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UNLABELLED: Coccidioidomycosis, also known as Valley fever, is a disease caused by the fungal pathogen Coccidioides. Unfortunately, patients are often misdiagnosed with bacterial pneumonia, leading to inappropriate antibiotic treatment. The soil Bacillus subtilis-like species exhibits antagonistic properties against Coccidioides in vitro; however, the antagonistic capabilities of host microbiota against Coccidioides are unexplored. We sought to examine the potential of the tracheal and intestinal microbiomes to inhibit the growth of Coccidioides in vitro. We hypothesized that an uninterrupted lawn of microbiota obtained from antibiotic-free mice would inhibit the growth of Coccidioides, while partial in vitro depletion through antibiotic disk diffusion assays would allow a niche for fungal growth. We observed that the microbiota grown on 2×GYE (GYE) and Columbia colistin and nalidixic acid with 5% sheeps blood agar inhibited the growth of Coccidioides, but microbiota grown on chocolate agar did not. Partial depletion of the microbiota through antibiotic disk diffusion revealed diminished inhibition and comparable growth of Coccidioides to controls. To characterize the bacteria grown and identify potential candidates contributing to the inhibition of Coccidioides, 16S rRNA sequencing was performed on tracheal and intestinal agar cultures and murine lung extracts. We found that the host bacteria likely responsible for this inhibition primarily included Lactobacillus and Staphylococcus. The results of this study demonstrate the potential of the host microbiota to inhibit the growth of Coccidioides in vitro and suggest that an altered microbiome through antibiotic treatment could negatively impact effective fungal clearance and allow a niche for fungal growth in vivo. IMPORTANCE: Coccidioidomycosis is caused by a fungal pathogen that invades the host lungs, causing respiratory distress. In 2019, 20,003 cases of Valley fever were reported to the CDC. However, this number likely vastly underrepresents the true number of Valley fever cases, as many go undetected due to poor testing strategies and a lack of diagnostic models. Valley fever is also often misdiagnosed as bacterial pneumonia, resulting in 60%-80% of patients being treated with antibiotics prior to an accurate diagnosis. Misdiagnosis contributes to a growing problem of antibiotic resistance and antibiotic-induced microbiome dysbiosis; the implications for disease outcomes are currently unknown. About 5%-10% of symptomatic Valley fever patients develop chronic pulmonary disease. Valley fever causes a significant financial burden and a reduced quality of life. Little is known regarding what factors contribute to the development of chronic infections and treatments for the disease are limited.

BACKGROUND: The trauma mortality rate is higher in the elderly compared with younger patients. Ageing is associated with physiological changes in multiple systems and correlated with frailty. Frailty is a risk factor for mortality in elderly trauma patients. We aim to provide evidence-based guidelines for the management of geriatric trauma patients to improve it and reduce futile procedures. METHODS: Six working groups of expert acute care and trauma surgeons reviewed extensively the literature according to the topic and the PICO question assigned. Statements and recommendations were assessed according to the GRADE methodology and approved by a consensus of experts in the field at the 10th international congress of the WSES in 2023. RESULTS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage, including drug history, frailty assessment, nutritional status, and early activation of trauma protocol to improve outcomes. Acute trauma pain in the elderly has to be managed in a multimodal analgesic approach, to avoid side effects of opioid use. Antibiotic prophylaxis is recommended in penetrating (abdominal, thoracic) trauma, in severely burned and in open fractures elderly patients to decrease septic complications. Antibiotics are not recommended in blunt trauma in the absence of signs of sepsis and septic shock. Venous thromboembolism prophylaxis with LMWH or UFH should be administrated as soon as possible in high and moderate-risk elderly trauma patients according to the renal function, weight of the patient and bleeding risk. A palliative care team should be involved as soon as possible to discuss the end of life in a multidisciplinary approach considering the patients directives, family feelings and representatives desires, and all decisions should be shared. CONCLUSIONS: The management of elderly trauma patients requires knowledge of ageing physiology, a focused triage based on assessing frailty and early activation of trauma protocol to improve outcomes. Geriatric Intensive Care Units are needed to care for elderly and frail trauma patients in a multidisciplinary approach to decrease mortality and improve outcomes.

The emergence of antibiotic-resistant bacteria (ARB) has necessitated the development of alternative therapies to deal with this global threat. Bacteriophages (viruses that target bacteria) that kill ARB are one such alternative. Although phages have been used clinically for decades with inconsistent results, a number of recent advances in phage selection, propagation, and purification have enabled a reevaluation of their utility in contemporary clinical medicine. In most phage therapy cases, phages are administered in combination with antibiotics to ensure that patients receive the standard-of-care treatment. Some phages may work cooperatively with antibiotics to eradicate ARB, as often determined using non-standardized broth assays. We sought to develop a solid media-based assay to assess cooperativity between antibiotics and phages to offer a standardized platform for such testing. We modeled the interactions that occur between antibiotics and phages on solid medium to measure additive, antagonistic, and synergistic interactions. We then tested the method using different bacterial isolates and identified a number of isolates where synergistic interactions were identified. These interactions were not dependent on the specific organism, phage family, or antibiotic used. A priori susceptibility to the antibiotic or the specific phage were not requirements to observe synergistic interactions. Our data also confirm the potential for the restoration of vancomycin to treat vancomycin-resistant Enterococcus (VRE) when used in combination with phages. Solid media assays for the detection of cooperative interactions between antibiotics and phages can be an accessible technique adopted by clinical laboratories to evaluate antibiotic and phage choices in phage therapy.IMPORTANCEBacteriophages have become an important alternative treatment for individuals with life-threatening antibiotic-resistant bacteria (ARB) infections. Because antibiotics represent the standard-of-care for treatment of ARB, antibiotics and phages often are delivered together without evidence that they work cooperatively. Testing for cooperativity can be difficult due to the equipment necessary and a lack of standardized means for performing the testing in liquid medium. We developed an assay using solid medium to identify interactions between antibiotics and phages for gram-positive and gram-negative bacteria. We modeled the interactions between antibiotics and phages on solid medium, and then tested multiple replicates of vancomycin-resistant Enterococcus (VRE) and Stenotrophomonas in the assay. For each organism, we identified synergy between different phage and antibiotic combinations. The development of this solid media assay for assessing synergy between phages and antibiotics will better inform the use of these combinations in the treatment of ARB infections.

Carbohydrate intolerance, commonly linked to the consumption of lactose, fructose, or sorbitol, affects up to 30% of the population in high-income countries. Although sorbitol intolerance is attributed to malabsorption, the underlying mechanism remains unresolved. Here, we show that a history of antibiotic exposure combined with high fat intake triggered long-lasting sorbitol intolerance in mice by reducing Clostridia abundance, which impaired microbial sorbitol catabolism. The restoration of sorbitol catabolism by inoculation with probiotic Escherichia coli protected mice against sorbitol intolerance but did not restore Clostridia abundance. Inoculation with the butyrate producer Anaerostipes caccae restored a normal Clostridia abundance, which protected mice against sorbitol-induced diarrhea even when the probiotic was cleared. Butyrate restored Clostridia abundance by stimulating epithelial peroxisome proliferator-activated receptor-gamma (PPAR-γ) signaling to restore epithelial hypoxia in the colon. Collectively, these mechanistic insights identify microbial sorbitol catabolism as a potential target for approaches for the diagnosis, treatment, and prevention of sorbitol intolerance.

Wildfires affect soils in multiple ways, leading to numerous challenges for colonizing microorganisms. Although it is thought that fire-adapted microorganisms lie at the forefront of postfire ecosystem recovery, the specific strategies that these organisms use to thrive in burned soils remain largely unknown. Through bioactivity screening of bacterial isolates from burned soils, we discovered that several Paraburkholderia spp. isolates produced a set of unusual rhamnolipid surfactants with a natural methyl ester modification. These rhamnolipid methyl esters (RLMEs) exhibited enhanced antimicrobial activity against other postfire microbial isolates, including pyrophilous Pyronema fungi and Amycolatopsis bacteria, compared to the typical rhamnolipids made by organisms such as Pseudomonas spp. RLMEs also showed enhanced surfactant properties and facilitated bacterial motility on agar surfaces. In vitro assays further demonstrated that RLMEs improved aqueous solubilization of polycyclic aromatic hydrocarbons, which are potential carbon sources found in char. Identification of the rhamnolipid biosynthesis genes in the postfire isolate, Paraburkholderia kirstenboschensis str. F3, led to the discovery of rhlM, whose gene product is responsible for the unique methylation of rhamnolipid substrates. RhlM is the first characterized bacterial representative of a large class of integral membrane methyltransferases that are widespread in bacteria. These results indicate multiple roles for RLMEs in the postfire lifestyle of Paraburkholderia isolates, including enhanced dispersal, solubilization of potential nutrients, and inhibition of competitors. Our findings shed new light on the chemical adaptations that bacteria employ to navigate, grow, and outcompete other soil community members in postfire environments.

Currently, there is a high demand for novel sorbents for wastewater treatment. Nanostructured materials are often considered as more promising sorbents compared to their microsized counterparts, which, however, requires experimental verification. In this work, two types of h-BN materials (micro- and nanosized) are compared as candidates for antibiotic sorption. The initial h-BN was in the form of microsized pellets. Nanostructurued h-BN was obtained by high energy ball milling of the initial powder. The effect of ball milling on the microstructure, morphology, chemical composition and surface chemical state was investigated by SEM, TEM, STEM, EDX, XRD, XPS, FTIR and BET techniques. Adsorption properties were studied on samples in the form of pellets and powders. Activated carbon powder was used as a reference material. The antibiotic adsorption process was studied using tetracycline and linezolid. The influence of the h-BN structure on the adsorption characteristics was elucidated using DFT calculations. [ABSTRACT FROM AUTHOR]

Photocatalysis is regarded as a potent alternative to conventional treatment methods with low removal efficiency (e.g., activated sludge process) against refractory/recalcitrant antibiotics in wastewater. Here, the potential utility of bismuth oxyiodide (BiOI)-based materials has been evaluated as visible-light–driven photocatalysts (bandgap energy < 2.0 eV) with unique optical structure for the enhanced treatment of tetracyclines (TCs) as a representative antibiotic product. The effects of key modification strategies (e.g., elemental doping and heterojunction formation) on the photocatalytic activity of BiOI-based photocatalysts are assessed against TCs in terms of the key performance metrics such as quantum efficiency (QE) and space-time yield (STY). This review also highlights the challenges and promising opportunities for the photocatalytic application of BiO-based materials against TCs in real effluents. Accordingly, zinc-doped BiOI is recognized to have the maximum efficiency with QE of 2.95 × 10−5 molecules photon−1 and STY of 2.95 × 10−7 molecules photon−1 mg−1. This review is expected to help deepen the exploration path to the construction of efficient BiOI-based systems based on their performance evaluation along with the discussions on their perspectives. [ABSTRACT FROM AUTHOR]

This article reports on the development of an atmospheric pressure filtering electrospray ionization (FESI) source – composed of a syringe, a filter, and the ESI source – for the determination of furazolidone, amoxicillin, nitrofurantoin, and nitrofural, common antibiotics. Spiked food samples were also analyzed; the analytes were placed in the filter head, and the flow rate of the extraction solution from the syringe pump was adjusted. Using a mixture of oleic acid and antibiotics, hydrophilic and hydrophobic filters were compared, demonstrating the advantage of FESI in reducing the background and noise for the mixture. The device simplifies not only the experimental procedure but also the sample pretreatment process. Additionally, the limits of detection of the antibiotics were determined to be 1 mg L−1 for furazolidone, amoxicillin, and nitrofurantoin and 2 mg L−1 for nitrofural. The linear regression coefficients (R2) of the antibiotic standard solutions were all ≥0.99. Furthermore, the spiked recovery rates of pork, chicken, and egg samples ranged from 73.3% to 107.5%, with relative standard deviations (RSDs) from 1.1% to 15.6%. This study uncovers the potential capabilities of ion trap mass spectrometry (ITMS) for the on-site detection of antibiotics and offers a new method for ensuring food safety. [ABSTRACT FROM AUTHOR]

We have created a novel synthetic biology expression system allowing easy refactoring of biosynthetic gene clusters (BGCs) as monocistronic transcriptional units. The system is based on a set of plasmids containing a strong kasOp* promoter, RBS and terminators. It allows the cloning of biosynthetic genes into transcriptional units kasOp *-gene(s)-terminator flanked by several rare restriction cloning sites that can be sequentially combined into the artificial BGC in three compatible Streptomyces integration vectors. They allow a simultaneous integration of these BGCs at three different attB sites in the Streptomyces chromosome. The system was validated with biosynthetic genes from two known BGCs for aromatic polyketides landomycin and mithramycin. • A new synthetic biology-based system for investigating antibiotic biosynthesis. • Efficient rabelomycin production using the initial landomycin biosynthetic genes. • Efficient 4-DMPC production using the initial mithramycin biosynthetic genes. [ABSTRACT FROM AUTHOR]

The application of antibiotics in the poultry and veterinary sectors is very common practice in India. Owing to the seriousness of antimicrobial resistance (AMR), the present study has illustrated the overall scenario of AMR in the poultry and veterinary sectors in India through an in-depth scoping review and key informant interview (KII). In the poultry sector, most of the studies reviewed have reported resistant bacteria isolated from chicken meat, eggs, cloacal swabs, and fecal samples, and only a few have reported the presence of resistant bacteria in and around the environment of poultry farms. The major resistant bacteria that have been reported are E. coli, Salmonella spp., S. aureus, Campylobacter jejuni, and K. pneumoniae. These bacterial isolates exhibited resistance to various antibiotics, such as azithromycin (21.43%), tetracycline (11.30-100%), chloramphenicol (4.76-100%), erythromycin (75-83.33%), ciprofloxacin (5.7-100%), gentamicin (17-100%), amikacin (4.76%), cotrimoxazole (42.2-60%), trimethoprim (89.4%), ceftriaxone (80%), and cefotaxime (14.29-70%). Like the poultry sector, different antibiotics are also used for treating clinical and subclinical bovine mastitis, which is one of the major problems plaguing the dairy sector. Several AMR bacterial strains, such as E. coli, Staphylococcus aureus, S. epidermidis, and Klebsiella pneumoniae, have been reported by many researchers and showed resistance against tetracycline (74%), oxytetracycline (47.37%), ciprofloxacin (51%), streptomycin (57.89%), cephalosporin (100%), and trimethoprim (70%). The KIIs have revealed several reasons behind these AMR scenarios, of which the growing need for the production of food animals and their products with inadequate infrastructure and a lack of proper knowledge on farm management among the farmers are the major ones. Though several government legislations and policies have been laid down, proper implementation of these policies, strict surveillance on antibiotic application in the poultry and veterinary sectors, awareness generation among farmers, and infrastructure development can help minimize the development and transmission of AMR bacteria within and from these sectors. [ABSTRACT FROM AUTHOR]

The emission of glyphosate and antibiotic residues from human activities threatens the diversity and functioning of the microbial community. This study examines the impact of a glyphosate-based herbicide (GBH) and common antibiotics on Gram-negative bacteria within the ESKAPEE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli). Ten strains, including type and multidrug-resistant strains for each species were analysed and eight antibiotics (cefotaxime, meropenem, aztreonam, ciprofloxacin, gentamicin, tigecycline, sulfamethoxazole-trimethoprim, and colistin) were combined with the GBH. While most combinations yielded additive or indifferent effects in 70 associations, antagonistic effects were observed with ciprofloxacin and gentamicin in five strains. GBH notably decreased the minimum inhibitory concentration of colistin in eight strains and displayed synergistic activity with meropenem against metallo-β-lactamase (MBL)-producing strains. Investigation into the effect of GBH properties on outer membrane permeability involved exposing strains to a combination of this GBH and vancomycin. Results indicated that GBH rendered strains sensitive to vancomycin, which is typically ineffective against Gram-negative bacteria. Furthermore, we examined the impact of GBH in combination with three carbapenem agents on 14 strains exhibiting varying carbapenem-resistance mechanisms to assess its effect on carbapenemase activity. The GBH efficiently inhibited MBL activity, demonstrating similar effects to EDTA (ethylenediaminetetraacetic acid). Chelating effect of GBH may have multifaceted impacts on bacterial cells, potentially by increasing outer membrane permeability and inactivating metalloenzyme activity. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance in agriculture is a global concern that is growing every day. As a result, there is increasing interest in investigating different approaches to disease control in both plants and animals. Research on the identification and synthesis of antimicrobial compounds derived from plants and microbes has exploded in the last few years. The purpose of this review is to give a broad overview of the current knowledge regarding antimicrobials derived from plants and microbes and their possible uses in agricultural practises. It discusses a number of topics, such as the origins of these antimicrobial agents, how they work, and how well they work to fight infections in plants and animals. Furthermore, the difficulties pertaining to their execution and potential outcomes are examined. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion One of the goals established by the United States National Action Plan to Combat Antibiotic‐Resistant Bacteria is to reduce inappropriate outpatient antibiotic prescriptions by 50% by 2020. Recent data on the achievement of this goal is lacking. The objective of our study was to examine recent trends in the appropriateness of oral antibiotic prescriptions dispensed to a commercially insured population in outpatient settings in the United States to quantify the relative trend in inappropriate antibiotic prescribing from 2010 to 2018.Our cross‐sectional analysis examined oral antibiotic prescriptions dispensed in outpatient settings using the IBM MarketScan Commercial Data from January 2010 to December 2018. Trends in the annual proportion of antibiotic prescriptions classified as appropriate, potentially appropriate, inappropriate, or without any medical visit during a 7 days look‐back period were estimated using multivariable generalized linear models with Poisson distribution adjusting for beneficiaries' demographic and infectious conditions.Approximately 170 million oral antibiotic prescriptions were dispensed to 86 million beneficiaries during 2010 to 2018. The mean age of the study population was 34.5 (±19.1) years, with 58.4% females and 24.6% children. We observed a 12.9% (95% Confidence Interval [CI] = 12.6%–13.2%; p < 0.01) decline in rates of antibiotic use, from 832 to 727 prescriptions per 1000 beneficiaries, from 2010 to 2018. The proportion of prescriptions classified as appropriate increased by 36.7% (95% CI = 36.4%–36.9%; p < 0.01); potentially appropriate prescriptions increased by 9.3% (95% CI = 9.1%–9.4%; p < 0.01); whereas inappropriate prescriptions and those without a medical visit declined by 11.3% (95% CI = 11.2%–11.4%; p < 0.01) and 14.0% (95% CI = 13.9%–14.2%; p < 0.01), respectively. Similar declining trends were observed in use and proportion of inappropriate prescriptions for broad‐spectrum antibiotics. In 2018, amoxicillin and azithromycin were the most common appropriate and inappropriate prescription fills, respectively.Although antibiotic use and inappropriate prescribing declined steadily from 2010 to 2018 in the United States, this study demonstrates that we have not achieved the national goal of reducing inappropriate antibiotic prescribing by 50%. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic value of metagenomic next-generation sequencing (mNGS) in detecting pathogens from joint infection (JI) synovial fluid (SF) samples with previous antibiotic exposure. Methods: From January 2019 to January 2022, 59 cases with suspected JI were enrolled. All cases had antibiotic exposure within 2 weeks before sample collection. mNGS and conventional culture were performed on SF samples. JI was diagnosed based on history and clinical symptoms in conjunction with MSIS criteria. The diagnostic values, including sensitivity, specificity, positive/negative predictive values (PPV/NPV), and accuracy, were in comparison with mNGS and culture. Results: There were 47 of the 59 cases diagnosed with JI, while the remaining 12 were diagnosed with non-infectious diseases. The sensitivity of mNGS was 68.1%, which was significantly higher than that of culture (25.5%, p<0.01). The accuracy of mNGS was significantly higher at 71.2% compared to the culture at 39.0% (p <0.01). Eleven pathogenic strains were detected by mNGS but not by microbiological culture, which included Staphylococcus lugdunensis, Staphylococcus cohnii, Finegoldia magna, Enterococcus faecalis, Staphylococcus saprophytics, Escherichia coli, Salmonella enterica, Pseudomonas aeruginosa, Acinetobacter pittii, Brucella ovis, andCoxiella burnetii. Antibiotic therapy was adjusted based on the mNGS results in 32 (68.1%) patients, including 12 (25.5%) and 20 (42.6%) patients, in whom treatment was upgraded and changed, respectively. All JI patients underwent surgery and received subsequent antibiotic therapy. They were followed up for an average of 23months (20-27 months), and the success rate of treatment was 89.4%. Out of the 33 patients who had positive results for pathogens, reoperation was performed in 1 case (3.03%), while out of the 14 cases with negative results for both mNGS and cultures, reoperation was performed in 4 cases (28.6%). Conclusions: mNGS has advantages over conventional culture in detecting pathogens in SF samples from JI patients previously treated with antibiotics, potentially improving clinical outcomes. [ABSTRACT FROM AUTHOR]

Key Points: Question: Do commonly prescribed oral antibiotics carry differential risks of cutaneous adverse drug reactions (cADRs) leading to an emergency department visit or hospitalization? Findings: In this population-based, nested case-control study spanning 2 decades, sulfonamide antibiotics and cephalosporins carried the highest risk of serious cADRs relative to macrolides, followed by nitrofurantoin, penicillins, and fluoroquinolones. Meaning: All commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamide antibiotics and cephalosporins carrying the highest risk. Importance: Serious cutaneous adverse drug reactions (cADRs) are potentially life-threatening drug hypersensitivity reactions involving the skin and internal organs. Antibiotics are a recognized cause of these reactions, but no studies have compared relative risks across antibiotic classes. Objectives: To explore the risk of serious cADRs associated with commonly prescribed oral antibiotics, and to characterize outcomes of patients hospitalized for them. Design, Setting, and Participants: Nested case-control study using population-based linked administrative datasets among adults aged 66 years or older who received at least 1 oral antibiotic between 2002 and 2022 in Ontario, Canada. Cases were those who had an emergency department (ED) visit or hospitalization for serious cADRs within 60 days of the prescription, and each case was matched with up to 4 controls who did not. Exposure: Various classes of oral antibiotics. Main Outcomes and Measures: Conditional logistic regression estimate of the association between different classes of oral antibiotics and serious cADRs, using macrolides as the reference group. Results: During the 20-year study period, we identified 21 758 older adults (median age, 75 years; 64.1% female) who had an ED visit or hospitalization for serious cADRs following antibiotic therapy and 87 025 matched controls who did not. In the primary analysis, sulfonamide antibiotics (adjusted odds ratio [aOR], 2.9; 95% CI, 2.7-3.1) and cephalosporins (aOR, 2.6; 95% CI, 2.5-2.8) were most strongly associated with serious cADRs relative to macrolides. Additional associations were evident with nitrofurantoin (aOR, 2.2; 95% CI, 2.1-2.4), penicillins (aOR, 1.4; 95% CI, 1.3-1.5), and fluoroquinolones (aOR, 1.3; 95% CI, 1.2-1.4). The crude rate of ED visits or hospitalization for cADRs was highest for cephalosporins (4.92 per 1000 prescriptions; 95% CI, 4.86-4.99) and sulfonamide antibiotics (3.22 per 1000 prescriptions; 95% CI, 3.15-3.28). Among the 2852 case patients hospitalized for cADRs, the median length of stay was 6 days (IQR, 3-13 days), 9.6% required transfer to a critical care unit, and 5.3% died in the hospital. Conclusion and Relevance: Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate. This population-based case-control study assesses the association of commonly prescribed oral antibiotics with serious cutaneous adverse drug reactions and characterizes outcomes of patients hospitalized for them. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial stewardship (AMS) aims to improve antibiotic use while reducing resistance and its consequences. There is a paucity of data on the availability of AMS programmes in southern Nigeria. Further, there is no data on Nigerian healthcare professionals' knowledge of the WHO 'Access, Watch and Reserve' (AWaRe) classification of antibiotics. This study sought to assess knowledge of AMS and the AWaRe classification of antibiotics among frontline healthcare professionals in Akwa Ibom State, Nigeria. Methods: This was a cross-sectional survey of 417 healthcare professionals, comprising medical doctors, pharmacists and nurses, across 17 public hospitals in Akwa Ibom State, Nigeria. A paper-based self-completion questionnaire was used to collect data from the participants during working hours between September and November 2023. Statistical analysis was done using SPSS version 25.0, with p < 0.05 indicating statistical significance. Results: Four hundred and seventeen out of the 500 healthcare professionals approached agreed to participate, giving an 83.4% response rate. Most of the participants were female (62.1%) and nurses (46.3%). Approximately 57% of participants were familiar with the term antibiotic/antimicrobial stewardship, however, only 46.5% selected the correct description of AMS. Majority (53.0%) did not know if AMS programme was available in their hospitals. 79% of participants did not know about AWaRe classification of antibiotics. Among the 87 (20.9%) who knew, 28.7% correctly identified antibiotics into the AWaRe groups from a given list. Only profession significantly predicted knowledge of AMS and awareness of the AWaRe classification of antibiotics (p < 0.001). Pharmacists were more likely to define AMS correctly than medical doctors (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.16–3.52, p = 0.012), whereas nurses were less likely to be aware of the WHO AWaRe classification of antibiotics than medical doctors (OR = 0.36, 95% CI = 0.18–0.72, p = 0.004). Conclusions: There was a notable knowledge deficit in both AMS and the AWaRe classification of antibiotics among participants in this study. This highlights the need for educational interventions targeted at the different cadres of healthcare professionals on the role of AMS programmes in reducing antimicrobial resistance and its consequences. [ABSTRACT FROM AUTHOR]

New, first-in-class oral antibiotics like zoliflodacin, developed in a public–private partnership, require an optimal introduction strategy while ensuring antibiotic stewardship. Zoliflodacin, given as a single dose for uncomplicated urogenital gonorrhoea, recently demonstrated non-inferiority to ceftriaxone plus azithromycin and safety in a phase 3 randomised controlled trial. Following regulatory approval, zoliflodacin could improve sexually transmitted infection (STI) management and help address the threat of untreatable gonorrhoea, as levels of resistance to current first-line treatments increase. The Global Antibiotic Research & Development Partnership (GARDP) convened an expert meeting during the 2023 STI and HIV World Congress to discuss key questions about the introduction of zoliflodacin in low- and middle-income countries (LMICs). The questions included: which patients to treat in which situations, the timing of introduction, and what additional evidence is needed to change policy for the use of new antibiotics for gonorrhoea. Recommendations from the expert group included: the generation of evidence for the role of a drug like zoliflodacin in clinical treatment failures; the need for additional antimicrobial resistance surveillance; investigation of the role of novel diagnostic approaches, such as point-of-care tests, to improve stewardship; study of preferences and values among the population in need; and modelling of the emergence of N. gonorrhoeae resistance and transmission in different scenarios. Forthcoming World Health Organization (WHO) global guidelines could outline recommendations for a new oral antibiotic like zoliflodacin based on existing evidence, and rational approaches for certain populations or use cases, while the evidence base is further strengthened. [ABSTRACT FROM AUTHOR]

Background: Severe trauma is the leading cause of disability and mortality in the patients under 35 years of age. Surgical site infections (SSI) represent a significant complication in this patient population. However, they are often inadequately investigated, potentially impacting the quality of patient outcomes. The aim of this study was to investigate the epidemiology of SSI and risk factors in severe trauma patients. Methods: We conducted a multicenter retrospective cohort study screening the severe trauma patients (STP) admitted to two intensive care units of an academic institution in Marseille between years2018 and 2019. Those who underwent orthopedic or spinal surgery within 5 days after admission were included and classified into two groups according to the occurrence of SSI (defined by the Centers for Disease Control (CDC) international diagnostic criteria) or not. Our secondary goal was to evaluate STP survival at 48 months, risk factors for SSI and microbiological features of SSI. Results: Forty-seven (23%) out of 207 STP developed an SSI. Mortality at 48-months did not differ between SSI and non-SSI patients (12.7% vs. 10.0%; p = 0.59). The fractures of 22 (47%) severe trauma patients with SSI were classified as Cauchoix 3 grade and 18 (38%) SSI were associated with the need for external fixators. Thirty (64%) severe trauma patients with SSI had polymicrobial infection, including 34 (72%) due to Gram-positive cocci. Empirical antibiotic therapy was effective in 31 (66%) cases. Multivariate analysis revealed that risk factors such as low hemoglobin, arterial oxygenation levels, hyperlactatemia, high serum creatinine and glycemia, and Cauchoix 3 grade on the day of surgery were associated with SSI in severe trauma patients. The generated predictive model showed a good prognosis performance with an AUC of 0.80 [0.73–0.88] and a high NPV of 95.9 [88.6–98.5] %. Conclusions: Our study found a high rate of SSI in severe trauma patients, although SSI was not associated with 48-month mortality. Several modifiable risk factors for SSI may be effectively managed through enhanced perioperative monitoring and the implementation of a patient blood management strategy. [ABSTRACT FROM AUTHOR]

Biofilm formation and toxin production are some of the virulence factors of Clostridioides difficile (C. difficile), which causes hospital-acquired C. difficile infection (HA-CDI). This work investigated the prevalence and distribution of different strains recovered from HA-CDI patients hospitalized in 4 medical centres across Israel, and characterized strains' virulence factors and antibiotic susceptibility. One-hundred and eighty-eight faecal samples were collected. C. difficile 's toxins were detected by the CerTest Clostridium difficile GDH + Toxin A + B combo card test kit. Toxin loci PaLoc and PaCdt were detected by whole-genome sequencing (WGS). Multi-locus sequence typing (MLST) was performed to classify strains. Biofilm production was assessed by crystal violet. Antibiotic susceptibility was determined using Etest. Fidaxomicin susceptibility was tested via agar dilution. Sequence type (ST) 42 was the most (13.8%) common strain. All strains harboured the 2 toxins genes; 6.9% had the binary toxin. Most isolates were susceptible to metronidazole (98.9%) and vancomycin (99.5%). Eleven (5.85%) isolates were fidaxomicin-resistant. Biofilm production capacity was associated with ST (p < 0.001). In conclusion, a broad variety of C. difficile strains circulate in Israel's medical centres. Further studies are needed to explore the differences and their contribution to HA-CDI epidemiology. [ABSTRACT FROM AUTHOR]

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening skin lesion triggered by hypersensitive drug reaction. They are characterized by extensive epidermal necrosis and skin exfoliation. Fulminant type 1 diabetes mellitus (FT1DM) is featured by a rapid-onset of hyperglycemia with ketoacidosis due to severely destroyed β-cell function. Fulminant type 1 diabetes mellitus as a sequela of SJS/TEN has rarely been reported. Case presentation: We present a 73-year-old female patient who developed SJS/TEN skin allergic reaction after taking carbamazepine and phenytoin for 35 days. Then, hyperglycemia and diabetic ketoacidosis occurred 20 days after discontinuation of antiepileptic drugs. A very low serum C-peptide level (8.79 pmol/l) and a near-normal glycosylated hemoglobin level met the diagnostic criteria for fulminant T1DM. Intravenous immunoglobulin (IVIG) and insulin were promptly administered, and the patient recovered finally. Conclusions: This rare case indicates that monitoring blood glucose is necessary in SJS/TEN drug reaction, and comprehensive therapy with rehydration, insulin, antibiotics, and IVIG may improve the prognosis. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To evaluate the available literature on ureteric stent‐related infections, the use of antibiotics and bacterial colonisation to identify the current incidence of stent‐related infections, unveil knowledge gaps and generate potential hypotheses for future research.A literature review was conducted using PubMed, Cochrane and urological association websites identifying relevant English literature published between 1983 and January 2024.There is a worldwide lack of guidelines for antibiotic prophylaxis for stent placement, exchange or extraction. In patients with a negative preoperative urine culture undergoing ureteroscopy and stent placement, it may be considered to only provide prophylaxis in presence of risk factors. However, in pre‐stented patients a preoperative urine culture is important to guide prophylaxis during endourological surgery. During stent indwell time, antibiotic prophylaxis does not show any advantage in preventing urinary tract infections (UTIs). There is no strong evidence to support the use of antibiotics at time of stent removal. In the absence of any clear evidence, management strategies for treating UTIs in patients with ureteric stents vary widely. Stent exchange could be considered to remove the biofilm as a potential source of bacteria. Stent culture can help to guide treatment during infection as urine culture and stent culture can differ.In terms of good antibiotic stewardship, urologists should be aware that unnecessary use of antibiotics provokes bacterial resistance. There is a great need for further research in the field of antibiotic prophylaxis and stent‐related infections to develop evidence that can help shape clear guidelines for this very common urological practice. [ABSTRACT FROM AUTHOR]

Introduction Bloodstream infections are a significant threat to soldiers wounded in combat and contribute to preventable deaths. Novel and combination therapies that can be delivered on the battlefield or in lower roles of care are urgently needed to address the threat of bloodstream infection among military personnel. In this manuscript, we tested the antibacterial capability of silver ions (Ag+), with long-appreciated antibacterial properties, against ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species, and Escherichia coli) pathogens. Materials and Methods We used the GENESYS (RAIN LLC) device to deliver Ag+ to Gram-positive and Gram-negative ESKAPEE organisms grown in broth, human blood, and serum. Following the Ag+ treatment, we quantified the antibacterial effects by quantifying colony-forming units. Results We found that Ag+ was bactericidal against 5 Gram-negative organisms, K pneumoniae, A baumannii, P aeruginosa , E cloacae , and E coli , and bacteriostatic against 2 Gram-positive organisms, E faecium and S aureus. The whole blood and serum inhibited the bactericidal activity of Ag+ against a common agent of bloodstream infection, P aeruginosa. Finally, when Ag+ was added in conjunction with antibiotic in the presence of whole blood, there was no significant effect of Ag+ over antibiotic alone. Conclusions Our results confirmed that Ag+ has broad-spectrum antibacterial properties. However, the therapeutic value of Ag+ may not extend to the treatment of bloodstream infections because of the inhibition of Ag+ activity in blood and serum. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to create resorbable nanoparticles (NPs) using poly(lactic-co-glycolic acid) (PLGA) to develop novel antibacterial therapeutics for the treatment of chronic wound infections that are susceptible to recurrent infections. By first performing a release study, it was possible to predict the behavior of the different PLGA NP formulations and assess the efficacy of the nanocomposite drug delivery system. These PLGA NP formulations consisted of varying ratios of PLGA without polyvinyl alcohol (PVA) and PLGA with PVA (PLGA-PVA) (i.e. 25:75[PLGA25], 50:50[PLGA50], and 75:25[PLGA75]). Then, different antibiotics (i.e. ciprofloxacin and gentamicin) were incorporated into the PLGA NP formulations to test the antibacterial efficacy of these antimicrobial NPs against different pathogens (i.e. methicillin-resistant Staphylococcus aureus USA300 [MRSA], Pseudomonas aeruginosa FRD1, and Acinetobacter baumannii BAA1605). Of particular interest was testing against the MRSA strain USA300 and the P. aeruginosa strain FRD1. This was possible by measuring the zone of inhibition. A 3-day period was used to monitor the antibacterial efficacy of the different PLGA NP formulations (i.e. PLGA25, PLGA50, and a 1:1 combination of PLGA25:PLGA50) against A. baumannii BAA1605 , MRSA, and P aeruginosa FRD1. Throughout the study, A. baumannii was a negative control and was resistant to all the PLGA NP formulations loaded with ciprofloxacin and gentamicin. At the end of the 3-day period, the PLGA and PLGA50 ciprofloxacin-loaded formulations produced zones of inhibition of 27 mm and 23 mm, respectively, against P. aeruginosa FRD1. This indicated that P. aeruginosa FRD1 was susceptible to both formulations. The mixed formulations with equal parts PLGA25:PLGA50 loaded with ciprofloxacin produced a zone of inhibition (i.e. 25 mm). This again indicated that P. aeruginosa FRD1 was susceptible to ciprofloxacin. The formulations tested against MRSA showed that only gentamicin-loaded formulations produced intermediate results, and that ciprofloxacin-loaded formulations were ineffective. The PLGA25 and the PLGA50 NP formulations loaded with gentamicin both produced zones of inhibition of 13 mm. This indicated that MRSA was intermediate to both the formulations. The PLGA25:PLGA50 loaded with gentamicin produced a zone of inhibition of 14 mm, which again showed that MRSA was intermediate to this formulation. Overall, these PLGA NP formulations showed the sustained antibacterial potential of a burst release, followed by a sustained release of antibiotics from antibiotics loaded PLGA NPs in a controlled manner. In the future, this can help prevent the emergence of recurrent infections in the treatment of chronic wounds and reduce the number of medical dressing changes. [ABSTRACT FROM AUTHOR]

Periprosthetic joint infection (PJI) is a devastating complication following both total hip (THA) and knee (TKA) arthroplasty. Extended oral antibiotic (EOA) prophylaxis has been reported to reduce PJI following TJA in high-risk patients. The purpose of this study was to determine if EOA reduces PJI in all-comers and high-risk THA and TKA populations. This is a retrospective cohort study, including 4,576 patients undergoing primary THA or TKA at a single institution from 2018 to 2022. Beginning in 2020, EOA prophylaxis was administered for 10 days following THA or TKA at our institution. Patients were separated into 2 cohorts (1,769 EOA, 2,807 no EOA) based on whether they received postoperative EOA. The 90-day and 1-year outcomes, with a focus on PJI, were then compared between groups. A subgroup analysis of high-risk patients was also performed. There was no difference in 90-day PJI rates between cohorts (EOA 1 versus no EOA 0.8%; P =.6). The difference in the rate of PJI remained insignificant at 1 year (EOA 1 versus no EOA 1%; P =.9). Similarly, our subgroup analysis of high-risk patients demonstrated no difference in postoperative PJI between EOA (n = 254) and no EOA (n = 396) (0.8 versus 2.3%, respectively; P =.2). Reassuringly, we also found no differences in the incidence of Clostridium difficile infection (EOA 0.1 versus no EOA 0.1%; P >.9) or in antibiotic resistance among those who developed PJI within 90 days (EOA 59 versus no EOA 83%; P =.2). With the numbers available for analysis, EOA prophylaxis was not associated with PJI risk reduction following primary TJA when universally deployed. Furthermore, among high-risk patients, there was no statistically significant difference. While we did not identify increased antibiotic resistance or Clostridium difficile infection, we cannot recommend wide-spread adoption of EOA prophylaxis, and clarification regarding the role of EOA, even in high-risk patients, is needed. [ABSTRACT FROM AUTHOR]

Background: With the widespread use of antibiotics, more attention has been paid to their side effects. We paid extra attention to the impact of antibiotics on children's bodies. Therefore, we analyzed the characteristic changes in the gut microbiota of children after antibiotic treatment to explore the pathogenesis of antibiotic-associated diseases in more depth and to provide a basis for diagnosis and treatment. Methods: We recruited 28 children with bronchopneumonia in the western district of Zhuhai, China, and divided them into three treatment groups based on antibiotic type. We took stool samples from children before and 3–5 days after antibiotic treatment. 16S rRNA gene sequencing was used to analyze the effects of antibiotic therapy on the gut microbiota of children. Continuous nonparametric data are represented as median values and analyzed using the Wilcoxon rank-sum test. Results: While alpha diversity analysis found no significant changes in the mean abundance of the gut microbiota of children after a short course of antibiotic treatment, beta diversity analysis demonstrated significant changes in the composition and diversity of the gut microbiota of children even after a short course of antibiotic therapy. We also found that meloxicillin sulbactam can inhibit the growth of Proteobacteria, Bacteroidetes, and Verrucomicrobia, ceftriaxone inhibits Verrucomicrobia and Bacteroides, and azithromycin inhibits Fusobacteria, Actinobacteria, Proteobacteria, and Verrucomicrobia. We further performed a comparative analysis at the genus level and found significantly different clusters in each group. Finally, we found that azithromycin had the greatest effect on the metabolic function of intestinal microbiota, followed by ceftriaxone, and no significant change in the metabolic process of intestinal microbiota after meloxicillin sulbactam treatment. Conclusions: Antibiotic treatment significantly affects the diversity of intestinal microbiota in children, even after a short course of antibiotic treatment. Different classes of antibiotics affect diverse microbiota primarily, leading to varying alterations in metabolic function. Meanwhile, we identified a series of intestinal microbiota that differed significantly after antibiotic treatment. These groups of microbiota could be used as biomarkers to provide an additional basis for diagnosing and treating antibiotic-associated diseases. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance in Escherichia coli presents a global challenge associated with nosocomial infections and increased mortality rates. Understanding resistance profiles is crucial for guiding treatment strategies and ensuring effective antibiotic use. This study aimed to investigate the prevalence and in vitro resistance of E. coli to community-acquired and nosocomial infections. Various clinical samples from 700 patients were cultured on MacConkey's medium and blood agar. The disk diffusion method was used to determine the antibiotic susceptibility profile of the E. coli isolates following the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Urine, pus, seminal fluid, vaginal swabs, and other body fluids were among the clinical samples analyzed. Of the 112 E. coli isolates, 48.2% were from inpatients and 51.8% were from outpatients, with the majority (66%) isolated from urine samples. Higher resistance levels were observed in the urinary isolates than that in the previously recorded data from the same institutions. Notably, isolates exhibited high resistance to penicillin (98.2%), ampicillin (97.3%), first-generation cephalosporins (90.2%), erythromycin (72.2%), and roxithromycin (95.4%), whereas lower resistance was noted against piperacillin-tazobactam (25.0%), nitrofurantoin (12.5%), and imipenem (9.8%). The overall multidrug resistance rate was 62.5%, with higher rates observed in nosocomial infections (70%) compared to community-acquired isolates (55.6%). However, this difference was not statistically significant (p>0.05). This study underscores the prevalence of E. coli isolates (27.0%) and highlights the concerning level of resistance, particularly to older antibiotics. These findings emphasize the importance of judicious antibiotic use and ongoing surveillance. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) is a very common human pathogenic microorganism that can cause a variety of infectious diseases, including skin and soft tissue infections, endocarditis, osteomyelitis, bacteremia, and lethal pneumonia. About one-third of the common population is colonized with S. aureus. MRSA is a formidable pathogen known to cause high mortality & morbidity, that poses a significant threat to public health worldwide. Presence of MRSA strains, resistant to multiple antibiotics especially in hospital stay, has complicated the management of infections caused by this bacterium. The aim of this study was to shed light on the prevalence and antimicrobial sensitivity pattern of MRSA among patients in a tertiary care center located in Faridabad, Haryana. This cross-sectional observational study was conducted in the Department of Microbiology, ESIC Medical College & Hospital, a 510 bedded tertiary care teaching hospital in Faridabad, Haryana, India. All wound samples including pus, exudates, wound swab and tissue samples received for aerobic culture and antimicrobial sensitivity from various clinical departments from January 2019 to July 2019 were included in this study. A total of 747 samples were received from January 2019-July 2019. Mean age of this study population was found to be 50.7 ± 14.8 years. Out of 747 samples, 226 (30.25%) were culture positive. Among the S. aureus isolates, methicillin resistance was seen amongst 39 (58.2%). Antibiotic Susceptibility results of S. aureus showed 100% resistance to Penicillin along with 100% resistance to Fluoroquinolones in both MRSA and MSSA. High prevalence of MRSA amongst patients highlights the importance of continued surveillance and implementation of antimicrobial stewardship program to control the menace of antimicrobial resistance. Strict adherence to Infection Control practices its regular follow up to assess the effectiveness of any hospital infection control measures taken is the key. [ABSTRACT FROM AUTHOR]

To assess frequency and methods of PID (primary immune deficiency) screening among patients with bronchiectasis by pneumologists in clinical practice. All the patients hospitalized in the department of pneumology of the Poitiers University Hospital between April 2013 and April 2020 with a diagnosis of bronchiectasis on chest computerized tomography were included. Patients aged 70 and over and those with already known PID were excluded. Primary endpoint was the proportion of patients having had serum immunoglobulin (Ig) assay and serum protein electrophoresis (SPE) analysis. Secondary endpoints were factors associated with prescription of SPE and/or Ig assay, proportion of patients with newly diagnosed PID and their characteristics and factors associated with repeated courses of antibiotics. Among the 133 patients included, 43% had SPE + Ig assay, 34% SPE only and 23% neither. The proportion of patients with asthma was higher in the "SPE + Ig assay" group (33.3%) compared to the "SPE only" (11.1%) and the "Neither SPE nor Ig assay" groups (6.4%) (P = 0.002). Four patients were newly diagnosed for PID of whom 3 had subclass IgG deficiency. Factors associated with repeated courses of antibiotics were generalized bronchiectasis (P = 0.02) and asthma (P = 0.04). PID is underscreened by pneumologists among patients with bronchiectasis. Association of SPE + Ig assay + IgG subclass assay appears as the most accurate combination. [ABSTRACT FROM AUTHOR]

Background Bacterial RNA polymerase (RNAP) is a promising target for antimicrobial chemotherapy due to its indispensable role in bacterial growth and survival. Among its components, only the rpoB gene encoding the β-subunit is known for its association with rifampicin resistance. We recently identified a variant of the RNAP α-subunit (RpoA) in Pseudomonas aeruginosa, conferring heightened bacterial susceptibility to antimicrobials. This susceptibility was attributed to the specific down-regulation of the MexEF-OprN efflux pump. Objectives We asked how to distinguish antimicrobial-susceptible variant strains from clinical isolates. Methods In this study, we identified various P. aeruginosa RpoA variants from clinical sources. Using the sequence alignment of different bacterial RpoA species, we computed the positional conservation of substitutions in RpoA variants using Shannon Entropy. Results Our findings revealed that selective RpoA variant strains exhibited distinct profiles of antimicrobial susceptibility. Notably, RpoA variant strains, containing single-substitutions in the C-terminal domain (α-CTD) but not the N-terminal domain (α-NTD), showed attenuated MexEF-OprN expression and increased susceptibility to MexEF-OprN-specific antibiotics. Furthermore, we observed a close correlation between the susceptibility of these α-CTD RpoA variant strains to antibiotics and the conservation degrees of positional substitutions. Conclusions Our findings demonstrate the prevalence of antimicrobial-susceptible RpoA variant strains among P. aeruginosa clinical isolates. The identified positional conservation pattern in our study facilitates the rapid classification of RpoA variant strains with distinct drug resistances. Given the high conservation of RNAP across bacterial species, our findings open a new therapeutic perspective for precisely and efficiently combating pathogenic RpoA variant strains with specific antimicrobials. [ABSTRACT FROM AUTHOR]

Background MRSA is a major contributor to AMR-related deaths. The WHO's global action plan emphasizes a One Health approach, acknowledging the connection between humans and their companion animals. It is agreed on that comprehensive AMR surveillance is needed. Objectives This study provides a large-scale overview of MRSA occurrence in cats and dogs in Germany, serving as a foundation for continuous surveillance. Methods The study analysed all results of canine and feline bacterial diagnostic samples from a large laboratory, encompassing samples received from veterinary practices between January 2019 and December 2021. MRSA prevalence between host species, sample types and geographical distribution were compared. Additionally, data were contrasted with human MRSA surveillance data from Germany. Results Samples originated from 3491 German veterinary practices, representing 33.1% of practices and clinics nationally. Bacterial examination results from 175 171 samples were analysed, identifying S. aureus in 5526 of these samples (3.2% isolation rate). S. aureus in clinical samples was more prevalent in cats (5.6%) than dogs (2.0%). Methicillin resistance was found in 17.8% of S. aureus samples and was higher in dogs (20.4%, 95%CI 18.9–22.0) than cats (15.6%, 95%CI 14.3–17.0). The highest MRSA prevalence was found in canine wound samples (32%), compared to skin/soft tissue, respiratory tract and other (<23% respectively). Conclusion The study reveals a 17.8% MRSA prevalence, which is higher than the human outpatient MRSA prevalence (5.4%). Restriction and regulation of veterinary antibiotic use should be validated with AMR surveillance. Our study shows that this is feasible in companion animals with significant coverage. [ABSTRACT FROM AUTHOR]

Background The COVID-19 pandemic has resulted in great incertitude and overwhelming changes in healthcare that have had a direct impact on antibiotic prescription. However, the influence of this pandemic on antibiotic consumption in patients undergoing surgery has not yet been analysed. The goal of this study was to analyse antimicrobial consumption and prescription in the same period of 2019 (pre-COVID-19), 2020 (beginning of the COVID-19 pandemic) and 2021 (established COVID-19) according to the DDD system in surgical patients at a tertiary-level hospital. Methods A prospectively maintained database was analysed. All patients who underwent elective or emergency gastrointestinal surgery during the same period (2019, 2020 and 2021) were included. Those who received at least 1 of the 10 most frequently prescribed antimicrobials during those periods were analysed. Results A total of 2975 patients were included in this study. In 2020, the number of procedures performed decreased significantly (653 versus 1154 and 1168 in 2020 versus 2019 and 2021, respectively; P  = 0.005). Of all patients who underwent surgery during these periods, 45.08% received at least one of the antimicrobials studied (45.8% in 2020 versus 22.9% and 22.97% in 2019 and 2021, respectively; P  = 0.005). Of these, 22.97% of the patients received a combination of these antimicrobials, with ceftriaxone/metronidazole being the most frequent. Hepato-Pancreato-Biliary and Liver Transplant, Emergency Surgery and Colorectal Surgery units had higher antibiotic consumption. Conclusions The COVID-19 pandemic has resulted in a significant decrease in surgical activity and higher post-operative antimicrobial prescription compared with previous and subsequent years. [ABSTRACT FROM AUTHOR]

Objectives The measurement of VOCs release in the headspace of a bacterial culture represents a new approach to rapidly assess antimicrobial susceptibility. Herein, we evaluated the diagnostic performance of the VITEK® REVEAL™ system directly from a collection of Gram-negative positive blood cultures. Materials and methods One hundred and twenty-eight positive blood cultures were included in the analysis (Enterobacterales, n  = 95; Pseudomonas aeruginosa , n  = 21; Acinetobacter baumannii complex, n  = 12). Samples were processed using VITEK® REVEAL™ according to the manufacturer's recommendations, and MICs of 22 antimicrobials were compared with those obtained using reference methods. Categorical agreement (CA), essential agreement (EA) and categorical errors were calculated. Results Overall, 2220 strain/antibiotic pair combinations were analysed. Of these, most were classified as resistant by reference antimicrobial susceptibility testing (1091/2220; 48.7%). The overall CA and EA were 97.6% and 97.7%, respectively. CA ranged from 97.5% in Enterobacterales to 97.9% in both P. aeruginosa and A. baumannii complex. The overall number of categorical discrepancies were: 18 very major errors (1.6%), 13 major errors (1.2%) and 22 minor errors (2.4%). EA ranged from 95.2% in P. aeruginosa to 98.1% in Enterobacterales. Screening test for ESBL phenotype was positive, indeterminate and negative in 13.7%, 32.6% and 27.4% of Enterobacterales isolates tested by both VITEK® REVEAL™ and the reference method, showing 100% CA. Conclusions VITEK® REVEAL™ represents a reliable tool to obtain antimicrobial susceptibility results of the main Gram-negative species directly from positive blood cultures with time to results of less than 8 h. [ABSTRACT FROM AUTHOR]

Objectives Temocillin, a carbapenem-sparing β-lactam antibiotic, is commonly used at the standard 4 g/day dosage for treating complicated urinary tract infections (cUTIs). However, pharmacokinetic/pharmacodynamic (PK/PD) data supporting this regimen is limited. This study evaluated the plasma pharmacokinetics (PK) and PTA of temocillin in non-critically ill cUTI patients with varying degrees of renal insufficiency (RI). Methods In this single-centre clinical study, 22 cUTI patients received a fixed 4 g/day (2 g q12h, intravenously) temocillin dose, irrespective of renal function (no RI: n  = 5, mild RI: n  = 8, moderate RI: n  = 9). Plasma samples were collected post-dosing for LC-MS analysis of total and unbound temocillin levels. Monte Carlo simulations were performed based on the established PK/PD target of ≥35% f T > MIC (minimal inhibitory concentration). Results Among patients, the highest plasma drug exposure and PK/PD target attainment were observed in those with moderate RI (median AUC0–12h = 1143 h.mg/L and % f T > MIC = 68%), followed by mild RI patients (median AUC0–12h = 918 h.mg/L and % f T > MIC = 34%), and the lowest in those with healthy kidney function (median AUC0–12h = 692 h.mg/L and % f T > MIC = 26%). Simulations indicated that the 4 g/day temocillin dose achieves 90% PTA only for glomerular filtration rate < 60 mL/min and MIC ≤ 8 mg/L. Conclusion The standard temocillin dose may need to be increased from 4 to 6 g/day to treat non-critically ill cUTI patients, in line with recent EUCAST recommendations. For patients with moderate RI, who experience higher exposure due to reduced renal drug clearance, 4 g/day temocillin remains appropriate. [ABSTRACT FROM AUTHOR]

Background β-lactam antibiotics, which inhibit penicillin-binding protein 3 (PBP3) that is required for cell division, play a key role in treating P. aeruginosa infections. Some sequence variations in PBP3 have been associated with β-lactam resistance but the effects of variations on antibiotic susceptibility and on cell division have not been quantified. Antibiotic efflux can also reduce susceptibility. Objectives To quantify the effects of PBP3 variations on β-lactam susceptibility and cell morphology in P. aeruginosa. Methods Nineteen PBP3 variants were expressed from a plasmid in the reference strain P. aeruginosa PAO1 and genome engineering was used to construct five mutants expressing PBP3 variants from the chromosome. The effects of the variations on β-lactam minimum inhibitory concentration (MIC) and cell morphology were measured. Results Some PBP3 variations reduced susceptibility to a variety of β-lactam antibiotics including meropenem, ceftazidime, cefepime and ticarcillin with different variations affecting different antibiotics. None of the tested variations reduced susceptibility to imipenem or piperacillin. Antibiotic susceptibility was further reduced when PBP3 variants were expressed in mutant bacteria overexpressing the MexAB-OprM efflux pump, with some variations conferring clinical levels of resistance. Some PBP3 variations, and sub-MIC levels of β-lactams, reduced bacterial growth rates and inhibited cell division, causing elongated cells. Conclusions PBP3 variations in P. aeruginosa can increase the MIC of multiple β-lactam antibiotics, although not imipenem or piperacillin. PBP3 variations, or the presence of sub-lethal levels of β-lactams, result in elongated cells indicating that variations reduce the activity of PBP3 and may reduce bacterial fitness. [ABSTRACT FROM AUTHOR]

Background Fosfomycin is gaining increasing attention for its activity against MDR or XDR pathogens. Currently, IV fosfomycin is a potential option for treating various infections, including urinary tract infections, pneumonia and skin infections when first-line treatments fail. Objectives To evaluate the demographic, clinical, microbiological and treatment modality of children received IV fosfomycin to treat infections caused by MDR pathogens since there are few data on the use of fosfomycin in children. Methods This study was conducted retrospectively with patients under 18 years of age who were treated with IV fosfomycin for at least 72 h due to infections caused by MDR pathogens between January 2019 and October 2023 at Marmara University Pendik Training and Research Hospital, İstanbul, Türkiye. Data on demographic and clinical features, microbiological findings, treatment modalities and side effects were evaluated. Results Twenty-five children, for a total of 32 cases of infection episodes, with a mean age of 11.4 ±   3.92 years who received IV fosfomycin were included. The most frequent comorbidity was chronic pulmonary diseases, and the most common infection needed for IV fosfomycin was MDR Pseudomonas aeruginosa pneumonia. In all cases, fosfomycin was administered in combination with other antibiotics, mainly meropenem–colistin (68.7%) or meropenem (15.6%). Twenty-two (71.9%) cases had favourable clinical responses at the end of therapy. Conclusions Our results suggest that IV fosfomycin may be an effective treatment option for MDR pathogens in the paediatric population. Nevertheless, careful stewardship is necessary to maintain efficacy and reduce antimicrobial resistance selection risk. [ABSTRACT FROM AUTHOR]

Background Clostridioides difficile infection (CDI), a leading cause of nosocomial deaths, is a microbiota-mediated disease. As such, the use of broader spectrum antibiotics, such as vancomycin and metronidazole, can prime the gastrointestinal tract to become more prone to CDI recurrences. Fidaxomicin, a narrow-spectrum antibiotic, has been demonstrated to be superior in preventing recurrence and in preserving the intestinal microbiota; however, widespread employment worldwide has been hindered due to high acquisition costs. Objectives To integrate the currently available guidelines on the management of CDI and to shed light on the timeliest employment of fidaxomicin. Methods An expert panel was gathered to obtain consensus using Delphi methodology on a series of statements regarding the management of CDI and on appropriate antibiotic use. Results Consensus was reached on 21 of the 25 statements addressing the management of CDI. Conclusions Delphi methodology was used to achieve consensus on the management of CDI, on the identification of patients at risk of recurrences or severe infection, and on the most appropriate use of fidaxomicin, with the final aim of fostering clinical practice application of treatment algorithms proposed by previous guidelines, in absolute synergy. It could be an important tool to promote more appropriate and cost-effective CDI treatments in European settings with limited resources, like Italy. [ABSTRACT FROM AUTHOR]

Background: Jaw osteoradionecrosis (ORN) is a complication in patients with previous head and neck radiotherapy. Its incidence increases with dental extractions. Hence, this review aimed to evaluate the efficacy of adjunctive treatment modalities undertaken at the time of extraction in previous head and neck radiotherapy patients in preventing ORN. Methods: A systematic review was conducted, where studies with data on ORN incidence after extraction with or without adjunctive interventions were included. Meta‐analyses were conducted to estimate the pooled prevalence of ORN per intervention and the pooled odds ratio for incidence of ORN between interventions. Results: In total, 1520 patients in 29 studies were included. Interventions identified were hyperbaric oxygen (HBO), pentoxifylline‐tocopherol (PENTO), antibiotics (ABX), platelet‐rich fibrin and photobiomodulation. The pooled prevalence of ORN for HBO (4.6%), PENTO (3.4%) and ABX (3.8%) was significantly lower than the Control (17.6%). For studies with direct comparisons between groups, HBO had lower but not significant odds of developing ORN than the Control (OR 0.27) and ABX (OR 0.57). Conclusions: HBO, PENTO and ABX may reduce the incidence of ORN compared to no intervention. Given that all three have similar incidences of ORN, ABX may be the most cost‐effective and accessible adjunctive modality. [ABSTRACT FROM AUTHOR]

Antibiotics can be introduced from aquaculture facilities into marine sediments, where they may affect benthic communities and generate antimicrobial resistance (AMR). Antibiotics can be used in tandem with antiparasitics, and the effects of their combined usage could affect AMR patterns and transmit antibiotic resistance genes. This study compiles patterns of antibiotic and antiparasitic drug usage from 2016 to 2021 in British Columbia, New Brunswick, Newfoundland and Labrador, and Nova Scotia (Canada) and compares them internationally. There is an overall reduction in rates of antibiotic use per fish produced in Canadian aquaculture sites from 2016 to 2021. Compared to other salmon-producing countries, Canadian antibiotic rates per tonne of fish are lower than in Chile, but higher, on average, than in Norway and Scotland. Florfenicol (FLO) and oxytetracycline (OTC) are the prevalent antibiotics used in most salmon-producing countries, including Canada. We also note that <30% of sites used two drugs per year and <18% of sites used three drugs, with most of these sites using one antibiotic and one antiparasitic. There is an increase in FLO and a decrease use in OTC use in Canada, which could be positive environmentally considering FLO's lower dose and environmental persistence. The east and west coasts show comparable antibiotic rates, with an average rate of 78 mg/kg in BC and 76 mg/kg in the Atlantic provinces; however, they have differences in the type of antibiotic (average use of OTC: BC 38 mg/kg vs. Atlantic 214 mg/kg; average use of FLO: BC 40 mg/kg vs. Atlantic 10 mg/kg). Other distinctions between coasts include variation in the timing of treatments, with seasonal use in the Atlantic provinces (May–November) and year-round use in BC. This pattern is likely influenced by differences in water temperature and, subsequently, potential susceptibility to aquatic diseases. Disease prevalence and veterinarian choice/preferred treatments are factors that, we hypothesize, may impact treatment choice; however, additional information is required to adequately comment on this point. This data compilation includes spatial descriptions that could be used for area prioritization in future studies. [ABSTRACT FROM AUTHOR]

Background: The efficacy of combination empiric antibiotic therapy for all intensive care unit (ICU) patients with community-acquired sepsis is a subject of ongoing debate in the era of increasing antibiotic resistance. This study was conducted to evaluate the patterns of antibiotic usage and microbial resistance in sepsis patients admitted to the ICU with both hemodynamically stable (HS) and unstable states and to analyze their clinical outcomes. Methods: In this observational study, patients aged 18 years and above who received antibiotics upon admission and had a culture report were included. These patients were categorized into the following groups: HS and hemodynamically unstable (HU), single or combined antibiotics group (more than one antibiotic used empirically to cover one or more groups of organisms), culture-positive and culture-negative group. The microbiological isolates were grouped according to their identified resistance patterns. The outcome parameters involved assessing the differences in empiric antibiotics use upon admission and microbial resistance with hemodynamic stability and investigating any associations with ICU and hospital outcomes. Results: The study included a total of 2675 patients, of which 70.3% were in the HS group, and 29.7% in the HU group. The use of combination antibiotics was significantly higher (p < 0.0001) across all groups. Carbapenems were used more frequently in the single antibiotic group (p < 0.001). The culture was positive in 27.8% (n = 747) of patients. A significantly higher number of patients in the HU group (p < 0.001) were found to have carbapenem-resistant and multidrug-resistant organisms. The ICU and hospital mortality rates were significantly higher in the HU group (p < 0.001), the culture-positive group with resistance (p < 0.001), and the HS patients who received combination antibiotics. Conclusion: The usage of combination antibiotics, coupled with the presence of resistant organisms, emerged as an important variable in predicting ICU and hospital mortality rates in cases of community-acquired sepsis. [ABSTRACT FROM AUTHOR]

Nosocomial pneumonia is defined as pneumonia occurring ≥ 48 h after hospital admission in a patient without severe immunosuppression. It can occur in spontaneously breathing patients or with noninvasive ventilation (NIV) and mechanically ventilated patients. In patients with suspected ventilator-associated pneumonia (VAP) (semi)quantitative cultures of tracheobronchial aspirates or bronchoalveolar lavage fluid should be perfomed. The initial empirical antimicrobial treatment is determined by the risk for multidrug-resistant pathogens (MDRP). The advantage of combination treatment increases with the prevalence of MDRPs. The antibiotic treatment should be adapted when the microbiological results are available. After 72 h a standardized re-evaluation including the response to treatment and also checking of the suspected diagnosis of pneumonia in a structured form is mandatory. Treatment failure can occur as a primary or secondary failure and in the case of primary progression necessitates another comprehensive diagnostic work-up before any further antibiotic treatment. [ABSTRACT FROM AUTHOR]

Necrotizing soft tissue infections are a heterogeneous group of severe infections of the skin, connective tissue and muscles in which necrotic destruction of the tissue occurs at the site of infection. Various bacteria are known as "typical" triggering pathogens and the infection can occur on the entire surface of the body. Necrotizing soft tissue infections are always a time-sensitive emergency associated with high mortality. Many affected patients are critically ill and require treatment in an intensive care unit. The rapid and radical surgical treatment is an essential part of management and in addition an adequate and timely antimicrobial treatment is of great importance. The health consequences for surviving patients are often severe, as extensive soft tissue damage leads to functional impairments. In many cases extensive plastic surgery follow-up is necessary. Therefore, necrotizing soft tissue infections are "complicated" in every phase of the disease and require interprofessional treatment. This review article provides a current overview of various aspects of the diagnostics, treatment and aftercare of necrotizing soft tissue infections. [ABSTRACT FROM AUTHOR]

Background: Infection is a common cause of mortality within intensive care units (ICUs). Antibiotic resistance patterns and culture data are used to create antibiograms. Knowledge of antibiograms facilitates guiding empiric therapies and reduces mortality. Most major hospitals utilize data collection to create hospital-wide antibiograms. Previous studies have shown significant differences in susceptibility patterns between hospital wards and ICUs. We hypothesize that institutional or combined ICU antibiograms are inadequate to account for differences in susceptibility for patients in individual ICUs. Methods: Culture and susceptibility data were reviewed over a 1-year period for 13 bacteria in the following ICUs: Surgical/Trauma, Medical, Neuroscience, Burn, and Emergency department. Antibiotic management decisions are made by individual teams. Results: Nine species had sufficient data for inclusion into an All-ICU antibiogram. E coli and S aureus were the most common isolates. Seven species had significant differences in susceptibility patterns between ICUs. E cloacae showed higher rates of resistance to multiple antibiotics in the STICU than other ICUs. P aeruginosa susceptibility rates in the NSICU and BICU were 88% and 92%, respectively, compared to 60% and 55% in the STICU and MICU. Cephalosporins and Aztreonam had reduced efficacy against E coli in the NSICU, however remain effective in other ICUs. Conclusions: The results of this study show that different ICUs do have variability in antibiotic susceptibility patterns within a single hospital. While this only represents a single institution, it shows that the use of hospital-wide antibiograms is inadequate for creating empiric antibiotic protocols within individual ICUs. [ABSTRACT FROM AUTHOR]

Introduction: Acute pediatric mastoiditis is a bacterial infection of the mastoid bone most commonly associated with acute otitis media. Complicated mastoiditis is traditionally characterized by intracranial complications or subperiosteal abscess, but definitions are inconsistent in the literature. Surgical intervention is identified as the main treatment for complicated mastoiditis, but there is some evidence to support medical management of uncomplicated mastoiditis. This study sought to clarify the diagnostic criteria and management of uncomplicated acute mastoiditis. Methods: All cases of acute pediatric mastoiditis were identified from a single institution over a 16-year period and reviewed for demographic and clinical data. Two different definitions of uncomplicated mastoiditis were compared; the traditional one that excluded patients with intracranial complications or subperiosteal abscess (SPA) and the proposed definition that also excluded patients with any evidence of bony erosion including coalescence, not just SPA. Univariate and multivariate analysis was conducted. Results: Eighty cases were identified. Using the traditional definition of uncomplicated mastoiditis, 46.3% of cases were uncomplicated, compared to 36.2% when using the proposed definition. Truly uncomplicated patients, categorized with the proposed definition, were treated more consistently: no patients underwent mastoidectomy and they were less likely to receive a long term course of antibiotics. On multivariate regression analysis, only categorization with the proposed definition of uncomplicated mastoiditis was independently associated with less long-term antibiotic therapy and non-surgical management. Conclusion: Uncomplicated acute mastoiditis should be defined using clinical criteria and exclude any cases with evidence of bony erosion, including coalescence or subperiosteal abscess. These truly uncomplicated patients often do not require mastoidectomy and can be prescribed a shorter course of antibiotics. Further research into treatment pathways is necessary to optimize the management of uncomplicated acute pediatric mastoiditis. [ABSTRACT FROM AUTHOR]