Resistant Infections Research Articles

Antibiotic resistant infections in England surpass pre-pandemic levels

Antibiotic resistant infections in England surpass pre-pandemic levels

FAGOTERAPIA COMO ALTERNATIVA NO COMBATE A INFECÇÕES RESISTENTES: AVANÇOS E DESAFIOS NO TRATAMENTO DE E. COLI UPEC E EPEC

Resistant bacterial infections represent one of the biggest public health challenges today, resulting in a significant increase in morbidity and mortality linked to infectious diseases. On the other hand, Escherichia coli stands out as one of the most significant bacteria, particularly the uropathogenic (UPEC) and enteropathogenic (EPEC) variants. Infections caused by these strains have become a problem due to their ability to develop resistance to various antibiotics, thus harming therapeutic alternatives. The objective of this research was to investigate the effectiveness of phage therapy as an alternative in combating resistant bacterial infections, focusing on UPEC and enteropathogenic EPEC strains of Escherichia coli. Methodologically, it was an exploratory and comparative bibliographic review through qualitative research. As a result, it was found that future directions in phage therapy present a promising outlook, full of technological innovations, research needs and ethical considerations. The success of phage therapy as a viable alternative to treating resistant bacterial infections will depend on collaboration between different disciplines, careful consideration of ethical implications, and a commitment to ensuring that new technologies benefit society as a whole. The development of robust guidelines and regulations, along with increased public awareness, will be critical to the effective integration of phage therapy into clinical practice and public health. It was concluded that progress in this area represents a response to the bacterial resistance crisis, as it opens up new perspectives for biomedical research and clinical practice. Therefore, the continued engagement of researchers, health professionals and policy makers will be essential to ensure that phage therapy is established as an integral component in the fight against bacterial infections, benefiting public health in a broad and effective way.

Photodynamic inactivation and its effects on the heterogeneity of bacterial resistance.

Antimicrobial resistance is a growing threat to global public health, requiring innovative approaches for its control. Photodynamic inactivation (PDI) with light-activated photosensitizers has emerged as a strategy to combat resistant bacteria, challenging the intrinsic heterogeneity of bacterial populations. This study evaluates the impact of PDI on both heterogeneity and shape of the distribution profile of resistant bacterial populations, specifically on strains of Staphylococcus aureus resistant to amoxicillin, erythromycin, and gentamicin, for exploring its potential as an adjuvant therapy in the fight against bacterial resistance. Curcumin (10 µM) was used as a photosensitizer and five cycles of PDI were applied on Staphylococcus aureus strains under 450nm irradiation of 10J/cm² energy density. The resistance variations amongst bacterial subpopulations were investigated by calculating the minimum inhibitory concentration (MIC) before and after PDI treatment. MIC was significantly reduced by the antibiotics tested post-PDI and a reduction in the heterogeneity of bacterial populations was recorded, suggesting PDI can effectively decrease the resistance diversity of Staphylococcus aureus. The result reinforces the potential of PDI as a valuable adjuvant therapy, offering a promising avenue for mitigating bacterial resistance and promoting more effective treatment strategies against resistant infections.

Antibiotic consumption patterns in older adults: a comparative study of people 65 years and older in and outside nursing homes, Belgium, 2016 to 2022.

BackgroundInappropriate antimicrobial consumption (AMC) drives the emergence of antimicrobial resistance. Institutionalised, older populations are associated with antimicrobial treatments of longer duration and broader spectrum than recommended, higher rates of multidrug-resistant infections and poorer outcomes for resistant infections. Yet systematic, national monitoring of AMC in nursing home (NH) residents is lacking.AimTo perform a retrospective analysis of antibiotic consumption in Belgian NHs, we compared analogous populations inside and outside NHs. We aimed to provide a blueprint for establishing surveillance of NH AMC, based on national reimbursement data.MethodsThe National Institute for Health and Disability Insurance supplied reimbursement AMC data for outpatients from 2016 to 2022. Data were classified by the Anatomical Therapeutic Chemical system, expressed as defined daily doses (DDD) and aggregated by prescription month, patient age, sex and residency inside/outside a NH. The number of ensured beneficiaries, aggregated by the same demographic variables, was collected from the Intermutualistic Agency. We compared the DDDs per 1,000 beneficiaries per day, along with secondary metrics for national and international targets for analogous populations inside and outside NHs.ResultsTotal antibiotic consumption decreased in both populations but remained twofold higher in NH residents. Proxy prescription quality metrics were consistently less favourable within NHs and diverged further during the COVID-19 pandemic. Distinct consumption patterns and greater seasonal fluctuations were observed in NH residents.ConclusionGiven the different infection risks and higher antibiotic consumption of NH residents, AMC surveillance and antimicrobial stewardship efforts targeting this fragile population are needed.

Navigating antibiotic therapy in acute cholangitis: Best practices and new insights.

Globally, antibiotic resistance is linked to increased morbidity, mortality, and healthcare costs, which necessitates further research on optimal antibiotic usage. Acute cholangitis (AC), a common cause of community-acquired bacteremia, often requires antimicrobial therapy. Therefore, studying the appropriate use of antibiotics for AC is considered crucial for suppressing the emergence of resistant bacteria and reducing adverse antibiotic-associated events. The Tokyo Guidelines 2018 (TG18) recommend 4-7 days of antibiotics post-biliary drainage. However, this lacks strong evidence and is based primarily on various evidence and expert opinions. Recent retrospective studies advocate for a shorter 1-3-day antibiotic course for AC, thereby prompting a need to reassess the treatment duration to balance therapeutic efficacy and minimize resistance and adverse effects. Choosing the appropriate duration and antibiotics based on susceptibility to pathogens causing cholangitis is important. Awareness of local resistance patterns and understanding patients' risks of resistant pathogens are prerequisite for effective treatment. We must explore the applicability of these guidelines in specific scenarios such as severe AC, positive blood cultures, fever, or hilar biliary obstructions due to malignancy. This comprehensive review considers both the duration and type of antibiotics and aims to enhance treatment outcomes while reducing the risk of resistant bacterial infections.

Doxifluridine effectively kills antibiotic-resistant Staphylococcus aureus in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality globally, often exacerbated by infections such as methicillin-resistant Staphylococcus aureus (MRSA). The rise in antibiotic-resistant strains complicates treatment and underscores the need for novel therapeutic drugs. In this paper, we further investigated the antimicrobial potential of a fluoropyrimidine anticancer drug doxifluridine against multidrug-resistant S. aureus. Determination of minimum inhibitory concentration (MIC) or minimum bactericidal concentration (MBC), monitoring of growth curve, time-kill assays, biofilm bactericidal assays, and chequerboard studies were conducted to evaluate the antibacterial efficacy of doxifluridine. Safety was assessed via hemolysis and cytotoxicity assays, and an in vivo Galleria mellonella larvae model was employed to test protective effects. Doxifluridine demonstrated significant antibacterial activity against clinical multidrug resistance (MDR) S. aureus isolates, with MIC and MBC values ranging from 0.5 to 2 µg/mL and 1 to 4 µg/mL, respectively. The results revealed doxifluridine's potent bactericidal effects within 8 hours. Moreover, doxifluridine-treated bacteria showed a substantial reduction in biofilm mass and viability. Furthermore, chequerboard assays indicated synergistic interactions between doxifluridine and other antibiotics, reducing MIC values by two- to eightfold. More importantly, safety evaluations confirmed that doxifluridine did not exhibit hemolytic toxicity or cytotoxicity. Finally, doxifluridine significantly increased the survival rate of MRSA-infected G. mellonella larvae in vivo. In brief, doxifluridine exhibited promising in vitro and in vivo antibacterial activity against MRSA, suggesting its potential as a repurposed drug for treating resistant bacterial infections in COPD patients.IMPORTANCEThe study provides robust evidence for the antibacterial efficacy of doxifluridine against Methicillin-resistant Staphylococcus aureus in chronic obstructive pulmonary disease (COPD) patients. Its rapid action, ability to disrupt biofilms, and synergistic effects with other antibiotics, combined with a favorable safety profile, highlight its potential as a repurposed therapeutic agent. Future clinical trials will be essential to confirm these findings and pave the way for its integration into clinical practice. This work not only provides candidate for tackling the management of bacterial infections in COPD but also exemplifies the potential of drug repurposing in combating antibiotic-resistant infections.

Altered genomic methylation promotes Staphylococcus aureus persistence in hospital environment

Staphylococcus aureus can cause outbreaks and becomes multi-drug resistant through gene mutations and acquiring resistance genes. However, why S. aureus easily adapts to hospital environments, promoting resistance and recurrent infections, remains unknown. Here we show that a specific S. aureus lineage evolved from a clone that expresses the accessory gene regulator (Agr) system to subclones that reversibly suppressed Agr and caused an outbreak in the hospital setting. S. aureus with flexible Agr regulation shows increased ability to acquire antibiotic-resistant plasmids, escape host immunity, and colonize mice. Bacteria with flexible Agr regulation shows altered cytosine genomic methylation, including the decreased 5mC methylation in transcriptional regulator genes (pcrA and rpsD), compared to strains with normal Agr expression patterns. In this work, we discover how altered genomic methylation promotes flexible Agr regulation which is associated with persistent pathogen colonization in the hospital environment.

Nanoparticle-Based Nitric Oxide Donors: Exploring Their Antimicrobial and Anti-Biofilm Capabilities

Background: Nitric oxide (NO) is an antimicrobial and anti-biofilm agent with significant potential for combating biofilm-associated infections and antibiotic resistance. However, owing to its high reactivity due to the possession of a free radical and short half-life (1–5 s), the practical application of NO in clinical settings is challenging. Objectives: This review explores the development of NO-releasing nanoparticles that provide a controlled, targeted delivery system for NO, enhancing its antimicrobial efficacy while minimizing toxicity. The review discusses various NO donors, nanoparticle platforms, and how NO disrupts biofilm formation and eradicates pathogens. Additionally, we examine the highly encouraging and inspiring results of NO-releasing nanoparticles against multidrug-resistant strains and their applications in medical and environmental contexts. This review highlights the promising role of NO-based nanotechnologies in overcoming the challenges posed by increasing antibiotic resistance and biofilm-associated infections. Conclusions: Although NO donors and nanoparticle delivery systems show great potential for antimicrobial and anti-biofilm uses, addressing challenges related to controlled release, toxicity, biofilm penetration, resistance, and clinical application is crucial.

Proline-Modified RWn Peptides: Enhanced Antifungal Efficacy and Synergy with Conventional Antibiotics for Combating Resistant Fungal Infections

Proline-Modified RWn Peptides: Enhanced Antifungal Efficacy and Synergy with Conventional Antibiotics for Combating Resistant Fungal Infections

Antimicrobial Peptide Delivery Systems as Promising Tools Against Resistant Bacterial Infections

The extensive use of antibiotics during recent years has led to antimicrobial resistance development, a significant threat to global public health. It is estimated that around 1.27 million people died worldwide in 2019 due to infectious diseases caused by antibiotic-resistant microorganisms, according to the WHO. It is estimated that 700,000 people die each year worldwide, which is expected to rise to 10 million by 2050. Therefore, new and efficient antimicrobials against resistant pathogenic bacteria are urgently needed. Antimicrobial peptides (AMPs) present a broad spectrum of antibacterial effects and are considered potential tools for developing novel therapies to combat resistant infections. However, their clinical application is currently limited due to instability, low selectivity, toxicity, and limited bioavailability, resulting in a narrow therapeutic window. Here we describe an overview of the clinical application of AMPs against resistant bacterial infections through nanoformulation. It evaluates metal, polymeric, and lipid AMP delivery systems as promising for the treatment of resistant bacterial infections, offering a potential solution to the aforementioned limitations.

Bacterial isolates and antibiotic sensitivity in canine bacterial keratitis in Korea.

To analyze bacterial isolates associated with canine bacterial keratitis and their antibiotic susceptibility patterns in Korea, focusing on multidrug resistance (MDR) and identifying effective antibiotic combinations for clinical treatment. A total of 146 dogs diagnosed with suspected bacterial keratitis between October 2022 and October 2023 in Korea, with 157 eye samples collected for analysis. Eye samples were cultured to isolate bacteria, and antibiotic susceptibility testing was performed using the minimum inhibitory concentration (MIC) method. Bacterial identification was conducted using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF). The study assessed the efficacy of individual antibiotics and combination therapies. Bacteria were isolated in 55.4% of the samples. The most common genera were Staphylococcus species (48.5%, 48/99), Streptococcus species (13.1%, 13/99), Pseudomonas species (9.1%, 9/99), and Escherichia coli (9.1%, 9/99). Amikacin (84.8%) showed the highest antibiotic susceptibility, while doxycycline exhibited the lowest (17.2%). The most effective antibiotic combinations were amikacin-moxifloxacin (93%). MDR isolates accounted for 52.5% (52/99) of the total bacterial samples. Staphylococcus species were the most common isolates, with 52.5% showing MDR, underscoring the need to curb antibiotic misuse. While antibiotics like amikacin demonstrated high susceptibility rates, their use should be reserved for resistant infections to prevent further resistance development. Rather than focusing solely on finding effective combinations of antibiotics, it is crucial to consider alternative treatment strategies that offer more sustainable solutions. Rather than relying on antibiotic combinations, attention should shift to sustainable alternatives to treat bacterial keratitis and reduce antibiotic dependence in clinical practice.

Microbial Spectrum, Antimicrobial Resistance, and Prevalence of MDR/XDR Pathogens in Medical Device-Associated Infections

Background: Medical device-associated infections (MDAIs) are a major healthcare concern due to their high morbidity, mortality, and rising prevalence of MDR and XDR bacteria. This study examined the microbiological composition, antimicrobial susceptibility, and prevalence of MDR/XDR infections in MDAI patients at Dr. D.Y. Patil Medical College, Pune. Methods: One-year retrospective research included 100 MDAI patients. Antimicrobial susceptibility testing was done on microbial isolates from blood, urine, and wound swabs according to CLSI standards. The prevalence of MDR and XDR pathogens was determined. Results: Escherichia coli (30%) and Klebsiella pneumoniae (20%) caused most infections, while Staphylococcus aureus (25%) was the most common Gram-positive bacteria. Antimicrobial susceptibility testing showed that 40% of the isolates were MDR and 15% were XDR. Klebsiella pneumoniae had the highest resistance rate (70%), followed by Pseudomonas aeruginosa. Conclusion: The study shows that MDAIs are dominated by MDR and XDR infections, mainly Gram-negative bacteria, making therapy difficult. These findings highlight the critical need for improved infection control, antimicrobial stewardship, and regular surveillance to address medical device-associated resistance infections. Keywords: Medical device infections, multidrug-resistant, extensively drug-resistant organisms, antimicrobial susceptibility, microbiological profile, healthcare-associated infections.

Antibiofilm and antivirulence efficacy of Pleurotus platypus methanolic extract against Staphylococcus aureus through ROS generation and cell membrane disruption

Multi-drug resistance is recognized as a significant worldwide public health concern in the current century. Biofilm formation further exacerbates bacterial resistance to antibacterial medications, host immunological responses, and phagocytosis, resulting in long-lasting chronic illnesses. Investigating natural resources is a very potent approach for developing alternative anti-infective medications to effectively control multi-drug resistant bacterial infections. In this study, a unique mushroom species namely Pleurotus platypus had been discovered from the Terai-Duars region of West Bengal, India. The myco-chemical profiling and preliminary chemical analysis of Pleurotus platypus methanolic extract determined the significant presence of metabolites belonging to several major chemical classes such as flavonoid, alkaloid, triterpenoid, polyphenol, benzoic acids, coumarin, flavone etc. Most intriguingly, the extract possessed effective antibacterial, antibiofilm and antivirulence properties against Staphylococcus aureus and Methicillin resistant Staphylococcus aureus, one of the most notable drug-resistant opportunistic and nosocomial pathogens. Mechanistically, the mushroom extract enhanced the production of Reactive Oxygen Species (ROS) inside the targeted bacteria, causing alterations in membrane potential, damage to the cellular membrane and further release of intracellular DNA, destined to cell death. Moreover, the methanolic extract reported the eradication of pre-existing biofilms from the urinary catheter surface, hinting towards its future application in the related field. To summarize, Pleurotus platypus methanolic extract could be an excellent alternative antibacterial and antibiofilm therapeutic candidate for the effective management of Staphylococcus infections with improved outcome.

Prevalence of carbapenem-resistant Enterobacterales (CRE) in Saudi Arabia: A systematic review and meta-analysis

Antimicrobial resistance is a significant public health issue. In addressing the threat of multidrug resistant bacterial infections, carbapenems have been used. The carbapenem-resistant Enterobacterales (CRE) are, however, rapidly expanding worldwide. Since the issue of CRE is also a problem in Saudi Arabia, the current meta-analysis was performed to comprehensively evaluate the resistance rates to the main carbapenem antibiotics and determine the actual prevalence of CRE in the country. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was followed. Different web databases including PubMed, Scopus, Web of Science, and ScienceDirect were searched for relevant records. Data were extracted, and summary estimates for resistance to carbapenems were calculated using DerSimonian-Laird method of meta-analysis and the random-effects model. From a total of 787 retrieved records, 69 studies were found fully eligible and were included in the final analyses. More than 50 % of all the studies were conducted after 2010, and the most frequently examined members of the Enterobacterales were Escherichia coli and Klebsiella pneumoniae. The pooled prevalence estimate for imipenem resistance was 6.6 % (95 % CI: 4.7–9.2), 9.1 % (95 % CI: 6.7–12.3) for meropenem, and 18.6 % (95 % CI: 11.9–27.9) for ertapenem. High heterogeneity (I2 > 97 %, p < 0.001) was observed for all the estimates. Compared to other regions of the country, there was higher resistance rates in the Al-Qassim and Al-Jouf provinces. Additionally, resistance to ertapenem was as high as 34.2 % in the most recent study period (2021–2024). Proteus spp was the most prevalent CRE (26.2 %). This review highlights an increasing rate of carbapenem resistance among Enterobacterales, emphasizing the need for collaborative efforts to implement strict infection control and prevention measures. Consistent surveillance is indispensable for safeguarding public health, guiding clinical decisions, and strengthening efforts to tackle the challenges of antibiotic resistance.

Biogenic silver nanoparticles synthesized using rose petals: Potential to inhibit multidrug-resistant bacterial pathogens in disabled patients

BackgroundDrug resistant bacterial infections can be fatal for disabled people needing multiple medications and new effective antibacterial drugs such as biosynthesized nanoparticles are needed. A cost-effective and green method was studied for the biosynthesis of silver nanoparticles using pink rose petals. Materials and methodsSilver nanoparticles (AgNP) were synthesized using the petals of pink rose flowers. The AgNPs were characterized using FITR, SEM, XRD, and EDS analyses. The antibacterial activity of the AgNPs against multidrug-resistant bacterial pathogens Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, and colistin-resistant Klebsiella pneumoniae were studied using the microplate method. ResultsTh AgNPs had a spherical shape and an average size of 26 nm. XRD analysis showed that the nanoparticles were Ag0. Antibacterial activity was the highest against the multidrug-resistant S. aureus the minimum inhibitory concentration (MIC) being 400 µg/ml AgNPs. The multidrug-resistant E. coli, multidrug-resistant A. baumannii, and colistin-resistant K. pneumoniae MICs were 800 µg/ml, 3200 µg/ml, and 1600 µg/ml, respectively. ConclusionThe green synthesized of AgNPS using pink rose petals and their antibacterial effects offer material for the treatments of common multidrug-resistant bacterial pathogens.

Schiff Base Mediated Synthesis of Novel Imidazolidine-4-One Derivatives for Potential Antimicrobial and Anthelmintic Activities.

This study focuses on developing novel antimicrobials to combat drug-resistant pathogens, addressing compounds failing clinical trials due to inadequate physicochemical properties. Sixteen imidazolidine-4-one derivatives were synthesized by extensive evaluation using molecular docking, absorption, distribution, metabolism, excretion (ADME) predictions, and antimicrobial testing. Molecular docking studies conducted with Schrödinger's Glide revealed that compounds S4 and G8 exhibited superior docking scores of -7.839 and -7.776, respectively. The G series outperformed the S series in scores. ADME analysis confirmed all compounds adhered to Lipinski's rule of five. In addition, IR and NMR provided details about the structure of the compounds. Antimicrobial activity was assessed against Escherichia coli, Staphylococcus aureus, and Candida albicans, with compounds G2 and S2 showing exceptional minimum inhibitory concentration (MIC) values of 6.25 μg/mL against E. coli. S2 also demonstrated impressive activity against S. aureus (MIC 3.12 μg/mL), and S4 exhibited potent activity against C. albicans (MIC 0.8 μg/mL) than fluconazole (1.6 μg/mL). Additionally, antihelmintic activity was evaluated, with G1, G3, G8, S2, S4, S7, and S8 showing effective paralysis and death time 20 min and below at 50 mg/mL concentration. These results underscore the potential of new imidazolidine-4-one derivatives as suitable sources to develop a drug candidate to treat resistant infections.

Multienzyme-mimic Fe single-atom nanozymes regulate infection microenvironment for photothermal-enhanced catalytic antibacterial therapy

The rational design of nanozymes with highly efficient reactive oxygen species (ROS) generation to overcome the resistant infection microenvironment still faces a significant challenge. Herein, the highly active Fe single-atom nanozymes (Fe SAzymes) with a hierarchically porous nanostructure were prepared through a colloidal silica-induced template method. The proposed Fe SAzymes with satisfactory oxidase (OD)-like and peroxidase (POD)-like activity can transform O2 and H2O2 to superoxide anion free radical (•O2-) and hydroxyl radical (•OH), which possess an excellent bactericidal effect. Also, the glutathione peroxidase (GPX)-like activity of Fe SAzymes can consume glutathione in the infection microenvironment, thus facilitating ROS generation to enhance the sterilization effect. Besides, the intrinsic photothermal effect of Fe SAzymes further significantly boosts the enzyme-like activity to generate much more reactive oxygen species for efficient antibacterial therapy. Accordingly, both in vitro and in vivo results indicate that the Fe SAzymes with synergistically photothermal-catalytic performances exhibit satisfactory antibacterial effects and biocompatibility. This work provides new insights into designing highly efficient SAzymes for effective sterilization applications by an amount of ROS generation.

Flexible Development Programs for Antibacterial Drugs to Address Unmet Medical Needs.

The US Food and Drug Administration recognizes the unmet medical need for antibacterial drugs to treat serious bacterial diseases caused by resistant pathogens for which effective therapies are limited or lacking. The agency also recognizes that designing and conducting clinical trials to assess the safety and efficacy of drugs to treat resistant infections is challenging, especially for drugs only active against a single or a few bacterial species, and that a more flexible development program might be appropriate. In this article, we discuss several regulatory considerations for flexible development programs for antibacterial drugs intended to meet an unmet medical need. As an example, we use the recent approval of sulbactam for injection and durlobactam for injection (XACDURO) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.

Intersecting social and environmental determinants of multidrug-resistant urinary tract infections in East Africa beyond antibiotic use

The global health crisis of antibacterial resistance (ABR) poses a particular threat in low-resource settings like East Africa. Interventions for ABR typically target antibiotic use, overlooking the wider set of factors which drive vulnerability and behaviours. In this cross-sectional study, we investigated the joint contribution of behavioural, environmental, socioeconomic, and demographic factors associated with higher risk of multi-drug resistant urinary tract infections (MDR UTIs) in Kenya, Tanzania, and Uganda. We sampled outpatients with UTI symptoms in healthcare facilities and linked their microbiology data with patient, household and community level data. Using bivariate statistics and Bayesian profile regression on a sample of 1610 individuals, we show that individuals with higher risk of MDR UTIs were more likely to have compound and interrelated social and environmental disadvantages: they were on average older, with lower education, had more chronic illness, lived in resource-deprived households, more likely to have contact with animals, and human or animal waste. This suggests that interventions to tackle ABR need to take account of intersectional socio-environmental disadvantage as a priority.

Unlocking Nitrofurantoin: Understanding Molecular Mechanisms of Action and Resistance in Enterobacterales.

Antimicrobial resistance (AMR) is a global health crisis that has already claimed millions of lives and is projected to affect millions more unless urgent action is taken. Effective control of AMR requires the correct choice and dosage of antibiotics, as well as robust surveillance and research. Understanding the mechanisms of antibiotic action and the emergence of resistance phenotypes along with their genotypes is essential. This knowledge, combined with insights into resistance prevalence and spread, empowers clinicians to propose alternative therapies. Nitrofurantoin, a 70-year-old antibiotic, remains effective for the treatment of uncomplicated lower UTIs. Preventing emergence and spread of nitrofurantoin resistant superbugs would preserve the efficacy of this antibiotic which is crucial for ongoing and future AMR efforts. Nitrofurantoin resistance evolves slowly, leading to low prevalence compared to other antibiotics. However, it is often linked with extensive drug resistance, complicating treatment outcomes. Even a minor percentage of nitrofurantoin-resistant bacteria can cause significant clinical challenges due to irreversible evolution. While detailed study of these mechanisms can guide the development of strategies to combat nitrofurantoin resistance, early detection of resistant infections is critical for saving lives. The current review aims to provide a comprehensive analysis of nitrofurantoin's mechanisms of action, resistance evolution, prevalence, and resistance prediction. Our goal is to offer valuable insights for researchers and clinicians to enhance nitrofurantoin use and address the challenges posed by AMR.