Intermittent Infusion Research Articles

Under-Recognized Medication Loss With the Administration of Small-Volume Intermittent Infusions

Background: Most antibiotics administered via intermittent IV infusion are diluted in 50 to 100 ml of diluent. The primary infusion set for the BD Alaris® pumps can hold 25 ml of volume in its tubing, potentially contributing up to a 50% drug loss if residual volume is present after administration is complete. In the case of antibiotics, this may lead to significant underdosing, potentially contributing to reduced therapeutic response and emergence of antimicrobial resistance. Many organizations lack departmental policies and procedures for the administration of small-volume intermittent infusions. Developing a clear policy and procedure can increase drug delivery efficiency. Previous studies propose several recommendations, such as using a secondary infusion set, adding carrier fluids, and flushing the line to account for overfill. Objective: Our aim was to implement pilot new guidance in 2 patient units (an ICU and a non-ICU) to address the administration of small-volume intermittent infusions and determine if this results in more complete medication administration. Methods: This was an observational quality improvement initiative assessing the new guidance established for the administration of small-volume intermittent infusions to current practices. The primary outcome of this study was the incidence of residual drug volume in the IV line before the air-detector, IV bag, or IV vial. This was done through observation, and data collected through a survey. Results: In total, 203 IV administrations were observed, 86% of which were antibiotics. There were 124 IV administrations being observed before policy guidance initiation and 79 after initiation. The results showed a statistically significant reduction in the incidence of fluid remaining in the IV line before the air-detector (85% vs 27%; P < .001), the IV bag (59% vs 7.6%; P < .001), and in the IV vial (47% vs 24%; P < .001.). Conclusion: The proposed interventions significantly decreased the incidence of fluid remaining in the IV line before the air detector in the BD Alaris Pump, IV bag, and IV vial, presumably decreasing medication loss.

Utilizing an Opportunistic Clinical Study and Population-Based Pharmacokinetic Models to Identify Rational Empiric Dosing Regimens for Piperacillin-Tazobactam in Critically Ill Patients.

Determining an effective dosing regimen for piperacillin-tazobactam in critically ill patients is challenging due to substantial pharmacokinetic variability caused by complex pathophysiological changes. To address this need, a prospective clinical study was conducted, which enrolled 112 critically ill patients and employed an opportunistic sampling strategy. Population modeling and simulation were performed to characterize the pharmacokinetics (PK) and probability of target attainment (PTA) of piperacillin-tazobactam under various dosing regimens. Both piperacillin and tazobactam final models were one-compartment models with zero-order input and first-order elimination. Significant covariates included lean body weight for piperacillin and creatinine clearance along with continuous renal replacement therapy (CRRT) for both drugs. Monte Carlo simulations demonstrated that continuous infusion can achieve higher PTA than intermittent and extended infusions. When considering the minimum inhibitory concentration (MIC) of 16 mg/L for Pseudomonas aeruginosa (a frequently encountered bacterial pathogen among critically ill patients) and a PK/PD target of 100% fT >MIC, continuous infusion of 6 g/day is recommended for critically ill patients with a CLcr <60 mL/min, 9 g/day for patients with CLcr in the range of 60 to 129 mL/min, and 12 g/day for patients with a CLcr ≥130 mL/min. In addition, extended infusion represents a good alternative, especially the 3 g q6h or 4 g q6h regimens which can achieve the designated European Committee on Antimicrobial Susceptibility Testing (EUCAST) non-species-related PK/PD breakpoint of 8 mg/L. Our study provided valuable insight into PTA outcomes, which, together with individual renal function of future patients and institution-specific piperacillin susceptibility patterns, may assist physicians when making dosing decisions.

A multicenter retrospective study on comparing the efficacy and safety of the therapy of intermittent cyclophosphamide and corticosteroids versus rituximab for primary membranous nephropathy.

Few clinical studies compare the long-term remission, relapse, and safety of rituximab (RTX) or a combination of intermittent intravenous infusion of cyclophosphamide (CTX) and oral corticosteroid for primary membranous nephropathy (PMN) patients. We collected multicenter retrospective data on PMN patients with nephrotic syndrome who received RTX or intermittent intravenous CTX with oral corticosteroids between 1 January 2019 and 31 January 2024. Patients were followed up until two years after receiving immunotherapy. The primary outcomes were a composite of complete or partial remission rates at 6, 12, and 24months. The secondary outcomes were the relapse and safety evaluation. Forty patients treated with RTX and 27 with the CTX regime were available for analysis. No significant difference in the remission rate at 6, 12, or 24months was observed between the two groups (p>.05). Kaplan-Meier's survival analysis showed that the relapse-free cumulative survival rate of the RTX group was superior to that of the CTX group (p=.023). Compared with baseline, both the media of urine protein and serum albumin levels in the two groups showed a significant improvement at 6months and maintained through to the second year. No significant difference in the occurrence of total side effects between the two groups (p=.160). There was no difference in remission rates and safety between RTX versus intermittent intravenous CTX combined with oral corticosteroid treatment for patients with PMN within 2years. RTX appeared to have benefits in terms of prolonging relapse-free survival.

Reprint of: Does Two-Step Infusion Improve the Pharmacokinetics/Pharmacodynamics Target Attainment of Meropenem in Critically Ill Patients?

The optimal method for administering meropenem remains controversial. This study was conducted to explore the optimal two-step infusion strategy (TIT), and to investigate whether TIT is superior to intermittent infusion therapy (IIT) and prolonged infusion therapy (PIT). A physiologically based pharmacokinetics model for critically ill patients was established and evaluated. The validated model was utilized to evaluate the pharmacokinetics/pharmacodynamics (PK/PD) target attainment of meropenem. The PK/PD target attainment of different TITs varied greatly, and the total infusion duration and the first-step dose greatly affected these values. The optimal TIT was 0.25 g (30 min) + 0.75 g (150 min) at MICs of ≤2 mg/L, and 0.25 g (45 min) + 0.75 g (255 min) at MICs of 4-8 mg/L. The PK/PD target attainment of optimal TIT, PIT, and IIT were 100 % at MICs of ≤1 mg/L. When MIC increased to 2-8 mg/L, the PK/PD target attainment of optimal TIT was similar to that of PIT and higher than IIT. In conclusion, TIT did not significantly improve the PK/PD target attainment of meropenem compared with PIT. IIT is adequate at MICs of ≤1 mg/L, and PIT may be the optimal meropenem infusion method in critically ill patients with MICs of 2-8 mg/L.

Evaluation of the Clinical Outcomes of Cyclosporine Short Infusion Versus Continuous Infusion Postallogenic Stem Cell Transplantation.

Cyclosporin A (CsA) exhibits a narrow therapeutic index and large inter-individual variation in pharmacokinetics. Two intermittent and 24-h continuous infusions (CI) are both commonly used regimens in hematopoietic stem cell transplantation (HSCT), with no universal consensus. The objective of this study was to assess whether CsA as a 2-h, twice-daily intravenous infusion (2 h/12 h) is non-inferior to 22h CI every 24 h (22h-CI/24 h) in terms of acute graft-versus-host disease (aGVHD) incidence and adverse events in allogeneic HSCT adult patients. An open-label randomized trial recruited 31 allogeneic HSCT patients to receive the 2 h/12 h or 22 h-CI/24 h regimen. The primary outcomes were the incidence of aGVHD and CsA-related adverse events. The secondary outcomes included the correlation between the time concentration and area under the concentration-time curve (AUC) of 2 h/12 h versus 22 h-CI/24 h regimens. Six (19.4%) patients developed aGVHD. There was no statistically significant difference between the two groups concerning the incidence of aGVHD (13.3% in 2 h/12 h vs. 25% in 22 h-CI/24 h; p = 0.359). The distribution of different aGVHD types (p = 0.20) and mortality (p = 0.9) were not significantly different between the two groups. The two groups did not differ at any time with respect to AUCs, nephrotoxicity, hepatotoxicity, or electrolyte disturbance. The study suggested that the 2 h/12 h regimen is non-inferior to the conventional regimen (22 h CI/24 h) in terms of aGVHD incidence and adverse events. Further research is necessary to validate these findings and to guide practice, considering the small sample size of this study. ClinicalTrials.gov identifier NCT04575779 with initial release on 19 September 2020-Retrospectively registered, https://clinicaltrials.gov/study/NCT04575779 .

DDEL-06. CONVECTION-ENHANCED DELIVERY OF SEVEN DIFFERENT MOLECULES SHOW LARGE DIFFERENCES IN CONVECTIVE PROPERTIES BETWEEN MOLECULES. INFORMED DECISION MAKING FOR OPTIMIZED CATHETER PLACEMENT AND SUBSEQUENT INFUSION STRATEGIES

Abstract INTRODUCTION Glioblastoma (GBM) trials based on convection-enhanced drug delivery (CED) bypassing the blood-brain barrier have failed to prove efficient until now. Many factors influence CED. In this study we evaluated CED of seven different molecules using dynamic PET/MRI during infusion. This enabled in-depth evaluation of drug distribution and concentration gradients providing a more precise understanding of the Vd/Vi ratio and the extent of efficacy level across the Vd zone. Novel surgical catheter placement software algorithms, results in more informed-decision-making for catheter positioning and subsequent infusion planning strategies. METHODS Pigs were implanted with neuroinfuse™ drug delivery systems enabling intermittent drug infusions. Gadolinium, [124I]-UdR, [55Co]Co-DOTA-hEGF, [55Co]Co-DOTA-SP4, [18F]PSMA-1007 and three differently sized [64Cu]-labelled nanocarriers were evaluated in both pigs with and without a brain resection cavity. Gadolinium distribution was followed by MRI. PET imaging was used for the rest. To inform clinical trial design, strategic catheter placement and volumes to be infused, planning was investigated on several historical GBM cases. RESULTS Vd/Vi ratios ranged between 1.00 – 3.77. where large-sized liposomes performed best. Catheters stayed patent during weeks of repeated infusions. In the resected animals no leakage of drugs into the brain resection cavity was observed. Effective 3D modelling of novel catheter infusion planning aids provided visualized representations of tailor-made infusion plumes, capable of being suitably positioned to optimize surgical planning of catheters and transcutaneous reaccess port. CONCLUSION Large differences in convective properties between different molecules were observed. Large-sized liposomes as drug-carrier system showed superior performance to all other molecules. Vd/Vi ratios for promising drugs should be determined before initiating future clinical CED trials. Infusion concentration gradients to facilitate more precise Vd/Vi ratios provided important performance metrics for visualised infusion planning aids of a novel chronic drug delivery system, illustrating informed decision making for optimised catheter placement and subsequent infusion strategies is clinically translatable for GBM indications.

Usefulness of hot shot intermittent infusion online hemodiafiltration plus far-infrared therapy for dialysis patients with lower extremity arterial disease: a case report

BackgroundLower extremity arterial disease (LEAD) occurs at a high frequency in dialysis patients and is associated with a poor prognosis. In recent years, intermittent infusion online hemodiafiltration (I-OHDF) combined with far-infrared therapy (FIR) has been reported as being useful in dialysis patients with LEAD. However, there are also reports of worsening of the ulcers and gangrene in some cases. Hot shot I-OHDF (HS I-OHDF), which involves intermittent infusion of heated dialysate, is reported as being more effective than conventional I-OHDF for improving the plasma refilling rate (PRR) and peripheral circulation. We report the case of a patient in whom a lower extremity ulcer healed only after we switched from I-OHDF + FIR to HS I-OHDF + FIR, and the usefulness of this treatment.Case presentationThe patient was a 41-year-old male dialysis patient with LEAD who showed worsening of the ulcers in the lower extremity before he was switched from I-OHDF plus FIR to HS I-OHDF plus FIR; we compared the changes in the lower extremity blood flow, PRR, degree of wound healing, and subjective symptoms over time after the switch to HS I-OHDF plus FIR as compared with the values prior to the switching. As compared with the values during I-OHDF plus FIR, the lower extremity blood flow and PRR increased markedly during HS I-OHDF plus FIR. The wounds in the lower extremity improved over time during HS I-OHDF plus FIR and showed complete healing after 6 months; evaluation by visual analog scales (VASs) showed improved scores for all of fatigue, pain, coldness, and insomnia, and the patient reported improved subjective symptoms. The mechanism underlying the effectiveness of HS I-OHDF plus FIR in promoting wound healing is unknown, however, we speculated that the temperature change in the intermittent infusion solution resulted in increased blood flow in the true capillaries (resting vessels) and transfer of the nonthermal effects of FIR to more peripheral vessels.ConclusionsThis case demonstrates that combined use of HS I-OHDF with FIR can enhance the efficacy of FIR in dialysis patients with LEAD by increasing the lower extremity blood flow and PRR, which is useful for wound healing.

Intermittent levosimendan infusions for advanced heart failure: a systematic review and meta-analysis of randomized controlled trials

Abstract Background Intermittent intravenous infusions of levosimendan have been shown to provide benefits in patients with advanced heart failure (AHF), preventing HF rehospitalization and mortality. Purpose We aim to investigate the efficacy of intermittent intravenous levosimendan infusion in patients with AHF. Methods A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until September 2023. We used the random-effects model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI). Finally, we implemented a trial sequential analysis (TSA) to improve the reliability of our results. Results We included 15 RCTs with 1,181 patients. Intermittent levosimendan was significantly associated with an improved left ventricular ejection fraction (LVEF) compared to placebo (MD: 6,39, 95% CI [3.04, 9.73], P= 0.002; I2=75, P=0.0005), with cumulative Z-score of change after ≤ 1 week passing the monitoring boundaries favors the levosimendan but did not cross the required information size. Additionally, there was a significant improvement in the all-cause mortality rate favoring levosimendan (RR: 0.60, 95% CI [0.40, 0.90], P= 0.01; I2=9, P=0.36). However, There was no difference between intermittent levosimendan and placebo in all-cause rehospitalization rate (RR: 0.75, 95% CI [0.46, 1.22], P= 0.25; I2=70, P=0.04) or event-free survival rate (RR: 0.97, 95% CI [0.72, 1.30], P= 0.84; I2=63, P=0.03). Conclusion In patients with AHF, intermittent levosimendan significantly improved LVEF and all-cause mortality rate. However, there was no effect on rehospitalization or event-free survival.Figure 1.LVEF and TSAFigure 2.Mortality, Rehospital, Surviva

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.

Enhancing Stability and Investigating Target Attainment of Benzylpenicillin in Outpatient Parenteral Antimicrobial Therapy: Insights from In Vitro and In Vivo Evaluations.

Background/Objective: Narrow-spectrum beta-lactam antibiotics such as benzylpenicillin and flucloxacillin are increasingly used in outpatient parenteral antimicrobial therapy (OPAT) programs to mitigate the adverse effects associated with broad-spectrum antibiotics. These beta-lactams require continuous administration via portable infusion devices during OPAT. However, the use of benzylpenicillin in OPAT requires special consideration because of its limited stability at elevated temperatures. Methods: We tested the benzylpenicillin stability, pH, and degradation of products in elastomeric pumps at different concentrations in saline and in buffered solution containing sodium citrate during a prolonged storage and at high temperatures (seven days at 2-8 °C followed by 24 h at 37 °C). Additionally, drug concentrations during intermittent bolus infusion and during OPAT were determined in five patients. The concentrations and degradation products of benzylpenicillin were measured using liquid chromatography mass spectrometry (LC-MS/MS). Results: Unbuffered benzylpenicillin solutions that were already degraded during refrigerator storage and analyte concentration were not measurable after 8 days. The stability of the buffered solutions was acceptable at all three of the tested concentrations (97.6 ± 1.3%, 96.3 ± 0.8%, and 94.9 ± 1.1% for 10 Mio IU, 20 Mio IU, and 40 Mio IU of benzylpenicillin). The stability was influenced by benzylpenicillin concentration, and several breakdown products were identified. Benzylpenicillin concentrations were measured in five patients during OPAT and ranged from 7.2 to 60 mg/L. Conclusions: Benzylpenicillin buffered with sodium citrate is a safe and convenient option for use in continuous infusions during OPAT and should be favored over broad-spectrum antibiotics. Therapeutic drug monitoring data indicate sufficient to high plasma levels when patients received benzylpenicillin as continuous infusions.

Linezolid Pharmacokinetics in Critically Ill Patients: Continuous Versus Intermittent Infusion.

Linezolid has been found to have considerable interindividual variability, especially in critically ill patients, which can lead to suboptimal plasma concentration. To overcome this shortcoming, several solutions have been proposed. These include using loading dose, higher maintenance doses, and dose stratification according to the patient's particularities, therapeutic drug monitoring, and drug administration via continuous infusion (CI) instead of intermittent infusion (II). In the present study, we aim to compare the pharmacokinetic (PK) parameters of linezolid after administration as II versus CI to critically ill patients. In a prospective study conducted in an intensive care unit, we compared the same two daily doses of linezolid administered via II versus CI. The serum concentration was measured, and pharmacokinetic parameters were calculated. The pharmacokinetic/pharmacodynamic (PK/PD) indices for efficacy chosen were area under the concentration-time curve at steady state divided by the minimum inhibitory concentration over 80 (AUC24-48/MIC > 80). Greater serum concentration variability was observed in the II group than in the CI group. The %T > MIC > 80% was achieved for MICs of 1 and 2 µg/mL 100% of the time, whereas for the II group, this was 93% and 73%, respectively. AUC24-48/MIC > 80 was reached in 100% of cases in the CI group compared with 87% in the II group for a MIC of 1 µg/mL. The two infusion methods may be used comparably, but utilizing CI as an alternative to II may have potential benefits, including avoiding periods of suboptimal concentrations, which may enhance safety profiles and clinical outcomes. Considering the relatively few studies performed on linezolid to date, which are increasing in number, the results of the present study may be of interest.

Efficacy and Nephrotoxicity of Extended versus Intermittent Infusion of Beta-Lactams for the Treatment of Ventilator Associated Pneumonia

Abstract Background Patients in the intensive care unit (ICU) are at risk for dying not only from their critical illness but also from secondary processes such as nosocomial infection. Pneumonia is the second most common nosocomial infection in critically ill patients. Eighty-six percent of nosocomial pneumonias are associated with mechanical ventilation and are termed ventilator- associated pneumonia (VAP). Ventilator-associated pneumonia is defined as pneumonia occurring more than 48 h after patients have been intubated and received mechanical ventilation. Diagnosing VAP requires a high clinical suspicion combined with bedside examination, radiographic examination, and microbiologic analysis of respiratory secretions. Aim of the Work to compare the Efficacy and nephrotoxicity of extended versus intermittent infusion of beta-lactams for the treatment of ventilator associated pneumonia. Patients and Methods This Retrospective cohort study has been held in Intensive Care Units in Ain Shams University Hospitals on critically ill patients with ventilator associated pneumonia after applying exclusion criteria, in the period from April 2023 till December 2023. After approval of Ethical &amp; Research committee of Ain Shams University. Results The current study results compared between the extended infusion group and the intermittent infusion group based on bacterial eradication, statistically significant differences were observed. In the extended infusion group, 70.0% of patients achieved bacterial eradication, whereas in the intermittent infusion group, only 45.0% achieved bacterial eradication. The p-value for this comparison was 0.024, indicating statistical significance. These findings suggest that patients in the extended infusion group had a higher rate of bacterial eradication compared to those in the intermittent infusion group. This implies that extended infusion of beta-lactam antibiotics may be more effective in eliminating bacteria associated with ventilator-associated pneumonia. The current study results compared between the extended infusion group and the intermittent infusion group based on the incidence of acute kidney injury (AKI), no statistically significant differences were observed. In the extended infusion group, 35.0% of patients experienced AKI, while in the intermittent infusion group, 40.0% experienced AKI. The p-value for this comparison was 0.644, indicating no significant difference. These findings suggest that there were similar incidences of AKI between the two infusion groups. Conclusion Our study comparing extended infusion versus intermittent infusion of beta-lactam antibiotics for the treatment of ventilator-associated pneumonia (VAP) has provided valuable insights. Extended infusion demonstrated superiority over intermittent infusion in terms of shorter time to normalization of white cell count and C-reactive protein, fewer ventilator days, increased ventilator-free days, higher rates of ICU survival, and improved bacterial eradication. However, there were no significant differences between the two groups2 regarding demographic data, comorbidities, microbiologic characteristics, minimum creatinine clearance reached, and incidence of acute kidney injury. These findings suggest that extended infusion of beta-lactam antibiotics may offer clinical benefits in the management of VAP, particularly in terms of efficacy and patient outcomes, without substantially increasing the risk of nephrotoxicity.

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.

Intermittent versus continuous intravenous epoprostenol for the treatment of digital ischemia.

Digital ischemia can be a painful complication of Raynaud's phenomenon or systemic sclerosis, which is caused by narrowing of blood vessels in the toes and hands. Epoprostenol is a potent vasodilator that may be used to treat digital ischemia in this patient population. Our institution provides epoprostenol infusion using two different administration techniques: a 30-h continuous infusion option and a 5-day intermittent 6-h infusion. In this retrospective chart review, we compared two administration techniques of intravenous epoprostenol administered to patients with digital ischemia. The primary outcome was to compare the efficacy of intravenous epoprostenol 30-h continuous infusion versus 5-day intermittent infusion, as defined by the presence of treatment failure. Between June 2019 and June 2020, 72 adult patient encounters met the inclusion criteria (intermittent: n = 20; continuous: n = 52). The primary outcome did not achieve a statistically significant difference between the two groups: intermittent 20% versus continuous 33.3% p = 0.390, odds ratio = 0.57 (95% confidence interval = 0.17-1.90). Adverse reactions were documented in 28% of patients across both treatment groups, and there was no difference detected when treatment groups were compared (25% vs 28.8%). Patients who received the 5-day infusion experienced a significantly longer average length of stay, with a mean of 8.9 days versus 3 days for those treated with the continuous 30-h infusion (p < 0.05; 95% confidence interval = 2.15-9.47). This study determined that the efficacy and safety profiles of the two administration techniques may not be comparable. Each protocol offers advantages over the other, and selection should be guided by patient history and risk factors to optimize management.

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.

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.

Cost comparison analysis of continuous versus intermittent antimicrobial therapy infusions in inpatient and outpatient care: real-world data from Finland

ObjectiveThis study compared the costs and nursing time associated with the delivery of continuous infusion of antibiotics via elastomeric infusion pumps (EIP) versus conventional intermittent infusion (CII) across different care...

In sepsis, continuous and intermittent infusion of β-lactam antibiotics did not differ for mortality at 90 d.

Dulhunty JM, Brett SJ, De Waele JJ, et al; BLING III Study Investigators. Continuous vs intermittent β-lactam antibiotic infusions in critically ill patients with sepsis: the BLING III randomized clinical trial. JAMA. 12 June 2024. [Epub ahead of print.] 38864155.

In sepsis or septic shock, prolonged vs. intermittent infusion of β-lactam antibiotics reduces mortality at 90 d.

Abdul-Aziz MH, Hammond NE, Brett SJ, et al. Prolonged vs intermittent infusions of β-lactam antibiotics in adults with sepsis or septic shock: a systematic review and meta-analysis. JAMA. 12 June 2024. [Epub ahead of print.] 38864162.

Antimicrobial infusion practices within intensive care units: Carbapenem infusion preparation and administration process errors

ObjectiveTo describe nurse preparation and administration of intermittent carbapenem infusions. Research methodology/designThis observational study documented the carbapenem infusion process to adult patients in three general intensive care units. Main outcome measuresTiming and duration of infusions were observed. Volumetric analysis of infusion items was conducted to determine loss of reconstituted carbapenem during preparation and administration phases. ResultsCarbapenem infusions (n = 223) administered to twenty adult patients were observed. Infusion duration guidance was variable, with two ICUs following current literature recommendations, and one ICU referring to medication package insert information. Within these parameters, only 60 % of infusions complied with infusion duration. Non-compliance with planned time of administration impacted on desired dosing intervals. Incomplete delivery of intended dose was found during: sub-optimal reconstitution of vials, incorrect number of vials reconstituted, failure to administer a dose (missed dose), and discarding antibiotic residue in infusion items. Volumetric analysis of infusion items showed mean dose losses of 4.9 % and 1.2 % in discarded vials and syringes. Mean drug losses of 6.3 % and 30.8 % occurred in discarded infusion bags and infusion lines respectively. No flushing guidance or practice was observed. ConclusionIncorrect nurse administration of antibiotics resulted in varying durations of infusions and the non-delivery of prescribed dose. Under-dosing has the potential to contribute to selection pressure for bacterial antibiotic resistance. The increasing frequency of intravenous delivery of antimicrobial agents through infusions requires an understanding of the required duration of administration and how to manage residual drug remaining in the intravenous line once the infusion is completed. Implications for clinical practiceFlushing of administration lines is not common practice following intermittent antimicrobial infusions. Although there are multi-factorial risk factors for antimicrobial resistance in the critical care arena, nurse infusion practice must ensure that patients receive intended antimicrobial treatment. Attention must be given to the potential for antimicrobial resistance from environmental contamination with the disposal of infusion items containing undelivered antimicrobial medication.