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Background: ß-Lactams remain the most reported drug allergy globally, with the volume and diversity of related drug allergy research continuing to accumulate. Recognizing evolving research trends can help inform future directions and encourage synergistic collaborations. Objective: We conducted a comprehensive bibliometric analysis of all publications relevant to ß-lactam allergy, with a focus on longitudinal publication rates, international collaborations, and key word/trend analysis. Methods: Meta-data from all original articles, letters, and reviews relevant to ß-lactam allergy on the Web of Science Core Collection up until December 31, 2023, were analyzed. Results: From 1966 to 2023, there were 4451 records (3536 articles, 631 reviews, and 284 letters) from 78 countries. There was an exponential increase in publications, especially during the past decade, with half of all publications on ß-lactam allergy published during this time (50.6% [2252 of 4452]). Overall, 18.1% of the publications (805 of 4452) involved international coauthorships, with a significant increase since the previous decade (12.7% vs 23.3% [P < .001]). The most frequent key words in the first published half of articles were skin testing (84 of 1919), IgE (57 of 1919), and anaphylaxis (49 of 1919); in contrast to the key word skin testing (137 of 3351), the key words drug provocation test (121 of 3351), antimicrobial resistance (120 of 3351), and antimicrobial stewardship (118 of 3351) were the most frequent key words in the latter half. Conclusion: There has been a surge in publications, international collaboration, and shifting paradigms in ß-lactam allergy research. The field has evolved beyond focusing on in vitro tests or desensitization toward antimicrobial stewardship. However, there still seems to be relatively fewer collaborations with non-Western countries. Further international collaborations to harmonize delabeling strategies against the threat of mislabeled ß-lactam allergy should be encouraged.

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Febrile neutropenia is a common complication of conditioning chemotherapy for hematopoietic stem cell transplant (HSCT), but a major barrier for optimal treatment of febrile neutropenia is historical penicillin allergies. Our group recently published a development of a clinical pipeline for delabeling penicillin allergies in adult patients planned to undergo hematopoietic stem cell transplant (HSCT). In this retrospective cohort study, we followed patients to evaluate their outcomes during inpatient admission for HSCT. We hypothesized that, among patients planned for HSCT with a self-reported penicillin allergy, completing penicillin allergy testing (amoxicillin ingestion challenge with or without concomitant penicillin skin testing) prior to HSCT admission would be associated with differences in inpatient treatment for febrile neutropenia (including antibiotic selection and timing of antibiotic administration) and improved inpatient resource utilization (including nursing and inpatient physician consults). We identified patients with a self-reported penicillin allergy who answered a penicillin allergy questionnaire and were subsequently admitted to our institution for HSCT. We divided the cohort into 2 groups: patients whose penicillin allergy was evaluated prior to admission (EPTA) and patients whose penicillin allergy was not evaluated prior to admission (NEPTA). We then performed comparison between the 2 groups for general clinical outcomes of HSCT admission (duration of admission, need for ICU transfer, readmission rate, etc.), febrile neutropenia treatment, and inpatient resource utilization. Statistics were calculated using the nonparametric 2-tailed Fisher exact test for categorical outcomes and the nonparametric 2-tailed Mann-Whitney U test for numerical outcomes. Within our cohort, 35 patients completed penicillin allergy testing prior to HSCT admission (EPTA) and 44 patients did not (NEPTA). Demographics were similar between these groups, and there was no significant difference in the rate of febrile neutropenia during HSCT admission (EPTA 64% versus NEPTA 66%, P = 1.00). EPTA patients were significantly more likely to receive standard first-line antibiotics (cefepime or ceftazidime) for febrile neutropenia (EPTA 95% versus NEPTA 65%, P = .015) and time between febrile neutropenia onset and antibiotic administration was shorter (EPTA mean 66 mins versus NEPTA mean 121 mins, P = .0058). No patients in the EPTA group experienced an immediate hypersensitivity reaction (hives, anaphylaxis, etc.) or severe cutaneous adverse reaction (SCAR) during HSCT admission. EPTA patients were also significantly less likely to require 1:1 nursing for antibiotic test doses, challenges, and desensitizations (EPTA 0% versus NEPTA 49%, P < .0001); less likely to require inpatient allergy consult (EPTA 0% versus NEPTA 12%, P = .031); and less likely to require inpatient antimicrobial stewardship consult (EPTA 0% versus NEPTA 13%, P = .013) during their HSCT admission. In summary, patients who completed penicillin allergy testing prior to HSCT admission were more likely to receive first-line antibiotics and received antibiotics more rapidly for treatment of febrile neutropenia. Furthermore, patients who completed penicillin allergy testing prior to HSCT admission were less likely to require 1:1 nursing, inpatient allergy consults, and inpatient antimicrobial stewardship consults during HSCT admission.

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INTRODUCTION: Infections caused by multidrug-resistant gram-negative bacilli (MDR-GNB) in critically ill patients present a challenge for timely and appropriate antibiotic treatment. This is particularly important in patients undergoing extracorporeal life support techniques such as renal replacement therapy and extracorporeal membrane oxygenation. These techniques can introduce additional pharmacokinetic alterations, potentially leading to suboptimal exposure to antibiotics. This study aims to outline dosing strategies and therapeutic drug monitoring protocols for new ß-lactam antibiotics effective against MDR-GNB in critically ill patients undergoing extracorporeal life support techniques at a national level. Additionally, the study seeks to develop a consensus document, based on available evidence. METHODS: The project will comprise two main phases: I) A national survey, and II) the development of a consensus document. This consensus document, undertaken according to ACCORD guidelines, will encompass: a) establishment of a multidisciplinary panel of experts, b) prospective registration of the consensus, c) evidence synthesis, d) modified Delphi rounds. The antimicrobials to be included will be: meropenem, ceftazidime/avibactam, ceftolozane/tazobactam, cefiderocol, meropenem/vaborbactam, imipenem/relebactam, and aztreonam. Extracorporeal life support techniques will include continuous renal replacement therapy, conventional intermittent hemodialysis, and extracorporeal membrane oxygenation. DISCUSSION: The availability of extracorporeal life support techniques has expanded significantly in recent years, alongside a rise in the prevalence of infections caused by multidrug-resistant gram-negative bacilli (MDR-GNB). There is a need to develop evidence-based tools of high quality to standardize dosing and monitoring strategies for new ß-lactam antibiotics.

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Antibiotics are the super drugs that have revolutionized modern medicine by curing many infectious diseases caused by various microbes. They efficiently inhibit the growth and multiplication of the pathogenic microbes without causing adverse effects on the host. However, prescribing suboptimal antibiotic and overuse in agriculture and animal husbandry have led to the emergence of antimicrobial resistance, one of the most serious threats to global health at present. The efficacy of a new antibiotic is high when introduced; however, a small bacterial population attains resistance gradually and eventually survives. Understanding the mode of action of these miracle drugs, as well as their interaction with targets is very complex. However, it is necessary to fulfill the constant need for novel therapeutic alternatives to address the inevitable development of resistance. Therefore, considering the need of the hour, this article has been prepared to discuss the mode of action and recent advancements in the field of antibiotics. Efforts has also been made to highlight the current scenario of antimicrobial resistance and drug repurposing as a fast-track solution to combat the issue.

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BACKGROUND: The prevalence of allergies to beta-lactam antibiotics is significantly overestimated based on anamnestic data - with significant medical and economic consequences. The aim of the study was to determine the frequency of immediate and delayed type reactions to beta-lactam antibiotics in order to optimize diagnostics and therapy. One focus was on the time interval between reaction and testing. PATIENTS AND METHODOLOGY: Anamnestic and diagnostic data of patients with suspected allergy to beta-lactam antibiotics who were examined in our department between 2020 and 2022 were analyzed. RESULTS: 27/116 (23%) patients reacted in the skin tests. Type I sensitizations were detected in 4/35 patients (11%), type IV sensitizations in 23/83 (28%). In the case of negative in vitro diagnostics and skin testing, inpatient provocation tests were performed in 41/89 (46%). Type I allergies were confirmed in two of the 13 provoked patients (15%) with immediate type reactions, type IV allergies in three of 29 (10%) with delayed type reactions. The results were clearly related to the time interval after reaction. At less than one year, 19% (22/116) reacted, whereas only 4% (5/116) reacted at more than one year (for type I reaction 9% vs. 3%; for type IV reaction 23% vs. 5%).  CONCLUSIONS: The importance of the time interval between clinical event and allergological testing supports the guideline recommendation for skin testing within one year. Guideline recommendations on the diagnostic procedure for unclear reactions that occurred in the more distant past are desirable in order to rule out allergies to beta-lactam antibiotics.

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Human Adenovirus (HAdV) infections in immunocompromised patients can result in disseminated diseases with high morbidity and mortality rates due to the absence of available treatments for these infections. Ircinia felix sponge was selected for the significant anti-HAdV activity displayed by its organic extracts. Its chemical analysis yielded three novel sesterterpene lactams, ircinialactams J-L, along with three known sesterterpene furans which structures were established by a deep spectrometric analysis. Ircinialactam J displayed significant antiviral activity against HAdV without significant cytotoxicity, showing an effectiveness 11 times greater than that of the standard treatment, cidofovir®. Some structure-activity relationships were deduced. Mechanistic assays suggest that ircinialactam J targets an early step of the HAdV replicative cycle before HAdV genome reaches the nucleus of the host cell. The first total synthesis of ircinialactam J was also accomplished to prove the structure and to provide access to analogues. Key steps are a regio- and stereoselective construction of the trisubstituted Z-olefin at Δ7 by iron-catalyzed carbometallation of a homopropargylic alcohol, a stereoselective methylation to generate the stereogenic center at C18, and the formation of the (Z)-Δ20 by stereoselective aldol condensation to introduce the tetronic acid unit. Ircinialactam J is a promising antiviral drug against HAdV infections.

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Objective: Our aim was to elucidate the resistance mechanisms and assess the combined synergistic and bactericidal activities of aztreonam in combination with ceftazidime/avibactam (CZA), meropenem/vaborbactam (MEV), and imipenem/relebactam (IMR) against Enterobacterales strains producing dual carbapenemases. Methods: Species identification, antimicrobial susceptibility testing and determination of carbapenemase type were performed for these strains. Plasmid sizes, plasmid conjugation abilities and the localization of carbapenemase genes were investigated. Whole-genome sequencing was performed for all strains and their molecular characteristics were analyzed. In vitro synergistic and bactericidal activities of the combination of aztreonam with CZA, MEV and IMR against these strains were determined using checkerboard assay and time-kill curve assay. Results: A total of 12 Enterobacterales strains producing dual-carbapenemases were collected, including nine K. pneumoniae, two P. rettgeri, and one E. hormaechei. The most common dual-carbapenemase gene pattern observed was bla (KPC-2+NDM-5) (n=4), followed by bla KPC-2+IMP-26 (n=3), bla (KPC-2+NDM-1) (n=2), bla (KPC-2+IMP-4) (n=1), bla (NDM-1+IMP-4) (n=1) and bla (KPC-2+KPC-2) (n=1). In each strain, the carbapenemase genes were found to be located on two distinct plasmids which were capable of conjugating from the original strain to the receipt strain E. coli J53. The results of the checkerboard synergy analysis consistently revealed good synergistic effects of the combination of ATM with CZA, MEV and IMR. Except for one strain, all strains exhibited significant synergistic activity and bactericidal activity between 2 and 8 hours. Conclusion: Dual-carbapenemase-producing Enterobacterales posed a significant threat to clinical anti-infection treatment. However, the combination of ATM with innovative ß-lactam/ß-lactamase inhibitor compounds had proven to be an effective treatment option.

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Treatment of Mycobacterium abscessus pulmonary disease requires multiple antibiotics including intravenous ß-lactams (e.g., imipenem). M. abscessus produces a ß-lactamase (BlaMab) that inactivates ß-lactam drugs but less efficiently carbapenems. Due to intrinsic and acquired resistance in M. abscessus and poor clinical outcomes, it is critical to understand the development of antibiotic resistance both within the host and in the setting of outbreaks. We compared serial longitudinally collected M. abscessus subsp. massiliense isolates from the index case of a cystic fibrosis center outbreak and four outbreak-related strains. We found strikingly high imipenem resistance in the later patient isolates, including the outbreak strain (MIC > 512 µg/mL). The phenomenon was recapitulated upon exposure of intracellular bacteria to imipenem. Addition of the ß-lactamase inhibitor avibactam abrogated the resistant phenotype. Imipenem resistance was caused by an increase in ß-lactamase activity and increased blaMab mRNA level. Concurrent increase in transcription of the preceding ppiA gene indicated upregulation of the entire operon in the resistant strains. Deletion of the porin mspA coincided with the first increase in MIC (from 8 to 32 µg/mL). A frameshift mutation in msp2 responsible for the rough colony morphology and a SNP in ATP-dependent helicase hrpA cooccurred with the second increase in MIC (from 32 to 256 µg/mL). Increased BlaMab expression and enzymatic activity may have been due to altered regulation of the ppiA-blaMab operon by the mutated HrpA alone or in combination with other genes described above. This work supports using carbapenem/ß-lactamase inhibitor combinations for treating M. abscessus, particularly imipenem-resistant strains.

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BACKGROUND: Antimicrobial resistance is a critical global health issue, significantly contributing to patient mortality. Recent antibiotic developments have aimed to counteract carbapenemase-producing Enterobacterales; however, the impact of their use on the emergence of antibiotic resistance is unknown. This study investigates the first case of a non-carbapenemase-producing, pan-ß-lactam-resistant Escherichia coli strain from a patient previously treated with ceftolozane-tazobactam and cefiderocol. METHODS: This study describes the clinical progression of a 39-year-old ICU patient who developed multiple infections, culminating in the isolation of a pan-ß-lactam-resistant E. coli strain (EC554). The resistance profile was characterised through MIC determination, whole-genome sequencing, the use of the ß-lactam inactivation method, RT-qPCR, efflux pump inhibition assays, outer membrane protein analysis, and blaTEM transformation. FINDINGS: The EC554 isolate displayed resistance to all tested ß-lactams and ß-lactam-ß-lactamase inhibitor combinations. Whole-genome sequencing revealed four plasmids in EC554, with the only ß-lactamase gene being blaTEM-252 on the pEC554-PBR-X1-X1 plasmid. We found that the extremely resistant phenotype was attributable to a combination of different mechanisms: a high expression of TEM-252, efflux pump activity, porin loss, and PBP3 mutations. INTERPRETATION: The findings illustrate the complex interplay of multiple resistance mechanisms in E. coli, highlighting the potential for high-level resistance even without carbapenemase production. This study underscores the importance of comprehensively characterising resistance mechanisms in order to inform effective treatment strategies and mitigate the spread of resistant strains.

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INTRODUCTION: Beta-lactam antibiotics (BLAs) commonly cause hypersensitivity reactions in children. These reactions are categorized into immediate reactions, which include urticaria, angioedema, bronchospasm, and anaphylaxis, and non-immediate reactions, such as maculopapular rashes and delayed-onset urticaria/angioedema. Rashes in children, often caused by infections, may be misdiagnosed as BLA allergy. However, over 90% tolerate the medication following an allergic evaluation. METHODS: We aimed to evaluate patients with negative single-day drug provocation test (sdDPT) results for subsequent reactions and to determine the negative predictive value (NPV) of sdDPT for immediate (less than 1 h) and non-immediate (more than 1 h) suspected BLA allergy. In addition, non-immediate reactions were assessed by classifying them as occurring within 1-6 h or after 6 h. Patients who underwent sdDPT for suspected BLA allergy and tested negative between 2019 and 2023 were included in the study. They were questioned via telephone interviews about their reuse of the tested drug. RESULTS: 404 patients who underwent sdDPT for suspected BLA allergy were evaluated. The NPV of BLA sdDPT was determined to be 97.3%. When patients were categorized based on the time interval between the last dose and the reaction, the NPV was 97% for those experiencing a reaction within the first hour of drug use and 96.7% for reactions occurring after more than 1 h. Non-immediate reactions were further evaluated, revealing an NPV of 98.7% for reactions occurring between 1 and 6 h, and 92.5% for reactions occurring after 6 h. CONCLUSION: Our findings demonstrate that sdDPT has a high NPV for both immediate and non-immediate reactions. However, the NPV of sdDPT was lower for reactions occurring more than 6 h after the last dose.

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An immunoassay method based on penicillin-binding protein (PBP) was developed for the quantitative determination of 10 kinds of beta-lactam antibiotics (BLAs). First, two kinds of PBPs, which are named PBP1a and PBP2x, were expressed and purified, and they were characterized by SDS-PAGE and western blotting analysis. Then, the binding activity of PBP1a and PBP2x to template BLAs, cefquinome (CEFQ) and ampicillin (AMP), was determined. The effect of the buffer solution system, e.g., pH, ion concentration, and organic solvent, on the immune interaction efficiency between PBPs and BLAs was also evaluated. In the end, the PBP-based immunoassay method was developed and validated for the detection of 10 kinds of BLAs. Under optimal conditions, PBPs exhibited high binding affinity to BLAs. In addition, this method showed a high sensitivity for the detection of 10 kinds of BLAs with the limits of detection from 0.21 to 9.12 ng/mL, which are much lower than their corresponding maximum residual limit of European Union (4-100 ng/mL). Moreover, the developed PBP-immunoassay was employed for BLA detection from milk samples, and satisfactory recoveries (68.9-101.3 %) were obtained.

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Clinical studies investigating the benefits of beta-lactam therapeutic drug monitoring (TDM) among critically ill patients are hindered by small patient groups, variability between studies, patient heterogeneity, and inadequate use of TDM. Accordingly, definitive conclusions regarding the efficacy of TDM remain elusive. To address these challenges, we propose an innovative approach that leverages data-driven methods to unveil the concealed connections between therapy effectiveness and patient data, collected through a randomized controlled trial (DRKS00011159; 10th October 2016). Our findings reveal that machine learning algorithms can successfully identify informative features that distinguish between healthy and sick states. These hold promise as potential markers for disease classification and severity stratification, as well as offering a continuous and data-driven "multidimensional" Sequential Organ Failure Assessment (SOFA) score. The positive impact of TDM on patient recovery rates is demonstrated by unraveling the intricate connections between therapy effectiveness and clinically relevant data via machine learning.

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Antibiotic therapy alters bacterial abundance and metabolism in the gut microbiome, leading to dysbiosis and opportunistic infections. Bacteroides thetaiotaomicron (Bth) is both a commensal in the gut and an opportunistic pathogen in other body sites. Past work has shown that Bth responds to ß-lactam treatment differently depending on the metabolic environment both in vitro and in vivo. Studies of other bacteria show that an increase in respiratory metabolism independent of growth rate promotes susceptibility to bactericidal antibiotics. We propose that Bth enters a protected state linked to an increase in polysaccharide utilization and a decrease in the use of simple sugars. Here, we apply antibiotic susceptibility testing, transcriptomic analysis, and genetic manipulation to characterize this polysaccharide-mediated tolerance (PM tolerance) phenotype. We found that a variety of mono- and disaccharides increased the susceptibility of Bth to several different ß-lactams compared to polysaccharides. Transcriptomics indicated a metabolic shift from reductive to oxidative branches of the tricarboxylic acid cycle on polysaccharides. Accordingly, supplementation with intermediates of central carbon metabolism had varying effects on PM tolerance. Transcriptional analysis also showed a decrease in the expression of the electron transport chain (ETC) protein NQR and an increase in the ETC protein NUO, when given fiber versus glucose. Deletion of NQR increased Bth susceptibility while deletion of NUO and a third ETC protein NDH2 had no effect. This work confirms that carbon source utilization modulates antibiotic susceptibility in Bth and that anaerobic respiratory metabolism and the ETC play an essential role.IMPORTANCEAntibiotics are indispensable medications that revolutionized modern medicine. However, their effectiveness is challenged by a large array of resistance and tolerance mechanisms. Treatment with antibiotics also disrupts the gut microbiome which can adversely affect health. Bacteroides are prevalent in the gut microbiome and yet are frequently involved in anaerobic infections. Thus, understanding how antibiotics affect these bacteria is necessary to implement proper treatment. Recent work has investigated the role of metabolism in antibiotic susceptibility in distantly related bacteria such as Escherichia coli. Using antibiotic susceptibility testing, transcriptomics, and genetic manipulation, we demonstrate that polysaccharides reduce ß-lactam susceptibility when compared to monosaccharides. This finding underscores the profound impact of metabolic adaptation on the therapeutic efficacy of antibiotics. In the long term, this work indicates that modulation of metabolism could make Bacteroides more susceptible during infections or protect them in the context of the microbiome.

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Among patients with hematopoietic stem cell transplants, infections, particularly multidrug-resistant infections, pose a grave threat. In this setting, penicillin allergy labels are both common and harmful. Though the majority of patients who report penicillin allergy can actually tolerate penicillin, penicillin allergy labels are associated with use of alternative antibiotics, which are often more broad spectrum, less effective, and more toxic. In turn, they are associated with more severe infections, multidrug-resistant infections, Clostridium difficile, and increased mortality. Evaluating penicillin allergy labels can immediately expand access to preferred therapeutic options, which are critical to care in patients with recent hematopoietic stem cell transplants. Point-of-care assessment and clinical decision tools now exist to aid the nonallergist in assessment of penicillin allergy. This can aid in expanding use of other beta-lactam antibiotics and assist in risk-stratifying patients to determine a testing strategy. In patients with low-risk reaction histories, direct oral challenges can be employed to efficiently delabel patients across clinical care settings. We advocate for multidisciplinary efforts to evaluate patients with penicillin allergy labels prior to transplantation.

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ß-Lactam antibiotics are a class of antibiotics commonly used to treat bacterial infections. However, the effects of ß-lactam antibiotics on term neonatal intestinal flora have not been fully elucidated. Hospitalized full-term newborns receiving ß-lactam antibiotics formed the antibiotic group (n = 67), while those without antibiotic treatment comprised the non-antibiotic group (n = 47). A healthy group included healthy full-term newborns (n = 16). Stool samples were collected for 16 S rDNA sequencing to analyze gut microbiota variations. Further investigation was carried out within the ß-lactam antibiotic group, exploring the effects of antibiotic use on the newborns' gut microbiota in relation to the duration and type of antibiotic administration, delivery method, and feeding practices. The antibiotic group exhibited significant difference of microbial community composition compared to the other groups. Genera like Klebsiella, Enterococcus, Streptococcus, Alistipes, and Aeromonas were enriched, while Escherichia-Shigella, Clostridium sensu stricto 1, Bifidobacterium, and Parabacteroides were reduced. Klebsiella negatively correlated with Escherichia-Shigella, positively with Enterobacter, while Escherichia-Shigella negatively correlated with Enterococcus and Streptococcus. Regardless of neonatal age, ß-lactam antibiotics induced an elevated abundance of Klebsiella and Enterococcus. The impact on gut microbiota varied with the duration and type of antibiotic (cefotaxime or ampicillin/sulbactam). Compared to vaginal delivery, cesarean delivery after ß-lactam treatment heightened the abundance of Klebsiella, Enterobacteriaceae_Unclassified, Lactobacillales_Unclassified, and Pectobacterium. Feeding patterns minimally influenced ß-lactam-induced alterations. In conclusion, ß-lactam antibiotic treatment for neonatal pneumonia and sepsis markedly disrupted intestinal microbiota, favoring Klebsiella, Enterococcus, Streptococcus, Alistipes, and Aeromonas. The impact of ß-lactam varied by duration, type, and delivery method, emphasizing heightened disruptions post-cesarean delivery.

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Introduction: Aminoglycosides possess activity against aerobic gram-negative organisms and are often used in combination with beta-lactam antibiotics. Previous studies evaluating combination therapy in gram-negative bacteremia have not shown clear benefits, however antimicrobial resistance was not prevalent in these studies. Our objective is to elucidate potential benefits of adding a single dose of an aminoglycoside to a beta-lactam in patients with gram-negative bacteremia. Methods: This study was a single-center, retrospective, cohort study including patients 18 years old or older and treated for at least 24 hours for a confirmed gram-negative bacteremia. Patients were divided into two groups: receipt of beta-lactam monotherapy (n = 164) and receipt of a beta-lactam in addition to a single dose of an aminoglycoside (n = 79) within 24 hours of bacteremia onset. The primary endpoint was infection-related 30-day mortality per provider documentation. Key secondary outcomes include incidence of acute kidney injury (AKI) and time to improvement of AKI. Data were analyzed using Chi-square or Fisher's exact tests, student's T test, and descriptive statistics as appropriate. Results: The primary outcome occurred in 13/164 vs 2/79 patients in the monotherapy and combination groups (P = 0.10). Incidence of AKI (14% vs. 12%) and time to recovery from AKI (90 hours; IQR [50 - 133] vs 78 hours; IQR [42 - 128]) were comparable between groups (P = 1.00 and P = 0.73, respectively). Conclusions: The addition of a single-dose aminoglycoside was not significantly associated with reduced mortality or increased time to recovery from AKI in our patient population. Larger studies, particularly in more severely ill patient populations, are needed.

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OBJECTIVES: The purpose of this study was to define current practices related to beta-lactam/beta-lactamase inhibitor (BL/BLI) dose descriptions in hospitals that provide care for pediatric patients and to identify perceived implications of standardizing BL/BLI dose communication and ordering to a total drug-based strategy. METHODS: A 27-item electronic survey was distributed via 4 pediatric pharmacy and infectious diseases listservs. Survey questions pertained to hospital demographics, dosing communication practices, BL/BLI ordering and labeling practices, obstacles to safe BL/BLI use, and the effects of potential standardization to a total drug communication strategy. SPSS was used for quantitative analysis and MAXQDA was used for qualitative analysis. RESULTS: A total of 140 unique survey responses were analyzed after exclusion of incomplete responses and reconciliation of multiple responses from the same institution. Overall, 56.2% of institutions order BL/BLIs by BL component for pediatric patients, and 22% of institutions order by BL component for adult patients. Approximately half (51.8%) of respondents felt that standardizing to total drug would have a negative effect at their institution; perception of potential effect varied based on the institution's ordering strategy. CONCLUSION: Communication and ordering of BL/BLIs is inconsistent across institutions and between pediatric and adult patients. In the short term, the perception is that standardization would compound institutional challenges.

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OBJECTIVE: Analyse the incidence, risk factors, antimicrobial susceptibility profile, and fatality in neonates infected with oxacillin-resistant Staphylococcus spp. (ORS). METHODS: In this retrospective observational descriptive cohort study, the medical records of neonates admitted to the Neonatal Intensive Care Unit (NICU) from January 2015 to June 2022 were analysed. Participants were monitored daily through the National Healthcare Safety Network. RESULTS: Among the 1610 neonates, 193 (12 %) developed ORS infections, primarily in the bloodstream (96.8 %). The incidence of these infections/patient-days decreased by 51.8 % between 2016 (8.3) and 2022 (4). The median age of affected neonates was 17.5 days (IQR:12-28.7). Pre-emptive prescription of fourth-generation cephalosporins (OR=14.36; P<0.01) emerged as a risk factor in the multivariate analysis. Staphylococcus epidermidis was the most prevalent species (60.1 %), with one isolate showing a "susceptible, increased exposure" profile to vancomycin. Additionally, 2 % of pathogens were extensively drug-resistant (XDR). ORS infections were associated with prolonged hospital stays (from 10 to 46 days) and increased mortality (from 10.2 % to 19.2 %). The median time between infection and the fatal outcome was 15 days (IQR:8-40), and Staphylococcus capitis was the most lethal species (26.7 %). CONCLUSIONS: The high incidence of ORS infections was linked to extended hospitalisation and increased mortality, highlighting the complexity of this situation - a "perfect storm." This underscores the urgency of implementing effective interventions for managing and preventing ORS infections in the NICU.

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AIMS: Population pharmacokinetics (PK) models may be effective in improving antibiotic exposure with individualized dosing. The aim of the study is to assess cefazolin exposure using a population PK model in critically ill children. METHODS: We conducted a single-centre observational study including children under 18 years old who had cefazolin plasma monitoring before and after a cefazolin model implementation. The first concentration at steady state of each cefazolin course was analysed. The optimal exposure was defined by concentration values ranging from free concentration over four times the minimal inhibitory concentration (MIC) for 100% of the dosing interval to total trough or plateau concentration under 100 mg. L-1. RESULTS: A total of 58 patients were included, of whom 39 and 19 children received conventional dosing or model-informed dosing, respectively. Median [range] age was 2.3 [0.1-17] years old, and median weight was 14.2 [2.9-72] kg. There were more continuous infusions (CI) in the model group than in the conventional group (n = 19/19 [100%] vs. n = 23/39 [59%]). Compared to conventional dosing, model-informed dosing provided more optimal exposure (n = 17/39 [44%] vs. n = 15/19 [79%], P = .01) and less underexposure (n = 18/39 [46%] vs. n = 2/19 [10%], P = .008), without increasing overexposure (n = 4/39 [10%] vs. n = 2/19 [11%], P = 1). Moreover, the time to C-reactive protein decrease by 50% was significantly shorter in the model group than the conventional group (3 [0.5-13] vs. 4 [1-34]; P = .045). CONCLUSIONS: Use of individualized cefazolin model-informed dosing improves critically ill children's exposure. Further studies are needed to assess the clinical benefit of cefazolin PK model application.