OBJECTIVE:This study evaluated the in vitro activity of sulbactam/durlobactam and comparators against carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream isolates from Italy and investigated genomic mechanisms underlying resistance. METHODS:A total of 110 consecutive CRAB isolates (2021-2023) were tested for susceptibility to sulbactam/durlobactam, cefiderocol, colistin, and comparators. Whole-genome sequencing (WGS) was performed on sulbactam/durlobactam-resistant isolates to characterise β-lactamase genes, outbreak dynamics, and mutations in penicillin-binding proteins (PBPs). RESULTS:Sulbactam/durlobactam inhibited 87.3% of isolates (MIC₅₀ = 2 mg/L; MIC₉₀ > 64 mg/L), while 12.7% were resistant. Cefiderocol and colistin showed 91.8% and 96.4% susceptibility rates, respectively. All resistant isolates carried blaOXA-23, and three also harbored blaNDM-1. WGS revealed close clonal relationships (average nucleotide identity > 99%) among blaNDM-1 positive isolates (ST231) and among OXA-23-only isolates (ST837/ST369), indicating local outbreak dynamics. Comparative PBP analysis identified recurrent substitutions P112S and G137R (PBP1b), N392T and A515V (PBP3), and S329N (PBP5). Structural correlation suggests these mutations reduce β-lactam binding and may contribute to resistance, particularly when combined with NDM-1. CONCLUSIONS:This study provides early evidence of sulbactam/durlobactam resistance in treatment-naïve CRAB from Italy, driven by NDM-1 co-production and PBP alterations. The coexistence of epidemic ST231 and ST837/ST369 clones highlights the need for continuous genomic surveillance and prudent antibiotic stewardship to prevent dissemination of resistant A. baumannii lineages.

Moraxella species are fastidious Gram-negative bacteria capable of causing opportunistic infections, including bloodstream infections, especially in immunocompromised patients. Data on their epidemiology, antimicrobial susceptibility, and phylogenomics in Europe remains limited. We conducted a multicentre, retrospective, observational study across 56 European hospital centres between January 1st 2020 and December 31st 2024. All Moraxella species isolated from blood cultures (BCs) were included. Species distribution and antimicrobial susceptibility profiles were analysed. We also performed a phylogenomic analysis of Moraxella genomes deposited in GenBank. A total of 709 Moraxella isolates were included. Moraxella osloensis (61.1

Cefepime combined with late-generation β-lactamase inhibitors-enmetazobactam, zidebactam, and taniborbactam-represents a promising strategy to treat multidrug-resistant Gram-negative infections. These combinations expand the therapeutic armamentarium beyond established β-lactam/β-lactamase inhibitor regimens, offering targeted activity against ESBL-, AmpC-, and carbapenemase-producing Enterobacterales, as well as multidrug-resistant Pseudomonas aeruginosa. In vitro studies highlight potent and broad activity, with mechanisms including β-lactamase inhibition and, in the case of zidebactam, dual β-lactam enhancement through PBP2 binding. Clinical evidence demonstrates efficacy in complicated urinary tract infections and suggests potential for treating extensively drug-resistant infections, including those unresponsive to conventional β-lactam/β-lactamase inhibitors. Emerging resistance mechanisms-such as PBP alterations, porin loss, efflux pump overexpression, and evolving KPC or NDM variants-underscore the need for ongoing surveillance and robust susceptibility testing. This review provides a comprehensive overview of the mechanisms of action, in vitro activity, pharmacokinetic/pharmacodynamic properties, clinical outcomes, and resistance patterns of these cefepime-based combinations. It also highlights future directions, including the establishment of clinical breakpoints, evaluation in severe infections, and exploration of combination strategies to counteract complex resistance. Overall, these agents exemplify a strategic evolution in β-lactam therapy, offering versatile options to reduce carbapenem reliance while maintaining high efficacy against multidrug-resistant Gram-negative pathogens.

Background/Objectives: Rapid pathogen identification is essential to optimize antimicrobial therapy and improve patient outcomes, particularly in severe infections. Syndromic molecular diagnostics have been introduced to overcome the limitations of conventional culture-based methods. This study evaluated the diagnostic performance and real-life implementation of BioFire® FilmArray® syndromic panels compared with routine microbiological diagnostics. Methods: A total of 955 clinical specimens collected between 2022 and June 2025 were retrospectively analyzed, including positive blood cultures (n = 400), lower respiratory tract samples (n = 309), cerebrospinal fluid (n = 158) and stool specimens (n = 88). FilmArray® BCID2, Pneumonia Plus, Meningitis/Encephalitis and Gastrointestinal panels were performed on the Biofire Fimarray® instrument according to clinical indication and compared with conventional culture-based identification and phenotypic antimicrobial susceptibility testing. Results: Overall diagnostic concordance between BioFire® FilmArray® syndromic panels and conventional methods was high across all specimen types, with the highest positive percent agreement (PPA) observed for bloodstream infections (97.7%) and gastrointestinal pathogens (100%). In respiratory samples, the Pneumonia Plus panel detected a considerable number of microorganisms that could not be identified by culture, including viral pathogens and fastidious bacteria. Molecular detection of antimicrobial resistance markers showed excellent concordance with phenotypic profiles, with 100% agreement for CTX-M, carbapenemases (KPC, NDM, OXA-48-like, IMP), and vanA/B, while lower concordance was observed for mecA/C in staphylococci. In parallel, semi-quantitative bacterial loads provided by the Pneumonia Plus panel showed a strong essential agreement with culture-based quantification (97.4%, ±1 log10). Across all panels, syndromic testing significantly reduced diagnostic turnaround time. Conclusions: Syndromic molecular panels provide rapid and reliable simultaneous detection of pathogens, as well as early resistance marker detection, thereby supporting timely antimicrobial optimization and stewardship when integrated with conventional microbiological diagnostics.

Introduction Aeromonas species are Gram-negative bacilli capable of causing bloodstream infections in both immunocompromised and otherwise healthy individuals. However, data on their epidemiology and antimicrobial resistance remain limited in Europe. Methods We conducted a multicentre, retrospective, observational study that included all Aeromonas species isolates recovered from blood cultures in 56 European hospitals between January 1st 2020 and December 31st 2024. Epidemiological features and antimicrobial susceptibility profiles were analyzed. Results A total of 590 Aeromonas isolates were included. Most were recovered from polymicrobial blood cultures (73.1%), and catheter-related bloodstream infections were frequent (21.7%). The most commonly reported species were A. caviae (30.1%), isolates without conclusive species identification (Aeromonas spp., 24.8%), A. hydrophila (20.7%), and A. veronii (19.1%). At the genus level, susceptibility to aztreonam, ceftazidime, and cefepime exceeded 90%. Resistance to fluoroquinolones (∼10%) and sulfamethoxazole/trimethoprim (up to 11%) was observed. Species-level analyses showed higher resistance rates to fluoroquinolones and sulfamethoxazole/trimethoprim among A. caviae and A. hydrophila, and increased resistance to ceftazidime among Aeromonas spp. Conclusions Aeromonas species in Europe showed high susceptibility to ceftazidime and cefepime, alongside with emerging resistance to fluoroquinolones and sulfamethoxazole/trimethoprim. Species-specific findings should be interpreted cautiously due to limitations in routine identification methods, underscoring the need for sustained surveillance and harmonised diagnostic standards across Europe.

Background: Nonfermenting Gram-negative bacilli other than Pseudomonas and Acinetobacter species are increasingly recognized as opportunistic pathogens in pediatric populations, yet their epidemiology and antimicrobial resistance remain poorly defined. Methods: We conducted a multicenter retrospective analysis across 56 hospital centers in 25 European countries, including pediatric blood culture isolates collected between January 2020 and December 2024. Species distribution and antimicrobial susceptibility profiles according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Clinical and Laboratory Standards Institute (CLSI) current guidelines were analyzed. Results: A total of 382 isolates were included, spanning 19 genera and 40 species. Stenotrophomonas maltophilia was the most frequently identified species (46.9%; n = 179), followed by Roseomonas mucosa (10%; n = 38) and Sphingomonas paucimobilis (7.6%; n = 29). Susceptibility profiles were heterogeneous, with notable resistance across several species. For S. maltophilia , resistance to trimethoprim/sulfamethoxazole exceeded 10% (EUCAST), while full in vitro susceptibility to aztreonam/avibactam was observed. Preserved activity of carbapenems but high resistance to ceftazidime (EUCAST/CLSI), piperacillin/tazobactam (EUCAST/CLSI) and ciprofloxacin (CLSI) was observed for S. paucimobilis . Achromobacter several species showed concerning resistance patterns to carbapenems, piperacillin/tazobactam and trimethoprim/sulfamethoxazole (CLSI). Conclusions: Nonfermenting Gram-negative bacilli other than Pseudomonas and Acinetobacter species were frequently associated with healthcare exposure and complex resistance profiles. Their management is challenged by a lack of evidence and standardized susceptibility criteria. To optimize management, enhanced surveillance, improved diagnostic standardization and further clinical studies on emerging therapies are needed.

Objectives To investigate the clinical and molecular drivers of in-vivo cross-resistance to ceftazidime/avibactam (CZA) and cefiderocol (FDC) in infections caused by KPC-producing Klebsiella pneumoniae (KPC-Kp). Material and Methods We conducted a retrospective case series of patients initially infected or colonized by CZA- and FDC-susceptible KPC-Kp who subsequently developed infections due to strains co-resistant to both agents. Whole-genome sequencing (WGS) and cloning of blaKPC alleles into E. coli were performed to elucidate resistance mechanisms. Results Three patients developed bloodstream infections with KPC-Kp resistant to both CZA and FDC following CZA exposure. WGS identified blaKPC variants featuring substitutions within or adjacent to the Ω-loop: KPC-31 (D179Y), KPC-49 (R164S), and KPC-167 (D179Y with a DDKYSE 270-loop duplication). All resistant isolates belonged to ST512 and exhibited porin alterations (OmpK35 truncation and OmpK36 GD insertion). Cloning experiments demonstrated that these KPC variants markedly increased CZA MICs and modestly elevated FDC MICs, confirming their functional contribution to the resistance phenotype. Conclusions These findings demonstrate the in-vivo emergence of cross-resistance to CZA and FDC driven by stepwise selection of KPC Ω-loop and 270-loop variants combined with permeability defects.

INTRODUCTION:Non-fermenting Gram-negative bacilli (NFGNB) other than Pseudomonas and Acinetobacter species remain largely underrepresented in systematic surveillance programs across Europe. METHODS:We conducted a multicentre retrospective observational study analysing all minor NFGNB isolates recovered from blood cultures in 56 European Hospital Centres over a 5-year period (2020-2024). Diagnostic approach, epidemiology and antimicrobial susceptibility according to European Committee on Antimicrobial Susceptibility Testing v. 15.0 were investigated. RESULTS:A total of 4420 minor NFGNB isolates were included. In 43.6% of cases, the isolates were recovered from polymicrobial blood cultures, and 40.6% were detected during microbiologically defined catheter-related bloodstream infections. Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-ToF) mass spectrometry was the most widely used tool for species identification (98%). Antimicrobial susceptibility testing was conducted in all centres, using mostly broth microdilution commercial systems (57%), disk diffusion (57%) and gradient diffusion MIC strip (54%) methods, mainly according to European Committee on Antimicrobial Susceptibility Testing guidelines (67.9%). The most prevalent species were Stenotrophomonas maltophilia (52.4%), Achromobacter xylosoxidans (7.8%), Sphingomonas paucimobilis (5.3%) and the Burkholderia cepacia complex (4.8%). S. maltophilia displayed a high rate of resistance to sulfamethoxazole/trimethoprim (11%), and 2% of the isolates were found to be likely resistant to cefiderocol. A. xylosoxidans showed high resistance to meropenem (10%), piperacillin/tazobactam (24%) and sulfamethoxazole/trimethoprim (53%) when tested by MIC methods, while showing over 90% susceptibility to meropenem when tested by disk diffusion. S. paucimobilis displayed over 90% susceptibility to amoxicillin/clavulanate, ampicillin/sulbactam, imipenem, meropenem and tetracycline. CONCLUSIONS:This study provides an updated overview of the diagnostic approaches and epidemiology of minor NFGNB across Europe, supporting future comparative analyses and improved diagnostic and antimicrobial strategies.

The carbapenemase-producing Gram-negative organisms represent an urgent clinical and public health concern, as they have been associated with increased mortality and high dissemination in healthcare settings. Although overall incidence rates of infections sustained by metallo-β-lactamase (MβL)-producers have remained lower than those sustained by other carbapenemase-producers, albeit with substantial geographic differences, a significant increase in the prevalence of MβL-producers has been observed over the last decade. The recent development of new antimicrobials expanded the armamentarium to counter the challenge of metallo-β-lactamase (MβL)-producers. Cefiderocol and aztreonam/avibactam are already clinically available and recommended by international guidelines. In addition, two new classes of β-lactam/ β-lactamase combinations are under clinical evaluation: (i) combination of β-lactam with novel boronic-derived inhibitors (e.g. taniborbactam and xeruborbactam), (ii) combination of β-lactam with last generation diazabicyclooctane β-lactamase inhibitors (e.g. zidebactam and nacubactam), active on most of serine-β-lactamases but also showing strong intrinsic activity on PBP-2. This review aims to provide up-to-date data on the characteristics, activity and emerging resistance mechanisms of the armamentarium of clinically available or soon-to-be introduced drugs for the treatment of MβL-producing Gram-negative organisms.

Infections caused by anaerobes are common in children. However, limited data are available on bloodstream infections caused by these bacteria in Europe. A multicentre retrospective observational study was conducted over a 4-year period (2020-2023) across 44 European hospitals to analyze all anaerobes isolated from blood cultures. The study examined the epidemiology and antimicrobial resistance profiles of anaerobes identified in paediatric patients, comparing the findings with those observed in adults. Among the 14,527 total anaerobic isolates, 186 (1.3%) were detected from paediatric patients. These were predominantly Gram-positive (70%) and Gram-negative (22%) bacilli. The most prevalent species in paediatric patients were Cutibacterium acnes (24.7%), Schaalia odontolytica (9.7%), Actinomyces oris (8.1%), and Bacteroides fragilis (7.5%). Relative feature importance based on the mean SHAP (SHapley Additive exPlanations) values distinguished paediatric patients and adults based on their antibiotic resistance patterns with high accuracy. Compared to those from adult patients, Gram-positive bacilli detected in paediatric samples displayed higher resistance rates for meropenem (15% vs. 9%), metronidazole (52% vs. 24%), and vancomycin (27% vs. 6%), and lower resistance to benzylpenicillin (11% vs. 17%), amoxicillin/clavulanate (9% vs. 17%), and clindamycin (30% vs. 36%). Gram-negative bacilli in paediatric samples displayed lower resistance to benzylpenicillin (18% vs. 29%), piperacillin/tazobactam (26% vs. 33%), and clindamycin (20% vs. 27%), and they were highly susceptible to imipenem, meropenem, and metronidazole as those detected in adult patients. Bacteroides species detected in paediatric and adult patients displayed high resistance to piperacillin/tazobactam (33% vs. 39%) and clindamycin (38% vs. 29%), while they were highly susceptible to metronidazole. Compared to those from adult samples, Cutibacterium acnes in paediatric patients displayed lower resistance to benzylpenicillin (none vs. 15%) and clindamycin (17% vs. 29%). The comparison of species and susceptibility profiles of anaerobes detected in paediatric and adult patients highlighted the importance of reporting antimicrobial susceptibility surveillance data by age group.

Introduction: Despite being implicated in a wide spectrum of community-and healthcare-acquired infections, anaerobes have not yet been incorporated into systematic surveillance programs in Europe. Methods: We conducted a multicentre retrospective observational study analysing all anaerobic strains isolated from blood cultures in 44 European Hospital Centres over a 4-y period (2020-2023). Diagnostic approach, epidemiology, and antimicrobial susceptibility according to EUCAST v. 15.0 were investigated. Results: Our study included 14,527 anaerobes, most of which were Gram-positive (45%) or Gram-negative (40%) bacilli. MALDI-TOF coupled to mass spectrometry was the most widely used tool for species identification (98%). Antimicrobial susceptibility testing was performed in the vast majority of centres, using mostly gradient diffusion strip (77%) and disk diffusion (45%) methods according to EUCAST guidelines. The most prevalent species were Cutibacterium acnes (18.7%), Bacteroides fragilis (16.3%), Clostridium perfringens (5.3%), Bacteroides thetaiotaomicron (4.2%), Fusobacterium nucleatum (3.5%), and Parvimonas micra (3.4%). C. acnes showed high resistance to benzylpenicillin (18%), clindamycin (39%), and imipenem (19% and 13% by MIC methods and disk diffusion, respectively). B. fragilis showed high resistance to amoxicillin/clavulanate (24%), piperacillin/tazobactam (22% and 14% by MIC methods and disk diffusion, respectively), clindamycin (22% by both MIC methods and disk diffusion), meropenem (13%), and metronidazole (10%, only by disk diffusion). A similar resistance pattern was observed in B. thetaiotaomicron, Bacteroides ovatus, and Parabacteroides distasonis. C. perfringens showed high resistance to clindamycin (69% and 45% by MIC methods and disk diffusion, respectively), while benzylpenicillin and metronidazole maintained over 90% activity. F. nucleatum showed high resistance to benzylpenicillin (11%), while Fusobacterium necrophorum showed alarming rates of resistance to clindamycin (12%), meropenem (16%) and metronidazole (11%). Conclusions: This study presented an up-to-date analysis of the diagnostics and epidemiology of anaerobic bacteria in Europe, providing insights for future comparative analyses and the development of antimicrobial diagnostic and management strategies, as well as the optimization of current antibiotic treatments. (c) 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Novel β-lactam/β-lactamase inhibitor combinations (BL/BLICs) such as ceftazidime/avibactam (CAZ/AVI), meropenem/vaborbactam (MEM/VAB), imipenem/relebactam (IMP/REL) and aztreonam/avibactam (ATM/AVI) have expanded therapeutic choices against KPC-producing K. pneumoniae. However, emerging resistance threatens their long-term efficacy. We investigated the prevalence, genomic mechanisms, and clinical correlates of resistance to these agents among KPC-producing K. pneumoniae bloodstream isolates. Consecutive KPC-producing K. pneumoniae bloodstream isolates collected between 2021 and 2024 at a tertiary university hospital were tested for susceptibility to novel BL/BLICs and comparators. Whole-genome sequencing (WGS) was performed on isolates resistant to any BL/BLIC to characterise genetic backgrounds. Clinical data from corresponding patients were analysed to explore risk factors and outcomes. Among 178 K. pneumoniae isolates, ATM/AVI, IMP/REL and MEM/VAB retained excellent in vitro activity (≥ 96

To evaluate diagnostic performance of four diagnostic methods for rapid determination of methicillin resistance in S. aureus positive blood cultures (BCs). Clinical and spiked BCs were subjected to the evaluation of the following methods and protocols: a. Eazyplex® MRSA Plus loop‐mediated isothermal amplification (LAMP) assay directly from BC fluid; b. MALDI-TOF MS subtyping on BC pellet extracted with Rapid Sepsityper® protocol and on 4-h short-term subculture; c. Clearview™ Culture Colony PBP2a SA immunochromatography assay on BC pellet and on 4-h short-term subculture; d. EUCAST RAST cefoxitin screen test performed directly from BC and including reading times at 4-h, 6-h and 16–20-h. Eazyplex® MRSA plus exhibited the best performance, showing 100

INTRODUCTION:Multi-carbapenemases producing Enterobacterales (MCP-EB) represents a new public health challenge due to their ability to display complex resistance phenotypes. METHODS:MCP-EB isolates identified from patients admitted to an Italian Center in the period 2020-2024 were included. Clinical features were collected. RESULTS:Among 3,117 carbapenemase-producing Enterobacterales clinical strains, 31 (1 %) were MCP-EB and were detected from 28 patients. The most common MCP-EB species was Klebsiella pneumoniae (78.6 %; n = 22). Six combinations of two different carbapenemases were observed: KPC+VIM (75 %; n = 21), KPC+NDM (10.7 %; n=3), VIM+NDM (10.7 %; n = 3), KPC+OXA-48-like (3.6 %; n = 1), VIM+OXA-48-like (7.1 %; n = 2), and NDM+OXA-48-like (3.6 %; n = 1). Patients with MCP-EB had a median age of 67 years [IQR 59-73], were predominantly men (57.1 %; n = 16), and a median Charlson Comorbidity Index of 5 [IQR 4-6]. The comorbidities mainly observed were cardiovascular disease (53.6 %; n = 15), chronic respiratory disease (39.3 %; n = 11), and chronic kidney disease (32.1 %; n = 9). Fifty per cent (n = 14) of patients had been hospitalized in the previous 180 days and 75 % (n = 21) had been exposed to antibiotics in the previous 30 days. Median time from admission to MCP-EB specimen collection was 16 days [IQR 10-24] and 28.6 % (n = 8) of patients showed to carry MCP-EB in more than two body districts. Fourteen-day, 30-day, and in-hospital mortality were 10.7 %, 25 %, and 32.1 %, respectively. MCP-EB showed high rates of resistance to all antibiotics tested except aztreonam/avibactam. Patients with MCP-EB infection (35.7 %; n = 10) were treated with combination regimens, mainly including aztreonam plus ceftazidime/avibactam or cefiderocol. Two patients (20 %) had a recurrence of MCP-EB infection and four (40 %) patients did not survive hospitalisation. CONCLUSION:Clinical features of patients with MCP-EB are common in the hospital population with chronic diseases and showed high mortality rates both in infected and carriers-only patients. Aztreonam/avibactam and cefiderocol could be promising treatment options against MCP-EB infections.

Carbapenem-resistant Acinetobacter baumannii (CRAB) are a leading cause of nosocomial infections and subsequently present an urgent global public health threat. 1 OXA-23 is the most frequently reported carbapenemase in CRAB and such isolates are most often multidrug-resistant, leaving few therapeutic options. 1 Cefiderocol (FDC), a recently approved siderophore cephalosporin, represents a promising treatment option for CRAB infections, particularly since reported resistance rates in non-metallo-betalactamase-producing CRAB remain low. 2 FDC resistance in A. baumannii has previously been reported to be associated with mutations and/or deletions in the TonB-dependent receptors PiuA and PirA, 3 the carriage of certain beta-lactamases (e.g.MBLs and PER-type), 4 and mutations within the penicillin binding protein PBP-3, the main target of FDC. 3 In this study, we describe the in vivo development of FDC resistance following treatment, mediated by a previously undescribed mutation in the promoter region of TonB-dependent receptor, PiuA.An 80-year-old woman was admitted to the ICU of the University Hospital 'Città della salute e della scienza di Torino' (Turin, Italy) due to a severe burn injury (20% TBSA).Empirical antibiotic therapy with piperacillin/tazobactam plus amikacin was started.On day 52, she presented with fever and elevation of inflammatory markers.Blood cultures were positive for an FDC-susceptible CRAB isolate (AB1).FDC plus fosfomycin were

Respiratory Syncytial Virus (RSV) is responsible for a considerable burden of respiratory disease among children and older adults. Several prophylactic strategies have recently been introduced. We review the available evidence on the interplay between RSV infection and HIV, looking at the specific role of RSV prophylactic strategies in individuals affected by or exposed to HIV. We conducted a systematic review on the association between HIV infection and RSV incidence and severity. We searched in PubMed/MEDLINE for clinical epidemiological studies covering outcomes such as RSV-associated illness, severity, and mortality in individuals affected by or exposed to HIV. A total of 36 studies met the inclusion criteria and were included, the majority conducted in sub-Saharan Africa. There was no compelling evidence suggesting a higher incidence of RSV illness among HIV-infected people. A higher risk of severe disease was consistent among both HIV-positive and HIV-exposed but uninfected (HEU) children. Case fatality rates were also higher for these groups. Evidence on a differing risk among adults was scarce. HIV-positive pregnant women should be given priority for recently approved RSV vaccination, for protection of their newborns. HIV-infected and HEU infants should be considered risk groups for nirsevimab prophylaxis in their first year of life and possibly beyond.

Background: Klebsiella pneumoniae is a concerning pathogen, responsible for hospital-associated outbreaks. Multi drug resistant (MDR) strains are especially hard to treat. We conducted whole-genome sequencing on a MDR K. pneumoniae strain in order to identify genomic features potentially linked to its phenotype. Methods: DNA sequencing was performed on the Illumina iSeq 100 platform. Genome assembly was carried out with SPAdes. The genome was annotated with RASTtk. Typing was performed with MLST and Kaptive. Antibiotic resistance genes were detected with AMRFinderPlus and Abricate, and further verified with BLAST. Results: The strain exhibited resistance to ceftazidime/avibactam and cefiderocol, but remained susceptible to carbapenems. The strain belonged to sequence type ST101, serotype O1:K17. The analysis of antibiotic resistance genes indicated that the strain carried a novel KPC variant, designated as KPC-203, featuring a EL deletion at amino acid position 166–167, within the Ω-loop, and a nine-amino-acid insertion (LAVYTRAPM) at position 259. Sequence alterations were found in porin genes ompK35 and ompK36. Unlike molecular testing, which was able to detect the KPC-203 variant, all phenotypic carbapenemase detection methods achieved negative results. Conclusions: KPC-203, a novel KPC variant, showed a sequence modification in a cephalosporin resistance-associated hotspot. Interestingly, such alterations typically correlate with the restoration of carbapenem susceptibility. We hypothesize that KPC-203 likely led to resistance to ceftazidime/avibactam and cefiderocol, while maintaining susceptibility to carbapenems.