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The first example of applying salicylaldehyde derivatives, as well as coumarin with the formyl group at the C8 position in its structure, as carbonyl partners in a three-component Passerini reaction, is presented. As a result of research on the conditions of the Passerini reaction, the important role of the hydroxyl group in the salicylaldehyde used in the course of the multicomponent reaction was revealed. When an aldehyde with an unprotected hydroxyl group is used, only two-component α-hydroxy amide products are obtained. In contrast, the use of acylated aldehyde results in three-component α-acyloxy amide products with high efficiency. The developed protocol gives access to structurally diversified peptidomimetics with good yield. The compounds were also evaluated as antimicrobial agents against selected strains of nosocomial pathogenic bacteria. The structure–activity relationship revealed that inhibitory activity is strongly related to the presence of the trifluoromethyl group (CF3) or the methyl group at the C4 position in an unsaturated lactone ring of the coumarin scaffold. MIC and MBC studies were carried out on eight selected pathogenic bacteria strains (Gram-positive pathogenic Staphylococcus aureus strain (ATCC 23235), as well as on Gram-negative E. coli (K12 (ATCC 25404), R2 (ATCC 39544), R3 (ATCC 11775), and R4 (ATCC 39543)), Acinetobacter baumannii (ATCC 17978), Pseudomonas aeruginosa (ATCC 15442), and Enterobacter cloacae (ATCC 49141) have shown that the tested compounds show a strong bactericidal effect at low concentrations. Among all agents investigated, five exhibit higher antimicrobial activity than those observed for commonly used antibiotics. It should be noted that all the compounds tested showed very high activity against S. aureus, which is the main source of nosocomial infections that cause numerous fatalities. Additionally, the cytotoxicity of sixteen derivatives was measured with the use of the MTT test on BALB/c3T3 mouse fibroblast cell lines. The cytotoxicity studies revealed that the tested substances exert a similar or lower effect on cell proliferation than that observed for commonly used antibiotics within the range of therapeutic doses. A parallel MTT assay using ciprofloxacin, bleomycin, and cloxacillin showed that these antibiotics are more cytotoxic when tested in mammalian cells, and cell viability is in the range of 85.0–89.9%. Furthermore, we have shown that the studied coumarin-based peptidomimetics, depending on their structural characteristics, are nonselective and act efficiently against various Gram-positive and Gram-negative pathogens, which is of great importance for hospitalised patients. [ABSTRACT FROM AUTHOR]

Objectives The risk factors and outcomes associated with persistent bacteraemia in Gram-negative bloodstream infection (GN-BSI) are not well described. We conducted a follow-on analysis of a retrospective population-wide cohort to characterize persistent bacteraemia in patients with GN-BSI. Methods We included all hospitalized patients >18 years old with GN-BSI between April 2017 and December 2021 in Ontario who received follow-up blood culture (FUBC) 2–5 days after the index positive blood culture. Persistent bacteraemia was defined as having a positive FUBC with the same Gram-negative organism as the index blood culture. We identified variables independently associated with persistent bacteraemia in a multivariable logistic regression model. We evaluated whether persistent bacteraemia was associated with increased odds of 30- and 90-day all-cause mortality using multivariable logistic regression models adjusted for potential confounders. Results In this study, 8807 patients were included; 600 (6.8%) had persistent bacteraemia. Having a permanent catheter, antimicrobial resistance, nosocomial infection, ICU admission, respiratory or skin and soft tissue source of infection, and infection by a non-fermenter or non-Enterobacterales/anaerobic organism were associated with increased odds of having persistent bacteraemia. The 30-day mortality was 17.2% versus 9.6% in those with and without persistent bacteraemia (aOR 1.65, 95% CI 1.29–2.11), while 90-day mortality was 25.5% versus 16.9%, respectively (aOR 1.53, 95% CI 1.24–1.89). Prevalence and odds of developing persistent bacteraemia varied widely depending on causative organism. Conclusions Persistent bacteraemia is uncommon in GN-BSI but is associated with poorer outcomes. A validated risk stratification tool may be useful to identify patients with persistent bacteraemia. [ABSTRACT FROM AUTHOR]

Background Stenotrophomonas maltophilia is a carbapenem-resistant Gram-negative pathogen increasingly responsible for difficult-to-treat nosocomial infections. Objectives To describe the contemporary clinical characteristics and genome epidemiology of patients colonized or infected by S. maltophilia in a multicentre, prospective cohort. Methods All patients with a clinical culture growing S. maltophilia were enrolled at six tertiary hospitals across Japan between April 2019 and March 2022. The clinical characteristics, outcomes, antimicrobial susceptibility and genomic epidemiology of cases with S. maltophilia were investigated. Results In total, 78 patients were included representing 34 infection and 44 colonization cases. The median age was 72.5 years (IQR, 61–78), and males accounted for 53 cases (68%). The most common comorbidity was localized solid malignancy (39%). Nearly half of the patients (44%) were immunosuppressed, with antineoplastic chemotherapy accounting for 31%. The respiratory tract was the most common site of colonization (86%), whereas bacteraemia accounted for most infection cases (56%). The 30 day all-cause mortality rate was 21%, which was significantly higher in infection cases than colonization cases (35% versus 9%; adjusted HR, 3.81; 95% CI, 1.22–11.96). Susceptibility rates to ceftazidime, levofloxacin, minocycline and sulfamethoxazole/trimethoprim were 14%, 65%, 87% and 100%, respectively. The percentage of infection ranged from 13% in the unclassified group to 86% in genomic group 6A. The percentage of non-susceptibility to ceftazidime ranged from 33% in genomic group C to 100% in genomic groups 6 and 7 and genomic group geniculate. Conclusions In this contemporary multicentre cohort, S. maltophilia primarily colonized the respiratory tract, whereas patients with bacteraemia had the highest the mortality from this pathogen. Sulfamethoxazole/trimethoprim remained consistently active, but susceptibility to levofloxacin was relatively low. The proportions of cases representing infection and susceptibility to ceftazidime differed significantly based on genomic groups. [ABSTRACT FROM AUTHOR]

Enterococcus faecalis is an opportunistic pathogen frequently causing nosocomial infections. The virulence of this organism is underpinned by its capacity to evade phagocytosis, allowing dissemination in the host. Immune evasion requires a surface polysaccharide produced by all enterococci, known as the enterococcal polysaccharide antigen (EPA). EPA consists of a cell wall‐anchored rhamnose backbone substituted by strain‐specific polysaccharides called 'decorations', essential for the biological activity of this polymer. However, the structural determinants required for innate immune evasion remain unknown, partly due to a lack of suitable validated assays. Here, we describe a quantitative, in vitro assay to investigate how EPA decorations alter phagocytosis. Using the E. faecalis model strain OG1RF, we demonstrate that a mutant with a deletion of the locus encoding EPA decorations can be used as a platform strain to express heterologous decorations, thereby providing an experimental system to investigate the inhibition of phagocytosis by strain‐specific decorations. We show that the aggregation of cells lacking decorations is increasing phagocytosis and that this process does not involve the recognition of lipoproteins by macrophages. Collectively, our work provides novel insights into innate immune evasion by enterococci and paves the way for further studies to explore the structure/function relationship of EPA decorations. [ABSTRACT FROM AUTHOR]

Nanoparticles capped with natural products can be a cost-effective alternative to treat drug-resistant nosocomial infections. Therefore, silibinin-loaded chitosan-capped silver nanoparticles (S-C@AgNPs) were synthesized to evaluate their antimicrobial and anti-inflammatory potential. The S-C@AgNPs plasmon peak was found at 430 nm and had a particle size distribution of about 130 nm with an average hydrodynamic diameter of 101.37 nm. The Scanning Electron Microscopy images showed the presence of sphere-shaped homogeneous nanoparticles. The Fourier Transform Infrared Spectroscopy analysis confirmed the loading of silibinin and chitosan on the AgNPs surface. The minimum inhibitory concentration of the S-C@AgNPs was reported between 3.12 μg/ml to 12.5 μg/ml and a minimum bactericidal concentration between 6.25 μg/ml to 25 μg/ml against drug-resistant nosocomial pathogens. Moreover, concentration-dependent significant inhibition of the biofilm formation was reported against P. aeruginosa (70.21%) and K. pneumoniae (71.02%) at 30 μg/ml, and the highest destruction of preformed biofilm was observed at 100 μg/ml against P. aeruginosa (89.74%) and K. pneumoniae (77.65%) as compared to individual bacterial control. Additionally, the fluorescence live/dead assay for bacterial biofilm confirmed that 100 µg/ml effectively inhibits the biofilm formed by these pathogens. S-C@AgNPs also showed anti-inflammatory activity, which is evident by the significant decrease in the proinflammatory cytokines and chemokines level in THP1 cells treated with LPS. This study concluded that S-C@AgNPs have potent antimicrobial, antibiofilm, and anti-inflammatory properties and could be a potential option for treating drug resistant nosocomial infections. [ABSTRACT FROM AUTHOR]

Background: There is high incidence of nosocomial in developing countries and the bacteria responsible are becoming more resistant to commercially available antibiotics, hence, the need for this research. Methods: Isolation and identification of microorganisms from different wards of Ilara-Mokin health centers was done using standard methods. The bacteria isolated were identified and subjected to susceptibility test using four extracts and standard antibiotics for comparative study. Results: A high bacterial load of 52.00 ± 3.46 cfu/ml obtained was from the toilet in maternity ward, while the least bacterial load of 2.67 ± 0.67 cfu/ml was obtained from the floor of the male ward. A total of twelve (12) bacteria were isolated and identified, while nine (9) fungi were equally isolated and identified. The susceptibility of the bacteria isolates to ethanol extracts of castor, garlic, beniseed and bitter cola showed that garlic extract is most effective on the isolates having the highest diameter of zone of inhibition, Bacillus licheniformis with a diameter of 18.20±2.05 mm. Conclusion: The garlic ethanol extract was the most effective on the isolates while Pseudomonas was the most unsusceptible to all the extracts. The extracts tested in this work comparatively exceeded the potency of antibiotics, however, the Gram-negative bacteria are not very susceptible to the extracts. Therefore, these extracts can be used in development of novel antibiotics, especially to help curb resistance of pathogenic microorganisms implicated in nosocomial infections. [ABSTRACT FROM AUTHOR]

Background: The recently emerged E. coli ST131 clone is now a predominant cause of UTIs. There is a need to understand the virulence characteristics of this clone to limit its dissemination. Aim of work: We aimed to detect the presence of ST131 clones among E. coli strains isolated from UTI infections and compare the virulence carriage capacity between ST131 and non-ST131 strains. Methods: A total of 89 (63.5%) E. coli strains isolated from 140 patients with UTI were investigated for six different virulence genes using PCR-based assays. Results: Overall, 65 of 89 (73%) E. coli isolates belonged to the ST131 clone. Of these, 61 isolates (93.8%) were of the O25-ST131 clone, and only 4 isolates (6.2%) were of the O16-ST131 clone. From 24 catheterized patients, 20 (83.3%) were positive for the ST131 clone. Regarding the adhesin virulence genes, the fimH gene was detected in all studied isolates. Then, papEF, sfa(sfa/foc), and papA genes were found in 59.6%, 53.9%, and 30.3% of isolates, respectively. However, the iroN and hylA genes were found in 52.8% and 16.9%, respectively. Conclusion: E. coli ST131 isolates exhibited a higher prevalence among hospital-acquired UTIs than community-acquired UTIs, raising concern that this emerging clone has become a threat to nosocomial infections. The high virulence potential among E. coli ST131 isolates suggests that the virulence characterizations of this clone are in a continuous step-up evolution. More importantly, increased carriage of adhesin genes among ST131 isolates was demonstrated and can be targeted to develop new management strategies for UTI infections. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) disinfection technologies are well-known tools for microbial prevention in indoor public places which are frequently employed for disinfecting air, surfaces, and water. Such technologies have drawn a great deal of interest due to its potential application, especially in the domain of healthcare. This article discusses the shortcomings of chemical disinfectants and analyzes the current research standing on the development of various types of UV disinfection technologies for their prospective usage in the healthcare industry. Furthermore, the article provides a thorough analysis and in-depth evaluation of the current antibacterial studies using UV lamps and light-emitting diodes (LEDs) for the treatment of frequently encountered pathogens associated with healthcare. According to the systematic review, UV-LEDs have shown to be a potential source for delivering disinfection which is equally efficient or more effective than traditionally used UV lamps. The findings also provide valuable considerations for potentially substituting conventional lamps with LEDs that would be less expensive, more efficient, more robust, non-fragile and safer. With greater effectiveness and advantages, UV-LEDs have shown to be the potential UV source that could fundamentally be able to transform the disinfection industry. Therefore, the study supports the employment of UV-LED technology as a better and workable approach for effective disinfection applications. The study also offers insightful information that will help to direct future studies in the domain of hygienic practices used in healthcare facilities. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are associated with poor outcomes depending on patient's conditions, clinical severity and type of infection, and treatment is challenging given the limited therapeutic options available. The aim of this study was to describe the clinical and microbiological characteristics of two outbreaks caused by CRAB in an intensive care unit (ICU). In addition, the mechanisms of resistance detected in these strains and the treatment chosen according to the available therapeutic options were analyzed. Overall, 28 patients were included. Ten patients (35.71%) had ventilator-associated pneumonia (VAP), ten (35.71%) had a bloodstream infection (BSI), and eight (28.57%) were only colonized. Recurrent infection occurred in 25% (5/20) of infected patients. Two different strains of A. baumannii were isolated from the index patient of the first outbreak. The first strain belonged to the ST85 and carried the blaNDM-1 carbapenemase gene, while the second belonged to the ST2 and carried blaOXA-23, and blaOXA-66 carbapenemase genes. The phylogenetic analysis revealed that the ST2 strain was the cause of the major outbreak, and mutations in the AmpC gene were related to progressive increasing minimum inhibitory concentration (MIC) and finally, cefiderocol-resistance in one strain. The CRAB isolates from the second outbreak were also identified as ST2. Cefiderocol-resistant strains tests identified by the disc diffusion method were involved in 24% (6/25) of nosocomial infections. Using broth microdilution (BMD) ComASP® only, 33.3% (2/6) of these strains were cefiderocol-resistant. All-cause ICU mortality was 21.4%. Conclusions: Cefiderocol is the first approved siderophore cephalosporin for the treatment of CRAB infections. Cefiderocol-resistant strains were related with blaNDM-1 carbapenemase and mutations in the AmpC gene. Cefiderocol-resistant strains or that cannot be properly interpreted by disk diffusion, should be retested using BMD for definitive categorization. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is an opportunistic pathogen in humans and a frequent cause of severe nosocomial infections and fatal infections in immunocompromised individuals. Its ability to form biofilms has been the main driving force behind its resistance to almost all conventional antibiotics, thereby limiting treatment efficacy. In an effort to discover novel therapeutic agents to fight P. aeruginosa-associated biofilm infections, the truncated analogs of scorpion venom-derived peptide IsCT were synthesized and their anti-biofilm properties were examined. Among the investigated peptides, the IsCT-Δ6-8 peptide evidently showed the most potential anti-P. aeruginosa biofilm activity and the effect was not due to bacterial growth inhibition. The IsCT-Δ6-8 peptide also exhibited inhibitory activity against the production of pyocyanin, an important virulence factor of P. aeruginosa. Furthermore, the IsCT-Δ6-8 peptide significantly suppressed the production of inflammatory mediators nitric oxide and interleukin-6 in P. aeruginosa LPS-induced macrophages. Due to its low cytotoxicity to mammalian cells, the IsCT-Δ6-8 peptide emerges as a promising candidate with significant anti-biofilm and anti-inflammatory properties. These findings highlight its potential application in treating P. aeruginosa-related biofilm infections. [ABSTRACT FROM AUTHOR]

Carbapenemase-producing Pseudomonas aeruginosa strains present a specific geographical distribution regarding the type of carbapenemase-encoding genes that they harbor. For more than twenty years, VIM-type enzymes were the only major carbapenemases that were detected among P. aeruginosa isolates in Greece until the emergence of NDM-1-encoding P. aeruginosa in early 2023. In the present study, we present the rapid reversal of the carbapenemase-producing P. aeruginosa epidemiology from blaVIM- to blaNDM-harbouring isolates that occurred in our hospital since then. Between January 2023 and February 2024, 139 isolates tested positive for carbapenemase production with the NG-Test CARBA 5 immunochromatographic assay. Eight isolates were processed with the Hybrispot antimicrobial resistance direct flow chip molecular assay, and the first NDM-producing isolate was further analyzed through whole genome sequencing and bioinformatics analysis. Multiple resistance genes were detected by molecular techniques in accordance with the extensively drug-resistant phenotype. The isolate that was subjected to whole-genome sequencing belonged to the P. aeruginosa high-risk clone ST308, and the blaNDM was located in the chromosome in accordance with previously reported data. During the study period, NDM-producing isolates were increasingly detected, and only five months after their emergence, they overcame VIM producers. Our results indicate the potential of this new clone to spread rapidly and predominate within healthcare institutions, further restricting the already limited treatment options. [ABSTRACT FROM AUTHOR]

Background: Antibiotic resistance is a worldwide concern. This study retrospectively analyzed patients admitted to the ICU of a tertiary hospital over a period of 7 months who were rectally colonized by multidrug-resistant microorganisms. The incidence of concomitant nosocomial infections was estimated, thus providing the risk of a colonizing microorganism producing a nosocomial infection. Methods: Infections with the same microorganism (concomitant) or different microorganisms (non-concomitant) were analyzed in order to adjust the empirical antibiotic treatment. Patients with rectal colonization by at least one multidrug-resistant bacterium (MDRB) on admission or after ICU admission were included. All patients had complete selective digestive decontamination (SDD) prophylaxis. For univariate analysis, categorical variables are expressed as frequencies and percentages and continuous variables as means and standard deviations, or as medians and interquartile ranges. For multivariate analysis, the model is summarized with p-values and hazard ratios with 95% confidence intervals. Survival analysis was conducted using the Kaplan–Meier method, which was performed to evaluate the time elapsed from colonization to infection by the same bacteria. Statistical significance was considered at p < 0.05. Results: Of the 130 patients with MDRB bacterial colonization analyzed, 98 remained free of infection, while 22 developed non-concomitant infections and 10 had infections concomitant to rectal colonizing bacteria. OXA-48-producing bacteria and MDR-Pseudomonas spp. incidences were 18.9% (95% CI: 7.96–35.2) and 44.4% (CI: 13.7–78.8), respectively. Conclusions: OXA-48-producing bacteria and MDR-Pseudomonas spp. were the only bacteria associated with the development of infections concomitant to rectal colonization in an SDD setting. The incidence of MDRB infections was low. [ABSTRACT FROM AUTHOR]

To prevent nosocomial infection, it is important to screen for potential vancomycin‐resistant Enterococcus (VRE) among patients. In this study, we analyzed enterococcal isolates from inpatients in one hospital without any apparent outbreak of VRE. Enterococcal isolates were collected from inpatients at Hiroshima University Hospital from April 1 to June 30, 2021 using selective medium for Enterococci. Multilocus sequence typing, antimicrobial susceptibility testing, and whole‐genome sequencing were performed. A total of 164 isolates, including Enterococcus faecium (41 isolates), Enterococcus faecalis (80 isolates), Enterococcus raffinosus (11 isolates), Enterococcus casseliflavus (nine isolates), Enterococcus avium (12 isolates), Enterococcus lactis (eight isolates), Enterococcus gallinarum (two isolates), and Enterococcus malodoratus (one isolate), were analyzed. We found one vanA‐positive E. faecium, which was already informed when the patient was transferred to the hospital, nine vanC‐positive E. casseliflavus, and two vanC‐positive E. gallinarum. E. faecium isolates showed resistance to ampicillin (95.1%), imipenem (95.1%), and levofloxacin (87.8%), and E. faecalis isolates showed resistance to minocycline (49.4%). Ampicillin‐ and levofloxacin‐resistant E. faecium had multiple mutations in penicillin‐binding protein 5 (PBP5) (39/39 isolates) and ParC/GyrA (21/36 isolates), respectively. E. raffinosus showed resistance to ampicillin (81.8%), imipenem (45.5%), and levofloxacin (45.5%), and E. lactis showed resistance to ampicillin (37.5%) and imipenem (50.0%). The linezolid resistance genes optrA and cfr(B) were found only in one isolate of E. faecalis and E. raffinosus, respectively. This study, showing the status of enterococci infection in hospitalized patients, is one of the important information when considering nosocomial infection control of VRE. [ABSTRACT FROM AUTHOR]

Candida albicans is often implicated in nosocomial infections with fatal consequences. Its virulence is contributed to hydrolytic enzymes and biofilm formation. Previous research focused on studying these virulence factors individually. Therefore, this study aimed to investigate the impact of biofilm formation on the hydrolytic activity using an adapted low-cost method. Eleven strains of C. albicans were used. The biofilms were formed on pre-treated silicone discs using 24-well plates and then deposited on the appropriate agar to test each enzyme, while the planktonic cells were conventionally seeded. Biofilms were analysed using Raman spectroscopy, fluorescent and scanning electron microscopy. The adapted method provided an evaluation of hydrolytic enzymes activity in C. albicans biofilm and showed that sessile cells had a higher phospholipase and proteinase activities compared with planktonic cells. These findings were supported by spectroscopic and microscopic analyses, which provided valuable insights into the virulence mechanisms of C. albicans during biofilm formation. [ABSTRACT FROM AUTHOR]

Bloodstream infections (BSIs) can be primary or secondary, with significant associated morbidity and mortality. Primary bloodstream infections (BSIs) are defined as infections where no clear infection source is identified, while secondary BSIs originate from a localized infection site. This study aims to compare patterns, outcomes, and medical costs between primary and secondary BSIs and identify associated factors. Conducted at the University Hospital of Patras, Greece, from May 2016 to May 2018, this single-center retrospective cohort study included 201 patients with confirmed BSIs based on positive blood cultures. Data on patient characteristics, clinical outcomes, hospitalization costs, and laboratory parameters were analyzed using appropriate statistical methods. Primary BSIs occurred in 22.89% (46 patients), while secondary BSIs occurred in 77.11% (155 patients). Primary BSI patients were younger and predominantly nosocomial, whereas secondary BSI was mostly community-acquired. Clinical severity scores (SOFA, APACHE II, SAPS, and qPitt) were significantly higher in primary compared to secondary BSI. The median hospital stay was longer for primary BSI (21 vs. 12 days, p < 0.001). Although not statistically significant, mortality rates were higher in primary BSI (43.24% vs. 26.09%). Total care costs were significantly higher for primary BSI (EUR 4388.3 vs. EUR 2530.25, p = 0.016), driven by longer hospital stays and increased antibiotic costs. This study underscores the distinct clinical and economic challenges of primary versus secondary BSI and emphasizes the need for prompt diagnosis and tailored antimicrobial therapy. Further research should focus on developing specific management guidelines for primary BSI and exploring interventions to reduce BSI burden across healthcare settings. [ABSTRACT FROM AUTHOR]

Sepsis is among the most frequent diagnoses on admission to the intensive care unit (ICU). A systemic inflammatory response, activated by uncontrolled infection, fosters hypoperfusion and multiorgan failure and often leads to septic shock and mortality. These infections arise from a specific anatomic source, and how the infection foci influence the outcomes is unknown. All patients admitted to the ICU of Hospital de Vila Franca de Xira, between 1 January 2017 and 31 June 2023, were screened for sepsis and categorized according to their infection foci. During the study period, 1296 patients (32.2%) had sepsis on admission. Their mean age was 67.5 ± 15.3 and 58.1% were male; 73.0% had community-acquired infections. The lung was the main focus of infection. Septic shock was present in 37.9% of the patients and was associated with hospital mortality. Severe imbalances were noted in its incidence, and there was lower mortality in lung infections. The hospital-acquired infections had a slightly higher mortality but, after adjustment, this difference was non-significant. Patients with secondary bacteremia had a worse prognosis (one-year adjusted hazard ratio of 1.36, 95% confidence interval 1.06–1.74, p = 0.015), especially those with an isolated non-fermenting Gram-negative infection. Lung, skin, and skin structure infections and peritonitis had a worse prognosis, whilst urinary, biliary tract, and other intra-abdominal infections had a better one-year outcome. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, changes occurred within the surgical patient population. An increase in the frequency of resistant Gram-negative bacteria has since been recorded worldwide. After the start of the COVID-19 pandemic, microbiological diagnostics in our institution was performed using MALDI-TOF mass spectrometry. With this study, we wanted to confirm whether it contributed to a greater number of pathogenic bacteria detected in surgical ICU patients. A total of 15,033 samples taken from 1781 surgical patients were compared during the period from 2016 to February 2020 and during the COVID-19 pandemic from March 2020 to February 2023. On patients' admission, pathogenic bacteria were mostly isolated from the respiratory system (43.1% and 44.9%), followed by urine cultures (18.4 vs. 15.4%) before and during the pandemic. After the onset of the COVID-19 pandemic, there was a significant increase in the frequency of isolation of Enterobacter spp. (5.4 before vs. 9%, p = 0.014) and other enterobacteria (6.9 vs. 10.8%, p = 0.017) on patients' admission to the ICU, respectively. Despite this change, mortality in the ICU during the post-COVID-19 period was reduced from 23 to 9.6% (p < 0.001). The frequency of bacterial isolation did not change with the application of MALDI-TOF technology. By identifying the microorganism while simultaneously recognizing some resistance genes, we were able to start targeted therapy earlier. With the application of other infection control methods, MALDI-TOF may have contributed to the reduction in mortality in surgical ICU patients during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

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Ventilator-associated pneumonia (VAP) affects up to 20% of critically ill patients and induces significant antibiotic prescription pressure, accounting for half of all antibiotic use in the ICU. VAP significantly increases hospital length of stay and healthcare costs yet is also associated with long-term morbidity and mortality. The diagnosis of VAP continues to present challenges and pitfalls for the currently available clinical, radiological and microbiological diagnostic armamentarium. Biomarkers and artificial intelligence offer an innovative potential direction for ongoing future research. In this Review, we summarise the pathobiological heterogeneity and diagnostic challenges associated with VAP. Ventilator-associated pneumonia (VAP) is a nosocomial infection that significantly affects critically ill patients undergoing mechanical ventilation in the Intensive Care Unit (ICU). This review presents the diagnostic challenges associated with VAP in ICU. [ABSTRACT FROM AUTHOR]

Introduction: Acinetobacter baumannii contributes significantly to the global issue of multidrug-resistant (MDR) nosocomial infections. Often, these strains demonstrate resistance to carbapenems (MDR-CRAB), the first-line treatment for infections instigated by MDR A. baumannii. Our study focused on the antimicrobial susceptibility and genomic sequences related to plasmids from 12 clinical isolates of A. baumannii that carry both the blaOXA-58 and blaNDM-1 carbapenemase genes. Methods: Whole-genome sequencing with long-read technology was employed for the characterization of an A. baumannii plasmid that harbors the blaOXA-58 and blaNDM-1 genes. The location of the blaOXA-58 and blaNDM-1 genes was confirmed through Southern blot hybridization assays. Antimicrobial susceptibility tests were conducted, and molecular characterization was performed using PCR and PFGE. Results: Multilocus Sequence Typing analysis revealed considerable genetic diversity among blaOXA-58 and blaNDM-1 positive strains in Brazil. It was confirmed that these genes were located on a plasmid larger than 300 kb in isolates from the same hospital, which also carry other antimicrobial resistance genes. Different genetic contexts were observed for the co-occurrence of these carbapenemaseencoding genes in Brazilian strains. Discussion: The propagation of blaOXA-58 and blaNDM-1 genes on the same plasmid, which also carries other resistance determinants, could potentially lead to the emergence of bacterial strains resistant to multiple classes of antimicrobials. Therefore, the characterization of these strains is of paramount importance for monitoring resistance evolution, curbing their rapid global dissemination, averting outbreaks, and optimizing therapy. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial stewardship (AMS) for ventilator-associated pneumonia (VAP) or ventilated hospital-acquired pneumonia (vHAP) in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) carriers is challenging. BioFire® FilmArray® Pneumonia plus Panel (mPCR) can detect bacteria and antibiotic resistance genes, including blaCTX-M, the most common ESBL-encoding gene. Methods: This monocentric, prospective study was conducted on a group of ESBL-E carriers from March 2020 to August 2022. The primary objective was to evaluate the concordance between the results of mPCR and conventional culture performed on respiratory samples of ESBL-E carriers to investigate suspected VAP/vHAP. The secondary objective was to appraise the impact of performing or not mPCR on initial antibiotic therapy adequacy in ESBL-E carriers with confirmed VAP/vHAP. Results: Over the study period, 294 patients with ESBL-E carriage were admitted to the ICU, of who 168 (57%) were mechanically ventilated. (i) Diagnostic performance of mPCR was evaluated in suspected 41 episodes of VAP/vHAP: blaCTX-M gene was detected in 15/41 (37%) episodes, where 9/15 (60%) were confirmed ESBL-E-induced pneumonia. The culture and blaCTX-M were concordant in 35/41 (85%) episodes, and in all episodes where blaCTX-M was negative (n = 26), the culture never detected ESBL-E. (ii) The impact of mPCR on initial antibiotic therapy adequacy was assessed in 95 episodes of confirmed VAP/vHAP (22 episodes were tested with mPCR and 73 without); 47 (49%) episodes were ESBL-E-induced, and 24 (25%) were carbapenem-resistant bacteria-induced. The use of mPCR was significantly associated with higher prescription of adequate empirical antibiotic therapy in the multivariable logistic regression (adjusted odds ratio (aOR) (95% CI) of 7.5 (2.1–35.9), p = 0.004), propensity-weighting (aOR of 5.9 (1.6–22.1), p = 0.008), and matching-cohort models (aOR of 5.8 (1.5–22.1), p = 0.01). Conclusion: mPCR blaCTX-M showed an excellent diagnostic value to rule out the diagnosis of ESBL-E related pneumonia in ESBL-E carriers with suspected VAP/vHAP. In addition, in patients with confirmed VAP/vHAP, a mPCR-based antibiotic therapy was associated with an increased prescription of adequate empirical antibiotic therapy. Performing mPCR on respiratory samples seems to be a promising tool in ESBL-E carriers with suspected vHAP/VAP. However, if mPCR is used in very low pre-test clinical probability of pneumonia, due to the high sensitivity and the rate of overdiagnosed pneumonia, the risk of overconsumption of carbapenem may prevail. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae causes community- and healthcare-associated infections in children and adults. Globally in 2019, an estimated 1.27 million (95% Uncertainty Interval [UI]: 0.91–1.71) and 4.95 million (95% UI: 3.62–6.57) deaths were attributed to and associated with bacterial antimicrobial resistance (AMR), respectively. K. pneumoniae was the second leading pathogen in deaths attributed to AMR resistant bacteria. Furthermore, the rise of antimicrobial resistance in both community- and hospital-acquired infections is a concern for neonates and infants who are at high risk for invasive bacterial disease. There is a limited antibiotic pipeline for new antibiotics to treat multidrug resistant infections, and vaccines targeted against K. pneumoniae are considered to be of priority by the World Health Organization. Vaccination of pregnant women against K. pneumoniae could reduce the risk of invasive K. pneumoniae disease in their young offspring. In addition, vulnerable children, adolescents and adult populations at risk of K. pneumoniae disease with underlying diseases such as immunosuppression from underlying hematologic malignancy, chemotherapy, patients undergoing abdominal and/or urinary surgical procedures, or prolonged intensive care management are also potential target groups for a K. pneumoniae vaccine. A 'Vaccine Value Profile' (VVP) for K. pneumoniae, which contemplates vaccination of pregnant women to protect their babies from birth through to at least three months of age and other high-risk populations, provides a high-level, holistic assessment of the available information to inform the potential public health, economic and societal value of a pipeline of K. pneumoniae vaccines and other preventatives and therapeutics. This VVP was developed by a working group of subject matter experts from academia, non-profit organizations, public–private partnerships, and multi-lateral organizations, and in collaboration with stakeholders from the WHO. All contributors have extensive expertise on various elements of the K. pneumoniae VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information. [ABSTRACT FROM AUTHOR]

Background: Acinetobacter baumannii (A. baumannii) is a common opportunistic pathogen in hospitals that causes nosocomial infection. In order to understand the phenotypic and genotypic characteristics of A. baumannii isolates, we sequenced and analyzed 62 A. baumannii isolates from a hospital in Gansu province. Results: Non-repeated 62 A. baumannii isolates were collected from August 2015 to November 2021. Most isolates (56/62) were resistant to multiple drugs. All the 62 A. baumannii isolates were resistant to aztreonam and contained blaADC-25 gene which exists only on chromosome contigs. The 62 isolates in this study were not clustered in a single clade, but were dispersed among multiple clades in the common genome. Seven sequence types were identified by Multilocus sequence type (MLST) analysis and most isolates (52/62) belonged to ST2. The plasmids were grouped into 11 clusters by MOB-suite. Conclusions: This study furthers the understanding of A. baumannii antimicrobial-resistant genotypes, and may aid in prevention and control nosocomial infection caused by drug-resistant A. baumannii. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii, which is resistant to multiple drugs, is an opportunistic pathogen responsible for severe nosocomial infections. With no antibiotics available, phages have obtained clinical attention. However, since immunocompromised patients are often susceptible to infection, the appropriate timing of administration is particularly important. During this research, we obtained a lytic phage vB_AbaM_P1 that specifically targets A. baumannii. We then assessed its potential as a prophylactic treatment for lung infections caused by clinical strains. The virus experiences a period of inactivity lasting 30 min and produces approximately 788 particles during an outbreak. Transmission electron microscopy shows that vB_AbaM_P1 was similar to the Saclayvirus. Based on the analysis of high-throughput sequencing and bioinformatics, vB_AbaM_P1 consists of 107537 bases with a G + C content of 37.68%. It contains a total of 177 open reading frames and 14 tRNAs. No antibiotic genes were detected. In vivo experiments, using a cyclophosphamide-induced neutrophil deficiency model, tested the protective effect of phage on neutrophil-deficient rats by prophylactic application of phage. The use of phages resulted in a decrease in rat mortality caused by A. baumannii and a reduction in the bacterial burden in the lungs. Histologic examination of lung tissue revealed a decrease in the presence of immune cells. The presence of phage vB_AbaM_P1 had a notable impact on preventing A. baumannii infection, as evidenced by the decrease in oxidative stress in lung tissue and cytokine levels in serum. Our research offers more robust evidence for the early utilization of bacteriophages to mitigate A. baumannii infection. Key points: •A novel Saclayvirus phage infecting A. baumannii was isolated from sewage. •The whole genome was determined, analyzed, and compared to other phages. •Assaying the effect of phage in preventing infection in neutrophil-deficient models. [ABSTRACT FROM AUTHOR]

Background: The human oral and nasal cavities can act as reservoirs for opportunistic pathogens capable of causing acute infection. These microbes asymptomatically colonize the human oral and nasal cavities which facilitates transmission within human populations via the environment, and they routinely possess clinically significant antibiotic resistance genes. Among these opportunistic pathogens, the Klebsiella genus stands out as a notable example, with its members frequently linked to nosocomial infections and multidrug resistance. As with many colonizing opportunistic pathogens, the essential transmission factors influencing the spread of Klebsiella species among both healthy and diseased individuals remain unclear. Results: Here, we explored a possible explanation by investigating the ability of oral and nasal Klebsiella species to outcompete their native microbial community members under in vitro starvation conditions, which could be analogous to external hospital environments or the microenvironment of mechanical ventilators. When K. pneumoniae and K. aerogenes were present within a healthy human oral or nasal sample, the bacterial community composition shifted dramatically under starvation conditions and typically became enriched in Klebsiella species. Furthermore, introducing K. pneumoniae exogenously into a native microbial community lacking K. pneumoniae, even at low inoculum, led to repeated enrichment under starvation. Precise monitoring of K. pneumoniae within these communities undergoing starvation indicated rapid initial growth and prolonged viability compared to other members of the microbiome. K. pneumoniae strains isolated from healthy individuals' oral and nasal cavities also exhibited resistance to multiple classes of antibiotics and were genetically similar to clinical and gut isolates. In addition, we found that in the absence of Klebsiella species, other understudied opportunistic pathogens, such as Peptostreptococcus, increased in relative abundance under starvation conditions. Conclusions: Our findings establish an environmental and microbiome community circumstance that allows for the enrichment of Klebsiella species and other opportunistic pathogens. Klebsiella's enrichment may hinge on its ability to quickly outgrow other members of the microbiome. The ability to outcompete other commensal bacteria and to persist under harsh environmental conditions could be an important factor that contributes to enhanced transmission in both commensal and pathogenic contexts. 2NMbQE6jVjinwr48dC_rNo Video Abstract [ABSTRACT FROM AUTHOR]

Intensive care unit-acquired infections are complicating events in critically ill patients. In this study we analyzed the incidence, microbiological patterns, and outcome in patients with COVID-19 versus influenza in the intensive care unit (ICU). We included all adult patients treated with invasive mechanical ventilation due to (1) COVID-19 between January 2020 and March 2022, and (2) influenza between January 2015 and May 2023 at Sahlgrenska University Hospital, Sweden. Of the 480 participants included in the final analysis, 436 had COVID-19. The incidence rates of ICU-acquired infections were 31.6/1000 and 9.9/1000 ICU-days in the COVID-19 and influenza cohorts, respectively. Ventilator-associated lower respiratory tract infections were most common in both groups. In patients with COVID-19, corticosteroid treatment was associated with an increased risk of ICU-acquired infections and with higher 90-day mortality in case of infection. Furthermore, ICU-acquired infection was associated with a prolonged time in the ICU, with more difficult-to-treat gram-negative infections in late versus early ventilator-associated lower respiratory tract infections. Further research is needed to understand how the association between corticosteroid treatment and incidence and outcome of ICU-acquired infections varies across different patient categories. [ABSTRACT FROM AUTHOR]

Severe acute respiratory infections, such as community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia, constitute frequent and lethal pulmonary infections in the intensive care unit (ICU). Despite optimal management with early appropriate empiric antimicrobial therapy and adequate supportive care, mortality remains high, in part attributable to the aging, growing number of comorbidities, and rising rates of multidrug resistance pathogens. Biomarkers have the potential to offer additional information that may further improve the management and outcome of pulmonary infections. Available pathogen-specific biomarkers, for example, Streptococcus pneumoniae urinary antigen test and galactomannan, can be helpful in the microbiologic diagnosis of pulmonary infection in ICU patients, improving the timing and appropriateness of empiric antimicrobial therapy since these tests have a short turnaround time in comparison to classic microbiology. On the other hand, host-response biomarkers, for example, C-reactive protein and procalcitonin, used in conjunction with the clinical data, may be useful in the diagnosis and prediction of pulmonary infections, monitoring the response to treatment, and guiding duration of antimicrobial therapy. The assessment of serial measurements overtime, kinetics of biomarkers, is more informative than a single value. The appropriate utilization of accurate pathogen-specific and host-response biomarkers may benefit clinical decision-making at the bedside and optimize antimicrobial stewardship. [ABSTRACT FROM AUTHOR]

Introduction: Lysosomal storage diseases (LSDs) constitute a group of metabolic disorders characterized by the accumulation of substrates within lysosomes. For their treatment, disease-specific enzyme replacement therapy (ERT) is employed. In cases of hypersensitivity reactions that may occur during these treatments, desensitization of enzyme therapy becomes necessary. Repeated desensitization procedures may result some degree of tolerance. This study presents cases of patients received abbreviated desensitization protocols following repeated desensitization procedures. Method: During the period between September 2019 and January 2024, pediatric patients who experienced anaphylactic reactions to ERT and whose desensitization protocols were abbreviated after receiving uneventful treatment with desensitization for at least a year were included in the study. Result: Six patients, four with Pompe disease, one with mucopolysaccharidosis type 2, and one with mucopolysaccharidosis type 4, had been receiving uninterrupted ERT by desensitization for at least 1 year. The mean age of the patients was 117.6 months (median: 104.5, IQR: 85.2–144). All patients experienced anaphylaxis as the initial reaction. Skin and intradermal tests were repeated on patients prior to protocol abbreviation. Premedication previously given to all patients was discontinued, and desensitization protocols were subsequently shortened by increasing the infusion rate and/or reducing the number of steps. Conclusion: The study investigated patients whose desensitization protocols were abbreviated. It demonstrated that some level of tolerance could be attained through repeated applications. This approach aims to identify concise, safe, and efficient protocols, thereby reducing hospitalizations, nosocomial infections, and treatment expenses. [ABSTRACT FROM AUTHOR]

AbstractThe increasing global incidence of multidrug-resistant (MDR) bacterial infections threatens public health and compromises various aspects of modern medicine. Recognising the urgency of this issue, the World Health Organisation has prioritised the development of novel antimicrobials to combat ESKAPEE pathogens. Comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli, such pathogens represent a spectrum of high to critical drug resistance, accounting for a significant proportion of hospital-acquired infections worldwide. In response to the waning efficacy of antibiotics against these resilient pathogens, phage therapy (PT) has emerged as a promising therapeutic strategy. This review provides a comprehensive summary of clinical research on PT and explores the translational journey of phages from laboratory settings to clinical applications. It examines recent advancements in pre-clinical and clinical developments, highlighting the potential of phages and their proteins, alone or in combination with antibiotics. Furthermore, this review underlines the importance of establishing safe and approved routes of phage administration to patients. In conclusion, the evolving landscape of phage therapy offers a beacon of hope in the fight against MDR bacterial infections, emphasising the imperative for continued research, innovation and regulatory diligence to realise its full potential in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Nosocomial infections are a worldwide healthcare issue, especially in intensive care units (ICUs), and they had a prevalence of 21.1% in 2023 in Spain. Numerous predisposing risk factors have been identified, with the most relevant being invasive techniques, including renal replacement therapies (RRTs). Several outstanding strategies have been published that prevent or reduce their incidence, including the nationwide ZERO in Spain, which consists of structured guidelines to be implemented to tackle this problem. One of these strategies, which is defined as 'highly recommended' in these projects, is selective digestive decontamination (SDD). The main aim of this study is to compare the incidences of ICU-acquired infections, including those due to multidrug-resistant bacteria (MDRB), in two cohorts of RRT with or without SDD. Methods: We conducted a multicenter, prospective, observational study at two tertiary hospitals in Spain. In total, 140 patients treated with RRT were recruited based on their exposure to SDD. Surveillance microbiological samples and nosocomial infection risk factors were obtained. Infection rates per 1000 days of exposure and the MDRB incidence density ratio were determined. Results: SDD statistically significantly reduced RRT-associated nosocomial infections (OR: 0.10, 95% CI: (0.04–0.26)) and the MDRB incidence density ratio (IDR: 0.156, 95% CI = 0.048–0.506). However, mechanical ventilation (OR: 7.91, 95% CI: (2.54–24.66)) and peripheral vascular disease (OR: 3.17, 95% CI: (1.33–7.56)) were significantly associated with increases in infections. Conclusions: Our results favor the use of SDD in ICU patients with renal failure undergoing CRRT as a tool for infection control. [ABSTRACT FROM AUTHOR]

Carbapenemase-producing Enterobacterales are increasingly being recognized in nosocomial infections. The performance of a flow cytometry-based rapid assay for their detection and differentiation was evaluated. This is a disruptive phenotypic technology, phenotypic and growth-independent, that searches for the lesions produced by drugs acting on cells after a short incubation time. Overall, 180 Gram-negative bacteria were studied, and results were compared with those obtained molecularly by PCR and phenotypically by 'KPC, MBL and OXA-48 Confirm Kit'. This phenotypic method was used as reference for comparison purposes. Susceptibility to carbapenems (imipenem, meropenem, and ertapenem) was determined by standard broth microdilution. Overall, 112 isolates (62.2%) were carbapenemase producers, 41 KPCs, 36 MβLs, and 31 OXA-48, and 4 strains were KPC + MβL co-producers. Sixty-eight isolates were carbapenemase-negative. The percentage of agreement, sensitivity, and specificity were calculated according to ISO 20776-2:2021. The FASTinov assay showed 97.7% agreement with the reference method for carbapenemase detection. Discrepant flow cytometry results were obtained in four isolates compared with both reference and PCR results. The sensitivity and specificity of this new technology were 95.3% and 98.5%, respectively, for KPCs, 97.6% and 99.3% for MβLs, and 96.9% and 98% for OXA-48 detection. In conclusion, we describe a rapid flow cytometry assay with high accuracy for carbapenemase detection and the differentiation of various carbapenemases, which should impact clinical microbiology laboratories and patient management. [ABSTRACT FROM AUTHOR]

Background Desirability of outcome ranking (DOOR) is an innovative approach to clinical trial design and analysis that uses an ordinal ranking system to incorporate the overall risks and benefits of a therapeutic intervention into a single measurement. Here we derived and evaluated a disease-specific DOOR endpoint for registrational trials for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP). Methods Through comprehensive examination of data from nearly 4000 participants enrolled in six registrational trials for HABP/VABP submitted to the Food and Drug Administration (FDA) between 2005 and 2022, we derived and applied a HABP/VABP specific endpoint. We estimated the probability that a participant assigned to the study treatment arm would have a more favorable overall DOOR or component outcome than a participant assigned to comparator. Results DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 48.3% to 52.9% and were not statistically different. There were no significant differences between treatment arms in the component analyses. Although infectious complications and serious adverse events occurred more frequently in ventilated participants compared to non-ventilated participants, the types of events were similar. Conclusions Through a data-driven approach, we constructed and applied a potential DOOR endpoint for HABP/VABP trials. The inclusion of syndrome-specific events may help to better delineate and evaluate participant experiences and outcomes in future HABP/VABP trials and could help inform data collection and trial design. [ABSTRACT FROM AUTHOR]

Background: Aminoglycosides have been a cornerstone of the treatment of nosocomial infections caused by Pseudomonas aeruginosa for over 80 years. However, escalating emergence of resistance poses a significant challenge. Therefore, this study aimed to investigate the prevailing patterns of aminoglycoside resistance among clinical isolates of P. aeruginosa in Iran; as well as the underlying resistance mechanisms observed in patients referred to Ardabil hospitals. Methods: A total of 200 isolates from five hospitals were evaluated. The resistance profiles of P. aeruginosa isolates to tobramycin, amikacin, and netilmicin were determined using the disk diffusion method. The capacity of aminoglycoside-resistant isolates to form biofilms was assessed through a phenotypic assay, and the results were confirmed using the gene amplification technique. The presence of genes associated with aminoglycoside resistance was detected using polymerase chain reaction (PCR). Quantitative reverse transcription PCR (qRT-PCR) was performed to measure the expression levels of genes encoding the MexXY-OprM efflux pump and PhoPQ two-component system (TCS). Results: The prevalence of aminoglycoside-resistant P. aeruginosa isolates was 48%, with 94.7% demonstrating multidrug resistance (MDR). All aminoglycoside-resistant P. aeruginosa strains exhibited biofilm-forming capabilities and harbored all the genes associated with biofilm production. Among the nine genes encoding 16S rRNA methylase and aminoglycoside-modifying enzymes, three genes were detected in these isolates: aac(6')-Ib (85.4%), ant(2")-Ia (18.7%), and aph(3')-VI (3.1%). Additionally, all aminoglycoside-resistant P. aeruginosa isolates carried mexY and phoP genes, although the expression levels of mexY and phoP were 75% and 87.5%, respectively. Conclusion: Given the considerably high prevalence of aminoglycoside-resistant P. aeruginosa strains, urgent measures are warranted to transition towards the use of novel aminoglycosides and to uphold vigilant surveillance of resistance patterns. [ABSTRACT FROM AUTHOR]

Background: Nosocomial infections with heavy disease burden are becoming a major threat to the health care system around the world. Through long-term, systematic, continuous data collection and analysis, Nosocomial infection surveillance (NIS) systems are constructed in each hospital; while these data are only used as real-time surveillance but fail to realize the prediction and early warning function. Study is to screen effective predictors from the routine NIS data, through integrating the multiple risk factors and Machine learning (ML) methods, and eventually realize the trend prediction and risk threshold of Incidence of Nosocomial infection (INI). Methods: We selected two representative hospitals in southern and northern China, and collected NIS data from 2014 to 2021. Thirty-nine factors including hospital operation volume, nosocomial infection, antibacterial drug use and outdoor temperature data, etc. Five ML methods were used to fit the INI prediction model respectively, and to evaluate and compare their performance. Results: Compared with other models, Random Forest showed the best performance (5-fold AUC = 0.983) in both hospitals, followed by Support Vector Machine. Among all the factors, 12 indicators were significantly different between high-risk and low-risk groups for INI (P < 0.05). After screening the effective predictors through importance analysis, prediction model of the time trend was successfully constructed (R2 = 0.473 and 0.780, BIC = -1.537 and -0.731). Conclusions: The number of surgeries, antibiotics use density, critical disease rate and unreasonable prescription rate and other key indicators could be fitted to be the threshold predictions of INI and quantitative early warning. [ABSTRACT FROM AUTHOR]

Introduction: The presence of secondary infections in critically ill patients and antibiotic resistance are often determining factors in the clinical evolution of these patients. Objective: To describe the pathogens isolated in blood cultures and tracheal secretion cultures in ICU patients with COVID-19 and to evaluate the association between the presence of secondary infections and 60-day mortality. Methods: Retrospective analytical cohort study conducted in 273 adults admitted to the ICU with COVID-19 at the Subred Integrada de Servicios de Salud del Sur - Hospital El Tunal, Bogotá, Colombia between April and December 2020. Data from records of blood or tracheal secretion cultures were collected . A bivariate analysis was performed using a Cox proportional-hazards regression model to assess the association between the development of secondary infections and 60-day mortality. Results: At least one positive blood culture was reported in 96/511 patients (18.8%). Of the 214 blood cultures performed within 48 hours after ICU admission, 7.7% were positive. A total of 127 germs were isolated from blood cultures - mostly gram-negative bacteria (61.4%) - followed by fungi (25.2%). Additionally, 39.5% were multidrug-resistant, and carbapenem resistance was the most common antibiotic resistance pattern (33.3% of all gram-negative bacteria isolates). Finally, in this cohort, the presence of secondary infections was not associated with 60-day mortality (HR: 1.012, 95%CI: 0.721- 1.420; p= 0.946). Conclusions: Although the prevalence of superinfection was moderately high, the prevalence of coinfection was low. Gram-negative bacteria were predominant, and almost one third of the germs were multidrug-resistant. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Coronavirus disease 2019 (COVID-19) caused morbidity and mortality worldwide. Besides the acute effects, subacute and long-term effects are defined as long-COVID causing morbidity. The intensive care unit (ICU) data of long-COVID-19 cases were evaluated with the participation of 11 centers. MATERIAL AND METHODS: Study was designed by Turkish Thoracic Society Respiratory Failure and Intensive Care Working Group to evaluate long COVID-19 patients. All patients followed up in the ICU with long-COVID diagnosis were included in point prevelance study. RESULTS: A total of 41 long COVID-19 patients from 11 centers were included in the study. Half of the patients were male, mean age was 66 ± 14, body mass index was 27 ± 5. Hypertension, diabetes mellitus, lung cancer, malignancy, and heart failure rates were 27%, 51%, 34%, 34%, and 27%, respectively. Eighty percent had received COVID vaccine. Patients had moderate hypoxemic respiratory failure. APACHE II, SOFA score was 18 (14-26), 6 (3-8), respectively. Forty-six percent received invasive mechanical ventilator support, 42% were sepsis, 17% were septic shock. Bilateral (67%), interstitial involvement (37%) were most common in chest x-ray. Fibrosis (27%) was detected in thorax tomography. Seventy-one percent of patients received antibiotherapy (42% carbapenem, 22% linezolid). Sixty-one percent of the patients received corticosteroid treatment. CONCLUSION: More than half of the patients had pneumonia and the majority of them used broad-spectrum antibiotics. Presence of comorbidities and malignancies, intensive care severity scores, intubation, and sepsis rates were high. Receiving corticosteroid treatment and extensive bilateral radiologic involvement due to COVID-19 might be the reasons for the high re-admission rate for the ICUs. [ABSTRACT FROM AUTHOR]

Tetracyclines constitute a unique class of antibiotic agents, widely prescribed for both community and hospital infections due to their broad spectrum of activity. Acting by disrupting protein synthesis through tight binding to the 30S ribosomal subunit, their interference is typically reversible, rendering them bacteriostatic in action. Resistance to tetracyclines has primarily been associated with changes in pump efflux or ribosomal protection mechanisms. To address this challenge, tetracycline molecules have been chemically modified, resulting in the development of third-generation tetracyclines. These novel tetracyclines offer significant advantages in treating infections, whether used alone or in combination therapies, especially in hospital settings. Beyond their conventional antimicrobial properties, research has highlighted their potential non-antibiotic properties, including their impact on immunomodulation and malignancy. This review will focus on third-generation tetracyclines, namely tigecycline, eravacycline, and omadacycline. We will delve into their mechanisms of action and resistance, while also evaluating their pros and cons over time. Additionally, we will explore their therapeutic potential, analyzing their primary indications of prescription, potential future uses, and non-antibiotic features. This review aims to provide valuable insights into the clinical applications of third-generation tetracyclines, thereby enhancing understanding and guiding optimal clinical use. [ABSTRACT FROM AUTHOR]

The Gram-negative ESKAPE bacterium Pseudomonas aeruginosa has become a pathogen of serious concern due its extensive multi-drug resistance (MDR) profile, widespread incidences of hospital-acquired infections throughout the United States, and high occurrence in wound infections suffered by warfighters serving abroad. Bacteriophage (phage) therapy has received renewed attention as an alternative therapeutic option against recalcitrant bacterial infections, both as multi-phage cocktails and in combination with antibiotics as synergistic pairings. Environmental screening and phage enrichment has yielded three lytic viruses capable of infecting the MDR P. aeruginosa strain PAO1. Co-administration of each phage with the carbapenem antibiotics ertapenem, imipenem, and meropenem generated enhanced overall killing of bacteria beyond either phage or drug treatments alone. A combination cocktail of all three phages was completely inhibitory to growth, even without antibiotics. The same 3× phage cocktail also disrupted PAO1 biofilms, reducing biomass by over 75% compared to untreated biofilms. Further, the phage cocktail demonstrated broad efficacy as well, capable of infecting 33 out of 100 diverse clinical isolate strains of P. aeruginosa. Together, these results indicate a promising approach for designing layered medical countermeasures to potentiate antibiotic activity and possibly overcome resistance against recalcitrant, MDR bacteria such as P. aeruginosa. Combination therapy, either by synergistic phage-antibiotic pairings, or by phage cocktails, presents a means of controlling mutations that can allow for bacteria to gain a competitive edge. [ABSTRACT FROM AUTHOR]

Introduction: Hospital-acquired infections (HAIs) after stroke are associated with additional morbidity and mortality, but whether HAIs increase long-term cognitive decline in stroke patients is unknown. We hypothesized that older adults with incident stroke with HAI experience faster cognitive decline than those having stroke without HAI and those without stroke. Methods: We performed a longitudinal analysis in the population-based prospective Cardiovascular Health Study. Medicare-eligible participants aged ≥65 years with and without incident stroke had cognition assessed annually. HAIs were assessed by hospital discharge codes. Global cognitive function was assessed annually by the Modified Mini-Mental State Examination (3MSE) and executive function by the Digit Symbol Substitution Test (DSST). We used linear mixed models to estimate the mean decline and 95% confidence intervals (95% CI) for 3MSE and DSST scores by incident stroke and HAI status, adjusted for demographics and vascular risk factors. Results: Among 5,443 participants ≥65 years without previous history of stroke, 393 participants had stroke with HAI (SI), 766 had a stroke only (SO), and 4,284 had no stroke (NS) throughout a maximum 9-year follow-up. For 3MSE, compared with NS participants, SO participants had a similar adjusted mean decline (additional 0.08 points/year, 95% CI: −0.15, 0.31), while SI participants had a more rapid decline (additional 0.28 points/year, 95% CI: 0.16, 0.40). Adjusted mean decline was 0.20 points/year faster (95% CI: −0.05, 0.45) among SI than SO participants. For DSST, compared with NS participants, SO participants had a faster adjusted mean decline (additional 0.17 points/year [95% CI: 0.003, 0.33]), as did SI participants (additional 0.27 points/year [95% CI: 0.19, 0.35]). Conclusion: Stroke, when accompanied by HAI, leads to a faster long-term decline in cognitive ability than in those without stroke. The clinical and public health implications of the effect of infection on post-stroke cognitive decline warrant further attention. [ABSTRACT FROM AUTHOR]

Purpose: To investigate bacterial contamination of indirect ophthalmoscopes and condensing lenses used in three UK veterinary referral centers, and the impact of an implemented cleaning protocol. Methods: Bacteriology samples from 10 indirect ophthalmoscopes and 10 condensing lenses were taken at each center (n = 30 T0), before initiating one of three cleaning frequencies (every 2 weeks/once weekly/daily) for 28 days. The most contaminated indirect ophthalmoscope and condensing lens from each center were re‐sampled 30 min prior to (T1; n = 9) and 30 min after (T2; n = 9) the final clean. Sensitivity testing was completed using MIC. Results: Seventy‐three isolates representing 15 different bacterial populations (genus/species) were cultured from 36 of 48 (75%) swabs tested. The most frequently cultured isolates were Staphylococcus spp. 30%, Micrococcus 22%, and Bacillus 14%. Pseudomonas aeruginosa, Pantoea, and Staphylococcus pseudintermedius demonstrated resistance to >50% of antibiotics against which they were tested. Eighty‐three percent of T0 samples (54 isolates across 11 species, median 2 isolates/swab), all T1 samples (15 isolates across 8 species, median 2 isolates/swab), and 22% of T2 samples (4 isolates across 4 species, median 0 isolates/swab) were contaminated. Head contact points were most contaminated irrespective of time point. A T1 sample was 57 times more likely (95% CI: 2.4–1376) to have a positive culture than a T2 sample (p =.01). Conclusions: Baseline contamination was high, representing a potential source of nosocomial infection in ophthalmic patients and handlers of diagnostic equipment. No center implemented a cleaning protocol prior to this study. Routine cleaning reduces bacterial contamination. [ABSTRACT FROM AUTHOR]

Background: Hospital-acquired infections (HAIs) are a significant concern in intensive care units (ICUs), leading to increased morbidity, mortality, and healthcare costs. This study aims to determine the incidence, types, risk factors, and outcomes of HAIs in the ICUs. Materials and Methods: A prospective observational study was conducted, including 100 patients admitted to the ICUs for more than 48 hours. Data on patient demographics, clinical details, and infection monitoring were collected. Statistical analysis, including univariate and multivariate methods, was used to identify risk factors for HAIs. Results: The incidence of HAIs was 30%, with Ventilator-Associated Pneumonia (VAP) being the most common (40%). Other infections included Catheter-Associated Urinary Tract Infections (CAUTIs) (30%), Central LineAssociated Bloodstream Infections (CLABSIs) (20%), and Surgical Site Infections (SSIs) (5%). Significant risk factors for HAIs included prolonged ICU stay (p = 0.02), use of invasive devices (p = 0.01), broad-spectrum antibiotic use (p = 0.03), and comorbidities (p = 0.04). Patients with HAIs had longer ICU stays (15 vs. 8 days, p = 0.01), higher mortality rates (25% vs. 10%, p = 0.03), and more complications (30% vs. 5%, p = 0.02). Conclusion: The study highlights a high incidence of HAIs in ICUs, with significant impacts on patient outcomes. Targeted interventions and stringent infection control measures are essential to mitigate these infections [ABSTRACT FROM AUTHOR]

Aims Urinary tract infections are the most common hospital-acquired infection, 80% of which are associated with catheterization. Diagnostic methods may influence the reported identities of these pathogens, and phenotypic testing under laboratory conditions may not reflect infection phenotypes. This study aimed to evaluate the efficacy of diagnostic methods and whether medium composition alters phenotypes by characterizing catheter-associated urinary tract infection isolates from a UK hospital. Methods and results We compared five bacterial identification methods, including biochemical testing, matrix-assisted laser desorption/ionization biotyping, and genome sequencing, finding differences in genus- or species-level identifications. Antibiotic susceptibility comparisons between phenotypic assays and genomic predictions showed high agreement only in multidrug-resistant strains. To determine whether growth rate and biofilm formation were affected by medium composition, strains were grown in both planktonic and biofilm states. Low planktonic growth and significant biofilm formation were observed in artificial urine compared to rich laboratory media, underscoring the importance of assay design. Conclusions This study highlights the risks of relying on a single diagnostic method for species identification, advocating for whole-genome sequencing for accuracy. It emphasizes the continued importance of phenotypic methods in understanding antibiotic resistance in clinical settings and the need for characterization conditions that mirror those encountered by pathogens in the body. [ABSTRACT FROM AUTHOR]

Introduction: Bacterial meningitis poses significant medical challenges due to its acute inflammatory nature and potential for severe neurological complications, emphasizing the need for prompt diagnosis and treatment. Limited data exists on its epidemiology and antimicrobial resistance trends among hospitalized patients in Saudi Arabia. This study aimed to investigate these factors at a tertiary care hospital over six years. Methods: A retrospective analysis was conducted on cerebrospinal fluid samples results from 222 bacterial meningitis cases among hospitalized patients between 2018 and 2023. Demographic, clinical, microbiological data, and antibiotic susceptibility patterns were collected and analyzed. Results: Pseudomonas aeruginosa (43%) was the predominant pathogen isolated. Neonates (16%) and children (47%) were most affected population. Nosocomial meningitis accounted for 92% of cases, mainly in the intensive care settings (50.45%). Extended-spectrum beta-lactamase was the leading resistance pattern (12.2%). Seasonal variation was observed, with a peak incidence in October-November. Conclusion: The study highlights the substantial burden of bacterial meningitis among hospitalized patients, especially among high-risk groups. Emerging antimicrobial resistance emphasizes the need for optimized surveillance and stewardship. Future prospective research employing molecular techniques across multiple centers in the country is warranted to enhance understanding and guide public health strategies in Saudi Arabia. [ABSTRACT FROM AUTHOR]

Enterococci are a group of microorganisms that have a controversial position from some scientific points of view. The species of the greatest clinical importance are E. faecalis and E. faecium, which are common agents of nosocomial infections. However, enterococci also have important applications in the dairy industry, as they are used as non-starter lactic acid bacteria (NSLAB) in a variety of cheeses, especially artisanal cheeses. The aim of this study was to determine the presence of representatives from the Enterococcus genus using PCR and MALDI-TOF MS methods on samples of raw milk, processing environment swabs, and cheese from four different artisanal dairy plants in Slovakia. Among the 136 isolates of enterococci, 9 species of genus Enterococci (E. faecalis, E. faecium, E. durans, E. devriesi, E. hirae, E. italicus, E. casseliflavus, E. malodoratus, and E. gallinarum) were identified and were tested for their antimicrobial resistance (AMR) to 8 antibiotics (amoxicillin, penicillin, ampicillin, erythromycin, levofloxacin, vancomycin, rifampicin, and tetracycline); most of them were resistant to rifampicin (35.3%), ampicillin (22.8%), and tetracycline (19.9%). A PCR analysis of vanA (4.41%) and tetM (14.71%) revealed that antimicrobial resistance genes were present in not only phenotypic resistant isolates of enterococci but also susceptible isolates. The investigation of antimicrobial resistance in enterococci during the cheesemaking process can be a source of valuable information for public health in the concept of "One Health". [ABSTRACT FROM AUTHOR]

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease that often requires hospitalization. Most hospitalizations are due to infections and/or disease activity, for which several risk factors have been described in non-Mestizo patients. Objective: To identify risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). Methods: This was an observational case-control study of patients with SLE in San Luis Potosí, Mexico, evaluated from January 2019 to October 2020. We compared hospitalized lupus patients with non-hospitalized lupus patients. We used descriptive statistics and logistic regression to describe potential risk factors. Results: Of a total of 202 patients, 89 (45.1%) were hospitalized; these patients were younger, had shorter disease duration, higher disease activity scores (systemic lupus erythematosus disease activity index-SLEDAI), and more accumulated damage than non-hospitalized patients. The primary reasons for hospitalization were disease activity (60.7%), kidney disease, infection, and drug toxicity (5.6%). Multivariate analysis revealed several risk factors associated with hospitalization, including elevated creatinine, C-reactive protein, neutrophil levels, and constitutional symptoms, while prolonged international normalized ratio (INR), longer stay in the intensive care unit (ICU), and vasopressor use were associated with mortality. The use of antimalarials was a protective factor against hospitalization. Survival analysis revealed that patients with hospital-acquired infections had a lower probability of survival. Conclusions: Disease activity was the most common reason for hospitalization; kidney, constitutional, and hematological factors were associated with hospitalization; and the use of antimalarial was a protective factor for hospitalization. [ABSTRACT FROM AUTHOR]

Recently, a large number of nosocomial infections have been caused by an emerging pathogen that is rising as a worldwide issue in human health: Candida auris. This yeast is considered resistant to antifungals of the first-line therapies, and consequently it is related to morbidity and mortality. Therefore, the aim of this research was to determine the in vitro anti-C. auris activity against twenty-three resistant clinical strains of different essential oils (EOs), pure or in combination with traditional antifungal agents, mainly caspofungin, fluconazole, micafungin and 5-flucytosine. Broth dilution assay was performed to evaluate the fungistatic and fungicidal effectiveness of fifteen EOs towards all the C. auris isolates. The data demonstrated that EOs were able to prevent C. auris growth, with MIC values ranging from 0.03 to 1% for the efficacious EOs (thyme, cinnamon, geranium, clove bud, lemongrass and mentha of Pancalieri), whereas the MICs were >1% for the ineffective ones. Thereafter, the six most effective EOs were used to perform the checkerboard experiments by assaying simultaneously the activity of EOs and traditional antifungals towards two selected strains. The most promising synergic combinations towards C. auris, depending on the isolate, were those with micafungin and geranium, thyme, cinnamon, lemongrass or clove bud EOs, with fluconazole and mentha of Pancalieri EO, and with 5-flucytosine and mentha of Pancalieri EO. These EOs and their combinations with antifungal drugs may provide a useful therapeutic alternative that could reduce the dose of the individual components, limiting the overall side effects. These associations might be a prospective option for the future treatment of infections, thus helping to overcome the challenging issue of resistance in C. auris. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae, a member of the ESKAPE pathogen group, is a prominent cause of hospital-acquired infections. The WHO has recognized carbapenem-resistant K. pneumoniae as a critical-one priority pathogen. These resilient superbugs have the ability to form biofilms and present a significant global threat. In the present study, we isolated and characterized a bacteriophage SAKp02, from hospital sewage, infectious to carbapenem-resistant K. pneumoniae patient isolates. SAKp02 could infect 43 of 72 clinical isolates, indicating a broad host spectrum. Whole genome analysis classified SAKp02 within the family Casjensviridae, with a 59,343 bp genome encoding 82 ORFs. Comparative genomic analysis revealed significant differences between SAKp02 and its closest viruses, indicating a distinct genetic makeup positioning it as a novel phage strain within the lineage. The SAKp02 genome comprises bacteriolytic enzymes, including holin, endolysin, and phage depolymerase, crucial for bacterial lysis and biofilm disruption. It reduced biofilm biomass by over threefold compared to the control and eradicated 99% of viable cells within a 4 h treatment period. Scanning electron microscopy corroborated the ability of the phage to dismantle biofilm matrices and lyse bacterial cells. Safe and effective treatments are warranted, and hence, the fully characterized lytic phages with therapeutic potential against drug-resistant clinical isolates of bacteria are needed. Our study is the first to report the antibacterial and antibiofilm activity of Casjensviridae phages, and our discovery of a novel K. pneumoniae phage broadens the arsenal against the bacteria. [ABSTRACT FROM AUTHOR]

Corynebacterium striatum occasionally causes nosocomial infections, such as catheter-related bloodstream infection and pneumonia; however, C. striatum- related infective endocarditis or septic arthritis is uncommon. We present the case of an 85-year-old woman with infective endocarditis at the native valve and septic arthritis at the native shoulder joint caused by C. striatum. The patient was admitted for a 10-day history of fever and right shoulder pain. She had no history of artificial device implantation, injury, arthrocentesis, or hospitalization. A physical examination revealed conjunctival petechiae, a systolic heart murmur, and right shoulder joint swelling. C. striatum was observed in two blood culture sets. Transesophageal echocardiography revealed vegetation in the right aortic coronary cusp. Arthrocentesis at the right shoulder aspirated pyogenic fluid and C. striatum was detected in the culture. The patient was diagnosed with infective endocarditis and septic arthritis caused by C. striatum, and ampicillin was administered based on antimicrobial susceptibility test results. The patient's condition was initially stable; however, she developed pulmonary congestion on day 56 and eventually died. An autopsy demonstrated perforation of the aortic left coronary cusp with vegetation. C. striatum may cause native valve endocarditis and native joint septic arthritis. [ABSTRACT FROM AUTHOR]

Background: Staphylococcus aureus, a commensal bacterium, colonizes the skin and mucous membranes of approximately 30% of the human population. Apart from conventional resistance mechanisms, one of the pathogenic features of S. aureus is its ability to survive in a biofilm state on both biotic and abiotic surfaces. Due to this characteristic, S. aureus is a major cause of human infections, with Methicillin-Resistant Staphylococcus aureus (MRSA) being a significant contributor to both community-acquired and hospital-acquired infections. Results: Analyzing non-repetitive clinical isolates of MRSA collected from seven provinces and cities in China between 2014 and 2020, it was observed that 53.2% of the MRSA isolates exhibited varying degrees of ability to produce biofilm. The biofilm positivity rate was notably high in MRSA isolates from Guangdong, Jiangxi, and Hubei. The predominant MRSA strains collected in this study were of sequence types ST59, ST5, and ST239, with the biofilm-producing capability mainly distributed among moderate and weak biofilm producers within these ST types. Notably, certain sequence types, such as ST88, exhibited a high prevalence of strong biofilm-producing strains. The study found that SCCmec IV was the predominant type among biofilm-positive MRSA, followed by SCCmec II. Comparing strains with weak and strong biofilm production capabilities, the positive rates of the sdrD and sdrE were higher in strong biofilm producers. The genetic determinants ebp, icaA, icaB, icaC, icaD, icaR, and sdrE were associated with strong biofilm production in MRSA. Additionally, biofilm-negative MRSA isolates showed higher sensitivity rates to cefalotin (94.8%), daptomycin (94.5%), mupirocin (86.5%), teicoplanin (94.5%), fusidic acid (81.0%), and dalbavancin (94.5%) compared to biofilm-positive MRSA isolates. The biofilm positivity rate was consistently above 50% in all collected specimen types. Conclusions: MRSA strains with biofilm production capability warrant increased vigilance. [ABSTRACT FROM AUTHOR]

Background: Infections due to Citrobacter species are increasingly observed in hospitalized patients and are often multidrug-resistant. Yet, the magnitude and burden of Citrobacter spp. resistance in the hospital setting have not been reported. We aimed to evaluate the epidemiology of Citrobacter spp. infections among hospitalized patients, their main resistance patterns and Citrobacter spp. involvement in hospital outbreaks. Methods: We conducted a systematic review and meta-analysis of published literature (PROSPERO registration Jan-2023, CRD42023390084). We searched Embase, Medline and grey literature for studies on hospitalized patients diagnosed with Citrobacter spp. infections, and nosocomial outbreaks due to Citrobacter spp. published during the years 2000–2022. We included observational, interventional, surveillance studies and outbreak reports. Outcomes of interest were the frequency of Citrobacter spp. infections among hospitalized patients and 3rd generation cephalosporin and/or carbapenem resistance percentages in these infections. We used random-effects models to generate pooled outcome estimates and evaluated risk of bias and quality of reporting of outbreaks. Results: We screened 1609 deduplicated publications, assessed 148 full-texts, and included 41 studies (15 observational, 13 surveillance and 13 outbreak studies). Citrobacter spp. urinary tract- and bloodstream infections were most frequently reported, with Citrobacter freundii being the main causative species. Hospital-acquired infection occurred in 85% (838/990) of hospitalized patients with Citrobacter infection. After 2010, an increasing number of patients with Citrobacter spp. infections was reported in observational studies. Pooled frequency estimates for Citrobacter spp. infections could not be generated due to lack of data. The pooled prevalence of ESBL and carbapenemase producers among Citrobacter isolates were 22% (95%CI 4–50%, 7 studies) and 18% (95%CI 0–63%, 4 studies), respectively. An increased frequency of reported Citrobacter outbreaks was observed after 2016, with an infection/colonization ratio of 1:3 and a case-fatality ratio of 7% (6/89 patients). Common outbreak sources were sinks, toilets, contaminated food and injection material. Implemented preventive measures included environmental cleaning, isolation of positive patients and reinforcement of hand hygiene. Only seven out of 13 outbreaks (54%) were definitively controlled. Conclusion: This review highlights the clinical importance of endemic and epidemic Citrobacter spp. in healthcare settings. As an emerging, multidrug‑resistant nosocomial pathogen it requires heightened awareness and further dedicated surveillance efforts. [ABSTRACT FROM AUTHOR]