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PubMedDate not supplied

Pharmacokinetic analysis of vancomycin in steady state in pediatric cancer patients.

Thirty children suffering from different types of malignancies, neutropenic fever, and suspected staphylococcal bacteremia were evaluated for the pharmacokinetics of vancomycin in steady-state conditions and compared with eight children suffering from proven methicillin-resistant staphylococcal infection. All the studied population received intravenous vancomycin at 40 mg/kg daily divided into four daily doses. The individual pharmacokinetic parameters were calculated using a one-compartment model for two blood vancomycin samples. The mean (+/- SD) half-time (t1/2, hours), clearance (L/h/kg), Vss (L/kg), Cmax (microgram/mL), and Cmin (microgram/mL) were 10.5 (7.9) and 14.9 (9.1) hours; 0.11 (0.14) and 0.06 (0.06) L/h/kg; 0.62 (0.33) and 1.3 (0.6) L/kg; 28.3 (11.8) and 22.3 (9.8) micrograms/mL; and 5.7 (6.0) and 7.4 (4.8) micrograms/mL for the malignancy and control groups, respectively. The malignancy group had a significantly shorter t1/2 (P = .005), higher clearance (P = .005), and lower Cmin (P = .03) in comparison with the control group. It is suggested that the prescription of vancomycin at 40 mg/kg daily, divided into four daily doses, is safe and will provide a peak blood level of vancomycin sufficient to cover the broad spectrum of staphylococcal bacteria. The vancomycin dose should be individualized, based on an individual pharmacokinetic profile.

Anti-Bacterial Agents↗

PubMed1999

No influence of large volume blood loss on serum vancomycin concentrations during orthopedic procedures.

We prospectively studied orthopedic patients with either large or small blood loss who also received vancomycin prophylaxis to determine the effect of intraoperative volume shifts on serum vancomycin concentrations. There were 6 index patients in the large blood loss group (greater than 2 L), and 7 in the control group (less than 2 L). Mean estimated blood loss for index and controls was 4.4 L and 1.0 L, respectively. Mean intraoperative fluid resuscitation, excluding blood products, was 12.4 L and 5.1 L, respectively. There was a modest inverse correlation between blood loss and intraoperative serum half-life of vancomycin. Although controls maintained slightly higher intraoperative vancomycin concentrations at each time-point, there was no statistically significant difference between the groups with regard to absolute concentrations or rate of decline. After 8 hours, the serum vancomycin concentration exceeded the MIC-90 for Staphylococcus aureus by approximately eightfold in all but one case patient. This was a morbidly obese patient with massive blood loss. Thus, blood loss during orthopedic procedures has minimal effects on intraoperative kinetics of vancomycin. Redosing is rarely indicated, although a preoperative 1.5 gram-dose should be considered for patients weighing more than 90 kg.

Adult↗

PubMed2005

Vancomycin and home health care.

The Hospital Infection Control Practices Advisory Committee published guidelines for prudent use of vancomycin to combat increasing resistance to antimicrobial drugs. Studies examining compliance with these guidelines primarily involve hospitalized patients. The growing practice of home use of antimicrobial drugs led to this retrospective cohort study that evaluated parenteral vancomycin use in patients receiving it through a homecare agency. We found that 39.2% of outpatients received vancomycin outside the guidelines, mainly because of prolonged empiric therapy, dosing convenience, and prolonged use after surgery. Patients were more likely to receive vancomycin appropriately if they were >65 years of age, had a history of malignancy, or were discharged from a medical service. In addition, obtaining wound cultures and attempting a microbiologic diagnosis led to more appropriate vancomycin use. Recommendations for prudent vancomycin use are often overlooked when selecting antimicrobial drugs for home infusion. The public health impact of this practice remains unknown.

Adult↗

PubMed2000

Vancomycin resistance and antibiotic susceptibility of enterococci in raw meat.

The purpose of this study was to investigate antimicrobial resistance, in particular to vancomycin, of enterococci in samples (100) of meat (beef, chicken, turkey, lamb, and pork) sold in retail outlets of Catanzaro (Italy). Enterococci were identified to the species level. Antimicrobial susceptibility tests for a large spectrum of antibiotics including glycopeptides were performed by the disk diffusion method. Kappa statistic was used to evaluate associations of resistance to vancomycin with other antimicrobials. Enterococci were isolated from 45% of the samples, mostly from chicken meat (65.4%). Overall, 29% of samples were contaminated by vancomycin-resistant enterococci (VRE), whereas among those positive they represented 64.4% of isolates. Higher prevalence of vancomycin resistance was found in chicken samples (76.5%). The overall resistance to teicoplanin (TRE) was 30%, whereas among those positive, TRE represented 66.7% of isolates. The most frequent isolates were Enterococcus faecium (35.6%) and Enterococcus faecalis (33.3%). Resistance to vancomycin and teicoplanin was observed in 75% and 78.5% of E. faecium, and in 40% and 46.7% of E. faecalis, respectively. Most strains were susceptible to ampicillin (80%), while 88.9% were resistant to methicillin. The most effective antimicrobials were imipenem (73.3% susceptible) and rifampin (80%). The highest prevalence of resistance was for streptomycin (88.9%), tetracycline (84.4%), and erythromycin (75.6%). Resistance to vancomycin was significantly associated to methicillin, teicoplanin, erythromycin, tetracycline, and chloramphenicol. Further investigations about enterococcal colonization and infections in community and hospital subjects are needed.

Animals↗

PubMed1999

Vancomycin and teicoplanin use in Victorian hospitals. The Victorian Drug Usage Evaluation Group.

OBJECTIVE: To determine patterns of prescribing of glycopeptide antibiotics (vancomycin and teicoplanin) in Victorian hospitals and identify areas for targeted intervention. DESIGN: A concurrent, observational, multisite evaluation of drug use. SETTING: Thirty-five Victorian hospitals, 1-14 September 1997. STUDY POPULATION: Patients commencing a glycopeptide antibiotic course. MAIN OUTCOME MEASURES: Rate of glycopeptide antibiotic use; indications; duration of use; main hospitals using glycopeptide antibiotics. RESULTS: 293 patients (269 adults and 24 neonates) commenced on 302 glycopeptide antibiotic courses: 296 intravenous (i.v.) vancomycin courses and three each of oral vancomycin and parenteral teicoplanin. The overall rate of use was 10.3 courses per 1000 inpatient separations. Of 271 i.v. vancomycin courses for adults, 176 (65%) were for treatment--120 empirically. The median duration of treatment courses was 4.7 days (interquartile range, 2.0-8.2 days). A flucloxacillin-resistant organism was confirmed for 44% of treatment courses. Ninety-five i.v. vancomycin courses were for prophylaxis, including for cardiac (54%) and vascular surgery (21%); 82% of prophylactic courses were administered for less than 24 hours. Of all the glycopeptide antibiotic courses, 69% were administered at five major metropolitan hospitals. CONCLUSIONS: Glycopeptide antibiotic use in Victoria is concentrated in the major metropolitan hospitals. Prolonged durations of vancomycin therapy, including for surgical prophylaxis and empirical therapy not subsequently confirmed by microbiology findings, would be suitable targets for interventional strategies.

Administration, Oral↗

PubMed1995

Cooperativity between non-polar and ionic forces in the binding of bacterial cell wall analogues by vancomycin in aqueous solution.

The clinically important glycopeptide antibiotic vancomycin binds to bacterial cell wall peptides of Gram-positive bacteria which terminate in -Lys-D-Ala-D-Ala, thereby inhibiting cell wall synthesis resulting in cell death. We have removed the N-terminal leucine residue of vancomycin by an Edman degradation and acylated the exposed amino group of residue 2 with N-Me-Gly, N-Me-D-Ala, acetyl, butyl, and isohexyl groups to generate novel vancomycin analogues. The binding of vancomycin and these vancomycin analogues to the bacterial cell wall analogue di-N-Ac-L-Lys-D-Ala-D-Ala (DALAA) was studied by NMR techniques and UV spectroscopy. The effects that these structural modifications of the carboxylate binding pocket of vancomycin have on the antibiotic-DALAA recognition process show that a cooperative effect between non-polar and ionic forces appears to be partly responsible for the highly efficient sequestering of the DALAA C-terminal carboxylate from aqueous solution.

Amino Acid Sequence↗

PubMedDate not supplied

Vancomycin: an overview for the podiatric physician.

An increased reliance on vancomycin to treat bacterial infections has led to the emergence of vancomycin-resistant organisms. The podiatric physician must select and use vancomycin with due caution. This article presents a general review of vancomycin's pharmacology, pharmacokinetics, and dosing recommendations. Literature citations of clinically based evidence regarding the development and use of vancomycin nomograms are also presented. A vancomycin dosing nomogram is introduced as an effective tool for the prescribing podiatric physician. Appropriate use of the information presented may improve patient outcomes and enable the podiatric physician to treat patients with less effort and at a lower cost.

Anti-Bacterial Agents↗

PubMed1993

Teicoplanin vs vancomycin: cost-effectiveness comparisons.

The rising incidence of methicillin-resistant staphylococci and resistant enterococci in recent years has led to increased use of vancomycin as an active combatant in the treatment of gram-positive infections. Teicoplanin is an investigational glycopeptide that shares a similar spectrum of activity with vancomycin and appears to have similar efficacy. Teicoplanin offers several theoretical advantages compared with vancomycin including once-daily dosing, fewer side effects, and the option for intramuscular administration. While these may be perceived as substantial advances in the glycopeptide class of antibiotics, teicoplanin will probably not replace the now generically available vancomycin on hospital formularies. If competitively priced as a once-daily dosing regimen, teicoplanin will likely gain initial acceptance as an alternative in patients with an intolerance to vancomycin infusion-related side effects or in patients placed on combination aminoglycoside therapy for extended periods of treatment, as an intramuscular antibiotic in patients with poor venous access, and for routine antibiotic prophylaxis where protection from resistant gram-positive pathogens is important. The use of teicoplanin in the hospital may become more widespread as its side effect profile and economic advantages of less frequent dosing compared with vancomycin become better understood.

Cost-Benefit Analysis↗

PubMed2000

Preoperative vancomycin prophylaxis for newly placed peritoneal dialysis catheters prevents postoperative peritonitis.

The role of vancomycin and other antibiotics in treatment of acute peritonitis in peritoneal dialysis patients is well established. However, the role of preoperative vancomycin or cephalosporins in preventing early infection in newly placed peritoneal dialysis catheters remains controversial. We performed a prospective randomized study to examine the role of vancomycin or cefazolin prophylaxis in decreasing the incidence of postoperative peritonitis. Over 8-year period, 265 patients undergoing 305 permanent peritoneal catheter placement procedures were randomized into three groups. Group I (103 procedures) received a single intravenous (i.v.) dose of 1000 mg vancomycin 12 hours before the peritoneal catheter placement procedure. Group II (102 procedures) received a single i.v. dose of 1000 mg of Ancef (cefazolin) 3 hours before the procedure. Group III (100 procedures) received no antibiotics preoperatively for a least one week before the procedure. Patients were monitored for peritonitis during the following 14 days. Peritonitis developed in 1 patient (1%) in Group I (vancomycin group) compared to 12 patients (12%) in Group III (control group), p = 0.002, and in 9 patients (9%) in Group II (cefazolin group) compared to Group III, p = 0.68. We conclude that the use of preoperative single-dose i.v. vancomycin prophylaxis for permanent peritoneal dialysis catheter placement reduces the risk of postoperative peritonitis. Cefazolin did not achieve a statistically significant difference from the control group and may not provide adequate prophylaxis.

Adolescent↗

PubMed1999

Ability of teicoplanin and vancomycin to induce contraction of, and histamine release from, pulmonary tissue of humans, monkeys and guinea pigs.

To assess the safety of teicoplanin and vancomycin with respect to airway tissue, we evaluated whether these two antibiotics induce pulmonary tissue contraction and histamine release in human, monkey and guinea pig specimens in vitro. The effects of these drugs on the release of histamine from monkey blood leucocytes and mouse bone marrow-derived mast cells (BMMC) were also studied. Neither teicoplanin nor vancomycin (10(-6)-10(-3) g/mL) induced contractions of guinea pig trachea or lung parenchyma. Similarly, these drugs induced no appreciable change in the resting tonus of cynomolgus monkey bronchus or lung parenchyma. The tonus of monkey trachea was not influenced by teicoplanin, whereas 10(-3) g/mL vancomycin caused contraction. The spontaneous tonus of human lung parenchyma was not altered by teicoplanin or vancomycin, and that of the bronchus was not influenced by teicoplanin; however, 10(-3) g/mL vancomycin elicited obvious contraction of the bronchus. Neither drug promoted the release of significant amounts of histamine from these pulmonary tissues or from monkey blood leucocytes and BMMC. These results suggest that, compared with vancomycin, teicoplanin may be associated with a lower risk of inducing bronchospasm when used for inhalation therapy.

Animals↗

PubMed2001

Vancomycin-resistant organisms on a burn unit.

The incidence of infections due to vancomycin-resistant organisms has significantly increased during the past several years. This is important because vancomycin has been the drug of choice for treatment of infections due to methicillin-resistant Staphylococcus aureus (MRSA). Enterococci resistant to vancomycin are now emerging, and MRSA organisms with intermediate resistance to vancomycin have been identified in some centers. Cross transfer of resistance will eventually lead to the widespread development of organisms that are more difficult to eradicate. In our burn unit, we have encountered six patients (five with burns, one with necrotizing fasciitis) who had wound infections with vancomycin-resistant enterococci. Four patients died, and two recovered after prolonged hospital stays. Attempts to limit development of vancomycin-resistant enterococci are important.

Adult↗

PubMed2001

Serum and synovial vancomycin concentrations following prophylactic administration in knee arthroplasty.

A single preoperative dose of 15 mg/kg of total body weight, to a maximum of 1 g of vancomycin, was administered intravenously to patients undergoing knee arthroplasty prior to anesthesia. Vancomycin concentration levels were examined in 39 patients. Vancomycin levels were analyzed preoperatively, intraoperatively, and postoperatively. Results confirmed effective serum and synovial vancomycin levels during surgery. Effective therapeutic levels of vancomycin remained in the knee >20 hours postoperatively. Although vancomycin is not commonly used as a prophylactic antibiotic in arthroplasty, it should be considered in patients with known hypersensitivity to penicillin, or when methicillin-resistant Staphylococcus aureus in present.

Aged↗

PubMed2002

Staphylococcus aureus resistant to vancomycin--United States, 2002.

Staphylococcus aureus is a cause of hospital- and community-acquired infections. In 1996, the first clinical isolate of S. aureus with reduced susceptibility to vancomycin was reported from Japan. The vancomycin minimum inhibitory concentration (MIC) result reported for this isolate was in the intermediate range (vancomycin MIC=8 microg/mL) using interpretive criteria defined by the National Committee for Clinical Laboratory Standards. As of June 2002, eight patients with clinical infections caused by vancomycin-intermediate S. aureus (VISA) have been confirmed in the United States. This report describes the first documented case of infection caused by vancomycin-resistant S. aureus (VRSA) (vancomycin MIC > or = 32 microg/mL) in a patient in the United States. The emergence of VRSA underscores the need for programs to prevent the spread of antimicrobial-resistant microorganisms and control the use of antimicrobial drugs in health-care settings.

Adult↗

PubMed2003

[Pharmacokinetics of vancomycin in continuous veno-venous hemofiltration].

OBJECTIVE: To investigate the pharmacokinetics of vancomycin in continuous veno-venous hemofiltration(CVVH) in order to determine appropriate vancomycin dosing strategies for patients receiving CVVH. METHODS: The serum concentrations of vancomycin were measured by TDx and the pharmacokinetics parameters were calculated. RESULTS: The pharmacokinetics of vancomycin during CVVH was fitted with open two-compartment model. At the beginning of CVVH, the pharmacokinetic parameters were: maximum plasma concentration (Cmax)=22.18 mg/L, minimum plasma concentration attained (Cmin)=5.82 mg/L, half-life of drug (T1/2)=5.75 h, apparent volume of distribution (Vd)=21.92 L, total body clearance of drug(CL)=3.49 L/h. On the 16 d of CVVH, the pharmacokinetic parameters were Cmax=38.70 mg/L, Cmin=16.50 mg/L, T1/2=33.32 h, Vd=12.92 L, CL=0.38 L/h. CONCLUSION: CVVH can significantly augment the clearance of vancomycin in acute renal failure patients. Dosing strategies for individualization of vancomycin therapy in patients receiving CVVH are proposed. Monitoring the serum concentration during CVVH is necessary.

Half-Life↗

PubMed1992

[In vitro activity of vancomycin and teicoplanin against gram-positive cocci].

The activities of vancomycin and teicoplanin against 148 strains of Gram-positive cocci were tested using agar diffusion and liquid microdilution MIC determination. Tested strains included 84 staphylococci, 32 S. aureus, 52 coagulase-negative staphylococci (CNS), 52 enterococci, and 12 streptococci. Most strains (136) were susceptible to both agents, with inhibition diameters of 17 mm or more. MRSA strains exhibited lower geometric MIC means with teicoplanin (0.90 micrograms/ml) than with vancomycin (1.79 micrograms/ml); this difference was found for methicillin-susceptible S. aureus strains (1.07 and 1.38 micrograms/ml for teicoplanin and vancomycin, respectively). In contrast, methicillin-susceptible and methicillin-resistant strains of CNS exhibited similar MICs (1.60 micrograms/ml approximately). Enterococci were more susceptible to teicoplanin (MIC 0.25 micrograms/ml) than to vancomycin (MIC 1.35 micrograms/ml). Both vancomycin and teicoplanin were thus found to be consistently effective against Gram-positive cocci; however, teicoplanin proved more effective than vancomycin against enterococci and methicillin-resistant S. aureus strains and may therefore be a valuable therapeutic alternative for these multiresistant organisms.

Anti-Bacterial Agents↗

PubMed2004

Significance of vancomycin resistant enterococci from urinary specimens at a tertiary care centre in northern India.

BACKGROUND & OBJECTIVES: There is a paucity of information on vancomycin resistance in enterococci from India. In the present study, enterococci isolated from urine specimen were screened for vancomycin resistance. METHODS: 144 enterococci isolates obtained in pure and significant numbers (>10(5) cfu/ml) from 9664 urine specimens were subjected to agar screen method of National Committee for Clinical Laboratory Standard (NCCLS) for presence/absence of vancomycin resistance. Minimum inhibitory concentration (MIC) was performerd by E-test and agar dilution method. RESULTS: Eight vancomycin resistant enterococci (VRE) were obtained, namely, 5 Enterococcus faecium, 1 each of Enterococcus faecalis, E. casseliflavus and E. pseudoavium. The MIC ranged from 8 to 32-microgm/ml. The records of these 8 patients were retrospectively reviewed for clinical details. Five patients had nosocomial urinary tract infection (UTI), while in 2 patients UTI was community acquired. One patient had asymptomatic bacteriuria. Two patients with nosocomial UTI developed clinical sepsis and died in spite of vancomycin treatment. Urinary catheterization, surgery on genitourinary tract, prior exposure to third generation cephalosporins and metronidazole were present in 6,5,3 and 2 patients respectively. INTERPRETATION & CONCLUSION: Although the frequency of isolation of VRE is not very high in our setting as compared to West, this may just be the beginning of the problem. Screening for vancomycin resistance is recommended in all patients with suspected UTI who have significant bacterial counts.

Adult↗

PubMedDate not supplied

Vancomycin and ciprofloxacin: systemic antibiotic administration for peritoneal dialysis-associated peritonitis.

OBJECTIVES: Peritonitis due to peritoneal dialysis (PD) is best treated empirically while waiting for the results of the dialysate culture. Thus, antibiotic therapy must cover both gram-positive and gram-negative micro-organisms. First, over a period of 9 years in a multicenter study we evaluated the efficiency of a vancomycin and ciprofloxacin combination given as the first-line treatment protocol for PD peritonitis. Second, we evaluated whether a systemic route of administration of the antibiotics could be an interesting alternative to the usual cumbersome intraperitoneal drug administration. METHODS: Vancomycin 15 mg/kg body weight, intravenous, and oral ciprofloxacin 250 mg two times per day (500 mg twice per day if residual creatinine clearance was above 3 mL/minute) were prescribed at diagnosis of peritonitis. Vancomycin injections were repeated (when blood trough level was expected to be below 12 microg/mL) in cases of gram-positive organisms for a total duration of 3 weeks. Ciprofloxacin was given for a total of 3 weeks in cases of gram-negative and a total of 10 days for susceptible gram-positive infections. RESULTS: A total of 129 episodes of peritonitis occurred; 28 of them were not included in the study because of protocol violation (n = 15) or fungal (n = 7) or fecal (n = 6) peritonitis, leaving 101 peritonitis episodes for analysis. 52 (51.5%) gram-positive and 28 (27.7%) gram-negative organisms were grown; 38 gram-positive organisms were coagulase-negative staphylococci. No organism was identified in 8 peritonitis episodes, whereas 13 peritonitis episodes were caused by more than 1 organism. 35% of the coagulase-negative staphylococci were resistant to first-generation cephalosporin and methicillin, whereas all were susceptible to vancomycin. For gram-negative bacilli, the susceptibility rate was 96% and 95% for ciprofloxacin and ceftazidime respectively. The overall treatment success rate was 77.2% (78 of the 101 peritonitis episodes): 61.4% at first intention and 15.8% after optimization of the antibiotic therapy (second intention). The protocol failed in 22.8% of the peritonitis episodes. Hospitalization was required in 52% of the peritonitis episodes; average hospitalization was 11 (range 1-45) days. CONCLUSION: Systemic vancomycin and ciprofloxacin administration is a simple and efficient first-line protocol antibiotic therapy for PD peritonitis. In our opinion, vancomycin should still be used for gram-positive infections because of its high susceptibility rate compared with first-generation cephalosporins, providing a close monitoring of the local epidemiology. Oral ciprofloxacin provides satisfactory results in gram-negative infections, comparable to those obtained with intraperitoneal ceftazidime or aminoglycosides.

Administration, Oral↗

PubMed2006

Health economics assessment study of teicoplanin versus vancomycin in Gram-positive infections.

The objective of this study, conducted at Hospital Clínico San Carlos, Madrid, Spain, was to compare the cost of treatment of Gram-positive infections with teicoplanin and vancomycin under normal conditions. Using a prospective observational study design for drug utilization and economic assessment, we evaluated the comparability of the sample, adverse events, features of treatment with teicoplanin/vancomycin and factors influencing the consumption of resources until the end of glycopeptide treatment or discharge (whichever occurred later) using Health System perspective. Costs were assigned using the hospital's evaluation at the time of the study. Analyses made: multivariate, sensitivity (by modifying staff or acquisition costs) and simulation of reduction of stay by early discharge in the teicoplanin group. Study participants included 201 patients who had been using teicoplanin (n=100) or vancomycin (n=101) for at least four days. Data collected daily outside morning work timetable. Costs of acquisition, administration and monitoring by course of treatment (mean+/-SD, in euros) were lower in the vancomycin group (teicoplanin euro647.62+/-euro572.75 vs. vancomycin euro378.11+/-euro225.90); when total costs (including hospital stay) were considered, no differences were found (teicoplanin euro4,432.04+/-euro3,383.46 vs. vancomycin euro4,364.44+/-euro2,734.24). Conditions of use and results were similar for both antibiotics. The economic results of acquisition, administration and monitoring were advantageous for vancomycin; when global costs of care were taken into account, these differences were not evident. Tolerability was significantly advantageous in the teicoplanin group (with regard to phlebitis and elevation of creatininemia), without differences in clinical or economic outcomes. The formulation of teicoplanin did not take advantage of its potential benefits of administration.

Adult↗