Days Of Vancomycin Research Articles

Comparing rates of recurrent infection for first occurrence of Clostridioides difficile between tapered oral vancomycin and standard vancomycin: a retrospective, propensity matched cohort study.

To compare rates of Clostridioides difficile infection (CDI) recurrence following initial occurrence treated with tapered enteral vancomycin compared to standard vancomycin. Retrospective cohort study. Community health system. Adults ≥18 years of age hospitalized with positive C. difficile polymerase chain reaction or toxin enzyme immunoassay who were prescribed either standard 10-14 days of enteral vancomycin four times daily or a 12-week tapered vancomycin regimen. Retrospective propensity score pair matched cohort study. Groups were matched based on age < or ≥ 65 years and receipt of non-C. difficile antibiotics during hospitalization or within 6 months post-discharge. Recurrence rates were analyzed via logistic regression conditioned on matched pairs and reported as conditional odds ratios. The primary outcome was recurrence rates compared between standard vancomycin versus tapered vancomycin for treatment of initial CDI. The CDI recurrence rate at 6 months was 5.3% (4/75) in the taper cohort versus 28% (21/75) in the standard vancomycin cohort. The median time to CDI recurrence was 115 days versus 20 days in the taper and standard vancomycin cohorts, respectively. When adjusted for matching, patients in the taper arm were less likely to experience CDI recurrence at 6 months when compared to standard vancomycin (cOR = 0.19, 95% CI 0.07-0.56, p < 0.002). Larger prospective trials are needed to elucidate the clinical utility of tapered oral vancomycin as a treatment option to achieve sustained clinical cure in first occurrences of CDI.

Drug Administration Patterns in Patients on Extracorporeal Membrane Oxygenation

AbstractThis study aimed to identify drug administration patterns in patients of all ages supported with extracorporeal membrane oxygenation (ECMO) across multiple institutions and determine which of the most commonly administered drugs lack published dosing guidance.We conducted a retrospective, multicenter database study using the TriNetX data network and the Pediatric Health Information Systems database. All adults and children supported with ECMO were included for analysis. Drug exposure and days of use were described according to age category (Infants [&lt;2 years], Children [≥2 and &lt;18 years], and Adults [≥18 years]). The literature was reviewed for the top 50 most commonly administered drugs in all ages; all pharmacokinetic and ex vivo studies were included.A total of 17,909 patients were analyzed. The patient population comprised 24% adults (n = 4,253), 18% children (n = 3266), and 58% infants (n = 10,390). The 10 most commonly administered drugs, by days of use, were heparin, furosemide, midazolam, morphine, fentanyl, vancomycin, milrinone, hydrocortisone, epinephrine, and lorazepam. Published literature comprised 86 studies, including 66 pharmacokinetic studies (77%) and 20 ex vivo studies (23%). Of these, 29% (n = 19) were conducted in adults, 14% (n = 9) were conducted in children, and 60% (n = 39) were performed in infants. ECMO-specific dosing guidance for any age was available for only 28% (n = 14) of the top 50 most commonly administered drugs.Sedatives, antimicrobials, and cardiovascular agents are among the most commonly administered drugs in patients supported with ECMO. This study highlights an urgent need for evidence-based dosing guidance in this patient population.

Streptococcus gallolyticus subspecies pasteurianus causing late onset neonatal sepsis and meningitis: a case report

Streptococcus gallolyticus is a gram-positive microbe rarely isolated from cases of neonatal sepsis. Prompt identification, management and monitoring is necessary in such cases due to potential complications like meningitis and endocarditis. We report a preterm baby referred to us on day 18 of life with fever, respiratory distress and lethargy with seizure. Blood culture revealed S. gallolyticus subspecies pasteurianus with meningitis on cerebrospinal fluid examination. He was treated with 21 days of injectable vancomycin and teicoplanin. Baby had no neurological sequelae or other end organ complications. To the best of our knowledge, this is the first case report from eastern India describing sepsis secondary to this rare organism.

Is shorter also better in the treatment of Clostridioides difficile infection?

To assess the effectiveness of shortened regimens of vancomycin or fidaxomicin in the treatment of Clostridioides difficile infection (CDI). Adult patients with CDI hospitalized from January 2022 to May 2023 were included in this observational study. In patients with CDI treated with vancomycin or fidaxomicin, antibiotic treatment was discontinued after either 5 or 7 days of vancomycin or 5 days of fidaxomicin if there was a clinical response and improvement in laboratory parameters. The control cohort was treated with the standard 10 day regimen of either vancomycin or fidaxomicin. The follow-up was 60 days. Causative C. difficile strains were characterized by ribotyping and toxin gene detection when available. Twenty-five patients (median age 76 years) received shortened treatment with vancomycin (n = 21), or fidaxomicin (n = 4). Five cases fulfilled the criteria for severe CDI. Twenty-three patients completed follow-up; two died from causes other than CDI, and two developed recurrent CDI (8.0%). Ribotypes (RTs) 001 and 014 were the most prevalent with 20% each. In two C. difficile isolates, binary toxin genes were detected (RTs 078 and 023). In the control group of 22 patients recurrent CDI developed in 5 patients (22.7%). No statistically significant differences were found between the groups. Shortened treatment regimens for CDI with vancomycin and fidaxomicin were shown to be effective in our cohort of patients compared with 10 days of treatment. The recurrence rate was lower in the study group. A larger, prospective, double-blind, randomized, multicentre study is needed to support our findings.

A Randomized, Double-Blind, Phase 3 Safety and Efficacy Study of Ridinilazole Versus Vancomycin for Treatment of Clostridioides difficile Infection: Clinical Outcomes With Microbiome and Metabolome Correlates of Response.

Exposure to antibiotics predisposes to dysbiosis and Clostridioides difficile infection (CDI) that can be severe, recurrent (rCDI), and life-threatening. Nonselective drugs that treat CDI and perpetuate dysbiosis are associated with rCDI, in part due to loss of microbiome-derived secondary bile acid (SBA) production. Ridinilazole is a highly selective drug designed to treat CDI and prevent rCDI. In this phase 3 superiority trial, adults with CDI, confirmed with a stool toxin test, were randomized to receive 10 days of ridinilazole (200 mg twice daily) or vancomycin (125 mg 4 times daily). The primary endpoint was sustained clinical response (SCR), defined as clinical response and no rCDI through 30 days after end of treatment. Secondary endpoints included rCDI and change in relative abundance of SBAs. Ridinilazole and vancomycin achieved an SCR rate of 73% versus 70.7%, respectively, a treatment difference of 2.2% (95% CI: -4.2%, 8.6%). Ridinilazole resulted in a 53% reduction in recurrence compared with vancomycin (8.1% vs 17.3%; 95% CI: -14.1%, -4.5%; P = .0002). Subgroup analyses revealed consistent ridinilazole benefit for reduction in rCDI across subgroups. Ridinilazole preserved microbiota diversity, increased SBAs, and did not increase the resistome. Conversely, vancomycin worsened CDI-associated dysbiosis, decreased SBAs, increased Proteobacteria abundance (∼3.5-fold), and increased the resistome. Although ridinilazole did not meet superiority in SCR, ridinilazole greatly reduced rCDI and preserved microbiome diversity and SBAs compared with vancomycin. These findings suggest that treatment of CDI with ridinilazole results in an earlier recovery of gut microbiome health. Clinical Trials Registration.Ri-CoDIFy 1 and 2: NCT03595553 and NCT03595566.

Implementation of vancomycin AUC/MIC dosing vs traditional trough dosing and incidence of acute kidney injury at a rural community hospital.

Vancomycin treats methicillin-resistant Staphylococcus aureus infections in hospitalized patients, yet nephrotoxicity is a major risk. Dosing based on the ratio of vancomycin 24-hour area under the curve to minimum inhibitory concentration (AUC/MIC) is preferred over a trough-only vancomycin dosing approach to minimize the risk of acute kidney injury (AKI). This study compares the safety of AUC/MIC-guided and trough-only vancomycin dosing at a 255-bed hospital. A retrospective cohort study of adult patients with stable renal function who received at least 3 days of intravenous vancomycin via either AUC/MIC or trough-only dosing was conducted. The primary outcome was AKI occurrence during treatment. Secondary outcomes included the frequencies of therapeutic, subtherapeutic, and supratherapeutic vancomycin troughs. Relative risk calculations were performed for all outcomes. 600 patients from the trough-only group and 561 patients from the AUC/MIC group were included. 121 patients from the trough-only group and 87 patients from the AUC/MIC group experienced AKI during treatment (relative risk [RR], 0.769; 95% CI, 0.599-0.988; P = 0.0397). Compared with the trough-only group, the AUC/MIC group was significantly less likely to have supratherapeutic troughs (RR, 0.703; 95% CI, 0.611-0.809; P < 0.0001) and significantly more likely to have therapeutic troughs (RR, 1.14; 95% CI, 1.069-1.211; P < 0.0001), with no significant between-group difference in subtherapeutic troughs (RR, 1.03; 95% CI, 0.854-1.25; P = 0.74). AUC/MIC dosing was associated with significantly lower risk of AKI, a lower risk of supratherapeutic trough levels, and a higher risk of therapeutic trough levels, with no significant difference in subtherapeutic troughs when compared to trough-only dosing. Limitations of this study included its retrospective nature and reliance on manual chart review.

Preliminary Safety Results of the Open-Label Phase of a 2-Part Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of an Investigational Microbiome Therapeutic, SER-155, in Adults Undergoing Hematopoietic Cell Transplantation

Background: In patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT), low gastrointestinal (GI) microbial diversity is associated with risk of bloodstream infections (BSIs), acute graft-versus-host disease (aGvHD), and death. SER-155 is an investigational cultivated microbiome therapeutic rationally designed to improve clinical outcomes in allo-HCT patients by preventing pathogen domination, promoting epithelial barrier integrity, and reducing colonic inflammation. SER-155-001 is a 2-part, Phase 1b study evaluating the safety, tolerability, pharmacokinetics, and efficacy of SER-155 in adults undergoing allo-HCT. Here, we present preliminary safety and tolerability data from the open-label Cohort 1 through Day 100 post HCT. Study Design and Methods: Adult recipients of allo-HCT were eligible for screening. Patients were excluded if they: a) were planned for umbilical cord blood or ex vivo T-cell depletion, b) had received a fecal microbiota transplant or any live biotherapeutic product within 3 months prior to screening, and/or c) had evidence of relapse or progression of hematologic malignancy (minimal residual disease was allowed). HCT conditioning and aGvHD prophylaxis were per investigator discretion. Following screening, patients received two treatment courses (before conditioning and after neutrophil engraftment) comprised of microbiome conditioning with 4 days of oral vancomycin (to facilitate engraftment of SER-155 strains) followed by 10 days of oral SER-155 (see study design schematic, Figure 1). The primary endpoint was the incidence and severity of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs), designated as invasive infection, BSI, and GI infection. Results: Fifteen adult patients were enrolled and 13 received study drug (safety population). Of these 13 patients, the median age was 67.0, all were White, and 54% were male. Underlying diseases included acute myeloid leukemia (6 patients [46.2%]); myelodysplastic syndromes and myeloproliferative neoplasms (2 patients each [15.4%]; and acute lymphoblastic leukemia, chronic myeloid leukemia, and classic Hodgkin's lymphoma (1 patient each [7.7%]). Ten patients (76.9%) received peripheral blood stem cells; 9 (69.2%) had an unrelated donor, 8 (61.5%) underwent a reduced-intensity conditioning regimen, and 3 (23.1%) received myeloablative conditioning. Eleven patients received allo-HCT, all patients had neutrophil engraftment within the expected timeframe and 10 had 100-day follow-up data available. Nine of these patients (81.8%) received tacrolimus/methotrexate-based GvHD prophylaxis. SER-155 was generally well-tolerated ( Table 1). Treatment-emergent AEs (TEAEs) were observed in all patients as is expected in this patient population. One TEAE considered unrelated to study drug, resulted in study discontinuation. Most AEs were gastrointestinal in nature with diarrhea being the most common AE. No SAEs were considered related to SER 155, and most SAEs and AESIs occurred after HCT and before starting the second course of SER-155. No deaths occurred prior to Day 100. Three deaths occurred after Day 100, all deemed to be unrelated to study drug by the investigators. No BSIs attributable to organisms in SER-155 occurred. Commencement of the double-blind, randomized, placebo-controlled Cohort 2 (n=60) was initiated following approval of the Data Safety Monitoring Committee. Conclusions: In patients enrolled in this open-label Cohort 1 of this Phase 1b study, SER-155 was well-tolerated through Day 100. Although sample size is limited, the observed safety and tolerability profile of SER-155 in this patient population is consistent with multiple preclinical assessments supporting the safety of SER-155 for therapeutic use. Enrollment in the double-blind, randomized, placebo-controlled second cohort to assess safety, efficacy, and changes in microbiome composition and function is ongoing.

Vancomycin modestly attenuates symptom severity during onset of and recovery from exertional heat stroke in mice.

Increased intestinal permeability during exertion and subsequent leakage of bacteria into circulation is hypothesized to accelerate exertional heat stroke (EHS) onset and/or exacerbate EHS severity. To provide proof of concept for this theory, we targeted intestinal microbiota via antibiotic prophylaxis and determined whether vancomycin would delay EHS onset and/or mitigate EHS severity and mortality rates using a mouse model of EHS. Mice were 1) designated as EHS or Exercise Control (ExC) and 2) given 7 days of vancomycin (VEHS, VExC) or untreated water (EHS, ExC) before EHS/Exercise. Following EHS/ExC, mice were euthanized immediately (0 h) or returned to their home cage (25°C) and euthanized after 3 h or 24 h. VEHS mice exhibited reduced abundance and altered composition of fecal bacteria (with notable decreases in genera within orders Clostridiales and Bacteroidales); increased water consumption, lower core temperature (TC) before and during heating (TCMax), lower circulating markers of organ damage and inflammation at 24 h; and reduced hepatic activation of stress pathways at 0 and 3 h compared with EHS mice. Vancomycin-induced alterations to the intestinal microbiota likely influenced EHS outcomes, but it is unconfirmed whether this is due to attenuated bacterial leakage into circulation or other (in)direct effects on physiology and behavior (e.g., decreased TC, increased water consumption). To our knowledge, this is the first study quantitating antibiotic effects in conscious/unanesthetized, exertional HS animals.NEW & NOTEWORTHY Vancomycin prophylaxis lowered core temperature before and during EHS, mitigated EHS-associated rise of hepatic biomarkers and cytokines/chemokines in circulation (particularly at 24 h), and corresponded to inhibited phosphorylation of hepatic c-Jun NH2-terminal kinase on Threonine 183/Tyrosine 185 at 0 and 3 h in conscious, unanesthetized mice. However, vancomycin also induced cecal enlargement suggesting its off-target effects could limit its utility against EHS.

Case report: Diagnosis and resolution of hepatic abscess in a neonate

BACKGROUND: Hepatic abscesses in the neonatal age can be caused by multiple etiologies and their variability in clinical presentation makes their diagnosis difficult. The incidence of infectious liver abscesses is low, however, their mortality is high and their timely diagnosis and early resolution are essential to improve prognosis and life expectancy, since therapeutic management is the cause of prolonged hospitalization due to the administration of long-lasting intravenous antimicrobials. The following is a case report of a neonatal patient with this pathology. CLINICAL REPORT: neonatal patient born by cesarean section, 38 weeks of gestation, male, admitted to the neonatology department due to the need for mechanical ventilation; with umbilical catheters for 72 hours. At 48 hours of life, he presented febrile peaks and elevation of acute phase reactants, later, abdominal distension, feeding intolerance and hepatomegaly, so antibiotic therapy was administered with suspicion of septic ileus. Due to persistent hepatomegaly, an abdominal ultrasound was performed in which cystic images were observed at the hepatic level. EVOLUTION: after the diagnosis of liver abscesses, it was decided to maintain antibiotic therapy with Meropenem and Vancomycin. Due to persistence of the abscesses despite treatment, surgical drainage was required on two occasions, the first at day 30 of life, and the second at 47 days of life. The newborn received, from the onset of symptoms and clinical symptoms, a total of 60 days of Meropenem and 48 days of Vancomycin, with complete resolution of the lesions after 68 days of hospitalization. CONCLUSION: Hepatic abscesses are rare in the neonatal age, of bacterial origin in most cases, related to hematic propagation due to umbilical catheterization. The pathology involves long hospitalizations and long-term antibiotic therapy; however, its prognosis is good with early diagnosis and timely treatment.

Oritavancin vs Standard of Care for Treatment of Nonendovascular Gram-Positive Bloodstream Infections.

Data is limited comparing oritavancin (ORT) to the standard-of-care (SOC) for the treatment gram-positive blood stream infections (BSI). This was a retrospective study of all patients in the Veteran's Affairs Health Care System treated with at least 1 dose of oritavancin or at least 5 days of vancomycin, daptomycin, ceftaroline, ampicillin, ampicillin-sulbactam, nafcillin, oxacillin, or cefazolin for a documented gram-positive BSI from 1 January 2015 to 30 June 2021. Patients with polymicrobial blood cultures or positive cultures from other sites were included if the organisms were sensitive to the incident antimicrobial; no concomitant antimicrobials could be used once the incident agent was started. Individuals were also excluded if they were diagnosed with endocarditis, had a neutrophil count 96-hours of treatment before the incident antimicrobial was started.The primary composite outcome was clinical failure, defined as all-cause mortality within 30-days from the end of therapy, or blood cultures positive for the incident organisms ≥72 hours after administration of the first dose and ≤30 days after the administration of the final dose of the study antimicrobial, or any drug or line-related readmissions within 30-days of hospital discharge. Two hundred-forty patients were identified for screening with 96 meeting criteria (27 in ORT and 69 in SOC groups). Baseline characteristics were generally balanced between groups except more patients in the ORT group received >96-hours of treatment before the incident antimicrobial was started (70.3% (19/27) vs 13.04% 9/69); P < .001). The pathogen most prevalent was methicillin susceptible Staphylococcus aureus (MSSA) (ORT 33.3% (9/27) vs SOC 46.4% (32/69)). Clinical failure occurred in 7.4% (2/27) in the ORT group and 17.4% (12/69) in SOC (P = .34). No components of the primary outcome were significantly different between groups, but AKI did occur more commonly in the SOC group (27.5% (19/69) vs 3.7% (1/27); P = .01). ORT appears to be a safe and effective option when directly compared to the SOC for non-endocarditis BSIs.

Evaluation of microbial and vancomycin treatments in ulcerative colitis in murine models.

Despite the number of available therapies for ulcerative colitis (UC), severe side effects and high cost has limited their clinical application. Thus, finding new alternative strategies with minimal side effects is inevitable. Therefore, this study aimed to compare the effectiveness of different therapeutic approaches in DSS-induced colitis. Firstly, we designed oral bio-therapeutic products, Live Bacterial Products (LBP), which include a mixture of fecal bacteria strains isolated from healthy mice and prepared by microencapsulation and freeze-dried techniques. Then we investigated the efficiency of 7 days of freeze-dried FMT, LBP, and vancomycin treatments in DSS-induced colitis. Secondly, we compared the effect of 15 days of microbial therapies (freeze-dried powder of FMT and LBP microcapsules) and seven days of oral vancomycin on the severity of colitis in mice. Furthermore, the levels of IL-1β and TNF-α were measured in serum by ELISA, and the fecal microbiota diversity was analyzed by high-throughput sequencing for all mice groups. After seven days of treatments, our results indicated that oral vancomycin reduced the severity of DSS-induced colitis in mice, where weight gain and a decrease in IL-1 β and TNF-α levels were observed in the vancomycin group compared with other treatment groups. While after two weeks of treatment, the LBP microcapsules were able to reduce the severity of colitis. And at the end of the treatment period, weight gain and a decrease in the DAI scores and the levels of IL-1β and TNF-α were noted in the LBP treatment group compared to other treatment groups. By high-throughput sequencing of the 16S rRNA gene, our results showed that while the microcapsules LBP treatment increased the fecal microbial diversity, after vancomycin therapy, most of the fecal microbiota genera and operational taxonomic units (OTUs) were depleted. Our results concluded that treatment duration and preparation methods affect the microbial therapies' efficiency in UC. Furthermore, this study highlighted the negative consequences of oral vancomycin administration on gut health that should be known before using this medication.

Teaching NeuroImages: Hemimeningitis mimicking acute ischemic stroke

A 78-year-old man with sudden-onset right-sided weakness and mutism had no history of fever, seizures, or headache. On examination, abulia, transcortical motor aphasia, and right dense hemiplegia were noted. Contrast-enhanced brain MRI suggested meningitis (figure 1) and ruled out stroke (figure 2). On CSF analysis, lymphocytic (94%) pleocytosis (163 cells/mm3), abundant Gram-positive cocci, and hyperproteinorrachy (48 mg/dL) with normal CSF:serum glucose ratio were noted. After 14 days of ceftriaxone plus vancomycin and recovery of hemiparesis (MRC 4/5), speech (improved fluency), and CSF–pleocytosis resolution (2 cells/mm3), the patient was discharged. Localized meningitis is rare. We found 2 reports: one stroke mimic1 and another associated with necrotizing vasculitis.2

Abscesso epidural espinhal na adolescência: relato de caso

Spinal epidural abscess (SEA) is a rare infectious emergency and capable of causing severe neurological deficits, especially in childhood. The mortality rate in adults varies from 5 to 23%, but in children the rates are even lower. This report aims to contribute to the scientific field by discussing a case of SEA in pediatrics. It is a teenager, 17 years old, presenting fever, low back pain and sebaceous cyst infected on her back for three days. She reports a history of drainage two days ago and a cesarean section with spinal anesthesia a year ago. Magnetic resonance imaging (MRI) of the lumbar showed posterior L1-L4 epidural collection. Epidural abscess drainage surgery was performed, with L3-L4 laminectomy, and positive culture for Methicillin-resistant Staphylococcus aureus (MRSA), sensitive to Vancomycin and Rifampicin. She was discharged after 21 days of intravenous Vancomycin, with a prescription for oral Rifampicin for three weeks. Previous skin infection is considered a classic precedent of SEA, suggesting that the patients condition was preceded by furunculosis. The microorganism responsible for 86% of SEA cases in childhood is Staphylococcus aureus. Back pain after spinal anesthesia, fever, skin infection and possible condition of immunosuppression indicated investigation for SEA. Gadolinium-contrast MRI corresponds to the gold standard diagnostic approach for SEA. The suspicion of the disease in pediatrics is extremely important in front of fever, back pain and spinal sensitivity, and should receive due attention and investigation before an indicative clinic.

1845. Oritavancin Compared to the Standard-of-Care for the Treatment of Gram-positive Blood Stream Infections

Abstract Background Data is limited comparing oritavancin (ORT) to the standard-of-care (SOC) for the treatment gram-positive blood stream infections (BSI). Methods This was a retrospective study of all patients in the Veteran’s Affairs Health Care System treated with at least 1 dose of oritavancin or at least 5 days of vancomycin, daptomycin, ceftaroline, ampicillin, ampicillin-sulbactam, nafcillin, oxacillin, or cefazolin for a documented gram-positive BSI from 1 January 2015 to 30 June 2021. Patients with polymicrobial blood cultures or positive cultures from other sites were included if the organisms were sensitive to the incident antimicrobial; no concomitant antimicrobials could be used once the incident agent was started. Individuals were also excluded if they were diagnosed with endocarditis, had a neutrophil count &amp;lt; 500 cells/mm3, or had a diagnosis of Human Immunodeficiency Virus (HIV) on their problem list. The primary composite outcome was clinical failure, defined as all-cause mortality within 30-days from the end of therapy, or blood cultures positive for the incident organisms ≥72 hours after administration of the first dose and ≤30 days after the administration of the final dose of the study antimicrobial, or any drug or line-related readmissions within 30-days of hospital discharge. Secondary outcomes included all-cause 30-day readmission and rates of acute kidney injury (AKI). Results Two hundred-forty patients were identified for screening with 96 meeting criteria (27 in ORT and 69 in SOC groups). Baseline characteristics were generally balanced between groups except more patients in the ORT group received &amp;gt; 96-hours of treatment before the incident antimicrobial was started (70.3% (19/27) vs. 13.04% (9/69); p&amp;lt;0.001). The pathogen most prevalent was methicillin-susceptible Staphylococcus aureus (MSSA) (ORT 33.3% (9/27) vs. SOC 46.4% (32/69)). Clinical failure occurred in 7.4% (2/27) in the ORT group and 17.4% (12/69) in SOC (p=0.34). No components of the primary outcome were significantly different between groups, but AKI did occur more commonly in the SOC group (27.5% (19/69) vs. 3.7% (1/27); p=0.01). Conclusion ORT appears to be a safe and effective option when directly compared to the SOC for non-endocarditis BSIs. Disclosures Ryan P. Moenster, Pharm.D., FIDSA, Melinta Therapeutics: Grant/Research Support|Melinta Therapeutics: Honoraria.

1791. Leveraging EMR Alerts for Vancomycin Time Outs

Abstract Background Vancomycin represented the most used antibiotic at our academic medical center from 2014-2022. To enhance compliance with the “antibiotic time out” part of the CDC Core Elements for Stewardship, we designed an electronic medical record (EMR) best practice alert (BPA) to assist providers in identifying patients eligible for vancomycin discontinuation. Methods This is a single center, retrospective pre (06/01/14-2/24/20)/post (02/25/20-03/31/22) comparison of vancomycin utilization after the introduction of a locally validated automated vancomycin time-out. The BPA alerted on patients who had received vancomycin for 72h, had no microbiological evidence of methicillin resistant S. aureus, and had no infectious diseases consult. While other vancomycin reduction strategies had previously been implemented as part of the stewardship program, no other intervention debuted during the same time period. An interrupted time series analysis was performed to assess immediate and ongoing trend changes of institutional vancomycin use. Wilcoxon rank sum and chi2 analyses were also performed. Results There were 36,817 inpatient vancomycin orders placed. The BPA triggered during 1,881 (15.7%) orders in the post-BPA period, which was 49.6% of the 3,794 orders still active at 72h. After BPA introduction, there was an immediate decrease in vancomycin days of therapy (DOT)/1000 patient days (PD) ±SE (-8.5 ±3.6; P = 0.021) followed by a significant decrease in the monthly trend relative to the pre-intervention trend (-0.7 DOT/1000 PD ±0.2; P&amp;lt; 0.001). Median vancomycin DOT/1000 PD decreased from 145.9 (IQR 140.2-153.0) to 117.3 (IQR 107.7-122.6) in pre and post periods respectively (P&amp;lt; 0.001). Length of therapy (LOT) decreased, orders were more commonly discontinued by day 5, and orders were more likely to be discontinued prior to discharge. Separate analysis including only orders with &amp;gt;72h showed similar results (Table 1). Table 1Vancomycin length of therapy (LOT) pre and post-BPA Time Out.Figure 1Vancomycin days of therapy per 1000 patient days (DOT/1000PD) trends pre and post-BPA Time Out. Conclusion Introduction of an EMR automated vancomycin time out was an effective tool to decrease vancomycin utilization at an academic medical center. Disclosures All Authors: No reported disclosures.

PARANOID ABOUT RASHES: OLANZAPINE INDUCED DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS

<h3>Introduction</h3> Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a severe adverse reaction caused by more than 50 prescription drugs. Although antiepileptics and antibiotics account for most cases, the variety of potential drug classes can make identifying the causative agent challenging. <h3>Case Description</h3> Thirty-year-old male was initially admitted to the medical ICU for treatment of alcoholic hepatitis. Hospital course was complicated by an upper GI bleed, hepatic encephalopathy, respiratory failure, and multiple infections requiring repeated courses of antibiotics. Two months into the hospital stay, he developed a diffuse pruritic maculopapular rash that progressed to cover his trunk, neck and extremities. Workup revealed elevated aminotransferases along with worsening creatinine, leukocytosis, and eosinophilia concerning for DRESS. Medication review revealed the patient received several days of vancomycin in addition to a month-long course of olanzapine for paranoia suffered while inpatient. Patient first received olanzapine 8 weeks prior to symptom onset. HLA-A*32:01 was obtained and negative. Topical steroids were applied, and potential offending medications held. Rash resolved over the next few weeks followed by clinical improvement. Olanzapine was added to the allergy list to avoid future episodes. <h3>Discussion</h3> The diagnosis of DRESS can be challenging as it often occurs in the inpatient setting with patients exposed to varying amounts of multiple drugs, including less common agents such as olanzapine. When multiple culprit drugs have been administered, evaluating factors such as timeline of exposure and genetic predisposition may be helpful in identifying the cause. This can lead to prompt removal of the offending drug minimizing morbidity and mortality.

Nephrotoxic Exposures and Acute Kidney Injury in Noncritically Ill Children Stratified by Service

The Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) program is a multicenter, quality improvement initiative that identifies patients at risk for nephrotoxic medication-associated acute kidney injury (NTMx-AKI). The purpose of this study was to (1) evaluate the prevalence and types of NTMx exposures and (2) determine the prevalence of NTMx-AKI categorized by service. Exploratory analysis evaluated potential associations between hospital measures and NTMx-AKI. This is a single-center, retrospective chart review of NTMx exposures from January 2019 to June 2020 in noncritically ill children. High NTMx exposures were defined as ≥3 simultaneous nephrotoxins or ≥3 days of either intravenous vancomycin or aminoglycoside. Prevalence of high NTMx and NTMx-AKI rate were normalized to 1000 patient days. A retrospective case-control analysis assessed for potential associations with development of NTMx-AKI. There were 609 NTMx exposures in 565 patients and 44 (7.2%) episodes of NTMx-AKI. The NTMx prevalence rate per 1000 patient days was highest among liver, neurosurgery, and gastroenterology services. The most commonly used NTMx were vancomycin, intravenous contrast, and nonsteroidal antiinflammatory drugs. The NTMx-AKI rate in exposed patients ranged from 0% to 14% across service lines. AKI was most often attributable to vancomycin. Univariable analyses suggest type and duration of NTMx exposure are associated with development of NTMx-AKI but not with severity. NTMx exposures and NTMx-AKI are variable across services. Partnerships with antimicrobial stewardship and multicenter studies are needed to modify NTMx-AKI risk. Ongoing surveillance is needed in patients who do not have normalization of creatinine before discharge.

Prior Vancomycin Treatment Mitigates Coagulation and Death in a Severe Exertional Heat Stroke Mouse ModelPrior Vancomycin treatment mitigates coagulation and death in a severe Exertional Heat Stroke mouse model

During exercise, intestinal leakage of lipopolysaccharide (LPS or endotoxin: a component in the cell walls of Gram‐negative bacteria) into circulation is hypothesized to accelerate exertional heat stroke (EHS) onset and/or increase EHS severity. Conceptually, decreasing intestinal microbe populations via antibiotic treatment could counteract EHS. Accordingly, we determined whether prior treatment with the antibiotic Vancomycin would delay EHS onset and/or mitigate EHS severity and mortality rates using a recently developed mouse model of severe EHS that more accurately recapitulates the human condition. Using a 2X2 treatment design, mice were 1) designated as EHS or Exercise Control (ExC) specimens and 2) given 7 days of Vancomycin or untreated water. Mice were placed in a forced‐running wheel that gradually increased from low‐to‐moderate speed (3.0 to 8.5 m/min, increasing 0.5 m/min every 10 minutes). Ambient temperature was set at 25°C for ExC and 37.5°C for EHS specimens while humidity was set at 30‐70% for all conditions. Treated and untreated EHS mice ran in the wheels until losing consciousness. Each EHS mouse and a conscious, similarly treated ExC counterpart were left undisturbed in their respective chambers for an additional 20 minutes before being sacrificed immediately (0h) or returned to their home cage (25°C) and sacrificed after 3 hours (3h) or 24 hours (24h). Across all timepoints, mortality was higher in untreated (14/63) vs. Vancomycin‐treated (6/47) EHS mice, and percentage of dehydration was attenuated in Vancomycin‐treated vs. untreated EHS mice. Core body temperatures (Tc) and thermal load of Vancomycin EHS mice were lower than untreated EHS mice at the time of heat collapse despite both groups running over comparable times and distances. At 24 hours following the exercise/heat bout, student’s T‐tests indicated that serum alanine aminotransferase (ALT) in untreated EHS is greater than levels in Vancomycin EHS mice, indicating accelerated hepatic recovery with antibiotic treatment. Our working hypothesis is that Vancomycin treatment decreased intestinal bacteria populations, leading to decreased microbial release into circulation and protecting other organs (e.g., liver) from detrimental effects of bacteremia. Consequently, Vancomycin mitigated EHS phenotype in treated mice compared to what was observed in untreated EHS mice.DisclaimerThe opinions or assertions contained herein are the private views of the author(s) and are not to be construed as official or as reflecting the views of the Army or the Department of Defense. Citations of commercial organizations and trade names in this report do not constitute an official Department of the Army endorsement or approval of the products or services of these organizations. No conflicts of interest, financial or otherwise, are declared by the authors.

Impact of decreasing vancomycin exposure on acute kidney injury in stem cell transplant recipients.

To evaluate the change in vancomycin days of therapy (DOT) and vancomycin-associated acute kidney injury (AKI) after an antimicrobial stewardship program (ASP) intervention to decrease vancomycin use in stable patients after hematopoietic stem cell transplantation (HSCT). Retrospective cohort study and quasi-experimental interrupted time series analysis. Change in unit-level vancomycin DOT per 1,000 inpatient days after the intervention was assessed using segmented Poisson regression. Subject-specific risk of vancomycin-associated AKI was evaluated using a random intercept logistic regression model with mediation analysis. HSCT unit at a single quaternary-care pediatric hospital. Inpatients aged 3 months and older who underwent HSCT between January 1, 2015, and March 31, 2019 (27 months before and after the intervention) who received any dose of vancomycin. An ASP intervention in April 2017 creating a new practice guideline to decrease prolonged (>72 hours) vancomycin courses for stable HSCT patients with febrile neutropenia. Overall, 439 vancomycin exposures (234 before the intervention and 205 after the intervention) occurring across 300 transplants and 259 subjects were included. The mean vancomycin DOT was 307 per 1,000 inpatient days (95% confidence interval [CI], 272-342) and decreased after the intervention to 207 per 1,000 inpatient days (95% CI, 173-240). In multivariable analyses, the odds of AKI in the postintervention period were 37% lower than in the preintervention period (adjusted OR, 0.63; 95% CI, 0.42-0.95; P = .0268); 56% of the excess risk was mediated by vancomycin DOT. An ASP intervention successfully decreased vancomycin use after HSCT and resulted in a decrease in AKI. Reducing empiric antibiotic exposure for stable patients after HSCT can improve clinical outcomes.

78. Impact of Methicillin-Resistant Staphylococcus aureus (MRSA) Nares Screen on Vancomycin Utilization for Respiratory Tract Infections

Background S. aureus, including MRSA, is a common colonizer of the nares. Recent data have shown that a negative MRSA nares screen by PCR has a negative predictive value of 98%. This implies that the absence of colonization can significantly reduce empiric vancomycin utilization. This study aimed to determine the utilization of MRSA nares screening on patients receiving vancomycin for respiratory tract infections (RTI) following the addition of the screen to the institutional RTI management guidelines. MethodsThis was a retrospective chart review of adult inpatients presenting to two community-teaching hospitals who were prescribed vancomycin for the treatment of RTIs. Patients were divided into pre-guideline (Jan-Feb 2019), post-guideline 1 (Jan-Feb 2020), and post-guideline 2 (Jan-Feb 2021) groups. The primary endpoint was the difference in percent of vancomycin orders discontinued within 24 hours of a negative screen. Secondary endpoints included the percent of screens ordered, re-initiation of vancomycin within seven days for RTI, and total vancomycin days of therapy (DOT) per 1000 patient days (PD). ResultsOf 493 vancomycin orders screened, 100 orders in each arm were analyzed. There was an absolute increase of 20.6% in vancomycin orders discontinued within 24 hours of a negative screen between the pre-guideline and post-guideline 2 groups (59.1% vs. 79.7%, p = 0.0177). When compared to the pre-guideline group, utilization of the screen increased by 15% in the post-guideline 1 group (48% vs. 63%, p = 0.0328) and 26% in the post-guideline 2 group (48% vs. 74%, p = 0.000164). There was no difference in re-initiation of vancomycin. A statistically significant reduction in total vancomycin DOT/1000PD from the pre-guideline to the post-guideline 1 and 2 groups (66 to 63 to 60, respectively) was also observed. ConclusionThe addition of the MRSA nares screen to the institutional RTI guidelines increased utilization of the test and demonstrated a reduction in vancomycin utilization. With an increase in education, prospective audit and feedback, and prescriber comfort with the use of the MRSA nares screen in the post-guideline 2 group, there was significant improvement in MRSA nares screen utilization, vancomycin discontinuation after a negative screen, and vancomycin utilization.Disclosures All Authors: No reported disclosures