Potent neutralizing human monoclonal antibodies protect from inhalational Rift Valley fever virus.

Rift Valley fever (RVF) is an emerging arboviral disease affecting both humans and livestock. In humans, RVF displays a spectrum of clinical manifestations, including encephalitis. To date, there are no FDA-approved vaccines or therapeutics for human use, although several are in pre-clinical development. Few small animal models of RVF encephalitis exist, further complicating countermeasure assessment. Human mAbs RVFV-140, RVFV-268 and RVFV-379 are recombinant potently neutralizing antibodies that prevent infection by binding the RVFV surface glycoproteins. Previous studies showed that both RVFV-268 and RVFV-140 improve survival in a lethal mouse model of disease, and RVFV-268 has prevented vertical transmission in a pregnant rat model of infection. Despite these successes, evaluation of mAbs in the context of brain disease has been limited. This is the first study to assess neutralizing antibodies for prevention of RVF neurologic disease using a rat model. Administration of RVFV-140, RVFV-268, or RVFV-379 twenty-four hours prior to aerosol exposure to the virulent ZH501 strain of RVFV results in substantially enhanced survival and lack of neurological signs of disease. These results using a stringent and highly lethal aerosol infection model supports the potential use of human mAbs to prevent the development of RVF encephalitis.

NKT cells promote Th1 immune bias to dengue virus that governs long term protective antibody dynamics.

NKT cells are innate-like T cells, recruited to the skin during viral infection, yet their contributions to long-term immune memory to viruses are unclear. We identified granzyme K, a product made by cytotoxic cells including NKT cells, is linked to induction of Th1-associated antibodies during primary dengue virus (DENV) infection in humans. We examined the role of NKT cells in vivo using DENV-infected mice lacking CD1d-dependent (CD1ddep) NKT cells. In CD1d-KO mice, Th1-polarized immunity and infection resolution were impaired, which was dependent on intrinsic NKT cell production of IFN-γ, since it was restored by adoptive transfer of WT but not IFN-γ-KO NKT cells. Furthermore, NKT cell deficiency triggered immune bias, resulting in higher levels of Th2-associated IgG1 than Th1-associated IgG2a, which failed to protect against a homologous DENV re-challenge and promoted antibody-dependent enhanced disease during secondary heterologous infections. Similarly, Th2-immunity, typified by a higher IgG4:IgG3 ratio, was associated with worsened human disease severity during secondary infections. Thus, CD1ddep NKT cells establish Th1 polarity during the early innate response to DENV, which promotes infection resolution, memory formation and long-term protection from secondary homologous and heterologous infections. These observations illustrate how early innate immune responses during primary infections can influence secondary infection outcomes.

Infectious disease research in the Association of Southeast Asian Nations region: a scientometric analysis.

Objectives: This study compared the research output of Association of Southeast Asian Nations (ASEAN) countries to understand research trends and clarify past, present, and future patterns using scientometric techniques. Methods: This scientometric study systematically mined health and social science publications from the Web of Science and Scopus databases using keywords associated with infectious disease. The analysis included only English-language articles and review articles by authors from any ASEAN country. Publication, citation, and text co-occurrence network analyses were performed. R Studio and VOSviewer enabled data management, analysis, and visualization. Results: Searches identified 12,511 articles published between 1925 and 2022, with a notable increase in research publications since 2003. The leading journals on infectious disease were associated with established publishing houses, including BMC, BMJ, and The Lancet. The most-cited articles were primarily global burden of disease studies, with 7,367 citations. Among ASEAN countries, Thailand, Malaysia, and Singapore had the most publications and collaborative efforts on the topic. Analysis of keyword co-occurrence revealed clusters related to global health, dengue, bacterial studies, non-dengue viral topics, and diagnostics. Most early studies examined diagnostics, gene and sequencing methodologies, and virology; later, the focus shifted toward herbal and alternative medicine. Conclusion: Recently, the research capacity of Southeast Asia has expanded dramatically, with substantial contributions from high-income countries (HICs). Intense cooperation between member states is essential, emphasizing the role of HICs in supporting their neighbors. Increased research efforts must be dedicated to innovative approaches to combat persistent health conditions, along with emerging issues like climate change.

From Policy to Prediction: Assessing Forecasting Accuracy in an Integrated Framework with Machine Learning and Disease Models.

To improve the forecasting accuracy of the spread of infectious diseases, a hybrid model was recently introduced where the commonly assumed constant disease transmission rate was actively estimated from enforced mitigating policy data by a machine learning (ML) model and then fed to an extended susceptible-infected-recovered model to forecast the number of infected cases. Testing only one ML model, that is, gradient boosting model (GBM), the work left open whether other ML models would perform better. Here, we compared GBMs, linear regressions, k-nearest neighbors, and Bayesian networks (BNs) in forecasting the number of COVID-19-infected cases in the United States and Canadian provinces based on policy indices of future 35 days. There was no significant difference in the mean absolute percentage errors of these ML models over the combined dataset [H(3)=3.10,p=0.38]. In two provinces, a significant difference was observed [H(3)=8.77,H(3)=8.07,p<0.05], yet posthoc tests revealed no significant difference in pairwise comparisons. Nevertheless, BNs significantly outperformed the other models in most of the training datasets. The results put forward that the ML models have equal forecasting power overall, and BNs are best for data-fitting applications.

Blood culture bottles meet the operating room: enhancing the diagnostic accuracy of infectious spondylitis through open microsurgical biopsy and intraoperative inoculation.

PURPOSE: Infectious spondylitis is caused by hematogenous seeding or adjacent soft tissue infection. No study has provided evidence that incubating biopsy specimens in blood culture bottles could enhance detection rates, nor has any study compared this method with conventional culture techniques. We aimed to assess the diagnostic yield of open microsurgical biopsies for infectious spondylitis and the efficacy of various culture media in the presence and absence of pre-biopsy antibiotic therapy. METHODS: This retrospective study, which was conducted at a university-affiliated teaching hospital in Korea, enrolled 165 adult patients with suspected infectious spondylitis between February 2014 and September 2020. The diagnostic yield of open biopsy was compared among three culture media, namely, blood culture bottles, swab culture using transport media, and tissue culture using plain tubes, while considering preoperative antibiotic exposure. RESULTS: Causative bacteria were identified in 84.2% of all cases. Blood culture bottles had the highest positivity rate (83.5%), followed by swab cultures (64.4%) and tissue cultures (44.9%). The differences in positivity rates were significant (P < 0.001). Preoperative antibiotic therapy reduced detection rates across all media, particularly in tissue cultures. CONCLUSIONS: We established the high diagnostic yield of open microsurgical biopsy using blood culture bottles, suggesting that pre-biopsy antibiotic therapy significantly affects bacterial detection, thereby underscoring the importance of culture medium selection in the diagnosis of infectious spondylitis.

Metabolic disruption impairs ribosomal protein levels, resulting in enhanced aminoglycoside tolerance.

Aminoglycoside antibiotics target ribosomes and are effective against a wide range of bacteria. Here, we demonstrated that knockout strains related to energy metabolism in Escherichia coli showed increased tolerance to aminoglycosides during the mid-exponential growth phase. Contrary to expectations, these mutations did not reduce the proton motive force or aminoglycoside uptake, as there were no significant changes in metabolic indicators or intracellular gentamicin levels between wild-type and mutant strains. Our comprehensive proteomics analysis unveiled a noteworthy upregulation of proteins linked to the tricarboxylic acid (TCA) cycle in the mutant strains during the mid-exponential growth phase, suggesting that these strains compensate for the perturbation in their energy metabolism by increasing TCA cycle activity to maintain their membrane potential and ATP levels. Furthermore, our pathway enrichment analysis shed light on local network clusters displaying downregulation across all mutant strains, which were associated with both large and small ribosomal binding proteins, ribosome biogenesis, translation factor activity, and the biosynthesis of ribonucleoside monophosphates. These findings offer a plausible explanation for the observed tolerance of aminoglycosides in the mutant strains. Altogether, this research provides valuable insights into the mechanisms of aminoglycoside tolerance, paving the way for novel strategies to combat such cells.

Bacteria that are resistant to antibiotic drugs pose a significant challenge to human health around the globe. They have acquired genetic mutations that allow them to survive and grow in the presence of one or more antibiotics, making it harder for clinicians to eliminate such bacteria from human patients with life-threatening infections. Some bacteria may be able to temporarily develop tolerance to an antibiotic by altering how they grow and behave, without acquiring any new genetic mutations. Such drug-tolerant bacteria are more likely to survive long enough to gain mutations that may promote drug resistance. Recent studies suggest that genes involved in processes collectively known as energy metabolism, which convert food sources into the chemical energy cells need to survive and grow, may play a role in both tolerance and resistance. For example, Escherichia coli bacteria develop mutations in energy metabolism genes when exposed to members of a family of antibiotics known as the aminoglycosides. However, it remains unclear what exact role energy metabolism plays in antibiotic tolerance. To address this question, Shiraliyev and Orman studied how a range of E. coli strains with different genetic mutations affecting energy metabolism could survive in the presence of aminoglycosides. The experiments found that most of the mutant strains had a higher tolerance to the drugs than normal E. coli. Unexpectedly, this increased tolerance did not appear to be due to the drugs entering the mutant bacterium cells less than they enter normal cells (a common strategy of drug resistance and tolerance). Further experiments using a technique, known as proteomics, revealed that many genes involved in energy metabolism were upregulated in the mutant bacteria, suggesting these cells were compensating for the genetic abnormalities they have. Furthermore, the mutant bacteria had lower levels of the molecules the antibiotics target than normal bacteria. The findings of Shiraliyev and Orman offer critical insights into how bacteria become tolerant of aminoglycoside antibiotics. In the future, this may guide the development of new strategies to combat bacterial diseases.

Cytomegalovirus immunity in high-risk liver transplant recipients following preemptive antiviral therapy vs. prophylaxis.

Cytomegalovirus (CMV)-specific T-cells, NK cells, and neutralizing antibodies (nAb) were assessed in a randomized trial of CMV prevention with preemptive antiviral therapy (PET) vs. prophylactic antiviral therapy (PRO) in donor seropositive/recipient seronegative (D+R-) liver transplant recipients (LTxR), at 100 days (end of intervention), and at 6 and 12 months post-transplant. The PET group had significantly increased numbers of circulating polyfunctional T-cells, NK cells, and nAb compared to the PRO group at day 100 and several CMV immune parameters remained significantly higher by 12 months post-transplant. Among PET recipients, preceding CMV viremia (vs. no preceding viremia) was associated with significantly higher levels of most CMV immune parameters at day 100. Higher numbers of CMV-specific polyfunctional T-cells and NKG2C+ NK cells at day 100 were associated with a decreased incidence of CMV disease in multivariable Cox regression. The strongest associations with protection against CMV disease were with increased numbers of CMV-specific polyfunctional CD4 T-cells, CD3negCD56dimCD57negNKG2Cpos, and CD3negCD56dimCD57posNKG2Cpos NK cells. PET is superior to PRO for CMV disease prevention by allowing low-level CMV replication and associated antigen exposure that is promptly controlled by antiviral therapy and facilitates enhanced CMV protective immunity in D+R- LTxR.

Absence of Cerebrospinal Fluid Pleocytosis in Encephalitis.

BACKGROUND: Early diagnosis of encephalitis involves identifying signs of neuroinflammation, including cerebrospinal fluid (CSF) pleocytosis. However, absence of CSF pleocytosis in encephalitis has been described, most notably in autoimmune encephalitis. We examined clinical characteristics and outcomes associated with the absence or presence of CSF white blood cell pleocytosis (≥ 5 cells/µL), to inform timely diagnosis and management of encephalitis. METHODS: This retrospective study compares initial CSF profiles in 597 adult patients with all-cause encephalitis. RESULTS: Of the 597 patients, 446 (74.7%) had CSF pleocytosis while 151 (25.3%) did not. CSF pleocytosis occurred more commonly in infectious cases (200/446, 44.8%), along with 59 (13.2%) autoimmune cases, comprised chiefly of anti-NMDAR encephalitis (37/59, 62.7%). Notably, the group without pleocytosis was comprised of similar proportions of infectious (47/151, 31.1%) and autoimmune (38/151, 25.92%; p>0.05) encephalitis. Among those with infectious encephalitis, 47/247 (19%) had absent pleocytosis, including 18/76 (23.7%) with HSV-1 encephalitis. The absence of pleocytosis was associated with a decreased rate of acyclovir administration (47.7% in patients without pleocytosis vs. 71.1% in patients with pleocytosis, p<0.001). Despite pleocytosis being associated with some measures of clinical severity at admission such as a Full Outline of UnResponsiveness (FOUR) score ≤14, it was not associated with mortality or prolonged hospitalization. CONCLUSION: CSF pleocytosis is an important criterion for encephalitis diagnosis, but 25.3% of patients with all-cause encephalitis and 23.7% of those with HSV-1 encephalitis exhibit absence of pleocytosis on initial LP. Acyclovir initiation should not be delayed in the absence of pleocytosis in patients with suspected encephalitis.

Surveillance of antibiotics use in inpatients at Benjamin Mkapa Zonal Referral Hospital in Dodoma, Tanzania: a point prevalence survey.

OBJECTIVE: To assess antibiotics prescribing and use patterns for inpatients at Benjamin Mkapa Zonal Referral Hospital (BMH) using the WHO-Point Prevalence Survey (WHO-PPS). DESIGN: A cross-sectional survey. SETTING: The Benjamin Mkapa Zonal Referral Hospital, Dodoma, Tanzania. PARTICIPANTS: Inpatient prescriptions, regardless of whether antibiotics were prescribed (n=286) on the day of PPS. OUTCOME MEASURES: Our study analysed the prevalence of antibiotic use at BMH for inpatients, the type of antibiotics used, the indications for use and the proportion of oral and parenteral antibiotics. We also assessed prescription-prescribed antibiotics after a positive antimicrobial susceptibility testing (AST) result. RESULTS: A survey was conducted on 286 prescriptions, which revealed that 30.07% of them included antibiotics. On average, each prescription contained at least 1.6 antibiotics. All prescriptions that included antibiotics were written in generic names, and 77.91% (67/86) of them followed the Standard Treatment Guidelines. Of the prescriptions that included antibiotics, 58.14% (50/86) had a single antibiotic, 20.93% (18/86) had parenteral antibiotics and 79.07% (68/86) had oral antibiotics. Based on AWaRe's (Access, Watch and Reserve) categorisation of antibiotics, 50% (8/16) were in the Access group, 31.25% (5/16) were in the Watch group, 12.50% (2/16) were in the Reserve group and 6.25% (1/16) were not recommended antimicrobial combinations. Out of 86 prescriptions included antibiotics, only 4.65% showed positive culture growth. However, antibiotics were still prescribed in 29.07% of prescriptions where there was no growth of bacteria, and in 66.28% of prescriptions, antibiotics were prescribed empirically without any requesting of bacteria culture and AST. CONCLUSION: BMH has reduced inpatient Antibiotic Use by half compared with the 2019 WHO-PPS. Adherence to National Treatment Guidelines is suboptimal. Clinicians should use AST results to guide antibiotic prescribing.

Detection strategies of infectious diseases via peptide-based electrochemical biosensors.

Infectious diseases have threatened human life for as long as humankind has existed. One of the most crucial aspects of fighting against these infections is diagnosis to prevent disease spread. However, traditional diagnostic methods prove insufficient and time-consuming in the face of a pandemic. Therefore, studies focusing on detecting viruses causing these diseases have increased, with a particular emphasis on developing rapid, accurate, specific, user-friendly, and portable electrochemical biosensor systems. Peptides are used integral components in biosensor fabrication for several reasons, including various and adaptable synthesis protocols, long-term stability, and specificity. Here, we discuss peptide-based electrochemical biosensor systems that have been developed over the last decade for the detection of infectious diseases. In contrast to other reports on peptide-based biosensors, we have emphasized the following points i) the synthesis methods of peptides for biosensor applications, ii) biosensor fabrication approaches of peptide-based electrochemical biosensor systems, iii) the comparison of electrochemical biosensors with other peptide-based biosensor systems and the advantages and limitations of electrochemical biosensors, iv) the pros and cons of peptides compared to other biorecognition molecules in the detection of infectious diseases, v) different perspectives for future studies with the shortcomings of the systems developed in the past decade.

Defining the Functional Properties of Cyclopropane Fatty Acid Synthase from Pseudomonas aeruginosa PAO1.

Cyclopropane fatty acid synthases (CFAS) catalyze the conversion of unsaturated fatty acids to cyclopropane fatty acids (CFAs) within bacterial membranes. This modification alters the biophysical properties of membranes and has been correlated with virulence in several human pathogens. Despite the central role played by CFAS enzymes in regulating bacterial stress responses, the mechanistic properties of the CFAS enzyme family and the consequences of CFA biosynthesis remain largely uncharacterized in most bacteria. We report the first characterization of the CFAS enzyme from Pseudomonas aeruginosa (PA) - an opportunistic human pathogen with complex membrane biology that is frequently associated with antimicrobial resistance and high tolerance to various external stressors. We demonstrate that CFAs are produced by a single enzyme in PA and that cfas gene expression is upregulated during the transition to stationary phase and in response to oxidative stress. Analysis of PA lipid extracts reveal a massive increase in CFA production as PA cells enter stationary phase and help define the optimal membrane composition for in vitro assays. The purified PA-CFAS enzyme forms a stable homodimer and preferentially modifies phosphatidylglycerol lipid substrates and membranes with a higher content of unsaturated acyl chains. Bioinformatic analysis across bacterial phyla shows highly divergent amino acid sequences within the lipid binding domain of CFAS enzymes, perhaps suggesting distinct membrane binding properties among different orthologues. This work lays an important foundation for further characterization of CFAS in Pseudomonas aeruginosa and for examining the functional differences between CFAS enzymes from different bacteria.

Human milk antibodies to global pathogens reveal geographic and interindividual variations in IgA and IgG.

BACKGROUNDThe use of high-throughput technologies has enabled rapid advancement in the knowledge of host immune responses to pathogens. Our objective was to compare the repertoire, protection, and maternal factors associated with human milk antibodies to infectious pathogens in different economic and geographic locations.METHODSUsing multipathogen protein microarrays, 878 milk and 94 paired serum samples collected from 695 women in 5 high and low-to-middle income countries (Bangladesh, Finland, Peru, Pakistan, and the United States) were assessed for specific IgA and IgG antibodies to 1,607 proteins from 30 enteric, respiratory, and bloodborne pathogens.RESULTSThe antibody coverage across enteric and respiratory pathogens was highest in Bangladeshi and Pakistani cohorts and lowest in the U.S. and Finland. While some pathogens induced a dominant IgA response (Campylobacter, Klebsiella, Acinetobacter, Cryptosporidium, and pertussis), others elicited both IgA and IgG antibodies in milk and serum, possibly related to the invasiveness of the infection (Shigella, enteropathogenic E. coli "EPEC", Streptococcus pneumoniae, Staphylococcus aureus, and Group B Streptococcus). Besides the differences between economic regions and decreases in concentrations over time, human milk IgA and IgG antibody concentrations were lower in mothers with high BMI and higher parity, respectively. In Bangladeshi infants, a higher specific IgA concentration in human milk was associated with delayed time to rotavirus infection, implying protective properties of antirotavirus antibodies, whereas a higher IgA antibody concentration was associated with greater incidence of Campylobacter infection.CONCLUSIONThis comprehensive assessment of human milk antibody profiles may be used to guide the development of passive protection strategies against infant morbidity and mortality.FUNDINGBill and Melinda Gates Foundation grant OPP1172222 (to KMJ); Bill and Melinda Gates Foundation grant OPP1066764 funded the MDIG trial (to DER); University of Rochester CTSI and Environmental Health Sciences Center funded the Rochester Lifestyle study (to RJL); and R01 AI043596 funded PROVIDE (to WAP).

GS-441524 and molnupiravir are similarly effective for the treatment of cats with feline infectious peritonitis.

Although not registered for feline infectious peritonitis (FIP) in Japan, nucleoside analogs have shown efficacy and we have been offering them to owners of cats with FIP at our clinic since January 2020. The aim of this study was to investigate outcomes in cats with FIP who received GS-441524 or molnupiravir. Diagnosis of FIP was based on clinical signs, laboratory test results, and the presence of feline coronavirus RNA in blood or effusion aspirate. After providing verbal and written information, owners of cats with a presumptive diagnosis of FIP with a were offered antiviral treatment with commercially sourced GS-441524 from June 2020, and either GS-441524 or compounded molnupiravir from January 2022. Dosing was 12.5-25 mg/kg/day for GS-441524 and 20-40 mg/kg/day for molnupiravir, depending on the presence of effusion and neurological and/or ocular signs, and continued for 84 days. Overall, 118 cats with FIP (effusive in 76) received treatment, 59 with GS-4421524 and 59 with molnupiravir. Twenty cats died, 12/59 (20.3%) in the GS-441524 group and 8/59 (13.6%) in the molnupiravir group (p = 0.326), with most deaths within the first 10 days of starting treatment. Among survivors, neurological and ocular signs resolved in all but one cat, who had persistent seizures. Of the cats completing treatment, 48/48 in the GS-441524 group and 51/52 in the molnupiravir group achieved remission. Laboratory parameters normalized within 6 to 7 weeks of starting drug administration. Adverse events, such as primarily hepatic function abnormalities, were transient and resolved without specific intervention. Our data indicate that GS-441524 and molnupiravir show similar effects and safety in cats with FIP.

A Mixed Methods Pilot Study to Evaluate User Engagement with MedMicroMaps: A Novel Interactive E-learning Tool for Medical Microbiology.

Educators are witnessing the unfolding of the era of artificial intelligence, raising the question of how to transfer the benefits of yesterday's pedagogy to the future of education. An interactive digital mind map of infectious diseases was developed for second-year medical students (n = 865). Analysis of user engagement showed global distribution with 498 QR scans on a single day. Student responses (n = 79, 9.1% response rate) indicated positive feedback on the resources of Extremely Satisfied (range 65-75%, n = 59-51). The findings of the study support further expansion of MedMicroMaps to cross-platform interfaces with adaptations for diverse audiences within allied health fields. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-024-02047-3.

An Atypical Presentation of Viral Myocarditis Masquerading as Non-ST-Elevation Myocardial Infarction (NSTEMI).

Coxsackie B virus is primarily associated with fever, pharyngitis, and gastrointestinal symptoms, while myocarditis is rarely reported. We present a rare case of a 47-year-old male with a history of hypertension and obesity, who developed Coxsackie B virus-induced myositis, myocarditis, and polyarthralgia. The patient presented with worsening back pain radiating to his chest, migratory arthralgia, exertional dyspnea, and bilateral shoulder pain with arm weakness. Initial investigations revealed elevated creatinine kinase (CK) levels and troponin I, alongside a high white blood cell (WBC) count and C-reactive protein (CRP) levels. Given the patient's symptoms and uptrending troponin without EKG changes, there was a high concern for non-ST-elevation myocardial infarction (NSTEMI), leading to initial treatment with aspirin and IV heparin. However, further questioning revealed a recent sore throat and contact with an ill family member, prompting investigations for an infectious etiology. A viral panel confirmed Coxsackie B virus infection. The patient made a full recovery with supportive care. This case highlights the importance of considering viral causes, particularly the Coxsackie B virus, in patients presenting with muscle pain, cardiac symptoms, and joint pain. Comprehensive viral testing is crucial for early identification and appropriate management to prevent long-term complications. Understanding the mechanisms of Coxsackie B virus infection is essential for developing effective treatment strategies addressing both the viral infection and the inflammatory response.

Clinical, organizational, and pharmacoeconomic perspectives of dalbavancin vs standard of care in the infectious disease network.

Introduction: The therapeutic approach to the patient with acute bacterial skin and skin structure infection (ABSSSI) and complicated infections often involves the early transition from intravenous to oral therapy (early switch) or early discharge. Our study aimed to evaluate sustainable and innovative care models that can be transferred to community healthcare and the economic impact of dalbavancin therapy vs Standard of Care (SoC) therapy for the treatment of ABSSSI and other Gram-positive infections including those by multidrug-resistant organisms. We also described the organization of an infectious disease network that allows optimizing the treatment of ABSSSI and other complex infections with dalbavancin. Materials and Methods: We retrospectively studied all patients treated with dalbavancin in the University Hospital "S. Anna" of Ferrara, Italy, between November 2016 and December 2022. The clinical information of each patient was collected from the hospital's SAP database and used to evaluate the impact of dalbavancin in early discharge with reduction of length of stay promoting dehospitalization and in improving adherence to antibiotic therapy. Results: A total of 287 patients (165 males and 122 females) were included in the study of which 62 were treated with dalbavancin. In 13/62 patients dalbavancin was administered in a single dose at the completion of therapy to facilitate early discharge. Assuming a 12-day hospitalization required for the treatment of ABSSSI or to complete the treatment of osteomyelitis or spondilodiscitis, the treatment with dalbavancin results in a cost reduction of more than €3,200 per single patient compared to SoC (dancomycin, linezolid or vancomycin). Conclusions: Dalbavancin has proven to be a valid therapeutic aid in the organization of a territorial infectious disease network given its prolonged action, which allows the dehospitalization with management of even patients with complex infections in outpatient parenteral antimicrobial therapy.

A Case Report of a Rare Pulmonary Opportunistic Infection in an Infant Caused by Tsukamurella tyrosinosolvens.

This case report describes the case of a female infant hospitalized for severe pneumonia. During the treatment process, various antibiotics are used to treat and prevent further infection. The child had a weak physical condition, combined with neuroblastoma, paraneoplastic syndrome, and low immune function, leading to Tsukamurella tyrosinosolvens infection. The treatment was eventually abandoned owing to poor prognosis. This study aims to through the medium, dyeing, electron microscope observation, 16s rRNA and high-throughput sequencing investigated the morphological characteristics, staining properties, electron microscope morphology, antibiotic resistance, and genomic characteristics of Tsukamurella tyrosinosolvens. The aim of the study is to provide data reference for clinical laboratory staff in bacteria identification research, and to provide relevant help for clinicians in diagnosis and treatment.

Can Marburg virus be sexually transmitted?

Background and Aim: Marburg virus (MARV) is a highly virulent virus of animal origin and the cause of a lethal infection (known as Marburg virus disease [MVD]) with a case-fatality ratio ranging from 24% to 90%. While the potential nonzoonotic routes of virus spread are plausible, the risk is not yet fully determined. Here, we described the ways by which MARV spreads within the human population focusing mainly on the potential of sexual transmission. In addition, we addressed some measures that should be taken to minimize the risk of sexual spread of the virus and proposed a future research agenda on the risk of sexual transmission. Methods: For this perspective, we searched four electronic databases (i.e., PubMed, Scopus, Web of Science, and Google Scholar) and included the most relevant studies published since the first identification of the virus in 1967. We used "Marburg virus," "Marburg virus disease," "Seminal fluid," "Sexually-transmitted virus," "Sexual transmission," and "Emerging infectious disease" as keywords. Results: MARV is transmitted to humans via both direct and indirect contact with infected animals (most importantly bats) and individuals who have recently been diagnosed with or died of the disease. The virus transmission through sexual contact has been previously suspected (exclusively from men to their sexual partners). Studies suggest that this virus persists predominantly in testicular Sertoli cells within seminiferous tubules over a relatively long period and is released through seminal fluid (in some reports >200 days post onset of infection) both could potentially threaten sexual health. In addition to men, women could theoretically, although less probably contribute to the sexual transmission of the disease. Conclusion: MVD, however, rarely, could be passed through sex, and men appear to be the main carriers in this regard. Taking preventive countermeasures and practicing safe sex are recommended to reduce the risk of interhuman transmission.

The Value of Serum Procalcitonin, Thromboelastography Combined with Platelet Count in Predicting the Short-Term Progression of Septic Shock in the Intensive Care Unit.

Objective: By evaluating the level of serum procalcitonin (PCT), thromboelastography (TEG) and platelet count (PLT) of patients with septic shock in intensive care unit (ICU), the predictive value of the combination of the three indicators on the short-term progression was discussed, which provided a new basis for early clinical diagnosis and disease evaluation. Methods: The clinical data of 130 patients with septic shock admitted to the IUC of our hospital from December 2021 to December 2023 were analyzed retrospectively. These subjects were divided into good prognosis group (n=78) and poor prognosis group (n=52) according to the 28 d deaths. The influencing factors were explored using the Multivariate logistic regression analysis. The value of single or combined PCT, PLT and TEG in predicting poor short-term prognosis was assessed using the receiver operating characteristic (ROC) curve. Results: The patients in poor prognosis group had higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, serum PCT level, coagulation reaction time (R value) and coagulation formation time (K value), but lower PLT levels, final strength of coagulation (MA value) and coagulation formation rate (α angle) than those in good prognosis group (P<0.001). PCT, R value and K value were risk factors (P<0.001), while PLT, MA value and α angle were protective factors (P<0.001). The area under the curve (AUC) of PCT, PLT and TEG predicting poor short-term progression was 0.813, 0.658 and 0.752, respectively. The AUC of combined three indicators was 0.905, which had the highest predictive value. Conclusion: Serum levels of PCT, PLT and TEG had certain value in predicting poor short-term progression of septic shock patients, and their combined diagnostic value was higher. Therefore, regular monitoring of these three indicators could provide certain guiding significance for the prevention and treatment of poor short-term prognosis in patients with septic shock.