Doses Of Antibiotics Research Articles

The Impact of Redosing Antibiotics for Pediatric Patients Undergoing Appendectomy for Complicated Appendicitis.

Currently, there is no universally accepted, standardized protocol for pre-operative antibiotic administration in the setting of appendectomy for complicated appendicitis among pediatric patients. Strategies to mitigate surgical site infections (SSIs) must be balanced with optimal antibiotic use and exposure. We conducted a retrospective chart review to compare outcomes between patients treated pre-operatively with a single pre-operative dose of antibiotics with those who received additional antibiotics prior to laparoscopic appendectomy for complicated appendicitis between 2020 and 2022. Of 124 pediatric patients, 18% received an additional dose of pre-operative antibiotics after initial treatment dose. Surgical site infection rates between the two groups were not statistically significant (P-value = .352), thereby suggesting that redosing antibiotics closer to the time of incision may not impact SSI rates. Additional studies are necessary to make clinical recommendations.

The level of knowledge of medical and dental students regarding prophylaxis for infective endocarditis.

Infective endocarditis is a rarely seen disease, but has a high mortality rate. Therefore, it is extremely important that the guidelines are followed correctly. The main aim of this study was to evaluate and compare the level of knowledge and attitude of infective endocarditis of fourth- and fifth-year dentistry students in clinical residency and fifth- and sixth-year medical students. A 42-item questionnaire evaluating the type and dosage of antibiotics administered as infective endocarditis prophylaxis in medical conditions and dentistry procedures was delivered online to the study participants. The data obtained were examined using descriptive statistics and analyzed with the chi-square test. The questionnaire was completed by a total of 332 participants. The statistical analyses showed a good level of knowledge in 55% of the dentistry faculty students and in 43.5% of the medical faculty students. When considering that dental and medical faculty students are not expected to receive additional training on antimicrobial management after graduation, the findings of this study have raised significant attitude for the improvement of our education system in this field.

Cold Plasma Deposition of Tobramycin as an Approach to Localized Antibiotic Delivery to Combat Biofilm Formation.

Hospital-acquired infections (HAIs) remain a significant factor in hospitals, with implant surfaces often becoming contaminated by highly resistant strains of bacteria. Recent studies have shown that electrical plasma discharges can reduce bacterial load on surfaces, and this approach may help augment traditional antibiotic treatments. To investigate this, a cold atmospheric plasma was used to deposit tobramycin sulphate onto various surfaces, and the bacterial growth rate of K. pneumoniae in its planktonic and biofilm form was observed to probe the interactions between the plasma discharge and the antibiotic and to determine if there were any synergistic effects on the growth rate. The plasma-deposited tobramycin was still active after passing through the plasma field and being deposited onto titanium or polystyrene. This led to the significant inhibition of K. pneumoniae, with predictable antibiotic dose dependence. Separate studies have shown that the plasma treatment of the biofilm had a weak antimicrobial effect and reduced the amount of biofilm by around 50%. Combining a plasma pre-treatment on exposed biofilm followed by deposited tobramycin application proved to be somewhat effective in further reducing biofilm growth. The plasma discharge pre-treatment produced a further reduction in the biofilm load beyond that expected from just the antibiotic alone. However, the effect was not additive, and the results suggest that a complex interaction between plasma and antibiotic may be at play, with increasing plasma power producing a non-linear effect. This study may contribute to the treatment of infected surgical sites, with the coating of biomaterial surfaces with antibiotics reducing overall antibiotic use through the targeted delivery of therapeutics.

Preoperative antibiotics are not indicated prior to closure of oroantral communication

AbstractObjectiveThe aim of this paper was to determine whether the use of preoperative antibiotics improves surgical outcomes following oroantral communication (OAC) closure.Materials and MethodsA single‐centre, retrospective study was conducted on all OAC repair procedures over a 24‐month period assessing a number of datapoints including the site of OAC occurrence, time to repair, local anaesthetic or general anaesthetic, and any complications noted. Patient follow‐up was up to 3 months post‐operative OAC closure. Data outputs primarily included descriptive statistics for demographic datasets included in the study. Fisher's exact test was used to determine non‐random associations between categorical variables (preoperative antibiotics vs. no preoperative antibiotics; successful closure vs. failed closure).ResultsThirty‐one patients met the inclusion criteria and timeframe of this study. All OACs were a result of dental extraction. For patients who had an OAC visualised immediately after extraction, 18 had an OAC repair completed on the same day. Fifteen patients had a delayed closure, defined as a closure over 48 h following the development of OAC. Thirteen patients had their procedure completed under local anaesthetic; none had preoperative antibiotics prior to surgery. Only one patient with delayed closure of an OAC who had a procedure completed under local anaesthetic had a prophylactic dose 1 h prior to surgery. Patients who underwent OAC closure under general anaesthetic received an intra‐operative dose of antibiotics. Using Fisher's exact test, there was no significant difference between the two groups (preoperative antibiotics given vs. no preoperative antibiotics given) with regard to the likelihood of success following OAC closure (p = 0.1419).ConclusionThis study demonstrates that the routine use of preoperative antibiotics may not improve surgical outcomes following the closure of oroantral communication.

Abstract CT030: Randomized placebo-controlled, biomarker-stratified phase 1b microbiome modulation trial for metastatic melanoma demonstrates impact of antibiotic pre-conditioning regimen on the microbiome and immunity

Abstract Background: Gut microbiota modulation shows promise in improving immune checkpoint blockade (ICB) response; however, precision biomarker-driven trials using rationally-designed consortia are lacking. To address this, we performed a multi-center, randomized placebo-controlled, biomarker-stratified phase 1 trial in patients with ICB-naïve unresectable or metastatic melanoma using SER-401, a bacterial consortia enriched for Firmicutes spores and Ruminococcaceae. Methods: MCGRAW was a multi-center, randomized, blinded, and placebo-controlled phase 1b study in patients with advanced melanoma. Patients were randomized 2:1 to the SER-401 active or placebo arm, respectively, and stratified by baseline stool Ruminococcaceae abundance. Patients received an oral vancomycin (vanco) preparative regimen+SER-401 (vanco+SER-401 arm), versus placebo antibiotic+placebo (Placebo arm), followed by nivolumab. Stool, blood and tumor samples were collected at baseline and on treatment. The primary endpoint was safety, with additional secondary endpoints (SER-401 microbiome engraftment, overall response rate (ORR), disease control rate (DCR), and other translational endpoints). The study was not powered for comparison between arms. Results: 14 patients were randomized (n=8 vanco+SER-401, n=6 placebo). In the vanco+SER-401 arm, ORR was 25.0% and DCR was 37.5%, with no Grade 3-4 treatment-related adverse events (TRAE); in the placebo arm, ORR was 66.7% and DCR was 83.3%, with 1 (17%) TRAE. Notably, pre-conditioning with vanco was associated with significant shift in the microbiome taxonomic composition, with depletion of target families such as Ruminococcaceae (p=0.008, Wilcoxon signed-rank test), and other spore-formers, followed by their recovery post dosing with SER-401. There was a significant increase in multiple ICB-resistance associated pathways (e.g. butyrate synthesis, p<0.0001), and a decrease in response-associated pathways after vanco preconditioning; these changes did normalize by nivolumab initiation. There was corresponding increase in systemic proteomic markers of inflammation after vanco, which also normalized by first dose of immunotherapy. Conclusions: This first-of-its-kind, placebo-controlled, randomized biomarker-driven microbiome modulation trial demonstrated that SER-401 and anti-PD1 are a safe combination in melanoma patients. The study was limited by poor accrual during the COVID-19 pandemic. Nonetheless, important insights were gained via translational analyses, suggesting that antibiotic preconditioning and interventional drug dosing regimens should be carefully considered when designing such trials. Additional placebo-controlled biomarker-driven microbiome trials are needed in this age of precision medicine. Trial registration: ClinicalTrials.gov (NCT03817125) Citation Format: Isabella C. Glitza Oliva, Yongwoo David Seo, Christine N. Spencer, Jennifer R. Wortman, Elizabeth M. Burton, Farah A. Alayli, Christopher Loo, Shikha Gautam, Ashish V. Damania, Julie Densmore, Justin Fairchild, Christopher Cabanski, Matthew C. Wong, Christine B. Peterson, Brian Weiner, Nathan Hicks, John Aunins, Christopher McChalicher, Michael T. Tetzlaff, Omid Hamid, Patrick A. Ott, Genevieve M. Boland, Ryan J. Sullivan, Kenneth F. Grossmann, Nadim J. Ajami, Theresa M. LaVallee, Matthew R. Henn, Hussein A. Tawbi, Jennifer A. Wargo. Randomized placebo-controlled, biomarker-stratified phase 1b microbiome modulation trial for metastatic melanoma demonstrates impact of antibiotic pre-conditioning regimen on the microbiome and immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT030.

Single-Dose First-Generation Cephalosporin for Extremity Gunshot Wounds Offers Sufficient Infection Prophylaxis

Antibiotic prophylaxis for extremity gunshot wounds (GSWs) is highly variable. The objective of the present study is to quantify the adherence rate to a protocol for single-dose cephalosporin prophylaxis for extremity GSWs and the impacts on post-injury infection rates. We reviewed patients presenting to a level 1 trauma center with an extremity gunshot wound between 2019 and 2021. Infection rates were compared for patients following the protocol or not, and for patients presenting before or after the protocol’s implementation. Overall, 94% of patients received antibiotic treatment at presentation, but only 34% followed the single-dose antibiotic protocol. The rate of protocol adherence increased from 15% to 39% after the protocol was implemented in the hospital in January 2020 (p = 0.081). Infection rates were not different before and after the protocol implementation (25% vs. 18%, p = 0.45). Infection rates were also not different between patients who did and did not follow the protocol (15% vs. 20%, p = 0.52). The implementation of a single-dose cephalosporin protocol increased adherence to the protocol in a level 1 trauma center without increasing infection rates. These findings support conservative treatment along with a single dose of first-generation cephalosporin antibiotic for uncomplicated extremity GSWs in order to decrease healthcare costs without compromising infection risk.

Randomized Placebo-Controlled, Biomarker-Stratified Phase Ib Microbiome Modulation in Melanoma: Impact of Antibiotic Preconditioning on Microbiome and Immunity.

Gut-microbiota modulation shows promise in improving immune-checkpoint blockade (ICB) response; however, precision biomarker-driven, placebo-controlled trials are lacking. We performed a multicenter, randomized placebo-controlled, biomarker-stratified phase I trial in patients with ICB-naïve metastatic melanoma using SER-401, an orally delivered Firmicutesenriched spore formulation. Fecal microbiota signatures were characterized at baseline; patients were stratified by high versus low Ruminococcaceae abundance prior to randomization to the SER-401 arm (oral vancomycin-preconditioning/SER-401 alone/nivolumab + SER-401), versus the placebo arm [placebo antibiotic/placebo microbiome modulation (PMM)/nivolumab + PMM (NCT03817125)]. Analysis of 14 accrued patients demonstrated that treatment with SER-401 + nivolumab was safe, with an overall response rate of 25% in the SER-401 arm and 67% in the placebo arm (though the study was underpowered related to poor accrual during the COVID-19 pandemic). Translational analyses demonstrated that vancomycin preconditioning was associated with the disruption of the gut microbiota and impaired immunity, with incomplete recovery at ICB administration (particularly in patients with high baseline Ruminococcaceae). These results have important implications for future microbiome modulation trials. Significance: This first-of-its-kind, placebo-controlled, randomized biomarker-driven microbiome modulation trial demonstrated that vancomycin + SER-401 and anti-PD-1 are safe in melanoma patients. Although limited by poor accrual during the pandemic, important insights were gained via translational analyses, suggesting that antibiotic preconditioning and interventional drug dosing regimens should be carefully considered when designing such trials.

A Pharmacy-Based Cross-Sectional Study to Assess the Antibiotic Prescription Pattern by Medical and Dental Practitioners in Saudi Arabia

ABSTRACT Introduction: The misuse and overuse of antibiotics in dental practice are well known and have become widespread worldwide. Its potential effect and high risk of serious reaction have emphasized the need to reduce and limit the precipitation. In this study we aimed to identify the prevalence, type, dose, and duration of antibiotics prescribed by general medical and dental practitioners in Saudi Arabia. Materials and Methods: This cross-sectional study was performed from April 2020 to December 2020. A total of 45,100 antibiotic prescriptions were collected from different governmental and private pharmacies and screened to be included in this study. Data extraction from all prescriptions followed a standardized form that included the following information: Doctor specialty, type of antibiotic, duration, and dose of antibiotic. Results: A total of 38,175 antibiotic prescriptions prescribed by licensed doctors practicing in governmental or private hospitals were included in this study. Thirty-five thousand one hundred and seventy-eight (92%) outpatient antibiotics were prescribed by medical practitioners, and 2997 (8%) antibiotics were prescribed by dentists. The most commonly prescribed antibiotic was Augmentin (60%), followed by metronidazole and amoxicillin (35%). The most common dose and duration prescribed by dentists for Augmentin was 625 mg, 3 times per day for 5 days, whereas that of metronidazole was 500 mg, 3 times per day for 7 days. Prescribed dose and duration of amoxicillin was 500 mg, 3 times per day for 7 days. Conclusions: This study helps in understanding healthcare practitioners’ patterns and adds to the knowledge on how to deal with odontogenic infections. Further national studies are recommended to include more regions in Saudi Arabia and to illustrate the misuse of outpatient antibiotics.

Optimization of periodic treatment strategies for bacterial biofilms using an agent-based in silico approach.

Biofilms are responsible for most chronic infections and are highly resistant to antibiotic treatments. Previous studies have demonstrated that periodic dosing of antibiotics can help sensitize persistent subpopulations and reduce the overall dosage required for treatment. Because the dynamics and mechanisms of biofilm growth and the formation of persister cells are diverse and are affected by environmental conditions, it remains a challenge to design optimal periodic dosing regimens. Here, we develop a computational agent-based model to streamline this process and determine key parameters for effective treatment. We used our model to test a broad range of persistence switching dynamics and found that if periodic antibiotic dosing was tuned to biofilm dynamics, the dose required for effective treatment could be reduced by nearly 77%. The biofilm architecture and its response to antibiotics were found to depend on the dynamics of persister cells. Despite some differences in the response of biofilm governed by different persister switching rates, we found that a general optimized periodic treatment was still effective in significantly reducing the required antibiotic dose. As persistence becomes better quantified and understood, our model has the potential to act as a foundation for more effective strategies to target bacterial infections.

Action of photodynamic inactivation in antibiotic failures

SignificanceThe increase in the number of microorganisms resistant to antimicrobials motivates the search for strategies that recover the use of traditional antibiotics. Photodynamic Inactivation (PDI) is an alternative to antibiotics because the combination of a photosensitizer with light leads to the production of reactive oxygen species that promote the elimination of undesirable cells. ApproachCurcumin and light at 450 nm are applied at regular intervals and new values of minimum inhibitory concentration of antibiotics are obtained. ResultsWe demonstrated that the application of PDI reduces the necessary dosage of antibiotics for the elimination of the bacterial cell, proving to be an efficient strategy for application in resistant strains. Furthermore, we verified that the interaction of the photosensitizer with the antibiotics promotes alterations in the metabolism and the bacterial biomolecules. ConclusionsThese results are essential to transfer in vitro studies to the clinical implementation of DIF as an adjuvant to antibiotic therapy.

Action of photodynamic inactivation in antibiotic failures

SignificanceThe increase in the number of microorganisms resistant to antimicrobials motivates the search for strategies that recover the use of traditional antibiotics. Photodynamic Inactivation (PDI) is an alternative to antibiotics because the combination of a photosensitizer with light leads to the production of reactive oxygen species that promote the elimination of undesirable cells. ApproachCurcumin and light at 450 nm are applied at regular intervals and new values of minimum inhibitory concentration of antibiotics are obtained. ResultsWe demonstrated that the application of PDI reduces the necessary dosage of antibiotics for the elimination of the bacterial cell, proving to be an efficient strategy for application in resistant strains. Furthermore, we verified that the interaction of the photosensitizer with the antibiotics promotes alterations in the metabolism and the bacterial biomolecules. ConclusionsThese results are essential to transfer in vitro studies to the clinical implementation of DIF as an adjuvant to antibiotic therapy.

Postoperative antibiotic prophylaxis for percutaneous nephrolithotomy and risk of infection: a systematic review and meta-analysis.

The aim of this study is to perform a high-quality meta-analysis using only randomized controlled trials (RCT) to better define the role of postoperative antibiotics in patients undergoing percutaneous nephrolithotomy (PCNL). A literature search for RCTs in EMBASE, PubMed, and Web of Science up to May 2023 was conducted following the PICO framework: Population-adult patients who underwent PCNL; Intervention-postoperative antibiotic prophylaxis until nephrostomy tube withdrawal; Control-single dose of antibiotic during the induction of anesthesia; and Outcome-systemic inflammatory response syndrome (SIRS) or sepsis and fever after PCNL. The protocol was registered on the PROSPERO database (CRD42022361579). We calculated odds ratios (OR) and 95% confidence intervals (CI). A random-effects model was employed, and the alpha risk was defined as < 0.05. Seven articles, encompassing a total of 629 patients, were included in the analysis. The outcome of SIRS or sepsis was extracted from six of the included studies, while the outcome of postoperative fever was extracted from four studies. The analysis revealed no statistical association between the use of postoperative antibiotic prophylaxis until nephrostomy tube withdrawal and the occurrence of SIRS/sepsis (OR 1.236, 95% CI 0.731 - 2.089, p=0.429) or fever (OR 2.049, 95% CI 0.790 - 5.316, p=0.140). Our findings suggest that there is no benefit associated with the use of postoperative antibiotic prophylaxis until nephrostomy tube withdrawal in patients undergoing percutaneous nephrolithotomy (PCNL). We recommend that antibiotic prophylaxis should be administered only until the induction of anesthesia in PCNL.

Antimicrobial photodynamic response in Rhyzopus oryzae

Mucormycosis is an extremely aggressive fungal disease that has a high mortality rate. Conventional treatment consists of high doses of antibiotics and antifungal agents associated with surgical resections, but even with this aggressive treatment, the mortality rate is still high. The antimicrobial photodynamic therapy (aPDT), also called photodynamic inactivation (PDI), it is an interesting alternative to antifungal therapy because it has non-specific biological site action and can also be an additional method of treatment in conjunction with surgery and antifungal therapy. In this work we studied the evaluation of the photodynamic antimicrobial response in different phases of fungus growth (conidium and hyphae in the white and black phases) and for different protocols of PDI with PDZ, varying the concentration of photosensitizer, the incubation time, the association with surfactant and the fluence of light at 660 nm. In this work, PDI showed great potential in the in vitro study of R. oryzae.

Comparative study of elective cholecystectomy with and without antimicrobial prophylaxis: A prospective randomized study

Background: Cholecystectomy is one of the most common, clean, and contaminated surgery operations performed by surgeons worldwide. Antibiotic prophylaxis in elective cholecystectomy is a controversial issue and our study was undertaken to evaluate the rate of infection and the usefulness and efficacy of antibiotic prophylaxis in elective cholecystectomies. Aims and Objectives: The aims and objectives are to study antimicrobial prophylaxis on elective laparoscopic cholecystectomy and to compare surgical site infections (SSI) between the two groups after laparoscopic cholecystectomy with respect to (a) duration of surgery, (b) post-operative pain, (c) complications encountered, and (d) post-operative hospital stay. Materials and Methods: Patients were randomly divided into the study group (Group A) and the control group (Group B). Antibiotic dose of ceftriaxone + sulbactam 1.5 g will be administered intravenously 2 h before induction of anesthesia for the patients in the study Group A (n=30), and no antibiotic will be administered prophylactically to the control Group B (n=30). Results: In the study group, one patient developed fever, and in the control Group, 4 patients developed fever. In this study, SSIs were considered. In the study group, two patients (6.67%) developed pus discharge from the port site which was considered superficial infection, and in the control group, five patients (16.67%) developed pus discharge. Conclusion: Based on our study, in elective cholecystectomy, a single dose of intravenous ceftriaxone + salbactam 1.5 g given before the operative procedure does not lead to a higher SSI rate as compared to the conventionally given antibiotics which are continued postoperatively for a variable length of time.

An ambispective observational study on antibiotics in pulmonology department in a tertiary care hospital

Background: Respiratory tract infections (RTIs) caused by various viruses and bacteria are a major cause of morbidity and mortality worldwide. Although they are usually more severe in children, the elderly and people with weakened immune systems, people of all ages and backgrounds are susceptible to these infections. Antibiotics are commonly prescribed for RTIs in primary care in adults and children. The main purpose of this study is to monitor the use of different antibiotics for respiratory infections. Methods: It is an ambispective observational study, during which data are collected on specially designed data collection forms. The study lasted 6 months (from December 2022 to May 2023). Results: The source of data is a total of 100 patients who were prescribed at least one dose of antibiotics. Out of 100 people, 53% were men and 47% were women. LRTI and URTI are the most common conditions for which antibiotics are prescribed, and we found that the most commonly prescribed antibiotics are a higher percentage of patients using cephalosporins. Of the various cephalosporins, the most commonly prescribed is ceftriaxone, a third-generation cephalosporin. Conclusions: From this particular observational study, we concluded that the most frequently prescribed antibiotics for respiratory infections were cephalosporins, ceftriaxone, third-generation cephalosporins were most frequently prescribed, followed by macrolides, penicillin, tetracyclines, lincomycin, fluoroquinolones, oxazolidinones. The use of antibiotics helps to improve patient care by reducing side effects such as antibiotic resistance, hypersensitivity reactions, respiratory difficulties and risks associated with respiratory infections.

Neutrophil to lymphocyte ratio in odontogenic infection: a systematic review

BackgroundWe conducted this systematic review to compile the evidence for the role of neutrophil to lymphocyte ratio (NLR) in odontogenic infection (OI) and to determine whether NLR is elevated in patients with OI. This was done to aid physicians in better understanding this condition for clinical management.MethodsThe search was conducted on PubMed, Scopus, and Web of Science libraries on March 30, 2023. Two reviewers independently screened the studies using Endnote software. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies.ResultsA total of nine studies were included in the review. Among patients with OI, positive and statistically significant correlations of NLR were seen with more severe disease, a prolonged hospital stay, postoperative requirement of antibiotics, and total antibiotic dose needed. In the receiver operating characteristics (ROC) analysis, the optimum cut–off level of NLR was 5.19 (specificity: 81, sensitivity: 51). In addition, NLR was correlated with preoperative fever (p = 0.001). Among patients with Ludwig’s Angina, NLR could predict disease severity and length of stay in the hospital (p = 0.032 and p = 0.033, respectively). In addition, the relationship between the NLR and mortality was statistically significant (p = 0.026, specificity of 55.5%, and sensitivity of 70.8%). Among patients with severe oral and maxillofacial space infection, a positive correlation was found between IL-6 and CRP with NLR (rs = 0.773, P = 0.005 and rs = 0.556, P = 0.020, respectively). Also, a higher NLR was considered an essential predictor of organ involvement (P = 0.027) and the number of complications (P = 0.001). However, among diabetes mellitus (DM) patients afflicted with submandibular abscesses, NLR had no association with therapeutic response.ConclusionsMany people around the world suffer from OI, and a cheap and fast biomarker is needed for it. Interestingly, inflammation plays a role in this infection, and elevated NLR levels can be a good biomarker of inflammation and, as a result, for OI progression.

The REPAIR study: oral antibiotics to prevent infection and wound dehiscence after obstetric perineal tear—a double-blinded placebo controlled randomized trial

BackgroundApproximately 85% of women experience an obstetric tear at delivery and up to 25% subsequently experience wound dehiscence and/or infection. Previous publications suggest that intravenous antibiotics administrated during delivery reduces this risk. We do not know if oral antibiotics given after delivery can reduce the risk of wound dehiscence or infection. Our aim is to investigate whether three doses of oral antibiotics (amoxicillin 500 mg/clavulanic acid 125 mg) given after delivery can reduce the risk of wound dehiscence and infection in patients with a second-degree obstetric tear or episiotomy.MethodsWe will perform a randomized, controlled, double-blinded study including 221women in each arm with allocation 1:1 in relation to the randomization. The study is carried out at Department of Obstetrics & Gynecology, Herlev University Hospital, Copenhagen, Denmark. The women will be included after delivery if they have had a second-degree tear or episiotomy. After inclusion, the women will have a clinical follow-up visit after 1 week. The tear and healing will be evaluated regarding signs of infection and/or dehiscence. The women will again be invited for a 1-year clinical examination including ultrasound. Questionnaires exploring symptoms related to the obstetric tear and possible complications will be answered at both visits. Our primary outcome is wound dehiscence and/or wound infection, which will be calculated using χ2 tests to compare groups. Secondary outcomes are variables that relate to wound healing, as pain, use of painkillers and antibiotics, need for further follow-up, as well as outcomes that may be related to the birth or healing process, urinary or anal incontinence, symptoms of prolapse, female body image, and sexual problems.DiscussionReducing the risk of wound dehiscence and/or infection would decrease the number of control visits, prevent the need for longer antibiotic treatment, and possibly also decrease both short-term and long-term symptoms. This would be of great importance so the mother, her partner, and the baby could establish and optimize their initial family relation.Trial registrationThe conduction of this study is approved the 2/2–2023 with the EU-CT number: 2022–501930-49–00. ClinicalTrials.gov Identifier: NCT05830162.

Association of antibiotic exposure with residual cancer burden in HER2-negative early stage breast cancer

Antibiotic exposure during immunotherapy (IO) has been shown to negatively affect clinical outcomes in various cancer types. The aim of this study was to evaluate whether antibiotic exposure in patients with high-risk early-stage HER2-negative breast cancer (BC) undergoing treatment with neoadjuvant pembrolizumab impacted residual cancer burden (RCB) and pathologic complete response (pCR) in the pembrolizumab-4 arm of the ISPY-2 clinical trial. Patients received pembrolizumab for four cycles concurrently with weekly paclitaxel for 12 weeks, followed by four cycles of doxorubicin plus cyclophosphamide every 2 or 3 weeks. Patients who received at least one dose of systemic antibiotics concurrently at the time of immunotherapy (IO) were included in the antibiotic exposure group (ATB+). All other participants were included in the control group (ATB-). RCB index and PCR rates were compared between the ATB+ and ATB- groups using t-tests and Chi-squared tests, and linear and logistic regression models, respectively. Sixty-six patients were included in the analysis. 18/66 (27%) patients were in the ATB+ group. Antibiotic use during IO was associated with a higher mean RCB index (1.80 ± 1.43 versus 1.08 ± 1.41) and a lower pCR rate (27.8% versus 52.1%). The association between antibiotic use and the RCB index remained significant in multivariable linear regression analysis (RCB index-coefficient 0.86, 95% CI 0.20–1.53, P = 0.01). Our findings suggest that concurrent antibiotic exposure during neoadjuvant pembrolizumab in HER2-negative early-stage BC is associated with higher RCB. Further validation in larger cohorts is needed to confirm these findings.

A New Dosing Frontier: Retrospective Assessment of Effluent Flow Rates and Residual Renal Function Among Critically Ill Patients Receiving Continuous Renal Replacement Therapy.

In 2020, cefiderocol became the first Food and Drug Administration-approved medication with continuous renal replacement therapy (CRRT) dosing recommendations based on effluent flow rates (QE). We aimed to evaluate the magnitude and frequency of factors that may influence these recommendations, that is, QE intrapatient variability and residual renal function. Retrospective observational cohort study. ICUs within Hartford Hospital (890-bed, acute-care hospital) in Connecticut from 2017 to 2023. Adult ICU patients receiving CRRT for greater than 72 hours. CRRT settings including QE and urine output (UOP) were extracted from the time of CRRT initiation (0 hr) and trends were assessed. To assess the impact on antibiotic dosing, cefiderocol doses were assigned to 0 hour, 24 hours, 48 hours, and 72 hours QE values per product label, and the proportion of antibiotic dose changes required as a result of changes in inpatient's QE was evaluated. Among the 380 ICU patients receiving CRRT for greater than 72 hours, the median (interquartile range) 0 hour QE was 2.96 (2.35-3.29) L/hr. Approximately 9 QE values were documented per patient per 24-hour window. QE changes of greater than 0.75 L/hr were observed in 21.6% of patients over the first 24 hours and in 7.9% (24-48 hr) and 5.8% (48-72 hr) of patients. Approximately 40% of patients had UOP greater than 500 mL at 24 hours post-CRRT initiation. Due to QE changes within 24 hours of CRRT initiation, a potential cefiderocol dose adjustment would have been warranted in 38% of patients (increase of 21.3%; decrease of 16.6%). QE changes were less common after 24 hours, warranting cefiderocol dose adjustments in less than 15% of patients. Results highlight the temporal and variable dynamics of QE and prevalence of residual renal function. Data also demonstrate a risk of antibiotic under-dosing in the first 24 hours of CRRT initiation due to increases in QE. For antibiotics with QE-based dosing recommendations, empiric dose escalation may be warranted in the first 24 hours of CRRT initiation.

The Combination of Membrane Disruption and FtsZ Targeting by a Chemotherapeutic Hydrogel Synergistically Combats Pathogens Infections.

The emergence of multidrug-resistant (MDR) bacteria poses a significant challenge to global health. Due to a shortage of antibiotics, alternative therapeutic strategies are urgently needed. Unfortunately, colistin, the last-resort antibiotic, has unavoidable nephrotoxicity and hepatotoxicity, and its single killing mechanism is prone to drug resistance. To address this challenge, a promising combinatorial approach that includes colistin, a membrane-disrupting antimicrobial agent, and chelerythrine (CHE), a FtsZ protein inhibitor is proposed. This approach significantly reduces antibiotic dose and development of resistance, leading to almost complete inactivation of MDR pathogens in vitro. To address solubility issues and ensure transport, the antimicrobial hydrogel system LNP-CHE-CST@hydrogel, which induced reactive oxygen species (ROS) and apoptosis-like cell death by targeting the FtsZ protein, is used. In an in vivo mouse skin infection model, the combination therapy effectively eliminated MDR bacteria within 24 h, as monitored by fluorescence tracking. The findings demonstrate a promising approach for developing multifunctional hydrogels to combat MDR bacterial infections.