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PubMed2001

Determination of vancomycin in human serum by micellar electrokinetic capillary chromatography with direct sample injection.

BACKGROUND: Vancomycin (VCM) has a bacteriostatic effect on gram-positive bacteria such as the methicillin-resistant Staphylococcus aureus. METHODS: A new assay for measuring vancomycin concentration by micellar electrokinetic capillary chromatography using direct serum injection was developed. A borate buffer (pH 10.0) containing 100 mmol/l sodium dodecyl sulfate was used as an electrophoresis buffer, and the detection was at 210 nm. The migration time of vancomycin was approximately 7 min. RESULTS: The linearity was from 0 to 100 microg/ml, with the limit of detection of 1.0 microg/ml (S/N=3). The within-run CV was 3.99-5.53%, and the recovery rate was 91-103% for a concentration range of 6.5-45.5 microg/ml. The between-day CV was 6.76% at 22.2 microg/ml. There was no interference from 32 other antibiotics. The correlation coefficient between the assay and fluorescence polarization immunoassay and direct injection HPLC was 0.982 and 0.985, respectively. The assay required no sample preparation of serum and used only microquantities of an electrophoresis buffer and samples. CONCLUSIONS: This assay is cost-effective and suitable for routine clinical use.

Anti-Bacterial Agents↗
PubMed2000

Immobilisation and evaluation of a vancomycin chiral stationary phase for capillary electrochromatography.

The macrocyclic antibiotic, vancomycin, is covalently bonded to LiChrospher diol silica packed columns and evaluated in capillary electrochromatography (CEC) both in the reversed-phase and polar organic mode. Initially, capillaries were packed with 5 microm LiChrospher 100 A diol silica and evaluated in CEC with a reversed-phase biphenyl-pyrene achiral test resulting in resolution and efficiency values of ca. 2.5 and 100000 plates meter(-1), respectively. Repeatability for this test (resolution and efficiency) was also examined and found to be acceptable for both run-to-run (n=5, 0.74% and 1.5%) and column-to-column (n=5, 3.4% and 9.0%), respectively. Similar results were obtained when the 10 microm LiChrospher 1000 A diol silica was examined with the exception of efficiency, where a reduced plate height value of four times lower was obtained compared to the 100 A material. A simple three step in-situ vancomycin immobilisation procedure was subsequently carried out on these packed diol columns. Selectivity was obtained for thalidomide enantiomers on this vancomycin chiral stationary phase in reversed-phase CEC with resolution and efficiency values of ca. 2.5 and 80000 plates meter(-1), with acceptable repeatability (n=8) 0.9% and 3.0%, respectively. Selectivity was also obtained for thalidomide enantiomers on this phase in the polar organic mode with resolution and efficiency values of ca. 2.5 and 120000 plates meter(-1), with acceptable repeatability (n=7) 0.9% and 2.0%, respectively. It was possible to deduce from a chemometric design carried out for evaluating the mobile phase component effects that organic modifier ratio, MeOH/MeCN, played a significant role in controlling both resolution and efficiency. It was also possible to separate a number of basic analytes including four beta-adrenergic blocking agents in the polar organic mode albeit with lower resolution and efficiency values, ca. 1.5 and 45000 plates meter(-1), respectively.

Chromatography, Micellar Electrokinetic Capillary↗
PubMed1987

Vancomycin.

Vancomycin is a narrow-spectrum bactericidal antibiotic used primarily for treatment of serious staphylococcal infections. It is the alternative therapy of choice when the penicillins and cephalosporins cannot be used. Vancomycin is also used in (1) methicillin-resistant Staphylococcus aureus infections; (2) streptococcal endocarditis in conjunction with an aminoglycoside in patients intolerant of penicillin or ampicillin; (3) infections, including those involving prosthetic devices, caused by gram-positive organisms with multiple antibiotic resistance; (4) antibiotic-induced enterocolitis caused by Clostridium difficile; and (5) prophylaxis for endocarditis in patients who are at risk and cannot tolerate a penicillin, cephalosporin, or erythromycin. The major toxic effect associated with the use of vancomycin is ototoxicity, which may develop when serum levels exceed 30 micrograms/ml.

Bacterial Infections↗
PubMed1982

Vancomycin.

While vancomycin is thus not as nephrotoxic as once feared, its use by the parenteral route should be avoided if possible when other nephrotoxic drugs are being given. Used properly, vancomycin appears efficacious and can be given with safety to infants, children, and adults. Vancomycin is incompatible with many other drugs in intravenous solutions, especially chloramphenicol, adrenocorticosteroids, and methicillin.

Bacteria↗
PubMed1995

Reducing the spread of antimicrobial-resistant microorganisms. Control of vancomycin-resistant enterococci.

Strategies to reduce the spread of hospital-acquired microorganisms resistant to multiple antimicrobial agents are discussed. Because hospitals have experienced a rapid increase in the incidence of infection and colonization with vancomycin-resistant enterococci (VRE) in the past 5 years, the Hospital Infection Control Practices Advisory Committee of the Centers for Disease Control and Prevention has issued recommendations for preventing the spread of vancomycin resistance. Controlling VRE dissemination in pediatric patients requires prompt detection of VRE by microbiology laboratories, education of staff and families about VRE, use of infection control measures to prevent person-to-person VRE transmission, and prudent vancomycin use.

Child↗
PubMed1997

Calcium phosphate ceramic coatings as carriers of vancomycin.

Infection in the setting of total joint arthroplasty remains a challenging problem. Attention has turned to developing methods of local delivery of antibiotics for prophylaxis. Vancomycin loaded into calcium phosphate ceramic coatings on titanium alloy substrates is a clinically relevant concept in the setting of total joint arthroplasty. Drug loading was accomplished by immersion of ceramic-coated discs in vancomycin-containing simulated physiological solution; in some experiments drug loading by immersion was followed by lipid coating in egg phosphatidylcholine solutions. The kinetics of vancomycin release and the efficacy of drug inhibition of Staphylococcus aureus were determined in vitro in comparison to the release from currently used antibiotic-laden poly(methyl methacrylate) (PMMA). The loading by immersion provided effective release and inhibition at early time points (up to 24 h); however, the lipid-coated samples demonstrated significant release and effective bacterial inhibition up to 72 h. The two-step procedure, i.e. drug loading followed by lipid coating in order to slow antibiotic elution, is more effective than the conventional one-step loading. The study indicated that the osteoconductive calcium phosphate coatings have the potential to serve as drug carriers to prevent infection in the setting of total joint arthroplasty.

Alloys↗
PubMed1986

Treatment of experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis with intravitreal vancomycin.

Endophthalmitis remains a dreaded complication of intraocular surgery and penetrating eye trauma. Subconjunctival, topical, and systemic antibiotics have been largely ineffective in the treatment of endophthalmitis, whereas intravitreal antibiotics have proved efficacious. Methicillin-resistant Staphylococcus epidermidis has become an important pathogen in many infections, including endophthalmitis. Toxicity, clearance, and efficacy of intravitreal vancomycin were evaluated in the treatment of experimental methicillin-resistant S. epidermidis endophthalmitis. No evidence of retinal toxicity was found and therapeutic levels were demonstrated six days after injection. The treated rabbit eyes showed a marked beneficial effect when compared to the untreated eyes. If experience confirms the safety of intravitreal vancomycin in human eyes, vancomycin should be considered the drug of choice for methicillin-resistant S. epidermidis endophthalmitis.

Animals↗
PubMed1999

Cystoid macular edema after cataract surgery with intraocular vancomycin.

OBJECTIVE: To determine whether the use of supplemental prophylactic vancomycin in the irrigating solution during extracapsular lens extraction is associated with increased incidence of cystoid macular edema. DESIGN: Prospective, randomized, double-masked clinical study. PARTICIPANTS: Consecutive series of 118 patients 60 years of age or older undergoing cataract surgery. INTERVENTION: The study group received an irrigating balanced salt solution supplemented with vancomycin (10 microg/ml), and the control group received the salt solution only. Fluorescein angiography was performed 1 and 4 months after surgery. MAIN OUTCOME MEASURES: Evidence of angiographic and clinical cystoid macular edema, and visual acuity at 1 and 4 months after surgery. RESULTS: The rate of postoperative angiographic cystoid macular edema was significantly higher in the study patients than in the control group at 1 month (55% vs. 19%, P = 0.0006) and 4 months (26% vs. 4%, P = 0.0099). The rates of clinical macular edema were 23% and 7%, respectively, at 1 month (P = 0.011) and 20% versus 0% at 4 months (P = 0.006). Visual acuity of 20/30 or better was noted at 4 months after surgery in 76% of the study group compared to 95.5% of the control group. CONCLUSIONS: The role of preventive intracameral vancomycin during intraocular surgery should be reassessed in view of the associated increase in the incidence of angiographic cystoid macular edema.

Aged↗
PubMed2001

Synergistic chiral separations using the glycopeptides ristocetin A and vancomycin.

The effectiveness of using a mixture of the chiral selectors vancomycin and ristocetin A to achieve chiral recognition was examined in this study. The results of using the mixed chiral selector vancomycin and ristocetin A in capillary electrophoresis were compared with the results of using each chiral selector alone. Chiral separations were carried out using a coated capillary column to suppress electroosmotic flow and minimize interactions with the capillary wall. We employed a countercurrent process where the solute reaches the detection cell window after the chiral selector has cleared the window, minimizing the background absorbance from the chiral selector and improving sensitivity. Using a mixture of vancomycin and ristocetin A, separations were achieved which often exceeded the resolving power of either chiral selector when used alone. The effect of voltage on resolution was also studied, and the optimal voltage was found to be between -5 and -8 kV.

Anti-Bacterial Agents↗
PubMed1997

Isolation of vancomycin resistant Enterococcus faecium from food.

In a survey of vancomycin resistant Enterococcus faecium (VREF) in Danish meat products, VREF could be detected in 16% of 160 samples of broilers collected at slaughterhouses and in 15% of 26 samples of pork collected from the retail trade. VREF were isolated by enrichment for 24 h in nutrient broth supplemented with vancomycin (50 micrograms/ml) prior to plating on Slanetz and Bartley agar. Using direct plating on Slanetz and Bartley agar, VREF could be isolated from only 1.7% of 540 samples of broilers from slaughterhouses and 2.2% of 90 samples of broilers from retail outlets. VREF was not detected in 124 samples of pork and 128 samples of beef from retail outlets by the direct plating method. An additional enrichment step in nutrient broth supplemented with vancomycin enhanced the detection rate of VREF by approximately three times compared to the direct plating method when investigating the same 160 samples of broilers by the two methods. The implications and public health aspects of VREF in food is discussed.

Animals↗
PubMed1998

The toilet as a transmission vector of vancomycin-resistant enterococci.

An elderly woman, admitted to the intensive care unit of a large university teaching hospital, was found to be colonized with vancomycin-resistant enterococci leading to the temporary closure of the unit. She had acquired the organism nosocomially, most likely from an environmental source, which had been contaminated when the toilet of a former patient, also colonized with vancomycin-resistant enterococci, had become blocked and overflowed throughout his and the adjoining room. This is the first report of a hospital toilet as the transmission vector for vancomycin-resistant enterococci.

Aged↗
PubMed1999

Implications of vancomycin-resistant Staphylococcus aureus.

Strains of Staphylococcus aureus with reduced susceptibility to glycopeptides have been reported from Japan (multiple strains), the United States (four strains), and Europe (France, the UK and Spain) and the Far East (Hong Kong and Korea). The isolates from the US, France, and strain Mu50 from Japan, demonstrate vancomycin MICs of 8 microg/mL by broth microdilution testing and appear to have developed from pre-existing methicillin-resistant S. aureus (MRSA) infections. The strain from the UK and other parts of Europe appears heteroresistant to vancomycin and has MIICs in the 1-2 microg/mL range. Many of the isolates with reduced susceptibility to glycopeptides have been associated with therapeutic failures with vancomycin. Although nosocomial spread of the glycopeptide-intermediate S. aureus (GISA) strains has not been observed in US hospitals or in Europe, spread of GISA strains has apparently occurred in Japan. Laboratory studies have indicated that the disk diffusion test, the Stoke's method, and several automated methods of antimicrobial susceptibility testing do not detect GISA strains. The requirement to choose from a relatively small number of acceptable techniques for screening may well influence the ability of laboratories to conduct surveillance for these organisms. Finally, the isolation of such strains in three geographically distinct regions suggests that this phenomenon will continue to occur worldwide.

Forecasting↗
PubMed1996

Experience with a hospital-wide outbreak of vancomycin-resistant enterococci.

BACKGROUND: Vancomycin-resistant enterococci (VRE) were first detected in our institution in 1991. An outbreak was recognized in late 1992 when there was a sudden rise in the number of patients per month with VRE. Little information exists concerning the natural history of infection with these pathogens, and the effect of antimicrobial therapy is unclear. Recent guidelines emphasize prudent use of vancomycin and prompt institution of barrier precautions to limit the spread of vancomycin resistance. METHODS: Data were obtained by review of microbiologic and clinical records. Patients were categorized according to site of infection, and outcome of therapy was assessed. Hospital antibiotic usage was analyzed to determine any correlation with the outbreak. Infection control measures instituted in 1993 included patient isolation, environmental cleaning, and a reemphasis of barrier precautions. Surveillance cultures were performed to assess the extent of the outbreak in January 1995. RESULTS: VRE were detected in clinical cultures from 159 patients from 1991 through 1994. Mortality rate was 48%, but in most cases death could not be attributed to enterococcal infection. Patients with wound infections healed without specific therapy. Many patients with bacteremia had resolution with ampicillin or without specific therapy. Patients were widely scattered throughout the hospital from the beginning of the outbreak. Hospital usage of cefotaxime correlated with the number of cases. Infection control measures were not successful. Surveillance culture results in January 1995 revealed that 53% of all medical and surgical inpatients had fecal colonization with VRE. Genetic analysis of selected isolates revealed that one strain predominated, but at least seven distinct strains were identified. CONCLUSIONS: Our data suggest that many infections with VRE resolve without specific therapy. The infection control measures we used were ineffective, possibly because of the multiple strains present in our hospital. Isolation of all patients with VRE is impractical when there is widespread fecal carriage.

Adult↗
PubMed1997

Epidemiology and control of vancomycin-resistant enterococci in an adult and children's hospital.

BACKGROUND: The incidence of vancomycin-resistant enterococci (VRE) has reached endemic proportions in many medical centers. To initiate an effective infection control program, an understanding of the epidemiologic attributes of the genus in medical facilities is imperative. METHODS: We studied 138 consecutive cases of VRE from April through December 1995. We created a database to analyze the risk factors for patients in both an adult hospital and a children's hospital and screened all specimens, submitted for routine microbiologic analysis, for VRE. RESULTS: One hundred twenty-three cases (89%) occurred in the adult acute care hospital, and 15 (11%) occurred in the children's hospital. Eighty patients (58%) were colonized with VRE, and 58 (42%) had an infection with VRE. Eighty-three percent of all the cases of VRE were nosocomially acquired. The majority of cases occurred in the medical service. Urine was the most important clinical specimen infected or colonized. Prior use of an antibiotic, other than vancomycin, was the most important risk factor for all nosocomial cases, followed by prior vancomycin use for surgical patients and residence in a unit with other patients infected with VRE for the medical service. Direct admission from another hospital was the most important risk factor for community-acquired cases. Special microbiologic screening of cultures yielded 48% of all VRE identified. Enterococcus faecium was the predominant resistant isolate recovered. CONCLUSIONS: The control of VRE in the hospital setting is difficult for several reasons. Almost half of all patients carrying VRE would not have been identified without special microbiologic screening efforts, as would patients, admitted from the community, who are already colonized with VRE. Controlling antibiotic use both in the hospital and the community is basic for controlling these organisms. Continuous education of all staff about VRE and other nosocomially significant organisms is the key to controlling the spread of these bacteria.

Adolescent↗
PubMed1999

Molecular epidemiology of vancomycin-resistant enterococci from 6 hospitals in New York State.

BACKGROUND: Vancomycin resistance among enterococci is an emerging nosocomial problem. Consequently, it is important to understand the distribution of vancomycin-resistant enterococci (VRE) within and between hospitals to implement appropriate infection control measures. METHODS: In this study, 116 VRE isolates obtained from patients in 6 New York State hospitals were analyzed by antibiotic susceptibility testing, pulsed-field gel electrophoresis (PFGE) fingerprinting, plasmid profile analysis, vanA and vanB polymerase chain reaction, and DNA:DNA hybridization with vanA and vanB probes. RESULTS: PFGE and plasmid typing generally agreed, but plasmid profiles were more variable. These analyses revealed that genetic heterogeneity among isolates from within each of the 6 hospitals varied considerably. Among 23 Enterococcus faecium isolates from one hospital, there were only 3 PFGE types, and 20 isolates had the same type. However, in another hospital, each isolate was genetically distinct. Closely related strains were not found in separate hospitals. VRE strains with vanA genes and strains with vanB genes were found in 3 hospitals. Both plasmid and chromosomal carriage of these genes was detected. CONCLUSIONS: PFGE typing showed that nosocomial VRE transmission had occurred in some hospitals. However, there was no evidence for it in others. Neither was there evidence for intrahospital transmission or for emergence of an endemic strain. These observations demonstrate that it is important to evaluate genetic heterogeneity among VRE before implementation of infection control measures. PFGE is the method of choice for epidemiologic typing, but polymerase chain reaction, plasmid, and hybridization studies can provide important information concerning the presence and potential for transfer of vancomycin resistance genes.

DNA Probes↗
PubMed2002

The use of linezolid in the treatment of vancomycin-resistant enterococcal septicaemia in two patients with burn injuries.

Vancomycin-resistant enterococci (VRE) are multi-resistant micro-organisms that have emerged as important nosocomial pathogens during the last decade. Emergence of this organism has been blamed mainly on the increased and inappropriate use of antibiotics, in particular, the cephalosporins and the glycopeptide, vancomycin. Burns patients are highly vulnerable to acquiring VRE infections, being both debilitated and immunocompromised, and often receiving antibiotics that further diminish their intrinsic microbial flora. We report on two patients with large burn injuries who acquired vancomycin-resistant enterococcal septicaemia during their in-patient stay. Both patients were successfully treated using the antibiotic, linezolid. Linezolid is the first in a new class of antibiotics known as the oxazolidinones whose mode of action inhibits early bacterial protein synthesis. Linezolid has a spectrum of activity against Gram-positive micro-organisms including methicillin-resistant Staphylococcus aureus (MRSA) and VRE, and can provide a useful treatment alternative to the glycopeptides.

Acetamides↗
PubMed2001

New sensitive assay of vancomycin in human plasma using high-performance liquid chromatography and electrochemical detection.

A method using reversed-phase high-performance liquid chromatography with electrochemical detection for the analysis of vancomycin in human plasma was developed. Chromatographic conditions included an octadecyl column, a mobile phase of acetonitrile-sodium phosphate buffer (pH 7) (12:88), a total run time of 12 min, and coulometric electrochemical detection at +700 mV. Linear detector response was found in the range 5-100 microg ml(-1) after a 1:80 dilution or from 0.5 to 50 microg ml(-1) after a 1:20 dilution of the samples. In both cases the correlation coefficient (r) of the calibration curve standard was better than 0.995. Vancomycin determination was based on a denaturation of plasma proteins with methanol, then a dilution with mobile phase was performed. Recovery of vancomycin from plasma was 103.1+/-3.9%, and no interference from commonly used drugs or endogenous compounds was observed. A significant correlation was shown with the EMIT assay (r=0.92, P<0.001) using clinical samples from children. This HPLC technique is simple, sensitive, rapid, precise, selective and requires only 100 microl of plasma for completion.

Anti-Bacterial Agents↗
PubMed2000

In vitro activity of GAR-936 against vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae.

We report the activity of the new glycylcycline antimicrobial agent GAR-936 against 37 clinical isolates of vancomycin-resistant enterococci (including organisms carrying the vanA, vanB, vanC-1, and vanC-2/3 genes), 26 clinical isolates of methicillin-resistant S. aureus and 30 clinical isolates of high-level penicillin-resistant S. pneumoniae. All isolates of vancomycin-resistant enterococci, methicillin-resistant S. aureus, and penicillin-resistant S. pneumoniae were inhibited by < or = 1, < or = 2, or < or = 0.25 microg/ml of GAR-936, respectively. Time kill experiments using vancomycin-resistant enterococci did not demonstrate synergy or antagonism between 2 microg/ml of GAR-936 and 0.25 microg/ml of quinupristin/dalfopristin.

Anti-Bacterial Agents↗