Vancomycin Serum Trough Research Articles

Comparison of vancomycin and teicoplanin trough serum levels in patients with infected orthopedic devices: new data for old therapies

We compared retrospectively vancomycin and teicoplanin trough serum levels after loading doses and, subsequently, after high daily doses, in 52 patients (26 in each group) who had developed infections after implantation of an orthopedic device. The target trough serum level was > 25 mg/l. Trough levels were significantly higher at 2 days (±1) and 5 days (±1) in patients who received teicoplanin compared with patients who received a continuous perfusion of vancomycin (26.1 vs. 16 mg/l at day 2 ± 1, P = 0.01; 27.8 vs. 19.9 mg/l at day 5 ± 1, P = 0.01). One of the 26 patients taking vancomycin reached the target trough serum level by day 2 (±1), whereas 10 of the 26 patients taking teicoplanin reached the target by that time (P = 0.002). At day 5 (±1), 6/26 patients taking vancomycin reached the target, versus 13/26 patients taking teicoplanin (P = 0.04). However, physicians should remain cautious when administering teicoplanin empirically because of the higher MIC₉₀ values observed for coagulase-negative staphylococci compared with vancomycin.

Vancomycin: the need to suit serum concentrations in hemodialysis patients

The vancomycin dose for hemodialysis (HD) patients should be adjusted by monitoring drug serum concentrations. However, this procedure is not available in most health services in Brazil, which usually adopts protocols based on published studies. The trials available are controversial, and several have not been conducted with current dialyzers. This study aimed at assessing the suitability of vancomycin serum concentrations in HD patients at a public hospital. Blood samples of HD patients were collected from November 2006 to May 2007, at time intervals of 48, 96, 120, or 168 hours after vancomycin administration. Drug measurement was performed with polarized light immunofluorescence. Approximately 86% of trough vancomycin serum concentrations were below the recommended value, indicating exposure to subtherapeutic doses and a higher risk for selecting resistant microorganisms.

Pharmacokinetics of vancomycin in adult cancer patients

gram-positive infections are prevalent among cancer patients and vancomycin therapy is often initiated empirically. A typical vancomycin pharmacokinetics is observed in such patients. The aim of the study was to evaluate the pharmacokinetics of vancomycin in this patient population and compare it to that of normal population. the pharmacokinetics of vancomycin was examined retrospectively in two groups of patients - 18 cancer patients (age 43.4 ± 22.1 years) and 13 patients without cancer (age 48.5 ± 20.2 years). Following the administration of intermittent intravenous infusion of 15 mg/kg of vancomycin, peak and trough vancomycin serum concentration were determined after the third dose or at steady state as per standard of care. Vancomycin data were analyzed according to a one-compartment open model. Pharmacokinetic parameters such as clearance (CL), volume of distribution (Vd), and K elimination (ke) were calculated. Both Vd and CL were significantly higher in the cancer group (Mean Vd was 70 ± 45 L in the cancer group and 31.1 ± 8.3 L in the noncancer group, p-value 0.002; CL mean was 110.1 ± 42 mL/min in the cancer group and 71.2 ± 22.2 mL/min in the noncancer group, p-value 0.005). There was no significant difference in K elimination and half-life (t(1/2)). cancer patients may require higher than usual dosing regimens to ensure optimal therapeutic concentrations, since vancomycin CL and Vd is significantly higher in these patients, a dosing schedule as high as 60 mg/kg/day may be needed for cancer patients.

Optimizing Vancomycin Dosing through Pharmacodynamic Assessment Targeting Area under the Concentration-Time Curve/Minimum Inhibitory Concentration

Because of its activity against multidrug resistant gram-positive organisms, vancomycin is one of the antimicrobials most utilized in health care systems worldwide. Despite its widespread use, application of the pharmacodynamic principles governing vancomycin efficacy are not frequently considered in contemporary clinical practice. Although the vancomycin trough serum concentration has been used historically to assess the adequacy of a prescribed dose, data validating that this practice leads to improved patient outcomes do not exist. Alternatively, both in vitro and clinical outcomes data demonstrate improved results when an area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) of 400 mcg•h/mL or greater is achieved. This article describes the process through which individualized vancomycin dosing regimens targeting an AUC/MIC of 400 mcg•h/mL or greater, rather than trough serum concentration, at the beside can be derived. The equations, methodology, thought processes, benefits, potential pitfalls, and practical applicability of this method are specifically examined. Obtaining the actual MIC value—not an interpretation—from the microbiology laboratory and/or the MIC distribution for Staphylococcus aureus within one's own institution is essential for implementation of this method. Although vancomycin dosing recommendations suggested in contemporary practice guidelines are likely adequate for most patients, using the methods described here may lead to improved clinical outcomes for nonstandard conditions in patients who are critically ill and would benefit from an individualized dosing approach.

Nephrotoxicity of Vancomycin and Teicoplanin Alone and in Combination with an Aminoglycoside

Background and Purpose: Vancomycin and teicoplanin are considered first line medications for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections but these agents are also associated with the side-effect of nephrotoxicity. This study investigated the association between treatment with vancomycin monotherapy, teicoplanin monotherapy and combinations of these drugs with aminoglycoside antibiotics, and the occurrence of nephrotoxicity. Methods: Patients treated with vancomycin or teicoplanin, either alone or in combination with an aminoglycoside antibiotic from June to December 2003 were included. Data analyzed included age, gender, renal function (before and after drug administration), days of antibiotics administration, location of infection, other antibiotics used in combination factors affecting renal function. Results: A total of 96 patients, comprising 50 males and 46 females, with a mean age of 67.97±13.43 years were included. Multivariate logistic regression analysis revealed no association between treatment with vancomycin or teicoplanin and gender, chronic renal function impairment, dialysis treatment, diabetes, hypertension, mean age, combination with an aminoglycoside, or treatment in the ICU. Among the 28 courses of vancomycin treatment for which there were adequate serum concentration monitoring data, 16 (57.1%) courses resulted in high trough vancomycin concentration, 8 (28.6%) courses were in the normal range, and 4 (14.3%) courses were low trough concentration. Vancomycin trough serum concentrations were significantly higher in ICU patients (p=0.003). Conclusion: There was no significant difference (p＞0.05) in nephrotoxicity among patients treated with vancomycin or teicoplanin alone or in combination with an aminoglycoside. Vancomycin trough serum concentrations were highest in critically ill patients. Additional serum concentration monitoring in ICU patients was therefore advised after the use of vancomycin, in order to make necessary dosage adjustment. This can avoid unnecessary drug expenditure and reduce the likelihood of side-effects.

Accuracy of vancomycin trough levels: An experience at a large university based hospital

To analyze the results from the clinical monitoring of serum vancomycin levels among our patients receiving this drug, we have done a retrospective study of data from routine monitoring of serum vancomycin concentrations. The study population includes adult patients who received vancomycin for more than 3 days and had a trough vancomycin serum concentration documented. We obtained 30 vancomycin concentrations from our patients. With a mean trough concentrations was 12.3 micrograms/mL. Only 32% of the patients were on the normal ranges, 27% were above the range and 40% under the lower limit. Also we found that only in 25% of the time the initial dosage of the vancomycin was calculated correctly based on the patient's actual body weight and only in < 50% of the time the maintenance dose of vancomycin was calculated based on the creatinine clearance. This might be explained by the type of the population sampled, reflecting a selection bias by detecting levels only among patients with an increased risk for toxicity. Finally, we stress the importance of accurately documenting dose, timing, and renal function in the records of all patients subjected to serum vancomycin determinations.

Vancomycin Heteroresistance in Methicillin-resistantStaphylococcus aureus, Taiwan

Vancomycin Heteroresistance in Methicillin-resistant<i>Staphylococcus aureus</i>, Taiwan

Vancomycin population pharmacokinetics in neonates.

Recently the value of vancomycin therapeutic drug monitoring, as well as the required therapeutic range, has been subject of debate, resulting in new recommendations. This study was performed to incorporate these new insights in an up-to-date dosing scheme for neonates of various gestational ages. In this retrospective study with prospective validation, 108 newborns with suspected central line-related septicemia during the first month of life received 30 mg/kg/day vancomycin divided into two doses regardless of gestational or postconceptional age. Trough and peak vancomycin serum concentrations were determined before and after the third dose. Vancomycin data were analyzed according to a one-compartment open model with use of NONMEM population pharmacokinetic software. Model parameters were evaluated and then used to simulate vancomycin dosing for different dose and dose interval combinations. Targets were a trough concentration between 5 and 15 mg/L and a peak below 40 mg/L. In the prospective study, the optimal scheme was tested in 22 patients. Of the 108 patients, 34.3% of measured trough concentrations and 17.6% of peak concentrations were outside the desired therapeutic range. The model that best fitted the data included clearance and volume per kilogram and was independent of gestational age. Simulation of various dosing schemes showed that a dosing schedule of 30 mg/kg/day, irrespective of gestational age, in three doses was optimal, and this scheme was prospectively tested. Mean trough concentrations before the second dose were 8.2 +/- 2.2 mg/L versus a predicted trough of 8.9 +/- 2.5 mg/L. No peak levels higher than 40 mg/L were found. The use of the proposed schedule leads to adequate vancomycin trough serum concentrations, and there is no need for routine monitoring of peak serum concentrations.

Optimisation of Vancomycin Regimen in Neutropenic Haematological Patients with Normal Renal Function

Objective: To assess the appropriateness, on a pharmacokinetic basis, of a twice-daily regimen of vancomycin 1g in neutropenic patients with normal renal function, a regimen frequently used in the empirical treatment of this patient group. The study also used a Bayesian pharmacokinetic approach to predict vancomycin concentrations in order to determine the optimal dosage frequency of the drug (two or four daily doses) in this population. Patients and Methods: Data were collected retrospectively as part of routine therapeutic drug monitoring (TDM) of vancomycin in 16 adult neutropenic patients. TDM of vancomycin peak (Cmax) and trough (Cmin) serum concentrations was performed after twice daily administration of vancomycin lg as a 1-hour intravenous infusion for 48 hours. According to TDM results (Cmin≥7 or <7 mg/L), the vancomycin regimen was individualised (total daily dose split into two or four divided doses) by means of a Bayesian-based pharmacokinetic computer programme. TDM was then repeated on day 7. Optimal Cmin were defined as with the range of 7 to 10 mg/L. Results: On day 3 of therapy, nine patients had subtherapeutic Cmin (3.97 ± 0.59 mg/L; range 2.98 to 4.95 mg/L) according to ahigh estimated creatinine clearance (CLcr 1.79 ± 0.49 ml/kg/min; range 1.39 to 2.79 ml/kg/min), and another three patients had Cmin <7 mg/L. On day 7, higher vancomycin Cmin were achieved (8.92 ± 2.87 mg/L) in the 12 patients in whom their total daily dose was split into four (Cmin were optimal in nine and supratherapeutic in three patients), despite no major differences in the total daily dosage of vancomycin (29.77 ± 5.89 vs 30.85 ± 6.68 mg/kg; p = 0.79) and CLcr (1.63 ± 0.43 vs 1.90 ± 0.45 ml/kg/min; p = 0.19) versus day 3. Dose-normalised results suggested large interindividual pharmacokinetic variability. Conclusion: Since the volume of distribution and/or clearance of vancomycin can be increased in patients with haematological malignancies and normal renal function, increasing the number of daily doses from two to four (with the same total daily dose) may increase t > MIC, an important determinant of vancomycin efficacy. However, because of interpatient variability, TDM of vancomycin is strongly recommended to individualise therapy in this subpopulation.

Vancomycin dosage requirements among pediatric intensive care unit patients with normal renal function

Purpose: The purpose of this study was to determine a vancomycin dosage regimen among pediatric intensive care unit (PICU) patients with normal renal function resulting in desired peak and trough serum concentration and to determine the predictability of vancomycin peak concentrations based on reported trough concentrations. Materials and Methods: The medical records of all PICU patients who received vancomycin over a 12-month period were identified through a hospital computer search and were obtained from the hospital's Department of Medical Records. Demographic and laboratory data as well as the patient's vancomycin dosing history were recorded. Patients who lacked appropriately timed vancomycin peak and trough concentrations or who exhibited renal dysfunction were excluded from the study population. The optimal vancomycin dose and the predictability of peak concentrations based on trough concentrations were assessed. Results: A total of 135 patients were identified as having received vancomycin therapy during their PICU hospitalization between June 1997 and June 1998. Fifty-nine patients were excluded due to renal dysfunction or inappropriate vancomycin concentrations resulting in 76 patients representing our study population. The initial mean dose of vancomycin was 47 mg/kg/day resulting in a mean peak and trough serum concentration of 19 and 6 μg/mL, respectively. A mean of 2.2 (range, 1 to 5) and 2.1 (range, 1 to 5) peak and trough serum concentrations were reported for each patient, respectively. A mean of 1.1 (range, 0 to 4) dosing changes per patient was noted resulting in a final mean dose of 60 mg/kg/day corresponding to a mean peak and trough serum concentration of 26 and 8 μg/mL, respectively. A vancomycin trough concentration >5 μg/mL was highly predictive for a corresponding peak concentration >20 μg/mL ( P > .0001). Eighty percent of the trough concentrations <5 μg/mL were associated with peak concentrations <20 μg/mL, whereas 81% of trough concentrations > 5 μg/mL were associated with corresponding peak concentrations >20 μg/mL. Conclusions: PICU patients required higher doses of vancomycin than are typically prescribed to achieve conventionally accepted peak and trough vancomycin serum concentrations. In the absence of renal impairment, we recommend an initial dosage regimen of 60 mg/kg/day divided every 8 hours. Vancomycin trough concentrations are highly predictive of corresponding peak concentrations and therefore may negate the need to obtain routine peak concentrations. Copyright © 2000 by W.B. Saunders Company

Do Vancomycin Serum Levels Predict Failures of Vancomycin Therapy or Nephrotoxicity in Cancer Patients?

The purpose of this study was to determine if patients with high vancomycin (VAN) serum levels experience more toxicity than underdosed patients with lower (VAN) levels, and whether low VAN serum levels cause therapeutic failures in patients with Gram-positive bacteremia. In 198 cancer patients trough and peak serum levels of VAN were measured. Acute toxicity (Red Man syndrome) appeared in 3 patients (1.5%). Patients previously or currently treated with other nephrotoxic compounds (134 patients) presented the same incidence of nephrotoxicity as those receiving VAN for the first time in monotherapy (64 patients). VAN did not increase the toxicity when patients were dosed simultaneously or previously with aminoglycosides or amphotericin B.Our second observation, when studying serum levels in our 198 patients was that high VAN trough serum levels (trough > 15μg/mL) were associated with significantly more nephrotoxicity (33.3% vs. 11.1%, P < 0.03) than low levels in the subgroups of either pretreated patients or unpretreated with other nephrotoxic drugs. None of 198 patients who had trough levels below 15 μg/mL had peak levels exceeding 40 μg/mL. This suggests that only serum monitoring of trough levels may predict nephrotoxicity.A case control study was conducted to compare a group of 22 VAN failures with 22 successfully treated patients matched in underlying disease and neutropenia who were treated in the same period, under the same antibiotic policy, at the same cancer center, for Gram-positive bacteremia. Persisting, enterococcal, or mixed enterococcal plus staphylococcal bacteremia were the only statistically significant risk factors which predicted therapy failure in cancer patients. Neither peak nor trough VAN serum levels predicted failure or cure of Gram-positive bacteremia in cancer patients.

Comparison of Vancomycin Pharmacokinetics in Hospitalized Elderly and Young Patients Using a Bayesian Forecaster

Limited data have been published that compare the pharmacokinetic parameters of vancomycin in elderly versus young patients. This study was designed to assess vancomycin pharmacokinetics in 148 elderly (> or = 60 years of age) and 140 young (18-59 years of age) hospitalized infected patients. Serum vancomycin concentrations were determined using fluorescence polarization immunoassay. Serum concentration-versus-time data were fitted to a two-compartment Bayesian forecasting program. Elderly versus young vancomycin pharmacokinetic parameters derived were as follows (patients with serum creatinine < or = 1.5 mg/dL); mean +/- standard deviation terminal disposition half-life (t1/2) of 17.8 +/- 11.8 versus 7.5 +/- 6.7 hours, respectively, P < .05; volume of distribution (Vz) of 74.2 +/- 32.3 versus 67.0 +/- 30.7 L, respectively, P = .16; and total body clearance (CL) of 0.71 +/- 0.41 versus 1.22 +/- 0.50 mL/min/kg, respectively, P < .05. Comparing subjects with normal serum creatinine values (< or = 1.5 mg/dL), the elderly required smaller daily doses as compared with the young group to maintain target peak and trough vancomycin serum concentrations (18.2 +/- 5.8 verus 25.2 +/- 7.8 mg/kg/day, P < .05). Stepwise multiple regression models for the pharmacokinetic parameters were developed to assess the predictive power of age, controlling for the effects of gender, total body weight, serum creatinine, and creatinine clearance. Age was consistently an independent and significant predictor of t1/2, Vz, and CL. These data demonstrate that elderly patients exhibit significant differences in vancomycin pharmacokinetic parameters compared with young patients and constitute a patient population in need of individualized vancomycin dosing due to substantial heterogeneity in physiologic and pharmacokinetic parameters.

Risk of nephrotoxicity with combination vancomycin-aminoglycoside antibiotic therapy.

One hundred five patients receiving concurrent aminoglycoside and vancomycin therapy of at least 5 days' duration were retrospectively reviewed for development of nephrotoxicity. All had their vancomycin and aminoglycoside serum concentrations controlled by a clinical pharmacokinetics service. Nephrotoxicity occurred in 28 (27%) of the patients. Twenty-two of the 28 had other factors that are known to contribute to renal failure (amphotericin B therapy, sepsis, liver disease, obstructive uropathy, pancreatitis, anesthesia). The remaining six developed nephrotoxicity without other known contributing factors. Logistic regression analysis revealed associations between nephrotoxicity and age, sex, aminoglycoside trough and vancomycin peak and trough serum concentrations, length of aminoglycoside and vancomycin therapy, concurrent amphotericin B therapy, liver disease, neutropenia, and peritonitis (p less than 0.05). In addition to factors previously reported, this study found that neutropenia and peritonitis are associated with an increased risk of nephrotoxicity. Patients with one or more risk factors warrant close monitoring of renal function as well as vancomycin and aminoglycoside serum concentrations.

Nephrotoxicity of vancomycin, alone and with an aminoglycoside

The incidence of nephrotoxicity in patients receiving vancomycin alone or in combination with an aminoglycoside was prospectively evaluated. A total of 231 courses of antibiotic therapy in 224 patients were consecutively monitored over 28-month period. One hundred and sixty-eight patients received vancomycin alone, 63 patients received vancomycin with an aminoglycoside, and 103 patients received gentamicin. Nephrotoxicity was defined as an increase in serum creatinine of 0.5 mg/dl or a 50% increase above baseline, whichever was greater. Eight patients (5%) receiving vancomycin alone, 14 patients (22%) receiving vancomycin with an aminoglycoside, and 11 patients (11%) receiving gentamicin alone were found to have nephrotoxicity. Factors found to be associated with increased risk of nephrotoxicity in patients receiving vancomycin were concurrent therapy with an aminoglycoside, length of treatment with vancomycin (greater than 21 days), and vancomycin trough serum concentration (greater than 10 mg/l). Although the incidence of vancomycin nephrotoxicity is low, patients receiving vancomycin therapy with the above risk factors should be closely monitored.

Evaluation of a new vancomycin dosing method.

Thirty-one patients who were prescribed vancomycin therapy at our institution since January 1, 1986, were dosed using the guidelines as described by Lake and Peterson. Peak and trough vancomycin serum concentrations were measured at steady state: 24 (77%) peak serum concentrations were within the range of 20-30 mg/L, and 24 (77%) trough serum concentrations were within the range of 5-10 mg/L. We have found that the method of Lake and Peterson is satisfactory for initiating vancomycin therapy in most patients. Some, however, may not achieve optimal serum concentrations using these guidelines alone, and their regimens may have to be adjusted based upon actual serum concentration data.

Increased Vancomycin Dosage Requirements in Young Burn Patients

Vancomycin dosage requirements were studied in six young burn patients, in whom initial doses ordered by house officers were monitored using peak and trough vancomycin serum concentration measurements. Dosage regimens were adjusted to produce peak and trough levels within the recommended range of 30

Vancomycin pharmacokinetics in critically ill patients.

Peak and trough vancomycin serum levels were measured in 37 severely ill patients following dosing using the Moellering nomogram. The peak and trough serum concentrations were 61.2 +/- 23 and 22.6 +/- 16.5 mg/l, respectively, and higher than expected. Vancomycin pharmacokinetics obtained from 10 other patients were also studied. In five patients with a creatinine clearance greater than 1 ml min-1 kg-1, a mean plasma elimination half-life of 7.8 +/- 2.8 h was calculated. In the five other patients with markedly reduced renal function (creatinine clearance less than or equal to 1 ml min-1 kg-1), the mean elimination half-life was 18.3 +/- 10.2 h. A correlation was observed between the vancomycin and creatinine clearance. Important inter-patient variations of vancomycin clearance for the same creatinine clearance was also noted. Tubular damage in critically ill patients with severe sepsis may explain our results of the decreased vancomycin elimination.