Dose Of Prophylaxis Research Articles

Efficacy of Bd metabolite prophylaxis dose and duration on host defence against the deadly chytrid fungus Batrachochytrium dendrobatidis

Abstract Batrachochytrium dendrobatidis (Bd), an aquatic pathogenic fungus, is responsible for the decline of hundreds of amphibian species worldwide and negatively impacts biodiversity globally. Prophylactic exposure to the metabolites produced by Bd can provide protection for naïve tree frogs and reduce subsequent Bd infection intensity. Here, we used a response surface design crossing Bd metabolite prophylaxis concentration and exposure duration to determine how these factors modulate prophylactic protection against Bd in Pacific chorus frog (Pseudacris regilla) tadpoles (5 × 5 surface design) and metamorphs (3 × 3 surface design). We exposed individuals every weekday to one of five Bd metabolite concentrations or a water control for 1–5 weeks, after which all animals were challenged with live Bd to evaluate their susceptibility. Exposure to the Bd metabolite prophylaxis reduced Bd load and prevalence compared to the control for both the tadpoles and metamorphs. Increasing Bd metabolite prophylaxis concentration did not confer additional protection for either life stage, but increasing duration of exposure did benefit metamorphs by decreasing Bd prevalence but not Bd load. On average, control tadpoles and metamorphs had 66.2% and 99.4% higher Bd loads, respectively, than tadpoles and metamorphs exposed to any Bd metabolite prophylaxis. Additionally, Bd metabolite prophylaxis reduced Bd prevalence relative to controls in both tadpoles (20.5% vs. 56.3%, respectively) and metamorphs (21.9% vs. 87.5%, respectively). Synthesis and applications: The efficacy of short‐term exposures of relatively low concentrations of Bd metabolites at reducing Bd infections suggests that this approach has the potential to be scaled up to field use to aid in disease mitigation and conservation. Our results, combined with additional research on Bd metabolite prophylaxis for other amphibian species, suggest that this strategy may represent a broadly useful tool to protect at‐risk amphibian populations.

Single dose vs prolonged antibiotic prophylaxis of fosfomycin for transrectal prostate biopsy: a single-center prospective, randomized, controlled trial

BackgroundTransrectal prostate biopsy is a commonly performed urological procedure in which antibiotic prophylaxis is recommended. Fluoroquinolone-type antibiotics are no longer acceptable in the EU. Fosfomycin-trometamol may be used, but there is no evidence regarding its ideal dose and administration time. MethodsPatients who underwent prostate biopsy between 2021 and 2023 were evaluated prospectively. 204 patients were randomized into two arms: 102 patients (Arm A) received a single dose of fosfomycin-trometamol one hour before surgery, and 102 patients (Arm B) received one additional dose of fosfomycin-trometamol 48 hours after the first dose. Urine tests and questionnaires were administered during the postoperative period and the subsequent four weeks to identify any symptoms, infectious, or other complications. ResultsThere was no statistical difference in the rate of asymptomatic bacteriuria (4.90% (5) vs 8.82% (9), p = 0.27) symptomatic UTI (0% (0) vs 1.96% (2), p = 0.50), or febrile UTI (0% (0) vs 0.98% (1), p = 1) between the groups. Only haematuria was significantly more common in Arm B (6.86% (7) vs 16.67% (17), p = 0.03), whereas other complications did not differ significantly. There was no statistical difference in hospitalization (0.98% (1) vs 2.94 (3), p = 0.62) or mortality rate (0 % (0) vs 0.98% (1), p = 1). Sub-group analysis of previous antibiotic users showed no difference in terms of complications. ConclusionThere is no significant difference in infectious complications between single dose and prolonged prophylaxis of fosfomycin-trometamol for transrectal prostate biopsy. A single dose of fosfomycin one hour before biopsy is an ideal choice with a better ecological impact compared with prolonged antibiotic prophylaxis for transrectal prostate biopsy.

Identification of the Most Common Antibiotics Used for Broiler Chicken Production in Bangladesh

The use of antibiotics indiscriminately in broiler without any veterinary consultation added in feed and water in sub-therapeutic doses for prophylaxis and growth promotion has increased antibiotic resistant bacteria transmitting to human. The aim of the study was to identify the most common antibiotic used by the broiler in Bangladesh. In this survey engaged 208 Upazila Livestock Offices (ULO) for interviewing 385 broiler farmers and veterinary medicine sales representative in all 8 divisions. Use of antimicrobial drugs for broiler production in different farm, medicine and feed used in the current flock were targeted to identify. Factor analysis was used to select respondents’ knowledge variables and multinomial logistic regression was followed to determine factors associated with antibiotic used in broiler production. According to opinion of 208 Upazila Livestock officers, interview with farmer and veterinary medicine sales representative, everyone agreed the most of the farmers use antimicrobials for broiler production. The most common antibiotics were Amoxcillin (182/208), Ciprofloxacin (179/208), Colistin sulphate (167/208), oxytetracyclin (165/208), Enrofloxacin (146/208), Erythromycin (133/208), sulfaquinoxaline (46/208), followed by Gentamycin, Norfloxacin, Tiamulin, Tilmicosin, Toltrazuril, Doxicycline, flumequine, Neomycin, Tylosin, lincomycin, Flavomycin, Florfenicol and Clortetracycline. Under above circumstances large-scale use of antimicrobials had led to its resistance and residues in broiler chicken meat and liver which can lead to public health problems. The major broiler farm used antibiotics (amoxicillin and ciprofloxacin) and they did not follow withdrawal period. Although national regulations is in favor of control use of antibiotics, but were not well enforced.

Topiramate-induced uveal effusion with myopia without angle closure: A case report

Topiramate-induced acute angle closure is a well-known entity with onset of symptoms at 2 weeks following treatment initiation. We report a 24-year-old female with blurring of vision 2 days after increasing the topiramate dose for migraine prophylaxis. Examination showed increase in manifest myopia with normal intraocular pressure and absence of angle closure. Provisional diagnosis of topiramate-induced myopia (TIM) was made, confirmed by presence of uveal effusion on B-scan and ultrasound biomicroscopy. Early presentation during the course could be the reason for isolated myopia. She was advised to stop topiramate and was started on cycloplegics. This case highlights that awareness about TIM among patients helps in prompt management, thus preventing the site-threatening acute angle closure.

Evaluating chemical venous thromboembolism prophylaxis in trauma patients at a single Australian center.

Trauma patients are at an elevated risk of developing venous thromboembolism (VTE), with the subsequent mortality in patients requiring intensive care unit admission ranging from 25% to 38%. There remains significant variability in clinical practice related to VTE prophylaxis in trauma patients due to the frequent presence of contraindications impacting the timing and consistency of application. This study aimed to assess the effectiveness of the current practice of chemical VTE prophylaxis in trauma patients at a single Australian center. A prospective review was conducted on patients admitted to the ACT Trauma Service (Canberra, Australia) from July to November 2022. The included patients were 18 years or older, without a direct contraindication to anticoagulation, who received chemical VTE prophylaxis with low-molecular-weight heparin (enoxaparin) for at least three doses and underwent subsequent testing of anti-factor Xa (aFXa) levels. During the study period, 187 patients were admitted, of whom 63 were included in the study. Of these, 47 patients achieved therapeutic levels of anticoagulation as determined by their aFXa levels, while 16 were subtherapeutic. The only statistically significant difference between the two groups was in weight, with patients in the subtherapeutic group weighing an average of 91.9 kg compared to 79.1 kg in the therapeutic group (P<0.05). A fixed-dose enoxaparin regimen was utilized, with limited individualization based on patient factors, such as injuries, comorbidities, and other biological factors. Sixteen patients (25%) had subtherapeutic VTE prophylaxis, as measured by aFXa levels. Higher weight was significantly correlated with inadequate VTE prophylaxis dosing. While age, sex, and smoking status might play important roles in clinical decision-making, weight-based dosing of low-molecular-weight heparin may be more effective in achieving adequate VTE prophylaxis.

EP51 - Uses of pharmaceutical and mechanical VTE prophylaxis - A clinical audit

Abstract Aim Venous thromboembolism (VTE) is a serious global health care safety concern for both patients and staff. Although it has been amply demonstrated that pharmaceutical and mechanical methods of prophylaxis against VTE are effective, their application has been uneven and insufficient. The purpose of this audit was to assess junior physicians working in general surgery, regarding their adherence to local and NICE guidelines regarding the pharmacological VTE prophylaxis practice as well as the mechanical prophylaxis Methodology Pre-intervention audit took place for two weeks. Throughout the course, it covered every adult general surgical emergency inpatient admission at conquest hospital who were deemed indicated for VTE prophylaxis. Each evening while the patients were still in the hospital, data was collected using the prescription charts, nursing and medical notes. The proforma used for data collection detailed the characteristics of VTE risk, the prophylactic medication prescribed for each patient, TED stockings and whether or not this aligned with the NICE clinical guideline (CG) 46,6.8. Post intervention took place for two weeks after teaching of junior doctors and the same as above was carried out, using the new proforma Results Pre-intervention showed that 87% of patients had the proforma filled in and 100% of patients received the appropriate dose of pharmaceutical prophylaxis. However, less than 40% of patients received the appropriate mechanical prophylaxis. Therefore, intervention was made in the form of a new proforma and teaching to junior. Post intervention data is currently being carried out Conclusion Implementation was necessary to ensure that at-risk patients receive appropriate prophylaxis.

The electronic health record: does it enhance or distract from patient safety?

The electronic health record (EHR) is an invaluable tool that may be used to improve patient safety. With a variety of different features, such as clinical decision support and computerized physician order entry, it has enabled improvement of patient care throughout medicine. EHR allows for built-in reminders for such items as antibiotic dosing and venous thromboembolism prophylaxis. In anesthesiology, EHR often improves patient safety by eliminating the need for reliance on manual documentation, by facilitating information transfer and incorporating predictive models for such items as postoperative nausea and vomiting. The use of EHR has been shown to improve patient safety in specific metrics such as using checklists or information transfer amongst clinicians; however, limited data supports that it reduces morbidity and mortality. There are numerous potential pitfalls associated with EHR use to improve patient safety, as well as great potential for future improvement.

Dexamethasone-Sparing Antiemetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting in Highly and Moderately Emetogenic Chemotherapy: The SHEILD Study.

Chemotherapy-induced nausea and vomiting (CINV) significantly impacts patient's quality of life and treatment adherence. This study investigated the efficacy of Generic Netupitant and Palonosetron tablets (Nykron) with dexamethasone single dose for CINV prophylaxis in patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).Additionally, this approach aligns with the principles of the SHIELD study (Sparing High Efficacy Intervention for Low Dose Dexamethasone), which focuses on maximizing antiemetic effectiveness while minimizing dexamethasone use. This multicenter retrospective study evaluates data from patients who received HEC/MECand were administered a fixed-dose combination of Generic NEPA (Netupitant 300 mg and Palonosetron 0.5 mg tablets, Nykron combi-pack) along with a single dose of dexamethasone (12 mg/8 mg) before chemotherapy. The data were collected from September 2022 till September 2023. Outcomes measuredincluded complete response (no vomiting and no need for rescue medications), complete protection (no significant nausea (<2.5 cm on VAS), no vomiting, and no use of rescue medication), and complete control (no emetic episodes, no rescue therapy, and no nausea [0 cm on VAS])during the acute phase (0-24 hours) and delayed phase (24-120 hours) post-chemotherapy. The data of 372 patients was evaluated in which breast cancer was the most common cancer with 223 (59.95%) patients for which doxorubicin and cyclophosphamide (192, 51.61%) was the most administered chemotherapy combination. The second most common cancer was gastrointestinal (GI) cancer with stomach cancer in 47 (12.6%), colorectal cancer in 4 (1%), and pancreatic cancer in 2 (0.54%). A total of 360 (96.8%) patients received an HEC regimen across the cycle, while only 5 (1.3%) received an MEC regimen. The regimen demonstrated exceptional efficacy with a 96.9% overall response rate across all cycles. Complete control rates for acute CINV were 92% and 90% for delayed CINV across chemotherapy cycles. Complete response rates remained consistently high (94%-98%) across all cycles and overall phases. Only 3% of patients experienced anticipatory CINV. This dexamethasone-sparing Generic NEPA regimen showed remarkable efficacy in CINV management for HEC/MEC regimen-receiving patients, maintaining high response rates in both acute and delayed across all cycles. These findings indicate a potential paradigm shift in CINV prophylaxis, necessitating further investigation through prospective, randomized controlled trials to validate long-term safety and efficacy.

A comparative study of propranolol versus amitriptyline at a low dose for prophylaxis of episodic migraine at a tertiary care centre

A comparative study of propranolol versus amitriptyline at a low dose for prophylaxis of episodic migraine at a tertiary care centre

Sulfamethoxazole-Trimethoprim Prophylaxis in Pediatric Oncology Patients With Glucose-6-Phosphate Dehydrogenase Deficiency.

We sought to determine whether Pneumocystis jirovecii pneumonia prophylaxis with sulfamethoxazole-trimethoprim (SMX-TMP) is associated with an increased frequency of acute hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency versus non-G6PD-deficient controls in a pediatric oncology population. There was no statistically significant difference in change in hemoglobin or transfusion requirements after starting SMX-TMP between groups. These findings suggest no increased risk of acute hemolytic anemia with SMX-TMP administered at prophylaxis doses in patients with G6PD deficiency.

Preoperative single dose versus conventional antibiotic prophylaxis in thyroid surgery

Preoperative single dose versus conventional antibiotic prophylaxis in thyroid surgery

Evaluation of the Adherence to the Antimicrobial Prophylaxis Guidelines before Cardiac Surgeries in a Specialized University Hospital: A Unicenter Cross-Sectional Study from Iran

Background: Surgical site infection (SSI) is the most common reason for patient readmission after surgery. Because most cases of surgical site infection are preventable with antimicrobial prophylaxis, adherence to appropriate guidelines is critical. The aim of this study was to evaluate adherence to guideline recommendations for antimicrobial prophylaxis of surgical site infections at Shahid Chamran Heart Hospital, Isfahan, Iran. Methods: This cross-sectional observational study was conducted using prospective data collected from December 2021 to June 2022 in the cardiac surgery ward of Chamran Hospital. Adherence to "Clinical practice guidelines for antimicrobial prophylaxis in surgery (2013)" was assessed using data from patient records regarding the type, dosage, timing, and duration of antimicrobial prophylaxis. Results: A total of 363 patients were included in this study. The compliance rate with the guideline in terms of the type, dosing, initiation time, redosing and duration of the antimicrobial agent was 99.72%, 1.6%, 98.8%, 29.28%, and 0% respectively. Conclusion: The present study revealed relatively low adherence to the guidelines in terms of dosing, re-dosing and duration of antimicrobial prophylaxis at Chamran Heart Hospital. Based on the results, developing a local guideline is highly recommended.

Characterizing Enoxaparin's Population Pharmacokinetics to Guide Dose Individualization in the Pediatric Population.

Pediatric dosing of enoxaparin was derived based on extrapolation of the adult therapeutic range to children. However, a large fraction of children do not achieve therapeutic anticoagulation with initial dosing. We aim to use real-world anti-Xa data obtained from children receiving enoxaparin per standard of care to characterize the population pharmacokinetics (PopPK).Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Also, kindly confirm the details in the metadata are correct.The author names are accurately presented and the metadata are correct. METHODS: A PopPK analysis was performed using NONMEM, and a stepwise covariate modeling approach was applied for the covariate selection. The final PopPK model, developed with data from 1293 patients ranging in age from 1 day to 18 years, was used to simulate enoxaparin subcutaneous dosing for prophylaxis and treatment based on total body weight (0-18 years, TBW) or fat-free mass (2-18 years, FFM). Simulated exposures in children with obesity (body mass index percentile ≥95th percentile) were compared with those without obesity. A linear, one-compartment PopPK model that included allometric scaling using TBW (<2 years) or FFM (≥2 years) characterized the enoxaparin pharmacokinetic data. In addition, serum creatinine was identified as a significant covariate influencing clearance. Simulations indicated that in patients aged <2 years, the recommended 1.5 mg/kg TBW-based dosing achieves therapeutic simulated concentrations. In pediatric patients aged ≥2 years, the recommended 1.0 mg/kg dose resulted in exposures more comparable in children with and without obesity when FFM weight-based dosing was applied. Using real-world data and PopPK modeling, enoxaparin's pharmacokinetics were characterized in pediatric patients. Using FFM and twice-daily dosing might reduce the risk of overdosing, especially in children with obesity.

OPTIMIS PRO – A Novel Algorithm to Improve Perioperative Antibiotic Administration

Objectives The selection and dosing of surgical antimicrobial prophylaxis (SAP) to prevent surgical site infections (SSIs) is often improvisational and inappropriate in clinical settings resulting in increased risk of SSI. We therefore developed and implemented a novel computer decision support tool, OPTIMIS PRO (OPTIMIzing PROphylaxis), to improve appropriate SAP selection specific to each patient’s procedure and clinical context. Methods: This quality improvement study was conducted at a tertiary hospital network over 2 years, divided into pre-intervention (June 2021-June 2022) and post-intervention (June 2022-June 2023) periods. The intervention was a computer decision support tool programmed within the hospital’s health information system to provide patient-specific SAP recommendations based on four variables: procedure name, patient’s beta-lactam allergy status, MRSA status, and weight. Approximately 3046 unique surgical procedures were identified and a specific best practice SAP recommendation for each surgery was identified based on international practice guidelines, up-to-date literature, and panel expertise input from 14 surgical divisions at our institution. Safety of cefazolin prophylaxis among patients with self-reported beta-lactam allergy was established in the pre-operative clinic using a validated simple two-item questionnaire (Figure 1). During each standard preoperative preparation, a best practice SAP recommendation alert was then provided to the responsible anesthesiologist based on the inputs from the four aforementioned variables (Figure 2). To assess the impact of the OPTIMIS PRO tool on antibiotic prescribing, we retrospectively audited SAP selection before and after implementation, also assessing appropriateness for each of the specific inputs using evidence-based criteria. Results: Over 30 000 OPTIMIS PRO recommendation alerts were logged in the 12-month post-intervention period. A random sample audit of 408 surgical encounters were selected from the pre- and post-intervention period for analysis. Overall, appropriate antibiotic administration rose from 77% (161/208) to 92.5% (185/200) (x2=18.0, p &lt; 0 .001) post-intervention. Usage of cefazolin among patients reporting a beta lactam allergy rose from 48% (16/33) to 100% (12/12). None of these 12 patients experienced adverse reactions as a result of beta lactam exposure. Appropriate antibiotic selection based on MRSA status was high pre- and post-implementation (98.4% vs 99.4%); but significant improvements were made for procedure-specific antibiotic selection (80.5 vs 94.5%; x2=19.3, p &lt; 0 .001) and weight-based dosing (92.5% vs 98.4%; x2=7.45, p=0.006). Conclusion: In this first-ever intervention designed to direct SAP prescribing based on patient specific variables, we significantly improved appropriate SAP selection across a comprehensive list of surgical procedures. Future analysis should include assessing potential reductions in SSIs as result of using the support

The Uncharted Patterns of Antibiotic Prescribing in Urology Ambulatory Practices: A Four-Year Analysis

Background: Urinary tract infections (UTIs) represent a prevalent indication for outpatient antibiotic usage, yet limited data exist regarding antibiotic prescriptions within urology specialties. This study aimed to assess antibiotic prescribing patterns in urology offices over a four-year period, providing insights for potential stewardship interventions. Methods: The analysis focused on antibiotic prescribing trends in adults between 2018 and 2021 during both visit and non-visit (e.g. telephone and chart messages) encounters across 15 ambulatory Urology clinics in an academic medical center in Western New York. Exclusions were made for antivirals, antiparasitics, antifungals, oral suspensions, selected non-UTI antibiotics, duplicate orders on the same day or week, and prescriptions exceeding 28 days. Prescriptions were categorized into single doses administered in the clinic and those prescribed for 2-28 days, with descriptive statistics and trend analyses conducted using SAS v9.14. Results: Over the four-year period, 54,282 prescriptions were analyzed. Of these, 26,944 (49.7%) were single doses administered in the clinic, predominantly for pre-procedure prophylaxis. The most commonly prescribed antibiotics for prophylaxis were fluoroquinolones (FQ) (47.5%), followed by ceftriaxone (19.2%), nitrofurantoin (13.2%), trimethoprim/sulfamethoxazole (8.6%), and gentamicin (4.2%). Among the 27,288 prescriptions for 2-28 days, 72.3% were from non-visit encounters, with 61.6% prescribed by advanced practice providers (APPs) (Figure 1). The mean number of prescriptions per patient was 2.07, with women receiving more prescriptions than men (2.39 vs. 1.88, P &lt; 0.001). FQ remained the most commonly prescribed antibiotics during all encounters (23.7%), followed by nitrofurantoin (23.0%) (Figure 2). The antibiotic duration was longer for visit-based compared to non-visit-based prescriptions (mean 10 vs. 7 days, P &lt; 0.001). Notably, there was a significant decrease in fluoroquinolone use between Q1 2018 and Q4 2019 for both male and female patients, followed by insignificant changes thereafter. Conclusions: Antibiotic use in urology outpatient settings is substantially underestimated if only prescriptions made during visit encounters are considered. More than two-thirds of prescriptions for 2-28 days were from non-visit encounters, with the majority originating from APPs. The average therapy duration exceeded guideline recommendations. Moreover, approximately half of the antibiotics were administered in the office for pre-procedure prophylaxis. To enhance antibiotic prescribing in these specialized clinics, interventions should focus on non-visit prescriptions and provide education for APPs, alongside adjustments to default durations in electronic orders. Further evaluation is essential to assess the appropriateness of single doses for pre-procedure prophylaxis.

Clinician Interpretation and Management of Discordant PCR+/Toxin- Clostridioides difficile Testing Results Post-COVID

Background: Our institution utilizes a two-step algorithm consisting of an initial polymerase chain reaction (PCR) test with positive results reflexed to an enzyme immunoassay (EIA) for toxin. Institutional guidelines implemented during the COVID-19 pandemic recommended applying clinical judgment to patients with PCR+/Toxin- (discordant) results when determining if treatment is indicated. Pre-pandemic, we found that clinicians continued CDI-directed therapy in 56% of patients following the Toxin- result. Our study aims to identify how clinicians interpret PCR+/Toxin- results and reasons for management decisions post-pandemic. Methods: At an academic medical center, we conducted a retrospective cohort study of the first 50 inpatient charts with PCR+/Toxin- results from August to October 2022. Data was abstracted from clinical, pharmacy, and microbiology databases. The primary outcome was the proportion of patients continued on CDI-directed therapy for ≥24 hours after the Toxin- result became available. Secondary outcomes included the proportion of patients prescribed a full treatment course for CDI and the reasons for continuing treatment. Results: There were 37 patients (74%) who started CDI-directed treatment after initial PCR+ Results: Of these patients, 59% (22/37) were continued on treatment for ≥24 hours after the Toxin- result (primary outcome). 77% (17/22) of these patients who met the primary outcome completed full treatment courses. Three patients were transitioned to prophylaxis dosing after the Toxin- result. The most common reason for continuing treatment after discordant results was high clinical suspicion for CDI (Figure). There were no CDI-related complications in this 50-patient cohort. In immunocompromised patients, 70% (16/23) started treatment after initial PCR+ results and 81% (13/16) met the primary outcome. In patients admitted specifically to immunocompromised inpatient services, 90% (9/10) started treatment after initial PCR+ results and 100% (9/9) met the primary outcome. Conclusion: The majority of patients started on treatment after the PCR+ result were continued on treatment following the Toxin- result, though several of these patients did not complete full treatment courses. Treatment rates were similar to our pre-pandemic baseline. When patients were continued on treatment after discordant results, clinicians cited appropriate high clinical suspicion. Notably, every patient admitted to an immunocompromised service was continued on treatment after Toxin- Results: Overall, clinicians are following institutional guidelines by applying clinical judgement when interpreting discordant Results: Further research will help identify what variables affect clinician interpretation and management practices for discordant results, which will help shape institutional guideline updates, clinician education, and additional stewardship interventions.

A 30-year perspective of low-dose dexamethasone, a single dose of mannitol and antiseizures prophylaxis on the prognosis of pneumococcal meningitis

Objectives This study details the accumulated experience of more than 31 years using a low-dose systematic dexamethasone protocol with mannitol and antiseizure prophylaxis for the treatment of suspected pneumococcal meningitis. Methods Data have been prospectively collected for the period1977–2018. From 1987, patients with suspected pneumococcal meningitis received 12 mg dexamethasone followed by 4 mg/6 h for 48 h, started before or with the first antibiotic dose. They also received (1) a single intravenous dose of 0.5–1 g/Kg mannitol, and (2) antiseizure prophylaxis with phenytoin. Results In total, 363 episodes of pneumococcal meningitis were recorded. Of these, 242 were treated with the dexamethasone protocol after 1987 and 121 were treated without the protocol. Overall mortality was 11.6% (28/242) among patients treated with dexamethasone and 35% (43/121) among those treated without dexamethasone (p = 0.000). Early mortality was significantly lower at 5.8% (14/242) with dexamethasone and 24% (29/121) without dexamethasone (p = 0.000). Finally, neurological mortality was significantly lower at 7.4% (18/242) with dexamethasone and 23% (28/121) without dexamethasone (p = 0.000). Conclusions A low dose of dexamethasone along with a single dose of mannitol and antiseizures prophylaxis might be useful for reducing both overall and early mortality in pneumococcal meningitis in adult patients.

3-Position Biaryl Endochin-like Quinolones with Enhanced Antimalarial Performance.

ELQ-300 is a potent antimalarial drug with activity against blood, liver, and vector stages of the disease. A prodrug, ELQ-331, exhibits reduced crystallinity and improved in vivo efficacy in preclinical testing, and currently, it is in the developmental pipeline for once-a-week dosing for oral prophylaxis against malaria. Because of the high cost of developing a new drug for human use and the high risk of drug failure, it is prudent to have a back-up plan in place. Here we describe ELQ-596, a member of a new subseries of 3-biaryl-ELQs, with enhanced potency in vitro against multidrug-resistant Plasmodium falciparum parasites. ELQ-598, a prodrug of ELQ-596 with diminished crystallinity, is more effective vs murine malaria than its progenitor ELQ-331 by 4- to 10-fold, suggesting that correspondingly lower doses could be used to protect and cure humans of malaria. With a longer bloodstream half-life in mice compared to its progenitor, ELQ-596 highlights a novel series of next-generation ELQs with the potential for once-monthly dosing for protection against malaria infection. Advances in the preparation of 3-biaryl-ELQs are presented along with preliminary results from experiments to explore key structure-activity relationships for drug potency, selectivity, pharmacokinetics, and safety.

Effect of pneumatic leg compression on phenylephrine dose for hypotension prophylaxis via variable rate infusion at cesarean delivery: an unblinded randomized controlled trial

BackgroundPhenylephrine infusion is recommended to prevent spinal hypotension during cesarean delivery (CD) but may be associated with dose-dependent side effects. We hypothesized that adding intermittent pneumatic compression (IPC) of the lower legs to a variable-rate phenylephrine infusion will reduce the dose of phenylephrine required during CD. MethodsSeventy-six healthy women undergoing elective CD under combined spinal-epidural anesthesia were randomly assigned to IPC or control groups (n = 38 per group). After spinal anesthesia, IPC of the lower legs was initiated in the IPC group, and all women received a phenylephrine infusion starting at 25 μg·min−1 and increasing by 16.7 μg·min−1 for systolic blood pressure (SAP) < 90% baseline. If hypotension (SAP < 80% baseline) occurred, 100 μg phenylephrine bolus was administered. The primary outcome was the dose of phenylephrine per minute. ResultsThe dose of phenylephrine per minute (34.4 ± 7.3 μg·min−1 vs. 40.9 ± 9.5 μg·min−1, P = 0.001; mean difference −6.6 μg·min−1, 95% CI −10.5 to −2.7 μg·min−1) and the incidence of hypotension (24% vs. 55%, P = 0.005) were lower in the IPC group than in the control group. There were no significant differences between the two groups in the total dose of phenylephrine (603.2 ± 217.1 μg vs. 706.2 ± 247.5 μg, P = 0.058; mean difference −102.9 μg, 95% CI −209.4 to 3.5 μg), maternal side effects, or neonatal outcomes. ConclusionsIntermittent pneumatic compression combined with a variable-rate phenylephrine infusion reduced the phenylephrine dose per minute and the incidence of hypotension during CD under spinal anesthesia.

Real world incidence, prevention, and management of tumor lysis syndrome in patients with chronic lymphocytic leukemia treated with venetoclax in the inpatient and outpatient settings.

7045 Background: Venetoclax (ven) is a BCL2 inhibitor used for the treatment (tx) of chronic lymphocytic leukemia (CLL) which can cause clinical or laboratory (lab) tumor lysis syndrome (TLS). A dose ramp-up schedule and prophylaxis strategies are incorporated into NCCN guidelines and prescribing information. Prior reports have of TLS focused mostly on patients (pts) with relapsed/refractory CLL receiving ven as monotherapy. Methods: We included pts &gt;18y who were diagnosed with CLL or small lymphocytic lymphoma (SLL) and received tx with commercial ven in any line of therapy at our institution from 1/1/2016 to 12/31/2020. TLS was defined using the modified Cairo Bishop Criteria. TLS risk was based on the size of the largest lymph node (LN) on imaging or examination and the absolute lymphocyte count (ALC) as defined by ven prescribing information. Results: We included 616 ven escalations among 136 pts with CLL. Median age was 70 years and 86% were white. Ven was part of first line of tx for 48 pts (35%). 11% had high TLS risk at baseline; 37% among those escalated exclusively inpatient (IP) and 2% among those escalated exclusively outpatient (OP). Among those treated with ven, 47 pts (35%) received ven monotherapy. 74 (54%) of pts were escalated exclusively OP, 35 (26%) had at least one prophylactic hospitalization and 27 (20%) were escalated exclusively IP. During ven initiation, 86% of pts received allopurinol, 71% intravenous hydration, 18% phosphate binders, and 10% prophylactic rasburicase. Among the entire cohort, 8 pts (5.9%) developed lab TLS and zero developed clinical TLS. There were 11 TLS events; 2 pts developed TLS in more than one escalation. Incidence of TLS was 15% for those escalated exclusively IP, 5.7% for those with any prophylactic hospitalization and 2.7% for those escalated exclusively OP. Those who developed TLS were more likely to have a higher TLS risk at baseline, preceding isolated hyperuricemia, or CrCl measurement &lt; 60 mL/min (Table). Conclusions: In this single institution retrospective cohort study, lab TLS was observed, though clinical TLS was not. Baseline hyperuricemia and impaired renal function were more common among those who developed lab TLS compared to those who did not. Prophylactic measures, including use of IV hydration, may have contributed to low rates of observed TLS in the outpatient setting. [Table: see text]