Introduction. Klebsiella spp. are important bacteria that colonize the human intestine, especially in preterm infants; they can induce local and systemic disease under specific circumstances, including inflammatory bowel disease, necrotizing enterocolitis and colorectal cancer.Hypothesis. Klebsiella spp. colonized in the intestine of the neonates in the neonatal intensive care unit (NICU) may be associated with disease and antibiotic resistance, which will be hazardous to the children.Aim. Our aim was to know about the prevalence, antimicrobial resistance and genome characteristics of Klebsiella spp. in neonate carriers.Methodology. Genome sequencing and analysis, and antimicrobial susceptibility testing were mainly performed in this study.Results. The isolation rates of Klebsiella spp. strains were 3.7% (16/436) in 2014 and 4.3% (18/420) in 2021. Cases with intestinal-colonized Klebsiella spp. were mainly infants with low birth weights or those with pneumonia or hyperbilirubinemia. According to the core-pan genomic analysis, 34 stains showed gene polymorphism and a sequence type (ST) of an emerging high-risk clone (ST11). Eight strains (23.5%) were found to be resistant to 2 or more antibiotics, and 46 genes/gene families along with nine plasmids were identified that conferred resistance to antibiotics. In particular, the two strains were multidrug-resistant. Strain A1256 that is related to Klebsiella quasipneumoniae subsp. similipneumoniae was uncommon, carrying two plasmids similar to IncFII and IncX3 that included five antibiotic resistance genes.Conclusion. The prevention and control of neonatal Klebsiella spp. colonization in the NICU should be strengthened by paying increased attention to preventing antimicrobial resistance in neonates.

OBJECTIVE: To understand the microbial profile and investigate the independent predictors for healthcare-associated pneumonia (HCAP) pertinaciously caused by isolates of multidrug-resistant (MDR) Gram-negative bacteria (GNB).
METHODS: Multicenter ICU patients who received appropriate antibiotic treatments for preceding pneumonia due to MDR GNB isolates and subsequently developed HCAP caused by either MDR GNB (n = 126) or non-MDR GNB (n = 40) isolates in Taiwan between 2018 and 2023 were enrolled. Between the groups of patients with HCAP due to MDR GNB and non-MDR GNB, the proportions of the following variables, including demographic characteristics, important co-morbidities, nursing home residence, physiological severity, intervals between two hospitalizations, steroid use, the tracheostomy tube use alone, ventilator support, and the predominant GNB species involving HCAP, were analyzed using the chi-square test. Logistic regression was employed to explore the independent predictors for HCAP persistently caused by MDR GNB in the aforementioned variables with a P-value of <0.15 in the univariate analysis.
RESULTS: MDR-Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii complex were the three predominant species causing HCAP. Chronic structural lung disorders, diabetes mellitus, intervals of ≤30 days between two hospitalizations, use of the tracheostomy tube alone, and prior pneumonia caused by MDR A. baumannii complex were shown to independently predict the HCAP tenaciously caused by MDR GNB. Conversely, the preceding pneumonia caused by MDR P. aeruginosa was a negative predictor.
CONCLUSIONS: Identifying predictors for HCAP persistently caused by MDR GNB is crucial for prescribing appropriate antibiotics.

We compared clinical outcomes of patients who received monotherapy and combination therapy for treatment of MDR A. baumannii VAP. 170 patients were included. Vasopressor use and mortality rate were higher for combination therapy (69.3% versus 28.6%, p=0.024; 67.5% versus 14.3%, p=0.007; respectively). Majority received polymyxin B-based combination therapy, with higher mortality than those without polymyxin B (80.2% versus 19.8%, p=0.043). After adjusting for vasopressor use, monotherapy, dual combination, and triple combination therapy were not associated with mortality (aHR 0.24, 95% CI 0.03 to 1.79, p=0.169; aHR 1.26, 95% CI 0.79 to 2.00, p=0.367; aHR 0.93, 95% CI 0.57 to 1.49, p=0.744; respectively). There was no difference in adverse effects and length of stay between the two groups. Mortality from MDR A. baumannii VAP was high and not associated with monotherapy or combination therapy after adjustment for vasopressor use. Antibiotic regimens other than those containing polymyxin are urgently needed for the treatment of these infections.

Multidrug-resistant pathogens pose an earnest risk to human health. Therefore, new antibiotics need to be developed quickly. Most of the antibiotics we use today are derived from secondary metabolites, which are produced by plants. Genome mining tools allow us to detect biosynthetic gene clusters (BGCs) responsible for the production of secondary metabolites. Focusing on the most promising BGCs-coding antibiotics with unique pathways is currently a challenge. In silico approach like genome mining are used to visualise the action of these bioactive chemicals. Camelina sativa is a well-known medicinal plant and it would be interesting to study its secondary metabolites. In this work, we found seven bioactive compounds in this plant using the genome mining approach. Further, the clusters of genes involved in the biosynthesis of these compounds were analysed with their metabolic pathways. This work illuminates new ground on the evolution of BGCs for the nutritional improvement of C. sativa.

Slaughterhouses produce huge volumes of effluents throughout the production chain that, when discharged untreated into bodies of water, can become a source of environmental contamination. This is particularly worrisome if these effluents are used for irrigation since they increase contamination levels and spread pathogens and resistance determinants to humans and animals. Therefore, in this study, we assessed antimicrobial resistance in bacteria isolated from inlet water, equalization wastewater tanks, treatment plant wastewater, and treated wastewater in slaughterhouse facilities in Rio de Janeiro, Brazil. Four samples were collected at each of the collection points, between June 2021 and July 2022. Following bacterial isolation and identification, the samples were analyzed for antimicrobial resistance using the disk diffusion method to test aminoglycoside, beta-lactam, and fluoroquinolone antimicrobials. A total of 229 bacteria were isolated, with 74 isolates selected from the genera Citrobacter (12), Enterobacter (14), Klebsiella (35), Serratia (5), and Pseudomonas (8). Inlet water had the lowest number of isolates and was the only point with gentamicin-resistant isolates. Raw effluent from the equalization tank showed the highest number of isolated bacteria and resistance levels, followed by treated wastewater and the treatment plant. Across all samples, a high rate of cefoxitin-resistance was observed among the isolated bacteria. Klebsiella pneumoniae stood out as the species that demonstrated the greatest resistance to a variety of antimicrobials. These results highlight the importance of water quality monitoring in mitigating public health and environmental risks and high antimicrobial resistance levels.

UNASSIGNED: tuberculosis (TB) remains a leading cause of death in South Africa. KwaZulu-Natal (KZN) is one of the provinces with a high burden of TB/drug-resistant TB cases and deaths. We determined predictors for mortality among drug-resistant TB patients on treatment in KZN province.
UNASSIGNED: we conducted a retrospective cohort study using secondary data from the Electronic Drug-Resistant Tuberculosis Register. We used a modified Poisson regression model with robust standard errors to determine predictors for drug-resistant TB mortality.
UNASSIGNED: of the 7,692 eligible patients, 1,234 (16.0%) died. Males predominated (707, 57.3%) and the median age was 36 years (Interquartlile Range: 29-45 years). The majority (978, 79.2%) were HIV-TB co-infected with 911 (93%) on antiretroviral treatment (ART). The predictors included HIV-TB co-infection without ART (aIRR 3.4; 95% CI: 2.3-5.1), unknown ART status (aIRR: 1.8; 95% CI: 1.4-2.3), aged ≥60 years (aIRR: 2.1; 95% CI: 1.6-2.7), previous drug-resistant TB (aIRR: 1.5; 95% CI: 1.2-1.8) and exposure to second-line drugs (aIRR: 1.7; 95% CI: 1.4-2.0). Other predictors were hospitalization during treatment initiation (aIRR 2.5; 95% CI 2.0-3.1), initiation in other treatment facilities (aIRR: 2.2; 95% CI: 1.6-2.9) and rifampicin-resistant (aIRR: 1.2; 95% CI: 1.1-1.4). Bedaquiline fumarate was a significant protective factor against death (aIRR: 0.5; 95% CI: 0.4-0.5).
UNASSIGNED: older age, HIV co-infection without ART, hospitalization for treatment initiation, exposure to second-line drugs and a previous episode of drug-resistant TB were predictors for DR-TB mortality. Early treatment initiation and provision of antiretroviral treatment for all co-infected patients may reduce DR-TB mortality in the Province.

BACKGROUND: Mediastinitis remains one of the most serious complications of cardiac surgery. The reported incidence is 1-4%, while the related mortality varies from 10-47%.
METHODS: A patient with triple vessel disease (TVD) was hospitalized at our clinic for coronary artery bypass graft (CABG) surgery. The preoperative examination results were normal. We performed standard CABG under extracorporeal circulation. The patient had a favorable postoperative course. On the fifth postoperative day, the wound showed seropurulent drainage. The treatment of the patient\'s wound continued with open dressing, negative wound pressure device, debridement, minimal muscle plasticity, and total bilateral muscle pectoral flap plasticity. The infecting microorganism was identified as multidrug-resistant Acinetobacter baumani, and systemic antibiotic therapy was initiated. The patient had \"per secundum closure\" of the wound after all these efforts. The wound healed completely 2 months after discharge, and the patient was in good health.
CONCLUSIONS: Mediastinitis is associated with high mortality and high financial and human costs. The occurrence of this high-risk complication can be prevented through constant vigilance at every step from admission to discharge.

The continuous rise of multidrug-resistant (MDR) Gram-negative bacteria poses a severe threat to public health worldwide. Colistin(COL), employed as the last-line antibiotic against MDR pathogens, is now at risk due to the emergence of colistin-resistant (COL-R) bacteria, potentially leading to adverse patient outcomes. In this study, synergistic activity was observed when colistin and diclofenac sodium (DS) were combined and used against clinical COL-R strains of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), Acinetobacter baumannii (A. baumannii), and Pseudomonas aeruginosa (P. aeruginosa) both in vitro and in vivo. The checkerboard method and time-killing assay showed that DS, when combined with COL, exhibited enhanced antibacterial activity compared to DS and COL monotherapies. Crystal violet staining and scanning electron microscopy showed that COL-DS inhibited biofilm formation compared with monotherapy. The in vivo experiment showed that the combination of DS and COL reduced bacterial loads in infected mouse thighs. Synergistic activity was observed when COL and DS were use in combination against clinical COL-R strains of E. coli, K. pneumoniae, A. baumannii and P. aeruginosa both in vitro and in vivo. The synergistic antibacterial effect of the COL-DS combination has been confirmed by performing various in vitro and in vivo experiments, which provides a new treatment strategy for infections caused by MDR bacteria.

SUMMARYDespite the early recognition of their therapeutic potential and the current escalation of multidrug-resistant (MDR) pathogens, the adoption of bacteriophages into mainstream clinical practice is hindered by unfamiliarity with their basic pharmacokinetic (PK) and pharmacodynamic (PD) properties, among others. Given the self-replicative nature of bacteriophages in the presence of host bacteria, the adsorption rate, and the clearance by the host\'s immunity, their PK/PD characteristics cannot be estimated by conventional approaches, and thus, the introduction of new considerations is required. Furthermore, the multitude of different bacteriophage types, preparations, and treatment schedules impedes drawing general conclusions on their in vivo PK/PD features. Additionally, the drawback of acquired bacteriophage resistance of MDR pathogens with clinical and environmental implications should be taken into consideration. Here, we provide an overview of the current state of the field of PK and PD of bacteriophage therapy with a focus on its application against MDR Gram-negative infections, highlighting the potential knowledge gaps and the challenges in translation from the bench to the bedside. After reviewing the in vitro PKs and PDs of bacteriophages against the four major MDR Gram-negative pathogens, Klebsiella pneumoniae, Acinetobacter baumannii complex, Pseudomonas aeruginosa, and Escherichia coli, specific data on in vivo PKs (tissue distribution, route of administration, and basic PK parameters in animals and humans) and PDs (survival and reduction of bacterial burden in relation to the route of administration, timing of therapy, dosing regimens, and resistance) are summarized. Currently available data merit close scrutiny, and optimization of bacteriophage therapy in the context of a better understanding of the underlying PK/PD principles is urgent to improve its therapeutic effect and to minimize the occurrence of bacteriophage resistance.

Salmonella typhimurium (S. typhimurium) is one of the most common Salmonella serotypes in epidemiological surveys of poultry farms in recent years. It causes growth retardation, mortality, and significant economic losses. The extensive use of antibiotics has led to the emergence of multi-drug resistance (MDR) in Salmonella, which has become a significant global problem and long-term challenge. In this study, we investigated the prevalence and features of S. typhimurium strains in duck embryos and cloacal swabs from large-scale duck farms in Shandong, China, including drug resistance and virulence genes and the pathogenicity of an S. typhimurium strain by animal experiment. The results demonstrated that a total of 8 S. typhimurium strains were isolated from 13,621 samples. The drug resistance results showed that three of the eight S. typhimurium strains were MDR with the dominant resistance profile of CTX-DX-CTR-TE-AMX-AMP-CAZ. In particular, the virulence genes invA, hilA, pefA, rck, and sefA showed high positive rates. Based on the analysis of the biological characteristics of bacterial biofilm formation and mobility, a strain of S. typhimurium with the strongest biofilm formation ability, designated 22SD07, was selected for animal infection experiments with broiler ducklings. The results of animal experiments demonstrated that infection with 22SD07 reduced body weight and bursa index but increased heart and liver indexes compared to the control group. Histological examination revealed desquamation of the intestinal villous epithelium, the presence of large aggregates of lymphocytes, and a decrease in goblet cells following infection. Furthermore, the expression of IL-10 was significantly increased in the liver at 3 dpi, while TNF-α was significantly increased in the spleen at 7 dpi. The above results indicate that S. typhimurium may pose a potential threat to human health through the food chain. This helps us to understand the frequency and characteristics of S. typhimurium in duck farms and emphasizes the urgent need to strengthen and implement effective continuous monitoring to control its infection and transmission.