Search Results (1,221)

Objective: The impact of a febrile neutropenia (FN) emergency department (ED) triage screening tool and protocol on time to antibiotic administration (TTA) and patient outcomes was evaluated. Methods: This was a retrospective, quasi-experimental study of adult FN patients admitted through the ED from April 2014 to April 2017. In March 2016 a triage screening tool and protocol were implemented. In patients who screened positive, nursing initiated a protocol that included laboratory diagnostics and a pharmacy consult for empiric antibiotics prior to evaluation by a provider. Patients were evaluated pre- and post-protocol for TTA, 30-day mortality, ED length of stay (LOS), and hospital LOS. Results: A total of 130 patients were included in the study, 77 pre-protocol and 53 post-protocol. Median TTA was longer in the pre-protocol group at 174 min (interquartile range [IQR] 105–224) vs. 109 min (IQR 71–214) post-protocol, p = 0.04. Thirty-day mortality was greater at 18.8% pre-protocol vs. 7.5% post-protocol, p = 0.12. There was no difference in hospital LOS. Pre-protocol patients compared to post-protocol patients who had a pharmacy consult demonstrated a further reduction in TTA (174 min [IQR 105–224] vs. 87.5 min [IQR 61.5–135], p < 0.01) and a reduced mortality (18% vs. 0%, p = 0.04). Conclusions: To our knowledge, this is the first report of a protocol for febrile neutropenia that allows pharmacists to order antibiotics based on a nurse triage assessment. Evaluation of the protocol demonstrated a significant reduction in TTA and trend toward improved mortality. Full article

Background: Broad-spectrum antibiotics are often used for suspected infections in patients with hematologic malignancies due to the risk of severe infections. Although antibiotic use can lead to antimicrobial resistance and microbiome dysbiosis, the effects of antibiotics on the microbiome and resistome in patients with acute myeloid leukemia (AML) undergoing remission induction chemotherapy (RIC) are not well understood. Methods: Various statistical models were utilized to examine the effects of antibiotic administration on the microbiome and resistome over time, as well as differences in AR-infection (ARI) and colonization (ARC) by important CDC-threats in 119 AML patients. Results: A greater number of unique antibiotic classes administered correlated with a loss of unique antibiotic resistance genes (ARGs) (R = −0.39, p = 0.008). Specifically, although a greater number of oxazolidinone administrations was correlated with a greater loss of diversity (R = −0.58, p < 0.001), each additional day of linezolid reduced the risk of ARC by ~30% (HR: 0.663, p = 0.047) and decreased the odds of acquiring genes predicted to confer macrolide (HR: 0.50, p = 0.026) resistance. Conclusions: The number of antibiotic administrations and the types of antibiotics used can influence the risk of antibiotic resistance gene (ARG) expansion and ARC events in AML patients undergoing RIC. While certain antibiotics may reduce microbial diversity, they are not always linked to an increase in ARGs or ARC events. Full article

Antibiotic residues in poultry pose health and resistance risks, necessitating breed-specific WDTs. In this study, the residue elimination patterns of seven antibiotics in Taihang chicken tissues under free-range conditions were studied and the appropriate WDT was formulated. A total of 240 healthy Taihang chickens aged 100 days were randomly divided into 8 groups, each comprising 30 chickens. Chickens in groups 1 to 7 were administered oxytetracycline, chlortetracycline, erythromycin, tylosin, tylvalosin, lincomycin, and tiamulin, respectively. Regarding the administration method, we adopted the highest dose and maximum course of treatment recommended by the Veterinary Pharmacopoeia of the People’s Republic of China. Group 8 served as the control group. Muscle, sebum, liver, and kidney samples were collected at 4 h, 1 d, 2 d, 3 d, 5 d, 7 d, 10 d, 13 d, and 16 d after drug withdrawal. Our results demonstrated that the drug residues after drug withdrawal gradually decreased with the increase in drug withdrawal days, and the elimination rate in the early stage of drug withdrawal was significantly faster than that in the later stage. At 4 h after drug withdrawal, the drug residues in various tissues reached their highest values. In most cases, the drug concentrations in the kidney and liver were higher than those in the muscles and sebum; however, some drugs also exhibited concentration peaks in the sebum. On the first day of drug withdrawal, the amount of residues in various tissues decreased rapidly. In general, the elimination rate of various drugs in the muscles, liver, and kidneys is faster but slower in the sebum. Based on the WDT calculation software WT1.4, the recommended WDTs for oxytetracycline, chlortetracycline, erythromycin, tylosin, tylvalosin, lincomycin, and tiamulin chickens are 4 d, 5 d, 11 d, 8 d, 13 d, 13 d, and 7 d, respectively. These findings support food safety and industry development. Full article

Hernia is a physiological condition that significantly impacts patients’ quality of life. Surgical treatment for hernias often involves the use of specialized meshes to support the abdominal wall. While this method is highly effective, it frequently leads to complications such as pain, infections, inflammation, adhesions, and even the need for revision surgeries. According to the Food and Drug Administration (FDA), hernia recurrence rates can reach up to 11%, surgical site infections occur in up to 21% of cases, and chronic pain incidence ranges from 0.3% to 68%. These statistics highlight the urgent need to improve mesh technologies to minimize such complications. The design and material composition of meshes are critical in reducing postoperative complications. Moreover, integrating drug-eluting properties into the meshes could address issues like infections and inflammation by enabling localized delivery of antibiotics and anti-inflammatory agents. Mesh design is equally important, with innovative structures like auxetic designs offering enhanced mechanical properties, flexibility, and tissue integration. These advanced designs can distribute stress more evenly, reduce fatigue, and improve performance in areas subjected to high pressures, such as during intense coughing, sneezing, or heavy lifting. Technological advancements, such as 3D printing, enable the precise fabrication of meshes with tailored designs and properties, providing new opportunities for innovation. By addressing these challenges, the development of next-generation mesh implants has the potential to reduce complications, improve patient outcomes, and significantly enhance quality of life for individuals undergoing hernia repair. Full article

Infections with multidrug-resistant (MDR) organisms remain a significant cause of morbidity and mortality among liver transplant recipients, despite advances in surgical techniques and immunosuppressive therapy. This prospective observational study aimed to evaluate the impact of targeted perioperative antibiotic prophylaxis against MDR Gram-negative bacteria on postoperative infections and mortality in liver transplant recipients. Seventy-nine adult patients who underwent liver transplantation and were admitted to the ICU for more than 24 h postoperatively were included. Demographics, disease severity scores, comorbidities, and lengths of ICU and hospital stay were recorded. Colonization with carbapenem-resistant Gram-negative bacteria was assessed via preoperative and postoperative cultures from the blood, urine, rectum, and tracheal secretions. Patients were divided into two groups: those with MDR colonization or infection who received targeted prophylaxis and controls who received standard prophylaxis. Infectious complications (30.4%) occurred significantly less frequently than non-infectious ones (62.0%, p = 0.005). The most common infections were bacteremia (22.7%), pneumonia (17.7%), and surgical site infections (2.5%), with most events occurring within 15 days post-transplant. MDR pathogens isolated included Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Although overall complication and mortality rates at 30 days and 3 months did not differ significantly between groups, the targeted prophylaxis group had fewer infectious complications (22.8% vs. 68.5%, p = 0.008), particularly bacteremia (p = 0.007). Infection-related mortality was also significantly reduced in this group (p = 0.039). These findings suggest that identification of MDR colonization and administration of targeted perioperative antibiotics may reduce septic complications in liver transplant patients. Further prospective studies are warranted to confirm benefits on outcomes and resource utilization. Full article

Introduction/Objective: Peritonitis remains a serious complication in patients undergoing automated peritoneal dialysis (APD), requiring prompt and effective antibiotic administration. This study evaluated whether delivering antibiotics directly through APD bags is as effective as administering them via an additional manual daytime exchange. Methods: We conducted a randomized, single-blind, non-inferiority clinical trial involving patients diagnosed with peritonitis. Participants were randomly assigned to receive Ceftazidime and Vancomycin, either via APD bags or through a combined approach of continuous ambulatory peritoneal dialysis (CAPD) plus APD. A total of 64 patients (32 per group) were enrolled, with comparable baseline demographic and clinical profiles, including laboratory markers of infection severity and dialysis history. Results: Peritonitis resolved in 90.6% of the patients treated via APD bags and in 81.3% of those receiving antibiotics through manual exchange plus APD. Although this difference did not reach statistical significance ($p$ = 0.281), the observed absolute difference of 9.3% was well within the predefined non-inferiority margin of 30%, supporting the clinical non-inferiority of the APD-only method. The mean time to resolution was similar between groups ($p$ = 0.593). Post hoc power analyses indicated limited statistical power (18.5% for the resolution rate and 9.2% for time to resolution), suggesting that modest differences may not have been detectable given the sample size. Nevertheless, the high resolution rates observed in both groups reflect valid and encouraging clinical outcomes. Conclusion: Antibiotic administration via APD bags demonstrated comparable clinical effectiveness to the combined manual exchange plus APD method for treating peritonitis. Given its operational simplicity and favorable results, the APD-only strategy may offer a pragmatic alternative in routine care. Further studies with larger sample sizes are recommended to confirm these findings and optimize treatment protocols. Trial registration: NCT04077996. Funding source: None to declare. Full article

Background: Aspiration pneumonia is increasingly recognized as a fatal pulmonary disease among older people. Although antipseudomonal antibiotics are commonly used in clinical practice, their efficacy in this population remains uncertain. Methods: Nationwide data collected from patients aged ≥65 years who were hospitalized due to aspiration pneumonia from January 2018 to December 2018 were analyzed. The in-hospital mortality between patients who received antipseudomonal antibiotics within 3 days of hospital admission and those who did not were compared. A logistic regression analysis was performed to assess the effect of antipseudomonal antibiotics on in-hospital mortality after adjusting for potential prognostic confounders. Results: This study included 46,980 patients, and 13,340 (28.4%) patients received antipseudomonal antibiotics. In total, 7011 (14.9%) patients died during hospitalization. Advanced age, male sex, a lower body mass index, decreased Barthel Index, impaired consciousness, interstitial pneumonia, malignancy, renal failure, and use of immunosuppressive agents were significantly associated with increased in-hospital mortality. After adjusting for the confounders, the use of antipseudomonal antibiotics was found to be associated with an elevated in-hospital mortality (odds ratio: 1.33; 95% confidence interval: 1.26–1.41; p < 0.001). Conclusions: In this nationwide data analysis of older patients with aspiration pneumonia, early antipseudomonal antibiotic administration did not improve prognosis. Therefore, the routine use of antipseudomonal antibiotics should be avoided in older patients with aspiration pneumonia. Full article

Infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-Es) pose a significant global threat with notable increases in prevalence worldwide. Carbapenems are often used as the first line of treatment. However, their overuse accelerates resistance development, highlighting the urgent need for clinically viable carbapenem-sparing strategies. Cefmetazole (CMZ) and flomoxef (FMOX) are parenteral antibiotics that are widely used in Japan and have emerged as potential carbapenem alternatives. Repositioning these agents effectively addresses the clinical need for carbapenem-sparing strategies and outpatient ESBL-E management. This review aims to reposition CMZ and FMOX for real-world clinical practice by synthesizing basic research, clinical studies, and pharmacokinetics/pharmacodynamics (PKs/PDs) analyses, which suggest that these agents may be effective in treating ESBL-E infections—particularly urinary tract infections, as evidenced by their minimum inhibitory concentration (MIC) values. The clinical outcomes of these interventions have been comparable to those of carbapenems, which support their role in antimicrobial stewardship. Their PK/PD characteristics emphasize the importance of dose optimization to ensure therapeutic efficacy, whereas recent insights into resistance mechanisms provide a foundation for appropriate use. As novel antibiotic development takes substantial time, revisiting existing options is increasingly important. Notably, the Infectious Diseases Society of America’s 2024 guidance on antimicrobial resistance has omitted CMZ and FMOX, owing to which clinicians have limited guidance on their use, particularly in regions like Japan where these antibiotics are widely employed. By addressing this knowledge gap, the present review offers a comprehensive evaluation of these drugs and highlights their potential as intravenous agents in ESBL-E management. Furthermore, it highlights the ongoing challenge of ensuring effective oral step-down therapy in an outpatient setting to reinforce the global relevance of CMZ and FMOX in a broader treatment framework, underscoring their potential for outpatient administration where clinically appropriate. Full article

Subclinical mastitis causes economic losses due to reduced milk yield and elevated somatic cell counts (SCCs), despite no visible clinical signs. A higher incidence of subclinical mastitis has been reported in cattle infected with bovine leukemia virus (BLV). Levamisole (LMS), known for its immunomodulatory properties, has been suggested as a potential alternative to antibiotics for mastitis treatment; however, its efficacy in BLV-infected cows, particularly in relation to proviral load (PVL), remains unclear. This study aimed to evaluate the therapeutic effect of LMS on subclinical mastitis and its impact on milk immune responses by classifying BLV-infected cows based on PVL. A total of 42 dairy cows with subclinical mastitis (48 quarters) were grouped as BLV-negative, low-PVL, or high-PVL using a PVL cut-off value of 17.8 copies/10 ng DNA, and were administered LMS orally. Changes in viable bacterial counts, SCCs, and milk leukocyte populations were compared. LMS administration significantly reduced the SCC and milk macrophage numbers, especially in BLV-negative and low-PVL cows. These results suggest that LMS may improve subclinical mastitis in certain BLV-infected cows and that PVL may serve as a useful indicator for treatment responsiveness. However, the limited effect in high-PVL cows and the small sample size have limitations, warranting further investigation. Full article

The anti-inflammatory effect of trypsin in animals and humans is the basis for the development of new veterinary and medical drugs and alternatives to antibiotics. The current experiment analyzed the effect of pig pancreatic tissue lyophilizate and crystalline trypsin on the hemodynamic and morpho-biochemical parameters of rabbit blood. The experiments were carried out on 20 rabbits of the Soviet chinchilla breed of 6–8 months of age. Animals were intramuscularly injected with sterile solution of 0.9% NaCl in 0.5 mL (group 1, n = 5), sterile solution of crystalline trypsin in 0.9% NaCl at a concentration of 0.25 mg/kg body weight (group 2, n = 5), sterile solution of crystalline trypsin in 0, 9% NaCl at a concentration of 0.5 mg/kg body weight (group 3, n = 5), or sterile suspension of pig pancreas lyophilizate at a concentration of 1 mg/kg body weight (group 4, n = 5). Animals were injected once daily for five consecutive days. Significant changes in arterial blood pressure, serum enzymes activity, and the count of various blood cellular components were induced by the administration of different trypsin preparations. All data obtained indicate the presence of a biologically active substance in the lyophilizate, the effect of which requires further animal studies to create a prototype for the development of new drugs for human and animal use. Full article

Background/Objectives: The increased use of antibiotics is raising concerns about environmental contamination and antibiotic resistance, exemplified by the case of cotrimoxazole, a widely prescribed combination of sulfamethoxazole and trimethoprim. After oral administration and absorption, both drugs are excreted in their parent and metabolized forms, which is a factor that is commonly considered in environmental studies. Many studies, however, rely on pharmacokinetic data from drug developers, who mostly investigate drug metabolism in healthy male volunteers rather than in actual patient populations. Methods: We investigated the real-world metabolism and urinary excretion of cotrimoxazole in an LC-SWATH/MS-based pharmacometabolomics study of 149 kidney transplant recipients who took part in the TransplantLines Biobank and Cohort Study (NCT0327284). Results: Our study confirmed (as “putatively characterized compound classes”) the presence of all the expected metabolites, and we (putatively) identified several previously unreported metabolites, including glucuronide conjugates of both drugs and two isoxazole ring-opened variants of sulfamethoxazole. The relative metabolite profiles furthermore indicated that the active drug trimethoprim accounted for 75% of the total signal intensity. For sulfamethoxazole, its acetylated metabolite was the main metabolite (59%), followed by the active parent drug (17%) and its glucuronide (7%). Alongside trimethoprim, these substances could serve as analytical targets for environmental cotrimoxazole monitoring, given their abundance (all three substances), activity (parent drug), and/or back-transformation potential (both conjugated metabolites). The isoxazole ring-opened variants (2–3%) may also warrant attention, considering their (presumed) absolute excreted quantities and potential pharmacological activity. Conclusions: This study underscores the value of pharmacometabolomics in elucidating real-world metabolite profiles, and it provides novel insights into cotrimoxazole metabolism and excretion, with implications for environmental and clinical monitoring. Full article

Background/Objectives: The gut microbiota (GM) is pivotal for immune regulation, metabolism, and neurodevelopment. Infants undergoing surgery for congenital gastrointestinal anomalies are especially prone to microbial imbalances, with a paucity of beneficial bacteria (e.g., Bifidobacteria and Bacteroides) and diminished short-chain fatty acid production. Dysbiosis has been associated with severe complications, including necrotizing enterocolitis, sepsis, and feeding intolerance. This narrative review aims to critically examine strategies for microbiota modulation in this high-risk cohort. Methods: An extensive literature analysis was performed to compare the evolution of GM in healthy neonates versus those requiring gastrointestinal surgery, synthetizing strategies to maintain eubiosis, such as early nutritional interventions—particularly the use of human milk—along with antibiotic management and supplementary treatments including probiotics, prebiotics, postbiotics, and lactoferrin. Emerging techniques in metagenomic and metabolomic analysis were also evaluated for their potential to elucidate microbial dynamics in these patients. Results: Neonates undergoing gastrointestinal surgery exhibit significant alterations in microbial communities, characterized by reduced levels of eubiotic bacteria and an overrepresentation of opportunistic pathogens. Early initiation of enteral feeding with human milk and careful antibiotic stewardship are linked to improved microbial balance. Adjunctive therapies, such as the administration of probiotics and lactoferrin, show potential in enhancing gut barrier function and immune modulation, although confirmation through larger-scale studies remains necessary. Conclusions: Modulating the GM emerges as a promising strategy to ameliorate outcome in neonates with congenital gastrointestinal surgical conditions. Future research should focus on the development of standardized therapeutic protocols and the execution of rigorous multicenter trials to validate the efficacy and safety of these interventions. Full article

Background: Cytokine release syndrome (CRS) is a life-threatening systemic inflammatory condition marked by excessive cytokine production, leading to multi-organ dysfunction. It is commonly associated with T-cell-engaging therapies such as chimeric antigen receptor (CAR) T cells, T-cell receptor bispecific molecules, and monoclonal antibodies. Carfilzomib, a proteasome inhibitor, is known to cause a range of adverse effects, primarily hematologic and cardiovascular. However, multiorgan failure grade 5 (fatal), resembling CRS has not been previously reported in association with Carfilzomib. Case Report: A 74-year-old male with relapsed multiple myeloma developed grade 5 multiorgan failure 60 min after the third dose of Carfilzomib, resulting in death within 24 h of symptom onset. The patient tolerated the first doses of Carfilzomib well with only fever and headache developing post infusion. Before the second dose, the patient developed worsening pancytopenia, prompting the discontinuation of Lenalidomide. After the second Carfilzomib infusion, he experienced fever and transient encephalopathy, which resolved with acetaminophen, corticosteroids, and supportive care. However, following the third dose, he rapidly deteriorated—developing fever, tachycardia, hypotension, hypoxia, and encephalopathy. Despite aggressive management with intravenous fluids, broad-spectrum antibiotics, corticosteroids, and tocilizumab, the patient progressed to refractory shock and multi-organ failure, culminating in death within 24 h. A comprehensive infectious workup was negative, ruling out sepsis and suggesting possible Carfilzomib-induced CRS. Conclusion: Grade 5 multiorgan failure with signs and symptoms similar with CRS following Carfilzomib administration is a rare but potentially fatal adverse drug reaction. Further research is needed to better define the risk factors and optimal management strategies for Carfilzomib-induced multiorgan failure and possible CRS. Full article

Due to the significant number of microbiologically negative periprosthetic joint infections (PJIs), understanding the trend in etiology and resistance patterns is essential for the correct management of these infections. Currently, few studies have been published in Spain. In this study, we analyzed the incidence, clinical characteristics, etiology, and antibiotic resistance in patients with PJIs over the last 5 years in Navarra. In this multicentric and retrospective study, all patients diagnosed with PJIs in Navarra from 2019 to 2023 were included. Of the total 156 PJIs, 23% had negative cultures and 56% of these patients had been treated with antibiotics prior to sampling. Staphylococcus epidermidis with methicillin resistance was the predominant etiological agent, followed by Staphylococcus aureus and Cutibacterium acnes. Forty percent of the Gram-positive cocci (GPC) and 35% of the Gram-negative bacilli (GNB) were multidrug-resistant organisms (MDROs). Quinolone resistance was 46% for staphylococci and 18% for Gram-negatives. In addition, 9% of staphylococci were resistant to rifampicin. Antibiotic therapy administration prior to sampling is one of the main problems for microbiological diagnosis and is present more frequently in culture-negative PJIs (56%). New sequencing techniques could improve this difficulty. The high percentage of resistance in the microorganisms causing PJI leads us to reconsider the empirical treatment for suspected PJI, with the use of different therapeutic approaches depending on the time of infection and the possible use of new non-antibiotic therapies. Full article

Background/Objectives: Early diagnosis and oral or, in severe cases, intravenous antibiotics are usually effective for Lyme disease, but some patients have persistent symptoms unresponsive to standards of care, requiring alternative therapies. Disulfiram (DIS), a drug for alcoholism, is under investigation as a potential adjunctive treatment, but its low bioavailability, rapid metabolism, and safety concerns urge the development of improved formulations for clinical translation. Methods: Screening dissolution and permeation studies were investigated for vehicle and excipient selection, following the pharmacopeia perspectives to develop and optimize the low-dose DIS rectal suppository intended for application in post-treatment Lyme disease syndrome (PTLDS). Further characterizations were carried out by differential scanning calorimetry, X-ray diffraction, and infrared spectroscopy. Results: Cyclodextrin (CD) encapsulation was investigated to improve the aqueous solubility of the hydrophobic drug. The dissolution of DIS from fatty base suppository was very slow; it was remarkably improved by the molecular encapsulation of the drug with CDs. The dissolution of DIS from a water-soluble base was more favorable, but incomplete. In the polyethylene glycol (PEG) based suppositories, the addition of CDs already in a physical mixture ensured the dissolution of the drug. The presented drug delivery system relates to a novel preparation for rectal administration comprising a low-dose disulfiram with improved solubility and permeability by the PEG and hydroxypropyl-β-cyclodextrin (HPBCD) synergistic matrix. Conclusions: The rectal dosage form containing the drug and CD in the physical mixture is advantageous, avoiding the hepatic first-pass effect, minimizing dose-limiting toxicity, simplifying production, and fasting the availability of the repositioned drug. Full article