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Journal of Medicinal Chemistry Jul 2024(Mtb), the infectious agent of tuberculosis (TB), causes over 1.5 million deaths globally every year. Host-directed therapies (HDT) for TB are desirable for their...
(Mtb), the infectious agent of tuberculosis (TB), causes over 1.5 million deaths globally every year. Host-directed therapies (HDT) for TB are desirable for their potential to shorten treatment and reduce the development of antibiotic resistance. Previously, we described a modular biomimetic strategy to identify , targeting PPM1A (IC = 1.19 μM), a metal-dependent phosphatase exploited by Mtb to survive intracellularly. restricted the survival of Mtb in macrophages and lungs of infected mice. Herein, we redesigned to create , which is a more potent inhibitor for PPM1A (IC = 180 nM). efficiently increased the level of phosphorylation of S403-p62 and the expression of LC3B-II to activate autophagy, resulting in the dose-dependent clearance of Mtb in infected macrophages. possesses a good pharmacokinetic profile and oral bioavailability ( = 74%). In vivo, is well tolerated up to 50 mg/kg and significantly reduces the bacteria burden in the spleens of infected mice.
PubMed: 38958057
DOI: 10.1021/acs.jmedchem.4c00513 -
Surgical Infections Jul 2024Hip fractures are the most common serious injury in the elderly, associated with disability, morbidity, and mortality. Surgical site infection (SSI) is a serious...
Hip fractures are the most common serious injury in the elderly, associated with disability, morbidity, and mortality. Surgical site infection (SSI) is a serious post-operative complication. This prospective cohort study outlines how our center made cumulative improvements in SSI incidence rates, reaching a 12-month average of 0.5%. All patients undergoing hip fracture operation between 2016 and 2021 were included. The primary outcome measure was confirmed SSI, according to the Public Health England definition. Results were compared with the baseline recordings by an independent SSI team in 2013. Demographic data were compared with National Hip Fracture Database records. Peri-operative infection control and wound management tactics introduced between 2014 and 2021 were collated to gain an overview care bundle. Baseline recordings identified a 9.0% SSI rate in a three-month observation period. In our study, 3,138 hip fracture operative cases were completed between October 2016 and December 2021. There were 9 superficial and 32 deep infections identified, yielding an overall infection rate of 1.3%. However, when analyzing the 12-month average, there was consistent decline in SSI from the baseline 9.0% in 2013 to 0.5% in 2021 (p < 0.05). A peri-operative care bundle included pre-operative bleeding risk assessment. Intra-operatively, double preparation and draping is used for arthroplasty. Broad-spectrum antibiotic agents and tranexamic acid are administered. Meticulous hemostasis and watertight wound closure are observed. Anti-coagulated patients received negative pressure dressings. Post-operatively, a dedicated senior lead team provided daily inpatient review of patients, with urgent consultant review of all wound healing concerns. Patients with a hip fracture have numerous risk factors for SSI. A dedicated multi-focal tactic, adopted by a multi-disciplinary department, can yield substantial risk reduction. Each intervention is evidence based and contributes to cumulative improvement. By prioritizing infection prevention, we have minimized the need for complex infection management interventions and achieved an annual saving of £860,000 for our trust.
PubMed: 38958043
DOI: 10.1089/sur.2024.019 -
Journal of Materials Chemistry. B Jul 2024Surgical site infection (SSI) caused by pathogenic bacteria leads to delayed wound healing and extended hospitalization. Inappropriate uses of antibiotics have caused a...
Surgical site infection (SSI) caused by pathogenic bacteria leads to delayed wound healing and extended hospitalization. Inappropriate uses of antibiotics have caused a surge in SSI and common antibiotics are proving to be ineffective against SSI. Antimicrobial peptides (AMPs) can be a potential solution to prevent SSI because of their broad spectrum of antimicrobial activities. In this study, naturally sourced AMPs were studied along with microfibers, fabricated by a novel wet-spinning method using sodium alginate and polycaprolactone. Afterward, fibers were functionalized by the catechol groups of dopamine immobilizing nucleophilic AMPs on the surface. Conjugation between PCL and alginate resulted in fibers with smooth surfaces improving their mechanical strength hydrogen bonds. Having an average diameter of 220 μm, the mechanical properties of the fiber complied with USP standards for suture size 3-0. Engineered microfibers were able to hinder the growth of spp., a pathogenic bacterium for at least 60 hours whereas antibiotic ceftazidime failed. When subjected to a linear incisional wound model study, accelerated healing was observed when the wound was closed using the engineered fiber compared to Vicryl. The microfibers promoted faster re-epithelialization compared to Vicryl proving their higher wound healing capacity.
PubMed: 38958038
DOI: 10.1039/d4tb00889h -
Foodborne Pathogens and Disease Jul 2024Goats are often asymptomatic carriers of , including the foodborne pathogen Infections can have significant and economically detrimental health outcomes in both humans...
Goats are often asymptomatic carriers of , including the foodborne pathogen Infections can have significant and economically detrimental health outcomes in both humans and animals. The primary objective of this study was to estimate the prevalence of in U.S. goat herds. species were isolated from 106 of 3,959 individual animals and from 42 of 277 goat operations that participated in fecal sample collection as part of the National Animal Health Monitoring System Goat 2019 study. Weighted animal-level prevalence was 2.3% (SE = 0.5%) and operation prevalence was 13.0% (SE = 3.2%). Animal-level prevalence ranged widely from 0 to 70.0%, however, 52.4% of positive operations (22/42) had only a single isolate. was the most frequently isolated species (68.9%; 73/106), followed by (29.3%, 31/106). A total of 46.2% (36/78) of viable isolates were pan-susceptible to 8 antimicrobials. Resistance to tetracycline (TET) was observed in 44.9% (35/78) of isolates, while 12.8% (10/78) were resistant to ciprofloxacin (CIP) and nalidixic acid (NAL). Among all isolates, a single resistance profile CIP-NAL-TET was observed in 3.8% (3/78) of isolates. A total of 35 unique sequence types (STs) were identified, 11 of which are potentially new. Multiple STs were observed in 48.1% (13/27) of positive operations. Goats with access to surface water, operations reporting antibiotics in the feed or water (excluding ionophores and coccidiostats), and operations reporting abortions and without postabortion management tasks had significantly greater odds of being positive. This snapshot of the U.S. goat population enriches the limited pool of knowledge on species presence in U.S. goats.
PubMed: 38957999
DOI: 10.1089/fpd.2023.0080 -
Surgical Infections Jul 2024Post-partum infection is a major contributor to maternal mortality and is responsible for approximately 10% of maternal fatalities worldwide. The risk of infection is...
Post-partum infection is a major contributor to maternal mortality and is responsible for approximately 10% of maternal fatalities worldwide. The risk of infection is substantially higher in cesarean section procedures. Approximately 8% of women who undergo cesarean sections are susceptible to infection. Although the body of evidence supporting the regular pre-operative utilization of prophylactic antibiotic treatment is steadily expanding, its usefulness in cesarean sections has not yet been standardized, and post-partum infection is still a serious medical challenge. We aimed to retrospectively assess the prophylactic effectiveness of cefazolin in combination with other antibiotic agents in cesarean sections. Both uni-variable and multi-variable analyses were conducted to identify factors that may affect cefazolin pre-operative antibiotic prophylaxis in elective cesarean section operations. The uni-variable analysis included timing of administration, operation duration, body mass index (BMI), and wound type. A multi-variable logistic regression model was then created to determine which variables provide independent information in the context of other variables. Time of administration did not affect prophylactic cefazolin efficacy. However, prophylactic cefazolin was 1.43 and 1.77 times more effective when the operation lasted for 45 minutes or more, compared with operations that were shorter than 45 minutes. Patients with a BMI ranging from 18 to 29 kg/m showed increased efficacy of prophylactic cefazolin compared with obese patients with a BMI exceeding 30 kg/m. The effectiveness of prophylactic cefazolin decreased by 95% in patients with clean-contaminated surgical incisions compared with those with clean surgical incisions. Our findings demonstrate that administering pre-operative prophylactic antibiotic agents to women undergoing cesarean section resulted in a reduction in post-partum infections, thereby reducing maternal mortality. Furthermore, optimal timing of administration, re-dosing if necessary, length of prophylactic medication, and dosing adjustments for obese patients are crucial factors in preventing surgical site infections and promoting antimicrobial stewardship.
PubMed: 38957977
DOI: 10.1089/sur.2024.048 -
Surgical Infections Jul 2024The prophylactic use of antibiotics in parotid region surgery continues to be a subject of debate. The aim of this study is to elucidate the impact of antibiotic...
The prophylactic use of antibiotics in parotid region surgery continues to be a subject of debate. The aim of this study is to elucidate the impact of antibiotic prophylaxis on surgical site infections (SSIs) in parotid region surgery. Patients who received antibiotic prophylaxis during the peri-operative period were designated as group 1, whereas those who did not were categorized into group 2. Group 1 cases were further subdivided into three subgroups based on different antibiotic usage patterns. Patient individual information was collected. Clinical data such as surgical duration, post-operative hospital stay, incision infection status, and antibiotic usage were recorded. All data were compared and analyzed among different groups. A total of 357 patients were included in the study, with no statistically significant differences in baseline characteristics. Pre-operative American Society of Anesthesiologists scores did not significantly differ between groups (p = 0.151), but there was a significant distinction in National Nosocomial Infection Surveillance (NNIS) index values (p = 0.044). Furthermore, surgical duration (p = 0.001) and pathology types (p = 0.016) differed significantly. The post-operative hospital stay in group 1 was longer than that in group 2 (p < 0.01). The post-operative SSI rate in group 1 was lower than that in group 2 without statistical significance (2.55% vs. 5.59%, p = 0.141). The logistic regression analysis showed that malignant tumors, longer surgical durations, and higher NNIS index scores correlated positively with post-operative SSI rates. Meanwhile, compared with non-use, all three different antibiotic use modes correlated negatively with SSI occurrence. Antibiotic prophylaxis in parotid gland surgery shows no significant reduction in SSI occurrence. If there is a compelling reason to administer prophylactic antibiotics, pre-operative single dose may be a relatively feasible measure for preventing SSIs.
PubMed: 38957972
DOI: 10.1089/sur.2024.054 -
Surgical Infections Jul 2024Surgical antimicrobial prophylaxis (SAP), when used appropriately based on evidence-based guidelines, can reduce the rate of infectious complications following...
Surgical antimicrobial prophylaxis (SAP), when used appropriately based on evidence-based guidelines, can reduce the rate of infectious complications following endourologic procedures without compromising patient outcomes. To investigate the appropriateness of the current SAP used in endourologic surgeries based on international guidelines and report their associated outcomes (urinary tract infection [UTI] and blood stream infection [BSI]). Prospective cross-sectional study. The medical records of patients undergoing endourologic procedures were reviewed to assess healthcare providers' adherence to international guideline recommendations. Assessed parameters included indication, duration, choice, and dose of the antibiotics used in endourologic procedures in two medical centers in Amman/Jordan. Furthermore, patients were asked to conduct laboratory urine tests to determine the rate of infectious complications within one month post-procedure. Three hundred and sixty-one patients were recruited for the study. The adherence rates to guidelines regarding indication, choice, and dose of pre-operative antibiotics were 90.3%, 2.8%, and 77.8%, respectively. The duration was concordant with guidelines in only 3.4% of participants. A total of 41.8% of patients completed follow-up. Among those, 4.6% developed bacterial UTIs, and 0.7% developed BSI. Adherence to SAP guidelines in endourologic procedures was far from optimal. Primary deviations in the implementation of guidelines' recommendations were pinpointed. These results are crucial for planning interventions that optimize SAP utilization.
PubMed: 38957965
DOI: 10.1089/sur.2024.008 -
Foodborne Pathogens and Disease Jul 2024Despite heavy contamination of the Bogotá River with domestic and industrial waste, it remains vital for various purposes, including agricultural use at La Ramada...
Despite heavy contamination of the Bogotá River with domestic and industrial waste, it remains vital for various purposes, including agricultural use at La Ramada Irrigation District. There are important concerns regarding pathogen concentrations in irrigation water at La Ramada, including the presence of antibiotic-resistant spp. This study aimed to estimate the risk of -related illness from consuming lettuce irrigated with Bogotá River water at La Ramada. We collected lettuce samples from 4 different sites, all irrigated with water from La Ramada. The methodology involved a process to detach spp. from lettuce leaves, quantification through plate counts on SS agar, and establishment of antibiotic-resistant bacteria concentrations through growth on media supplemented with ampicillin or ciprofloxacin. The results showed concentrations of spp. of 10,10, and 10 CFU/g lettuce at sites 1, 2, and 3, respectively, and ampicillin-resistant spp. of 10, 10, and 10 CFU/g lettuce at sites 1, 2, and 3, respectively. No colonies were obtained from lettuce samples collected from site 4. Notably, we detected no isolates resistant to ciprofloxacin at any of the sites. spp. concentrations varied greatly among sampling sites. spp. concentrations were used to predict the daily probability of illness, with a probability of 0.59 (0.33 to 0.78, CI 95%) for spp. and 0.3 (0.03 to 0.53, CI 95%) for ampicillin-resistant spp.
PubMed: 38957952
DOI: 10.1089/fpd.2024.0015 -
Ghana Medical Journal Dec 2023The study aimed to determine the prevalence of self-medication with antibiotics among attendants of the Out-patient Department (OPD) at Madina Polyclinic before seeking...
OBJECTIVES
The study aimed to determine the prevalence of self-medication with antibiotics among attendants of the Out-patient Department (OPD) at Madina Polyclinic before seeking medical consultation and associated factors.
DESIGN
Cross-sectional study.
SETTING
The study was conducted at Madina Polyclinic.
PARTICIPANTS
The study involved 319 general OPD attendants aged 18 years and above accessing healthcare services at the Madina Polyclinic between May and June 2019.
MAIN OUTCOME MEASURES
The prevalence of antibiotic self-medication and the factors associated with this practice.
RESULTS
From the study, 46.4% (95% CI 40.8%- 52.0%) had self-medicated with antibiotics before presenting for medical consultation at the hospital. Less than half of the respondents (44.5%) had adequate knowledge about the use of antibiotics. Having a tertiary level of education was significantly associated with self-medication (aOR= 8.09, 95% CI 2.31-28.4, p = 0.001), whilst adequate knowledge on the use of antibiotics reduced the odds of self-medication by 53% (aOR= 0.47, 95% CI 0.23- 0.66, p<0.001). The level of education modified the relationship between knowledge and self-medication with antibiotics.
CONCLUSION
The practice of antibiotic self-medication is rife among OPD attendants. Therefore, adequate public education on the use of antibiotics and the effects of using them inappropriately must be done. The Antimicrobial Resistance (AMR) policy ought to be reinforced and made known to all, especially among the pharmacies that dispense antibiotics indiscriminately.
FUNDING
None declared.
Topics: Humans; Self Medication; Male; Female; Adult; Cross-Sectional Studies; Anti-Bacterial Agents; Middle Aged; Health Knowledge, Attitudes, Practice; Young Adult; Outpatients; Adolescent; Aged; Educational Status
PubMed: 38957850
DOI: 10.4314/gmj.v57i4.8 -
Translational Medicine @ UniSa 2024Healthcare-associated infections (HCAIs) pose a significant challenge, impacting patient safety and treatment effectiveness. This retrospective study investigates the...
BACKGROUND AND OBJECTIVES
Healthcare-associated infections (HCAIs) pose a significant challenge, impacting patient safety and treatment effectiveness. This retrospective study investigates the correlation between pre-operative hospital stays and HCAIs in ICU cardiac surgery patients.
MATERIALS AND METHODS
Medical records of 35 patients who died post-cardiac surgery in the ICU were analyzed, focusing on the duration of pre-operative hospitalization.
RESULTS
Prolonged pre-operative stays strongly correlate (r = 0.993) with increased HCAIs, indicating a critical risk factor.
CONCLUSIONS
The duration of pre-operative hospital stays is pivotal in HCAI risk. Prospective multicenter studies are needed for validation, which is crucial for enhancing patient safety and treatment efficacy.
PubMed: 38957730
DOI: 10.37825/2239-9747.1051