Search

Background: The long peripheral intravenous catheter (long PIVC), a type of PIVC, has an indwelling time of 5–14 days and is one of the options for antibacterial therapy. However, there is no consensus regarding the impact of insertion site selection on the complications associated with long PIVCs. Methods: This randomized controlled trial included 90 participants randomly assigned to either the control or experimental group, with 45 patients in each group. In the control group, long PIVCs were placed in the forearm, while in the experimental group, they were inserted in the upper arm. The primary outcome was catheter-related complications, while secondary outcomes included the first-attempt insertion success rate, total procedure time, and indwelling catheter duration. Results: The incidence of catheter-related complication rates was significantly lower in the experimental group (25.0%) compared to the control group (66.7%) (χ2 = 14.528, P < 0.001). The median indwelling catheter duration (interquartile range [IQR]) in the experimental and control groups were 187 [129, 286] hours and 122 [96, 188] hours, respectively, and the difference was statistically significant (Z = 3.016, P < 0.001). The first-attempt insertion success rates were comparable between the experimental group (97.7%) and the control group (97.4%). Similarly, the median total procedure times (IQR) in the experimental and control groups were 5.55 [4.93, 7.48] minutes and 6.17 [5.00, 7.33] minutes, showed no statistically significant difference (Z = 0.511, P > 0.05). Conclusions: Selecting the upper arm as the insertion site for long PIVCs reduced the incidence of thrombophlebitis and extended indwelling catheter duration during antimicrobial therapy. Trial registration: ClinicalTrials.gov identifier: NCT06455228 (Initial Release: 05/30/2024). [ABSTRACT FROM AUTHOR]

Enterohemorrhagic Escherichia coli (EHEC) is a common pathotype of E. coli that causes numerous outbreaks of foodborne illnesses. EHEC is a zoonotic pathogen that is transmitted from animals to humans. Ruminants, particularly cattle, are considered important reservoirs for virulent EHEC strains. Humans can become infected with EHEC through the consumption of contaminated food and water or through direct contact with infected animals or humans. E. coli O157:H7 is one of the most commonly reported causes of foodborne illnesses in developed countries. The formation of attaching and effacing (A/E) lesions on the intestinal epithelium, combined with Shiga toxin production, is a hallmark of EHEC infection and can lead to lethal hemolytic–uremic syndrome (HUS). For the phage-dependent regulation of Shiga toxin production, antibiotic treatment is contraindicated, as it may exacerbate toxin production, limiting therapeutic options to supportive care. In response to this challenge and the growing threat of antibiotic resistance, phytochemicals have emerged as promising antivirulence agents. These plant-derived compounds target bacterial virulence mechanisms without promoting resistance. Therefore, the aim of this study is to summarize the recent knowledge on the use of phytochemicals targeting EHEC. We focused on the molecular basis of their action, targeting the principal virulence determinants of EHEC. [ABSTRACT FROM AUTHOR]

Background: Shorter courses of antimicrobial therapy have been shown to be non-inferior to longer durations for the management of several infections. However, data on critically ill patients with severe infections by multidrug-resistant Gram-negative bacteria (MDR-GNB) are scarce. In the duratiOn of theraPy in severe infecTIons by MultIdrug-reSistant gram-nEgative bacteria (OPTIMISE) trial, we assessed the non-inferiority of 7-day versus 14-day antimicrobial therapy for patients with intensive care unit (ICU)-acquired severe infections by MDR-GNB. Methods: This was a randomised multicenter, open-label, parallel controlled, non-inferiority trial. Adult patients with severe infections by MDR-GNB initiated ≥ 48 h of ICU admission were eligible if they were hemodynamically stable and without fever > 48 h on the 7th day of appropriate antimicrobial therapy. Patients were 1:1 randomised to discontinue antimicrobial therapy on the 7th (± 1) day or to continue for a total of 14 (± 1) days. The primary outcome was clinical failure, defined as death or relapse of infection within 28 days of randomisation. An upper edge of the two-tailed 95% confidence interval (CI) of the delta between the clinical failure rate in the 7- and the 14-day lower than 10% in both intention-to-treat (ITT) and per protocol (PP) analyses was set as the non-inferiority criteria. Results: A total of 106 patients composed the ITT population: 59 and 47 allocated to 7- and 14-day groups, respectively. The PP population included 75 patients: 47 and 28 in the 7- and 14-day groups, respectively. Clinical failure occurred in 42.4% and 44.7% of the ITT population in 7- and 14-day groups, respectively, (risk difference (RD) − 2.3, 95%CI − 21.3 to 16.7), and in 46.8% and 50.0% of the PP population in 7- and 14-day groups, respectively (RD − 3.2, 95%CI − 26.6 to 20.2). Most infections were of the respiratory tract (73/68.9%) and caused by carbapenem-resistant Enterobacterales (42/39.6%). The study was interrupted before reaching planned sample size due to low recruitment rate. Conclusion: The OPTIMISE trial could not determine the non-inferiority of 7-day compared to 14-day therapy for severe infections caused by MDR-GNB due to early termination related to the low recruitment rate. Trial registration: NCT05210387 on January 13, 2022. [ABSTRACT FROM AUTHOR]

Background and Objectives: Elizabethkingia species have become significant sources of infections acquired in hospital settings and are commonly linked to high mortality rates. Antimicrobial resistance can be influenced by Elizabethkingia species, geographical location, antimicrobial susceptibility testing methods, and the time of bacterial isolation. There are distinct antimicrobial susceptibility patterns among species, and the investigation into potential antibiotic susceptibility variations among species is beneficial. There is no guidance on the treatment of Elizabethkingia species infections in the literature. Consequently, the purpose of this review was to elaborate on the antimicrobial susceptibility patterns of Elizabethkingia species through a scoping review of existing studies on the antibiograms of the Elizabethkingia species and on the illness caused by Elizabethkingia species. Materials and Methods: A comprehensive literature search in PubMed and Web of Science between 1 January 2000 and 30 April 2024 identified all studies, including those that examined antimicrobial susceptibility patterns and antimicrobial therapy of infections caused by Elizabethkingia species. I considered studies on antimicrobial susceptibility testing for Elizabethkingia species in which only broth microdilution methods and agar dilution methods were used. Results: The sensitivity levels of Elizabethkingia meningoseptica to piperacillin–tazobactam (5–100%), ciprofloxacin (0–43.4%), levofloxacin (30–81.8%), trimethoprim–sulfamethoxazole (0–100%), tigecycline (15–100%), minocycline (60–100%), and rifampicin (94–100%) varied. The sensitivity levels of Elizabethkingia anophelis to piperacillin–tazobactam (3.3–93.3%), ciprofloxacin (1–75%), levofloxacin (12–100%), trimethoprim–sulfamethoxazole (1.02–96.7%), tigecycline (0–52.2%), minocycline (97.5–100%), and rifampicin (20.5–96%) varied. The sensitivity levels of Elizabethkingia miricola to piperacillin–tazobactam (41.6–94.0%), ciprofloxacin (14–75%), levofloxacin (77.0–100%), trimethoprim–sulfamethoxazole (18.0–100%), tigecycline (50%), minocycline (100%), and rifampicin (66–85.7%) varied. Conclusions: The majority of the isolates of Elizabethkingia species were susceptible to minocycline and rifampin. This issue requires professional knowledge integration and treatment recommendations. [ABSTRACT FROM AUTHOR]

Background: The optimal antimicrobial treatment duration for diabetes-related foot osteomyelitis (DFO) currently needs to be determined. We systematically reviewed the effects of short and long treatment durations on outcomes of DFO. Methods: We performed a systematic review searching Cochrane, CENTRAL, MEDLINE, Embase, and CINAHL Plus from inception up to 19 January 2024. Two independent reviewers screened the titles and abstracts of the studies. Studies comparing short (<6 weeks) and long (>6 weeks) treatment durations for DFO were included. The primary outcome was amputation; the secondary outcomes were remission, mortality, costs, quality of life, and adverse events. Risk of bias and GRADE were assessed. Results: We identified 2708 references, of which 2173 remained after removing duplicates. Two studies were included. Differences in methodology precluded a meta-analysis. The primary outcome, major amputation, was reported in one study, with a rate of 10% in both the intervention and comparison groups (p = 1.00), regardless of treatment duration. For the secondary outcome, remission rates, the first study reported 60% in the intervention group versus 70% in the comparison group (p = 0.50). In the second study, remission rates were 84% in the intervention group versus 78% in the comparison group (p = 0.55). Data for the outcomes mortality, costs, and quality of life were not available. Short treatment duration may lead to fewer adverse events. The risk of bias was assessed as low to moderate, and the level of evidence ranged from very low to moderate. Conclusions: Our findings suggest that for DFO, there is no difference between a shorter and more prolonged duration of antimicrobial treatment regarding amputation and remission, with potentially fewer adverse events with shorter treatment durations. However, the uncertainty stems from limited, heterogeneous studies and generally low-quality evidence marred by moderate biases, imprecision, and indirectness. More high-quality studies are needed to substantiate these findings. [ABSTRACT FROM AUTHOR]

Abstract Background Postoperative intracranial neurosurgical infections (PINI) complicate

Background: Postoperative intracranial neurosurgical infections (PINI) complicate < 5% neurosurgeries. Scarce attention was dedicated to the extension and characteristics of its antimicrobial management considering their high morbidity, not negligible mortality, delayed hospital stay and increased healthcare costs. Methods: We analyzed retrospectively (2014–2023) 162 PINI from eight Spanish third-level academic hospitals. Results: Elective clean craniotomies after tumor or vascular causes were the leading procedures. Epidural abscess (24.7%), scalp infections (19.8%), postsurgical meningitis (16.7%) and cranioplasty infections (16.7%) were the most frequent PINI. Gram negative bacteria (38.6%) and Staphylococcus spp (28.6%) were the predominant isolates. Overall 85.2% patients underwent pus drainage, mostly by craniotomy (40.3%). Interestingly 34% were already receiving antibiotics for extracranial infections before developing PINI while 16.8% did not receive pre-operative antibiotic prophylaxis. In total 77.2% patients started a combined intravenous (IV) antimicrobial therapy, of which 85.2% switched after 5 days to a second-line IV antibiotic regimen, in 41.3% cases combined, after pus culture results, for a median of 21 days. Overall 61.1% patients continued on oral antimicrobials after hospital discharge, 30.3% as a combined regimen, for a median of 42 days. Complete cure was obtained in 81.5% cases, while 11.1% relapsed, 7.4% failed to cure and 6.8% died after PINI complications. In the multivariate analysis oral antimicrobial therapy after hospital discharge (p = 0.001) was significantly associated with PINI cure with no effect on survival. Conclusions: We conclude that an extended 6 weeks sequential IV and oral antimicrobial therapy in addition to neurosurgical correction increases PINI cure rate with no effect on survival. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) are leading the way in nanotechnological innovation, combining the captivating properties of silver with the accuracy of nanoscale engineering, thus revolutionizing material science. Three main techniques arise within the alchemical domains of AgNP genesis: chemical, physical, and biological synthesis. Each possesses its distinct form of magic for controlling size, shape, and scalability—key factors necessary for achieving expertise in the practical application of nanoparticles. The story unravels, describing the careful coordination of chemical reduction, the environmentally sensitive charm of green synthesis utilizing plant extracts, and the precise accuracy of physical techniques. AgNPs are highly praised in the field of healthcare for their powerful antibacterial characteristics. These little warriors display a wide-ranging attack against bacteria, fungi, parasites, and viruses. Their critical significance in combating hospital-acquired and surgical site infections is highly praised, serving as a beacon of hope in the fight against the challenging problem of antibiotic resistance. In addition to their ability to kill bacteria, AgNPs are also known to promote tissue regeneration and facilitate wound healing. The field of cancer has also observed the adaptability of AgNPs. The review documents their role as innovative carriers of drugs, specifically designed to target cancer cells with accuracy, minimizing harm to healthy tissues. Additionally, it explores their potential as cancer therapy or anticancer agents capable of disrupting the growth of tumors. In the food business, AgNPs are utilized to enhance the durability of packing materials and coatings by infusing them with their bactericidal properties. This results in improved food safety measures and a significant increase in the duration that products can be stored, thereby tackling the crucial issue of food preservation. This academic analysis recognizes the many difficulties that come with the creation and incorporation of AgNPs. This statement pertains to the evaluation of environmental factors and the effort to enhance synthetic processes. The review predicts future academic pursuits, envisioning progress that will enhance the usefulness of AgNPs and increase their importance from being new to becoming essential within the realms of science and industry. Besides, AgNPs are not only a subject of scholarly interest but also a crucial component in the continuous effort to tackle some of the most urgent health and conservation concerns of contemporary society. This review aims to explore the complex process of AgNP synthesis and highlight their numerous uses, with a special focus on their growing importance in the healthcare and food business sectors. This review invites the scientific community to explore the extensive possibilities of AgNPs in order to fully understand and utilize their potential. [ABSTRACT FROM AUTHOR]

Skin and soft-tissue infections require significant consideration because of their prolonged treatment duration and propensity to rapidly progress, resulting in severe complications. The primary challenge in their treatment stems from the involvement of drug-resistant microorganisms that can form impermeable biofilms, as well as the possibility of infection extending deep into tissues, thereby complicating drug delivery. Dissolving microneedle patches are an innovative transdermal drug-delivery system that effectively enhances drug penetration through the stratum corneum barrier, thereby increasing drug concentration at the site of infection. They offer highly efficient, safe, and patient-friendly alternatives to conventional topical formulations. This comprehensive review focuses on recent advances and emerging trends in dissolving-microneedle technology for antimicrobial skin-infection therapy. Conventional antibiotic microneedles are compared with those based on emerging antimicrobial agents, such as quorum-sensing inhibitors, antimicrobial peptides, and antimicrobial-matrix materials. The review also highlights the potential of innovative microneedles incorporating chemodynamic, nanoenzyme antimicrobial, photodynamic, and photothermal antibacterial therapies. This review explores the advantages of various antimicrobial therapies and emphasizes the potential of their combined application to improve the efficacy of microneedles. Finally, this review analyzes the druggability of different antimicrobial microneedles and discusses possible future developments. [ABSTRACT FROM AUTHOR]

AIM: Investigation and identification of epidemiological characteristics, risk factors and treatment regimens effectivity in reducing morbidity and mortality. BACKGROUND: C.difficile remains the leading cause of health care associated diarrhea, usually as a result of irrational use of antimicrobial therapy. METHODS: Retrospective descriptive study (October 2020-january2024) included all patients with clinical symptoms of Clostridoides difficile infection (CDI) admitted at our clinic. Diagnosis is based on isolation with coproculture for C.difficile, toxin confirmation with immunochromatography, small number confirmed with PCR film array. RESULTS: 594 inpatients with clinical symptoms of CDI were evaluated and diagnosis was confirmed in 44. Average mean age was 58,5 (29-90)years, approximately with no differencies on sex representation. Comorbidities and previous hospitalisations were noted in two third of them, and 63% had used antimicrobial drugs, while 34% had history of corticosteroid usage and 4,5% imunosupressive therapy. Often used antibiotics cephalosporins, clindamycine, quinolones and macrolides. 68,2% had history of protein pump inhibitors usage. Culture positive were 38%, toxinA/B is confirmed with immunochromatography in 77% of patients, PCR film array confirmed C.difficile toxin A/B in the remaining patients. Treatment is carried out with oral vancomycine in 56% of patients, 15% with metronidazole and the remaining with combination of two drugs. Regarding outcomes 90% of patients were cured while 10% had fatal outcomes and CDI is not considered the main cause of death. CONCLUSION: Elderly patients with antibiotic history treatment, previous healthcare exposures and comorbidities were the most affected by CDI infection. Metronidazole and vancomycine has shown good therapeutic results.

BACKGROUND: Desirability of outcome ranking (DOOR) is a novel approach to clinical trial design that incorporates safety and efficacy assessments into an ordinal ranking system to evaluate overall outcomes of clinical trial participants. Here, we derived and applied a disease-specific DOOR endpoint to registrational trials for complicated intra-abdominal infection (cIAI). METHODS: Initially, we applied an a priori DOOR prototype to electronic patient-level data from 9 phase 3 noninferiority trials for cIAI submitted to the US Food and Drug Administration between 2005 and 2019. We derived a cIAI-specific DOOR endpoint based on clinically meaningful events that trial participants experienced. Next, we applied the cIAI-specific DOOR endpoint to the same datasets and, for each trial, estimated the probability that a participant assigned to the study treatment would have a more desirable DOOR or component outcome than if assigned to the comparator. RESULTS: Three key findings informed the cIAI-specific DOOR endpoint: (1) a significant proportion of participants underwent additional surgical procedures related to their baseline infection; (2) infectious complications of cIAI were diverse; and (3) participants with worse outcomes experienced more infectious complications, more serious adverse events, and underwent more procedures. DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 47.4% to 50.3% and were not significantly different. Component analyses depicted risk-benefit assessments of study treatment versus comparator. CONCLUSIONS: We designed and evaluated a potential DOOR endpoint for cIAI trials to further characterize overall clinical experiences of participants. Similar data-driven approaches can be utilized to create other infectious disease-specific DOOR endpoints.

Abstract The standard treatment duration for acute cholangitis (AC) involves a 4–7-day antimicrobial treatment post-biliary drainage; however, recent studies have suggested that a ≤ 2–3 days is sufficient. However, clinical practice frequently depends on body temperature as a criterion for discontinuing antimicrobial treatment. Therefore, in this study, we assessed whether patients with AC can achieve successful outcomes with a ≤ 7-day antimicrobial treatment, even with a fever, assuming the infection source is effectively controlled. We conducted a single-center retrospective study involving patients with AC, defined following the Tokyo Guidelines 2018 for any cause, who underwent successful biliary drainage and completed a ≤ 7-day antimicrobial treatment. Patients were categorized into the febrile and afebrile groups based on their body temperature within 24 h before completing antimicrobial treatment. The primary outcome was the clinical cure rate, defined as no initial presenting symptoms by day 14 post-biliary drainage without recurrence or death by day 30. The secondary outcome was a 3-month recurrence rate. Logistic regression with inverse probability of treatment weighting was used. Overall, 408 patients were selected, among whom 40 (9.8%) were febrile. The two groups showed no significant differences in the clinical cure and 3-month recurrence rates. Notably, the subgroups limited to patients with a ≤ 3-day antibiotic treatment duration also showed no differences in these outcomes. Therefore, our results suggest that discontinuing antibiotics within the initially planned treatment period was sufficient for successful drainage cases of AC, regardless of the patient's fever status during the 24 h leading up to termination.

Abstract Bacillus cereus is a bacterium capable of causing late-onset neonatal sepsis. By analyzing 11 cases, this study investigates the diagnosis, treatment, and prognosis of Bacillus cereus infections, aiming to provide insights into clinical diagnosis and therapy. The study scrutinized 11 instances of late-onset neonatal sepsis, including two fatalities attributable to Bacillus cereus, one accompanied by cerebral hemorrhage. An examination and analysis of these cases’ symptoms, signs, laboratory tests, and treatment processes, along with a review of related literature from 2010 to 2020, revealed a high mortality rate of 41.38% in non-gastrointestinal infections caused by Bacillus cereus. Our findings underscore the critical importance of rapid diagnosis and effective antimicrobial therapy in reducing mortality rates. Once the source of infection is identified, implementing effective infection control measures is essential.

Abstract Intra-abdominal infections (IAIs) are an important cause of morbidity and mortality in hospital settings worldwide. The cornerstones of IAI management include rapid, accurate diagnostics; timely, adequate source control; appropriate, short-duration antimicrobial therapy administered according to the principles of pharmacokinetics/pharmacodynamics and antimicrobial stewardship; and hemodynamic and organ functional support with intravenous fluid and adjunctive vasopressor agents for critical illness (sepsis/organ dysfunction or septic shock after correction of hypovolemia). In patients with IAIs, a personalized approach is crucial to optimize outcomes and should be based on multiple aspects that require careful clinical assessment. The anatomic extent of infection, the presumed pathogens involved and risk factors for antimicrobial resistance, the origin and extent of the infection, the patient’s clinical condition, and the host’s immune status should be assessed continuously to optimize the management of patients with complicated IAIs.

Abstract Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients’ safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts’ opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery.

Abstract Background Acinetobacter baumannii is a health threat due to its antibiotic resistance. Herein, antibiotic susceptibility and its association with the Toxin-antitoxin (TA) system genes in A. baumannii clinical isolates from Iran were investigated. Next, we prepared meropenem-loaded chitosan nanoparticles (MP-CS) and investigated their antibacterial effects against meropenem-susceptible bacterial isolates. Methods Out of 240 clinical specimens, 60 A. baumannii isolates were assessed. Antibiotic resistance of the isolates against conventional antibiotics was determined alongside investigating the presence of three TA system genes (mazEF, relBE, and higBA). Chitosan nanoparticles were characterized in terms of size, zeta potential, encapsulation efficiency, and meropenem release activity. Their antibacterial effects were assessed using the well diffusion method, minimum inhibitory concentration (MIC), and colony-forming unit (CFU) counting. Their cytotoxic effects and biocompatibility index were determined via the MTT, LDH, and ROS formation assays. Results Ampicillin, ceftazidime, and colistin were the least effective, and amikacin and tobramycin were the most effective antibiotics. Out of the 60 isolates, 10 (16.7%), 5 (8.3%), and 45 (75%) were multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR), respectively. TA system genes had no significant effect on antibiotic resistance. MP-CS nanoparticles demonstrated an average size of 191.5 and zeta potential of 27.3 mV alongside a maximum encapsulation efficiency of 88.32% and release rate of 69.57%. MP-CS nanoparticles mediated similar antibacterial effects, as compared with free meropenem, against the A. baumannii isolates with significantly lower levels of meropenem. MP-CS nanoparticles remarkably prevented A549 and NCI-H292 cell infection by the A. baumannii isolates alongside demonstrating a favorable biocompatibility index. Conclusion Antibiotic-loaded nanoparticles should be further designed and investigated to increase their antibacterial effect against A. baumannii and assess their safety and applicability in vivo settings.

Objective. To determine the level of knowledge of doctors on the rational use of antimicrobial drugs in clinical practice and to compare with data of the previous stage of the study and results obtained from students in a parallel project. Materials and Methods. A multicenter questionnaire survey of practitioners with analysis of results – stage of KANT project (full name of the project – «Physicians’ (Students’) knowledge in antimicrobials usage») conducted in 2020–2023. Results. A total of 336 participants were surveyed in 5 centers (10 Russian regions: Belgorod, Novosibirsk, Rostov, Voronezh, Lipetsk, Sakhalin, Primorsky, Krasnodar, and Krasnoyarsk regions, Republic of Tatarstan). The average level of correct answers (LCA) for the whole questionnaire was 47.5% (taking into account the extended analysis of sub-items questions No. 8 and 9 – 46.8%). Doctors showed the best results in answering questions about the time interval during which the effectiveness of antimicrobial therapy is evaluated (LCA – 84.2%); about choosing the most rational action if antimicrobial therapy (AMT) has a positive clinical effect, but requires a long course of therapy (LCA – 72.6%); selection of rational diagnostic/treatment action in the diagnosis of acute tonsillitis or pharyngitis, in a case where etiologic diagnosis is required (LCA – 63.1%). The worst results were recorded in answering to the following questions: indication of the antimicrobial drug of choice in the treatment of various infections (LCA – 29.1%); the choice of auxiliary drugs in addition to the justified appointment of antimicrobial drugs in the treatment of bacterial infections of the respiratory tract for the entire period of the disease or in certain phases (LCA – 26.6% – 35.1%); indication of a combination of antimicrobial drugs that is irrational to prescribe in clinical practice due to a similar mechanism and/or spectrum of activity against pathogens (LCA – 24.4%). Significant differences were found between centers in a number of questions, between physicians in KANT-III and KANT-IV projects (p < 0.001), and between physicians and students in a parallel project (KANT-IV students, LCA – 42.6%, p < 0.001). Conclusions. An unsatisfactory level of physicians’ knowledge of AMT and choice of adjuvant agents, as well as appropriateness of antimicrobial combination was found. The authors believe there is a need for making more efforts in areas of increasing physicians’ compliance to clinical recommendations, expertise and quality control of pharmacotherapy, recruitment of clinical pharmacologists; to optimize the educational process in universities, to expand the scope and availability of additional educational programs within the system of continuous education, as well as to train physicians in using modern sources of scientific medical information.

Aerococcus viridans (A. viridans) is an important opportunistic zoonotic pathogen that poses a potential threat to the animal husbandry industry, such as cow mastitis, due to the widespread development of multidrug-resistant strains. Phage lysins have emerged as a promising alternative antibiotic treatment strategy. However, no lysins have been reported to treat A. viridans infections. In this study, the critical active domain and key active sites of the first A. viridans phage lysin AVPL were revealed. AVPL consists of an N-terminal N-acetylmuramoyl-L-alanine amidase catalytic domain and a C-terminal binding domain comprising two conserved LysM. H40, N44, E52, W68, H147, T157, F60, F64, I77, N92, Q97, H159, V160, D161, and S42 were identified as key sites for maintaining the activity of the catalytic domain. The LysM motif plays a crucial role in binding AVPL to bacterial cell wall peptidoglycan. AVPL maintains stable activity in the temperature range of 4-45°C and pH range of 4-10, and its activity is independent of the presence of metal ions. In vitro, the bactericidal effect of AVPL showed efficient bactericidal activity in milk samples, with 2 μg/mL of AVPL reducing A. viridans by approximately 2 Log10 in 1 h. Furthermore, a single dose (25 μg) of lysin AVPL significantly reduces bacterial load (approximately 2 Log10) in the mammary gland of mice, improves mastitis pathology, and reduces the concentration of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in mammary tissue. Overall, this work provides a novel alternative therapeutic drug for mastitis induced by multidrug-resistant A. viridans. [ABSTRACT FROM AUTHOR]

Periodontitis-related oral microbial dysbiosis is thought to contribute to adverse pregnancy outcomes (APOs), infertility, and female reproductive inflammation. Since probiotics can modulate periodontitis and oral microbiome dysbiosis, this study examined the effects of a probiotic bacteriocin, nisin, in modulating the reproductive microbiome and inflammation triggered by periodontitis. A total of 24 eight-week-old BALB/cByJ female mice were randomly divided into four treatment groups (control, infection, nisin, and infection+nisin group), with 6 mice per group. A polymicrobial (Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum) mouse model of periodontal disease was used to evaluate the effects of this disease on the female reproductive system, with a focus on the microbiome, local inflammation, and nisin's therapeutic potential in this context. Moreover, 16s RNA sequencing was used to evaluate the changes in the microbiome and RT-PCR was used to evaluate the changes in inflammatory cytokines. Periodontal pathogen DNA was detected in the reproductive organs, and in the heart and aorta at the end of the experimental period, and the DNA was especially elevated in the oral cavity in the infection group. Compared to the control groups, only P. gingivalis was significantly higher in the oral cavity and uterus of the infection groups, and T. forsythia and F. nucleatum were significantly higher in the oral cavity of the infection groups. The infection and nisin treatment group had significantly lower levels of P. gingivalis, T. forsythia, and F. nucleatum in the oral cavity compared with the infection group. Since periodontal pathogen DNA was also detected in the heart and aorta, this suggests potential circulatory system transmission. The polymicrobial infection generally decreased the microbiome diversity in the uterus, which was abrogated by nisin treatment. The polymicrobial infection groups, compared to the control groups, generally had lower Firmicutes and higher Bacteroidota in all the reproductive organs, with similar trends revealed in the heart. However, the nisin treatment group and the infection and nisin group, compared to the control or infection groups, generally had higher Proteobacteria and lower Firmicutes and Bacteroidota in the reproductive organs and the heart. Nisin treatment also altered the microbiome community structure in the reproductive tract to a new state that did not mirror the controls. Periodontal disease, compared to the controls, triggered an increase in inflammatory cytokines (IL-6, TNF-α) in the uterus and oral cavity, which was abrogated by nisin treatment. Polymicrobial periodontal disease alters the reproductive tract's microbial profile, microbiome, and inflammatory status. Nisin modulates the microbial profile and microbiome of the reproductive tract and mitigates the elevated uterine inflammatory cytokines triggered by periodontal disease. [ABSTRACT FROM AUTHOR]

Bacillus cereus is a bacterium capable of causing late-onset neonatal sepsis. By analyzing 11 cases, this study investigates the diagnosis, treatment, and prognosis of Bacillus cereus infections, aiming to provide insights into clinical diagnosis and therapy. The study scrutinized 11 instances of late-onset neonatal sepsis, including two fatalities attributable to Bacillus cereus, one accompanied by cerebral hemorrhage. An examination and analysis of these cases' symptoms, signs, laboratory tests, and treatment processes, along with a review of related literature from 2010 to 2020, revealed a high mortality rate of 41.38% in non-gastrointestinal infections caused by Bacillus cereus. Our findings underscore the critical importance of rapid diagnosis and effective antimicrobial therapy in reducing mortality rates. Once the source of infection is identified, implementing effective infection control measures is essential. Highlights: This study offers the first in-depth analysis of late-onset neonatal sepsis caused by Bacillus cereus. It reveals a high mortality rate associated with Bacillus cereus infections in neonates. The research uncovers potential links between late-onset sepsis and cerebral hemorrhage. The importance of timely diagnosis and antimicrobial therapy is emphasized. New strategies and perspectives for preventing and controlling Bacillus cereus infections are presented. [ABSTRACT FROM AUTHOR]

This paper explores the latest advancements in aerogel technology for antimicrobial therapy, revealing their interesting capacity that could improve the current medical approaches for antimicrobial treatments. Aerogels are attractive matrices because they can have an antimicrobial effect on their own, but they can also provide efficient delivery of antimicrobial compounds. Their interesting properties, such as high porosity, ultra-lightweight, and large surface area, make them suitable for such applications. The fundamentals of aerogels and mechanisms of action are discussed. The paper also highlights aerogels' importance in addressing current pressing challenges related to infection management, like the limited drug delivery alternatives and growing resistance to antimicrobial agents. It also covers the potential applications of aerogels in antimicrobial therapy and their possible limitations. [ABSTRACT FROM AUTHOR]

Acute cholecystitis is one of the most common surgical diseases, which may progress from mild to severe cases. When combined with bacteremia, the mortality rate of acute cholecystitis reaches up to 10–20%. The standard of care in patients with acute cholecystitis is early laparoscopic cholecystectomy. Percutaneous cholecystostomy or endoscopic procedures are alternative treatments in selective cases. Nevertheless, antibiotic therapy plays a key role in preventing surgical complications and limiting the systemic inflammatory response, especially in patients with moderate to severe cholecystitis. Patients with acute cholecystitis have a bile bacterial colonization rate of 35–60%. The most frequently isolated microorganisms are Escherichia coli, Klebsiella spp., Streptococcus spp., Enterococcus spp., and Clostridium spp. Early empirical antimicrobial therapy along with source control of infection is the cornerstone for a successful treatment. In these cases, the choice of antibiotic must be made considering some factors (e.g., the severity of the clinical manifestations, the onset of the infection if acquired in hospital or in the community, the penetration of the drug into the bile, and any drug resistance). Furthermore, therapy must be modified based on bile cultures in cases of severe cholecystitis. Antibiotic stewardship is the key to the correct management of bile-related infections. It is necessary to be aware of the appropriate therapeutic scheme and its precise duration. The appropriate use of antibiotic agents is crucial and should be integrated into good clinical practice and standards of care. [ABSTRACT FROM AUTHOR]

Background: Acinetobacter baumannii is a health threat due to its antibiotic resistance. Herein, antibiotic susceptibility and its association with the Toxin-antitoxin (TA) system genes in A. baumannii clinical isolates from Iran were investigated. Next, we prepared meropenem-loaded chitosan nanoparticles (MP-CS) and investigated their antibacterial effects against meropenem-susceptible bacterial isolates. Methods: Out of 240 clinical specimens, 60 A. baumannii isolates were assessed. Antibiotic resistance of the isolates against conventional antibiotics was determined alongside investigating the presence of three TA system genes (mazEF, relBE, and higBA). Chitosan nanoparticles were characterized in terms of size, zeta potential, encapsulation efficiency, and meropenem release activity. Their antibacterial effects were assessed using the well diffusion method, minimum inhibitory concentration (MIC), and colony-forming unit (CFU) counting. Their cytotoxic effects and biocompatibility index were determined via the MTT, LDH, and ROS formation assays. Results: Ampicillin, ceftazidime, and colistin were the least effective, and amikacin and tobramycin were the most effective antibiotics. Out of the 60 isolates, 10 (16.7%), 5 (8.3%), and 45 (75%) were multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR), respectively. TA system genes had no significant effect on antibiotic resistance. MP-CS nanoparticles demonstrated an average size of 191.5 and zeta potential of 27.3 mV alongside a maximum encapsulation efficiency of 88.32% and release rate of 69.57%. MP-CS nanoparticles mediated similar antibacterial effects, as compared with free meropenem, against the A. baumannii isolates with significantly lower levels of meropenem. MP-CS nanoparticles remarkably prevented A549 and NCI-H292 cell infection by the A. baumannii isolates alongside demonstrating a favorable biocompatibility index. Conclusion: Antibiotic-loaded nanoparticles should be further designed and investigated to increase their antibacterial effect against A. baumannii and assess their safety and applicability in vivo settings. [ABSTRACT FROM AUTHOR]

Intra-abdominal infections (IAIs) are an important cause of morbidity and mortality in hospital settings worldwide. The cornerstones of IAI management include rapid, accurate diagnostics; timely, adequate source control; appropriate, short-duration antimicrobial therapy administered according to the principles of pharmacokinetics/pharmacodynamics and antimicrobial stewardship; and hemodynamic and organ functional support with intravenous fluid and adjunctive vasopressor agents for critical illness (sepsis/organ dysfunction or septic shock after correction of hypovolemia). In patients with IAIs, a personalized approach is crucial to optimize outcomes and should be based on multiple aspects that require careful clinical assessment. The anatomic extent of infection, the presumed pathogens involved and risk factors for antimicrobial resistance, the origin and extent of the infection, the patient's clinical condition, and the host's immune status should be assessed continuously to optimize the management of patients with complicated IAIs. [ABSTRACT FROM AUTHOR]

Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients' safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts' opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery. [ABSTRACT FROM AUTHOR]

Aims: Little is known about the population pharmacokinetics (PPK) of vancomycin in neonates with perinatal asphyxia treated with therapeutic hypothermia (TH). We aimed to describe the PPK of vancomycin and propose an initial dosing regimen for the first 48 h of treatment with pharmacokinetic/pharmacodynamic target attainment. Methods: Neonates with perinatal asphyxia treated with TH were included from birth until Day 6 in a multicentre prospective cohort study. A vancomycin PPK model was constructed using nonlinear mixed‐effects modelling. The model was used to evaluate published dosing guidelines with regard to pharmacokinetic/pharmacodynamic target attainment. The area under the curve/minimal inhibitory concentration ratio of 400–600 mg*h/L was used as target range. Results: Sixteen patients received vancomycin (median gestational age: 41 [range: 38–42] weeks, postnatal age: 4.4 [2.5–5.5] days, birth weight: 3.5 [2.3–4.7] kg), and 112 vancomycin plasma concentrations were available. Most samples (79%) were collected during the rewarming and normothermic phase, as vancomycin was rarely initiated during the hypothermic phase due to its nonempirical use. An allometrically scaled 1‐compartment model showed the best fit. Vancomycin clearance was 0.17 L/h, lower than literature values for term neonates of 3.5 kg without perinatal asphyxia (range: 0.20–0.32 L/h). Volume of distribution was similar. Published dosing regimens led to overexposure within 24 h of treatment. A loading dose of 10 mg/kg followed by 24 mg/kg/day in 4 doses resulted in target attainment. Conclusion: Results of this study suggest that vancomycin clearance is reduced in term neonates with perinatal asphyxia treated with TH. Lower dosing regimens should be considered followed by model‐informed precision dosing. [ABSTRACT FROM AUTHOR]

Background: Despite advances in diagnostics and therapeutics, morbidity and mortality associated with brain abscess remains high. Until recently no evidence-based guidelines existed, resulting in heterogeneous practice. In this study we explore the impact of host, pathogen and therapy-related factors on clinical outcomes. Methods: We retrospectively reviewed adult patients with community-onset brain abscess from October 2016 to April 2020 using hospital databases. Clinical, radiological, biochemical, microbiological, and surgical data was collected. Primary outcome was the 6 month modified Rankin Scale (mRS), secondary outcomes included length of hospital stay (LOS), neurological sequelae, and 1-year mortality. Multivariate logistic regression was used to analyse factors influencing recovery and neurological sequelae; and multivariate Cox regression for LOS. Results: Sixty adults with brain abscess (median age 57 years; 63 % male) were identified. Forty-eight patients (80 %) had a solitary abscess, most commonly in the frontal lobe. A causative organism was identified in 49 of 54 cases (91 %) where samples were collected, with Streptococcus milleri group the most common organism. Median duration of intravenous and oral therapy was 21 and 28 days respectively. Forty-three patients had an mRS of ≤ 2 (slight disability or better) at 6 months, with CRP > 6 mg/l on admission associated with poor outcome (mRS > 2) (p = 0.036). Eight patients (13 %) died within one year. Age > 60 years (p = 0.001), CRP > 6 mg/l (p = 0.048) and prolonged intravenous therapy (>6 weeks) (p = 0.001) were all associated with extended LOS. Seizures on admission (p = 0.017) or presence of risk factors (p = 0.032) were associated with neurological sequelae at 6 months. Conclusions: This study reveals that a complex interaction of factors related to host, pathogen and therapy impacts clinical outcome in patients with brain abscess. While mortality and LOS are well described in previous literature, analysis of the mRS here adds to our understanding of morbidity following a diagnosis of brain abscess.

Background: Acute mediastinitis is rarely caused by haematogenous spread of a remote infection. In this respect, since the only medical therapy is usually unsuccessful, treating acute mediastinitis with no source of infection detected is very challenging and management not standardized. In this case report, we describe non-surgical management experience of acute mediastinitis caused by methicillin-sensitive Staphylococcus aureus. Case presentation: In a 79-year-old man judged not eligible for cardiac surgery, we attempted the infection source control through vacuum-assisted closure therapy, together with antimicrobial therapy. We observed gradual clinical, laboratory and radiologic improvements: reduced swelling and normalization of the white blood cell count and C-reactive protein level were associated with reduction in size of a periaortic abscess. Conclusion: We managed a clinical condition with high mortality risk with chronic antimicrobial therapy alone, a strategy that is rarely considered. With this medical strategy we achieved an optimal response to a clinical picture that does not allow any other approach.

IntroductionPeriodontitis-related oral microbial dysbiosis is thought to contribute to Alzheimer's disease (AD) neuroinflammation and brain amyloid production. Since probiotics can modulate periodontitis/oral dysbiosis, this study examined the effects of a probiotic/lantibiotic, nisin, in modulating brain pathology triggered by periodontitis.MethodsA polymicrobial mouse model of periodontal disease was used to evaluate the effects of this disease on brain microbiome dysbiosis, neuroinflammation, Alzheimer's-related changes, and nisin's therapeutic potential in this context.Results16S sequencing and real-time PCR data revealed that Nisin treatment mitigated the changes in the brain microbiome composition, diversity, and community structure, and reduced the levels of periodontal pathogen DNA in the brain induced by periodontal disease. Nisin treatment significantly decreased the mRNA expression of pro-inflammatory cytokines (Interleukin-1β/IL-1 β, Interleukin 6/IL-6, and Tumor Necrosis Factor α/TNF-α) in the brain that were elevated by periodontal infection. In addition, the concentrations of amyloid-β 42 (Aβ42), total Tau, and Tau (pS199) (445.69 ± 120.03, 1420.85 ± 331.40, 137.20 ± 36.01) were significantly higher in the infection group compared to the control group (193.01 ± 31.82, 384.27 ± 363.93, 6.09 ± 10.85), respectively. Nisin treatment markedly reduced the Aβ42 (261.80 ± 52.50), total Tau (865.37 ± 304.93), and phosphorylated Tau (82.53 ± 15.77) deposition in the brain of the infection group.DiscussionNisin abrogation of brain microbiome dysbiosis induces beneficial effects on AD-like pathogenic changes and neuroinflammation, and thereby may serve as a potential therapeutic for periodontal-dysbiosis-related AD.

Abstract Objective Healthcare-associated Gram-negative bacterial meningitis is a substantial clinical issue with poor outcomes, especially for neurosurgical patients. Here, we aimed to study the characteristics and treatment options of patients with healthcare-associated carbapenem-non-susceptible (Carba-NS) Gram-negative bacterial meningitis. Methods This observational cohort study was conducted at a teaching hospital from 2004 to 2019. The clinical characteristics of patients with meningitis with Carba-NS and carbapenem-susceptible (Carba-S) bacilli were compared, and the antimicrobial chemotherapy regimens and outcomes for Carba-NS Gram-negative bacterial meningitis were analyzed. Results A total of 505 patients were included, of whom 83.8% were post-neurosurgical patients. The most common isolates were Acinetobacter spp. and Klebsiella spp., which had meropenem-resistance rates of 50.6% and 42.5%, respectively, and showed a markedly growing carbapenem-resistance trend. Kaplan–Meier curve analysis revealed that Carba-NS Gram-negative bacilli were associated with a significantly higher in-hospital mortality rate (18.8%, 35/186) compared to the Carba-S group (7.4%, 9/122; P = 0.001). For Carba-NS Enterobacterales meningitis, aminoglycoside-based and trimethoprim-sulfamethoxazole-based regimens yielded significantly higher clinical efficacy rates than non-aminoglycoside-based and non-trimethoprim-sulfamethoxazole-based regimens (69.0% vs. 38.7%, P = 0.019 and 81.8% vs. 46.9%, P = 0.036, respectively). For Carba-NS A. baumannii complex meningitis, tetracycline-based (including doxycycline, minocycline, or tigecycline) therapy achieved a significantly higher clinical efficacy rate (62.9%, 22/35) than the non-tetracycline-based therapy group (40.4%, 19/47; P = 0.044). Conclusions Our findings revealed that Carba-NS Gram-negative bacilli are associated with higher in-hospital mortality in patients with healthcare-associated meningitis. The combination therapies involving particular old antibiotics may improve patients’ outcome. Trial registration This study was registered on the Chinese Clinical Trial Register under ChiCTR2000036572 (08/2020).

Omalhassan Amir Abdelkarim,1 Usman Abubakar,2 Mohamed A Hussain,3 Abd Elrahman Babiker Abadi,1 Ahmed Osman Mohamed,3 Wadah Osman,4,5 Asmaa E Sherif,4,6 Sara Altayep Ebrahim,1 Asmaa Hussein Ahmed,1 Marwa Omer Ahmed,1 Ahmed Ashour4,6 1Department of Pharmacy Practice and Clinical Pharmacy, Faculty of Pharmacy, International University of Africa, Khartoum, Sudan; 2Department of Clinical Pharmacy and Practice, College of Pharmacy, QU Health, Qatar University, Doha, Qatar; 3Department of Pharmaceutical Microbiology, Faculty of Pharmacy, International University of Africa, Khartoum, Sudan; 4Department of Pharmacognosy, Faculty of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-KharJ, Saudi Arabia; 5Department of Pharmacognosy, Faculty of Pharmacy, University of Khartoum, Khartoum, Sudan; 6Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptCorrespondence: Omalhassan Amir Abdelkarim, Department of Pharmacy Practice and Clinical Pharmacy, Faculty of Pharmacy, International University of Africa, Khartoum, PO Box 2469, Sudan, Email dromal409@gmail.comBackground: Adequate training in infectious diseases and antibiotic resistance is crucial for pharmacy students to participate in antibiotic stewardship programs and understand microbiology careers.Aim: The study was carried out to assess the knowledge and self-reported confidence in antibiotic resistance, antibiotic therapy, and antimicrobial stewardship (AMS) among final-year undergraduate pharmacy students in Sudan.Methods: A cross-sectional study was conducted in three universities using a 57-item online questionnaire between April and May 2022.Results: A total of 109 students (response rate 36%) participated and showed average knowledge scores of 5.6± 1.7 (out of 10.0) for antibiotic resistance, 4.9± 2.0 (out of 5.0) for appropriate antibiotic therapy, and 3.1± 1.4 (out of 5.0) for AMS. No significant differences were observed among schools. Some students reported poor knowledge about antibiotic therapy and the consequences of resistance. One-third of students lacked confidence in interpreting microbiological results. Knowledge of antibiotic resistance among students’ practice area after graduation was higher (p=0.017) and those interested in ID careers (5.8 vs 4.8) (p=0.037). Male students (5.6 vs 4.5) and those interested in ID careers (4.3 vs 3.4) (p< 0.001) had higher scores of appropriate antibiotic therapy. Students attended antibiotic resistance courses (51.5 vs 45.2), and those interested in ID significantly had higher self-confidence (55.3 vs 45.8) (p=0.008).Conclusion: Pharmacy students in Sudan have substantial knowledge of AMS and antibiotic resistance with poor knowledge of antibiotic therapy. Adequate training about infectious diseases and related topics is recommended to improve pharmacy students’ understanding of microbiological findings, other competencies, and skills to incorporate in antimicrobial stewardship.Keywords: antibiotic resistance, antimicrobial stewardship, antimicrobial therapy, Sudan, pharmacy students

Abstract Background The emergence of antimicrobial resistance in bacterial pathogens is a growing concern worldwide due to its impact on the treatment of bacterial infections. The "Trojan Horse" strategy has been proposed as a potential solution to overcome drug resistance caused by permeability issues. Objective The objective of our research was to investigate the bactericidal activity and mechanism of action of the "Trojan Horse" strategy using enterobactin conjugated with Ciprofloxacin and Fosfomycin against the antibiotic-resistant Escherichia coli strain OQ866153. Methodology Enterobactin, a mixed ligand of E. coli OQ866153, was conjugated with Ciprofloxacin and Fosfomycin individually to aid active absorption via specific enterobactin binding proteins (FepABCDG). The effectiveness of the conjugates was assessed by measuring their bactericidal activity against E. coli OQ866153, as well as their ability to inhibit DNA gyrase enzyme and biofilm formation. Results The Fe+3-enterobactin-Ciprofloxacin conjugate effectively inhibited the DNA gyrase enzyme (Docking score = -8.597 kcal/mol) and resulted in a lower concentration (25 μg/ml) required to eliminate supercoiled DNA plasmids compared to the parent drug (35 μg/ml; Docking score = -6.264 kcal/mol). The Fe+3-Enterobactin-Fosfomycin conjugate showed a higher inhibition percentage (100%) of biofilm formation compared to Fosfomycin (21.58%) at a concentration of 2 mg/ml, with docking scores of -5.481 and -3.756 kcal/mol against UDP-N acetylglucosamine 1-carboxyvinyltransferase MurA. Conclusion The findings of this study suggest that the "Trojan Horse" strategy using enterobactin conjugated with Ciprofloxacin and Fosfomycin can effectively overcome permeability issues caused by efflux proteins and enhance the bactericidal activity of these drugs against antibiotic-resistant strains of E. coli.

Abstract Introduction The impact of immunosuppression on prognosis of carbapenem-resistant organism (CRO) bloodstream infection (BSI) remains unclear. The aim of this study was to clarify the relationship between immunosuppression and mortality of CRO-BSI and to identify the risk factors associated with mortality in immunosuppressed patients. Methods This retrospective study included 279 patients with CRO-BSI from January 2018 to March 2023. Clinical characteristics and outcomes were compared between the immunosuppressed and immunocompetent patients. The relationship between immunosuppression and 30-day mortality after BSI onset was assessed through logistic-regression analysis, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Factors associated with mortality in immunosuppressed patients were analyzed using multivariable logistic regression analysis. Results A total of 88 immunocompetent and 191 immunosuppressed patients were included, with 30-day all-cause mortality of 58.8%. Although the 30-day mortality in immunosuppressed patients was significantly higher than in immunocompetent patients (46.6% vs. 64.4%, P = 0.007), immunosuppression was not an independent risk factor for mortality in multivariate logistic regression analysis (odds ratio [OR] 3.53, 95% confidence interval [CI] 0.74–18.89; P = 0.123), PSM (OR 1.38, 95% CI 0.60–3.18; P = 0.449,) or IPTW (OR 1.40, 95% CI 0.58–3.36; P = 0.447). For patients with CRO-BSI, regardless of immune status, appropriate antibiotic therapy was associated with decreased 30-day mortality, while Charlson comorbidity index (CCI), intensive care unit (ICU)-acquired infection and thrombocytopenia at CRO-BSI onset were associated with increased mortality. Conclusion Despite the high mortality rate of CRO-BSI, immunosuppression did not affect the mortality. Appropriate antibiotic therapy is crucial for improving the prognosis of CRO-BSI, regardless of the immune status.

Objective. To determine the level of basic knowledge of 5–6-year medical students in the issues of appropriate antimicrobial therapy. Materials and Methods. A multicenter questionnaire survey with analysis of results – stage of KANT project (full name of the project – «Physicians’ (Students’) knowledge in antimicrobials usage») conducted in 2020-2023. Results. A total of 277 students in 6 regions of Russia were surveyed. The average level of correct answers for the whole questionnaire amounted to 42.2%, taking into account the extended analysis of sub-items questions #8,9 – 42.6%. The respondents were best able to answer the questionnaire questions about the choice of time interval during which the effectiveness of antimicrobial therapy is assessed (average level of completeness of the answer – 90.6%); the choice of the most rational action when diagnosing acute tonsillitis or pharyngitis at the appointment (average level of completeness of the answer – 57.8%); indication of the regimen of different AMD (average level of completeness of the answer – 55.2%). The worst results were recorded when answering the following questions: justification of the situation of prolongation of antimicrobial therapy (AMT) for more than 5-7 days in a patient with positive clinical dynamics in the treatment of outpatient pneumonia (average level of completeness of the answer – 19.5%), indication of AMD of choice in the therapy of various infections (average level of completeness of the answer – 22.9%), prescription of auxiliary drugs to the justified prescription of AMD in the treatment of respiratory tract infections (average level of completeness of the answer – 21.3%). Conclusions. Having researched the results of this study, we can conclude that the level of knowledge of senior medical students in rational antibiotic therapy is quite low. In this regard, according to the authors, it is necessary to allocate an additional number of academic hours in the disciplines of "Pharmacology", "Clinical Pharmacology", specialized therapeutic disciplines, to optimize the educational program, as well as to provide students with modern sources of information that relate to the topic of rational antimicrobial therapy.

Background: The optimal antimicrobial treatment duration for diabetes-related foot osteomyelitis (DFO) currently needs to be determined. We systematically reviewed the effects of short and long treatment durations on outcomes of DFO. Methods: We performed a systematic review searching Cochrane, CENTRAL, MEDLINE, Embase, and CINAHL Plus from inception up to 19 January 2024. Two independent reviewers screened the titles and abstracts of the studies. Studies comparing short (6 weeks) treatment durations for DFO were included. The primary outcome was amputation; the secondary outcomes were remission, mortality, costs, quality of life, and adverse events. Risk of bias and GRADE were assessed. Results: We identified 2708 references, of which 2173 remained after removing duplicates. Two studies were included. Differences in methodology precluded a meta-analysis. The primary outcome, major amputation, was reported in one study, with a rate of 10% in both the intervention and comparison groups (p = 1.00), regardless of treatment duration. For the secondary outcome, remission rates, the first study reported 60% in the intervention group versus 70% in the comparison group (p = 0.50). In the second study, remission rates were 84% in the intervention group versus 78% in the comparison group (p = 0.55). Data for the outcomes mortality, costs, and quality of life were not available. Short treatment duration may lead to fewer adverse events. The risk of bias was assessed as low to moderate, and the level of evidence ranged from very low to moderate. Conclusions: Our findings suggest that for DFO, there is no difference between a shorter and more prolonged duration of antimicrobial treatment regarding amputation and remission, with potentially fewer adverse events with shorter treatment durations. However, the uncertainty stems from limited, heterogeneous studies and generally low-quality evidence marred by moderate biases, imprecision, and indirectness. More high-quality studies are needed to substantiate these findings.

Background and Objectives: Elizabethkingia species have become significant sources of infections acquired in hospital settings and are commonly linked to high mortality rates. Antimicrobial resistance can be influenced by Elizabethkingia species, geographical location, antimicrobial susceptibility testing methods, and the time of bacterial isolation. There are distinct antimicrobial susceptibility patterns among species, and the investigation into potential antibiotic susceptibility variations among species is beneficial. There is no guidance on the treatment of Elizabethkingia species infections in the literature. Consequently, the purpose of this review was to elaborate on the antimicrobial susceptibility patterns of Elizabethkingia species through a scoping review of existing studies on the antibiograms of the Elizabethkingia species and on the illness caused by Elizabethkingia species. Materials and Methods: A comprehensive literature search in PubMed and Web of Science between 1 January 2000 and 30 April 2024 identified all studies, including those that examined antimicrobial susceptibility patterns and antimicrobial therapy of infections caused by Elizabethkingia species. I considered studies on antimicrobial susceptibility testing for Elizabethkingia species in which only broth microdilution methods and agar dilution methods were used. Results: The sensitivity levels of Elizabethkingia meningoseptica to piperacillin–tazobactam (5–100%), ciprofloxacin (0–43.4%), levofloxacin (30–81.8%), trimethoprim–sulfamethoxazole (0–100%), tigecycline (15–100%), minocycline (60–100%), and rifampicin (94–100%) varied. The sensitivity levels of Elizabethkingia anophelis to piperacillin–tazobactam (3.3–93.3%), ciprofloxacin (1–75%), levofloxacin (12–100%), trimethoprim–sulfamethoxazole (1.02–96.7%), tigecycline (0–52.2%), minocycline (97.5–100%), and rifampicin (20.5–96%) varied. The sensitivity levels of Elizabethkingia miricola to piperacillin–tazobactam (41.6–94.0%), ciprofloxacin (14–75%), levofloxacin (77.0–100%), trimethoprim–sulfamethoxazole (18.0–100%), tigecycline (50%), minocycline (100%), and rifampicin (66–85.7%) varied. Conclusions: The majority of the isolates of Elizabethkingia species were susceptible to minocycline and rifampin. This issue requires professional knowledge integration and treatment recommendations.

Infectious diseases continue to pose significant global health challenges. In addition to the enduring burdens of ailments like malaria and HIV, the emergence of nosocomial outbreaks driven by antibiotic-resistant pathogens underscores the ongoing threats. Furthermore, recent infectious disease crises, exemplified by the Ebola and SARS-CoV-2 outbreaks, have intensified the pursuit of more effective and efficient diagnostic and therapeutic solutions. Among the promising options, antibodies have garnered significant attention due to their favorable structural characteristics and versatile applications. Notably, nanobodies (Nbs), the smallest functional single-domain antibodies of heavychain only antibodies produced by camelids, exhibit remarkable capabilities in stable antigen binding. They offer unique advantages such as ease of expression and modification and enhanced stability, as well as improved hydrophilicity compared to conventional antibody fragments (antigen-binding fragments (Fab) or single-chain variable fragments (scFv)) that can aggregate due to their low solubility. Nanobodies directly target antigen epitopes or can be engineered into multivalent Nbs and Nb-fusion proteins, expanding their therapeutic potential. This review is dedicated to charting the progress in Nb research, particularly those derived from camelids, and highlighting their diverse applications in treating infectious diseases, spanning both human and animal contexts. [ABSTRACT FROM AUTHOR]

Background: Pulmonary complications pose significant challenges in renal transplant recipients due to immunosuppression and diverse underlying renal diseases. Understanding their epidemiology, clinical presentation, microbial spectrum, and risk factors is crucial for optimal management. Methods: We conducted a prospective observational study over 24 months, following 458 renal transplant recipients. Data on demographics, clinical presentation, underlying renal diseases, and microbial spectrum were collected. Risk factors influencing pulmonary complications were analyzed. Results: Among the cohort, 45 incidents (9.8%) of pulmonary complications occurred, with fever (66.7%) being the most common symptom. The majority of complications (51%) occurred over six months post-transplantation, with infectious complications predominating (89%). Risk factors included leucopenia (24.4%), CMV infection (8.9%), HCV infection (8.9%), ART (20%), and NODAT (11.1%). Conclusion: Early detection and targeted antimicrobial therapy are essential in managing pulmonary complications in renal transplant recipients. Multidisciplinary approaches are crucial for optimizing patient outcomes. Further research is needed to explore the long-term implications on graft function and survival. [ABSTRACT FROM AUTHOR]

Animal bites are a common reason for children to visit primary care and emergency departments. Dog bites are the most prevalent, followed by cat bites at 20–30%. Other animals such as bats, monkeys, snakes, and rats collectively contribute less than 1% of cases. Hospitalization is necessary in only 4% of animal bite incidents. The main aim of this narrative review is to summarize the main protocols currently followed in pediatrics in cases involving the most common bites from different animal species. Analysis of the literature showed that the management of common animal bites in children presents a multifaceted challenge requiring a comprehensive understanding of the epidemiology, clinical presentation, and treatment modalities associated with each specific species. Effective wound management is paramount in reducing the risk of infection and promoting optimal healing outcomes. Additionally, tetanus vaccination status should be assessed and updated as necessary, and prophylactic antibiotics may be indicated in certain cases to prevent secondary infections. Furthermore, the role of rabies prophylaxis cannot be overstated, particularly in regions where rabies is endemic or following bites from high-risk animals. In addition to medical management, psychosocial support for both the child and their caregivers is integral to the overall care continuum. Future studies exploring the efficacy of novel treatment modalities, such as topical antimicrobial agents or advanced wound dressings, may offer new insights into optimizing wound healing and reducing the risk of complications. [ABSTRACT FROM AUTHOR]

Objective: Healthcare-associated Gram-negative bacterial meningitis is a substantial clinical issue with poor outcomes, especially for neurosurgical patients. Here, we aimed to study the characteristics and treatment options of patients with healthcare-associated carbapenem-non-susceptible (Carba-NS) Gram-negative bacterial meningitis. Methods: This observational cohort study was conducted at a teaching hospital from 2004 to 2019. The clinical characteristics of patients with meningitis with Carba-NS and carbapenem-susceptible (Carba-S) bacilli were compared, and the antimicrobial chemotherapy regimens and outcomes for Carba-NS Gram-negative bacterial meningitis were analyzed. Results: A total of 505 patients were included, of whom 83.8% were post-neurosurgical patients. The most common isolates were Acinetobacter spp. and Klebsiella spp., which had meropenem-resistance rates of 50.6% and 42.5%, respectively, and showed a markedly growing carbapenem-resistance trend. Kaplan–Meier curve analysis revealed that Carba-NS Gram-negative bacilli were associated with a significantly higher in-hospital mortality rate (18.8%, 35/186) compared to the Carba-S group (7.4%, 9/122; P = 0.001). For Carba-NS Enterobacterales meningitis, aminoglycoside-based and trimethoprim-sulfamethoxazole-based regimens yielded significantly higher clinical efficacy rates than non-aminoglycoside-based and non-trimethoprim-sulfamethoxazole-based regimens (69.0% vs. 38.7%, P = 0.019 and 81.8% vs. 46.9%, P = 0.036, respectively). For Carba-NS A. baumannii complex meningitis, tetracycline-based (including doxycycline, minocycline, or tigecycline) therapy achieved a significantly higher clinical efficacy rate (62.9%, 22/35) than the non-tetracycline-based therapy group (40.4%, 19/47; P = 0.044). Conclusions: Our findings revealed that Carba-NS Gram-negative bacilli are associated with higher in-hospital mortality in patients with healthcare-associated meningitis. The combination therapies involving particular old antibiotics may improve patients' outcome. Trial registration: This study was registered on the Chinese Clinical Trial Register under ChiCTR2000036572 (08/2020). [ABSTRACT FROM AUTHOR]

Over 21 months, 12 patients with invasive Candida infections detected during the course of treatment of bacterial endocarditis, including 11 with candidemia, were identified. Invasive Candida infections can occur as a complication of bacterial endocarditis and may occur more frequently in patients with injection drug use and broad-spectrum antibiotic exposure. [ABSTRACT FROM AUTHOR]