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PubMed2001

Pulmonary administration of perfluorodecaline- gentamicin and perfluorodecaline- vancomycin emulsions.

The aim of this study was to examine pharmacokinetics and pulmonary antibiotic tissue concentrations (PATC) of gentamicin and vancomycin after intrapulmonary administration of a perfluorodecaline (PFD)-gentamicin and a PFD-vancomycin emulsion during partial liquid ventilation (PLV). PLV was initiated in 19 healthy rabbits and 18 surfactant-depleted rabbits. The animals were randomized to receive either 5 mg/kg gentamicin and 15 mg/kg vancomycin intravenously, or 5 mg/kg gentamicin intrapulmonary, or 15 mg/kg vancomycin intrapulmonary. Antibiotic plasma levels were measured after 15, 30, 45, and 60 min, and hourly thereafter. After 5 h animals were sacrificed and lungs were removed to evaluate PATC and histology. PATC were significantly higher after intrapulmonary administration of both gentamicin and vancomycin. In healthy rabbits, peak plasma concentrations were lower and 5 h plasma concentrations were higher after intrapulmonary administration, whereas plasma concentrations were not different in surfactant-depleted rabbits. There were no differences in lung histology, hemodynamics, lung mechanics, or gas exchange between the treatment groups. We conclude that during PLV, higher PATC can be achieved after intrapulmonary administration of PFD-antibiotic emulsions compared with intravenous administration of the same dose without apparent short-term adverse effects. We speculate that intrapulmonary antibiotic administration during PLV may be beneficial in treating severe pneumonia.

Animals↗

PubMed1986

Vancomycin-induced neutropenia during treatment of osteomyelitis in an outpatient.

A case of vancomycin-associated neutropenia occurring during long-term outpatient therapy with vancomycin is described. Pharmacokinetic studies demonstrated that the patient's vancomycin serum levels were within an acceptable range during treatment. Eighteen other reported cases of vancomycin-associated leukopenia are discussed in brief. An immunologic mechanism has been proposed but a clear understanding is lacking. Patients receiving long-term vancomycin therapy should have their white blood cell counts periodically monitored.

Agranulocytosis↗

PubMed1991

Chemical peritonitis associated with intraperitoneal vancomycin.

A case of chemical peritonitis associated with intraperitoneal vancomycin is reported. A 23-year-old woman presented with signs and symptoms consistent with a chronic ambulatory peritoneal dialysis catheter exit-site infection. Intraperitoneal vancomycin (Vancoled) 1 g was given, followed by 25 mg/L into each subsequent exchange. On day 4 the patient developed abdominal pain and cloudy dialysis effluent. The vancomycin was discontinued, and the dialysate cleared by day 8. Fluid cultures were negative, and Staphylococcus aureus was isolated from the exit site. Subsequent intravenous vancomycin, and smaller intraperitoneal doses, failed to repeat the event. Fluid and serum white blood cell count, serum immunoglobulins and complement, culture results, and the temporal relationship are strongly suggestive of a vancomycin-induced chemical peritonitis.

Adult↗

PubMedDate not supplied

Vancomycin protein binding in patients with infections caused by Staphylococcus aureus.

The protein binding of vancomycin has been reported to range from less than 10 percent to 82 percent. We examined the binding of vancomycin in 34 patients (14 intravenous drug abusers, 10 burn patients, and 10 control patients) with Staphylococcus aureus infections. Blood samples were collected serially over an 8- or 12-hour dosing interval following a one-hour infusion. In vitro studies were also performed using albumin solutions of varying concentrations. Binding characteristics were determined through ultrafiltration with vancomycin concentrations analyzed for fluorescence polarization immunoassay. The unbound fraction of vancomycin ranged from 0.41 to 0.77 with a mean of 0.54 +/- 0.08. Unbound fractions was significantly correlated with serum albumin concentration (r = -0.344, p less than 0.046) and renal clearance (r = 0.394, p less than 0.021) but not with total body clearance or volume of distribution. In vitro data also showed an association between albumin concentration and unbound fraction (r = -0.94, p less than 0.017). Although vancomycin protein binding changes with serum albumin, this finding may have limited clinical significance.

Adult↗

PubMed1992

Stevens-Johnson-type reaction with vancomycin treatment.

OBJECTIVE: To report a case of Stevens-Johnson syndrome caused by vancomycin. CASE SUMMARY: Stevens-Johnson syndrome is an acute mucocutaneous process characterized by epidermal and mucosal desquamation. Its pathogenesis is poorly understood. Mortality rates have ranged from 30 to 100 percent. We describe a case of Stevens-Johnson syndrome related to the use of vancomycin in a 71-year-old woman with rheumatoid arthritis receiving treatment for an infected cervical fusion site. Classic "target" lesions distributed throughout the trunk and extremities along with erosive lesions involving the oral and vaginal mucosae were observed in this patient. DISCUSSION: A number of agents have been implicated in the etiology of Stevens-Johnson syndrome. Serious cutaneous reactions to vancomycin, however, have been uncommon. Cessation of vancomycin treatment in our patient led to eventual resolution of her symptoms. CONCLUSIONS: Vancomycin is a potential causative agent of Stevens-Johnson syndrome.

Aged↗

PubMed1995

Cyclosporine and vancomycin disposition during continuous venovenous hemodiafiltration.

OBJECTIVE: To report cyclosporine and vancomycin disposition during continuous venovenous hemodiafiltration (CVVHD) in a 41-year-old heart transplant patient while in the intensive care unit at a primary and tertiary care teaching hospital. CASE SUMMARY: The patient received a 60-mg infusion of cyclosporine over 24 hours and vancomycin 1 g over 1 hour. Blood samples subsequently were collected and analyzed using whole blood monoclonal radioimmunoassay and fluorescence polarization immunoassay, respectively. Blood samples were measured every hour from the arterial and venous lines of the apparatus, as were ultrafiltrate drug concentrations. Drug clearance rates into the ultrafiltrate subsequently were calculated. DISCUSSION: Measurements of ultrafiltrate detected no cyclosporine. A slight variation existed between arterial and venous drug concentrations, which was not statistically significant (p > 0.05, paired Student's t-test). Analysis of vancomycin samples revealed a steady decline of drug concentration, with 4.75% of the dose eliminated in the ultrafiltrate. Vancomycin arterial and venous concentrations decreased from 24.4 and 23.3 mg/L to 15.7 and 12.3 mg/L, respectively. CONCLUSIONS: Vancomycin is eliminated by CVVHD and it may be necessary for these patients to receive the drug more frequently. In contrast, cyclosporine is not removed effectively by CVVHD; therefore, replacement doses are not warranted.

Adult↗

PubMed1997

Vancomycin-induced thrombocytopenia: a challenge and rechallenge.

OBJECTIVE: To report a case of thrombocytopenia apparently associated with vancomycin use. CASE SUMMARY: A 58-year-old white man was admitted to the hospital with chronic osteomyelitis of the foot due to methicillin-resistant Staphylococcus aureus that later spread hematogenously to the cervical vertebrae. During the first course of therapy with vancomycin, his platelet count decreased from 397 x 10(3)/mm3 to 22 x 10(3)/mm3. After discontinuation of the drug, it increased to 310 x 10(3)/mm3. During the second course of vancomycin, the platelet count decreased to 77 x 10(3)/mm3, and increased to 404 x 10(3)/mm3 after discontinuation of the drug. DISCUSSION: Vancomycin has been reported as a rare cause of thrombocytopenia. Thrombocytopenia can occur as an adverse drug reaction by the following three mechanisms: direct toxic effect, drug absorption (hapten) formation, and an "innocent bystander" immune response. CONCLUSIONS: We suspect that the thrombocytopenia in this patient, which involved an increased number of megakaryocytes in the bone marrow, was due to vancomycin.

Anti-Bacterial Agents↗

PubMed1997

Evaluation of a sparse sampling strategy for determining vancomycin pharmacokinetics in preterm neonates: application of optimal sampling theory.

OBJECTIVE: To use optimal sampling theory to determine the fewest vancomycin concentrations required and the appropriate sampling times to calculate vancomycin pharmacokinetic parameters in neonates. DESIGN: Unblinded evaluation in neonates with presumed sepsis. SETTING: Level 3 community-based neonatal intensive care unit. PATIENTS: Eleven neonates with presumed sepsis. INTERVENTIONS: Twelve courses of intravenous vancomycin 20 mg/kg were administered. Blood samples were collected 3 and 9 hours after initiation of a 1-hour infusion of the first dose. MEASUREMENTS AND MAIN RESULTS: A two-compartment model was fit to vancomycin concentrations using iterative two-stage analysis. Pharmacokinetic parameter estimates were used for determination of optimal sampling times for two-, three-, and four-sample strategies with subsequent generation of two-, three-, and four-sample concentration data for 100 cases. Relative performance of strategies was compared through calculation and comparison of D efficiency for the determined strategies. Bias (median percent error) and precision (median percent absolute error) of pharmacokinetic parameter estimates for each strategy in the 100 simulated cases were determined. CONCLUSIONS: For estimation of total clearance and volume in the central and peripheral compartments, all strategies performed similarly with no difference in efficiency or bias and precision of estimates. Our results suggest that for clinical evaluations two appropriately timed samples (0.5 h after a 1-h infusion, trough concentration) are adequate for estimation of vancomycin clearance in neonates.

Aminoglycosides↗

PubMed1997

Effect of vancomycin and teicoplanin alone or in combination with fusidic acid or amikacin against methicillin-resistant staphylococci.

The action of two glycopeptides (vancomycin and teicoplanin) alone or in combination with amikacin or fusidic acid has been studied against 10 non-repetitive strains of methicillin-resistant Staphylococcus. The plotted killing curves show that the combination of vancomycin or teicoplanin plus fusidic acid always exhibited an antagonist effect at 24 h for the 10 strains. The combination vancomycin or teicoplanin plus amikacin shows the same effect at 24 h as vancomycin or teicoplanin alone. Thus, the combination glycopeptide plus amikacin does not alter the activity of the glycopeptide but does increase the spectrum of activity of the combination versus Gram-negative nosocomial bacteria (Pseudomonas aeruginosa, Acinetobacter sp). The vancomycin or teicoplanin plus fusidic acid combination may be responsible for bacteriological failure against methicillin-resistant Staphylococcus.

Amikacin↗

PubMed1997

A closer look at vancomycin, teicoplanin, and antimicrobial resistance.

The worldwide increase in the incidence of resistant Gram-positive infections has renewed interest in the glycopeptide class of antimicrobial agents. Two glycopeptides are available in many parts of the world--vancomycin and teicoplanin. These two agents appear to differ in several respects, including: potential for selecting microbial resistance, dosing convenience, safety, and efficacy in severe infection. Teicoplanin appears to have lower toxicity and greater convenience; however, its widespread acceptance has been plagued by concerns over antimicrobial resistance, efficacy, and appropriate dosing. A review of available studies suggests that teicoplanin, when dosed at 6 mg/kg/day, is better tolerated than vancomycin 15 mg/kg/q12h; however, at these doses, it appears to be somewhat less effective than vancomycin in serious Staphylococcus aureus infection, such as endocarditis. Although higher doses of teicoplanin, 12 mg/kg/day to 30 mg/kg/day, have been associated with efficacy comparable to that of vancomycin in serious S. aureus infections, such doses may eliminate some of the safety advantages conferred by lower teicoplanin doses. Teicoplanin has been associated with resistance among coagulase-negative staphylococci and the selection of resistance in S. aureus. There is some evidence that widespread use of teicoplanin might accelerate the development of S. aureus resistance to both teicoplanin and vancomycin. The selection of an appropriate glycopeptide in an individual patient should be based not only on convenience, but also on a determination of optimal efficacy, safety at an efficacious dose, and the potential for resistance.

Anti-Bacterial Agents↗

PubMed2004

Direct medical costs associated with using vancomycin in methicillin-resistant Staphylococcus aureus infections: an economic model.

OBJECTIVES: To quantify the direct medical costs associated with using vancomycin, as inpatient treatment, in methicillin-resistant Staphylococcus aureus infections, in four clinical indications: complicated skin and soft tissue infections (SSTI), bacteremia, infective endocarditis (IE), and hospital-acquired pneumonia (HAP). RESEARCH DESIGN AND METHODS: A decision-analytic model was constructed to evaluate the cost of administering intravenous vancomycin. Cost inputs included hospitalization, drug procurement, materials, preparation and administration, renal function and drug monitoring, treating adverse events, and treatment failure. Probabilities and lengths of stay and treatment were obtained from the literature, an antimicrobial therapy database and clinical expert opinion. Univariate and multivariate sensitivity analyses were conducted to confirm the robustness of the baseline scenario. MAIN OUTCOME MEASURES: The cost of using vancomycin in the four indications, including and excluding hospital cost. RESULTS: Whereas the drug acquisition price of vancomycin 1g is US dollars 9.01 per dose, when all costs associated with using vancomycin were included, the cost per dose rose to US dollars 29-US dollars 43 per patient. Total costs per patient receiving multiple doses in a single course of treatment, excluding hospital room costs, were for SSTI, bacteremia, IE, and HAP,US dollars 779, US dollars 749, US dollars 2261, and US dollars 768, respectively. Total costs, including hospital length of stay, were for SSTI US dollars 23616, bacteremia US dollars 26446, IE US dollars 48925, and HAP US dollars 22493. In univariate analyses varying per diem hospital costs and length of stay had the greatest impact. Results of the multivariate analysis were comparable to the costs in the baseline scenario for all indications. CONCLUSIONS: This analysis highlights the importance of capturing all costs associated with using a drug and not simply focusing on drug acquisition cost. Future economic analyses should identify and account for the key cost burdens of a particular treatment to calculate its true cost.

Anti-Bacterial Agents↗

PubMed2005

Histology of vancomycin-supplemented impacted bone allografts in revision total hip arthroplasty.

Vancomycin-supplemented allografts provide biological restoration of bone stock and sound fixation with a low incidence of re-infection. Experimental incorporation of these grafts is similar to allografts without vancomycin. However, the underlying biology remains unknown. We report the first histological observations of vancomycin-supplemented impacted bone allografts in two reconstructions performed 14 and 20 months after revision surgery because of a periprosthetic fracture. Areas of active bone remodelling (creeping substitution), as well as calcified bone trabeculae and graft particles embedded in dense fibrous tissue, were observed with osteoid and fibroconnective tissue surrounding polymethylmethacrylate particles. These pathological findings are similar to those reported in allografts without vancomycin and support the hypothesis that high levels of vancomycin do not affect the incorporation of bone graft.

Aged↗

PubMed2006

Predictors of mortality for methicillin-resistant Staphylococcus aureus health-care-associated pneumonia: specific evaluation of vancomycin pharmacokinetic indices.

OBJECTIVE: The goal of this investigation was to determine whether vancomycin pharmacokinetic indexes (eg, serum trough concentrations or area under the concentration curve [AUC] values) were associated with mortality for patients with health-care-associated pneumonia (HCAP) attributed to methicillin-resistant Staphylococcus aureus (MRSA). DESIGN: A retrospective, single-center, observational cohort study. SETTING: Barnes-Jewish Hospital, a 1,200-bed urban teaching facility. PATIENTS: Adult patients requiring hospitalization who were identified as having HCAP attributed to MRSA by BAL semi-quantitative cultures. INTERVENTIONS: Retrospective data collection from automated hospital, microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: One hundred two patients with MRSA HCAP were identified over a 6.5-year period. Thirty-two patients (31.4%) died during their hospitalization. The mean (+/- SD) vancomycin trough concentrations (13.6 +/- 5.9 vs 13.9 +/- 6.7 microg/mL, respectively; p = 0.866) and AUC values (351 +/- 143 vs 354 +/- 109 microg/h/mL, respectively; p = 0.941) did not differ between survivors and nonsurvivors. The stratification of the vancomycin trough concentrations and AUC values yielded no relationship with hospital mortality. CONCLUSIONS: We found no evidence that greater vancomycin trough concentrations or AUC values correlated with hospital outcome. Based on these results, aggressive dosing strategies for vancomycin (eg, trough concentrations of > 15 microg/mL) may not offer any advantage over traditional dose targets (range, 5 to 15 microg/mL).

Adult↗

PubMed2003

In vitro antimicrobial activity of linezolid tested against vancomycin-resistant enterococci isolated in Brazilian hospitals.

The emergence of vancomycin-resistant enterococci (VRE) has been described recently in Brazil. This is in contrast to the USA and Europe, where the VRE appeared in the late 1980s. The progressive increase in VRE isolation poses important problems in the antimicrobial therapy of nosocomial infections. Treatment options and effective antimicrobial agents for VRE are often limited and the possibility of transfer of vancomycin genes to other Gram-positive microorganisms continues. In the search for antimicrobial agents for multiresistant Gram-positive cocci, compounds such as linezolid and quinupristin/dalfopristin have been evaluated. The present study was conducted to evaluate the in vitro activity of the oxazolidinone linezolid and 10 other antimicrobial agents, including quinupristin-dalfopristin, against multiresistant enterococci isolated in Brazilian hospitals. Thirty-three vancomycin resistant isolates (17 Enterococcus faecium and 16 E. faecalis), were analyzed. Strains were isolated from patients at São Paulo Hospital, Oswaldo Cruz Hospital, Hospital do Servidor Público Estadual, Santa Marcelina Hospital, Santa Casa de Misericórdia de São Paulo, and Hospital de Clínicas do Paraná. The samples were tested by a broth microdilution method following the National Committee for Clinical Laboratory Standards (NCCLS) recommendations. All isolates were molecular typed using pulsed-field gel electrophoresis (PFGE). Linezolid was the most active compound against these multiresistant enterococci, showing 100% inhibition at the susceptible breakpoints. Quinupristin/dalfopristin and teicoplanin showed poor activity against both species. The molecular typing results suggest that there has been interhospital spread of vancomycin resistant E. faecium and E. faecalis among Brazilian hospitals. The results of this study indicate that linezolid is an appropriate therapeutic option for the treatment of vancomycin-resistant enterococci infections in Brazil.

Acetamides↗

PubMed2001

Biopsy-proved acute tubulointerstitial nephritis and toxic epidermal necrolysis associated with vancomycin.

A 70-year-old man receiving vancomycin for a methicillin-resistant Staphylococcus aureus (MRSA) abscess developed a drug-induced hypersensitivity reaction with rash, eosinophilia, and acute renal failure requiring dialysis. Renal biopsy revealed diffuse and marked interstitial and tubular infiltration by mononuclear cells and eosinophils; acute tubulointerstitial nephritis (TIN) was diagnosed. The rash progressed to erythema multiforme major after rechallenge with vancomycin in the setting of MRSA peritoneal catheter-related peritonitis and then to fatal toxic epidermal necrolysis in the setting of steroid taper and persistent serum vancomycin levels. This case further implicates vancomycin as a drug that infrequently can cause severe acute TIN and exfoliative dermatitis. When a renally excreted drug such as vancomycin is administered, serum drug levels should be serially monitored and high-dosage steroids be maintained or tapered slowly until serum drug levels become undetectable.

Acute Disease↗

PubMed2002

Vancomycin-induced neutropenia in a patient positive for an antineutrophil antibody.

A 48-year-old man, hospitalized after experiencing subarachnoid hemorrhage secondary to a basilar aneurysm, received vancomycin for methicillin-resistant Staphylococcus aureus sepsis. He developed neutropenia 16 days after the start of vancomycin therapy, and his white blood cell count decreased to a nadir of 1200 cells/mm3. Vancomycin was discontinued, and granulocyte-colony stimulating factor (G-CSF) therapy was begun. The patient was rechallenged with a single dose of vancomycin 1 g in preparation for intraarterial aneurysm coiling. His white blood cell count dropped to 600 cells/mm3 but returned to normal with continued G-CSF therapy. A diagnosis of vancomycin-induced neutropenia was considered. Subsequent testing by granulocyte agglutination and granulocyte immunofluorescence assays revealed that his serum was positive for an antigranulocyte antibody. A test for HLA antibody reactivity was negative. Monoclonal antibody immobilization of granulocyte antigens assay failed to determine the antigen specificity of his granulocyte antibody.

Anti-Bacterial Agents↗

PubMed2005

Probable vancomycin-associated toxic epidermal necrolysis.

A 52-year-old man with no previous drug allergies or skin disorders developed a widespread papulovesicular rash while receiving an antimicrobial regimen of piperacillin-tazobactam, tobramycin, and vancomycin. Skin biopsy suggested leukocytoclastic vasculitis, which responded well to antibiotic discontinuation and steroid therapy. Fifteen days later, during steroid tapering, an additional course of vancomycin was begun for suspected line infection. The subsequent maculopapular rash that developed was diagnosed as toxic epidermal necrolysis (TEN) based on a second skin biopsy and clinical presentation. This case is consistent with previous reports of vancomycin-associated TEN. Any patient who develops TEN while receiving vancomycin therapy should be evaluated for possible vancomycin-induced TEN.

Anti-Bacterial Agents↗

PubMedDate not supplied

Early switch and early discharge opportunities in intravenous vancomycin treatment of suspected methicillin-resistant staphylococcal species infections.

BACKGROUND: Patients with methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase negative staphylococci (MR-CoNS) infections are usually treated with intravenous (IV) vancomycin and remain hospitalized for the duration of IV therapy. Oral linezolid has excellent bioavailability and activity against MRSA and MR-CoNS and offers the potential for outpatient treatment of MRSA and MR-CoNS infections. OBJECTIVE: To determine the potential for early switch (ES) from IV vancomycin to oral linezolid and subsequent early discharge (ED) in hospitalized, adult patients treated for an MRSA or MR-CoNS infection. METHODS: We conducted a retrospective cohort study at the Veterans Administration Greater Los Angeles Healthcare System from January 1 through December 31, 2000. Potential reductions in vancomycin use, hospital length of stay (LOS), and economic savings were determined. RESULTS: A total of 103 of 177 (58%) treatment courses for MRSA or MR-CoNS infections were potentially eligible for ES, with annual and mean decreases in vancomycin use of 535 defined daily doses and 5.2 days per event. Of the ES cohort, 55 of 103 (53%) courses were potentially eligible for ED, with an annual and mean reduction in LOS of 181 days and 3.3 days per event. The total potential savings was $220,181, at an average of $3,478 per event. CONCLUSION: Early switch to oral linezolid for treatment of MRSA or MR-CoNS infections could reduce vancomycin use, hospital length of stay, and economic costs.

Acetamides↗