Search Results (27)

Background: The emergence of multidrug-resistant (MDR) Gram-negative pathogens, namely Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Helicobacter pylori, necessitates urgent therapeutic alternatives. This scoping review aimed to summarize the current evidence on the efficacy of lytic bacteriophages against these critical MDR pathogens, and to identify existing research gaps and implementation challenges. Methods: The literature search was conducted by searching PubMed, Web of Science, and Scopus AI for studies published from 2015 to 2025. The inclusion criteria focused on experimental and human studies evaluating phage therapy against MDR, extensively drug-resistant (XDR), or pan-drug-resistant (PDR) strains in the four target species. A total of 172 articles were included. Results: A number of studies showed an increasing trend (2015–2025), focusing mainly on K. pneumoniae (n = 65), P. aeruginosa (n = 55), and A. baumannii (n = 48). No eligible studies for MDR H. pylori were found. All 172 studies confirmed lytic activity, with phage cocktails showing superior antibacterial activity than single phages in four studies. Phages also demonstrated antibiofilm activity (n = 44). Most animal studies reported successful bacterial reduction in animals treated with phages, and 87.5% of 23 human case studies reported patient improvement or infection clearance. However, heterogeneity in the types of animal models used and in dosage and administration routes in human studies was notable. Conclusions: Lytic bacteriophages exhibit strong potential as a new therapeutic option. Key challenges include the lack of data for MDR H. pylori, heterogeneity in animal models, and a paucity of large-scale human clinical trials. Future research must prioritize standardization, mechanistic studies, and conducting robust human trials to enable clinical translation and regulatory acceptance. Full article

Background/Objectives: Klebsiella spp., particularly K. pneumoniae, are major opportunistic pathogens in healthcare settings driven by carbapenemase- and ESBL-producing strains. We assessed antimicrobial resistance and biofilm formation abilities in Klebsiella spp. from a Brazilian tertiary hospital and related environments and characterized capsular types. Methods: Over six months (July–December 2023), 303 carbapenem-resistant Klebsiella spp. were collected from clinical specimens (n = 198), ICU/non-ICU surfaces (n = 79), hospital sewage (n = 22), and stream water (n = 4). Species were identified by MALDI-TOF. Susceptibility testing covered eight antibiotic classes, focusing on carbapenems and polymyxin B. Biofilm formation was quantified by crystal violet, and capsular typing used wzi/K-locus approaches. Results: Most isolates (70.95%) had meropenem MICs ≥ 128 μg/mL, while 77.6% (n = 235) remained susceptible to polymyxin B. Resistance profiles largely consisted of extensive drug resistance (95.4%), with 1.3% exhibiting pandrug resistance, including isolates from bed rails. Biofilm formation was detected in 96.7% of isolates, mainly weak (67.6%) or moderate (28%), with 4.4% being strong producers. Among the Klebsiella isolates analyzed, 21 K types were identified with an uneven distribution dominated by K64, followed by K24, K173, and K50. K75 was the only K type detected across all sources—clinical isolates, bed-rail surfaces (non-ICU), wastewater, and fluvial water. Conclusions: Carbapenem-resistant Klebsiella spp. exhibited widespread resistance, with residual susceptibility to aminoglycosides, ceftazidime–avibactam, and polymyxins. Environmental reservoirs—hospital surfaces, sewage, and stream water—harbored resistant biofilm producers, reinforcing their role in persistence and dissemination. K-typing revealed concentrated distribution (predominantly K64) and cross-source K75. These findings underscore the urgency of integrated strategies combining molecular surveillance, antimicrobial stewardship, and environmental control. Full article

Background/Objectives: Antimicrobial resistance (AMR) is a major global health threat that undermines treatment in humans and animals. In Zambia, where livestock production underpins food security and livelihoods, AMR challenges are aggravated by limited surveillance, weak diagnostics, and poor regulatory enforcement, facilitating the spread of resistant pathogens across the human–animal–environment interface. This study aims to analyse AMR patterns of bacterial isolates collected from Zambia’s animal health sector between 2020 and 2024, to generate evidence that informs national AMR surveillance, supports antimicrobial stewardship (AMS) interventions, and strengthens One Health strategies to mitigate the spread of resistant pathogens. Methods: We conducted a retrospective descriptive analysis of previously collected routine laboratory data from five well-established animal health AMR surveillance sentinel sites between January 2020 and December 2024. Data were analysed by year, sample type, and antimicrobial susceptibility testing (AST) profiles using WHONET. Results: A total of 1688 samples were processed, with faecal samples accounting for 87.6%. Animal environmental samples (feed, manure, litter, abattoir/meat processing floor, wall, and equipment surface swabs) (collected from abattoirs, water, and farms) increased significantly over time (p = 0.027). Overall, Escherichia coli (E. coli) (50.4%) and Enterococcus spp. (30%) were the most frequently isolated bacteria. E. coli exhibited high resistance to tetracycline (74%) and ampicillin (72%) but remained susceptible to aztreonam (98%), nitrofurantoin (95%), and imipenem (93%). Enterococcus spp. were susceptible to penicillin (84%) and ampicillin (89%) but showed borderline resistance to vancomycin (53%) and linezolid (50%). Klebsiella spp. demonstrated resistance to ciprofloxacin (52%) and gentamicin (40%), whereas Salmonella spp. remained highly susceptible. Notably, resistance to amoxicillin/clavulanic acid rose sharply from 22.2% to 81.8% (p = 0.027). Across 1416 isolates, high levels of multidrug resistance (MDR) were observed, particularly in E. coli (48.4%) and K. pneumoniae (18.6%), with notable proportions progressing toward possible Extensively Drug-Resistant (XDR) and Pan-Drug-Resistant (PDR) states. Conclusions: The findings of this study reveal rising resistance to commonly used antibiotics in the animal health sector. Despite the lack of molecular analysis, our findings underscore the urgent need for AMS programs and integrated AMR surveillance under Zambia’s One Health strategy. Full article

Background/Objectives: Antimicrobial resistance (AMR) remains a major global threat, with the COVID-19 pandemic influencing its dynamics, although its overall impact remains uncertain. This study analyzed seven-year AMR trends, including the pandemic period, in a tertiary care hospital in Greece that served as a COVID-19 referral center. Methods: Multiresistant bacteria isolated from all biological specimens of hospitalized patients between January 2018 and December 2024 were recorded and classified as multidrug- (MDR), extensively drug- (XDR), or pandrug-resistant (PDR). Overall AMR was defined as the sum of these categories. Annual incidences of overall AMR, its categories, and predominant Gram-negative (A. baumannii, K. pneumoniae, P. aeruginosa) and Gram-positive [methicillin-resistant S. aureus (MRSA), vancomycin-resistant Enterococcus (VRE)] pathogens were analyzed for the entire hospital and by sector (medical, intensive care unit [ICU], surgical). Bloodstream infection (BSI) AMR was also evaluated. Trend analysis was performed using Joinpoint regression. Results: Overall AMR exhibited a transient peak around 2021 across the hospital, except in the surgical sector. A significant rise in average annual percentage change (AAPC) occurred only in the medical sector (p < 0.001). PDR incidence increased hospital-wide (p < 0.001). K. pneumoniae, P. aeruginosa, MRSA, and VRE rose significantly in the medical sector, whereas ICU incidences remained largely stable despite the 2021 peak. A. baumannii showed no significant change. BSI-related AMR increased in the medical sector (p < 0.001) but not in the ICU (p = 0.2). Conclusions: Although overall AMR did not rise uniformly, PDR organisms increased hospital-wide. These findings support updating empiric therapy guidelines, reinforcing infection prevention measures, and translating surveillance data into targeted stewardship actions to enhance patient care. Full article

Background: The emergence of pan-drug-resistant (PDR) Klebsiella pneumoniae has compromised the efficacy of last-line agents, leaving few therapeutic options. Repurposing zidovudine, an FDA-approved thymidine analog with antibacterial activity, may enhance existing therapies, but pharmacodynamic data under clinically relevant conditions are scarce. This study addresses this gap using static and dynamic in vitro models. Materials/methods: A PDR strain of Klebsiella pneumoniae harboring bla_NDM-1, bla_CMY-6, bla_CTX-M-15, bla_SHV-2, and disrupted mgrB was used in this study. Minimum inhibitory concentrations (MICs) followed by static time-kills were performed to investigate the synergistic interplay between zidovudine and last-line antibiotics (ceftazidime/avibactam, polymyxin B). To simulate human pharmacokinetics, a hollow-fiber infection model (HFIM) was employed using steady-state concentrations of zidovudine (4 mg/L), polymyxin B (4 mg/L), and avibactam (22 mg/L). Structural and morphological effects on bacterial cells were examined via fluorescence microscopy following glutaraldehyde fixation. Results: In this study, the PDR K. pneumoniae showed a ~5-fold reduction in polymyxin MIC when combined with zidovudine (from >4 µg/mL to 0.25 µg/mL). Time-kill assays demonstrated ≥2.5 log₁₀ CFU/mL bacterial reduction with zidovudine-based combinations, whereas monotherapies failed to inhibit bacterial growth. In the HFIM, the triple combination achieved rapid bactericidal activity (>3 log₁₀ CFU/mL reduction within 4 h) and sustained killing (>5–6 log₁₀ reduction maintained through 216 h), with bacterial counts remaining below 1 CFU/mL. In contrast, dual combinations initially reduced bacterial burden (1–3 log₁₀ reduction) but failed to maintain suppression, with significant regrowth (>10¹⁰ CFU/mL) observed by 168 h. Microscopy corroborated these findings, revealing extensive cellular damage in the zidovudine-containing treatment arms. These HFIM results underscore the potential of zidovudine-based triple therapy in overcoming resistance to last-line antibiotics in K. pneumoniae. Conclusions: Our results provide promising unprecedented insight into novel zidovudine-based combination therapies against difficult-to-treat MBL Gram-negatives. The observed synergy in MIC reduction, rapid killing in time-kill assays, and near-complete eradication in the HFIM underscore the therapeutic potential of this triple combination. Future studies will focus on broadening the application of these novel combinations to other ‘superbugs’, such as highly resistant strains of Acinetobacter baumannii and Pseudomonas aeruginosa. Full article

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

The global emergence of multidrug- and pandrug-resistant Klebsiella pneumoniae poses a critical threat to public health, particularly in hospital settings. This study describes a nosocomial outbreak caused by K. pneumoniae in a tertiary-care hospital in Mexico and provides a comprehensive genomic analysis of six clinical isolates. All isolates exhibited pandrug resistance, including carbapenems and colistin. Whole-genome sequencing identified 37 antimicrobial resistance genes, including blaNDM-1, blaOXA-1, blaCTX-M-15, and a pmrB R256G mutation associated with colistin resistance. Two conjugative plasmids (pAA046 and pAA276) carried multiple resistance genes and mobile genetic elements. Although all isolates harbored CRISPR-Cas type I-E systems, no spacers matched resistance plasmids, suggesting functional inactivity. Capsular typing identified the KL27 locus with the wzi187 allele. Phylogenetic and cgMLST analyses confirmed clonal dissemination and close genetic relatedness to strains from Europe and the USA. Despite the absence of classical hypervirulence markers, the presence of kfu, fimH, and mrkD genes indicates adaptation to the hospital environment. These findings confirm the clonal spread of pandrug-resistant K. pneumoniae ST392-KL27 in a Mexican hospital, underscoring the role of plasmid-mediated resistance and the potential for global dissemination. Full article

Background: Klebsiella pneumoniae represents a major cause of healthcare-associated infections in intensive care units, with resistance profiles ranging from multidrug-resistant to extensively drug-resistant and pandrug-resistant. Critically ill patients, who often require invasive devices and prolonged antibiotic therapy, are especially vulnerable to colonization and infection by these strains. Surveillance data on resistance trends and specimen-specific patterns in Romanian intensive care units (ICUs) remain limited. Methods: We conducted a four-year surveillance study (2021–2024) in a tertiary Romanian ICU, analyzing K. pneumoniae isolates collected from diverse clinical specimens. Resistance phenotypes were classified as MDR, XDR, PDR, or susceptible based on standard definitions. Trends over time were assessed using Cramér’s V and correspondence analysis, while stratification by specimen type evaluated associations between anatomical site and resistance profiles. Results: A total of 254 K. pneumoniae isolates were analyzed. MDR strains predominated in 2021 and 2022 but sharply declined by 2024 (from 80% to 8.3%). In parallel, XDR and PDR phenotypes increased substantially, indicating a shift toward more complex resistance profiles. A significant temporal association was found (Cramér’s V = 0.43), with 2024 marked by a sharp decline in MDR isolates and a predominance of XDR and PDR phenotypes, reflecting an advanced resistance profile. Specimen-type analysis showed tracheal aspirates as the main reservoir for resistant strains, followed by urine and blood cultures, with a weaker but meaningful association (Cramér’s V = 0.24). Conclusions: These findings reveal a change in resistance patterns in ICU-acquired K. pneumoniae infections, with MDR strains being displaced by XDR and PDR phenotypes. These findings highlight the urgent need for time- and specimen-informed resistance monitoring and adaptive antimicrobial stewardship. Without targeted interventions, gains made in controlling MDR strains risk being rapidly eclipsed by the spread of highly resistant organisms. Full article

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article

Background and Objectives: Klebsiella pneumoniae is a major nosocomial pathogen with a remarkable ability to develop resistance to multiple antibiotics, posing significant treatment challenges. This study aims to evaluate the antimicrobial resistance patterns among multidrug-resistant (MDR) and non-MDR strains of K. pneumoniae isolated over a six-year period (2018–2023) at the Clinical Hospital of Infectious Diseases and Pulmonology “Dr. Victor Babes” in Timisoara, Romania. The objectives include categorizing isolates based on their antibiotic resistance profiles and identifying trends in resistance to key antibiotics to optimize treatment strategies and enhance infection control measures. Materials and Methods: A cross-sectional analysis was conducted on K. pneumoniae isolates obtained from various clinical samples between January 2018 and December 2023. Identification was performed using standard bacteriological procedures, and antimicrobial susceptibility testing was conducted using the Kirby–Bauer disk diffusion method in accordance with EUCAST guidelines. Isolates were classified as susceptible, resistant, MDR, extensively drug-resistant (XDR), or pandrug-resistant (PDR) based on ECDC definitions. Data were analyzed using GraphPad Prism 6, with chi-square tests and Cochran–Armitage trend tests applied where appropriate. Statistical significance was set at p < 0.05. Results: A total of 1,081 K. pneumoniae isolates were identified over the six-year period, increasing from 118 isolates in 2018 to 319 in 2023. The proportion of XDR and PDR strains showed a significant upward trend from 30.5% in 2018 to 57.4% in 2023 (p < 0.001). Specifically, XDR strains increased from 22.9% in 2018 to 39.8% in 2023, while PDR strains rose from 7.6% to 17.6%. Among monomicrobial infections in 2023, XDR and PDR strains accounted for 42.4% and 16.5%, respectively. Resistance to carbapenems also showed a significant increase; for instance, resistance to ertapenem rose from 35.6% in 2018 to 54.2% in 2023 (p < 0.001). Subgroup analysis revealed that isolates from bronchial aspirates had the highest rates of XDR and PDR strains in 2023, at 38.0% and 17.2%, respectively. Additionally, polymicrobial infections where both K. pneumoniae and co-infecting pathogens were XDR/PDR increased from 24.2% in 2018 to 46.6% in 2023 (p < 0.001). Conclusions: The study demonstrates a significant escalation in antimicrobial resistance among K. pneumoniae isolates over the six-year period, particularly in XDR and PDR strains. The rising trend of resistance to critical antibiotics like carbapenems underscores the urgent need for enhanced antimicrobial stewardship and infection control measures. Targeted interventions are essential to curb the spread of these resistant strains and to optimize therapeutic strategies. Full article

Infections represent a major complication for burn-injured patients. The aim of this study was to highlight the changes in the incidence and antimicrobial resistance of bacterial strains isolated from burn patients, at the end of the COVID-19 pandemic, in relation to the antibiotics used during the pandemic. A comparative analysis of the demographic data and the microorganisms identified in the clinical samples of two groups of burn patients admitted to a university hospital in Romania was carried out. The first group consisted of 48 patients and the second of 69 patients, hospitalized in January–August 2020 and 2023, respectively. The bacterial species with the highest incidence were S. aureus, A. baumannii, Pseudomonas spp. The significant changes between 2023 and 2020 are reflected in the increase in the frequency of non-fermentative Gram-negative bacteria, especially S. maltophilia, and the increase in antimicrobial resistance of Pseudomonas and Klebsiella spp. Klebsiella spp. did not change in frequency (7%), but there was a significant increase in the incidence of K. pneumoniae strains with pan-drug resistant behaviour to antibiotics (40%), including colistin. The phenomenon can be explained by the selection of specimens carrying multiple resistance genes, as a result of antibiotic treatment during the COVID-19 period. The post-pandemic antimicrobial resistance detected in burn patients indicates the need for permanent surveillance of the resistance trends, primarily due to the limited therapeutic options available for these patients. Full article

The issue of bacterial infections in COVID-19 patients has received increasing attention. Scant data are available on the impact of bacterial superinfection and antibiotic administration on the outcome of hospitalized COVID-19 patients. We conducted a literature review from 1 January 2022 to 31 March 2024 to assess the current burden of bacterial infection and the evidence for antibiotic use in hospitalized COVID-19 patients. Published articles providing data on antibiotic use in COVID-19 patients were identified through computerized literature searches with the search terms [(antibiotic) AND (COVID-19)] or [(antibiotic treatment) AND (COVID-19)]. PubMed and SCOPUS databases were searched from 1 January 2022 to 31 March 2024. No attempt was made to obtain information about unpublished studies. English language restriction was applied. The quality of the included studies was evaluated by the tool recommended by the Joanna Briggs Institute. Both quantitative and qualitative information were summarized by means of textual descriptions. Five hundred fifty-one studies were identified, and twenty-nine studies were included in this systematic review. Of the 29 included studies, 18 studies were on the prevalence of bacterial infection and antibiotic use in hospitalized COVID-19 patients; 4 studies reported on the efficacy of early antibiotic use in COVID-19; 4 studies were on the use of sepsis biomarkers to improve antibiotic use; 3 studies were on the efficacy of antimicrobial stewardship programs and predictive models among COVID-19-hospitalized patients. The quality of included studies was high in 35% and medium in 62%. High rates of hospital-acquired infections were reported among COVID-19 patients, ranging between 7.5 and 37.7%. A high antibiotic resistance rate was reported among COVID-19 patients developing hospital-acquired infections, with a high in-hospital mortality rate. The studies evaluating multi-faceted antimicrobial stewardship interventions reported efficacy in decreasing antibiotic consumption and lower in-hospital mortality. Full article

In secondary healthcare, carbapenem-resistant Enterobacterales (CREs), such as those observed in Klebsiella pneumoniae, are a global public health priority with significant clinical outcomes. In this study, we described the clinical, phenotypic, and genotypic characteristics of three pan-drug-resistant (PDR) isolates that demonstrated extended resistance to conventional and novel antimicrobials. All patients had risk factors for the acquisition of multidrug-resistant organisms, while microbiological susceptibility testing showed resistance to all conventional antimicrobials. Advanced susceptibility testing demonstrated resistance to broad agents, such as ceftazidime-avibactam, ceftolozane–tazobactam, and meropenem–vaborbactam. Nevertheless, all isolates were susceptible to cefiderocol, suggested as one of the novel antimicrobials that demonstrated potent in vitro activity against resistant Gram-negative bacteria, including CREs, pointing toward its potential therapeutic role for PDR pathogens. Expanded genomic studies revealed multiple antimicrobial-resistant genes (ARGs), including bla_NMD-5 and bla_OXA derivative types, as well as a mutated outer membrane porin protein (OmpK37). Full article

Introduction: Gram-negative bacteria (GNB) account for about 70% of infections in the intensive care unit (ICU) setting and are associated with significant morbidity and mortality. In recent years, pan-drug resistant (PDR) strains, strains that are not susceptible to any antibiotic, have been emerged and new treatment strategies are required. Results: Fifty eligible patients were recruited in the three groups. A statistically significant reduction in the Sequential Organ Failure Assessment (SOFA) score was observed in the control group on day 4 in comparison to day 0 of VAP (p = 0.005). The Clinical Pulmonary Infection Score (CPIS) was also reduced on day 4 (p = 0.0016) and day 7 in comparison to day 0 (p = 0.001). Patients that received combination therapy, CAZ–AVI + ATM and DCT, presented with a lower SOFA score and CPIS on day 7 in comparison to day 0 (p = 0.0288 and p = 0.037, respectively). No differences in the ΔSOFA score and ΔCPIS were found between the groups. The control group presented with a significantly lower ICU stay and duration of mechanical ventilation (p = 0.03 and p = 0.02, respectively). There was no difference in mortality. Materials and methods: This is a retrospective analysis. This study was conducted in a mixed ICU in the University Hospital of Larissa, Thessaly, Greece during a three-year period (2020-2022). Patients suffering from ventilator associated pneumonia (VAP) due to carbapenem-resistant K. pneumonia (CR-KP) were divided in three different groups: the first one was treated using ceftazidime–avibactam plus aztreonam (CAZ–AVI + ATM group), the second was treated using double carbapenems (DCT group), and the last one (control group) received appropriate therapy since the strain was susceptible in vitro to at least to one antibiotic. Conclusions: Treatment with CAZ–AVI +ATM or DCT may offer a clinical benefit in patients suffering with infections due to PDR K. pneumoniae. Larger studies are required to confirm our findings. Full article

The Klebsiella pneumoniae complex is a commonly isolated bacteria in human infections. These opportunistic pathogens pose a serious threat to public health due to their potential transmission to the human population. Resistance to carbapenems is a significant antimicrobial resistance mechanism, leading to limited therapeutic options. Therefore, the aim of this study was to evaluate the in vitro activity of fosfomycin, colistin, ceftazidime–avibactam, and meropenem–vaborbactam against multidrug-resistant K. pneumoniae complex strains. This study involved 160 strains of Gram-negative rods, comprising 138 K. pneumoniae and 22 K. variicola. The minimal inhibitory concentration of fosfomycin was estimated using the agar dilution method, and for colistin, the microdilution method was employed. Susceptibility to ceftazidime–avibactam and meropenem–vaborbactam was determined using the gradient strip method. All analyzed K. pneumoniae complex isolates produced extended-spectrum β-lactamases, and 60.0% exhibited carbapenemases. The majority of the analyzed strains were susceptible to fosfomycin and colistin (62.5%). Among pandrug-resistant K. pneumoniae complex isolates, the highest susceptibility was observed with colistin (43.9%). Fosfomycin demonstrated good activity against ESβLs- and VIM-positive isolates from this complex. Colistin also exhibited satisfactory in vitro activity against VIM- and KPC-positive isolates from the K. pneumoniae complex. Ceftazidime–avibactam displayed good activity against K. pneumoniae complex strains producing ESβLs, KPC, and OXA enzymes. Additionally, meropenem–vaborbactam showed satisfactory in vitro activity against ESβLs- and KPC-positive isolates from this complex. Full article