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[Current studies on the neurobiology of chronic fatigue syndrome].

Cytokines are soluble mediators which are released by activated immune cells during infection and inflammation. The possibility that fatigue is mediated by the effects of cytokines on the central nervous system is supported by several converging lines of evidence: 1) infusions of cytokines to immunocompromised patients induce flu-like symptoms including fatigue and malaise; 2) peripheral and central injection of cytokines to laboratory rodents induce sickness behaviour; 3) symptoms of sickness behaviour occurring during experimental infections can be abrogated by administration of anti-cytokine treatments; 4) although many pitfalls in the detection of cytokines still exist, patients afflicted with the chronic fatigue syndrome have been found in some studies to display instances of excessive production of cytokines. Experimental studies have confirmed that cytokines are interpreted by the brain as internal signals for sickness. Furthermore, there is evidence that sickness is a motivation which reorganizes the organism's priorities in face of this particular threat which is represented by infectious pathogens. The elucidation of the mechanisms that are involved in these effects and in particular, the role of the cytokines which are produced in the brain in response to peripheral immune stimuli and to stressors, should give new insight on the way sickness and recovery processes are organized in the brain.

Adaptation, Psychological↗

MicroRNAs in Veterinary Viral Diseases: A Comprehensive Review from Molecular Mechanisms to Clinical Translation.

MicroRNAs (miRNAs) are small non-coding RNA molecules, approximately 22 nucleotides in length, that regulate post-transcriptional gene expression and have emerged as pivotal modulators of host-virus interactions. Veterinary viral diseases continue to pose substantial challenges to animal health, livestock productivity, food security, and public health, particularly due to their zoonotic potential. While miRNA research has advanced considerably, a comprehensive and critically integrated understanding of their biological functions and clinical applications across veterinary viral diseases remains incomplete. This comprehensive critical narrative synthesis addresses four overarching research questions: (1) What conserved and species-specific miRNA-mediated mechanisms govern major veterinary viral diseases? (2) What contextual factors determine antiviral vs. proviral duality? (3) To what extent do circulating miRNA signatures offer diagnostic and prognostic utility? (4) What translational barriers currently prevent clinical implementation, and how can the One Health framework help overcome them? Integrating three interconnected dimensions-molecular mechanisms, pathogen-specific responses, and translational applications-the review synthesizes evidence across PRRSV, avian oncogenic viruses (MDV, ALV), the immunosuppressive IBDV, FMD, BVDV, Ebola, Hendra, Rabies, and aquatic viral diseases. A key contribution of this review is the proposal of a four-axis contextual framework that explains the antiviral/proviral duality of miRNAs, and a 'One miRNA, One Health' convergence model with a concrete implementation roadmap. Key findings include: (a) a four-axis contextual framework (cell type, infection stage, viral strain, host-viral miRNA competition) that explains the antiviral/proviral duality; (b) virus-encoded miRNAs (v-miRNAs) as lower-risk therapeutic targets due to their absence from uninfected host genomes; (c) circulating miRNA biomarkers validated only at proof-of-concept stage (TRL 1-3), with no veterinary product yet at TRL ≥4; and (d) zoonotic conservation of miR-155, miR-146a, miR-21, and miR-122 across human and veterinary pathogens, supporting a 'One miRNA, One Health' convergence strategy. Critical short-term priorities are standardized pre-analytical protocols, open-access veterinary miRNA databases, and multicenter validation in natural infection cohorts.

Antiviral therapy↗

Detection of norovirus capsid protein in authentic standards and in stool extracts by matrix-assisted laser desorption ionization and nanospray mass spectrometry.

Mass spectrometry (MS) represents a rapid technique for the identification of microbial monocultures, and its adaptation to the detection of pathogens in real-world samples is a public health and homeland security priority. Norovirus, a leading cause of gastroenteritis in the world, is difficult to monitor because it cannot be cultured outside the human body. The detection of norovirus capsid protein was explored using three common MS-based methods: scanning of intact proteins, peptide mass fingerprinting, and peptide sequencing. Detection of intact target protein was limited by poor selectivity and sensitivity. Detection of up to 16 target peptides by peptide mass fingerprinting allowed for the reproducible and confident (P < 0.05) detection of the 56-kDa norovirus capsid protein in the range of 0.1 x 10(-12) to 50 x 10(-12) mol in authentic standards of recombinant norovirus virus-like particles (VLPs). To explore assay performance in complex matrixes, a non-gel-based, rapid method (2 to 3 h) for virus extraction from human stool was evaluated (72% +/- 12% recovery), and additional analyses were performed on norovirus-free stool extracts fortified with VLPs. Whereas peptide mass fingerprinting was rendered impractical by sample interferences, peptide sequencing using nanospray tandem MS facilitated unambiguous identification of > or =250 fmol of capsid protein in stool extracts. This is the first report on MS-based detection of norovirus, accomplished by using structurally identical, noninfective VLPs at clinically relevant concentrations. It represents an important milestone in the development of assays for surveillance of this category B bioterrorism agent.

Amino Acid Sequence↗

Study on the efficacy of nosocomial infection control (SENIC Project): results and implications for the future.

The purpose of the Study on the Efficacy of Nosocomial Infection Control (SENIC Project) was to evaluate nosocomial infection prevention and control programs in hospitals in the United States. The overall plan was to assess the surveillance and control activities in hospitals in the United States in 1970 and 1976, to measure the change in the nosocomial infection rates from 1970 to 1976 as determined from a carefully conducted retrospective chart review, and to assess the influence of changes in these programs on infection rates after controlling for other important changes that occurred during the interval. The SENIC 'bottom line' was that 32% of infections that would have occurred in the absence of well-organized infection surveillance and control programs were potentially preventable. However, only 6% of infections were actually being prevented by programs that existed in 1976. The critical components of an effective program were a balance between surveillance and control efforts, one infection control nurse for every 250 beds, a trained hospital epidemiologist, and feedback of surgical wound infection rates to practicing surgeons. In the United States, priorities for nosocomial infection prevention and control efforts include infections caused by emerging pathogens such as coagulase-negative staphylococci, enterococci, and Candida species; infections of the blood stream and surgical wounds; and infections in critical-care units. In addition, there is a critical need for timely analysis and dissemination of surveillance data and for continued training of infection control practitioners and physicians to maximize the effectiveness of prevention and control efforts.

Cross Infection↗

Melioidosis: insights into the pathogenicity of Burkholderia pseudomallei.

Burkholderia pseudomallei is a potential bioterror agent and the causative agent of melioidosis, a severe disease that is endemic in areas of Southeast Asia and Northern Australia. Infection is often associated with bacterial dissemination to distant sites, and there are many possible disease manifestations, with melioidosis septic shock being the most severe. Eradication of the organism following infection is difficult, with a slow fever-clearance time, the need for prolonged antibiotic therapy and a high rate of relapse if therapy is not completed. Mortality from melioidosis septic shock remains high despite appropriate antimicrobial therapy. Prevention of disease and a reduction in mortality and the rate of relapse are priority areas for future research efforts. Studying how the disease is acquired and the host-pathogen interactions involved will underpin these efforts; this review presents an overview of current knowledge in these areas, highlighting key topics for evaluation.

Bacterial Vaccines↗

The 2026 Bundibugyo Ebola Outbreak: A Warning for Global Preparedness for Future Epidemics.

Dear Editor, The 2026 Bundibugyo Ebolavirus (BDBV) outbreak has once again demonstrated that the threat of emerging diseases remains a major global health challenge. The outbreak, first detected in the Democratic Republic of Congo (DRC) and spread to Uganda, is not only a regional crisis but also a test of the world's preparedness for pathogens with epidemic potential. Unlike Zaire Ebolavirus (EBOV), which has benefited from effective vaccines and treatments in recent years, BDBV still lacks a licensed vaccine or specific treatment[1]. As of June 6, a total of 515 laboratory-confirmed cases and 91 deaths have been reported in DRC, while Uganda has reported 19 laboratory-confirmed cases and two deaths. The occurrence of unexplained deaths among both the community and healthcare workers, along with prior reports of an unidentified hemorrhagic fever, suggest that the outbreak has been likely originated in March 2026 or even earlier. Accordingly, the virus is believed to have spread unnoticed for several weeks before being identified through genomic sequencing in mid-May 2026[2]. The resurgence of Ebola in Africa results from a complex interaction of environmental, social, and political factors. Deforestation, the development of mining activities, the expansion of agriculture, and increased human contact with wildlife have elevated the likelihood of spillovers from wildlife reservoirs, particularly fruit bats, which are considered the most likely natural hosts of ebolaviruses. Moreover, weak disease surveillance systems and limited access to health services have delayed the identification of early cases. The similarity of the initial symptoms of Ebola to other endemic diseases in the region, such as malaria, makes early diagnosis difficult and provides ample opportunity for transmission to spread. Insecurity, misinformation, attacks on healthcare facilities, and armed conflict in the region have also posed serious challenges to the implementation of contact tracing programs and rapid response to the epidemic[3,4]. One of the most critical challenges highlighted by this outbreak is the weakness of diagnostic capacities in the affected areas. The initial 2007 outbreak of BDBV proved that delayed lab confirmation paralyzes public health responses[5]. Now, dealing with a much larger outbreak in 2026, the persistence of this challenge highlights a dangerous failure to invest in diagnostic infrastructure over the last 19 years. Many health facilities do not have access to molecular laboratories, rapid sample transport systems, and biosafety infrastructure[6]. These limitations delay the diagnosis and isolation of patients, thus perpetuating disease transmission. Investment in the development of mobile laboratories, rapid point-of-care diagnostic tests, and digital reporting systems can dramatically reduce the time to diagnosis and response to an outbreak. The BDBV outbreak shows that laboratory preparedness must be considered an essential part of global health security. Furthermore, the early detection of emerging pathogens depends not only on diagnostic technologies but also on the expertise of local scientists who are able to recognize unusual epidemiological and laboratory patterns. During the current outbreak, suspected Ebola cases initially tested negative using common diagnostic tests (designed for Zaire Ebola Virus), which delayed the identification of the BDBV. Specifically, field-based diagnostics in Bunia were calibrated exclusively to detect the EBOV responsible for recent Congolese outbreaks. Consequently, patient samples collected throughout late April and early May yielded negative results, requiring cross-country transport to Kinshasa for genomic confirmation[2]. This experience revealed a major vulnerability in outbreak preparedness: diagnostic tools designed for known threats may be ineffective in detecting less common or unexpected pathogens. Therefore, strengthening local scientific capacities, developing genomic surveillance, and expanding access to flexible and adaptable diagnostic platforms should be considered as a top priority for global health security. The lack of a licensed vaccine for BDBV was one of the most significant challenges of this epidemic. While the rVSV-ZEBOV vaccine has played a significant role in controlling Zaire ebolavirus, there is no licensed vaccine for BDBV. In response to this outbreak, efforts to develop mRNA-based vaccines, adenoviral vectors, rVSV-based vaccines, and multipotent vaccines have been accelerated[7]. However, the experience of this epidemic has shown that the development of medical products for rare diseases continues to face financial and investment constraints. This challenge highlights the need for sustained support from governments and international institutions for research and development of pathogens with epidemic potential. The 2026 Bundibugyo outbreak provides several key lessons for the global community. First, early detection and rapid diagnosis are the most important factors in containing the epidemic. The 19-year interval between the 2007 BDBV outbreak and the 2026 outbreak underscores persistent shortcomings in investment toward decentralized, pan-ebolavirus diagnostic infrastructure, with diagnostic delays hindering timely outbreak identification in both instances. Second, the trust and active participation of local communities are as important as medical interventions. Additionally, the rapid cross-border transmission dynamics between the DRC and Uganda demonstrate that blanket travel restrictions and border closures are impractical. As communities in the Great Lakes region routinely cross national borders for trade and healthcare, coordinated regional surveillance and timely information sharing are likely to be more effective than broad border closures in mitigating disease transmission[8]. Third, the protection of health workers must be a priority in preparedness plans. Fourth, a "One Health" approach is essential for simultaneous monitoring of humans, animals, and the environment. Although BDBV is not a new pathogen, the lack of licensed medical interventions and limited investment in research reflect many of the vulnerabilities associated with the concept of "Disease X."[9]. Unlike Zaire Ebola Virus, for which licensed vaccines and monoclonal antibody therapies are available, BDBV forces public health responses to rely almost entirely on non-pharmaceutical interventions such as isolation and infection control[10]. This gap reflects the structural inequity in global health research and development funding, with pathogens affecting resource-limited regions receiving insufficient attention until they spark an international emergency[2]. The BDBV outbreak proves that global epidemic preparedness cannot be pathogen-selective; it requires proactive investment in broad-spectrum countermeasures and resilient frontline health systems[8]. In conclusion, the 2026 BDBV outbreak is a serious wake-up call for the global health system. The epidemic revealed that gaps in surveillance systems, diagnostic capacities, vaccine development, and preparedness for emerging diseases persist. Investing in health infrastructure, developing Pan-Ebolavirus vaccines, strengthening laboratories, expanding the One-Health approach, and supporting research on emerging zoonotic pathogens must be at the top of global health security priorities. Otherwise, the BDBV outbreak may be just a prelude to larger crises to come.

Ebolavirus↗

CD40 signaling converts a minimally immunogenic antigen into a potent vaccine against the intracellular pathogen Listeria monocytogenes.

Conventional vaccination strategies have failed for numerous pathogens, and the development of novel approaches to vaccine development is a major public health priority. Killed or subunit vaccines represent an attractive approach due to their safety, but they suffer from low immunogenicity and generally require adjuvants. In this study, the possibility of harnessing CD40 signaling for enhancing the immunogenicity of killed vaccines was investigated. Intravenous immunization of C57BL/6 mice with heat-killed Listeria monocytogenes (HKL) induced minimal immunity, but HKL administered together with an agonistic anti-CD40 mAb induced high levels of both CD4(+) and CD8(+) T cells capable of producing IFN-gamma following in vitro HKL stimulation. HKL/anti-CD40 vaccination elicited robust protection against subsequent Listeria challenge. Approximately 1000-fold fewer bacteria were detected in the liver and spleen of vaccinated mice, and vaccinated mice were also able to resist a normally lethal Listeria challenge. CD40-mediated adjuvant activity required endogenous IL-12 at the time of vaccination, and protection was mediated by both CD8(+) and CD4(+) T cells. Thus, CD40 signaling can deliver potent adjuvant activity for vaccination against intracellular pathogens and is particularly effective for pathogens requiring both CD4(+) and CD8(+) T cells for effective control.

Adjuvants, Immunologic↗

Review on flavivirus vaccine development. Proceedings of a meeting jointly organised by the World Health Organization and the Thai Ministry of Public Health, 26-27 April 2004, Bangkok, Thailand.

In light of the continuous spread of human pathogenic flaviviruses, in particular the mosquito-transmitted species, vaccine development remains a high priority on the public health agenda. On 26-27 April 2004, a conference was held in Bangkok, Thailand, to review current status of flavivirus vaccine development and related issues, focussing on dengue (DEN) and Japanese encephalitis (JE). This event, co-sponsored by the World Health Organization (WHO) and the Thai Ministry of Public Health, reviewed the progress made with vaccine development, sero-epidemiological studies and other accompanying activities critical for vaccine development and vaccination. The considerable interest in and awareness of the flavivirus diseases and their prevention by public health decision makers, as well as the establishment of two dedicated programmes for dengue and Japanese encephalitis vaccine development raise hopes that new or improved vaccines will become available in the coming years.

Antibodies, Viral↗

In vitro evaluation of G1: a novel antimicrobial compound.

G1 (1-[5-bromofur-2-il]-2-bromo-2-nitroethene) is a novel antimicrobial compound developed in Cuba with reported broadspectrum activity against Gram-positive and -negative bacteria, yeasts and fungi. A compound of this nature may have considerable therapeutic potential. We tested the in vitro activity of this novel compound against 3595 organisms using microbroth dilution. The following are MIC50, MIC90 and range respectively for some of the microorganisms tested: E. coli 16, 16, 4 32; Klebsiella sp. 16, 16, 8 32; Citrobacter sp. 16, 16, 8 16; Enterobacter sp. 16, 16, 8-16; Proteus sp. 16, 16, 8-16; Coagulase-negative staphylococci 16, 32, 4-32; Enterococcus sp. 16, 32, 2-32; Staphylococcus aureus 8, 16, 4-16; Streptococcus agalactiae 4, 8, 4 8; Streptococcus pyogenes 4, 8, 0.25-16; Candida albicans 2, 2, 1-4; Candida tropicalis 4, 4, 2-4; Candida sp. 2,4, 1-4. MIC values appear lower for Gram-positive microorganisms and yeasts. G1 appears to be a novel antimicrobial agent with broad spectrum activity against bacterial and fungal pathogens. Defining the activity of this compound against multi-resistant bacteria is a priority.

Anti-Bacterial Agents↗

Prophylaxis and treatment of influenza virus infection.

Influenza virus infections remain an important cause of morbidity and mortality. Furthermore, a recurrence of pandemic influenza remains a real possibility. There are now effective ways to both prevent and treat influenza. Prevention of infection is most effectively accomplished by vaccination. Vaccination with the inactivated, intramuscular influenza vaccine has been clearly demonstrated to reduce serious morbidity and mortality associated with influenza infection, especially in groups of patients at high risk (e.g. the elderly). However, the inactivated, intramuscular vaccine does not strongly induce cell-mediated or mucosal immune responses, and protection induced by the vaccine is highly strain specific. Live, attenuated influenza vaccines administered intranasally have been studied in clinical trials and shown to elicit stronger mucosal and cell-mediated immune responses. Live, attenuated vaccines appear to be more effective for inducing protective immunity in children or the elderly than inactivated, intramuscular vaccines. Additionally, novel vaccine methodologies employing conserved components of influenza virus or viral DNA are being developed. Preclinical studies suggest that these approaches may lead to methods of vaccination that could induce immunity against diverse strains or subtypes of influenza. Because of the limitations of vaccination, antiviral therapy continues to play an important role in the control of influenza. Two major classes of antivirals have demonstrated ability to prevent or treat influenza in clinical trials: the adamantanes and the neuraminidase inhibitors. The adamantanes (amantadine and rimantadine) have been in use for many years. They inhibit viral uncoating by blocking the proton channel activity of the influenza A viral M2 protein. Limitations of the adamantanes include lack of activity against influenza B, toxicity (especially in the elderly), and the rapid development of resistance. The neuraminidase inhibitors were designed to interfere with the conserved sialic acid binding site of the viral neuraminidase and act against both influenza A and B with a high degree of specificity when administered by the oral (oseltamivir) or inhaled (zanamivir) route. The neuraminidase inhibitors have relatively low toxicity, and viral resistance to these inhibitors appears to be uncommon. Additional novel antivirals that target other phases of the life cycle of influenza are in preclinical development. For example, recombinant collectins inhibit replication of influenza by binding to the viral haemagglutinin as well as altering phagocyte responses to the virus. Recombinant techniques have been used for generation of antiviral proteins (e.g. modified collectins) or oligonucleotides. Greater understanding of the biology of influenza viruses has already resulted in significant advances in the management of this important pathogen. Further advances in vaccination and antiviral therapy of influenza should remain a high priority.

Amantadine↗

[DNA technology for diagnosis and characterization of agricultural animal pathogenic viruses].

Use of recombinant DNA for the development of diagnostic and therapeutic and preventive drugs became one of the priority trends in modern experimental veterinary. This paper discusses modern methods of virus analysis based on the DNA technologies: restriction mapping, nucleic acid hybridization, and polymerase chain reaction. Examples of utilization of these methods for clinical diagnosis and research of animal viruses are offered.

Animal Diseases↗

Eurocord position on ethical and legal issues involved in cord blood transplantation.

The Eurocord group held a round table discussion on the topic of ethical and legal issues involved in cord blood transplantation at the group's 2nd annual meeting at Annecy in May 1997. As chairman of the session the author was commissioned to put in writing the group's consensus on the subject. This covers the topics of: cord blood collections for autologous and intra-familiar usage; procreation for the purpose of haematopoietic progenitor cell donation for transplantation of a family member; cord blood banking including safety requirements and quality control regulations; patient priorities for usage of stored units; and patent rights. This paper's text was submitted for review to other participating members of the group. No amendments were made. The author feels confident that the paper faithfully reflects the consensus achieved.

Adult↗

Gordon Memorial Lecture. Chicken anaemia virus--a glimpse of the future?

This paper uses background information about chicken anaemia virus as a guide to how the study and control of virus diseases of poultry may develop in the future. It is predicted that "new' viruses will be discovered in poultry, many of which will be difficult to grow in vitro and whose pathogenicity may appear uncertain. When new diseases/syndromes arise in the future, it should be a priority activity to define their pathology. The limitations of currently available virus diagnostic methods are highlighted. The possibility of vaccinating against economically important subclinical disease is discussed, as is the use of recently developed technologies in differentiating virus strains and in developing new vaccines.

Animals↗

Antigen-specific immunodeficiency and its relation to the spectrum of American cutaneous leishmaniasis.

Delayed-type hypersensitivity (DTH) and antibodies against Leishmania have been studied in 207 Venezuelan patients with localized, muco-cutaneous and diffuse forms of American cutaneous leishmaniasis, representing the clinical spectrum of this disease. Muco-cutaneous disease appears to be related to inadequate immunomodulation or defective killing mechanisms; about 40% of these patients show exaggerated DTH, which is inversely related to antibody levels and is more pronounced in less extensive lesions. Patients with diffuse disease present severe antigen-specific immunodeficiency, apparently limited to T cell-mediated protection, DTH and its in vitro correlates. Treatment of patients with diffuse cutaneous leishmaniasis using a combination of chemotherapy and combined vaccine immunotherapy (heat-killed promastigotes plus BCG) has induced clinical inactivity and positive DTH in about one third of these patients, accompanied by marked lowering of antibody levels. These results are discussed in terms of Type 1 T cell responses, protective in cell-mediated immune reactions, and Type 2 T cell responses, non-protective in cell-mediated reactions, in the spectrum of leishmaniasis. Factors related to the induction of favorable Type 1 responses to intracellular pathogens are discussed in terms of a possible mechanism of the combined vaccine efficacy and priorities in vaccine development.

Animals↗

Molecular Pathogenesis, Global Epidemiological Trends, and Treatment Strategies for Pteropine Orthoreoviruses: A Narrative Review.

Pteropine orthoreoviruses are emerging bat-borne zoonotic viruses of the genus Orthoreovirus (family Reoviridae), increasingly recognized as causes of acute respiratory disease in humans. Originally grouped with the largely non-pathogenic mammalian orthoreoviruses, they have challenged that view through their association with severe influenza-like illness, evidence of human-to-human transmission, and a broad geographic range across the Old World. Maintained primarily in fruit bats of the family Pteropodidae, they are now linked to neurological as well as respiratory disease. This narrative review synthesizes current knowledge of their molecular pathogenesis, zoonotic ecology, and global epidemiology, integrating recent advances in phylogeography, reassortment-driven evolution, spillover dynamics, and translational biomedical applications within a unified One Health framework. Genomic diversity, reassortment potential, and the unique fusion-associated small transmembrane proteins together underpin viral adaptability and pathogenicity. Major gaps nonetheless remain in transmission dynamics, host adaptation, shedding ecology, and pandemic potential. Future priorities should include integrated genomic surveillance, improved diagnostic strategies, validated experimental models, and interdisciplinary One Health approaches to strengthen outbreak preparedness and prevention.

Bat-borne viruses↗

[Notes on the current discussion on the etiology of periodontopathies].

The aetiology and the therapy of periodontal diseases are main points of stomatological research. As to the methodological approach to aetiological studies, the use of materialistic dialectic proves profitable. For example, conclusions as to therapy result from the exact analysis of and the distinction between the causes of a disease and the pathogenic factors. In this way the exact evaluation of the importance of the known pathogenic factors becomes possible. The concept of multicausality proves to be unfavourable for the orientation to priority problems in aetiological research.

Humans↗

Effect of a vancomycin restriction policy on ordering practices during an outbreak of vancomycin-resistant Enterococcus faecium.

BACKGROUND: With the development of nosocomial pathogens that are resistant to multiple antimicrobial agents, reasonable restriction of antibiotic use has become a priority. METHODS: During an outbreak of vancomycin-resistant enterococcal infections, an audit of vancomycin hydrochloride use was conducted during October 3 through 21, 1994, and January 24 through February 2, 1995. During these periods, all orders for vancomycin were reviewed by clinical pharmacists. Use was classified as either appropriate or inappropriate based on recommendations by the Hospital Infection Control Practice Advisory Committee (HICPAC) of the Centers for Disease Control and Prevention, Atlanta, Ga. A policy restricting the use of vancomycin was adopted in November 1994. RESULTS: During the first audit in October 1994, 61% of vancomycin orders were considered inappropriate according to HICPAC criteria. At the time of this audit, the first cases of an outbreak of nosocomial vancomycin-resistant Enterococcus faecium had been detected. The follow-up audit showed that 30% of vancomycin orders were inappropriate by HICPAC criteria (P < .001). Overall use of vancomycin decreased by 50% and remained at this lower level for the following year. CONCLUSION: The institution of a vancomycin restriction policy was associated with a reduction of both inappropriate drug orders and total use.

Anti-Bacterial Agents↗

Stenotrophomonas maltophilia in the Antimicrobial Resistance Era: Species-Complex Taxonomy, Pathogenesis, Evolving Therapeutic Priorities, and Genomic Surveillance.

Stenotrophomonas maltophilia is a globally distributed, aerobic, non-fermenting Gram-negative bacillus increasingly recognized as an opportunistic pathogen in hospitalized and immunocompromised patients. Clinical interpretation is challenging because respiratory and device-associated isolates may represent colonization, polymicrobial infection, or true invasive disease. Recent genomic studies further suggest that organisms historically identified as S. maltophilia comprise a genetically diverse species complex, with implications for epidemiology, virulence, resistance surveillance, and susceptibility testing. Treatment is difficult because of biofilm formation, persistence in water-associated healthcare reservoirs, and intrinsic or acquired resistance mediated by L1 and L2 &#x3b2;-lactamases, multidrug efflux pumps, reduced permeability, mobile resistance determinants, and biofilm-associated tolerance. Current IDSA guidance identifies cefiderocol monotherapy as the preferred treatment for invasive S. maltophilia infection, whereas aztreonam-avibactam and agents such as trimethoprim-sulfamethoxazole, levofloxacin, and minocycline occupy alternative or combination-based roles. Nevertheless, the therapeutic evidence base remains uneven, and clinical decisions should integrate infection severity, source control, susceptibility findings, pharmacokinetic/pharmacodynamic (PK/PD) exposure, toxicity, infection site, and host-related factors. This review summarizes advances in taxonomy, epidemiology, pathogenesis, diagnostics, resistance, treatment, infection prevention, and genomic surveillance, and highlights the need for standardized identification, validated breakpoints, prospective comparative-effectiveness studies, and pragmatic or adaptive trial designs.

L1 &#x3b2;-lactamase↗