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PubMedDate not supplied

Clinical consequences and cost of limiting use of vancomycin for perioperative prophylaxis: example of coronary artery bypass surgery.

Routine us of vancomycin for perioperative prophylaxis is discouraged, principally to minimize microbial resistance to it. However, outcomes and costs of this recommendation have not been assessed. We used decision-analytic models to compare clinical results and cost-effectiveness of no prophylaxis, cefazolin, and vancomycin, in coronary artery bypass graft surgery. In the base case, vancomycin resulted in 7% fewer surgical site infections and 1% lower all-cause mortality and saved $117 per procedure, compared with cefazolin. Cefazolin, in turn, resulted in substantially fewer infections and deaths and lower costs than no prophylaxis. We conclude that perioperative antibiotic prophylaxis with vancomycin is usually more effective and less expensive than cefazolin. Data on vancomycin's impact on resistance are needed to quantify the trade-off between individual patients' improved clinical outcomes and lower costs and the future long-term consequences to society.

Aged↗

PubMed2003

Penicillin and vancomycin tolerance among clinical isolates of Streptococcus pneumoniae in Hong Kong.

OBJECTIVE: To determine the prevalence of penicillin and vancomycin tolerance in clinical isolates of Streptococcus pneumoniae. DESIGN: Laboratory testing of 50 consecutive clinical isolates. SETTING: District hospital, Hong Kong. PATIENTS: Fifty patients with pneumonia or meningitis who were admitted to a district hospital in Hong Kong between August and October 2002. MAIN OUTCOME MEASURES: Lysis, as assessed by loss of optical density at 4 hours at 540 nm, and reduction in viable count expressed as the log of the number killed ('log kill') after exposure of cultures to 10 times the minimum inhibitory concentration of penicillin and vancomycin. RESULTS: Of the 50 isolates, five (10%) were tolerant to penicillin and one (2%) was tolerant to vancomycin. CONCLUSION: This is the first report of vancomycin tolerance in Streptococcus pneumoniae in Hong Kong. Because vancomycin tolerance is associated with clinical failure in the treatment of pneumococcal meningitis, increased monitoring for resistant strains of organisms is suggested.

Drug Tolerance↗

PubMed2004

[Vancomycin resistant enterococci in the Netherlands].

Enterococci (Enterococcus faecalis and Enterococcus faecium) are relatively avirulent enteric bacteria that usually only cause infections in immunocompromised patients. Antimicrobial treatment, however, is hampered as enterococci are intrinsically resistant to many antibiotics. For years, vancomycin was considered the last available antibiotic. Plasmid-mediated resistance against vancomycin among enterococci was first described in the nineteen-eighties and since then incidences of infection caused by vancomycin-resistant enterococci (VRE) have increased dramatically, especially in the United States. In 2000, three outbreaks of VRE occurred in hospitals in the Netherlands and a set of infection-control measures was proposed to limit further transmission. These measures were based on the simultaneous isolation of VRE from multiple patients. All three outbreaks were controlled by these measures and no new outbreaks in Dutch hospitals have been reported since then. Epidemiological studies have shown that hospital outbreaks on three continents were caused by a subpopulation of E. faecium, which is characterized by the presence of a potential virulence gene (variant esp) and resistance to amoxicillin. This 'hospital strain' of E. faecium has probably been prevalent within hospital settings for some time, but only became clinically relevant when it had acquired vancomycin-resistance. Current advice is to implement the set of infection control measures formulated in 2000, only in those patients colonized by amoxicillin-resistant VRE. The potential dangers of VRE were recently underlined by the proven transmission of the vancomycin-resistance gene from VRE to methicillin-resistant Staphylococcus aureus (MRSA) in two patients in the United States. It is in the interest of the patients that prevalence of VRE and MRSA in Dutch hospitals should be kept as low as possible.

Disease Outbreaks↗

PubMed1989

Intravitreal antibiotic therapy with vancomycin and aminoglycoside. An experimental study of combination and repetitive injections.

We evaluated the retinal toxic reaction of combined intravitreal therapy with regimens of 1.0 mg of vancomycin hydrochloride and 400 micrograms of amikacin sulfate or 1.0 mg of vancomycin hydrochloride and 100 micrograms of gentamicin sulfate in the rabbit eye. The effects of reinjecting each combination a second or third time, separated by 48-hour intervals, were also examined by ophthalmoscopy and light and transmission electron microscopy. The initial administration of either regimen did not produce toxic reaction. After two injections, five of six eyes with vancomycin-gentamicin therapy and three of six eyes with vancomycin-amikacin therapy displayed focal areas of retinal toxic reaction on histologic study. After three injections, all eyes treated with either regimen showed histologic evidence of more advanced retinal toxic reaction primarily involving the outer retina and retinal pigment epithelium. The present study demonstrates the safety of an initial intravitreal injection of vancomycin and aminoglycoside but shows increasing retinal toxic reaction with repetitive combination therapy.

Amikacin↗

PubMed1990

Augmented gentamicin ototoxicity induced by vancomycin in guinea pigs.

Vancomycin has been reported to be an ototoxic drug in the clinical literature. At best, this literature is confusing. There are no reports of ototoxicity of vancomycin in experimental animals, even when it is administered concurrently with ethacrynic acid, a drug known to augment the ototoxic effect of most other ototoxic drugs. In most of the cases of permanent ototoxicity that have been reported, the patient was treated with an aminoglycoside antibiotic as well as vancomycin. This study found no evidence of vancomycin ototoxicity in guinea pigs, but found that vancomycin greatly enhanced the ototoxicity of gentamicin.

Acoustic Stimulation↗

PubMed2003

Fast enantiomeric separation with vancomycin as chiral additive by co-electroosmotic flow capillary electrophoresis: increase of the detection sensitivity by the partial filling technique.

A fast and sensitive method is described by using vancomycin as a chiral additive for enantiomeric separation by capillary electrophoresis (CE). In order to overcome disadvantages associated with use of vancomycin as chiral additive in CE, several strategies including the dynamic coating technique, the co-electroosmotic flow technique, and the partial filling technique were employed sequentially in this method. Using the polycationic polymer hexadimethrine bromide (HDB) as a buffer additive, the capillary wall was dynamically coated with a thin film formed by the adsorbed HDB. Consequently, the adsorption of vancomycin onto the capillary wall was minimized via electrostatic repulsion between the coating of the capillary wall and the vancomycin molecule. In addition, the reversed electroosmotic flow (from cathode to anode) produced by the positively charged capillary wall migrates in the same direction of negatively charged analytes (co-electroosmotic flow electrophoresis). Thereby the electrophoretic mobility of negatively charged analytes were drastically accelerated leading to a short separation time of less than 3.4 min. The separation time was further reduced by the use of a short-end-injection technique. For example, the analysis time was achieved by as short as 55 s for a baseline separation of dansyl-alpha-amino-n-butyric acid. Concurrently, the partial filling technique was used to avoid the loss of detection sensitivity caused by the presence of vancomycin in the running buffer. The effect of several parameters, such as HDB concentration, buffer pH, plug length of the chiral selector, concentration of the chiral selector and applied voltage, on enantioselectivity were investigated toward optimization. Besides the advantage of a very short separation time, the method is characterized by high detection sensitivity, high selectivity, and high efficiency.

Amino Acids↗

PubMed2001

Rapid bioanalysis of vancomycin in serum and urine by high-performance liquid chromatography tandem mass spectrometry using on-line sample extraction and parallel analytical columns.

A novel high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS) method is described for the determination of vancomycin in serum and urine. After the addition of internal standard (teicoplanin), serum and urine samples were directly injected onto an HPLC system consisting of an extraction column and dual analytical columns. The columns are plumbed through two switching valves. A six-port valve directs extraction column effluent either to waste or to an analytical column. A ten-port valve simultaneously permits equilibration of one analytical column while the other is used for sample analysis. Thus, off-line analytical column equilibration time does not require mass spectrometer time, freeing the detector for increased sample throughput. The on-line sample extraction step takes 15 seconds followed by gradient chromatography taking another 90 seconds. Having minimal sample pretreatment the method is both simple and fast. This system has been used to successfully develop a validated positive-ion electrospray bioanalytical method for the quantitation of vancomycin. Detection of vancomycin was accurate and precise, with a limit of detection of 1 ng/mL in serum and urine. The calibration curves for vancomycin in rat, dog and primate were linear in a concentration range of 0.001-10 microg/mL for serum and urine. This method has been successfully applied to determine the concentration of vancomycin in rat, dog and primate serum and urine samples from pharmacokinetic and urinary excretion studies.

Animals↗

PubMedDate not supplied

The microbiological efficacy of the combination of fosfomycin and vancomycin against clinically relevant staphylococci.

Infections with multiresistant strains of Staphylococcus aureus and Staphylococcus epidermidis pose severe clinical problems. The drug of choice in such cases, vancomycin, is potentially ototoxic and nephrotoxic and this may give rise to additional problems in the patient. Fosfomycin has been shown to be nephroprotective when given with vancomycin and with other nephrotoxic drugs. We report the inhibitory and bactericidal activity of fosfomycin and vancomycin alone and in combination against 26 clinically relevant strains of S. aureus and 48 strains of S. epidermidis. In most instances these two drugs showed indifferent or additive effects, synergism or antagonism was only rarely observed. Assessment of the bactericidal action of the combination revealed similar effects. The combination of fosfomycin and vancomycin may, therefore, be beneficial in clinical situations where the nephrotoxic effect of vancomycin cannot be tolerated.

Drug Combinations↗

PubMed1993

Pharmacokinetics of vancomycin during continuous hemodiafiltration.

OBJECTIVE: To study the pharmacokinetics of vancomycin in three patients with acute renal failure related to multi-organ failure during continuous venovenous hemodiafiltration (CVVHD). DESIGN: Prospective exploratory, open-labelled study. SETTING: Critical Care Unit in a University Medical Centre. PATIENTS: 3 patients exhibiting hemodynamic instability and oligo-anuric acute renal failure requiring extra-renal epuration were included in this study. INTERVENTION: Every patient received 7.5 mg/kg IV vancomycin over 1 h for a documented or suspected nosocomial staphylococcal infection. Serum and dialysate outlets samples were collected before infusion and 1, 3, 6, 12, 18, 24 after the end of infusion. MEASUREMENTS AND RESULTS: Mean age was 58.7 years (range 41-79) and mean SAPS 15.7 (9-23). The mean peak concentrations were 27.3 mg/l (range 15.6-45.6) one hour after the end of infusion. The average remaining vancomycin concentration 24 h after the onset of infusion was 3.6 mg/l (range 2.6-4.5). The mean terminal disposition rate constant and elimination half-life were 0.05 h-1 and 13.9 h respectively. Mean total body clearance was 38.9 +/- 4.3 ml/min and dialysate outlet (DO) clearance 4.2 +/- 1.3 ml/min. The mean volume of distribution was 47.4 +/- 6.4 l. CONCLUSION: CVVHD is effective for vancomycin elimination. In these patients, the elimination half-life is almost constant, involving a following injection of vancomycin 12 h later to achieve effective concentrations.

Acute Kidney Injury↗

PubMed1991

Teicoplanin in perspective. A critical comparison with vancomycin.

Teicoplanin is a new glycopeptide antibiotic with a chemical structure related to vancomycin. The proposed advantages of teicoplanin over vancomycin are discussed. These include lower incidence of side-effects, lower toxicity (especially in combination with aminoglycosides), lower dosage frequency and the possibility of intramuscular administration. There is only a limited number of studies comparing both agents; more studies are still needed before firm conclusions can be drawn. Therapeutic drug monitoring is not usually necessary for teicoplanin; the situation is not clear for vancomycin. There is some doubt whether the incidence of resistance is as infrequent for teicoplanin as it is for vancomycin. Teicoplanin appears to be a promising alternative to vancomycin, but more data are needed on the relative clinical efficacy and the development of resistance to both drugs.

Anti-Bacterial Agents↗

PubMed1989

Elimination of vancomycin during hemofiltration.

The study was designed to establish guidelines for vancomycin treatment of patients with acute renal failure undergoing hemofiltration. During 27 hemofiltration treatments in four anuric patients requiring daily consecutive hemofiltration therapy, plasma levels and elimination rates of vancomycin were measured. Regression analysis of the initial vancomycin concentration versus the total amount of vancomycin eliminated showed a clear linear relationship (r = 0.91), thus permitting prediction of the total elimination via hemofiltration by measurement of the initial plasma concentration. Applying these calculations the dosage in patients undergoing hemofiltration can be determined by monitoring the initial plasma concentration. The findings also indicate that hemofiltration is an effective method for treatment of vancomycin intoxication.

Acute Kidney Injury↗

PubMed1991

In vitro selection of resistance to vancomycin in bloodstream isolates of Staphylococcus haemolyticus and Staphylococcus epidermidis.

The purpose of the study was to determine whether vancomycin-resistant strains of Staphylococcus haemolyticus could be selected regardless of the initial MIC of vancomycin. Twenty-one bloodstream isolates of Staphylococcus haemolyticus were studied by broth and agar selection methods. The broth method selected strains for which MICs of vancomycin ranged from 4 to 32 micrograms/ml and MBCs from 16 to greater than 128 micrograms/ml. The agar method selected strains for which MICs ranged from 8 to 32 micrograms/ml and MBCs from 8 to greater than 128 micrograms/ml. For comparison, seven strains of Staphylococcus epidermidis were evaluated by the agar selection method. Final MICs of vancomycin ranged from 8 to 16 micrograms/ml; MBCs ranged from 16 to 64 micrograms/ml. Clearly, in vitro exposure to vancomycin can select strains of Staphylococcus haemolyticus and Staphylococcus epidermidis for which MIC values are beyond the susceptible breakpoint.

Bacteremia↗

PubMed1997

Influence of intraperitoneal vancomycin on peritoneal dialysis efficiency. A clinical study.

Peritonitis is a major complication of intermittent peritoneal dialysis (IPD); over 70% of the infections are caused by Gram-positive bacteria. Vancomycin (V) is the antibiotic of choice in the treatment of peritonitis caused by G(+). The influence of vancomycin on peritoneal transport in IPD patients has not been described before. We have investigated the effect of intraperitoneal vancomycin on dialysis efficiency in 8 IPD patients using dialysis solutions containing either lactate or acetate. The following parameters were measured: net ultrafiltration (UF), concentration ratios (D/P) of urea, creatinine, potassium, peritoneal clearances (ml/min) of urea, creatinine, potassium, mass transfer of sodium (MTNa), sodium sieving index (SCNa). It has been found that vancomycin significantly decreases D/P urea (p < 0.05) and creatinine (p < 0.05). We found also a significant decrease of mean clearance of urea (p < 0.05) and creatinine (p < 0.05). The mean clearance of potassium did not change significantly. There was no significant change in UF, MTNa, and SCNa. Our preliminary data suggest that vancomycin decreases the permeability of peritoneum for certain low molecules in IPD patients which may have a negative impact on dialysis efficiency.

Adult↗

PubMedDate not supplied

Positive blood cultures for coagulase-negative staphylococci in neonates: does highly selective vancomycin usage affect outcome?

The implication of highly-selective vancomycin usage on the outcome for infants with positive blood cultures for coagulase-negative staphylococci (CONS) was assessed retrospectively. The analysis was performed on partly prospective collected data from infants under 3 months of age with a least one CONS-positive blood culture in the neonatal intensive care unit at the Soroka University Medical Center between 1990 and 1996. During the study period, 239 episodes of CONS-positive blood cultures were identified from among 64,226 live births (3.7 per 1,000). Vancomycin was administered in 22 (9%) episodes, in all cases only after identification of the bacteria. The remaining 217 episodes were managed either without antibiotics or with continuation or initiation of empiric antibiotic therapy (usually ceftazidime +/- ampicillin) for suspected sepsis. Severity of the initial illness, subsequent morbidity and mortality were low regardless of the treatment administered. Only a single case of a blood-borne vancomycin resistant gram-positive organism was observed during the study period. The approach to CONS-positive blood cultures in neonates used here was associated with low morbidity and mortality. These findings support a policy of highly selective vancomycin usage in an era of emerging vancomycin resistance.

Anti-Bacterial Agents↗

PubMed1994

Comparison of the effects of three haemodialysis membranes on vancomycin disposition.

Polysulfone (PSF) and polyacrylonitrile (PAN) were recently introduced haemodialysis (HD) membranes. The effect of each on vancomycin disposition was compared with cuprophan (SCE) in 12 chronic HD patients who received 14 infusions. Vancomycin (1 g) was infused over 1 hour, followed by three 4-hour HD sessions over 5 days, beginning 1 hour after the end of infusion. The intradialytic clearances of vancomycin were 73, 54 and 15 ml/min for PSF, PAN and SCE, respectively. At the end of the third HD session, vancomycin concentration dropped to subtherapeutic level (< 7.5 micrograms/ml) only in patients dialysed with PSF and PAN. The corresponding elimination half-lives (t1/2 beta) were 61, 60 and 86 hours for the three membranes, respectively. According to these findings, vancomycin should be given every three HD sessions for PSF and PAN. The dosage interval should be extended up to every 5 HD sessions for patients on SCE. The peak (mean +/- S.D.) obtained one hour after the end of infusion was 34.2 +/- 11.4 micrograms/ml, which is within the therapeutic range.

Acrylic Resins↗

PubMedDate not supplied

Intracellular activity of vancomycin and Ly333328, a new semisynthetic glycopeptide, against methicillin-resistant Staphylococcus aureus.

The activity of vancomycin and Ly333328, a new semisynthetic glycopeptide, against eight strains of Staphylococcus aureus showing various susceptibilities to methicillin and ciprofloxacin was examined using a colony count method. We compared the growth of strains ingested by polymorphonuclear leucocytes and non-ingested strains. MICs of vancomycin and Ly333328 against staphylococci resistant and susceptible to methicillin were 2 mg/l and 2-4 mg/l, respectively. Against all the tested extracellular staphylococci, vancomycin had only bacteriostatic activity, whereas Ly333328 showed cidal activity at 10 MIC. Against ingested staphylococci, vancomycin had nearly no activity compared with the controls, regardless of the concentration of the drug. Ly333328 at concentrations of 1 MIC and above was highly active against ingested staphylococci regardless of their susceptibility pattern. The results suggest that Ly333328 in contrast to vancomycin is active against intracellular S. aureus.

Anti-Bacterial Agents↗

PubMed1998

Pharmacokinetics, uses, and limitations of vancomycin-loaded bone cement.

We have studied the mechanical and pharmacokinetic characteristics of an industrially-prepared bone cement containing 3 g of vancomycin per 60 g cement. A low viscosity cement was selected, to increase contact between the antibiotic and the infected surfaces. Resistance of compression (95 mPa) was well above the required standard (70 mPa) and similar to that of other cements with or without gentamicin. The concentrations in blood, urine and bone were measured in mg/l and mg/kg, and compared to the break point (BP) of susceptibility tests, which must be obtained to achieve control of infection. Diffusion tests were conducted in vitro (elution in saline from rods), and in 30 sheep femora implanted with the cement in vivo. In the animal study, bone levels during the first three months were three-fold higher than the BP (i.e., were > or = 12 mg/l) in 92% of specimens from all areas of bone studied and at all times since implantation; they exceeded five times the BP in 56% of specimens and were never lower than twice the BP. The mean level was four times the BP after six months and fell sharply during the next six months. A pharmacokinetic study in ten patients who had a primary total hip arthroplasty with vancomycin-loaded cement as prophylactic antibiotic therapy showed that blood levels were lower than 3 micrograms/ml, i.e., 30 times lower than the toxic threshold (90 micrograms/ml). Vancomycin was undetectable in urine after the tenth day. The levels in drainage fluids were five times the BP after 24 h and equal to it after four days. None of the ten patients treated prophylactically with vancomycin-loaded cement developed evidence of allergy, toxicity, intolerance or loosening during a two year period. No adverse events were recorded in 17 other patients treated with a vancomycin (2 g) plus gentamicin (0.8 g) loaded cement as adjuvant therapy for severe prosthetic infection.

Animals↗

PubMed1999

Treatment of vancomycin overdose using high-efficiency dialysis membranes.

Two children underwent acute hemodialysis using high-efficiency dialysis membranes for vancomycin intoxication (plasma levels 238 microg/ml and 182 microg/ml). During a 3-h treatment, plasma vancomycin removal was on average 60%, with a calculated vancomycin half-life (t(1/2)) of 2 h. This is in contrast to a recent report using charcoal hemoperfusion for vancomycin intoxication (plasma level of 137 microg/ml), which resulted in a 40% relative plasma clearance and a calculated vancomycin t(1/2) of 12.5 h for a 4-h treatment. The choice of optimal modality for clearing a toxin should take into account the availability of equipment, protein or lipid binding of the toxin, and inherent risks of charcoal hemofiltration (large extracorporeal circuit, reversible hypocalcemia, heat loss, reversible coagulation defects) versus risks of high-efficiency hemodialysis (large extracorporeal circuit).

Anti-Bacterial Agents↗