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PubMed1998

Tryptase levels are not increased during vancomycin-induced anaphylactoid reactions.

BACKGROUND: Anaphylaxis, mediated by immunoglobulin E, may be clinically indistinguishable but is mechanistically different than chemically mediated anaphylactoid reactions induced by drugs such as morphine, curare, and vancomycin. A test to distinguish anaphylactic from anaphylactoid reactions would clarify therapeutic and medicolegal issues. Tryptase levels identify anaphylactic reactions but have not been evaluated in vivo during anaphylactoid reactions. A prospective, randomized, double-blinded, placebo-controlled trial of antihistamine chemoprophylaxis for rapid vancomycin infusion was performed, and plasma tryptase was measured using a new immunoassay. Histamine release was established by measurement of plasma histamine and the ability of prophylactic H1 and H2 antagonists to prevent common histamine-associated side effects. Tryptase levels were compared with histamine levels and clinical symptoms. METHODS: Before elective arthroplasty, 40 patients received vancomycin infusion (1 g over 10 min) and pretreatment with either antihistamines (1 mg/kg diphenhydramine and 4 mg/kg cimetidine) or placebo. Changes in tryptase (at peak histamine and 10 min after vancomycin infusion), histamine levels, and histamine-mediated symptoms were assessed using Fisher's exact test, the Student's t test, or the paired t test, as appropriate. Logistic regression models were used to quantify the association of clinical symptoms with antihistamine treatment and serum levels. RESULTS: Plasma tryptase levels were unchanged (99% CI, -0.5 to 1.6) independent of increased histamine levels, antihistamine pretreatment, clinical symptoms, or all of these. Histamine levels >1 ng/ml were significantly associated with hypotension, moderate-to-severe rash, and stopped infusion. Antihistamine pretreatment significantly decreased the incidence and severity of the reactions. CONCLUSION: Plasma tryptase levels were not significantly elevated in confirmed anaphylactoid reactions, so they can be used to distinguish chemical from immunologic reactions.

Adult↗

PubMed1990

Clearance of vancomycin during continuous arteriovenous hemodiafiltration.

The clearance of vancomycin during therapy with continuous arteriovenous hemodiafiltration (CAVHD) has been measured in vivo. Vancomycin clearances (n = 16) were 0.636 +/- 0.269 L/h (10.5 +/- 4.46 ml/min). Effective drug clearances were proportional to ultrafiltrate volumes, reflecting convective clearance. Clearances of vancomycin on CAVHD were approximately twice the values seen with continuous arteriovenous hemofiltration. These data allow construction of a dosing schedule for vancomycin therapy in patients receiving renal support via CAVHD.

Acute Kidney Injury↗

PubMed2001

Successful treatment of vancomycin-resistant enterococcus meningitis with linezolid: case report and review of the literature.

OBJECTIVE: To describe the successful treatment of a case of vancomycin-resistant enterococcus meningitis with linezolid. DESIGN: Case report and review of the literature. PATIENTS: The patient is a 35-yr-old man who suffered a cerebellar hemorrhage after embolization of a cerebellar arteriovenous malformation. The patient underwent ventriculostomy drainage and craniectomy. The patient was on broad-spectrum antibiotics for pneumonia including vancomycin. The patient remained febrile and grew vancomycin-resistant Enterococcus faecium from the cerebrospinal fluid. INTERVENTIONS: The patient was treated with intravenous chloramphenicol without success. On postoperative day 16, the patient was begun on intravenous linezolid. MAIN RESULTS: The patient received 4 wks of intravenous linezolid with complete eradication of the meningitis. CONCLUSIONS: Intravenous linezolid appears to be a safe and effective therapy for vancomycin-resistant enterococcus meningitis.

Acetamides↗

PubMed1994

A prospective study of vancomycin pharmacokinetics and dosage requirements in pediatric cancer patients.

Pharmacokinetics of vancomycin and dosage requirements were evaluated prospectively in 28 pediatric cancer patients 9 months to 13 years of age. The predictive performance of a two-compartment Bayesian forecasting program was also evaluated. A mean (+/- SD) daily dosage of 75 +/- 22 mg/kg/day was necessary to attain a mean peak serum vancomycin concentration (SVC) of 23.1 +/- 5.8 mg/liter and a mean trough SVC of 6.2 +/- 2.3 mg/liter. Mean vancomycin clearance, volume of distribution and serum half-life were 0.153 +/- 0.033 liter/hour/kg, 0.63 +/- 0.08 liter/kg and 2.95 +/- 0.48 hours. Final peak SVCs, which reflected the last dosage regimens received, were predicted with minimal bias (mean prediction error, -1.2 mg/liter) and accurate precision (root mean-squared prediction error, 2.0 mg/liter) whereas trough SVCs were predicted with even smaller bias (mean prediction error, -0.1 mg/liter) and greater precision (root mean-squared prediction error, 0.8 mg/liter). This study showed that pediatric cancer patients with normal renal function required vancomycin dosage regimens substantially greater than the standard 40 mg/kg/day to attain the desired SVCs.

Adolescent↗

PubMed1996

Experimental posttraumatic Bacillus cereus endophthalmitis in a swine model. Efficacy of intravitreal ciprofloxacin, vancomycin, and imipenem.

PURPOSE: The authors compare the intravitreal efficacy of ciprofloxacin, vancomycin and imipenem, in treating experimental Bacillus cereus endophthalmitis. METHODS: Thirty-three Yorkshire pigs received a surgically induced injury to the right eye, which was then repaired and injected with 8400 colony forming units of live B. cereus. Nine pigs received no therapy and served as a natural history group. Twenty-four other pigs then were randomized into a treatment group with ciprofloxacin (n = 6), vancomycin (n = 6), imipenem (n = 6), or normal saline (n = 6). Eyes were examined clinically 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours after inoculation. After 24 hours, the eyes were enucleated for histologic study. RESULTS: Experimental disease was characterized by an aggressively developing endophthalmitis, with retinitis and vitritis developing at 4 hours. Histologic examination showed vitreous abscess and retinal necrosis. Both vancomycin- and imipenem-treated group had less inflammation and tissue destruction than control animals, based on the Wilcoxon rank sum test (P < 0.05). Ciprofloxacin-treated animals showed significantly more intraocular destruction and were indistinguishable from controls. CONCLUSION: Vancomycin and imipenem appear to limit inflammation and tissue destruction when given early in the course of experimental posttraumatic endophthalmitis caused by B. cereus. Results with ciprofloxacin are less conclusive and warrant further investigation.

Animals↗

PubMed1987

Overestimation of vancomycin concentrations utilizing fluorescence polarization immunoassay in patients on peritoneal dialysis.

During a study of vancomycin pharmacokinetics in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), a discrepancy was noted when serum concentrations were determined by high performance liquid chromatography (HPLC) in comparison to a fluorescence polarization immunoassay (FPI) technique. Following three weekly intraperitoneal doses (30 mg/kg/2 L), peak serum concentrations (at the end of the 6-h dwell) by FPI were 42.1 +/- 9.1, 43.1 +/- 8.7, and 45.6 +/- 7.4 micrograms/ml. In comparison, the same samples when analyzed by HPLC yielded 36.3 +/- 9.4, 32.2 +/- 8.9, and 31.6 +/- 9.1 micrograms/ml, respectively. A subsequent in vitro study of vancomycin (40 micrograms/ml) in serum indicated a degradation half-life of 693 (FPI) compared with 210 (HPLC) h. These data suggest that vancomycin degradation products accumulate in CAPD patients and lead to an overestimation of vancomycin serum concentrations when measured by FPI.

Chromatography, High Pressure Liquid↗

PubMed1994

Column-switching high-performance liquid chromatographic determination of vancomycin in serum.

Concentrations of vancomycin in serum were measured by an automatic high-performance liquid chromatographic (HPLC) micromethod. Vancomycin is a glycopeptide antibiotic with broad application in the therapy of gram-positive infections. As this drug is potentially nephro- and ototoxic, a method to maximize its therapeutic benefit while minimizing the risk of toxicity is desirable. This fully automated HPLC method did not involve a sample pretreatment step. The configuration of the apparatus permitted a solid phase extraction of the serum sample on two precolumns filled with a reversed-phase material, followed by a chromatographic separation of the sample constituents on an analytical column. The reversed phase analytical column (muBondapak C18) was flushed with a mobile phase of water-acetonitrile-triethylamine, 870: 130: 4 (vol/vol/vol); the pH was adjusted to 3.0 with orthophosphoric acid. Precision was expressed as the coefficient of variation (CV), which was always < or = 4.13% for intra- and inter-assays (n = 10) in the range 2-50 micrograms/ml. We compared this specific HPLC determination to an enzyme-multiplied immunoassay (EMIT). Fifty clinical samples obtained from patients under vancomycin therapy were assayed by each method and results compared using a linear regression analysis. There was a significant correlation between results from HPLC and EMIT: EMIT = 0.51 + 1 x HPLC (r = 0.963; p < 0.0001). The rapidity and specificity of this HPLC micromethod make it suitable for use in the monitoring of serum levels of vancomycin and for use in pharmacokinetic studies of this antibiotic.

Autoanalysis↗

PubMed1994

Vancomycin pharmacokinetics in a patient population: effect of age, gender, and body weight.

The effects of age, gender, and body weight on the pharmacokinetics of vancomycin were examined using data collected as part of routine therapeutic drug monitoring in patients. One thousand eighty-five sets of steady-state peak and trough serum concentrations obtained from 704 different patients were used to calculate elimination rate constant (k), volume of distribution (V), and clearance (Cl) using a one-compartment model. The median half-life of vancomycin was 6.5 h. Clearance was significantly correlated with creatinine clearance as estimated using the Cockcroft-Gault equation [Cl = 0.771 (Clcr) + 18.9; r = 0.63]. V averaged 0.69 L/kg ideal body weight (IBW) with increased values in females, patients over age 60, and obese patients. V ranged from 0.58 L/kg IBW in normal weight males under age 40 to 1.17 L/kg IBW in obese females over age 60. V was not different in underweight patients and those of normal weight (43.8 vs. 44.4 L). Regression analysis indicated that V was more predictable in women than in men and that vancomycin distributed into excess body weight (EBW) to a greater extent in women. However, the correlation coefficients from multiple regression analysis of V with IBW, EBW, and age did not exceed 0.60, and the high root mean square error values of 11-15 L suggest considerable variability in V is not accounted for by these factors alone. Despite these limitations, dosing of vancomycin may be improved by adjusting initial estimates of V for patient age, gender, and obesity.

Adult↗

PubMed1996

Changes in vancomycin pharmacokinetics during treatment.

Using data gathered in routine monitoring, the pharmacokinetics of vancomycin during the first 10 days of treatment were compared with the pharmacokinetics after 10 days of treatment in 46 adult patients with normal renal function, ages 17-85 years old (mean +/- SD: 50.8 +/- 17.5). The mean time from initiation of treatment to the first sample determination was 5.5 days, and the mean time to the second determination was 13.4 days. Statistical differences between the two periods were observed for all pharmacokinetic parameters, except for the steady-state distribution volume. After 10 days of treatment, the mean +/- SD of the vancomycin clearance and elimination rate constant decreased from 1.31 +/- 0.82 to 1.13 +/- 0.72 ml/kg/min (p = 0.0044) and from 0.13 +/- 0.08 to 0.10 +/- 0.06 h-1 (p = 0.091), respectively. The half-life (t1/2) increased from 8.01 +/- 6.82 to 10.02 +/- 8.00 h (p = 0.012). The median percentage of the increment of t1/2 was 9.4%. The increase in t1/2 was > 50% in 12 patients and > 100% in nine cases. No association was found between the increment of t1/2 and the cumulative vancomycin dose. Frequent monitoring of serum vancomycin seems indicated, given the risk of decreased elimination during prolonged treatment.

Adolescent↗

PubMed2000

The clinical impact of early gram-positive bacteremia and the use of vancomycin after allogeneic bone marrow transplantation.

BACKGROUND: Gram-positive bacteremia (GPB) is an increasing infection after allogeneic bone marrow transplantation (BMT). Our purpose was to identify risk factors for GPB, to evaluate its impact on early mortality and morbidity, and to compare prophylactic with empirical intravenous vancomycin. METHODS AND RESULTS: We studied 89 consecutive BMTs in adult patients. Early GPB occurred in 29% of posttransplantation episodes. T-cell depletion (odds ratio [OR]: 0.18) and vancomycin-prophylaxis (OR: 0.28) reduced the risk of GPB. Mortality at 6 weeks was not significantly different in patients with GPB (15% vs. 9.5%, P = 0.669). GPB was associated with the development of major complications, the use of amphotericin B, and prolonged neutropenia. Vancomycin prophylaxis led to an increased risk of early renal dysfunction (OR: 18.7). CONCLUSION: GPB contributes to overall morbidity during the early post-BMT episode but has no impact on mortality. Vancomycin prophylaxis is effective to reduce GPB but has a negative effect on renal function.

Adolescent↗

PubMed2006

Pharmacokinetics and total elimination of meropenem and vancomycin in intensive care unit patients undergoing extended daily dialysis.

OBJECTIVE: Extended daily dialysis (EDD) combines the advantage of both intermittent hemodialysis and continuous renal replacement therapy: excellent detoxification accompanied by cardiovascular tolerability. The aim of this study was to evaluate pharmacokinetics of meropenem and vancomycin in critically ill patients with renal failure undergoing EDD. DESIGN: Prospective clinical study. SETTING: Surgical intensive care unit in a tertiary care center. PATIENTS: We studied intensive care patients with anuric acute renal failure being treated with EDD and receiving meropenem (n = 10) or vancomycin (n = 10) therapy. INTERVENTIONS: The antibiotics were administered 6 hrs (1.0 g meropenem) or 12 hrs (1.0 g vancomycin) before EDD was started in order to study the pharmacokinetics before and during EDD. In addition to the application of different methods to calculate pharmacokinetic parameters, the total dialysate concentration of both drugs was measured. RESULTS: Based on the amount of the drug recovered from the collected spent dialysate, the fraction of drug removed by one dialysis treatment was 18% for meropenem and 26% for vancomycin. Dosing regimes for intermittent hemodialysis and continuous renal replacement therapy cannot be used for critically ill patients treated with EDD. CONCLUSION: Our data suggest that patients treated with EDD by means of a high-flux dialyzer (polysulphone; surface area, 1.3 m; blood and dialysate flow, 160 mL/min; EDD time, 480 mins) and current dosing regimens run the risk of being significantly underdosed, which may have detrimental effects on critically ill patients with life-threatening infections. The exact dose has to be tailored according to weight and severity of illness as well as the current minimal inhibitory concentration against the incriminated bacteria. Whenever possible, therapeutic drug monitoring should be performed.

Acute Kidney Injury↗

PubMed2005

Vancomycin-resistant staphylococci and enterococci: epidemiology and control.

PURPOSE OF REVIEW: This review updates information on the development and spread of vancomycin resistance in staphylococci and enterococci. RECENT FINDINGS: New information on the genetic characterization of vancomycin-resistant Staphylococcus aureus isolates from the US indicates that each of the four was the result of an independent genetic event. New data suggest that vancomycin-intermediate S. aureus isolates, particularly those showing heteroresistance, are clinically significant. Finally, vancomycin-resistant enterococci continue to be reported from around the world. Novel infection control measures, however, may aid in reducing the spread of these organisms in healthcare settings. SUMMARY: The exchange of genetic information, particularly the vanA gene, between and among staphylococci and enterococci will continue to challenge physicians, microbiologists, and infection control practitioners in efforts to identify, treat, and prevent infections with these pathogens.

Enterococcus↗

PubMed2006

Significant absorption of oral vancomycin in a patient with clostridium difficile colitis and normal renal function.

Orally-administered vancomycin is poorly absorbed in most patients, usually producing minimal or subtherapeutic serum concentrations. Bowel inflammation may enhance absorption of oral vancomycin, particularly in those with renal failure. A 77-year-old female with Clostridium difficile (C difficile) colitis and normal renal function was treated with high doses of oral vancomycin and achieved serum concentrations in the therapeutic range. To our knowledge, this is the first report of a patient with C difficile colitis and normal renal function to develop therapeutic serum concentrations following oral administration of vancomycin.

Absorption↗

PubMed2003

Moenomycin-resistance is associated with vancomycin-intermediate susceptibility in Staphylococcus aureus.

We have previously isolated a vancomycin-intermediate susceptibility mutant from methicillinresistant Staphylococcus aureus(MRSA) strain COL, and demonstrated the increased glycan-chain length and the decreased moenomycin-susceptibility. To further investigate the relationship between the resistance to vancomycin and to moenomycin, we isolated moenomycin-resistant mutants (4-16 fold higher compared to the parent) from 5 MRSA and 2 methicillin-sensitive S. aureus(MSSA) strains. The MRSA mutants showed a decreased susceptibility to vancomycin (2-4 fold), teicoplanin (2-4 fold) and an increased susceptibility to methicillin (2-8 fold). MSSA strains also showed similar results with those of MRSA strains except that there was no alteration of methicillin susceptibility. Among the mutants, three mutants including two MRSA mutants and one MSSA mutant were analyzed by electron microscopy, and they showed thickened cell walls compared to those of the parents. The glycan-chain length of the peptidoglycan of the mutant was shown to be slightly longer than that of the parent, but the muropeptide profile was very similar. The expression levels of all PBPs were similar to those of the parent. Furthermore, the nucleotide sequences of sgtA, sgtB and pbp2 in the mutant were identical to those of the parent. These results indicate that the moenomycin-resistance is closely associated with vancomycin-intermediate susceptibility in S. aureus.

Anti-Bacterial Agents↗

PubMed1992

Administration of vancomycin during cardiopulmonary bypass.

Vancomycin was given during cardiopulmonary bypass to 12 anaesthetised patients undergoing open heart surgery. Injection of vancomycin 1 g within 60 s via the venous inlet of the oxygenator resulted in a moderate and transient decrease of mean arterial pressure. This minimal reaction may be attributed to dilution of vancomycin by the extracorporeal circuit volume, to the bypassing of the lungs which are a major site of storage of vasoactive substances, or to the maintenance of adequate perfusion flow during cardiopulmonary bypass. The results suggest that the haemodynamic adverse reactions to vancomycin, given as antibiotic prophylaxis, may be decreased by its administration after initiation of cardiopulmonary bypass.

Adult↗

PubMed2006

Short course of linezolid treatment for vancomycin-resistant Enterococcus faecium meningitis.

Enterococci might be one of the meningitis pathogens, but meningitis is rarely caused by vancomycin-resistant enterococci. In this report, we present a 69-year-old man who had the underlying chronic obstructive pulmonary disease with long-term steroid treatment suffered from a meningitis episode after hospitalisation for the urinary tract infection. The cerebrospinal fluid culture of the patient grew Enterococcus faecium which was resistant to vancomycin. A vancomycin-resistant E. faecium was also isolated from the rectal swab of the patient. These two E. faecium isolates were found to harbour the vanA gene and to be identical by pulsed field gel electrophoresis typing. The patient was treated successfully with intravenous linezolid, 600 mg every 12 h for 2 weeks. This was the first case of meningitis caused by vancomycin-resistant E. faecium in Taiwan.

Acetamides↗

PubMed2005

Efficacy of a non-vancomycin-based peritoneal dialysis peritonitis protocol.

BACKGROUND: Peritonitis has a significant impact upon morbidity and mortality of peritoneal dialysis (PD) patients. Gram-positive organisms account for the majority of infections and vancomycin is a cost effective broad-spectrum antimicrobial treatment for PD peritonitis, but this may lead to the emergence of multiple antibiotic-resistant organisms. The purpose of the present paper was to evaluate the efficacy of a non-vancomycin-based protocol comprising cephazolin and gentamicin, which was introduced in the present PD population as empirical treatment for peritonitis. METHODS: The study involved 82 peritonitis episodes over a 4-year period in 58 patients, excluding those with previous methicillin-resistant staphylococcal peritonitis. RESULTS: With cephazolin and gentamicin there was no apparent difference in response or relapse rates in comparison to reported studies using vancomycin-based first-line therapy protocols. CONCLUSION: We advocate initial treatment of PD peritonitis with non-vancomycin-based therapy given similar efficacy and the potential for reduction of resistant organisms.

Adult↗

PubMed1997

Does vancomycine increase aminoglycoside nephrotoxicity?

Vancomycine and amikacin combined is an effective antibiotic combination used in the treatment of serious Gram-positive bacteremia in childhood. However, both drugs may have a potential nephrotoxic effect when used individually. The present study investigates whether the nephrotoxicity of these drugs that display a nephrotoxic effect when used separately increases when used in a combined manner. Ten 2-month-old rats were subjected to intraperitoneal injections of vancomycine (100 mg/kg) and amikacin (80 mg/kg) and ten other 2-month-old rats were administered amikacin (80 mg/kg) for a period of 15 days. The control group of animals consisting of five 2-month old rats were untreated. The renal tissues obtained by laparotomy were processed for both light and electron microscopy. Paraffin sections and ultrathin sections were evaluated in order to determine the renal structure of the control and the experimental groups. In addition, serum creatinine and blood, urea and nitrogen (BUN) levels were measured in blood samples obtained from the rats. In the amikacin and combined amikacin-vancomycine treatment groups, renal morphological changes were observed at the glomerular and tubular levels when compared to the control group, and the serum creatinine and BUN levels were also higher in these groups. Although both experimental groups were different from the control group, they had similar morphological and biochemical features. It was concluded that vancomycine did not influence the nephrotoxic effect of amikacin and both drugs could be used in a combined manner.

Amikacin↗