Search Results (135)

Carbapenem-resistant Enterobacterales (CREs) pose a critical threat to global public health, largely driven by the enzymatic activity of Klebsiella pneumoniae carbapenemase-2 (KPC-2), a class A serine β-lactamase that hydrolyzes most β-lactam antibiotics. While β-lactamase inhibitors like avibactam offer temporary relief, emerging KPC variants demand novel, sustainable inhibitory scaffolds. This study aimed to identify and characterize potential natural inhibitors of KPC-2 from Pongamia pinnata, leveraging a comprehensive in silico workflow. A curated library of 86 phytochemicals was docked against the active site of KPC-2 (PDB ID: 3DW0). The top-performing ligands were subjected to ADMET profiling (pkCSM), and 100 ns molecular dynamics simulations (GROMACS) to evaluate structural stability and interaction persistence, using avibactam as control. Ponganone V exhibited the most favorable binding energy (−9.0 kcal/mol), engaging Ser70 via a hydrogen bond and forming π–π interactions with Trp105. Glabrachromene II demonstrated a broader interaction network but reduced long-term stability. ADMET analysis confirmed high intestinal absorption, non-mutagenicity, and absence of hERG inhibition for both ligands. Molecular dynamics simulations revealed that Ponganone V maintained compact structure and stable hydrogen bonding throughout the 100 ns trajectory, closely mirroring the behavior of avibactam, whereas Glabrachromene II displayed increased fluctuation and loss of compactness beyond 80 ns. Principal Component Analysis (PCA) further supported these findings, with Ponganone V showing restricted conformational motion and a single deep free energy basin, while avibactam and Glabrachromene II exhibited broader conformational sampling and multiple energy minima. The integrated computational findings highlight Ponganone V as a potent and pharmacologically viable natural KPC-2 inhibitor, with strong binding affinity, sustained structural stability, and minimal toxicity. This study underscores the untapped potential of Pongamia pinnata phytochemicals as future anti-resistance therapeutics and provides a rational basis for their experimental validation. Full article

Background: There are many methods of identifying microbial resistance to therapeutic agents; however, they can generally be classified into two main categories: phenotypic and genotypic. The study aims to determine drug sensitivity and to analyze the correlation between the results obtained from cultures on commercial chromogenic media Brilliance^TM CRE (OXOID) and Brilliance^TM ESBL (OXOID) and the occurrence of specific resistance genes carbapenemase (IMP, NDM, VIM, KPC, OXA), ESBL β-lactamase (TEM, SHV, CTX-M), and AmpC (CMY, DHA), which will be used in drug sensitivity tests. Methods: The present study used bacteria, including Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli, obtained from patients hospitalized in military hospitals in Poland. All strains were plated on the commercial chromogenic media and subjected to antimicrobial susceptibility testing. Additionally, molecular assays detecting three main classes according to the mechanism of action, enzyme type carbapenemase (IMP, NDM, VIM, KPC, OXA), ESBL β-lactamase (TEM, SHV, CTX-M), and AmpC (CMY, DHA) were performed using the real-time PCR method. Results: The results of the studies indicate the presence of carbapenemases and ESBL genes. Among K. pneumoniae strains, the dominant gene was CTX-M-15 (88.89%), followed by the SHV (84.12%), NDM (46.03%), TEM (41.26%), KPC (34.92%), and OXA-48 (19.04%). In contrast, A. baumanii was dominated by carbapenemases from the OXA family (OXA-51 in 96.00% and OXA-24/40 in 84.00%). E. coli exhibits a high prevalence of CTX-M-15 (53.85%), TEM (46.15%), NDM (38.46%), and CMY-2 (30.77%). It was observed that the CTX-M-15 gene was commonly co-identified with SHV (n = 43). All tested strains grew on chromogenic Brilliance^TM CRE medium. In the case of Brilliance^TM ESBL medium, the genes determining the resistance mechanism were detected in 41.7% for A. baumannii, 53.8% for E. coli, and 100% for K. pneumoniae. Chromogenic media perfectly differentiate strains to species. A moderate positive correlation of the occurrence of the antibiotic resistance genes was observed for OXA-51 and OXA-24/40 genes, which were resistant to meropenem (rho = 0.45, p < 0.001). K-means cluster analysis performed on integrated genotype–phenotype data allowed for the identification of three distinct clusters characterized by distinct resistance gene profiles. These results demonstrate that selective agar media enable faster identification compared to other conventional techniques; however, the obtained results should be confirmed by other validated phenotypic methods, and, if possible, by a molecular assay. Full article

The production of β-lactamases is the main mechanism underlying carbapenem resistance. This study combined in silico and in vitro approaches to identify potential polyphenols as carbapenemase inhibitors. Molecular docking, molecular dynamics, and ADMET prediction were performed to assess the binding affinity, stability, and safety of quercetin, kaempferol, caffeic acid, and 3,4-dihydroxybenzoic acid against KPC-2, NDM-1, and OXA-48 carbapenemases. In vitro antibacterial assays and checkerboard analyses were conducted against Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa to assess antibacterial and synergistic effects. Then, the inhibition of the β-lactam hydrolytic activity was confirmed. In silico results showed that quercetin, kaempferol, and caffeic acid exhibited strong binding affinity and consistent stability towards the targets. Therefore, quercetin and kaempferol showed the strongest affinities (−8.0 kcal/mol) and stable interactions with key catalytic residues. ADMET profiles indicated good pharmacokinetic behavior and low acute toxicity. In vitro assays revealed that the polyphenols exhibited MIC values ranging from 12.5 to 25 mg/L and MBC values of 25–50 mg/L. Combined with cefotaxime, they enhanced bacterial susceptibility and inhibited β-lactam hydrolysis, with quercetin achieving complete inhibition at 200 mg/L. These findings highlight the potential of the four polyphenols as natural β-lactamase inhibitors. Further enzyme kinetics and in vivo studies are needed to confirm their therapeutic relevance. Full article

Background/Objectives: Klebsiella pneumoniae ST258 and ST11 are global high-risk antimicrobial-resistant clones known for their virulence and resistance gene dissemination. This study aims to identify these clones in a Greek tertiary hospital and understand their resistance profiles and transmission dynamics. Methods: In January 2025, we isolated two distinct carbapenem-resistant K. pneumoniae in a Greek tertiary hospital: INT18S from an ICU patient’s bronchioalveolar lavage and INT20U from a urine sample in the emergency unit. Antimicrobial susceptibility testing (via Microscan system) and Whole-Genome Sequencing (WGS) were conducted on both isolates and their genomes were submitted to the NCBI. Results: The INT18S isolate carried the bla_KPC-2 gene and belonged to the ST258 clone. The INT20U isolate carried the bla_NDM-1 gene and belonged to the ST11 clone lineage. Both isolates contained at least one of the extended spectra β-lactamase genes tested (TEM, SHV, OXA-1 and CTX-M group). Conclusions: The co-existence of the high-risk K. pneumoniae clones ST258 and ST11 in different hospital departments increases the risk of resistance gene transfer and suggests potential intra-hospital transmission pathways. Understanding their resistance profiles is critical for guiding treatment strategies and preventing the spread of multidrug-resistant pathogens. Full article

The global rise of multi-drug resistant (MDR) pathogens, including the widespread resistance to beta-lactams through the production of β-lactamases, like extended spectrum β-lactamases (ESBLs), has led to the increasing use of last-line antibiotics such as carbapenems. Subsequently, the worldwide emergence of carbapenemase-producing pathogens poses a formidable challenge. The combination ceftazidime/avibactam (CAZ/AVI) has emerged as a pivotal agent in the management of multidrug-resistant Gram-negative infections. Avibactam, a novel β-lactamase inhibitor, demonstrates a wider spectrum of activity against Ambler Class A, C, and partially D β-lactamases in comparison to older inhibitors, thus enhancing the antimicrobial activity of ceftazidime against organisms producing ESBL and carbapenemases, such as oxacillinase (OXA)-type and Klebsiella pneumoniae Carbapenemase (KPC). This review synthesizes findings from randomized controlled trials and cohort studies, evaluating the efficacy of CAZ/AVI across diverse clinical settings, including complicated intra-abdominal infections, urinary tract infections, nosocomial pneumonia, skin and soft tissue infections, and bloodstream infections. The non-inferiority of CAZ-AVI with respect to carbapenems and superiority over polymyxins in terms of both clinical outcomes and safety are outlined, along with evidence supporting the use of CAZ/AVI in high-risk populations such as immunocompromised and critically ill patients. Overall, CAZ/AVI represents a compelling therapeutic option with favorable efficacy and safety, thus appearing as a reasonable frontline treatment for resistant Gram-negative infections. Full article

Wastewater treatment plants (WWTPs) are recognized hotspots for the convergence and dissemination of antimicrobial-resistant bacteria (ARB) and antimicrobial resistance genes (ARGs) into the environment. Among ARB, carbapenem-resistant Enterobacterales (CR-E) and extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-Ec/Kp) are of particular concern due to their clinical relevance. We characterized 30 CR-E and 176 ESBL-Ec/Kp isolates (two of them were both ESBL-producing and carbapenem-resistant) recovered from influent, intermediate, effluent, sludge, and downstream river samples collected from two WWTPs in northern Spain. Isolates were evaluated for resistance phenotypes against 12 antimicrobials, and β-lactamase-encoding genes were assessed by PCR and sequencing. Notably, among CR-E isolates, bla_KPC-2 was the most prevalent (93%), followed by bla_OXA-48-like, detected in two isolates from non-treated and pasteurized sludge; both isolates also carried bla_CTX-M-15, a finding not previously reported specifically in sludge samples. Among ESBL-Ec/Kp, a broad diversity of ESBL genes was identified, including bla_{CTX-M group 1} (variants 1, 3, 15, 32, 55), bla_{CTX-M group 9} (variants 14, 27, 65, 97), bla_SHV-12 and bla_TEM-169. The most prevalent ESBL gene was bla_CTX-M-15 (48.3%), followed by bla_CTX-M-14, bla_CTX-M-32, and bla_SHV-12, detected in 10.8%, 8.5%, and 6.8% of isolates, respectively. CR-E and ESBL-Ec/Kp were found in all sample types and were still detectable at terminal stages, indicating persistence throughout treatment. These findings support the need to improve and optimize current wastewater treatment methods and underscore the importance of integrating culture-based and molecular methods into routine WWTP monitoring for early detection of microbiological hazards, although further research is still needed. Full article

In recent decades, the problem of resistant strains, which present resistance to different types of antimicrobials, has increased. Klebsiella pneumoniae is one of the most important species that exhibits an acquired resistance phenotype to at least one agent in three or more classes of antimicrobials and is thus characterized as a multidrug-resistant bacterium (MDR). 98 nosocomial strains of K. pneumoniae were isolated during the pre-COVID-19 period, and more specifically, from February 2015 to March 2019, were analyzed for the detection of class A, D, and B carbapenemase genes. The existence of KPC, OXA-48 like, IMP, VIM, and NDM carbapenemases has been examined. The immunochromatography showed that NDM carbapenemases are more frequently detected in the samples, reaching a percentage of 30.7%, while correspondingly the percentage for VIM carbapenemases was 7.68% among the strains with resistant phenotypes. No strain with carbapenemase IMP was found. Real-time multiplex polymerase chain reaction (PCR) showed, in contrast to immunochromatography kits, that a high percentage of bacterial isolates (94.26%) carry NDM and VIM carbapenemase genes, while no IMP carbapenemase genes were detected. Regarding the KPC enzymes, the immunochromatography kits showed that KPC positive strains are reaching 53.1%, and OXA-48 positive strains are reaching 3.1% among the strains with resistant phenotypes. Real-time multiplex polymerase chain reaction revealed a much higher percentage of 89.6% KPC positive isolates and a percentage of 14.6% OXA-48 carbapenemase producers. The aforementioned results indicate the dominance of the Multiplex Real-Time PCR as a “gold standard” method. This study could not fully support the usefulness of rapid immunochromatographic tests as a fast and useful diagnostic tool in the laboratory daily routine, as per the results of previous studies. Thus, more studies need to be conducted in this field to introduce these rapid tests safely into the daily laboratory workflow as a screening tool. Additionally, this study underlines the predominance of KPC enzymes from clinical isolates of ICUs and a significant shift over the OXA-48 like enzymes that are not limited to the ICU environment. Full article

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant therapeutic challenge, particularly when multiple resistance mechanisms, such as metallo-β-lactamases (MBLs) and Klebsiella pneumoniae carbapenemase (KPC), coexist. Case description: We describe a case of a 51-year-old male with a post-sternotomy surgical site infection and concurrent bacteremia caused by a CRKP. Sternal swab and mediastinal liquid culture results highlighted CRKP harboring bla_NDM and bla_KPC genes, while the blood isolate showed bla_CTX and bla_KPC, indicating phenotypic resistance to ceftazidime-avibactam. All the strains exhibited phenotypic susceptibility to meropenem-vaborbactam (MEV), despite having a high minimum inhibitory concentration. Following clinical failure of MEV-based therapy, combination treatment with aztreonam (ATM) and imipenem/cilastatin/relebactam (IMI/REL), plus gentamicin, was initiated. Therapy was well tolerated and resulted in microbiological eradication and full clinical recovery. The patient completed 49 days of ATM and IMI/REL without relapse over a 3-month follow-up period. This is, to the best of our knowledge, the first reported case of IMI/REL being used in combination with ATM. Full article

Background/Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKP) threatens Intensive Care Units (ICU), particularly in settings where serine (KPC) and metallo-β-lactamases (NDM) co-circulate. The aim of this study was to assess CRKP susceptibility especially to novel β-lactam/β-lactamase inhibitor combinations, characterize the genetic determinants of resistance, and contribute to the understanding of local epidemiology in the ICU of our hospital. Methods: We studied 32 non-duplicate CRKP isolates (30 ICU, 2 wards) collected at Hippokration General Hospital, Thessaloniki (May–Oct 2023). Bacterial identification and Antimicrobial susceptibility testing (AST) were performed by VITEK-2; Minimum inhibitory concentrations (MICs) for ceftazidime/avibactam (CAZ/AVI), meropenem/vaborbactam (MER/VAB), and imipenem/relebactam (IMI/REL) were determined by E-tests. Colistin MICs were performed by broth microdilution. Carbapenemases were screened phenotypically and by immunochromatography and confirmed by multiplex PCR. One bronchial isolate co-harboring bla_NDM and bla_KPC genes underwent WGS. Results: All isolates were carbapenem-resistant and showed extensive resistance to β-lactams and fluoroquinolones. By PCR, 8/32 (25%) carried bla_KPC alone, 8/32 (25.0%) bla_NDM alone, and 16/32 (50%) co-harbored bla_KPC and bla_NDM. KPC-only isolates were generally susceptible in vitro to CAZ/AVI, MER/VAB, and IMI/REL, whereas dual KPC-NDM producers were resistant to all three combinations. Tigecycline showed the highest retained activity; colistin remained active in a minority. WGS of one ST512 (CG258) isolate revealed co-harboring bla_NDM-1 and bla_KPC-3 with additional resistance determinants and plasmid replicons, consistent with high-risk spread. Conclusions: Half of CRKP isolates in this ICU-predominant series co-produced KPC and NDM, severely limiting β-lactam/β-lactamase inhibitor options. These data support routine screening for carbapenemases, strict infection prevention, antimicrobial stewardship, and access to agents active against MBLs. Full article

Background: Antimicrobial resistance (AMR) is a major global health threat, particularly in surgical site infections (SSIs), where multidrug-resistant (MDR) pathogens complicate treatment. Objective: This study aimed to identify antimicrobial resistance genes and assess their prevalence in bacterial species causing SSIs in Lebanon. Materials and Methods: The present research is a multicenter and prospective study that included patients who developed SSIs after surgery in seven hospitals, within the period of January 2024–September 2024. Bacterial isolates from wound swabs or tissue samples were identified using standard microbiological methods. Antimicrobial susceptibility was tested by disk diffusion, and resistance genes were detected by PCR. Data were analyzed using Statistical Package for the Social Sciences (SPSS). Results: Among 6933 surgical patients, 63 developed SSIs (0.91%; 95% CI [0.70–1.15]). Gram-negative bacteria predominated (73%), mainly Escherichia coli and Pseudomonas aeruginosa, while Gram-positive isolates accounted for 27%, mostly Staphylococcus aureus. MDR was observed in 71% of Gram-positive and 61% of Gram-negative isolates. The most frequent genes were mecA in S. aureus (100%) and coagulase-negative staphylococci (83.3%); bla_CTX-M in E. coli, Klebsiella pneumoniae, and Enterobacter cloacae (100%); and bla_NDM in E. cloacae (100%) and Acinetobacter baumannii (60%). bla_KPC was less common, and no isolates carried Imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), and Oxacillinase-48-like β-lactamase (OXA-48). Conclusions: This study highlights the high prevalence of antibiotic resistance in agents causing SSIs in Lebanese hospitals. Resistance genes, particularly mecA, bla_CTX-M, and blaNDM, were highly prevalent in SSI pathogens, underscoring the urgent need for surveillance and judicious antibiotic use in Lebanese hospitals. Full article

Background/Objectives: Carbapenem-resistant Gram-negative bacilli (CR-GNB) pose a growing challenge to public health worldwide due to limited treatment options. This cross-sectional study investigated the characteristics of CR-GNB isolated from clinical specimens in Lagos, Nigeria. Methods: Gram-negative bacilli (GNB) and clinical data were obtained from three multi-specialist private hospitals between March and June 2023. The GNB were identified using the Analytical Profile Index (API) and investigated for CR-GNB by disk diffusion. Antimicrobial resistance patterns and carbapenemase gene data for presumptive carbapenemase-producing Gram-negative bacilli (CP-GNB) were analyzed using Vitek-2 and polymerase chain reaction (PCR). Results: Of 317 GNB, 29.0% (n = 92) were CR-GNB. Significantly higher numbers of CR-GNB were reported from the intensive care unit and oncology department (p = 0.009). Of all CR-GNB, 17 isolates (18.5%) were classified as presumptive CP-GNB. In this subgroup, resistance rates of ampicillin/sulbactam (100.0%) and trimethoprim/sulfamethoxazole (100.0%) were highest. Ten (10) CP-GNB were confirmed, representing 3.15% of all GNB tested. Seven isolates of New Delhi Metallo-β-lactamase (bla_NDM) were found among P. aeruginosa, K. pneumoniae, E. coli, and A. baumannii. The bla_NDM was identified in strains classified as extensively drug-resistant (XDR) and pandrug-resistant. Conversely, the bla_KPC was detected solely in multidrug-resistant and XDR strains. Conclusions: Emerging CR-GNB, specifically CP-GNB, in Nigeria emphasize the need for specific therapeutic management of infected patients. Antimicrobial stewardship and long-term surveillance efforts must be implemented in healthcare settings, as well as improved, accelerated microorganism identification techniques. Full article

Introduction: Urinary tract infections (UTIs) caused by carbapenem-resistant pathogens are increasingly common and pose serious treatment challenges due to limited antibiotic options and high complication rates. Identifying patients at risk is essential for guiding empirical therapy and improving outcomes. The primary objective of this study was to identify risk factors associated with carbapenem-resistant (CR) UTIs by comparing them with carbapenem-susceptible (CS) UTIs. Secondary objectives included analyzing the types of microorganisms involved in both groups, their antibiotic susceptibility profiles, and the presence of carbapenemase enzymes among CR UTI cases. Method: We conducted a retrospective case-control study involving 127 hospitalized patients with UTIs caused by CR microorganisms and 91 patients with UTIs caused by multidrug-resistant (MDR) strains that retain susceptibility to carbapenems, admitted between 1 October 2023, and 31 March 2025. Results: In univariate analysis, CR UTI patients had significantly higher rates of neoplasia, neurological disorders, urosepsis at admission, septic shock, the presence of urinary catheters at diagnosis, permanent nephrostomy catheters, hospitalizations within the past 180 days, previous antibiotic exposure including carbapenems, and recent urological procedures. Multivariate analysis revealed four independent risk factors for CR UTIs: neoplasia (OR = 2.152; 95% CI: 1.044–4.436; p = 0.038), neurological disorders (OR = 7.427; 95% CI: 2.804–19.674; p < 0.0001), antibiotic use in the previous 180 days (OR = 2.792; 95% CI: 1.487–5.396; p = 0.001), and prior carbapenem treatment OR = 10.313; 95% CI: 1.277–83.248; p = 0.029). Most of the isolated organisms belonged to the Enterobacterales genus, with Klebsiella spp. and Pseudomonas aeruginosa being the most common pathogens in CR UTIs, accounting for over 90% of cases. Among patients tested for carbapenemase production, all but one tested positive for at least one carbapenemase. Conclusions: Neoplasia, neurological disorders, recent antibiotic therapy, and prior carbapenem use were significantly associated with increased risk of developing CR UTIs. Klebsiella spp. and Pseudomonas aeruginosa were the predominant causative organisms, with New Delhi metallo-β-lactamase (NDM) and Klebsiella pneumoniae carbapenemase (KPC) being the most frequently identified resistance mechanisms. Full article

Klebsiella pneumoniae, a member of the Enterobacterales Order, often colonises the gut and causes diverse infections, including bloodstream, urinary, and respiratory infections. The rise in carbapenem-resistant sFtrains, especially those producing enzymes like K. pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Oxacillinase 48 (OXA48), or combinations (NDM+OXA48-like), poses a significant threat across Europe, notably in Romania. These strains spread rapidly via mobile genetic elements, complicating treatment. Methods: A retrospective study of multidrug-resistant (MDR) K. pneumoniae strains isolated from clinical samples collected at an infectious diseases hospital in Romania. Results: We analysed the evolution of carbapenemases and their combinations from 2010 to 2024, with the rising antibiotic consumption, particularly during the COVID-19 pandemic. The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) rose from 4.9% in 2010 to 41.6% in 2024. There was an overall antibiotic use increase, especially colistin (186%) between 2019–2024. Additionally, we examined the dynamics of antibiotic susceptibility that decreased in 2023–2024 and found that susceptibility of NDM+OXA48-like isolates to colistin was 16.5% and to cefiderocol 58.5%. Conclusions: The rising prevalence of K. pneumoniae strains with complex resistance mechanisms, coupled with a significant reduction in available treatment options, demands a fundamental paradigm shift in the management of these infections. Full article

Background: The global impact of the SARS-CoV-2 pandemic on antimicrobial resistance (AMR) patterns has been significant. In northern Brazil, Carbapenem-resistant Klebsiella pneumoniae (CRKP) are a major concern, with an observed shift from Klebsiella pneumoniae carbapenemase (KPC) to New Delhi metallo-β-lactamase (NDM) during the pandemic. Methods: This cross-sectional study analyzed 775 carbapenem-resistant K. pneumoniae isolates collected from 25 hospitals in the Brazilian Amazon Region (states of Pará and Acre) between 2018 and 2021. The isolates were tested for the presence of carbapenemase genes (bla_KPC, bla_NDM, bla_OXA-48, bla_IMP, bla_VIM, bla_AIM, bla_DIM, bla_GIM and bla_SIM). Results: Of the isolates analyzed, n = 653/775 (84%) were carbapenemase producers, with the most prevalent being bla_KPC n = 446/775 (57.5%) and bla_NDM n = 243/775 (31.4%). A significant increase in NDM producers was observed during the pandemic, rising from n = 1/250 (8.4%) pre-pandemic to n = 222/525 (42.3%) during the pandemic, while KPC producers declined from n = 172/250 (68.8%) to n = 274/525 (52.2%) (p < 0.001). Adult intensive care units (ICUs) were the primary source of isolates n = 357/775 (46%), with a notable increase in tracheal secretion and surveillance swab samples during the pandemic. Regression analysis confirmed a strong upward trend in the prevalence of bla_NDM (R² = 0.778). Conclusions: The shift from KPC to NDM producers in northern Brazil highlights an evolving AMR landscape, partly driven by the pandemic. Strengthened infection control measures, antimicrobial stewardship and continuous surveillance are essential to mitigate the spread of NDM-producing K. pneumoniae in settings with limited resources. Full article

Background: The emergence of multidrug-resistant Gram-negative bacteria, particularly extended-spectrum β-lactamase (ESBL) and AmpC-producing Enterobacterales, has brought renewed interest in temocillin, a narrow-spectrum β-lactam antibiotic first introduced in the 1980s. Objectives: We aimed to provide a comprehensive overview of the microbiological, pharmacological, and clinical profile of temocillin. Methods: We conducted a narrative review of the literature using the PubMed database to identify relevant studies concerning the microbiology, pharmacokinetics, pharmacodynamics, clinical applications, and safety of temocillin. Results: Temocillin shows strong in vitro activity against ESBL- and AmpC-producing organisms, and partial efficacy against certain Klebsiella pneumoniae carbapenemase (KPC)-producing strains. Its pharmacokinetic and pharmacodynamic characteristics, including β-lactamase stability and low ecological impact, support its use in urinary tract infections, bloodstream infections, intra-abdominal infections, pneumonia, and central nervous system infections. Additionally, evidence supports its utility in outpatient parenteral antimicrobial therapy (OPAT), including subcutaneous administration, and in vulnerable populations such as pediatric, elderly, and immunocompromised patients. Temocillin demonstrates a favorable safety profile, minimal disruption of gut microbiota, and cost-effectiveness. It also exhibits synergistic activity with agents like fosfomycin, further enhancing its clinical value. Most of the current evidence is derived from retrospective and observational studies. Conclusions: Temocillin emerges as a promising carbapenem-sparing option for the treatment of challenging infections caused by multidrug-resistant Gram-negative bacteria. Full article