Search Results (561)

Background: Carbapenem-resistant K. pneumoniae (CRKP) represents a major challenge in hospitalized patients because of its association with healthcare exposure, restricted antimicrobial options, and adverse clinical outcomes. Microbiological isolation alone does not define invasive disease; therefore, clinical interpretation requires separation of colonization, localized infection, invasive infection, and carbapenem-resistant Enterobacterales (CRE)-associated sepsis. This study evaluated epidemiological features, resistance phenotypes, treatment adequacy, and clinical outcomes among hospitalized adults with K. pneumoniae isolates, using a clinical framework that distinguishes colonization from active infection and invasive disease. Methods: This single-center retrospective observational cohort study included 157 consecutive adults admitted between January and July 2025 to a tertiary-care hospital with at least one microbiologically confirmed K. pneumoniae isolate recovered from clinical specimens and/or CRE surveillance rectal swabs. Isolates were assigned hierarchically to four mutually exclusive phenotypic groups: carbapenem-susceptible K. pneumoniae (CSKP), extended-spectrum beta-lactamase (ESBL)-producing carbapenem-susceptible K. pneumoniae (ESBL), carbapenem-resistant non-carbapenemase-producing K. pneumoniae (CRKP), and carbapenemase-producing K. pneumoniae (CP-KP). A prespecified secondary analysis compared carbapenem-resistant isolates (CRKP + CP-KP) with non-carbapenem-resistant isolates (CSKP + ESBL). Clinical adjudication distinguished colonization-only cases, non-invasive infection, bloodstream infection, device-associated infection, and CRE-associated sepsis; ventilator-associated pneumonia (VAP) was considered when source data allowed reliable attribution. Sepsis was defined according to Sepsis-3 criteria; quick Sequential Organ Failure Assessment (qSOFA) was used only as a bedside screening tool. Statistical tests were selected according to variable type, distribution, and expected cell counts. Results: The cohort comprised 157 unique patients, with a median age of 71 years (interquartile range [IQR], 61–76). Current CRE colonization was documented in 79/154 patients with available colonization status (51.3%). Complete-case in-hospital mortality was higher in the carbapenem-resistant group (CRKP + CP-KP, n = 46) than in the non-carbapenem-resistant group (CSKP + ESBL, n = 111): 11/42 (26.2%) versus 5/108 (4.6%; Fisher exact odds ratio (OR) 7.31, 95% confidence interval (CI) 2.36–22.65; p < 0.001); overall complete-case mortality was 16/150 (10.7%). Multivariable logistic regression for carbapenem resistance (N = 150; five prespecified covariates; events per variable (EPV) = 9.0) identified age 65 years or older (adjusted odds ratio [aOR] 3.78, 95% CI 1.32–10.86), recent hospitalization within 30 days (aOR 2.56, 95% CI 1.16–5.63), and current colonization (aOR 2.96, 95% CI 1.24–7.05) as independent predictors. CRE-associated sepsis was excluded a priori because of definitional circularity with the case definition. Male sex showed a non-significant protective trend (aOR 0.50, 95% CI 0.22–1.12). CRE-associated sepsis showed a strong bivariate association with carbapenem resistance (OR 9.90, 95% CI 3.91–25.09; p < 0.001), and this association is reported descriptively because the variable was excluded from the multivariable model owing to definitional circularity. Model performance was acceptable, with area under the curve (AUC) 0.77, Hosmer–Lemeshow p = 0.95, and Nagelkerke R² = 0.25. Of 99 molecularly characterized isolates, OXA-48-like was detected in 78 (78.8%), NDM in 71 (71.7%), KPC in 6 (6.1%), and NDM + OXA-48-like dual production in 54 (54.5%); VIM and IMP were uniformly negative. Conclusions: In this high-risk hospital cohort, carbapenem resistance in K. pneumoniae was associated with advanced age, recent healthcare exposure, current CRE colonization, and a pronounced unadjusted mortality signal. Interpretation of sepsis and mortality requires explicit separation of colonization from active infection and invasive disease. These findings support intensified CRE surveillance, source-specific clinical interpretation, rapid resistance detection, and risk-adapted empirical antimicrobial strategies in high-risk hospital settings. Full article

Carbapenem-resistant Enterobacterales represent a major global public health concern, and the rapid and reliable detection of carbapenemase production is of critical importance. In this study, real-time PCR was used as the reference method for carbapenemase detection, and the performance of immunochromatographic and phenotypic methods was comparatively evaluated. A total of 96 carbapenem-resistant Enterobacterales isolates were included, and all were identified as carbapenemase producers by the reference method. Diagnostic performance was assessed using positive percent agreement (PPA) and overall percent agreement (OPA); negative percent agreement and negative predictive value could not be calculated due to the absence of negative isolates. The immunochromatographic test showed complete agreement with real-time PCR in detecting carbapenemase production (PPA and OPA: 100%). At the gene level, sensitivity and specificity were 100% for OXA-48 and NDM, while sensitivity for KPC was 91.7%. In the modified carbapenem inactivation method (mCIM), PPA and OPA values were 97.9% due to false-negative results observed in two isolates producing OXA-48 and NDM by the reference method, and its performance was slightly lower than that of the immunochromatographic method. These findings indicate that the immunochromatographic method is a rapid, reliable, and practical option for carbapenemase detection, particularly in OXA-48-endemic intensive care settings where rapid identification is critical for timely infection control and appropriate antimicrobial therapy. Full article

To improve clinical decision-making about Carbapenem-resistant Gram-negative bacteria (CR-GNB) infections and halt the spread of resistant microbes, quicker and less expensive diagnostic techniques are required. Thus, the purpose of this study was to thoroughly evaluate the diagnostic efficiency (sensitivity, specificity, and concordance) of direct-from-specimen multiplex lateral flow immunoassay (LFIA) across diverse raw clinical specimens and pathogen types from critically sick patients. A total of 300 non-duplicate samples were tested to detect CR-GNB. Five major Carbapenemase genes were detected directly from the specimen using carbapenem-resistant K.N.I.V.O. detection K-Set and from culture using culture-enhanced multiplex PCR. Turnaround time (TAT) of each method was calculated. The direct LFIA revealed 100% specificity for NDM, KPC, and IMP enzymes in all tested clinical matrices (blood, urine, and respiratory samples). The study demonstrated 100% sensitivity and specificity with perfect categorical agreement (κ = 1.000) for the blaKPC in the Klebsiella pneumoniae and for blaOXA-48 and blaIMP in the Acinetobacter baumannii; however, sensitivity of blaVIM was significantly diminished across all isolates and samples. TAT decreased significantly (p < 0.001) from 30 to 70 h to about 50 min. The tested direct LFIA facilitates the prompt enhancement of lifesaving tailored antibiotic treatment for severe illnesses. Full article

Background/Objectives: The global spread of carbapenemase-producing Gram-negative bacteria (CP-GNB) represents a major clinical challenge, causing severe hospital-acquired infections with limited treatment options. Accurate and rapid detection is essential for guiding antimicrobial therapy and implementing infection control measures. Lateral flow immunoassays (LFIAs) targeting the five main carbapenemase families are increasingly used in routine diagnostics, and many new commercial assays have recently become available, often without thorough assessment. The continuous evolution of these enzymes under antibiotic pressure requires regular reassessment of assay performance. Methods: In this study, we evaluated the Beright Carba-5 assay (Alltest Biotech, Hangzhou, China) targeting the five main carbapenemases (KPC, NDM, OXA-48-like, IMP, and VIM), on a panel of 77 whole-genome sequenced Gram-negative bacterial (GNB) isolates exhibiting reduced susceptibility to carbapenems. Seventy-three were carbapenemase-producing (CP) GNBs, including six VIM-, 18 OXA-48-, 14 KPC-, 9 NDM-, 8 IMP-, 10 multiple carbapenemase-, and eight non-targeted carbapenemase-producers. Results: The assay was rapid and easy to use, showing 100% (CI: 73.54% to 100%) specificity, with no false positive results. However, overall sensitivity of CP-GNB detection was lower than expected at 63.08% (CI: 50.20% to 74.72%), with numerous false negatives, particularly among IMP and NDM producers, and to a lesser extent, KPC producers. Detection was more reliable for VIM and OXA-48-like variants. Practical limitations, including insufficient buffer supply, reduced the number of tested isolates from the planned 100 to 77. Conclusions: Overall, the Beright assay demonstrated insufficient sensitivity for routine diagnostic use. Full article

Urinary tract infections (UTIs), predominantly caused by Escherichia coli, constitute a major global health issue due to the escalating antimicrobial resistance. This study was designed to assess the in vitro susceptibility of fosfomycin among clinical uropathogenic Escherichia coli (UPEC) isolates and to detect plasmid-mediated fosA3 and fosC2 genes in those exhibiting fosfomycin resistance. A total of 158 non-duplicated UPEC strains were collected from urine samples of patients with UTIs. Antimicrobial susceptibility of these isolates was evaluated. Phenotypic detection of extended-spectrum β-lactamases (ESBL) and carbapenemase producers in UPEC was assessed. Identification of plasmid mediated fosA3 and fosC2 genes in those exhibiting fosfomycin resistance was carried out by PCR. A total of 72% of the isolates demonstrated multidrug resistance (MDR). Extensively drug-resistant (XDR) isolates represented 15%, while PDR isolates were rare (0.6%, 1/158). ESBLs were detected in 40% of the isolates, and 31% exhibited carbapenemase production. Fosfomycin resistance was detected in 9.5% of UPEC isolates, with the fosA3 gene identified in 33% of these resistant strains, whereas fosC2 gene was not identified in any isolate. Fosfomycin demonstrated considerable in vitro activity against carbapenemase-producing, ESBL-producing, and MDR isolates with susceptibility rates of 78%, 84%, and 97%, respectively. Fosfomycin resistance among UPEC isolates is emerging but still at a relatively low level of resistance. Continuous surveillance and antimicrobial stewardship are essential to preserve fosfomycin efficacy. Full article

Background/Objectives: Given the ongoing threat of antimicrobial resistance, the identification and characterization of multidrug-resistant isolates are essential. An increase in antimicrobial-resistant bacteria has been reported in Romania, but national data are still scarce. This study aimed to evaluate beta-lactamase-producing Gram-negative bacteria (GNB) isolated over two years at a Romanian nephrology hospital, while comparing carbapenemase detection phenotypic methods. Methods: Gram-negative bacterial isolates collected between January 2022 and May 2024 that met antimicrobial resistance screening criteria were evaluated. After identification, extensive disk diffusion antibiograms were performed, read, and interpreted, complemented by testing on cloxacillin/oxacillin-supplemented Mueller–Hinton agar. The colistin minimum inhibitory concentration (MIC) was not assessed, and aztreonam–avibactam was not tested for Enterobacterales. For non-fermenter GNB, the colistin MIC was determined. Phenotypic carbapenemase production tests were performed for all strains (BlueCarba Test, CIM, mCIM, zCIM, and rCIM). Carbapenemase detection immunochromatographic tests were performed for a set of strains. Results: Among the 397 evaluated strains, 335 (84.38%) were Enterobacterales and 62 (15.62%) non-fermenter GNB, showing high antimicrobial resistance levels. Of these, 188 (47.35%) were Klebsiella pneumoniae; 139/188 (73.93%) showed carbapenem resistance and carbapenemase production; 49/188 (26.06%) produced two carbapenemases; and 45/188 (23.93%) presented resistance to all tested antimicrobials. MALDI-TOF identified 28 KPC-producing K. pneumoniae strains. Lateral flow assays revealed NDM, VIM, KPC, and OXA-48-like enzymes in 48 of 56 tested Enterobacterales; 12/48 strains produced two carbapenemases. Of the 62 non-fermenter GNB, 33 were Pseudomonas spp. and 20 Acinetobacter baumannii; one Pseudomonas spp. was susceptible only to colistin and seven only to cefiderocol; four A. baumannii were susceptible only to colistin and three only to cefiderocol. Lateral flow assays detected VIM or IMP enzymes in 13/33 Pseudomonas spp. and OXA-23 and/or OXA-40/-58 enzymes in all 20 A. baumannii. Conclusions: Among the evaluated strains, many showed resistance to multiple antimicrobial classes. Furthermore, strains co-producing two carbapenemases were identified. Full article

Empirical management of acute pyelonephritis in Eastern Europe is increasingly constrained by extended-spectrum β-lactamase (ESBL)-producing Enterobacterales and by uropathogen phenotypes—such as strong biofilm formation—which may further blunt antimicrobial activity. We aimed to characterise resistance mechanisms, minimum inhibitory concentration (MIC) distributions, biofilm-forming capacity, and the in vitro performance of carbapenem-sparing agents and to test whether these microbiological features improve prediction of clinical failure beyond standard bedside risk scores. We retrospectively analysed 102 Enterobacterales isolates recovered from 129 consecutive culture-confirmed adult pyelonephritis admissions at “Victor Babeș” University Hospital, Timișoara (March 2022–March 2025). MIC values were determined by Vitek 2 and interpreted using EUCAST v13 breakpoints; ESBL, AmpC, and carbapenemase phenotypes were confirmed by combination disk and modified carbapenem inactivation methods. Biofilm formation was quantified by the microtiter-plate crystal-violet assay. Mediation, Restricted Mean Survival Time (RMST), and decision-curve analyses were used to assess added clinical value. ESBL was confirmed in 30/102 (29.4%) isolates, AmpC in 9 (8.8%), and carbapenemase in 4 (3.9%). ESBL+ isolates were more often strong biofilm formers (33.3% vs. 12.5%; p = 0.014) and showed a 4- to 16-fold rightward MIC shift for cefepime, piperacillin–tazobactam, and ciprofloxacin. Among carbapenem-sparing agents, ceftazidime–avibactam (96.7% S), fosfomycin (80.0% S), and amikacin (73.3% S) retained the highest activity against ESBL+ isolates. Strong biofilm formation and the ESBL phenotype were independently associated with worse outcomes (adjusted OR 3.5 and 4.7); an exploratory mediation analysis suggested that biofilm formation may explain part of the observed association between the ESBL phenotype and treatment failure and that delayed effective therapy may account for a further portion of this association. A microbiology-enhanced model that added the ESBL phenotype, biofilm strength, and acquisition setting to routine clinical variables improved discrimination over a clinical-only baseline (AUC 0.89 vs. 0.71) and showed a higher net benefit on exploratory decision-curve analysis across the 10–40% threshold range. These predictive findings derive from a single-centre cohort with a small number of events and were only internally validated; they require validation in independent cohorts before any clinical application can be considered. The ESBL phenotype and strong biofilm formation were each independently associated with worse outcomes in pyelonephritis and may help identify candidate isolates for carbapenem-sparing strategies anchored on ceftazidime–avibactam, fosfomycin, and amikacin; given the observational, single-centre design, these associations should be regarded as hypothesis-generating. Full article

Multidrug-resistant organisms, particularly carbapenem-resistant Enterobacterales (CRE), represent a major global health threat. In settings with endemic circulation of carbapenem-resistant organisms, early identification of colonised patients before hospital admission may play a critical role in limiting in-hospital spread and guiding infection prevention strategies. We conducted a retrospective monocentric observational study including all patients evaluated for hospital admission in 2025. Patients presenting predefined epidemiological or clinical risk factors underwent risk-based pre-admission screening for CRE. Patient-level deduplication was applied to microbiologically positive records. Among 2694 patients evaluated for hospital admission, 1084 met predefined screening criteria and underwent rectal swab testing. Overall, 191 unique patients were confirmed as carriers of carbapenemase-producing Enterobacterales, corresponding to 17.6% of screened patients and 7.1% of the overall cohort evaluated for admission. KPC was the most prevalent carbapenemase gene (102/191, 53.4%), followed by NDM (57/191, 29.8%) and KPC/NDM co-production (14/191, 7.3%). Less frequent gene profiles included VIM, OXA-48, and combined carbapenemase patterns. In high-endemic healthcare settings, risk-based pre-admission screening may represent a pragmatic component of infection prevention pathways by supporting early identification of patients with probable CRE/CPE carriage. When analysed at the patient level, such programmes can provide useful operational and epidemiological information for admission management and infection control planning. Full article

Background/Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is of great concern because of the difficulties encountered in the management of infections it may cause. This study aims to identify possible difficulties in the management of K. pneumoniae infections in the current context of antibiotic resistance, particularly regarding carbapenem resistance. Methods: This is a retrospective, cross-sectional study that analyses epidemiological, clinical and bacteriological features identified in all patients with CRKP infections/colonization admitted during 2024 in an infectious diseases hospital. Results: Carbapenemase-producing K. pneumoniae isolates were co-harboring NDM+OXA-48 in 55.2% of cases. NDM+OXA-48-producing K. pneumoniae (116 isolates, 55.2%) was correlated with high resistance to aztreonam (100%, p = 0.01), ceftazidime–avibactam (100%, p < 0.01), trimethoprim–sulfamethoxazole (99.1%, p < 0.01), gentamycin (94.8%, p < 0.01), amikacin (93.8%, p < 0.01), colistin (79.8%, p < 0.01). OXA-48-producing K. pneumoniae (29 isolates, 13.8%) was correlated with lower resistance to ceftazidime–avibactam (11.5%, p < 0.01), amikacin (48.1%, p < 0.01), colistin (51.7%, p = 0.01), and gentamycin (65.5%, p < 0.01). We found in vitro synergistic effects of ceftazidime/avibactam + aztreonam for 32/32 CRKP isolates and of colistin + tigecycline for 12/14 CRKP isolates. Higher recurrence of CRKP infections was recorded in patients with urinary tract conditions (RR = 11.58, 95%CI: 1.58–81.91) and upper urinary tract devices (RR = 3.53, 95% CI: 1.72–7.22). In this study, adequate antibiotic treatment, compared to excessive antibiotic treatment in CRKP infections, was associated with shorter treatment duration (p = 0.02) and shorter length of hospitalization (p = 0.04). Conclusions: In our study, CRKP is frequently coharboring NDM+OXA-48, having limited treatment options. Implementing new treatment strategies, testing antibiotic synergies for older antibiotics in order to identify alternative treatment options and avoiding unnecessary carbapenem consumption are essential for decreasing the burden of CRKP infections. Full article

Background/Objectives: The increased prevalence of multidrug-resistant Escherichia coli and carbapenemase-producing Enterobacteriaceae poses a critical threat to global health and food safety. Antimicrobial Blue Light (aBL) in the 400–470 nm spectrum has emerged as a promising, chemical-free disinfection strategy that targets intracellular porphyrins and flavins to induce oxidative stress. However, the influence of wavelength, dosimetry, and environmental stressors on endogenous photoinactivation remains poorly standardized regarding optical parameters and biological exposure protocols. This systematic review aimed to evaluate the antimicrobial efficacy of pure blue light (400–470 nm) against E. coli across various phenotypes and environmental conditions, excluding the use of exogenous photosensitizers. Methods: PubMed, Scopus, and Web of Science were searched for studies that utilized 400–470 nm light as an antimicrobial agent against E. coli. Data extraction focused on spectral efficiency, total fluence (J/cm²), and log₁₀ reduction. The Risk of Bias was assessed using an adapted Office of Health Assessment and Translation tool for in vitro studies. Results: Synthesis of 11 high-quality studies indicated that wavelengths near 405 nm have the highest germicidal efficiency due to the Soret band absorption of endogenous porphyrins. Efficacy is highly dose-dependent: significant log₁₀ reductions were achieved in planktonic cells, although biofilms required substantially higher fluences. Sub-lethal environmental stressors such as acidic pH, high salinity, and thermal fluctuations demonstrated a synergistic effect, which significantly enhanced the rate of photoinactivation. Multidrug-resistant and carbapenemase-producing Enterobacteriaceae strains showed similar susceptibility to aBL relative to antibiotic-sensitive strains, suggesting no cross-resistance between light and traditional drugs. Conclusions: Endogenous blue light is a highly effective, non-thermal technology for E. coli decontamination. Its efficacy is modulated by the interplay between optical parameters and environmental conditions. These findings provide a framework for the development of standardized protocols for applying aBL to clinical wound care and food industry use cases. They also highlight the potential of aBL as a critical tool in the post-antibiotic era. This systematic review was registered in the International prospective register of systematic reviews (PROSPERO) under protocol CRD420261331871. Full article

Background/Objectives: In Europe, Pseudomonas aeruginosa is the second most common cause of ventilator-associated pneumonia in intensive care units. Intrinsic antibiotic resistance and acquired carbapenemases can lead to high mortality. To guide more targeted antimicrobial therapy and adequate infection control measures, we performed a multicenter study on the prevalence and genetic basis of carbapenem resistance among P. aeruginosa (CR-PA) across 17 community hospitals in Austria. Methods: During a 3-month period, we collected 621 P. aeruginosa isolates from 560 patients. Antibiotic susceptibility testing was performed according to EUCAST guidelines, and all CR-PA isolates were subjected to whole genome sequencing. Results: Antibiotic susceptibility testing revealed carbapenem resistance in 5.41% (36/621) of the investigated P. aeruginosa isolates. Only 3 produced a carbapenemase (2 Verona Integron-encoded Metallo- ß-lactamases and 1 Imipenemase Metallo-ß-lactamase) and carried a carbapenemase-encoding gene. Among the studied P. aeruginosa isolates there was a high genetic diversity, excluding a single driving epidemic lineage in the included Austrian hospitals. Conclusions: The absence of interhospital clonal dominance suggests that carbapenem resistance emerged independently in different centers, likely driven by local antibiotic selection pressures rather than regional clonal spread. Full article

Background/Objectives: The co-production of New Delhi metallo-β-lactamases (NDM) and OXA-48-like carbapenemases in Klebsiella pneumoniae represents a major therapeutic challenge due to extensive drug resistance and limited treatment options. This study aimed to investigate the molecular epidemiology, resistance profiles, and mechanisms associated with reduced susceptibility to cefiderocol in clinical isolates co-producing NDM and OXA-48-like carbapenemases. Methods: A total of 45 clinical K. pneumoniae isolates collected in healthcare settings in Northern Italy were analyzed. Antimicrobial susceptibility testing, including cefiderocol and aztreonam/avibactam, was performed according to EUCAST guidelines. Whole-genome sequencing was used to characterize sequence types, resistance determinants, virulence factors, plasmid replicons, and phylogenetic relationships. Mutations in iron uptake and transport genes were investigated in cefiderocol-resistant isolates. Results: Most isolates belonged to the high-risk clone ST147 (44/45) and were grouped into three main phylogenetic clusters. The isolates exhibited extensive multidrug resistance, with universal susceptibility only for aztreonam/avibactam. Cefiderocol resistance was observed in 42.2% of isolates and was unevenly distributed across the phylogeny. Mutations in iron uptake genes, particularly cirA and chrA, were identified in the majority of resistant isolates, although several strains retained wild-type sequences, indicating heterogeneous resistance mechanisms. Comparative phylogenetic analysis demonstrated close relatedness to international isolates, suggesting the global dissemination of related lineages. Conclusions: NDM- and OXA-48-like carbapenemase co-producing K. pneumoniae isolates are characterized by clonal dissemination, complex resistance profiles, and emerging cefiderocol resistance driven by multifactorial mechanisms. The preserved activity of aztreonam/avibactam highlights its potential as a key therapeutic option against these high-risk pathogens. Full article

During the COVID-19 pandemic carbapenem-resistant Acinetobacter baumannii (CRAB) was found to be the major pathogen associated with ventilator-associated pneumonia in mechanically ventilated patients. This prompted us to analyze the post-pandemic mechanisms of carbapenem resistance, antibiotic resistance trends, and molecular epidemiology of CRAB in Croatia. In total, 94 CRAB isolates from two hospital centers, including outpatient settings, were investigated. Antimicrobial susceptibility testing was performed by broth microdilution. PCR was used to detect genes encoding carbapenemases of group A, B and D and extended-spectrum β-lactamases (ESBL). Randomly selected isolates were subjected to whole resistome analysis by Inter-array CarbaResist Kit and whole-genome sequencing (WGS). Phylogenetic tree and sequence types (STs) were retrieved from WGS. Plasmid incompatibility groups were determined by PCR-based replicon typing (PBRT). All isolates were extensively drug resistant (XDR), showing resistance to ceftazidime, cefepime, piperacillin–tazobactam, imipenem, meropenem, gentamicin, amikacin and ciprofloxacin, and 13% (n = 12) were also resistant to colistin. The Hodge and CIM test exhibited poor sensitivity with only 32 and 30% of isolates being identified as carbapenemase producers, respectively. PCR identified bla_OXA-23 as the dominant carbapenemase gene in both hospitals, found in 71% of the isolates (67/94). In an outpatient setting, bla_OXA-24/40 was dominant. bla_OXA-23 and bla_OXA-72 were the only allelic variants. The Inter-array CarbaResist Kit and whole-genome sequencing (WGS) identified a variety of aminoglycoside (armA, ant(3″)-IIa, aph(3″)-Ib, aph(6)-Id) and sulphonamide resistance (sul1 and sul2) genes. The representative bla_OXA-23-positive isolates belonged to ST2, while bla_OXA-72-positive isolates were allocated to ST492. These data show that there are different populations of XDR A. baumannii between hospital and outpatients. Full article

Background: Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) central nervous system (CNS) infections represent a major therapeutic challenge in neurosurgical patients. Intraventricular or intrathecal polymyxin B sulfate (PMB) is commonly used as salvage therapy but is limited by substantial neurotoxicity. Ceftazidime–avibactam (CZA) exhibits potent in vitro activity against KPC-Kp; however, prospective clinical and pharmacokinetic evidence supporting its use in CNS infections remains limited. Methods: In this prospective, single-centre observational study, adult neurosurgical patients with culture-confirmed KPC-Kp CNS infections admitted to the neurointensive care unit of Huashan Hospital were enrolled. Patients received either intravenous CZA (CZA group, n = 15) or intrathecal/intraventricular PMB-based therapy (PMB group, n = 10). Primary outcomes included clinical cure, microbiological eradication, 28-day mortality, and safety. Therapeutic drug monitoring was performed to determine steady-state plasma and cerebrospinal fluid (CSF) concentrations of ceftazidime, avibactam, and polymyxin B, enabling assessment of CSF penetration and exposure–toxicity relationships. Results: Overall clinical cure and microbiological eradication rates were 68.0% and 84.0%, respectively, with a 28-day mortality of 20.0%. Compared with PMB, CZA was associated with a significantly higher clinical cure rate (86.7% vs. 40.0%, p = 0.024) and a numerically higher eradication rate (93.3% vs. 70.0%). No neurological adverse events occurred in the CZA group, whereas neurological toxicity was observed in 60.0% of PMB-treated patients (p < 0.001). Functional outcomes favoured the CZA group, with lower modified Rankin Scale scores at discharge and at 6 months. Pharmacokinetic analyses demonstrated that steady-state CSF concentrations of ceftazidime and avibactam exceeded commonly accepted pharmacodynamic targets, while markedly elevated PMB CSF concentrations were observed in patients with neurological toxicity. Conclusions: While intravenous CZA showed potentially favourable efficacy and safety compared with local PMB in this cohort, these preliminary findings should be interpreted as hypothesis-generating given the small sample size and non-randomised design. These results provide a rationale for further validation in larger multicentre, randomised controlled trials. Full article

Background/Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKp) remains a critical driver of antimicrobial resistance (AMR) in hospital settings worldwide. Methods: This study examined trends in CRKp bloodstream infections over a seven-year period (2019–2025) in a tertiary care hospital in Greece, with particular attention given to resistance patterns and patient outcomes, including the impact of the COVID-19 pandemic. Results: A total of 671 non-duplicate CRKp isolates were analyzed and classified into three groups: KPC producers (67.4%), dual carbapenemase producers (dual CP) (17.4%), and single metallo-β-lactamase (MBL) producers (15.2%). Overall incidence showed a slight but non-significant increase over time. KPC-producing strains rose significantly until 2022 (p < 0.001), followed by a marked decline (p < 0.001). In contrast, dual CPs—mainly KPC combined with VIM or NDM—and single-MBL producers, particularly NDM, increased steadily, indicating a notable epidemiological shift. Resistance to aminoglycosides and tigecycline increased around 2021, followed by partial declines, whereas colistin resistance demonstrated a continuous upward trend throughout the study period. Despite phenotypic differences, overall mortality remained high, with no statistically significant differences between groups (p = 0.37), likely reflecting either the severity of patients’ clinical condition or inadequate empirical antibiotic therapy. Conclusions: This study highlights a dynamic evolution in CRKp epidemiology with decreasing KPC dominance and increasing prevalence of MBL- and dual CP strains. This transition, which became evident during and after the COVID-19 pandemic, underscores ongoing epidemiological adaptation and the urgent need for improved antimicrobial stewardship, rapid diagnostics, and broader access to effective therapies. Full article