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PubMed2006

Topical versus systemic vancomycin for deep sternal wound infection caused by methicillin-resistant Staphylococcus aureus in a rodent experimental model.

In 37 Wistar albino rats, we investigated the effects of topical vancomycin on deep sternal wound infection caused by methicillin-resistant Staphylococcus aureus. Partial median sternotomy was performed under sterile conditions. Group I (n=6) was the sham, and group II (n=7) was the control. Group III (n=8) received topical vancomycin, group IV (n=8) received systemic vancomycin, and group V (n=8) received topical and systemic vancomycin (combined). Rats in groups II through V were inoculated with 0.5 mL x 10(8) CFU/mL methicillin-resistant S. aureus in the mediastinum and sternum. No medication was given to groups I and II. Twenty-four hours after surgery, 40 mg/kg/day vancomycin was given topically in group III; systemically in group IV; and topically and systemically in group V After 7 days, smear samples from the mediastinum and tissue cultures from the sternum were obtained. We found 5.00 +/- 0 CFU/mL microorganisms in the mediastinum in group II, 1.90 +/- 1.70 in group III, 3.33 +/- 0.48 in group IV and 1.70 +/- 1.08 in group V. The quantity of microorganisms per gram of tissue in the sternum was 736 +/- 0.23 in group II, 6.01 +/- 0.33 in group III, 5.81 +/- 0.81 in group IV and 3.99 +/- 2.47 in group V The quantity of microorganisms was less in the 3 treatment groups than in the control group (P < 0.05). We conclude that topical plus systemic vancomycin treatment might be more effective in patients with deep sternal wound infections caused by methicillin-resistant S. aureus.

Administration, Topical↗

PubMed1990

Zeta potential and vancomycin-red blood cell interactions.

Vancomycin hydrochloride is a polycationic antibiotic that we have previously reported to cause spontaneous aggregation of red blood cells (RBCs) in vitro at concentrations of more than 3.0 mg/mL, and false-positive direct antiglobulin tests at concentrations of 2.0 and 2.5 mg/mL. These latter reactions were abolished when the RBCs were pretreated with the proteolytic enzyme ficin suggesting an interaction with sialoglycoproteins. In this study we show that prior addition of vancomycin did not block binding of antibodies to several blood group antigens, nor does vancomycin precipitate in an Ouchterlony assay with any of several sialic acid moieties. Finally, we show that vancomycin possesses fluorescent properties but fails to be detected on the RBC surface by flow cytometry. These data indicate that vancomycin may be acting through its polycationic properties. Our findings do not support protein binding of vancomycin to the RBC surface, but underline the importance of the zeta potential in RBC serologic reactions.

Erythrocyte Membrane↗

PubMed1989

Mild nephrotoxicity associated with vancomycin use.

Nephrotoxicity related to vancomycin hydrochloride therapy has been reported at overall rates of 7% to 16% and as high as 35% when combined with an aminoglycoside antibiotic. We conducted a prospective study in older men. A group that received vancomycin was compared with a control group to determine the incidence of nephrotoxicity secondary to vancomycin therapy alone and in combination with aminoglycosides, to identify possible risk factors associated with nephrotoxicity, and to determine the incidence of other adverse effects associated with vancomycin use. Nephrotoxicity occurred in 11 (17%) of 66 patients receiving vancomycin and in 3 (5%) of 57 controls overall. Stepwise logistic-regression analysis failed to identify underlying illnesses or concurrent risks that may have contributed to the development of nephrotoxicity associated with vancomycin. Adverse effects, including phlebitis (14%), neutropenia (1%), rash (0%), and red neck syndrome (0%), occurred at rates similar to previous reports.

Aged↗

PubMed1988

Chromatographically purified vancomycin: therapy of serious infections caused by Staphylococcus aureus and other gram-positive bacteria.

Fourteen patients with serious infections caused by Staphylococcus aureus and other gram-positive bacteria were prospectively treated with chromatographically purified vancomycin in an open-label, nonrandomized study, between December 1986 and June 1987. Five patients were excluded from the evaluation of efficacy. Among the nine evaluable patients, cure was achieved in six patients--a success rate of 67%. One patient had a relapse of osteomyelitis, and cultures of draining pus were positive for oxacillin-resistant S aureus within three weeks after the discontinuation of vancomycin therapy. One patient failed to respond to vancomycin therapy for S aureus-induced endocarditis, meningitis, and osteomyelitis; in another patient, the treatment failed to reverse the course of S aureus septicemia. No serious drug toxicity, for example, nephrotoxicity, was encountered in any patient. One patient (7%) experienced mild ototoxicity. Four patients (29%) had mild phlebitis, two patients (14%) had a transiently positive Coombs' test, and one patient (7%) had a "red neck syndrome" and "pain and spasm syndrome." Chromatographically purified vancomycin is an effective antibiotic in the treatment of serious infections caused by susceptible gram-positive bacteria. Some minor side effects of vancomycin may not be due to impurities in the preparation but rather to the vancomycin itself.

Adolescent↗

PubMed1977

Inhibition of ristocetin-induced platelet agglutination by vancomycin.

Ristocetin and vancomycin are structurally similar glycopeptide antibiotics. Both vancomycin and ristocetin in high concentrations (3.0 mg/ml) cause the precipitation of fibrinogen, plasminogen, and IgG from platelet-poor plasma (PPP). In contrast to ristocetin, vanomycin (0.5-1.5 mg/ml) does not agglutinate platelets in normal platelet-rich plasma (PRP) or formalin-treated platelets in the presence of normal PPP. Preincubation of vancomycin (0.5-1.25 mg/ml) with normal PRP, von Willebrand platelets in normal PPP, or formalinized platelets results in inhibition of platelet agglutination induced by ristocetin (0.7-1.25 mg/ml) or ristocetin and normal PPP. This inhibition can be overcome by increasing the final concentration of ristocetin in the platelet suspension. Preincubation of formalin-treated platelets with the major fraction obtained by carboxymethyl-Sephadex C-50 chromatography of commercial vancomycin also results in inhibition of agglutination induced by ristocetin and normal PPP. Incubation with vancomycin (1.25 mg/ml) does not interfere with von Willebrand factor (vWF) or factor VIII coagulant activities in normal PPP or in Sepharose 4B void volume fractions of PPP. These results indicate that vancomycin interacts with normal, von Willebrand, and formalin-treated platelets and inhibits the binding of ristocetin (or ristocetin-vWF complexes).

Binding, Competitive↗

PubMed1986

Stability of vancomycin hydrochloride in 5% dextrose and 0.9% sodium chloride injections.

The stability of vancomycin hydrochloride mixed with 5% dextrose and 0.9% sodium chloride injections was studied. Vancomycin hydrochloride powder was mixed with each of the two diluents in final concentrations of 5 mg/mL. Duplicate samples of each admixture were divided into four parts and stored at 24 degrees C in glass and in plastic i.v. bags for 17 days and at 5 degrees C and -10 degrees C in glass for 63 days. To additional samples, hydrochloric acid or phosphate buffer was added; these were stored at 24 degrees C for 17 days. At various storage times, clarity and pH of the samples were recorded and vancomycin concentrations were measured in triplicate by high-performance liquid chromatography. Except for the buffered samples, all solutions remained clear and pH was unchanged. Vancomycin concentrations decreased less than 6% during 17 days at room temperature. In the refrigerated and frozen samples, vancomycin concentrations decreased less than 1% throughout the study. Vancomycin hydrochloride is stable in admixtures with 5% dextrose injection and 0.9% sodium chloride injection for 17 days at 24 degrees C and for 63 days at 5 degrees C and -10 degrees C.

Chromatography, High Pressure Liquid↗

PubMed1978

The selectivity of vancomycin and lincomycin in NYC medium for the recovery of N. gonorrhoeae from clinical specimens.

Varying concentrations of vancomycin and lincomycin were tested separately in NYC medium to determine the degree of their selectivity and sensitivity for isolation of N. gonorrhoeae from clinical specimens. Results indicate that 2 microgram/ml of vancomycin used in conjunction with colymycin, amphotericin B, and trimethoprim lactate provide adequate selectivity and reduce the possibility of losses of vancomycin-sensitive strains of gonococci seen with 3 microgram/ml of vancomycin. The same medium with concentrations of from 1 to 4 microgram/ml of lincomycin substituted for vancomycin permitted more contamination and fewer recoveries of gonococci as compared with 2 microgram/ml of vancomycin.

Amphotericin B↗

PubMedDate not supplied

Vancomycin for treatment of bacterial meningitis.

Clinical experience with vancomycin for the treatment of bacterial meningitis has not been extensive. Presently available data indicate that when meningeal inflammation is present intravenously administered vancomycin penetrates into cerebrospinal fluid and therapeutically effective levels of drug therein are frequently attained. Treatment of meningitis with vancomycin has been effective in clinical situations that precluded the use of the commonly administered agents, i.e., in infections due to resistant strains or to unusual organisms, in patients allergic to penicillin, and in patients for whom therapy with a first-choice antibiotic has failed. When response to intravenously administered vancomycin was unsatisfactory, the addition of intrathecal therapy resulted in a favorable outcome in some patients. Combination therapy with agents that act synergistically with vancomycin has been beneficial. Vancomycin warrants serious consideration as a useful alternate antibiotic for the treatment of bacterial meningitis.

Adult↗

PubMedDate not supplied

Vancomycin therapy for infective endocarditis.

The use of vancomycin is increasing for the treatment of serious life-threatening staphylococcal and other bacterial infections, including infective endocarditis, in patients who are allergic to the penicillins. The literature through 1978 reveals approximately 55 cases of infective endocarditis treated with vancomycin alone or with combined antibiotic therapy. Many of these 55 patients were treated by different clinicians, were given variable regimens of therapy, received other therapy before vancomycin, had associated valve replacement; various amounts of data were provided for the reported cases. A summary of these reports indicates a cure in 48 (87%) of the 55 patients. Recent in vitro and in vivo animal and patient data indicate that vancomycin alone or as part of combined therapy is bactericidal and curative in patients allergic to penicillin for infective endocarditis caused by staphylococci and streptococci-both enterococcal and nonenterococcal (Streptococcus bovis and viridans group streptococci) infections. In this study, 10 patients with infective endocarditis were treated with vancomycin or combined therapy; seven were cured. Five of the 10 patients with infective endocarditis caused by viridans streptococci were cured with combined vancomycin-streptomycin given in short-term therapy for two weeks.

Adolescent↗

PubMed1994

[Continuous infusion of vancomycin during the neonatal period].

Twenty-five infants with suspected or confirmed coagulase negative staphylococcal infection were studied. Continuous administration of vancomycin was used because it is usual with infusions prepared daily for catheterized patients, and because continuous infusions are well tolerated and achieve better penetration in tissues and CSF. Vancomycin acts as a time-dependent antibiotic. The aim was to obtain a level of 20-25 mg/l. in serum. Fifteen newborns term 27-35 weeks (m = 30.3) aged 7-30 days (m = 16.1) received 10 to 45 mg/kg/day of vancomycin and were monitored for 2 to 12 days. The sample for assay was taken in a peripheral vein, and the results were the same during the infusion or 15 minutes after its end. The daily dose of vancomycin necessary varied from 25 to 40 mg/kg for newborns with serum creatinine < 70 mmol/l and 10 to 30 mg/kg with serum creatinine > or = 90 mmol/l. Except for a newborn with multiorgan failure, serum creatinine rapidly decreased. Four newborns term 38-40 weeks (m = 39.5) aged 2-12 days (m = 8.3) received 20 to 45 mg/kg/day of vancomycin and were monitored for 2 to 12 days. The daily dose necessary varied from 30 to 40 mg/kg/day with important individual variations, and 20 mg/kg/day in a newborn with a high level of creatinine. In 6 infants aged 2-22 months receiving 22-45 mg/kg/day of vancomycin, a mean daily dosage of 40-45 mg/kg was adequate, with important individual variations.(ABSTRACT TRUNCATED AT 250 WORDS)

Creatine↗

PubMed1993

Effect of oral activated charcoal on vancomycin clearance in rabbits with acute renal failure.

The effect of oral administration of activated charcoal on total body clearance of vancomycin administered intravenously (7.5 mg/kg) has been studied in normal rabbits and rabbits with induced renal failure. Gastric intubation of a single dose (10 g) of activated charcoal to normal rabbits did not produce a statistically significant effect on any pharmacokinetic parameter for vancomycin. The mean vancomycin clearances were (mean +/- s.d.) 80.82 +/- 6.8 and 75.24 +/- 9.61 ml/h/kg with and without activated charcoal administration, respectively. To examine whether renal failure would influence the effect of activated charcoal and enhance the systemic clearance of vancomycin, uranyl nitrate was used (0.75 mg/kg, i.v.) to induce acute renal failure in rabbits. The derived pharmacokinetic parameters of vancomycin were consistent with renal failure. No significant differences were observed in any of the calculated pharmacokinetic parameters between the control and charcoal treated rabbits. The lack of effect may be attributed to the large molecular weight of vancomycin.

Acute Kidney Injury↗

PubMed1996

Bloodstream infections with vancomycin-resistant enterococci.

OBJECTIVES: To describe the population in whom bloodstream infections with vancomycin-resistant enterococci occur and the clinical and microbiologic features of infection. METHODS: From June 1, 1991, to January 31, 1994, 73 patients with bloodstream infections with vancomycin-resistant enterococci were identified by retrospective review of hospital charts and microbiology records. RESULTS: Fifty-two (73%) of 71 patients with evaluable data were hospitalized in an intensive care, unit, the adult oncology unit, or the acquired immunodeficiency syndrome unit. Before the development of the bloodstream infection with vancomycin-resistant enterococci, patients were hospitalized and received antibiotics for a median of 26 and 25.5 days, respectively. A hematologic malignancy, respiratory failure, or renal failure requiring dialysis was present in 59 patients (83%). Acute Physiology and Chronic Health Evaluation II scores of the patients ranged from 6 to 35 (median, 17). Forty-five (63%) of the patients died. Compared with 37 patients who had only a single positive blood culture, the 34 patients with 2 or more blood cultures positive for vancomycin-resistant enterococci more often were neutropenic or had acquired immunodeficiency syndrome (74% vs 35%; P = .002). CONCLUSIONS: Bloodstream infections with vancomycin-resistant enterococci predominantly affect severely ill patients who have received extensive antibiotic treatment during a prolonged hospitalization. Immunocompromised patients are more likely to have a persistent blood-stream infection with vancomycin-resistant enterococci.

Anti-Bacterial Agents↗

PubMed1996

The effect of vancomycin on the corneal endothelium.

Possible toxic effects of vancomycin on the corneal endothelium were assessed in rabbit eyes and subsequently in corneal transplant recipients. Fifteen New Zealand White rabbits were divided into five groups of three rabbits each. A paracentesis was performed on right eyes only. One hundred microliters of aqueous humor was removed followed by anterior chamber injection of 100 mu l of balanced salt solution (BSS) or varying concentrations of vancomycin (150, 750, 1,875, 7,500 mu g/ml). Left eyes served as untreated controls. Endothelial cell morphology and density were assessed by contact specular microscopy 48 h postinjection. There was no statistically significant difference in endothelial cell density between left (control) or right (treated) eyes receiving either BSS or varying concentrations of vancomycin. Transmission electron microscopy of rabbit corneal endothelium exposed to varying concentrations of vancomycin (150, 750, 1,875, 7,500 mu g/ml) showed no toxic effects. Six patients undergoing penetrating keratoplasty (PKP) received donor corneas stored in Optisol containing gentamicin to which vancomycin was added to make a final concentration of 150 mu g/ml. Eight patients undergoing PKP received corneas stored in Optisol alone. Specular microscopy was performed preoperatively and 3, 6, and 12 months postoperatively. No statistically significant difference in mean endothelial cell change was observed (Wilcoxon signed-rank test) at any time point postoperatively. Endothelial cell morphology and function are not adversely affected by therapeutic doses of vancomycin.

Animals↗

PubMedDate not supplied

Vancomycin-binding characteristics in patients with serious infections.

STUDY OBJECTIVE: To examine the extent, variability, and factors affecting vancomycin protein binding. DESIGN: Prospective, open-label, cohort study. SETTING: A general hospital. PATIENTS: Forty-four adults [mean (+/- SD) age 50.9 +/- 17.1 yrs, range 16.8-92.0 yrs] with serious infections. INTERVENTIONS: Unbound (Vu) and total (Vtot) vancomycin concentrations were determined by fluorescence polarization immunoassay. A statistical analysis model used the maximum likelihood method to evaluate the association between several important variables and log Vu while controlling for log Vtot effects. MEASUREMENTS AND MAIN RESULTS: The mean fraction percentage of unbound vancomycin was 79.5 +/- 6.0% (range 53.0-96.3%). While controlling for Vtot the total variability of Vu was 8.3%, suggesting that vancomycin binding is relatively constant in sick adults. We were able to demonstrate a significant statistical interaction effect between gender and globulin protein concentration on Vu (p = 0.022). Globulin protein concentration in men was negatively associated with Vu (p = 0.0009), but there was no association in women (p = 0.645). Age, race, peak-trough association, serum creatinine, serum albumin, serum prealbumin, and hemodialysis were not significantly associated with log Vu in the statistical model. CONCLUSION: Compared with earlier studies in healthy adults, vancomycin binding appears to be decreased during acute illness, and intrapatient and interpatient variability are relatively small. Unbound vancomycin concentration appears to be gender dependent.

Adolescent↗

PubMed1997

[Severe methicillin-resistant Staphylococcus aureus infections. Emergence of resistance to fusidic acid or fosfomycin during treatment with continuous infusion of vancomycin].

OBJECTIVES: To evaluate the development of resistance to fosfomycin or fucidic acid in severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and to assess the relationship with serum levels of vancomycin METHODS: A retrospective study was performed in patients hospitalized in our intensive care unit during a 3-year period (1993-1995) who were treated for severe MRSA infection with continuous infusion vacomycin and fosfomycin or fucidic acid. We analyzed the development of resistance and serum levels of vancomycin. RESULTS: During this period, only 20 patients received continuous infusion vancomycin plus fucidic acid or fosfomycin. MSRA resistant to fucidic or fosfomycin developed in 9. Vancomycin serum levels were significantly lower in patients who developed resistance to focidic acid or fosfomycin, both during the first 5 days of treatment (16.68 +/- 1.07 micrograms/ml vs. 22.64 +/- 1.05 mg/ml, p < 0.01) and throughout treatment duration (17.29 +/- 1.07 micrograms/ml vs. 21.85 +/- 0.78 microgram/ml, p < 0.01). CONCLUSIONS: Our findings confirm that in spite of continuous vancomycin infusion at an initial rate of 2 g/24 h, Staphylococcus aureus resistance to fosfomycin or fucidic acid an develop during ongoing treatment. Vancomycin levels of at least 20 micrograms/ml should be obtained as rapidly as possible.

Anti-Bacterial Agents↗

PubMed1997

Vancomycin-resistant enterococci: improving treatments.

Recent issues of Morbidity and Mortality Weekly Report (MMWR), a publication of the Centers for Disease Control and Prevention (CDC), described clinical isolates of Staphylococcus aureus with intermediate resistance to vancomycin in patients in Michigan and New Jersey. As described last month in the first installment of this article, vancomycin has been the only approved antibiotic to which S. aureus had been uniformly sensitive. Media coverage of this latest example of increasing antibiotic resistance included the September 4, 1997, issue of The Wall Street Journal, which carried a report of a large study of the appropriateness of vancomycin use being coordinated by the Health Care Financing Administration (HCFA). The article reported study findings that "63 percent of orders for the drug vancomycin violated guidelines from the Centers for Disease Control and Prevention." In this report, we provide additional details about that study, as well as results specific to the Pennsylvania hospitals that participated in this project. The journal article failed to point out that each of the hospitals volunteered to participate in this 15-state study, beginning in late 1995, as part of their strategy to prevent and control the spread of vancomycin-resistant enterococci (VRE). These facilities agreed with experts that optimizing vancomycin use was an important part of this strategy, in addition to traditional infection control measures such as appropriate handwashing practices, prompt and accurate identification of resistant organisms, and isolation of infected and colonized patients when indicated.

Aged↗

PubMed1998

[Bacteremia due to vancomycin-resistant enterococci in neutropenic cancer patients].

BACKGROUND: The aim of this study was to determine the incidence, clinical characteristics and outcome of vancomycin-resistant enterococcal bacteremia. PATIENTS AND METHODS: We included all cases of enterococcal bacteremia in neutropenic cancer patients documented between January 1986 and December 1995 in a 1,000-bed university hospital, where a prospective surveillance of all cases of bacteremia is regularly done. Molecular typing was performed on all vancomycin-resistant strains with the analysis of chromosomic DNA by macrorestriction. RESULTS: Seventeen cases of enterococcal bacteremia were documented. Seven (41%) were caused by vancomycin-resistant strains (E. faecium 3 and E. gallinarum 4), six of which occurred in the last 5 years of the study period. The average age of patients was 43 years (18-69) and most of them had acute leukemia. Eighty percent of these patients had received vancomycin and/or cephalosporins within 2 weeks prior to bacteremia. Previous administration of antibiotics was more frequent in patients with bacteremia caused by vancomycin-resistant enterococci than in those with bacteremia caused by susceptible strains (86% vs 30%; p < 0.05). The mean number of previous antibiotics (2.4 vs 0.8; p < 0.05) as well as days of treatment (13.6 vs 4.3; p = 0.05) were also higher among patients with resistant enterococcal bacteremia. The overall mortality was 57%. CONCLUSIONS: This study shows the emergence of sporadic cases of bacteremia caused by vancomycin-resistant enterococci in neutropenic cancer patients in our area. This fact seems to be related with the previous administration of antibiotics and advice that a rational use of these agents is needed.

Adolescent↗

PubMed2003

Epidemiological and microbiological characterization of infections caused by Staphylococcus aureus with reduced susceptibility to vancomycin, United States, 1997-2001.

Infections caused by Staphylococcus aureus with reduced vancomycin susceptibility (SA-RVS; minimum inhibitory concentration [MIC], >or=4 microg/mL), including vancomycin-intermediate S. aureus (VISA; MIC, 8 microg/mL), are a new clinical and public health dilemma. Prospective surveillance and a nested case-control study of patients in the United States infected with SA-RVS was conduced from March 1999 through December 2000. Control patients were persons infected with oxacillin-resistant S. aureus (MIC of vancomycin, <or=2 microg/mL). Among 19 case patients, 4 infections were due to VISA and 15 were due to non-VISA SA-RVS. Case patients with and those without VISA infection had similar clinical presentations and outcomes; the overall attributable mortality rate was 63%. Isolates recovered from case patients had heterogeneous pulsed-field gel electrophoresis banding patterns, regardless of the MIC of vancomycin. Neither dialysis nor chronic renal failure were predictive of case status compared with control status. Independent risk factors for being a case patient included antecedent vancomycin use and prior oxacillin-resistant S. aureus infection 2 or 3 months before the current infection.

Adult↗