Infusion Of Vancomycin Research Articles

P-735. Acute Bacterial Skin and Skin Structure Infections: A Comparison of Outpatient One-Hour Infusion Oritavancin and Inpatient Vancomycin Use

Abstract Background Patients with acute bacterial skin and skin structure infections (ABSSSI) who present to the emergency department (ED) are commonly admitted for intravenous (IV) antibiotic treatment. At AtlantiCare Regional Medical Center (ARMC), oritavancin is utilized in the ED as a single 1200 mg dose to prevent ABSSSI admissions. The purpose of this study is to compare 30-day ABSSSI readmission rates between one-hour ED oritavancin infusion and inpatient vancomycin therapy transitioned to oral antibiotics. A financial assessment of both groups will also be presented.Table 1.Patient characteristics and outcomes analyzed via Student’s t-test or χ2 test. Methods Subjects with ABSSSI were included in this retrospective study if they were administered oritavancin in the ARMC ED between November 2022 and August 2023, or given IV vancomycin as an inpatient between January and August 2023. Data collection included patient demographics, history of ABSSSI, injection drug use, and length of stay (LOS). A financial analysis was performed based on diagnosis-related group (DRG) reimbursement and hospital-specific expenditures. Collected data were analyzed using a Student’s t-test or χ2 test as appropriate. Results A total of 191 patients were included in this study with 140 and 51 in the oritavancin and vancomycin arms, respectively (Table 1). The 30-day ABSSSI readmission rates were significantly lower in the oritavancin arm (n=8, 5.7%) compared to the vancomycin arm (n=10, 19.6%), p=.004. Amongst the 8 oritavancin readmissions, only 4 (2.9%) were considered oritavancin candidates based on our hospital protocol criteria which defines appropriate patients. The estimated cost after DRG-based reimbursement for a single patient in the vancomycin arm was approximately $10,300. The estimated cost avoidance for each oritavancin patient, not accounting for drug reimbursement or the subsequent decrease in readmissions, was approximately $7,240. Conclusion Oritavancin as a one-hour infusion in our ED appears to be an effective treatment option in preventing admissions and significantly decreasing 30-day ABSSSI readmissions. The financial benefits of preventing hospital admissions with single-dose oritavancin should be considered when treating ABSSSI patients in the ED setting. Disclosures Joseph Reilly, B.S., Pharm.D., Melinta Therapeutics: Advisor/Consultant

P-1181. Comparing the outcomes of ceftaroline versus vancomycin for the treatment of osteomyelitis and septic arthritis in pediatric patients

Abstract Background The most common cause of osteomyelitis and septic arthritis is Staphylococcus aureus. Vancomycin is a glycopeptide antibiotic used to treat proven or suspected methicillin-resistant S. aureus (MRSA). It is known to have serious adverse effects like nephrotoxicity and vancomycin infusion syndrome. Ceftaroline, a fifth-generation cephalosporin active against MRSA, is not approved by the Food and Drug Administration (FDA) for osteomyelitis or septic arthritis; but it is commonly used to treat bone and joint infections due to its range of activity and safety profile when compared to vancomycin.Table 1.Demographic, clinical and microbiological characteristics of patients treated with vancomycin, vancomycin followed by ceftaroline, and ceftaroline Methods This is a retrospective study of osteomyelitis and/or septic arthritis cases in children (0-18 years old) treated with Vancomycin and/or Ceftaroline between October 1st, 2019 to October 1st, 2023 admitted at Ochsner LSU Health Shreveport. Demographic data, pertinent medical history, days of antibiotic therapy, surgeries and microbiology results were collected. Complications during clinical course and treatment failure were reported.Table 2.Clinical outcomes of patients treated with vancomycin, vancomycin followed by ceftaroline, and ceftaroline.Fisher’s exact test was performed for all categorical variables. Results During the study period, 63 patients were admitted with osteomyelitis and/or septic arthritis and received either vancomycin (n=32), vancomycin followed by ceftaroline (n=21) or ceftaroline (n=10). Demographic, clinical, and microbiological data are presented in Table 1. Among treatment groups, one or more complications were reported per patient during admission. These included sepsis, multifocal disease, repeat imaging and additional surgeries. Treatment failure was defined as recrudescence, relapse, wound dehiscence, chronic osteomyelitis and non-union (Table 2). The vancomycin group had more treatment failures, with 9 patients (28%), when compared to 2 (20%) in the ceftaroline group and 1 (5%) in the group of vancomycin followed by ceftaroline. This difference was not statistically significant (p= 0.09) (Fig. 1). Side effects were only seen in the vancomycin group.Figure 1:Treatment failure per treatment group. Treatment failure was reported in 9 (28%) of 32 patients who received vancomycin alone, 2 (20%) of 10 patients on the ceftaroline group and 1 (5%) among 21 patients treated with vancomycin followed by ceftaroline. Fisher’s exact test was performed with a p value of 0.09. Conclusion This small retrospective study showed that children treated with vancomycin alone for bone and joint infections experienced more treatment failures. Side effects were only reported with vancomycin alone. Ceftaroline should be considered a safe alternative and promising empiric agent to treat osteomyelitis and septic arthritis in children. Disclosures John Vanchiere, MD, PhD, Biocryst: Advisor/Consultant|Biocryst: Grant/Research Support|Enanta: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Tetraphase Pharmaceutical: Advisor/Consultant|Tetraphase Pharmaceutical: Grant/Research Support

P-1247. Cerebrospinal Fluid Penetration of Multiple Antibiotics in Patients With Intracranial Hemorrhage: A Prospective, Observational, Clinical Study

Abstract Background External ventricular drains (EVD) are used for acute hydrocephalus in intracranial hemorrhage(ICH), potentially causing ventriculostomy-associated cerebrospinal fluid infection (VAI). Variable meningeal inflammation in VAI can result in unpredictable antibiotic penetration in cerebrospinal fluid (CSF). This observational study aimed to assess CSF penetration of intravenous antibiotics for suspected VAI treatment in neurosurgical patients. Time to concentrations in CSF and plasma among the patients. The figure presented the concentrations of blood and cerebrospinal fluid (CSF) measured at different time points for each patient. REVD right-sided external ventricular drain. LEVD left-sided external ventricular drain. Methods Adults with EVD for ICH who were receiving antibiotics, including vancomycin, ceftazidime, cefepime and meropenem, for VAI from January 2023 to April 2024 in two north Taiwan medical centers were enrolled in this study. The primary outcome was the area under the concentration (AUC) ratio between CSF and plasma (AUCCSF/plasma). Factors influencing CSF concentration was also investigated. In addition, the probability of target attainment (PTA) of anti-Pseudomonal antibiotics were calculated. A summary of the permeability of vancomycin into the cerebrospinal fluid in this study. ARC augmentation renal clearance. L Left-side external ventricular drain R Right-side external ventricular drain. a. AUC was calculated from the first observation point to the last observation point. b. It was resistant to vancomycin. Results A total of 9 patients (6 male) with VAI were enrolled, and contributed 7 vancomycin, 3 ceftazidime, 2 cefepime and 2 meropenem treatment courses. One patient provided two courses. The ranges of AUCCSF/plasma for vancomycin, ceftazidime, cefepime, or meropenem were as follows 0.85-15.61%, 6.74-15.61%, 0.16-128.73%, and 0.09-13.24%, respectively. The CSF to plasma concentration ratio at the end of vancomycin infusion and at the middle of dosing interval showed good correlation with AUCCSF/plasma (Spearman's coefficient 0.8 and 0.783, p-value ≦0.01) For ceftazidime, both CSF and plasma achieved at least 98% fT >MIC=8 under 2 gram every 8 hours regimen. For meropenem, the fT >MIC=2 for CSF and plasma were 0-100 % and 95.7-99.8% under 2 gram every 8 hours regimen, respectively. For cefepime, the fT >MIC=16 for CSF and plasma were 0-100% and >97%, respectively. Conclusion This is the first study to report real-world data of antibiotic CSF penetration in neurosurgical population in Taiwan. Ceftazidime showed adequate penetration and achieved sufficient PTA in the CSF. Additionally, the single-point ratio of vancomycin at the end of infusion and during the mid-dosing interval may serve as a surrogate for AUCCSF/plasma. Disclosures All Authors: No reported disclosures

Impact of vancomycin area under the curve in early or later phase on efficacy and nephrotoxicity in patients with enterococcal bloodstream infections: a multicenter study

BackgroundThe optimal pharmacokinetic and pharmacodynamic (PK/PD) parameters of vancomycin that can improve outcomes in enterococcal infections remain controversial. To clarify the therapeutic target for this antibiotic, this study aimed to determine vancomycin PK/PD parameters associated with efficacy in the early (during 72 h) or later (after 72 h) phase of treatment and nephrotoxicity in enterococcal bloodstream infection patients.MethodsThis multicenter retrospective study reviewed medical records of patients with enterococcal bloodstream infections treated with intravenous vancomycin infusion for at least 72 h between January 2016 and March 2024 at Phramongkutklao Hospital or Nopparatrajathanee Hospital in Bangkok, and Rachaburi Hospital in Rachaburi Province, Thailand. Patients with data available on serum vancomycin concentration were analyzed. The primary outcomes were 30-day mortality and acute kidney injury. The estimates of the mean 24-h area under the curve in the first 72 h (AUC24) and in steady state (AUCss) were determined by Bayesian theorem.ResultsOverall, 201 vancomycin concentrations were measured within the first 72 h after vancomycin treatment, while 156 were in a steady state (> 72 h). According to Classification and Regression Tree analysis, vancomycin AUC at 420 mg·h/l was the PK/PD target for 30-day mortality. Results reveal that patients with AUC24 (early phase) and AUCss < 420 mg·h/l (later phase) had significantly higher 14-day, 30-day, and in-hospital mortality than AUC ≥ 420 mg·h/l groups. In addition, patients with AUC24 ≥ 420 mg·h/l in the early phase had significantly reduced microbiological failure (p = 0.004). Patients with AUC ≥ 700 mg·h/l in early and later phases had significantly increased acute kidney injury risk. In addition, patients receiving concomitant nephrotoxic drugs had an AUC cutoff value of 650 mg·h/l. Multivariate Cox regression analysis showed that vancomycin AUCss < 420 mg·h/l, unknown source of bacteremia, and acute kidney injury were significantly associated with 30-day mortality.ConclusionsAUC 420–650 mg·h/l in early and later phases was the target of vancomycin’s PK/PD in enterococcal bacteremia patients for efficacy and to prevent acute kidney injury. This study suggests close monitoring of vancomycin levels to ensure efficacy and safety.

Comparison of Vancomycin AUC24 Calculation Methods for Neonates and Infants.

For neonates and infants receiving intermittent vancomycin infusions, the area under the concentration-timecurve during 24 h (AUC24) is often estimated with Bayesian forecasting using one or more measured vancomycin concentrations. When practical peak and trough concentrations are measured at steady state, AUC24 can also be calculated with first-order steady-state equations for a one-compartment model (Sawchuk-Zaske method), but previously this method has been applied only for adults. The objective of this studywas to compare AUC24 values obtained with the Sawchuk-Zaske method and two Bayesian models. AUC24 values were estimated retrospectively for 18 neonates and infants with steady-state peak and trough concentrations using traditional compartmental analysis with a one-compartment model (reference method), the Sawchuk-Zaske method, and Bayesian forecasting with two previously published models. In Bayesian forecasting, both original and modified residual error models were used. In the modified models, the residual error was reduced by setting the additive residual error to zero and the proportional error to 15%. AUC24 estimates obtained with the Sawchuk-Zaske method differed -2.7 to 0.9% from the reference method. When both peak and trough concentrations were used in Bayesian forecasting, 61% and 33% of AUC24 estimates obtained with two original models differed less than 15% from the reference method, and these fractions increased to 83% and 72% with the modified models, respectively. When practical peak and trough concentrations are measured at steady state, the simple Sawchuk-Zaske method is very useful for AUC24 estimation in neonates and infants. In Bayesian forecasting, the reduced residual error model can be used to improve the model fit.

Synovial vancomycin and meropenem concentrations in periprosthetic joint infection treated by single-stage revision combined with intra-articular infusion.

We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach. We included 14 patients with PJI as noted in their medical records between November 2021 and August 2022, comprising eight hip and seven knee joint infections, with one patient experiencing bilateral knee infections. The patients underwent single-stage revision surgery, followed by intra-articular infusion of vancomycin and meropenem (50,000 µg/ml). Synovial fluid samples were collected to assess antibiotic concentrations using high-performance liquid chromatography. The peak concentrations of vancomycin and meropenem in the joint cavity were observed at one hour post-injection, with mean values of 14,933.9 µg/ml (SD 10,176.3) and 5,819.1 µg/ml (SD 6,029.8), respectively. The trough concentrations at 24 hours were 5,495.0 µg/ml (SD 2,360.5) for vancomycin and 186.4 µg/ml (SD 254.3) for meropenem. The half-life of vancomycin was 6 hours, while that of meropenem ranged between 2 and 3.5 hours. No significant adverse events related to the antibiotic administration were observed. This method can achieve sustained high antibiotic concentrations within the joint space, exceeding the reported minimum biofilm eradication concentration. Our study highlights the remarkable effectiveness of intra-articular antibiotic infusion in delivering high intra-articular concentrations of antibiotics. The method provided sustained high antibiotic concentrations within the joint cavity, and no severe side-effects were observed. These findings offer evidence to improve clinical treatment strategies. However, further validation is required through studies with larger sample sizes and higher levels of evidence.

Continuous Versus Intermittent Vancomycin Infusions for Coagulase-negative Staphylococcus Bacteremia in Neonates: A Propensity-matched Cohort Study.

Coagulase-negative staphylococci (CONS) are a major cause of late-onset neonatal sepsis, particularly in preterm infants, with high morbidity and mortality. While vancomycin is the first-line treatment for these infections, the optimal administration in neonates remains uncertain. We aim to compare the outcomes of neonates with CONS bacteremia treated with adjusted continuous infusion (CIV) versus standard intermittent infusion (IIV) of vancomycin. This retrospective study included 110 neonates, with 29 in the CIV group and 47 in the IIV group after propensity score matching. The primary outcome was treatment failure defined by the persistence of a positive blood culture for the same organism after at least 48 hours of vancomycin treatment. After matching, the CIV group exhibited significantly lower treatment failure rates [5/29 (17%) vs. 26/47 (44%); P = 0.014] and a higher rate of achieving therapeutic vancomycin levels after 24 hours [20/29 (69%) vs. 26/47 (44%); P = 0.002] compared to the IIV group. No significant differences were observed in terms of acute kidney failure between the 2 groups. Adjusted continuous vancomycin infusion in neonates with CONS bacteremia is associated with a lower treatment failure rate without an increase in renal toxicity compared to standard intermittent infusion. However, due to the observational design, larger prospective studies are needed to validate these results.

The performance and complications of long peripheral venous catheters: A retrospective single-centre study.

Intravenous therapies are essential for hospitalised patients. The rapid dissemination of portable ultrasound machines has eased ultrasound-guided intravenous access and facilitated increased use of long peripheral venous catheters (LPCs). This study aimed to evaluate the clinical performance and complications of LPCs. Retrospective, observational single-site study. Data from all consecutively inserted LPCs during a period of 18 months was evaluated. The primary endpoint was the all-cause incidence rate of catheter removal. Secondary endpoints included specific reasons for the catheter removal and the associations between predefined characteristics of the patients, the infusions and the catheters with catheter failure. During the period, 751 PVCs were inserted in 457 patients. The reasons for catheter removal were recorded in 563 cases. The overall incidence rate of catheter removal was 95.8/1000 catheter days (95% CI 88.4-103.8). The median dwell time was 8 days (IQR 5-14), and the total dwell time was 6136 days. Catheter failure occurred in 283 (50.3%) cases, of which the most common cause was phlebitis (n = 101, 17.9%). In multivariable analyses, the use of the cephalic vein was significantly associated with both all-cause catheter failure (p < .001) and catheter failure due to phlebitis (p < .001). In multivariable analyses, vancomycin infusion was not significantly associated with all-cause catheter failure (HR 1.15 (0.55-2.42), p = .71) or catheter failure due to phlebitis (HR 1.49 (0.49-4.53), p = .49). The overall incidence rate of catheter removal was 95.8/1000 catheter days, and the most common causes of catheter failure were phlebitis, infiltration and unintended catheter removal. The use of the cephalic vein was significantly associated with catheter failure in multivariable analyses. We did not find an association between vancomycin infusion and catheter failure in multivariable analyses.

A Skin Testing Strategy for Non–IgE-Mediated Reactions Associated With Vancomycin

Vancomycin infusion reaction (VIR), reportedly mediated through Mas-Related G Protein-Coupled Receptor-X2, is the primary vancomycin-induced immediate drug reaction. Clinically, distinguishing the underlying drug-induced immediate drug reaction mechanisms is crucial for future treatment strategies, including drug restriction, re-administration, and pretreatment considerations. However, the lack of validated diagnostic tests makes this challenging, often leading to unnecessary drug restriction. To determine whether intradermal tests (IDTs) and, separately, the basophil activation test (BAT) differentiate VIR from vancomycin-tolerant subjects. This was a cross-sectional study of vancomycin-exposed adults with and without a history of VIR. Data on demographics, allergy-related comorbidities, history of vancomycin exposures, and VIR characteristics were collected. IDT with vancomycin was performed. IDT dose-response EC50, IDT-related local symptoms, and BAT results were compared between groups. A total of 11 VIR and 10 vancomycin-tolerant subjects were enrolled. The most reported VIR symptoms were pruritus (82%), flushing (82%), hives (46%), angioedema (27%), and dyspnea (19%). The IDT dose-response mean EC50 was 328 μg/mL (95% CI, 296-367) in the VIR versus 1166 μg/mL (95% CI, 1029-1379) in the tolerant group (P < .0001). All VIR subjects reported IDT-related local pruritus compared with 60% of tolerant subjects (P= .0185). The %CD63+ basophils were consistently less than 2%, without significant differences between groups (P < .54). Variations in skin test methodologies could help identify other immediate drug reaction mechanisms beyond IgE. This skin test protocol holds the potential for identifying VIR, particularly in cases where patients have received multiple drugs while BAT is insufficient. Future studies will validate and delineate its predictive value, assessing the risk of VIR.

Association between prolonged vancomycin infusion and trough concentrations in children. Retrospective study.

Introduction: This study investigated the serum concentration of vancomycin during prolonged infusion in children. Population and methods: This retrospective cohort study included pediatric patients who received vancomycin from June 2017 to June 2020 at a tertiary referral hospital. The patients were divided into two groups according to infusion strategy, the SII (standard intermittent infusion) group and the PI (prolonged infusion) group. Demographic details, infusion period, serum creatinine, duration of vancomycin therapy, trough concentration of vancomycin, and pediatric intensive care unit stay were reviewed. Differences of the concentrations were measured. Results: Sixty-eight patients were included: 31 in the SII group and 37 in the PI group. The trough concentration of vancomycin was significantly higher in the PI group than in SII group (11.2 mg/L [5.9-13.7] vs. 7 mg/L [3.5- 9.3]; p = 0.02). The target attainment rate was higher in the PI group than in the SII group (59.4% and 19.3%, respectively; p = 0.001). There were no significant differences between the SII and PI groups regarding the peak concentrations of vancomycin, final creatinine and peak creatinine. There were no differences between the SII and PI groups regarding the failure events, PICU stay and duration of vancomycin therapy. The multivariable analysis showed that PI was significantly associated with higher trough serum concentrations of vancomycin (OR = 2.27; p = 0.005). Conclusion: Compared to the SII strategy, the PI strategy may be an optimized option to children with severe infection, as it can achieve higher trough concentrations and target concentration attainment.

After primary shoulder arthroplasty appropriate vancomycin antibiotic prophylaxis does not lead to increased infectious complications when compared to cefazolin

INTRODUCTIONIn primary shoulder arthroplasty (SA), intravenous (IV) cefazolin has demonstrated lower rates of infectious complications when compared to IV vancomycin. However, previous analyses included SA cohorts with both complete and incomplete vancomycin administration. Therefore, it is currently unclear whether cefazolin still maintains a prophylactic advantage to vancomycin when it is appropriately indicated and sufficiently administered at the time of surgical incision. This study evaluated the comparative efficacy of cefazolin and complete vancomycin administration for surgical prophylaxis in primary shoulder arthroplasty with respect to infectious complications. METHODSA retrospective cohort study was conducted utilizing a single institution total joint registry database, where all primary SA types (hemiarthroplasty, anatomic total shoulder arthroplasty, reverse shoulder arthroplasty) performed between 2000 to 2019 for elective and trauma indications using IV cefazolin or complete vancomycin administration as the primary antibiotic prophylaxis were identified. Vancomycin was primarily indicated for patients with a severe self-reported penicillin or cephalosporin allergy and/or MRSA colonization. Complete administration was defined as at least 30 minutes of antibiotic infusion prior to incision. All included SA had at least 2 years of clinical follow-up. Multivariable Cox proportional hazard regression was used to evaluate all-cause infectious complications including survival free of prosthetic joint infection (PJI). RESULTSThe final cohort included 7,177 primary SA, 6,879 (95.8%) received IV cefazolin and 298 (4.2%) received complete vancomycin administration. Infectious complications occurred in 120 (1.7%) SA leading to 81 (1.1%) infectious reoperations. Of the infectious complications 41 (0.6%) were superficial infections and 79 were (1.1%) PJIs. When categorized by administered antibiotics, there were no differences in rates of all infectious complications (1.6% vs. 2.3%; P = .352), superficial complications (0.5% vs. 1.3%; P = .071), PJI (1.1% vs. 1.0%; P = .874), or infectious reoperations (1.1% vs. 1.0%; P = .839). On multivariable analyses, complete vancomycin infusion demonstrated no difference in rates of infectious complications compared to cefazolin administration (hazard ratio [HR], 1.50 [95% confidence interval (CI), 0.70 to 3.25]; P = .297), even when other independent predictors of PJI (male sex, prior surgery, and Methicillin-resistant Staphylococcus aureus colonization) were considered. CONCLUSIONSIn comparison to cefazolin, complete administration of vancomycin (infusion to incision time greater than 30 minutes) as the primary prophylactic agent does not adversely increase the rates of infectious complications and PJI. Prophylaxis protocols should promote appropriate indications for the use of cefazolin or vancomycin, and when necessary, ensure complete administration of vancomycin to mitigate additional infectious risks after primary SA.

Comparison of the Areas Under the Curve of Vancomycin Continuous vs. Intermittent Infusion in Critically Ill Pediatrics: A Randomized Clinical Trial.

Providing data on the superior efficacy of vancomycin administered based on the area under the curve over 24 hours to the minimum inhibitory concentration of vancomycin (AUC24/MIC) is crucial. However, data on dosing and monitoring of vancomycin pharmacokinetics in the pediatric population are limited. Previous findings have showed that intermittent infusion of vancomycin (IIV) may not achieve the desired levels, continous infusions of vancomycin (CIV) reach the desired serum concentration faster than IIV and are associated with reduced nephrotoxicity. This study aimed to compare the serum concentrations, AUC24, clinical variables, and adverse effects of two vancomycin administration methods in the pediatric population. This study was a double-blind, randomized, controlled clinical trial conducted at a tertiary children's teaching hospital. Inclusion criteria were age between 2 months and 15 years and weight less than 67 kilograms, with exclusion criteria including renal impairment. Participants were divided into CIV and IIV groups following distinct administration protocols. Demographic, clinical, and laboratory data, including vancomycin serum concentrations, were compiled. Assessments included pediatric mortality risk, pediatric sequential organ failure assessment, and regular temperature monitoring. Pharmacokinetic analysis was conducted using Monolix software 2023R1. Primary endpoints were vancomycin serum levels and AUC24 between cohorts on day three, with nephrotoxicity and additional adverse drug responses evaluated. Sixty-eight patients in the pediatric intensive care unit (PICU) were allocated to either CIV (33) or IIV (35) for vancomycin treatment. In the CIV group, 82% of patients achieved an AUC24 ≥ 400 mg.h/L, compared to 23% in the IIV group. Continuous infusions of vancomycin demonstrated a greater AUC24 (587.7 ± 184.4 mg.h/L vs. 361.9 ± 113.2 mg.h/L, P < 0.05) compared to IIV. Two cases of nephrotoxicity were reported, one in each group, with mortality and adverse events being comparable between the two groups. This study demonstrated that continuous vancomycin infusion has a higher success rate in safely achieving therapeutic vancomycin levels in PICU patients compared to intermittent vancomycin infusion.

Effects of lung inflammation and injury on pulmonary tissue penetration of meropenem and vancomycin in a model of unilateral lung injury

The timing and dosing of antimicrobial therapy are key in the treatment of pneumonia in critically ill patients. It is uncertain whether the presence of lung inflammation and injury affects tissue penetration of intravenously administered antimicrobial drugs. The effects of lung inflammation and injury on tissue penetration of two antimicrobial drugs commonly used for pneumonia were determined in an established model of unilateral lung injury. Unilateral lung injury was induced in the left lung of 13 healthy pigs through cyclic rinsing; the right healthy lung served as control. Infusions of meropenem and vancomycin were administered and concentrations of these drugs in lung tissue, blood, and epithelial lining fluid (ELF) were compared over a period of 6 h. Median vancomycin lung tissue concentrations and penetration ratio were higher in inflamed and injured lungs compared with uninflamed and uninjured lungs (AUC0-6h: P = 0.003 and AUCdialysate/AUCplasma ratio: P = 0.003), resulting in higher AUC0-24/MIC. Median meropenem lung tissue concentrations and penetration ratio in inflamed and injured lungs did not differ from that in uninflamed and uninjured lungs (AUC0-6: P = 0.094 and AUCdialysate/AUCplasma ratio: P = 0.173). The penetration ratio for both vancomycin and meropenem into ELF was similar in injured and uninjured lungs. Vancomycin penetration into lung tissue is enhanced by acute inflammation and injury, a phenomenon barely evident with meropenem. Therefore, inflammation in lung tissue influences the penetration into interstitial lung tissue, depending on the chosen antimicrobial drug. Measurement of ELF levels alone might not identify the impact of inflammation and injury.

Development of a model to predict vancomycin serum concentration during continuous infusion of vancomycin in critically ill pediatric patients.

Vancomycin is a frequently used antibiotic in intensive care units, and the patient's renal clearance affects the pharmacokinetic characteristics of vancomycin. Several advantages have been reported for vancomycin continuous intravenous infusion, but studies on continuous dosing regimens based on patients' renal clearance are insufficient. The aim of this study was to develop a vancomycin serum concentration prediction model by factoring in a patient's renal clearance. Children admitted to our institution between July 1, 2021, and July 31, 2022 with records of continuous infusion of vancomycin were included in the study. Sex, age, height, weight, vancomycin dose by weight, interval from the start of vancomycin administration to the time of therapeutic drug monitoring sampling, and vancomycin serum concentrations were analyzed with the linear regression analysis of the mixed effect model. Univariable regression analysis was performed using the vancomycin serum concentration as a dependent variable. It showed that vancomycin dose (p < 0.001) and serum creatinine (p = 0.007) were factors that had the most impact on vancomycin serum concentration. Vancomycin serum concentration was affected by vancomycin dose (p < 0.001) and serum creatinine (p = 0.001) with statistical significance, and a multivariable regression model was obtained as follows: Vancomycin serum concentration (mg/l) = -1.296 + 0.281 × vancomycin dose (mg/kg) + 20.458 × serum creatinine (mg/dl) (adjusted coefficient of determination, R2 = 0.66). This prediction model is expected to contribute to establishing an optimal continuous infusion regimen for vancomycin.

Impact of humanized vancomycin infusion on kidney function and kidney injury in a translational rat model

Allometric dose scaling aims to create isometric exposures between animals and humans and is often employed in preclinical pharmacokinetic/pharmacodynamic models. Bolus-administration with allometric scaling is the most simple and commonly used strategy in pre-clinical kidney injury studies; however, it is possible to humanize drug exposures. Currently, it is unknown if dose-matched, bolus-administration with allometric scaling results in similar outcomes compared to humanized infusions in the vancomycin induced kidney injury model. We utilized a preclinical Sprague-Dawley rat model to compare traditional allometrically-scaled, dose-matched, bolus-administration of vancomycin to an infusion-pump controlled, humanized infusion scheme to assess for differences in iohexol-measured kidney function and urinary kidney injury biomarkers. Following 24 h of vancomycin administration, rats in the humanized infusion group had equivalent area under the curve exposures to animals in the dose-matched bolus group (93.7 mg·h/L [IQR 90.2-97.2] vs. 99.5 mg·h/L [IQR 95.1-104.0], P = 0.07). No significant differences in iohexol-measured kidney function nor meaningful differences in urinary kidney injury biomarkers, kidney injury molecule-1, clusterin, and osteopontin, were detected. Administration of intravenous vancomycin as either a humanized infusion or dose-matched bolus resulted in similar vancomycin exposures. No differences in iohexol-measured GFR nor meaningful differences in urinary kidney injury biomarkers were observed among male Sprague-Dawley rats.

Evaluation of Continuous Infusion Vancomycin in a Pediatric Hematology/Oncology Population.

Continuous infusion vancomycin (CIV) may benefit children who are unable to achieve therapeutic concentrations with intermittent vancomycin dosing and may facilitate outpatient administration by alleviating the burden of frequent dosing intervals. Previous studies have used variable dosing regimens and steady-state concentration goals. The purpose of this study was to evaluate the total daily dose (TDD) of CIV required to achieve therapeutic steady-state concentrations of 15-25 µg/mL in pediatric hematology/oncology patients. A single-center retrospective study was performed for patients treated with CIV from January 2017 to June 2019. The primary outcome was the TDD required to achieve therapeutic steady-state concentrations on CIV. Secondary outcomes included time to reach therapeutic steady-state concentrations, CIV indications and adverse events associated with CIV. Data were collected for 71 courses of CIV in 60 patients. Median patient age was 4 years (range: 0.4-20 years). The median TDD required to achieve initial therapeutic concentrations was 50.3 mg/kg/d (interquartile range: 38.8-59.2) and was further divided into age-based cohorts. TDD in mg/kg was significantly lower in the older cohort ( P < 0.001), but there was no statistically significant difference between age-based cohorts with TDD in mg/m 2 ( P = 0.97). Median time to achieve first therapeutic concentration was 19.3 hours (range: 8.6-72.3 hours). The most common indication for CIV was ease of outpatient administration (69.0%). Acute kidney injury incidence was minimal (4.2%). CIV is associated with rapid attainment of target concentrations in pediatric hematology/oncology patients and is safe and well tolerated.

'The Year of Living Dangerously': Successful Rhodococcus Equi Therapy in an Immunosuppressed Patient with Minimal Toxicity by One Year of Continuous Intravenous Vancomycin Therapy Combined with Oral Levofloxacin And Rifampicin.

Rhodococcus equi is a Gram-positive microorganism that causes infections, particularly in immunocompromised patients. Treatment duration can be prolonged. While vancomycin is an effective drug in this scenario, its use may lead to renal damage. Studies have shown that continuous vancomycin infusion appears to be a safe strategy in terms of adverse effects compared to bolus administration. We present the case of a 71-year-old female liver transplant recipient. After being diagnosed with a mediastinal infection caused by Rhodococcus equi with poor response to initial therapy, she required 12 months of continuous intravenous domiciliary infusion of vancomycin combined with oral levofloxacin and rifampicin. There was no drug-related complication throughout the follow-up. The use of continuous vancomycin infusion has emerged as a safer, more efficient, and cost-effective alternative to intermittent administration. We want to emphasise the uniqueness of this case, where despite the unprecedented treatment duration, no adverse effects occurred. Vancomycin therapy based on continuous infusion represents a safer and cheaper strategy than classic intermittent administration.The use of continuous infusion facilitates the management of complex infections with outpatient antimicrobial therapy.

P09 Lancashire and South Cumbria Critical Care Network Vancomycin Project

Abstract Background This project was a collaborative piece of work across a critical care network that included specialist advice from colleagues including aseptic/technically trained pharmacists and microbiology to optimize care for critical care patients in Lancashire and South Cumbria. We used several members of our workforce including pharmacists, nursing staff, microbiologists, rotational doctors and consultants to work towards a harmonized guideline. Methods During our initial meeting, we identified that different centres were using different glycopeptides and administering them differently: East Lancashire Hospitals (ELHT)—continuous vancomycin infusion; Blackpool Cardiac and Blackpool General—continuous vancomycin infusion, with no formal guideline in place but adopted from ELHT; Lancashire Teaching Hospitals—intermittent vancomycin infusions; and University Hospitals Morecambe Bay—teicoplanin is glycopeptide of choice. Our consultant microbiologist discussed the use of glycopeptides and what infections they are used for in critical care. The pharmacokinetics of vancomycin and the benefit of using a continuous infusion was also discussed. We decided to undertake a clinical audit of our vancomycin guidelines at ELHT to ensure that we had an evidence base to implement our guideline and provide assurance to the working group. We agreed to reconvene the working group after this audit was completed and after the concerns of colleagues had been addressed. Results and conclusions We presented the results of our audit and highlighted the opportunities harmonizing this guideline would provide. We discussed various scenarios such as stepping up from a ward protocol to a continuous infusion and the different methods of calculating creatinine clearance and if this would influence the first 24 h of the infusion. One comment was concerning the administration of vancomycin and the number of times nurses will be changing bags for patients requiring higher doses, i.e. the majority of patients would usually be on 3 g/day or more depending on concentrations. This would mean changing the bag more than twice a day; as much as there is a therapeutic benefit to continuous vancomycin infusions, considering the max. concentration for peripheral and central lines allows for larger volumes, it would be beneficial (except in fluid restricted cases) to have a slightly larger volume to reduce the number of bag changes and plastic consumption. We considered this comment and discussed it with our aseptic services lead pharmacist. We attended a meeting of the ICS Aseptics Working Party across Lancashire and South Cumbria. WE discussed the proposed guideline and requested that aseptic units across Lancashire and South Cumbria developed worksheets to manufacture 5 g in 600 mL or 10 g in 1.2 L for central use to stop breaking the line when changing a bag and reducing plastic consumption. We also met with critical care practice educators across the network to discuss how we can promote this guideline and ensure nursing staff and prescribers are aware of how to prescribe and administer continuous vancomycin infusions. One of our units noted that they have had a few incidents with incorrect concentrations of vancomycin being made up for patients. We developed an e-learning package to educate our workforce.

Vancomycin and Gentamicin Removal with the HA380 Cartridge during Experimental Hemoadsorption

Introduction: Hemoadsorption has emerged as an adjunctive therapy for sepsis, but its impact on antibiotic levels remains poorly defined. We conducted an in vivo experimental study to investigate the removal of vancomycin and gentamicin during hemoadsorption using the HA380 cartridge, a novel styrene-divinylbenzene copolymer cartridge. Methods: Six surgically prepared sheep were administered 2 g of vancomycin and 400 mg of gentamicin over 30 min, followed by a continuous infusion of vancomycin (20 mg/h). Hemoadsorption was implemented with a styrene-divinylbenzene copolymer HA380 cartridge at a blood flow of 120 mL/min. The removal ratio, sorbent-based clearance, and the mass removal rate were calculated for each time point. Results: The mean 10-min vancomycin removal ratio exceeded 90% and declined to 68.0% at 30 min; 52.8% at 60 min, and 28.0% by 4 h. Due to constant plasma flow, clearance varied proportionally with the removal ratio. Over 4 hours, the total mass removal was 556 mg (SD 106.3). For gentamicin, the mean 10-min removal ratio was 96.9% and the final ratio at 4 h remained 53.0%, with clearances changing proportionately. The total mass removal of gentamicin was 138 mg (SD 26.6) over 4 h. The sorbent-based clearance of vancomycin was significantly lower than that of gentamicin (P_group < 0.0001). Conclusion: The novel HA380 sorbent cartridge appears safe and achieves significant vancomycin and gentamicin removal over a four-hour period. This information can be used by clinicians to guide their prescription and consider the additional dosing of at least an extra 25–35% amount in patients receiving HA380 hemoadsorption therapy during sepsis.

Peripheral vascular access as exclusive access mode in pediatric intensive care unit.

The type of vascular access (central or peripheral) in pediatric critical care depends on several factors, including the duration of treatment, the properties of the medication (osmolarity or vesicant), and the need for central pressure monitoring. The utilization of peripheral intravascular catheters (PIVCs) has shown a notable increase in the number of patients being treated. Extended dwell or midline catheters are another peripheral access option in addition to PIVCs. However, there are currently no established guidelines on their placement. The aim of this study is to estimate the duration of dwell time for PIVCs, analyze the specific parameters affecting it, and develop recommendations for switching to extended dwell and midline catheter placement as an alternative to peripheral access. The study enrolled patients aged 0-18 years admitted to the pediatric intensive care unit (PICU) for over 24 h and managed with peripheral access only over 2 years (2019-2021). A total of 484 patients met the specified criteria. Patients who had peripheral access exhibited a lower PRISM score and a shorter length of stay in the PICU, with mean values of 18 (SD: 8.5) and 9.5 (SD: 6.4) days, respectively, compared with patients who had central access with mean values of 8.9 (SD: 5.9) and 5.7 (SD: 3.6) days, respectively. The PIVC dwell time was found to be 50.1 h (SD: 65.3) and required an average of 1.6 insertion attempts. Patients with three or more insertions exhibited an increased odds ratio of 5.2 (95% CI: 3.1-8.5) for receiving an extended dwell or midline insertion. Increased dwell time was associated with female gender, 59.5 h (P < 0.001), first attempt insertion, 53.5 h (P < 0.001), use of 24 Ga bore, 56.3 h (P = 0.04), left-sided insertions, 54.9 (P = 0.07), less agitation, 54.8 h (P = 0.02), and less edema, 61.6 (P < 0.001). Decreased dwell time was associated with the use of vancomycin infusion at 24.2 h (P < 0.001) and blood transfusions at 29.3 h (P < 0.001). Extended catheters last longer than PIVCs in PICU patients. Extended catheter placement requires consideration of the length of treatment, as well as the overall body edema, the level of the patient's restlessness, and the need for vancomycin infusion or blood transfusions, as these factors reduce PIVC dwell time and expose the patients to painful insertions. For such cases, an extended dwell catheter may be a better option, even if the projected treatment time is less than 6 days.