Fifteen Years of Data Reveal an Alarming Rise of Drug-Resistant E. coli Across Iran

A sweeping new analysis of antimicrobial resistance in Iran has delivered one of the most detailed pictures yet of how drug-resistant Escherichia coli has spread through a single country’s hospitals, farms, food, and waterways. The systematic review and meta-analysis, published in MicrobiologyOpen, pooled data from 368 studies covering more than 43,000 E. coli isolates collected between 2010 and January 2025. Its central message is stark: resistance is not confined to clinics. It is entrenched across every sector that the One Health framework recognizes—humans, animals, and the environment—and for several critically important antibiotics, the trend line is still pointing upward.

The scale of the underlying evidence base is itself remarkable. Researchers searched six databases, including Scopus, PubMed, Web of Science, and Iranian national repositories, and screened nearly 5,200 records before settling on the 368 studies that met rigorous methodological criteria, including adherence to recognized susceptibility testing standards from CLSI or EUCAST. More than 90 percent of the isolates came from human samples, with animal and environmental sources contributing smaller but crucial shares. The study was registered prospectively on PROSPERO, and the authors applied the JBI critical appraisal checklist to control for bias, using random-effects models and, where appropriate, meta-regression to track how resistance shifted across three distinct time periods: before Iran’s first national action plan on antimicrobial resistance, the interval between that plan and the COVID-19 pandemic, and the pandemic years and beyond.

The headline numbers are sobering. Resistance to penicillin reached 82.7 percent, ampicillin nearly 70 percent, and amoxicillin 71 percent across all isolates. Tetracycline resistance stood at 59 percent, trimethoprim–sulfamethoxazole at 54 percent, and nalidixic acid, an older quinolone, at nearly 56 percent. At the class level, penicillins showed the highest pooled resistance at 71.7 percent, followed by macrolides and tetracyclines, both at 58.9 percent, and cephems at 57.3 percent. By contrast, several drugs retained their effectiveness: nitrofurantoin resistance was just 13.3 percent, fosfomycin 8 percent, colistin 4.9 percent, and the carbapenem doripenem a mere 3.8 percent. These low-resistance agents, the authors note, could inform revisions of empirical treatment guidelines, particularly for urinary tract infections where oral options are dwindling.

Perhaps the most consequential finding concerns extended-spectrum beta-lactamase production, the mechanism that renders most penicillins and third- and fourth-generation cephalosporins useless. Across 136 studies, 47.2 percent of E. coli isolates were phenotypically ESBL-producing, with human isolates at 46.2 percent and environmental samples, including food, at a striking 42 percent. The molecular underpinnings were equally clear: the blaCTX-M gene family dominated at 68.2 percent prevalence, followed by blaTEM at 59.4 percent, and the combination of CTX-M and TEM was the most frequent co-occurrence at 23.3 percent. ESBL-producing isolates were significantly more resistant than their non-ESBL counterparts to nearly every antibiotic tested, spanning beta-lactams, fluoroquinolones, aminoglycosides, and folate pathway antagonists—only fosfomycin escaped the pattern.

Beyond ESBLs, the analysis documented quieter but deeply worrying signals. AmpC-producing isolates accounted for roughly 20 percent of tested strains, with the blaCIT gene present in 62 percent of molecularly characterized AmpC isolates. Metallo-beta-lactamase production was detected in 14.1 percent of isolates across 11 studies, with blaNDM—the gene behind some of the most untreatable infections worldwide—found in 30 percent of characterized MBL strains. Carbapenem resistance overall remained comparatively low, with meropenem at 7.3 percent and imipenem at 11.9 percent, but meta-regression revealed statistically significant upward trends for ertapenem, imipenem, and colistin, a last-resort polymyxin. Given that global WHO surveillance already records a 12.5 percent annual rise in imipenem resistance among E. coli bloodstream infections, the Iranian trajectory aligns with, and in some national surveillance data exceeds, the international curve.

The One Health lens exposed how differently resistance is distributed across reservoirs. Human isolates showed peak resistance to penicillin, erythromycin, and amoxicillin, reflecting clinical prescribing pressures. Animal isolates, drawn from 51 studies, were most resistant to flumequine and erythromycin, agents tied to veterinary and food-animal production, and showed rising resistance to chloramphenicol, streptomycin, and trimethoprim–sulfamethoxazole—older drugs still exerting selection pressure in agriculture. Environmental isolates, from 38 studies covering water, wastewater, and food, carried heavy burdens of amoxicillin, tetracycline, and ampicillin resistance, consistent with the environment’s role as a collecting basin for antibiotic residues and resistant bacteria from hospitals, farms, and communities. The authors are careful to note that these distinct profiles do not prove direct transmission between sectors, since the underlying studies lacked longitudinal and genomic linkage data, but they underscore that no single-sector intervention can succeed alone.

Geographic mapping added another layer of concern. ESBL-producing E. coli prevalence varied widely by province, peaking at 65.3 percent in Sistan and Baluchistan and 64.9 percent in Khuzestan. Provincial maps of resistance by antibiotic class revealed that no province exceeded 40 percent resistance in the penem, fosfomycin, or nitroheterocyclic classes, but the spatial heterogeneity elsewhere suggests that empirical prescribing decisions in Iran cannot rely on national averages alone. The sequence typing data, though sparse due to the cost barriers of multilocus sequence typing, identified the globally pandemic ST131 clone—famous for carrying CTX-M-15 and fluoroquinolone resistance—circulating in Iranian clinical settings with allelic profiles identical to international strains, alongside regionally restricted lineages such as ST77, ST506, and ST1007.

The temporal analysis also captured the shadow of the pandemic. Antibiotic prescribing in Iran reportedly surged by 87 percent in 2020–2021 compared with the prior year, driven largely by empirical azithromycin and beta-lactam use for respiratory symptoms, and the study found significant increases in resistance to ceftizoxime, ertapenem, streptomycin, piperacillin–tazobactam, and colistin over the time points. Consumption data compound the problem: only 48.6 percent of antibiotics used in Iran in 2024 belonged to the WHO Access group, well below the 60 percent target recommended in the AWaRe framework, while Watch-group drugs made up 51.3 percent of consumption. That imbalance, the authors argue, signals an urgent need for stewardship reform spanning hospitals, veterinary practice, and agriculture.

The study is not without limitations, and the authors are candid about them. Human isolates vastly outnumber animal and environmental ones, reflecting surveillance inequities rather than true epidemiology; grey literature was excluded, raising the possibility of publication bias; and substantial heterogeneity across 15 years of studies, varying specimen types, and inconsistent breakpoints limits the precision of pooled estimates. Hospital-based studies dominate the dataset, potentially masking community-level patterns. Yet even with these caveats, the analysis stands as the most comprehensive baseline ever assembled for Iran’s National Action Plan on antimicrobial resistance. Its conclusion is unambiguous: without coordinated, multisectoral stewardship, mandatory environmental surveillance, and a binding commitment to the One Health paradigm, the country’s most versatile pathogen will keep acquiring the genes that make its infections untreatable.

Subject of Research: Antimicrobial resistance in Escherichia coli across human, animal, and environmental reservoirs in Iran

Article Title: Iran's Escherichia coli AMR Landscape (2010–2025): A One Health Systematic Review and Meta‐Analysis

Article References: Dehghan, A., Arabian, M., Tahmasebi, Z., Fakhri‐Demeshghieh, A., Baseri, N., Mostafavi, E., Badmasti, F., Abnaroodhelleh, F., Seifi, A., & Bagheri Amiri, F. (2026). Iran's Escherichia coli AMR Landscape (2010–2025): A One Health Systematic Review and Meta‐Analysis. MicrobiologyOpen, 15(5), Article e70420. https://doi.org/10.1002/mbo3.70420

Image Credits: AI Generated

DOI: 10.1002/mbo3.70420

Keywords: antimicrobial resistance, Escherichia coli, One Health, ESBL, carbapenem resistance, Iran, meta-analysis, blaCTX-M, antimicrobial stewardship, public health surveillance, beta-lactamase genes, environmental reservoirs