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PubMed1995

Protein binding and serum bactericidal activities of vancomycin and teicoplanin.

In a randomized crossover study, the protein binding and serum bactericidal activities (SBAs) of vancomycin and teicoplanin against Staphylococcus aureus and Streptococcus pyogenes were investigated in six healthy volunteers. Total concentrations in serum 1 h postadministration of vancomycin and teicoplanin were 25.5 +/- 2.7 and 10.8 +/- 8.9 mg/liter, respectively; mean free concentrations were 14.6 +/- 2.0 and 0.6 +/- 0.9 mg/liter, respectively. Protein binding for vancomycin was 36.9% +/- 2.87%, and that for teicoplanin was 97.4% +/- 2.6%. SBA determined in pooled human serum at 1 h against S. aureus ranged from 1:8 to 1:32 for both vancomycin and teicoplanin. Against S. pyogenes SBA at 1 h ranged from 1:16 to 1:128 for vancomycin and 1:256 to 1:2,048 for teicoplanin. In vitro kill curve studies showed that vancomycin is slowly bactericidal and that teicoplanin is bacteriostatic. Despite having less in vitro cidal activity against the study isolates and having low or unrecordable levels of free drug in serum, teicoplanin demonstrated a similar or better SBA than vancomycin. SBA was more closely related to the total drug level (r = 0.77 for S. aureus and r = 0.79 for S. pyogenes) than the free level of teicoplanin (r = 0.59 for S. aureus and r = 0.56 for S. pyogenes). The high level of protein binding of teicoplanin did not seem to impair its antibacterial activity as measured by its SBA.

Adult↗

PubMed1996

Pharmacokinetics of vancomycin in adult cystic fibrosis patients.

Although the depositions of many antibiotics are altered in cystic fibrosis patients, that of vancomycin has not been studied. To assess vancomycin pharmacokinetics, 10 adult cystic fibrosis patients were given a parenteral dose of vancomycin (15 mg/kg) during the first 72 h of hospitalization for acute bronchopulmonary exacerbation. Blood samples were obtained at 0, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 15, and 24 h. The mean (standard deviation) weight, measured creatinine clearance, and Taussig clinical score were 51 (13) kg, 130 (39) ml/min/1.73 m2, and 64 (13), respectively. Multicompartmental pharmacokinetic parameters were best described by a two-compartment model. The mean (standard deviation) volume of distribution, total body clearance, and terminal elimination rate constant were 0.58 (0.15) liter/kg, 91 (19) ml/min/1.73 m2, and 0.123 (0.05) h-1, respectively. These values were consistent with vancomycin pharmacokinetic parameters obtained in previous studies of healthy adult volunteers. Vancomycin dosages predicted by using a two-compartment Bayesian model were approximately 15 mg/kg every 8 to 12 h. There were poor correlations between clinical score or creatinine clearance and any pharmacokinetic parameter (r values of < 0.32). The coefficient of correlation between urine flow rate and total body clearance was 0.7 (P < 0.05). Adult cystic fibrosis patients exhibit a disposition of vancomycin similar to that exhibited by healthy adults, and thus cystic fibrosis does not alter vancomycin pharmacokinetics.

Adult↗

PubMed1996

In vivo activities of ceftriaxone and vancomycin against Borrelia spp. in the mouse brain and other sites.

Borrelia burgdorferi, the agent of Lyme disease, and B. turicatae, a neurotropic agent of relapsing fever, are susceptible to vancomycin in vitro, with an MIC of 0.5 microgram/ml. To determine the activity of vancomycin in vivo, particularly in the brain, we infected adult immunocompetent BALB/c and immunodeficient CB-17 scid mice with B. burgdorferi or B. turicatae. The mice were then treated with vancomycin, ceftriaxone as a positive control, or normal saline as a negative control. The effectiveness of treatment was assessed by cultures of blood and brain and other tissues. Ceftriaxone at a dose of 25 mg/kg of body weight administered every 12 h for 7 to 10 days eliminated cultivable B. burgdorferi or B. turicatae from all BALB/c or scid mice in the study. Vancomycin at 30 mg/kg administered every 12 h was effective in eliminating infection from immunodeficient mice if treatment was started within 3 days of the onset of infection. If treatment with vancomycin was delayed for 7 days or more, vancomycin failed to eradicate infection with B. burgdorferi or B. turicatae from immunodeficient mice. The failure of vancomycin in eradicating established infections in immunodeficient mice was associated with the persistence of viable spirochetes in the brain during antibiotic treatment.

Animals↗

PubMed1997

Activities of vancomycin and teicoplanin against penicillin-resistant pneumococci in vitro and in vivo and correlation to pharmacokinetic parameters in the mouse peritonitis model.

The activities of glycopeptides against pneumococci were studied in vitro and in vivo. The MICs of two glycopeptides, vancomycin and teicoplanin, in different media against 10 strains of pneumococci with different susceptibilities to penicillin were determined. The MICs of teicoplanin were four times lower than those of vancomycin in Mueller-Hinton media supplemented with 5% blood, but the MICs were similar in mouse and human sera supplemented with 5% blood. The serum protein binding levels in mouse and human sera were 90% for teicoplanin in both and 25 and 35%, respectively, for vancomycin. The MICs for vancomycin and teicoplanin were only correlated in human serum (P < 0.001). The single doses giving protection to 50% of the animals in the mouse peritonitis model after a lethal challenge of pneumococci, the ED50s, were similar for vancomycin and teicoplanin, between 0.1 and 1 mg/kg of body weight for all 10 strains. The log ED50s were significantly correlated only to the log MICs of teicoplanin determined for mouse serum with 5% blood (P = 0.01) and to the log MICs of vancomycin determined by the E test (P = 0.03). Among the pharmacokinetic parameters analyzed at the ED50s, the most constant parameter was the time for which the drug concentration exceeded the MIC (T(>MIC)) when each drug was considered separately; however, when both drugs were considered together, the maximum concentration of drug in serum (Cmax) varied the least. This indicates that both these parameters are of importance for predicting the effect of the drugs. We conclude that the effect of glycopeptides was not influenced by the penicillin resistance of the pneumococci, either in vitro or in vivo, and that the superior activity of teicoplanin over that of vancomycin in vitro was abolished in vivo, an effect which probably was due to the high serum protein binding of teicoplanin. Both the pharmacokinetic parameters T(>MIC) and Cmax are important predicting the effect of glycopeptides, but the pharmacodynamics of glycopeptides are still not completely elucidated.

Animals↗

PubMed1999

Pharmacodynamics of vancomycin for the treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis.

With the emergence of beta-lactam antibiotic resistance among strains of Streptococcus pneumoniae, vancomycin has assumed an important role in the treatment of bacterial meningitis. Using the rabbit meningitis model, we evaluated the pharmacokinetics and pharmacodynamics of vancomycin in this setting. Animals were given 80 mg/kg of body weight daily in two or four divided doses to determine the penetration and activity of vancomycin in cerebrospinal fluid (CSF); each regimen was administered with and without dexamethasone. Mean peak (2 h) concentrations in CSF that were four- to eightfold higher than the minimum bactericidal concentration (MBC; 0.5 microgram/ml) for the pathogen were adequate for bacterial clearance. In both groups concentrations in CSF remained higher than the MBC for greater than 80% of the respective dosing intervals, and the penetration of vancomycin into CSF was 20%. Mean concentrations in CSF at 24 to 36 h of therapy were lower than those achieved during the first 12 h, consistent with a decline in the level of antibiotic entry into CSF as inflammation wanes. Rates of bacterial clearance were similar for the two regimens, and for all animals cultures of CSF were sterile by 36 h. The coadministration of dexamethasone significantly reduced the penetration of vancomycin into CSF by 29% and significantly lowered the rate of bacterial clearance during the first 6 h in animals receiving 20-mg/kg doses of vancomycin. For animals receiving 40-mg/kg doses, therapeutic peak concentrations in CSF were obtained even with steroid use, suggesting that the effect of steroids may be circumvented by the use of larger daily doses of vancomycin.

Animals↗

PubMed2004

Impact of high-inoculum Staphylococcus aureus on the activities of nafcillin, vancomycin, linezolid, and daptomycin, alone and in combination with gentamicin, in an in vitro pharmacodynamic model.

We evaluated the impact of high (9.5 log10 CFU/g) and moderate (5.5 log10 CFU/g) inocula of methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) on the activities of nafcillin, linezolid, vancomycin, and daptomycin, alone and in combination with gentamicin in an in vitro pharmacodynamic model with simulated endocardial vegetations over 72 h. Human therapeutic dosing regimens for nafcillin, daptomycin, vancomycin, linezolid, and gentamicin were simulated. At a moderate inoculum, nafcillin (MSSA only), vancomycin, and daptomycin demonstrated equivalent and significant (P < 0.01) bactericidal (99.9% kill) activities (decreases of 3.34 +/- 1.1, 3.28 +/- 0.4, and 3.34 +/- 0.8 log10 CFU/g, respectively). Bactericidal activity was demonstrated at 4 h for nafcillin and daptomycin and at 32 h for vancomycin. Linezolid demonstrated bacteriostatic activity over the course of the study period. At a high inoculum, daptomycin exhibited bactericidal activity against both MSSA and MRSA by 24 h (decrease of 5.51 to 6.31 +/- 0.10 log10 CFU/g). Nafcillin (versus MSSA), vancomycin, and linezolid (MSSA and MRSA) did not achieve bactericidal activity throughout the 72-h experiment. The addition of gentamicin increased the rate of 99.9% kill to 8 h for daptomycin (P < 0.01) and 48 h for nafcillin (MSSA only) (P = 0.01). The addition of gentamicin did not improve the activity of vancomycin or linezolid for either isolate for the 72-h period. Overall, high-inoculum Staphylococcus aureus had a significant impact on the activities of nafcillin and vancomycin. In contrast, daptomycin was affected minimally and linezolid was not affected by inoculum.

Acetamides↗

PubMed2005

Linezolid versus vancomycin in treatment of complicated skin and soft tissue infections.

Skin and soft tissue infections (SSTIs) are a common cause of morbidity in both the community and the hospital. An SSTI is classified as complicated if the infection has spread to the deeper soft tissues, if surgical intervention is necessary, or if the patient has a comorbid condition hindering treatment response (e.g., diabetes mellitus or human immunodeficiency virus). The purpose of this study was to compare linezolid to vancomycin in the treatment of suspected or proven methicillin-resistant gram-positive complicated SSTIs (CSSTIs) requiring hospitalization. This was a randomized, open-label, comparator-controlled, multicenter, multinational study that included patients with suspected or proven methicillin-resistant Staphylococcus aureus (MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or burns (<10% of total body surface area). Patients were randomized (1:1) to receive linezolid (600 mg) every 12 h either intravenously (i.v.) or orally or vancomycin (1 g) every 12 h i.v. In the intent-to-treat population, 92.2% and 88.5% of patients treated with linezolid and vancomycin, respectively, were clinically cured at the test-of-cure (TOC) visit (P=0.057). Linezolid outcomes (124/140 patients or 88.6%) were superior to vancomycin outcomes (97/145 patients or 66.9%) at the TOC visit for patients with MRSA infections (P<0.001). Drug-related adverse events were reported in similar numbers in both the linezolid and the vancomycin arms of the trial. The results of this study demonstrate that linezolid therapy is well tolerated, equivalent to vancomycin in treating CSSTIs, and superior to vancomycin in the treatment of CSSTIs due to MRSA.

Acetamides↗

PubMed2005

Efficacy of Telavancin in a rabbit model of aortic valve endocarditis due to methicillin-resistant Staphylococcus aureus or vancomycin-intermediate Staphylococcus aureus.

The activities of telavancin and vancomycin were compared in vitro and in the rabbit model of aortic valve endocarditis against a methicillin-resistant Staphylococcus aureus strain, COL, and a vancomycin-intermediate S. aureus (VISA) strain, HIP 5836. Telavancin was bactericidal in time-kill studies at a concentration of 5 microg/ml against both COL and HIP5836. Vancomycin was bacteriostatic at 5 microg/ml and bactericidal at 10 microg/ml against COL and was bacteriostatic at 10 microg/ml against VISA strain HIP 5836. Compared to untreated controls, a twice-daily regimen of 30 mg/kg of telavancin reduced mean aortic valve vegetation titers of the COL strain by 4.7 log(10) CFU/g after 4 days of therapy and sterilized 6/11 vegetations compared to 3.4 log(10) CFU/g with 3/10 vegetations sterilized for a regimen of twice-daily vancomycin, 30 mg/kg; these differences were not statistically significant. Telavancin was significantly more effective than vancomycin in the VISA model, producing a 5.5 log(10) CFU/g reduction versus no reduction in CFU with vancomycin. In experiments comparing 2-day regimens of telavancin at 30 mg/kg and 50 mg/kg twice daily, organisms were rapidly eliminated from vegetations, but the effect was not different between the two doses. These results suggest that telavancin may be an effective treatment for endocarditis and other serious staphylococcal infections accompanied by bacteremia, including infections caused by staphylococci not susceptible to vancomycin.

Aminoglycosides↗

PubMed2006

Impaired target site penetration of vancomycin in diabetic patients following cardiac surgery.

Soft tissue infections constitute a serious complication following surgery in diabetic patients and frequently require the administration of vancomycin. However, despite antibiotic treatment, mortality of patients with postoperative infections remains high and might be related to an impaired penetration of anti-infective agents to target tissues. Therefore, the present study was designed to measure vancomycin tissue concentrations in six diabetic and six nondiabetic patients after cardiac surgery. Vancomycin was administered as a continuous intravenous infusion at an infusion rate of 80 to 120 mg/h. Vancomycin concentrations in soft tissues and plasma were measured in all patients during steady state as "therapeutic window" concentrations in plasma by microdialysis on day 8+/-4 after initiation of vancomycin treatment. Vancomycin tissue concentrations in diabetic patients were significantly lower than in nondiabetics (3.7 mg/liter versus 11.9 mg/liter; P=0.002). The median vancomycintissue/vancomycinplasma concentration ratio was 0.1 in diabetic patients and 0.3 in nondiabetics (P=0.002). Our study demonstrated that vancomycin penetration into target tissues is substantially impaired in diabetic patients versus nondiabetics. Insufficient tissue concentrations could therefore possibly contribute to failure of antibiotic treatment and the development of antimicrobial resistance in diabetic patients.

Aged↗

PubMed2004

Persistence of vancomycin-resistant enterococci in New Zealand broilers after discontinuation of avoparcin use.

Large amounts of tylosin, zinc-bacitracin, and avilamycin are currently used as prophylactics in New Zealand broiler production. Avoparcin was also used from 1977 to 2000. A total of 382 enterococci were isolated from 213 fecal samples (147 individual poultry farms) using enrichment broths plated on m-Enterococcus agar lacking antimicrobials. These isolates were then examined to determine the prevalence of antimicrobial resistance. Of the 382 isolates, 5.8% (22 isolates) were resistant to vancomycin, and 64.7% were resistant to erythromycin. The bacitracin MIC was > or =256 microg/ml for 98.7% of isolates, and the avilamycin MIC was > or =8 microg/ml for 14.9% of isolates. No resistance to ampicillin or gentamicin was detected. Of the 22 vancomycin-resistant enterococci (VRE) isolates, 18 (81.8%) were Enterococcus faecalis, 3 were Enterococcus faecium, and 1 was Enterococcus durans. However, when the 213 fecal enrichment broths were plated on m-Enterococcus agar containing vancomycin, 86 VRE were recovered; 66% of these isolates were E. faecium and the remainder were E. faecalis. Vancomycin-resistant E. faecium isolates were found to have heterogenous pulsed-field gel electrophoresis (PFGE) patterns of SmaI-digested DNA, whereas the PFGE patterns of vancomycin-resistant E. faecalis isolates were identical or closely related, suggesting that this VRE clone is widespread throughout New Zealand. These data demonstrate that vancomycin-resistant E. faecalis persists in the absence and presence of vancomycin-selective pressure, thus explaining the dominance of this VRE clone even in the absence of avoparcin.

Animal Husbandry↗

PubMed1990

Resistance to vancomycin and teicoplanin: an emerging clinical problem.

Vancomycin and teicoplanin are glycopeptides active against a wide range of gram-positive bacteria. For 30 years following the discovery of vancomycin in 1956, vancomycin resistance was not detected among normally susceptible bacteria recovered from human specimens. Since 1986, however, bacteria resistant to vancomycin or teicoplanin or both have been described. Strains of the genera Leuconostoc, Lactobacillus, Pediococcus, and Erysipelothrix seem inherently resistant to glycopeptides. Species and strains of enterococci and coagulase-negative staphylococci appear to have acquired or developed resistance. There are at least two categories of glycopeptide resistance among enterococci, characterized by either high-level resistance to vancomycin (MIC, greater than or equal to 64 mg/liter) and teicoplanin (MIC, greater than or equal to 8 mg/liter) or lower-level vancomycin resistance (MIC, 32 to 64 mg/liter) and teicoplanin susceptibility (MIC, less than or equal to 1 mg/liter). The two categories appear to have similar resistance mechanisms, although genetic and biochemical studies indicate that they have arisen independently. Among coagulase-negative staphylococci, strains for which vancomycin MICs are up to 20 mg/liter or teicoplanin MICs are 16 to 32 mg/liter have been reported, but cross-resistance between these glycopeptides varies. The selective advantage accorded to glycopeptide-resistant bacteria and the observation that high-level resistance in enterococci is transferable suggest that such resistance may be expected to increase in incidence. Clinicians and microbiologists need to be aware of this emerging problem.

Animals↗

PubMed1981

Neisseria gonorrhoeae strains inhibited by vancomycin in selective media and correlation with auxotype.

Strains of Neisseria gonorrhoeae that failed to grow on Thayer-Martin (T-M) and Martin-Lewis (M-L) media accounted for 2.0% of isolates at the University of Colorado Hospital and its Venereal Disease Clinic. A total of 31 inhibited and 31 control strains were compared by agar dilution testing for their susceptibilities to 13 antimicrobial agents used for treatment or in selective media. All 62 isolates were resistant to lincomycin, colistin, nystatin, amphotericin B, trimethoprim lactate, polymyxin B, and anisomycin. Vancomycin was the inhibitory antibiotic for N. gonorrhoeae in both T-M and M-L media. The vancomycin-inhibited strains were also significantly more sensitive to penicillin and ampicillin than were the control strains (P less than 0.001). The presence of the other antibiotics in selective media did not affect the minimum inhibitory concentrations of vancomycin for gonococci. All 31 inhibited strains were sensitive to 8.0 micrograms of vancomycin per ml, and 26 of these were sensitive to 2.0 microgram/ml. Decreasing the size of inoculum of gonococci results in greater inhibition by any given concentration of vancomycin. The vancomycin-sensitive strains contained significantly more arginine- hypoxanthine-, and uracil-requiring auxotypes (28 out of 31) than did the control strains (9 out of 31). As with T-M medium, some strains of gonococci will be missed when M-L medium with 4.0 micrograms of vancomycin per ml is the only medium used for the diagnosis of gonorrhea. This may be of particular importance in the confirmation of disseminated infection with Arg- Hyx- Ura- auxotypes of N. gonorrhoeae when cultures of blood, joint fluid, or skin lesions are negative.

Anti-Bacterial Agents↗

PubMed1982

Comparison of vancomycin and penicillin for viral isolation.

Penicillin was compared with vancomycin for use in diagnostic virology to inhibit bacterial contamination of clinical specimens. Vancomycin when combined with gentamicin and amphotericin B was found to be more effective in lowering the overall contamination rate than when penicillin was combined with these antibiotics (penicillin group, 14.9% versus vancomycin group, 6.2%; P less than 0.001). Of the contaminants grown in the presence of penicillin, 72% were gram-positive cocci, primarily coagulase-negative staphylococci. The number of gram-positive contaminants in the presence of vancomycin was reduced to zero. There was little difference in the rates of gram-negative rod or fungus contamination. The viral isolation rate in noncontaminated specimens was similar with either penicillin or vancomycin, but was reduced when specimens became contaminated. The time for virus detection and the morphology of cytopathology were similar in penicillin- and vancomycin-treated specimens. Vancomycin is an effective alternative to penicillin in reducing the growth of contaminants in viral isolation specimens.

Amphotericin B↗

PubMed1993

Epidemiologic analysis and genotypic characterization of a nosocomial outbreak of vancomycin-resistant enterococci.

We are reporting on a nosocomial outbreak of 213 cases of vancomycin-resistant enterococcus infection involving 2,812 enterococcal isolates from patients over a period of 36 months. In 1990, the Enterococcus faecium vancomycin susceptibility rate was found to be 85.7% (36 of 42 cases), and an incidence of 10.9% (42 of 383) was noted. The 1991 data showed E. faecium with a vancomycin susceptibility rate of 61.8% (110 of 178) and an incidence of 26.0% (178 of 684). Subsequently, in 1992, the incidence of E. faecium increased to 34.0% (599 of 1,745), with a decreased vancomycin susceptibility rate of 25.8% (155 of 599). The E. faecalis vancomycin susceptibility rate remained near 97% (1,768 of 1,823) over the 36-month period. Of 115 vancomycin-resistant enterococcus (VRE) clinical isolates identified by the MicroScan MIC Combo-6 panels (Baxter Healthcare, Sacramento, Calif.), the agar dilution method indicated the resistance rate to be 92.3% (106 of 115) (high level), 3.5% (4 of 115) midlevel, and 3.5% (4 of 115) (low level). Genotypic characterization of 32 different VRE isolates by field-inversion gel electrophoresis demonstrated 19 dissimilar restriction endonuclease patterns, with 9 patterns associated with VRE quinolone resistance. Statistical analysis of case-control data for 32 patients with VRE infections indicated a positive association with intrabdominal surgical procedures (odds ratio, 24.12), multidrug therapy (odds ratio, 37.80), preexposure to vancomycin (odds ratio, 20.21), and death (odds ratio, 17.50).

Case-Control Studies↗

PubMed1996

Factors influencing the vitek gram-positive susceptibility system's detection of vanB-encoded vancomycin resistance among enterococci.

Studies were conducted to identify factors contributing to the inability of the Vitek Gram-Positive Susceptibility system (GPS; bioMerieux, Vitek, Inc., Hazelwood, Mo.) to reliably detect vanB-mediated vancomycin resistance among enterococci. To some extent the accuracy of the GPS depended on a particular strain's level of resistance, as all isolates for which vancomycin MICs were > or = 128 mu g/ml were readily detected but detection of resistance expressed by several strains for which MICs were < or = 64 mu g/ml was sporadic. Factors besides the level of resistance were studied in two vanB strains. For one strain (Enterococcus faecium U8304), the ability of GPS to detect resistance was accurate and consistent, while for the other (Enterococcus faecalis V583), GPS results were inconsistent and unreliable. Using these isolates, we established that growth medium had the most notable effect on the detection of resistance. In the absence of vancomycin, Vitek GPS broth supported growth comparable to that obtained with brain heart infusion broth for both E. faecium U8304 and E. faecalis V583. However, in the presence of vancomycin the growth patterns changed dramatically so that neither VanB strain grew well in Vitek broth, and growth of V583 was barely detectable after 8 h of incubation. In contrast, good growth of both strains was observed in brain heart infusion broth supplemented with vancomycin. Additionally, the same medium effect was observed with other inducibly resistant VanB strains. In conclusion, although Vitek broth can support good enterococcal growth, this medium does not sufficiently support expression of vancomycin resistance by certain strains to allow them to be detected by the Vitek automated system. Furthermore, this observation establishes that the type of growth medium used can substantially influence the expression of vancomycin resistance and indicates that medium-based strategies should be explored for the enhancement of resistance detection among commercial systems.

Anti-Bacterial Agents↗

PubMed2004

Comparison of the Roche LightCycler vanA/vanB detection assay and culture for detection of vancomycin-resistant enterococci from perianal swabs.

We compared the performance characteristics of a real-time PCR method, the LightCycler vanA/vanB detection assay (Roche Diagnostics Corporation, Indianapolis, Ind.) to that of Enterococcosel agar (BBL, Sparks, Md.) for direct detection of vancomycin-resistant enterococci (VRE) from 894 perianal stool swabs. For 421 of 894 swabs, the result for LightCycler PCR was compared to an Enterococcosel plate containing vancomycin at 6 microg/ml; for the remaining 473 swabs, the result for LightCycler PCR was compared to an Enterococcosel plate containing 8 microg/ml vancomycin. The LightCycler method produced considerably more positive results than either the Enterococcosel plate containing vancomycin at 6 microg/ml (n = 25 versus n = 11; sensitivity, 100%; specificity, 97%; positive predictive value [PPV], 42%; negative predictive value [NPV], 100%) or the Enterococcosel plate containing vancomycin at 8 microg/ml (n = 31 versus n = 10; sensitivity, 100%; specificity, 95%; PPV, 32%; NPV, 100%). When possible, additional testing, including culture, LightCycler PCR, and/or a conventional PCR method (PCR-restriction fragment length polymorphism assay), were performed on either the original specimens or original cultures or subsequent specimens for cases in which the original specimen was positive by LightCycler PCR but the Enterococcosel plate was negative. This additional testing demonstrated positive results for 7 of 14 (50%) evaluable discordant specimens which initially tested as LightCycler PCR positive but culture negative using the Enterococcosel plate containing vancomycin at 6 microg/ml and 12 of 17 (71%) evaluable discordant specimens which initially tested as LightCycler positive but culture negative using the Enterococcosel plate containing vancomycin at (8 microg/ml). These results demonstrate that the LightCycler VRE detection assay is considerably more sensitive than the standard culture method for detecting VRE directly from perianal swab specimens. The LightCycler assay also provides results much faster than culture (approximately 3.5 versus > or =72 h). The use of this test could have important implications for the effective control and prevention of nosocomial outbreaks of VRE.

Anal Canal↗

PubMed1983

Relapse of antibiotic associated colitis: endogenous persistence of Clostridium difficile during vancomycin therapy.

This study reports 24 patients with antibiotic associated colitis due to Clostridium difficile. Fifteen patients were treated with vancomycin due to the severity of the colitis and in eight of these a clinical relapse of the colitis occurred after vancomycin therapy was stopped. Bacteriological investigations of these patients indicated that C difficile was able to persist in stool samples during vancomycin therapy in the absence of detectable cytotoxin. This was in contrast with the seven patients successfully treated with vancomycin without relapse, and those not treated with vancomycin where both stool cultures and cytotoxin assays became negative. These results suggest that patients being treated with vancomycin for antibiotic associated colitis due to C difficile should have stool cultures done during and after treatment. Persistence of the organism in the absence of detectable cytotoxin may identify those patients who relapse and lead to either recommencement of vancomycin or alternative therapeutic approaches.

Adolescent↗

PubMedDate not supplied

Modified high-performance liquid chromatography technique for detection of vancomycin in human vitreous.

PURPOSE: To standardize the technique and methodology for estimating the level of vancomycin in human vitreous using a modified high-performance liquid chromatographic method. METHODS: Sample preparation involved spiking the vitreous with known quantities of the drug followed by a brief treatment with 30% trichloroacetic acid. Samples were analyzed on a C18 reverse-phase column using a mobile phase of 50 mM phosphate buffer (pH 4.0) and 10% acetonitrile. RESULTS: Vancomycin was detected at 198 nm. It showed a retention time of 2.2 min in the vitreous. A linear increase in the area under the peak corresponding to the drug was observed with increase in concentration of vancomycin in the vitreous. The method was applied to detect the vancomycin levels in vitreous of 5 patients with exogenous endophthalmitis, 24-48 h after intravitreal injection of vancomycin 1 mg/0.1 ml. The mean concentration of vancomycin in these samples was 120.022 +/- 59.87 microg/ml (43.859-179.09 microg/ml). The present technique allowed a quantification limit of 1 microg/ml. CONCLUSION: This technique is suitable to estimate vancomycin levels in human vitreous in a variety of clinical and experimental studies. It has the added advantages of being less expensive, simple and rapid.

Anti-Bacterial Agents↗