Search Results (271)

Background/Objectives: Ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) are critical therapeutic options for multidrug-resistant Gram-negative infections; however, their comparative pharmacodynamics against carbapenem-resistant Pseudomonas aeruginosa (CRPA) remain incompletely defined. This study aimed to compare the bactericidal activity of C/T and CZA administered by intermittent infusion (II) or continuous infusion (CI) using a hollow fiber infection model (HFIM) against a clinical isolate of CRPA. Methods: Clinically relevant concentration–time profiles for C/T and CZA based on prescribing information were simulated in the HFIM. The standard P. aeruginosa strain ATCC 27853 and a GES-producing clinical CRPA isolate were utilized. The primary endpoint was bactericidal activity (≥3 log₁₀ CFU/mL reduction from baseline), while secondary endpoints included regrowth prevention and resistance development based on population analysis profiles (PAPs). Results: Against the standard strain, both agents achieved rapid killing without regrowth. However, for the GES-producing clinical isolate, C/T failed to achieve bactericidal activity. In contrast, CZA demonstrated sustained bacterial killing activity with the most pronounced early-phase bactericidal activity with CI of CZA (−4.25 log₁₀ CFU/mL at 24 h). The bactericidal activity was persistent over 7 days without bacterial regrowth after treatment discontinuation. Conversely, bacterial regrowth occurred with II of CZA after drug withdrawal. PAPs showed the lack of resistance development against CZA, whereas resistance to C/T developed within 48 h after initiating therapy. Conclusions: In this HFIM study, CI of CZA demonstrated the most sustained suppression of bacterial growth and prevented resistance emergence against the tested clinical isolate of CRPA producing GES β-lactamases. Future clinical studies are warranted to assess the effectiveness of the CI regimen. Full article

Background/Objectives: The impact of antimicrobial susceptibility testing methodology on the categorization and positioning of cefiderocol and aztreonam-avibactam against metallo-β-lactamase (MBL)-producing Gram-negative bacilli remains unclear. This study aimed to evaluate the in vitro activity of cefiderocol and aztreonam-avibactam against clinical MBL-producing isolates and to assess the agreement between different cefiderocol susceptibility testing methods. Methods: A total of 299 non-duplicate clinical MBL-producing Gram-negative isolates were collected from clinical samples between 2022 and 2025. Antimicrobial susceptibility testing was performed using broth microdilution, disc diffusion, and gradient strip diffusion according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Carbapenemase genes were identified by immunochromatography and multiplex PCR. Categorical agreement and error rates between cefiderocol testing methods were analyzed. Results:Klebsiella pneumoniae was the predominant species, mainly producing NDM alone or in combination with OXA-48-like carbapenemases. Aztreonam-avibactam demonstrated complete activity against all Enterobacterales isolates (262/262, 100%) and high activity against Pseudomonas spp. (33/37, 89%). Cefiderocol susceptibility among Enterobacterales varied markedly depending on the testing method. Disc diffusion yielded 14% susceptibility (37/262), which increased to 52% (136/262) after ATU resolution, whereas broth microdilution showed 85% susceptibility (224/262). This resulted in low categorical agreement (42%) and a high rate of major errors (58%), with no very major errors detected. Cefiderocol activity did not differ substantially across carbapenemase types and was highest against VIM-producing Pseudomonas spp. Conclusions: Aztreonam-avibactam showed consistent in vitro activity against MBL-producing Enterobacterales, whereas cefiderocol activity was strongly influenced by the susceptibility testing methodology. Disc diffusion substantially underestimated cefiderocol susceptibility compared with broth microdilution. These findings highlight the critical impact of testing methodology on cefiderocol categorization and support the therapeutic role of last-line agents in the management of MBL-producing Gram-negative infections, with direct implications for clinical microbiology laboratories and antimicrobial stewardship programs. Full article

Carbapenem-resistant Gram-negative infections have become one of the most formidable challenges in intensive care units (ICUs). Critically ill patients—often exposed to invasive procedures, prolonged hospitalization, and broad-spectrum antibiotics—are highly susceptible to infections by carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB). These pathogens are associated with mortality exceeding 40%, prolonged ICU stays, and increased healthcare costs. Therapeutic advances have reshaped management in recent years. New β-lactam/β-lactamase inhibitor combinations—ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam, and sulbactam–durlobactam—along with cefiderocol, have provided safer and more effective alternatives to previously used regimens. Yet, none are universally effective, particularly against carbapenemase-producing organisms, especially metallo-β-lactamase (MBL) producers, and resistance may still emerge during treatment. Rapid molecular and phenotypic diagnostics, when integrated into antimicrobial stewardship, have improved early therapy alignment and reduced unnecessary broad-spectrum use. Beyond antibiotics, colonization surveillance and infection control remain pivotal, as colonization often precedes invasive infection. Biofilm formation on devices such as endotracheal tubes and catheters further promotes persistence and relapse. Strategies targeting biofilm disruption, improved dosing guided by pharmacokinetic/pharmacodynamic optimization, and therapeutic drug monitoring are crucial in ICU practice. The future of managing these infections will depend on integrating precision tools—rapid diagnostics, mechanism-based therapy, and stewardship-guided decisions—with emerging treatments and adjunctive options such as immunomodulators, bacteriophages, and AI-driven decision support. Continued research in ICU-specific populations, especially regarding pharmacokinetics in patients on ECMO or CRRT, is urgently needed. In summary, while the therapeutic landscape for carbapenem-resistant Gram-negative infections has evolved substantially, sustained success will rely on a multifaceted strategy combining innovation, precision, and prevention to improve outcomes for the most vulnerable patients. Full article

Objectives: The primary objective was to evaluate the antimicrobial susceptibility of Pseudomonas aeruginosa causing infection in elderly (≥65 years old) patients hospitalized in intensive care units (ICUs) of United States medical centers. Susceptibility results from isolates of elderly patients in ICUs were compared to isolates from elderly patients not in ICUs (elderly non-ICU) and adult ICU patients (18 to 64 years old; adult ICU). Methods: P. aeruginosa isolates were consecutively collected from 74 US medical centers in 2021–2025 and susceptibility tested by reference broth microdilution in the monitoring laboratory (Element Iowa City [JMI Laboratories]). The organism collection included 999 isolates from elderly ICU, 2027 isolates from elderly non-ICU, and 1022 isolates from adult ICU patients. Results: The most active agents against P. aeruginosa from all three patient groups were ceftazidime-avibactam (95.8% to 97.3% susceptible), ceftolozane-tazobactam (96.0% to 98.3% susceptible), imipenem-relebactam (97.6% to 98.7% susceptible), and tobramycin (91.4% to 94.7% susceptible). Susceptibility to piperacillin-tazobactam, ceftazidime, cefepime, meropenem, and imipenem were markedly lower among isolates from elderly and adult ICU patients compared to elderly non-ICU patients. Susceptibility to levofloxacin and tobramycin were lower among isolates from adult ICU patients compared to elderly ICU and non-ICU patients. Moreover, the frequency of multidrug-resistant (MDR) isolates was markedly higher among elderly (18.4%) and adult (22.4%) ICU patients compared to elderly non-ICU (11.0%) patients. An annual analysis of susceptibility to selected β-lactams showed a slight variation in susceptibility rates without a clear trend. Conclusions: Ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-relebactam were highly active and exhibited similar coverage against a large contemporary collection of P. aeruginosa isolates from ICU elderly, non-ICU elderly, and ICU adult patients. Cross-resistance among these β-lactamase inhibitor combinations (BLICs) varied markedly, indicating that all three should be tested in the clinical laboratory and available for clinical use. Full article

Background/Objectives: The aztreonam/avibactam combination represents a promising therapeutic option for severe infections caused by multidrug-resistant Gram-negative pathogens, particularly in critically ill patients. Due to marked pharmacokinetic variability and the need to achieve joint pharmacokinetic/pharmacodynamic (PK/PD) targets of both agents, therapeutic drug monitoring (TDM) may play a pivotal role in optimizing treatment. This study aimed to develop and validate two rapid, accurate, and sensitive UHPLC–qTOF MS/MS sequential methods for quantifying aztreonam and avibactam in human plasma, suitable for routine clinical TDM. Methods: Plasma concentrations were determined by means of ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC–qTOF MS/MS), operating in positive and negative electrospray ionization modes for aztreonam and avibactam, respectively. Sample preparation consisted of protein precipitation with isotopically labeled internal standards. The method’s validation was performed according to the European Medicines Agency guidelines, by assessing selectivity, linearity, precision, accuracy, recovery, matrix effects, carry-over, and stability. Clinical applicability was evaluated by reprocessing plasma samples, which were already previously collected for routine clinical practice from 20 hospitalized patients undergoing treatment with ceftazidime-avibactam plus aztreonam. Results: The methods showed excellent linearity (R² ≥ 0.999) over ranges of 0.2–100 µg/mL for aztreonam and 0.1–50 µg/mL for avibactam. Lower limits of quantification were 0.2 µg/mL and 0.1 µg/mL, respectively. Intra- and inter-day precision and accuracy met the EMA criteria at all of the quality control levels. Extraction recovery exceeded 90% for both analytes, and matrix effects were effectively compensated by internal standards. Stability testing highlighted the need for careful sample handling, particularly for aztreonam under repeated freeze–thaw conditions. Clinical application revealed substantial inter-individual variability in steady-state concentrations. Conclusions: The validated UHPLC–qTOF MS/MS assays provide robust and sensitive sequential quantification of aztreonam and avibactam in human plasma, supporting TDM-guided dose optimization in clinical practice. Full article

Carbapenems are essential for the treatment of severe infections caused by Gram-negative bacteria, particularly in critically ill and immunocompromised patients. However, the global rise of carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa, and Acinetobacter baumannii has significantly eroded their effectiveness, and the phenomenon is now recognized as a major public health threat. Resistance is driven by the complex and evolving interplay of enzymatic and non-enzymatic mechanisms, occurring within highly successful clonal lineages and mobile genetic platforms. This review summarizes advances since 2020 in the molecular basis of carbapenem resistance, integrating enzymatic mechanisms across Ambler classes A, B, C, and D with emerging non-enzymatic contributors, including porin remodeling, efflux pump upregulation, target-site alterations, and outer-membrane adaptations. Particular attention is given to adaptive genome dynamics, such as IS26-mediated gene amplification, plasmid multimerization, and heteroresistance, that generate unstable resistance phenotypes and complicate routine susceptibility testing. Newly introduced β-lactam/β-lactamase inhibitor combinations exert distinct selective pressures: ceftazidime–avibactam favors KPC Ω-loop variants and permeability defects, often restoring carbapenem susceptibility, whereas meropenem–vaborbactam and imipenem–relebactam resistance is driven mainly by porin loss and β-lactamase gene amplification. Cefiderocol resistance is multifactorial, frequently involving impaired siderophore uptake and heteroresistance, while sulbactam–durlobactam remains active against OXA-producing A. baumannii but is compromised by metallo-β-lactamases and PBP3 alterations. Carbapenem resistance is increasingly characterized by convergent, multi-layered adaptations that undermine both established and novel therapies. While high-level randomized evidence remains limited for some resistance mechanisms, emerging mechanistic, microbiological, and clinical data support the need for mechanism-aware diagnostics, repeated susceptibility assessment during therapy, and stewardship strategies informed by resistance biology. Integrating molecular context into routine practice will be critical to preserving emerging treatment options and limiting the global impact of carbapenem resistance. Full article

Background: The increasingly indiscriminate use of antibiotic therapy in the neonatal period has led to the emergence of multidrug-resistant organisms (MDROs), which are responsible for sepsis that is increasingly difficult to treat and associated with high morbidity and mortality. Increasingly frequently, in neonatal intensive care units (NICUs), it is necessary to use last-generation antibiotics belonging to the RESERVE group according to the current classification of the World Health Organization (WHO). Methods: Among these drugs, ceftazidime-avibactam, ceftolozane-tazobactam and meropenem-vaborbactam are increasingly used in infections caused by Enterobacterales (i.e., E. cloacae complex, Klebsiella spp.), which are often responsible for late-onset sepsis (LOS) in newborns, especially in preterms. Results: Here, we present the experience of four newborn patients in the city of Palermo, treated over a period of 3 years. Conclusions: The comparison between different diagnostic–therapeutic management approaches and a review of the most recent literature can contribute to identifying more standardized pharmacological schemes, especially in the neonatal period, where scientific evidence about this topic is still very limited. Full article

Background/objectives: A rise in infections associated with carbapenem-resistant Providencia species (CRPS) has been observed worldwide. This study presents a genomic analysis of CRPS isolates from four hospitals in Croatia and the outpatient setting, in order to determine the extent of the spread of CRPS in Croatia. In the present study, we applied a combination of phenotypic characterization and molecular analysis of resistance traits to determine the mechanisms and the routes of spread of CRPS. Material and methods: The antibiotic susceptibility testing was performed using disk-diffusion and broth dilution methods. The nature of extended-spectrum β-lactamases (ESBLs), carbapenemases, and fluoroquinolone resistance determinants was investigated by polymerase chain reaction (PCR). In order to obtain an insight into the whole resistome, selected isolates were subjected to the Interarray Genotyping Kit CarbaResist and whole genome sequencing (WGS). Results: In total, 30 isolates were collected from four centers, located in different geographic regions of Croatia. There was uniform resistance to piperacillin-tazobactam, cefuroxime, expanded-spectrum cephalosporins (ESCs), imipenem, ertapenem, meropenem, and ciprofloxacin. Immunochromatographic testing and PCR revealed OXA-48 and NDM carbapenemase in 15 isolates, respectively. Phenotypic tests for ESBLs were positive in all OXA-48 and one NDM-positive organism (16 isolates). The isolates were categorized as extensively drug-resistant (XDR). OXA-48-producing isolates were susceptible only to ceftazidime-avibactam, whereas NDM producers were susceptible to cefiderocol and, in the majority of cases, also to amikacin. WGS identified a plethora of genes encoding resistance to aminoglycosides, such as aadA1 and aadA2, (aph(3″)-Ib and aph(6)-Id, sulfonamides sul1 and sul2, trimethoprim dfrA1, dfrA10, and dfrA12, tetracyclines tet(A) and tet(B), and chloramphenicol catA3 and catA5. Conclusions: Providencia spp., in spite of being a rare pathogen, should be included in the surveillance studies across the medical centers in Croatia. Full article

Background: Cefiderocol, a siderophore cephalosporin, is approved for the treatment of infections caused by multi-drug-resistant Gram-negative bacteria (MRGN). At present, few data are available on the pharmacokinetics of this substance in critically ill patients, particularly for the treatment of central nervous system infections. Patients and Methods: Here, we reported on a 22-year-old male patient after severe open head trauma. Initial screening revealed colonization with 4MRGN A. baumannii (OXA-23) (perianal) and 4MRGN K. pneumoniae (KPC) (tracheal). Unfortunately, he developed ventriculitis (4MRGN A. baumannii). According to microbiological testing, the patient with normal renal function received 3 × 2 g/d i.v. cefiderocol as a prolonged infusion (3 h) and colistin 3 × 3 Mio. IU/d i.v. for 2 weeks. In addition to serum trough levels, drug monitoring was performed in the cerebrospinal fluid (CSF) via external ventricular drainage (24 h aliquots). Results: Serum and CSF specimens analyzed by liquid chromatography–mass spectroscopy (LC-MS) in the presence of severe meningeal inflammation yielded average CSF concentrations of cefiderocol from 5.48 to 8.40 (median 6.98) μg/mL and a concentration ratio C_{CSF mean}/C_{serum trough} from 0.38 to 0.76 (median 0.48). The cefiderocol levels in the CSF were sufficient for eradication of A. baumannii. A subsequent CSF infection with K. pneumoniae (found initially in screening and resistant to cefiderocol) after completed treatment with cefiderocol was successfully treated with gentamicin (intrathecally) and ceftazidime/avibactam (i.v.). However, the patient died due to a Candida tropicalis infection detected in the CSF on day 71. Conclusions: Our results indicate that standard dosages of cefiderocol are sufficient for treatment of CNS infections in the presence of a severe disruption of the blood–CSF barrier. Full article

Background/Objectives: Carbapenem-resistant Klebsiella spp. (CRK) causes healthcare-associated infections with high mortality. This study evaluated the clinical outcomes of ceftazidime–avibactam (CZA) therapy in CRK infections. Methods: Patients hospitalized in a tertiary care hospital in Türkiye between June 2021 and December 2022 with CRK-positive cultures, CZA susceptibility, and ≥72 h of CZA treatment were retrospectively analyzed. Results: Ninety-nine patients (61.6% male; mean age 63.7 ± 17.5 years) were included, 89.9% of whom were treated in the intensive care unit (ICU). Hypertension (29.3%), diabetes (28.3%), and malignancy (26.3%) were the most frequent comorbidities. The main infection types were bloodstream infection (56.6%) and ventilator-associated pneumonia (29.3%). CZA was used as monotherapy in 49.5%, and in combination in 50.5% of cases. The mean treatment duration was 13.2 ± 6.3 days. Clinical improvement occurred at 3.4 ± 1.2 days and microbiological eradication at 4.7 ± 2.1 days. Treatment success was achieved in 76.8% of patients, while 30- and 90-day mortality rates were 48.5% and 72.7%, respectively. Only treatment duration significantly affected clinical outcome (p < 0.001). Conclusions: CZA demonstrates favorable outcomes in CRK infections, with no significant difference between monotherapy and combination therapy. These findings support the use of CZA as an effective treatment option for severe CRK infections in real-world clinical settings and may help guide antimicrobial stewardship strategies in high-risk hospitalized patients. Full article

Background/Objectives: Antimicrobial resistance (AMR) is considered a major threat by the healthcare community. In this context, the AWaRe (Access, Watch, Reserve) classification of antibiotics is a valuable tool that can assist physicians during the clinical decision process and pharmacists in promoting the rational use of antibiotics. Pharmacovigilance studies based on real-world evidence offer valuable insight into the AMR phenomenon. The aim of this study was the assessment of the resistance, ineffectiveness, and off-label use signals of all five cephalosporins belonging to the Reserve group (ceftazidime/avibactam, ceftaroline, cetolozane/tazobactam, ceftobiprole, and cefiderocol). Methods: The study was conducted using descriptive approaches on EudraVigilance data and disproportionality analyses comparing each of the fourteen cephalosporins in the Watch group. Results: Ceftazidime/avibactam (n = 904, 38.6%) topped the reports, followed by ceftaroline (n = 559, 23.9%) and ceftolazane/tazobactam (n = 560, 23.9%). The lowest number of reports was submitted for cefiderocol (n = 176, 7.5%) and ceftobiprole (n = 146, 6.2%). The resistance to ceftazidime/avibactam, cefiderocol, and ceftolozane/tazobactam was reported with a higher probability than all others, the strongest signal being observed for cefiderocol against cefixime (ROR: 171.25, 95% CI 79.64–368.27). All cephalosporins from the Reserve group (except ceftobiprole) have higher probability for reporting ineffectiveness than cephalosporins from the Watch group; the strongest signal was observed for cefiderocol–cefditoren (ROR: 14.70, 95% CI 6.73–32.11). All cephalosporines from the Reserve group had a higher probability of reporting off-label use by comparison with the ones from the Watch group, except for two cases of no disproportionate signal between cefiderocol–cefoperazone and cefiderocol–ceftizoxime; the strongest signal was observed for ceftolozane/tazobactam–cefotaxim (ROR: 43.61, 95% CI 30.14–63.09). Conclusions: This analysis supplements information from clinical trials and current clinical practice, underscoring the critical need for rigorous antibiotic stewardship programs. Notably, even restricted use of cephalosporins demonstrated therapeutic failure and inappropriate utilization. Full article

Antimicrobial resistance (AMR) continues to represent a significant global public health concern. Gram-negative bacilli (GNB) are the primary causative agents of severe nosocomial infections and possess a notable capacity to develop resistance mechanisms that restrict therapeutic options. The objective of this study was to characterize the antimicrobial susceptibility profiles of GNB isolated at a secondary-level hospital in Guadalajara, Mexico, with the aim of identifying predominant resistance patterns and the most effective therapeutic alternatives. A descriptive, retrospective, cross-sectional study was conducted using clinical isolates of Acinetobacter spp., Pseudomonas spp., Escherichia coli, Klebsiella spp., Morganella morganii, Proteus spp., and Enterobacter spp. collected during 2024. The identification and susceptibility testing were carried out using the VITEK^® 2 automated system, and the results were interpreted in accordance with CLSI guidelines. High resistance rates were observed in Acinetobacter spp. and Pseudomonas spp., particularly to carbapenems (>50% and >40%, respectively). Escherichia coli and Klebsiella spp. demonstrated resistance to third-generation cephalosporins and trimethoprim/sulfamethoxazole, exhibiting high susceptibility to amikacin and carbapenems (>90%). New-generation β-lactam/β-lactamase inhibitor combinations, such as ceftazidime/avibactam and ceftolozane/tazobactam, have demonstrated high efficacy against resistant strains. Overall, GNB isolates in this secondary-level hospital demonstrated elevated resistance levels, particularly to β-lactams and carbapenems, which pose a significant therapeutic challenge. Nevertheless, amikacin, carbapenems, and new-generation β-lactams persist as valuable therapeutic options. In order to contain the spread of multidrug-resistant organisms, it is imperative to strengthen local surveillance, optimize antibiotic stewardship, and reinforce infection control measures. Full article

Background/Objectives: Therapeutic drug monitoring (TDM) of β-lactams (BL), BL/β-lactamase inhibitor (BLI) combinations (BL/BLIc), and of fosfomycin may play a key role in optimizing antimicrobial therapy and in preventing resistance development, especially when used by continuous infusion in critically ill or immunocompromised patients. Unfortunately, analytical methods for simultaneously quantifying multiple BL/BLIc in plasma are still lacking. Methods: The aim of this study was to develop and validate two rapid, sensitive, and accurate UPLC–qTOF–MS/MS methods for the simultaneous quantification of five novel β-lactam or β-lactam/β-lactamase inhibitor combinations (ceftolozane/tazobactam, ceftazidime/avibactam, meropenem/vaborbactam, cefiderocol, and ceftobiprole) along with fosfomycin. Methods: Human plasma samples were prepared by protein precipitation using methanol containing isotopically labeled internal standards. Chromatographic separation was achieved within 10–12 min using two Agilent Poroshell columns (EC-C18 and PFP) under positive and negative electrospray ionization modes. The method was validated according to the EMA guidelines by assessing selectivity, linearity, precision, accuracy, matrix effects, extraction recovery, and stability. Results: The methods exhibited excellent linearity (R² ≥ 0.998) across the calibration ranges for all of the analytes (1.56–500 µg/mL), with limits of quantification ranging from 1.56 to 15.62 µg/mL. Intra- and inter-day precision and accuracy were always within ±15%. Extraction recovery always exceeded 92%, and the matrix effects were effectively corrected through isotopic internal standards. No carry-over or isobaric interferences were observed. All the analytes were stable for up to five days at 4 °C, but the BL and BL/BLIc stability was affected by multiple freeze–thaw cycles. Conclusions: These UPLC-qTOF-MS/MS multi-analyte methods enabled a simultaneous, reliable quantification in plasma of five novel beta-lactams and of fosfomycin. Robustness, high throughput, and sensitivity make these multi-methods feasible for real-time TDM, supporting personalized antimicrobial dosing and improved therapeutic outcomes in patients with severe or multidrug-resistant infections. Full article

Background: In China, Carbapenem-resistant Klebsiella pneumoniae (CRKP) is dominated by sequence type 11 (ST11) harbouring KPC-2, with KL64 displacing KL47 and KL25 emerging. ST859 (ST11 variant) has caused outbreaks, but its epidemiology is unclear. Materials and Methods: A total of 99 non-duplicate CRKP isolates were collected from June to December 2024. Antimicrobial susceptibility was determined by broth microdilution. The genomic sequences of the strains were obtained using next-generation sequencing technology. Resistance genes, virulence loci, and plasmid replicons were identified with Kleborate, Abricate, and MOB-suite, respectively. Results: ST11 accounted for 63.64% and ST859 for 15.15%. All ST859 were KL19, while ST11 were mainly KL25 (60.32%) and KL64 (26.98%). 76.8% co-harbored carbapenemase and extended-spectrum beta-lactamase (ESBL) genes, with KPC-2 and CTX-M-65 being the predominant types. Susceptibility rates were 100% to tigecycline, and 78.79% to ceftazidime/avibactam. ST859 CRKP isolates exhibited higher phenotypic resistance to tetracycline and colistin than ST11 CRKP isolates (p < 0.05), and carrying LAP-2, QnrS1, QnrS10, and tet(A) more frequently. ST11-KL25 showed higher resistance to amikacin, gentamicin, and chloramphenicol, with increased prevalence of CTX-M-65, TEM-1, rmtB, catA2, and dfrA14 compared to ST11-KL64 (p < 0.05). IncF was the most prevalent replicon and both ST859 and ST11 CRKP carry conjugative resistance plasmids, and the host range is predominantly Enterobacterales. Conclusions: ST859-KL19 ranks second to ST11 with higher resistance to tetracyclines and colistin. ST11-KL25 may have already displaced ST11-KL64 as the predominant capsular type in Shanghai, with distinct resistance profiles between KL variants. Long-term, multicenter surveillance is urgently needed to delineate the evolutionary trajectory and clinical impact of these emerging clones. Full article

Background: Difficult-to-treat resistant Pseudomonas aeruginosa (DTR-PA) infections are associated with high morbidity and mortality, but data on prognostic factors remain limited. Given the limited real-world data on outcomes of DTR-PA infections, we aimed to identify clinical predictors of mortality and response to therapy in this setting. Methods: We conducted a single-center retrospective cohort study of 51 patients with DTR-PA infections. The primary endpoint was 30-day all-cause mortality; secondary endpoints were clinical and microbiological cure at end of therapy. An exploratory analysis evaluated 30-day infection-related mortality. Logistic regression models (univariable, multivariable and Firth bias-reduced) were used to identify independent predictors. Results: Median age was 64 years (IQR 22); 63% were male and 71% were in the ICU at infection onset. Sepsis occurred in 80% and septic shock in 45%. Thirty-day all-cause mortality was 49% (25/51). According to multivariable analysis, septic shock was an independent predictor of mortality (aOR 5.52, 95% CI 1.04–29.27; p = 0.045) as younger age (aOR 1.06, 95% CI 1.00–1.12; p = 0.052), whereas targeted therapy with ceftazidime/avibactam or ceftolozane/tazobactam is a protective factor (aOR 0.15, 95% CI 0.02–1.17; p = 0.070) did not reach significance in the final model. Clinical cure occurred in 33% (17/51) and was negatively associated with device burden and bloodstream infection, whereas microbiological cure (45%, 23/51) was more likely with targeted therapy and absence of sepsis. The exploratory analysis of infection-related mortality (35%) showed similar predictors. Conclusions: DTR-PA infections are associated with high mortality. Septic shock and older age predict death, while the use of novel β-lactam/β-lactamase inhibitors is associated with improved outcomes. Early recognition of severe illness and timely administration of active therapy may improve survival in these infections. Full article