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PubMed1992

Exchange transfusion and multidose activated charcoal following vancomycin overdose.

The inadvertent administration of a concentrated vancomycin solution to a 47 day-old premature male twin resulted in extremely high vancomycin levels and altered renal function. A 1.5 volume exchange transfusion did not change the measured vancomycin level. Multiple doses of oral activated charcoal, 1 g/kg, were administered beginning 5 h after the exchange transfusion. A calculated half-life of vancomycin before the exchange transfusion was 35 h. The half-life after the exchange transfusion and during charcoal administration was calculated to be 12 h. The only apparent adverse effect of this vancomycin overdose was reversible nephrotoxicity. The infant's hearing, tested by brainstem auditory responses, was normal. The higher volume of distribution of vancomycin in infants may preclude removing significant amounts of this drug by exchange transfusion. Gastrointestinal dialysis with activated charcoal warrants consideration in cases of vancomycin overdose in neonates.

Charcoal↗

PubMed1992

Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo-controlled trial.

OBJECTIVE: To compare the efficacy of vancomycin and metronidazole for eradication of asymptomatic Clostridium difficile fecal excretion as a means of controlling nosocomial outbreaks of C. difficile diarrhea. DESIGN: Randomized, placebo-controlled, non-blinded trial. SETTING: Six hundred-bed regional referral Veterans Affairs Medical Center. PATIENTS: Thirty patients excreting C. difficile without diarrhea or abdominal symptoms. INTERVENTIONS: All patients were randomized to receive 10 days of oral vancomycin, 125 mg four times daily; metronidazole, 500 mg twice daily; or placebo, three times daily. MEASUREMENTS: Stool cultures were obtained during treatment and for 2 months after treatment. All C. difficile isolates were typed by restriction endonuclease analysis (REA). RESULTS: Clostridium difficile organisms were not detected during and immediately after treatment in 9 of 10 patients treated with vancomycin compared with 3 of 10 patients treated with metronidazole (P = 0.02) and 2 of 10 patients in the placebo group (P = 0.005). The fecal vancomycin concentration was 1406 +/- 1164 micrograms/g feces, but metronidazole was not detectable in 9 of 10 patients. Eight of the nine evaluable patients who had negative stool cultures after treatment with vancomycin began to excrete C. difficile again 20 +/- 8 days after completing treatment. Three of these patients received additional antibiotics before C. difficile excretion recurred, and five acquired new C. difficile REA strains. Four of six patients who received only vancomycin before C. difficile excretion recurred were culture-positive at the end of the study compared with one of nine patients who received only placebo (P = 0.047). CONCLUSIONS: Asymptomatic fecal excretion of C. difficile is transient in most patients, and treatment with metronidazole is not effective. Although treatment with vancomycin is temporarily effective, it is associated with a significantly higher rate of C. difficile carriage 2 months after treatment and is not recommended.

Aged↗

PubMed1998

Serum and bone concentrations of teicoplanin and vancomycin: study in an animal model.

Teicoplanin and vancomycin are antibiotics widely used in the therapy of bone and joint infections. The aim of this study was to compare bone and serum concentrations of each antibiotic in guinea pigs after administration of 50 mg/kg of teicoplanin or vancomycin by the intravenous route. Serum and bone concentrations were determined immediately before and 0.5, 1, 2, 6, 12 and 24 h after drug administration by means of high performance liquid chromatography. Teicoplanin concentrations were always higher than vancomycin levels. Area under the concentration/time curve was significantly greater for teicoplanin than for vancomycin. In bone, teicoplanin concentration increased up to 6 h, while vancomycin reached its peak after 2 h. Moreover, teicoplanin showed markedly higher levels at 6, 12 and 24 h than vancomycin. In conclusion, the ability of teicoplanin to penetrate bone in greater amount than vancomycin confirms the potential use of teicoplanin in the treatment of bone infections and in the prophylaxis of orthopedic surgery.

Analysis of Variance↗

PubMed2001

[Vancomycin-resistant enterococci(VRE)].

The incidence of Enterococcal nosocomial infection has increased since 1980s. Most Enterococci are intrinsically resistant to many kinds of antibiotics, therefore, therapeutic drugs for enterococal infectious disease are limited to a few antibiotics such as ampicillin, gentamicin and vancomycin. However, since the first report of penicillinase producing E. faecalis in 1983, ampicillin-resistant strains have been increasing, furthermore, these strains often associated with high-level resistance to aminoglycosides. The yearly usage of vancomycin increased because vancomycin was only effective drug against such resistant strains and worldwide spread of multidrug-resistant MRSA which vancomycin is only effective. However, High-level vancomycin-resistance strains of E. faecium were first isolated in England in 1986. In 1990s, VRE have been spreading all over the world, especially, the emergency of multidrug-resistant strains, which are resistant to high concentrations of ampicillin or gentamicin or to vancomycin in USA, brought serious therapeutic dilemmas. This review focuses on the background in emergence of VRE, the relation with use of avoparcin, is used for growth promotion in farm animals, the mechanism of resistance, and the prevention of the spread of vancomycin resistance.

Cross Infection↗

PubMedDate not supplied

Intravenous vancomycin pharmacokinetics in automated peritoneal dialysis patients.

The pharmacokinetics of intravenous (i.v.) vancomycin was studied in automated peritoneal dialysis (APD) patients who received a single i.v. dose of vancomycin (15 mg/kg total body weight). Dialysate samples were collected at the beginning, middle, and end of dwells 1-3 (on-cycler), and at the end of dwells 4 and 5 (off-cycler), for a 24-hour period. Blood samples were collected at the beginning, middle, and end of dwells 1-3 (on-cycler), and at the end of dwell 5 (off-cycler) for a 24-hr period. Pharmacokinetics parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and vancomycin clearance (CI) values were normalized to 1.73 m2. Ten patients [4 males, 6 females; 47.4 +/- 9.9 years of age (mean +/- SD)] who had received PD for a median 3.5 months (range 2-66 months) were studied. Dwell times were 2.3 +/- 0.1 hours on cycler and 7.3 +/- 0.1 hours off cycler. Vancomycin half-life was significantly different on-cycler than off-cycler (11.6 +/- 5.2 hr vs 62.8 +/- 33.0 hr; p < 0.001). Vancomycin total CI (CI(T)) was 7.4 +/- 2.0 mL/min. Renal CI (CI(R)) and PD CI (CI(PD)) accounted for 23.6% and 28.0% of CI(T). respectively. CI(R) correlated with GFR (CI(R) = 0.90 GFR - 1.01; r2 = 0.79; p = 0.008). Mean vancomycin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (5 micro/mL) for the first cycler and the second ambulatory exchanges only. The results of this study suggest that, to provide adequate concentrations for susceptible organisms over a 24-hour period, current intermittent vancomycin dosing recommendations for PD-related peritonitis need to be changed to 35 mg/kg intraperitoneally on day 1, then 15 mg/kg i.p. thereafter (i.e., once daily) in APD patients.

Adult↗

PubMed1975

Effects of vancomycin on platelets, plasma proteins and hepatitis B surface antigen.

The antibiotic vancomycin shares many similarities with ristocetin, an agent noted for its effects on platelets and plasma fibrinogen. Vancomycin did not aggregate platelets as ristocetin, but platelets were incorporated into precipitates induced by vancomycin. Fibrinogen and factor VIII were precipitated from plasma at low concentrations of vancomycin. The precipitated fibrinogen remained clottable. Hepatitis B surface antigen was selectively precipitated from serum and could be recovered from the precipitate. Rabbits receiving bolus intravenous injections of high doses of vancomycin developed hypofibrinogenemia and thrombocytopenia within minutes and often went on to die. Studies with 125I-vancomycin revealed little stable binding of the antibiotic to platelets or fibrinogen. A relationship is suggested between the potent protein precipitating effects and phlebitis at the infusion site commonly associated with vancomycin therapy.

Animals↗

PubMedDate not supplied

Comparison of vancomycin versus cefazolin as initial therapy for peritonitis in peritoneal dialysis patients.

The incidence of peritonitis ranges from 1 episode every 24 patient treatment months to 1 episode every 60 patient treatment months [Keane WF, et al. ISPD Guidelines/Recommendations. Adult peritoneal dialysis-related peritonitis treatment recommendations: 2000 update. Perit Dial Int 2000; 20:396-411.]. Gram-positive organisms account for over 80% of continuous ambulatory peritoneal dialysis (PD)-associated peritonitis. Recent fear of vancomycin-resistant enterococci (VRE) has prompted suggestions of limiting vancomycin use. Fifty-one episodes of peritonitis in 30 patients studied over 2 years were evaluated. Cloudiness of the PD fluid and/or abdominal pain were considered suggestive of peritonitis and were confirmed by cell count and culture. Baseline cell count, Gram stain, and cultures were obtained, with periodic follow-up. Patients were randomized to receive either vancomycin 1 g/L intraperitoneally (IP) as loading dose, repeated on day 5 or day 8, depending on residual renal function, for 2 weeks, or cefazolin 1 g in the first PD bag and continued with 125 mg/L every exchange for 2 or 3 weeks, depending on culture results. All patients also received gentamicin 40 mg IP every day until the culture results were available. A similar randomized trial comparing vancomycin and cefazolin in the past used a lower concentration of cefazolin 50 mg/L [Flanigan MJ, Lim VS. Initial treatment of dialysis associated peritonitis: a controlled trial of vancomycin versus cefazolin. Perit Dial /nt 1991; 11:31-7.]. Peritoneal dialysate fluid cultures revealed 31(60.7%) gram-positive organisms, 7(13.7%) gram-negative organisms, and 2 (3.9%) cultured yeast; 11 (21.5%) cultures yielded no growth. The incidence of peritonitis at our center was 1 episode every 42 patient treatment months. No case of VRE was noted. There was no statistical difference in clinical response or relapse rate for the two protocols. It was the authors' and nurses' observation that patient compliance and satisfaction was better with vancomycin, and the cost per treatment was 23% less than cefazolin. Based on these data we believe vancomycin should still be considered for first-line treatment of PD-associated peritonitis.

Adult↗

PubMed1992

[Initial dosage of vancomycin in neutropenic hematologic patients].

PURPOSE: To evaluate the percentage of neutropenic patients who reach the therapeutic threshold when vancomycin is given at standard initial doses of 500 mg/6 hr, and to assess the creatinine clearance and body vancomycin clearance in such patients. MATERIAL AND METHODS: The study was performed on 37 haematological patients with normal renal function. They received intravenous vancomycin at an initial 500 mg/6 hr doses. The plasma concentration of the drug was assessed 48-72 hr later, pharmacokinetic parameters being calculated. Creatinine clearance was estimated by two different methods. RESULTS: The concentration attained was beyond the therapeutic threshold in 100% of the patients. The correlations between vancomycin and creatinine clearance were r = 0.42 and r = 0.47 when the Cockroft-Gault's and the Jellife's methods, respectively, were used. Administration of vancomycin at initial doses of 500 mg/6 hr renders a very high percentage of patients with plasma concentration of the drug beyond the therapeutic margin. CONCLUSIONS: 1) The poor correlation between creatinine and vancomycin clearance in the patients with normal renal function does not allow using nomograms based on such values for estimation of the initial doses. 2) The estimation of initial doses based on the patient's weight (20-25 mg/kg) may render a higher percentage of patients with therapeutic concentrations from the beginning of treatment. The maintenance doses can be adjusted at 48-72 hr, after measuring the plasma concentrations. 3) Therefore, it seems advisable to perform further clinical assays on different groups in order to verify an increase of the drug's efficacy with no higher toxicity when the initial vancomycin doses is adjusted according to the patient's weight, as recommended here.

Adolescent↗

PubMedDate not supplied

[Pharmacologic clinical monitoring of serum vancomycin levels in pediatric patients].

OBJECTIVE: To analyze the results from the clinical monitoring of serum vancomycin levels among pediatric patients receiving this drug. METHODS: Retrospective study of data from routine monitoring of serum vancomycin concentrations. The study population includes children who received vancomycin for more than 3 days and had peak and trough vancomycin serum concentration documented. The vancomycin concentrations were measured by an immunoassay procedure. RESULTS: We obtained 70 vancomycin concentrations from pediatric patients whose ages ranged from newborn to 13 years old. Mean peak and trough concentrations were 45.7 +/- 8.0 and 18.7 +/- 9.6 micrograms/mL, respectively. We used as a reference normal ranges for Cpmax of 25-40 micrograms/mL and Cpmin of 5-40 micrograms/mL. Only 26.1% of the patients were on Cpmax normal ranges, 47.8% were above the range and 26% under the lower limit. In regards to the Cpmin 17% of the cases were between the accepted limits, 41% above the upper limit and 41% under the normal range. CONCLUSION: Our data suggest that less than a fifth of the patients have serum levels on therapeutic range and almost half of these population had serum levels above the normal range. This might be explained by the type of the population sampled, reflecting a selection bias by detecting levels only among patients with an increased risk for toxicity. Finally, we stress the importance of accurately documenting dose, timing, and renal function in the records of all patients subjected to serum vancomycin determinations.

Adolescent↗

PubMed2005

Susceptibility of methicillin-resistant Staphylococcus aureus to vancomycin, teicoplanin, linezolid, pristinamycin and other antibiotics.

BACKGROUND: Methicillin-resistant Staphylococcus aureus is a major nosocomial pathogen worldwide. Vancomycin is the traditional drug of choice, but decreasing susceptibility to vancomycin and other glycopeptides has been reported since 1996. OBJECTIVES: To test the in vitro activity of linezolid (oxazolidinone) and other antimicrobial agents against MRSA isolates recovered from hospitalized patients. METHODS: We tested 150 MRSA isolates recovered from hospitalized patients. The minimal inhibitory concentration of vancomycin, teicoplanin, pristinamycin (quinupristin-dalforistin) and linezolid was determined by the Etest method. Susceptibility to other antibiotics was tested by the disk diffusion method. RESULTS: All isolates were sensitive to vancomycin, teicoplanin, pristinamycin, and linezolid. The MIC90 was 2.0 microg/ml for vancomycin and teicoplanin (range 0.5-2.0 microg/ml and 0.125-2.0 microg/ml, respectively), and 0.5 microg/ml for pristinamycin and linezolid (range 0.125-0.75 microg/ml and 0.125-0.5 microg/ml, respectively). Of the other antibiotics, fusidic acid showed the best in vitro activity, with 96.7% susceptibility, associated with trimethoprim/sulfamethoxazole (85.8%) and minocycline (84%). Penicillin was associated with the lowest susceptibility (1.3%), associated with ofloxacin (3%) and erythromycin (14%). An increase in the minimal inhibitory concentration value of vancomycin was associated with a significant decrease in resistance to TMP-SMZ (P < 0.01) and an apparent increase in resistance to other antibiotics. CONCLUSION: The excellent in vitro activity of linezolid and its reported in vivo effectiveness renders it an important therapeutic alternative to vancomycin in the treatment of MRSA infection.

Acetamides↗

PubMed1988

Single- and multiple-dose pharmacokinetics of intravenously administered vancomycin in dogs.

Vancomycin was administered IV to healthy adult female dogs at a dosage of 15 mg/kg of body weight every 12 hours for 10 days. Pharmacokinetic values were determined after the first and last doses. The disposition of vancomycin was not altered by multiple dosing, and little accumulation attributable to multiple dosing was observed. Serum vancomycin concentration after the first and last dose were described, using a 2-compartment open model with first-order elimination. The distribution and elimination half-lives after the single dose were 15.4 +/- 2.7 minutes and 137 +/- 21.8 minutes (geometric mean +/- pseudo-SD), respectively; whereas the distribution and elimination half-lives after the last dose were 11.3 +/- 2.61 minutes and 104 +/- 11.2 minutes, respectively. The mean (+/- SD) area-derived volume of distribution was 396 +/- 156 ml/kg and 382 +/- 160 ml/kg after the first and last dose, respectively. Serum vancomycin clearance was 2.13 +/- 0.35 ml/min/kg and 2.49 +/- 0.79 ml/min/kg after the first and last dose, respectively, and 25 to 49% of the total dose of vancomycin was recovered in the urine in the first 24 hours after the single dose administered IV. Mean serum vancomycin concentration reached 101.8 +/- 30.6 micrograms/ml and 99.7 +/- 28.0 micrograms/ml at 5 minutes after a single dose and the last of the multiple doses, respectively, and decreased to 0.94 +/- 0.58 microgram/ml and 1.51 +/- 1.44 micrograms/ml, respectively, at 12 hours after administration. The side effects that accompany vancomycin treatment in human beings were not observed in the dogs; all remained healthy through the end of the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Stability of vancomycin hydrochloride in various concentrations of dextrose injection.

The stability of vancomycin hydrochloride in plastic syringes containing high concentrations of dextrose injection after storage for 24 hours in a refrigerator followed by storage for two hours at room temperature was studied. Vancomycin hydrochloride was reconstituted with sterile water for injection to a concentration of 50 mg/mL. One-milliliter samples were added to 9 mL of various concentrations of dextrose injection (5, 10, 15, 20, 25, and 30%) in 10-mL plastic syringes. Ten syringes of each concentration were stored at 4 degrees C for 24 hours. At various storage times, samples were assayed in triplicate for vancomycin using high-performance liquid chromatography. After 24 hours, the syringes were removed from the refrigerator, and the vancomycin concentration was determined after storage for two hours at room temperature. Percent change in vancomycin concentration during storage for 24 hours was less than 6% in all cases except for 5% dextrose injection at 4 and 24 hours. Vancomycin concentration did not change (percent change 0.7-5%) during storage for two hours at room temperature. Vancomycin hydrochloride is stable in various concentrations of dextrose injection when stored in plastic syringes for 24 hours in the refrigerator followed by two hours at room temperature.

Drug Stability↗

PubMedDate not supplied

The antibacterial action of vancomycin.

Vancomycin inhibits the second stage of cell wall synthesis in susceptible bacteria. Furthermore, there is evidence that vancomycin also alters the permeability of the cell membrane and selectively inhibits ribonucleic acid synthesis. Stable L-phase variants are susceptible to vancomycin, but induction of bacterial L-phase variants with vancomycin is very difficult. Vancomycin is active against a large number of species of gram-positive cocci and bacilli, such as Staphylococcus aureus (including methicillin-resistant strains), Staphylococcus epidermidis (including multiply resistant strains). Streptococcus pneumoniae (including multiply resistant strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus bovis, viridans group Streptococcus, enterococcus, Clostridium species, diphtheroids, Listeria monocytogenes, Actinomyces species, and Lactobacillus species. Antimicrobial activity can be enhanced with the combination of vancomycin and an aminoglycoside against S. aureus, S. bovis, enterococcus, and viridans Streptococcus. The combination of vancomycin and rifampin also has enhanced activity against S. aureus.

Actinomyces↗

PubMed1982

Vancomycin in rabbits: pharmacokinetics, extravascular diffusion, renal excretion and interactions with furosemide.

The pharmacokinetics, renal excretion, protein binding and extravascular diffusion of vancomycin in rabbits were studied. The effects of furosemide on these different parameters also were investigated. We observed a T 1/2 of 55 min and protein binding of 65% as determined in vitro by equilibrium dialysis. Vancomycin appeared to be secreted by renal tubules (fractional excretion: 177 +/- 44%). In vitro, furosemide (5 micrograms/ml) slightly decreased the vancomycin protein binding (from 65 to 57%). Furosemide significantly increased the renal excretion of vancomycin, through a tubular process without any effect on the filtered load. Vancomycin appeared slowly and at low concentrations in the extravascular fluid. The extravascular concentrations were higher when the antibiotic was administered by a 6-hr continuous infusion than when given by a 20-min infusion of the same dose. Our results suggested that the in vivo antibacterial effect to vancomycin could be enhanced by prolonged infusion. Also, it was demonstrated that furosemide has only a small effect on the kinetics of vancomycin.

Animals↗

PubMedDate not supplied

Toxicology of vancomycin in laboratory animals.

The 50% lethal dose (LD50) of vancomycin for rodents was higher than that of tobramycin but much lower than that of cefamandole nafate. The rodents died in clonic convulsions immediately after receiving vancomycin. The LD50 for dogs similar to that for rodents; however, deaths occurred several days after administration of vancomycin and resulted from renal failure. Rapid intravenous administration of vancomycin to dogs produced a significant decrease in blood pressure that was prevented by pretreatment with the antihistamine methapyrilene. Subchronic administration of vancomycin to laboratory animals in doses of 12.5-400 mg/kg caused no systemic toxicity. Concomitant administration of vancomycin and tobramycin to rats resulted in significantly increased nephrotoxicity compared to that caused by either agent alone. The nephrotoxic response of rats receiving vancomycin was only partially reversed by large volumes of water given orally before and after the drug.

Animals↗

PubMedDate not supplied

Association of vancomycin serum concentrations with outcomes in patients with gram-positive bacteremia.

We attempted to determine if an association exists between vancomycin serum concentrations resulting from traditional dosing regimens, and efficacy and toxicity outcomes. We reviewed the medical charts of 273 consecutive patients prescribed 273 courses of vancomycin therapy for documented, gram-positive bacteremia. Of the 273 courses of therapy, 45 and 31 patients met all criteria and were evaluated for toxicity and efficacy, respectively. The duration of fever and abnormal white blood cell counts, length of hospital stay, overall mortality, serum creatinine, and serum vancomycin concentrations were evaluated retrospectively. No association between initial peak or trough levels with mortality was noted. However, patients were more likely to become afebrile within 72 hours if peak and trough concentrations were 20 micrograms/ml or greater and 10 micrograms/ml or greater, respectively (p < 0.01). Patients were also more likely to have their white blood cell count return to normal within 72 hours if trough concentrations were 10 micrograms/ml or above (p < 0.01). No statistically significant correlation between nephrotoxicity and initial serum creatinine, days of hospital stay, or days of vancomycin therapy were found. Serum concentrations of vancomycin, assessed before the development of nephrotoxicity, were significantly higher in patients who became nephrotoxic. Mean (SD) trough concentrations were 23.2 (2.5) micrograms/ml and 10.2 (3.8) micrograms/ml in nephrotoxic and nonnephrotoxic patients, respectively. Our results suggest that the commonly accepted therapeutic range for vancomycin trough concentrations (< 10 micrograms/ml) may be too restrictive in patients receiving vancomycin therapy alone.

Adult↗

PubMed1995

Central venous catheter-related infections after bone marrow transplantation in patients with malignancies: a prospective study with short-course vancomycin prophylaxis.

Infections associated with double-lumen central venous catheters (CVCs) in patients undergoing BMT are presented. We prospectively studied infections occurring with 46 CVCs in 40 patients with malignancies during and up to 30 days after BMT. We randomised patients with insertions of CVCs to receive either a short course of vancomycin 500 mg x 3 peri-operatively (16 CVCs) or no VCM (11 CVCs). Six per cent of CVCs in the group with vancomycin prophylaxis became infected with Gram positive microorganisms compared with 55% in the control group (P < 0.05). Next, 19 patients with CVCs were all given prophylaxis, so finally 35 patients were given vancomycin compared with 11 patients with no vancomycin. In a total of 11 CVC-related infections, 79% of the microbiological isolates were staphylococci, all of which were sensitive to vancomycin. Vancomycin prophylaxis reduced the number of infected CVCs to 11% compared with 45% (P < 0.05) and bacteraemias to 6% compared with 45% (P < 0.01). All infections responded to antibiotic treatment. Prophylactic short-duration vancomycin during insertion of CVCs may reduce the incidence of line-associated infections and Gram positive bacteraemias in patients undergoing BMT.

Bacteremia↗

PubMed1994

Vancomycin anaphylaxis and successful desensitization.

This report describes vancomycin anaphylaxis and successful desensitization. A 35-year-old woman who tolerated vancomycin initially, developed generalized urticaria and respiratory distress when the drug was readministered. Symptoms recurred following infusion of vancomycin at a lowered rate and dose despite premedication with antihistamines and corticosteroids. Intradermal skin tests with vancomycin were positive at a concentration of 0.1 micrograms/mL. Control subjects reacted at a concentration of 10 micrograms/mL or greater. A rapid 1-day desensitization protocol was unsuccessful. The patient then was "desensitized" by sequential increments in intravenous vancomycin doses over 13 days. After the full therapeutic dose was tolerated, there was a loss of skin test reactivity to vancomycin. We conclude that desensitization to vancomycin is possible and may be the only means to treat an allergic patient adequately when there are no viable therapeutic alternatives.

Adult↗