Antimicrobial Resistance Patterns in Pseudomonas Aeruginosa Isolated from Chronic Suppurative Otitis Media

By Sadaf Razzak¹, Muhammad Sohail², Fakhur Uddin³, Muhammad Razzaq Dogar⁴

Affiliations

1. Department of Pathology, Sindh Medical College, Jinnah Sindh Medical University, Karachi, Pakistan
2. Department of Microbiology, University of Karachi, Karachi, Pakistan
3. Department of Microbiology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi, Pakistan
4. Department of ENT, Head, and Neck Surgery, Jinnah Postgraduate Medical Centre, Karachi, Pakistan

doi: 10.29271/jcpsp.2025.07.866

ABSTRACT                  
Objective: To investigate the frequency, antimicrobial susceptibility, and associated risk factors for Pseudomonas aeruginosa in chronic suppurative otitis media (CSOM) infections.
Study Design: A cross-sectional, descriptive study.
Place and Duration of the Study: Department of Microbiology, University of Karachi, in collaboration with Jinnah Postgraduate Medical Centre and Jinnah Sindh Medical University, Karachi, Pakistan, from March 2022 to March 2023.
Methodology: Ear discharge samples were collected from 302 patients diagnosed with CSOM. Demographics and previous clinical history of the patients were recorded. Microbial cultures were analysed to identify pathogens. CLSI (2022) guidelines were followed to test the antibiotic susceptibility of P. aeruginosa. The chi-square test was applied to assess associations between categorical variables, with a p-value of <0.05 considered as significant.
Results: Out of 302 patients, P. aeruginosa was isolated from 141 (46.7%) cases, while Staphylococcus aureus was obtained from 71 (19.29%) cases. P. aeruginosa not only appeared as a mono-microbial infection but also as co-infections with S. aureus. Antibiotic susceptibility testing revealed high resistance rates to piperacillin (46.1%), ceftazidime (35.5%), and cefepime (34.8%). Carbapenems were the most effective beta-lactams showing imipenem resistance (24.8%) and meropenem resistance (22%). The isolates showed no resistance to colistin.
Conclusion: P. aeruginosa is a predominant pathogen in CSOM, exhibiting concerning resistance patterns to commonly used antibiotics and co-infection with other microorganisms. These findings underscore the importance of targeted antibiotic stewardship and tailored interventions to mitigate resistance and improve outcomes in CSOM management.

Key Words: Antibiotics, Bacterial infections, Drug resistance, Otitis media, Pseudomonas aeruginosa.

INTRODUCTION

Pseudomonas (P.) aeruginosa is among the aetiological agents responsible for causing chronic suppurative otitis media (CSOM).¹ This condition is characterised by repeated otorrhoea via tympanic membrane perforation of the ear.² Although some otolaryngologists expand this requirement to include discharge from the ear that lasts for six weeks to three months, the World Health Organization (WHO) states that otorrhoea that lasts for at least two weeks is sufficient to confirm CSOM diagnosis.^3,4

CSOM affects ~31 million individuals of all ages annually worldwide, with an average incidence rate of 4.76 per 1,000 people, highlighting its significance as a global health concern. It disproportionately affects those from lower socioeconomic backgrounds with 90% patients residing in countries in Southeast Asia, Western Pacific regions, and Africa.^2,5,6 In the paediatric population, the highest prevalence rates of CSOM are found in Alaska, Canada, Greenland, and in American Indians and Australian Aborigines.⁷ The estimated incidence and prevalence of CSOM in the USA are 0.03% and 0.46%, respectively.⁸ Non-industrialised countries have a high frequency of CSOM. In Asia, China has the highest rate of 25.9% which is mainly found in 51 to 60 years old individuals.⁹ Its prevalence in India is 23% with P. aeruginosa being the leading aetiological agent.⁴

One of the serious complications of CSOM is conductive hearing loss which constitutes a risk factor for permanent sensorineural hearing loss because of inner ear injury as well as intracranial complications.¹⁰ Worldwide, 21,000 individuals succumb every year to complications due to CSOM.¹¹ Antibiotics are generally used empirically but may lead to the emergence of resistant bacterial strains. Identifying the bacterial spectrum and susceptibility to antimicrobials is essential for efficient empirical treatment and would help better understand CSOM. As the primary cause of recurrent suppuration and one of the most common pathogens linked to CSOM is P. aeruginosa, its isolation from this infection and characterisation for antimicrobial susceptibility would enable the discovery of therapeutic targets and the creation of efficient treatment plans by antibiotic stewardship programmes. Therefore, this study will provide guidelines to healthcare professionals to prescribe effective antibiotic treatment while minimising the risk of treatment failure due to resistance. The objective of this study was to investigate the frequency, antimicrobial susceptibility, and associated risk factors for P. aeruginosa in CSOM infections.

METHODOLOGY

This cross-sectional study was conducted at the Department of Microbiology, University of Karachi in collaboration with Jinnah Postgraduate Medical Centre and Jinnah Sindh Medical University, Karachi, Pakistan, from March 2022 to March 2023. The ethical approval was taken from the Institutional Review Board of JPMC (IRB No: F.2-81/2022-GENL/132/JPMC). Purposive sampling technique was used with a sample size of 302 patients after getting informed consent.¹² The inclusion criteria were those patients who presented to the ENT outpatient department with a history of ear discharge occurring in one or both ears and were clinically diagnosed as a case of CSOM awaiting treatment and management. The exclusion criteria were patients taking antibiotics, having had recent ear surgery within a year, having had congenital ear abnormalities, or having had ear discharge due to any other cause.

The relevant medical data were entered in a proforma including demographics and history of any previous antibiotic use. The information was obtained from each patient as the majority were taking antibiotics before presenting to the ENT outpatient department. However, samples were collected only from patients who had not received antibiotics at the time of sampling or had discontinued antibiotics for at least one week before sample collection. After all aseptic precautions, a sterile swab were stick was stretched into the middle ear through the perforated eardrum, and the purulent discharge was collected and taken to the laboratory for microbiological examination.

The collected purulent swabs were subjected to Gram-staining, cultured on Blood and MacConkey agar plates, and incubated at 37°C for 24 hours. Pathogen identification was carried out by Gram-staining results, phenotypic characteristics, and biochemical tests.¹³ Definitive species of isolates were confirmed using the RapID NF Plus (Remel, UK) identification kit. Antibiotic susceptibility testing was undertaken, and results were interpreted following Clinical and Laboratory Standard Institute (CLSI, 2022) guidelines. Colistin susceptibility was determined using the broth microdilution method in a 96-well microtitre plate (Trek Diagnostic Systems, West Sussex, UK), following CLSI, 2022 guidelines. Interpretation was based on CLSI breakpoints; ≤2 µg/mL was considered susceptible and ≥4 µg/mL was considered resistant.

Data were analysed using SPSS (version 26.0 for Windows). Quantitative variables were presented as frequency (n) and percentages (%) to illustrate the distribution and the resistance patterns of P. aeruginosa and the Chi-square test was employed to assess the associations between P. aeruginosa infection status (positive and negative) and infection type (monomicrobial or polymicrobial), as well as co-infection with other microorganisms. A p-value of <0.05 was considered statistically significant in interpreting the results in the context of available treatment options.

RESULTS

Pus samples were collected from 302 patients, who were diagnosed as CSOM. The mean age was calculated to be 25.47 ± 18.82 years. The study population consisted of 142 (47%) males and 160 (53%) females. The right ear was affected in 135 (44.7%) patients while bilateral involvement was observed in 29 (9.6%) cases. Among the study participants, 122 (40.4%) had a history of hospital admissions during the recent year, while surgical history in previous years was reported in 77 (25.5%) patients. The majority of patients 266 (88.1%) had already taken various antibiotics and not responded to them before coming to the ENT outpatient department. Recent use of indwelling devices was reported in 62 (20.5%) patients, while 180 (59.6%) patients had a history of chronic disease. Nasal allergies were present in 217 (71.9%) patients, and 71 (23.5%) were diagnosed with diabetes. Major complaints of the patients were hearing loss as reported in 269 (89.1%) of the patients.

Three-hundred two, out of which 269 (89.1%) samples were growth- positive. Of these growth-positive samples, 368 isolates were obtained and identified. Most of the infections were due to P. aeruginosa (141; 38.31%) followed by S. aureus (71; 19.29%), Coagulase negative Staphylococci (CONs) (45; 12.22%), Streptococci (39; 10.59%), E. coli (18; 4.89%), Klebsiella sp. (17; 4.61%), Proteus sp. (19; 5.16%), and Fungi (18; 4.89%). In patients younger than 18 years, the same pattern was observed, P. aeruginosa being the most frequent followed by S. aureus (Table I).

The cross-tabulation revealed that among P. aeruginosa-positive cases, 57 (40.42%) were monomicrobial infections, while 84 (59.97%) were polymicrobial infections. In contrast, among P. aeruginosa-negative cases, 112 (69.56%) were monomicrobial infections, and 16 (9.93%) were polymicrobial infections (Table II). However, no bacterial or fungal pathogen was isolated in 33 (10.92%) cases. Among co-infection cases, P. aeruginosa was frequently isolated with the Gram-positive S. aureus and Streptococci. yet the majority of the samples had P. aeruginosa alone (Table III).

Among beta-lactam antibiotics, 65 (46.1%) P. aeruginosa isolates were resistant to piperacillin but the addition of tazobactam improved susceptibility, reducing resistance to 50 (35.5%) isolates.

Table I: Frequency of pathogens from 302 pus samples collected from the patients of various age groups suffering from CSOM.

Age group (years)	Prevalence of pathogens (n, %)								No growth	Total isolates cultured
	S. aureus	CoNS1	Streptococci	E. coli	Klebsiella sp.	Proteus sp.	P. aeruginosa	Fungi
0.6-18	28 (16.7)	16 (9.5)	17 (10.2)	9 (5.4)	10 (5.9)	11 (6.6)	70 (41.9)	6 (3.5)	13 (7.7)	167 (45.4)
19-35	24 (24.7)	13 (13.4)	11 (11.3)	5 (5.2)	3 (3.1)	5 (5.2)	28 (28.9)	8 (8.2)	10 (10.3)	97 (26.4)
36-60	18 (20.0)	13 (14.4)	10 (11.1)	4 (4.4)	3 (3.3)	2 (2.2)	37 (41.1)	3 (3.33)	6 (6.7)	90 (24.5)
≥60	1 (7.14)	3 (21.4)	1 (7.1)	0 (0)	1 (7.1)	1 (7.1)	6 (42.9)	1 (7.1)	1 (7.1)	14 (3.8)
Total	71 (19.2)	45 (12.2)	39 (10.6)	18 (4.9)	17 (4.6)	19 (5.2)	141 (38.3)	18 (4.9)	30 (8.2)	368 (100)
1Coagulase negative Staphylococci. Values are given as number of cases with percentage (%).

Table II: Distribution of P. aeruginosa in mono- and poly-microbial CSOM cases. The cases without the involvement of P. aeruginosa have also been given.

P. aeruginosa	Infection type			Total	p-value
	Mono-microbial	Poly-microbial	No growth
Positive	57 (40.4)	84 (60.0)	0 (0)	141 (46.7)	<0.05*
Negative	112 (69.6)	16 (10.0)	33 (20.5)	161 (53.3)	-
Total	169 (56.0)	100 (33.1)	33 (10.9)	302 (100)	-
*p-value, as determined by Chi-square test, shows statistical association of P. aeruginosa infection in poly-microbial cases. Values are mentioned with percentages (%).

Table III: Distribution of P. aeruginosa co-infection with other microorganisms in CSOM.

P. aeruginosa	Co-infection of Pathogens with P. aeruginosa											p-value
	S. aureus	CoNS	Streptococci	E. coli	Klebsiella	Proteus	P. aeruginosa (mono-culture)	Fungal	Mixed infections	No growth	Total
Positive	21 (14.89)	20 (14.18)	21 (14.89)	5 (3.54)	7 (4.96)	5 (3.54)	57 (40.42)	5 (3.54)	0 (0)	0 (0)	141 (46.68)	≤0.05
Negative	45 (27.95)	21 (13.04)	17 (10.55)	8 (4.96)	0 (0)	9 (5.59)	0 (0)	13 (8.07)	15 (9.31)	33 (20.49)	161 (53.31)
Total	66 (21.85)	41 (13.57)	38 (12.58)	13 (4.30)	7 (2.31)	14 (4.63)	57 (18.87)	18 (5.96)	15 (4.96)	33 (10.92)	302 (100)
*p-value as determined by Chi-square test shows statistically significant association with other pathogens. Values are mentioned with percentages (%).

Figure 1: Resistance pattern of P. aeruginosa isolated from CSOM cases.

Moreover, 50 (35.5%) and 49 (34.8%) P. aeruginosa isolates showed resistance to ceftazidime and cefepime, respectively. The use of a combination of ceftazidime-avibactam improved susceptibility with sensitivity seen in 97 (68.8%) isolates. Carbapenems were the most effective beta-lactams with resistance observed to imipenem in 35 (24.8%) isolates and to meropenem in 31 (22%) isolates. Notably, all P. aeruginosa isolates were susceptible to colistin by minimum inhibitory concentration of 2 µl/ml. Among monobactams, resistance to aztreonam was observed in 26 (18.4%) isolates. For aminoglycosides, resistance to tobramycin was detected in 62 (44%) isolates, indicating a moderate effectiveness of this class. In the fluoroquinolone group, P. aeruginosa exhi-bited a sensitivity rate of 93 (66%) to levofloxacin, with 44 (31.2%) isolates being resistant, and 4 (2.8%) demonstrating an intermediate susceptibility. Similarly, ciprofloxacin resistance was observed in 48 (34%) isolates, while 87 (61.7%) were susceptible, and 6 (4.3%) exhibited an intermediate susceptibility (Figure 1).

DISCUSSION

The current study highlights different microorganisms, especially P. aeruginosa, infecting the ears of CSOM patients and their antibiotic resistance pattern, emphasising the challenge posed by this resistant pathogen in clinical settings. In this study, the mean age of 25 years is alarming as a younger population finds themselves facing complications of deafness, ultimately leading to a surgical procedure at this young age; this age group has been reported earlier from another city of Pakistan to have a higher rate of CSOM.¹⁴ Females were predominantly CSOM patients with larger population in the younger age group of less than 18 years.¹⁵ Prevalence of P. aeruginosa followed by S. aureus as depicted in this study was in agreement with earlier studies.^14,16 In contrast, some studies showed S. aureus as the most frequently isolated pathogen from CSOM patients.^17,18 The incidence of S. aureus in middle ear infections can be endorsed due to their ubiquitous nature and high presence in the external auditory canal and upper respiratory tract. Interestingly, the presence of P. aeruginosa is more strongly associated with being a polymicrobial infection in CSOM compared to monomicrobial infections. The establishment of this pathogen in the ear canal can be attributed to its biofilm formation abilities, which enhance bacterial survival, promote resistance to antibiotics, and contribute to the chronicity of infection, thus reducing treatment efficacy.^19,20

Although most infections were monomicrobial in nature, co- infections of Gram-positive bacteria with P. aeruginosa are also observed as depicted in other studies. Similar studies reported slight variation in their findings.²¹ Coagulase-negative staphylococci (CoNS) are generally considered as non-pathogenic and their association in CSOM cases can be attributed to the extremely low resistance in the middle ear due to invasion by other organisms.²² The presence of coliforms such as E. coli and Klebsiella may indicate a low socioeconomic status and unhygienic conditions in the patients.²³ Among the antibiotics tested, carbapenems were found effective with only 22% resistance to meropenem and 25% to imipenem, demonstrating superior efficacy. While these findings align with global trends, the minimal difference in resistance between these two is concerning. The emerging resistance to these agents is alarming, as it leaves limited therapeutic options, particularly for critically ill patients. The universal susceptibility to colistin in this study is reassuring but must be cautiously interpreted, as overuse could lead to resistance against this last-resort antibiotic.

Piperacillin, a commonly used beta-lactam, demonstrated limited efficacy with 51.1% sensitivity, and combination with tazobactam improved results to 60%. This underscores the utility of beta-lactamase inhibitors in overcoming resistance mechanisms, though their efficacy remains suboptimal in some cases.²⁴ Similarly, cephalosporins such as ceftazidime and cefepime showed moderate effectiveness, and the combination of ceftazidime with avibactam provided a modest improvement, reinforcing the value of combination therapies in managing resistant infections which are in accordance with earlier investigators.^25,26

Aminoglycosides and fluoroquinolones showed moderate effi-cacy, demonstrating their potential role in combination regimens.¹⁴ However, the relatively high resistance rates for these agents reflect the impact of prior antimicrobial exposure and underline the need for judicious prescribing practices. One of the causes for this could be that most of these patients usually present in the ENT OPD after having experienced treatment failure with previous antibiotics management. Cultures are only requested when commonly used antibiotics have failed to eradicate the infection causing it to be another important factor. However, antibiotic usage without culture sensitivity testing is an important factor leading to rising antibiotic resistance in CSOM.

CONCLUSION

This study emphasises the complex interplay of patient factors, clinical interventions, and microbial characteristics associated with antimicrobial resistance in P. aeruginosa from CSOM patients. The findings underscore the importance of robust infection control practices, judicious use of antibiotics, and continuous surveillance to mitigate the threat of resistant infections. Further research with larger cohorts is needed to validate these findings and explore novel therapeutic approaches.

ETHICAL  APPROVAL:
Ethical approval was taken from the Institutional Review Board of Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan (IRB No: F.2-81/2022-GENL/132/JPMC).

PATIENTS’ CONSENT:
An informed consent was obtained from all the patients inclu-ded in the study.

COMPETING  INTEREST:
The authors declared no conflict of interest.

AUTHORS’ CONTRIBUTION:
SR: Contribution to the conception of the work, acquisition, analysis, and interpretation of data.
MS: Final approval of the version to be published.
FU: Critical revision of the manuscript for important intellectual content.
MRD: Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
All authors approved the final version of the manuscript to be published.

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