In this retrospective surveillance study, MRSA accounted for 24.4% of all
Staphylococcus aureus isolates recovered from two tertiary healthcare facilities in Qazvin. This prevalence is consistent with reports describing moderate MRSA rates in several regional settings, although it is lower than estimates reported from some other areas of Iran and neighboring countries. Differences among studies are expected because of variations in patient populations, specimen sources, study periods, and laboratory methods (
1,
9,
23). For example, investigations based on nasal carriage among healthy individuals are not directly comparable with studies of clinical isolates obtained from hospitalized patients (
24). Similarly, differences in infection control practices and antimicrobial prescribing policies may contribute to regional variation in MRSA prevalence.
The high prevalence of penicillin resistance (96.1%) observed in this study is consistent with the widespread production of β-lactamase among
S. aureus isolates worldwide (
3). Similar resistance patterns have been reported in previous Iranian and international studies, indicating that penicillin has limited value for the empirical treatment of suspected
S. aureus infections (
7,
16). Resistance to erythromycin (61.1%), clindamycin (57.4%), and ciprofloxacin (55.1%) was also common, suggesting substantial selective pressure from antimicrobial use within healthcare settings. Comparable findings have been reported in regions where prolonged or inappropriate antibiotic use has contributed to increasing resistance (
25,
26). In contrast, gentamicin showed the lowest resistance rate (8.0%) among the antimicrobial agents evaluated. This finding suggests that gentamicin may remain a useful component of combination therapy when clinically appropriate and supported by susceptibility testing. However, treatment decisions should continue to rely on local antibiograms and individual patient characteristics rather than on resistance rates alone.
Although overall resistance patterns were broadly similar between the two participating hospitals, significant differences were observed in resistance to erythromycin and trimethoprim-sulfamethoxazole. These findings may reflect differences in local prescribing practices, patient case mix, referral patterns, or infection prevention strategies. Institution-specific surveillance therefore remains important, as resistance profiles may vary even within the same geographic region. Environmental reservoirs may also contribute to the persistence of resistant organisms within healthcare settings. Recent studies have identified antimicrobial-resistant
S. aureus in hospital wastewater, supporting the possibility that environmental contamination plays a role in maintaining and disseminating resistant strains (
14). Although environmental sampling was beyond the scope of the present study, this mechanism should be considered when designing comprehensive infection prevention and antimicrobial stewardship programs.
Analysis by specimen source identified clinically relevant differences in antimicrobial susceptibility. Wound isolates showed the highest resistance to ciprofloxacin, erythromycin, and trimethoprim-sulfamethoxazole, whereas blood isolates exhibited the lowest resistance to gentamicin and trimethoprim-sulfamethoxazole. These observations suggest that resistance profiles may vary by site of infection. Similar findings have been reported previously and may reflect differences in antimicrobial exposure, tissue microenvironment, bacterial population dynamics, and prescribing practices across clinical settings. The significant association between specimen source and resistance to erythromycin and trimethoprim-sulfamethoxazole further supports the importance of considering the site of infection during empirical antimicrobial selection. Nevertheless, empirical therapy should be guided primarily by local susceptibility data and adjusted once culture and susceptibility results become available.
Comparison of MRSA and MSSA isolates showed that MRSA strains were more frequently resistant to several non-β-lactam antimicrobial agents, including ciprofloxacin, erythromycin, gentamicin, and trimethoprim-sulfamethoxazole. This pattern is consistent with the accumulation of multiple resistance determinants among MRSA lineages and reflects the well-recognized association between methicillin resistance and multidrug resistance (
27). These findings reinforce the importance of accurate microbiological diagnosis and antimicrobial susceptibility testing to support appropriate treatment decisions.
5.1. Temporal Trends in Antimicrobial Resistance
No statistically significant temporal trends in antimicrobial resistance were observed between 2021 and 2024. Although resistance rates fluctuated slightly across the study period, these variations did not reach statistical significance. Several factors may explain this finding. The relatively small number of isolates collected during the first study year reduced the statistical power to detect temporal changes. In addition, the unequal distribution of isolates across study years and the retrospective design limited the precision of trend analyses. Changes in healthcare delivery, infection prevention practices, and antimicrobial prescribing during the COVID-19 pandemic may also have influenced resistance patterns. These variables were not available for analysis and therefore could not be evaluated systematically. Consequently, the absence of significant temporal trends should be interpreted cautiously and should not be considered evidence that resistance patterns remained unchanged.
5.2. Clinical Relevance of the Findings
This study provides contemporary antimicrobial resistance data from two major referral hospitals in Qazvin, Iran. These findings contribute to regional surveillance efforts and establish a reference point for future monitoring.
The observed MRSA prevalence indicates that methicillin resistance remains an important concern in hospitalized patients. Continued surveillance is therefore necessary to detect changes in resistance patterns and to support antimicrobial stewardship programs. The consistently low resistance to gentamicin suggests that this agent may remain an appropriate therapeutic option in selected clinical situations when supported by antimicrobial susceptibility testing. Likewise, the identification of specimen-specific resistance profiles may assist clinicians in selecting empirical therapy before culture results become available.
The differences observed between the participating hospitals also underscore that local resistance data should guide empirical treatment recommendations. Hospital-specific antibiograms are likely to provide more useful information for clinical decision-making than regional estimates alone. An additional finding was the absence of D-testing for inducible clindamycin resistance during the study period. Because inducible resistance may lead to therapeutic failure despite apparent in vitro susceptibility, routine implementation of the D-test would improve laboratory reporting and support more appropriate antimicrobial selection.
Overall, these findings add to the available evidence describing antimicrobial resistance among S. aureus isolates in Iran and provide data that may assist local infection prevention and antimicrobial stewardship initiatives.
5.3. Strengths and Limitations
Several limitations should be considered when interpreting the findings of this study.
First, the retrospective design limited the availability of clinical information and prevented adjustment for important confounding variables, including previous antimicrobial exposure, duration of hospitalization, severity of illness, and underlying comorbidities. Second, MRSA identification was based on phenotypic cefoxitin resistance without molecular confirmation of mecA or mecC. Consequently, the study could not evaluate resistance mechanisms, characterize circulating clones, or investigate the molecular epidemiology of MRSA isolates. Third, inducible clindamycin resistance was not assessed because D-testing was unavailable. As a result, the reported clindamycin resistance rates may underestimate the true prevalence of clinically relevant resistance. Fourth, incomplete demographic and clinical data limited the assessment of patient-level risk factors and reduced the ability to explore associations between antimicrobial resistance and clinical characteristics. Finally, the unequal number of isolates collected across study years reduced the statistical power of temporal trend analyses. Therefore, the absence of significant changes over time should be interpreted with caution.
Despite these limitations, the study has several strengths. It includes a relatively large number of clinical isolates collected over four consecutive years from two major referral hospitals. Standardized microbiological methods and CLSI susceptibility criteria were used throughout the study period, allowing consistent assessment of antimicrobial resistance. The inclusion of analyses by specimen source and hospital also provides information that may support local antimicrobial stewardship and empirical treatment recommendations.
The findings provide updated regional surveillance data and may serve as a baseline for future multicenter studies incorporating molecular characterization, comprehensive clinical information, and prospective data collection.
5.4. Clinical Implications
The findings of this study have several implications for clinical practice and antimicrobial stewardship. Given the high resistance rates observed for penicillin, erythromycin, clindamycin, and ciprofloxacin, empirical use of these agents should be guided by local susceptibility data and culture results whenever possible. Hospital antimicrobial stewardship programs should regularly review prescribing practices to reduce unnecessary use of antibiotics associated with high resistance rates.
Gentamicin demonstrated the lowest overall resistance rate and may remain an appropriate treatment option in selected patients, particularly when used as part of combination therapy and supported by antimicrobial susceptibility testing. Because resistance patterns differed by specimen source, hospital-specific antibiograms that incorporate site-specific susceptibility data may improve empirical antibiotic selection. The study also supports continued investment in infection prevention measures, including adherence to hand hygiene, contact precautions for patients colonized or infected with MRSA, environmental cleaning, and surveillance of high-risk patient populations. These measures remain essential for limiting healthcare-associated transmission.
Routine implementation of the D-test for erythromycin-resistant, clindamycin-susceptible isolates should be considered to identify inducible clindamycin resistance and reduce the risk of treatment failure. Continued microbiological surveillance using standardized laboratory methods, together with periodic evaluation of local resistance patterns, will help guide empirical therapy and support evidence-based antimicrobial stewardship within the participating institutions.
5.5. Conclusions
This study found that nearly one-quarter of Staphylococcus aureus isolates recovered from hospitalized patients in two referral hospitals in Qazvin were methicillin resistant. Resistance to several commonly prescribed antimicrobial agents, particularly penicillin, erythromycin, clindamycin, and ciprofloxacin, remained high throughout the study period, whereas gentamicin retained relatively good in vitro activity. Resistance patterns differed by specimen source and between hospitals for selected antibiotics, highlighting the importance of institution-specific surveillance and local antibiograms when selecting empirical therapy. No statistically significant temporal changes in antimicrobial resistance were identified between 2021 and 2024.
These findings support continued antimicrobial stewardship, regular surveillance of resistance patterns, and ongoing infection prevention efforts. Future prospective studies incorporating molecular characterization of MRSA isolates and more detailed clinical data would improve understanding of resistance mechanisms and factors associated with antimicrobial resistance in this setting.