Extended Infusion Research Articles

8654 Real-World Performance Of The Medtronic Extended Infusion Set In The United States

Abstract Disclosure: T. Kwa: Employee; Self; Medtronic Minimed. G. Zhang: Employee; Self; Medtronic Minimed. J. Kiehl: Employee; Self; Medtronic Minimed. V. Putcha: Employee; Self; Medtronic Minimed. A. Patel: Employee; Self; Medtronic Minimed. S. Chattaraj: Employee; Self; Medtronic Minimed. O. Cohen: Employee; Self; Medtronic Minimed. R.A. Vigersky: Employee; Self; Medtronic Minimed. Real-World Performance of the Medtronic Extended Infusion Set in the United States Objective: The Medtronic extended infusion set (EIS) is the first and only infusion set approved for up to 7-day use and its pivotal trial established clinical safety and efficacy.[1] The purpose of this retrospective analysis was to assess real-world EIS performance and overall glycemic outcomes based on United States (US) data uploaded by MiniMed™ 770G system (MM770G) users at an aggregate level. Methods: Infusion set occlusion alarm events and time in (TIR, 70-180 mg/dL), below (TBR, <70 mg/dL) and above (TAR, >180 mg/dL) range of EIS-MM770G users (N=393) with >30-day device use in the U.S. were analyzed and compared against the data of a cohort of the same median age of 50 years (N=77219) using the MM770G with a standard 2/3-day infusion set (at an aggregate level). Results: EIS users experienced a lower occlusion alarm rate (median 0.011 alerts/patient day) compared to 0.016 alerts/patient day with the standard set (p = 0.005). TIR for EIS users was 69.4%, which was numerically greater than the 69.1% for standard set users (p = 0.258). While TAR was not significantly different (28.9% for EIS and 29.0% for standard set, p = 0.995), TBR was significantly lower (0.5% for EIS and 1.3% for standard set, p = 0.000). The difference in the total daily dose (TDD) of insulin between the two groups (53.0 units for EIS, 49.4 units for standard set) was not statistically significant (p = 0.961). Conclusion: Since the U.S. launch, the EIS has continued to perform similarly to the pivotal trial results and an early real-world analysis of EIS use outside of the US.2 The decreased burden of fewer set changes comes with a lower occlusion alarm rate and does not compromise time spent in target range.

Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients (BEATLE): a randomized, multicentre, open-label, superiority clinical trial

ObjectivesThe efficacy of extended infusions (EI) of β-lactam antibiotics for optimising outcomes in febrile neutropenia is unclear. We assessed whether the administration of β-lactams was more effective in EI than in intermittent infusion (II) for the treatment of febrile neutropenia. MethodsWe performed a randomized, open-label, superiority clinical trial of patients with febrile neutropenia at four Spanish university hospitals. Patients undergoing haematopoietic stem cell transplantation or with acute leukaemia receiving chemotherapy who required empirical antibiotic treatment for febrile neutropenia were randomly assigned (1:1) to receive EI of β-lactam or II after a first dose in bolus. The choice of antipseudomonal β-lactam was left to the discretion of the attending physician. The primary endpoint was treatment success at day 5, defined as defervescence without modifying the antibiotic treatment. Secondary endpoints included adverse events, attainment of the pharmacokinetic/pharmacodynamic target of 50%, 75%, and 100%ƒuT > MIC, and 30-day mortality. ResultsFrom November 19, 2019 to June 22, 2022, 295 patients were screened for eligibility, of whom 150 were randomly assigned to receive EI (n = 77) or II (n = 73) of the antipseudomonal β-lactam of choice. In the intention-to-treat analysis, treatment success at day 5 was achieved in 39/77 patients (50.6%) receiving EI versus 46/73 patients (63.0%) receiving II (risk difference, −12.4%; 95% CI, −29.4 to 4.7; p 0.17). The pharmacokinetic/pharmacodynamic targets of 75% and 100% ƒuT > MIC for empirical treatment were achieved more frequently in the EI group. No statistically significant differences were found between groups in terms of adverse events or 30-day mortality. DiscussionOur findings do not support the routine use of empirical EI of β-lactams in febrile neutropenia. Further studies should consider the clinical heterogeneity of febrile neutropenia and focus on patients with sepsis or septic shock and microbiologically documented infections, particularly those with infections caused by microorganisms less susceptible to β-lactams.

A Retrospective Analysis of Intravenous Push versus Extended Infusion Meropenem in Critically Ill Patients.

Meropenem is a broad-spectrum antibiotic used for the treatment of multi-drug-resistant infections. Due to its pharmacokinetic profile, meropenem's activity is optimized by maintaining a specific time the serum concentration remains above the minimum inhibitory concentration (MIC) via extended infusion (EI), continuous infusion, or intermittent infusion dosing strategies. The available literature varies regarding the superiority of these dosing strategies. This study's primary objective was to determine the difference in time to clinical stabilization between intravenous push (IVP) and EI administration. We performed a retrospective pilot cohort study of 100 critically ill patients who received meropenem by IVP (n = 50) or EI (n = 50) during their intensive care unit (ICU) admission. There was no statistically significant difference in the overall achievement of clinical stabilization between IVP and EI (48% vs. 44%, p = 0.17). However, the median time to clinical stability was shorter for the EI group (20.4 vs. 66.2 h, p = 0.01). EI administration was associated with shorter hospital (13 vs. 17 days; p = 0.05) and ICU (6 vs. 9 days; p = 0.02) lengths of stay. Although we did not find a statistically significant difference in the overall time to clinical stabilization, the results of this pilot study suggest that EI administration may produce quicker clinical resolutions than IVP.

Clinical Challenge: Standard Versus Extended Meropenem Infusion in Children.

The management of Gram-negative bacterial infections poses a significant challenge due to the emergence of highly effective antibiotic-resistant mechanisms, leading to treatment failures, particularly among hospitalized children. This patient population experiences elevated rates of both mortality and morbidity, and the available antibiotic options against these bacteria are limited. Carbapenems, such as meropenem, represent one of the choices for treatment. While meropenem is highly effective against Gram-negative bacteria, the prevalence of multidrug-resistant infections in hospitals has become a growing concern. In response to this challenge, exploring innovative strategies is crucial. One such strategy is the implementation of high-dose extended meropenem infusion treatment. Researchers propose that extended meropenem treatment may offer a viable solution to combat resistant bacteria. Despite a limited number of studies focusing on the effectiveness of this strategy in children, our comprehensive review of the literature revealed promising findings. Our examination specifically compared extended infusion with standard infusion approaches. The evidence suggests that extended infusion of meropenem provides more benefits compared to standard infusion methods. Researchers consistently reported positive results in their observations, with the exception noted in very low birth weight neonates and children with infections caused by carbapenem-resistant Enterobacteria and Acinetobacter baumannii spp. In conclusion, extended meropenem infusion treatment emerges as a promising option for managing resistant infections. However, it is essential to underscore the need for further studies to robustly support the observed benefits of this treatment regimen.

The Practice of Prolonging Meropenem Infusion: A Narrative Review of Literatures Over the Last Decade

Background: The emergence of Antimicrobial Resistance (AMR) has forced clinicians and medical professionals to implement a strict Antimicrobial Stewardship policy. One of the pillar of Antimicrobial Stewardship is by optimizing the use of antibiotic agents. Beta-lactams demonstrate a time-dependent effect in combating bacteria. Since it is pharmacodynamically supported, a prolonged exposure via intravenous administration could be a feasible strategy to maximize the bactericidal effect. Meropenem, a beta-lactam antibiotic of carbapenems sub-class, also falls into the category above. However, there are questions to be answered regarding its stability, compatibility, safety, and clinical outcomes superiority compared to the standard intermittent infusion, before we can determine its effectiveness to be delivered as prolonged or extended infusion. Aims: This article would like to review literatures regarding the rationale behind the practice of prolonging meropenem infusion from the last decade. Method: For this narrative review we utilized articles extracted from Cochrane Library, ScienceDirect, and SageJournals databases from the last ten years. We also added complementary related articles from UpToDate®. Selected articles were limited to those published in english. Inclusion criteria specifically only including related articles to the practice of prolonging meropenem infusion on adult patients. A total of 18 articles were reviewed for the synthesis of this narrative review. Conclusion: Meropenem is eligible for prolonged infusion protocol since it is theoretically supported, adequate in stability, less concern for incompatibility, and potentially can provide better clinical outcomes compared to standard intermittent infusion.

Dose optimization of meropenem for critically ill patients by pharmacokinetic/ pharmacodynamic simulation

Recent pharmacokinetic/pharmacodynamic (PK/PD) studies revealed that prolonged infusion, especially continuous infusion could improve probability of target attainment (PTA) of meropenem. However, the implementation of continuous meropenem infusion in the clinical environment can be limited due to the solution’s instability, which results in a diminished effectiveness of the drug. The two-step infusion approach has been expected as a promising novel approach to address this issue. The aim of this study was to assess the probability of target attainment for finding the optimal dosage regimens of meropenem in critically ill patients. Monte Carlo simulation using Ehmann population pharmacokinetic model was performed to evaluate the following different intravenous infusion regimens including extended infusion (EI), continuous infusion (CI) and two-step infusion (TS) with three total daily doses (3g, 4.5g and 6g). The PK/PD target was defined as the probability of achieving a fractional time above the MIC of ≥ 98% on the first day of therapy. Subsequently, dosing regimens were suggested based on renal function which was estimated by the Cockcroft & Gault creatinine clearance (Clcr =10-30, 31-50, 51-70, 71-90, 91-130, and over 130 mL/min). Simulations also revealed that the 1000mg q8h EI regimen is suitable to reach MICs of 1 mg/L, regardless of the patient’s renal function. For higher MICs and up to 16 mg/L, continuous infusion therapy with a loading dose of 0.5 g and a maintenance dose of 3 g to 6 g per day should be considered in clinical practice. The two-step infusion approach did not demonstrate superior PTA compared to extended infusion therapy and was significantly lower than that of continuous infusion at the same dosage level.

Phase 1/2 Trial to Jointly Optimize Dose and Administration Schedule of Evomela in Newly Diagnosed Multiple Myeloma Patients Undergoing Autologous Hematopoietic Cell Transplantation

Background: Eligible patients with multiple myeloma (MM) are offered autologous hematopoietic cell transplantation (auto-HCT) in their first remission. The usual conditioning regimen consists of melphalan (Alkeran) 200 mg/m 2 infused over ~ 30 minutes due to its limited stability. Evomela is a newer formulation of melphalan, which is stable at room temperature for ~ 24 hours. The current trial studied the dose escalation and compared the short versus extended infusion time of evomela used as a conditioning regimen before auto-HCT. Methods: Patients with newly diagnosed MM, age ≤ 70, were eligible. Two dose levels, 200 and 225 mg/m 2 were studied. Patients were randomized between two infusion schedules: 30-60 minutes (short) and an extended infusion of 8-9 hours. Disease response was measured using IMWG criteria. Minimal residual disease (MRD) was measured by flow cytometry at 10 -5. Results: Sixty patients were enrolled. The first 3 patients in each arm were treated at evomela 200 mg/m 2. Since no dose-limiting toxicity (DLT) was observed, all subsequent patients (n=54; 27 in each arm) were treated at evomela 225 mg/m 2. The results are presented for patients treated at evomela 225 mg/m 2. Patient characteristics were evenly distributed (Table 1). The median age was 58.6 years (range: 42.6 -70.3). Twelve (22%) patients had high-risk cytogenetics (4 [15%] in the short infusion; 8 [30%] in the extended infusion arm), p-value 0.19. There were no deaths, and no patient experienced grade > 3 adverse events (AE). Grade 2-3 AEs were seen in 53 (98%) patients (26 [96%] in the short infusion; 27 [100%] in the extended infusion). Twenty-four (44%) patients experience grade 2-3 diarrhea (16 [60%] in the short infusion; 8 [30%] in the extended infusion). Grade 2-3 esophagitis was seen in 3 (6%) patients overall (0 in the short infusion; 3 [11%] in the extended infusion). Atrial fibrillation was seen in one patient (grade 2, extended infusion). Before transplant, six (22%) patients were in stringent complete remission (sCR) or CR in the short infusion arm vs. 4 (15%) patients in the extended infusion arm. At day-90 post-transplant, 13 (48%) patients in each arm were in sCR/CR, and 17 (63%) patients in each arm achieved MRD-negative status. Overall, 23 (43%) patients achieved MRD-negative plus sCR/CR status at day-90 (11 [41%] in short and 12 [50%] in the extended infusion arm). The median follow-up was 14.5 (range: 6-40) months (13.8 months in the short infusion and 14.8 months in the extended infusion arm). The median progression-free survival (PFS) was not reached in the overall trial population (Figure). The median PFS in the short infusion arm was not reached vs. 28.2 months in the extended infusion arm. The 2-year progression-free survival (PFS) was 91% in the short infusion arm vs. 77% in the extended infusion arm (hazard ratio (HR)=9.5 with 95% CI: 1- 91.2), p-value=0.022. On multivariate analysis, controlling for age and cytogenetic risk category, the extended infusion arm was associated with a shorter PFS (HR 10.96; 95% CI 1.18 - 102.02), p-value 0.0355, although the range for HR was notably wide, which could be attributed to a small number of events in each arm. Conclusions: Dose escalation of evomela to 225 mg/m 2 is safe and associated with an acceptable toxicity profile and a high response rate. Short and extended infusions of evomela are well-tolerated and associated with high response rates. The PFS is longer with the short infusion schedule, however, to affirm these preliminary observations, additional follow-up is needed.

Are We Dosing Correctly? Population Pharmacokinetic Modeling of Cefepime, Piperacillin-Tazobactam, and Meropenem in Individuals with Cystic Fibrosis

Abstract Background Patients with cystic fibrosis (CF) experience recurrent bacterial pulmonary exacerbations. The management of these infections becomes increasingly complex due to decreased antimicrobial susceptibility and inadequate pharmacokinetic/pharmacodynamic (PK/PD) characterization of the most commonly used antimicrobial agents in this population. Methods One hundred fifty-five pediatric and adult participants receiving cefepime (n=82), meropenem (n=42), or piperacillin-tazobactam (n=31) were enrolled. Opportunistic blood samples were obtained during hospitalization. Population PK (PopPK) analysis was conducted using nonlinear mixed effects modeling in NONMEM, and clinical and demographic characteristics were evaluated as potential covariates. Monte Carlo simulations evaluated the probability of PK/PD target attainment (PTA) for different dosing regimens. Multiple targets, defined as percentage of a 24-h time period that the free drug concentration exceeds the MIC (fT> MIC), were selected based on prior studies of beta-lactam antibiotics. Results Preliminary PopPK modeling results show that lean body weight, creatinine clearance, daily dose, mode of administration (standard vs. extended infusion), and age affect PK parameters, with varying effects by drug. As anticipated, extended or continuous infusions resulted in higher PTA (Table 1). In the cefepime group, the 3-h infusion regimen achieved higher PTAs than the 0.5-h regimen across all age groups. Estimated breakpoints (in which ≥ 90% of patients are expected to achieve a PK/PD target) were 2-4 fold higher in pediatric participants receiving a 3-h infusion vs. 0.5-h infusion, based on age and target fT> MIC. In the meropenem group, increased creatinine clearance led to reduced PTA, and in the piperacillin-tazobactam group, total daily dose and interval were the principal drivers of PTA. Conclusions To our knowledge, this is the largest PopPK study to date of these antimicrobials in individuals with CF. Clinicians should incorporate local antibiograms with these PopPK models to determine optimal dosing in patients with CF, since standard dosing regimens may fail to achieve specific PK/PD targets. This population may also benefit from beta-lactam therapeutic drug monitoring.

Utilizing Ceftazidime/Avibactam Therapeutic Drug Monitoring in the Treatment of Neurosurgical Meningitis Caused by Difficult-to-Treat Resistant Pseudomonas aeruginosa and KPC-Producing Enterobacterales.

Central nervous system (CNS) infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales and difficult-to-treat resistant (DTR) Pseudomonas aeruginosa represent a formidable clinical challenge. Antimicrobial regimens that efficiently penetrate the cerebrospinal fluid (CSF) and achieve sufficient concentrations associated with microbiologic and clinical cure are limited. We evaluated therapy with ceftazidime-avibactam (CAZ-AVI) in order to guide precise dosing in the treatment of CNS infections. Therapeutic drug monitoring (TDM) was performed in 3 patients with health care-associated ventriculitis and meningitis (HAVM) using CAZ-AVI 2.5 g infused intravenously every 8 hours as standard and extended infusion. Simultaneous CSF and plasma samples were obtained throughout the dosing interval in each patient. Concentrations of CAZ and AVI were determined by liquid chromatography/mass spectrometry. Bacterial identification revealed KPC-producing Klebsiella pneumoniae (KPC-Kp), DTR Pseudomonas aeruginosa, and KPC-producing Enterobacter cloacae (KPC-Ent.c). All isolates were resistant to carbapenems. The minimum inhibitory concentrations (MICs) of CAZ-AVI were 0.25/4, 4/4, and 0.25/4 μg/mL, respectively. CAZ and AVI concentrations were determined in CSF samples ranging from 29.0 to 15.0 µg/mL (CAZ component) and 4.20 to 0.92 µg/mL (AVI component), respectively. AVI achieved concentrations ≥1 µg/mL in 11 out of 12 CSF samples collected throughout the dosing interval. Clinical and microbiologic cure were attained in all patients. Postinfusion concentrations of CAZ-AVI were measured in plasma and CSF samples obtained from 3 patients with complicated CNS infections caused by antimicrobial-resistant isolates. The measured concentrations revealed that standard CAZ and AVI exposures sufficiently attained values correlating to 50% fT > MIC, which are associated with efficient bacterial killing.

International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists.

Intravenous β-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PIs) can be applied during the administration of intravenous β-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of PI β-lactams developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug-monitoring considerations, and the use of PI β-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of β-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

International consensus recommendations for the use of prolonged-infusion beta-lactam antibiotics: Endorsed by the American College of Clinical Pharmacy, British Society for Antimicrobial Chemotherapy, Cystic Fibrosis Foundation, European Society of Clinical Microbiology and Infectious Diseases, Infectious Diseases Society of America, Society of Critical Care Medicine, and Society of Infectious Diseases Pharmacists: An executive summary.

Intravenous β-lactam antibiotics remain a cornerstone in the management of bacterial infections due to their broad spectrum of activity and excellent tolerability. β-lactams are well established to display time-dependent bactericidal activity, where reductions in bacterial burden are directly associated with the time that free drug concentrations remain above the minimum inhibitory concentration (MIC) of the pathogen during the dosing interval. In an effort to take advantage of these bactericidal characteristics, prolonged (extended and continuous) infusions (PI) can be applied during the administration of intravenous β-lactams to increase time above the MIC. PI dosing regimens have been implemented worldwide, but implementation is inconsistent. We report consensus therapeutic recommendations for the use of β-lactam PI developed by an expert international panel with representation from clinical pharmacy and medicine. This consensus guideline provides recommendations regarding pharmacokinetic and pharmacodynamic targets, therapeutic drug monitoring considerations, and the use of PI β-lactam therapy in the following patient populations: severely ill and nonseverely ill adult patients, pediatric patients, and obese patients. These recommendations provide the first consensus guidance for the use of β-lactam therapy administered as PIs and have been reviewed and endorsed by the American College of Clinical Pharmacy (ACCP), the British Society for Antimicrobial Chemotherapy (BSAC), the Cystic Fibrosis Foundation (CFF), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the Infectious Diseases Society of America (IDSA), the Society of Critical Care Medicine (SCCM), and the Society of Infectious Diseases Pharmacists (SIDP).

Optimizing Betalactam Clinical Response by Using a Continuous Infusion: A Comprehensive Review.

Antimicrobial resistance is a major healthcare issue responsible for a large number of deaths. Many reviews identified that PKPD data are in favor of the use of continuous infusion, and we wanted to review clinical data results in order to optimize our clinical practice. We reviewed Medline for existing literature comparing continuous or extended infusion to intermittent infusion of betalactams. In clinical studies, continuous infusion is as good as intermittent infusion. In the subset group of critically ill patients or those with an infection due to an organism with high MIC, a continuous infusion was associated with better clinical response. Clinical data appear to confirm those of PK/PD to use a continuous infusion in severely ill patients or those infected by an organism with an elevated MIC, as it is associated with higher survival rates. In other cases, it may allow for a decrease in antibiotic daily dosage, thereby contributing to a decrease in overall costs.

Effectiveness of Extended or Continuous vs. Bolus Infusion of Broad-Spectrum Beta-Lactam Antibiotics for Febrile Neutropenia: A Systematic Review and Meta-Analysis.

This systematic review aimed to compare extended infusion or continuous infusion with bolus infusion for febrile neutropenia (FN). We included clinical trials comparing extended or continuous infusion with bolus infusion of beta-lactam antibiotics as empirical treatment for FN and evaluated the clinical failure, all-cause mortality, and adverse event rates. Five articles (three randomized controlled trials (RCTs) and two retrospective studies) from 2014 to 2022 were included. Clinical failure was assessed with a risk ratio (RR) (95% coincident interval (CI)) of 0.74 (0.53, 1.05) and odds ratio (OR) (95% CI) of 0.14 (0.02, 1.17) in the 2 RCTs and retrospective studies, respectively. All-cause mortality was assessed with an RR (95% CI) of 1.25 (0.44, 3.54) and OR (95% CI) of 1.00 (0.44, 2.23) in the RCTs and retrospective studies, respectively. Only 1 RCT evaluated adverse events (with an RR (95% CI) of 0.46 (0.13, 1.65)). The quality of evidence was "low" for clinical failure and all-cause mortality in the RCTs. In the retrospective studies, the clinical failure and all-cause mortality evidence qualities were considered "very low" due to the study design. Extended or continuous infusion of beta-lactam antibiotics did not reduce mortality better than bolus infusion but was associated with shorter fever durations and fewer adverse events.

Clinical Outcomes With Extended Versus Intermittent Infusion of Anti-Pseudomonal Beta-Lactams in Patients With Gram-Negative Bacteremia.

Administration of doses via an extended infusion (EI) is an important strategy to optimize beta-lactams. Available data on the impact of EI on outcomes largely focus on clinical cure or mortality in critically ill patients or those with resistant pathogens. The potential benefits of EI extend beyond these populations and outcomes, and further study is warranted. This was a retrospective cohort study of adult patients who received cefepime, piperacillin/tazobactam, or meropenem for Gram-negative bacteremia via EI or intermittent infusion. Patients were matched 1:1 based on study drug, sepsis severity, intensive care unit (ICU) status, bacteremia source, and pathogen. Outcomes assessed included time to clinical stabilization, rates of treatment failure, mortality, recurrence, and length of stay (LOS). Two hundred sixty-eight patients were included. Baseline characteristics were similar between groups. Forty-two percent of patients were in the ICU at infection onset and the most common pathogen was Escherichia coli (41%). After adjusting for residual differences between groups, receipt of EI was independently associated with shorter time to clinical stability (adjusted odds ratio, 0.32; 95% confidence interval, .22-.47), time to defervescence, and time to white blood cell count normalization. Furthermore, EI was associated with a lower incidence of treatment failure, decreased recurrence of bacteremia, and shorter LOS. There was no difference in mortality. These findings were consistent regardless of patient location (ICU vs ward), baseline renal function, source of bacteremia, or study drug received. These findings suggest that EI beta-lactams are an important stewardship strategy to improve clinical outcomes in patients with Gram-negative bacteremia.

Optimization of β-Lactam Dosing Regimens in Neonatal Infections: Continuous and Extended Administration versus Intermittent Administration.

In neonates, β-Lactam antibiotics are almost exclusively administered by intermittent infusion. However, continuous or prolonged infusion may be more beneficial because of the time-dependent antibacterial activity. In this pharmacokinetic/pharmacodynamic simulation study, we aimed to compare treatment with continuous, extended and intermittent infusion of β-lactam antibiotics for neonates with infectious diseases. We selected population pharmacokinetic models of penicillin G, amoxicillin, flucloxacillin, cefotaxime, ceftazidime and meropenem, and performed a Monte Carlo simulation with 30,000 neonates. Four different dosing regimens were simulated: intermittent infusion in 30min, prolonged infusion in 4h, continuous infusion, and continuous infusion with a loading dose. The primary endpoint was 90% probability of target attainment (PTA) for 100% ƒT>MIC during the first 48h of treatment. For all antibiotics except cefotaxime, continuous infusion with a loading dose resulted in a higher PTA compared with other dosing regimens. Sufficient exposure (PTA>90%) using continuous infusion with a loading dose was reached for amoxicillin (90.3%), penicillin G (PTA 98.4%), flucloxacillin (PTA 94.3%), cefotaxime (PTA 100%), and ceftazidime (PTA 100%). Independent of dosing regimen, higher meropenem (PTA for continuous infusion with a loading dose of 85.5%) doses might be needed to treat severe infections in neonates. Ceftazidime and cefotaxime dose might be unnecessarily high, as even with dose reductions, a PTA >90% was retained. Continuous infusion after a loading dose leads to a higher PTA compared with continuous, intermittent or prolonged infusion, and therefore has the potential to improve treatment with β-lactam antibiotics in neonates.

Application of autonomous extended infusion therapy systems in treatment of patients with hemoblastoses. Experience of the Oncohematology Division of the Clinical Hospital “Lapino”

Use of microinfusion elastomeric pumps for extended administration of antitumor drugs improves patients’ quality of life during prolonged cyclic treatment because of the absence of venous complications and infusion allergic reactions during administration of cytostatic agents and targeted drugs.

SNAPTIMED study: does the Scottish and Newcastle Antiemetic Protocol achieve timely intervention and management from the emergency department to discharge for paracetamol poisoning?

BackgroundThis study aimed to establish whether the modified 12-hour Scottish and Newcastle Antiemetic Protocol (SNAP) for paracetamol poisoning is associated with improvement in hospital length of stay (LoS), as well...

Impact of extended-infusion piperacillin-tazobactam in a Canadian community hospital

BackgroundStudies have demonstrated improved clinical outcomes with extended infusion (EI) piperacillin/tazobactam (TZP) compared to standard infusion (SI). However, there is less evidence on its benefits in noncritically-ill patients. Hospital-wide EI TZP was implemented at our site on February 21, 2012. Our objectives were to compare clinical, safety and economic outcomes between EI and SI TZP. MethodsA retrospective cohort study of all adult patients who received EI TZP (3.375 g IV q8h infused over 4 hours and SI TZP for ≥ 48 hours during 3 years pre-and postimplementation was conducted. The primary study outcome was 14-day mortality while secondary outcomes included length of hospital stay (LOS), nursing plus pharmacy cost, occurrence of Clostridioides difficile infection, readmission within 30 days and change in Pseudomonas aeruginosa minimum inhibitory concentration (MIC) distribution for TZP. The primary outcome and binary secondary outcomes were analyzed using a logistic regression model. LOS was examined using time to event analysis. Cost was examined using linear regression modelling. ResultsOverall, 2034 patients received EI TZP and 1364 patients received SI TZP. EI TZP was associated with lower odds of mortality (OR 0.76, 95% CI 0.63–0.91), lower odds of C. difficile infection (OR 0.59, 95% CI 0.41–0.84) and 8% lower cost (estimate 0.92, 95% CI 0.87–0.98) compared to SI TZP. ConclusionsHospital-wide implementation of EI TZP was associated with lower odds of 14-day mortality and incidence of C. difficile infection with cost savings at our institution.

Chemical stability and physical compatibility of meropenem in admixtures for continuous and extended intravenous infusions

IntroductionProlonged intravenous infusion of beta-lactams increase the clinical cure rate compared to conventional administration in critical or septic patients. This study aimed to determine chemical stability and physical compatibility of meropenem at conditions used in clinical practice to evaluate the stability of the preparation during its administration and the possibility of anticipated preparation. MethodsAdmixtures in study were: (i) meropenem 6g in 0.9% sodium chloride (NS) in infusor of 2mL/h 50mL or 10mL/h 240mL; (ii) meropenem 1 or 2g in NS in infusion bag of 250mL. Temperatures of study were: (i) infusor: 4.5°C, 32°C or 12h at 4.5°C followed by 32°C; (ii) Infusion bag: 4.5°C, 24.5°C or 6h at 4.5°C followed by 24.5°C. Time of study was 5–6 days in infusor and 1 day in infusion bag. Chemical stability was evaluated by high performance liquid chromatography and physical compatibility by measuring pH and visual inspection. ResultsChemical stability and physical compatibility of meropenem in admixtures in infusors were reduced at high meropenem concentration and high temperature. Admixtures in infusion bag show chemical stability and physical compatibility for at least 1 day. ConclusionAdministration of meropenem 6g in infusion of 24h in 240mL of 0.9% NaCl in infusor of 10mL/h could be possible if the admixture is infused at 4.5°C. Extended infusion of meropenem 1 or 2g in 0.9% NaCl in infusion bag (250mL) in 3–4h is also feasible. Anticipated preparation of the admixtures in infusion bag is possible with a stability of 24h.

Evaluation of the safety of piperacillin-tazobactam extended infusion in pediatric cystic fibrosis patients.

Patients with cystic fibrosis (CF)may be treated with piperacillin-tazobactam (PZT)for acute pulmonary exacerbations. Extending the infusion of PZT is one strategy to increase efficacy. Direct comparison, with respect to the incidence of acute kidney injury (AKI),between these two strategies has not been evaluated in pediatric patients with CF. The primary objective of this study was to compare the incidence of AKI in pediatric CF patients receiving extended infusion (EI) PZT versus traditional infusion (TI). This IRB-approved, retrospective analysis included patients ages 30 days to 18 years that received PZT for at least 48 h between January 1, 2008, and January 1, 2020. PZT was infused over 30 min(TI group) or 4 h(EI group). Two hundred and four patients were included (TI: 109, EI: 95). Median age was 8 years (4-13) and 7 years (3-12) in the TI and EI groups (p = 0.15). The groups did not differ significantly in their baseline characteristics. There were 12 (11%) AKIs in the TI group and 8 (8.4%) in the EI group (p = 0.53). There was one occurrence of serum sickness in the TI group and none in the EI group. The incidence of thrombocytopenia was similar between the two groups. Median treatment duration was 8 days (5-11) and 9 days (5-13) for the TI and EI groups, respectively (p = 0.24). There was no significant increase in AKI in pediatric patients with CF receiving PZT by EI compared withTI. EI may be utilized to optimize the pharmacokinetics of PZT in pediatric CF patients.