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Vancomycin serum protein binding determination by ultrafiltration.

Sixty-two serum concentrations were obtained from 12 infected patients enrolled in a vancomycin pharmacokinetic study. Both unbound and total serum vancomycin concentrations were measured using ultrafiltration and a commercial fluorescent polarization immunoassay. Ultrafiltrates were obtained by centrifugation at 1000 X g for ten minutes at room temperature and their assay indicated a range in protein binding from 7.9 to 71 percent. The mean protein binding (mean +/- SD) was 41.95 +/- 14.15 percent. No measurable adsorption of vancomycin onto the ultrafiltration membrane was noted. Orthogonal regression of unbound versus total vancomycin concentrations was described by the equation y = 0.597x-0.362 with a correlation coefficient of 0.948.

Adult↗

Use of vancomycin and tobramycin polymethylmethacrylate impregnated beads in the management of chronic osteomyelitis.

Over the past several years there has been a growing interest in the use of locally implanted beads containing antibiotics for the treatment of chronic osteomyelitis. This method has been popularized in Europe and, with few exceptions, gentamicin has been the only antibiotic used. There have been only a few reports from the U.S. and there is little information regarding the pharmacokinetics of antibiotics used in this fashion. To our knowledge this is the first report using vancomycin. Three patients with chronic osteomyelitis were treated with vancomycin and/or tobramycin polymethylmethacrylate beads. These beads were extemporaneously compounded and implanted for up to six weeks. From the site of bead implantation local fluid aliquots were collected for the measurement of antibiotic concentrations. In two patients, initial tobramycin concentrations exceeded 400 mg/L. In one patient receiving vancomycin, initial localized concentrations were approximately 100 mg/L. In all three patients therapeutic concentrations of localized antibiotic were maintained with immeasurable systemic concentrations throughout the period of bead placement. Localized antibiotic therapy for the management of chronic osteomyelitis represents a potential therapeutic alternative to long-term parenteral therapy. Data presented here suggest that other antibiotics, such as vancomycin and tobramycin, can be used successfully in polymethylmethacrylate beads and provide preliminary facts for future investigations of such applications.

Adult↗

Paresthesia and back pain in a patient receiving vancomycin during hemodialysis.

A 36-year-old woman was admitted for initiation of hemodialysis for chronic renal failure. Two days after catheter placement the patient developed a fever that persisted and resulted in subsequent removal of the catheter. Although blood cultures were negative, cultures of the catheter tip were positive for Staphylococcus epidermidis. An initial vancomycin dose was well tolerated, but the patient later experienced numbness and tingling of her lower back accompanied by pain ten minutes after initiation of the second dose. Symptoms abated when the vancomycin infusion was discontinued, and the drug was subsequently well tolerated when reinstituted at a slower infusion rate. Similar symptoms were observed five minutes into a vancomycin infusion a week later that also resolved after decreasing the infusion rate. Patients on hemodialysis receiving vancomycin should be carefully monitored during drug administration for the development of paresthesia and spasmodic lower back pain.

Adult↗

Vancomycin-associated exfoliative dermatitis.

We describe a 51-year-old patient with endstage renal disease who developed vancomycin-associated exfoliative dermatitis. After four weeks of vancomycin hydrochloride treatment for staphylococcal pericarditis this patient developed a hypersensitivity reaction characterized by intermittent fevers, lymphadenopathy, peripheral eosinophilia, and exfoliative dermatitis. The reaction persisted for five weeks, probably because of inability to rapidly eliminate vancomycin secondary to underlying renal failure. Maculopapular rashes have been reported in two to six percent of patients who receive this drug, with severe skin reactions rarely reported. In addition to this case report, a review of the literature including 11 Eli Lilly/Food and Drug Administration case reports is presented. Although severe skin reactions to vancomycin rarely occur, they prolong morbidity, particularly in patients with renal failure.

Dermatitis, Exfoliative↗

Gentamicin and vancomycin removal by continuous venovenous hemofiltration.

The dispositions and dose requirements for vancomycin and gentamicin were investigated in a 58-year-old man who was receiving long-term continuous venovenous hemofiltration. Estimates of clearance were obtained using a Bayesian parameter estimation program and stayed remarkably consistent throughout the therapy. Single daily doses of both vancomycin and gentamicin generally maintained the profiles for both drugs around the target ranges of peak 5-10 mg/L (gentamicin) and 25-40 mg/L (vancomycin) and trough less than 2 mg/L (gentamicin) and less than 10 mg/L (vancomycin).

Bayes Theorem↗

Aerosolized vancomycin therapy facilitating nursing home placement.

OBJECTIVE: To demonstrate a novel method of eliminating nasopharyngeal colonization by methicillin-resistant Staphylococcus aureus (MRSA) in a debilitated, hospitalized patient. DESIGN: Single-patient, nonblind, nonplacebo, case study. SETTING: Community hospital, Brooklyn, NY. PATIENT: Hospitalized patient with recalcitrant nasopharyngeal MRSA colonization that could not be eliminated by conventional therapeutic interventions. INTERVENTIONS: Aerosolized vancomycin hydrochloride 120 mg q6h administered in room air via face mask together with vancomycin nasal drops, 2 drops to each nostril q6h. MAIN OUTCOME MEASURE: Elimination of MRSA from the nasopharynx of the patient. RESULTS: Successful elimination of MRSA colonization after four days of therapy. CONCLUSIONS: Aerosolized vancomycin in combination with vancomycin nasal drops is beneficial in eliminating nasopharyngeal colonization by MRSA. Clinical trials are warranted to confirm this clinical observation.

Administration, Inhalation↗

Elution of vancomycin and tobramycin bonded to vascular grafts.

The elution of vancomycin and tobramycin from vascular grafts sealed with collagen and human blood was studied in vitro. The release of antibiotics was measured in three different types of soaked grafts, including grafts soaked with antibiotic after being sealed with albumin, those sealed with antibiotic and albumin mixture and those impregnated with fresh blood and antibiotic mixture. Each antibiotic was tested at two different concentrations, i.e. 5 mg/ml and 10 mg/ml for vancomycin and 2 mg/ml and 5 mg/ml for tobramycin. The eluted antibiotic concentrations were determined by the fluorescence polarization immunoassay. Initially large quantities of antibiotics were quickly eluted, depending on the amount of antibiotic mixture. A measurable amount of vancomycin was released for 3 days. There was no difference between the elution kinetics of the two antibiotics from the three different soaked grafts (p>0.05). Antibiotic-soaked grafts provided zones of inhibition against Staphylococcus aureus on Trypticase soy agar plate for up to 24 h. These results suggest that local application for 24 h of vancomycin or tobramycin with vascular grafts may be effective to prevent graft infection as shown by the fluorescence polarization immunoassay.

Analysis of Variance↗

The resazurin microplate method for rapid detection of vancomycin resistance in enterococci.

Vancomycin-resistant enterococci (VRE) are a serious challenge for physicians because of the limited treatment options for infections caused by this organism. Prevention of VRE transmission in hospitals requires early detection of infected or colonized patients. Therefore rapid and correct detection of vancomycin resistance is essential. In this study, we use the resazurin microplate method (RMM), which is a modification of the NCCLS and BSAC broth microdilution methods to rapidly determine the susceptibilities of clinical enterococci isolates to vancomycin. The alteration in the RMM was relevant to the final bacterial count. In this method, inoculum that was 10-fold higher than standard methods was used. A total of 80 enterococci, including 11 VRE isolates and 6 vancomycin intermediate isolates, were screened with this modified colorimetric broth microdilution method. After 4 h of incubation 30 microl of 0.01% resazurin solution were added to each well and the plates were reincubated for color change for 5-10 min. The MICs were obtained at the 4th h. The results were in exact agreement with the NCCLS and the BSAC microdilution methods. Absolute and essential agreements were 100% and there were no minor, major or very major errors. In conclusion, this modified colorimetric broth microdilution method can be used as a reliable, easy, cheap and rapid method for early detection of VRE. Moreover, this method has the potential of being used to test the susceptibilities of different bacteria to other antibiotics.

Colony Count, Microbial↗

Clinical review: use of vancomycin in haemodialysis patients.

Following intravenous administration, vancomycin is poorly metabolized and is mainly excreted unchanged in urine. Total body clearance is thus dependent on the kidney, and is correlated with glomerular filtration rate and creatinine clearance. Accumulation of vancomycin in patients with renal insufficiency may therefore occur, and this may lead to toxic side effects if dosage is not modified according to the degree of renal failure. Furthermore, vancomycin easily diffuses through dialysis membranes. The aim of the present review is to establish guidelines for handling this drug in such patients. We indicate how and when plasma concentrations of vancomycin should be determined in dialysis patients.

Anti-Bacterial Agents↗

Prevention of gram-positive infections after bone marrow transplantation by systemic vancomycin: a prospective, randomized trial.

Gram-positive bacteria are the most commonly isolated organisms after bone marrow transplantation (BMT) and severe streptococcus septicemia has been reported. In order to evaluate the benefit of a gram-positive prophylaxis after BMT, we conducted a prospective, randomized trial of systemic vancomycin among 60 patients undergoing BMT for hematologic malignancies. Patients were randomized to receive (n = 30) or not receive (n = 30) prophylactic vancomycin 15 mg/kg every 12 hours from day -2 until resolution of neutropenia or until the first episode of fever. All patients were treated in laminar air-flow rooms, received sterile diet, total gut decontamination, and had central venous catheters placed surgically. Vancomycin was found to be highly effective in preventing gram-positive infections that occurred in 11 of 30 patients in the control group versus zero of 30 in the vancomycin group (P less than .002). All gram-positive infections occurring in the control group were symptomatic (nine septicemia and two local infections), and one patient with Streptococcus septicemia died with pneumonia. Thus, gram-positive prophylaxis was found to decrease infection morbidity after BMT. Moreover, the number of days with fever (P less than .001), and empiric antibiotic therapy (P less than .01) was reduced without added toxicity or cost. This study confirmed the high prevalence of gram-positive infections after BMT and emphasized the clinical benefits of an adapted prophylaxis.

Adolescent↗

Vancomycin penetration of a brain abscess: case report and review of the literature.

A 56-year-old man developed an abscess within a right parietal cystic anaplastic astrocytoma 3 days after removal of iodine-125 sources placed 9 days earlier for interstitial radiation therapy. After treatment with cephalosporin antibiotics proved unsuccessful, the patient was treated with intravenous vancomycin and intermittent percutaneous drainage of the abscess. Vancomycin levels obtained from the brain abscess fluid, both before and during later operative removal of the abscess, were 15 and 18 micrograms/ml, respectively; the serum vancomycin level was 21 micrograms/ml. This is the first report of the excellent penetration of vancomycin into brain abscess fluid.

Astrocytoma↗

Influences of everninomicin, vancomycin and teicoplanin on chemical mediator release from rat peritoneal mast cells.

We examined influences of certain antibiotics on the release of chemical mediators from isolated rat peritoneal mast cells in vitro. Isolated peritoneal mast cells were obtained from male Wistar strain rats. Everninomicin (0.06-1.2 mg/ml), vancomycin (0.05-1.0 mg/ml), teicoplanin (0.07-1.4 mg/ml) and concanavalin A (0.01 mg/ml) were used. Isolated mast cells were incubated in the presence of various concentrations of the test compound at 37 degrees C for 10 min. Histamine contents of the supernatant and cell pellet were measured by an automated fluorometric method. Prostaglandin D2 (PGD2) contents of the supernatant were determined by enzyme immunoassay. Everninomicin (0.06-1.2 mg/ml) had no influence on histamine and PGD2 release from mast cells. On the other hand, vancomycin significantly released both histamine (0.5 and 1.0 mg/ml) and PGD2 (1.0 mg/ml) from mast cells, but vancomycin did not affect concanavalin A-induced histamine and PGD2 release. Teicoplanin (more than 0.07 mg/ml) significantly stimulated histamine and PGD2 release from mast cells and it also significantly potentiated concanavalin A-induced histamine and PGD2 release. These results suggest that everninomicin causes no chemical mediator release from mast cells, different from vancomycin and teicoplanin.

Aminoglycosides↗

Vancomycin-supplemented impacted bone allografts in infected hip arthroplasty. Two-stage revision results.

Bone allografts can store and release high levels of vancomycin. We present our results of a two-stage treatment for infected hip arthroplasty with acetabular and femoral impaction grafting using vancomycin-loaded allografts. We treated 29 patients (30 hips) by removal of the implants, meticulous debridement, parenteral antibiotic therapy and second-stage reconstruction using vancomycin-supplemented impacted bone allografts and a standard, cemented Charnley femoral component. The mean follow-up was 32.4 months (24 to 60). Infection control was obtained in 29 cases (re-infection rate of 3.3%; 95% confidence interval 0.08 to 17) without evidence of progressive radiolucent lines, demarcation or graft resorption. One patient had a further infection ten months after revision caused by a different pathogen. Associated post-operative complications were one traumatic periprosthetic fracture at 14 months, a single dislocation in two hips and four displacements of the greater trochanter. Vancomycin-supplemented allografts restored bone stock and provided sound fixation with a low incidence of further infection.

Adult↗

Comparison of two commercially available selective media to screen for vancomycin-resistant enterococci.

Campylobacter medium (CAMPY, Becton Dickinson [BD] Microbiology Systems, Cockeysville, MD) and Vancomycin Screen Agar (VSA, BD) were compared for their ability to screen for vancomycin-resistant Enterococcus (VRE) from primary plates. A microdilution minimal inhibitory concentration (MIC) assay (Pasco, BD) served as the reference vancomycin MIC. In the random sample of 200 enterococcal clinical isolates tested, the distribution of isolates was as follows: Enterococcus faecium, 113 (97 VRE); Enterococcus faecalis, 71(12 VRE); Enterococcus gallinarum, 10; and Enterococcus casseliflavus, 6. Of the 75 vancomycin-susceptible strains, none grew on CAMPY and 4 grew on VSA, whereas all 109 VRE isolates grew on both screen plates. Of the 16 strains with a Van C phenotype, ie, E. gallinarum and E. casseliflavus, 2 grew on CAMPY and 14 on VSA. Of the 899 clinical specimens plated onto both agars, 45 of 67 VRE were detected with both media, 20 were detected only with CAMPY and 2 were not detected by either screen plate. CAMPY compared with VSA as a primary plating medium was more sensitive and, when used to screen for VRE isolates from primary plates, was more specific for strains displaying Van A and B phenotypes.

Culture Media↗

Vancomycin intermediate-resistant Staphylococcus aureus.

OBJECTIVE: To describe further details about the third reported case of vancomycin intermediate-resistant Staphylococcus aureus (VISA). CASE SUMMARY: A patient with a history of recurrent methicillin-resistant S. aureus (MRSA) bacteremia was treated with several courses of vancomycin for 18 of 23 possible weeks on an inpatient/outpatient basis. After 6 months of repeated courses, an isolate of MRSA showed a minimum inhibitory concentration of 8 micrograms/mL, indicating intermediate resistance to vancomycin. The patient continued to receive a vancomycin/aminoglycoside/rifampin regimen and, when he was hospitalized several weeks later, no further MRSA or VISA was detected. DISCUSSION: Prolonged, intermittent vancomycin use (18 of 23 possible weeks) for MRSA bacteremia on an inpatient/outpatient basis most likely contributed to the development of VISA. Infection control measures prevented the spread of VISA among patients and healthcare workers. CONCLUSIONS: Infection control measures and evaluation of antimicrobial prescribing need to be strongly enforced to further prevent the spread and development of resistant organisms.

Aged↗

Proton pump inhibitor use and risk of community-acquired Clostridium difficile-associated disease defined by prescription for oral vancomycin therapy.

BACKGROUND: The association between the use of proton pump inhibitors and the risk of Clostridium difficile-associated disease (CDAD) is controversial. In this study we re-examined a previously reported association between the use of proton pump inhibitors and the development of community-acquired CDAD, this time using an alternative case definition of the disease. METHODS: We performed a case-control study of community-acquired CDAD using a United Kingdom clinical research database. Patients receiving oral vancomycin therapy were identified as having CDAD, the only indication for this drug. Each case subject was matched with up to 10 control subjects. Neither the cases nor the controls had been admitted to hospital in the year before the date of the vancomycin prescription (index date). Conditional logistic regression analysis was used to adjust for key covariates. RESULTS: We identified 317 cases of community-acquired CDAD treated with oral vancomycin therapy and 3167 matched control subjects. Exposure to a proton pump inhibitor in the 90 days before the index date was associated with an increased risk of CDAD (odds ratio [OR] 3.5, 95% confidence interval [CI] 2.3-5.2). Antibiotic exposure in the 90 days before the index date was also a significant risk factor for community-acquired CDAD (OR 8.2, 95% CI 6.1- 11.0), even though 45% of the case subjects had not received a prescription for an antibiotic during that period. Certain comorbidities, in particular renal failure, inflammatory bowel disease and malignant disease, as well as prior methicillin-resistant Staphylococcus aureus infection, were also associated with an increased risk. INTERPRETATION: Proton pump inhibitor use was associated with an increased risk of community-acquired CDAD, when cases were defined by receipt of prescription for oral vancomycin therapy. Prior antibiotic exposure was also a significant risk factor, but a significant proportion of the patients with community-acquired CDAD had no such exposure.

Aged↗

Comparison of vancomycin and teicoplanin for prophylaxis of sepsis with coagulase negative staphylococci (CONS) in very low birth weight (VLBW) infants.

A prospective randomized study was performed to evaluate the efficacy of a low dose (5 mg/kg/day bid) vancomycin compared with a low dose (5 mg/kg/day once daily) teicoplanin therapy to prevent CONS sepsis in VLBW-infants. All infants received this therapy after their 4th day of life or after an eventual therapy of early onset sepsis as long as an i.v. line was in place or 1500 g body weight. Twenty-seven infants were treated with vancomycin (birth weight 1103 +/- 286 g, gest. age 28.8 +/- 1.9 weeks), 28 with teicoplanin (birth weight 1133 +/- 226 g, gest. age 29.04 +/- 2.2 weeks). The infants were observed for clinical and laboratory signs of sepsis. On day 4 of therapy and every 3rd day during therapy serum creatinine levels, tracheal aspirates, stool cultures and vancomycin/teicoplanin peak and trough levels were obtained. We could not detect any case of blood culture positive sepsis and 1 case of suspected sepsis (neg. blood cultures) in both groups, as compared with a former CONS sepsis rate of 24% in our institution's VLBW infants without antibiotic prophylaxis. Nine patients in the vancomycin and five in the teicoplanin group had tracheal colonization with CONS. In both groups peak and trough levels of antibiotics were in the bactericidal range. Serum creatinine was not normal in both groups. We conclude that teicoplanin is preventing CONS sepsis as well is vancomycin. The minimal inhibitory concentrations of both antibiotics against grampositive isolates in units using this strategy have to be observed carefully to detect emerging resistance.

Anti-Bacterial Agents↗

[Incidence of vancomycin-resistant Enterococcus at a university hospital in Brazil].

OBJECTIVE: Vancomycin-resistant Enterococcus (VRE) is today one of the principal microorganisms implicated in nosocomial infections. Thus, a study was carried out with the objective of evaluating its epidemiology at a tertiary-level teaching hospital. METHODS: This was a three-year retrospective epidemiological study conducted from 2000 to 2002. Samples of VRE-positive clinical cultures at a 660-bed university hospital were analyzed. The incidence of VRE and the main anatomical sites and hospital units from which it was isolated were defined. Differences between the variables over the three years of the study were verified, and these were considered significant when p<0.05. RESULTS: There was a progressive increase in the vancomycin resistance in the clinical cultures that were positive for Enterococcus spp., over the three years of the study. In 2000, 9.5% of the samples were vancomycin-resistant, and this increased to 14.7% in 2001 and 15.8% in 2002. The hospital units with the largest numbers of isolates were, respectively, the emergency ward (19.5%) and the general intensive care unit (15%). The anatomical sites with the highest amounts of isolates included: urine (36%) and blood (20%). CONCLUSIONS: With the progressive increase in the incidence of vancomycin resistance and the VRE rate, it is concluded that more effective control measures are needed for deterring the dissemination of VRE.

Brazil↗