Macrolide Therapy Research Articles

Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis.

Long-term macrolide therapy reduces rates of pulmonary exacerbation in bronchiectasis. However, little is known about the potential for macrolide therapy to alter the composition and function of the oropharyngeal commensal microbiota or to increase the carriage of transmissible antimicrobial resistance. We assessed the effect of long-term erythromycin on oropharyngeal microbiota composition and the carriage of transmissible macrolide resistance genes in 84 adults with bronchiectasis, enrolled in the Bronchiectasis and Low-dose Erythromycin Study (BLESS) 48-week placebo-controlled trial of twice-daily erythromycin ethylsuccinate (400mg). Oropharyngeal microbiota composition and macrolide resistance gene carriage were determined by 16S rRNA gene amplicon sequencing and quantitative PCR, respectively. Long-term erythromycin treatment was associated with a significant increase in the relative abundance of oropharyngeal Haemophilus parainfluenzae (P = 0.041) and with significant decreases in the relative abundances of Streptococcus pseudopneumoniae (P = 0.024) and Actinomyces odontolyticus (P = 0.027). Validation of the sequencing results by quantitative PCR confirmed a significant decrease in the abundance of Actinomyces spp. (P = 0.046). Erythromycin treatment did not result in a significant increase in the number of subjects who carried erm(A), erm(B), erm(C), erm(F), mef(A/E), and msrA macrolide resistance genes. However, the abundance of erm(B) and mef(A/E) gene copies within carriers who had received erythromycin increased significantly (P < 0.05). Our findings indicate that changes in oropharyngeal microbiota composition resulting from long-term erythromycin treatment are modest and are limited to a discrete group of taxa. Associated increases in levels of transmissible antibiotic resistance genes within the oropharyngeal microbiota highlight the potential for this microbial system to act as a reservoir for resistance.IMPORTANCE Recent demonstrations that long-term macrolide therapy can prevent exacerbations in chronic airways diseases have led to a dramatic increase in their use. However, little is known about the wider, potentially adverse impacts of these treatments. Substantial disruption of the upper airway commensal microbiota might reduce its contribution to host defense and local immune regulation, while increases in macrolide resistance carriage would represent a serious public health concern. Using samples from a randomized controlled trial, we show that low-dose erythromycin given over 48weeks influences the composition of the oropharyngeal commensal microbiota. We report that macrolide therapy is associated with significant changes in the relative abundances of members of the Actinomyces genus and with significant increases in the carriage of transmissible macrolide resistance. Determining the clinical significance of these changes, relative to treatment benefit, now represents a research priority.

Macrolide antibiotics for bronchiectasis.

Macrolide antibiotics for bronchiectasis.

Comparison of the Oral Steroids, Macrolides and Combination Therapy in Nasal Polyposis Patients.

Objectives:In this study, our aim was to compare oral steroid therapy with macrolide therapy and with oral steroid + macrolide (combine) therapy in patients with nasal polyposis (NP).Methods:All patients were treated with nasal steroid therapy for eight weeks and divided randomly into three groups as follows: Oral steroid group, oral macrolide group and combine group. All patients underwent endoscopic staging, radiological grading, odour testing and completed the sino-nasal outcome test-22 (SNOT-22) questionnaire before and after treatment.Results:Significant improvement was observed in all parameters after treatment in all three groups. All parameters were significantly better in the combined group than in the macrolide group. Comparison of the oral steroid group and macrolide group revealed significantly better radiological grading and odour test changes for the oral steroid group, but no statistically significant differences existed according to endoscopic staging and SNOT-22. The post-treatment SNOT-22 score was significantly better in the combined group than in the steroid group. A comparison of the combined and steroid groups showed better results for the combined group for all parameters, but the differences were not significant.Conclusion:All treatment protocols were effective and the successful use of macrolide indicates its potential as an alternative in patients with contraindications to oral steroid treatment. The combined treatment may demonstrate significantly better results than steroid treatment alone if larger studies with more patients are performed.

Macrolide therapy is associated with reduced mortality in acute respiratory distress syndrome (ARDS) patients.

Macrolides have been associated with favorable immunological effects in various inflammatory disease states. We investigated the association between macrolide therapy and mortality in patients with the acute respiratory distress syndrome (ARDS). This was an unplanned secondary analysis of patients with ARDS within a large prospective observational study of critically ill patients in the intensive care units (ICUs) of two university-affiliated hospitals in the Netherlands. The exposure of interest was low-dose macrolide use prescribed for another reason than infection; we excluded patients who received high-dose macrolides for an infection. The primary endpoint was 30-day mortality. The association between macrolide therapy and mortality was determined in the whole cohort, as well as in a propensity score matched cohort; the association was compared between pulmonary versus non-pulmonary ARDS, and between two biological phenotypes based on plasma levels of 20 biomarkers. In total, 873 patients with ARDS were analyzed, of whom 158 patients (18%) received macrolide therapy during stay in ICU for a median duration of 3 (interquartile range, 1-4) days. Erythromycin was the most frequent prescribed macrolide (97%). Macrolide therapy was associated with reduced 30-day mortality in the whole cohort [22.8% vs. 31.6%; crude odds ratio (OR), 0.64 (interquartile range, 0.43-0.96), P=0.03]. The association in the propensity score matched cohort remained significant [22.8% vs. 32.9%; OR, 0.62 (interquartile range, 0.39-0.96), P=0.03]. Propensity matched associations with mortality were different in patients with non-pulmonary ARDS vs. pulmonary ARDS and also varied by biological phenotype. These data together show that low-dose macrolide therapy prescribed for another reason than infection is associated with decreased mortality in patients with ARDS.

Long-term macrolides in diffuse interstitial lung diseases.

In the present review we provide currently available evidence for the use of macrolides in the treatment of diffuse interstitial lung diseases (ILDs). Up to now, research on macrolides has mainly focused on three areas. First, macrolides have shown some promising results in cellular models and case reports as antifibrotic agents, by promoting autophagy and clearance of intracellular protein aggregates and acting as regulators of surfactant homeostasis. Secondly, macrolides have an immunomodulatory effect, which has been applied in some organising pneumonia cases. In particular, macrolides have been tested in association with systemic corticosteroids as steroid-sparing agents and alone as either first-line agents in mild cases or second-line agents where steroids were poorly tolerated or had failed. Thirdly, a recent area of research concerns the possible role of macrolides as modulators of lung microbiota and the host-microbiota interaction. This function has been particularly studied in idiopathic pulmonary fibrosis patients, in whom changes in microbiota have been proved to be associated with disease progression. However, the lack of high-quality studies makes the application of macrolide therapy in ILDs a field in which research should be conducted on a large scale.

Prevention of COPD exacerbations: a European Respiratory Society/American Thoracic Society guideline.

This document provides clinical recommendations for the prevention of chronic obstructive pulmonary disease (COPD) exacerbations. It represents a collaborative effort between the European Respiratory Society and the American Thoracic Society.Comprehensive evidence syntheses were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts.After considering the balance of desirable (benefits) and undesirable consequences (burden in the form of adverse effects and cost), quality of evidence, feasibility, and acceptability of various interventions, the Task Force made recommendations for mucolytic, long-acting muscarinic antagonist, phosphodiesterase-4 inhibitor (roflumilast) and macrolide therapy, as well as a conditional recommendation against fluoroquinolone therapy. All of the recommendations were conditional, except for a strong recommendation for the use of a long-acting antimuscarinic agent versus a long-acting β2-adrenergic, indicating that there was uncertainty about the balance of desirable and undesirable consequences of the intervention, and that well-informed patients may make different choices regarding whether to have or not have the specific intervention.The guideline summarises the evidence and provides recommendations for pharmacological therapy for the prevention of COPD exacerbations.

Evaluation of severity score-guided approaches to macrolide use in community-acquired pneumonia.

International guidelines including those in the UK, Japan, Australia and South Africa recommend the avoidance of macrolides in patients with low-severity community-acquired pneumonia (CAP). We hypothesised that severity scores are poor predictors of atypical pneumonia and response to macrolide therapy, and thus, inadequate tools for guiding antibiotic prescriptions.Secondary analysis of four independent prospective CAP datasets was conducted. The predictive values of the CURB-65 and pneumonia severity index (PSI) for clinically important groups of causative pathogens were evaluated. The effect of macrolide use according to risk class was assessed by multivariable analysis.Patients (3297) were evaluated, and the predictive values of CURB-65 and PSI for atypical pathogens were poor (AUC values of 0.37 and 0.42, respectively). No significant differences were noted among the effects of macrolide use on mortality in patients with mild, moderate and severe CAP, according to either CURB-65 (interaction testing severe versus mild disease OR=0.74 (0.29-1.89)) or PSI (severe versus mild disease OR=3.4 (0.055-2.10)), indicating that severity scores were not significant modifiers of response to macrolide therapy.Severity scores did not accurately predict response to macrolide therapy in CAP, suggesting that current guidance to use these tools for empirical antibiotic choices might not be justified.

Inhaled or nebulised ciprofloxacin for the maintenance treatment of bronchiectasis

ABSTRACTIntroduction: Inhaled or nebulised antibiotics are a major topic of ongoing research interest in reducing exacerbations in bronchiectasis. There are no licenced inhaled or nebulised antibiotics currently in bronchiectasis.Areas covered: Inhaled or nebulised ciprofloxacin as a long-term treatment in bronchiectasis.Expert opinion: Results from the Phase III ongoing trials on inhaled or nebulised ciprofloxacin will be key for the outcome of the drugs but additionally, cost-effectiveness and longer-term studies will be necessary to determine the viability of the drug. Head to head studies are needed to decide on the optimum inhaled or nebulised antibiotic and their place with or without long term macrolide therapy. It is also important to determine what treatment is viable for acute exacerbations due to P. aeruginosa. Ciprofloxacin is the only currently available oral agent for exacerbations due to P. aeruginosa. The concern is that using inhaled or nebulised ciprofloxacin will prevent the use and efficacy of its oral equivalent, by developing resistance.

Macrolide-associated sensorineural hearing loss: A systematic review.

To investigate the potential association of macrolide antibiotics with sensorineural hearing loss (SNHL) and which agents and dosage may be related. To evaluate whether an optimal treatment exists for reversing SNHL that occurs after macrolide therapy. Systematic review of the literature. Computerized (PubMed, EMBASE, Cochrane Library) and manual searches were performed to identify human studies of all ages (patients) who received macrolides (intervention, with or without control) and documented SNHL (outcome). All study designs were assessed. Extracted data included macrolide regimen details, as well as the timing, severity, and reversibility of SNHL with drug cessation alone or with additional medical intervention. Study designs and the associated risk of bias were assessed. The 44 publications (3 prospective, 41 retrospective) that met these criteria described 78 cases of audiometrically confirmed SNHL. SNHL was associated with oral and intravenous macrolide administration at standard and elevated doses. SNHL was irreversible in six cases, despite macrolide cessation (n = 5) and oral steroid treatment (n = 1). Irreversible SNHL was observed following 2 to 3 days of exposure. SNHL was reversible with macrolide cessation alone in 70 cases. In two cases, macrolide cessation coupled with oral steroid administration restored hearing. Reversible cases improved within hours to days. Nine studies also described 42 cases of subjective patient-reported hearing loss. Limitations in the data arose from study design, related comorbidities, and concomitant drug administration. SNHL may follow macrolide exposure, even at standard oral doses. Further research is needed to understand the incidence, prevalence, and biological mechanism of its ototoxicity. Laryngoscope, 128:228-236, 2018.

Long-Term Macrolide Therapy for Uncontrolled Asthma

Macrolide antibiotics have antibacterial, antiviral, and anti-inflammatory effects and thus have generated interest for treating patients with asthma.

Detection of markers predictive of macrolide and fluoroquinolone resistance in Mycoplasma genitalium from patients attending sexual health services in England

ObjectivesResistance to both macrolides and fluoroquinolones has been reported in Mycoplasma genitalium; however, due to limited diagnostics, studies are often small and confined to specific geographical areas. This study sought...

Diagnosis and management of bronchiectasis.

KEY POINTS Following a diagnosis of bronchiectasis, it is important to investigate for an underlying cause. Goals of management are to suppress airway infection and inflammation, to improve symptoms and health-related quality of life. There are now validated scoring tools to help assess disease severity, which can help to stratify management. Good evidence supports the use of both exercise training and long-term macrolide therapy in long-term disease management.

Macrolide therapy for community-acquired pneumonia due to atypical pathogens: outcome assessment at an early time point

BackgroundTherapy directed against atypical pathogens in patients with community-acquired pneumonia (CAP) is often recommended. This post-hoc analysis evaluated the effect of addition of a macrolide to ceftaroline fosamil or ceftriaxone treatment in atypical CAP. MethodsTwo phase 3, double-blind, comparative safety and efficacy studies of ceftaroline fosamil vs. ceftriaxone, FOCUS 1 and FOCUS 2, enrolled adults with CAP. Only FOCUS 1 included 24-h adjunctive clarithromycin therapy for all patients on day 1. Day 4 and test-of-cure (TOC) outcomes were compared for adjunctive vs. no adjunctive therapy. ResultsOf 1240 enrolled patients, 130 patients with CAP due to atypical pathogens alone were included (FOCUS 1, n = 64; FOCUS 2, n = 66). Among patients infected with Mycoplasma pneumoniae and/or Chlamydophila pneumoniae alone, a higher clinical response rate was observed with clarithromycin plus ceftaroline fosamil or ceftriaxone compared with treatment without additional clarithromycin at day 4 [38/49 (77.6%; FOCUS 1) vs. 24/43 (55.8%; FOCUS 2)], but not at the TOC assessment [42/49 (85.7%; FOCUS 1) vs. 41/43 (95.3%; FOCUS 2)]. In patients infected with Legionella pneumophila alone, a higher clinical response rate with adjunctive clarithromycin therapy was observed at the TOC assessment alone [12/12 (100%; FOCUS 1) vs. 14/19 (73.7%; FOCUS 2)]. The unadjusted odds ratio of a favourable clinical response at day 4 with adjunctive clarithromycin vs. no adjunctive clarithromycin was 2.4 (95% confidence interval 1.1–5.1; P = 0.0299) for all pathogens combined. ConclusionsThese results suggest that empirical antibiotic therapy against atypical pathogens may improve early clinical response rate. This hypothesis is best evaluated in a prospective trial.

O30 Treatment failure in mycoplasma genitalium among gum clinic attendees

IntroductionMacrolide resistance inMycoplasma genitalium(MG) is of growing concern in countries where azithromycin is used to treat non-gonococcal urethritis(NGU) but UK data is lacking. Patients with NGU or pelvic inflammatory disease (PID) are routinely tested for MG at our clinic and offered test of cure (TOC) 4 weeks post-treatment. We aim to determine rates of MG-positivity 4 weeks after treatment and their associations.MethodsNotes of MG-positive cases between December 2015 and November 2016 were reviewed and data collected on management.Results114 cases of MG were identified. 91(80%) were symptomatic and 12(11%) were MG contacts. Should be 52/339(15%) men with NGU and 15/160(9.4%) women with PID were MG-positive.80/114(78%) were given an azithromycin regimen first line. 59/114(53%) returned for TOC and 24/59(40%) were positive (23 following azithromycin; 1 following moxifloxacin). 19 returned for a second TOC and 14 were negative (1 following azithromycin and 13 following moxifloxacin second line). 5/19(26%) were positive (3 following azithromycin and 2 following moxifloxacin second line). One male patient with confirmed resistance to macrolide and quinolone therapy achieved microbiological cure with pristinamycin.Having a positive TOC was significantly associated with risk of reinfection (p=0.01) and being symptomatic at TOC (p&lt;0.001), but not significantly associated with gender, sexual orientation, HIV status, concurrent STI (p=0.053) and azithromycin use.DiscussionMG-positivity rates at 4 week TOC are high raising concerns of treatment failure although re-infection may also contribute. As commercial assays are imminently available, diagnoses of MG will increase and where possible should be accompanied by antimicrobial resistance testing.

Clarithromycin inhibits TNF-α-induced MUC5AC mucin gene expression via the MKP-1-p38MAPK-dependent pathway

Clarithromycin is a 14-membered macrolide antibiotic. Low-dose, long-term macrolide therapy is effective in patients with chronic airway diseases, such as diffuse panbronchitis, chronic bronchitis, and chronic sinusitis. However, the mechanism underlying this clinical efficacy remains unclear. The dual specificity phosphatase MKP-1 (MAPK phosphatase-1), also called DUSP (dual specificity phosphatase-1), was initially identified as an in vitro ERK-specific phosphatase, but depending on the cell type, it can also dephosphorylate other members of the MAPK family, such as p38 and JNK, and thus suppress downstream signaling of these kinases. It was recently reported that MKP-1 appears to mediate the effects of several anti-inflammatory drugs, including glucocorticoids, but the role of MKP-1 on mucin gene expression in the presence of macrolides in the human airway remains unknown. Here, we demonstrate that the MKP-1 protein is induced by clarithromycin and that clarithromycin suppresses TNF-α-induced MUC5AC mucin gene expression in a p38 MAPK-dependent manner in human airway epithelial (NCI-H292) cells. Our study thus provides new insights into the role of MKP-1 in mediating the effects of macrolides and may help in the development of new therapeutic strategies against mucin overproduction.

Analysis of clinical characteristics and epidemic genotypes of children with Mycoplasma pneumoniae pneumonia

Objective To explore the clinical features of children infected with macrolide-resistant (MR) Mycoplasma pneumonia(MP) isolates and genetic typing of all isolates. Methods Polymerase chain reaction(PCR) of MP positive in 96 nasopharyngeal or bronchoalveolar lavage fluid (BALF) samples were collected from patients diagnosed as MP pneumonia in the Affiliated Children′s Hospital of the Capital Institute of Pediatrics from January 2013 to October 2015.Fifty-five cases were male, 41 cases were female; 19 cases(19.8%) were 1 to 3 years old, 18 cases(18.7%) were more than 3 to 5 years old, 59 cases(61.5%) were more than 5 to 13 years and 2 months old.These samples were tested for MR associated mutations in the 23S rRNA of MP, and were divided into the MR group and the macrolide-sensitive (MS) group.Furthermore, the genotype of all the isolates were performed by conducting P1- restriction fragment length polymorphism(P1-RFLP) analysis and multiple-locus variable-number tandem-repeat analysis(MLVA) method.The clinical characteristics including the age, gender, hospitalization duration, symptoms, signs, fever duration, fever duration after macrolide therapy, white blood cell count, C-reactive protein (CRP), chest X-ray and/or chest computed tomography, which were compared between different groups.SPSS 11.5 software was used to analyze the statistical data.Statistical significance was determined at the 0.05 level of a two-tailed test. Results MR mutations were identified in the 23S rRNA gene in 81 specimens(84%), and the 96 specimens were divided into MR group(81 cases) and MS group(15 cases). There were statistical differences in fever duration, hospitalization duration, the incidence of complications and CRP level between the MR group and MS group (t=2.061, Z=-3.368, χ2=5.856, Z=-2.165, all P 0.05). All the 96 isolates were performed by adopting P1-RFLP typing, but 5 isolates were not typed successfully, while 81 cases(89.0%)isolates were typed as P1-Ⅰ and 10 isolates(11%) were typed as P1-Ⅱc.The hospitalization duration and the fever duration after macrolide therapy in the P1-Ⅰ were longer than the P1-Ⅱc group, and the difference was statistically significant (Z=-2.197, 2.237, all P 0.05). Seventy-three cases (90%)of P1-Ⅰ group were MR isolates, 8 cases (10%) were MS isolates; 3 cases(30%) of the P1-Ⅱc group were MR isolates, 7 cases (70%) were MS isolates.The MR isolates in P1-Ⅰ group were much more than P1-Ⅱc group.There was obvious statistical difference in the proportion of MR isolates between 2 groups(χ2=19.209, P 0.05). Seventy-four cases (90%)of the M4-5-7-2 group were MR isolates, 8 cases (10%) were MS isolates; 4 cases (36%) of the M3-5-6-2 group were MR isolates, 7 cases (64%) were MS isolates.The MR isolates in M4-5-7-2 group were much more than M3-5-6-2 group.There was obviously statistical difference in the proportion of MR isolates between 2 groups(χ2=17.022, P<0.01). Conclusions In the MR group, the children had longer fever duration and hospitalization duration, higher incidence of complications and higher CRP level than those in the MS group.The MR rates of MP in China was high.P1-Ⅰ and M4-5-7-2 are the predominate genotypes.There may be a correlation between genotype and MR. Key words: Mycoplasma pneumoniae; Drug resistance; Macrolides; Genotype

The Role of Macrolides in Chronic Rhinosinusitis (CRSsNP and CRSwNP).

We assess the literature on the pharmacokinetics, indications, important considerations, and effectiveness of long-term, low-dose macrolide antibiotics in chronic rhinosinusitis (CRS). The key to effective implementation of macrolide therapy in CRS is appropriate patient selection. Macrolides have demonstrated the most benefit in Th1-mediated non-eosinophilic CRS when used for durations of at least 3months. Macrolide antibiotics have demonstrated great benefit when used for their anti-inflammatory or immunomodulatory properties, which include the blockage of pro-inflammatory cytokines, such as interleukin (IL)-8 and tumor necrosis factor-α (TNF-α). They have been used in CRS patients not responding to traditional corticosteroid-based treatment regimens, but appear to be most effective specifically in Th1-mediated non-eosinophilic CRS in long durations and low doses. Further research is needed to better identify characteristics known to correlate with macrolide response so early directed therapy can be implemented.

Clinical analysis of mycoplasma pneumoniae pneumonia with 23SrRNA A2063G gene mutation in 24 cases

Objective To analyse the clinical manifestations of mycoplasma pneumoniae pneumonia(MPP) with 23SrRNA A2063G gene mutation, and improve the ability of diagnosis and treatment of patient infected with MPP. Methods MP-DNA was detected by fluorescent quantitative real-time PCR in sputum specimens from 36 children with MPP, then we detected the drug resistance gene mutation sites by nest-PCR and DNA sequencing, on this basis we classified into two groups of macrolide-resistant MP and macrolide-sensitive MP, and compared the clinical manifestations, laboratory findings, chest imagings and treatment between two groups. Results Of these 36 cases of MPP, 24 cases had macrolide -resistant gene mutation with an A2063G transition in domain V of the 23SrRNA, 12 cases had no macrolide-resistant gene mutation.Compared to macrolide-sensitive MP group, macrolide-resistant MP group had longer hospitalization duration, longer total cough period, longer total febrile period, longer fever duration after macrolide therapy, longer course of disease, and had higher white blood cells counts and CRP.In the macrolide-resistant MP group, the temperature subsided within 5 days after macrolide treatment alone of 12 cases, 3 cases needed switch to fluoroquinolones therapy, 10 cases combined with glucocorticoids and 6 cases combined with intravenous immunoglobulin, all 24 patients had good outcomes.While in macrolide-sensitive MP group, the temperature susided between 12 hours to 3 days after macrolide treatment of 8 cases. Conclusions Compared to patients infected by macrolide-sensitive MP, those mycoplasma pneumoniae pneumonia patients with 23SrRNA A2063G gene mutation have longer hospitalization duration, longer total cough period, longer total febrile period, longer fever duration after macrolide therapy, longer course of disease, and have higher white blood cells counts and CRP.Some macrolide-resistant MPP patients have good response to macrolide antibiotics treatment, while the severe cases need combined with glucocorticoids and immunoglobulin, or should change antibiotics. Key words: Mycoplasma pneumoniae pneumonia; Clinical manifestation; 23SrRNA gene mutation; Drug resistance; Glucocorticoids

Effectiveness of Long-Term Macrolide Therapy in Cryptogenic Organising Pneumonia

Background: Cryptogenic organising pneumonia (COP) is an idiopathic pneumonic process featured by a high sensitivity to steroids, but also by a fairly high relapse rate. Accordingly, treatment needs to be protracted more than expected, leading to occurrence of side effects and need for therapeutic changes in many patients. There is an increasing evidence that long-term macrolides can effectively control disease in such situations. Keywords: BOOP, COP, cryptogenic organising pneumonia, idiopathic bronchiolitis obliterans with organising pneumonia, Immunomodulation, macrolide.

The role of infection and antibiotics in chronic rhinosinusitis.

ObjectiveTo review the current understanding of the role of infection and antibiotics in chronic rhinosinusitis.Review methodsPubMed literature searchResultsChronic rhinosinusitis (CRS) in adults is an inflammatory condition and the role of infection is unclear. Biofilms are present in both CRS and normal patients so their role in CRS is unknown. Sinus cultures in CRS demonstrate a mixture of aerobic and anaerobic bacteria but may be hard to interpret due to contaminating nasal flora. Staphylococcus aureus is common in CRS patients but also present in 20‐30% of nasal cultures in the normal population; eradicating this organism did not lead to symptom improvement versus placebo in a randomized controlled trial (RCT). In CRS patients who develop an episode of acute rhinosinusitis (ARS), bacteria typical of ARS can generally be cultured and require short‐course treatment. For CRS, topical antibacterial or antifungal agents have shown no benefit over placebo in RCTs, although RCTs of topical antibacterial agents have been small. Oral macrolides and doxycycline, antibiotics with anti‐inflammatory properties, are the only systemic antibiotics that have been evaluated in RCTs. One RCT found 3 weeks of doxycycline beneficial in patients with polyps but follow up was short (<3 months); RCTs of prolonged macrolide therapy have produced mixed results, and most show no benefit after cessation of therapy. Long‐term antibiotic therapy may produce side effects and select increasingly resistant flora. The American Academy of Otolaryngology—Head and Neck Surgery guidelines recommend against treatment of CRS with antifungal agents but do not comment on the role of antibacterial treatment.ConclusionThe role of infection in CRS is unknown, and the only well‐defined role for antibiotics is for treatment of ARS episodes or their infectious complications.Level of EvidenceN/A.