Intermittent Infusion Group Research Articles

Continuous vs Intermittent β-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis

Whether β-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients with sepsis is uncertain. To evaluate whether continuous vs intermittent infusion of a β-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all-cause mortality at 90 days in critically ill patients with sepsis. An international, open-label, randomized clinical trial conducted in 104 intensive care units (ICUs) in Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom. Recruitment occurred from March 26, 2018, to January 11, 2023, with follow-up completed on April 12, 2023. Participants were critically ill adults (≥18 years) treated with piperacillin-tazobactam or meropenem for sepsis. Eligible patients were randomized to receive an equivalent 24-hour dose of a β-lactam antibiotic by either continuous (n = 3498) or intermittent (n = 3533) infusion for a clinician-determined duration of treatment or until ICU discharge, whichever occurred first. The primary outcome was all-cause mortality within 90 days after randomization. Secondary outcomes were clinical cure up to 14 days after randomization; new acquisition, colonization, or infection with a multiresistant organism or Clostridioides difficile infection up to 14 days after randomization; ICU mortality; and in-hospital mortality. Among 7202 randomized participants, 7031 (mean [SD] age, 59 [16] years; 2423 women [35%]) met consent requirements for inclusion in the primary analysis (97.6%). Within 90 days, 864 of 3474 patients (24.9%) assigned to receive continuous infusion had died compared with 939 of 3507 (26.8%) assigned intermittent infusion (absolute difference, -1.9% [95% CI, -4.9% to 1.1%]; odds ratio, 0.91 [95% CI, 0.81 to 1.01]; P = .08). Clinical cure was higher in the continuous vs intermittent infusion group (1930/3467 [55.7%] and 1744/3491 [50.0%], respectively; absolute difference, 5.7% [95% CI, 2.4% to 9.1%]). Other secondary outcomes were not statistically different. The observed difference in 90-day mortality between continuous vs intermittent infusions of β-lactam antibiotics did not meet statistical significance in the primary analysis. However, the confidence interval around the effect estimate includes the possibility of both no important effect and a clinically important benefit in the use of continuous infusions in this group of patients. ClinicalTrials.gov Identifier: NCT03213990.

Continuous vs intermittent induction of labor with oxytocin in nulliparous patients: a randomized controlled trial

Oxytocin is considered the drug of choice for the induction of labor, although the optimal protocol and infusion duration remain to be determined. This study aimed to assess whether the duration of oxytocin infusion increases 24-hour delivery rates and affects the length of time-to-delivery and patient's experience. A randomized controlled trial was performed at a single tertiary medical center, between January 1, 2020 and June 30, 2022. Nulliparous patients with a singleton pregnancy at a vertex presentation and a Bishop score ≥6 were randomly assigned to receive either continuous (16 hours, with a 4 hours pause in between infusions) or intermittent (8 hours, with a 4 hours pause in between infusions) oxytocin infusion, until delivery. In both groups, infusion was halted when signs of maternal or fetal compromise were observed. Randomization was conducted with a computer randomization sequence generation program. The primary outcome was delivery within 24 hours from the first oxytocin infusion and the secondary outcome included time-to-delivery, mode of delivery, and additional maternal and neonatal outcomes. Seventy-two patients per group were randomized to reach 80% statistical power with a 20% difference in the primary outcome according to previous studies. A total of 153 patients were randomized, 72 to the continuous oxytocin infusion group and 81 to the intermittent infusion group. The total oxytocin infusion time was similar between the groups. Patients in the continuous arm were more likely to deliver within 24 hours from oxytocin initiation (79.73% vs 62.96%, P<.05), and had a shorter oxytocin-to-delivery time interval, compared with patients receiving intermittent treatment (9.3±3.7 hours vs 21±11.7 hours, P<.001). Furthermore, time from ruptured membranes to delivery was shorter (9.3±3.7 hours vs 21±11.7 hours; P<.0001) and chorioamnionitis was less frequent (9.46% vs 21%; P<.05) in the continuous compared with the intermittent arm. Cesarean delivery rate was 20% in both groups (P=.226). There was no difference in postpartum hemorrhage, or adverse neonatal outcomes between the groups. Patients receiving continuous oxytocin infusion were more satisfied with the birthing experience. Continuous infusion of oxytocin for labor induction in nulliparous patients with a favorable cervix may be superior to intermittent oxytocin infusion, because it shortens time-to-delivery, decreases chorioamnionitis rate, and improves maternal satisfaction, without affecting adverse maternal or neonatal outcomes.

Clinical efficacy and safety of prolonged versus intermittent administration of antipseudomonal beta-lactam antibiotics in adults with severe acute infections: A meta-analysis of randomized controlled trials

IntroductionIn order to compare the clinical efficacy and safety of prolonged versus intermittent antipseudomonal beta-lactam antibiotic infusion for the treatment of severe acute infections in adult patients, a meta-analysis of randomized controlled trials (RCTs) was performed. MethodsWe systematically searched MEDLINE and Cochrane Library databases until December 2022. The outcomes were all-cause mortality, clinical success, microbiological eradication and adverse events. The pooled risk ratios (RR) were estimated by the fixed or random effect methods according to heterogeneity statistics. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the certainty of evidence for each outcome. ResultsTwenty eligible RCTs with 2081 participants were included in the meta-analysis. The risk of all-cause mortality was significantly lower in the prolonged infusion group than in the intermittent infusion group (RR 0.77, 95% confidence interval [CI] 0.63–0.95, p = 0.01, I2 = 0%; moderate certainty). Treatment with prolonged infusion showed significant benefit in clinical success (RR 1.09, 95% CI 1.02–1.17, p = 0.008, I2 = 19%; moderate certainty). There were no significant differences in microbiological eradication (RR 1.12, 95% CI 0.99–1.28, p = 0.07, I2 = 49%; low certainty), any adverse events (RR 0.96, 95% CI 0.86–1.08, p = 0.50, I2 = 27%; moderate certainty) and serious adverse events (RR 0.99, 95%CI 0.70–1.39 p = 0.95, I2 = 0%; low certainty). ConclusionsProlonged antipseudomonal beta-lactam infusion probably decreases all-cause mortality. Additionally, it probably increases clinical success in adults with severe acute infections. This infusion strategy may result in little to no difference in microbiological eradication and is probably not associated with a rise in any adverse events.The evidence suggests that prolonged infusion may not increase serious adverse events.

The clinical and paraclinical effectiveness of four-hour infusion vs. half-hour infusion of high-dose ampicillin-sulbactam in treatment of critically ill patients with sepsis or septic shock: An assessor-blinded randomized clinical trial

PurposeThis study was conducted to determine whether critically ill patients admitted to the intensive care unit (ICU) with sepsis and septic shock may benefit from extended infusion of ampicillin/sulbactam compared with those receiving intermittent infusion. Material and methodsThis randomized assessor-blinded clinical trial was conducted in the ICUs of Nemazee and Shahid Rajaee hospital, Shiraz, Iran, from August 2019 to August 2021. The participants randomly received 9 g Ampicillin/Sulbactam every 8 h by either extended (infused over 4 h) or intermittent (infused over 30 min) intravenous infusion if their estimated glomerular filtration rate based on Cockrorft-Gault formula was higher than 60 ml/min. ResultsTotally, 136 patients were enrolled and allocated to the intervention and control groups, each with 68 patients. Clinical cure was significantly higher in the extended group (P = 0.039), but ICU and hospital length of stay did not differ between the groups (P = 0.87 and 0.83, respectively). The ICU (P = 0.031) and hospital (P = 0.037) mortality rates in the extended infusion group were significantly lower than those in the intermittent infusion group. ConclusionThese data should be replicated in larger clinical trials before providing any recommendation in favor of this method of administration in clinical practice.

Extended infusion of piperacillin–tazobactam versus intermittent infusion in critically ill egyptian patients: a cost-effectiveness study

Extended infusion of piperacillin/tazobactam over 4 h has been proposed as an alternate mode of administration to the 30-min intermittent infusion to optimize treatment effects in patients with gram-negative bacterial infections. The study aimed to evaluate the extended infusion regimen of piperacillin/tazobactam in standings of efficacy, safety, and cost to the intermittent one in the treatment of gram-negative bacterial infections. A prospective randomized comparative study was performed on 53 patients, 27 in the intermittent infusion group and 26 in the extended infusion group. The primary outcome was the mean number of days to clinical success and the percentage of patients who were clinically cured after treatment. The secondary outcomes included mortality, readmission within 30-days, and cost-effectiveness analysis based on the mean number of days to clinical success. The clinical success rate was comparable in the two groups. Days on extended infusion were significantly lower than intermittent infusion (5.7 vs 8.9 days, respectively, p = 0.0001) as well as days to clinical success (4.6 vs 8.5 days, respectively, p = 0.026). The extended infusion was superior to the intermittent infusion regarding cost-effectiveness ratio ($1835.41 and $1914.09/expected success, respectively). The more cost-effective regimen was the extended infusion. Both regimens had comparable clinical and microbiological outcomes.

Therapeutic Drug Monitoring and Prolonged Infusions of Ceftolozane/Tazobactam for MDR/XDR Pseudomonas aeruginosa Infections: An Observational Study.

Prolonged infusion of ceftolozane/tazobactam (C/T) is a strategy used to increase achievement of pharmacokinetic/pharmacodynamic targets for the treatment of multi- or extensively drug-resistant MDR/XDR Gram-negative microorganisms. The objective of this studywas to describe our therapeutic drug monitoring (TDM) experience of C/T administered by prolonged infusion or intermittent infusion to patients with MDR/XDR Pseudomonas aeruginosa infections. Our outcomes of interest were pharmacokinetic/pharmacodynamic target achievement and clinical cure. Patients with MDR/XDR P. aeruginosa infections treated with C/T were enrolled between February 2018 and February 2020. Blood samples were obtained as part of a TDM program. The pharmacokinetic/pharmacodynamic therapeutic target of C/T was defined as 100% of the duration of the dosing interval that free concentrations are above the minimum inhibitory concentration (MIC) (100 %ƒT≥MIC) of the causative pathogen. Dose changes were performed according to TDM results. Forty patients were included: 13 (32.5%) with a proven MDR and 27 (67.5%) with a XDR P. aeruginosa infection. C/T was administered by prolonged infusion in 32 (80%) patients and by intermittent infusion in 8 (20%) patients. Lower doses were administered in the prolonged infusion compared to the intermittent infusion group [3 (9.4%) vs. 5 (62.5%] patients received a dose of 9g/day (ceftolozane 2g+ tazobactam 1g, every 8 h; p=0.004). All patients achieved the pharmacokinetic/pharmacodynamic target and C/T concentrations exceeded 10 × MIC in > 50% of patients in both groups. TDM-recommended dose reductions occurred in 19 (47.5%) patients, being 16 (84.2%) in the prolonged infusion group. A high proportion of patients achieved clinical cure (82.5%). The administration of C/T by prolonged infusion with TDM-guided dosing allowed the achievement of a pharmacokinetic/pharmacodynamic target even at lower doses. C/T showed a high efficacy for treating MDR/XDR P. aeruginosa infections.

Continuous Versus Intermittent Linezolid Infusion for Critically Ill Patients with Hospital-Acquired and Ventilator-Associated Pneumonia: Efficacy and Safety Challenges.

High variability of linezolid blood concentrations with partial subtherapeutic levels was observed in critically ill patients who received a standard intravenous dose of linezolid, contributing to drug resistance and toxicity. Continuous infusions of linezolid have been suggested as an alternative and provide good serum and alveolar levels without fluctuations in trough concentration. This study aimed to assess the effectiveness and safety of continuous linezolid infusion versus the standard regimen in critically ill patients. A prospective randomized controlled study was conducted on 179 patients with nosocomial pneumonia. Patients were randomized into two groups. The first group received IV linezolid 600 mg twice daily, while the second group received 600 mg IV as a loading dose, followed by a continuous infusion of 1200 mg/day (50 mg/h) for at least 8–10 days. The continuous infusion group showed a higher clinical cure rate than the intermittent infusion group (p = 0.046). Furthermore, efficacy was proven by greater improvement of P/F ratio (p = 0.030) on day 7 of treatment, a lower incidence of developing sepsis after beginning treatment (p = 0.009), and a shorter time to reach clinical cure (p < 0.001). Hematological parameters were also assessed during the treatment to evaluate the safety between the two groups. The incidence of thrombocytopenia was significantly lower in the continuous infusion group than in the intermittent infusion group. In addition, a stepwise logistic regression model revealed that the intermittent infusion of linezolid was significantly associated with thrombocytopenia (OR =4.128; 95% CI = 1.681–10.139; p =0.001). The current study is the first to assess the clinical aspects of continuous infusion of linezolid beyond pharmacokinetic studies. Continuous infusion of linezolid outperforms intermittent delivery in safety and improves clinical effectiveness in critically ill patients with Gram-positive nosocomial pneumonia.

Continuous-Infusion Foscarnet Facilitates Administration in Hematopoietic Stem Cell Transplantation Patients

Infections due to herpesviruses resistant to first-line antivirals remains an ever-present and serious complication in recipients of hematopoietic cell transplantation (HCT) and other cellular therapies. Foscarnet is the most common therapy for patients who have resistant herpesvirus infections or intolerable cytopenias due to ganciclovir or valganciclovir; however, the widespread use of foscarnet is limited by its associated nephrotoxicity and challenges in administration. In the earliest published small case series investigating the optimal infusion modality, patients with acquired immunodeficiency syndrome (AIDS) due to the human immunodeficiency virus (HIV) received either continuous infusion or intermittent dosing of foscarnet. Moreover, there was no standardization of hydration strategies to minimize side effects. Eventually, intermittent foscarnet infusions became the standard of care; however, the true impact of hydration and infusion duration on nephrotoxicity has not been adequately studied, and the reports of foscarnet administration in HCT patients has been limited primarily to intermittent infusions. In this report, we characterize the administration of foscarnet as a 24-hour continuous infusion in both the inpatient and outpatient settings compared with intermittent infusion in HCT recipients. This retrospective, single-center, observational study at Stanford University Medical Center assessed HCT recipients who received foscarnet between January 2009 and May 2019. Twenty-eight of 45 patients (62.2%) who received continuous-infusion foscarnet experienced an acute kidney injury (AKI) as defined by the Kidney Disease Improving Global Outcomes classification, compared with 39 of 62 patients (62.9%) who received conventional infusion (P=.94). The average duration of outpatient antiviral days for the continuous infusion group was 9 days (range, 0 to 121 days), compared with 6.3 days (range, 0 to 70 days) in the intermittent infusion group (P=.54). Our findings suggest that foscarnet given as a continuous infusion or as an intermittent infusion have similar rates of adverse reactions, most notably similar rates of AKI. Administering foscarnet as a continuous infusion is a feasible option to facilitate outpatient treatment.

Comparison of intermittent versus continuous-infusion vancomycin for treating severe patients in intensive care units

PurposeThe aim of this study was to compare pharmacokinetic characteristics between intermittent infusion and continuous infusion of vancomycin for critically ill patients admitted to intensive care units. MethodsIntermittent therapy was administered for 60minutes and prescribed as a loading dose of 30mg/kg and continued with 15mg/kg q12h. Continuous infusion was prescribed as a loading dose of 30mg/kg followed by 30mg/kg on constant infusion pump. Blood samples from vancomycin intermittent infusion group were collected 1h before third dose, 1h, 8h and 24h after third dose infusion. Blood samples from vancomycin continuous infusion group were collected 1h after loading dose, 12h, 24h, 36h, and 48h after continuous infusion initiation. ResultsMedian serum concentration of continuous infusion group at 24-hour was 23.59μg/mL [14.52–28.97], while of intermittent infusion group at 23-hour was 12.30μg/mL [7.27–18.12] and on 25-hour was 17.58μg/mL [12.5–22.5]. Medians AUC24–48h were 357.2mg.h/L and 530.2mg.h/L for intermittent infusion and continuous infusion groups, respectively (p=0.559). ConclusionVancomycin CI reached steady state earlier, which guaranteed therapeutic levels from the first day and made it possible to manage therapeutic drug monitoring faster.

Clinical Trial Assessment of Intermittent and Continuous Infusion Dose of N-Acetylcysteine on Redox Status of the Body in Patients with Sepsis Admitted to the ICU.

Conflicting results exist regarding the efficacy of N-acetyl cysteine (NAC) in sepsis treatment. A pivotal factor affecting the therapeutic potency of NAC in sepsis is timing and dosing of its infusion. We aimed to assess the effect of NAC on redox status of patients with sepsis and to compare its efficacy in intermittent and continuous infusion with the objective of developing the infusion regimen and optimizing the timing. A prospective, randomized clinical trial was designed to compare the antioxidative effect of NAC in intermittent infusion group (IV: 25 mg/kg bolus and then 25 mg/kg/8 hours 3 times) and continuous infusion group (IV: 25 mg/kg bolus and then 75 mg/kg over 24 hours) in 60 critically ill patients with sepsis (20 patients in each group). Blood samples were collected immediately before and after intervention for total antioxidant capacity (TAC) and malondialdehyde (MDA) assessment. N-acetyl cysteine considerably increased TAC levels in both intermittent (0.68 ± 0.60; P value = .036) and continuous (0.69 ± 0.64; P value = .015) infusion groups when compared to placebo (0.61 ± 0.10); however, the difference in TAC levels between the intermittent and the continuous infusion did not reach statistical significance (P value = .942). Likewise, NAC treatment decreased MDA levels in both intermittent (19.45 ± 4.18; P value = 0.001) and continuous (22.47 ± 6.68; P value = .002) infusion groups when compared to placebo (31.76 ± 11.06), while the difference in MDA levels between the intermittent and the continuous infusion did not reach statistical significance (P value = .481). Our data confirmed the antioxidative effect of NAC treatment in patients with sepsis, with no significant difference in intermittent and continuous infusion.

Administration of Vancomycin at High Doses in Patients with Post Neurosurgical Meningitis: A Comprehensive Comparison between Continuous Infusion and Intermittent Infusion.

Poor penetration of vancomycin into Central Nervous System (CNS) can lead to treatment failure. The aim of this study was to evaluate and compare CSF concentration and serum pharmacokinetics of high dose vancomycin by continuous infusion vs. intermittent infusion in post neurosurgical meningitis patients. Twenty patients were divided into two groups. Patients in intermittent infusion group received vancomycin as a loading dose of 25 mg/kg over two hours, followed by 25 mg/kg over two hours every 12 h. In the Continuous Infusion group, patients received vancomycin as a loading dose of 25 mg/kg over two hours, followed by 50 mg/kg/day by continuous infusion. In the intermittent infusion group, mean ± SD of serum trough, peak and CSF concentrations were 17.49 ± 2.46 mg/L, 41.33 ± 2.73 mg/L, and 4.83 ± 1.05 mg/L, respectively. Mean of CSF/trough% ratio was 27.39 ± 2.43%. A positive linear correlation was found between the serum trough levels and CSF levels (r = 0.970, P < 0.001). In continuous infusion group, mean ± SD of serum and CSF concentrations were 24.76 ± 2.02 mg/L and 6.20 ± 1.31 mg/L respectively. Mean ± SD of CSF/serum% ratio was 24.84% ± 3.54%. The serum and CSF levels revealed positive linear correlation (r = 0.902, P < 0.001). The mean of CSF concentration in CI group was 6.20 ± 1.31 mg/L which was significantly higher than II group (4.83 ± 1.05 mg/L, P < 0.019). CSF/serum ratio did not show any significant difference between the two groups. Continuous infusion of vancomycin makes it possible to achieve faster and constant target level in serum but did not have any significant effect on the penetration (CSF/Serum ratio) of vancomycin in to the CNS.

Influence of β-Lactam Infusion Strategy on Acute Kidney Injury.

Limited literature is available assessing nephrotoxicity with prolonged β-lactam infusions. This study compared the incidence of acute kidney injury (AKI) associated with a prolonged β-lactam infusion or an intermittent infusion. This was a retrospective, matched-cohort study at an academic medical center from July 2006 to September 2015. Adult patients who received piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) for at least 48 h were evaluated. Patients were excluded for preexisting renal dysfunction or pregnancy. The primary outcome was difference in incidence of AKI evaluated using the RIFLE (risk, injury, failure, loss, and end-stage) criteria. Patients in the intermittent group were matched 3:1 to patients in the prolonged-infusion group based on the following: β-lactam agent, age, gender, Charlson comorbidity index, baseline creatinine clearance, hypotension, receipt of vancomycin, and treatment in an intensive care unit. A total of 2,390 patients were included in the matched analysis, with 1,700 receiving intermittent infusions and 690 receiving prolonged infusion. The incidence of AKI was similar in the prolonged-infusion group to that in the intermittent-infusion group (21.6% versus 18.6%; P = 0.1). After multivariate regression, prolonged infusion was not associated with increased odds of AKI (odds ratio [OR], 1.07; 95% confidence interval [95% CI], 0.83 to 1.39). Independent predictors of AKI included TZP therapy, concomitant nephrotoxins, hypotension, and heart failure. Although AKIs were numerically more common in patients receiving prolonged β-lactam infusions than those receiving intermittent infusions, prolonged infusion was not an independent risk factor for AKI.

Metoclopramide as intermittent and continuous infusions in critically ill patients: a pilot randomized clinical trial.

Metoclopramide is commonly used as a prokinetic agent in critically ill patients with enteral feeding intolerance. In this study, noninferiority of metoclopramide as intermittent versus continuous infusion was examined in critically ill patients with enteral feeding intolerance. Forty critically ill adults patients were assigned to receive metoclopramide as either intermittent (10 mg every 6 h) or continuous (2 mg/h) infusion. Frequency of feeding intolerance and adverse effects of metoclopramide were assessed during 7 days of study. Number of patients with feeding intolerance during different times of the course was not different between the groups. Although not statistically significant, diarrhea and cardiac rhythm were more common in continuous than intermittent infusion group. Continuous and intermittent infusions of metoclopramide showed equivalent effectiveness in critically ill patients.

Infusion Methods for Continuous Interscalene Brachial Plexus Block for Postoperative Pain Control after Arthroscopic Rotator Cuff Repair.

BackgroundInfusion methods during regional analgesia using perineural catheters may influence the quality of postoperative analgesia. This study was conducted to compare the effects of combined or bolus-only infusion of 0.2% ropivacaine on the postoperative analgesia in interscalene brachial plexus block (ISBPB) with perineural catheterization.MethodsPatients scheduled for arthroscopic rotator cuff repair were divided into two groups, one that would receive a combined infusion (group C, n = 32), and one that would receive intermittent infusion (group I, n = 32). A perineural catheter was inserted into the interscalene brachial plexus (ISBP) using ultrasound (US) and nerve stimulation, and 10 ml of 0.2% ropivacaine was administered. After the operation, group C received a continuous infusion of 4 ml/h, and a 4 ml bolus with a lockout interval of 60 min. Group I received only a 4 ml bolus, and the lockout interval was 30 min. Postoperative pain by the numeric rating scale (NRS) and the forearm muscle tone by the manual muscle test (MMT) were checked and evaluated at the following timepoints: preoperative, and postoperative 1, 4, 12, 24, 36, and 48 h. Supplemental opioid requirements, total consumed dose of local anesthetic, and adverse effects were compared between the two groups.ResultsSixty-four patients completed the study and the postoperative values such as operation time, time to discharge, and operation site were comparable. There were no differences in NRS scores and supplemental opioid requirements between the two groups. The MMT scores of group I at 4 and 12 h after surgery were significantly higher than those of group C (P < 0.05). The total consumed dose of local anesthetic was significantly lower in group I than in group C (P < 0.05). The adverse effects were not different between the groups.ConclusionsThe bolus-only administration of 0.2% ropivacaine provided a similar analgesic effect with a lower total volume of local anesthetic and decreased motor weakness compared to combined infusion. Therefore, bolus-only administration is an effective postoperative analgesic method in ISBPB with perineural catheterization after rotator cuff repair.

Prolonged vs intermittent infusion of piperacillin/tazobactam in critically ill patients: A narrative and systematic review

PurposeThe purpose of this study is to review the rationale of prolonged (ie, extended or continuous) infusion of piperacillin/tazobactam (PIP/TAZ) in critically ill patients and to perform a systematic review that compare the effectiveness of prolonged infusion with intermittent bolus of PIP/TAZ. Materials and methodsA search of Medline, Web of Science, Embase, and Cochrane databases was conducted up to April 2014. For systematic review, studies comparing the effectiveness of prolonged and bolus administration of PIP/TAZ were included. The level of evidence is determined using best-evidence synthesis, which consisted of 5 possible levels of evidence: strong, moderate, limited, conflicting, or no evidence. ResultsThe pharmacokinetic/pharmacodynamic studies that account for an eventual benefit of prolonged PIP/TAZ infusion were reviewed. In the systematic review, 1 randomized controlled trial was identified that showed higher “cure” in the prolonged than in the intermittent infusion group, yet the chosen clinical outcome in this study, decline in mean Acute Physiology and Chronic Health Evaluation II score is controversial. Of 6 retrospective cohort studies, 4 showed either less mortality, a higher clinical cure rate, or shorter length of hospital stay with prolonged PIP/TAZ treatment. The level of evidence supporting a better clinical outcome with prolonged infusion of PIP/TAZ is moderate. ConclusionPharmacokinetic/pharmacodynamic studies provide a robust rationale to prefer prolonged above intermittent infusion of PIP/TAZ. However, although some studies suggest a better outcome in critically ill patients receiving prolonged infusion, the level of evidence is moderate.

Lack of difference between continuous versus intermittent heparin infusion on maintenance of intra-arterial catheter in postoperative pediatric surgery: a randomized controlled study

OBJECTIVE: To compare two systems of arterial catheters maintenance in postoperative pediatric surgery using intermittent or continuous infusion of heparin solution and to analyze adverse events related to the site of catheter insertion and the volume of infused heparin solution. METHODS: Randomized control trial with 140 patients selected for continuous infusion group (CIG) and intermittent infusion group (IIG). The variables analyzed were: type of heart disease, permanence time and size of the catheter, insertion site, technique used, volume of heparin solution and adverse events. The descriptive variables were analyzed by Student's t-test and the categorical variables, by chi-square test, being significant p<0.05. RESULTS: The median age was 11 (0-22) months, and 77 (55%) were females. No significant differences between studied variables were found, except for the volume used in CIG (12.0±1.2mL/24 hours) when compared to IIG (5.3±3.5mL/24 hours) with p<0.0003. CONCLUSIONS: The continuous infusion system and the intermittent infusion of heparin solution can be used for intra-arterial catheters maintenance in postoperative pediatric surgery, regardless of patient's clinical and demographic characteristics. Adverse events up to the third postoperative day occurred similarly in both groups. However, the intermittent infusion system usage in underweight children should be considered, due to the lower volume of infused heparin solution [ClinicalTrials.gov Identifier: NCT01097031].

Prolonged Infusion Antibiotics for Suspected Gram-Negative Infections in the ICU: A Before-After Study

ß-Lactam antibiotics demonstrate time-dependent killing. Prolonged infusion of these agents is commonly performed to optimize the time the unbound concentration of an antibiotic remains greater than the minimum inhibitory concentration and decrease costs, despite limited evidence suggesting improved clinical results. To determine whether prolonged infusion of ß-lactam antibiotics improves outcomes in critically ill patients with suspected gram-negative infection. We conducted a single-center, before-after, comparative effectiveness trial between January 2010 and January 2011 in the intensive care units at Barnes-Jewish Hospital, an urban teaching hospital affiliated with the Washington University School of Medicine in St. Louis, MO. Outcomes were compared between patients who received standardized dosing of meropenem, piperacillin-tazobactam, or cefepime as an intermittent infusion over 30 minutes (January 1, 2010, to June 30, 2010) and patients who received prolonged infusion over 3 hours (August 1, 2010, to January 31, 2011). A total of 503 patients (intermittent infusion, n = 242; prolonged infusion, n = 261) treated for gram-negative infection were included in the clinically evaluable population. Approximately 50% of patients in each group received cefepime and 20% received piperacillin-tazobactam. More patients in the intermittent infusion group received meropenem (35.5% vs 24.5%; p = 0.007). Baseline characteristics were similar between groups, with the exception of a greater occurrence of chronic obstructive pulmonary disease (COPD) in the intermittent infusion group. Treatment success rates in the clinically evaluable group were 56.6% for intermittent infusion and 51.0% for prolonged infusion (p = 0.204), and in the microbiologically evaluable population, 55.2% for intermittent infusion and 49.5% for prolonged infusion (p = 0.486). Fourteen-day, 30-day, and inhospital mortality rates in the clinically evaluable population for the intermittent and prolonged infusion groups were 13.2% versus 18.0% (p = 0.141), 23.6% versus 25.7% (p = 0.582), and 19.4% versus 23.0% (p = 0.329). Routine use of prolonged infusion of time-dependent antibiotics for the empiric treatment of gram-negative bacterial infections offers no advantage over intermittent infusion antibiotic therapy with regard to treatment success, mortality, or hospital length of stay. These results were confirmed after controlling for potential confounders in a multivariate analysis.

Continuous intravenous administration of vancomycin in medical intensive care unit patients

PurposeThe aim of this study was to evaluate continuous vancomycin infusion (contV) in intensive care unit patients. Materials and MethodsA retrospective study in 164 patients treated with contV was conducted. They were compared with 75 patients treated with intermittent vancomycin infusion. ResultsThe median duration of vancomycin therapy in the contV group was 6 (5%-95% percentile range, 2-21) days. The median daily vancomycin dose in the contV group was 960 (526-1723) mg, resulting in a median serum vancomycin plateau concentration of 19.8 (9.8-29.4) mg/L (target: 15-25 mg/L). The contV administration regime was sufficient regarding achievement of the target serum vancomycin concentration. However, in the contV group, serum vancomycin levels were frequently in a subtherapeutic range on treatment days 1 (44%), 2 (29%), and 3 (23%). In the contV group, serum vancomycin concentration determinations per treatment day were performed significantly less often compared with the intermittent vancomycin infusion group (0.38 [0.15-0.75] vs 0.43 [0.22-1.00], P = .041). ConclusionsIn medical intensive care unit patients, contV is sufficient to achieve target serum vancomycin concentrations. Because contV frequently resulted in subtherapeutic drug levels on the first days of therapy, a higher loading or starting dose might be necessary.

Continuous versus intermittent administration of piperacillin-tazobactam in intensive care unit patients with ventilator-associated pneumonia

Background and Aims:Ventilator-associated pneumonia (VAP) is one of the most common Intensive Care Unit (ICU)-acquired infection. The aim of this study was to compare the clinical outcome of continuous and intermittent administration of piperacillin–tazobactam by serial measurements of the Clinical Pulmonary Infection Score (CPIS).Subjects and Methods:Groups were designed as parallel and the study was designed as quasi-experimental and conducted at a semi-closed ICU between September 2008 and May 2010. Patients received 3.375 g (piperacillin 3 g/tazobactam 0.375 g) either through intermittent infusion every 6 h for 30 min [Intermittent Infusion (II) group; n = 30] or through continuous infusion every 8 h for 4 h [Continuous Infusion (CI) group; n = 31]. CPIS was used to assess the clinical diagnosis and outcome of VAP patients.Results:Sex, age, Acute Physiology and Chronic Health Evaluation II II score on ICU admission, diagnosis and underlying disease of VAP patients were not significantly different in the CI (n = 31) and II (n = 30) groups. Duration of mechanical ventilation, length of stay, total number of antibiotics used per patient and duration of piperacillin/tazobactam treatment were similar in both groups. Mortality rates of VAP patients were similar between both groups during hospitalization.Conclusion:There was no significant difference in clinical outcomes of patients receiving piperacillin–tazobactam via CI or II when measured by serial CPIS score.

Retrospective Study of Prolonged Versus Intermittent Infusion Piperacillin-Tazobactam and Meropenem in Intensive Care Unit Patients at an Academic Medical Center

Background: Prolonged infusions of A-lactams are increasingly being utilized because of increased antimicrobial resistance and a lack of new antibiotics in the pipeline. Methods: A retrospective, observational study evaluated adult patients who received at least 72 hours of piperacillin-tazobactam or meropenem in a medical and surgical intensive care unit (ICU) at an academic medical center. In the first 6 months of the study, all patients received conventional intermittent dosing; in the second 6 months, all patients received these antibiotics by prolonged infusions. The main outcome comparisons between groups were duration of ventilator support, duration of ICU and hospital length of stay, and in-hospital mortality. Results: A total of 121 patients were included: 54 patients in the intermittent (67% piperacillin-tazobactam, 33% meropenem) and 67 patients in the prolonged group (81% piperacillin-tazobactam, 19% meropenem). The prolonged group demonstrated a significant decrease in ventilator days (j7.2 days; 95% confidence interval [CI], j12.4 to j2.4), ICU length of stay (j4.5 days; 95% CI, j8.3 to j1.4), and hospital length of stay (j8.5 days; 95% CI, j18.7 to j1.2) compared with the intermittent group. The risk of in-hospital mortality was 12.4% in the prolonged infusion group and 20.7% in the intermittent infusion group corresponding to an odds ratio of 0.54 (0.18Y1.66). Conclusions: The results of this study show that the use of prolonged infusions of piperacillin-tazobactam and meropenem could potentially improve clinical outcomes in critically ill populations. As antibiotic resistance continues to increase in gram-negative pathogens, these A-lactam dosing strategies will be important for appropriate treatment.