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PubMed1987

Treatment of methicillin-resistant Staphylococcus aureus experimental osteomyelitis with ciprofloxacin or vancomycin alone or in combination with rifampin.

Therapy with vancomycin alone or ciprofloxacin alone did not significantly reduce the number of methicillin-resistant Staphylococcus aureus (MRSA) in bone in rats with experimental osteomyelitis, compared with the number in control rats. Treatment with rifampin significantly (p less than 0.01) decreased the number of MRSA per gram of bone compared with the number in control animals. There was no significant difference in the results of therapy with rifampin compared with the results obtained with the combination of vancomycin plus rifampin. The combination of ciprofloxacin plus rifampin was the most effective regimen for the treatment of MRSA experimental osteomyelitis and the results of therapy were significantly (p less than 0.01) superior to those following treatment with rifampin alone or the combination of vancomycin and rifampin. Following cessation of antimicrobial therapy, significant (p less than 0.01) regrowth of MRSA in bone occurred in animals treated with rifampin alone or ciprofloxacin plus rifampin. The emergence of resistance of MRSA during treatment occurred in two rats treated with rifampin alone and in one treated with rifampin plus vancomycin.

Animals↗

PubMed1986

Pharmacist interventions to improve prescribing of vancomycin and tobramycin.

The effect of clinical pharmacist interventions that promoted the use of nafcillin rather than vancomycin and of gentamicin rather than tobramycin, when appropriate, was evaluated. Physician information sheets and criteria describing appropriate use of the target drugs vancomycin and tobramycin were developed by a clinical pharmacist and infectious disease physicians. When drugs were prescribed for indications that did not meet the established criteria, the clinical pharmacist either contacted the prescribing physician or left the sheet in the patient's chart if the physician was not available. The average use of the target drugs and their alternatives was evaluated monthly during two six-month study periods and compared with the average use of these drugs during a three-month period before the target-drug programs were initiated. Throughout the 12-month study, on a per-patient basis, nafcillin use increased 31% while vancomycin use decreased 27% compared with the reference period; gentamicin use increased 21% while tobramycin use decreased 12% during the same period. These changes in use resulted in a net decrease in drug expenditures of $161,396. Approximately 0.5 full-time equivalent was spent on the program, and the return on investment for the service was greater than 10 to 1. Clinical pharmacist interventions through target-drug programs were effective in improving the appropriateness of vancomycin and tobramycin prescribing based on literature-derived criteria. The effects achieved by these interventions may decrease with time, and ongoing drug-use monitoring and physician education are necessary.

Anti-Bacterial Agents↗

PubMed1985

Vancomycin pharmacokinetics in premature infants.

Vancomycin pharmacokinetics were studied in nine premature infants. Infants weighing less than 1,000 gm had significantly larger volumes of drug distribution and consequently longer drug half-lives than larger premature infants, regardless of postconceptual or actual age. These differences alter the vancomycin dosing recommendations in these two groups of premature infants. We recommend initial dosage regimens consisting of a loading dose of vancomycin of 25 mg/kg followed by doses of 15 mg/kg every 12 hours for infants with weights less than 1,000 gm. Infants weighing over 1,000 gm should receive 10 mg/kg every 12 hours, with a loading dose of 12.5 mg/kg. Serum vancomycin concentration should be monitored, however, for final optimization of therapy.

Birth Weight↗

PubMed1979

Peritoneal clearance and total body elimination of vancomycin during chronic intermittent peritoneal dialysis.

Vancomycin is a useful antimicrobial agent in patients undergoing chronic hemodialysis treatment; its efficacy in chronic peritoneal dialysis (CPD) has not been established. Serum (VS) and peritoneal fluid (VPF) vancomycin concentrations were measured in two CPD patients with staphylococcal peritonitis. Half-life of VS agreed with the half-life of VPF in each patient, and the VS/VPF ratio was 1.27 in both patients. Distribution volumes were 37.2 and 58.7 l, values approximating total body water in these patients. VS and VPF persisted in the therapeutic range (greater than 5 microgram/ml) for more than 16 days. In one patient, mean peritoneal clearacne was 9.8 ml/min, and overall drug clearance averaged 2.3 ml/min; in the other patient, overall clearance was 2.1 ml/min. These results indicate that therapeutic vancomycin levels can be maintained for more than 16 days with a single 1 g intravenous dose in patients receiving intermittent CPD, as is the case for hemodialysis patients. Because of this, parenteral vancomycin is useful in the treatment of staphylococcal peritonitis in CPD patients.

Adult↗

PubMed1980

[Ability of vancomycin-group antibiotics to induce or to inhibit thrombocyte agglutination].

The effect of 4 vancomycin antibiotics on factor VIII-dependent agglutination of thrombocytes was studied. Significant similarity, both quantitative and qualitative, between ristocetin and ristomycin was found. In this connection ristomycin may be used for determination of the so-called ristocetin cofactor. Actinoidin and vancomycin inhibited agglutination of platelets induced by ristocetin or ristomycin in platelet-enriched plasma with citrate or EDTA the same as in the system contaning platelets treated with formalin and did not inhibit agglutination induced by the bovine factor VIII. The 4 antibiotics induced precipitation of the plasma protein. Vancomycin was most active and actinoidin ws lest active in this respect. Ristocetin and ristomycin also possessed such capacity, the effect of the latter being higher. Actinoidin and vancomycin did not prevent the immediate effect of light absorption increasing due to addition of ristocetin or ristomycin to fixed platelets in concentrations completely inhibiting agglutination of platelets in the presence of the protein cofactor. Inhibition of this direct effect of ristocetin and ristomycin was observd only at higher concentrations, which indicated that this effect was not probably associated with agglutination. The results of the study on various ristomycin derivatives showed that methylated carboxylic groups and free hydroxyls of phenol may play the main role in ristomycin binding with the thrombocytic membrane and/or protein cofactor.

Dose-Response Relationship, Drug↗

PubMed1984

[Electron microscopic characteristics of the action of penicillin and vancomycin on Rickettsia conorii and Rickettsia akari in vitro].

The possibility of L-transformation for two species of Rickettsia of the tick group (R. conorii and R. akari) was studied with light and electron microscopy. The experiments were performed on the cultures of L-cells (murine fibroblasts). Penicillin and vancomycin were used as the transforming agents. Electron microscopy revealed clear changes in the morphological structure of both species when the doses of penicillin and vancomycin were 50-100 and 250-1500 micrograms/ml, respectively. The antibiotics had a morphologically analogous effect on both species of Rickettsia. The resulting morphological structures were large oval spheroplast-like cells with significant expansion of the periplasmic space up to 1 X 1.75 micron under the effect of penicillin and 0.5 X 0.7 micron under the effect of vancomycin. R. akari was somewhat more sensitive to the antibiotics. Electron microscopy of the morphological changes in the Rickettsia induced by penicillin and vancomycin showed that they were similar to the changes observed in gram-negative bacteria on their L-transformation and to the penicillin forms of chlamydia (galprovia) and R. prowazekii. They may be considered as a phase of unbalanced growth and represent the initial stage of L-transformation.

Cell Wall↗

PubMed1980

Symptomatic relapse after oral vancomycin therapy of antibiotic-associated pseudomembranous colitis.

Twenty patients with antimicrobiol-associated diarrhea had a symptomatic relapse after oral vancomycin therapy. All patients had stool examinations which implicated C. difficile as the causative agent, and 16 had pseudomembranous colitis. Clinical courses were characterized by resolution of symptoms with recurrence of diarrhea at 4--21 days after vancomycin was discontinued. Studies of stools collected sequentially showed that vancomycin failed to eliminate C. difficile despite susceptibility to this agent with in vitro testing. A review of our records shows the incidence os symptomatic relapse is approximately 14%. This experience emphasizes the importance of adequate follow-up in patients treated with oral vancomycin for antibiotic-associated diarrhea or colitis due to C. difficile.

Anti-Bacterial Agents↗

PubMed1982

Vancomycin pharmacokinetics in patients undergoing chronic intermittent peritoneal dialysis.

The pharmacokinetics of vancomycin were studied during six episodes of peritonitis in four patients with chronic renal failure managed with chronic intermittent peritoneal dialysis. Following intravenous administration of vancomycin peritoneal concentrations ranged from undetectable to 22.5 micrograms/ml, and were 0-96% (mean 27%) of simultaneous serum concentrations. In view of the unpredictable penetration of vancomycin from serum into peritoneal fluid, we recommend that therapy for peritonitis due to staphylococci in patients undergoing peritoneal dialysis should include intraperitoneal administration of vancomycin.

Ascitic Fluid↗

PubMedDate not supplied

Structural features of vancomycin.

Recent analytical methods have advanced knowledge of the structure of vancomycin from a description of only several molecular fragments to a complete understanding of the intact molecule. The molecular weight is 1,448. The molecule consists of a seven-membered peptide chain that is formed by parts of three phenylglycine systems, two chlorinated tyrosine units, aspartic acid, and N-methylleucine. Two ether bonds and a carbon-carbon bond join the various substituents on the peptide chain into three large rings. A disaccharide, composed of glucose and vancosamine, is also present but is not part of the cyclic structure. Details of the vancomycin structure have been related to hydrogen bonding between the antibiotic and bacterial cell-wall precursors that have a D-alanyl-D-alanine carboxyl terminus; such bonding would provide a molecular basis for the cell-wall mode of action for vancomycin. With one carboxyl, two amino, and three phenolic groups, vancomycin undergoes a variety of ionic interactions in solutions of different pH and composition.

Binding Sites↗

PubMedDate not supplied

Pharmacokinetics of vancomycin in normal subjects and in patients with reduced renal function.

Recent novel clinical applications of vancomycin have stimulated reinvestigations of the pharmacologic properties of this drug. Absorption from the gastrointestinal tract is negligible, and oral administration is appropriate only for patients with certain staphylococcal and clostridial diarrheas. After intravenous administration (the intramuscular route being painful), vancomycin is excreted by glomerular filtration, with virtually total recovery in the urine. Distribution is consistent with a three-compartment open pharmacokinetic model. Serum half-life values are usually greater than 8 min in the distribution phase, 30 min to 1.5 hr in the intermediate phase, and between 5 and 11 hr in the elimination phase. The level of binding to human serum proteins is 55%. Since the relation between the vancomycin clearance and the creatinine clearance (but not the level of creatinine in serum) is linear in both normal and impaired renal function, a nomogram has been prepared that delineates dosages that will produce a mean steady-state concentration in serum of 15 micrograms/ml. Vancomycin penetrates well into pericardial, pleural, synovial, and ascitic fluid in humans, but concentrations in cerebrospinal fluid after parenteral administration may be insufficient for the successful treatment of certain cases of meningitis.

Administration, Oral↗

PubMed1978

Pseudomembranous colitis: isolation of two species of cytotoxic clostridia and successful treatment with vancomycin.

Lincomycin-resistant Clostridium sporogenes obtained from the stools of a patient with lincomycin-associated pseudomembranous colitis produced a heat-stable cytotoxin in low titre when grown in chopped meat medium. Vancomycin eradicated this strain and all other clostridia, and controlled the symptoms. When diarrhea recurred 7 days after treatment with vancomycin was stopped, clostridia including C. sporogenes and C. difficile were again isolated. The C. difficile produced a heat-labile cytotoxin in high titre that was unaffected by growth in various media and induced colitis in hamsters. Treatment with vancomycin, to which all the clostridia were sensitive, eradicated both toxic species and controlled the diarrhea. Antibiotic-induced pseudomembranous colitis may be associated with more than one species of toxin-producing clostridia. Vancomycin therapy should be continued for 10 days or more in patients with severe disease to eradicate the responsible organism.

Aged↗

PubMed1980

[Pseudomembranous entercolitis after antibiotic treatment: vancomycin therapy].

After reporting the case of a child suffering from pseudomembranous colitis (PMC) rapidly cured by vancomycin, the authors present current knowledge which had led to this new mode of therapy. A patient of 2 years 7 months was treated with amoxycillin per os for 8 days for otitis media. A week after this treatment, diffuse abdominal pains appeared, with 8-12 diarrhoeic stools per day containing blood and mucus and recurrent episodes of rectal prolapsus. PMC was diagnosed after rectoscopy and rectal biopsy. The symptomatology persisted for 4 weeks at which time a treatment was begun with vancomycin 4 x 125 mg/day per os. Improvement of the gastrointestinal symptoms occurred 36 hours later, and a new rectal biopsy demonstrated recovery from PMC. Clinical and experimental studies have demonstrated that PMC is due to the proliferation of a toxin producing anaerobic bacterium, clostridium difficile. This organism is highly sensitive to vancomycin. Treatment with vancomycin eliminates clostridium difficile and its toxin from the stools of patients suffering from PMC and permits clinical and histological recovery.

Amoxicillin↗

PubMed1995

Are serum levels of vancomycin useful in the first week of therapy?

Controversy exists regarding the need to monitor serum concentrations of vancomycin with some investigators recommending measurement of peak and trough concentrations in the first week of therapy and regularly thereafter, whereas others contend that empiric dosing produces safe and effective drug concentrations so that testing is unnecessary. Since vancomycin concentrations are measured, routinely in our hospital in the first week of therapy, we conducted a 12 month study to assess their clinical value in patients who were treated when gram positive cocci were detected in blood culture smears. One-hundred-five patients had gram positive cocci on blood culture smears. These bacteria were pathogens in 15 patients with Staphylococcus aureus and in 18 with coagulase negative staphylococci based on microbiologic criteria and a chart review confirming their clinical significance. Ten patients with S. aureus and 8 patients with coagulase negative staphylococci that were pathogens and 10 patients with coagulase negative staphylococci that were contaminants were treated with vancomycin. Serum peak and trough concentrations of vancomycin obtained within the first 5 days of therapy in these 28 patients were 14 to 40 micrograms/ml and 4.8 to 20 micrograms/ml. These concentrations were much above the MIC's of the microorganisms (< 4 micrograms/ml). Five patients had increases of serum creatinine of more than 0.6 mg% and in each patient the increases were attributable to other causes-shock, heart failure, and preexisting renal failure. Fifty five peak and trough concentrations 19 of which were drawn in patients with contaminated cultures were measured at a cost of $2,475.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteremia↗

PubMed1995

Vancomycin, trimethoprim-sulfamethoxazole, and rifampin.

Vancomycin is a safe, effective antibiotic for a variety of serious gram-positive infections. Because of emerging vancomycin-resistant enterococci and the threat of spread of vancomycin-resistant genes to other gram-positive organisms, judicious use of vancomycin should be promoted. Trimethoprim-sulfamethoxazole, a broad-spectrum synergistic combination, continues to find widespread use in gram-negative bacterial infections, especially involving the urinary tract. It has enjoyed enormous success in prophylaxis and therapy of Pneumocystis carinii pneumonia. Rifampin remains of paramount significance as a cidal agent against Mycobacterium tuberculosis; however, increasing reports of strains of MDR-tuberculosis are of great concern.

Anti-Bacterial Agents↗

PubMed1994

Vancomycin pharmacokinetics in middle-aged and elderly men.

A study was conducted to establish new values for vancomycin volume of distribution (V) and clearance (CL) that would result in more accurate predictions of serum vancomycin concentrations (SVCs). All patients who had received vancomycin at a Veterans Affairs medical center were divided into two groups: those for whom SVCs had been measured between August 13, 1990, and February 12, 1991 (group 1), and those for whom SVCs had been measured between February 13, 1991, and October 4, 1991 (group 2). Data for group 1 were used to derive new values for V and CL by means of Bayesian analysis. SVCs for each patient in group 2 were calculated by using the new pharmacokinetic values, and the predictive performance of these values was compared with that of accepted population values (V = 0.70 L/kg, CL = 0.65 times creatinine clearance [CLcr]). Forty-four men with 95 SVCs were entered into group 1, and 69 men with 171 SVCs were entered into group 2. The mean +/- S.D. ages for groups 1 and 2 were 61.6 +/- 12.9 and 64.3 +/- 11.3 years, respectively. There were no significant differences between the groups. V could not be evaluated because of inadequate sample size. Compared with the method employing the conventional CL value, the method that assumed a CL of 0.90CLcr was more precise and less biased in estimating group 2 SVCs. In middle-aged and elderly men, use of a CL value of 0.90CLcr produced estimates of serum vancomycin concentration that were more precise and less biased than did use of a CL value of 0.65CLcr.

Aged↗

PubMed1993

Should vancomycin be used empirically in febrile patients with prolonged and profound neutropenia? Results of a randomized trial.

OBJECTIVES: We conducted a randomized trial with ceftazidine alone or associated with amikacin or vancomycin to investigate the efficacy of the daily 3 g dosage of ceftazidime and the efficacy of monotherapy with ceftazidime and to determine if vancomycin should be added empirically. METHODS: Patient inclusion criteria were: age over 10 years, therapeutically-induced neutropenia and fever for at least three hours above 38.5 degrees C in absence of a clear non-infectious aetiology. Patients were randomized into three groups: group C, ceftazidime alone 3 g/day; group CA, ceftazidime 3 g/day plus amikacin 15 mg/kg/day; or group C, ceftazidime 3 g/day plus vancomycin 1.5 g/day. RESULTS: Results from one hundred and two episodes of fever were analyzed. The underlying diseases were haematological malignancies (89 patients) and solid tumours (13 patients). The median duration of neutropenia (< 0.5 x 10(9) PMN/L) was 18 days and the minimum duration of 7 days. The main criterion for the analysis of efficacy was the onset of a major infectious event, i.e. death related to documented or suspected infection and any infectious event considered life-threatening or hindering future treatment of the underlying disease. Eight (22%) patients in group C developed major infectious events compared with four (13%) in group CA and none in group CV (p < 0.01). Major infectious events were mainly due to Gram-positive organisms, particularly Streptococcus species. CONCLUSION: We conclude that: 1) ceftazidime alone and in association with amikacin is effective in preventing Gram-negative major infectious events; and 2) vancomycin should not be added only when a Gram-positive infection is documented, but used empirically.

Adolescent↗

PubMed1993

[Treatment with vancomycin of experimental endocarditis caused by Streptococcus sanguis II resistant to penicillin].

BACKGROUND: Streptococcus viridans continues to be the most frequent causal agent of infective endocarditis. Treatment has become more complicated due to the increase in resistance to penicillin and cephalosporins. In order to study the possible efficacy of vancomycin, this antibiotic was investigated in rabbits as a monotherapy and in association with gentamicin. The effects were compared with a control group and a group given classical penicillin-gentamicin treatment. MATERIAL AND METHODS: Minimum inhibitory concentration, minimum bactericidal concentration, lethality curves and synergism were determined against Streptococcus sanguis II. Infective endocarditis was induced in 80 rabbits, which were infected via catheter. Treatment was started 48 hours after infection, and lasted 5 days. The animals were divided into 4 groups of 20 rabbits each: 1, untreated controls; 2, penicillin-gentamicin; 3, vancomycin; 4, vancomycin-gentamicin. Response to therapy was evaluated with mortality curves, negativization of blood cultures, concentration of Streptococcus sanguis II in aortic vegetations, rate of sterilization of vegetations, body weight and serum bactericidal capacity. RESULTS: Vegetations weight was significantly lower in treated groups than in controls; lower weights were found in groups 2 and 4. The lowest vegetation weight was recorded in group 4, the only treatment that sterilized 75% of vegetations. Death occurred only in the control group (10%). Negativization of blood cultures was greatest and most rapid in group 4. Serum bactericidal capacity was greater after the two combined treatments, and highest in group 4. CONCLUSIONS: Combined treatment with vancomycin-gentamicin may be highly efficacious in patients with endocarditis caused by penicillin-resistant Streptococcus viridans.

Animals↗

PubMed1993

Computer dosing program for the initiation of vancomycin therapy.

The predictive performance of a computer dosing program used for initiating vancomycin therapy was studied. Initial serum vancomycin concentrations in 31 adult patients receiving vancomycin were estimated by using a computer program (T.D.M.S.) incorporating a two-compartment open model. Sixty-two serum vancomycin concentrations at steady state (Css) were obtained before and after one-hour infusions and compared with estimated Css values. Bias and precision were evaluated by calculating median error (ME) and median absolute error (MAE), respectively. Population-based estimates of volume of distribution (V) and clearance (CL) were compared with those obtained by fitting each patient's data set by using Bayesian analysis (BA) and non-linear least-squares regression (NLLS). Median (mean +/- S.D.) bias and precision for peak Css were 7.7 (10.2 +/- 10.8) and 7.7 (10.6 +/- 10.5) mg/L, and for trough Css were 7.4 (7.7 +/- 7.6) and 7.4 (8.8 +/- 6.2) mg/L. The medians were significantly different from zero. Estimated median (mean +/- S.D.) V, CL, and half-life were 0.72 L/kg, 0.60 (0.67 +/- 0.21) mL/min/kg, and 11.59 (12.87 +/- 3.91) hours. Median (mean +/- S.D.) CL values determined by BA and NLLS were 0.86 (0.89 +/- 0.32) and 0.85 (0.92 +/- 0.34) mL/min/kg, respectively. Both CL values were significantly greater than the population-based estimate. However, median V values determined by BA and NLLS did not differ from the population-based estimate. A revised clearance model derived from Bayesian analysis of data for the first 21 patients was tested in the 10 other patients and appeared to improve the predictive performance of the a priori model.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗