confidence interval; LK = Lund-Kennedy.. Discussion Acute exacerbations of CRS (AECRS) contribute to a significant decrease in patient QOL and represent a large healthcare economic burden. Treatment guidelines for AECRS have not been well established. According to the International Consensus statement, there is a tendency to treat AECRS as an episode of acute rhinosinusitis or recurrent acute rhinosinusitis.16 Oral antibiotics are the most frequently prescribed treatment for CRS exacerbations with guidelines supporting short courses of culture-directed antibiotics.4 However, microorganisms that are obtained by cultures may not fully capture the disease microbiome, which often includes a variety of pathogens.14 Many experts have the experience of empirically prescribing an antibiotic only to discover a different culture-directed target, but when the patient is contacted, they still report an improvement on the previously chosen drug. No studies have evaluated the added benefit of obtaining a culture compared to empirically prescribing antibiotics in the setting of acute CRS exacerbations. In our study, when we compared the probability of patients achieving SNOT-22 MCID, there was no difference between the non–culture-directed and. International Forum of Allergy & Rhinology, Vol. 8, No. 9, September 2018. 1031.

(5) Yan et al.. culture-directed groups. This suggests that empirically prescribed antibiotics are as likely to help a patient obtain clinically significant improvement in sinonasal outcomes as culture-guided antibiotics. These findings may reflect on the limited utility of a standard culture in capturing the disease sinus microbiome. In the short term, both culture-directed and empirically prescribed antibiotics improve LK endoscopy scores to the same degree. However, culture-directed patients were more likely to have improved LK endoscopy scores compared to non–culture-directed patients at long-term follow up. This finding may be skewed by the fact that the culture-directed patients were more likely to have undergone prior surgery and had higher baseline LK scores. The sinuses can be evaluated with more granularity postsurgically. Hence, the culture-directed patients may have greater changes in LK score. Similarly, we postulate that topical antibiotic irrigations were more commonly used in the culture-directed group as it is a more often utilized treatment once the sinus cavities have been opened surgically. However, it is important to note that baseline LK scores, prior sinus surgery, along with all patient demographics and clinical characteristics were adjusted for in our multivariate statistical models. Thus, the improved long-term LK endoscopy scores in the culture-directed group may be a true finding. A prior study suggested that in the short term, patients who receive culture-inappropriate antibiotics have less QOL improvement based on change in SNOT-22 score compared to those who receive culture-appropriate antibiotics.8 However, this difference was insignificant after a 6-month follow-up. Our study found a potential value in culture-guidance in nasal endoscopy scores between 1 and 6 months posttreatment but not within 1 month posttreatment. However, there was no additional clinically significant QOL improvement using culture-guided therapy. Also, our study was specifically directed at comparing empirically chosen antibiotics (which in the majority of cases do end up being appropriate therapy) to culture-directed therapy, rather than comparing that with specifically cultureinappropriate antibiotics. In a study by Zhang et al.,8 only 7% of patients treated empirically with trimethoprim/sulfamethoxazole and clindamycin were found to have culture-inappropriate antibiotics. This is far less than 2 other studies that reported a 51.4% and 77% change in antibiotics based on culture results.5, 7 In our study, we do not know how many of the empirically prescribed antibiotics patients received culture-inappropriate antibiotics. Rather, both groups benefited equally from antibiotic therapy when evaluating clinical QOL improvement and only a difference in nasal endoscopy scores was noted in the long term. The microorganisms found in the cultures obtained in our study had a higher than previously reported frequency of Staphylococcus aureus19 and in particular, a high frequency of MSSA (46%). Amoxicillin clavulanate was also. 1032. the most commonly prescribed antibiotic for both culturedirected and empirically-treated antibiotic groups. MSSA is typically sensitive to amoxicillin clavulanate and this coverage may explain why both groups on average showed improvement to antibiotics. Amoxicillin clavulanate was more efficacious than cefuroxime in a randomized control trial for treatment of acute and chronic exacerbations of CRS.20 As amoxicillin clavulanate is a first choice recommendation for treating acute sinusitis exacerbations in multiple guidelines,21, 22 this would likely translate appropriately to real-life prescribing patterns in this country. The limitations of this study include the retrospective nature of the study design and thus the difficulty in controlling for certain variables. Notably, the culture-directed group had a higher baseline LK score, higher percentage who had undergone prior surgery, and more frequent use of topical antibiotic therapy. These variables were adjusted for in our statistical model. A significant number of our CRS patients were treated for acute exacerbations during this study time frame but were excluded from this study as they had either received antibiotics from another provider within 30 days, were not seen for evaluation pre-antibiotic therapy, or did not follow up for evaluation posttreatment within 1 month. This may create an inherent bias in our results as often patients do not follow up because they are symptomatically better. However, this bias would be present in both groups. A randomized prospective study could help control for these different variables and give us more concrete guidelines on whether culture-directed antibiotics should be the mainstay in the routine treatment of AECRS. A further limitation in this study is the inability to detect anaerobic pathogens in our routine cultures. By practice, our in-office cultures capture all aerobic bacteria, but anaerobic cultures are not routinely obtained. Specific anaerobic isolates including Prevotella and Porphyromonas, Fusobacterium, and Peptostreptococcus spp. have been implicated in sinusitis pathogenesis.23 While many of these anaerobes are present in recurrent acute sinusitis of odontogenic origin, studies have shown that they may also be found in cases of chronic indwelling infection.23 Notably, the first-line therapy for CRS exacerbations, amoxicillin clavulanate, generally provides excellent coverage of anaerobic pathogens and this was the most commonly prescribed antibiotic for both groups. Of note, there are many subcategories of the CRS patient population in which we know antibiotic resistance runs high, such as cystic fibrosis (CF) patients and other groups with a history of chronic antibiotic use. Although these patients were included and accounted for in our retrospective review, each subcategory may not have had a high enough number to note specific variances in outcomes. The aim of this study was to evaluate the typical, standard CRS patient population, and at-risk populations should be considered separately.. International Forum of Allergy & Rhinology, Vol. 8, No. 9, September 2018.

(6) Utility of routine culture in sinusitis treatment. Conclusion CRS is one of the most common diseases in the United States, causing significant morbidity and decreased QOL. While culture-directed antibiotics have been encouraged, the additional costs and delay in treatment in obtaining cultures should be considered. In this study we found that culture-directed therapy improved long-term endoscopy. scores compared to empiric therapy but did not yield an advantage in improving short-term endoscopy scores and did not show any advantage in either short-term or longterm QOL scores in CRS patients. A prospective study is necessary to examine the relevance of routine microbiologic cultures in typical CRS patients.. References 1.. 2.. 3.. 4.. 5.. 6.. 7.. Centers for Disease Control and Prevention (CDC). National Center for Health Statistics. National Health Interview Survey (NHIS). Summary Health Statistics: National Health Interview Survey, 2015. Table A-2. Selected respiratory diseases among adults aged 18 and over, by selected characteristics: United States. Atlanta, GA: CDC; 2016. NCHs/NHIS/SHS/2015_SHS_Table_A-2.pdf Boase S, Foreman A, Cleland E, et al. The microbiome of chronic rhinosinusitis: culture, molecular diagnostics and biofilm detection. BMC Infect Dis. 2013;13:210. Smith SS, Evans CT, Tan BK, Chandra RK, Smith SB, Kern RC. National burden of antibiotic use for adult rhinosinusitis. J Allergy Clin Immunol. 2013;132:1230–1232. Fokkens WJ, Lund VJ, Mullol J, et al. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology. 2012;50:1–12. Cincik H, Ferguson BJ. The impact of endoscopic cultures on care in rhinosinusitis. Laryngoscope. 2006;116:1562–1568. Sabino HA, Valera FC, Aragon DC, et al. Amoxicillin clavulanate for patients with acute exacerbation of chronic rhinosinusitis: a prospective, double-blinded, placebo-controlled trial. Int Forum Allergy Rhinol. 2017;7:135–142. Jiang ZY, Kou Y-F, Batra PS. Endoscopic culturedirected antibiotic therapy: impact on patient. 8.. 9.. 10.. 11.. 12.. 13.. 14.. symptoms in chronic rhinosinusitis. Am J Otolaryngol. 2015;36:642–646. Zhang Z, Palmer JN, Morales KH, et al. Cultureinappropriate antibiotic therapy decreases quality of life improvement after sinus surgery. Int Forum Allergy Rhinol. 2014;4:403–410. Feazel LM, Frank DN, Ramakrishnan VR. Update on bacterial detection methods in chronic rhinosinusitis: implications for clinicians and research scientists. Int Forum Allergy Rhinol. 2011;1:451–459. Liu CM, Soldanova K, Nordstrom L, et al. Medical therapy reduces microbiota diversity and evenness in surgically recalcitrant chronic rhinosinusitis. Int Forum Allergy Rhinol. 2013;3:775–781. Merkley MA, Bice TC, Grier A, Strohl AM, Man L-X, Gill SR. The effect of antibiotics on the microbiome in acute exacerbations of chronic rhinosinusitis. Int Forum Allergy Rhinol. 2015;5:884–893. Hoggard M, Wagner Mackenzie B, Jain R, Taylor MW, Biswas K, Douglas RG. Chronic rhinosinusitis and the evolving understanding of microbial ecology in chronic inflammatory mucosal disease. Clin Microbiol Rev. 2017;30:321–348. Browne HP, Forster SC, Anonye BO, et al. Culturing of “unculturable” human microbiota reveals novel taxa and extensive sporulation. Nature. 2016;533:543–546. Hauser LJ, Feazel LM, Ir D, et al. Sinus culture poorly predicts resident microbiota. Int Forum Allergy Rhinol. 2015;5:3–9.. 15. Miller C, Davis GE. Are multiple sinus cultures necessary during sinus surgery for chronic rhinosinusitis? Int Forum Allergy Rhinol. 2018;8:504–508. 16. Orlandi RR, Kingdom TT, Hwang PH, et al. International Consensus Statement on Allergy and Rhinology: Rhinosinusitis. Int Forum Allergy Rhinol. 2016;6(Suppl 1):S22–S209. 17. Hopkins C, Gillett S, Slack R, Lund VJ, Browne JP. Psychometric validity of the 22-item Sinonasal Outcome Test. Clin Otolaryngol. 2009;34:447–454. 18. Quan H, Li B, Couris CM, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol. 2011;173:676-682. 19. Brook I. Microbiology of chronic rhinosinusitis. Eur J Clin Microbiol Infect Dis. 2016;35:1059–1068. 20. Namyslowski G, Misiolek M, Czecior E, et al. Comparison of the efficacy and tolerability of amoxycillin/clavulanic acid 875 mg b.i.d. with cefuroxime 500 mg b.i.d. in the treatment of chronic and acute exacerbation of chronic sinusitis in adults. J Chemother. 2002;14:508–517. 21. Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, et al. Clinical practice guideline (update): adult sinusitis. Otolaryngol Head Neck Surg. 2015;152(2 Suppl):S1– S39. 22. Chow AW, Benninger MS, Brook I, et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012;54:e72– e112. 23. Brook I. 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TABLE 1. Patient demographics *  Non–culture-directed (n = 61) Culture-directed(n= 61) p


Patient demographics * Non–culture-directed (n = 61) Culture-directed(n= 61) p p.3
TABLE 2. Pathogens found on 61 endoscopic-directed sinus cultures * Pathogen Frequency (%) MSSA 35 (57.3) MRSA 8 (13.1) Pseudomonas aeruginosa 7 (11.5) Haemophilus influenza 6 (9.8) Corynebacterium sp


Pathogens found on 61 endoscopic-directed sinus cultures * Pathogen Frequency (%) MSSA 35 (57.3) MRSA 8 (13.1) Pseudomonas aeruginosa 7 (11.5) Haemophilus influenza 6 (9.8) Corynebacterium sp p.3
TABLE 3. Non-culture-directed and culture-directed treatments prescribed for CRS exacerbations *


Non-culture-directed and culture-directed treatments prescribed for CRS exacerbations * p.4
TABLE 4. Logistic regression model evaluating predicted probability of achieving the MCID level of 8.9 SNOT-22


Logistic regression model evaluating predicted probability of achieving the MCID level of 8.9 SNOT-22 p.4



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