Healthcare-associated infections (HAIs) caused by multidrug-resistant Klebsiella spp. represent a critical and escalating global public health threat. Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been designated a critical-priority pathogen by the World Health Organization, and in the 2024 WHO Bacterial Priority Pathogens List, it was the top-ranked pathogen overall. The convergence of carbapenem resistance with hypervirulence in emerging strains has further complicated therapeutic decision-making. This review provides a narrative synthesis of the evidence published between 2020 and 2025 on the prevalence, resistance mechanisms, molecular epidemiology, clinical outcomes, and therapeutic strategies for Klebsiella pneumoniae infections acquired in healthcare settings, with particular attention to the Eastern European and Romanian context. PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library were searched for relevant publications from January 2020 to June 2025, supplemented by WHO and ECDC surveillance reports. Studies were selected narratively for their relevance to the themes addressed. No new quantitative pooling was undertaken; all summary estimates reported below are cited from the published meta-analyses and surveillance reports that generated them. In the most recent global meta-analysis of hospital-acquired CRKP infection, which pooled 61 studies and 513,307 patients from 14 countries, the global prevalence of CRKP among nosocomial K. pneumoniae infections was 28.69% (95% CI: 26.53–30.86%), with pronounced regional variation from 14.29% in high-income North America to 66.04% in South Asia, and 42.05% in Western Europe. Pooled mortality among patients infected with CRKP has been estimated in a separate meta-analysis at 42.14%, compared with 21.16% among patients infected with carbapenem-susceptible strains, rising to 54.30% in bloodstream infections. Surveillance data place Romania third in Europe for carbapenem resistance among invasive K. pneumoniae isolates, at 50.30%, with a distinctive predominance of NDM plus OXA-48-like co-producers. Ceftazidime-avibactam is recommended for KPC- and OXA-48-producing strains, whereas metallo-beta-lactamase producers require aztreonam-containing combinations. CRKP in HAIs constitutes a global epidemiological emergency characterised by marked regional heterogeneity in carbapenemase distribution, high attributable mortality and rapidly evolving molecular profiles. Locally adapted surveillance, rapid molecular diagnostics, and stewardship programmes are required since empirical therapy cannot be standardised across regions.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is the pathogen driving the deterioration of the European antimicrobial resistance landscape, and the burden falls disproportionately on Romania and South-Eastern Europe. The objective of this review was to synthesise evidence published between 2020 and 2025 on the epidemiology, molecular characteristics, clinical impact, and pandemic-era trajectory of CRKP healthcare-associated infections across South-Eastern Europe, including Romania. This retrospective, qualitative narrative review combined the international literature with a deliberately multilingual search of national-language sources in Romanian, Bulgarian, Greek, Croatian, Slovenian, and Serbian, including congress abstract books, doctoral theses, national reference-laboratory reports, and agency surveillance series that are absent from PubMed. Three findings emerge. First, the region is not epidemiologically uniform: estimated incidence of carbapenem-resistant K. pneumoniae bloodstream infection in 2024 ranged from 0.62 per 100,000 population in Slovenia to 20.31 in Romania, against a European Union/European Economic Area (EU/EEA) figure of 3.46, and the steepest relative rise between 2019 and 2024 was recorded in Bulgaria (+374.1%). Second, a distinctive molecular signature has consolidated in the northern half of the region: co-production of a metallo-β-lactamase with an OXA-48-like enzyme (OXA-48, a class D, oxacillinase-type carbapenemase), reported in 44.4–61.2% of characterised Romanian isolates across independent centres, which removes ceftazidime-avibactam from the therapeutic repertoire and leaves aztreonam-avibactam and cefiderocol as the principal remaining options. Third, the pandemic did not produce a single regional signal but a consistent sequence—a transient interruption of upward trends during 2020, a marked acceleration from 2021, and persistence of the elevated level after 2022—with national-language surveillance from Croatia and Slovenia showing that the direction of the apparent pandemic effect depends on whether incidence or resistance proportion is measured. The national-language literature adds granularity unavailable in English, but the evidence base remains structurally uneven: Albania, Kosovo, and North Macedonia contribute almost no primary data, and no country in the region has published a CRKP-attributable mortality estimate for the review period. CRKP in Romania and South-Eastern Europe now maps onto three molecular zones—OXA-48 predominance in the Western Balkans and Croatia, a KPC-to-metallo-β-lactamase transition in Greece, and metallo-β-lactamase plus OXA-48-like co-production in Romania and increasingly Bulgaria—that require different empirical therapy; the COVID-19 pandemic did not create this burden but accelerated and entrenched it, and closing the region’s mortality-data and Western Balkan surveillance gaps should be a priority for future research.

Background: Healthcare-associated infections (HAIs) caused by multidrug-resistant Klebsiella spp. represent a critical and escalating global public health threat. Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been designated a critical-priority pathogen by the World Health Organization, and in the 2024 WHO Bacterial Priority Pathogens List it was the top-ranked pathogen overall. The convergence of carbapenem resistance with hypervirulence in emerging strains has further complicated therapeutic decision-making. Aim: To provide a narrative synthesis of the evidence published between 2020 and 2025 on the prevalence, resistance mechanisms, molecular epidemiology, clinical outcomes and therapeutic strategies for Klebsiella spp. infections acquired in healthcare settings, with particular attention to the Eastern European and Romanian context. Approach: PubMed/MEDLINE, Embase, Web of Science and the Cochrane Library were searched for relevant publications from January 2020 to June 2025, supplemented by WHO and ECDC surveillance reports. Studies were selected narratively for their relevance to the themes addressed. No new quantitative pooling was undertaken; all summary estimates reported here are cited from the published meta-analyses and surveillance reports that generated them. Key findings: In the most recent global meta-analysis of hospital-acquired CRKP infection, which pooled 61 studies and 513,307 patients from 14 countries, the global prevalence of CRKP among nosocomial K. pneumoniae infections was 28.69% (95% CI: 26.53–30.86%), with pronounced regional variation from 14.29% in high-income North America to 66.04% in South Asia, and 42.05% in Western Europe. Pooled mortality among patients infected with CRKP has been estimated at 42.14%, compared with 21.16% among patients infected with carbapenem-susceptible strains, rising to 54.30% in bloodstream infections. Surveillance data place Romania third in Europe for carbapenem resistance among invasive K. pneumoniae isolates, at 50.30%, with a distinctive predominance of NDM plus OXA-48-like coproducers. Ceftazidime-avibactam is recommended for KPC- and OXA-48-producing strains, whereas metallo-beta-lactamase producers require aztreonam-containing combinations. Conclusions: CRKP in HAIs constitutes a global epidemiological emergency characterised by marked regional heterogeneity in carbapenemase distribution, high attributable mortality and rapidly evolving molecular profiles. Locally adapted surveillance, rapid molecular diagnostics and stewardship programmes are required, since empirical therapy cannot be standardised across regions.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is the pathogen driving the deterioration of the European antimicrobial resistance landscape, and the burden falls disproportionately on Romania and South-Eastern Europe. This narrative review synthesises evidence published between 2020 and 2025 on the epidemiology, molecular characteristics, clinical impact and pandemic-era trajectory of CRKP healthcare-associated infections across Romania, Bulgaria, Greece, Croatia, Slovenia, Serbia, Bosnia and Herzegovina, Montenegro, North Macedonia, Albania and Kosovo. The search was deliberately multilingual: alongside the international literature we interrogated national-language sources in Romanian, Bulgarian, Greek, Croatian, Slovenian and Serbian, including congress abstract books, doctoral theses, national reference-laboratory reports and agency surveillance series that are absent from PubMed. Three findings emerge. First, the region is not epidemiologically uniform: estimated incidence of carbapenem-resistant K. pneumoniae bloodstream infection in 2024 ranged from 0.62 per 100,000 population in Slovenia to 20.31 in Romania, against an EU/EEA figure of 3.46, and the steepest relative rise between 2019 and 2024 was recorded in Bulgaria (+374.1%). Second, a distinctive molecular signature has consolidated in the northern half of the region: co-production of a metallo-β-lactamase with an OXA-48-like enzyme, reported in 44.4–61.2% of characterised Romanian isolates across independent centres, which removes ceftazidime-avibactam from the therapeutic repertoire and leaves aztreonam-avibactam and cefiderocol as the principal remaining options. Third, the pandemic did not produce a single regional signal but a consistent sequence — a transient interruption of upward trends during 2020, a marked acceleration from 2021, and persistence of the elevated level after 2022 — with national-language surveillance from Croatia and Slovenia showing that the direction of the apparent pandemic effect depends on whether incidence or resistance proportion is measured. The national-language literature adds granularity unavailable in English, but the evidence base remains structurally uneven: Albania, Kosovo and North Macedonia contribute almost no primary data, and no country in the region has published a CRKP-attributable mortality estimate for the review period.

Clostridioides difficile infection (CDI) has evolved from a sporadic, antibiotic-associated illness into a leading European healthcare-associated infection (HAI). Romania is an instructive case: hypervirulent ribotype 027 (RT027) has dominated locally since 2011–2012, and national surveillance traces four phases — emergence, consolidation, pandemic-era distortion, and recent resurgence. This review synthesises 102 Romanian and pan-European sources (ECDC, ECDIS-Net, COMBACTE-CDI, ESCMID/IDSA-SHEA guidance) to characterise CDI’s epidemiology, molecular typing, and clinical outcomes in Romania relative to Europe. Romanian RT027 prevalence (68–82.6% of typed isolates) far exceeds the 2008 pan-European baseline (5%); national confirmed cases rose from 5,845 in 2015 to a pre-pandemic peak of 12,068 in 2019, fell during the pandemic despite persistently elevated calculated incidence, and resurged to 11,651 in 2022; hospital incidence more than tripled between 2020 and 2023 at one tertiary centre; a 2026 multicentre analysis found CDI caused over half of reported HAIs, amid high antibiotic consumption despite low official HAI rates; and treatment access remains constrained, with limited fidaxomicin reimbursement data and just 31 active faecal microbiota transplantation centres continent-wide. Romania exemplifies a surveillance-bias-masked endemic pattern in which true CDI burden is likely underestimated; priorities include mandatory notification, systematic ribotyping, disciplined antimicrobial stewardship, and equitable access to guideline-recommended therapy.

Extensively drug-resistant (XDR) and pandrug-resistant (PDR) Gram-negative bacteria—principally carbapenem-resistant Acinetobacter baumannii (CRAB), carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat resistant (DTR) Pseudomonas aeruginosa—account for a growing share of severe nosocomial infection and rank among the World Health Organization’s critical-priority pathogens. Because monotherapy is frequently inadequate or unavailable, combination regimens remain central to bedside decision-making, and antimicrobial synergy testing has moved from a niche laboratory exercise to a question with direct clinical relevance. This narrative review synthesises recent literature identified through a structured, reproducible search reported in accordance with the SANRA framework (Section 2), across four linked domains. First, the molecular mechanisms that determine which combinations are rational: carbapenemase production, efflux- and porin-mediated impermeability, lipid A modification and polymyxin resistance, and iron-transport alterations underlying emerging cefiderocol resistance. Second, the laboratory methods used to detect synergy—the checkerboard assay and fractional inhibitory concentration index, time-kill assays, and dynamic pharmacokinetic/pharmacodynamic models including the hollow-fibre infection model—and the genotype-dependence that limits their generalisability. Third, two agents whose combination behaviour is atypical: cefiderocol, whose iron-transport-dependent uptake makes its synergy testing uniquely medium-dependent and for which combination regimens have paradoxically underperformed monotherapy in meta-analysis, and intravenous fosfomycin, whose unique MurA target and rapid monotherapy resistance make combination a necessity rather than an option. Fourth, the clinical evidence, from the ATTACK randomised trial of sulbactam-durlobactam in CRAB to large multicentre cohorts of ceftazidime-avibactam plus aztreonam in metallo-β-lactamase-producing Enterobacterales. We conclude that in vitro synergy testing retains clear value for individualising therapy when no single active agent can be identified, but that its translation to the bedside requires genotype-aware interpretation, pharmacokinetic/pharmacodynamic context, and corroboration against comparative clinical data rather than extrapolation from checkerboard results alone.