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PubMed2006

Levels of vancomycin in cerebrospinal fluid of adult patients receiving adjunctive corticosteroids to treat pneumococcal meningitis: a prospective multicenter observational study.

BACKGROUND: Evidence from a recent randomized controlled trial suggests that dexamethasone as adjunct therapy in adult pneumococcal meningitis reduces mortality and neurological sequelae. However, adding dexamethasone has the potential to reduce penetration of vancomycin into the cerebrospinal fluid (CSF). We sought to determine concentrations of vancomycin in serum and CSF of patients with suspected or proven pneumococcal meningitis receiving dexamethasone to assess the penetration of vancomycin into the CSF during steroid therapy. METHODS: In an observational open multicenter study, adult patients admitted to the intensive care unit because of suspected pneumococcal meningitis received recommended treatment for pneumococcal meningitis, comprising intravenous cefotaxime (200 mg per kg of body weight per day), vancomycin (administered as continuous infusion of 60 mg per kg of body weight per day after a loading dose of 15 mg per kg of body weight), and adjunctive therapy with dexamethasone (10 mg every 6 h). Vancomycin levels in CSF were measured on day 2 or day 3 of therapy and were correlated with protein levels in CSF and vancomycin levels in serum (determined at the same time as levels in CSF). RESULTS: Fourteen patients were included. Thirteen had proven pneumococcal meningitis; 1 patient, initially suspected of having pneumococcal meningitis, was finally determined to have meningitis due to Neisseria meningitidis. Mean levels of vancomycin in serum and CSF were 25.2 and 7.2 mg/L, respectively, and were positively correlated (r=0.6; P=.025). A positive correlation was also found between the ratio of vancomycin in CSF to vancomycin in serum and the level of protein in CSF (r=0.66; P=.01). CONCLUSIONS: Appropriate concentrations of vancomycin in CSF may be obtained even when concomitant steroids are used. Dexamethasone can, therefore, be used without fear of impeding vancomycin penetration into the CSF of patients with pneumococcal meningitis, provided that vancomycin dosage is adequate. This study is registered at http://www.ClinicalTrials.gov/ (registration number NCT00162578).

Adrenal Cortex Hormones↗

PubMed2002

CAHP-210 dialyzer influence on intra-dialytic vancomycin removal.

BACKGROUND: Vancomycin is often administered during the last hour of haemodialysis because it was not removed significantly by older hemodialyzers. However, newer higher permeability hemodialyzers remove vancomycin, although the amount removed varies considerably between dialyzers. The purpose of this study was to determine the apparent amount of vancomycin removed during the last hour of haemodialysis with a CAHP-210 hemodialyzer. METHODS: Eight subjects with end-stage renal disease (ESRD) received i.v. vancomycin 15 mg/kg after their regular haemodialysis session ended. Serum samples for the determination of vancomycin concentrations were obtained serially for 44 h. After a 3-week washout, the study was repeated with the vancomycin infused during the last hour of their regular haemodialysis session using a CAHP-210 hemodialyzer. Vancomycin concentrations were determined by the Enzyme Multiplied Immunoassay Technique. Differential equations describing a two-compartment open infusion model were fitted to the serum concentration vs time data and pharmacokinetic parameters and apparent vancomycin removal was estimated. RESULTS: The median age and weight of the subjects were 52 years (range 37-71) and 75.6 kg (range 37.6-89.8), respectively. The apparent vancomycin intra-dialytic removal was 0.24 (range -0.07-0.35), which was statistically significantly different from zero. CONCLUSIONS: Vancomycin administered during the last hour of CAHP-210 dialysis results in 24% less vancomycin exposure than when administered post-haemodialysis. This intra-dialytic drug loss should be accounted for when dosing vancomycin in this manner.

Adult↗

PubMed2004

A retrospective drug utilization evaluation of vancomycin usage in paediatric patients.

OBJECTIVE: To evaluate the appropriateness of use of vancomycin in paediatric patients at KK Women's and Children's Hospital, the major paediatric hospital in Singapore to identify potential problems in prescribing practices that may necessitate intervention to optimize vancomycin usage. METHODS: A retrospective drug utilization evaluation was performed for paediatric patients who received intravenous vancomycin from 1 June 1998 to 31 June 1999. The outcome measures were consistency of vancomycin indication with recommended guidelines, dosing regimens, microbiological data, monitoring of serum drug levels, renal function, clinical outcomes and adverse drug reactions (ADRs). RESULTS: A total of 96 cases was available for evaluation. Sixty-two (64.6%) courses of vancomycin were consistent with guidelines for indication of therapy. Eighty-six (89.6%) of the dosing regimen were consistent. All infusion times that were recorded (56.3%) were consistent with criteria. Of the patients treated with vancomycin for more than 1 day, peak and/or trough serum vancomycin levels were ordered for 70 cases. Of the 56 cases with paired levels ordered, 46 cases had at least one level that fell outside the therapeutic range. Nineteen (19.8%) cases of ADRs were documented. Fifty-eight (60.4%) cases received concurrent nephrotoxic drugs. However, a substantial portion of vancomycin courses were apparently not prescribed for appropriate indications, and there was poor recording of vancomycin administration information and sampling time. CONCLUSION: The majority of dosing regimens of vancomycin was consistent with guideline criteria. The most evident problem was the sub-optimal use of the monitoring of vancomycin serum levels. The information derived from this study may be used as a for further study and for the development of strategies for optimize vancomycin usage.

Adolescent↗

PubMed1989

Activity of glycopeptides against vancomycin-resistant gram-positive bacteria.

Gram-positive bacteria resistant to vancomycin are rare; but they include members of the genera Leuconostoc, Lactobacillus, and Pediococcus, as well as recently emerging vancomycin-resistant strains of Enterococcus faecium and Enterococcus faecalis. Vancomycin, teicoplanin, and several vancomycin derivatives were tested for their activities against vancomycin-resistant gram-positive bacteria. Vancomycin-resistant E. faecium and E. faecalis were generally cross-resistant to other glycopeptides, but some N-substituted vancomycin derivatives were active against the resistant strains, with MICs of 2 to 32 micrograms/ml. These vancomycin derivatives also had significant levels of activity against intrinsically vancomycin-resistant organisms such as Leuconostoc sp. While vancomycin resistance in E. faecium and E. faecalis was inducible, resistance in members of the genera Leuconostoc, Lactobacillus, and Pediococcus appeared to be expressed constitutively. Antibody to a vancomycin-induced membrane protein found in membranes of resistant enterococci did not detect a cross-reacting protein in other vancomycin-resistant species.

Drug Resistance, Microbial↗

PubMedDate not supplied

Vancomycin stability in heparin and total parenteral nutrition solutions: novel approach to therapy of central venous catheter-related infections.

To facilitate therapy of central venous catheter-related Gram-positive bacterial infection in patients who require total parenteral nutrition (TPN) therapy, we studied the stability of vancomycin in a commonly used TPN solution (V-TPN) at final concentrations of 0.5 mg/mL and 1.0 mg/mL and in heparin (100 U/mL in 0.9% NaCl) at 25 micrograms/mL (V-H). Vancomycin concentrations in V-TPN and V-H after storage at 4 degrees C over 35 and 14 days, respectively, were stable (within 10% of the prestorage vancomycin concentration). After 14 days at 4 degrees C heparin activity in V-H solution was 100 +/- 4% of that noted initially. Vancomycin remained stable (100 +/- 6% of the original vancomycin concentration) when the previously refrigerated V-TPN was held for an additional 24 hours at 22 degrees C. When the previously refrigerated V-H was held for an additional 24 hours at 37 degrees C, vancomycin concentrations decreased to 78 +/- 9% of the baseline concentrations (p less than .001). The stability of vancomycin in this TPN solution allows the daily dose of vancomycin to be mixed with the solution and then infused over 10 hours. As shown with pharmacokinetic modeling, this form of therapy will achieve serum vancomycin concentrations within the therapeutic range throughout a 24-hour period. The relative stability of vancomycin in a heparin line-flush solution allows vancomycin concentration in the lumen of the catheter to be maintained at greater than or equal to 15 micrograms/mL during the interval between catheter flushing and the subsequent TPN infusion. A simplified method of administering vancomycin to patients receiving concurrent TPN is possible.

Catheterization, Central Venous↗

PubMed1995

Influence of cellulose triacetate hemodialyzers on vancomycin pharmacokinetics.

This study was designed to evaluate the pharmacokinetics of vancomycin during hemodialysis with cellulose triacetate (CT) high-flux dialyzers and to assess the influence of membrane surface area on intradialytic clearance. In a randomized crossover fashion, the pharmacokinetics of vancomycin were evaluated during dialysis with the CT 110 and CT 190 membranes. Six hemodialysis patients received 1 g of vancomycin immediately after the completion of a dialysis session, and subsequently, blood samples were obtained over a 5-day study period. On Day 3 subjects were dialyzed with CT 110 or CT 190 membranes. The mean intradialytic clearance of vancomycin was 56.7 +/- 7.5 and 100.70 +/- 10.7 mL/min with the CT 110 and CT 190 membranes, respectively (P < 0.05). Significant rebound in vancomycin serum concentrations occurred after dialysis; this rebound appeared to be complete 3 h postdialysis. On the basis of postrebound concentrations, the apparent percent removal of vancomycin was 23.6 +/- 1.2 and 25.2 +/- 8.6% for CT 110 and CT 190 membranes, respectively (not significant). Vancomycin is significantly cleared during dialysis with cellulose triacetate membranes, and its clearance is dependent on membrane surface area. Although a small supplemental dose of vancomycin could be administered after dialysis to replace drug lost during dialysis, it may be more efficient to give a larger dose of vancomycin after several dialysis periods. The determination of vancomycin removal can be used to estimate vancomycin serum concentrations as well as dosage requirements. This in conjunction with serum concentration monitoring can be used to optimize vancomycin dosing.

Adult↗

PubMed2004

Pharmacodynamics of vancomycin and other antimicrobials in patients with Staphylococcus aureus lower respiratory tract infections.

BACKGROUND: Vancomycin is commonly used to treat staphylococcal infections, but there has not been a definitive analysis of the pharmacokinetics of this antibacterial in relation to minimum inhibitory concentration (MIC) that could be used to determine a target pharmacodynamic index for treatment optimisation. OBJECTIVE: To clarify relationships between vancomycin dosage, serum concentration, MIC and antimicrobial activity by using data gathered from a therapeutic monitoring environment that observes failures in some cases. METHODS: We investigated all patients with a Staphylococcus aureus lower respiratory tract infection at a 300-bed teaching hospital in the US during a 1-year period. Clinical and pharmacokinetic information was used to determine the following: (i) whether steady-state 24-hour area under the concentration-time curve (AUC24) divided by the MIC (AUC24/MIC) values for vancomycin could be precisely calculated with a software program; (ii) whether the percentage of time vancomycin serum concentrations were above the MIC (%Time>MIC) was an important determinant of vancomycin response; (iii) whether the time to bacterial eradication differed as the AUC24/MIC value increased; (iv) whether the time to bacterial eradication for vancomycin differed compared with other antibacterials at the same AUC24/MIC value; and (v) whether a relationship existed between time to bacterial eradication and time to significant clinical improvement of pneumonia symptoms. RESULTS: The median age of the 108 patients studied was 74 (range 32-93) years. Measured vancomycin AUC24/MIC values were precisely predicted with the A.U.I.C. calculator in a subset of our patients (r2 = 0.935). Clinical and bacteriological response to vancomycin therapy was superior in patients with higher (> or = 400) AUC24/MIC values (p = 0.0046), but no relationship was identified between vancomycin %Time>MIC and infection response. Bacterial eradication of S. aureus (both methicillin-susceptible and methicillin-resistant) occurred more rapidly (p = 0.0402) with vancomycin when a threshold AUC24/MIC value was reached. S. aureus killing rates were slower with vancomycin than with other antistaphylococcal antibacterials (p = 0.002). There was a significant relationship (p < 0.0001) between time to bacterial eradication and the time to substantial improvement in pneumonia score. CONCLUSIONS: Vancomycin AUC24/MIC values predict time-related clinical and bacteriological outcomes for patients with lower respiratory tract infections caused by methicillin-resistant S. aureus.

Adult↗

PubMed1995

Enterococci resistant to multiple antimicrobial agents, including vancomycin. Establishment of endemicity in a university medical center.

OBJECTIVES: To determine the distribution of and risk factors for colonization and infection with vancomycin-resistant enterococci; to evaluate the molecular epidemiology of these strains; and to assess the effect of interventions, including 1) strict adherence to infection control procedures and 2) restricted use of vancomycin. DESIGN: Problem identification based on descriptive studies, point-prevalence surveys, and case-control studies and followed by specific interventions and evaluation of the response to these interventions. SETTING: University medical center. PARTICIPANTS: All patients hospitalized between May 1992 and June 1994 (59,196 admissions). MAIN RESULTS: 75 active infections attributed to vancomycin-resistant enterococci were identified. Thirty-one patients (41%) had bloodstream infections and 6 (8%) died. The incidence of active infection was highest in the organ transplantation unit (13.2 infections/1000 admissions). In the point-prevalence studies, vancomycin-resistant enterococci were isolated from 20% of a random sample of hospitalized patients in July, August, and September 1993 (adjusted prevalence, 16.9%). Case-control studies showed significant associations between colonization and infection and 1) receipt of antimicrobial agents, particularly vancomycin, and 2) severity of illness. Although several small case clusters had isolates with identical banding patterns on pulsed field gel electrophoresis, at least 45 different banding patterns were noted among medical center isolates. Interventions took place in November and December 1993. Vancomycin restriction policies resulted in a 59% decrease in intravenous vancomycin use and an 85% decrease in oral vancomycin use. Point-prevalence surveys done in April, May, and June 1994 showed a consistent 20% level of colonization with vancomycin-resistant enterococci strains (adjusted prevalence, 18.7%). No significant changes were seen in rates of vancomycin-resistant enterococci infection. CONCLUSIONS: Vancomycin-resistant enterococci are an important cause of illness and death in the study institution, particularly among organ transplant recipients and other seriously ill persons; they have also become a common intestinal colonizer among hospitalized patients. The diversity of isolates (based on molecular typing studies) suggests that resistant organisms have been introduced from multiple sources. Interventions that effectively lower the overall level of colonization with vancomycin-resistant enterococci must still be identified.

Case-Control Studies↗

PubMed1995

Analysis of responses to vancomycin in carotid blood flow in the male rat.

Vancomycin is known to cause vasodilation, and hypotension secondary to histamine release. We studied the actions of two forms of vancomycin, a clinically available preparation, clinical vancomycin, and a research grade preparation, laboratory vancomycin, in the presence of an H1 receptor blockade and during H2 receptor blockade with Doppler flow probe analysis of carotid artery flow rate. Clinical vancomycin, laboratory vancomycin, and histamine, increased the mean carotid artery blood flow from baseline in a dose-dependent manner. Diphenhydramine, H1 receptor antagonist, attenuated the increase in mean carotid artery blood flow for the highest dose of clinical vancomycin and for each dose of histamine. Famotidine, H2 receptor antagonist, significantly attenuated the increase in mean carotid artery blood flow for the highest dose of clinical vancomycin, the two higher doses of laboratory vancomycin, and with each dose of histamine. Both diphenhydramine and famotidine attenuated the increase of mean carotid artery blood flow with clinical vancomycin, laboratory vancomycin, and histamine. These data suggest that the change in carotid flow produced by vancomycin, is dependent, in part, on either H1 or H2 receptor activation.

Animals↗

PubMed2002

Effectiveness of pharmacy policies designed to limit inappropriate vancomycin use: a population-based assessment.

OBJECTIVE: In Oregon in 1994, a population-based study of 66 nonpsychiatric hospitals indicated that 40% of vancomycin orders were inappropriate according to Centers for Disease Control and Prevention guidelines. We repeated the study to determine whether vancomycin use had been affected by pharmacy policies implemented following the 1994 study. METHODS: We surveyed pharmacists in nonpsychiatric hospitals in Oregon regarding vancomycin use policies in their hospitals. Using pharmacy records, we identified and abstracted the charts of all patients in Oregon hospitals receiving vancomycin during a 3-week period to determine appropriate use of vancomycin. RESULTS: Thirteen (20%) of 64 hospitals had implemented a vancomycin restriction policy since 1994; none ofthe remaining hospitals in the study had a policy. In 1999, hospitals with vancomycin restriction policies had substantially decreased rates of inappropriate vancomycin use compared with hospitals without such policies (1.0 vs 1.8 orders per 1,000 patient-days; P = .01). Compared with 1994 baseline rates of inappropriate use, hospitals that adopted policies experienced a decrease (from 1.5 orders per 1,000 patient-days in 1994 to 1.0 in 1999; P= .13), whereas hospitals without policies experienced a statistically significant increase (from 0.9 orders per 1,000 patient-days in 1994 to 1.8 in 1999; P= .001). Restriction policies were most effective at reducing rates of inappropriate use for treatment of confirmed gram-positive infections and prophylaxis. CONCLUSION: Vancomycin restriction policies were associated with a decrease in inappropriate therapeutic and prophylactic vancomycin use, but had no effect on inappropriate empiric use. Hospitals considering limits regarding inappropriate use should consider implementation of institution-based vancomycin restriction policies as part of an overall strategy.

Anti-Bacterial Agents↗

PubMed2005

A vancomycin-heparin lock solution for prevention of nosocomial bloodstream infection in critically ill neonates with peripherally inserted central venous catheters: a prospective, randomized trial.

OBJECTIVE: Critically ill neonates are at high risk for vascular catheter-related bloodstream infection (CRBSI), most often caused by coagulase-negative staphylococci. Most CRBSIs with long-term devices derive from intraluminal contaminants. The objective of this study was to ascertain the safety and the efficacy of a vancomycin-heparin lock solution for prevention of CRBSI. METHODS: A prospective, randomized double-blind trial was conducted during 2000-2001 at a community hospital level III NICU. Very low birth weight and other critically ill neonates with a newly placed peripherally inserted central venous catheter were randomized to have the catheter locked 2 or 3 times daily for 20 or 60 minutes with heparinized normal saline (n = 43) or heparinized saline that contained vancomycin 25 microg/mL (n = 42). The origin of each nosocomial bloodstream infection (BSI) was studied by culturing skin, catheter hubs, and implanted catheter segments and blood cultures, demonstrating concordance by restriction-fragment DNA subtyping. Surveillance axillary and rectal cultures were performed to detect colonization by vancomycin-resistant organisms. The main outcome measures were (1) CRBSIs and (2) colonization or infection by vancomycin-resistant Gram-positive bacteria. RESULTS: Two (5%) of 42 infants in the vancomycin-lock group developed a CRBSI as compared with 13 (30%) of 43 in the control group (2.3 vs 17.8 per 1000 catheter days; relative risk: 0.13; 95% confidence interval: 0.01-0.57). No vancomycin-resistant enterococci or staphylococci were recovered from any cultures. Vancomycin could not be detected in the blood of infants who did not receive systemic vancomycin therapy. Twenty-six neonates (8 vancomycin-lock group, 18 control group) had at the end of a catheter-lock period asymptomatic hypoglycemia that resolved promptly when glucose-containing intravenous fluids were restarted. CONCLUSIONS: Prophylactic use of a vancomycin-heparin lock solution markedly reduced the incidence of CRBSI in high-risk neonates with long-term central catheters and did not promote vancomycin resistance but was associated with asymptomatic hypoglycemia. The use of an anti-infective lock solution for prevention of CRBSI with long-term intravascular devices has achieved proof of principle and warrants selective application in clinical practice.

Anti-Bacterial Agents↗

PubMed2026

Vancomycin Effectiveness in Reducing Surgical Site Infection in Posterior Spinal Fusion Surgery: A Retrospective Data Analysis of the STRIVE Trial.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: To re-evaluate vancomycin as a preventive measure for surgical site infection (SSI). SUMMARY OF BACKGROUND DATA: Intrawound vancomycin powder is used to prevent SSIs in spinal surgery. Prior studies, often limited to single institutions or small samples, have shown mixed efficacy and potential increases in non- S. aureus and Gram-negative infections. We hypothesized that SSIs rates would be similar with and without intrawound vancomycin in posterior spinal fusion (PSF) surgery. METHODS: Prospectively collected data from the 3595 patients in the STaphylococcus aureus suRgical Inpatient Vaccine Efficacy (STRIVE) trial were stratified by intrawound antibiotic usage. Multivariate logistic regression assessed the effect of vancomycin use on SSI, adjusting for patient demographics and SSI-associated risk factors. Secondary outcomes included critical care stay, reoperation, sepsis, and hospital readmission. RESULTS: Of 3311 patients who underwent surgery, 847 (26%) received only intrawound vancomycin and 1534 (46%) received no intrawound antibiotics. Sixty (8%) patients developed postoperative SSI, of whom 20 (33%) had received intrawound vancomycin. Receiving intrawound vancomycin was not associated with SSI incidence versus no intrawound antibiotics [odds ratio (OR): 0.77; 95% CI: 0.42-1.42], critical care stay (OR: 0.94; 95% CI: 0.78-1.12), or sepsis (OR: 2.04; 95% CI: 0.62-6.73). However, intrawound vancomycin was associated with increased odds of hospital readmission (OR: 1.82; 95% CI: 1.28-2.6; P < 0.001) and reoperation (OR: 1.75; 95% CI: 1.18-2.6; P = 0.005). Factors significantly associated with intrawound vancomycin use included intraoperative antibiotic readministration (OR: 2.97; 95% CI: 1.36-6.5; P =0.006) and hospital location, lower odds in Europe (OR: 0.13; 95% CI: 0.06-0.29; P < 0.001) or Asia (OR: 0.02; 95% CI: 0-0.08; P < 0.001) versus North America. CONCLUSIONS: Intraoperative vancomycin use was not associated with reduced SSI incidence compared with no intrawound antibiotics after PSF surgery. LEVEL OF EVIDENCE: Level II.

Humans↗

PubMed1991

The effect of tobramycin on the renal handling of vancomycin.

Studies in experimental animals and humans have suggested that enhanced renal and auditory toxicity occur with concurrent vancomycin and aminoglycoside treatment. In volunteers, systemic vancomycin clearance at steady-state was measured simultaneously with renal clearances of vancomycin, creatinine, inulin, and para-aminohippurate. Group 1 (n = 9) received vancomycin 5 mg/kg IV for 1 hour, then 1.1 mg/kg/hr for 3 hours. Group II (n = 7) received vancomycin plus tobramycin (2 mg/kg IV over 30 min). Groups did not differ demographically. Audiograms were obtained before and after vancomycin. Plasma samples were collected serially for vancomycin and tobramycin pharmacokinetic studies. Serum concentration versus time data were fit to a two-compartment model for vancomycin and a one-compartment model for tobramycin. For all volunteers, creatinine, inulin and para-aminohippurate clearance, and audiograms were not altered from baseline and were not statistically different between groups. No significant effect of tobramycin on vancomycin pharmacokinetics was observed. conversely, vancomycin had no significant effect on tobramycin pharmacokinetics. The nephrotoxic synergism of vancomycin and tobramycin is not explained by short-term differences in renal handling.

Adult↗

PubMed1999

Vancomycin clearance during continuous venovenous haemofiltration in critically ill patients.

OBJECTIVE: To study the pharmacokinetics of vancoymcin in critically ill patients with acute renal failure treated with continuous venovenous haemofiltration (CVVHF). DESIGN: Open-label study. SETTING: Hospital pharmacy centre and medical intensive care unit of the University Medical Centre Utrecht. MATERIALS AND METHODS: In a laboratory setting, the sieving coefficient (s) of vancomycin by polyacrilonitrile (PAN) haemofilters of different surface areas was studied. In one patient, the pharmacokinetics of vancomycin were studied following a single dose of vancomycin. Another patient was treated with a vancomycin dosing regimen based on data from the literature, but high trough concentrations made dose reduction necessary after 24 h of withholding therapy. After two doses of 250 mg, serum and ultrafiltrate samples were collected for pharmacokinetic evaluation. INTERVENTIONS++: CVVHF with the following operational characteristics: blood flow 200 ml/min, ultrafiltrate flow 25 ml/min, postdilution, PAN 06 hollow fibre haemofilter. MEASUREMENTS AND RESULTS: The average sieving coefficient in vitro was 0.73 +/- 0.06, 0.86 +/- 0.11, and 0.80 +/- 0.06 for the PAN 03, 06, and 10 haemofilters, respectively. Changes in the sieving coefficient by increasing the ultrafiltration rate were not clinically significant. The first patient was given a single dose of vancomycin, 1000 mg by intravenous infusion. The following pharmacokinetic data were obtained: apparent volume of distribution (Vd) 55.8 l, terminal half-life time (t(1/2 term)) 15.4 h, total clearance (Cl(tot)) 2.5 l/h, CVVHF clearance (CL(CVVHF, form 1)) 1.4 l/h, and body clearance (Cl(body)) 1.1 l/h. The average sieving coefficient during the study period was 0.89 +/- 0.03. In the second patient, the pharmacokinetics of vancomycin were studied following dose reduction: Vd 41.7 l, (1/2 term) 20.3 h, Cl(tot) 1.4 l/h, Cl(CVVHF, form 1) 1.4 l/h, and Cl(body) < 0.1 l/h. The average sieving coefficient during the study period was 0.88 +/- 0. 03. The cumulative amount of vancomycin removed by means of CVVHF during the 12-h study period was 245 mg in patient 1 and 228 mg in patient 2. CONCLUSIONS++: CVVHF with a PAN 06 haemofilter effectively removed vancomycin in two critically ill patients. The amount of vancomycin removed with CVVHF was about 250 mg per 12 h. A clear difference in body clearance in the two patients was observed. Our dosage recommendation for vancomycin in critically ill patients receiving CVVHF is a loading dose of 15-20 mg/kg followed after 24 h by 250 to 500 mg twice daily with close monitoring of the serum and ultrafiltrate vancomycin concentration.

Acrylic Resins↗

PubMed2006

Are higher vancomycin doses needed in ventricle-external shunted patients?

OBJECTIVE: Hydrocephalus is usually resolved by diverting cerebrospinal fluid through a surgically implanted intra-ventricular catheter (shunt). The aim of this study was to characterize vancomycin pharmacokinetic (PK) parameters and optimal dosage in shunted patients under vancomycin treatment. SETTING: Intensive Care and Neurosurgical Units. University Hospital. METHODS: Retrospective data of vancomycin blood concentrations, demographics and biochemical parameters, from a Therapeutic Drug Monitoring (TDM) program, in ventricle-external shunted patients (Group A) and controls (Group B) were collected. In all subjects, several blood samples at steady state conditions were drawn. Individual PK parameters such as drug clearance (CL) and volume of distribution (V) were estimated by using an one-compartmental PK model and later, dosage regimens were individually adjusted by Bayesian analysis. The obtained CL and V mean +/- standard deviation were compared between both groups (A versus B). Vancomycin dosage regimens between both groups were also compared. MAIN OUTCOME MEASURES: Patients demographics, clinical records, creatinine clearance by Cockcroft-Gault, vancomycin blood levels, vancomycin pK parameters and optimal initial IV vancomycin dosage. RESULTS: Forty-five patients were included in the study: 15 patients in group A and 30 subjects in group B. Significant differences between CL(A) and CL(B) means were observed, while not between V(A) and V(B). In shunted patients, the required vancomycin daily dose to reach target concentrations was significantly higher than the dose needed in the control group (49.25 +/- 12.28 mg/kg/day vs. 31.74 +/- 6.70 mg/kg/day; P < 0.0005). CONCLUSIONS: Greater vancomycin clearance was found in our shunted patients, thus they required higher vancomycin daily doses compared to the control group. Consequently, vancomycin TDM in shunted patients should be advisable in order to guarantee antibiotic blood concentrations within the recommended therapeutic range.

Adult↗

PubMed2001

Association of vancomycin and calcium phosphate by dynamic compaction: in vitro characterization and microbiological activity.

Dynamic compaction has rarely been used to produce drug-delivery devices in granule form. This report considered four processes associating vancomycin and compared dynamic compaction with wet granulation, a classical method. In the wet granulation study, vancomycin was associated with biphasic calcium-phosphate (BCP) granules either by adsorption or incorporation with a new granulation. In the dynamic compaction study, BCP powder was compacted at 1.1, 1.5 and 1.9 MPa. The compacts obtained were crushed and sieved (200-500 microm), and the vancomycin solution was adsorbed on the resulting granules. After crushing and sieving, the compaction of BCP and vancomycin powders produced vancomycin-loaded granules. In each study, 4.76% of vancomycin was associated with BCP. Granules were characterized in terms of porosity, vancomycin release and vancomycin biological activity. Physicochemical studies of BCP and vancomycin showed their structural integrity after dynamic compaction, which prolonged vancomycin release time from 1 to 6 days. However, a microbiological assay indicated that vancomycin had been altered since only 27.7% was found to be active.

Anti-Bacterial Agents↗

PubMed1998

Appropriateness of vancomycin use in the emergency department.

STUDY OBJECTIVE: The emergence of vancomycin-resistant organisms is a major problem at many hospitals. Vancomycin use is associated with development of resistance. The objective of this study was to determine the appropriateness of vancomycin use in the emergency department. In addition, we sought to determine whether appropriateness of vancomycin use increased after the publication of the Centers for Disease Control and Prevention guidelines for prudent vancomycin use. METHODS: This retrospective study was conducted at a tertiary care university hospital, and all patients who received vancomycin while in the ED during the first 6 months of each year from 1995-1997 were eligible for study. We developed appropriateness criteria based on national and local guidelines. Vancomycin use was determined to be appropriate or inappropriate according to these guidelines. RESULTS: Vancomycin use increased each year of the 3-year study period; 40% of use was considered inappropriate. However, appropriateness increased in a linear fashion (P <.001). A resistant organism was cultured from 17% of those with appropriate use and none of those with inappropriate use. Most patients, regardless of the appropriateness of drug use, continued to receive vancomycin after admission. CONCLUSION: Overall vancomycin use rose each year despite an increase in the proportion with appropriate use. However, inappropriate use remained common. Emergency physicians and consultants should become familiar with national and local guidelines for prudent vancomycin use.

Adult↗

PubMed1999

The use of vancomycin and tobramycin in acrylic bone cement: biomechanical effects and elution kinetics for use in joint arthroplasty.

We examined the effects of vancomycin on the compressive strength and fatigue life of bone cement and the pharmacokinetics and antimicrobial activity against methicillin-resistant Staphylococcus aureus of vancomycin eluted from bone cement, both alone and in combination with tobramycin. Two cements, Palacos and Simplex, were tested. Three antibiotic preparations were tested: lyophilized vancomycin (vancomycin-L), vancomycin powder (vancomycin-P), and tobramycin powder (Lilly, Indianapolis, IN). Although antibiotics did not significantly affect compressive strength, the fatigue life of bone cement was significantly decreased with vancomycin. Thus, fatigue testing revealed effects on cement strength not apparent by compression testing. Vancomycin-P had a substantially less detrimental effect on fatigue strength than vancomycin-L. Vancomycin-P elutes less efficiently than tobramycin. Although relatively little vancomycin-P eluted from bone cement, it retained biologic activity.

Anti-Bacterial Agents↗