European Journal of Cardiovascular Medicine

Multidrug-resistant Staphylococcus aureus (MDR-SA) poses a significant global health threat, causing a wide range of debilitating infections and fatalities.(1) Multidrug resistance (MDR) is defined as non-susceptibility to at least one agent in three or more antimicrobial categories. Within the definition of MDR, finding an isolate resistant to oxacillin or cefoxitin predicts non-susceptibility to all β-lactam antimicrobial categories listed, with the exception of anti-MRSA cephalosporins (i.e., all categories of penicillins, cephalosporins, β-lactamase inhibitors, and carbapenems). Thus, an MRSA isolate will always be characterized as MDR because it meets the definition for MDR.(2)  Moreover, multidrug resistance among methicillin-susceptible isolates is increasing. (3) The emergence and spread of methicillin-resistant (MRSA) and vancomycin-resistant strains (VRSA) has further complicated treatment options, necessitating the development of novel antibiotics for effective control.(1,4) The slow progression of new antibiotics, limited treatment choices, and scarcity of new drug approvals create immense obstacles in addressing this crisis.(1)

Globally, the prevalence of MDR-MRSA among S. aureus bloodstream infections varied widely, from 2.2% in Canada to 35.6% in the Asia-Pacific region.(5) In Iowa, USA, individuals with current swine exposure were six times more likely to carry multidrug-resistant S. aureus compared to those without exposure. (6) In Bangladesh, 96% of S. aureus isolates from buffalo milk samples were multidrug-resistant.(7) In India, the overall prevalence of MRSA in humans was found to be 37% from 2015 to 2019, with regional variations ranging from 33% to 43% across different zones.(8)  The incidence of methicillin-resistant MDR Staphylococcus aureus isolates has gradually escalated both globally and regionally. In China, 44.4% of MSSA strains exhibited multidrug resistance, with high resistance to penicillin, erythromycin, and clindamycin.(9) Also, a study from Nepal, which borders India, found that 52.12% of MSSA isolates were multidrug-resistant.(3) These observations of increasing prevalence of both MRSA and MDR-MSSA, raise concerns for total MDR Staphylococcus aureus burden emphasizing the urgent need for continuous monitoring and updated antimicrobial stewardship strategies to guide empirical therapy effectively.(10)

However, there is a paucity of comprehensive data from West Bengal regarding the prevalence and antimicrobial susceptibility patterns of MDR S. aureus isolated from clinical samples. Understanding the regional epidemiology of MDR-SA, including its resistance trends, is critical for the formulation of evidence-based treatment protocols. The lack of updated local data hinders effective infection control policies, making it necessary to bridge this knowledge gap through targeted research. This study aimed to determine the prevalence of MDR S. aureus among clinical isolates from a tertiary care hospital in West Bengal. Additionally, we sought to analyze the antimicrobial susceptibility patterns of these isolates, highlighting resistance trends to commonly used antibiotics. These findings will contribute to a better understanding of the local epidemiology of MDR S. aureus and support the development of more effective infection control strategies and empirical treatment guidelines.

Study setting

This study was conducted at Burdwan Medical College and Hospital (BMCH), a tertiary care teaching hospital in Purba Bardhaman, West Bengal, India. The BMCH serves as a referral center for a diverse patient population, encompassing both urban and rural communities. The hospital provides comprehensive medical services, including intensive care, surgery, and specialized infectious disease management. The study setting is significant given the high patient load, frequent antimicrobial use, and varying healthcare access, which contribute to the emergence of multidrug-resistant Staphylococcus aureus. These factors provide a relevant epidemiological context for the interpretation of trends in antimicrobial resistance.

Study design

This hospital-based cross-sectional study was conducted over nine months at Burdwan Medical College, a tertiary care hospital in Purba Bardhaman.

Study population

The study involved collection of all relevant clinical samples such as blood, pus, urine, sputum, wound swabs, and other body fluids following proper aseptic methods from a broad spectrum of patients, encompassing both those hospitalized and those treated as outpatients. Participants varied in age and sex and belonged to a wide array of medical and surgical disciplines. Once submitted to our department, these samples were processed in the microbiology laboratory using standard operating procedures.

Sample size

Over a span of nine months, the study considered 2820 individual patients who aseptically submitted samples such as blood, pus, urine, sputum, wound swabs, and other body fluids in our microbiology laboratory.

Study procedure

All relevant clinical samples, including blood, pus, urine, sputum, wound swabs, and body fluids, collected aseptically from both inpatients and outpatients across multiple medical and surgical specialties were processed in the microbiology laboratory using standard operating procedures. During processing of the aseptically collected samples, S. aureus was identified using Gram staining, catalase test, slide and tube coagulase tests, and growth characteristics on selective media such as Mannitol Salt Agar. Confirmation of the isolates and antimicrobial susceptibility testing were performed using the Kirby-Bauer disk diffusion method on Mueller-Hinton agar, following the Clinical and Laboratory Standards Institute (CLSI) guidelines. When required, automated systems, such as VITEK 2, were utilized for additional confirmation and expanded susceptibility profiling. Antibiotic panels included cefoxitin (as a surrogate for methicillin resistance), azithromycin, clindamycin, ciprofloxacin, levofloxacin, moxifloxacin, tetracycline, doxycycline, tigecycline, trimethoprim-sulfamethoxazole, amikacin, gentamicin, netilmicin, linezolid, fosfomycin, teicoplanin and vancomycin.

Detection of Multidrug resistance (MDR)

Multidrug resistance (MDR) was defined as non-susceptibility to at least one agent in three or more antimicrobial categories. Within the definition of MDR, a unique rule was applied when defining the antimicrobial resistance of an S. aureus isolate. Finding an isolate resistant to oxacillin or cefoxitin predicts non-susceptibility to all β-lactam antimicrobial categories listed, with the exception of anti-MRSA cephalosporins (i.e., all categories of penicillins, cephalosporins, β-lactamase inhibitors, and carbapenems). (2)

Table 1: Staphylococcus aureus: Antimicrobial Categories and Agents (2)

An MRSA isolate will thus always be characterized as MDR because it meets the definition for MDR, ‘non-susceptible to at least one antimicrobial agent in three or more categories.’ (Table 1)

Detection of MRSA

To identify MRSA, cefoxitin disc (30 µg) was used. Staphylococcus isolates were categorized as methicillin-sensitive if they exhibited inhibition zones of 22 mm or larger, indicating cefoxitin susceptibility. Conversely, Staphylococcus aureus isolates displaying inhibition zones measuring 21 mm or less were deemed methicillin-resistant.(11)

Data collection

Patient demographic and clinical data, including age, sex, hospital ward, diagnosis, sample type, and prior antibiotic use, were collected using pre-designed structured proformas. Laboratory and clinical data were double-entered independently by two trained personnel using Microsoft Excel to minimize data entry errors. Cross-verification of entries was performed to identify discrepancies, which were resolved through a review of source documents such as laboratory registers and patient records.

For data validation, periodic audits (10% of the total entries) were conducted, and data consistency was ensured through logical checks, range checks, and standard coding. Quality control measures included the use of ATCC 25923 S. aureus as a control strain for susceptibility testing. The final validated dataset was used for statistical analysis to evaluate the prevalence and antimicrobial resistance patterns of MDR Staphylococcus aureus strains in the study setting.

Data analysis

Data were analyzed using SPSS Statistics (version 16.0; SPSS for Windows; SPSS Inc., Chicago, IL, USA). Descriptive statistics were used to summarize the demographic characteristics and prevalence rates, and categorical variables were expressed as frequencies and percentages. Continuous data were presented as mean±SD, and frequency (%) tables were generated for categorical variables. The χ2 test and Fisher’s exact test, where necessary, were used to compare categorical variables. All the data were analyzed at 95% CI, and their corresponding 5% margin of error with a value of p<0.05 was considered to be statistically significant for all analyses. The association between potential risk factors and MDR Staphylococcus aureus was assessed using Fisher’s exact test. Statistical significance was set at p < 0.05.

Human participant protection

This study was approved by the Institutional Human Ethics Committee of Burdwan Medical College, Purba Bardhaman, West Bengal. All patient identifiers were anonymized to ensure confidentiality. The requirement for informed consent was waived because only de-identified clinical samples were used. No deviation from the approved study protocol was observed during the study period.

Demographic characteristics

Of the 2,820 clinical samples processed during the study period, Staphylococcus aureus was isolated from 539 samples, yielding an overall prevalence of 19.1%. The median age of patients from whom S. aureus was isolated was 32 years, with an interquartile range (IQR) of 21–35 years, indicating a relatively young patient population. Gender-wise distribution showed a slight male predominance, with 290 out of 539 isolates (53.8%) obtained from male patients and 249 (46.2%) from females.

The distribution of S. aureus across different sample types revealed that the majority was isolated from pus or wound swab specimens, with 343 out of 539 (63.6%), highlighting skin and soft tissue infections as the most common clinical presentation. Blood samples were obtained from 66 isolates (12.2%), followed by sputum samples from 52 isolates (9.6%). Urine samples accounted for 43 isolates (7.9%), whereas 35 isolates (6.5%) were obtained from various sterile body fluids, such as pleural or ascitic fluid. (Table 2)

Table 2: Demographic characteristics

Prevalence of Staphylococcus aureus

Of the 539 Staphylococcus aureus isolates recovered from various clinical specimens, 253 (46.9%) were identified as methicillin-resistant Staphylococcus aureus (MRSA), while the remaining 286 (53.1%) were methicillin-sensitive Staphylococcus aureus (MSSA). This indicates a moderately high prevalence of MRSA within the study population, underscoring the persistent challenge of multidrug-resistant pathogens in a tertiary care setting. The 95% confidence interval (CI) for MRSA prevalence ranged from 40.6% to 52.3%, whereas that for MSSA ranged from 48.7% to 59.4%, reflecting statistical reliability in the observed proportions. (Table 3)

Table 3: Prevalence of Staphylococcus aureus (N= 539)

Antimicrobial susceptibility pattern of Methicillin sensitive Staphylococcus aureus (MSSA) isolates to different antimicrobial agents belonging to different antimicrobial categories

Among the 286 Staphylococcus aureus isolates identified as methicillin-sensitive (MSSA), their susceptibility to various antimicrobial agents across multiple categories revealed significant variation. Notably, all 286 isolates (100%) exhibited complete susceptibility to glycopeptides, such as vancomycin and teicoplanin, and to the oxazolidinone class, represented by linezolid, indicating their continued efficacy against MSSA. Similarly, high susceptibility was observed for clindamycin (273/286; 95.5%) and tigecycline (267/286; 93.4%), highlighting their potential as reliable therapeutic options.

Within the macrolide group, azithromycin showed moderate susceptibility, with 197 of 286 isolates (68.9%) being sensitive. In the tetracycline class, doxycycline demonstrated a higher efficacy (217/286; 75.9%) than tetracycline (149/286; 52.1%), reflecting a preference for doxycycline in empirical management. Among aminoglycosides, amikacin showed a relatively higher susceptibility (181/286; 63.3%) than gentamicin (130/286; 45.5%) and netilmicin (142/286; 49.7%), indicating intra-class variability.

Fluoroquinolone resistance was prominent, with ciprofloxacin being the least effective; only 95 of 286 isolates (33.2%) were susceptible. In contrast, levofloxacin and moxifloxacin showed moderately better results, with susceptibility rates of 54.9% (of 157/286) and 62.6% (of 179/286), respectively. Trimethoprim-sulfamethoxazole also showed a lower susceptibility rate (115/286, 40.2%). Among the phosphonic acid agents, fosfomycin showed moderate efficacy, with 167 of the 286 isolates (58.4%) being susceptible. (Table 4)

Table 4. Antimicrobial susceptibility patterns of methicillin-sensitive Staphylococcus aureus (MSSA) isolates to different antimicrobial agents belonging to different antimicrobial categories. (N= 286)

Distribution of multidrug resistance (MDR) among clinical isolates of Methicillin sensitive Staphylococcus aureus (MSSA) isolates

Among the 286 clinical isolates of methicillin-sensitive S. aureus (MSSA) evaluated in the present study, multidrug resistance (MDR) was identified in 85 isolates, accounting for 29.7% of the total population (85/286). These MDR-MSSA strains exhibited resistance to at least three different categories of antimicrobial agents. A detailed analysis of the distribution revealed that 39 isolates (13.7%) were resistant to three antimicrobial drugs belonging to different antimicrobial categories, whereas 25 isolates (8.7%) demonstrated resistance to four such drugs. Furthermore, a small but significant subset of 21 isolates (7.3%) showed resistance to more than four antimicrobial agents in four different categories, indicating a higher degree of resistance. (Table 5)

Table 5: Distribution of multidrug resistance among clinical isolates of Methicillin sensitive Staphylococcus aureus isolates

Prevalence of MDR Staphylococcus aureus

Among the 539 Staphylococcus aureus isolates obtained from various clinical samples, 338 (62.7%) were identified as multidrug-resistant (MDR), indicating a high overall burden of resistance. Of these, 253 isolates (46.9%) were methicillin-resistant Staphylococcus aureus (MRSA), which constituted the predominant MDR phenotype. Additionally, 85 isolates (15.8%) were methicillin-sensitive but still exhibited multidrug resistance (MDR MSSA), reinforcing the presence of significant resistance even among non-MRSA strains. (Table 6)

Table 6: Prevalence of MDR Staphylococcus aureus (N= 338)

Distribution of MDR-SA and Non MDR-SA in study participants with demographic and different clinical specimens

Among the 539 Staphylococcus aureus isolates included in the study, 338 (62.7%) were identified as multidrug-resistant (MDR-SA), while 201 (37.3%) were classified as non-multidrug-resistant (non-MDR-SA). The gender-wise distribution revealed a higher proportion of MDR-SA isolates among male patients, with 237 out of 338 (70.1%) MDR-SA isolates obtained from males, compared to 134 out of 201 (66.6%) in the non-MDR-SA group. Conversely, female representation was slightly higher in the non-MDR-SA group 67 (33.3%) than in the MDR-SA group 101 (29.9%); however, the gender-based difference was not statistically significant (p > 0.05).

Age-wise analyses revealed a significant shift in the distribution pattern. Children aged less than 1 year and those aged 1–14 years accounted for only 7 (2.1%) and 19 (5.6%) of the MDR-SA cases, respectively; however, but significantly constituted 43 (21.4%) and 89 (44.3%) of the non-MDR-SA group, respectively. In contrast, MDR-SA was more prevalent in adults, especially among individuals aged 25–34 years, who accounted for the highest proportion of 119 (35.2%) of 338 MDR-SA cases, compared to only 25 (12.4%) of 201 non-MDR-SA isolates in the same age group. This was followed by the 15–24 and 35–44 years age groups, contributing 97 (28.7%) and 47 (13.9%) to the MDR-SA category, respectively. The differences in age distribution between the MDR-SA and non-MDR-SA groups, although striking, were not statistically significant (p > 0.05).

With respect to clinical specimens, pus and swab samples were the predominant sources of both MDR and non-MDR S. aureus isolates. A total of 187 of 338 MDR-SA isolates (55.3%) were recovered from pus/swab samples, which was comparable to 102 of 201 (50.7%) in the non-MDR-SA group. Blood specimens yielded 52 MDR-SA (15.4%) and 43 non-MDR-SA isolates (21.3%). Body fluids, including pleural, peritoneal, and cerebrospinal fluids, accounted for 47 (13.9%) MDR-SA isolates and 35 (17.4%) non-MDR-SA isolates. The urinary isolates comprised 30 (8.9%) MDR-SA cases and 13 (6.5%) non-MDR-SA cases. Sputum specimens accounted for the fewest isolates overall, contributing 22 (6.5%) to the MDR-SA group and 8 (3.9%) to the non-MDR-SA group. Across all specimen types, the differences in proportions between the two groups were not statistically significant (p > 0.05). (Table 7)

Table 7: Distribution of MDR-SA and Non MDR-SA in study participants with demographic and different clinical specimens

Antimicrobial susceptibilities of MDR Staphylococcus aureus and Non MDR Staphylococcus aureus isolates.

Comparative analysis of antimicrobial susceptibilities between multidrug-resistant Staphylococcus aureus (MDR-SA) isolates (n = 338) and non-MDR Staphylococcus aureus (non-MDR-SA) isolates (n = 201) revealed notable differences across various antibiotic classes. Universal susceptibility (100%) to vancomycin, linezolid, and teicoplanin was observed in both MDR-SA and non-MDR-SA groups, confirming their consistent efficacy in treating infections caused by S. aureus strains in this setting.

Among aminoglycosides, susceptibility to amikacin was markedly lower in the MDR-SA isolates (141/338; 41.7%) than in the non-MDR-SA isolates (127/201; 63.2%). A similar trend was noted with gentamicin, where only 149/338 (44.1%) MDR-SA isolates were susceptible versus 48/201 (23.9%) in the non-MDR group, a statistically significant difference (p < 0.05). In contrast, netilmicin displayed relatively similar susceptibility rates between the two groups, with 203/338 (60.1%) in the MDR-SA group and 110/201 (54.7%) in the non-MDR-SA group, and this difference was not statistically significant (p > 0.05).

With regard to fluoroquinolones, ciprofloxacin and levofloxacin showed reduced activity in both groups, but susceptibility to ciprofloxacin was significantly higher in MDR-SA (125/338; 36.9%) than in non-MDR-SA (52/201; 25.9%) (p < 0.05). However, levofloxacin susceptibility did not differ significantly (197/338, 58.3% in MDR-SA vs. 97/201, 48.3% in non-MDR-SA; p > 0.05).

Among macrolides and lincosamides, azithromycin demonstrated a stark contrast in susceptibility rates, being effective against only 81/338 (23.9%) MDR-SA isolates, but significantly higher in non-MDR-SA isolates (157/201; 78.1%) (p < 0.05). However, clindamycin showed activity comparable to that of 299/338 (88.5%) MDR-SA and 175/201 (87.1%) non-MDR-SA isolates (p > 0.05), suggesting its retained efficacy across both groups.

In the tetracycline class, doxycycline was notably more effective in non-MDR-SA (172/201; 85.6%) than in MDR-SA (91/338; 26.9%), with a statistically significant difference (p < 0.05). Similarly, tetracycline susceptibility was significantly higher in non-MDR-SA isolates (135/201; 67.2%) than in MDR-SA isolates (141/338; 41.7%) (p < 0.05).

All non-MDR-SA isolates were sensitive to cefoxitin (201/201; 100%), whereas only 85/338 (25.1%) of the MDR-SA isolates were susceptible to β-lactam antibiotics. Resistance to ceftriaxone was more pronounced in the MDR group, with 239/338 (70.7%) resistant isolates versus only 13/201 (6.5%) in the non-MDR group, indicating a highly significant difference (p < 0.05).

Trimethoprim-sulfamethoxazole (TMP/SMX) demonstrated greater efficacy in non-MDR-SA isolates (102/201; 50.7%) than in MDR-SA isolates (120/338; 35.5%), and the difference was statistically significant (p < 0.05). (Table 8)

Table 8. Antimicrobial susceptibilities of MDR Staphylococcus aureus and Non MDR Staphylococcus aureus isolates.

S^1: Sensitive, R²: Resistant. ³P value: Resistance rates of antibiotics among MDR Staphylococcus aureus (MDR-SA) compared with those among Non MDR Staphylococcus aureus (non-MDR-SA) isolates.

This study provides comprehensive insights into the prevalence and antimicrobial susceptibility patterns of multidrug-resistant Staphylococcus aureus (MDR-SA) isolated from clinical specimens in a tertiary care hospital in West Bengal. These findings highlight the significant burden of MDR-SA and explore the comparative resistance trends between MDR and non-MDR isolates. The results further reflect the need for continuous surveillance and informed antimicrobial stewardship, which is elaborated upon in the following discussion.

Demographic characteristics

The overall prevalence of Staphylococcus aureus at 19.1% aligns with prior reports from tertiary care hospitals across borders, where rates between 6% and 16% have been observed.(3,12) The younger median age (32 years, IQR: 21–35 years) suggests increased vulnerability among economically active individuals, potentially owing to higher exposure risks. The male predominance (53.8%) corroborates trends noted in similar hospital-based studies, often attributed to gender-related occupational or behavioral factors.(13) The predominance of pus/wound swab specimens (63.6%) underscores skin and soft tissue infections as major presentations, which is consistent with the findings of Rai et al. (2017).(14) The unexpectedly high isolation rate from urine (7.9%) could indicate an emerging uropathogenic role of S. aureus, warranting further investigation.

Prevalence of Staphylococcus aureus

The MRSA prevalence of 46.9% observed in this study aligns closely with findings from other Indian tertiary centers, where rates have ranged from 26–69%.(3,15) This indicates a sustained burden of MRSA in hospital settings, potentially driven by overuse of broad-spectrum antibiotics, inadequate infection control, and high patient turnover. Notably, the MSSA proportion remained relatively high (53.1%), suggesting a possible shift in strain dynamics. (16) Further genomic studies could explore whether clonal spread or horizontal gene transfer contributes to this balance, an area warranting future investigation as a hypothesis generation point.

Antimicrobial susceptibility pattern of Methicillin sensitive Staphylococcus aureus (MSSA) isolates to different antimicrobial agents belonging to different antimicrobial categories

The universal susceptibility of MSSA isolates to vancomycin, teicoplanin, and linezolid in the present study (100%) reaffirms the preserved efficacy of glycopeptides and oxazolidinones against S. aureus, aligning with findings by Gitau et al.(17) High clindamycin (95.5%) and tigecycline (93.4%) activities are consistent with regional studies from North India and Malaysia, where these agents remain effective alternatives to vancomycin for serious MSSA infections. (18,19)Azithromycin showed moderate susceptibility (68.9%), possibly reflecting the partial preservation of macrolide sensitivity due to its infrequent empirical use. Doxycycline (75.9%) outperformed tetracycline (52.1%), contrasting intra-class variability reported by Kengne et al. (2024), and suggesting an area to explore by further research.(20)

Among the aminoglycosides, amikacin (63.3%) remained superior to gentamicin (45.5%) and netilmicin (49.7%), supporting its empirical role. However, increasing gentamicin resistance may stem from longstanding overuse and poor stewardship practices in outpatient settings.

Fluoroquinolone resistance was notably high for ciprofloxacin (33.2%), a widely reported trend across South Asia, possibly due to the horizontal transfer of plasmid-mediated resistance genes. (21)Fosfomycin (58.4%) demonstrated moderate efficacy, opening a possible avenue for its repurposing, especially in urinary tract or biofilm-associated infections, meriting further clinical correlation and evaluation. This intra-class heterogeneity and persistent fluoroquinolone resistance warrant a hypothesis-driven exploration of the underlying resistance mechanisms and antibiotic utilization patterns in tertiary care settings.

Distribution of multidrug resistance (MDR) among clinical isolates of Methicillin sensitive Staphylococcus aureus (MSSA) isolates

The detection of multidrug resistance in 29.7% of MSSA isolates aligns with findings from other Indian and global studies, which report MDR-MSSA rates ranging from 44% to 52% depending on geographic and clinical context.(3,22) The observed gradient of resistance, from three to over four drug classes, indicates the selective antibiotic pressure and clonal persistence of resistant strains. The presence of MDR, even among MSSA, raises concerns about silent reservoirs of resistance, thereby challenging conventional treatment algorithms. The unexpectedly high proportion (7.3%) of strains resistant to more than four categories may reflect plasmid-mediated gene exchange, warranting genomic surveillance as a future research hypothesis.(3)

Prevalence of MDR Staphylococcus aureus

The observed MDR prevalence (62.7%) with MRSA as the dominant subtype (46.9%) aligns with regional studies from Nepal reporting similar burdens of resistance.(3) Notably, 15.8% MDR-MSSA prevalence highlights emerging resistance among methicillin-sensitive strains—which is significantly lesser than Himalayan country, Nepal.(3) These finding merits genomic investigation to explore mobile resistance elements, even in MSSA populations.

Distribution of MDR-SA and Non MDR-SA in study participants with demographic and different clinical specimens

Our study showed a male predominance among both MDR-SA and Non-MDR-SA cases, consistent with previous regional findings that suggest increased healthcare exposure and occupational risks in males.(23) The lower MDR-SA detection in children parallels other studies where younger age groups tend to have community-acquired, less resistant strains.(3) Pus/swab dominance reaffirms skin/soft tissue infections as common sources of S. aureus isolates.(3) These findings underscore the need for targeted antimicrobial stewardship interventions focused on adults in their productive years and expanded surveillance to monitor emerging trends in community-associated S. aureus resistance

Antimicrobial susceptibilities of MDR Staphylococcus aureus and Non MDR Staphylococcus aureus isolates

Comparative analysis between MDR-SA and non-MDR-SA isolates in this study revealed distinct antimicrobial susceptibility patterns. This study is unique in nature, as all other studies have compared antimicrobial susceptibility patterns between MRSA and MSSA. The 100% susceptibility to vancomycin, teicoplanin, and linezolid in both groups is encouraging as a last-resort antibiotic for resistant gram-positive infections. While linezolid has shown high efficacy against various Gram-positive bacteria, including drug-resistant strains, the susceptibility to vancomycin and teicoplanin is not uniformly 100% across all studies.(24,25)

Aminoglycosides showed differential efficacy: amikacin was significantly more effective in non-MDR strains (63.2%) than in MDR strains (41.7%), possibly due to less prior exposure among the former. Fluoroquinolones, such as ciprofloxacin and levofloxacin, showed an overall reduced susceptibility, with ciprofloxacin paradoxically more effective in MDR-SA than in non-MDR-SA (36.9% vs. 25.9%). Although a reduced susceptibility to fluoroquinolones was noted against resistant S. aureus strains, MRSA demonstrated significantly higher resistance than MSSA.(26) Hence, this unexpected finding in our study warrants molecular resistance profiling as a hypothesis-generating area.

Macrolide resistance, particularly to azithromycin, was significantly higher in MDR-SA patients (23.9%) than in non-MDR-SA patients (78.1%). Schmitz et al. (2000) reported that the ermA gene, associated with macrolide resistance, was more common in MRSA isolates (88%) compared to methicillin-susceptible S. aureus (MSSA) isolates (38%) suggesting a higher prevalence of macrolide resistance in MRSA, which are often multidrug-resistant.(27) However, clindamycin remained consistently effective, reinforcing its therapeutic utility, especially in skin and soft tissue infections. Tetracycline-class antibiotics, especially doxycycline, demonstrated significantly better efficacy in non-MDR-SA (85.6%) than in MDR-SA (26.9%). Several studies indicated that tetracycline-class antibiotics, including doxycycline, were more effective against MSSA than MRSA.(3)

β-lactam resistance, particularly to cefoxitin and ceftriaxone, was a hallmark of the MDR-SA group, as expected. It was observed that 74.9% of MDR-SA isolates were cefoxitin-resistant, confirming MRSA status, while 70.7% were resistant to ceftriaxone versus 6.5% in non-MDR strains. These findings align with studies highlighting extensive β-lactamase activity and altered penicillin-binding proteins among MRSA strains.(3)

Trimethoprim-sulfamethoxazole (TMP-SMX) also showed diminished efficacy against MDR strains (35.5% vs. 50.7%). The higher resistance in MDR-SA likely reflects widespread over-the-counter use and the organism’s adaptive response to sulphonamide pressure. However, studies indicate that TMP-SMX remains effective against many S. aureus strains, including MRSA, as observed by Forcade et al. (2011) who reported 100% susceptibility of community acquired MRSA (CA-MRSA) isolates to TMP-SMX in primary care clinics in Texas.(28)

In conclusion, although vancomycin, linezolid, and teicoplanin remain universally effective, there is a decline in the efficacy of commonly used antibiotics against MDR strains across most drug classes. The higher ciprofloxacin susceptibility in MDR-SA is an unexpected observation and may merit further molecular analysis of resistance determinants. This study underscores the need for region-specific empirical therapy protocols and continued surveillance to mitigate the spread of MDR Staphylococcus aureus infections.

Implications of the findings

This study underscores the substantial burden of multidrug-resistant Staphylococcus aureus (MDR-SA) in a tertiary care setting, highlighting its predominance, even among methicillin-sensitive isolates. These findings have critical implications for antimicrobial stewardship programs, empirical therapy selection, and infection-control policies. The observed resistance patterns call for periodic local antibiogram surveillance, restrictive antibiotic policies, and rational prescribing behaviour. Moreover, the study emphasizes the urgent need for enhanced diagnostic capabilities and continuous training of healthcare personnel to effectively manage MDR pathogens, thereby aiding in reducing morbidity, hospital stay, and healthcare costs.

Strengths of the study

This study has several strengths. First, its feasibility was ensured by using routinely collected clinical samples across various specimen types, allowing for real-world applicability without an additional burden on patients or resources. The interestingness lies in its dual focus on MRSA and MDR-MSSA, a less commonly explored subset in the Indian context. In terms of novelty, this is probably the first study in India that offers a comparative antimicrobial susceptibility profile of MDR and non-MDR Staphylococcus aureus isolates, particularly from a tertiary care center. Ethical standards were upheld through institutional ethics approval and no identifiable patient data were used. The study is also highly relevant in light of the increasing antimicrobial resistance globally, especially in low- and middle-income countries.

Limitations of the study

However, this study had several limitations. Being single-center, the findings may not be generalizable to other regions with different antimicrobial usage patterns. Moreover, molecular characterization of resistance genes and biofilm-forming capacity, which could further elucidate resistance mechanisms, was not performed because of resource constraints. This omission may limit the interpretation of causality and the evolution of resistance.

Future studies should include multicenter data, molecular typing, and genomic surveillance to map resistance trends more comprehensively. Additionally, longitudinal surveillance to track the emergence or decline of specific resistance patterns over time would provide better epidemiological insights and aid in updating the institutional antimicrobial stewardship policies.

This study highlights the significant burden of MDR Staphylococcus aureus with distinct susceptibility patterns. These findings underscore the need for continuous surveillance, rational antibiotic use, and targeted infection control strategies to curb resistance, supporting the study’s objective of guiding empirical therapy and stewardship practices in tertiary care settings. Regular antimicrobial resistance surveillance, periodic antibiogram updates, and the integration of molecular resistance detection are recommended. Future multicenter studies with molecular typing and intervention trials should assess the impact of antimicrobial stewardship and infection control programs to curb the burden of MDR S. aureus in tertiary healthcare settings.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Acknowledgement

I express my heartfelt thanks and gratitude to the administration, faculty members, and staff of the Department of Microbiology, Burdwan Medical College and Hospital, for allowing me to conduct this study.

Funding

Funding: This study was supported by the authors.

1. Salikin, N. H., et al. “Combating Multidrug‑Resistant (MDR) Staphylococcus aureus Infection Using Terpene and Its Derivative.” World Journal of Microbiology and Biotechnology, vol. 40, no. 12, 4 Dec. 2024, p. 402.
2. Magiorakos, A. P., et al. “Multidrug‑Resistant, Extensively Drug‑Resistant and Pandrug‑Resistant Bacteria: An International Expert Proposal for Interim Standard Definitions for Acquired Resistance.” Clinical Microbiology and Infection, vol. 18, no. 3, 2012, pp. 268–281.
3. Adhikari, P., et al. “Prevalence, Antimicrobial Susceptibility Pattern and Multidrug Resistance of Methicillin‑Resistant Staphylococcus aureus Isolated from Clinical Samples at a Tertiary Care Teaching Hospital: An Observational, Cross‑Sectional Study from the Himalayan Country, Nepal.” BMJ Open, vol. 13, no. 5, 10 May 2023.
4. Mwangi, J., X. Hao, R. Lai, and Z. Y. Zhang. “Antimicrobial Peptides: New Hope in the War against Multidrug Resistance.” Zoological Research, vol. 40, no. 6, 2019, pp. 488–505.
5. Diekema, D. J., et al. “Genetic Relatedness of Multidrug‑Resistant, Methicillin (Oxacillin)‑Resistant Staphylococcus aureus Bloodstream Isolates from SENTRY Antimicrobial Resistance Surveillance Centers Worldwide, 1998.” Microbial Drug Resistance, vol. 6, no. 3, Jan. 2000, pp. 213–221.
6. Wardyn, S. E., et al. “Swine Farming Is a Risk Factor for Infection With and High Prevalence of Carriage of Multidrug‑Resistant Staphylococcus aureus.” Clinical Infectious Diseases, vol. 61, no. 1, 1 July 2015, pp. 59–66.
7. Hoque, M. N., et al. “Antibiogram and Virulence Profiling Reveals Multidrug Resistant Staphylococcus aureus as the Predominant Aetiology of Subclinical Mastitis in Riverine Buffaloes.” Veterinary Medicine and Science, vol. 8, no. 6, 22 Nov. 2022, pp. 2631–2645.
8. Patil, S. S., et al. “Prevalence of Methicillin‑Resistant Staphylococcus aureus in India: A Systematic Review and Meta‑analysis.” Oman Medical Journal, vol. 37, no. 4, 31 July 2022, e440.
9. Yang, Y., et al. “Molecular and Phenotypic Characterization Revealed High Prevalence of Multidrug‑Resistant Methicillin‑Susceptible Staphylococcus aureus in Chongqing, Southwestern China.” Microbial Drug Resistance, vol. 23, no. 2, Mar. 2017, pp. 241–246.
10. Salikin, N. H. “Combating Multidrug‑Resistant (MDR) Staphylococcus aureus Infection Using Terpene and Its Derivative.” World Journal of Microbiology and Biotechnology, vol. 40, no. 12, Dec. 2024.
11. M100 Performance Standards for Antimicrobial Susceptibility Testing: A CLSI Supplement for Global Application. 32nd ed., Clinical and Laboratory Standards Institute, 2022, www.clsi.org.
12. Wolde, W., et al. “Nasal Carriage Rate of Staphylococcus aureus, Its Associated Factors, and Antimicrobial Susceptibility Pattern among Health Care Workers in Public Hospitals, Harar, Eastern Ethiopia.” Infection and Drug Resistance, vol. 16, 2023, pp. 3477–3486.
13. Westgeest, A. C., et al. “Female Sex and Mortality in Patients with Staphylococcus aureus” JAMA Network Open, vol. 7, no. 2, 27 Feb. 2024, e240473.
14. Rai, S., et al. “Bacteriological Profile and Antimicrobial Susceptibility Patterns of Bacteria Isolated from Pus/Wound Swab Samples from Children Attending a Tertiary Care Hospital in Kathmandu, Nepal.” International Journal of Microbiology, 2017, art. ID 1–5.
15. Patil, S. S., et al. Same as citation 8.
16. Jackson, K. A., et al. “Public Health Importance of Invasive Methicillin‑Sensitive Staphylococcus aureus Infections: Surveillance in 8 US Counties, 2016.” Clinical Infectious Diseases, vol. 70, no. 6, 3 Mar. 2020, pp. 1021–1028.
17. Gitau, W., et al. “Antimicrobial Susceptibility Pattern of Staphylococcus aureus Isolates from Clinical Specimens at Kenyatta National Hospital.” BMC Research Notes, vol. 11, no. 1, 3 Dec. 2018, art. ID 226.
18. Che Hamzah, A. M., et al. “Tigecycline and Inducible Clindamycin Resistance in Clinical Isolates of Methicillin‑Resistant Staphylococcus aureus from Terengganu, Malaysia.” Journal of Medical Microbiology, vol. 68, no. 9, 1 Sept. 2019, pp. 1299–1305.
19. Arjyal, C., J. KC, and S. Neupane. “Prevalence of Methicillin‑Resistant Staphylococcus aureus in Shrines.” International Journal of Microbiology, vol. 2020, Mar. 2020, art. ID 1–10.
20. Kengne, M. F., et al. “Antibiotic Resistance Profile of Staphylococcus aureus in Cancer Patients at Laquintinie Hospital in Douala, Littoral Region, Cameroon.” BioMed Research International, 15 May 2024, art. ID 1–10.
21. Blumberg, H. M., et al. “Rapid Development of Ciprofloxacin Resistance in Methicillin‑Susceptible and ‑Resistant Staphylococcus aureus.” Journal of Infectious Diseases, vol. 163, no. 6, 1 June 1991, pp. 1279–1285.
22. Yang, Y., et al. Same as citation 9.
23. Humphreys, H., et al. “Gender Differences in Rates of Carriage and Bloodstream Infection Caused by Methicillin‑Resistant Staphylococcus aureus: Are They Real, Do They Matter and Why?” Clinical Infectious Diseases, vol. 61, no. 11, 1 Dec. 2015, pp. 1708–1714.
24. Henwood, C. J. “Susceptibility of Gram‑Positive Cocci from 25 UK Hospitals to Antimicrobial Agents Including Linezolid.” Journal of Antimicrobial Chemotherapy, vol. 46, no. 6, 1 Dec. 2000, pp. 931–940.
25. Stevens, D. L., et al. “Linezolid versus Vancomycin for the Treatment of Methicillin‑Resistant Staphylococcus aureus” Clinical Infectious Diseases, vol. 34, no. 11, June 2002, pp. 1481–1490.
26. Chang, V. S., et al. “Antibiotic Resistance in the Treatment of Staphylococcus aureus” Cornea, vol. 34, no. 6, June 2015, pp. 698–703.
27. Schmitz, F. J., et al. “Prevalence of Macrolide‑Resistance Genes in Staphylococcus aureus and Enterococcus faecium Isolates from 24 European University Hospitals.” Journal of Antimicrobial Chemotherapy, vol. 45, no. 6, 1 June 2000, pp. 891–894.
28. Forcade, N. A., et al. “Prevalence, Severity, and Treatment of Community‑Acquired Methicillin‑Resistant Staphylococcus aureus (CA‑MRSA) Skin and Soft Tissue Infections in 10 Medical Clinics in Texas: A South Texas Ambulatory Research Network (STARNet) Study.” The Journal of the American Board of Family Medicine, vol. 24, no. 5, Sept. 2011, pp. 543–550.