Capnocytophaga canimorsus and Capnocytophaga cynodegmi are commensal bacteria in the oral cavities of dogs. Both are zoonotic pathogens that could infect humans via dog bites. C. canimorsus may cause life-threatening infections in humans, whereas C. cynodegmi infections tend to be milder and more localized. Capsular serovars A-C of C. canimorsus seem to be virulence-associated. Some of the C. canimorsus serovars described to date can also be detected in other Capnocytophaga species, including C. cynodegmi. The objective of this pilot study was to investigate the emergence of C. canimorsus and C. cynodegmi after birth in oral cavities of puppies and to evaluate the impact of the dam\'s Capnocytophaga spp. carrier status on the emergence. Ten litters, altogether 59 puppies, were included in the study. The puppies and their dams were sampled at five time points over seven weeks after whelping. Oral swab samples taken were investigated for the presence of C. canimorsus and C. cynodegmi by species-specific polymerase chain reaction (PCR), the specificity of which was verified by sequencing a selection of the PCR products. Samples that were positive in Capnocytophaga PCR reactions were also capsular-typed by PCR to gain more knowledge about the Capnocytophaga spp. present in the samples. Altogether 10.2% and 11.9% of puppies, or 20.0% and 30.0% of litters tested PCR-positive for C. canimorsus and C. cynodegmi, respectively. Capnocytophaga PCR-positive puppy samples were always positive for only C. cynodegmi or C. canimorsus, not both. Most Capnocytophaga PCR-positive puppies became positive at the age of 5 to 7 weeks. Only a minority (5/16) of the C. cynodegmi PCR-positive dog samples were positive in capsular typing PCR, whereas all C. canimorsus PCR-positive dog samples were negative in capsular typing PCR. For all Capnocytophaga PCR-positive puppies, their dam was positive for the same Capnocytophaga species. These results suggest that puppies become colonized by C. cynodegmi or C. canimorsus from their dams at the time of deciduous teeth eruption.

UNASSIGNED: Current evidence is conflicting for associations of extended-infusion β-lactam (EI-BL) therapy with clinical outcomes.
UNASSIGNED: To investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI).
UNASSIGNED: This cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion β-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023.
UNASSIGNED: EI-BL (ie, ≥3-hour infusion).
UNASSIGNED: EI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the β-lactam used to treat the index GN-BSI).
UNASSIGNED: Among the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35).
UNASSIGNED: In this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.

Spiroplasma, belonging to the class Mollicutes, is a small, helical, motile bacterium lacking a cell wall. Its host range includes insects, plants, and aquatic crustaceans. Recently, a few human cases of Spiroplasma infection have been reported. The diseases caused by Spiroplasma have brought about serious economic losses and hindered the healthy development of agriculture. The pathogenesis of Spiroplasma involves the ability to adhere, such as through the terminal structure of Spiroplasma, colonization, and invasive enzymes. However, the exact pathogenic mechanism of Spiroplasma remains a mystery. Therefore, we systematically summarize all the information about Spiroplasma in this review article. This provides a reference for future studies on virulence factors and treatment strategies of Spiroplasma.

Solid organ transplant (SOT) recipients are particularly susceptible to infections caused by multidrug-resistant organisms (MDRO) and are often the first to be affected by an emerging resistant pathogen. Unfortunately, their prevalence and impact on morbidity and mortality according to the type of graft is not systematically reported from high-as well as from low and middle-income countries (HIC and LMIC). Thus, epidemiology on MDRO in SOT recipients could be subjected to reporting bias. In addition, screening practices and diagnostic resources may vary between countries, as well as the availability of new drugs. In this review, we aimed to depict the burden of main Gram-negative MDRO in SOT patients across HIC and LMIC and to provide an overview of current diagnostic and therapeutic resources.

UNASSIGNED: Red blood cells (RBCs), also known as erythrocytes, are underestimated in their role in the immune system. In mammals, erythrocytes undergo maturation that involves the loss of nuclei, resulting in limited transcription and protein synthesis capabilities. However, the nucleated nature of non-mammalian RBCs is challenging this conventional understanding of RBCs. Notably, in bony fishes, research indicates that RBCs are not only susceptible to pathogen attacks but express immune receptors and effector molecules. However, given the abundance of RBCs and their interaction with every physiological system, we postulate that they act in surveillance as sentinels, rapid responders, and messengers.
UNASSIGNED: We performed a series of in vitro experiments with Cyprinus carpio RBCs exposed to Aeromonas hydrophila, as well as in vivo laboratory infections using different concentrations of bacteria.
UNASSIGNED: qPCR revealed that RBCs express genes of several inflammatory cytokines. Using cyprinid-specific antibodies, we confirmed that RBCs secreted tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). In contrast to these indirect immune mechanisms, we observed that RBCs produce reactive oxygen species and, through transmission electron and confocal microscopy, that RBCs can engulf particles. Finally, RBCs expressed and upregulated several putative toll-like receptors, including tlr4 and tlr9, in response to A. hydrophila infection in vivo.
UNASSIGNED: Overall, the RBC repertoire of pattern recognition receptors, their secretion of effector molecules, and their swift response make them immune sentinels capable of rapidly detecting and signaling the presence of foreign pathogens. By studying the interaction between a bacterium and erythrocytes, we provide novel insights into how the latter may contribute to overall innate and adaptive immune responses of teleost fishes.

OBJECTIVE: Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety.
METHODS: A Model-Based Meta-Analysis (MBMA) of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-day survival rates.
RESULTS: In the study involving 96 articles and 9,716 patients, polymyxin B\'s daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% CI: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), p=0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), p<0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, p=0.54. The 30-day Overall Survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with β-lactam drugs.
CONCLUSIONS: The dosage of Polymyxin B doesn\'t significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like Pseudomonas aeruginosa are associated with higher mortality. Combining Polymyxin B with other antibiotics, especially β-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.

UNASSIGNED: To limit the use of antimicrobials without disincentivising the development of novel antimicrobials, there is interest in establishing innovative models that fund antimicrobials based on an evaluation of their value as opposed to the volumes used. The aim of this project was to evaluate the population-level health benefit of cefiderocol in the NHS in England, for the treatment of severe aerobic Gram-negative bacterial infections when used within its licensed indications. The results were used to inform the National Institute for Health and Care Excellence guidance in support of commercial discussions regarding contract value between the manufacturer and NHS England.
UNASSIGNED: The health benefit of cefiderocol was first derived for a series of high-value clinical scenarios. These represented uses that were expected to have a significant impact on patients\' mortality risks and health-related quality of life. The clinical effectiveness of cefiderocol relative to its comparators was estimated by synthesising evidence on susceptibility of the pathogens of interest to the antimicrobials in a network meta-analysis. Patient-level costs and health outcomes of cefiderocol under various usage scenarios compared with alternative management strategies were quantified using decision modelling. Results were reported as incremental net health effects expressed in quality-adjusted life-years, which were scaled to 20-year population values using infection number forecasts based on data from Public Health England. The outcomes estimated for the high-value clinical scenarios were extrapolated to other expected uses for cefiderocol.
UNASSIGNED: Among Enterobacterales isolates with the metallo-beta-lactamase resistance mechanism, the base-case network meta-analysis found that cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.32, 95% credible intervals 0.04 to 2.47), but the result was not statistically significant. The other treatments were also associated with lower susceptibility than colistin, but the results were not statistically significant. In the metallo-beta-lactamase Pseudomonas aeruginosa base-case network meta-analysis, cefiderocol was associated with a lower susceptibility relative to colistin (odds ratio 0.44, 95% credible intervals 0.03 to 3.94), but the result was not statistically significant. The other treatments were associated with no susceptibility. In the base case, patient-level benefit of cefiderocol was between 0.02 and 0.15 quality-adjusted life-years, depending on the site of infection, the pathogen and the usage scenario. There was a high degree of uncertainty surrounding the benefits of cefiderocol across all subgroups. There was substantial uncertainty in the number of infections that are suitable for treatment with cefiderocol, so population-level results are presented for a range of scenarios for the current infection numbers, the expected increases in infections over time and rates of emergence of resistance. The population-level benefits varied substantially across the base-case scenarios, from 896 to 3559 quality-adjusted life-years over 20 years.
UNASSIGNED: This work has provided quantitative estimates of the value of cefiderocol within its areas of expected usage within the NHS.
UNASSIGNED: Given existing evidence, the estimates of the value of cefiderocol are highly uncertain.
UNASSIGNED: Future evaluations of antimicrobials would benefit from improvements to NHS data linkages; research to support appropriate synthesis of susceptibility studies; and application of routine data and decision modelling to assess enablement value.
UNASSIGNED: No registration of this study was undertaken.
UNASSIGNED: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Policy Research Programme (NIHR award ref: NIHR135591), conducted through the Policy Research Unit in Economic Methods of Evaluation in Health and Social Care Interventions, PR-PRU-1217-20401, and is published in full in Health Technology Assessment; Vol. 28, No. 28. See the NIHR Funding and Awards website for further award information.
This project tested new methods for estimating the value to the NHS of an antimicrobial, cefiderocol, so its manufacturer could be paid fairly even if very little drug is used in order to reduce the risk of bacteria becoming resistant to the product. Clinicians said that the greatest benefit of cefiderocol is when used for complicated urinary tract infections and pneumonia acquired within hospitals caused by two types of bacteria (called Enterobacterales and Pseudomonas aeruginosa), with a resistance mechanism called metallo-beta-lactamase. Because there were no relevant clinical trial data, we estimated how effective cefiderocol and alternative treatments were by doing a systematic literature review of studies that grew bacteria from infections in the laboratory and tested the drugs on them. We linked this to data estimating the long-term health and survival of patients. Some evidence was obtained by asking clinicians detailed questions about what they thought the effects would be based on their experience and the available evidence. We included the side effects of the alternative treatments, some of which can cause kidney damage. We estimated how many infections there would be in the UK, whether they would increase over time and how resistance to treatments may change over time. Clinicians told us that they would also use cefiderocol to treat intra-abdominal and bloodstream infections, and some infections caused by another bacteria called Stenotrophomonas. We estimated how many of these infections there would be, and assumed the same health benefits as for other types of infections. The total value to the NHS was calculated using these estimates. We also considered whether we had missed any additional elements of value. We estimated that the value to the NHS was £18–71 million over 20 years. This reflects the maximum the NHS could pay for use of cefiderocol if the health lost as a result of making these payments rather than funding other NHS services is not to exceed the health benefits of using this antimicrobial. However, these estimates are uncertain due to limitations with the evidence used to produce them and assumptions that had to be made.

The misuse of antibiotics and the emergence of antimicrobial resistance (AMR) is a concern in the aquaculture industry because it contributes to global health risks and impacts the environment. This study analyzed the AMR of sentinel bacteria associated with striped catfish (Pangasisanodon hypophthalmus) and giant snakehead (Channa micropeltes), the two main fish species reared in the pond culture in Cambodia. Phenotypic and genotypic characterization of the recovered isolates from fish, water, and sediment samples revealed the presence of bacteria, such as 22 species belonging to families Aeromonadaceae, Enterobacteriaceae, and Pseudomonadaceae. Among 48 isolates, Aeromonas caviae (n = 2), Aeromonas hydrophila (n = 2), Aeromonas ichthiosmia (n = 1), Aeromonas salmonicida (n = 4) were detected. A. salmonicida and A. hydrophilla are known as fish pathogens that occur worldwide in both fresh and marine water aquaculture. Antibiotic susceptibility testing revealed antibiotic resistance patterns of 24 (50 %) isolates among 48 isolates with higher multiple antibiotic resistance index (> 0.2). All the isolates of Enterobacteriaceae were susceptible to ciprofloxacin. Ciprofloxacin is a frontline antibiotic that is not recommended to use in aquaculture. Therefore, its use has to be strictly controlled. This study expands our knowledge of the AMR status in aquaculture farms which is very limited in Cambodia.

We present a case of bilateral endogenous endophthalmitis with an extremely rare etiology of Capnocytophaga canimorsus. A 42-year-old asplenic patient with bilateral deterioration of visual acuity presented to the Emergency Department. The sudden deterioration of visual acuity, which prompted the patient to visit the ophthalmologist, was the first sign of the onset of sepsis. The physicians\' attention, in addition to poor visual acuity and intense inflammation on ophthalmologic examination, was drawn to the reported flu-like symptoms. They were accompanied by high C-reactive protein results and abnormalities in echocardiography. A blood culture isolated the bacterium Capnocytophaga canimorsus. Immunocompromised patients are particularly susceptible to C. canimorsus infection. Endophthalmitis of this etiology has a very aggressive course, both ophthalmic and systemic. Therefore, quick diagnosis and initiation of adequate therapy are crucial.

Grass Carp Reovirus (GCRV) and Aeromonas hydrophila (Ah) are the causative agents of haemorrhagic disease in grass carp. This study aimed to investigate the molecular mechanisms and immune responses at the miRNA, mRNA, and protein levels in grass carp kidney cells (CIK) infected by Grass Carp Reovirus (GCRV, NV) and Aeromonas hydrophilus (Bacteria, NB) to gain insight into their pathogenesis. Within 48 h of infection with Grass Carp Reovirus (GCRV), 99 differentially expressed microRNA (DEMs), 2132 differentially expressed genes (DEGs), and 627 differentially expressed proteins (DEPs) were identified by sequencing; a total of 92 DEMs, 3162 DEGs, and 712 DEPs were identified within 48 h of infection with Aeromonas hydrophila. It is worth noting that most of the DEGs in the NV group were primarily involved in cellular processes, while most of the DEGs in the NB group were associated with metabolic pathways based on KEGG enrichment analysis. This study revealed that the mechanism of a grass carp haemorrhage caused by GCRV infection differs from that caused by the Aeromonas hydrophila infection. An important miRNA-mRNA-protein regulatory network was established based on comprehensive transcriptome and proteome analysis. Furthermore, 14 DEGs and 6 DEMs were randomly selected for the verification of RNA/small RNA-seq data by RT-qPCR. Our study not only contributes to the understanding of the pathogenesis of grass carp CIK cells infected with GCRV and Aeromonas hydrophila, but also serves as a significant reference value for other aquatic animal haemorrhagic diseases.