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PubMed1994

Serum vancomycin concentrations: reappraisal of their clinical value.

Although monitoring serum vancomycin concentrations in clinical practice is commonplace, the data supporting this practice are meager. The rationale for monitoring these concentrations is to improve the effectiveness and/or reduce the toxicity of the drug. However, there are no data to suggest that monitoring serum vancomycin concentrations improves the effectiveness of therapy. In addition, despite many case reports of vancomycin-associated nephrotoxicity and ototoxicity, it is unclear whether this agent truly causes such conditions. Moreover, there is no evidence that adherence to specific ranges of vancomycin concentrations will preclude these events. Finally, vancomycin pharmacokinetics are sufficiently predictable that adequate serum drug concentrations can be obtained with dosing methods that take into account the patient's age, weight, and renal function. Safe and effective vancomycin dosage regimens can be constructed with these empirical dosing methods, whereas monitoring vancomycin levels increases the cost of therapy without improving the safety or efficacy of treatment.

Bacterial Infections↗

PubMed1994

The appropriateness of initial vancomycin dosing.

BACKGROUND: Vancomycin use has markedly increased over the past several years because of an increased incidence of resistant organisms, particularly methicillin-resistant Staphylococcus aureus. Despite the availability of dosing nomograms and the use of peak and trough levels, vancomycin dosing has remained problematic. METHODS: All intravenous vancomycin orders over a 3-month period in a community and teaching hospital were screened for appropriateness of initial dosing based on available dosing nomograms. RESULTS: Of the 48 patients who received intravenous vancomycin, only 19 (39.6%) were given initial doses that achieved the desired serum concentration. There were no significant differences in the appropriateness of initial dosing between family medicine residents, attending physicians, and private staff physicians. Older patients in our study were at higher risk for overdosing, whereas younger patients were more likely to be underdosed. In this study, nomogram use could have yielded correct initial dosages in 40 of the 48 patients (83.3%). CONCLUSIONS: Our study indicates a high percentage of inappropriate initial vancomycin dosing in a community and teaching hospital. The investigators believe inappropriate initial vancomycin dosing is common and may result in unnecessary expense, increased risk of therapeutic failures, and greater potential for adverse drug reactions. Increased use of vancomycin dosing nomograms could improve the rate of correct initial dosages.

Adult↗

PubMed1995

Vancomycin levels after intravitreal injection. Effects of inflammation and surgery.

OBJECTIVE: Vancomycin hydrochloride for intraocular injection is the drug of choice for the treatment of suspected gram-positive endophthalmitis. To study its intraocular pharmacokinetics, we injected vancomycin into the vitreous cavity of phakic, aphakic, and aphakic-vitrectomized rabbit eyes and determined its rate of clearance. Inflamed eyes were compared to control eyes in each group. METHODS: Three groups of eyes were prepared. The eyes in Group 1 were phakic, the eyes in Group 2 had the lens removed, and the eyes in Group 3 had both the lens and central vitreous removed. Each group was subdivided into a control group and a group made inflamed by injection of heat-killed Staphylococcus epidermidis. Vancomycin hydrochloride 1 mg in 0.1 cc of diluent was injected into the midvitreous cavity and samples obtained at 2 or 3, 8, 24, and 48 hours after injection. Vancomycin concentrations were measured and clearance rates were calculated for each of the groups. RESULTS: Vancomycin was cleared substantially faster from aphakic-vitrectomized eyes (half-life 9.0 hours) and aphakic eyes (half-life 8.9 hours) than phakic eyes (half-life 25.1 hours). Inflammation increased the rate of elimination of vancomycin only in the aphakic group. CONCLUSIONS: Clearance of vancomycin from the phakic eye is prolonged compared to that of beta-lactam antibiotics, an important pharmacokinetic advantage in treating endophthalmitis. Its clearance from aphakic-vitrectomized eyes is dramatically faster than from phakic eyes and is similar to that of other antimicrobial agents.

Animals↗

PubMed1996

Pharmacokinetics of vancomycin in patients with severely impaired renal function.

The pharmacokinetics of 1 g dose of intravenous vancomycin was studied in 8 patients with severe renal failure. Serum vancomycin levels were determined by fluorescence polarization immunoassay. After single dose of vancomycin peak concentrations ranged from 37.8 microg.ml-1 to 109.3 microg.ml-1 (mean 64.9 +/- 21.7 microg.ml-1). Vancomycin trough concentration 168h after administration of the antibiotic ranged from 2.23 microg.ml-1 to 11.42 microg.ml-1 (mean 6.55 +/- 2.8 microg.ml-1). The data were analyzed using a PCNONLINE computer program, and in all patients a triexponential model described how concentrations decreased in time. Three-compartment parameters obtained from the 8 patients were t1/2 alpha = 0.312 +/- 0.242 h, t1/2 beta 6.012 +/- 5.36 h, and t1/2 gamma = 131.0 +/- 46.7 h. Vd = 0.158 +/- 0.121 1.kg-1, Vdss = 0.920 +/- 0.248 1.kg-1 and total Cl = 0.10 +/- 0.049 1.h-1 per kg of weight. Between 1.5% and 21.2% of the administered vancomycin dose was eliminated during hemodialysis. The dialysis clearance of vancomycin ranged from 50.6 ml.min-1 to 76.8 ml.min-1 (average: 62.4 +/- 10.4 ml.min-1. However, after dialysis plasma concentrations returned to pre-dialysis values. In accordance to our kinetic study 1 g of vancomycin given every 7 days is adequate treatment for methicillin-resistant Staphylococcus aureus infections in patients with severe renal failure whose creatinine clearance is lower than 10 ml.min-1.

Adult↗

PubMed1997

[Evaluation of reduced vancomycin susceptibility of MRSA strain Mu50 with various conditions of antibiotic susceptibility tests].

We evaluated a clinical strain of methicillin-resistant Staphylococcus aureus (MRSA), Mu50, for vancomycin susceptibility. Mu50 was isolated from a patient with infection of a surgical incision site which resisted vancomycin therapy. Mu50 showed a decrease in susceptibility to vancomycin, but this strain did not carry vanA or vanB or vanC genes as judged from PCR amplification. MICs of vancomycin against Mu50 and vancomycin-susceptible S. aureus FDA209P, S. aureus ATCC-29213, and MRSA H-1 were 8, 1, 1, and 1 microgram/ml, respectively by agar dilution and macro-broth dilution methods according to NCCLS. MIC values with agar dilution method using MHA + 20% horse serum, HIA, and BHIA agreed with the MIC values with micro- and macro-broth dilution method. Population analysis revealed that vancomycin concentration required for inhibition of ca. 10(7) cells of Mu50, S. aureus FDA209P, S. aureus ATCC29213, and MRSA H-1 were 36, 2, 2, and 2 micrograms/ml, respectively. These results showed that the activity of vancomycin against Mu50 was at least 8-fold decreased compared to that against S. aureus FDA209P, S. aureus ATCC29213, and MRSA H-1.

Anti-Bacterial Agents↗

PubMed2006

Vancomycin tolerance, a potential mechanism for refractory gram-positive bacteremia observational study in patients with cancer.

BACKGROUND: The clinical significance of infections caused by vancomycin-tolerant (Vt) gram-positive organisms in patients with cancer remains unclear. METHODS: Twenty-five patients with nonenterococcal gram-positive bloodstream infection, which was refractory to vancomycin therapy, were identified by reviewing the Infectious Diseases consultation database at the tertiary care cancer center. Among these, 8 patients in whom vancomycin-tolerance was documented are described. Antibiotic tolerance was defined as a > 32 times increase in minimum bactericidal concentration compared with minimum inhibitory concentration. RESULTS: Eight patients with persistent fever and bacteremia of > 72 hours' duration after the initiation of vancomycin therapy were treated. The median age of these patients, which included 3 men and 5 women, was 44 years +/- 11 years. Solid tumors were more common (6 patients) and 2 patients had acute leukemia. Six patients (75%) were neutropenic (absolute neutrophil count < 500/mm3), including 2 breast cancer patients who had undergone autologous stem cell transplantation. The causative organisms were Staphylococcus aureus (n = 3 patients), group G streptococci (n = 2 patients), and Staphylococcus epidermidis, Streptococcus mitis, and Streptococcus sanguis (1 patient each). All isolates demonstrated a minimum bactericidal concentration for vancomycin that was at least 32 times greater than the minimum inhibitory concentration. Rapid defervescence (< or = 24 h) and resolution of bacteremia occurred with the addition of gentamicin (4 patients) or gentamicin plus rifampin (4 patients). None of these infections recurred after discontinuation of therapy. CONCLUSIONS: Lack of clinical and/or microbiologic response to vancomycin should raise the suspicion of possible infection due to Vt gram-positive bacteria, and alternative bactericidal therapy should be instituted early, especially in patients with underlying immune suppression.

Adult↗

PubMed2001

Vancomycin resistance among strains of Staphylococcus epidermidis: effects on adherence to silicone.

Nosocomial device-related infections with Gram-positive cocci and their resistance to vancomycin are of increasing occurrence. We examined clinical isolates of relatively avirulent coagulase-negative staphylococci for their resistance to vancomycin and for their capabilities to adhere in vitro to medical grade silicone. Vancomycin resistance was found in 9 of 20 isolates, but there was no correlation between adherence capacity to silicone in the absence of vancomycin and vancomycin resistance for a given strain. Vancomycin in the medium, adsorbed to the surface of medical grade silicone or adsorbed on nongrowing cells, reduced adherence of representative Staphylococcus epidermidis to medical grade silicone.

Adsorption↗

PubMed2000

The Internet: a practical example of the use of new technology in the assessment of vancomycin use in pediatrics. The Pediatric Prevention Network.

BACKGROUND: The rapid emergence of both new infections and new technologies has revolutionized health care during the past 50 years. Increased use of the Internet has enabled health care professionals to educate, interact, and collaborate throughout the world in ways never before possible. Increased use of vancomycin has been associated with the emergence of organisms with decreased susceptibility to vancomycin, such as Enterococcus and staphylococcal species. The purpose of this article is to describe our experience using Internet technology to assess vancomycin use at children's hospitals in the United States. METHODS: A Web-based evaluation was developed and distributed on the Internet to 57 Pediatric Prevention Network hospitals. The evaluation was structured to collect summary statistics on vancomycin use and admissions data by service for 1997 and 1998. RESULTS: Twenty-four hospitals were able to provide archived vancomycin use and patient admissions data; completed evaluations were returned from 15 hospitals (62.5% response rate). Personnel at 6 (40%) hospitals completed the evaluation directly on the Internet. CONCLUSIONS: In our study, Internet technology facilitated a more efficient evaluation of vancomycin use, but fewer than half of the personnel at Pediatric Prevention Network hospitals completed the evaluation directly on the Internet. It is unclear whether personnel at these hospitals were limited in Internet access, support, or understanding. Efforts should be directed to educate health care personnel on the advantages of the Internet. Furthermore, many of the pharmacy databases used in our assessment were not standardized across hospitals nor systematically validated. Understanding that limitations still remain-within the source of the data studied, the health care system sampled, and the Internet tools available-is essential because the Internet offers health care professionals today a tool both to protect patients and to improve quality throughout the world.

Attitude to Computers↗

PubMed2000

Association between resistance to vancomycin and death in cases of Enterococcus faecium bacteremia.

We conducted a retrospective cohort study to determine the association between resistance to vancomycin and mortality among hospitalized patients with Enterococcus faecium bacteremia. We compared outcomes for patients infected with vancomycin-resistant versus vancomycin-susceptible E. faecium among 69 patients with bacteremia defined according to the National Nosocomial Infections Surveillance system. The univariate odds ratio (OR) for death associated with vancomycin resistance was 2.1 (P=.172). After controlling for severity of illness, we found that vancomycin resistance was not associated with mortality (OR, 1.74; 95% confidence interval, 0.5-6.12; P=.39). Vancomycin resistance does not independently increase mortality among patients with E. faecium bacteremia.

Adolescent↗

PubMed2002

Evidence for a continuum of decreased vancomycin susceptibility in unselected Staphylococcus aureus clinical isolates.

Some Staphylococcus aureus isolates have glycopeptide minimal inhibitory concentrations (MICs) in the susceptible range but have subpopulations that grow on >or=4 microg/mL vancomycin. Clinical laboratory methods for determining susceptibility have proven to be inadequate for detecting these strains. Among methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) clinical isolates, 149 (66.2%) of 225 and 17 (56.6%) of 30, respectively, grew on brain-heart infusion (BHI) medium containing 2 microg/mL vancomycin; 17 (7.5%) of the MRSA and 2 (6.6%) of the MSSA isolates grew on BHI screening plates containing 4 microg/mL vancomycin. One isolate grew on plates containing 6 microg/mL vancomycin. This isolate escaped detection by routine testing but had a vancomycin MIC of 6 microg/mL when tested in BHI medium. This isolate also had decreased Triton X-100-induced autolysis and killing when incubated in broth media containing vancomycin, properties accorded to glycopeptide-intermediate S. aureus isolates. These observations suggest that glycopeptide-intermediate-like S. aureus isolates are circulating undetected and that a continuum of decreased susceptibility exists in unselected isolates.

Adult↗

PubMed2004

Accessory gene regulator group II polymorphism in methicillin-resistant Staphylococcus aureus is predictive of failure of vancomycin therapy.

We studied methicillin-resistant Staphylococcus aureus (MRSA) isolates to determine if the group II polymorphism at the accessory gene regulator (agr) locus demonstrated any relationship with the clinical efficacy of vancomycin. One hundred twenty-two MRSA isolates from 87 patients treated with vancomycin were evaluated. Forty-five of 87 patients had no clinical or bacteriological response to vancomycin. Among the 36 clinically evaluable patients with the agr group II polymorphism, 31 had an infection that failed to respond to vancomycin, whereas only 5 had an infection that responded successfully to vancomycin. This finding is of interest in light of our previous findings that glycopeptide-intermediately resistant S. aureus (GISA) and hetero-GISA clinical isolates in the United States and Japan are enriched for the agr group II polymorphism, and it suggests a possible intrinsic survival advantage of some S. aureus clones with this genetic marker under vancomycin selective pressure.

Adult↗

PubMed1999

Expression and detection of hetero-vancomycin resistance in Staphylococcus aureus.

Isolates of Staphylococcus aureus resistant to vancomycin have been reported but appear to be extremely rare. However, isolates displaying hetero-resistance to vancomycin (hVRSA) are reportedly common in parts of Japan (9.3% of MRSA isolated from a group of university hospitals). We have investigated the reliability of the proposed method for detection of hetero-resistant isolates and the ability of clinical S. aureus isolates to express vancomycin resistance. The original method for identification of hVRSA was found to have poor reproducibility and may select for, rather than detect, vancomycin resistance. There appears to be a spectrum of heterogeneity in the expression of resistance to vancomycin among S. aureus. Until there is a clearer understanding of the mechanism and control of vancomycin resistance in S. aureus, and reliable tests are devised, the clinical relevance of different degrees of hetero-resistance cannot be assessed.

Anti-Bacterial Agents↗

PubMed2001

Development of vancomycin and lysostaphin resistance in a methicillin-resistant Staphylococcus aureus isolate.

Glycopeptide resistance in Staphylococcus aureus is poorly understood. The diversity of change documented in cell walls of clinical glycopeptide-intermediate S. aureus (GISA) isolates is evidence that a single genetic or biochemical change cannot account for resistance in all isolates described to date. Therefore, identification of new GISA clinical isolates provides an opportunity to gain insight into the range of adaptive strategies employed by staphylococci to survive in the presence of glycopeptides. In April 1999, a GISA isolate was obtained from the blood of a 63-year-old dialysis patient in Illinois. This isolate was one of six clonally identical MRSA isolates (A-F) serially obtained from the blood of this patient who was receiving vancomycin therapy. All isolates were resistant to oxacillin (MIC > 256 mg/L). The initial isolate had an MIC of vancomycin of 1 mg/L. However, the presence of a subpopulation that could grow in the presence of 5 mg/L of vancomycin indicated that this isolate was predisposed to the acquisition of the GISA phenotype (MIC of vancomycin 10-12 mg/L), which occurred 13 days later, associated with an increased MIC of the endopeptidase lysostaphin and slightly increased cell wall thickness. The first and last isolates in the series, A and F, resisted killing when incubated in vancomycin 2 mg/L, resisted autolysis when incubated in Triton X-100 and had a decreased expression of a c. 116 kDa autolytic band, properties that were different from glycopeptide-susceptible control isolates. Lysostaphin resistance was not accompanied by alterations in the peptidoglycan pentaglycine cross-bridge or a decrease in oxacillin MIC. These data, when taken together with the demonstration of increased cross-linking in isolate F compared with isolate A, demonstrate that vancomycin resistance in these isolates probably occurred by a mechanism different from that of other GISA isolates described to date.

Anti-Bacterial Agents↗

PubMed2002

Emergence of vancomycin-intermediate Staphylococcus aureus in a Belgian hospital: microbiological and clinical features.

In 1999, all clinical Staphylococcus aureus isolates from patients admitted to a Belgian University hospital were tested for decreased vancomycin susceptibility. Three vancomycin-intermediate Staphylococcus aureus (VISA) and four hetero-VISA strains were detected among 2145 isolates tested. They emerged from strains that belonged to locally endemic methicillin-resistant S. aureus (MRSA) genotypes in three patients who had received repeated courses of vancomycin therapy. A cystic fibrosis patient with MRSA/VISA-associated broncho-pulmonary exacerbation was successfully treated by continuous vancomycin infusion plus fusidic acid followed by oral minocycline-fusidic acid. Two other patients had VISA recovered from specimens of undetermined clinical significance. Emergence of VISA variants of endemic MRSA strains in Belgium warrants active microbiological surveillance and careful monitoring of vancomycin therapy. Therapy with high-dose vancomycin administered by continuous infusion in combination with other antimicrobials may be a therapeutic option worth investigating for VISA infection.

Adolescent↗

PubMed2001

Does the empiric use of vancomycin in pediatrics increase the risk for Gram-negative bacteremia?

BACKGROUND: Gram-negative bacteremia in children, a major cause of morbidity and mortality, may in part be induced by intensive treatment procedures and nonspecific use of antibiotics. Our primary objective was to study the causal relationship between the use of vancomycin and Gram-negative bacteremia, for which this antibiotic is not specifically indicated. METHODS: The study was conducted in a 105-bed tertiary care children's hospital in the period of 1994 to 1997. The study pertains to a cohort of children with suspected bacteremia, in whom a blood culture was performed during hospital stay. Using the bacteriologic laboratory registration system, we selected all pediatric cases with bacteriologically proved Gram-negative bacteremia (n = 105) and a random sample of 225 pediatric controls with negative blood cultures. Using logistic regression analysis we examined associations between Gram-negative bacteremia and the following factors: preceding use of antibiotics, antacids, corticosteroids, surgery, mechanical ventilation, parenteral nutrition, and invasive instrumentation; and the intensity of care assessed with the Therapeutic Intensity Scoring System (TISS 28). RESULTS: Gram-negative bacteremia was positively associated with the use of aminoglycosides, cephalosporins, surgical interventions, central venous catheters, parenteral nutrition, antacids and dexamethasone. The strongest association was with the use of vancomycin (odds ratio, 8.1; 95% confidence interval, 3.1 to 20.9). In a multiple logistic regression model containing all above-mentioned variables, the use of vancomycin remained positively and strongly associated with Gram-negative bacteremia (odds ratio, 3.88; 95% confidence interval, 1.34 to 11.21). Further adjustments and restrictions in the analysis did not materially change these findings concerning vancomycin. CONCLUSIONS: Among children suspected of bacteremia there are several drugs and clinical procedures influencing the risk for Gram-negative bacteremia. Empiric use of vancomycin is strongly and independently associated with Gram-negative bacteremia. The safety of using vancomycin solely on the basis of suspicion of bacteremia in children may not be warranted.

Adrenal Cortex Hormones↗

PubMed2005

Dehydroepiandosterone induction of increased resistance to vancomycin in Staphylococcus aureus clinical isolates (MSSA, MRSA).

AIMS: To investigate whether dehydroepiandosterone (DHEA), an androgen present throughout life, alters the response of Staphylococcus aureus clinical isolates to vancomycin. METHODS AND RESULTS: DHEA in physiologically relevant concentrations (0.1, 0.5, 1.0 and 5.0 micromol l(-1)) was tested for its effect on methicillin-sensitive S. aureus (MSSA, n = 53) and methicillin-resistant S. aureus (MRSA, n = 73) response to vancomycin using standard protocols. Mutant selection was determined by serial transfer of selected isolates (n = 5). DHEA-mediated at least a fourfold increase in vancomycin MIC for 42% of MSSA and 21% of MRSA. For five of the isolates (0.1 and 0.5 micromol l(-1) DHEA) the MIC was increased to levels (8 microg ml(-1)) defined as vancomycin-intermediate resistance. CONCLUSION: Resistance was detected only in the presence of DHEA, and was not related to altered generation time, indicating induction of phenotypic resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings require further investigation to determine what role DHEA plays in clinical vancomycin treatment failure that has been reported in the absence of vancomycin genotypic resistance or heteroresistance.

Dehydroepiandrosterone↗

PubMed2003

[Epidemiological investigation of "beta-lactam antibiotic induced vancomycin-resistant MRSA (BIVR)"].

Mu3 strain with heterogeneous intermediated-resistance to vancomycin (hetero-VISA) reported in 1997, also have possessed a character of an antagonistic effect of beta-lactam antibiotics and vancomycin. Mu3 is only strain which satisfies the definition of hetero-VISA in Japan. But, MRSA with antagonistic effects of beta-lactam antibiotics and vancomycin, was reported by many institutions. To separate hetero-VISA, we called "beta-lactam antibiotic induced vancomycin-resistant MRSA (BIVR)". But the detection rate of clinical isolated BIVR in Japan is unknown, we reported on the detection method and the epidemiological investigation for BIVR. Mu 3 agar containing 4 micrograms/mL of vancomycin is used to detect BIVR. Mu3 strains were spread on the agar, BIVR can grow around the paper disc impregnated with ceftizoxime or grow on the whole surface on Mu 3 agar after incubation. The detection rate of BIVR was 45 in 717 (6.3%) clinical isolated strains. In detected strains as BIVR, the number of strains with grown on the whole surface of Mu3 agar showing a high resistance to vancomycin were 10 strains (1.4%). Besides, from 106 strains of blood isolates MRSA, BIVR were detected 16 strains (15.1%), from 611 strains of non-blood isolates MRSA, BIVR were detected 29 strains (4.7%) (P < 0.0001). In BIVR strains grown on the whole surface of Mu3 agar, the number of BIVR strains isolated from blood were 8 in 106 (7.5%), from non-blood were 2 in 611 (0.3%) (P < 0.0001). On one side, hetero-VISA were not detected from all of BIVR growing on the whole surface of Mu3 agar. As a result, detection method and the definition of BIVR were quite different from those of hetero-VISA. An existence of BIVR in Japan was confirmed, we thought that the high detection rate of BIVR isolated from blood compared with that of non-blood showed the pathogenecity of BIVR which contribute to MRSA infections.

Anti-Bacterial Agents↗

PubMed2000

Mupirocin prophylaxis against methicillin-susceptible, methicillin-resistant, or vancomycin-intermediate Staphylococcus epidermidis vascular-graft infection.

A rat model was used to investigate the efficacy of mupirocin in the prevention of vascular prosthetic graft infection due to Staphylococcus epidermidis strains with different susceptibility patterns (methicillin susceptible, methicillin resistant, and with intermediate resistance to vancomycin). The effect of mupirocin-soaked Dacron was compared to that of perioperative intraperitoneal prophylaxis with vancomycin. Graft infections were established in the back subcutaneous tissue of adult male Wistar rats by implantation of Dacron prostheses (1 cm(2)) followed by topical inoculation with 5 x 10(7) CFU of one staphylococcal strain. The study included a control group (no graft contamination), three contaminated groups that did not receive any antibiotic prophylaxis, three contaminated groups that received mupirocin-soaked grafts, three contaminated groups in which perioperative intraperitoneal vancomycin prophylaxis (10 mg/kg of body weight) was administered, and three contaminated groups that received mupirocin-soaked grafts and perioperative intraperitoneal vancomycin prophylaxis (10 mg/kg). The grafts were sterilely removed 7 days after implantation, and the infection was evaluated by using sonication and quantitative agar culture. Data analysis showed the efficacy of mupirocin against all three strains, with growth of the strains in treated rats significantly different than that in the untreated control. In addition, mupirocin was more effective than vancomycin against the strain with intermediate susceptibility to the glycopeptide. Finally, the combination of mupirocin and vancomycin produced complete suppression of the growth of all of the strains.

Aminoglycosides↗