Investigation into Antimicrobial Resistance Profiles of Staphylococcus

Introduction

Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease of the upper respiratory tract, primarily characterized by nasal congestion, excessive nasal discharge, headache, and loss of smell, which significantly disrupts patients’ daily life.¹ It is estimated that approximately 12% of adults worldwide are affected by CRS, and the incidence rate continues to rise.² Although most cases can be alleviated with routine treatments such as antibiotics and nasal corticosteroids, some patients experience prolonged disease courses and recurrent symptoms that are difficult to control, often necessitating surgical intervention.³ Furthermore, CRS not only affects patients’ quality of life but may also lead to complications such as chronic cough, pharyngitis, bronchitis, and even impair heart and lung functions.⁴ Therefore, the treatment and management of CRS have become significant challenges for clinicians. The development of CRS is associated with multiple factors, and bacterial infections are considered an important trigger.⁵

Staphylococcus aureus (S. aureus) is one of the most common pathogens in CRS, especially in patients with long-term recurrent symptoms.⁶ This bacterium has strong pathogenicity and produces various toxins that damage the nasal and sinus mucosal barriers, leading to localized inflammatory responses.⁷ Meanwhile, due to its frequent clinical occurrence, the issue of antibiotic resistance in S. aureus has gradually become prominent, particularly with the emergence of methicillin-resistant Staphylococcus aureus (MRSA). MRSA strains are resistant to multiple commonly used antibiotics, and their infections not only complicate treatment but also prolong the course of illness, potentially leading to severe complications such as sepsis and pneumonia, which severely impact prognosis.^8,9 Moreover, due to their high resistance and limited treatment options, MRSA infections significantly increase medical costs, placing a heavy burden on patients and the healthcare system.

Previous studies^10–12 have shown that MRSA infection may be related to several clinical factors, including gender, age, smoking history, disease duration, comorbidities, and the frequency and duration of antibiotic use. However, there is still a lack of systematic research on the specific factors influencing MRSA infection in CRS patients, particularly on how to effectively screen for and prevent MRSA infections.

Therefore, the present study retrospectively analyzed the clinical data of 180 CRS patients in our hospital, aiming to investigate the antibiotic resistance characteristics of S. aureus and to explore the influencing factors of MRSA infection, with the goal of providing valuable reference for clinical diagnosis, prevention, and treatment strategies.

Materials and Methods

Study Subjects

This retrospective analysis included 180 CRS patients admitted to our hospital between February 2022 and July 2024. Inclusion criteria: (1) Met the clinical diagnostic criteria for CRS;¹³ (2) Age ≥18 years, regardless of sex; (3) CRS history >6 months before admission, with recurrent acute exacerbations or chronic symptoms; (4) Nasal secretion samples collected for S. aureus isolation upon admission; (5) Provided written informed consent. Exclusion criteria: (1) Severe immune system diseases (eg, AIDS, immunosuppressive states), malignant tumors, severe heart disease, or liver/kidney dysfunction; (2) Acute sinusitis with a course <12 weeks or recent acute upper respiratory infection; (3) Received systemic antibiotic treatment within the past 6 months; (4) Pregnancy or lactation; (5) Voluntary withdrawal during the study.

Ethical Approval

This study was approved by the Medical Ethics Committee of the People’s Hospital Affiliated to Shandong First Medical University (Approval No.: EBK-GR240012), and was conducted in accordance with the Declaration of Helsinki.

MRSA Identification and Screening

Under nasal endoscopic visualization, sterile cotton swabs were used to collect sinus secretion samples, which were immediately placed in sterile containers and transported to the laboratory. Specimens were considered qualified when the number of squamous epithelial cells was <10 and the number of white blood cells was >25 under low magnification, or the ratio of squamous epithelial cells to white blood cells was <1:2.5. Bacterial identification was performed using the VITEK-2 automated microbiology system (BioMérieux, France). The Kirby–Bauer (K–B) disk diffusion method was used for susceptibility testing, with quality control strain S. aureus ATCC 25923 (National Health and Family Planning Commission Clinical Testing Center). According to the latest Clinical and Laboratory Standards Institute (CLSI) guidelines,¹⁴ strains resistant to oxacillin or cefoxitin were classified as MRSA, and the rest as methicillin-sensitive Staphylococcus aureus (MSSA).

Antibiotic Susceptibility Testing

Susceptibility testing was performed against the following antibiotic classes and agents, with concentrations (μg) indicated for each disk: β-lactams: Cefoxitin (FOX, 30 μg); Aminoglycosides: Amikacin (AK, 30 μg); Fluoroquinolones: Ciprofloxacin (CIP, 5 μg), Levofloxacin (LFX, 5 μg); Oxazolidinones: Linezolid (LIN, 30 μg); Lipopeptides: Daptomycin (DAP, 30 μg); Sulfonamides: Trimethoprim–sulfamethoxazole (SXT, 1.25/23.75 μg); Lincosamides: Clindamycin (CLI, 2 μg); Nitrofurans: Nitrofurantoin (NIT, 300 μg); Macrolides: Erythromycin (E, 15 μg); Rifamycins: Rifampicin (RIF, 5 μg); Glycopeptides: Teicoplanin (TEC, 30 μg), Vancomycin (VA, 30 μg); Tetracyclines: Tetracycline (TE, 30 μg). According to the latest CLSI guidelines.

Analysis of Factors Influencing MRSA Infection

Potential risk factors included sex, age, BMI, disease duration, comorbidities, smoking status, nasal polyps, history of intranasal corticosteroid use, previous nasal surgery, Lund–Kennedy score,¹⁵ frequency/duration of acute infections, nasal septum deviation, allergic rhinitis, frequency/duration of antibiotic use, gastroesophageal reflux, drainage obstruction, combined antibiotic therapy, and serum albumin (ALB) levels. Significant factors in univariate analysis were entered into multivariate logistic regression.

Statistical Analysis

Statistical analyses were performed with SPSS 25.0. Categorical data were expressed as n (%) and analyzed using the chi-square (χ²) test. Continuous variables were expressed as () and compared using the independent-sample t-test. A two-sided P-value <0.05 was considered statistically significant. Graphs were generated using GraphPad Prism 8.

Results

Demographic and Clinical Characteristics

A total of 180 patients with chronic rhinosinusitis were included in this study, comprising 116 males (64.44%) and 64 females (35.56%), with a mean age of 45.20 ± 11.49 years and a mean BMI of 22.32 ± 2.27 kg/m².

Antibiotic Susceptibility Test Results

Among the 180 S. aureus isolates, 74 strains were identified as MRSA and 106 strains as MSSA. The antibiotic resistance profiles are presented in Tables 1 and 2. As shown in Table 1, MRSA exhibited markedly higher resistance rates to FOX, AK, CIP, LFX, CLI, E, RIF, and TE compared with MSSA, and the differences were statistically significant (P < 0.05). No resistance was observed to LIN, TEC, or VA in either group.

Table 1 Antibiotic Susceptibility Results of S. aureus Isolates [n (%)]

Table 2 Comparative Resistance Patterns Between MRSA and MSSA

Univariate Analysis of Factors Influencing MRSA Infection

The results of the univariate analysis showed that, in the MRSA group, male gender, CRS duration >5 years, smoking, allergic rhinitis, nasal structural abnormalities, history of nasal surgery, poor drainage, frequency of acute infections >3 times/year, frequency of recurrent upper respiratory tract infections >3 times/year, frequency of antibiotic use ≥3 times/year, antibiotic use duration >14 days, and use of ≥3 combined antibiotics had statistically significant differences compared with the MSSA group (P<0.05), as shown in Table 3.

Table 3 Univariate Analysis of Factors Influencing MRSA Infection (, n[%])

Multivariate Logistic Regression Analysis of MRSA Infection Factors

Taking whether CRS patients have MRSA infection as the dependent variable (0 = absent, 1 = present), and assigning values to the possible influencing factors obtained from Table 2 as independent variables (see Table 4), a multivariate logistic regression analysis model was established. The results showed that male gender, nasal structural variations, history of nasal surgery, poor drainage, frequency of acute infections >3 times/year, frequency of recurrent upper respiratory infections >3 times/year, antibiotic use frequency ≥3 times/year, antibiotic use duration >14 days, and use of ≥3 antibiotics were all independent risk factors for MRSA infection in CRS patients (P < 0.05), as shown in Table 5.

Table 4 Variable Assignment Table

Table 5 Multivariate Logistic Regression Analysis of Factors Affecting MRSA Infection

Discussion

MRSA, with its powerful resistance and rapid transmission capabilities, poses a severe challenge to the treatment of CRS.¹⁶ Among the 180 CRS patients analyzed in this study, the incidence of MRSA was 41.11%, which is slightly higher than previous related studies.^17,18 This finding highlights the significance of MRSA in CRS patients, especially in the context of increasing antibiotic resistance, suggesting the need for more in-depth research and effective prevention and control measures. The study also showed that, compared with other antibiotics, S. aureus demonstrated significant resistance to macrolide antibiotics (erythromycin E), with a resistance rate of 65.56%, which further increased to 81.08% in MRSA strains. This phenomenon might be related to the frequent application of macrolide antibiotics in treating CRS. Macrolides not only inhibit sinus infections but also help by suppressing bacterial biofilm formation and reducing inflammatory responses, leading to their widespread use.^19,20 Therefore, prolonged use may exert selective pressure and accelerate the emergence of resistant strains. In addition, this study also revealed the issue of MRSA’s resistance to multiple antibiotics. The resistance rates of FOX, CIP, CLI, and TE exceeded 40%. These high resistance rates reflect the considerable difficulties CRS patients face during treatment and indicate that drug sensitivity testing should be emphasized during clinical treatment to ensure the rationality and effectiveness of medication and reduce the further spread of resistance. At the same time, strengthening hospital infection control is particularly important, in addition to antimicrobial therapy for MRSA infections. Medical staff should strictly adhere to sterile procedures, regularly provide hand hygiene education and training, and use antimicrobial-functional medical gloves, among other measures, to reduce the risk of MRSA transmission.²¹ Additionally, strict monitoring of antibiotic usage in patients is necessary to avoid overuse of antibiotics, which is crucial for reducing the formation and spread of resistant bacteria.

This study used univariate and multivariate analyses to explore the impact of various factors on MRSA infection in CRS patients. The results show that male CRS patients are more likely to be infected with MRSA than females, a finding consistent with existing literature.^22,23 Male patients typically have higher risk factors in terms of lifestyle, such as smoking, alcohol use, and occupational exposure, which may lead to reduced immune function and damage to the nasal barrier, making them more susceptible to resistant bacterial infections.²⁴ Furthermore, male patients tend to seek medical attention later in the disease course, leading to delayed treatment, which is a major factor in the development of resistance. Since male CRS patients are more prone to MRSA infections, early intervention and close monitoring of male patients in clinical practice should be emphasized, particularly regarding antibiotic use, which should be rational and precise. Nasal structural variations, such as septal deviation, nasal polyps, and other nasal anatomical abnormalities, have been shown to be closely associated with MRSA infection.²⁵ Nasal structural abnormalities lead to poor sinus drainage, creating a local environment conducive to the growth of pathogens, especially highly resistant bacteria like MRSA, which can thrive in such environments and form biofilms,²⁶ increasing the persistence of infections and treatment difficulty. A history of nasal surgery (eg, sinus surgery, polypectomy) is also an important risk factor. While surgery may improve structural problems, it can also cause local tissue damage, alter the nasal immune barrier, and further promote bacterial colonization and the growth of resistant bacteria.²⁷ For CRS patients with nasal structural variations or a history of surgery, clinical treatment should be more individualized, considering long-term antibiotic prophylaxis and nasal care measures to prevent bacterial colonization after surgery. The results of this study indicate that the frequency of acute infections in CRS patients is significantly related to the risk of MRSA infection. MRSA infection rates were significantly higher in patients with frequent acute infections and recurrent upper respiratory infections. This may be due to repeated infections leading to prolonged inflammation of the nasal and sinus mucosa, and a decline in immune function, especially during acute exacerbations, creating a local environment more favorable for the growth of resistant bacteria like MRSA.²⁸ Additionally, frequent acute infections are often accompanied by antibiotic use, and inappropriate or excessive use of antibiotics is a major factor in the development of resistant bacteria.^29,30 Therefore, long-term management of CRS patients should be strengthened in clinical practice, with appropriate scheduling of antibiotic use, avoiding overuse of antibiotics, and emphasizing patients’ and families’ awareness of auxiliary treatments, such as nasal cleaning and humidification. Moreover, this study also found that MRSA infection risk was significantly increased in patients with antibiotic use ≥3 times/year, antibiotic use duration >14 days, and those using ≥3 types of antibiotics in combination. This may be because excessive use of antibiotics can disrupt the normal nasal flora, allowing resistant strains to replace it. Furthermore, the combined use of multiple antibiotics is often due to ineffective infection control, and although combining antibiotics can temporarily control bacterial growth, it significantly increases the selective pressure on resistant bacteria.^31,32 In light of this, clinical treatment should avoid unnecessary antibiotics and strictly select the most appropriate antibiotics based on bacterial culture and sensitivity test results. For patients with known resistant strains, broad-spectrum antibiotics should be avoided, and MRSA-targeted drugs should be chosen for treatment.

Based on the findings of this study, we recommend the following measures in the treatment of CRS: (1) Strengthening microbiological testing and antibiotic susceptibility analysis: For all recurrent CRS patients, especially those with high-risk factors, routine nasal secretion cultures and sensitivity tests should be conducted to understand the types of pathogens and their resistance patterns, guiding clinical treatment. (2) Optimizing antibiotic use strategies: Clinically, rational antibiotic use policies should be formulated to avoid overuse. For patients with MRSA infections, targeted antibiotics such as vancomycin or linezolid should be selected based on sensitivity results. For patients without clear evidence of infection, antibiotic treatment should be avoided whenever possible. (3) Strengthening patient management: For patients with nasal structural variations, frequent acute infection histories, and a long history of antibiotic use, regular follow-up and management should be strengthened. The disease status should be periodically evaluated, and treatment plans should be adjusted. When necessary, surgical treatment to improve nasal ventilation and drainage function should be considered. (4) Advocating for rational antibiotic use education: Not only should healthcare professionals strengthen education on rational antibiotic use, but patients and their family members also need to improve their awareness of antibiotic use. Avoiding self-medication with antibiotics or misuse in non-medical institutions is key to reducing the emergence of resistant bacteria.

Conclusion

MRSA has a high infection rate in CRS patients and exhibits significant resistance to several commonly used antibiotics. Factors such as gender, nasal structural variations, nasal surgery history, frequent acute infections, and inappropriate antibiotic use are independent risk factors for MRSA infection. Based on these findings, clinical treatment should emphasize microbiological testing, rational use of antibiotics, and the optimization of long-term patient management to improve CRS treatment outcomes and reduce MRSA infections. Future research could delve deeper into the molecular mechanisms of MRSA infections to further understand the development process of its resistance. Furthermore, larger prospective studies should be conducted to evaluate the efficacy of different antibiotic treatment strategies in CRS patients, in order to provide more precise clinical treatment guidelines.

Disclosure

The authors report no conflicts of interest in this work.

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