Search Results (187)

Background/Objectives: Urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL) Enterobacterales have become more frequent. Therefore, strategies for assessing the risks posed by ESBL-producing infections have been developed, creating the need for local validation. The aim of this study was to validate the scoring system designed by Tumbarello et al. to identify ESBL producers in patients with a UTI that require hospital care in a region with a high prevalence of ESBL Escherichia coli. Methods: A retrospective cohort study was conducted in a third-level hospital in Bogotá (Colombia) between 2013 and 2020.The study included 817 patients, who were hospitalized due to pyelonephritis and treated with cefuroxime (the first-line antibiotic according to local guidelines), with an ESBL frequency of 9.68%. Diagnostic performances were estimated for a modified version of Tumbarello’s score (omitting admission from another healthcare facility) evaluating the area under the curve (AUC) for ESBL presence with respect to resistance to second- and third-generation cephalosporins. Results: With an index cut-off of ≥6, the score showed a sensitivity of 18% and a specificity of 83%. The AUC for this cut-off was 0.47. This threshold index could not efficiently predict either third- (AUC = 0.49) or second-generation cephalosporin resistance (AUC = 0.51). Conclusions: In Colombia, a region with a high prevalence of ESBL E. coli producers, as the use of the Tumbarello index would result in excessive utilization of wide-spectrum antibiotics, it is not recommended in this specific scenario for UTIs. Further studies are required in order to develop accurate tools to assess the risk of ESBL producers in high-prevalence settings. Full article

Background: Urinary tract infections (UTIs) are among the most common bacterial infections in children, with Escherichia coli as the leading pathogen. The rise in antimicrobial resistance, particularly extended-spectrum β-lactamase (ESBL) production, complicates empirical therapy, especially in countries with limited surveillance like Romania. Methods: We conducted a retrospective study on 248 pediatric patients aged 0–17 years diagnosed with E. coli UTI and admitted to a children hospital from Bucharest, Romania, between 2022 and 2024. Data collected included clinical presentation, laboratory values, and antimicrobial susceptibility testing. Patients were divided into ESBL and non-ESBL groups, and statistical comparisons were performed using SPSS v25. Results: Infants accounted for 68.1% of cases, with male sex predominating in this group (85.3%). ESBL-producing strains were identified in 19% of patients, more frequently in males (25% vs. 13.6%, p = 0.024). While inflammatory markers (CRP, leukocytes, neutrophils) were higher in complicated infections, they were paradoxically lower in ESBL cases. Non-ESBL isolates were highly susceptible to fosfomycin, third-generation cephalosporins, nitrofurantoin, and gentamicin. ESBL isolates showed resistance to most β-lactams but retained high susceptibility to fosfomycin (100%), carbapenems (>89%), cefoxitin (89.4%), and amikacin (85.1%). Conclusions: Our findings support the use of fosfomycin, nitrofurantoin, and selected aminoglycosides as viable empirical options in pediatric UTIs. Given the substantial ESBL prevalence and resistance to commonly used oral agents, local antibiogram data should guide empirical treatment strategies to preserve antibiotic efficacy and combat resistance. Full article

Background: The Citrobacter genus harbors class C (AmpC) and class A β-lactamases. Citrobacter freundii produces an inducible AmpC β-lactamase controlled by the LysR-type transcriptional regulator AmpR and cytosolic amidase AmpD. Citrobacter sedlakii produces the class A β-lactamase Sed-1, whose expression is believed to be regulated by the transcriptional regulator SedR and AmpD. Objectives:C. sedlakii NR2807, isolated in Japan, is resistant to third-generation cephalosporins and displays extended-spectrum β-lactamase characteristics. Here, we sought to understand the mechanism for successful resistance to third-generation cephalosporins by investigating the regulators controlling Sed-1 production. Methods: Plasmids containing bla_Sed-1 and sedR (pCR2807) or truncated sedR (pCR2807ΔSedR) were constructed and introduced into Escherichia coli. Antibiotic-resistant mutants of NR2807 were obtained, and enzyme kinetics were assessed. Results: The AmpD mutant (pCR2807/ML4953) showed an 8-fold increase in cefotaxime MIC and an 8.46-fold increase in Sed-1 activity compared to the wild-type (pCR2807/ML4947). However, induction of pCR2807/ML4947 also led to a 1.32-fold higher Sed-1 activity, indicating semi-inducibility. Deletion of sedR (pCR2807ΔSedR/ML4947) led to a 4-fold decrease in cefotaxime MIC and 1.93-fold lower Sed-1 activity, confirming SedR as an activator. While wild-type C. sedlakii ATCC51115 is susceptible to third-generation cephalosporins, the AmpD mutation in NR2807 led to Sed-1 overproduction and resistance to this class of antibiotics. Finally, mutagenesis revealed that amino acid substitution in Sed-1 conferred resistance to ceftazidime and extended-spectrum β-lactamase characteristics. Conclusions: Sed-1 producers, though usually susceptible to third-generation cephalosporins, may develop extended-spectrum β-lactamase traits due to AmpD or Sed-1 mutations, thereby requiring careful monitoring. Full article

Background/objectives: Proteus mirabilis is a frequent causative agent of urinary and wound infections in both community and hospital settings. It develops resistance to expanded-spectrum cephalosporins (ESCs) due to the production of extended-spectrum β-lactamases (ESBLs) or plasmid-mediated AmpC β-lactamases (p-AmpCs). Recently, carbapenem-resistant isolates of P. mirabilis emerged due to the production of carbapenemases, mostly belonging to Ambler classes B and D. Here, we report an outbreak of infections due to carbapenem-resistant P. mirabilis that were observed in a psychiatric hospital in Zagreb, Croatia. The characteristics of ESBL and carbapenemase-producing P. mirabilis isolates, associated with an outbreak, were analyzed. Materials and methods: The antibiotic susceptibility testing was performed by the disk-diffusion and broth dilution methods. The double-disk synergy test (DDST) and inhibitor-based test with clavulanic and phenylboronic acid were applied to screen for ESBLs and p-AmpCs, respectively. Carbapenemases were screened by the modified Hodge test (MHT), while carbapenem hydrolysis was investigated by the carbapenem inactivation method (CIM) and EDTA-carbapenem-inactivation method (eCIM). The nature of the ESBLs, carbapenemases, and fluoroquinolone-resistance determinants was investigated by PCR. Plasmids were characterized by PCR-based replicon typing (PBRT). Selected isolates were subjected to molecular characterization of the resistome by an Inter-Array Genotyping Kit CarbaResisit and whole-genome sequencing (WGS). Results: In total, 20 isolates were collected and analyzed. All isolates exhibited resistance to amoxicillin alone and when combined with clavulanic acid, cefuroxime, cefotaxime, ceftriaxone, cefepime, imipenem, ceftazidime–avibactam, ceftolozane–tazobactam, gentamicin, amikacin, and ciprofloxacin. There was uniform susceptibility to ertapenem, meropenem, and cefiderocol. The DDST and combined disk test with clavulanic acid were positive, indicating the production of an ESBL. The MHT was negative in all except one isolate, while the CIM showed moderate sensitivity, but only with imipenem as the indicator disk. Furthermore, eCIM tested positive in all of the CIM-positive isolates, consistent with a metallo-β-lactamase (MBL). PCR and sequencing of the selected amplicons identified VIM-1 and VIM-4. The Inter-Array Genotyping Kit CarbaResist and WGS identified β-lactam resistance genes bla_VIM, bla_CTX-M-15, and bla_TEM genes; aminoglycoside resistance genes aac(3)-IId, aph(6)-Id, aph(3″)-Ib, aadA1, armA, and aac(6′)-IIc; as well as resistance genes for sulphonamides sul1 and sul2, trimethoprim dfr1, chloramphenicol cat, and tetracycline tet(J). Conclusions: This study revealed an epidemic spread of carbapenemase-producing P. mirabilis in two wards in a psychiatric hospital. Due to the extensively resistant phenotype (XDR), therapeutic options were limited. This is the first report of carbapenemase-producing P. mirabilis in Croatia. Full article

Antibiotics are frequently used in the poultry industry, which has led to the emergence of bacterial strains that are resistant to antimicrobial treatments. The main objectives of this research were to conduct a multimodal risk assessment, to determine the extent of contamination of chicken meat with Escherichia coli, assess the prevalence of strains resistant to extended-spectrum cephalosporins (ESC), and characterise the genes associated with resistance and virulence. A standardised procedure involving enrichment in buffered peptone water and isolation of E. coli on MacConkey agar was carried out on 100 chicken carcasses. Subsequently, the sensitivity of the strains was tested against 21 antibiotic discs. Additionally, ESBL production was detected using a double synergy test. Specific PCRs were employed to identify resistance to critical antibiotics in human medicine (such as cephalosporins, carbapenems, fluoroquinolones, and colistin), as well as the presence of virulence genes. The contamination rate of chicken meat with E. coli was 82%. The prevalence of ESC-resistant isolates was 91.2%. Furthermore, 76.5% of the isolates exhibited ESBL production, with the different beta-lactamase genes (bla_CTXM, bla_TEM, and bla_SHV). The mcr-1 gene, associated with colistin resistance, was detected in four strains (5.9%). Some isolates also carried resistance genes such as sul1, sul2, sul3, tetA, tetB, qnrB, and qnrS. In addition, several virulence genes were detected. In our study, we were able to link the expression of AMR to the iron metabolic regulatory elements using a multimodal machine learning approach; this mechanism could be targeted to mitigate the bacteria virulence and resistance. The high prevalence of ESBL-producing and multi-resistant E. coli strains in poultry presents significant human health risks, with the focus on antibiotic-resistant uropathogenic strains since poultry meat could be an important source of uropathogenic strains, underscoring the danger of hard-to-treat urinary tract infections, stressing the need for controlled antibiotic use and thorough monitoring. Full article

Acute diarrhoeal disease caused by antibiotic-resistant diarrhoeagenic bacteria is a significant global public health issue, particularly in low- and middle-income countries. This study provides the first molecular characterisation of antimicrobial resistance profiles, including the detection of CTX-M-15 and CTX-M-55 extended-spectrum beta-lactamases (ESBLs), among diarrhoeagenic Enterobacterales in Bioko Island, Equatorial Guinea, offering novel epidemiological insights into an understudied region. This study investigated the antibiotic resistance profiles of pathogenic bacteria isolated from diarrhoeal samples on Bioko Island. A total of 153 clinical isolates were collected between 1 February and 30 May 2014, and antimicrobial susceptibility testing was performed at Loeri Comba Polyclinic (Malabo) using the Kirby–Bauer method. The molecular characterisation of β-lactamase-associated genes was performed on different isolates of diarrhoeagenic pathotypes—144 Escherichia coli, 7 Salmonella enterica, and 2 Shigella flexneri—at the National Centre for Microbiology (Majadahonda, Spain). High resistance rates were detected against ampicillin (98%), tetracycline (93.5%), sulfonamides (94.8%), sulfamethoxazole–trimethoprim (88.2%), and cefotaxime (78.8%), while moderate rates of resistance were noted for ciprofloxacin (26.7%), and all isolates remained susceptible to imipenem. Of the isolates, 107 (69.9%) produced either single or multiple β-lactamases. Among these, 73 (68.2%) harbored classical β-lactamases, specifically TEM and OXA-1 types, representing 47.7% of the total sample. Additionally, 34 (31.8%) of the isolates were identified as producers of extended-spectrum β-lactamases (ESBLs), specifically CTX-M enzymes. Sequencing identified CTX-M-15 and CTX-M-55 variants. The predominant ESBL-producing bacteria were enteroaggregative Escherichia coli (56.2%), followed by enteropathogenic and enterotoxigenic E. coli. These findings confirm the circulation of multidrug-resistant diarrhoeagenic Enterobacterales in Equatorial Guinea, raising concerns about limited treatment options due to widespread resistance to multiple antibiotic classes, including third-generation cephalosporins and quinolones. The most important conclusion drawn from this study is that a high percentage of diarrhoeagenic bacteria have an antibiotic resistance and multi-resistance profile, especially to beta-lactams and other groups of antibiotics such as tetracyclines and sulphonamides. There is also a moderate prevalence of isolates carrying ESBLs on Bioko Island, Equatorial Guinea, which could indicate the inappropriate use of antimicrobials. Full article

This study examines temporal patterns in pathogens isolated from prosthetic joint infection (PJI) cases and antimicrobial resistance patterns at a Romanian orthopedic center. We have conducted a retrospective cohort study that included 674 patients undergoing hip or knee replacement revision surgery between January 2016 and December 2023. From these, 102 confirmed PJI cases requiring surgical intervention were selected for analysis. We isolated 27 microorganisms from acute PJI cultures and 82 from chronic PJIs. Staphylococcus epidermidis (33 cases, 30.3%; 95% CI 22.0–40.3) was the predominant pathogen, with coagulase-negative Staphylococci (22 cases, 20.18%; 95% CI 0.9–41.3) and Enterobacteriaceae (13 cases, 11.9%; 95% CI 6.4–18.3) also prevalent. Methicillin resistance was identified in 43.6% of coagulase-negative staphylococci and 45.5% of Staphylococcus aureus isolates. All Gram-positive isolates remained susceptible to vancomycin, linezolid, and tigecycline. Among Gram-negative bacilli, Klebsiella oxytoca and Proteus mirabilis showed resistance to third-generation cephalosporins, with phenotypic profiles suggestive of extended-spectrum β-lactamase (ESBL) production. All Escherichia coli, Enterobacter spp., and Citrobacter freundii strains were fully susceptible to tested agents, while Pseudomonas aeruginosa exhibited reduced susceptibility to ciprofloxacin, aztreonam, and imipenem. Among the isolated strains, 47 were multidrug-resistant (MDR), with Staphylococcus aureus accounting for the highest MDR count, including methicillin resistance. The distribution of microorganism types and MDR strains remained consistent throughout the study period, with no significant association between infection type and MDR strain presence or between infection site and microorganism presence except for a strong association between MDR strains and the type of microorganism (p < 0.05). The microbial profile and resistance patterns in PJIs have remained stable over eight years. Our observations do not suggest that MDR PJIs are more commonly acute cases, contrary to what has been highlighted in previous reports. The ongoing prevalence of MDR strains underscores the importance of targeted antimicrobial treatments based on local susceptibility profiles. Full article

Diabetic foot infections (DFIs) are a severe complication of diabetes and are increasing in prevalence globally. The microbiology of DFIs exhibits significant regional variation, with Acinetobacter baumannii frequently emerging as the predominant pathogen. This study aimed to investigate the microbiological profile of A. baumannii in DFIs of different Wagner grades. Pus and tissue specimens from 480 diabetic patients treated for DFIs between September 2016 and August 2019 were collected, and antimicrobial susceptibility testing was performed. Multiplex PCR was conducted to amplify extended spectrum β-lactamase (ESBL) and metallo-β-lactamase (MBL) genes. A. baumannii had a prevalence of 14.58% in DFIs, with 100% resistance to cephalosporins. Among the 70 A. baumannii isolates, 19 (27.14%) were ESBL producers and 43 (61.43%) were MBL producers. blaTEM was the most prevalent gene (52.94%) in ESBL producers; blaNDM-1 was the most prevalent gene (52.94%) in MBL producers. Our findings highlight the need for regular antimicrobial susceptibility testing, molecular surveillance, and robust antimicrobial stewardship programmes to effectively manage A. baumannii DFIs and mitigate their resistance. Full article

Background: High-risk Escherichia coli clones, such as sequence type (ST)131 and ST1193, along with multidrug-resistant (MDR) Klebsiella pneumoniae, are globally recognized for their significant role in urinary tract infections (UTIs). This study aimed to provide an overview of the virulence factors, clonal diversity, and antibiotic resistance profiles of extended-spectrum cephalosporin (ESC)-E. coli and K. pneumoniae causing UTIs in humans in the Tebessa region of Algeria. Methods: Forty E. coli and 17 K. pneumoniae isolates exhibiting ESC-resistance were recovered (July 2022–January 2024) from urine samples of patients at three healthcare facilities to be phenotypically and genotypically characterized. Whole genome sequencing (WGS) was performed on the ST1193 clone. Results: Among K. pneumoniae isolates, all except one harbored CTX-M-15, with a single isolate carrying bla_CTX-M-194. Additionally, two K. pneumoniae isolates co-harboring bla_CTX-M-15 and bla_NDM exhibited phenotypic and genotypic hypervirulence traits. Fluoroquinolone resistance (FQR) was detected in 94.1% of K. pneumoniae isolates. The E. coli isolates carried diverse ESC-resistance genes, including CTX-M-15 (87.5%), CTX-M-27 (5%), CTX-M-1, CMY-59, and CMY-166 (2.5% each). Co-carriage of bla_ESC and bla_OXA-48 was identified in three E. coli isolates, while 62.5% exhibited FQR. Phylogenetic analysis revealed that 52.5% of E. coli belonged to phylogroup B2, including the high-risk clonal complex (CC)131 CH40-30 (17 isolates) and ST1193 (one isolate). In silico analysis of the ST1193 genome determined O75:H5-B2 (CH14-64), and the carriage of IncI1-I(Alpha) and IncF [F-:A1:B10] plasmids. Notably, core genome single-nucleotide polymorphism (SNP) analysis demonstrated high similarity between the Algerian ST1193 isolate and a previously annotated genome from a hospital in Northwest Spain. Conclusions: This study highlights the spread and genetic diversity of E. coli CC131 CH40-30 and hypervirulent K. pneumoniae clones in Algeria. It represents the first report of a CTX-M-15-carrying E. coli ST1193 in the region. The findings emphasize the urgent need for antibiotic optimization programs and enhanced surveillance to curb the dissemination of high-risk clones that pose an increasing public health threat in Algeria. A simplified method based on virulence traits for E. coli and K. pneumoniae is proposed here for antimicrobial resistance (AMR) monitoring. Full article

Background/Objectives: Proteus mirabilis is a frequent causative agent of urinary tract and wound infections in community and hospital settings. It develops resistance to expanded-spectrum cephalosporins (ESC) due to the production of extended-spectrum β-lactamases (ESBLs) or plasmid-mediated AmpC β-lactamases (p-AmpC). Here, we report the characteristics of ESBLs and p-AmpC β-lactamases encountered among hospital and community isolates of P. mirabilis in two hospitals and the community settings in Zagreb, Croatia. Methods: Antibiotic susceptibility testing was performed using disk-diffusion and broth dilution methods. The double-disk-synergy test (DDST) and inhibitor-based test with clavulanic and cloxacillin were applied to screen for ESBLs and p-AmpC, respectively. PCR investigated the nature of ESBL, carbapenemases, and fluoroquinolone resistance determinants. Selected strains were subjected to molecular analysis of resistance traits by the Inter-Array CarbaResist Kit and whole-genome sequencing (WGS). Results: In total, 39 isolates were analyzed. Twenty-two isolates phenotypically tested positive for p-AmpC and seventeen for ESBLs. AmpC-producing organisms exhibited uniform resistance to amoxicillin-clavulanate, ESC, ciprofloxacin, and sulphamethoxazole-trimethoprim, and uniform susceptibility to carbapenems and piperacillin-tazobactam and all harbored bla_CMY-16 genes. ESBL-positive isolates demonstrated resistance to amoxicillin-clavulanate, cefuroxime, cefotaxime, ceftriaxone, and ciprofloxacin but variable susceptibility to cefepime and aminoglycosides. They possessed bla_CTX-M genes that belong to cluster 1 (n = 5) or 9 (n = 12), with CTX-M-14 and CTX-M-65 as the dominant allelic variants. Conclusions: The study demonstrated the presence of CTX-M ESBL and CMY-16 p-AmpC among hospital and community-acquired isolates. AmpC-producing isolates showed uniform resistance patterns, whereas ESBL-positive strains had variable degrees of susceptibility/resistance to non-β-lactam antibiotics, resulting in more diverse susceptibility patterns. The study found an accumulation of various resistance determinants among hospital and outpatient isolates, mandating improvement in detecting β-lactamases during routine laboratory work. Full article

Background/Objectives: Antimicrobial resistance is one of the foremost global health concerns of today, and it could offset much of the progress accrued in healthcare over the last century. Excessive antibiotic use accelerates this problem, but it is recognised that specific agents differ in their capacity to promote resistance, a concept recently promoted by the World Health Organisation in the form of its Access, Watch, Reserve (AWaRe) schema. Which, if any, agents should be construed as having a high proclivity for selection of resistance has been contested. The European Antimicrobial Resistance Surveillance Network (EARS-NET) and European Surveillance of Antimicrobial Consumption Network (ESAC-NET) curate population level data over time and throughout the European Economic Area (EEA). EARS-NET monitors resistance to antimicrobials amongst invasive isolates of sentinel pathogens whereas ESAC-NET tracks usage of systemic antimicrobials. Together, data from these networks were interrogated to delineate correlations between antimicrobial consumption and resistance. Methods: Using univariate and multivariate regression analyses, spatiotemporal associations between the use of specific antimicrobial classes and 14 key resistance phenotypes in five sentinel pathogens were assessed methodically for 29 EEA countries. Results: Use of second and third generation cephalosporins, extended spectrum penicillin/β-lactamase inhibitor combinations, carbapenems, fluoroquinolones, nitroimidazoles and macrolides strongly correlated with key resistance phenotypes, as did overall antimicrobial consumption. Conclusions: The data obtained mostly support the WHO AWaRe schema with critical caveats. They have the potential to inform antimicrobial stewardship initiatives in the EEA, highlighting obstacles and shortcomings which may be modified in future to minimise positive selection for problematic resistance. Full article

Background/Objectives: Over the past decade, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have emerged as a significant public health concern due to their potential to spread beyond clinical settings and healthy carriers, in various environments, including in animal source foods. This study seeks to investigate the molecular characteristics of ESBL-producing E. coli strains isolated from food of animal origin, with a focus on chromosomal typing, plasmid typing, and the description of the associated resistance genes’ genetic environment. Methods: Ninety-seven food of animal origin samples were tested for E. coli isolates resistant to cefotaxime. The resulting isolates were then subjected to antimicrobial susceptibility testing and PCR analysis to detect beta-lactamase genes. Additional assays, encompassing mating-out procedures, molecular typing utilizing Pulsed-Field Gel Electrophoresis, Multilocus Sequence Typing Analysis, and Oxford Nanopore Technology Lite whole plasmid sequencing, were also conducted. Results: E. coli was detected in 26 raw food specimens, generating a percentage of 27%. Fourteen of the current isolates (14%) were resistant to third generation cephalosporins, producing CTX-M-1, CTX-M-15, CTX-M-55, and SHV-12 beta-lactamases. The respective genes were accompanied by Insertion Sequences ISEcp1 and IS26, facilitating their transfer. Among plasmids harboring ESBL genes, representatives belonging to incI1 incompatibility group prevailed (5/8), followed by IncY and IncX3. Most plasmids proved conjugative. Diversity of molecular fingerprints of ESBL producing E. coli was revealed. Conclusions: To the best our knowledge, this study is the first to describe the molecular characteristics of E. coli isolates producing ESBLs sourced from foods of animal origin in Greece. The prevalence of ESBLs in our confined food collection is primarily associated with the very successful IncI1 plasmids, which were not linked to a specific E. coli genetic background. This lack of association confirms that horizontal plasmid transfer plays a more significant role than clonal dissemination in the spread of ESBL-mediated cephalosporin resistance. Full article

Extended-spectrum cephalosporin-resistant Escherichia coli (ESC-EC) poses a significant public health concern, with its presence increasingly detected in healthy humans and various animal species. This study explores the transmission dynamic of ESC-EC within the Danish population as well as the transmission impact of a range of food and animal sources. We developed a compartmental model encompassing farmers, pet owners, and the general population. Additionally, we applied an established source attribution model to estimate the contributions to the transmission of different sources using Danish surveillance data on the distribution of resistance genes in E. coli. Our findings highlight the central role of human-to-human transmission while also showing the significant contributions of food and animal sources to the spread of ESC-EC in sporadic human infections. Imported food, pets, and livestock were estimated to contribute importantly to human infections. The results emphasize the complexity of ESC-EC transmission dynamics and the critical value of employing a One Health approach in modeling disease transmission and in the development of targeted intervention strategies. Full article

Background/Objectives: Fosfomycin, a critically important antibiotic, is widely used to treat urinary tract infections (UTIs) caused by multidrug-resistant (MDR) Escherichia coli, particularly those producing extended-spectrum β-lactamases (ESBLs). However, its increasing use in livestock has raised concerns about resistance development and global dissemination. This study investigated fosfomycin resistance in E. coli isolates from 400 fecal samples collected at Brazilian broiler farms. Methods: The samples were tested for their minimum inhibitory concentration (MIC), screened with PCR for specific resistance genes, and selected isolated were whole genome sequenced. Results: Phenotypic resistance to fosfomycin was detected in 19% (75/400) of the isolates, while the fosA3 gene, encoding enzymatic resistance, was identified in 4% (16/400) via PCR screening. Long-read sequencing of seven fosA3-positive isolates revealed the presence of fosA3 on IncFII and IncX plasmids, often co-located with bla_CTX-M-55 within a conserved IS26-flanked transposon. Comparative genomic analysis of 133,541 global E. coli genomes from EnteroBase showed that 35% harbored similar transposon structures, with 2% carrying fosA3. These fosA3-positive isolates were significantly associated with South America and exhibited high co-carriage of ESBL genes, particularly in environmental and poultry-associated isolates. Phylogenetic analysis demonstrated no clustering by host or geographic origin, highlighting the global dissemination of these resistance determinants. Conclusions: Our findings emphasize the role of poultry production in the spread of fosfomycin and ESBL resistance, driven by transmissible plasmids and co-selection with third-generation cephalosporins. Improved antimicrobial stewardship, surveillance programs, and alternative management strategies are urgently needed to mitigate the dissemination of resistance and preserve fosfomycin’s efficacy in human medicine. Full article

The management of infectious diseases has proven to be a daunting task for clinicians worldwide, and the rapid development of antibiotic resistance among Gram-negative bacteria is making it even more challenging. The first-line therapy is empirical, and it most often comprises β-lactam antibiotics. Among Gram-negative bacteria, Proteus mirabilis, an important community and hospital pathogen associated primarily with urinary tract and wound infection, holds a special place. This review’s aim was to collate and examine recent studies investigating β-lactam resistance phenotypes and mechanisms of Proteus species and the global significance of its β-lactam resistance evolution. Moreover, the genetic background of resistance traits and the role of mobile genetic elements in the dissemination of resistance genes were evaluated. P. mirabilis as the dominant pathogen develops resistance to expanded-spectrum cephalosporins (ESC) by producing extended-spectrum β-lactamases (ESBL) and plasmid-mediated AmpC β-lactamases (p-AmpC). β-lactamase-mediated resistance to carbapenems in Enterobacterales, including Proteus spp., is mostly due to expression of carbapenemases of class A (KPC); class B (metallo-β-lactamases or MBLs of IMP, VIM, or NDM series); or class D or carbapenem-hydrolyzing oxacillinases (CHDL). Previously, a dominant ESBL type in P. mirabilis was TEM-52; yet, lately, it has been replaced by CTX-M variants, particularly CTX-M-14. ESC resistance can also be mediated by p-AmpC, with CMY-16 as the dominant variant. Carbapenem resistance in Proteus spp. is a challenge due to its intrinsic resistance to colistin and tigecyclin. The first carbapenemases reported belonged to class B, most frequently VIM-1 and NDM-5. In Europe, predominantly France and Belgium, a clonal lineage positive for OXA-23 CHDL spreads rapidly undetected, due to its low-level resistance to carbapenems. The amazing capacity of Proteus spp. to accumulate a plethora of various resistance traits is leading to multidrug or extensively drug-resistant phenotypes. Full article