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Prevention of bacteremia attributed to luminal colonization of tunneled central venous catheters with vancomycin-susceptible organisms.

Forty-five children with oncologic or hematologic disorders requiring tunneled central venous catheters (TCVC) for the administration of immunosuppressive therapy were randomized to receive either 10 U/mL heparin (H) (24 patients) or a solution of 10 U/mL H and 25 micrograms/mL vancomycin (H-V) (21 patients) for all catheter flushes. Episodes of fever or suspected sepsis were evaluated to determine whether the addition of vancomycin to the flush solution would alter the incidence of symptomatic bacteremia attributed to luminal colonization of TCVC with vancomycin-susceptible bacteria. Patients were enrolled for 247 +/- 150 days, accounting for a total of 11,095 days of catheter use. Bacteremia attributed to luminal colonization with vancomycin-susceptible organisms occurred in five patients (six infections) receiving H alone compared with zero patients receiving H-V (P = .035). The time to the first episode of bacteremia with vancomycin-susceptible organisms, analyzed by Kaplan-Meier survival curves, was significantly longer in patients receiving H-V (P = .04). There were no differences in the incidence of other infections including bacteremia attributed to luminal colonization with vancomycin-resistant organisms, other bacteremias (including those arising from the catheter exit site), exit-site cellulitis, or fungal infections. No organisms resistant to vancomycin were identified. Vancomycin could not be detected in the peripheral blood of patients receiving vancomycin in the flush solution. No vancomycin-related toxicities were noted. We conclude that the use of an H-V flush solution in immunocompromised patients with TCVC can decrease the frequency of bacteremia attributed to luminal colonization with vancomycin-susceptible bacteria.

Adolescent↗

The antimicrobial activity of vancomycin in the presence and absence of sodium carboxymethyl starch.

The purpose of this work was to determine any effects the presence of sodium carboxymethyl starch may have on the antimicrobial activity of vancomycin given a previously described interaction between vancomycin and sodium carboxymethyl starch. In particular, the in-vitro activity of vancomycin against two clinically relevant bacteria, Staphylococcus aureus and Enterococcus faecalis, was studied in the presence of varying concentrations of sodium carboxymethyl starch. From two independent studies conducted using an agar dilution method, it appeared that the binding of vancomycin to sodium carboxymethyl starch had no effect on the in-vitro antimicrobial activity of vancomycin. The minimum inhibitory concentration of vancomycin against S. aureus in the presence of as much as 1 mg mL(-1) sodium carboxymethyl starch was similar to that of the control where no sodium carboxymethyl starch was added (1-4 microg mL(-1) vs 1-2 microg mL(-1), respectively). Likewise, the minimum inhibitory concentration of vancomycin against E. faecalis in the presence of 1 mg mL(-1) sodium carboxymethyl starch was also similar to that of the control where no sodium carboxymethyl starch was added (1-4 microg mL(-1) vs 1-4 microg mL(-1), respectively). However, there may be factors in the in-vitro method, such as high ionic strength, that could disrupt the interaction between vancomycin and sodium carboxymethyl starch. Therefore, the possibility of diminished vancomycin activity in-vivo cannot be ruled out. A small percentage (8-10%) of vancomycin was determined to be bound to sodium carboxymethyl starch in broth media. Given these results, the impact of sodium carboxymethyl starch on the in-vitro antimicrobial activity of vancomycin is expected to be minimal. Binding studies could not be conducted with gelled agar due to its semi-solid state.

Anti-Bacterial Agents↗

Urinary tract infection with an Enterococcus faecalis isolate that requires vancomycin for growth.

OBJECTIVE: To characterize the nutritional requirements and potential origin of a fastidious urinary tract Enterococcus faecalis isolate that apparently requires the antimicrobial agent vancomycin to grow. DESIGN: Case report and detailed microbiologic and molecular epidemiologic analysis. SETTING: University teaching hospital. MEASUREMENTS: Growth of the vancomycin-dependent strain was monitored using various standard laboratory media with and without supplementation with vancomycin and other substrates. This strain was compared with other vancomycin-resistant but nondependent E. faecalis strains by examining plasmid profiles and pulsed-field gel electrophoresis patterns of genomic DNA and by analyzing vancomycin-resistance genes identified by the polymerase chain reaction. RESULTS: An E. faecalis isolate, strain TJ310, was isolated repeatedly from the urine of a patient receiving long-term vancomycin therapy. This strain grew in primary culture but not on subculture, suggesting an unusual growth requirement, and ultimately was found to require the glycopeptide antibiotic vancomycin to grow. Strain TJ310 appeared to be closely related to other vancomycin-resistant but nondependent E. faecalis isolates with the vanB genotype previously isolated from the same patient, suggesting that vancomycin dependence may have evolved in vivo in a vancomycin-resistant enterococcal strain during continuous exposure to high concentrations of vancomycin in the urine. CONCLUSIONS: This is the first reported example of a clinical bacterial isolate that requires an antimicrobial agent to grow.

Drug Resistance, Microbial↗

Comparative study of cefazolin, cefamandole, and vancomycin for surgical prophylaxis in cardiac and vascular operations. A double-blind randomized trial.

Three-hundred twenty-one adults undergoing cardiac or major vascular operations were randomized to receive intravenous cefazolin, cefamandole, or vancomycin for prophylaxis against surgical infection in a double-blind trial. All three regimens provided therapeutic blood levels throughout operation in patients studied undergoing cardiopulmonary bypass. The prevalence of surgical wound infection was lowest with vancomycin (4 infections [3.7%] versus 14 [12.3%] and 13 [11.5%] in the cefazolin and cefamandole groups, respectively; p = 0.05); there were no thoracic wound infections in cardiac operations in the vancomycin group (p = 0.04). The mean duration of postoperative hospitalization was lowest in the vancomycin group (10.1 days; p < 0.01) and highest in the cefazolin group (12.9 days). Prophylaxis with vancomycin or cefamandole, compared with cefazolin, did not prevent nosocomial cutaneous colonization by methicillin-resistant coagulase-negative staphylococci; colonization or infection with vancomycin-resistant staphylococci or enterococci was not detected. Adverse effects attributable to the prophylactic regimen were infrequent in all three groups. Eight patients given vancomycin became hypotensive during administration of a dose, despite infusion during a 1-hour period; however, slowing the rate of administration and pretreating with diphenhydramine allowed vancomycin to be resumed and prophylaxis completed uneventfully in five of the patients. We conclude that administration of vancomycin (approximately 15 mg/kg), immediately preoperatively, provides therapeutic blood levels for surgical prophylaxis throughout most cardiac and vascular operations, resulting in protection against postoperative infection superior to that obtained with cefazolin or cefamandole. Vancomycin deserves consideration for inclusion in the prophylactic regimen (1) for prosthetic valve replacement and prosthetic vascular graft implantation, to reduce the risk of implant infection by methicillin-resistant coagulase-negative staphylococci and enterococci; (2) for any cardiovascular operation if the patient has recently received broad-spectrum antimicrobial therapy; and (3) for all cardiovascular operations in centers with a high prevalence of surgical infection with methicillin-resistant staphylococci or enterococci. Guidelines for dosing and administration of vancomycin for cardiovascular surgical prophylaxis are provided.

Adult↗

Proficiency of determination of vancomycin susceptibility in enterococci by clinical laboratories in Taiwan.

Eighty clinical microbiology laboratories in Taiwan were evaluated for proficiency in the determination of vancomycin susceptibility of enterococci. Each laboratory was given 1 vancomycin-sensitive isolate and 3 vancomycin-resistant enterococci (VRE) isolates to determine the levels of vancomycin resistance. Among a total of 240 tests performed, 153 (63.8%) correctly determined the levels of vancomycin resistance of the survey isolates. Seventy eight (98%) of the 80 laboratories accurately identified the high level of vancomycin resistant isolates [Enterococcus faecalis; minimum inhibitory concentration (MIC) >256 microg/mL]. Seventy two laboratories (90%) correctly determined the level of vancomycin resistance of another VRE with a vancomycin MIC of 64 microg/mL. Only 3 of the 80 laboratories correctly determined the intermediate-level vancomycin resistant isolates (Enterococcus casseliflavus; MIC = 8 microg/mL). Eight laboratories reported the vancomycin-susceptible isolate as being vancomycin-resistant or of intermediate susceptibility. This survey demonstrated that clinical microbiology laboratories in Taiwan are proficient in detecting high-level but not low-level VRE, suggesting a need to improve their proficiency in VRE detection.

Enterococcus↗

Clinical usefulness of vancomycin.

The antibacterial spectrum, pharmacokinetics, and clinical uses of vancomycin are reviewed. Vancomycin interferes with peptidoglycan biosynthesis in multiplying organisms and is bactericidal. It is supplied as the hydrochloride salt and is available in 500-mg ampuls. Vancomycin is usually administered intravenously or orally. I.V. vancomycin should be administered slowly (over 30--60 min) and in an adequate volume (100--250 ml) of 5% dextrose injection. Usual adult dose is 500 mg every six hours or 1 g every 12 hours. Serum vancomycin kinetics are best explained on the basis of a two- or three-compartment open model. Vancomycin is almost completely eliminated through the kidneys. Mean vancomycin concentrations in the presence of inflamed meninges, pleural fluid, pericardial fluid, ascitic fluid, synovial fluid, and bile are approximately 15% of the serum concentrations. Vancomycin is used prophylactically to prevent infections caused by gram-positive cocci. Vancomycin is an ideal drug for prophylaxis in prosthetic implant surgery because of its long serum half-life and activity against Staphylococcus epidermidis and Staph. aureus. Vancomycin has been used in the prevention and treatment of shunt infection in hemodialysis patients. It can be used adjunctly with a number of antibiotics to treat a variety of bacterial infections. Vancomycin is recognized as one of the most potent antistaphylococcal drugs available. It is the drug-of-choice in the treatment of serious methicillin-resistant Staph. aureus infections. It is the preferred therapy for Clostridium difficile (antibiotic-associated) colitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗

The epidemiology of intravenous vancomycin usage in a university hospital. A 10-year study.

OBJECTIVES: To examine the trends of intravenous vancomycin usage during a 10-year period, to classify the indications for which physicians prescribed the antibiotic, and to identify the independent predictors for empirical use of vancomycin. DESIGN: A descriptive epidemiological study, a cross-sectional study, and a case-control study were performed. SETTING: A 900-bed university-teaching hospital. MAIN OUTCOME MEASURES: The annual crude usage (grams) and incidence density (grams/1000 patient-days) of vancomycin were measured for 10 years (July 1981 to July 1991). In 109 randomly selected patient medical records, we evaluated the proportion of usage of vancomycin classified as prophylaxis, empirical therapy, or specifically directed therapy. Univariate and multivariate analyses were performed to identify determinants of empirical administration of vancomycin vs a penicillase-resistant penicillin to 64 case patients and 64 control patients. RESULTS: The rate of vancomycin usage increased 20-fold from 5.72 g/1000 patient-days in 1981 to 121.25 g/1000 patient-days in 1991. The use of vancomycin was significantly higher (P < .0001) in hematology-oncology areas compared with that in other hospital areas. The rates for each indication for vancomycin were 35.0% for prophylaxis 31.8% for empirical therapy, and 33.2% for therapy specifically directed by culture results. In a multivariate analysis, the presence of "plastic" medical devices was the best independent predictor for patients receiving vancomycin: intravenous lines (odds ratio [OR], 6.23; 95% confidence interval [CI], 2.28 to 17.06; P < .001), Hickman catheters (OR, 76.12; 95% CI, 15.06 to 384.73; P < .001), and other medical devices (OR, 10.50; 95% CI, 2.54 to 43.38; P = .001). CONCLUSIONS: Vancomycin use has increased linearly in the last decade primarily related to the presence of indwelling vascular devices in hematology-oncology patients. Use of vancomycin is equally divided among empirical therapy, prophylaxis, and specific therapy for a documented infection.

Case-Control Studies↗

Vancomycin-intermediate Staphylococcus aureus strains have impaired acetate catabolism: implications for polysaccharide intercellular adhesin synthesis and autolysis.

The most common mechanism by which Staphylococcus aureus gains resistance to vancomycin is by adapting its physiology and metabolism to permit growth in the presence of vancomycin. Several studies have examined the adaptive changes occurring during the transition to vancomycin-intermediate resistance, leading to a model of vancomycin resistance in which decreased cell wall turnover and autolysis result in increased cell wall thickness and resistance to vancomycin. In the present study, we identified metabolic changes common to vancomycin-intermediate S. aureus (VISA) strains by assessing the metabolic and growth characteristics of two VISA strains (vancomycin MICs of 8 microg/ml) and two isogenic derivative strains with vancomycin MICs of 32 microg/ml. Interestingly, we observed the parental strains had impaired catabolism of nonpreferred carbon sources (i.e., acetate), and this impairment became more pronounced as vancomycin resistance increased. To determine if acetate catabolism impairment is common to VISA strains, we assessed the ability of VISA and vancomycin-sensitive S. aureus (VSSA) clinical isolates to catabolize acetate. As expected, a significantly greater percentage of VISA strains (71%) had impaired acetate catabolism relative to VSSA (8%). This is an important observation because staphylococcal acetate catabolism is implicated in growth yield and antibiotic tolerance and in regulating cell death and polysaccharide intercellular adhesin synthesis.

Acetates↗

Cloxacillin versus vancomycin for presumed late-onset sepsis in the Neonatal Intensive Care Unit and the impact upon outcome of coagulase negative staphylococcal bacteremia: a retrospective cohort study.

BACKGROUND: Coagulase negative staphylococcus (CONS) is the main cause of late-onset sepsis in Neonatal Intensive Care Units (NICU). Although CONS rarely causes fulminant sepsis, vancomycin is frequently used as empiric therapy. Indiscriminate use of vancomycin has been linked to the emergence of vancomycin resistant organisms. The objective of this study was to compare duration of CONS sepsis and mortality before and after implementation of a policy of selective vancomycin use and compare use of vancomycin between the 2 time periods. METHODS: A retrospective study was conducted of infants > or =4 days old, experiencing signs of sepsis with a first positive blood culture for CONS, during two 12-month periods. Late-onset sepsis was treated empirically with vancomycin and gentamicin during period 1, and cloxacillin and gentamicin during period 2. The confidence interval method was used to assess non-inferiority of the outcomes between the two study groups. RESULTS: There were 45 episodes of CONS sepsis during period 1 and 37 during period 2. Duration of sepsis was similar between periods (hazard ratio of 1.00, 95%CI: 0.64, 1.57). One death during period 2 was possibly related to CONS sepsis versus none in period 1. Vancomycin was used in 97.8% of episodes in period 1 versus 81.1% of episodes in period 2. CONCLUSION: Although we failed to show non-inferiority of duration of sepsis in the cloxacillin and gentamicin group compared to the vancomycin and gentamicin group, duration of sepsis was clinically similar. Restricting vancomycin for confirmed cases of CONS sepsis resistant to oxacillin appears effective and safe, and significantly reduces vancomycin use in the NICU.

Anti-Bacterial Agents↗

[Detection of vancomycin-resistant enterococci by a fully automated microbiology system, RAISUS].

A fully automated microbiology system, RAISUS recently developed (Nissui Pharmaceuticals Co., Ltd., Tokyo) was evaluated for identification of enterococci and for detection of vancomycin-resistant enterococci (VRE). When a total of 124 enterococcal isolates were tested, RAISUS correctly identified 122 (98.4%) isolates. Two isolates resulted in species-identifications disagreed with the reference but agreed as belonging to the genus of Enterococcus. When a total of fifty-seven VRE isolates confirmed to be positive for vanA and/or vanB genes were tested against vancomycin, the current RAISUS susceptibility program version 1.76 could detect 41 (71.9%) isolates of VRE as having > or = 32 microg/ml MIC for vancomycin, but one was intermediate (MIC, 8.0 microg/ml) and the remaining 15 vanB-type isolates were incorrectly interpreted as vancomycin-susceptible (MIC, < or = 4.0 microg/ml). The test program based on the algorism to determine bacterial growth in the presence of vancomycin was developed and evaluated. With this test program, all the VRE isolates positive for vanA and/or vanB genes were identified as being vancomycin-resistant or intermediate interpretation. However, eight of 19 clinical isolates of E. casseliflavus and E. gallinarum intrinsically possessing vanC gene were determined as being < or = 4.0 microg/ml MIC for vancomycin. With the influence of program revision, RAISUS became to incubate the test plate longer than with the current program, but 50% of enterococcal isolates including vancomycin-resistant and vancomycin-susceptible isolates were determined within 5 hour-incubations and 90% were within 9 to 10 hour-incubations. With these results, we can conclude that the revised test program for enterococcal isolates could rapidly and correctly identify vancomycin-resistance, and will be applicable to the routine susceptibility test in clinical laboratories.

Bacteriological Techniques↗

Prospective surveillance of vancomycin-resistant enterococci in a neonatal intensive care unit.

A point-prevalence study of vancomycin-resistant enterococci colonization of the gastrointestinal tract in an Israeli hospital revealed that 14.7% of the 320 inpatients were colonized. Vancomycin-resistant enterococci colonization was detected in most departments except the neonatal intensive care unit. Hence, a prospective longitudinal study of the prevalence of vancomycin-resistant enterococci colonization in the neonatal intensive care unit was conducted. A rectal swab was obtained from every newborn on admission to the neonatal intensive care unit and once weekly thereafter until the patient was discharged. Enterococci were isolated and tested for susceptibility to vancomycin. A total of 84 neonates were enrolled and monitored on average for 3 weeks (SD +/- 3.9, range 1-20 weeks). Mean gestational age was 35.7 weeks (SD +/- 3.9, range 25-42 weeks), and mean birth weight was 2.4 kg (SD +/- 0.9, range 0.45-4.1 kg). Most patients had one or more of the known risk factors associated with colonization with vancomycin-resistant enterococci. Eighty percent of the patients received antibiotics during the study, and 14.3% received vancomycin. The median duration of vancomycin treatment was 12.5 days (SD +/- 16.8, range 5-55 days). Fifty-one of 84 (61%) patients acquired enterococci sensitive to vancomycin during the study period, but no newborn had vancomycin-resistant enterococci. Possible explanations for this finding may be physical isolation of the neonatal intensive care unit from the rest of the hospital, intrinsic differences in the bowel milieu of this age group and the lack of exposure to food and other environmental sources of vancomycin-resistant enterococci from the community.

Adolescent↗

A randomized, controlled trial of the efficacy of a heparin and vancomycin solution in preventing central venous catheter infections in children.

OBJECTIVE: To determine whether adding vancomycin to central venous catheter (CVC) flush solution would significantly reduce the incidence of bacteremia attributable to luminal colonization with vancomycin-susceptible organisms. STUDY DESIGN: Fifty-five children with cancer and eight children given total parenteral nutrition by the surgery or nutrition support services were randomly assigned to receive a heparin CVC flush solution (n = 31) or a heparin-vancomycin CVC flush solution (n = 32). RESULTS: During 9158 catheter days, 6.5% of the patients in the heparin group and 15.6% of the patients in the heparin-vancomycin group had bacteremia attributable to luminal colonization with vancomycin-susceptible organisms (p = 0.43). The mean rates of bacteremia attributable to luminal colonization with vancomycin-susceptible organisms were 0.6/1000 catheter days in the heparin group and 1.4/1000 catheter days in the heparin-vancomycin group (p = 0.25). There was no significant difference between the groups when the time to the first episode of bacteremia attributable to luminal colonization with a vancomycin-susceptible organism was compared by means of Kaplan-Meier survival estimates. Streptococcus viridans infection was not attributable to luminal colonization. CONCLUSION: The addition of vancomycin to heparin CVC flush solution did not reduce bacteremia with vancomycin-susceptible organisms. Bacteremia with Streptococcus viridans was not related to the use of a CVC.

Adolescent↗

In vivo development of decreased susceptibility to vancomycin in clinical isolates of methicillin-resistant Staphylococcus aureus.

To investigate the possibility of in vivo development of decreased vancomycin susceptibility, the vancomycin susceptibilities of 12 methicillin-resistant Staphylococcus aureus (MRSA) isolates serially recovered from six patients with vancomycin therapy were tested by standard MIC determination method and population analysis. While all of the MRSA isolates were susceptible to vancomycin (MICs, 1-2 microg/ml) by standard method, population analysis showed the upward shifts indicating decreased vancomycin susceptibility among serial isolates from two patients. These bacteria with decreased vancomycin susceptibility could be selected by using vancomycin selection of pre-therapy isolates under laboratory conditions. Furthermore, the reversion phenomenon of decreased vancomycin susceptibility was confirmed after 20 serial passages of the post-therapy isolates on drug-free agar. These data suggest that in vivo isolates may develop decreased vancomycin susceptibility that is not of such magnitude to cross a breakpoint threshold. This resistance may be unstable, and appears to result from a selective or inducible process that occurs in MRSA clinical strains during vancomycin therapy.

Aged↗

Tandem action of glycosyltransferases in the maturation of vancomycin and teicoplanin aglycones: novel glycopeptides.

The glycopeptides vancomycin and teicoplanin are clinically important antibiotics. The carbohydrate portions of these molecules affect biological activity, and there is great interest in developing efficient strategies to make carbohydrate derivatives. To this end, genes encoding four glycosyltransferases, GtfB, C, D, E, were subcloned from Amycolatopsis orientalis strains that produce chloroeremomycin (GtfB, C) or vancomycin (GtfD, E) into Escherichia coli. After expression and purification, each glycosyltransferase (Gtf) was characterized for activity either with the aglycones (GtfB, E) or the glucosylated derivatives (GtfC, D) of vancomycin and teicoplanin. GtfB efficiently glucosylates vancomycin aglycone using UDP-glucose as the glycosyl donor to form desvancosaminyl-vancomycin (vancomycin pseudoaglycone), with k(cat) of 17 min(-1), but has very low glucosylation activity, < or = 0.3 min(-1), for an alternate substrate, teicoplanin aglycone. In contrast, GtfE is much more efficient at glucosylating both its natural substrate, vancomycin aglycone (k(cat) = 60 min(-1)), and an unnatural substrate, teicoplanin aglycone (k(cat) = 20 min(-1)). To test the addition of the 4-epi-vancosamine moiety by GtfC and GtfD, synthesis of UDP-beta-L-4-epi-vancosamine was undertaken. This NDP-sugar served as a substrate for both GtfC and GtfD in the presence of vancomycin pseudoaglycone (GtfC and GtfD) or the glucosylated teicoplanin scaffold, 7 (GtfD). The GtfC product was the 4-epi-vancosaminyl form of vancomycin. Remarkably, GtfD was able to utilize both an unnatural acceptor, 7, and an unnatural nucleotide sugar donor, UDP-4-epi-vancosamine, to synthesize a novel hybrid teicoplanin/vancomycin glycopeptide. These results establish the enzymatic activity of these four Gtfs, begin to probe substrate specificity, and illustrate how they can be utilized to make variant sugar forms of both the vancomycin and the teicoplanin class of glycopeptide antibiotics.

Actinomycetales↗

A randomized trial of surgical antimicrobial prophylaxis with and without vancomycin in organ transplant patients.

BACKGROUND: Gram-positive organisms, including vancomycin-resistant enterococci (VRE), have emerged as major pathogens on the organ transplant service at our institution. We hypothesized that our use of vancomycin as part of routine surgical prophylaxis increased the risk of VRE colonization and infection; conversely, there was concern that failure to use vancomycin prophylaxis would increase peri-operative morbidity due to gram-positive organisms. METHODS: Renal transplant recipients (n = 88) were randomized to receive either a) vancomycin/ceftriaxone or b) cefazolin; and pancreas transplants (n = 24) to receive either a) vancomycin/gentamicin or b) cefazolin/gentamicin. Stool samples or rectal swabs were obtained for culture for enterococci within 24 h of transplantation and weekly while hospitalized. RESULTS: Enterococci were isolated on stool culture from 38 (34%) of 102 patients at the time of transplantation; 4 (11%) of the isolates were VRE. The percentage of patients who subsequently acquired VRE was low (1-7% per wk) but remained constant during hospitalization. There was no association between new VRE detection and vancomycin use for either prophylactic or therapeutic purposes. Forty-four patients (39%) had a post-operative infection with 46% of these infections due to gram-positive organisms; rates were unaffected by prophylactic vancomycin use. Pancreas transplant patients who did not receive vancomycin prophylaxis had a significantly longer initial hospitalization (p = 0.03); however, differences were not statistically significant when total length of stay (LOS) within the first 90 d of transplantation was compared. CONCLUSIONS: Vancomycin surgical prophylaxis does not appear to have an effect on VRE colonization or infection, or on rates of infection with gram-positive bacteria. Elimination of vancomycin prophylaxis in renal transplant patients may be a reasonable part of an overall program to limit vancomycin usage, although as a single measure, its impact may be minimal. Vancomycin surgical prophylaxis may be of greater importance in pancreas transplants.

Adult↗

The in vitro elution characteristics of vancomycin and tobramycin from calcium sulfate beads.

The purpose of this study was to determine the elution characteristics of vancomycin and tobramycin when mixed with calcium sulfate to form antibiotic beads. Calcium sulfate was combined with vancomycin and tobramycin separately to form 2 types of antibiotic beads, which were packaged and labeled separately. The packaged calcium sulfate beads with vancomycin and tobramycin were then gas sterilized. The beads were placed in phosphate-buffered saline and kept at 36 degrees C for 6 weeks. Two separate series of assays were run simultaneously for both types of beads. In one assay, a bead containing vancomycin was placed in a fresh vial of phosphate buffered saline after each assay. The same was done with beads containing tobramycin. In the second series of assays, 9 vials of phosphate buffered saline each containing 1 vancomycin bead and 9 vials of phosphate buffered saline each containing 1 tobramycin bead was arranged. The phosphate-buffered saline was then assayed at predetermined times for both the vancomycin bead series and the tobramycin bead series. The amount of vancomycin and tobramycin assayed nearly equaled the calculated amount of antibiotic per bead measured before bead construction. Also, the elution of antibiotic from the calcium sulfate was complete within 72 hours. In conclusion, the construction and gas sterilization of calcium sulfate beads containing vancomycin and tobramycin does not destroy vancomycin and tobramycin. Also, the complete elution of available vancomycin and tobramycin in calcium sulfate beads occurs within 72 hours.

Anti-Bacterial Agents↗

The role of the novel Fem protein VanK in vancomycin resistance in Streptomyces coelicolor.

The non-pathogenic, non-glycopeptide-producing actinomycete Streptomyces coelicolor carries a cluster of seven genes (vanSRJKHAX) that confers inducible, high level resistance to vancomycin. The vanK gene has no counterpart in previously characterized vancomycin resistance clusters, yet vanK is required for vancomycin resistance in S. coelicolor. VanK belongs to the Fem family of enzymes, which add the branch amino acid(s) to the stem pentapeptide of peptidoglycan precursors. Upon exposure to vancomycin, the VanRS two-component system switches on expression of all seven van genes, and the VanHAX enzymes reprogram the cell wall such that precursors terminate D-Ala-D-lactate (Lac) rather than D-Ala-D-Ala, thus conferring resistance to vancomycin, which only binds D-Ala-D-Ala-containing precursors. Here we provide biochemical and genetic evidence that VanK is required for vancomycin resistance because the constitutively expressed FemX enzyme, encoded elsewhere on the chromosome, cannot recognize D-Lac-containing precursors as a substrate, whereas VanK can. Consistent with this view, D-Lac-containing precursors carrying the Gly branch are present in the wild type transiently exposed to vancomycin but are undetectable in a vanK mutant treated in the same way. Further, femX null mutants are viable in the presence of vancomycin but die in its absence. Because only VanK can recognize D-Lac-containing precursors, vancomycin-induced expression of VanHAX in a vanK mutant is lethal, and so vanK is required for vancomycin resistance.

Amino Acids↗

Effect of vancomycin on intestinal flora of patients who previously received antimicrobial therapy.

To evaluate the ecological disturbances of peroral vancomycin administration following cephalosporin administration, 20 healthy volunteers received cefuroxime axetil tablets (250 mg) perorally twice a day for 1 week, and 10 of these volunteers subsequently received vancomycin capsules (125 mg) perorally four times daily for 7 days. The concentration of vancomycin in feces after 1 week of vancomycin administration was high (mean +/- SD, 520 +/- 197 mg/kg), which correlated with the ecological disturbances noted in the vancomycin recipients. Vancomycin administration resulted in a rapid decrease in the numbers of intestinal Enterococcus faecium, Enterococcus faecalis, and Enterococcus durans (P < or = .05), while there was a significant emergence of motile enterococci with decreased susceptibility to vancomycin (Enterococcus gallinarum and Enterococcus casseliflavus; minimum inhibitory concentration, 4-16 mg/L) (P < or = .01). Because of vancomycin administration, there was also a significant overgrowth of vancomycin-resistant Pediococcus species and lactobacilli as well as of Klebsiella species, Citrobacter species, and Enterobacter species (P < or = .01). The numbers of bifidobacteria and Bacteroides species were significantly reduced during vancomycin administration. None of the enterococcal strains carried vanA or vanB. Twenty-two of the 27 motile enterococci carried the vanC-1 gene specific for E. gallinarum, whereas five strains carried the vanC-2(C-3) gene, thus implicating that they were E. casseliflavus or Enterococcus flavescens.

Administration, Oral↗