Tracing the Enterococci from Paleozoic Origins to the Hospital.

We examined the evolutionary history of leading multidrug resistant hospital pathogens, the enterococci, to their origin hundreds of millions of years ago. Our goal was to understand why, among the vast diversity of gut flora, enterococci are so well adapted to the modern hospital environment. Molecular clock estimation, together with analysis of their environmental distribution, phenotypic diversity, and concordance with host fossil records, place the origins of the enterococci around the time of animal terrestrialization, 425-500 mya. Speciation appears to parallel the diversification of hosts, including the rapid emergence of new enterococcal species following the End Permian Extinction. Major drivers of speciation include changing carbohydrate availability in the host gut. Life on land would have selected for the precise traits that now allow pathogenic enterococci to survive desiccation, starvation, and disinfection in the modern hospital, foreordaining their emergence as leading hospital pathogens.

Association of dynamics of anellovirus loads with hospital-acquired pneumonia in brain-injured patients during the intensive care unit stay.

BACKGROUND: Critical illness induces immune disorders associated with an increased risk of hospital-acquired pneumonia (HAP) and acute respiratory distress syndrome (ARDS). Torque Teno Virus (TTV), from the Anelloviridae family, are proposed as a biomarker to measure the level of immunosuppression. Our objective was to describe the kinetics of TTV DNA loads and their association with critical-illness related complications. METHODS: We performed a longitudinal study in 115 brain-injured patients from a prospective cohort, collected endotracheal and blood samples at three time points (T1, T2, T3) during the two weeks post-admission in intensive care unit, and measured viral DNA loads using the TTV R-gene® kit (Biomerieux) and a pan-Anelloviridae in house qRT-PCR. RESULTS: TTV DNA was detected in the blood of 69, 71, and 64% of brain-injured patients at T1, T2 and T3 respectively. Time-associated variations of TTV and Anellovirus (AV) DNA loads were observed. Using a linear mixed-effects model, we found that HAP and ARDS were associated with lower blood AV DNA loads. CONCLUSION: Our results show that HAP or ARDS in critically ill patients are associated to changes in AV DNA loads, and should be evaluated further as a biomarker of immune disorders leading to these complications.

Exploration of a Potential DOOR Endpoint for Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia Using Six Registrational Trials for Antibacterial Drugs.

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.

Preventability of Hospital Deaths in Patients with Non-Ventilator Hospital-Acquired Pneumonia.

BACKGROUND: Crude and adjusted mortality rates for patients with non-ventilator hospital-acquired pneumonia (NV-HAP) are amongst the highest of all healthcare-associated infections, leading to calls for greater prevention. Patients prone to NV-HAP, however, tend to be severely ill at baseline making it unclear whether their high mortality rates are due to NV-HAP, underlying conditions, or both. METHODS: Two infectious disease physicians conducted detailed medical record reviews on 150 randomly selected adults from 4 hospitals who died in-hospital following an NV-HAP event between April 2016 and May 2021. Reviewers abstracted risk factors, estimated the preventability of NV-HAP, identified causes of death, and adjudicated the preventability of death. RESULTS: Patients' median age was 69.3 (IQR 60.7-77.4) and 43.3% were female. Comorbidities were common: 57% had cancer, 30% chronic kidney disease, 29% chronic lung disease, and 27% heart failure. At least one hospice-eligible condition was present before NV-HAP in 54% and "Do Not Resuscitate" orders in 24%. Most (99%) had difficult-to-modify NV-HAP risk factors: 76% altered mental status, 35% dysphagia, and 27% nasogastric/orogastric tubes. NV-HAP was deemed possibly or probably preventable in 21% and hospital death likely or very likely preventable in 8.6%. CONCLUSIONS: Most patients who die following NV-HAP have multiple, severe underlying comorbidities and difficult-to-modify risk factors for NV-HAP. Only 1 in 5 NV-HAPs that culminated in death and 1 in 12 deaths following NV-HAP were judged potentially preventable. This does not diminish the importance of NV-HAP prevention programs but informs expectations about the potential magnitude of their impact on hospital deaths.

Moving Beyond Mortality: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia.

BACKGROUND: Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are frequently caused by multidrug-resistant organisms. Patient-centered endpoints in clinical trials are needed to develop new antibiotics for HABP/VABP. Desirability of outcome ranking (DOOR) is a paradigm for the design, analysis, and interpretation of clinical trials based on a patient-centered, benefit-risk evaluation. METHODS: A multidisciplinary committee created an infectious diseases DOOR endpoint customized for HABP/VABP, incorporating infectious complications, serious adverse events, and mortality. We applied this to 2 previously completed, large randomized controlled trials for HABP/VABP. ZEPHyR compared vancomycin to linezolid and VITAL compared linezolid to tedizolid. For each trial, we evaluated the DOOR distribution and probability, including DOOR component and partial credit analyses. We also applied DOOR in subgroup analyses. RESULTS: In both trials, the HABP/VABP DOOR demonstrated similar overall clinical outcomes between treatment groups. In ZEPHyR, the probability that a participant treated with linezolid would have a more desirable outcome than a participant treated with vancomycin was 50.2% (95% confidence interval [CI], 45.1%--55.3%). In VITAL, the probability that a participant treated with tedizolid would have a more desirable outcome than a participant treated with linezolid was 48.7% (95% CI, 44.8%-52.6%). The DOOR component analysis revealed that participants treated with tedizolid had a less desirable outcome than those treated with linezolid when considering clinical response alone. However, participants with decreased renal function had improved overall outcomes with tedizolid. CONCLUSIONS: The HABP/VABP DOOR provided more granular information about clinical outcomes than is typically presented in clinical trials. HABP/VABP trials would benefit from prospectively using DOOR.

Hospital- and Ventilator-associated Pneumonia early after Lung Transplantation: a prospective Study on Incidence, Pathogen Origin and Outcome.

BACKGROUND: Hospital- (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 (07/2019-01/2020 and 10/2021-11/2022) were prospectively included. We assessed incidence and presentation of pneumonia and evaluated the impact of associated factors using regression models. In addition, we 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-transplant; 30- and 90-day mortality were similar. CONCLUSIONS: Prospectively assessed early pneumonia incidence occurred in around 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.

Lowering the Acquisition of Multi-drug Resistant Organism (MDROs) with Pulsed-xenon (LAMP) Study: a cluster randomized controlled, double-blinded, interventional crossover trial.

BACKGROUND: Environmental disinfection is essential for reducing spread of healthcare associated infections (HAIs). Previous studies report conflicting results regarding the effects of ultraviolet light (UV) in reducing infections. This trial evaluated the impact of adding pulsed xenon UV (PX-UV) to standard terminal cleaning in reducing environmentally-implicated HAIs (eiHAIs). METHODS: The LAMP trial was conducted in 2 hospitals (15 inpatient wards) utilizing a cluster randomized controlled, double-blinded, interventional crossover trial comparing standard terminal cleaning followed by either pulsed xenon ultraviolet (PX-UV) disinfection (intervention arm) or sham disinfection (control arm). The primary outcome was incidence of eiHAIs from clinical microbiology tests on the 4th day of stay or later or within 3 days after discharge from the study unit. EiHAIs included clinical cultures positive for vancomycin-resistant enterococci (VRE), extended spectrum beta-lactamase-producing Escherichia coli or Klebsiella pneumonia, methicillin-resistant Staphylococcus aureus (MRSA), and Acinetobacter baumannii, and stool PCR positive for Clostridiodes difficile. FINDINGS: Between May 18, 2017 to Jan 7, 2020, 25,732 patients were included, with an incidence of 601 eiHAI and 180,954 patient days. There was no difference in the rate of eiHAIs in the intervention and sham arms (3.49 vs 3.17 infections/1000 patient days respectively, RR 1.10 CI (0.94, 1.29, p= 0.23)). Study results were similar when stratified by eiHAI type, hospital, and unit type. CONCLUSION: The LAMP study failed to demonstrate an effect of the addition of UV light disinfection following terminal cleaning on reductions in rates of eiHAIs. Further investigations targeting hospital environmental surfaces and the role of no touch technology to reduce HAIs are needed.

Opportunistic Elizabethkingia miricola Infections in Intensive Care Unit, Spain.

In 2021, we identified a cluster of Elizabethkingia miricola cases in an intensive care unit in Spain. Because E. miricola is not considered a special surveillance agent in Spain, whole-genome sequencing was not performed. The bacterial source was not identified. All Elizabethkingia species should be listed as special surveillance bacteria.

Identifying Contact Time Required for Secondary Transmission of Clostridioides difficile Infections by Using Real-Time Locating System.

Considering patient room shortages and prevalence of other communicable diseases, reassessing the isolation of patients with Clostridioides difficile infection (CDI) is imperative. We conducted a retrospective study to investigate the secondary CDI transmission rate in a hospital in South Korea, where patients with CDI were not isolated. Using data from a real-time locating system and electronic medical records, we investigated patients who had both direct and indirect contact with CDI index patients. The primary outcome was secondary CDI transmission, identified by whole-genome sequencing. Among 909 direct and 2,711 indirect contact cases, 2 instances of secondary transmission were observed (2 [0.05%] of 3,620 cases), 1 transmission via direct contact and 1 via environmental sources. A low level of direct contact (113 minutes) was required for secondary CDI transmission. Our findings support the adoption of exhaustive standard preventive measures, including environmental decontamination, rather than contact isolation of CDI patients in nonoutbreak settings.

Understanding blaNDM-1 gene regulation in CRKP infections: toward novel antimicrobial strategies for hospital-acquired pneumonia.

BACKGROUND: The escalating challenge of Carbapenem-resistant Klebsiella pneumoniae (CRKP) in hospital-acquired pneumonia (HAP) is closely linked to the blaNDM-1 gene. This study explores the regulatory mechanisms of blaNDM-1 expression and aims to enhance antibacterial tactics to counteract the spread and infection of resistant bacteria. METHODS: KP and CRKP strains were isolated from HAP patients' blood samples. Transcriptomic sequencing (RNA-seq) identified significant upregulation of blaNDM-1 gene expression in CRKP strains. Bioinformatics analysis revealed blaNDM-1 gene involvement in beta-lactam resistance pathways. CRISPR-Cas9 was used to delete the blaNDM-1 gene, restoring sensitivity. In vitro and in vivo experiments demonstrated enhanced efficacy with Imipenem and Thanatin or Subatan combination therapy. RESULTS: KP and CRKP strains were isolated with significant upregulation of blaNDM-1 in CRKP strains identified by RNA-seq. The Beta-lactam resistance pathway was implicated in bioinformatics analysis. Knockout of blaNDM-1 reinstated sensitivity in CRKP strains. Further, co-treatment with Imipenem, Thanatin, or Subactam markedly improved antimicrobial effectiveness. CONCLUSION: Silencing blaNDM-1 in CRKP strains from HAP patients weakens their Carbapenem resistance and optimizes antibacterial strategies. These results provide new theoretical insights and practical methods for treating resistant bacterial infections.

A new model of endotracheal tube biofilm identifies combinations of matrix-degrading enzymes and antimicrobials able to eradicate biofilms of pathogens that cause ventilator-associated pneumonia.

Ventilator-associated pneumonia is defined as pneumonia that develops in a patient who has been on mechanical ventilation for more than 48 hours through an endotracheal tube. It is caused by biofilm formation on the indwelling tube, which introduces pathogenic microbes such as Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans into the patient's lower airways. Currently, there is a lack of accurate in vitro models of ventilator-associated pneumonia development. This greatly limits our understanding of how the in-host environment alters pathogen physiology and the efficacy of ventilator-associated pneumonia prevention or treatment strategies. Here, we showcase a reproducible model that simulates the biofilm formation of these pathogens in a host-mimicking environment and demonstrate that the biofilm matrix produced differs from that observed in standard laboratory growth medium. In our model, pathogens are grown on endotracheal tube segments in the presence of a novel synthetic ventilated airway mucus medium that simulates the in-host environment. Matrix-degrading enzymes and cryo-scanning electron microscopy were employed to characterize the system in terms of biofilm matrix composition and structure, as compared to standard laboratory growth medium. As seen in patients, the biofilms of ventilator-associated pneumonia pathogens in our model either required very high concentrations of antimicrobials for eradication or could not be eradicated. However, combining matrix-degrading enzymes with antimicrobials greatly improved the biofilm eradication of all pathogens. Our in vitro endotracheal tube model informs on fundamental microbiology in the ventilator-associated pneumonia context and has broad applicability as a screening platform for antibiofilm measures including the use of matrix-degrading enzymes as antimicrobial adjuvants.

Modelling lung infection with Klebsiella pneumoniae after murine traumatic brain injury.

Pneumonia is a common comorbidity in patients with severe traumatic brain injury (TBI), and is associated with increased morbidity and mortality. In this study, we established a model of intratracheal Klebsiella pneumoniae administration in young adult male and female mice, at 4 days following an experimental TBI, to investigate how K. pneumoniae infection influences acute post-TBI outcomes. A dose-response curve determined the optimal dose of K. pneumoniae for inoculation (1 x 10^6 colony forming units), and administration at 4 days post-TBI resulted in transient body weight loss and sickness behaviors (hypoactivity and acute dyspnea). K. pneumoniae infection led to an increase in pro-inflammatory cytokines in serum and bronchoalveolar lavage fluid at 24 h post-infection, in both TBI and sham (uninjured) mice. By 7 days, when myeloperoxidase + neutrophil numbers had returned to baseline in all groups, lung histopathology was observed with an increase in airspace size in TBI + K. pneumoniae mice compared to TBI + vehicle mice. In the brain, increased neuroinflammatory gene expression was observed acutely in response to TBI, with an exacerbated increase in Ccl2 and Hmox1 in TBI + K. pneumoniae mice compared to either TBI or K. pneumoniae alone. However, the presence of neuroinflammatory immune cells in the injured brain, and the extent of damage to cortical and hippocampal brain tissue, was comparable between K. pneumoniae and vehicle-treated mice by 7 days. Examination of the fecal microbiome across a time course did not reveal any pronounced effects of either injury or K. pneumoniae on bacterial diversity or abundance. Together, these findings demonstrate that K. pneumoniae lung infection after TBI induces an acute and transient inflammatory response, primarily localized to the lungs with some systemic effects. However, this infection had minimal impact on secondary injury processes in the brain following TBI. Future studies are needed to evaluate the potential longer-term consequences of this dual-hit insult.

Mycobacterium immunogenum acquisition from hospital tap water: a genomic and epidemiologic analysis.

We identified 23 cases of Mycobacterium immunogenum respiratory acquisition linked to a colonized plumbing system at a new hospital addition. We conducted a genomic and epidemiologic investigation to assess for clonal acquisition of M. immunogenum from hospital water sources and improve understanding of genetic distances between M. immunogenum isolates. We performed whole-genome sequencing on 28 M. immunogenum isolates obtained from August 2013 to July 2021 from patients and water sources on four intensive care and intermediate units at an academic hospital. Study hospital isolates were recovered from 23 patients who experienced de novo respiratory isolation of M. immunogenum and from biofilms obtained from five tap water outlets. We also analyzed 10 M. immunogenum genomes from previously sequenced clinical (n = 7) and environmental (n = 3) external control isolates. The 38-isolate cohort clustered into three clades with pairwise single-nucleotide polymorphism (SNP) distances ranging from 0 to 106,697 SNPs. We identified two clusters of study hospital isolates in Clade 1 and one cluster in Clade 2 for which clinical and environmental isolates differed by fewer than 10 SNPs and had less than 0.5% accessory genome variation. A less restrictive combined threshold of 40 SNPs and 5% accessory genes reliably captured additional isolates that met clinical criteria for hospital acquisition, but 12 (4%) of 310 epidemiologically unrelated isolate pairs also met this threshold. Core and accessory genome analyses confirmed respiratory acquisition of multiple clones of M. immunogenum from hospital water sources to patients. When combined with epidemiologic investigation, genomic thresholds accurately distinguished hospital acquisition.

Effects of clinically achievable pulmonary antibiotic concentrations on the recovery of bacteria: in vitro comparison of the BioFire FILMARRAY Pneumonia Panel versus conventional culture methods in bronchoalveolar lavage fluid.

Empiric antibiotics may affect bacterial pathogen recovery using conventional culture methods (CCMs), while PCR-based diagnostics are likely less affected. Herein, we conducted an in vitro study of bronchoalveolar lavage fluid (BAL) inoculated with bacteria and clinically relevant antibiotic concentrations to compare the recovery between the BioFire FILMARRAY Pneumonia Panel (Pn Panel) and CCMs. Remnant clinical BAL specimens were inoculated to ~105 cfu/mL using 12 clinical isolates. Isolates consisted of one wild-type (WT) and one or more resistant strains of: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus. Piperacillin-tazobactam, cefepime, meropenem, levofloxacin, or vancomycin was added to achieve pulmonary epithelial lining fluid peak and trough concentrations. Post-exposure cfu/mL was quantified by CCMs and simultaneously tested by the PN Panel for identification and semi-quantitative genetic copies/mL. CCM results were categorized as significant growth (SG) (≥1 × 104), no significant growth (NSG) (≥1 × 103, <1 × 104), or no growth (NG) (<1 × 103). The PN Panel accurately identified all isolates, resistance genes, and reported ≥106 genetic copies/mL regardless of antibiotic exposure. The CCM also identified all S. aureus strains exposed to vancomycin. For WT Gram-negative isolates exposed to antibiotics, SG, NSG, and NG were observed in 7/52 (13%), 18/52 (35%), and 27/52 (52%) of CCM experiments, respectively. For resistant Gram-negatives isolates, SG, NSG, and NG were observed in 62/88 (70%), 17/88 (19%), and 9/88 (10%), respectively. These in vitro data demonstrate that the PN Panel is able to identify Gram-negative pathogens in the presence of clinically significant antibiotic concentrations when CCM may not.

Characterization and genetic analysis of extensively drug-resistant hospital acquired Pseudomonas aeruginosa isolates.

BACKGROUND: The incidence of hospital-acquired infections in extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) has been increasing worldwide and is frequently associated with an increase in mortality and morbidity rates. The aim of this study was to characterize clinical XDR-PA isolates recovered during six months at three different hospitals in Egypt. RESULTS: Seventy hospital-acquired clinical isolates of P. aeruginosa were classified into multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR), according to their antimicrobial resistance profile. In addition, the possession of genes associated with mobile genetic elements and genes encoding antimicrobial resistance determinants among isolates were detected using polymerase chain reaction. As a result, a significant percentage of the isolates (75.7%) were XDR, while 18.5% were MDR, however only 5.7% of the isolates were non-MDR. The phenotypic detection of carbapenemases, extended-spectrum ß-lactamases (ESBLs) and metallo ß-lactamase (MBL) enzymes showed that 73.6% of XDR-PA isolates were carbapenemases producers, whereas 75.5% and 88.7% of XDR-PA isolates produced ESBLs and MBL respectively. In addition, PCR screening showed that oxa gene was the most frequently detected gene of carbapenemases (91.4%), while aac(6')-lb gene was mostly detected (84.3%) among the screened aminoglycosides-resistance genes. Furthermore, the molecular detection of the colistin resistance gene showed that 12.9% of isolates harbored mcr-1 gene. Concerning mobile genetic element markers (intI, traA, tnp513, and merA), intI was the highest detected gene as it was amplified in 67 isolates (95.7%). Finally, phylogenetic and molecular typing of the isolates via ERIC-PCR analysis revealed 10 different ERIC fingerprints. CONCLUSION: The present study revealed a high prevalence of XDR-PA in hospital settings which were resistant to a variety of antibiotics due to several mechanisms. In addition, 98% of the XDR-PA clinical isolates contained at least one gene associated with movable genetic elements, which could have aided the evolution of these XDR-PA strains. To reduce spread of drug resistance, judicious use of antimicrobial agents and strict infection control measures are therefore essential.

Current and novel therapies for management of Acinetobacter baumannii-associated pneumonia.

Acinetobacter baumannii is a common pathogen associated with hospital-acquired pneumonia showing increased resistance to carbapenem and colistin antibiotics nowadays. Infections with A. baumannii cause high patient fatalities due to their capability to evade current antimicrobial therapies, emphasizing the urgency of developing viable therapeutics to treat A. baumannii-associated pneumonia. In this review, we explore current and novel therapeutic options for overcoming therapeutic failure when dealing with A. baumannii-associated pneumonia. Among them, antibiotic combination therapy administering several drugs simultaneously or alternately, is one promising approach for optimizing therapeutic success. However, it has been associated with inconsistent and inconclusive therapeutic outcomes across different studies. Therefore, it is critical to undertake additional clinical trials to ascertain the clinical effectiveness of different antibiotic combinations. We also discuss the prospective roles of novel antimicrobial therapies including antimicrobial peptides, bacteriophage-based therapy, repurposed drugs, naturally-occurring compounds, nanoparticle-based therapy, anti-virulence strategies, immunotherapy, photodynamic and sonodynamic therapy, for utilizing them as additional alternative therapy while tackling A. baumannii-associated pneumonia. Importantly, these innovative therapies further require pharmacokinetic and pharmacodynamic evaluation for safety, stability, immunogenicity, toxicity, and tolerability before they can be clinically approved as an alternative rescue therapy for A. baumannii-associated pulmonary infections.

Association between continued metformin use during hospital admission and hospital-acquired complications.

AIMS: The safety of continuing metformin during a hospital admission has not been robustly demonstrated. We evaluated the association of continuing metformin in hospital with the risk for a hospital-acquired complication (HAC). METHODS: This is a retrospective observational study of patients admitted to a medical or surgical ward. We considered those with diabetes who continued metformin (DM/MET group), those who discontinued metformin upon admission (DM/MET-STOP), and those with diabetes not on metformin just prior to and during admission (DM/NoMET). We prepared propensity score-matched (PSM) control groups from admitted patients without diabetes. The likelihood of a HAC was determined using a Kaplan-Meier survival analysis. A Cox proportional hazards model was employed to calculate the hazard ratio, adjusted for covariates. RESULTS: Of the 4446 (14%) patients with diabetes, 3331 (10%) were prescribed metformin on admission, and it was continued in 2557 patients. HAC occurred in 5.5% of DM/MET group and 6.4% of the PSM control group. Continuation of metformin was associated with a lower likelihood of HAC, adjusted hazard ratio 0.85 (95% CI 0.69, 1.04), p = 0.117 compared to a PSM-matched control group without diabetes. The DM/NoMET and DM/MET-STOP groups had an increased risk for HAC, adjusted HR 1.77 (1.44, 2.18), p < 0.001 and 2.57 (2.10, 3.13), p < 0.001, as compared to their respective PSM control groups. CONCLUSION: An individualized assessment to continue metformin during hospital admission was associated with a reduced likelihood of HAC, with the caveat that there was limited matching to non-diabetes controls. This finding warrants further exploration.

Evaluation of the impact of diagnostic blood loss and red blood cell transfusion in very-low-birth-weight anaemic neonates during hospitalization: A multi-centre retrospective clinical study.

BACKGROUND AND OBJECTIVES: Diagnostic blood loss is a significant factor in the development of anaemia in neonates with very low birth weight. This study aimed to assess the clinical efficacy of intervention approaches involving varying diagnostic blood loss and red blood cell transfusion volumes in neonates with very low birth weights experiencing anaemia during hospitalization. MATERIALS AND METHODS: A total of 785 newborns with anaemia weighing less than 1500 g were enrolled from 32 hospitals in China. The study involved monitoring diagnostic blood loss and red blood cell transfusion and evaluating relevant interventions such as red blood cell transfusion and clinical outcomes. Three intervention approaches were established based on the difference between blood loss and transfusion (Intervention Approaches 0, 1 and 2). The primary outcomes measured were unsatisfactory weight gain during hospitalization and neonatal mortality. The secondary outcomes included related complications. RESULTS: In the non-hospital-acquired anaemia group, Intervention Approach 2 had the highest incidence of below-normal weight gain (odds ratio [OR]: 3.019, 95% confidence interval [CI]: 1.081-8.431, p = 0.035). Multivariate analysis revealed that Intervention Approach 1 had a protective effect on weight gain. In the hospital-acquired anaemia group, Intervention Approach 2 had the highest incidence of below-normal weight gain (OR: 3.335, 95% CI: 1.785-6.234, p = 0.000) and mortality (OR: 5.341, 95% CI: 2.449-11.645, p = 0.000), while Intervention Approach 1 had the lowest incidence of intraventricular haemorrhage. Intervention Approach 1 demonstrated favourable outcomes in both anaemia groups. CONCLUSION: Intervention Approach 1 improved weight gain and reduced mortality and complications in both the non-hospital-acquired and hospital-acquired anaemia groups.

Understanding bacterial diversity, infection dynamics, prevention of antibiotic resistance: an integrated study in an Algerian hospital context.

PURPOSE: Bacterial infections, particularly bacteremia, urinary tract infections (UTIs), and pus infections, remain among hospitals' most worrying medical problems. This study aimed to explore bacterial diversity, infection dynamics, and antibiotic resistance profiles of bacterial isolates. METHODS: We analyzed data from 1750 outpatients and 920 inpatients, of whom 1.6% and 8.47% respectively had various bacterial infections. RESULTS: The analysis revealed that UTIs were the most prevalent at 41.01%, particularly affecting women. UTIs also showed a distinct distribution across admission departments, notably in emergency (23.07%) and pediatric (14.10%) units. The most frequently isolated microorganisms were Escherichia coli (E. coli), followed by Klebsiella ornithinolytica. Skin infections followed UTIs, accounting for 35.88% of cases, more prevalent in men, with Staphylococcus aureus (S. aureus) being the primary pathogen (57%). Gram-negative bacteria (GNB) like E. coli and Pseudomonas aeruginosa contributed significantly to skin infections (43%). Bacteremia cases constituted 11.52% of bacterial infections, predominantly affecting women (67%) and linked to GNB (78%). A comparative study of antibiotic susceptibility profiles revealed more pronounced resistance in GNB strains isolated from inpatients, particularly to antibiotics such as Amoxicillin/clavulanic acid, Tetracyclin, Gentamicin, Chloramphenicol, and Ampicillin. In contrast, strains from ambulatory patients showed greater resistance to Colistin. Gram-positive bacteria from hospitalized patients showed higher resistance to quinolones and cephalosporins, while ambulatory strains showed high resistance to aminoglycosides, macrolides, fluoroquinolones, and penicillin. Furthermore, these analyses identified the most effective antibiotics for the empirical treatment of both community-acquired and nosocomial infections. Ciprofloxacin, aztreonam, and amikacin exhibited low resistance rates among GNB, with gentamicin and chloramphenicol being particularly effective for community-acquired strains. For S. aureus, ciprofloxacin, rifampicin, and cefoxitin were especially effective, with vancomycin showing high efficacy against community-acquired isolates and fosfomycin and chloramphenicol being effective for hospital-acquired strains. CONCLUSION: These results are essential for guiding antibiotic therapy and improving clinical outcomes, thus contributing to precision medicine and antimicrobial stewardship efforts.

Association between nurse staffing level in intensive care settings and hospital-acquired pneumonia among surgery patients: result from the Korea National Health Insurance cohort.

This study examined the association between the number of nursing staff in intensive care units (ICUs) and hospital-acquired pneumonia (HAP) among surgical patients in South Korea. Data were obtained between 2008 and 2019 from the Korean National Health Insurance Service Cohort Database; 37,706 surgical patients who received critical care services were included in the analysis. Patients with a history of pneumonia 1 year prior to surgery or those who had undergone lung-related surgery were excluded. The ICU nursing management fee is an admission fee that varies based on the grading determined by nurse-to-bed ratio. Using this grading system, we classified four groups from the highest to the lowest level based on the proportion of beds to nurses (high, high-mid, mid-low, and low group). HAP was defined by the International Classification of Disease, 10th revision (ICD-10) code. Multilevel logistic regression was used to investigate the relationship between the level of ICU nurse staffing and pneumonia, controlling for variables at the individual and hospital levels. Lower levels of nurse staffing were associated with a greater incidence of HAP than higher levels of nurse staffing (mid-high, OR: 1.33, 95% CI: 1.12-1.57; mid-low, OR: 1.61, 95% CI: 1.27-2.04; low, OR: 2.13, 95% CI: 1.67-2.71). The intraclass correlation coefficient value was 0.177, and 17.7% of the variability in HAP was accounted for by the hospital. Higher ICU nursing management fee grades (grade 5 and above) in general and hospital settings were significantly associated with an increased risk of HAP compared to grade 1 admissions. Similarly, in tertiary hospitals, grade 2 and higher ICU nursing management fees were significantly associated with an increased risk of HAP compared to grade 1 admissions. Especially, a lower level of nurse staffing was associated with bacterial pneumonia but not pneumonia due to aspiration. In conclusion, this study found an association between the level of ICU nurse staffing and HAP among surgical patients. A lower level of nurse staffing in the ICU was associated with increased rates of HAP among surgical patients. This indicates that having fewer beds assigned to nurses in the ICU setting is a significant factor in preventing HAP, regardless of the size of the hospital.