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PubMedDate not supplied

Monitoring the treatment of sepsis with vancomycin in term newborn infants.

UNLABELLED: A prospective study was conducted to determine if standardized vancomycin doses could produce adequate serum concentrations in 25 term newborn infants with sepsis. PURPOSE: The therapeutic response of neonatal sepsis by Staphylococcus sp. treated with vancomycin was evaluated through serum concentrations of vancomycin, serum bactericidal titers (SBT), and minimum inhibitory concentration (MIC). METHOD: Vancomycin serum concentrations were determined by the fluorescence polarization immunoassay technique, SBT by the macro-broth dilution method, and MIC by diffusion test in agar. RESULTS: Thirteen newborn infants (59.1%) had adequate peak vancomycin serum concentrations (20 - 40 mg/mL) and one had peak concentration with potential ototoxicity risk (>40 microg/mL). Only 48% had adequate trough concentrations (5 - 10 mg/mL), and seven (28%) had a potential nephrotoxicity risk (>10 microg/mL). There was no significant agreement regarding normality for peak and trough vancomycin method (McNemar test : p = 0.7905). Peak serum vancomycin concentrations were compared with the clinical evaluation (good or bad clinical evolution) of the infants, with no significant difference found (U=51.5; p=0.1947). There was also no significant difference between the patients' trough concentrations and good or bad clinical evolution (U = 77.0; p=0.1710). All Staphylococcus isolates were sensitive to vancomycin according to the MIC. Half of the patients with adequate trough SBT (1/8), also had adequate trough vancomycin concentrations and satisfactory clinical evolution. CONCLUSIONS: Recommended vancomycin schedules for term newborn infants with neonatal sepsis should be based on the weight and postconceptual age only to start antimicrobial therapy. There is no ideal pattern of vancomycin dosing; vancomycin dosages must be individualized. SBT interpretation should be made in conjunction with the patient's clinical presentation and vancomycin serum concentrations. Those laboratory and clinical data favor elucidation of the probable cause of patient's bad evolution, which would facilitate drug adjustment and reduce the risk of toxicity or failing to achieve therapeutic doses.

Anti-Bacterial Agents↗

PubMed1995

Pharmacokinetic optimisation of vancomycin therapy.

Renewed interest in vancomycin over the past decade has led to an abundance of data concerning the pharmacokinetics of vancomycin, and its dosage selection and concentration-response relationships. No definitive data exist that correlate vancomycin serum concentrations with clinical outcomes. However, inconsistencies in sampling times for peak serum concentrations and differences in infusion times make interpreting vancomycin serum concentrations difficult. Furthermore, the evidence implicating vancomycin as a cause of oto- or nephrotoxicity is circumstantial, and these adverse effects may occur only in high-risk populations. Owing to the variability in its dose-serum concentration relationship and multicompartmental pharmacokinetics, several methodologies have been developed for instituting and adjusting vancomycin dosages. Nomograms rely on a fixed volume of distribution and the relationship between vancomycin clearance and creatinine clearance. Since both of these factors may be altered in certain populations, dosage methodologies (both traditional and Bayesian) that use population- or patient-specific pharmacokinetic data perform better than standard nomograms for initiating vancomycin therapy. Controversy still exists as to whether a 1- or a 2-compartment model is more appropriate for making dosage adjustments; however, steady-state rather than non-steady-state vancomycin serum concentrations should be used for dosage adjustments. Certain pathophysiological states such as age, bodyweight and renal function contribute to altered pharmacokinetics and may alter the design of the dosage regimen. Since no definitive relationship exists between vancomycin serum concentrations and either clinical outcome or adverse effects, considerable controversy surrounds the utility of monitoring serum vancomycin concentrations. Therefore, routine vancomycin serum concentration monitoring may be warranted only in specific populations, such as patients receiving concurrent aminoglycoside therapy or those receiving higher than usual dosages of vancomycin, patients undergoing haemodialysis and patients with rapidly changing renal function.

Dose-Response Relationship, Drug↗

PubMed2003

Treatment of staphylococcal ventriculitis associated with external cerebrospinal fluid drains: a prospective randomized trial of intravenous compared with intraventricular vancomycin therapy.

OBJECT: Staphylococcal ventriculitis may be a complication in temporary external ventricular drains (EVDs). The limited penetration of vancomycin into the cerebrospinal fluid (CSF) is well known; the pharmacodynamics and efficacy of systemically compared with intraventricularly administered vancomycin is examined in this prospective study. METHODS: Ten patients in whom EVDs were implanted to treat intracranial hemorrhage and who were suffering from drain-associated ventriculitis were randomized into two treatment groups. Five of these patients (median age 47 years) were treated with 2 g/day vancomycin administered intravenously (four infusions/day, Group 1), and the other five(median age 49 years) received 10 mg vancomycin intraventricularly once daily (Group 2). Vancomycin levels were measured in serum and CSF six times a day. The maximum vancomycin level in CSF was 1.73 +/- 0.4 micro/ml in Group 1 and 565.58 +/- 168.71 microg/ml 1 hour after vancomycin application in Group 2 (mean +/- standard deviation). Vancomycin levels above the recommended trough level of 5 microg/ml in CSF were never reached in Group 1, whereas in Group 2 they below the trough level (3.74 +/- 0.66 microg/ml) only at 21 hours after intraventricular vancomycin application. The vancomycin level in the serum was constant within therapeutic levels in Group 1, whereas in Group 2 in most instances vancomycin was almost below a measurable concentration. In both groups bacteriologically and laboratory-confirmed CSF clearance could be obtained. CONCLUSIONS: Intraventricular vancomycin application is a safe and efficacious treatment modality in drain-associated ventriculitis, with much higher vancomycin levels being achieved in the ventricular CSF than by intravenous administration.

Adult↗

PubMed1996

A comparison of the effect of universal use of gloves and gowns with that of glove use alone on acquisition of vancomycin-resistant enterococci in a medical intensive care unit.

OBJECTIVE: To determine the efficacy of the use of gloves and gowns compared with that of the use of gloves alone for the prevention of nosocomial transmission of vancomycin-resistant enterococci. DESIGN: Epidemiologic study and controlled, nonrandomized clinical trial. SETTING: University-affiliated, 900-bed, urban teaching hospital in which vancomycin-resistant enterococci are endemic. PATIENTS: 181 consecutive patients admitted to the medical intensive care unit for 48 hours or more. INTERVENTION: It was determined that all hospital employees would always use gloves and gowns when attending 8 particular beds in the medical intensive care unit and would always use gloves alone when attending 8 others. Compliance with precautions was monitored weekly. Rectal surveillance cultures were taken from patients daily. Cultures of environmental surfaces, such as those of bed rails, bedside tables, and other frequently touched objects in patient rooms and common areas, were taken monthly. Pulsed-field gel electrophoresis was used for molecular epidemiologic typing of vancomycin-resistant enterococci. MEASUREMENTS: The number of patients becoming colonized by vancomycin-resistant enterococci; the number of days to acquisition of vancomycin-resistant enterococci; and other measurements, including nosocomial infections, length of hospital stay, and mortality rates. RESULTS: The 93 patients in glove-and-gown rooms and the 88 patients in glove-only rooms had similar demographic and clinical characteristics. Fifteen (16.1%) patients in the glove-and-gown group and 13 (14.8%) in the glove-only group had vancomycin-resistant enterococci on admission to the medical intensive care unit. Twenty-four (25.8%) patients in the glove-and-gown group and 21 (23.9%) in the glove-only group acquired vancomycin-resistant enterococci in the medical intensive care unit. The mean times to colonization among the patients who became colonized were 8.0 days in the glove-and-gown group and 7.1 days in the glove-only group. None of these comparisons were statistically significant. Risk factors for acquisition of vancomycin-resistant enterococci induced length of stay in the medical intensive care unit, use of enteral feeding, and use of sucralfate. Compliance with precautions was 79% in glove-and-gown rooms and 62% in glove-only rooms (P < 0.001). Only 25 of 397 (6.3%) environmental cultures were positive for vancomycin-resistant enterococci. Nineteen types of vancomycin-resistant enterococci were documented by pulsed-field gel electrophoresis during the study period. CONCLUSIONS: Universal use of gloves and gowns was no better than universal use of gloves only in preventing rectal colonization by vancomycin-resistant enterococci in a medical intensive care unit of a hospital in which vancomycin-resistant enterococci are endemic. Because the use of gowns and gloves together may be associated with better compliance and may help prevent transmission of other infectious agents, this finding may not be applicable to outbreaks caused by single strains or hospitals in which the prevalence of vancomycin-resistant enterococci is low.

Adult↗

PubMedDate not supplied

A clinical decision process model for evaluating vancomycin use with modified HICPAC guidelines. Hospital Infection Control Practice Advisory Committee.

OBJECTIVE: The objective of this study was to evaluate a clinical decision process model for the appropriateness of vancomycin use, using modified Hospital Infection Control Practice Advisory Committee (HICPAC) guidelines. DESIGN: All nondialysis vancomycin use was reviewed using the retrospective chart review method. The HICPAC guidelines were modified to distinguish between documented and suspected infections and appropriateness of vancomycin use initially and after 3 days of therapy. Data were collected on both vancomycin-use orders and vancomycin-use days. SETTING: 446-bed health maintenance organization teaching hospital. RESULTS: 758 uses of vancomycin from 1993 through 1995 were evaluated using the modified HICPAC guidelines. Initial use was appropriate in 71% of the cases, with 26% used for documented infections and 74% for suspected infections. Of the 536 orders of initial appropriate use, 176 courses of treatment with vancomycin were discontinued appropriately within 3 days. Ongoing use evaluation after 3 days revealed appropriate use in 45%, inappropriate ongoing use in 25%, and empirical ongoing use in 30% of the cases. There were adequate clinical or laboratory data available in 70% of cases after 3 days to discontinue vancomycin or to reclassify from suspected to documented infections or indications. Vancomycin-use evaluation solely after 3 days would not have disclosed 537 initial inappropriate vancomycin-use days, which were 44% of the total inappropriate use days. CONCLUSIONS: Comprehensive evaluation of vancomycin use with HICPAC guidelines should include a modification to encompass initial and 3-day reevaluation, because most initial use is for suspected, and not documented, infections. HICPAC guidelines do not address the issues of differentiating suspected from documented infection indications or ongoing empirical use. The clinical decision process model is a framework for documentation and data collection for use evaluation and addresses issues not covered in HICPAC vancomycin guidelines. This model could be used by other medical centers for evaluation of vancomycin or other antibiotics.

Anti-Bacterial Agents↗

PubMed2000

[Effects of restrictions on use of vancomycin in a German university hospital].

BACKGROUND: Recently, increasing antibiotic resistance has been observed among gram-positive bacteria. However, only few isolates were found to be resistant against glycopeptides. Therefore, internationally accepted guidelines recommend a restricted use of vancomycin and other glycopeptide antibiotics in order to prevent the development of resistance against these clinically important antibiotics. In many countries, the hospital pharmacies play a key role in control and reinforcement of antibiotic formulary restrictions. In Germany, however, the hospital pharmacies usually do not take over such control functions, and most wards keep a stock of regularly used drugs including antibiotics, which makes reinforcement of restrictions difficult. METHODS: In an attempt to achieve a restriction of vancomycin use, the pharmacy of our university hospital was advised to deliver vancomycin to the wards only on request with a special order form signed by an attending, individually for every patient who should receive vancomycin. The efficacy of this restriction measure was evaluated in 3-month periods before and after the restriction became effective. RESULTS: Hospitalwide, this led to a 20.1% reduction of i.v. vancomycin and an 85.7% reduction of oral vancomycin use per 1000 patient days. If the hematology/oncology units were not considered, the reduction of i.v. vancomycin use was 41.8%, and the total use after the restriction 24.2 g per 1000 patient days. Microbiology results which justified the use of vancomycin decreased by 8.3% (10.9% hematology/oncology units not considered) between the 2 observation periods. Assuming a 7-day mean course of i.v. vancomycin therapy, the empirical use of i.v. vancomycin decreased from 39.9% to 8% after the restriction had been instituted. CONCLUSION: Allowing only experienced physicians (attendings) to decide on the use of vancomycin therapy, proved in our experience to be an effective measure to reduce unnecessary vancomycin use.

Drug Utilization↗

PubMed2005

Reduced susceptibility of Staphylococcus aureus to vancomycin and platelet microbicidal protein correlates with defective autolysis and loss of accessory gene regulator (agr) function.

Loss of agr function, vancomycin exposure, and abnormal autolysis have been linked with both development of the GISA phenotype and low-level resistance in vitro to thrombin-induced platelet microbicidal proteins (tPMPs). We examined the potential in vitro interrelationships among these parameters in well-characterized, isogenic laboratory-derived and clinical Staphylococcus aureus isolates. The laboratory-derived S. aureus strains included RN6607 (agrII-positive parent) and RN6607V (vancomycin-passaged variant; hetero-GISA), RN9120 (RN6607 agr::tetM; agr II knockout parent), RN9120V (vancomycin-passaged variant), and RN9120-GISA (vancomycin passaged, GISA). Two serial isolates from a vancomycin-treated patient with recalcitrant, methicillin-resistant S. aureus (MRSA) endocarditis were also studied: A5937 (agrII-positive initial isolate) and A5940 (agrII-defective/hetero-GISA isolate obtained after prolonged vancomycin administration). In vitro tPMP susceptibility phenotypes were assessed after exposure of strains to either 1 or 2 mug/ml. Triton X-100- and vancomycin-induced lysis profiles were determined spectrophotometrically. For agrII-intact strain RN6607, vancomycin exposure in vitro was associated with modest increases in vancomycin MICs and reduced killing by tPMP, but no change in lysis profiles. In contrast, vancomycin exposure of agrII-negative RN9120 yielded a hetero-GISA phenotype and was associated with defects in lysis and reduced in vitro killing by tPMP. In the clinical isolates, loss of agrII function during prolonged vancomycin therapy was accompanied by emergence of the hetero-GISA phenotype and reduced tPMP killing, with no significant change in lysis profiles. An association was identified between loss of agrII function and the emergence of hetero-GISA phenotype during either in vitro or in vivo vancomycin exposure. In vitro, these events were associated with defective lysis and reduced susceptibility to tPMP. The precise mechanism(s) underlying these findings is the subject of current investigations.

Anti-Bacterial Agents↗

PubMed2001

Nationwide survey shows that methicillin-resistant Staphylococcus aureus strains heterogeneously and intermediately resistant to vancomycin are not disseminated throughout Japanese hospitals.

A total of 6,625 methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates obtained from 278 hospitals throughout Japan were obtained between November and December 1997 and were examined for their sensitivities to vancomycin using Mueller Hinton (MH), brain heart infusion (BHI), agar plates, or the broth microdilution method. A concentrated inoculum of an MRSA strain or the use of highly enriched medium, such as BHI medium, allows an individual cell to grow on agar plates containing a vancomycin concentration greater than the MIC for the parent strain. However, cells of the colonies which grew on BHI agar plates containing the higher vancomycin concentrations did not acquire a level of vancomycin resistance greater than that of the parent strain and were not subpopulations of heterogeneously vancomycin-resistant MRSA. There was no significance in the fact that these colonies grew on the higher concentration of vancomycin: none showed stable resistance to vancomycin at a concentration above the MIC for the parent strain, and no cell from these colonies showed a relationship between the MIC and the ability of these colonies to grow on higher concentrations of vancomycin. The vancomycin MIC was not above 2 microg/ml for any of the cells originating from these colonies. No Mu3-type heterogeneously resistant MRSA strains, which constitutively produce subpopulations from MRSA clinical isolates with intermediate vancomycin resistance at a high frequency, were detected. There was a unipolar distribution of the MICs ranging from 0.25 to 2 microg of vancomycin/ml among the 6,625 MRSA clinical isolates, indicating that there was no Mu50-type intermediately vancomycin-resistant MRSA (MIC, 8 microg/ml by National Committee for Clinical Laboratory Standards criteria) among the clinical isolates, and there was no evidence of dissemination of Mu3-type MRSA heteroresistant to vancomycin.

Anti-Bacterial Agents↗

PubMed2006

Emergence of vancomycin resistant Staphylococcus aureus (VRSA) from a tertiary care hospital from northern part of India.

BACKGROUND: Glycopeptides such as vancomycin are frequently the antibiotics of choice for the treatment of infections caused by methicillin resistant Staphylococcus aureus (MRSA). For the last 7 years incidence of vancomycin intermediate S. aureus and vancomycin resistant S. aureus (VISA and VRSA respectively) has been increasing in various parts of the world. The present study was carried out to find out the presence of VISA and VRSA in the northern part of India. METHODS: A total 1681 staphylococcal isolates consisting of 783 S. aureus and 898 coagulase negative staphylococci (CoNS) were isolated from different clinical specimens from various outpatient departments and wards. All S. aureus and 93 CoNS were subjected to MIC testing (against vancomycin, teicolplanin and oxacillin); Brain Heart Infusion (BHI) vancomycin screen agar test; disc diffusion testing, and PCR for mecA, vanA and vanB genes detection. RESULTS: Out of 783 S. aureus two S. aureus strains were found to be vancomycin and teicoplanin resistant (one strain with MIC 32 microg/ml and the other strain with MIC 64 microg/ml); six strains of S. aureus have shown to be vancomycin intermediate (two strains with MIC 16 microg/ml and four strains with MIC 8 microg/ml); and two strains with teicoplanin intermediate (MIC 16 microg/ml). One CoNS strain was resistant to vancomycin and teicoplanin (MIC 32 microg/ml), and two CoNS strains were intermediate to vancomycin and teicoplanin (MIC 16 microg/ml). All VRSA, VISA and vancomycin resistant CoNS had shown growth on BHI vancomycin screen agar (vancomycin 6 microg/ml) and were mecA PCR positive. None of these isolates have demonstrated vanA/vanB gene by PCR. CONCLUSION: The present study reveals for the first time emergence of VISA/VRSA from this part of world and indicates the magnitude of antibiotic resistance in and around the study area. The major cause of this may be unawareness and indiscriminate use of broad-spectrum antibiotics.

Anti-Bacterial Agents↗

PubMed1999

Prospective vancomycin audit in Auckland healthcare hospitals.

AIM: In response to emerging vancomycin resistance among gram-positive cocci, it is recommended that hospitals develop guidelines for the appropriate use of glycopeptides and identify situations where glycopeptide use should be discouraged. The aim of this study was to audit the use of vancomycin in Auckland Healthcare hospitals. METHOD: Patients prescribed vancomycin were recorded by pharmacy staff at Auckland, Starship, Green Lane and National Women's Hospitals. Clinical and laboratory information was collected for each course of vancomycin treatment. Standard definitions were used to classify prophylactic, empirical or specific directed therapy as appropriate or inappropriate. Continuing vancomycin when cultures were negative for beta-lactam-resistant, gram-positive organisms and/or initial choice of vancomycin when it was not necessary for the presumed source of infection were reasons for inappropriate empirical use. Reasons for inappropriate specific directed therapy included vancomycin prescribed for methicillin susceptible S. aureus and coagulase-negative staphylococci, or penicillin susceptible viridans streptococci when there was no history of beta-lactam allergy. RESULTS: One hundred and sixty-eight courses of vancomycin were prescribed for 146 patients; 42 in children (<16 years) and 126 in adults. Thirty-two per cent of all vancomycin courses were in renal patients, 26% in surgical specialities, 17% in haematology/oncology patients, 14% in medical specialities and 10% in intensive care unit patients. Eighty-six (51%) courses of vancomycin were considered inappropriate. The majority, 54/86 (63%) of inappropriate use, was for empirical therapy. It was an inappropriate initial choice in 25 instances, the duration of treatment was inappropriate, given no beta-lactam-resistant organisms were isolated in nine instances and both its initial choice and duration were inappropriate in 20 instances. Switching to other antimicrobial agents sooner when culture results and susceptibilities became available would have shortened the duration of 58/86 (67%) of the inappropriate courses. Of the inappropriate courses, 44/86 (51%) were prescribed for renal patients, 22 for empirical use, e.g. for peritoneal dialysis-related peritonitis, wound infections and presumed line infections and 22 for specific therapy of beta-lactam susceptible isolates because of dosing convenience in patients with renal failure. CONCLUSION: Half of the vancomycin use in Auckland Healthcare hospitals could potentially be modified. The majority of inappropriate use (63%) was for empirical therapy. The microbiology laboratory's ability to promptly and accurately report culture and susceptibility results and convey these to the prescribing clinician is important in reducing unnecessary doses. This study identified areas where interventions will be focused to reduce vancomycin use.

Adolescent↗

PubMed1999

Vancomycin concentration in the vitreous after intravenous and intravitreal administration for postoperative endophthalmitis.

OBJECTIVES: To measure the concentrations of vancomycin in the vitreous of patients with postoperative endophthalmitis after administration of 1 g of vancomycin hydrochloride intravenously and injection of 1 mg of vancomycin hydrochloride into the vitreous, and to determine whether these concentrations are adequate for treatment of gram-positive infections. METHODS: Patients with acute postoperative endophthalmitis were treated with intravenous administration of 1 g of vancomycin hydrochloride followed by vitrectomy and collection of vitreous samples 1 to 5 hours later. Intravitreal vancomycin and ceftazidime were given. Vitreous samples were cultured and their vancomycin concentrations assayed. Minimal inhibitory concentrations of vancomycin for the isolated vitreal pathogens, and serum and vitreous cidal activity were determined. RESULTS: Eighteen patients with acute postoperative endophthalmitis were studied. Fourteen vitreous samples were available after intravenous vancomycin administration, and 4 vitreous samples were available after intravitreal vancomycin administration. After intravenous injection, vitreous vancomycin concentrations ranged from 0.4 to 4.5 microg/mL. Minimal inhibitory concentrations in these samples, obtained from 10 bacterial isolates, were below the therapeutic levels for most causative organisms, including staphylococci. Vitreous cidal activity values were negative at a dilution of 1:2 in 9 of 10 patients examined. After a 1-mg intravitreal injection, vancomycin concentrations in vitreous samples obtained by a second tap from 4 patients 44 to 72 hours later were 182, 138, 58, and 25 microg/mL. In 2 patients in whom measurements were obtained, vitreous cidal activity values were 1:512 and 1:32. CONCLUSION: Vitreous vancomycin concentrations for the treatment of gram-positive endophthalmitis were nontherapeutic after intravenous administration but therapeutic after intravitreal administration.

Anti-Bacterial Agents↗

PubMed1991

Factors influencing the protein binding of vancomycin.

Various factors influencing the protein binding of vancomycin were examined using equilibrium dialysis method. Four per cent human serum albumin (HSA) and/or 0.08 per cent alpha-1-acid glycoprotein (AAG), dissolved in isotonic phosphate buffer, were dialyzed against isotonic phosphate buffer of pH 7.4 using Spectrapor 2 membrane. The protein binding of vancomycin to 0.08 per cent AAG was dependent on vancomycin concentrations; the values ranged from 21.1 per cent at the vancomycin concentration of 20 micrograms ml-1 to 5.30 per cent at 2400 micrograms ml-1. However, binding to 4 per cent HSA was relatively constant, 8.79 +/- 2.43 per cent over a vancomycin concentration range of 20-2400 micrograms ml-1. The values to 4 per cent HSA alone and 0.08 per cent AAG alone did not predict the greater binding of vancomycin in the presence of both proteins, especially at higher concentrations of vancomycin; the values to 4 per cent HSA with 0.08 per cent AAG were constant, 26.3 +/- 3.74 per cent, at the vancomycin concentration range of 20-2400 micrograms ml-1. This suggested an interaction between the proteins, which resulted in enhanced binding of vancomycin. The protein binding of vancomycin to 4 per cent HSA with 0.08 per cent AAG was not influenced by the different incubation temperatures (4 degrees, 22 degrees, and 37 degrees), quantities of heparin (up to 40 units ml-1) or AAG (up to 0.16 per cent), or buffers (isotonic phosphate buffer of pH 7.4, phosphate buffer of pH 7.4 and 0.9 per cent NaCl solution) at the vancomycin concentration of 80 micrograms ml-1. Vancomycin was found to be stable in human serum albumin or in isotonic phosphate buffer of pH 7.4.

Blood Proteins↗

PubMed1990

Vancomycin pharmacokinetics in hydrocephalic shunt prophylaxis and relationship to ventricular volume.

Vancomycin pharmacokinetics were determined in 25 patients receiving ventriculoperitoneal shunts for hydrocephalus. Computed tomography scan-derived ventricular-brain ratio as an expression of hydrocephalus varied between 9.3% and 15.4% (12.9% +/- 1.7%). One hour prior to surgery each patient received 1 g of vancomycin infused intravenously over 60 minutes. Samples of cerebrospinal fluid and venous blood were obtained 1 hour later and vancomycin levels assayed by fluorescence polarization immunoassay. There were 11 females and 14 males, with a mean age of 44.5 +/- 10.3 years and a mean weight of 72.0 +/- 11.4 kg. All had normal renal function. Levels of vancomycin in the cerebrospinal fluid at 1 hour ranged from 0.1 to 1.5 micrograms/mL (0.9 +/- 0.3). Weight did not affect these values (p greater than 0.1). Simultaneous blood vancomycin levels varied between 9.1 and 38.7 micrograms/mL (22.3 +/- 8.3). Ventricular volume, expressed as the ventricular-brain ratio, did not correlate with cerebrospinal fluid vancomycin levels (p greater than 0.5). There was no significant increase in concentrations of vancomycin in CSF as cerebrospinal fluid protein concentration increased, nor when blood vancomycin concentration was greater than 20 mg/dL (therapeutic range) (p greater than 0.1). No patient had evidence of infection at 6 months follow up. These results indicate minimal cerebrospinal fluid penetrance of vancomycin when administered systemically 1 hour prior to shunt surgery. In addition concentrations of vancomycin in cerebrospinal fluid bear no relationship to weight, ventricular volume, meningeal inflammation, or blood levels in the therapeutic range. The minimum inhibitory concentration of vancomycin for staphylococci is 1.5 to 3.1, and as bactericidal levels of 5 to 8 minimum inhibitory concentration are needed to kill organisms, a combination of both systemic and intraventricular vancomycin may be needed to ensure adequate cerebrospinal fluid and tissue concentration of antibiotic during shunt prophylaxis.

Adult↗

PubMed1995

The challenge of vancomycin-resistant enterococci: a clinical and epidemiologic study.

BACKGROUND: Vancomycin-resistant enterococci have been recovered with increasing frequency from hospitalized patients. Risk factors, mode of nosocomial transmission, extent of colonization in hospitalized patients, and treatment options for these organisms have not been completely delineated. METHODS: We studied 53 patients (group A) with vancomycin-resistant enterococci isolated from various clinical specimens and also surveyed for vancomycin-resistant enterococci in stool specimens submitted for Clostridium difficile toxin assays (group B). Stool specimens submitted for identification of bacterial pathogens and stool specimens from hospital employees were also analyzed for vancomycin-resistant enterococci. RESULTS: Seventy-six isolates of vancomycin-resistant enterococci were recovered in group A. Five of these patients harbored vancomycin-resistant enterococci on admission. Fifty-three of 289 group B stool specimens submitted for C. difficile toxin assays yielded vancomycin-resistant enterococci. Cephalosporins and vancomycin were the most common antimicrobial agents received by both groups of patients. Enterococcus faecium isolates were more resistant than Enterococcus faecalis isolates to antimicrobial agents. All isolates exhibited high-level aminoglycoside resistance and were not beta-lactamase producers. There were at least 15 different molecular clones of E. faecium and three of E. faecalis. Vancomycin-resistant enterococcal bacteremia was associated with a 100% in-hospital mortality rate. CONCLUSIONS: Multidrug-resistant and vancomycin-resistant enterococci have become important nosocomial pathogens that are difficult to treat. Vancomycin-resistant enterococcal bacteremia was associated with a poor prognosis. We found a high rate of colonization in patients with suspected C. difficile toxin colitis. Judicious use of vancomycin and broad-spectrum antibiotics is recommended, and strict infection control measures must be implemented to prevent nosocomial transmission of these organisms.

Adult↗

PubMed1999

The threat of vancomycin resistance.

Vancomycin, produced in 1958, an essential antibiotic in the modern age, often is reserved for use in patients who are gravely ill or for infections caused by organisms resistant to penicillin, cephalosporin, or other antibiotics. Bacterial resistance to vancomycin has caused great concern among many healthcare professionals. First reported in 1986 in Europe and in 1988 in the United States, vancomycin-resistant enterococci (VRE) have become a major cause of nosocomial infections. During this time, scattered reports of clinical infections caused by vancomycin-resistant coagulase-negative staphylococci also were reported. Recently, enterococci that require vancomycin in media for growth, vancomycin-dependent enterococci (VDE), have been reported to cause clinically significant infections. Vancomycin or other glycopeptide intermediately resistant Staphylococcus aureus (VISA/GISA) also has emerged. The mechanisms of resistance to vancomycin for VRE, and probably for VISA/GISA, relate to the acquired ability of these organisms to circumvent the vancomycin-mediated disruption of bacterial cell wall synthesis. Risk factors that lead to VRE colonization or infection include prior antibiotic therapy, prolonged hospitalization, hospitalization in an intensive care unit, concomitant serious medical and surgical illnesses, exposure to equipment contaminated with VRE, and exposure to patients with VRE. Patients colonized or infected with VRE, healthcare workers with contaminated hands, and environmental surfaces in healthcare facilities are major reservoirs of VRE. Risk factors for VDE and VISA/GISA are less well understood, although both organisms emerge in patients receiving vancomycin or other glycopeptide antibiotics. Infection and antibiotic control procedures for both organisms, including restriction of vancomycin use, optimization of the antibiotic formulary, education of hospital personnel, early detection and reporting of vancomycin resistance, isolation of colonized patients, and appropriate cleansing of the environment are used to prevent the spread of these organisms in healthcare settings.

Anti-Bacterial Agents↗

PubMed1999

Improving the appropriateness of vancomycin use by sequential interventions.

BACKGROUND: Vancomycin usage is directly associated with the incidence of vancomycin-resistant enterococci. Optimal methods to reduce inappropriate use have not been delineated. We determined the appropriateness of vancomycin prescribing at our hospital on the basis of national guidelines and assessed the effect of sequential administrative and educational interventions. METHODS: In this prospective 3-phase study conducted in a Veterans Affairs Medical Center, we monitored vancomycin prescribing at baseline and in 2 follow-up periods. Administrative interventions included discussions with service chiefs and revising routine perioperative antibiotic prophylaxis orders. Educational interventions included in-services about vancomycin-resistant enterococci and appropriate vancomycin prescribing. In each monitoring period, 50 consecutive new vancomycin orders that could be evaluated were classified for appropriateness and categorized by indication. RESULTS: At baseline, 70% of vancomycin use was inappropriate. Surgical services accounted for 84% of orders. Interventions targeted services with high or frequently inappropriate vancomycin use. After administrative interventions, inappropriate vancomycin use dropped to 40% of orders (P =.003). Improvements were noted in targeted services. Educational interventions further decreased inappropriate vancomycin use, but the effect appeared transient. CONCLUSIONS: The simple, nonrestrictive administrative interventions used resulted in a statistically significant (30%) reduction in inappropriate vancomycin prescribing. However, educational interventions provided only transient benefit on institutional prescribing patterns.

Anti-Bacterial Agents↗

PubMed1996

Falsely elevated serum vancomycin concentrations in hemodialysis patients.

Fluorescence polarization immunoassay (FPIA) is the most widely used clinical vancomycin assay in the United States. Questions exist regarding the accuracy of this polyclonal assay in patients with end-stage renal disease (ESRD). While several studies have reported discrepancies in vancomycin serum concentrations determined by FPIA compared with other vancomycin assays, no study has investigated the accuracy of vancomycin serum concentrations determined by FPIA in patients with ESRD undergoing maintenance hemodialysis. Therefore, we compared the assay performance of FPIA and enzyme multiplied immunoassay technique (EMIT) in six subjects with ESRD receiving high-efficiency hemodialysis. Subjects underwent 6 consecutive weeks of hemodialysis treatment with a cellulose acetate dialyzer (CA210) and received 1 g vancomycin intravenously once weekly during the last hour of dialysis. Vancomycin serum concentrations were determined by both EMIT and FPIA methodologies. From the serum concentration results of both assays, vancomycin dosing recommendations were calculated to achieve a desired steady-state peak concentration of 35 mg/L and trough concentration of 10 mg/L. Overall, vancomycin serum concentrations reported by FPIA were significantly higher than those reported by EMIT. The mean difference between assays in the peak serum concentrations at weeks 1, 4, and 6 was 7.5, 11.5, and 11.2 mg/L, respectively. The mean difference in trough serum concentrations at weeks 1, 4, and 6 was 4.2, 6.2, and 5.2 mg/L, respectively. The FPIA overestimation of the EMIT values (calculated as FPIA-EMIT) varied widely among study subjects with a range of 0.0 mg/L to 27.0 mg/L for peak serum concentrations and 0.0 mg/L to 12.8 mg/L for trough serum concentrations. The mean doses calculated based on FPIA results were significantly lower than the EMIT-derived doses. No significant difference was observed in the calculated dosing intervals. These results demonstrate that FPIA significantly overestimates vancomycin serum concentrations compared with EMIT in patients with ESRD undergoing high-efficiency hemodialysis. The overestimation by FPIA may result in significantly different vancomycin dosing recommendations, leading to underdosing and the potential for therapeutic failures. Due to the unpredictability of the overestimation by FPIA, we were unable to formulate vancomycin dosing guidelines for institutions that use FPIA. Therefore, we recommend that the EMIT vancomycin assay be used in patients with ESRD to ensure appropriate dosing.

Adult↗

PubMed1997

Dosage recommendation of vancomycin during haemodialysis with highly permeable membranes.

The standard dosage of vancomycin in haemodialysis patients is usually 1 gram, once a week. The aim of our study was to investigate vancomycin clearance by two highly permeable membranes and to determine whether dosage adjustment is necessary in regular haemodialysis settings when using these type of dialyzers. 12 patients on regular haemodialysis and treated with vancomycin either prophylactically or therapeutically were prospectively randomised to either dialysis with a polyacrylonitril parallel membrane (AN-69) or a cellulose-acetate hollow fiber membrane. After administering vancomycin to the patient vancomycin plasma levels were measured at different intervals. The vancomycin clearance by the dialyzer was calculated from blood samples taken 1 hour after commencing dialysis. The data were used for pharmacokinetic computer simulation in order to develop a vancomycin dosage regimen for patients on regular haemodialysis with highly permeable membranes. The mean vancomycin dialysis clearance was 46 +/- 5 ml/min and did not differ between the two artificial kidneys. Dialysis clearance of vancomycin was independent of blood flow rate. Together with the dialyzer data a pharmacokinetic profile of each patient was calculated from the plasma samples. The average non-renal clearance was 3.3 ml/min/1.73 m2 while renal vancomycin clearance, as a fraction of creatinine clearance, was found to be 0.83 +/- 0.20. The computer calculations predicted that, irrespective of residual renal function, in most patients on regular haemodialysis and treated with these type of artificial kidneys, therapeutic and non-toxic vancomycin levels could be obtained by giving 1000 mg of vancomycin intravenously as a loading dosage and 500 mg during every subsequent dialysis.

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