Infusion Of Vancomycin Research Articles

Continuous infusion of antibiotics in the critically ill: The new holy grail for beta-lactams and vancomycin?

The alarming global rise of antimicrobial resistance combined with the lack of new antimicrobial agents has led to a renewed interest in optimization of our current antibiotics. Continuous infusion (CI) of time-dependent antibiotics has certain theoretical advantages toward efficacy based on pharmacokinetic/pharmacodynamic principles. We reviewed the available clinical studies concerning continuous infusion of beta-lactam antibiotics and vancomycin in critically ill patients. We conclude that CI of beta-lactam antibiotics is not necessarily more advantageous for all patients. Continuous infusion is only likely to have clinical benefits in subpopulations of patients where intermittent infusion is unable to achieve an adequate time above the minimal inhibitory concentration (T > MIC). For example, in patients with infections caused by organisms with elevated MICs, patients with altered pharmacokinetics (such as the critically ill) and possibly also immunocompromised patients. For vancomycin CI can be chosen, not always for better clinical efficacy, but because it is practical, cheaper, associated with less AUC24h (area under the curve >24 h)-variability, and easier to monitor.

Efficacy of linezolid compared to vancomycin in an experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus in ventilated pigs*

To assess the efficacy of linezolid compared with vancomycin in an experimental model of pneumonia induced by methicillin-resistant Staphylococcus aureus (MRSA) in ventilated pigs. Forty pigs (30 kg) were intubated and challenged via bronchoscopy with a suspension of 106 colony forming units of MRSA into every lobe. Afterwards, pigs were ventilated up to 96 hours. Twelve hours after bacterial inoculation, the animals were randomized into 4 groups of treatment: group 1, control; group 2, vancomycin twice daily; group 3, continuous infusion of vancomycin; and group 4, linezolid. Clinical and laboratory parameters were monitored throughout the study. Bacterial cultures of bronchoalveolar lavage fluid and lung tissue samples were performed at the end of the study. Measurements of histopathology derangements of lung samples and studies of intrapulmonary drug penetration were performed. A total of 34 animals completed the study. No differences in clinical and laboratory parameters were observed. The percentage of bronchoalveolar lavage fluid and lung tissue samples with positive cultures for MRSA in controls and groups 2, 3, and 4 was respectively 75%, 11%, 11%, and 0% (p < .01); 52%, 9%, 24%, and 2.5% (p < .01). Histopathology studies demonstrated signs of pneumonia in 95%, 69%, 58%, and 57% and signs of severe pneumonia in 48%, 29%, 22%, and 0% of controls and groups 2, 3, and 4, respectively (p < .01). In addition, pharmacokinetics/pharmacodynamics profile in serum and lung tissue showed better results for linezolid compared with both vancomycin treatments. In this animal model of MRSA pneumonia, linezolid showed a better efficacy than vancomycin showed because of a better pharmacokinetics/pharmacodynamics index.

Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis

To summarize available evidence on the effect of continuous infusion (CoI) of vancomycin compared with intermittent infusion (InI) in adult patients with Gram-positive infections. MEDLINE, EMBASE and Cochrane databases were searched. Randomized clinical trials (RCTs) and observational studies that comparatively assessed CoI and InI of vancomycin in terms of mortality, clinical cure, toxicity rates and serum drug exposure [trough concentration (C(min)) for InI and steady-state concentration (C(ss)) for CoI; area under the curve at 24 h (AUC(24)) for both] were included. Meta-analysis was conducted combining and analysing the relative risk (RR) and computing a summary RR of the effects with 95% confidence interval (CI). The standardized mean difference was calculated for continuous outcomes. The I(2) test was calculated to assess heterogeneity across studies. One RCT and five observational studies were included in the analysis. Compared with InI, CoI of vancomycin was associated with a significantly lower risk of nephrotoxicity (RR 0.6, 95% CI 0.4-0.9, P = 0.02; I(2)= 0). Overall mortality was not different between the two groups (RR 1.03, 95% CI 0.7-1.6, P = 0.9; I(2)= 0). Our meta-analysis suggests that administration of vancomycin for the treatment of Gram-positive infections by CoI is associated with a significantly lower risk of nephrotoxicity when compared with InI of the drug. RCTs are needed to define the impact on mortality rate and on the pharmacodynamic activity in terms of AUC/MIC ratio.

Reinfected Revised TKA Resolves With an Aggressive Protocol and Antibiotic Infusion

Revision of failed two-stage revision TKA for infection is challenging, and amputation often is the only alternative. We asked whether reinfection after two-stage revision for infection could be controlled with an aggressive revision protocol and intraarticular antibiotic infusion. We retrospectively reviewed 18 patients (12 women, six men) who underwent revision for failed reimplantation between January 1999 and January 2008. Mean time from revision for infection to rerevision for reinfection was 5 months (range, 1-18 months). All knees were treated with an individualized protocol that included aggressive exposure, extensive débridement, uncemented components, closure with muscle flaps (seven knees) and other plastic surgery procedures (three knees), and direct antibiotic infusion through Hickman catheters for 6 weeks. Ten knees had one-stage revision; five had débridement, cement spacer, and revision surgery 3 to 4 months later; and three had extensive soft tissue reconstruction before revision surgery. The minimum followup was 2.3 years (mean, 6.1 years; range, 2.3-12.0 years). The mean Knee Society scores improved from 33 preoperatively to 76. Seventeen of the 18 had control of infection and achieved durable fixation and a closed wound. One patient had recurrent infection 13 months after one-stage revision, was revised, and remained asymptomatic 28 months postoperatively after redébridement and vancomycin infusion for 6 weeks. In one patient, soft tissue closure was not obtained and the patient required amputation. Extensile exposure, débridement, and soft tissue flaps for closure combined with uncemented fixation of revision implants and antibiotic infusion into the knee controlled reinfection after revision TKA.

Continuous Infusion May Improve the Efficacy of Vancomycin in Treatment of Experimental Endocarditis Due to Heterogeneous Vancomycin-Intermediate Staphylococcus aureus

We read with interest the paper of Entenza and coworkers suggesting failure of continuous vancomycin infusion against experimental endocarditis due to heterogeneous vancomycinintermediate Staphylococcus aureus (hVISA) and VISA (1). In that study, it was stated that continuous vancomycin infusion for 5 days was unsuccessful, as 20 mg/liter was barely active against hVISA PC1 (6 of 13 sterile vegetations) and 40 mg/liter failed against VISA PC3 (2 of 9 sterile vegetations). Generally speaking, we agree that in this experimental model vancomycin led to suboptimal treatment of VISA infection; however, we believe that some findings related to the role that continuous infusion may have in improving the outcome of vancomycin treatment of hVISA infections deserve attention. Indeed, in the hVISA PC1 model (vancomycin MIC, 2 mg/ liter), there was a misinterpretation of the results, since it appears from Fig. 1 in that paper that the number of sterile vegetations obtained by continuous infusion was higher than stated (7/13 and not 6/13). More importantly, compared with intermittent vancomycin administration (peak and trough levels of at least 50 and 10 mg/liter, respectively), continuous infusion with a constant serum drug concentration of 20 mg/ liter was significantly more effective in sterilizing hVISA PC1 vegetations (54% versus 18%, P 0.05). Although fewer than 100% of the vegetations were sterilized, it must be highlighted that continuous infusion was the only bactericidal regimen, since it led to a more-than-4-log reduction of the mean bacterial burden in the vegetations at day 5 compared to that in the controls (3.57 2.1 versus 7.64 0.4 log 10 CFU/g [P 0.001]), which is different from what occurred with intermittent infusion (6.82 3.1 log 10 versus 7.64 0.4 log10 CFU/g [no statistically significant difference]). These data suggest that continuous infusion of vancomycin may significantly improve the treatment outcome of experimental endocarditis due to hVISA. Indeed, the incomplete sterilization seen even after 5 days of continuous vancomycin infusion may be in line with the time-dependent activity of this glycopeptide, which may take a much longer time for complete healing to occur, especially if the bacteria are embedded in biofilm (2). However, it is worth noting that by ensuring that the concentration persistently exceeds a value of at least four to five times the MIC, this strategy may also reduce the selective pressure due to very low trough levels (3) and may avert the development of frank vancomycin resistance, even in cases of long-term treatment (4). Considering that a recent systematic review and meta-analysis of the clinical significance of hVISA isolates (5) showed that hVISA infections were associated with a glycopeptide failure rate 2.37-fold greater than that obtained with vancomycinsusceptible S. aureus infections, we do believe that these experimental data may support the idea that continuous infusion may be worthwhile with the intent to decrease the failure rate of vancomycin treatment of humans with hVISA infections.

Pharmacokinetics and tissue penetration of vancomycin continuous infusion as prophylaxis for vascular surgery

To determine the tissue penetration of vancomycin into perivascular fat and arterial wall during a continuous infusion of vancomycin, given as prophylaxis for vascular surgery. Patients undergoing arterial reconstruction requiring antibiotic prophylaxis were included. Patients received a loading infusion of vancomycin the evening prior to surgery followed by a continuous 24 h infusion, calculated according to renal function. Three peri-operative serum samples and intra-operative perivascular fat and arterial wall samples were collected for vancomycin assay. Twenty-eight patients were included. Three serum samples were obtained from all patients, fat samples were available from 27 (96.4%) patients and vessel wall samples were available from 23 (82.1%) patients. Serum vancomycin concentrations were maintained within a relatively narrow range, while fat and arterial wall concentrations were highly variable. This study has shown that prophylactic administration of vancomycin with a loading infusion followed by a continuous infusion before and during vascular surgery achieves serum and vascular tissue concentrations that are above the MICs for most common organisms implicated in post-operative graft infection. However, penetration into perivascular fat tissues is poor.

Retrospective evaluation of possible renal toxicity associated with continuous infusion of vancomycin in critically ill patients

BackgroundContinuous infusion of vancomycin is increasingly preferred as an alternative to intermittent administration in critically ill patients. Intermittent vancomycin treatment is associated with an increased occurrence of nephrotoxicity. This study was designed to determine the incidence and risk factors of acute kidney injury (AKI) during continuous infusion of vancomycin.MethodsThis was a retrospective, observational, two-center, cohort study in patients with microbiologically documented Gram-positive pneumonia and/or bacteremia and normal baseline renal function. Vancomycin dose was adjusted daily aiming at plateau concentrations of 15-25 μg/mL. AKI was defined as an increase in serum creatinine of 0.3 mg/dL or a 1.5 to 2 times increase from baseline on at least 2 consecutive days after the initiation of vancomycin. Primary data analysis compared patients with AKI with patients who did not develop AKI. A binary logistic regression analysis using the forward stepwise method was used to assess the risk factors associated with AKI.ResultsA total of 129 patients were studied of whom 38 (29.5%) developed AKI. Patients with AKI had higher body weight (77.3 ± 15 vs. 70.5 ± 15.2 kg; p = 0.02), more diabetes (79% vs. 54%; p = 0.01), and a higher vasopressor need (87% vs. 59%; p = 0.002). Serum vancomycin levels, body weight, and SAPS 3 score were identified as variables contributing to AKI. The incidence of AKI increased substantially when treatment duration was prolonged (14.9 ± 9.8 vs. 9.2 ± 4.9 days; p = 0.05) and plasma levels exceeded 30 μg/mL.ConclusionsAKI is frequently observed during continuous vancomycin infusion, particularly when conditions that cause acute (shock) or chronic (diabetes) renal dysfunction are present and vancomycin levels above target range are achieved. Although this study challenges the concept that continuous vancomycin infusion might alleviate the risk of nephrotoxicity in critically ill patients, a direct relationship between vancomycin and nephrotoxicity remains to be proven.

Étude de la variabilité dans les reconstitutions de vancomycine intraveineuse en réanimation pédiatrique

In pediatric units, most of the intravenous medications are prepared by the attending nurse at the bedside that can be affected by an error margin, so can be imprecise. Despite the possible consequences of imprecise medications administration, published studies on the topic are scarce. The main objective of this study was to measure the difference between the prescribed vancomycine concentration and the actual concentration measured in the medication administered to the patient. The secondary objective was to determine which step in the preparation was linked to the difference in concentrations. It was a prospective study, setting in a pediatric and neonatal university hospital intensive care unit. Over a 3-month period, an aliquot from every preparation for continuous infusion of vancomycin, made at the bedside by a nurse, was collected and the modalities of the preparation noted. Vancomycin concentration was measured by high performance liquid chromatography. Sixty-four preparations, accounting for 24 patients (gestationnal age: 67 ± 75 weeks, weigh: 4.8 ± 6.5 kg) were included. Vancomycin concentrations ranged from 3.33 to 60.0mg/mL. Measured concentration were in mean 7% smaller than prescribed concentration (P<10(-3)), with a large confidence interval (75.8%-120.4% of the prescribed concentration). Imprecision the preparations was much higher than this admitted for manufactured preparation. We could not highlight any factor related to the difference in concentrations, but one third of the preparation did not respect all the ISO 7886 standards for syringes use. Bedside vancomycin preparations, like preparations for other molecules, are far more imprecise than industrial intravenous medications. Our results urge that all pediatric intravenous medications should be made only by manufacturers or pharmacists. However, it also urged clinical studies, in parallel to pharmacodynamic and pharmacokinetic studies, to make intravenous treatments as accurate as they should be.

The Last Issue of Our Inaugural Year: Reflections and a View to the Future

Let me open by thanking all the authors and contributors to ACS Chemical Neuroscience in our first year. The content and quality of the articles, letters, reviews, and viewpoints have been exceptional—some truly amazing neuroscience has been published. Submissions in all the major areas the journal hopes to cover are increasing, and international submissions are similarly on the rise. In addition, we witnessed a nice balance of manuscripts from both academia and industry in 2010. Indexing in PubMed is on the horizon—a frequently asked question—and one that just requires time for a new journal. Rest assured, all is proceeding as quickly as possible. Ani, Jennifer, Tara, and all the staff at ACS have done a phenomenal job aiding both myself and the associate editors as well as in promoting the journal at dozens of meetings and conferences. There is a phenomenal team behind this journal—thank you all—the ACS team and the Associate Editors, Arthur and Allan. Serving as Editor-in-Chief for ACS Chemical Neuroscience is amazing—I love this job—I love having my finger on the pulse of emerging neuroscience—I read every submission. What a phenomenal year 2010 proved to be and how very challenging. As most of you know, our 18 month old daughter Paige was diagnosed with stage II neuroblastoma in September, and this CNS disorder was the subject of the last editorial (1). I and my family were overwhelmed by the support and outpouring of concern generated by that piece—though that was not the intention. At the time I wrote the editorial, it was therapeutic for me, and I wanted to bring attention to a rare and neglected disease that is a CNS disorder that matures into a malignant cancer (2). Moreover, significantly more research and attention needs to be directed at neuroblastoma and other diseases of the sympathetic nervous system. The standard of care has changed little in the past 25 years. I am happy to report that Paige is cancer free! We enrolled her in a clinical trial where she received only two rounds of chemotherapy (versus the standard four). During the two cycles, there were problems—ER trips for fevers, vancomycin infusions for possible PICC line infections, and as anticipated, though hard to witness, Paige lost all of her hair by the end. However, CT scans demonstrated more than a 50% reduction in the volume of the tumor, which allowed for a full surgical resection, with clean margins. Paige was back on her feet within two days of surgery. However, the Horner’s Syndrome (3), which initially clued us in to the tumor, is more pronounced. Sympathetic nerves were cut during the resection, so we will have to wait and see if the symptoms diminish over time as the inflammation subsides and nerves regenerate. Our family’s battle with cancer was fortunately very short; however, during the ordeal, we met many families whose children are fighting prolonged, losing battles. Despite the prognosis, the children are so strong and positive—truly inspiring, yet heartbreaking. Now, ACS Chemical Neuroscience in 2011—where are we going? To begin with, I am happy to announce that Dr. Corey Hopkins (research professor of pharmacology at Vanderbilt University Medical Center and associate director of medicinal chemistry for the Vanderbilt Program in Drug Discovery) will be joining the editorial team of ACS Chemical Neuroscience in the role of Managing Editor in January. A regular contributor of Chemical Spotlight features and author, in his new role Corey will work with me to solicit reviews and manuscripts and ensure a presence for the journal at all relevant neuroscience meetings. As always, we are both happy to receive proposals for Chemical Spotlights, Viewpoints, and Reviews—keep them coming. The first issue of 2011 is an all-review issue focused on the chemical senses, and composed by thought leaders in the field—guaranteed to be a good and informative read. Moving forward, all issues will feature a review article, chemical spotlight, viewpoint(s), letters, and full articles. There are plans for thematic issues—at least two in 2011—more on that next month. Also in 2011 is a new feature: “Reflections and a View to the Future” wherein thought leaders across all areas of neuroscience have agreed to write a three page essay describing the state of neuroscience early in their careers, their perspective on the current state of neuroscience, and their views on where the field will move in the future. I am really excited about this new feature and the willingness of over 40 leading neuroscientists to contribute. 2011 is shaping up to be a great year for ACS Chemical Neuroscience—thanks again to everyone for making the journal’s launch successful. ACS Chemical Neuroscience is filling a niche and linking synthetic chemists with neuroscientists to create a new community of chemical neuroscientists to tackle translational research problems—join us.

A higher dose of vancomycin in continuous infusion is needed in critically ill patients

Compared with intermittent infusion, continuous infusion of vancomycin is cheaper and logistically more convenient, achieves target concentrations faster, results in less variability in serum vancomycin concentrations, requires less therapeutic drug monitoring and causes less nephrotoxicity. Given that critically ill patients may develop very large volumes of distribution as well as supranormal drug clearance, in this study it was shown, despite the limited number of patients studied, that to achieve a target plateau concentration of 25mg/L a daily dose of 3000 mg of vancomycin in continuous infusion is needed following an appropriate loading dose.

Failure of Vancomycin Continuous Infusion against Experimental Endocarditis Due to Vancomycin-Intermediate Staphylococcus aureus

Continuous infusion of vancomycin was evaluated against experimental endocarditis due to heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and VISA. Animals were infected with hVISA PC1 (vancomycin MIC, 2 mg/liter) or VISA PC3 (vancomycin MIC, 8 mg/liter) and treated for 5 days with constant serum levels of 20 or 40 mg/liter. Vancomycin continuous infusion was unsuccessful, as 20 mg/liter was barely active against PC1 (6 of 13 sterile vegetations) and 40 mg/liter failed against PC3 (2 of 9 sterile vegetations).

Intravascular Thrombophlebitis Related to the Peripheral Infusion of Amiodarone and Vancomycin

Patients on a telemetry unit experienced an increase in thrombophlebitis in 2004. The purpose of this research was to determine if peripheral IV amiodarone and vancomycin influenced the incidence of thrombophlebitis in an adult cardiothoracic population. Amiodarone phlebitis rates range up to 27%. In December 2004, Pharmacy diluted the amiodarone concentration to 600 mg/500 ml. By 2005, data demonstrated a consistent decrease in the incidence of thrombophlebitis. However, related to institutional policies and patient safety concerns, the amiodarone infusion concentration was reversed back to 900 mg/500 ml in October 2005. Thrombophlebitis increased after the return to a more concentrated amiodarone IV solution. Vancomycin infusion administration did not change during this time period. A retrospective chart review and observational, before and after study, demonstrated a correlation between amiodarone concentration and the incidence of thrombophlebitis. Vancomycin infusions appeared to prevent peripheral thrombophlebitis in the study population. Data was compelling and resulted in the institution standardizing the more dilute amiodarone IV concentration.

Comparison of Continuous and Intermittent IV Infusion of Vancomycin: Systematic Review

There is some evidence that administration of vancomycin by continuous infusion has pharmacokinetic and pharmacodynamic advantages over traditional intermittent dosing. Whether these advantages translate into clinical efficacy remains controversial. To review the literature comparing continuous infusion of vancomycin and conventional intermittent IV dosing in terms of efficacy and safety. A literature search was conducted in the PubMed/MEDLINE and Embase databases and the Cochrane Central Register of Controlled Trials, and by means of the Google search engine, and the reference lists of pertinent articles were searched manually. All human studies published in English or French that evaluated vancomycin given by continuous and intermittent IV infusion were reviewed. Articles that did not include a comparator arm and those that assessed continuous and intermittent intraperitoneal infusions were excluded. The level of evidence of each study was categorized according to the US Preventive Services Task Force rating scale. In total, 9 studies were identified: 1 in a pediatric population and 8 in adult populations. Of the 3 studies with the highest quality of evidence (level I), one demonstrated pharmacodynamic advantages with continuous infusion of vancomycin. Of the 6 studies representing a moderate level of evidence (level II), 3 also favoured continuous infusion in terms of pharmacokinetic and pharmacodynamic outcomes, but the findings in terms of clinical outcomes were mixed. Current evidence evaluating the pharmacokinetic and pharmacodynamic advantages and clinical efficacy of continuous versus intermittent vancomycin infusions is inconsistent and does not support the routine use of continuous infusion for the treatment of multidrug-resistant gram-positive infections.

Continuous Infusion of Vancomycin Less Effective and Safe than Intermittent Infusion, Based on Pharmacodynamic and Pharmacokinetic Principles

Continuous Infusion of Vancomycin Less Effective and Safe than Intermittent Infusion, Based on Pharmacodynamic and Pharmacokinetic Principles

Vancomycin Continuous Infusion as Prophylaxis for Vascular Surgery

Prosthetic graft infection is a devastating complication of vascular surgery that occurs in 3%-5% of clean prosthetic procedures. Staphylococci are the most frequently isolated pathogens, and thus surgical prophylaxis regimens often include vancomycin. However, the efficacy of these regimens in ensuring a required concentration of antibiotic is uncertain. This study aimed to determine if a continuous vancomycin infusion regimen administered perioperatively as surgical prophylaxis for vascular procedures maintained an adequate serum concentration. Thirty-four consecutive patients undergoing a vascular procedure requiring a prosthetic graft or patch were given vancomycin prophylaxis. Each patient received a loading dose calculated according to body weight 12 hours before surgery. A 24-hour continuous infusion was then started, based on calculated creatinine clearance. Serum vancomycin concentrations were checked on induction of anesthesia, 2 hours postoperatively, and at the end of the infusion. Perioperative fluid administration and blood loss were recorded. An estimated creatinine clearance was repeated on the second postoperative day. Of the 34 patients recruited, 7 did not have the anticipated procedure and 6 patients had incomplete sample collection. Twenty-one patients with complete sample collection were analyzed. The target concentration (10-25 mg/L) was achieved in 81% of all samples. All patients achieved the target concentration at 1 or more time points. The regimen employed provided appropriate concentrations at the time of intervention. No potentially toxic concentrations or adverse reactions to vancomycin were encountered. Vancomycin given as a continuous infusion delivers adequate serum concentration. Long-term graft infection rates are needed to show a clinical effect.

Optimisation de la prescription de la vancomycine : étude prospective observationnelle dans un centre hospitalo-universitaire parisien

Vancomycin is still the cornerstone of antibiotic therapy for patients with suspected or proven invasive methicillin resistant Staphylococcus aureus infections. However, clinical and pharmacodynamic studies underline that appropriate doses depend on the infection site, the patient's weight, his renal function, and the bacterial susceptibility.In this prospective study made in a Paris teaching hospital, our two goals were to describe the modalities of infusion and serum concentration obtained during therapy, in our pediatrics and adults population.In our hospital, vancomycin was administered every eight hours in 83 % (97/102) of the cases and the doses used were 30 mg/kg per day in 67 % of cases (68/102). Serum trough levels reached 15 mcg/ml and 20 mcg/ml in 36 % and 18 % of cases respectively. Moreover, despite adequate doses, trough levels of 15 mcg/ml were obtained in only 40 % of cases.Vancomycin infusion use could be optimized, by defining optimal serum concentrations and monitoring made by a mobile team of infectious diseases specialists.

In Vivo Assessment of the Antimicrobial Activity of a Calcium-Deficient Apatite Vancomycin Drug Delivery System in a Methicillin-Resistant Staphylococcus aureus Rabbit Osteomyelitis Experimental Model

The antimicrobial activities of calcium-deficient apatite loaded with different concentrations (25, 100, and 500 microg/mg) of vancomycin as a filling biomaterial were evaluated in a methicillin-resistant Staphylococcus aureus (MRSA) rabbit acute osteomyelitis model. Bacterial counts in bone, bone marrow, and joint fluid samples treated with forms of the apatite were compared to those in tissue samples receiving a constant intravenous vancomycin infusion after 4 days. This study demonstrates that using a calcium-deficient apatite loaded with vancomycin dramatically decreases the bacterial counts in bone and marrow.

Nephrotoxicity of continuous versus intermittent infusion of vancomycin in outpatient parenteral antimicrobial therapy

Intravenous (i.v.) vancomycin is increasingly used as outpatient parenteral antimicrobial therapy (OPAT). Despite the potential advantages of administration by continuous infusion (CI) compared with intermittent infusion (II), the relative nephrotoxicity of these two modes of delivery has not been well established. We compared the rate of nephrotoxicity of vancomycin given by CI and II. A retrospective cohort study of OPAT patients receiving i.v. vancomycin between January 2004 to June 2008 was performed. All patients had a normal baseline serum creatinine concentration. Propensity scoring analysis was used to adjust for risk factors of CI. The primary outcomes examined were the prevalence and rate of onset of nephrotoxicity. A total of 167 patients receiving vancomycin were identified, 112 by CI and 55 by II. The overall cumulative prevalence of nephrotoxicity was 15.6%. There were significant differences in baseline characteristics between the two groups. Matching based on propensity scores was undertaken, leaving 80 patients available for the analysis. Both in unadjusted and adjusted analyses, vancomycin CI was associated with a slower onset of nephrotoxicity but not a lower prevalence of nephrotoxicity. Both groups received a similar cumulative vancomycin dose. In adult OPAT patients with normal renal function, vancomycin CI was associated with a slower onset of nephrotoxicity.

Influence of Vancomycin on Renal Function in Critically Ill Patients after Cardiac Surgery

Vancomycin is frequently used in clinical practice to treat severe wound and systemic infections caused by Gram-positive bacteria after cardiac surgery. The drug is excreted almost entirely by glomerular filtration and might exhibit nephrotoxic side effects. This study compared the nephrotoxic impact of vancomycin during continuous versus intermittent administration. The authors analyzed 149 patients admitted to the intensive care unit during a 5-yr period. All patients were treated at the intensive care unit after elective open heart surgery. Thirty patients received a dosage of 1325 +/- 603 mg/d vancomycin (range 300-3400 mg/d) by intermittent infusion, and 119 patients received a mean dosage of 1935 +/- 688 mg/d (range 352-3411 mg/d) by continuous infusion. Nephrotoxicity occurred in 11 patients (36.7%) in the intermittent treatment group and in 33 patients (27.7%) in the continuous treatment group (P = 0.3; 95% CI = 0.283). Continuous veno-venous hemofiltration after vancomycin administration was required for 9 patients (9 of 30; 30%) in the intermittent treatment group and for 28 (28 of 119; 23.5%) in the continuous treatment group (P = 0.053; 95% CI = 0.256). A change of one unit (1 mg/l) in vancomycin serum concentration (DeltaVancoC) induced an average change of 0.04 mg/dl in creatinine (DeltaCrea) in the intermittent treatment group versus 0.006 mg/dl in the continuous treatment group (P < 0.001). The data show that both the intermittent and also the continuous application modality of vancomycin are associated with deterioration of renal function in critically ill patients after cardiac surgery. However, continuous infusion showed the tendency to be less nephrotoxic than the intermittent infusion of vancomycin.

Clinical and microbiological efficacy of continuous versus intermittent administration of vancomycin in critical care patients

Vancomycin is known to induce postantibiotic effect but some data suggest that bactericidal activity is time dependent. Presently, the optimal dosing regimen for administration of vancomycin remains unknown. The aim of this open prospective randomized study was to compare clinical and microbiological efficacy of continuous infusion versus intermittent administration of vancomycin in critically ill patients.