Search Results (1,326)

Background: Ventilator-associated pneumonia (VAP) is a leading cause of nosocomial infections in neonatal intensive care units (NICUs) and is associated with significant morbidity, mortality, and prolonged hospitalization, particularly in preterm neonates. Management is complicated by the emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens, with very limited evidence supporting the use of reserve antibiotics in this population. Case Presentation: We report a male neonate born at 25 weeks of gestation (birth weight 740 g) who developed severe VAP caused by XDR Acinetobacter calcoaceticus-baumannii complex and Pseudomonas aeruginosa. After failure of multiple antibiotic regimens, including ampicillin, amikacin, meropenem, vancomycin, cefepime with inhaled colistin, tigecycline, and ceftazidime-avibactam combined with fosfomycin, the infant was treated with sulbactam–durlobactam (25 mg/kg/dose every 6 h) in combination with ceftazidime-avibactam. After 12 days of this regimen, the neonate was successfully extubated. Conclusions: This case highlights the therapeutic challenges of XDR infections in extremely preterm neonates and suggests that sulbactam–durlobactam may represent a viable salvage treatment option. Further pharmacokinetic and clinical studies are needed to establish optimal dosing and safety in the neonatal population. Full article

Background: Nosocomial infections caused by multidrug-resistant microorganisms are a significant public health concern. Antimicrobial resistance (AMR) is closely linked to the excessive and indiscriminate use of antibiotics, which creates selective pressure and promotes the emergence of resistant pathogens. Objectives: This study evaluates the synergistic potential of intragenic antimicrobial peptides (IAPs) combined with plant alkaloids against susceptible and multidrug-resistant human pathogenic bacteria, assessing antimicrobial activity, biofilm inhibition, and hemocompatibility. Methods: The tested molecules included berberine, tomatidine, sinomenine, and the IAPs Hs02 and Gr01. Minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) assays were performed against both ATCC (E. coli ATCC 25922 and S. aureus ATCC 25923) and clinical strains (E. coli KPC+ HRAN 1812446 and S. aureus MDR LACEN 3730529). Synergistic interactions were evaluated by checkerboard assay, followed by biofilm inhibition and hemolysis assays using human red blood cells. Results: Berberine exhibited a MIC of 1024 µM when tested individually, while tomatidine and sinomenine showed no significant activity. As expected, the IAPs showed strong antimicrobial properties at 8 µM (Hs02) and 4 µM (Gr01). When tested in synergy, alkaloids and IAPs reduced the MIC by up to 128-fold. The combination of IAPs and alkaloids reduced the biofilm biomass of S. aureus and E. coli by 50%, by the crystal violet assay (p < 0.05). Notably, sinomenine had not previously been reported to have antimicrobial activity. Conclusions: These results highlight the importance of further exploring combinations of natural and synthetic bioactive molecules as promising antimicrobial candidates. This approach may help to extend the useful life of conventional antibiotics. However, further studies are needed to assess safety, cytotoxicity, genotoxicity, inflammation, and in vivo effects. Full article

Antimicrobial resistance (AMR) constitutes a critical and escalating global public health challenge, severely limiting the potential of existing antimicrobial drugs and escalating infection-associated morbidity and mortality rates. This analysis focuses on the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), which are prioritized by the World Health Organization (WHO) and represent a significant cause of nosocomial infections due to their extensive drug resistance. We provide an in-depth review of the global prevalence and specific antibiotic-resistant mechanisms of these pathogens. Due to the decline in the traditional antibiotic development pipeline, accelerated development of alternative therapeutic strategies is essential. The review comprehensively discusses innovative non-traditional therapies currently being explored to bypass traditional antibiotic limitations, such as phage therapy, antimicrobial peptides (AMPs), anti-virulence therapies, fecal microbiota transplantation (FMT), and targeted CRISPR-based approaches. Addressing the ESKAPE challenge requires a concerted, multi-sectoral strategy guided by the One Health principle, focusing on enhancing public awareness, improving surveillance and research, optimizing judicious antibiotic use, and cultivating sustainable investment in novel interventions. Full article

Healthcare-associated infections remain a major cause of morbidity and mortality in paediatric patients, particularly among those undergoing surgery or requiring intensive care. Distinguishing postoperative sterile inflammation from early sepsis is clinically challenging because conventional biomarkers such as C-reactive protein (CRP) and procalcitonin lack sufficient specificity. This narrative review aimed to analyse current evidence on pancreatic stone protein (PSP) as an emerging biomarker for the detection and risk stratification of infection in paediatric populations. A structured literature search was performed in PubMed and Web of Science for studies published between 2020 and 2026 using terms related to nosocomial infections, paediatric surgery, and PSP, identifying 147 articles; 54 met the inclusion criteria after screening. The analysed studies show that PSP levels increase significantly in children with sepsis compared with those with non-infectious systemic inflammation and are associated with bacteraemia, organ dysfunction, and mortality. In several paediatric cohorts, PSP demonstrated diagnostic performance comparable to or better than traditional markers, with reported AUROC values up to approximately 0.82 for distinguishing sepsis from non-infectious inflammation. Evidence from neonatal and high-risk populations also suggests strong sensitivity and specificity for early infection detection. Overall, PSP appears to be a promising biomarker for the early identification and prognostic stratification of paediatric sepsis; however, variability among studies highlights the need for larger multicentre prospective investigations and for integrating PSP into multimarker diagnostic algorithms. Full article

Background: Respiratory infections in critically ill patients remain a major challenge in intensive care units (ICUs), with high morbidity and mortality. Conventional microbiological methods often fail to identify the causative pathogen promptly, particularly in patients previously exposed to antibiotics. Multiplex molecular platforms, such as the BioFire FilmArray^® Pneumonia Panel Plus (FAPP), allow rapid detection of multiple respiratory pathogens and resistance markers, potentially improving early therapeutic decision-making. The objective of this work is to evaluate the impact of implementing FAPP on antimicrobial therapeutic decisions in critically ill patients with suspected respiratory infection. Methods: We conducted a retrospective cohort study in two mixed ICUs between 2023 and 2024. All respiratory samples in which FAPP was requested were analyzed. The results were compared with conventional cultures, and changes in antimicrobial therapy following the FAPP results were assessed, classified as escalation/initiation or de-escalation/discontinuation. Concordance between FAPP and culture was evaluated, and clinical and demographic variables were analyzed. Differences between groups were assessed using p-values obtained from the chi-square test or the Mann–Whitney test. Results: A total of 363 respiratory samples were included, 88.4% from mechanically ventilated patients. FAPP was positive in 65.3% of samples, whereas cultures were positive in 23.1%. Overall concordance between FAPP and culture was 57.3%. In 42.4% of cases, pathogens were detected exclusively by FAPP. Antimicrobial therapy was modified in 29.8% of patients, predominantly through de-escalation or discontinuation (69.4% of changes). Therapeutic modifications were more frequent in nosocomial infections and in patients with a positive FAPP result. Conclusions: The use of FAPP in critically ill patients with suspected respiratory infection provides rapid microbiological information that significantly influences antimicrobial decision-making, particularly by facilitating antibiotic de-escalation. Although discrepancies with conventional cultures remain and require careful clinical interpretation, FAPP represents a valuable tool for antimicrobial stewardship in the ICU setting. Full article

Klebsiella pneumoniae is an opportunistic pathogen associated with both community-acquired and nosocomial infections. Multidrug-resistant (MDR) strains are increasingly implicated in urinary tract infections (UTIs), traveller’s diarrhoea, bacteraemia, and sepsis. β-lactam antibiotics are commonly used for treatment; however, antimicrobial resistance has emerged largely due to the production of extended-spectrum β-lactamases (ESBLs), which confer resistance mainly to penicillins, oxyimino-cephalosporins, and monobactams, while cephamycins and carbapenems usually remain stable to ESBL-mediated hydrolysis and compromise therapeutic efficacy. ESBL-producing strains represent a major cause of severe Gram-negative infections. This study aimed to determine the prevalence of ESBL-producing K. pneumoniae among UTI patients in Jordanian hospitals (Al Mafraq, Ma’an, and Islamic Hospitals), evaluate their antimicrobial susceptibility patterns, and detect antimicrobial resistance genes at the molecular level. A total of 450 urine isolates of K. pneumoniae were collected from UTI patients between November 2023 and May 2024. Isolates were identified in hospital laboratories using standard microbiological methods. Antimicrobial susceptibility testing was performed, and molecular characterisation of ESBL-associated genes was conducted using polymerase chain reaction (PCR). Out of 450 K. pneumoniae isolates collected from UTI patients across three Jordanian regions, 72 (16%) were confirmed as ESBL producers. Among the 72 ESBL-positive K. pneumoniae isolates, 34 (47.2%) were recovered from the Central region, 20 (27.8%) from the North, and 18 (25.0%) from the South. Molecular analysis revealed that 41.7% of ESBL-producing isolates carried the blaCTX-M gene, while 33.3% harboured the blaOXA gene. All ESBL-producing isolates demonstrated antimicrobial resistance to third-generation cephalosporins. A significantly higher proportion of ESBL-producing isolates was identified in female patients (84.7%) compared with males (15.3%). A significant association was observed between blaOXA gene distribution and geographic region (p = 0.016), whereas blaCTX-M gene distribution showed no significant regional association. ESBL-producing K. pneumoniae accounted for a substantial proportion of UTI isolates in Jordan, with blaCTX-M identified as the predominant resistance gene. The higher burden observed in the Central region and among female patients highlights notable distribution patterns in this cohort. These findings emphasise the necessity for sustained molecular surveillance and strengthened antimicrobial stewardship strategies to limit the dissemination of ESBL-producing strains in Jordanian healthcare settings. Full article

Background/Objectives: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a priority nosocomial pathogen with limited therapeutic options and high attributable mortality, particularly in intensive care units (ICUs). Whether the pandemic-era rise in institutional CRAB burden resolved, persisted, or stabilized at a sustained high level remains incompletely characterized at the single-hospital level. Methods: We conducted a retrospective observational study of all non-duplicate clinical A. baumannii complex isolates recovered at a 450-bed regional teaching hospital in central Taiwan between January 2020 and December 2024. Isolates were classified as CRAB based on non-susceptibility (intermediate or resistant) to imipenem or meropenem. Annual and monthly isolation rates, ICU versus non-ICU distribution, and temporal trends were analyzed. Results: Among 582 A. baumannii complex isolates, 340 (58.4%) were classified as CRAB. The annual CRAB isolation rate differed significantly across the study period (p = 0.0099), rising sharply from 44.0% (51/116) in 2020 to 63.9% (76/119) in 2021 and subsequently remaining between 58.3% (60/103) and 63.2% (67/106) through 2024. Monthly isolation rates varied widely (16.7–100.0%) without a consistent seasonal pattern. The proportion of CRAB isolates originating from ICU settings varied year to year, rising from 45.1% (23/51) in 2020 to a peak of 67.4% (58/86) in 2022 and then declining to 49.3% (33/67) in 2024, without a statistically significant overall trend (p = 0.054). Conclusions: These findings suggest that CRAB isolation rates remained at a sustained elevated level after the acute pandemic phase and highlight ICUs as an important focus for institution-level infection prevention and antimicrobial stewardship efforts. Full article

Background: Acinetobacter baumannii is a non-fermenting Gram-negative bacillus responsible for severe nosocomial infections, particularly in intensive care units (ICUs). The increasing prevalence of multidrug-resistant (MDR) and carbapenem-resistant A. baumannii (CRAB) strains has become a significant challenge for infection control and antimicrobial therapy worldwide. Objectives: This study aimed to analyze the antimicrobial susceptibility patterns of clinical A. baumannii isolates recovered from a multi-profile hospital in years 2020–2024 in Lodz, Poland. Methods: Clinical isolates from various specimen types (blood, urine, wound swabs, biopsies, sputum, and bronchoalveolar lavage fluid) were obtained during routine microbiological diagnostics. Identification was performed using MALDI-TOF MS. Antimicrobial susceptibility testing (AST) was conducted using the automated VITEK^®2 system with EUCAST/CLSI interpretive criteria. Minimum inhibitory concentrations (MICs) for colistin were determined by broth microdilution. Carbapenemase production was assessed using the Carbapenem Inactivation Method (CIM) and immunochromatographic assays for OXA-23, OXA-40/58, and NDM detection. Results: A total of 244 A. baumannii isolates were recovered over the study period. Susceptibility to carbapenems (meropenem, imipenem) declined markedly, with resistance exceeding 90% by 2023–2024. Aminoglycosides exhibited variable activity, with gentamicin demonstrating the highest susceptibility rates (up to 88% in 2022). Resistance to ceftazidime and cefepime remained consistently high (>90% in 2023–2024). No fully susceptible isolates were identified for ciprofloxacin. Conclusions: The high prevalence of CRAB strains highlights the urgent need for effective infection control measures, optimized antimicrobial stewardship, and consideration of novel treatment options in the clinical setting. Full article

Antimicrobial resistance (AMR) is one of the most significant threats to healthcare systems, particularly in low- and middle-income nations where infection prevention and control, antimicrobial stewardship, and laboratory surveillance might not be optimal. Acinetobacter baumannii is a high-risk nosocomial pathogen that has a strong capacity to develop extreme resistance phenotypes. Still, the degree to which extensively drug-resistant (XDR) and pandrug-resistant (PDR) phenotypes reflect the cumulative impact of antimicrobial pressure at unit and system levels in Iraqi hospitals is not fully described. This was a cross-sectional surveillance study that was a laboratory-based investigation done in public hospitals in the Governorate of Kirkuk between January 2024 and January 2025. The BD Phoenix system identified 80 non-duplicate A. baumannii isolates that were obtained in high-risk hospital units. The interpretation of antimicrobial susceptibility testing was done according to CLSI guidelines. Internationally recognized definitions were adjusted to local therapeutic availability to classify isolates as XDR or PDR. Unadjusted odds ratios and Fisher’s exact test were used to assess the associations between the PDR phenotype and the chosen clinical or unit-level variables. Among the 80 isolates, 60 (75%) were XDR and 20 (25%) were PDR. Burn units and wound-related infections were disproportionately represented by PDR isolates. There were significant associations between the PDR phenotype and burn unit admission, wound infection, exposure to invasive devices, long hospitalization (greater than 14 days), and previous exposure to broad-spectrum antibiotics. ICU admission and respiratory infection were not significantly related. Cefepime had in vitro activity only in a subset of XDR isolates. Extreme resistance phenotypes can be used as convenient sentinel measures of cumulative antimicrobial pressure and system-level stress in resource-limited environments. There is an urgent need to strengthen infection prevention and control, antimicrobial stewardship, and laboratory surveillance to preserve the remaining therapeutic options. Full article

Background: The growing number of older adults undergoing surgical procedures requires care models that minimise hospital exposure, optimise safety, and support rapid recovery. Day surgery has become an increasingly attractive option for selected older patients, provided their medical, functional and psychosocial needs are carefully assessed. Recent developments in prehabilitation, geriatric-focused perioperative pathways and enhanced post-discharge follow-up have further expanded its potential. This narrative review aims not only to synthesise current evidence, but also to provide a clinically oriented framework for patient selection, perioperative optimisation, and safe implementation of day surgery pathways in older adults. Main findings: Evidence from the past decade indicates that day surgery can be safe and effective for adults aged ≥65 when supported by structured preoperative assessment, targeted optimisation, and clear discharge criteria. Older patients benefit particularly from reduced risks of hospital-acquired complications, including infection, delirium, immobility and functional decline. Prehabilitation programmes focusing on nutrition, strength, balance and medication review are associated with improved postoperative stability and faster return to baseline function. Multidisciplinary teamwork, integrating surgeons, anaesthetists, geriatricians, nurses, physiotherapists, dietitians and caregivers, play a key role in identifying modifiable risks and ensuring continuity of care. Studies also highlight the value of post-discharge telephone follow-up, caregiver engagement and close collaboration with primary care in preventing readmissions. Conclusions: Day surgery is a viable and patient-centred option for many older adults when careful selection and preparation are combined with age-sensitive perioperative care. Most adverse outcomes can be mitigated through systematic prehabilitation, thoughtful anaesthetic planning, early mobilisation and structured follow-up. The evidence suggests that older patients may benefit from reduced hospital stay, less exposure to harm, and faster functional recovery. Implications for practice: The findings support broader integration of geriatric day surgery into routine care pathways, especially within health systems facing capacity constraints. Clinicians should consider implementing standardised geriatric assessment, multidisciplinary optimisation strategies, and robust discharge and follow-up protocols to enhance safety and effectiveness. With appropriate preparation and coordinated teamwork, day surgery can contribute meaningfully to safer, more efficient and more patient-centred surgical care for older adults. Full article

Background: ESKAPE constitutes a group of six nosocomial bacteria that can evade available antimicrobials due to their great potential to develop multi-drug resistance and biofilm-forming abilities. These pathogens often cause hospital-acquired infections and pose a serious threat to public health. The search for efficient innovative therapeutic strategies to fight ESKAPE bacteria have been intensively investigated topics. One promising approach to fight resistant pathogens and their biofilms is combination therapy, which allows the effectiveness against microorganisms to be increased while reducing the applied concentrations and risks of potential unwanted side effects. Objectives: The object of the study was to determine if there is an interaction of short lipopeptides ((C₁₀)₂-KKKK-NH₂, C₁₆-KK-NH₂) together with erythromycin and tetracycline against pathogens of the ESKAPE group (Acinetobacter baumannii, Enterobacter aerogenes, Enterococcus faecium Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus). Methods: The checkerboard assay was used to examine the activity of compounds applied in combinations against ESKAPE strains in planktonic cells and toward biofilms formed by Staphylococcus aures and Pseudomonas aeruginosa. Results: The lipopeptides demonstrated a great potential of their application as additives to conventional antimicrobials against Gram-negative bacteria, including microorganisms within biofilms. Full article

Environmental disturbances from hospital demolition and construction can aerosolise pathogenic fungal spores, particularly those of Aspergillus species, posing a serious threat to immunocompromised patients. This paper presents a structured narrative review of representative case studies to evaluate the relationship between demolition activities and airborne Aspergillus exposure, with a focus on clinical risk and environmental monitoring. Three exemplar studies were selected to illustrate high-intensity short-duration demolition, prolonged mechanical demolition, and meteorologically integrated risk assessment. By examining these cases, this review identifies gaps in current knowledge, methodological limitations, and challenges in causal attribution. The analysis supports the development of a novel conceptual framework for assessing and managing Aspergillus-related risks during hospital redevelopment, offering a structured approach to future infection prevention and control strategies. This framework is intended as a conceptual tool to support evidence-informed decision-making while acknowledging the limitations inherent in a targeted narrative review rather than a systematic synthesis. Full article

Carbapenems comprise a class of β-lactam antibiotics with broad-spectrum hydrolytic activity and are often reserved as last-line agents for the treatment of serious multidrug-resistant (MDR) bacterial infections. Clinically important nosocomial MDR Gram-negative bacteria (GNB) include Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Carbapenem resistance among these organisms is predominantly mediated by the production of β-lactamases called carbapenemases, such as K. pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), and selected oxacillinase (OXA)-type carbapenemases. These enzymes degrade carbapenems, significantly compromising their clinical efficacy. To address escalating antimicrobial resistance, novel next-generation β-lactamase inhibitors (BLIs), partnered with established β-lactams (BLs), have been approved or are currently under development to inhibit carbapenemase activity. The present narrative review aims to synthesize the most current information on the major carbapenemases and discusses recently approved and investigational BL/BLI combination therapies in terms of their mechanisms of action, spectrum of activity, gaps in coverage, and available clinical and in vitro evidence. Development of resistance to novel BL/BLI combinations is also examined. Comparative analysis of inhibitory spectra and microbiological coverage indicates a continued need for metallo-β-lactamase inhibitors with direct pan-inhibitory activity, pathogen-specific BL/BLI regimens for carbapenem-resistant A. baumannii, and carbapenemase-targeted agents effective in the context of non-enzymatic resistance mechanisms. Treatment-emergent resistance to novel BL/BLIs and limitations in activity profiles underscore the critical need for continued innovation in pipeline development, vigilant global and local surveillance of carbapenemase epidemiology, and robust antimicrobial stewardship strategies to aid in preserving the efficacy of the antibacterial drug armamentarium. Full article

Multidrug-resistant Acinetobacter baumannii is a major nosocomial pathogen for which bacteriophages are being explored as alternative antibacterial agents. In this study, we isolated and characterized AUBFM01, a lytic phage active against MDR A. baumannii, and performed an initial assessment of its interaction with PMA-differentiated THP-1 macrophages. AUBFM01 was evaluated by host range testing, adsorption and one-step growth assays, lytic activity, stability testing, biofilm disruption, whole-genome sequencing, and flow cytometry-based macrophage profiling. The phage showed rapid adsorption, a short latent period of approximately 30 min, and a burst size of about 165 phage particles per infected cell. It remained stable under moderate temperature and near-neutral pH conditions and significantly reduced preformed A. baumannii biofilm biomass in vitro. Genomic analysis identified a 41,354-bp double-stranded DNA genome lacking detectable lysogeny-associated genes, antibiotic resistance determinants, and known bacterial virulence factors. In THP-1 macrophages, AUBFM01 exposure was associated with reduced cell viability and with enrichment of a resting/intermediate-like CD86-defined phenotype among the remaining cells, including after endotoxin reduction. These findings identify AUBFM01 as a lytic anti-Acinetobacter phage with antibiofilm activity and notable macrophage-associated effects that warrant further mechanistic and safety investigation. Full article