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PubMed1996

Imipenem or cefoperazone-sulbactam combined with vancomycin for therapy of presumed or proven infection in neutropenic cancer patients.

The purpose of this prospective randomized study was to compare the efficacy and safety of imipenem and cefoperazone-sulbactam combined with vancomycin for the treatment of fever in neutropenic cancer patients. Patients were assigned to either imipenem 500 mg/m2 (500 mg for bone marrow transplant recipients) every 6 h or cefoperazone (2 g)-sulbactam (1 g) every 8 h All patients received vancomycin 1 g every 12 h. A total of 457 febrile or infectious episodes occurring in 407 patients were entered in the study. The response rate was 73% for imipenem plus vancomycin and 74% for cefoperazone-sulbactam plus vancomycin among the 369 episodes that could be evaluated. Response rates were comparable for the two regimens with regard to infecting organism, administration of antimicrobial prophylaxis, and neutrophil count and trend. The frequency of side-effects was significantly higher for imipenem plus vancomycin (11% vs.5%, p = 0.02), due to therapy-associated nausea and vomiting (5.3% vs. 0%, p = 0.0004). The overall frequency of superinfections was similar with both regimens, but Clostridium difficile colitis occurred significantly more often in patients receiving imipenem plus vancomycin (5 vs. 0, p = 0.02). In this study cefoperazone-sulbactam plus vancomycin was an effective alternative to imipenem plus vancomycin for initial therapy of fever in neutropenic patients.

Adolescent↗

PubMed2005

Local delivery of vancomycin for the prophylaxis of prosthetic device-related infections.

PURPOSE: To evaluate the in vivo efficacy and pharmacokinetics of vancomycin delivered from glycerylmonostearate (GMS) implants in a prosthetic-device based biofilm infection model. METHODS: A biofilm infection model was developed in male Sprague-Dawley rats by implanting a vascular graft on the dorsal side of each rat and infecting it with 1.5 x 10(8) cfu/ml Staphylococcus epidermidis. The rats were divided into 3 groups of 6 rats each: 1) the control group that received no antibiotics, 2) the IM group that received multiple IM injections of vancomycin at a dose of 25 mg/kg every 6 h for a total of 12 doses, and 3) the implant group that received GMS implants designed to deliver vancomycin at a total dose of 300 mg/kg for a period of 4 days. The pharmacokinetics of vancomycin was determined from IM and implant groups by analyzing for vancomycin in blood using HPLC. In vivo efficacy was studied by evaluation of the wound site and the prosthetic device upon excision, for evidence of infection in the form of purulent discharge at the wound site and yellowish discoloration of the prosthetic device and inflammation as sign of biofilm formation. Microbiological evaluation on the wound site and the prosthetic device was performed by culturing the swabs at the wound site and the prosthetic device in sterile tryptic soy broth for 36-48 h at 37 degrees C. RESULTS: Vancomycin was successfully delivered in a sustained manner for 100 h from GMS implants and the resulting plasma profile showed that the concentrations, after an initial burst, plateaued at about of 4.77 +/- 1.43 mug/ml with less fluctuations than the IM group in which the plasma concentrations fluctuated between 2.73 +/- 0.94 mug/ml and 19.26 +/- 3.67 mug/ml. Upon excision of the wound site, all the animals in the control group developed infection in the form of purulent discharge and yellowish discoloration of the prosthetic device. However, none of the rats in the implant group showed evidence of infection clearly demonstrating the efficacy of the local delivery system in preventing infection. Systemically delivered vancomycin by IM injections failed to prevent infection in four out of six rats. Microbiological evaluation of the wound site and prosthetic device resulted in isolation of biofilm-producing organisms such as Staphylococcus epidermidis, Enterococcus faecalis, and Staphylococcus aureus. These organisms were isolated in greater number of animals in the control group compared to the IM and implant groups. CONCLUSIONS: The GMS implants as a delivery system for vancomycin were successful in preventing infection in all the animals compared to the IM and control groups demonstrating the efficacy of a local delivery system in a prosthetic device related biofilm infection model.

Animals↗

PubMed1981

Treatment of Clostridium difficile colitis and diarrhea with vancomycin.

Toxigenic Clostridium difficle is the major cause of antibiotic-associated colitis and is susceptible to vancomycin at fecal concentrations achieved with oral therapy. The effect of oral vancomycin was studied in 16 patients with C. difficile-related diarrhea or colitis, 12 of whom had colitis documented by endoscopy, biopsy, and/or barium enema. Four patients had antibiotic-associated diarrhea and possibly antibiotic-associated colitis, because sigmoidoscopy either showed normal results (two patients) or was not performed (two patients). Nineteen episodes of diarrhea were treated with oral vancomycin in two dosage regimens for three to 14 days. Twelve patients received 2 g daily, and four patients initially received 1 g or less per day. Within 48 hours of the start of vancomycin therapy, 14 of 16 patients (87 percent) showed a decrease in temperature, abdominal pain and diarrhea. Diarrhea ceased completely within two days of the start of vancomycin in nine episodes, within three to seven days in six episodes, and within eight to 14 days in the remaining four episodes, and within eight to 14 days in the remaining four episodes. Diarrhea recurred in two of these patients (12 percent) when the drug inciting the initial episode of colitis was given again 42 days or more after vancomycin therapy was stopped; both patients responded again to retreatment with vancomycin. Oral vancomycin is an effective treatment of C. difficile-related colitis and diarrhea.

Adolescent↗

PubMed1995

Trough serum vancomycin levels predict the relapse of gram-positive peritonitis in peritoneal dialysis patients.

We reviewed 31 episodes of gram-positive peritonitis that occurred in our peritoneal dialysis population between 1990 and 1993 in an attempt to identify the risk factor(s) for peritonitis relapse. All patients were treated with 4 weekly doses of intravenous vancomycin. Vancomycin doses no. 1 and 2 were based on body weight (15 mg/kg with a 1-g minimum); vancomycin doses no. 3 and 4 were adjusted in an attempt to maintain the trough serum vancomycin level at greater than 12 mg/L. Nine peritonitis episodes complicated by a relapse were identified. Peritonitis episodes preceding a relapse were similar to relapse-free episodes with respect to patient age, diabetes, peritoneal dialysis modality, duration of peritoneal dialysis treatment, residual urea clearance, peritoneal fluid cell count, causative organism, and weekly vancomycin dose. However, cumulative 4-week mean trough vancomycin levels were consistently lower during peritonitis episodes preceding a relapse (7.8 +/- 0.6 mg/L during relapse-prone episodes v 13.7 +/- 0.9 mg/L during relapse-free episodes; P = 0.0004). Furthermore, relapses developed during nine of 14 peritonitis episodes demonstrating a 4-week mean trough vancomycin level less than 12 mg/L compared with zero of 17 episodes with a 4-week trough level greater than 12 mg/L (P < 0.05). The detection of a low initial 7-day trough vancomycin level also was a useful marker for subsequent peritonitis relapse. In 13 peritonitis episodes associated with an initial trough level less than 9 mg/L, nine were complicated by a relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Gram-Positive Bacterial Infections↗

PubMed1995

Vancomycin removal by high-flux polysulfone hemodialysis membranes in critically ill patients with end-stage renal disease.

To define the pharmacokinetics of vancomycin in patients undergoing maintenance hemodialysis in an acute care setting and to characterize the rebound phenomenon occurring after hemodialysis, vancomycin t1/2 during the interdialytic and intradialytic phases and intradialytic clearance were measured in eight critically ill patients undergoing high-flux hemodialysis using F-80 or F-60 polysulfone dialyzers. Intradialytic clearance was determined using the recovery method. In patients dialyzed with F-80 dialyzers, interdialytic and intradialytic t1/2 for vancomycin were 162 +/- 69.8 hours and 4.7 +/- 1.3 hours, respectively. Intradialytic clearance was 108.5 +/- 16.3 mL/min, and 238 +/- 55 mg of vancomycin was recovered in the dialysate. In patients dialyzed with F-60 dialyzers, interdialytic and intradialytic t1/2 were 211.0 +/- 166.8 and 4.6 +/- 0.4 hours, respectively. Intradialytic clearance was 100.6 +/- 18.3 mL/min and the amount of vancomycin recovered was 252 +/- 79 mg. Vancomycin concentrations rebounded by 16% to 37% between 3 and 6 hours in patients dialyzed with the F-80 dialyzer and 15% to 38% between 2 and 3 hours in patient dialyzed with F-60 dialyzers. Hemodialysis with high-flux polysulfone dialyzers removes significant amounts of vancomycin in patients dialyzed in an acute care setting. A suggested scheme for vancomycin dosage adjustments in these patients is presented.

Adult↗

PubMed2005

The prophylactic efficacy of rifampicin-soaked graft in combination with systemic vancomycin in the prevention of prosthetic vascular graft infection: an experimental study.

OBJECTIVE: To investigate the prophylactic efficacy of systemic, topical, or combined antibiotic usage in the prevention of late prosthetic vascular graft infection caused by methicillin-resistant Staphylococcus epidermidis (MRSE) and the differential adherence of S. epidermidis to Dacron and ePTFE grafts in a rat model. MATERIALS AND METHODS: Graft infections were established in the back subcutaneous tissue of 120 adult male Wistar rats by implantation of 1-cm(2) Dacron/ePTFE prosthesis followed by topical inoculation with 2 x 10(7) CFU of clinical isolate of MRSE. Each of the series included one group with no graft contamination and no antibiotic prophylaxis (uncontaminated control), one contaminated group that did not receive any antibiotic prophylaxis (untreated control), one contaminated group in which perioperative intraperitoneal prophylaxis with vancomycin (10 mg/kg) was administered, two contaminated groups that received rifampicin-soaked (5 mg/1 ml) or vancomycin-soaked (1 mg/1 ml) grafts, and one contaminated group that received a combination of rifampicin-soaked (5 mg/1 ml) graft with perioperative intraperitoneal vancomycin prophylaxis (10 mg/kg). The grafts were removed sterilely 7 days after implantation and evaluated by using sonication and quantitative blood agar culture. RESULTS: MRSE had significantly greater adherence to Dacron than ePTFE grafts in the untreated contaminated groups (P < 0.001). Rifampicin had better efficacy than vancomycin in topical application, but the difference was not statistically significant (P > 0.05). Intraperitoneal vancomycin showed a significantly higher efficacy than topical vancomycin or rifampicin (P < 0.001). The best results were provided by a combination of intraperitoneal vancomycin in rifampicin-soaked graft groups (P < 0.001). CONCLUSIONS: The combination of rifampicin and intraperitoneal vancomycin seems to be the best choice for the prophylaxis of late prosthetic vascular graft infections caused by MRSE.

Animals↗

PubMed2004

Proliferative responses observed following vancomycin treatment in renal proximal tubule epithelial cells.

Vancomycin (VAN) is a glycopeptide antibiotic used to treat gram-positive infections. Nephrotoxicity is a common side effect observed with vancomycin therapy. However, the mechanism of vancomycin-induced nephrotoxicity has not been fully characterized. In this study we examined the effect of vancomycin on cellular proliferation in renal proximal tubule cells. A dose- and time-dependent increase in cell number and total cellular protein was observed following vancomycin exposure. Vancomycin exposure also caused an increase in BrdU incorporation followed by the accumulation of renal proximal tubule cells in G(2)/M phase of the cell cycle. These effects were inhibited by pretreatment with the mitogen-activated protein kinase inhibitor, PD098059, suggesting an association between the cell proliferative effect of VAN and the induction of the mitogen-activated protein kinase signaling pathway. Mitochondrial function in renal proximal tubule cells was assessed using oxygen consumption and ATP concentrations. We observed an increase in oxygen consumption and ATP concentrations following short-term exposure to vancomycin. Together, our data suggest that vancomycin treatment produces alterations in mitochondrial function that coincide with a cell proliferative response in renal proximal tubule epithelial cells.

Adenosine Triphosphate↗

PubMed1992

Vancomycin-enriched corneal storage medium.

Antibiotics in a corneal preservation solution probably have little effect during storage at 4 C, but are effective as the tissue is warmed. The tissue acts as a sponge, soaking up the antibiotic from the solution and releasing it into the eye, where the bactericidal effect is achieved. Currently, high concentrations of gentamicin (relative to the minimal inhibitory concentration) are used in the preserving solution for this purpose. Presumably, proportionately high concentrations of any proposed new antibiotic added to supplement the bactericidal effect of gentamicin, such as the vancomycin used in this study, would be required. However, neither the ability of donor tissue to tolerate high concentrations of vancomycin nor the stability of vancomycin at neutral pH in appropriate storage media has been documented. We evaluated the addition of vancomycin (100 micrograms/ml) to two corneal storage media that contained gentamicin in terms of stability of the antibiotic in solution and the effect on the endothelial cells of donor tissue stored for two weeks at 4 C. Vancomycin was stable in solution at neutral pH (7.2) during the five-month period of the study; the concentration exceeded 90 micrograms/ml for the first five weeks. The endothelial cells from donor tissue stored in the vancomycin-enriched media showed no notable differences from those stored in the same media without vancomycin in terms of cell shape, cell borders, cell swelling, and apical holes. The stability of vancomycin in storage and the absence of endothelial toxicity in vitro support the potential use of this antibiotic as a supplement to gentamicin for the prevention of endophthalmitis in patients receiving corneal transplants.

Aged↗

PubMed2001

[Decreasing susceptibility to vancomycin in isogenic Staphylococcus aureus strains isolated from a single patient].

BACKGROUND: We aimed at evaluating the microbiological characteristics and clinical implication of 7 isogenic strains of Staphylococcus aureus with decreased susceptibility to vancomycin. SUBJECT AND METHOD: A patient with nosocomial trival vularendocarditis due to methicillin-resistant S. aureus had positive blood cultures for 8 weeks despite antimicrobial therapy with vancomycin (normal serum levels) and rifampicin. The patient rejected surgical treatment but the process cured with antimicrobial therapy. The epidemiological relationship of strains was evaluated by pulsed field gel electrophoresis. The susceptibility to vancomycin was evaluated by microdilution and E-test using two different in ocula. The activity of oxacillin, ampicillin and cephalotin was evaluated in Mueller Hinton (MH) agar containing different concentrations of vancomycin (0.06 to 4 mg/l). Heteroresistant subpopulations were determined in both MH and brain heart infussion agar containing vancomycin (0.5 to 512 mg/l). All seven strains belonged to the same clone. Vancomycin MIC ranged from 1 mg/l (isolates 1 to 5) to 4 mg/l (isolates 6 and 7). Isolates 6 and 7 displayed differences in pigmentation and slower growth rates. The susceptibility of these isolates to betalactams inMH containing different concentrations of vancomycin was greater than that in controls. Subpopulations heteroresistant to vancomycin were not detected. CONCLUSION: The decreased susceptibility of the isogenic S. aureus strains evaluated in this study was not due to heteroresistance and did not cause therapeutic failure.

Aged↗

PubMed2000

Vancomycin prescribing practices in hospitalized chronic hemodialysis patients.

To determine the prevalence of and indications for vancomycin administration among hospitalized chronic hemodialysis patients, we performed a 3-month prospective cohort study at a tertiary care center. Modified guidelines for vancomycin use from the Hospital Infections Control Practices Advisory Committee of the Centers for Disease Control and Prevention were used. Vancomycin was administered during 56 of 144 admissions (39%) requiring chronic hemodialysis compared with 336 of 7,212 admissions (5%) not requiring hemodialysis (relative risk, 11; 95% confidence interval, 8 to 15; P < 0.001). Among chronic hemodialysis patients, vancomycin use was judged appropriate for 131 of the 164 vancomycin doses (80%). The most common appropriate indication was empiric therapy in a febrile patient before culture or susceptibility results. Of 32 infections identified in patients who received empiric vancomycin, 15 infections (47%) were caused by beta-lactam-resistant pathogens. Among the 33 doses (20%) judged inappropriate, continued therapy for a presumed infection despite failure to identify a beta-lactam-resistant pathogen was the most common indication. Although vancomycin administration was frequent among hospitalized chronic hemodialysis patients, its use was justified in the majority of cases. Efforts should focus on limiting vancomycin administration for treating infections caused by beta-lactam-sensitive pathogens.

Adult↗

PubMed1999

Rifampicin as an adjunct to vancomycin therapy in MRSA septicaemia in burns.

Rifampicin has been successfully used as an adjunct to vancomycin therapy in several clinical conditions of MRSA infections such as endocarditis, ventriculoperitoneal shunts and septicaemia. However, very little information is available in the literature regarding its use in MRSA septicaemia in burns. The present prospective study was conducted to evaluate the efficacy of rifampicin as an adjunct therapy in burn cases with MRSA septicaemia not responding well to vancomycin. Fourteen out of 36 MRSA septicaemia patients with burns who either did not or only partially responded to therapeutic doses of vancomycin within 5-6 days were treated with rifampicin as an adjunct therapy (600 mg, i.v., o.d) for 5 days during the study period between January 1995 to December 1998. All the patients had burns due to flame and the TBSA varied between 20-90% with a mean of 64%. Eleven patients had deep and three had mixed burns. MRSA septicaemic episodes usually followed 2 3 days of detection of the organism in burn wounds. All the isolates were sensitive to vancomycin with an MIC of < or = 1.0 mg/L and were treated with vancomycin, (500 mg, i.v., 6 hourly). The serum vancomycin levels in all the patients were within the therapeutic range. However, blood cultures still remained positive even after 5-6 days of therapy. Institution of rifampicin, as an adjunct to vancomycin therapy to which the MRSA isolates were susceptible, showed a dramatic clinical response and survival of grafts. Thirteen patients survived and one died who had 70% deep burns and blood cultures revealed a multiresistant Acinetobacter in addition to MRSA. The present study thus confirms the efficacy of clinical use of rifampicin as an adjunct in vancomycin nonresponding cases of MRSA septicaemia in burns.

Adolescent↗

PubMed1998

A ligand-mediated dimerization mode for vancomycin.

BACKGROUND: Vancomycin and related glycopeptide antibiotics exert their antimicrobial effect by binding to carboxy-terminal peptide targets in the bacterial cell wall and preventing the biosynthesis of peptidoglycan. Bacteria can resist the action of these agents by replacing the peptide targets with depsipeptides. Rational efforts to design new agents effective against resistant bacteria require a thorough understanding of the structural determinants of peptide recognition by vancomycin. RESULTS: The crystal structure of vancomycin in complex with N-acetyl-D-alanine has been determined at atomic resolution. Two different oligomeric interactions are seen in the structure: back-to-back dimers, as previously described for the vancomycin-acetate complex, and novel face-to-face dimers, mediated largely by the bound ligands. Models of longer, naturally occurring peptide ligands may be built by extension of N-acetyl-D-alanine. These larger ligands can form an extensive array of polar and nonpolar interactions with two vancomycin monomers in the face-to-face configuration. CONCLUSIONS: A new dimeric form of vancomycin has been found in which two monomers are related in a face-to-face configuration, and bound ligands comprise a large portion of the dimer interface. The relative importance of face-to-face and back-to-back dimers to the antimicrobial activity of vancomycin remains to be established, but face-to-face interactions appear to explain how increased antimicrobial activity may arise in covalent vancomycin dimers.

Anti-Bacterial Agents↗

PubMed2000

Vancomycin anaphylaxis and successful desensitization in a patient with end stage renal disease on hemodialysis by maintaining steady antibiotic levels.

BACKGROUND: Vancomycin anaphylaxis is a major management problem in patients with methicillin-resistant Staphylococcus aureus (MRSA) sepsis. Lerner et al in 1984 have described a protocol for desensitization to vancomycin; however, antibiotic blood levels have never been used as a guide in this process. CASE REPORT: A 46-year-old female with ESRD on hemodialysis who developed a dialysis-catheter related MRSA sepsis was found to have anaphylaxis to vancomycin. She underwent successful desensitization to vancomycin using Lerner's protocol. Periodic antibiotic blood levels were used to guide the amount and frequency of vancomycin infusion to successfully maintain desensitization thereafter. DISCUSSION: Lerner described loss of desensitization to vancomycin when antibiotic infusion was stopped after 18 hours followed by successful desensitization to the same drug via the same protocol. This observation points out that desensitization to vancomycin appears to be dependent on some minimal drug level. In our case report, we have for the first time used the concept of blood levels to maintain successful desensitization to an antibiotic. CONCLUSION: We hypothesize that desensitization to vancomycin can be induced and maintained by keeping a minimum antibiotic blood level. Further studies are needed to quantify this.

Anaphylaxis↗

PubMed2001

Formulation and evaluation of a folic acid receptor-targeted oral vancomycin liposomal dosage form.

PURPOSE: To demonstrate utility of folic acid-coated liposomes for enhancing the delivery of a poorly absorbed glycopeptide, vancomycin. via the oral route. METHODS: Liposomes prepared as dehydration-rehydration vesicles (DRVs) containing vancomycin were optimized for encapsulation efficiency and stability. A folic acid-poly(ethylene oxide)-cholesterol construct was synthesized for adsorption at DRV surfaces. Liposomes were characterized by differential scanning calorimetry (DSC) and assessed in vitro in the Caco-2 cell model and in vivo in male Sprague-Dawley rats. Non-compartmental pharmacokinetic analysis of vancomycin was conducted after intravenous and oral administration of solution or liposome-encapsulated vancomycin with or without 0.05 mole ratio FA-PEO-Chol adsorbed at liposome surfaces. RESULTS: Optimal loading of vancomycin (32%) was achieved in DRVs of DSPC:Chol:DCP, 3:1:0.25 mole ratio (m.r.) after liposome extrusion. Liposomes released less than 40% of the entrapped drug after 2 hours incubation in simulated gastrointestinal (GI) fluid and simulated intestinal fluid containing a 10 mM bile salt cocktail. Incorporation of FA-PEO-Chol in liposomes increased drug leakage by 20% but resulted in a 5.7-fold increase in Caco-2 cell uptake of vancomycin. Liposomal delivery significantly increased the area under the curve of oral vancomycin resulting in a mean 3.9-fold and 12.5-fold increase in relative bioavailability for uncoated and FA-PEO-Chol-coated liposomes, respectively, compared with an oral solution. CONCLUSIONS: The design of FA-PEO-Chol-coated liposomes resulted in a dramatic increase in the oral delivery of a moderate-size glycopeptide in the rat compared with uncoated liposomes or oral solution. It is speculated that the cause of the observed effect was due to binding of liposome-surface folic acid to receptors in the GI tract with subsequent receptor-mediated endocytosis of entrapped vancomycin by enterocytes.

Algorithms↗

PubMed2006

An in vitro study on the compatibility and concentrations of combinations of vancomycin, amikacin, and dexamethasone in human vitreous.

PURPOSE: To investigate the precipitation process of a mixture of vancomycin, amikacin, and dexamethasone by equilibrium dialysis and its subsequent effect on the levels of available-free antibiotics and steroid. METHODS: Concentrations of amikacin, vancomycin, and dexamethasone in an equilibrium dialysis chamber were measured during the equilibrium process by high-performance liquid chromatography and fluorescence polarisation immunoassay. Vitreous were used as the medium of dialysis, with the three medications prepared in normal saline (NS) and balanced salt solution plus (BSS Plus) separately. RESULTS: Amikacin showed no measurable loss in NS or BSS Plus, either alone or when mixed with vancomycin or dexamethasone. Vancomycin showed minimal loss in BSS Plus, either alone or when mixed with amikacin or dexamethasone. Dexamethasone showed a median loss of 16 and 15% when incubated alone in NS and BSS Plus, respectively, at 48 h. When mixed with vancomycin or amikacin in BSS Plus, it showed a median loss of 13 and 12%, respectively, at 48 h. There was no statistically significant difference in the loss of dexamethasone under various conditions. In equilibrium dialysis in vitreous, amikacin, vancomycin, and dexamethasone reached equilibrium within 24 h and with no loss up to 192 h. There was no difference observed when the medications were prepared in NS or BSS Plus. CONCLUSIONS: Both amikacin and vancomycin did not show precipitation or decrease in concentration in NS or BSS Plus. Dexamethasone showed relatively small percentage loss. As a result, treatment of endophthalmitis with vancomycin and amikacin combination is preferred.

Amikacin↗

PubMed2005

Adequacy of a vancomycin dosing regimen in patients receiving high-flux hemodialysis.

BACKGROUND: Some investigators have recommended the convenient practice of administering vancomycin doses during the last hour of the hemodialysis treatment. Accepting that a greater amount of vancomycin is lost to dialysis with this recent approach, the objective of this study is to determine the pharmacokinetics of vancomycin and assess the adequacy of this dosing regimen in maintaining therapeutic predialysis concentrations. METHODS: A sampling of 22 consecutive patients administered intradialytic vancomycin, 1 g, intravenously (IV) and maintenance doses of 500 mg during the last hour of high-flux dialysis sessions was studied. A population-modeling program and Bayesian pharmacokinetic analysis were used to identify all global and unique pharmacokinetic parameters of interest based on measured vancomycin predialysis concentrations. RESULTS: For the 22 patients studied, this regimen achieved the targeted predialysis concentration range of 5 to 20 microg/mL for 96% of levels, whereas more narrowly within 5 to 15 microg/mL for 86% of levels. Average amount of vancomycin removed during a standardized 3- to 4-hour dialytic session ranged from 30% +/- 7% to 38% +/- 8%. Average elimination half-life of vancomycin on hemodialysis treatment was 5.4 hours (interquartile range, 5.0 to 5.9 hours). Patients showed an average predialysis plasma concentration of 11 +/- 3 microg/mL for the first 7 days of therapy. CONCLUSION: Our results indicate that intradialytic dosing with vancomycin using a 1-g IV load and 500 mg IV with subsequent high-flux dialysis sessions conveniently maintains adequate predialysis plasma concentrations. The lack of drug accumulation with this regimen provides convincing support for a limited blood sampling approach to plasma concentration determinations.

Adult↗

PubMed2002

Vancomycin sequestration during cardiopulmonary bypass surgery.

OBJECTIVE: The present study was designed to analyze vancomycin disposition in adult patients undergoing coronary bypass grafting during and following cardiopulmonary bypass (CPB). METHODS: Coronary bypass surgery was performed on 11 adults with a mean age (SD) of 62.9 (9.0) years old, who received a mean (SD) vancomycin prophylactic dose of 12.7 (1.0) mg/kg in a mean period of 41 (0.7) min. Using a two-compartment open model for pharmacokinetic analysis, the following parameters were obtained: alpha half-life, minutes (t(1/2alpha)); beta half-life, hours (t(1/2beta)); apparent volume of distribution, (V(d) l/kg); volume of the central compartment, (V(c) l/kg), constant between the "central to the peripheral" compartment, (k(12)); constant between the "peripheral to the central" compartment, (k(21)); total area under the concentration-time curve, (AUC mg/lxh) and a vancomycin clearance, (Cl(van) ml/min), respectively. RESULTS: The mean (SD) calculated pharmacokinetic parameters were: t(1/2alpha)17.6 (6) min, t(1/2beta) 8.4 (3.8) h, V(d) 0.803 (0.259) l/kg, V(c) 0.270 (0.162) l/kg, k(12) 0.03 (0.015), k(21) 0.012 (0.012), total AUC 10377.2 (3687.6) mg/lxh. The mean (SD) vancomycin clearance by the CPB machine was 9.51 (2.66) l/h, and the mean (SD) total vancomycin sequestrated by CPB was 331.7 (84) mg. A significant difference (6.3%; p = 0.001) was measured between the mean measured AUC during CPB (1088.1 +/- 253.9) and the same calculated parameter (1160.2 +/- 282). Five minutes after starting CPB, a decrease in vancomycin level was detected; this difference was found to be nearly 11% in absolute values. CONCLUSIONS: This confirmatory study demonstrated that the vancomycin blood concentrations obtained during the study allow recommending a safety prophylactic dose of 12mg/kg in adults who undergo open-heart surgery under CPB conditions. Sequestration of vancomycin by the oxygenator or/and tubing system of the CPB machine had occurred and had been measured in this study.

Aged↗

PubMed2002

The in vitro elution characteristics of vancomycin combined with imipenem-cilastatin in acrylic bone-cements: a pharmacokinetic study.

The aim of this in vitro study was to compare the elution characteristics of vancomycin alone and in combination with imipenem-cilastatin from 3 acrylic bone-cements (CMW1 [DePuy International, Blackpool, UK], Palacos R [Schering-Plough, Wehrheim, Germany], and Simplex P [Howmedica International, London, UK]). Six groups of 3 antibiotic-loaded cement disks were prepared, incorporating 2 g of vancomycin (3 groups) and 2 g of vancomycin plus 2 g of imipenem-cilastatin (3 groups). The disks were placed in saline baths for 5 weeks, with the baths being sampled periodically and the elution rates calculated. The total amount of vancomycin released by the cements treated with vancomycin alone was 7.98 mg for CMW1, 7.74 mg for Palacos R, and 6.76 mg for Simplex P; with the addition of imipenem-cilastatin, the total amount of vancomycin released by the 3 cements increased by 30.58%, 50.52%, and 50.15%. CMW1 had better elution characteristics than the other cements when treated with vancomycin alone; the elution of Palacos R and Simplex P was better than that of CMW1 when vancomycin was combined with imipenem-cilastatin.

Acrylic Resins↗