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Background: Hospital-acquired pneumonia (HAP) is the most common hospital-acquired infection (HAI). HAP is associated with a high burden of morbidity and mortality, but the diagnosis is difficult to establish and the incidence uncertain. Methods: Patients aged ≥ 18 years hospitalised with radiologically verified non-ventilator hospital acquired pneumonia (NV-HAP) during 2018 were retrospectively identified at Drammen Hospital, a Norwegian general hospital. Infectious Diseases Society of America and the American Thoracic Society's definition of HAP was used. Results: In total 119 cases of NV-HAP were identified among 27,701 admissions. The incidence was 4.3 per 1000 admissions and 1.2 per 1000 patient-days. The median age was 74 years, 63% were male and median Charlson comorbidity index was 5. Coronary heart disease (42%) was the most common comorbidity. Median length of stay was 17.2 days. A blood culture was obtained in 53.8% of patients, while samples from lower airways were seldom obtained (10.9%). In-hospital mortality was 21%, accumulated 30-day mortality was 27.7% and accumulated 1-year mortality was 39.5%. Thirty-day readmission rate among survivors was 39.4%. Conclusion: NV-HAP was present in approximately 1 in 250 hospitalisations, most had multiple comorbidities, and 1 in 5 died in hospital. Although thorough microbiological sampling is recommended when NV-HAP is suspected, our data indicate that airway sampling is infrequent in clinical practice. Our findings underscore the need to develop microbiological diagnostic strategies to achieve targeted antimicrobial treatment that may improve patient outcomes and reduce broad-spectrum antibiotic usage. [ABSTRACT FROM AUTHOR]

Objectives: The emergence of deadly infections such as methicillin-resistant Staphylococcus aureus and COVID-19 (SARS-CoV-2) highlights the need for effective infection control (IC) procedures in healthcare facilities. The aim of the study was to assess the knowledge, attitudes, and practices (KAP) of healthcare workers (HCWs) on IC procedures. Methods: A cross-sectional survey was conducted among HCWs in western Jamaica from May to August 2015. A questionnaire based on the Jamaican Health Facilities Infection and Control Policies and Procedures Manual was used to collect data on staff training in IC, and their KAP of IC. Summary statistics, ANOVA, and multiple linear regression were applied for data analyses. Results: Among 227 participants, the mean knowledge scores were statistically higher among the younger HCWs, Physicians/Nurses, and those in clinical units. Older HCWs, non-physicians/nurses, non-clinical unit workers, HCWs at Western Regional Hospital A, and those who received ongoing IC training scored higher on attitude. The practice scores were significantly correlated with the attitude scores but not the knowledge scores. The attitude score was a significant predictor for IC practices. Conclusions: Six knowledge and three attitude variables were significant predictors of IC practices that the Western Regional Health Authority Officials can use to implement measures to improve IC practices among HCWs. [ABSTRACT FROM AUTHOR]

With the increasing rate of infections caused by multidrug‐resistant organisms (MDRO), selecting appropriate empiric antibiotics has become challenging. We aimed to develop and externally validate a model for predicting the risk of MDRO infections in patients with cirrhosis. Methods: We included patients with cirrhosis and bacterial infections from two prospective studies: a transcontinental study was used for model development and internal validation (n = 1302), and a study from Argentina and Uruguay was used for external validation (n = 472). All predictors were measured at the time of infection. Both culture‐positive and culture‐negative infections were included. The model was developed using logistic regression with backward stepwise predictor selection. We externally validated the optimism‐adjusted model using calibration and discrimination statistics and evaluated its clinical utility. Results: The prevalence of MDRO infections was 19% and 22% in the development and external validation datasets, respectively. The model's predictors were sex, prior antibiotic use, type and site of infection, MELD‐Na, use of vasopressors, acute‐on‐chronic liver failure, and interaction terms. Upon external validation, the calibration slope was 77 (95% CI.48–1.05), and the area under the ROC curve was.68 (95% CI.61–.73). The application of the model significantly changed the post‐test probability of having an MDRO infection, identifying patients with nosocomial infection at very low risk (8%) and patients with community‐acquired infections at significant risk (36%). Conclusion: This model achieved adequate performance and could be used to improve the selection of empiric antibiotics, aligning with other antibiotic stewardship program strategies. [ABSTRACT FROM AUTHOR]

Performing cardiac surgery on patients with bleeding diatheses poses significant challenges since these patients are at an increased risk for complications secondary to excessive bleeding. Despite its rarity, patients with factor VII (FVII) deficiency may require invasive procedures such as cardiac surgery. However, we lack guidelines on their pre-, peri-, and post-operative management. As FVII deficiency is rare, it seems unlikely to design and learn from large clinical studies. Instead, we need to base our clinical decision-making on single reported cases and registry data. Herein, we present the rare case of a patient with FVII deficiency who underwent double valve surgery. Pre-operatively, activated recombinant FVII (rFVIIa) was administered to reduce the risk of bleeding. Nevertheless, the patient experienced major bleeding. This case highlights the significance of FVII deficiency in patients undergoing cardiac surgery and emphasizes the importance of adequate and appropriate transfusion of blood products for these patients. [ABSTRACT FROM AUTHOR]

Free-living amoebae (FLA) are isolated from the hospital environments and known as Trojan horses for medical essential microorganisms. This study aimed to investigate the prevalence and the presence of FLA and two critical agents of nosocomial infections, in the hospital wards. Sixty samples were collected from four communities and cultured onto non-nutrient agar (NNA). After total DNA extraction, FLA were characterized using PCR and sequencing. The presence of Candida albicans and Staphylococcus aureus was evaluated using real-time and conventional PCR, respectively. Acanthamoeba sp. was characterized in 30 (50%) samples. Two (6.6%) and one (3.3%) samples were positive for Vahlkampfiidae and Vermamoeba vermiformis, respectively. S. aureus was detected in 13 (43.3%) of samples, while none of them were positive for methicillin-resistant gene. C. albicans DNA was detected in one (3.3%) FLA-positive sample. The isolation of FLA from hospital suggests an essential role these eukaryotes in the inter-ward circulation of nosocomial infections. [ABSTRACT FROM AUTHOR]

To clarify the infection control measures required in the event of a new infectious disease outbreak, we conducted a questionnaire survey on the infection control measures implemented against coronavirus disease 2019 (COVID-19). An invitation to participate in this survey was sent to the heads of 2689 facilities affiliated with the members of the Japanese Society for Infection Prevention and Control in February 2023, requesting responses to the online survey using Google Forms by March 2023. Six hundred and forty-five facilities, including 20 clinics and 625 hospitals, participated in the survey. This survey revealed that various infection control measures were implemented, including universal masking in the non-COVID-19 ward (96.5 %), screening tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on scheduled admission (89.0 %), SARS-CoV-2 tests (98.7 %), and isolation in private rooms (76.5 %) for inpatients with fever. However, nosocomial infections and clusters of COVID-19 occurred in 94.4 % and 90.9 % of cases during the investigation period, respectively. One of the reasons for these results is that healthcare personnel (HCP) and patients were common index cases of nosocomial infections, and the most common cause of clusters was the work of symptomatic HCPs. These results suggest that HCPs should understand that they can be index cases or spreaders. On the other hand, the most common support from external facilities was healthcare centers, followed by physicians or nurses from other hospitals. In response to the emergence of infections, it is important to consider implementing infection control measures for HCPs and patients. [ABSTRACT FROM AUTHOR]

Background: The extensively drug-resistant (XDR) strains of Acinetobacter baumannii have become a major cause of nosocomial infections, increasing morbidity and mortality worldwide. Many different treatments, including phage therapy, are attractive ways to overcome the challenges of antibiotic resistance. Methods: This study investigates the biofilm formation ability of 30 XDR A. baumannii isolates and the efficacy of a cocktail of four tempetate bacteriophages (SA1, Eve, Ftm, and Gln) and different antibiotics (ampicillin/sulbactam, meropenem, and colistin) in inhibiting and degrading the biofilms of these strains. Results: The majority (83.3%) of the strains exhibited strong biofilm formation. The bacteriophage cocktail showed varying degrees of effectiveness against A. baumannii biofilms, with higher concentrations generally leading to more significant inhibition and degradation rates. The antibiotics-bacteriophage cocktail combinations also enhanced the inhibition and degradation of biofilms. Conclusion: The findings suggested that the bacteriophage cocktail is an effective tool in combating A. baumannii biofilms, with its efficacy depending on the concentration. Combining antibiotics with the bacteriophage cocktail improved the inhibition and removal of biofilms, indicating a promising strategy for managing A. baumannii infections. These results contribute to our understanding of biofilm dynamics and the potential of bacteriophage cocktails as a novel therapeutic approach to combat antibiotic-resistant bacteria. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes severe nosocomial infections in susceptible individuals due to the emergence of multidrug-resistant strains. There are no approved vaccines against P. aeruginosa infections nor candidates in active clinical development, highlighting the need for novel candidates and strategies. Using a cell-blot proteomic approach, we reproducibly identified 49 proteins involved in interactions with human lung epithelial cells across four P. aeruginosa strains. Among these were cell division protein FtsZ and outer membrane protein OpmH. Escherichia coli BL21 cells overexpressing recombinant FtsZ or rOpmH showed a 66- and 15-fold increased ability to attach to 16HBE14o− cells, further supporting their involvement in host cell attachment. Both antigens led to proliferation of NK and CD8+ cytotoxic T cells, significant increases in the production of IFN-γ, IL-17A, TNF and IL-4 in immunised mice and elicited strong antigen-specific serological IgG1 and IgG2c responses. Immunisation with FtsZ significantly reduced bacterial burden in the lungs by 1.9-log CFU and dissemination to spleen by 1.8-log CFU. The protective antigen candidate, FtsZ, would not have been identified by traditional approaches relying on either virulence mechanisms or sequence-based predictions, opening new avenues in the development of an anti-P. aeruginosa vaccine. [ABSTRACT FROM AUTHOR]

Surveillance of antimicrobial resistance (AMR) is a crucial strategy to combat AMR. Using routine surveillance data, we could detect and control hospital outbreaks of AMR bacteria as early as possible. Previously, we developed a framework for automatic detection of clusters of AMR bacteria using SaTScan, a free cluster detection tool integrated into WHONET. WHONET is a free software used globally for microbiological surveillance data management. We applied this framework to data from the Japan Nosocomial Infections Surveillance (JANIS), one of the world's most comprehensive and largest national AMR surveillance systems. Although WHONET-SaTScan has several cluster detection algorithms, no published studies have compared how different algorithms can produce varying results in cluster detection. Here, we conducted a comparison to detect clusters of vancomycin-resistant enterococci (VRE), which has been rare in Japan, by analyzing combinations of resistance to several key antimicrobials ("resistance profiles") using the comprehensive national routine AMR surveillance data of JANIS and validated the detection capabilities of each algorithm using publicly available reports of VRE clusters. All publicly reported VRE hospital outbreaks were detected as statistical clusters using the space-time uniform algorithm implemented in WHONET-SaTScan. In contrast, only 18.8% of the publicly reported outbreaks were detected using another algorithm (space-time permutation). The space-time uniform algorithm was also effective in identifying hospital wards affected by outbreaks attributed to specific resistance profiles. Although half of the publicly reported outbreaks were attributed to VRE resistant to five particular antimicrobials, four other resistance profiles also contributed to the outbreaks, highlighting the diversity of AMR bacteria within these occurrences. Our comparison revealed a clear advantage in using an algorithm (space-time uniform) for detecting VRE clusters in WHONET-SaTScan based on national surveillance data and further demonstrated the capability to distinguish detected clusters based on resistance profiles. [ABSTRACT FROM AUTHOR]

Antibiotic resistance in bacteria leads to high mortality rates and healthcare costs, a significant concern for public health. A colonizer of the human respiratory system, Stenotrophomonas maltophilia is frequently associated with hospital-acquired infections in individuals with cystic fibrosis, cancer, and other chronic illnesses. The importance of this study is underscored by its capacity to meet the critical demand for effective preventive strategies against this pathogen, particularly among susceptible groups of cystic fibrosis and those undergoing cancer treatment. In this study, we engineered a multi-epitope vaccine targeting S. maltophilia through genomic analysis, reverse vaccination strategies, and immunoinformatic techniques by examining a total of 81 complete genomes of S. maltophilia strains. Our investigation revealed 1945 core protein-coding genes alongside their corresponding proteomic sequences, with 191 of these genes predicted to exhibit virulence characteristics. Out of the filtered proteins, three best antigenic proteins were selected for epitope prediction while seven epitopes each from CTL, HTL, and B cell were chosen for vaccine development. The vaccine was refined and validated, showing highly antigenic and desirable physicochemical features. Molecular docking assessments revealed stable binding with TLR-4. Molecular dynamic simulation demonstrated stable dynamics with minor alterations. The originality of this investigation is rooted in the thorough techniques aimed at designing a vaccine that directly targets S. maltophilia, a microorganism of considerable clinical relevance that currently lacks an available vaccine. This study not only responds to a pressing public health crisis but also lays the groundwork for subsequent research endeavors focused on the prevention of S. maltophilia outbreaks. Further evidence from studies in mice models is needed to confirm immune protection against S. maltophilia. [ABSTRACT FROM AUTHOR]

Background: Production of extended-spectrum β-lactamases (ESBLs) is a common resistance mechanism in Enterobacteriaceae, leading to serious hospital-acquired infections. This study aimed to assess phenotypic, phylogenetic, and antibiotic resistance patterns among ESBL-producing Escherichia coli isolates recovered from two rural tertiary hospitals in Thailand. Results: Among 467 Enterobacteriaceae isolates, E. coli was the most prevalent 356 (76.2%) followed by K. pneumoniae 88 (18.8%), K. aerogenes 8 (1.7%), K. variicola 3 (0.6%), K. quasipneumoniae 1 (0.2%%), K. oxytoca 1 (0.2%), and unidentified 9 (1.9%). Of the 202 cephalosporin-resistant E. coli isolates, 195 (96.5%) were ESBL-producing and 7 (3.5%) were non-ESBL-producing. Clermont typing revealed that phylogroup B2 was predominant (43.3%), followed by phylogroups F (11.3%), D (10.3%), C (9.7%), and A (8.7%). Among the beta-lactamase-encoding genes, blaCTX−M (83.6%) and blaTEM (81.0%) were widely found among the isolates, and blaCTX−M−1 (60.7%) was the most common among the five blaCTX−M subgroups detected. The predominant ESBL was blaCTX−M−15 (58.3%). All isolates were resistant to cefotaxime (100%) and ampicillin (100%), followed by ciprofloxacin (91.3 %), ceftazidime (72.8 %), and tetracycline (64.1%). Conclusion: Our findings show that phylogroup B2 was the most prevalent phylogroup among ESBL-producing E. coli isolates in northeastern Thailand. Notably, the isolates mostly carried the blaCTX−M gene(s). [ABSTRACT FROM AUTHOR]

Background: Neonatal Nosocomial infections (NNIs) are a significant cause of morbidity and mortality for neonates in an intensive care unit. Neonatal causes of death in healthcare facilities are attributed to different factors. We aimed to investigate factors associated with NNIs, estimate the burden of NNIs, and assess how the prediction effects help to save medical mortality and length of hospital stay. Method: A prospective longitudinal study was conducted and data were collected from January 2022 to June 2022 from Jimma University Medical Center (JUMC). The data were gathered in a variety of ways, including an in-person interview with the patient's caregiver, direct observations of neonatal patients, and a review of the study participants' charts. This study includes patients aged 3 to 28 days who were admitted to the JUMC neonatal ward and stayed for at least 48 h. Multi-state model formulation and multivariate logistic regression were used for data analysis. Results: A total of 545 neonates were included out of 688, and 30% (n = 164) of them acquired nosocomial infections (NIs); 98 (33%) of infected patients were born prematurely; and 71 (31.4%) were underweight at birth. NIs were higher in neonates with long hospital stay (AOR: 1.16, 95%CI: 1.13–1.20), use of urinary catheters (AOR: 3.09, 95%CI: 1.55–6.15), and undergoing surgical procedures (AOR: 2.42, 95%CI: 1.13–5.17). Patients who developed NIs had a higher risk of death (HR: 2, 95% CI: 1.31, 3.04). The burden of neonatal NIs was determined to have a risk of 0.3, a mortality rate of 9.6%, and an average duration of hospital stay of 14.6 days. Competing risk regression suggests that neonates with NIs have a significantly higher risk of death than those who are not infected (HR: 16.42, 95% CI: 8.70-30.98, p < 0.001). Assumed prevention that decreases the NIs rate in half would result in 101 lives and 1357 patient days saved from 10,000 neonatal inpatients. Conclusion: Urinary catheterization and surgical procedure increased neonatal NIs. Longer hospital stay can increase the risk of NIs and can also result from the NIs. Our finding indicated that effective prevention of NIs could help reduce neonatal deaths and their hospital stays. [ABSTRACT FROM AUTHOR]

Candida parapsilosis is an opportunistic fungal pathogen commonly isolated from the environment and associated with nosocomial infection outbreaks worldwide. We describe here the construction of a large collection of gene disruptions, greatly increasing the molecular tools available for probing gene function in C. parapsilosis. We use these to identify transcription factors associated with multiple metabolic pathways, and in particular to dissect the network regulating the assimilation of sulphur. We find that, unlike in other yeasts and filamentous fungi, the transcription factor Met4 is not the main regulator of methionine synthesis. In C. parapsilosis, assimilation of inorganic sulphur (sulphate) and synthesis of cysteine and methionine is regulated by Met28, a paralog of Met4, whereas Met4 regulates expression of a wide array of transporters and enzymes involved in the assimilation of organosulfur compounds. Analysis of transcription factor binding sites suggests that Met4 is recruited by the DNA-binding protein Met32, and Met28 is recruited by Cbf1. Despite having different target genes, Met4 and Met28 have partial functional overlap, possibly because Met4 can contribute to assimilation of inorganic sulphur in the absence of Met28. The fungus Candida parapsilosis is found in the environment and associated with nosocomial infection outbreaks. Here, Lombardi et al. generate a large collection of gene disruptions in this opportunistic pathogen and identify transcription factors associated with multiple metabolic pathways, revealing unique features in the regulation of sulphur assimilation. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus poses a significant threat as an opportunistic pathogen in humans, and animal medicine, particularly in the context of hospital-acquired infections (HAIs). Effective treatment is a significant challenge, contributing substantially to the global health burden. While antibiotic therapy remains the primary approach for staphylococcal infections, its efficacy is often compromised by the emergence of resistant strains and biofilm formation. The anticipated solution is the discovery and development of new antibacterial agents. However, this is a time consuming and expensive process with limited success rates. One potential alternative for addressing this challenge is the repurposing of existing antibiotics. This study investigated the potential of rifabutin (RFB) as a repurposed antibiotic for treating S. aureus infections. The minimum inhibitory concentration (MIC) of rifabutin was assessed by the broth microdilution method, in parallel to vancomycin, against 114 clinical isolates in planktonic form. The minimum biofilm inhibitory concentration (MBIC50) was determined by an adaptation of the broth microdilution method, followed by MTT assay, against a subset of selected 40 clinical isolates organized in biofilms. The study demonstrated that RFB MIC ranged from 0.002 to 6.250 µg/mL with a MIC50 of 0.013 µg/mL. RFB also demonstrated high anti-biofilm activity in the subset of 40 clinical isolates, with confirmed biofilm formation, with no significant MBIC50 differences observed between the MSSA and MRSA strains, in contrast to that observed for the VAN. These results highlight the promising efficacy of RFB against staphylococcal clinical isolates with different resistance patterns, whether in planktonic and biofilm forms. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is among the most important Gram-negative pathogens that can cause serious nosocomial infections. The emergence and prevalence of hypervirulent carbapenem-resistant K. pneumoniae (Hv-CRKP) pose a significant challenge to public health. In this study, we characterized thirty carbapenem-resistant K. pneumoniae (CRKP) strains from a tertiary care hospital in Sichuan province, China, by whole-genome sequencing and genome analysis. These strains were all highly resistant to carbapenem but remained susceptible to tigecycline. Of the 30 tested CRKP strains, 23 were positive for blaKPC−2 and seven for blaNDM−5. These blaKPC−2-positive strains all belonged to ST11, while blaNDM−5-positive strains belonged to five distinct STs. Phylogenetic analysis revealed a predominant intra-hospital transmission of ST11-KL64 in KPC-2-producing CRKP, and that both clonal and horizontal transmission of blaNDM−5 have occurred among NDM-5-producing CRKP strains in this hospital. Hypervirulence genes were commonly detected in the CRKP. The prevalent pLVKP-like plasmid and ICEKp seem to have contributed largely to the transmission of virulence genes in them. blaNDM−5 was located on highly similar IncX3 plasmids in the collected strains, and its truncated vision was highlighted. blaKPC−2 was primarily carried by IncFII/IncR plasmids in our collection. At least two IncFII/IncR plasmid subtypes were identified, exhibiting high similarity to many previously reported blaKPC−2-bearing plasmids from different parts of China. The findings provide an expanded knowledge of the genetic characteristics of CRKP, the transmission pattern of carbapenem-resistance genes, and also the convergence of Hv-CRKP. [ABSTRACT FROM AUTHOR]

Background Hospital-acquired (HAP) and ventilator-associated pneumonia (VAP) are important complications early (<30 days) after lung transplantation (LT). However, current incidence, associated factors, and outcomes are not well reported. Methods LT recipients transplanted at our institution (July 2019–January 2020 and October 2021–November 2022) were prospectively included. We assessed incidence and presentation of pneumonia and evaluated the impact of associated factors using regression models. We also evaluated molecular relatedness of respiratory pathogens collected peri-transplant and at pneumonia occurrence using pulsed-field gel electrophoresis (PFGE). Results In the first 30 days post-LT, 25/270 (9.3%) recipients were diagnosed with pneumonia (68% [17/25] VAP; 32% [8/25] HAP). Median time to pneumonia was 11 days (IQR, 7–13); 49% (132/270) of donor and 16% (44/270) of recipient respiratory peri-transplant cultures were positive. However, pathogens associated with pneumonia were not genetically related to either donor or recipient cultures at transplant, as determined by PFGE. Diagnosed pulmonary hypertension (HR, 4.42; 95% CI, 1.62–12.08) and immunosuppression use (HR, 2.87; 95% CI, 1.30–6.56) were pre-transplant factors associated with pneumonia. Pneumonia occurrence was associated with longer hospital stay (HR, 5.44; 95% CI, 2.22–13.37) and VAP with longer ICU stay (HR, 4.31; 95% CI, 1.73–10.75) within the first 30 days post-transplantation; 30- and 90-day mortality were similar. Conclusions Prospectively assessed early pneumonia incidence occurred in ∼10% of LT. Populations at increased risk for pneumonia occurrence include LT with pre-transplant pulmonary hypertension and pre-transplant immunosuppression. Pneumonia was associated with increased healthcare use, highlighting the need for further improvements by preferentially targeting higher-risk patients. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae has been identified as one of the most important opportunistic pathogens responsible for nosocomial infections. Antibiotic resistance and the ability to form biofilms are the two main factors involved in the persistence of infections. Conventional detection methods involve culture isolation and identification followed by biofilm assay that takes 48–72 h. Timely detection of biofilm-forming resistant pathogens is essential to appropriately treat the infection with the right dose and combinations. The present study focuses on evaluating an RT-PCR panel using mrkD, pgaC, and wcaJ genes to screen for biofilm-forming K. pneumoniae from ETA/BAL specimens. The assay accurately identified K. pneumoniae harboring samples with a limit of detection of 1 ng/µl total RNA. Representative culture-negative-PCR-positive samples were subjected to metagenomics which identified K. pneumoniae reads in these samples confirming the specificity of RT-PCR. mrkD and pgaC act as K. pneumoniae specific identification whereas wcaJ acts as a negative marker for biofilm-forming K. pneumoniae. In addition, RT-PCR results correlated well with the phenotypic biofilm-forming assay. This RT-PCR assay is the first of its kind for rapid identification of biofilm-forming K. pneumoniae. The result of this study highlights that the rapid detection of K. pneumoniae biofilms based on the RT-PCR results coupled with clinical conditions would be appropriate to treat emerging infections or to prevent re-infections in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Globally, extended-spectrum beta-lactamase-producing and carbapenem-resistant Enterobacterales are major causes of hospital-acquired infections and there are increasing concerns about their role in community-acquired infections. Objective: We aimed to investigate the prevalence of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and Carbapenemase-producing-Carbapenemresistant-Enterobacterales (CP-CRE) and associated factors in community settings in Gulele sub city, Addis Ababa, Ethiopia. Methods: A cross-sectional study was conducted among 261 healthy individuals. Stool samples were collected and processed using standard microbiological methods. Antimicrobial susceptibility and phenotypic ESBL and carbapenemase tests were performed. Antibiotic resistance genes were detected by Polymerase Chain Reaction (PCR). Results: The colonization rate of ESBL-PE and CP-CRE were 31.4% (82/261, 95% CI: 25.91–37.48) and 0.8% (2/261, 95% CI: 0.13–3.1), respectively by phenotypic method. Molecular detection of genes for ESBL-PE was 27.9% (73/261, 95% CI:22.7–33.9), and for CP-CRE was 0.8% (2/261, 95% CI: 0.13–3.1). The most prevalent genes were blaTEM [76.7% (56/73)] and blaCTX-M [45.2% (33/73)]. Previous antibiotic use (AOR:2.04, 95%CI: 1.35–4.41, P:0.041) and age between 42 and 53 years old (AOR:3.00, 95%CI:1.12–7.48, P:0.019) were significantly associated with ESBL-PE colonization. Conclusion: Intestinal colonization by ESBL-PE harboring the associated antibiotic resistance genes was substantially high but with low CP-CRE. Continued surveillance of community-level carriage of antimicrobial resistance Enterobacterales is warranted. [ABSTRACT FROM AUTHOR]

Background: Increasing nosocomial infections during the COVID-19 pandemic have been reported. However, data describing peripheral venous catheter associated bloodstream infections (PVC-BSI) are limited. Aims: To describe the epidemiology and risk factors for PVC-BSI during the COVID-19 pandemic. Methods: We conducted retrospective cohort study of prospectively collected PVC-BSI data in a 2100 bed hospital network in Switzerland. Adult patients with a PVC inserted between January 1, 2020 and December 31, 2021 were included. Risk factors for PVC-BSI were identified through descriptive analysis of patient and catheter characteristics, and univariable marginal Cox models. Results: 206,804 PVCs and 37 PVC-BSI were analysed. Most PVC-BSI were attributed to catheters inserted in the Emergency department (76%) or surgical wards (22%). PVC-BSI increased in 2021 compared to 2020 (hazard ratio 2021 vs. 2020 = 2.73; 95% confidence interval 1.19–6.29), with a numerically higher rate of Staphylococcus aureus (1/10, 10%, vs. 5/27, 19%) and polymicrobial infection (0/10, 0% vs. 4/27, 15%). PVC insertions, patient characteristics, and catheter characteristics remained similar across the study period. PVC-BSI risk was associated with admission to the intensive care unit (ICU), and use of wide gauge catheter (< = 16G). Conclusion: Increased PVC-BSI during the COVID-19 pandemic was not explained by catheter or patient factors alone, and may result from system-wide changes. PVC-BSI events are primarily attributed to acute care settings, including the emergency department, surgical wards, and the ICU. [ABSTRACT FROM AUTHOR]

Background and objectives: Nosocomial infections, including drug-resistant Acinetobacter baumannii infections, continue to impact the health of hospitalized patients. This study sought to determine the prevalence of these infections and assess the associated risk factors and clinical outcomes in Gorgan, Iran. Methods: A retrospective cross-sectional study was conducted on 143 infected patients with Acinetobacter baumannii in two educational hospitals in Gorgan city, Iran between 2016 and 2018. Patient information including age, gender, reason and duration of hospitalization, background of diseases, type of sample culture, symptoms, laboratory findings, prescribed antibiotics, and antibiogram were collected and analyzed. The Logistic regression and survival statistical methods were used by software of SPSS 26. Results: A total of 37 patients (25.87%) died during hospitalization. The less than one year and 45–65 years age groups demonstrated more deaths (29.7%; p-value < 0.001). Being single (not being married) was found to be a risk factor in increasing the chance of death among patients (OR = 2.154, 95% CI: 1.02–4.53; p = 0.048). Hospitalization in intensive care units (ICUs) was a risk factor for the death of patients (OR = 4.655, 95% CI: 7.6–83.2). The resistance to carbapenems was reported to be an important risk factor for the death of patients. Conclusions: Acinetobacter baumannii infections, particularly those resistant to carbapenems, are a significant risk for patients in ICUs and can lead to higher mortality rates. [ABSTRACT FROM AUTHOR]

Introduction: There are multiple ongoing outbreaks of carbapenem resistant Acinetobacter baumannii (CRAb) infection in Fiji's hospitals. CRAb is able to colonize and persist on various hospital surfaces for extended periods. We conducted a study to understand the extent of hospital environmental contamination and phylogenetic links with clinical isolates. Methods: Swabs were collected from high-touch surfaces at Colonial War Memorial Hospital (CWMH) September 2021 and December 2022; Lautoka Hospital (LTKH) August 2022; and Labasa Hospital (LBSH) November 2022. All bacterial isolates were identified, and antimicrobial susceptibility testing (AST) performed; isolates resistant to carbapenems and producing a carbapenemase underwent whole genome sequencing. Comparison was made to clinical isolates obtained from CWMH in 2016-2017 and 2019-2021 and from LTKH and LBSH from 2020-2021. Results: From the 180 environmental samples collected, ten (5.6%) CRAb were isolated; no other carbapenem-resistant gram-negative organisms were isolated. Seven (70%) of the CRAb were isolated from CWMH and three (30%) from LTKH; no CRAb were isolated from LBSH. Of the seven CWMH CRAb, two were sequence type 2 (ST2), three ST25, and two ST499. All LTKH isolates were ST499. The two environmental CRAb ST2 isolates were closely genetically linked to isolates obtained from patients in CWMH, LTKH, and LBSH 2020-2021. Similarly, the three environmental CRAb ST25 isolates were closely genetically linked to isolates obtained from patients admitted to CWMH in 2019-2021 and LBSH in 2020. The environmental CRAb ST499 isolates represented two distinct clones, with clone 1 comprising two genetically identical isolates from CWMH and clone 2 the three isolates from LTKH. Although no genetic linkages were observed when comparing environmental ST499 isolates to those from CWMH patients in 2020-2021, both clone 1 isolates were genetically identical to an isolate obtained from a patient admitted during the sampling period. Conclusion: Our study highlights the contamination of high-touch surfaces within Fiji hospitals with CRAb, suggesting that these may serve as important sources for CRAb. Phylogenetic linkages to CRAb isolated from patients since 2019 underscores the persistence of this resistant pathogen in hospital settings and the ongoing risk for hospital-acquired infections. [ABSTRACT FROM AUTHOR]

Escherichia coli A0 34/86 (EcO83) is a probiotic strain used in newborns to prevent nosocomial infections and diarrhoea. This bacterium stimulates both pro‐ and anti‐inflammatory cytokine production and its intranasal administration reduces allergic airway inflammation in mice. Despite its benefits, there are concerns about the use of live probiotic bacteria due to potential systemic infections and gene transfer. Extracellular vesicles (EVs) derived from EcO83 (EcO83‐EVs) might offer a safer alternative to live bacteria. This study characterizes EcO83‐EVs and investigates their interaction with host cells, highlighting their potential as postbiotic therapeutics. EcO83‐EVs were isolated, purified, and characterised following the Minimal Information of Studies of Extracellular Vesicles (MISEV) guidelines. Ex vivo studies conducted in human nasal epithelial cells showed that EcO83‐EVs increased the expression of proteins linked to oxidative stress and inflammation, indicating an effective interaction between EVs and the host cells. Further in vivo studies in mice demonstrated that EcO83‐EVs interact with nasal‐associated lymphoid tissue, are internalised by airway macrophages, and stimulate neutrophil recruitment in the lung. Mechanistically, EcO83‐EVs activate the NF‐κΒ signalling pathway, resulting in the nitric oxide production. EcO83‐EVs demonstrate significant potential as a postbiotic alternative to live bacteria, offering a safer option for therapeutic applications. Further research is required to explore their clinical use, particularly in mucosal vaccination and targeted immunotherapy strategies. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae (K. pneumoniae), a kind of zoonotic bacteria, is among the most common antibiotic-resistant pathogens, and it causes nosocomial infections that pose a threat to public health. In this study, the roles of synthetic bovine neutrophil β-defensin-5 (B5) in regulating inflammatory response and metabolic response against multidrug-resistant K. pneumoniae infection in a mouse model were investigated. Mice were administrated intranasally with 20 μg of B5 twice and challenged with K. pneumoniae three days after B5 pretreatment. Results showed that B5 failed to directly kill K. pneumoniae in vitro, but it provided effective protection against multidrug-resistant K. pneumoniae via decreasing the bacterial load in the lungs and spleen, and by alleviating K. pneumoniae-induced histopathological damage in the lungs. Furthermore, B5 significantly enhanced the mRNA expression of TNF-α, IL-1β, Cxcl1, Cxcl5, Ccl17, and Ccl22 and obviously enhanced the rapid recruitment of macrophages and dendritic cells in the lungs in the early infection phase, but significantly down-regulated the levels of TNF-α, IL-1β, and IL-17 in the lungs in the later infection phase. Moreover, RNA-seq results showed that K. pneumoniae infection activated signaling pathways related to natural killer cell-mediated cytotoxicity, IL-17 signaling pathway, inflammatory response, apoptosis, and necroptosis in the lungs, while B5 inhibited these signaling pathways. Additionally, K. pneumoniae challenge led to the suppression of glycerophospholipid metabolism, the phosphotransferase system, the activation of microbial metabolism in diverse environments, and metabolic pathways in the lungs. However, B5 significantly reversed these metabolic responses. Collectively, B5 can effectively regulate the inflammatory response caused by K. pneumoniae and offer protection against K. pneumoniae. B5 may be applied as an adjuvant to the existing antimicrobial therapy to control multidrug-resistant K. pneumoniae infection. Our study highlights the potential of B5 in enhancing pulmonary bacterial clearance and alleviating K. pneumoniae-caused inflammatory damage. [ABSTRACT FROM AUTHOR]

Corynebacterium striatum, present in the microbiota of human skin and nasal mucosa, has recently emerged as a causative agent of hospital-acquired infections, notable for its resistance to multiple antimicrobials. Its mobilome comprises several mobile genetic elements, such as plasmids, transposons, insertion sequences and integrons, which contribute to the acquisition of antimicrobial resistance genes. This study analyzes the contribution of the C. striatum mobilome in the transfer and dissemination of resistance genes. In addition, integrative and conjugative elements (ICEs), essential in the dissemination of resistance genes between bacterial populations, whose role in C. striatum has not yet been studied, are examined. This study examined 365 C. striatum genomes obtained from the NCBI Pathogen Detection database. Phylogenetic and pangenome analyses were performed, the resistance profile of the bacterium was recognized, and mobile elements, including putative ICE, were detected. Bioinformatic analyses identified 20 antimicrobial resistance genes in this species, with the Ermx gene being the most predominant. Resistance genes were mainly associated with plasmid sequence regions and class 1 integrons. Although an ICE was detected, no resistance genes linked to this element were found. This study provided valuable information on the geographic spread and prevalence of outbreaks observed through phylogenetic and pangenome analyses, along with identifying antimicrobial resistance genes and mobile genetic elements that carry many of the resistance genes and may be the subject of future research and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Ventilator-associated pneumonia (VAP) remains one of the most common hospital-acquired infections (HAI). Considering the complicated diagnosis and the lack of effective treatment, prophylactic measures are suggested as the new standard to prevent the disease. Although VAP often manifests a polymicrobial nature, Pseudomonas aeruginosa remains one of the pathogens associated with the highest morbidity and mortality rates within these mechanically ventilated patients. In this paper, we report on the development of an antibacterial hydrogel coating using the polymyxin B (PMB) peptide to prevent bacterial adhesion to the polymeric substrate. We fully characterized the properties of the coating using atomic force microscopy (AFM), scanning electron microscopy (SEM), wettability analyses and Fourier-transform infrared (FTIR) and Raman spectroscopy. Furthermore, several biological assays confirmed the antibacterial and anti-biofilm effect of the tubing for at least 8 days against P. aeruginosa. On top of that, the produced coating is compliant with the requirements regarding cytocompatibility stated in the ISO (International Organization for Standardization) 10993 guidelines and an extended release of PMB over a period of at least 42 days was detected. In conclusion, this study serves as a foundation for peptide-releasing hydrogel formulas in the prevention of VAP. [ABSTRACT FROM AUTHOR]

Klebsiella oxytoca is a causative agent of various community-acquired and nosocomial infections, including urinary tract infections, nosocomial pneumonia, antibiotic-associated diarrhea, etc. However, the virulence factors of the species are still incompletely understood. The adhesive potential of the urological isolate K. oxytoca NK-1 was characterized using several substrates. The strain was found to efficiently adhere to epithelial cell lines, glycosylated and nonglycosylated proteins, and polystyrene and to induce yeast cell agglutination, indicating the presence of type 1 and type 3 fimbriae, which are organelles that facilitate adhesion of enterobacteria to a wide range of substrates. Both type 1 and type 3 fimbrial operons were identified in the strain genome, the latter occurring in two copies. Mutants with inactivated fimbrial genes were constructed. Inactivation of type 1 fimbrial genes did not affect bacterial adhesion. Inactivation of type 3 fimbrial genes increased adhesion of K. oxytoca NK-1 to lung epithelial cells (line H1299), and mannose was shown to serve as an additional inducer of higher adhesion. Adhesion of the mutant to other substrates was not affected. The findings suggested a multifactorial nature for the K. oxytoca adhesive apparatus and the possibility of compensatory expression or overexpression of genes for alternative adhesins in the absence of type 1 and/or 3 fimbriae. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae, a Gram-negative bacterium that has emerged as a significant global threat, has been implicated in nosocomial infections. The objectives of this investigation encompassed: i) assessment of extended spectrum ß-lactamase (ESBL) synthesis and other forms of antibiotic resistance, ii) characterization of biofilm formation, adhesin (fimH), and capsule (uge) virulence genes, and iii) exploration of the existence of Class-1 integron (intI1) within the isolates. A total of 120 K. pneumoniae were obtained from clinical specimens and identified with automatic Vitek®2 compact systems. The rates of resistance to various antibiotics were as follows: levofloxacin 89.1%, amoxicillin-clavulanic acid 69.1%, ceftazidime 60%, fosfomycin 59.1%, aztreonam 57.5%, nalidixic acid 56.6%, piperacillin-tazobactam 54.1%, tobramycin 44.1%, chloramphenicol 40%, gentamycin and meropenem 39.1%, imipenem 35.8%. Combined disc testing identified 28 isolates (23.3%) as ESBL-producing K. pneumoniae. The frequency of genes encoding ESBLs is reported as follows: blaTEM 10 (8.3%), blaSHV 42 (35%), and blaCTX-M-I 23 (19.1%). The virulence genes encountered in isolates were adhesin and capsule, 22.5% fimH and 21.6% uge, respectively. The intI1 gene was detected in 70 (58.3%) isolates. Biofilm analysis revealed that 58 isolates (48.3%) were biofilm producers. This study is important for preventing K. pneumoniae infection as it reveals the relationship between antibiotic resistance of isolates, virulence factors, and biofilm formation. [ABSTRACT FROM AUTHOR]

Ice machines can harbor water-related organisms, and the use of ice or tap water for clinical care activities has been associated with infections in health care settings. During 2021–2022, a total of 23 cases of infection by Burkholderia multivorans (sequence type ST659) were reported at two southern California hospitals and linked to contaminated ice and water from ice machines. In addition to these 23 cases, this report also includes 23 previously unreported cases of B. multivorans ST659 infections that occurred during 2020–2024: 13 at a northern California hospital, eight at a hospital in Colorado, and two additional cases at one of the southern California hospitals. The same brand of ice machine and brands of filters, descaling, and sanitizing products were used by all four hospitals; B. multivorans was isolated from samples collected from ice machines in two of the hospitals. Whole genome sequencing indicated that all clinical and ice machine isolates were highly genetically similar (0–14 single nucleotide variant differences across 81% of the selected reference genome). Recommendations from public health officials to halt the outbreak included avoiding ice and tap water during clinical care activities. An investigation is ongoing to determine possible sources of ice machine contamination. During outbreaks of water-related organisms in health care facilities, health care personnel should consider avoiding the use of tap water, including ice and water from ice machines, for patient care. [ABSTRACT FROM AUTHOR]

The 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]

We aimed to analyze the effects of exclusive breastfeeding duration on the occurrence and course of pneumonia in infants aged up to 6 months. Prospective case-control study. This study was conducted from August 2020 to August 2022 at a maternity and child health hospital in China. A total of 218 infants up to 6 months of age with pneumonia were included in the analyses. Health data were obtained using a hospitalization information system or an interview-based questionnaire. Univariate and multivariate logistic regression analyses were performed to analyze the data. The incidence of pneumonia, hospitalization duration, and costs to participants were significantly affected by the duration of exclusive breastfeeding (p < 0.01). The incidence of pneumonia among participants with different exclusive breastfeeding durations also differed significantly (p < 0.01). The shorter the duration of exclusive breastfeeding, the higher the incidence of pneumonia among infants. We found that the longer the exclusive breastfeeding duration in infants up to 6 months of age, the lower the recurrence of pneumonia, the shorter the hospital stay, and the lower the hospital costs. The rate of exclusive breastfeeding for infants up to 6 months of age should be increased as much as possible to reduce the occurrence of pneumonia and hospital costs. [ABSTRACT FROM AUTHOR]

Nosocomial infections are associated with a significant morbidity, mortality, resource and financial burden in ICU. Critical care patients are at an increased risk of developing infections compared to patients elsewhere in hospital due to underlying comorbidities of the patient, the acute disease process and treatments required. There is a strong association with indwelling devices in the ICU population. As such, daily review of ongoing requirement for the invasive device and the application of care bundles, as well as the introduction of local policies targeting hand hygiene and infection control protocols to manage infections have been promoted. Ventilator-acquired pneumonia and catheter-related infections are most common. Management of these frequently involves empirical antimicrobials, although targeted therapy based on culture sensitivities and input from the local microbiology team and infection control team are suggested. There is an increasing burden of antimicrobial resistance in part due to the clinical condition of ICU patients and the frequent use of empirical broad-spectrum antibiotics. [ABSTRACT FROM AUTHOR]

Background: The WHO Regional Office for Africa developed a Member States (MS)-endorsed regional strategy to fast-track the implementation of MS' national action plans (NAP) on Antimicrobial resistance (AMR). This study explored the perspectives of AMR's national focal points in MS on the implementation of the priority interventions of the regional strategy in their countries. Methods: An online survey consisting of ratings and discussions covering the implementation of the six priority interventions was conducted. Sums of the scores per priority intervention were obtained, and their percentage to the total possible scores were calculated to categorize the implementation as inadequate (0–25%), basic (26–50%), intermediate (51–75%), or advanced (76–100%). Results: Thirty-six of the forty-seven national AMR focal points responded to the survey between 12 November 2023 and 8 January 2024. The implementations were rated as 37–62% (basic-to-intermediate), with the multisectoral coordination and collaboration committee receiving the highest overall rating (62%, 421/684), while the promotion of sustainable investment for the NAP on AMR received the least overall rating (37%, 257/700). The focal points mainly recommended awareness campaigns, capacity building, and regulations and guidelines to improve the implementation of the AMR strategy. Conclusions: The survey revealed a need to enhance awareness campaigns, support the establishment and functioning of AMR evaluation and monitoring systems, and build the capacity of AMR staff with cost-benefit analysis and budgeting skills. It also showed the necessity to improve awareness and conduct education on AMR, streamline evidence generation through One Health Surveillance systems, integrate initiatives to reduce hospital-acquired infections in the antimicrobial stewardship programs, and enhance regulations and guidelines to optimize the use of antimicrobials. [ABSTRACT FROM AUTHOR]

The increase in the number of hospital strains of hypervirulent and multidrug resistant (MDR) Pseudomonas aeruginosa is a major health problem that reduces medical treatment options and increases mortality. The molecular profiles of virulence and multidrug resistance of P. aeruginosa-associated hospital and community infections in Mexico have been poorly studied. In this study, we analyzed the different molecular profiles associated with the virulence genotypes related to multidrug resistance and the genotypes of multidrug efflux pumps (mex) in P. aeruginosa causing clinically critical infections isolated from Mexican patients with community- and hospital-acquired infections. Susceptibility to 12 antibiotics was determined using the Kirby–Bauer method. The identification of P. aeruginosa and the detection of virulence and efflux pump system genes were performed using conventional PCR. All strains isolated from patients with hospital-acquired (n = 67) and community-acquired infections (n = 57) were multidrug resistant, mainly to beta-lactams (ampicillin [96.7%], carbenicillin [98.3%], cefalotin [97.5%], and cefotaxime [87%]), quinolones (norfloxacin [78.2%]), phenicols (chloramphenicol [91.9%]), nitrofurans (nitrofurantoin [70.9%]), aminoglycosides (gentamicin [75%]), and sulfonamide/trimethoprim (96.7%). Most strains (95.5%) isolated from patients with hospital- and community-acquired infections carried the adhesion (pilA) and biofilm formation (ndvB) genes. Outer membrane proteins (oprI and oprL) were present in 100% of cases, elastases (lasA and lasB) in 100% and 98.3%, respectively, alkaline protease (apr) and alginate (algD) in 99.1% and 97.5%, respectively, and chaperone (groEL) and epoxide hydrolase (cif) in 100% and 97.5%, respectively. Overall, 99.1% of the strains isolated from patients with hospital- and community-acquired infections carried the efflux pump system genes mexB and mexY, while 98.3% of the strains carried mexF and mexZ. These findings show a wide distribution of the virulome related to the genotypic and phenotypic profiles of antibiotic resistance and the origin of the strains isolated from patients with hospital- and community-acquired infections, demonstrating that these molecular mechanisms may play an important role in high-pathogenicity infections caused by P. aeruginosa. [ABSTRACT FROM AUTHOR]

Enterococcal bacteremia (EB) is on the rise both in Sweden and globally. While Enterococcus faecalis (E. faecalis) is susceptible to ampicillin and piperacillin/tazobactam (pip/taz), Enterococcus faecium (E. faecium) is not. Historically, most enterococcal infections have been caused by E. faecalis, but the epidemiology is changing with increasing recognition of enterococci as nosocomial pathogens and the emergence of resistance to commonly used antimicrobial agents. The use of pip/taz has increased dramatically in Sweden, but it is unknown if this has affected the relative incidence of E. faecalis/E. faecium bacteremia. Here, we investigate whether the number and proportion of E. faecium bacteremia (EfmB) cases have increased. Additionally, risk factors associated with EfmB with a focus on prior antibiotic exposure are analyzed. Medical journals of 360 patients with EB admitted to Sahlgrenska University Hospital are reviewed. The proportion of EfmB cases increased from 41% in 2015 to 51% in 2021. Hospital-acquired infection, previous exposure to pip/taz, and carbapenems are identified as independent risk factors for EfmB. There are considerable patient-related differences between the EfmB and EfsB groups, but there is no difference in mortality rates. In conclusion, the increasing proportion of EfmB cases is concerning and is seen parallel to the expanding use of pip/taz, one possible contributing factor. Our findings suggest that a cautious approach to antibiotic use is essential to prevent the spread of antibiotic-resistant bacteria. [ABSTRACT FROM AUTHOR]

Purpose: Children with congenital heart disease (CHD) from low- to middle-income countries (LMIC) are suspected to have a high prevalence of antibiotic-resistant microorganisms (ARMOs) carriage, but data are currently lacking. Carriage of ARMOs could impact the post-operative course in pediatric intensive care unit (PICU). The aim of the study was to assess the prevalence of ARMOs carriage in children with CHD from LMIC and its impact on post-operative outcomes. Methods: This was a retrospective monocentric study from 01/2019 to 12/2022. Included patients were children (0–18 years) from a LMIC admitted after CHD surgery and with AMRO screening performed the week before. Infections and post-operative evolution were compared based on ARMOs carriage status. Findings: Among 224 surgeries (median age 38.5 months (IQR 22–85.5)), ARMOs carriage was evidenced in 95 cases (42.4%). Main organisms isolated were Extended Spectrum Beta-Lactamase (ESBL) producing E. coli (75/224) 33.5%)) and ESBL-K. pneumoniae (30/224) 13.4%)). Median mechanical ventilation duration was 1 day (IQR 0–1), PICU stay 3 days (IQR 2–4) and hospital stay 6.5 days (IQR 5–10). A total of 17 infectious episodes occurred in 15 patients, mostly consisting in hospital-acquired pneumonia (HAP) (12/17). Only two infections were caused by a colonizing ARMO. Occurrence of infections and patients' outcome were similar between ARMO carriers and non-carriers. Higher use of carbapenems (6 (6.3%) vs 1 (0.8%), p = 0.04) and a trend to a higher use of vancomycin (14 (13.7%) vs 9 (6.9%), p = 0.04) in case of ARMOs carriage. Applying current guidelines, negative swab screening could have led to sparing most of empirical vancomycin therapy (11/12) for HAP based on current guidelines. Conclusion: Prevalence of AMROs carriage is high in children from LMIC and has a limited impact on patients' outcome. However, ARMOs carriage leads to higher consumption of antibiotics. Screening may help saving use of broad-spectrum antibiotic in non-carrier patients. [ABSTRACT FROM AUTHOR]

Antibiotic resistance is currently becoming a more serious threat to global health, especially in severe nosocomial infections treatment by multidrug-resistant bacteria. This research provides a new way of synergizing green-synthesis for zinc oxide quantum dots (ZnO-QDs with hexagonal crystals) that are 7 nm in diameter and zero-valent Ag cubic crystals that are 67 nm in size embedded with nitazoxanide substrate (NAZ). Instrumental characterization like SEM, TEM, EDAX, and FT-IR and comprehensive antimicrobial studies were conducted to study the incorporation behavior of composites based on Ag NPs/ZnO QDs/NAZ. This combination has not been hitherto addressed anywhere else in the published literature, as well as commercial viability. In this context, we have precisely tuned nanoparticle to nitazoxanide ratio for designing the formulation demonstrating potent activity against MDR infections. By employing nitazoxanide as a scaffold and careful decoration thereof antimicrobial potency has been unlocked overriding conventional therapies. In addition, Ag NPs/ZnO-QDs/nitazoxanide (G6) formula exhibited a therapeutic efficacy span of 96.15 ± 1.68% to 99.57 ± 0.20% against MDR human infections post 48 h incubation; a breakthrough in therapeutic efficacy levels has been achieved by our method. Accordingly, ZnO QDs/Ag NPs/NAZ composite offered potential multidrug resistant human pathogens as a new trend of revolutionizing antimicrobial treatment. Schematic diagram of synthesis routev ZnO quantum dots/Ag NPs/Nitazoxanide Triumphs composite NPs. [ABSTRACT FROM AUTHOR]

Patients treated with ECMO are at great risk of nosocomial infections, and around 10% of isolates are gram-positive pathogens. Linezolid (LZD) is effective in the treatment of these infections but appropriate dosing is challenging. The aim was to evaluate the occurrence of thrombocytopenia during ECMO when treated with LZD. An LZD trough concentration of 8 mg/L was set as the cutoff value for thrombocytopenia occurrence among critically ill patients who received parenteral LZD therapy at a dose of 600 mg every 8 h during ECMO. Eleven patients were included in this prospective observational study. Median LZD trough concentrations were 7.85 (interquartile range (IQR), 1.95-11) mg/L. Thrombocytopenia was found in 81.8% of patients. Based on the median LZD trough concentrations cutoff value, patients were divided into two groups, 1.95 (IQR, 0.91–3.6) and 10.3 (IQR, 9.7–11.7) mg/L, respectively. Median platelet values differed significantly between groups on admission, ECMO day 0, ECMO day 1, and LZD sampling day [194 and 152.5, (p < 0.05)], [113 and 214, (p < 0.05)], [76 and 147.5, (p < 0.01)], and [26 and 96.5, (p < 0.01)], respectively. Duration of LZD therapy was similar between the groups. Significant platelet reduction was observed in both groups, emphasizing the need for closer monitoring to prevent LZD-associated thrombocytopenia. [ABSTRACT FROM AUTHOR]

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Acinetobacter baumannii is a worldwide Gram-negative bacterium with a high resistance rate, responsible for a broad spectrum of hospital-acquired infections. A computational chemogenomics framework was applied to investigate the repurposing of approved drugs to target A. baumannii. This comprehensive approach involved compiling and preparing proteomic data, identifying homologous proteins in drug-target databases, evaluating the evolutionary conservation of targets, and conducting molecular docking studies and in vitro assays. Seven drugs were selected for experimental assays. Among them, tavaborole exhibited the most promising antimicrobial activity with a minimum inhibitory concentration (MIC) value of 2 μg/ml, potent activity against several clinically relevant strains, and robust efficacy against biofilms from multidrug-resistant strains at a concentration of 16 μg/ml. Molecular docking studies elucidated the binding modes of tavaborole in the editing and active domains of leucyl-tRNA synthetase, providing insights into its structural basis for antimicrobial activity. Tavaborole shows promise as an antimicrobial agent for combating A. baumannii infections and warrants further investigation in preclinical studies. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is a pathogen that commonly causes hospital‐acquired infections. Bacterial biofilms are structured bacterial communities that adhere to the surface of objects or biological tissues. In this study, we investigated the genome homology and biofilm formation capacity of ESBL‐producing K. pneumoniae. Thirty ESBL‐producing K. pneumoniae isolates from 25 inpatients at Ruijin Hospital, Shanghai, were subjected to pulsed‐field gel electrophoresis (PFGE) to estimate genomic relatedness. Based on the chromosomal DNA patterns we obtained, we identified 21 PFGE profiles from the 30 isolates, eight of which had high homology indicating that they may have genetic relationships and/or potential clonal advantages within the hospital. Approximately 84% (21/25) of the clinical patients had a history of surgery, urinary tract catheterization, and/or arteriovenous intubation, all of which may have increased the risk for nosocomial infections. Biofilms were observed in 73% (22/30) of the isolates and that strains did not express type 3 fimbriae did not have biofilm formation capacity. Above findings indicated that a high percentage of ESBL‐producing K. pneumoniae isolates formed biofilms in vitro and even though two strains with cut‐off of PFGE reached 100% similarity, they generated biofilms differently. Besides, the variability in biofilm formation ability may be correlated with the expression of type 3 fimbriae. Thus, we next screened four ESBL‐producing K. pneumoniae isolates (Kpn5, Kpn7, Kpn11, and Kpn16) with high homology and significant differences in biofilm formation using PFGE molecular typing, colony morphology, and crystal violet tests. Kpn7 and Kpn16 had stronger biofilm formation abilities compared with Kpn5 and Kpn11. The ability of above four ESBL‐producing K. pneumoniae isolates to agglutinate in a mannose‐resistant manner or in a mannose‐sensitive manner, as well as RNA sequencing‐based transcriptome results, showed that type 3 fimbriae play a significant role in biofilm formation. In contrast, type 1 fimbriae were downregulated during biofilm formation. Further research is needed to fully understand the regulatory mechanisms which underlie these processes. [ABSTRACT FROM AUTHOR]

Enterococci, common hospital-acquired infections in immunocompromised patients, have garnered attention in clinical microbiology. To determine the clinical relevance of enterococci as food-borne pathogens, 116 fish, 90 vegetables, and 120 human diarrheal samples were tested for E. faecalis and E. faecium pathogenicity. Conventionally, 69 of 326 (21.17%) samples were positive for Enterococcus species, 52 (15.95%) of which were molecularly classified as E. faecalis and 13 (3.99%) as E. faecium. The E. faecalis contamination percentage of fresh fish (19.70%) was higher than frozen fish (4%). Cauliflower had the highest E. faecalis percentage (16.67%) when fish and vegetable samples didn't harbor the E. faecium atpA gene. 23.33% and 10.83% of participants' samples were molecularly confirmed as E. faecalis and E. faecium positive, respectively. E. faecalis isolates had all virulence genes, with gels being the most common (65.38%), while cylA and asa1 genes couldn't be detected in E. faecium isolates. E. faecalis showed the highest resistance against vancomycin and tetracycline (69.23%), whereas E. faecium extremely resisted tetracycline (76.92%) and erythromycin (69.23%) with the recognition of MDR among 44.2% of E. faecalis and 38.5% of E. faecium isolates. The great similarity of our isolates showed the clinical importance of food-borne antibiotic-resistant enterococci. [ABSTRACT FROM AUTHOR]

Antibody-dependent complement activation plays a key role in the natural human immune response to infections. Currently, the understanding of which antibody-antigen combinations drive a potent complement response on bacteria is limited. Here, we develop an antigen-agnostic approach to stain and single-cell sort human IgG memory B cells recognizing intact bacterial cells, keeping surface antigens in their natural context. With this method we successfully identified 29 antibodies against K. pneumoniae, a dominant cause of hospital-acquired infections with increasing antibiotic resistance. Combining genetic tools and functional analyses, we reveal that the capacity of antibodies to activate complement on K. pneumoniae critically depends on their antigenic target. Furthermore, we find that antibody combinations can synergistically activate complement on K. pneumoniae by strengthening each other's binding in an Fc-independent manner. Understanding the molecular basis of effective complement activation by antibody combinations to mimic a polyclonal response could accelerate the development of antibody-based therapies against problematic infections. Here, van der Lans et al describe an antigen-agnostic approach to identify antibodies against Klebsiella pneumoniae. Functional analysis of these antibodies indicates that their capacity to activate complement depends on their antigenic target. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is an opportunistic Gram-negative pathogen with exquisite survival capabilities under various environmental conditions and displays widespread resistance to common antibiotics. A. baumannii is a leading cause of nosocomial infections that result in high morbidity and mortality rates. Accordingly, when multidrug resistance rates surpass threshold levels, the percentage of A. baumannii clinical isolates surges. Research into A. baumannii has increased in the past decade, and multiple mechanisms of pathogenesis have been identified, including mechanisms underlying biofilm development, quorum sensing, exotoxin production, secretion system utilization, and more. To date, the two gold-standard strains used to investigate different aspects of A. baumannii pathogenesis include ATCC 17978 and ATCC 19606. Here, we report a comparative characterization study of three additional A. baumannii clinical isolates obtained from different infection types and derived from different anatomical regions of infected patients. The comparison of three clinical isolates in addition to the ATCC strains revealed that the hypervirulent bacteremia clinical isolate, known as HUMC1, employs a completely different mechanism of pathogenesis when compared to all its counterparts. In stark contrast to the other genetic variants, the hypervirulent HUMC1 isolate does not form biofilms, is antibiotic-susceptible, and has the capacity to reach higher levels of quorum compared to the other clinically relevant strains. Our data also reveal that HUMC1 does not shed endotoxin into the extracellular milieu, rather secretes the evolutionarily conserved, host-mimicking, Zonula occludens toxin (Zot). Taken together, our hypothesis that HUMC1 cells have the ability to reach higher levels of quorum and lack biofilm production and endotoxin shedding, accompanied by the substantial elaboration of Zot, suggests a novel mechanism of pathogenesis that appears to afford the hypervirulent pathogen with stealth-like capabilities when disseminating through the circulatory system in a state of bacteremia. [ABSTRACT FROM AUTHOR]

Background Klebsiella pneumoniae is infamous for hospital-acquired infections and sepsis, which have also been linked to Alzheimer disease (AD)-related neuroinflammatory and neurodegenerative impairment. However, its causative and mechanistic role in AD pathology remains unstudied. Methods A preclinical model of K. pneumoniae enteric infection and colonization is developed in an AD model (3xTg-AD mice) to investigate whether and how K. pneumoniae pathogenesis exacerbates neuropathogenesis via the gut-blood-brain axis. Results K. pneumoniae, particularly under antibiotic-induced dysbiosis, was able to translocate from the gut to the bloodstream by penetrating the gut epithelial barrier. Subsequently, K. pneumoniae infiltrated the brain by breaching the blood-brain barrier. Significant neuroinflammatory phenotype was observed in mice with K. pneumoniae brain infection. K. pneumoniae -infected mice also exhibited impaired neurobehavioral function and elevated total tau levels in the brain. Metagenomic analyses revealed an inverse correlation of K. pneumoniae with gut biome diversity and commensal bacteria, highlighting how antibiotic-induced dysbiosis triggers an enteroseptic "pathobiome" signature implicated in gut-brain perturbations. Conclusions The findings demonstrate how infectious agents following hospital-acquired infections and consequent antibiotic regimen may induce gut dysbiosis and pathobiome and increase the risk of sepsis, thereby increasing the predisposition to neuroinflammatory and neurobehavioral impairments via breaching the gut-blood-brain barrier. [ABSTRACT FROM AUTHOR]

Catheter-related infections are one of the most common nosocomial infections with increasing morbidity and mortality, and robust antibacterial or antifouling catheter coatings remain great challenges for long-term implantation. Herein, multifunctional hydrogel coatings were developed to provide persistent and self-adaptive antifouling and antibacterial effects with self-healing and lubricant capabilities. Polyvinyl alcohol (PVA) with β-cyclodextrin (β-CD) grafts (PVA-Cd) and 4-arm polyethylene glycol (PEG) with adamantane and quaternary ammonium compound (QAC) terminals (QA-PEG-Ad) were crosslinked through host-guest recognitions between adamantane and β-CD moieties to acquire PVEQ coatings. In response to bacterial infections, QACs exhibit reversible transformation between zwitterions (pH 7.4) and cationic lactones (pH 5.5) to generate on-demand bactericidal effect. Highly hydrophilic PEG/PVA backbones and zwitterionic QACs build a lubricate surface and decrease the friction coefficient 10 times compared with that of bare catheters. The antifouling hydrated layer significantly inhibits blood protein adsorption and platelet activation and reveals negligible hemolysis and cytotoxicity. The dynamic host-guest crosslinking achieves full self-healing of cracks in PVEQ hydrogels, and the mechanical profiles were recovered to over 90 % after rejuvenating the broken hydrogels, exhibiting a long-term stability after mechanical stretching, twisting, knotting and compression. After subcutaneous implantation and local bacterial infection, the retrieved PVEQ-coated catheters display no tissue adhesion and 3 log folds lower bacterial number than that of bare catheters. PVEQ coatings effectively prevent the repeated bacterial infections and there are few inflammatory reactions in the surrounding tissue, while substantial lymphoid infiltration and inflammatory cell aggregation occur in muscle tissues around the bare catheter. Thus, this study demonstrates a catheter coating strategy by on-demand bactericidal, self-adaptive antifouling, self-healing and lubricant hydrogels to address medical devices-related infections. It is estimated over two billion peripheral intravenous catheters are annually used in hospitals around the world, and catheter-associated infection has become a great clinical challenge with rapidly rising morbidity and mortality. Surface coating is considered a promising approach, but substantial challenges remain in the development of coatings that simultaneously satisfy both anti-fouling and antibacterial attributes. Even more, few attempts have been made to design mechanically robust coatings and reversible antibacterial or antifouling capabilities, which are critical for long-term medical implants. To address these challenges, we propose a concise strategy to develop hydrogel coatings from commercially available poly(ethylene glycol) and polyvinyl alcohol. In addition to self-healing and lubricant capabilities, the reversible conversion between zwitterionic and cationic lactones of quaternary ammonium compounds enables on-demand bactericidal and self-adaptive antifouling effects. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Extended-spectrum β-lactamase -producing Enterobacterales (ESBL-E) are important zoonotic pathogens that can cause serious clinical infections, also in horses. Preventing the spread of ESBL-E, especially in the equine hospital environment, is key to reducing the number of difficult-to-treat infections. Estimating the local prevalence of ESBL-E in horses is crucial to establish targeted infection control programs at equine hospitals. We conducted a prevalence and risk factor study in equine patients on admission to an equine teaching hospital in Finland through a rectal ESBL-E screening specimen of the horse and a questionnaire. Results: The prevalence of ESBL-E in admitted horses was 3% (5/161, 95% CI 1–7%); none of the tested factors remained statistically significant in multivariate analysis, although antimicrobial treatment within three months was borderline significant (p = 0.052). Extended-spectrum β-lactamase -producing Klebsiella pneumoniae ST6179:CTX-M-15 was detected in three horses using whole-genome sequencing, which in combination with patient records suggested nosocomial transmission. Escherichia coli isolates were ST1250:CTX-M-1 (n = 1), ST1079:CTX-M-1 (n = 1), and ST1245:CTX-M-14 (n = 1). Multiple virulence genes were detected in the ESBL-E isolates. In the ESBL-E positive horses enrolled in a one-year follow-up study, ESBL-E were unlikely to be isolated in rectal screening specimens after the initial positive specimen. Conclusions: The prevalence of ESBL-E in horses visiting a veterinary teaching hospital in Finland is low, indicating an overall low prevalence estimate in the country's equine population. No statistically significant risk factors were identified, likely due to the low number of cases. The duration of ESBL-E carriage is likely to be very short in horses. [ABSTRACT FROM AUTHOR]

Background: The WHO Infection Prevention and Control Assessment Framework (IPCAF) is a standardized tool to assess infection prevention and control (IPC) structures in healthcare facilities. The IPCAF reflects the eight WHO core components (CC) of IPC. Besides facility self-assessment, the IPCAF can be used for national surveys, and repeated usage can aid in describing trends concerning IPC structures. A previous survey in over 700 German hospitals conducted in 2018, yielded an overall high IPC level in participating hospitals, albeit with potentials for improvement. In 2023, the survey was repeated to describe once again the state of IPC implementation in German hospitals and compare findings to data from 2018. Methods: The German National Reference Center for the Surveillance of Nosocomial Infections (NRC) invited 1,530 German acute care hospitals participating in the national surveillance network "KISS", to complete a translated online version of the IPCAF between October 2023 and January 2024. The questionnaire-like nature of the IPCAF, where each answer corresponds to a number of points, allows for calculating an overall IPC score. Based on the overall score, hospitals were allocated to four different IPC levels: inadequate (0–200), basic (201–400), intermediate (401–600), and advanced (601–800). Aggregated scores were calculated and compared with results from 2018. Results: Complete datasets from 660 hospitals were received and analyzed. The median overall IPCAF score was 692.5 (interquartile range: 642.5–737.5), with 572 hospitals (86.6%) classified as advanced, and 87 hospitals (13.2%) as intermediate. One hospital (0.2%) fell into the basic category. The overall median score was virtually unchanged when compared to 2018 (690; data from 736 hospitals). The median score for the CC on workload, staffing and bed occupancy was markedly higher (85 vs. 75), whereas the median score for the CC on multimodal strategies was slightly lower than in 2018 (75 vs. 80). Conclusions: Repeated assessments of IPC structures at the national level with the IPCAF are feasible and a means to gain insights into the evolution of IPC structures. When comparing aggregated scores, a stable and high level of IPC key aspects in Germany was observed, with improvements over time in IPC indicators related to workload and staffing. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to develop and validate a nomogram for assessing the risk of nosocomial infections among obstetric inpatients, providing a valuable reference for predicting and mitigating the risk of postpartum infections. Methods: A retrospective observational study was performed on a cohort of 28,608 obstetric patients admitted for childbirth between 2017 and 2022. Data from the year 2022, comprising 4,153 inpatients, were utilized for model validation. Univariable and multivariable stepwise logistic regression analyses were employed to identify the factors influencing nosocomial infections among obstetric inpatients. A nomogram was subsequently developed based on the final predictive model. The receiver operating characteristic (ROC) curve was utilized to calculate the area under the curve (AUC) to evaluate the predictive accuracy of the nomogram in both the training and validation datasets. Results: The gestational weeks > = 37, prenatal anemia, prenatal hypoproteinemia, premature rupture of membranes (PROM), cesarean sction, operative delivery, adverse birth outcomes, length of hospitalization (days) > 5, CVC use and catheterization of ureter were included in the ultimate prediction model. The AUC of the nomogram was 0.828 (0.823, 0.833) in the training dataset and 0.855 (0.844, 0.865) in the validation dataset. Conclusion: Through a large-scale retrospective study conducted in China, we developed and independently validated a nomogram to enable personalized postpartum infections risk estimates for obstetric inpatients. Its clinical application can facilitate early identification of high-risk groups, enabling timely infection prevention and control measures. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance (AMR) is a global public health concern that is fueled by the overuse of antimicrobial agents. Low- and middle-income countries, including those in Africa,. Point prevalence surveys (PPS) have been recognized as valuable tools for assessing antimicrobial utilization and guiding quality improvement initiatives. This systematic review and meta-analysis aimed to evaluate the prescription rates, indications, and quality of antimicrobial use in African health facilities. Methods: A comprehensive search was conducted in multiple databases, including PubMed, Scopus, Embase, Hinari (Research4Life) and Google Scholar. Studies reporting the point prevalence of antimicrobial prescription or use in healthcare settings using validated PPS tools were included. The quality of the studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. A random-effects meta-analysis was conducted to combine the estimates. Heterogeneity was evaluated using Q statistics, I² statistics, meta-regression, and sensitivity analysis. Publication bias was assessed using a funnel plot and Egger's regression test, with a p-value of < 0.05 indicating the presence of bias. Results: Out of 1790 potential studies identified, 32 articles were included in the meta-analysis. The pooled prescription rate in acute care hospitals was 60%, with significant heterogeneity (I2 = 99%, p < 0.001). Therapeutic prescriptions constituted 62% of all the prescribed antimicrobials. Prescription quality varied: documentation of reasons in notes was 64%, targeted therapy was 10%, and parenteral prescriptions were 65%, with guideline compliance at 48%. Hospital-acquired infections comprised 20% of all prescriptions. Subgroup analyses revealed regional disparities in antimicrobial prescription prevalence, with Western Africa showing a prevalence of 65% and 44% in Southern Africa. Publication bias adjustment estimated the prescription rate at 54.8%, with sensitivity analysis confirming minor variances among studies. Conclusion: This systematic review and meta-analysis provide valuable insights into antimicrobial utilization in African health facilities. The findings highlight the need for improved antimicrobial stewardship and infection control programs to address the high prevalence of irrational antimicrobial prescribing. The study emphasizes the importance of conducting regular surveillance through PPS to gather reliable data on antimicrobial usage, inform policy development, and monitor the effectiveness of interventions aimed at mitigating AMR. [ABSTRACT FROM AUTHOR]