SEARCH · PubMed Health

Results for “vancomycin”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources

PubMed2006

Comparison of routine prophylaxis with vancomycin or cefazolin for femoral neck fracture surgery: microbiological and clinical outcomes.

OBJECTIVE: To assess the impact of antibiotic prophylaxis on the emergence of vancomycin-resistant strains of Enterococcus faecium, Enterococcus faecalis, and Staphylococcus aureus and the incidence of surgical site infection (SSI) after vancomycin or cefazolin prophylaxis for femoral neck fracture surgery. DESIGN: Prospective cohort study. SETTING: A hospital with a high prevalence of methicillin-resistant S. aureus (MRSA) carriage. PATIENTS: All patients admitted with a femoral neck fracture from March 1, 2004 through February 28, 2005 were prospectively identified and screened for MRSA and vancomycin-resistant (VRE) carriage at admission and at day 7. Deep incisional and organ/space SSIs were also recorded. RESULTS: Of 263 patients included in the study, 152 (58%) received cefazolin and 106 (40%) received vancomycin. At admission, the prevalence of MRSA carriage was 6.8%; it was 12% among patients with risk factors and 2.2% among patients with no risk factors (P=.002). At day 7 after surgery, there were 6 patients (2%) who had hospital-acquired MRSA, corresponding to 0.7% in the cefazolin group and 5% in the vancomycin group (P=.04); none of the MRSA isolates were resistant to glycopeptides. The rate of VRE carriage at admission was 0.4%. Three patients (1%) had acquired carriage of VRE (1 had E. faecium and 2 had E. faecalis); all 3 were in the cefazolin group (2% of patients) and none in the vancomycin group (P=.27). Eight SSIs (3%) occurred, 4% in the cefazolin group and 2% in the vancomycin group (P=.47). CONCLUSIONS: This preliminary study demonstrates that cefazolin and vancomycin prophylaxis have similar impacts on the emergence of glycopeptide-resistant pathogens. Neither MRSA infection nor increased rates of SSI with other bacteria were observed in the vancomycin group, suggesting that a larger multicenter study should be initiated.

Aged, 80 and over↗

PubMed2004

Characterization of an inducible vancomycin resistance system in Streptomyces coelicolor reveals a novel gene (vanK) required for drug resistance.

Vancomycin is the front-line therapy for treating problematic infections caused by methicillin-resistant Staphylococcus aureus (MRSA), and the spread of vancomycin resistance is an acute problem. Vancomycin blocks cross-linking between peptidoglycan intermediates by binding to the D-Ala-D-Ala termini of bacterial cell wall precursors, which are the substrate of transglycosylase/transpeptidase. We have characterized a cluster of seven genes (vanSRJKHAX) in Streptomyces coelicolor that confers inducible, high-level vancomycin resistance. vanHAX are orthologous to genes found in vancomycin-resistant enterococci that encode enzymes predicted to reprogramme peptidoglycan biosynthesis such that cell wall precursors terminate in D-Ala-D-Lac rather than D-Ala-D-Ala. vanR and vanS encode a two-component signal transduction system that mediates transcriptional induction of the seven van genes. vanJ and vanK are novel genes that have no counterpart in previously characterized vancomycin resistance clusters from pathogens. VanK is a member of the Fem family of enzymes that add the cross-bridge amino acids to the stem pentapeptide of cell wall precursors, and vanK is essential for vancomycin resistance. The van genes are organized into four transcription units, vanRS, vanJ, vanK and vanHAX, and these transcripts are induced by vancomycin in a vanR-dependent manner. To develop a sensitive bioassay for inducers of the vancomycin resistance system, the promoter of vanJ was fused to a reporter gene conferring resistance to kanamycin. All the inducers identified were glycopeptide antibiotics, but teicoplanin, a membrane-anchored glycopeptide, failed to act as an inducer. Analysis of mutants defective in the vanRS and cseBC cell envelope signal transduction systems revealed significant cross-talk between the two pathways.

Amino Acid Sequence↗

PubMed2006

Daptomycin bactericidal activity and correlation between disk and broth microdilution method results in testing of Staphylococcus aureus strains with decreased susceptibility to vancomycin.

A total of 207 Staphylococcus aureus strains, including 105 well-characterized strains with decreased susceptibility to vancomycin (17 vancomycin-intermediate S. aureus [VISA] and 88 heteroresistant VISA [hVISA] strains) and 102 wild-type methicillin-resistant S. aureus (MRSA-WT) strains were tested by reference/standardized broth microdilution and disk diffusion methods, as well as by Etest (AB BIODISK, Solna, Sweden), against daptomycin and vancomycin. The lowest concentration of antimicrobial agent that killed > or = 99.9% of the initial inoculum was defined as the minimum bactericidal concentration (MBC) endpoint, and time-kill curves were performed in selected strains to further evaluate bactericidal activity. All MRSA-WT and hVISA strains were inhibited by < or = 1 microg/ml of daptomycin, while the VISA strains showed slightly higher daptomycin MICs (range, 0.5 to 4 microg/ml). All daptomycin MBC results were at the MIC or twofold higher. In contrast, 14.7% of MRSA-WT, 69.3% of hVISA, and all VISA strains showed a vancomycin MBC/MIC ratio of > or = 32 or an MBC of > or = 16 microg/ml (tolerant). The correlation coefficients between broth microdilution and disk diffusion method results were low for daptomycin (0.07) and vancomycin (0.11). Eight (3.8%) strains (all hVISA or VISA) were "nonsusceptible" to daptomycin by broth microdilution methods but susceptible by the disk diffusion method. For vancomycin, 35 (16.9%) strains were nonsusceptible by broth microdilution methods but susceptible by disk diffusion methods. In conclusion, daptomycin was highly bactericidal against S. aureus strains, and its bactericidal activity was not affected by decreased susceptibility to vancomycin. In contrast, many (one in seven) contemporary MRSA-WT, the majority of hVISA, and all VISA strains showed vancomycin MBC/MIC ratios consistent with tolerance, a predictor of poor clinical response. Disk diffusion tests generally failed to detect strains categorized as nonsusceptible to daptomycin or vancomycin by the reference broth microdilution method or Etest, and reassessment of breakpoints should be immediately attempted for MIC methods suggested as the test of choice.

Anti-Bacterial Agents↗

PubMed2000

Characterization of passage-selected vancomycin-resistant Staphylococcus aureus strains of diverse parental backgrounds.

A series of 12 Staphylococcus aureus strains of various genetic backgrounds, methicillin resistance levels, and autolytic activities were subjected to selection for the glycopeptide-intermediate S. aureus (GISA) susceptibility phenotype on increasing concentrations of vancomycin. Six strains acquired the phenotype rapidly, two did so slowly, and four failed to do so. The vancomycin MICs for the GISA strains ranged from 4 to 16 microg/ml, were stable to 20 nonselective passages, and expressed resistance homogeneously. Neither ease of acquisition of the GISA phenotype nor the MIC attained correlated with methicillin resistance hetero- versus homogeneity or autolytic deficiency or sufficiency. Oxacillin MICs were generally unchanged between parent and GISA strains, although the mec members of both isogenic methicillin-susceptible and methicillin-resistant pairs acquired the GISA phenotype more rapidly and to higher MICs than did their susceptible counterparts. Transmission electron microscopy revealed that the GISA strains appeared normal in the absence of vancomycin but had thickened and diffuse cell walls when grown with vancomycin at one-half the MIC. Common features among GISAs were reduced doubling times, decreased lysostaphin susceptibilities, and reduced whole-cell and zymographic autolytic activities in the absence of vancomycin. This, with surface hydrophobicity differences, indicated that even in the absence of vancomycin the GISA cell walls differed from those of the parents. Autolytic activities were further reduced by the inclusion of vancomycin in whole-cell and zymographic studies. The six least vancomycin-susceptible GISA strains exhibited an increased capacity to remove vancomycin from the medium versus their parent lines. This study suggests that while some elements of the GISA phenotype are strain specific, many are common to the phenotype although their expression is influenced by genetic background. GISA strains with similar glycopeptide MICs may express individual components of the phenotype to different extents.

Anti-Bacterial Agents↗

PubMed2004

Derivatives of a vancomycin-resistant Staphylococcus aureus strain isolated at Hershey Medical Center.

Antimicrobial susceptibilities and genetic relatedness of the vancomycin-resistant Staphylococcus aureus strain (VRSA) isolated at Hershey, Pa. (VRSA Hershey), and its vancomycin-susceptible and high-level-resistant derivatives were studied and compared to 32 methicillin-resistant S. aureus strains (MRSA) isolated from patients and medical staff in contact with the VRSA patient. Derivatives of VRSA were obtained by subculturing six VRSA colonies from the original culture with or without vancomycin. Ten days of drug-free subculture caused the loss of vanA in two vancomycin-susceptible derivatives for which vancomycin MICs were 1 to 4 microg/ml. Multistep selection of three VRSA clones with vancomycin for 10 days increased vancomycin MICs from 32 to 1,024 to 2,048 microg/ml. MICs of teicoplanin, dalbavancin, and oritavancin were also increased from 4, 0.5, and 0.12 to 64, 1, and 32 microg/ml, respectively. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing analysis indicated that VRSA Hershey was the vanA-acquired variety of a common MRSA clone in our hospital with sequence type 5 (ST5). Three of five vancomycin-intermediate S. aureus strains tested from geographically different areas were also ST5, and the Michigan VRSA was ST371, a one-allele variant of ST5. Derivatives of VRSA Hershey had differences in PFGE profiles and the size of SmaI fragment that carries the vanA gene cluster, indicating instability of this cluster in VRSA Hershey. However induction with vancomycin increased glycopeptide MICs and stabilized the resistance.

Alleles↗

PubMed2006

Novel mechanism of antibiotic resistance originating in vancomycin-intermediate Staphylococcus aureus.

As an aggressive pathogen, Staphylococcus aureus poses a significant public health threat and is becoming increasingly resistant to currently available antibiotics, including vancomycin, the drug of last resort for gram-positive bacterial infections. S. aureus with intermediate levels of resistance to vancomycin (vancomycin-intermediate S. aureus [VISA]) was first identified in 1996. The resistance mechanism of VISA, however, has not yet been clarified. We have previously shown that cell wall thickening is a common feature of VISA, and we have proposed that a thickened cell wall is a phenotypic determinant for vancomycin resistance in VISA (L. Cui, X. Ma, K. Sato, et al., J. Clin. Microbiol. 41:5-14, 2003). Here we show the occurrence of an anomalous diffusion of vancomycin through the VISA cell wall, which is caused by clogging of the cell wall with vancomycin itself. A series of experiments demonstrates that the thickened cell wall of VISA could protect ongoing peptidoglycan biosynthesis in the cytoplasmic membrane from vancomycin inhibition, allowing the cells to continue producing nascent cell wall peptidoglycan and thus making the cells resistant to vancomycin. We conclude that the cooperative effect of the clogging and cell wall thickening enables VISA to prevent vancomycin from reaching its true target in the cytoplasmic membrane, exhibiting a new class of antibiotic resistance in gram-positive pathogens.

Cell Wall↗

PubMed1998

Mississippi mud in the 1990s: risks and outcomes of vancomycin-associated toxicity in general oncology practice.

BACKGROUND: Discrepancies between the severity of toxicities reported in early clinical trials and recent clinical experience with vancomycin have led to confusion regarding the need for routine serum vancomycin level monitoring and discontinuation of vancomycin when toxicities occur. Therefore, the authors examined the incidence, outcomes, and predictive factors of vancomycin-associated toxicities in general oncology practice with the goal of developing clinically relevant prediction rules and guidelines. METHODS: All 742 consecutive cancer patients who received vancomycin at a comprehensive cancer center during a 3-month period were followed prospectively for the development and outcome of phlebitis, rash, ototoxicity, and nephrotoxicity. Logistic regression was used to derive a multiple variable model of the risk of nephrotoxicity. A clinical prediction rule, the Nephrotoxicity Risk Score, was developed from the risk model and validated prospectively. RESULTS: Phlebitis occurred in 3% of patients (95% confidence interval [95% CI], 2-4%), predominantly those with recently inserted central venous catheters. Rashes occurred in 11% of patients (95% CI, 9-13%); however, all but 4 patients also were receiving beta-lactam antibiotics. Clinical evidence of ototoxicity developed in 6% of patients (95% CI, 4-9%) who were receiving vancomycin plus other ototoxic agents and only 3% of patients (95% CI, 2-5%) not receiving other ototoxic agents (P = 0.08). Nephrotoxicity occurred in 17% of patients (95% CI, 15-20%). Logistic regression revealed that factors associated with an increased risk of nephrotoxicity included administration of other mild to moderate (P = 0.01) or severely nephrotoxic agents (P < 0.001) or an acute physiology and chronic health evaluation (APACHE) score > 40 (P = 0.002). Elevated serum vancomycin peak levels did not reliably predict subsequent nephrotoxicity. CONCLUSIONS: Vancomycin-associated toxicities usually are mild and self-limiting. Some patients are at a significantly higher risk of nephrotoxicity but the authors believe these individuals can be identified reliably with the Nephrotoxicity Risk Index using information available at vancomycin initiation. Further testing of the Nephrotoxicity Risk Index is ongoing.

Adolescent↗

PubMed1996

Vancomycin as a chiral selector in capillary electrophoresis: an appraisal of advantages and limitations.

The properties of the macrocyclic antibiotic vancomycin, used as a chiral selector, were studied with aminoquinolycarbamate derivatives of amino acids, containing sulfur and selenium, as well as with other organic ions. Vancomycin combines the ability to resolve fully ionized anionic enantiomers, typical of proteins, with excellent separation efficiency, exceeding that of cyclodextrins. It allows better than baseline chiral separations of several anionic analytes within 3-5 min. The resolving power of vancomycin results from its great skill in discriminating enantiomers rather than from high affinities to the separated enantiomers. The association constants of vancomycin are of the same order of magnitude, 10(2) L/mol, as that found for beta-cyclodextrin (beta-CD). The difference in association constants of separated cystine enantiomers with vancomycin, 2 x 10(2) L/mol, is one order of magnitude higher than that of enantiomers separated with beta-CD. Analytically convenient mobility differences up to 1-2 x 10(9) m2V-1s-1, with only one of the enantiomers appreciably decelerated, are obtained at submillimolar vancomycin concentrations. Typical separation efficiencies are close to 250,000 theoretical plates per meter of capillary. Deceleration of various organic ions by millimolar vancomycin implies that chiral separations with vancomycin need not be restricted to carboxylic acids. The vancomycin-analyte interactions are strongly affected by the chemical composition and concentration of the buffer. An additional experimental variable, highly effective in manipulating the separation selectivity of analytes, is the buffer pH.

Amino Acids↗

PubMed1991

Vancomycin-induced release of histamine from rat peritoneal mast cells and a rat basophil cell line (RBL-1).

Rapid intravenous administration of the glycopeptide antibiotic, vancomycin, may cause a hypotensive reaction which can usually be prevented by infusing vancomycin in dilute solutions. The release of histamine from circulating cells such as basophils and tissue mast cells has been implicated in hypotensive reactions since the effects can be prevented by antihistamine pretreatment. The direct effects of vancomycin on histamine release were therefore investigated in rat peritoneal mast cells and rat leukemic basophils (RBL-1 cells). Suspension cultures of mast cells or RBL-1 cells were exposed to vancomycin for 30-60 minutes at concentrations comparable to those infused clinically (2.28 or 4.56 mg/ml). Vancomycin induced a time- and dose-dependent release of histamine into the culture media from both cell types. The reference degranulating agent, Compound 48/80 (CP 48/80), was also shown to induce histamine release from mast cells and RBL-1 cells. Mast cells were significantly more sensitive to vancomycin and CP 48/80 than RBL-1 cells and, unlike RBL-1 cells, were responsive to the inhibitory effects of cromolyn sodium on histamine release. Cromolyn sodium did not inhibit vancomycin-induced histamine release in RBL-1 or mast cells. Morphologically, mast cells exposed to either vancomycin or CP 48/80 exhibited dose-related degranulation. On the other hand, treatment-related degranulation effects of either vancomycin or CP 48/80 on RBL-1 cells could not be reliably distinguished from controls by qualitative evaluation. Based upon these findings it is concluded that mast cells may represent a more useful model to evaluate the potential of investigational agents to release histamine and to study mechanisms of histamine release than RBL-1 cells.

Animals↗

PubMedDate not supplied

Vancomycin ototoxicity and nephrotoxicity. A review.

Vancomycin has been in clinical use as a potent antistaphylococcal antibiotic for over 30 years. Most reports of ototoxicity and nephrotoxicity have been associated with early, relatively impure, formulations of vancomycin. This paper reviews the literature concerning vancomycin ototoxocity and nephrotoxicity and the evidence for their correlation with the therapeutic serum concentration range. There have been 28 reports of vancomycin-associated ototoxicity published in the medical literature since 1958. It remains unclear whether any diminution in hearing is permanent or reversible. Few patients in the literature had follow-up audiometry and the hearing impairment tends to be at higher frequencies. Several authors reported peak serum vancomycin concentrations, but the exact time these were drawn with respect to the last dose is mostly unclear. In other reports, the 'peak' concentrations noted 3 to 6 hours after the last dose are probably indicative of much higher concentrations because of vancomycin's rapid phase of distribution. More than half the 57 cases of reported nephrotoxicity due to vancomycin occurred within the first 6 years of the drug's use. Many of these patients also had pre-existing renal dysfunction or were concomitantly receiving other nephrotoxic agents. It is unclear whether the coadministration of aminoglycosides produces a synergistic toxicity. The exact incidence of nephrotoxicity is uncertain, but is probably less with the current, relatively pure, product. The correlation of nephrotoxicity with certain serum vancomycin concentrations remains to be clarified. Other aspects also require clarification, such as when to draw samples to determine peak serum concentrations and whether or not routine measurements are necessary at all. In the absence of better guidelines, efforts should be made to tailor individual patient's regimens to produce peak and trough serum vancomycin concentrations to within the widely accepted ranges of 30 to 40 and 5 to 10 mg/L, respectively. In addition, the concomitant use of other potentially nephrotoxic and ototoxic agents should be avoided.

Ear↗

PubMed1994

Vancomycin hypersensitivity: synergism with narcotics and "desensitization" by a rapid continuous intravenous protocol.

BACKGROUND: We examined the clinical spectrum of patients with persistent adverse reactions to vancomycin, assessed contributing factors, and evaluated the efficacy and safety of a rapid continuous intravenous "desensitization" protocol in these patients. METHODS: Seven patients with serious staphylococcal infections resistant to beta-lactam antibiotics whose adverse reactions to vancomycin persisted despite slowing of the vancomycin infusion and pretreatment with H1-antihistamine were studied. All seven patients underwent a rapid continuous intravenous desensitization protocol with multiple small increases in vancomycin concentration tightly regulated with a syringe pump. RESULTS: Most of the seven patients safely achieved, during the first day, a vancomycin infusion rate (VIR) sufficient, or close to sufficient, to provide the desired vancomycin dose. In three patients there appeared to be a threshold VIR beyond which adverse reactions were repeatedly elicited; these reactions abated when the VIR was slightly lowered. Narcotic administration was found to adversely affect treatment with vancomycin. After concurrent narcotic administration was discontinued in three patients, they and the other four patients successfully completed the full course of treatment with vancomycin. CONCLUSION: Patients whose adverse reactions to vancomycin did not respond to slowing of the infusion rate and additional H1-antihistamines can be safely treated with a rapid continuous intravenous desensitization protocol and discontinuance of narcotic administration.

Adolescent↗

PubMed1994

Colonization pattern of vancomycin-resistant Enterococcus faecium.

BACKGROUND: Vancomycin-resistant Enterococcus faecium is increasingly recognized as a serious problem by hospital epidemiologists. Understanding its colonization patterns may help in designing strategies to control its nosocomial spread in the hospital. METHODS: Twenty patients, selected at random, with vancomycin-resistant E. faecium isolated from cultures of various body sites were studied to determine sites of colonization. For 12 of these patients, cultures of environmental surfaces of their rooms and wards were also obtained. RESULTS: Eighteen patients (90%) had vancomycin-resistant E. faecium grown in stool cultures. In five patients (25%), vancomycin-resistant E. faecium was cultured from other sites: groins (four), popliteal fossae (three), mouth (one), and an open wound site (one). Patients with positive cultures from the groins and popliteal fossae also had growth of vancomycin-resistant E. faecium in cultures of diarrhea soiling those sites. No patients had the organism isolated from their nares. Vancomycin-resistant E. faecium grew in cultures obtained from bedside stand tables, over-bed tables, used linen, and bedside rails. CONCLUSIONS: In the 20 patients studied, colonization of vancomycin-resistant E. faecium was limited chiefly to the enteric tract. Absence of colonization of such a secluded area with poor antibiotic penetrability as the nares is encouraging. In our study, vancomycin-resistant E. faecium was isolated from various environmental surfaces from the rooms and wards of patients with vancomycin-resistant E. faecium in their stools.

Administration, Oral↗

PubMed1994

Enteric eradication of vancomycin-resistant Enterococcus faecium with oral bacitracin.

The emergence of vancomycin-resistant Enterococcus faecium (VREF) has produced a therapeutic dilemma. The colonization of the intestinal tract with VREF may predispose patients to infections by this organism and may contribute to its nosocomial spread. It is reasonable to attempt to eradicate VREF from colonized patients. The optimal regimen, however, is unknown and this study was designed to evaluate the efficacy of oral regimens of vancomycin and bacitracin for the elimination of VREF from the enteric tract. Enterococcal isolates were tested for susceptibilities to vancomycin, bacitracin, and ampicillin with median minimum inhibitory concentrations of > 512 micrograms/ml, 10 units/ml, and 128 micrograms/ml, respectively. All patients were given an initial trial of oral vancomycin 125 mg every 6 h for 10 days. Those who failed oral vancomycin were then given oral bacitracin 25,000 units every 6 h for 10 days due to its favorable in vitro activity. VREF was eradicated from the stools of 42% of patients (eight of 19) receiving oral vancomycin as compared with all eight patients receiving oral bacitracin (P < 0.01). The organism recurred in two bacitracin patients (25%) 8 and 20 days after completion of therapy. Whether prior vancomycin therapy predisposed patients to colonization by VREF was also examined. Ten (53%) of 19 patients had received prior vancomycin therapy before isolation of VREF from the stool. Our data suggest that oral bacitracin may be an effective alternative to commercially available oral vancomycin for the eradication of VREF from the enteric tract.

Administration, Oral↗

PubMed1998

The emergence of Staphylococcus aureus with reduced susceptibility to vancomycin in Japan.

Within the past year, infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains with reduced susceptibility to vancomycin (MIC=8 microg/mL) have been reported in both Japan and the United States. The emergence of these strains poses a potentially serious threat to public health. After 2 such strains (Mu3 and Mu50) were identified at Juntendo Hospital in 1996, a screening program to identify MRSA strains with reduced susceptibility to vancomycin was initiated. Of 970 MRSA strains tested at 195 nonuniversity hospitals throughout Japan, 13 (1.3%) were found to have subpopulations with reduced vancomycin susceptibility (heterogeneous vancomycin resistance). Among 129 MRSA strains identified at 7 university hospitals, 12 (9.3%) demonstrated heterogeneity for vancomycin resistance; 1 of these strains had a vancomycin MIC of 7 microg/mL. Although resistance in these strains is not the result of the transfer of enterococcal vancomycin resistance genes (vanA or vanB), the clonal dissemination of MRSA strains with vancomycin-resistant subpopulations is obviously undesirable. Intensified testing of MRSA strains for resistance to vancomycin and appropriate measures for the prevention of the spread of such strains are recommended.

Anti-Bacterial Agents↗

PubMed1997

A simple method for administering vancomycin in the spinal cord injured population.

OBJECTIVE: To examine the applicability in patients with spinal cord injury (SCI) of a modified version of the commonly used Lake and Peterson dosing regimen for vancomycin. DESIGN: Nonrandomized, prospective clinical trial with a historical control. SETTING: Spinal cord injury unit at a Veterans Affairs Medical Center. PATIENTS: Hospitalized patients with a history of SCI at least 6 months earlier and an estimated creatinine clearance of > or = 15 mL/min who required vancomycin therapy. The experimental group consisted of 15 evaluable patients, 8 with tetraplegia and 7 with paraplegia. INTERVENTION: Vancomycin regimens were initiated using a modified version of the guidelines of Lake and Peterson. MAIN OUTCOME MEASURE: After 4 to 8 doses, peak vancomycin concentrations in serum were obtained 15 minutes after a 1-hour infusion, and trough concentrations were drawn within 30 minutes of the next scheduled dose. RESULTS: Only 3 of 15 (20%) patients in the experimental group required a single adjustment in the dosing interval to achieve the targeted serum vancomycin concentrations. The proportion of patients who required dosing modification was significantly lower in the experimental group than in a group of 16 SCI control patients who received vancomycin according to the dosing recommendations in the drug insert (20% vs 75%, respectively; p = .002). CONCLUSION: These results support the need for tailored vancomycin dosing in the SCI population and the efficacy of this simple method of administering vancomycin in achieving desirable concentrations of vancomycin in the serum of SCI patients.

Adult↗

PubMed1994

Protamine sulfate and vancomycin are synergistic against Staphylococcus epidermidis prosthesis infection in vivo.

We have previously demonstrated that the quaternary amine, protamine sulfate (PS), is bactericidal against Staphylococcus epidermidis. In an attempt to decrease genitourinary prosthesis infection rates, we examined the ability of PS as a wound irrigant to inhibit Staphylococcus epidermidis viability. Eighty-seven Sprague-Dawley rats were studied by implanting a sterile silicone pellet in their dorsum. The pellet was inoculated with Staphylococcus epidermidis and the rats were divided into four groups based on the wound irrigant employed after inoculation: (1) control (sterile water) (2) vancomycin; (3) PS; (4) vancomycin + PS. All rats received perioperative and daily intramuscular vancomycin, and the pellets were explanted on postoperative day 28 and cultured. The infection rates were: (1) control 77%, (2) vancomycin 50%, (3) protamine sulfate 67%, and (4) protamine sulfate and vancomycin 19%. The differences between (2) vancomycin versus (4) vancomycin + PS and (3) PS versus (4) vancomycin + PS were significant (p = 0.05 and p < 0.005). The data suggest that PS potentiates vancomycin as a wound irrigant in prosthesis implantation.

Animals↗

PubMed1995

Synergy between protamine and vancomycin in the treatment of Staphylococcus epidermidis biofilms.

OBJECTIVES: To test for synergy between protamine and vancomycin by analyzing their bactericidal activities against slime-producing Staphylococcus epidermidis ATCC 35983 under planktonic and biofilm conditions. METHODS: We evaluated the activity of vancomycin and protamine separately against planktonic S epidermidis in broth by measuring the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for each agent according to the standard macrobroth dilution method. To assess the possibility of synergy between these two agents, planktonic S epidermidis was exposed to vancomycin and protamine together in varying concentrations. Biofilms containing S epidermidis were then prepared and subjected to incubation with vancomycin and protamine separately as well as combined in varying concentrations. The bacterial viability of S epidermidis in the planktonic and biofilm phases after exposure to these two agents was assessed by qualitative culture and determination of viable colony blots. RESULTS: Standard antibacterial susceptibility tests revealed that the MICs of protamine and vancomycin were 1 and 2 micrograms/mL, respectively, and their MBCs were 4 micrograms/mL. The MICs were unchanged when protamine and vancomycin were combined in varying concentrations. Neither agent exhibited significant bactericidal activity against S epidermidis in the biofilm phase at concentrations < or = 32 micrograms/mL. However, a combination of both agents, each at 32 micrograms/mL, resulted in a 7-log decrease in viable bacterial counts. CONCLUSIONS: Protamine alone exhibited significant antibacterial activity against planktonic S epidermidis. No synergy was noted between protamine and vancomycin against S epidermidis in the planktonic phase. However, synergy was demonstrated when a combination of protamine and vancomycin was used on S epidermidis in the biofilm phase. Thus, protamine shows promise as an adjunctive agent to vancomycin in the treatment of S epidermidis in biofilms.

Biofilms↗

PubMed2000

Isostatic compression, a new process for incorporating vancomycin into biphasic calcium phosphate: comparison with a classical method.

Isostatic compression has rarely been used to load calcium-phosphate biomaterials with therapeutic agents. This report, concerning four processes associating vancomycin, compares isostatic compression with wet granulation, a classical method. In the wet granulation study, vancomycin was associated with biphasic calcium-phosphate (BCP) granules either by adsorption or incorporation with a new granulation. In the isostatic compression study, BCP powder was compressed at 100, 140 and 200 MPa. The blocks obtained were crushed and 200-500 microm, sieved; thus, the vancomycin solution was absorbed on these granules. Compaction of BCP and vancomycin powders gave, after crushing and sieving, granules loaded with vancomycin. In each study, 5% vancomycin was associated with BCP. Vancomycin release profiles were assessed by an in vitro culture chamber dissolution test. Physicochemical studies of BCP and vancomycin showed their structural integrity after isostatic compression. Isostatic compression prolonged vancomycin release time from 3 to 7 days and the release time became greater as isostatic pressure increased, probably because of the porosity decrease of the granules during compression.

Calcium Phosphates↗