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. 2025 Aug 26;14:92. doi: 10.4103/abr.abr_262_25

Antimicrobial Resistance in Gram-Negative Bacterial Pneumonia After the COVID-19 Pandemic in Northern Iran

Golnar Rahimzadeh 1, Mahdieh Askari 2, Raha Rezai 1, Shaghayegh Rezai 1, Mohammad Sadegh Rezai 1,✉, Masoud Moradi 3
PMCID: PMC12435710  PMID: 40958933

Abstract

Background:

The irrational use of antibiotics has become a significant factor in the escalating global crisis of antimicrobial resistance (AMR). AMR is linked to an increasing burden of healthcare-associated infections caused by multidrug-resistant pathogens, which present substantial challenges for infection control and patient management. During the COVID-19 pandemic, the widespread use of antibiotics for treating and preventing secondary bacterial infections further exacerbated the threat of AMR worldwide. This study aimed to determine the antibiotic resistance profile of Gram-negative bacteria (GNB) causing pneumonia after COVID-19 in Northern Iran.

Materials and Methods:

In this cross-sectional study, respiratory specimens were collected from hospitalized patients with bacterial pneumonia at four hospitals in Northern Iran. The antimicrobial susceptibility profiles were assessed using the standard microdilution method in accordance with CLSI guidelines (2020). Additionally, resistance-associated genetic determinants were evaluated using multiplex PCR.

Results:

A total of 120 MDR GNB isolates were identified, primarily from sputum specimens (75.8%). Pseudomonas aeruginosa was the most common pathogen in the ICU, representing 35% of isolates. Resistance rates to antibiotics were high: Ciprofloxacin (85%), Ceftazidime (85%), Gentamicin (80%), and Colistin (77.5%), while Piperacillin-Tazobactam had a lower resistance rate of 33.3%.

Conclusions:

The present study highlights the increasing AMR among GNB causing pneumonia in ICU settings post COVID-19 pandemic in hospitals in Northern Iran. The prevalence of Pseudomonas aeruginosa and high resistance rates to new antibiotics such as Colistin pose significant challenges to treatment, while Piperacillin-Tazobactam shows relatively lower resistance and may be a potential option.

Keywords: Bacterial pneumonia, COVID-19, Gram-negative, multidrug resistance, multiplex polymerase chain reaction

INTRODUCTION

The global prevalence of antimicrobial resistance (AMR) poses a major threat to public health, with Gram-negative bacteria (GNB) at the forefront of this crisis due to their intrinsic and acquired resistance mechanisms. According to internationally recognized definitions endorsed by the European Center for Disease Prevention and Control and the Centers for Disease Control and Prevention, multidrug-resistant (MDR) organisms are those that exhibit non-susceptibility to at least one agent in three or more antimicrobial categories. Extensively drug-resistant (XDR) organisms show non-susceptibility to at least one agent in all but two or fewer antimicrobial categories. Pan-drug-resistant organisms are defined as being non-susceptible to all agents in all tested antimicrobial categories.[1]

GNB pneumonia has emerged as a significant clinical challenge, especially in hospitalized and immunocompromised patients. The respiratory tract, a frequent site of infection in critically ill individuals, has become a battleground where MDR organisms (MDROs) undermine conventional treatment protocols and compromise patient outcomes. The emergence of the COVID-19 pandemic further complicated this landscape. The surge in critically ill patients requiring prolonged mechanical ventilation, empirical broad-spectrum antibiotic therapy, and extended intensive care unit (ICU) stays created an ideal environment for the selection and dissemination of resistant Gram-negative pathogens, facilitating the horizontal transmission of MDR genes across COVID-19 wards and critical care units. Evidence suggests that secondary bacterial pneumonias, particularly those involving Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, were increasingly reported among COVID-19 patients, with alarmingly high resistance profiles.[2,3]

MDROs can lead to serious complications, including sepsis, respiratory failure, and lung fibrosis, and they are associated with high mortality rates worldwide. Community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) are acute respiratory infections that can occur within the first 48 h of hospital admission. Annually, CAP affects 9–14 individuals per 1,000, with 30%–46% of those requiring hospitalization. In the United States and some Asian countries, the estimated mortality rate for hospitalized patients with CAP ranges from 7.3% to 14%. Additionally, approximately 9%–14% of hospitalized patients with CAP need admission to the ICU, where the mortality rate for ICU patients is around 24%. HAP is the second most common hospital infection after urinary tract infections (UTIs), accounting for 30% of all hospital infections. Ventilator-associated pneumonia (VAP) constitutes 80% of all HAP cases. Early-onset pneumonia is typically caused by bacteria such as Staphylococcus aureus, Hemophilus influenzae, and Streptococcus pneumoniae. In contrast, late-onset pneumonia is often caused by resistant strains of Staphylococcus, Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter.[4,5,6,7,8,9,10]

The management of pneumonia caused by MDR-GNB strains presents a significant challenge. In addition to their colonization on mucous surfaces and their ability to form biofilms, they can develop resistance to antibiotics either through inherent traits or acquired mechanisms. These strains can produce beta-lactamases and aminoglycoside-modifying enzymes (AMEs), increase efflux pump expression, and reduce OprD protein production, which serves as an antibiotic entry channel. According to Ambler’s classification, beta-lactamases are divided into four classes: A, B, C, and D. Class B beta-lactamases, known as metallo-beta-lactamases (MBLs), have a broad spectrum of activity against most beta-lactam antibiotics, including carbapenems. In carbapenem-resistant strains, the production of various beta-lactamases, such as KPC, GES, IMP, NDM, GIM, FIM, SPM, VIM, and OXA-48, leads to a high level of resistance to carbapenems. ESBL strains are highly resistant to most beta-lactam antibiotics, including penicillins, cephalosporins, and aztreonam. They also exhibit resistance to carbapenems and quinolones such as Ciprofloxacin and Levofloxacin. This is due to the inhibition of DNA gyrase and topoisomerase IV, changes in topoisomerases 2 and 4, and the expression of plasmid-dependent efflux pumps OqxA and OqxB. In some cases, ESBL strains are modified to MDR and XDR, exhibiting a wide range of resistance.[11,12,13] Prescribing antibiotics without knowledge of the microbial resistance pattern has contributed to the development of antibiotic resistance. Especially, it is essential to assess changes in antibiotic resistance patterns following the COVID-19 pandemic in different regions of Iran. To address this issue, this study aimed to determine the antibiotic resistance profile of GNB causing pneumonia after COVID-19 in Northern Iran.

MATERIALS AND METHODS

Sample collection

This descriptive study was conducted in four hospitals located in Mazandaran province, Iran, from 2022 to 2023. The study included hospitalized patients with bacterial pneumonia who exhibited the following signs: chest X-ray infiltrates, fever greater than 37.8°C (100°F), purulent sputum, leukocytosis greater than 10,000 cells/μL, cough producing greenish or pus-like phlegm, and chills. Samples collected for the study included sputum, Bronchoalveolar lavage (BAL), endotracheal tube (ETT) samples, and pleural fluid [Table 1]. MDR Gram-negative strains, defined as being resistant to at least three categories of antibiotics, were included in the analysis. According to the guidelines outlined in the Clinical Microbiology Procedures Handbook, the MDR isolates were cultured on MacConkey agar and blood agar (QUELAB, USA) and then incubated for 24 h at 37°C. Conventional biochemical tests were used to identify the isolates.

Table 1.

Patients’ Demographic Information

Variable n (%)
Age
    <1 year old 5 (4.2)
    1–18 years old 23 (19.2)
    >18 years old 92 (76.7)
Gender
    Male 79 (65.8)
    Female 41 (34.2)
Unit
    ICU 67 (55.8)
    PICU 2 (19.2)
    Internal 12 (10)
    BICU 6 (5)
    NICU 5 (4.2)
    CCU 5 (4.2)
    Surgery 2 (1.6)
Sample
    Sputum 91 (75.8)
    Bronchoalveolar lavage (BAL) 14 (11.7)
    Endotracheal tube (ETT) 12 (10)
    Pleura 3 (2.5)
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Antimicrobial susceptibility testing (AST)

The antimicrobial susceptibility and minimum inhibitory concentration (MIC) of MDR isolates were determined using the standard microdilution method recommended by the Clinical and Laboratory Standards Institute guidelines (CLSI, 2020).[13]

Extended-spectrum beta-lactamase (ESBL) identification in bacterial isolates

To phenotypically detect ESBL-producing strains, a combined disk test (CDT) was performed. A bacterial colony suspension equivalent to 0.5 McFarland (1.5 × 108 CFU/mL) was prepared and cultured on Mueller-Hinton agar. Cephalosporin disks (e.g., Ceftriaxone, Cefotaxime, and Cefepime) were placed approximately 15–20 mm apart from a Cephalosporin + Beta-lactamase inhibitor disk (Clavulanic acid) on the agar plates. The plates were incubated at 37°C for 24 h to allow for bacterial growth. A positive result for ESBLs production is indicated if the zone of inhibition around the Ceftriaxone + Clavulanic acid disk is at least 5 mm larger than the zone around the Cephalosporin disk alone. This suggests that the bacteria are producing ESBLs.[13]

Genomic DNA extraction and genomic assays

The genomic DNA of MDR-GNB isolates was extracted using an extraction kit (Yekta Taghiz, Iran) according to the manufacturer’s protocol. The specific primers of E. coli included blaIMP, blaTEM, AcrA, AcrB, blaCTX, blaOXA-58, aaclb, blaSHV, and aacla.[13] The specific primers of A. baumannii included blaOXA-51, ampC, apA6, and blaNDM.[13] The specific primers of K. pneumoniae included blaSHV, blaCTX, blaTEM, acrAB, OqxAB, and blaIMP.[13] The specific primers of P. aeruginosa included blaSHV, blaCTX-M, blaAmpC, and blaIMP, blaSPM, and blaSIM. Multiplex PCR reaction was prepared, including Taq DNA polymerase (AMPLIQON, Denmark), primers (10 pM), template DNA (100 ng), and DNase-free distilled water. Multiplex PCR mixtures without template DNA and with DNA control; K. pneumoniae ATCC NO.7881 (blaCTXM, blaTEM, and blaSHV) and E. coli ATCC NO. 35218 (AcrA, AcrB, aaclb, aacla) were used as negative and positive controls, respectively. In summary, the amplification process involved a denaturation step at 94°C for 30 s, followed by 35 cycles at 61°C and 72°C for 30 min, and a final extension step at 72°C for 10 min. The multiplex PCR products were separated on a 1.5% agarose gel and were visualized using the gel documentation system (UVIDoc HD6 Touch, USA).[13]

Statistical analysis

Data were analyzed using SPSS version 22 is IBM Corp., Armonk, NY, US. Statistical analysis involved Chisquare and Fisher’s exact tests.

RESULTS

Table 1 presents the demographic and clinical data for 120 patients, with ages ranging from 9 days to 94 years, and a mean age of 48.64 years (SD = 27.87). The median age was 57.5 years (IQR: 49.5 (22.5–72)). Of the total sample, 65.8% were male. The most common specimen type collected for pneumonia diagnosis was sputum, accounting for 75.8% of the cases. Regarding the distribution of MDR infections, the ICU had the highest proportion of MDR P. aeruginosa infections (35%), while the lowest frequency of infections was observed for E. coli, which was present in only 3.3% of cases [Figure 1].

Figure 1.

Figure 1

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Frequency of MDR isolates from pneumonia cases

Antimicrobial susceptibility testing (AST)

Table 2 provides a detailed analysis of the antimicrobial susceptibility profiles of MDR isolates, determined using the microdilution method and MIC. The data includes both the GM MIC and the mode of MICs for various antibiotics, including Ampicillin-Sulbactam, Ceftazidime, Cefepime, Ciprofloxacin, Colistin, Co-amoxiclav, Gentamicin, Meropenem, and Piperacillin-Tazobactam. With regard to the MIC50 values, more than 50% of the MDR-GNB isolates exhibited resistance to the tested antibiotics. The results from the microdilution technique demonstrated significant resistance among the isolates, particularly to Ciprofloxacin (85%), Ceftazidime (85%), Gentamicin (80%), Ampicillin-Sulbactam (79.2%), and Colistin (77.5%). In contrast, Piperacillin-Tazobactam exhibited the lowest resistance rate.

Table 2.

Antimicrobial susceptibility of MDR isolates from bacterial pneumonia cases

MIC
Antibiotic		 A. baumannii (n=36) E. coli (n=4) K. pneumoniae (n=38) P. aeruginosa (n=42)
R S I MIC R S I MIC R S I MIC R S I MIC
50 90 50 90 50 90 50 90
Ciprofloxacin 97.2 0 2.8 250 >1000 100 0 0 250 -- 84.2 7.9 7.9 250 500 73.8 19 7.1 250 500
Meropenem 86.1 11.1 2.8 31 125 100 0 0 250 -- 73.7 15.8 10.5 31.2 500 47.6 45.2 7.1 4 <1000
Gentamicin 91.7 8.3 0 >1000 >1000 25 75 0 0.9 -- 76.3 21.1 2.6 <1000 <1000 78.6 21.4 0 500 <1000
Ceftazidime 91.7 2.8 5.6 500 >1000 75 25 0 250 -- 94.7 5.3 0 <1000 <1000 71.4 21.4 7.1 250 <1000
Colistin 77.8 22.2 0 3.9 >1000 25 75 0 0.9 -- 89.5 10.5 0 7.8 <1000 71.4 4.8 23.8 7.8 <1000
Piperacillin-Tazobactam 13.9 13.9 72.2 62.5 175 25 75 0 0.9 -- 50 31.6 18.4 93.8 <1000 35.7 40.5 23.8 32 <1000
Ampicillin-Sulbactam 66.7 5.6 27.8 62.5 <1000 75 25 0 1.9 -- 86.8 13.2 0 <1000 <1000 83.3 16.7 0 125 <1000
Co-Amoxiclav 100 0 0 >1000 >1000 100 0 0 250 -- 100 0 0 500 >1000 100 0 0 500 <1000
Cefepime 77.8 13.9 8.3 62.5 250 50 50 0 1.9 -- 92.1 2.6 5.3 250 <1000 45.2 45.2 9.5 16 <1000
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MIC= Minimum inhibitory concentration

Molecular epidemiology of MDR–NGB isolates

The frequency of resistance genes in E. coli is as follows: blaIMP (100%), blaTEM (100%), AcrA (100%), AcrB (100%), blaCTX (100%), aaclb (25%), blaSHV (25%), and aacla (50%).

The frequency of resistance genes of A. baumannii is as follows: blaOXA-51 (100%), ampC (100%), apA6 (88.9%), and blaNDM (77.8%).

The frequency of resistance genes of K. pneumoniae is as follows: blaSHV (73.7%), blaCTX (92.1%), blaTEM (97.14%), acrAB (97.4%), OqxAB (60.5%), and blaIMP (76.3%).

The frequency of resistance genes of P. aeruginosa is as follows: blaSHV (90.5%), blaCTX-M (76.2%), AmpC (93%), and blaIMP (97.6%). blaSPM and blaSIM were not observed among isolates.

In E. coli isolates, no significant relationship was found between resistance genes and antibiotic resistance [Figure 2]. In A. baumannii isolates, the blaNDM gene was significantly linked to resistance to Meropenem (P = 0.001) [Figure 3]. In P. aeruginosa isolates, the blaIMP gene was significantly associated with resistance to Meropenem (P = 0.001) [Figure 4]. In K. pneumoniae isolates, the blaSHV gene was significantly associated with resistance to Gentamicin (P = 0.01) and Ciprofloxacin (P = 0.05), the blaCTX gene was significantly associated with resistance to Gentamicin and Piperacillin-Tazobactam (P = 0.05 for both), and the blaIMP gene was significantly associated with resistance to Meropenem and Cefepime (P = 0.001 and P < 0.05, respectively) [Figure 5].

Figure 2.

Figure 2

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The frequency of resistance genes in E. coli isolates from cases of bacterial pneumonia. CIP: Ciprofloxacin, MEN: Meropenem, GM: Gentamicin, CAZ: Ceftazidime, CL: Colistin, PTZ: Piperacillin-Tazobactam, SAM: Ampicillin-Sulbactam, CPM: Cefepime

Figure 3.

Figure 3

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The frequency of resistance genes in A. baumannii isolates from cases of bacterial pneumonia. CIP: Ciprofloxacin, MEN: Meropenem, GM: Gentamicin, CAZ: Ceftazidime, CL: Colistin, PTZ: Piperacillin-Tazobactam, SAM: Ampicillin-Sulbactam, CPM: Cefepime

Figure 4.

Figure 4

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The frequency of resistance genes in P. aeruginosa isolates from cases of bacterial pneumonia. CIP: Ciprofloxacin, MEN: Meropenem, GM: Gentamicin, CAZ: Ceftazidime, CL: Colistin, PTZ: Piperacillin-Tazobactam, SAM: Ampicillin-Sulbactam, CPM: Cefepime

Figure 5.

Figure 5

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The frequency of resistance genes in K. pneumoniae isolates from cases of bacterial pneumonia. CIP: Ciprofloxacin, MEN: Meropenem, GM: Gentamicin, CAZ: Ceftazidime, CL: Colistin, PTZ: Piperacillin-Tazobactam, SAM: Ampicillin-Sulbactam, CPM: Cefepime

DISCUSSION

In this study, we evaluated the AMR profile of 120 MDR-ESBL-producing Gram-negative bacilli from hospitalized patients with bacterial pneumonia. The majority of samples were sputum, with Pseudomonas aeruginosa identified as the most prevalent pathogen within the ICU. Based on the MIC50 values, Piperacillin-Tazobactam exhibited the highest antimicrobial efficacy against infections caused by MDR-ESBL isolates. More than 50% of the MDR-ESBL isolates showed resistance to several antibiotics, including Ciprofloxacin, Ceftazidime, Gentamicin, Ampicillin-Sulbactam, Cefepime, and Meropenem. These results are consistent with reporting by Rahimzadeh et al.,[13] who reported a significant prevalence (59.65%) of GNB in the ICU, with sputum being the most frequently collected sample type in hospitals in Northern Iran. P. aeruginosa is responsible for approximately 7.1%–7.3% of all Healthcare-Associated Infections (HAIs). The prevalence of P. aeruginosa-associated pneumonia has increased over the past decade, driven by factors such as the widespread use of broad-spectrum antibiotics, the use of invasive medical devices, prolonged hospitalizations, and suboptimal infection control practices.[14] HAP and VAP are significant contributors to HAIs, accounting for up to 22% of all cases. P. aeruginosa is implicated in 10%–20% of VAP isolates, with associated mortality rates ranging from 32% to 42.8%.[15,16] A multicenter study revealed that P. aeruginosa was responsible for 26% of global VAP cases, with identified risk factors including prior colonization and extended hospital stays.[17]

During the COVID-19 pandemic, the incidence of HAIs caused by P. aeruginosa increased, particularly among patients with severe illness with prolonged hospitalizations. A meta-analysis of COVID-19 patients revealed that 8.4% of these patients had bacterial coinfections, while 39.9% developed secondary infections during their stay in the ICU.[18] In France, patients with COVID-19 in the ICU exhibited higher rates of P. aeruginosa bacteremia (12.4% vs. 8.9% in non-COVID patients) and VAP (16.8% vs. 16.1% in non-COVID patients). Co-infections were associated with a 74% mortality rate among these patients, with significantly higher mortality rates observed in those infected with resistant and MDR strains, compared to those infected with susceptible strains.[19,20]

In the current study, high resistance rates were observed for Ciprofloxacin (85%), Ceftazidime (85%), Gentamicin (80%), Ampicillin-Sulbactam (79.2%), and Colistin (77.5%) among the tested isolates, while Piperacillin-Tazobactam exhibited the lowest resistance rate at 33.3%. Before the COVID-19 pandemic, our surveillance study revealed that 53.6% of MDR-GNB isolates exhibited resistance to multiple antibiotics, including Ciprofloxacin (35.7%), Colistin (57.1%), and Imipenem (21%).[21] Rezai et al.[22] reported that MDR-ESBL-producing GNB isolates from patients with VAP demonstrated susceptibility rates of 79% to aminoglycosides and 82.8% to fluoroquinolones, but only 34.5% to colistin and 55.2% to carbapenems. In contrast, our surveillance study revealed higher resistance rates among MDR-GNB isolates, with 80% resistance to aminoglycosides, 85% resistance to fluoroquinolones and cephalosporins, and 69.2% resistance to carbapenems. Piperacillin-Tazobactam was identified as the most effective therapeutic option for managing MDR-ESBL-GNB infections. Resistance to Piperacillin-Tazobactam exhibits significant regional variation globally. For instance, Poland has reported a resistance rate of 94%, while in India, the sensitivity rate is notably lower, at 33.3%. These discrepancies can be attributed to several factors, including geographic differences, the absence of a standardized definition for MDR strains, variations in the distribution of resistance genes, differences in study populations (e.g., sample size and clinical settings), and the diversity of isolate sources.[13]

Before the COVID-19 pandemic, our studies in Northern Iran indicated that MDR-ESBL-producing GNB were responsible for 14.15% of VAP cases.[21,23] However, since the onset of the pandemic, there has been a notable increase in the incidence of ESBL-producing respiratory pathogens in ICUs.[2,3,21] A retrospective study revealed a significant rise in carbapenem-resistant GNB colonization rates, which increased from 6.7% in 2019 to 50% in 2020.[24,25,26]

Several factors have contributed to this surge in AMR among GNB during the COVID-19 pandemic, including prior antimicrobial exposure, the widespread use of broad-spectrum antibiotics in COVID-19 patients, challenges in differentiating between viral and bacterial infections, prolonged mechanical ventilation, and alterations in hospital operations and healthcare worker practices.[27]

Our study identified that MDR-ESBL-producing bacteria frequently harbor resistance-encoding genes, including blaIMP, blaTEM, AcrA-B, blaCTX, blaOXA-58, aacIb, blaSHV, and aacI. Previous research conducted prior to the COVID-19 pandemic revealed that the blaTEM gene was the most prevalent, detected in 49% of isolates, followed by blaSHV at 44% and blaCTX at 28%.[21,22]

Additionally, Bagheri Nesami et al.[23] reported a prevalence of ESBL-related genes, with blaSHV at 94.3%, blaCTX at 48.6%, blaVEB at 22.9%, and blaGES at 17.14%. Our results demonstrated a significant association between the blaSHV and blaCTX genes and resistance to fourth-generation cephalosporins as well as the β-lactamase inhibitor (P < 0.05). These findings highlight the major influence of resistance-associated genes in the development and dissemination of AMR, reinforcing the urgent need for ongoing research and the implementation of targeted infection control and antimicrobial stewardship strategies. The data suggest that the overuse of broad-spectrum antibiotics in healthcare environments promotes the horizontal transmission of ESBL-encoding genes, primarily via plasmid-mediated gene transfer, thereby facilitating the spread of resistance across diverse bacterial species. This underscores a clear association between the presence of these resistance genes and the emergence of ESBL-producing strains, which pose a significant therapeutic challenge due to their frequent resistance to multiple classes of antibiotics.[24,25,26]

Our results revealed a significant association between extended-spectrum ESBL-producing Gram-negative bacilli harboring the blaNDM and blaIMP genes and resistance to Meropenem (P = 0.001). The rising prevalence of carbapenem-resistant GNB (CR-GNB) poses a serious public health and clinical threat, highlighting the need for urgent investigation into resistance mechanisms and the implementation of targeted control strategies. Consistent with our observations, Boorgula et al.[27] reported that K. pneumoniae and A. baumannii were the most frequently identified pathogens causing secondary infections in COVID-19 patients and, alarmingly, the prevalence of carbapenem-resistant increased substantially from 5% in 2019 to 50% in 2020. The co-expression of metallo-β-lactamase (MBL) and Oxacillinases (OXA) genes appears to play a synergistic role in driving carbapenem resistance, particularly in A. baumannii. The potential for plasmid-mediated horizontal gene transfer of β-lactamase-encoding genes remains a major concern, as it accelerates the spread of resistance and undermines the efficacy of existing antimicrobial therapies, leading to increased rates of treatment failure. This study has limitations, including a small sample size, the absence of molecular typing, and the lack of antimicrobial susceptibility testing (AST) for Ceftaroline, Cefiderocol, Ceftazidime-avibactam, and Fosfomycin.

CONCLUSION

Our results reveal a troubling rise in AMR among Gram-negative pathogens responsible for pneumonia, particularly in ICUs in Northern Iran during the COVID-19 pandemic. We identified a high prevalence of MDR Pseudomonas aeruginosa, with resistance rates exceeding 50% against critical antibiotics such as Ciprofloxacin, Ceftazidime, Gentamicin, Ampicillin-Sulbactam, and Colistin. This trend indicates a reduction in treatment options for managing severe infections.

The rising resistance complicates infection management in critically ill patients, emphasizing the urgent need for effective infection control measures to maintain treatment effectiveness. The molecular epidemiology of these pathogens, characterized by the presence of β-lactamases, carbapenemases, and Extended-Spectrum β-lactamases (ESBLs), is essential for selecting appropriate antimicrobial therapies and guiding treatment protocols.

Piperacillin-Tazobactam seems to have relatively lower resistance rates. Overall, the AMR profile poses a significant clinical challenge, especially for critically ill patients who are at a higher risk of adverse outcomes.

These findings underscore the immediate need for prompt and sustained clinical interventions, including stringent infection control protocols, continuous molecular and phenotypic surveillance, and the optimization of antimicrobial stewardship programs. Such measures are crucial to prevent further proliferation of MDROs and to preserve the therapeutic efficacy of existing antimicrobial agents.

Ethics approval and consent to participate

This study was approved by the code of IR.MAZUMS.REC.1403.217 and received ethical approval from the Ethics Committee of Mazandaran University of Medical Sciences.

Author contributions

GR, Sh R, M A, RR, and MS R designed the project, collected data, and wrote and performed a critical review of the manuscript. MM performed the statistical analysis.

Conflicts of interest

There are no conflicts of interest.

Acknowledgment

The authors would like to thank the Pediatric Infectious Diseases Research Center Boo-Ali Sina Hospital, Sari, Iran for allowing us to use their equipment and materials in their laboratory.

Funding Statement

Nil.

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