A Prospective Clinical Study of Bacteriological Profile and their Antibiotic Susceptibilty Profile in Patients with Chronic Rhinosinusitis: The Recent Scenario in Northern India

Abstract

Objectives

1. To determine the prevailing scenario of the bacteriological profile of patients with CRS, 2. To identify their antibiotic susceptibility profile.

Material and methods

The study was conducted on 100 patients in the Department of ENT and Microbiology from December 2020–2022. Patients above the age of 12 years were evaluated. Those who received antibiotics in the last 12 months. and age < 12 years were excluded. Patients were subjected to a detailed history, clinical and radiological examination. After the informed consent of patients and ethical cleareance, samples were taken from the middle meatus area and studied for antibiotics sensitivity: levofloxacin, vancomycin, amikacin, amoxicillin-clavulanic acid and azithromycin.

Results

The study was male predominance (71%), with the maximum of patients in the age group 21–30 years (38%). The most common clinical features were nasal obstruction ( 96%) and mucopurulent discharge (100%). The most common isolate was Staphylococcus aureus (45.16%). In Gram-positive, the maximum resistance was shown to azithromycin and amoxicillin-clavulanic acid and the maximum sensitivity to vancomycin, levofloxacin and amikacin.

Conclusions

Antibiotic resistance seems to be emerging for azithromycin and amoxicillin-clavulanic acid at a higher rate. MRSA ( 19.35%) maintains a significant presence with associated increased levels of antibiotic resistance.

Introduction

Chronic Rhinosinusitis (CRS) is an inflammatory condition of the nose and paranasal sinuses that lasts for more than 12 weeks [1, 2]. According to the European Position paper on Rhinosinusitis (EPOS) 2020, the diagnostic criteria include two or more of the following signs and symptoms of nasal discharge, nasal obstruction/congestion, facial pain/fullness or decreased sense of smell for a period of more than twelve weeks. The inflammation is documented by one or more of the following findings: Purulent discharge (anterior, posterior, or both) or edema in the middle meatus or anterior ethmoid region, polyps in the nasal cavity or the middle meatus and/or radiographic imaging showing mucoperiosteal thickening or opacification of the paranasal sinuses [3, 4]. CRS is not a classic infectious disease but has a complex multifactorial etiology. While the underlying pathogenesis remains poorly understood, several mechanisms, mainly related to microorganisms, have been proposed and investigated extensively [5]. It is a prevalent disease process having multifactorial etiology in which bacteria are believed to play a major role in the propagation of inflammation.

Recognition of the unique microbiology is essential when selecting antimicrobial therapy for the patients of CRS. Bacteria, fungi, or viruses may be involved in many cases, but there may be some cases with no identifiable pathogenic organism. Generally, pathogen-positive cultures are recovered in 50 to 60% of the patients with CRS [6]. The literature is divided on the most commonly isolated organisms, though many speculate on polymicrobial etiology. According to the literature, Staphylococcus aureus and anaerobic bacteria are more common [7–11]. Because of the potential role of bacterial infection, most treatment guidelines recommend long courses of antibiotics before considering surgical therapy.

Antibiotics are by far the most commonly prescribed drugs for CRS because of the potential role of bacterial infection in CRS [12, 13]. As a result of failing to identify causative pathogens before the beginning of the treatment, there is a tendency to over-prescribe or sometimes to prescribe with an antibiotic to which the organisms have become resistant. Despite being aware of these potential issues, most cases are managed by general practitioners who do not have access to sinus cavity specimens [14]. There are additional concerns regarding the overuse of antibiotics and an associated increase in antibiotic resistance, which represents a considerable threat to the efficacy of these drugs.

To adequately treat patients and prevent the development of resistance, the appropriate antibiotics must be prescribed for the appropriate duration based on the sensitivity of the infective organism. Previous research has emphasized changes in bacterial pathogen patterns, their antibiotic sensitivity, and increased antibiotic resistance rates in individual patients [15]. The present study aims to determine the prevailing scenario of the bacteriological profile of patients with CRS and to identify their antibiotic sensitivity pattern in Northern India.

Methods and Materials

This prospective observational study was conducted over a period of two years (December 2020–December 2022) at the Department of Otorhinolaryngology and Microbiology. In this study, 100 patients with a clinical diagnosis (based on the clinical criteria EPOS-20) of CRS were included. The informed consent was obtained prior to the enrollment of the patients and the patients willing to participate in the study were included. This study was approved by institutional ethical committee.

Inclusion Criteria

1. Patients fulfilling the diagnostic criteria of CRS with or without nasal polyposis.

2. Age > 12 years.

Exclusion Criteria

1. Patients were not fulfilling the diagnostic criteria of CRS.

2. Age < 12 years.

3. Those who received antibiotics in the last 12 weeks.

4. Patients with sino-nasal malignancy.

Patients who presented with clinical features of chronic rhinosinusitis were subjected to a detailed history, clinical examination, and radiological examination; if required. The diagnosis was based on clinical features as proposed by EPOS 2020. The diagnostic nasal endoscopy was performed using a topical application of 4% xylocaine. A rigid nasal endoscope of zero-degree angulation was used. A 10 ml syringe filled with normal saline solution was then used to irrigate the nasal cavities. Then a sterile swab stick was used to take the endoscopically guided swab from the middle meatus area under strict aseptic conditions.

Samples were inoculated on 5% sheep blood agar, MacConkey, and chocolate agar for bacterial culture growth. Plates were incubated at 37 °C for 24 h. Standard microbiological procedures, including various biochemical tests, identified organisms. All isolates were subjected to antimicrobial susceptibility testing based on CLSI 2023 (Clinical Laboratory Standards Institute) guidelines on the Kerby-Bauer disc diffusion method.

The case details were filled in the case proforma of patients. The information was gathered in a Microsoft Excel sheet and manually analyzed by descriptive statistics before being presented as numbers and percentages.

Observations and Results

A total of 100 patients participated in this study with age above 12 years. The most common age group affected in the present study was between 21 and 30 years, approximately 38% of total patients while the least affected age group was above 60 years, 4% of the total population. In our study, a 65-year-old patient was the oldest participant, and a 12-year-old was the youngest. (Table 1)

Table 1.

Distribution of patients according to age group

Age group( in years)	Number of patients
12–20	28 (28%)
21–30	38 (38%)
31–40	15 (15%)
41–50	5 (5%)
51–60	10 (10%)
> 60	4 (4%)
Total	100

In our study seventy-one (71%) patients were males, and 29 (29%) patients were females, with a male: female ratio of 2.4:1. (Table 2)

Table 2.

Distribution of patients according to gender

Gender	Number Of Patients
Male	71 (71%)
Female	29 (29%)
Total	100

The patients registered in this study were more from the rural areas, i.e. 56%, than from urban areas, i.e. 44%. Region wise distribution showed the maximum number of patients were from Aligarh (57%). (Fig. 1 and 2)

Fig. 1.

Geographic-wise distribution

Fig. 2.

Region-wise distribution

The most common complaint was nasal obstruction seen in 96 patients, headache/facial pain in 48 patients and nasal discharge in 17 patients. Other symptoms like itching and watering of the eyes, hyposmia, and nosebleeds were also noted (Table 3). The most typical examination finding was mucopurulent discharge documented in all 100 patients and sinonasal polyps in 21 patients. (Table 4)

Table 3.

Distribution of patients according to symptoms

Symptoms	Number of patients
Nasal obstruction	96 (96%)
Headache/facial pain	48 (48%)
Nasal discharge /post-nasal drip	17 (17%)
Hyposmia	7 (7%)
Nose bleed	6 (6%)
Itching in ear and eyes	52 (52%)

Table 4.

Distribution of patients according to examination findings

Examination findings	Number of patients
Mucopurulent discharge	100 (100%)
Deviated nasal septum with inferior turbinate hypertrophy	55 (55%)
Sinonasal polyps	21 (21%)
Concha bullosa	15 (15%)

Out of 100 patients in the present study, 62 patients were positive on routine bacterial culture, whereas 38 patients showed no growth. Microbiological examination showed Gram-positive organisms in 45 patients (72.58%) and Gram-negative organisms in 17 patients (27.41%).

Overall, the most common bacteria isolated was Staphylococcus aureus, approximately 45% of the total bacterial culture, followed by methicillin-resistant Staphylococcus aureus (MRSA) around 19%. In Gram-negative isolates, Klebsiella species was maximum isolated (11.29%), followed by an equal population of Escherichia coli and Pseudomonas aeruginosa (6.45%). (Fig. 3)

Fig. 3.

Bacterial profile of patients

Antibiotic susceptibility patterns for frequently used antibiotics were examined in bacterial isolates in the present study. The most effective antibiotics against Staphylococcus aureus were vancomycin (100%) and levofloxacin (82.14%), followed by amikacin (75%), cotrimoxazole (60.71%), cefoxitin (50%), clindamycin (46.42%), amoxicillin-clavulanic acid (28.57%), and azithromycin (7.14%). Vancomycin (100%) showed the highest susceptibility to methicillin-resistant Staphylococcus aureus (MRSA), followed by levofloxacin (58.33%), clindamycin (25%), and azithromycin (33.33%). (Fig. 4)

Fig. 4.

Antibiotics sensitivity to Staphylococcus species

In the present study, the highest level of cotrimoxazole sensitivity (57.14%) was shown by Klebsiella species. Levofloxacin and piperacillin-tazobactam exhibited the maximum sensitivity against Pseudomonas aeruginosa (100%), while meropenem exhibited the maximum sensitivity against Escherichia coli (100%). Levofloxacin showed the highest level of sensitivity against Proteus mirabilis (100%). (Fig. 5)

Fig. 5.

Antibiotics sensitivity to Gram negative species

Discussion

Bacterial etiology, pathophysiology, and management of CRS have been among the most contentious topics of debate in otorhinolaryngology. The literature is sparse and challenging to interpret. Sinusitis severely affects India, with an estimated 134 million Indians being affected [16]. There are 18 to 22 million hospital visits per year caused by CRS, and healthcare spending is significant for sinusitis [17, 18]. According to extrapolated figures in India, the prevalence rates of CRS are close to 12.8% of the total population [19], similar to the prevalence rate of 12.5% observed in the US population [20].

Among 100 patients studied, the most common age group affected was 21–30 years, and those over 60 years were the least affected age group. According to Garg D et al. (2009), the age group of 18–27 years had the most patients, while the age group of 57–66 years had the fewest. Our study showed different results compared to Ayman Al Madani et al. (2007), where the most common age group was 40 years. In the current study, seventy-one (71%) were male, and twenty-nine (29%) were female. The male-to-female ratio was 2.4:1. The majority of the survey respondents reported male predominance, which could be attributed to the relatively higher involvement of males in outdoor activities, the higher prevalence of smoking, and the reluctance of females in social settings such as India to seek medical care.

Nasal obstruction was the most common symptom in our study, followed by headache or facial pain. Rekhade T et al. (2021) documented nasal obstruction as the primary complaint, followed by nasal discharge, while Garg D et al. (2019) documented nasal discharge as the most common symptom in 100% of patients. In the present study, mucopurulent discharge was seen in all patients. Rekhade T et al. (2021) obtained similar results where nasal discharge was the most common sign in patients (72%), followed by nasal mucosa congestion in 42% of patients.

In our study, Staphylococcus aureus accounted for 28 cases (45.16%), while MRSA accounted for 12 cases (19.35%). The prevalence rates of S aureus in chronic rhinosinusitis have varied considerably in the literature. Chan and Hadley (2021) discovered a prevalence of Staphylococcus aureus of only 3% in a community-based microbiological study on CRS [21]. Other researchers have discovered prevalences ranging from 13 to 19% in tertiary care rhinology practices. In Gram-negative isolates, Klebsiella species were isolated in (11.29%), followed by an equal population of Escherichia coli (6.45%) and Pseudomonas aeruginosa (6.45%).

In our study levofloxacin and vancomycin exhibited the highest antibiotic susceptibility, whereas azithromycin and amoxicillin-clavulanic acid exhibited the lowest sensitivity against Staphylococcus species. MRSA showed the maximum sensitivity to vancomycin (100%) and levofloxacin (58.33%). Only a small amount of sensitivity is shown for azithromycin (33.33%), clindamycin (25%), and cotrimoxazole (8.33%), 0n the other hand amikacin, amoxicillin-clavulanic acid, and cefoxitin all exhibit 100% resistance. Vancomycin was the most sensitive antibiotic in our study with 100% sensitivity, followed by levofloxacin (82.14%), amikacin (75%), cotrimoxazole (60.71%), and cefoxitin (50%). Singh NK et al. (2017) obtained comparable maximum sensitivity results to vancomycin. Davoudi et al. (2016) discovered vancomycin resistance in one isolate of Staphylococcus aureus. The isolates were only 28.75% sensitive to amoxicillin-clavulanic acid and 7.15% sensitive to azithromycin. Rezai et al. (2016) reported 40% sensitivity with ciprofloxacin and 20% sensitivity with gentamicin. According to Pol SA et al. (2020), the most sensitive antibiotic was cefixime, which had a sensitivity of 63.66%. Ciprofloxacin had a sensitivity of 42.42%, and amoxicillin-clavulanic acid (3.03%), polymyxin, neomycin, and ofloxacin had low sensitivity. This finding is cause for concern because amoxicillin-clavulanic acid is among the most commonly used medications.

Pseudomonas aeruginosa, in our study was 100% sensitive to levofloxacin, cefepime and piperacillin-tazobactam. Arun et al. (2020) reported the maximum sensitivity to ciprofloxacin (66.7%), followed by cefixime (33.3%), erythromycin (25%), polymyxin (16.7%), and amoxicillin-clavulanic acid (8.3%), and resistant to methicillin, gentamicin, erythromycin, chloramphenicol, neomycin and ofloxacin.

Musa E et al. (2019) reported [22] Staphylococcus aureus (35.14%) as the most common bacterial isolates in CRS, followed by Haemophilus influenzae (12.16%), Streptococcus viridians (10.81%) and Streptococcus pneumonia (6.76%). Amoxycillin and clavulanic acid, ciprofloxacin, and pefloxacin were found to be the most effective with 100% sensitivity, followed by levofloxacin, ceftriaxone, erythromycin, and cefuroxime in that order showing intermediate sensitivity. Most isolates were resistant to ampicillin and cloxacillin, amoxycillin, sulfamethoxazole, and trimethoprim.

According to Arun et al. (2020), the most sensitive antibiotic [23] was cefixime, which had a sensitivity of 63.66%, followed by ciprofloxacin, which had a sensitivity of 42.42%, and gentamicin which had a sensitivity of 39.39%, erythromycin 36.46%, methicillin 21.21%, cotrimoxazole 15.15%, and chloramphenicol 12.12% sensitivity. Amoxicillin-clavulanic acid (3.03%), polymyxin, neomycin, and ofloxacin showed the least sensitivity.

Antibiotic choices in treating chronic sinusitis should be guided by sinus cultures whenever possible. Our study showed Gram-positive bacteria have developed antimicrobial resistance, particularly to beta-lactam antibiotics and vancomycin and levofloxacin are currently the most effective antibiotics against them. Chronic sinusitis caused by MRSA is a growing problem in Northern India. Furthermore, the development of resistance affects the efficacy of different generations of cephalosporins in the treatment of chronic rhino-sinusitis. Pseudomonas aeruginosa exhibited the maximum sensitivity to levofloxacin and piperacillin-tazobactam. Escherichia coli exhibited the maximum sensitivity to meropenem, whereas Proteus mirabilis exhibited the maximum sensitivity to levofloxacin. It was a brief study with a small number of specimens. A more extensive study or more specimens are required for better and more significant results.

Conclusions

Chronic rhinosinusitis is an inflammatory disease of the nose and paranasal sinuses affecting primarily males in the second and third decades of their lives. The diagnosis of CRS is based on clinical criteria and investigations are required only for proper treatment and follow-up purposes. The most common clinical features are nasal obstruction and mucopurulent discharge around the middle meatus area. Staphylococcus aureus is still a significant pathogen in cases of culture-positive chronic rhinosinusitis and is frequently showing multidrug resistance. Levofloxacin and vancomycin show the maximum sensitivity to Staphylococcus species. Bacterial resistance to azithromycin and amoxicillin-clavulanic acid is on the rise. One possible method for reducing the prevalence of antimicrobial resistance in CRS patients is culture-directed therapy. More research and monitoring of antibiotic sensitivity patterns in CRS are needed.

Funding

None.

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