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Epidemiological, microbiological, clinical, and prognostic factors of bacteremia caused by high-level vancomycin-resistant Enterococcus species.

A case-control study was performed between 1994 and 1996 in order to study the epidemiological, microbiological, clinical, and prognostic features of high-level vancomycin-resistant enterococcal bacteremia. Seventeen consecutive patients who had clinically significant bacteremia due to vancomycin-resistant enterococci (vanA genotype: 16 Enterococcus faecalis, 1 Enterococcus faecium) were compared with 169 who had vancomycin-susceptible enterococcal bacteremia. The following were selected by multivariate analysis as independent risk factors that influenced the development of high-level vancomycin-resistant enterococcal bacteremia: prior glycopeptide therapy (P=0.049); inclusion in a hemodialysis program (P=0.046); prior therapy with corticosteroids or antineoplastic agents (P=0.029); and prior surgical treatment (P=0.022). The following other factors were selected by univariate analysis: tracheostomy (P=0.002); prolonged hospitalization (P=0.01); and any kind of puncture (P=0.02). The crude associated-mortality rate was 13.4%. Gene amplification of vanA was positive for 17 strains of enterococci. Pulsed-field gel electrophoresis of genomic DNA after SmaI digestion of vanA isolates revealed that one strain predominated (10 isolates), though at least four similar banding patterns were identified (6 isolates). The 16 strains closely related to the outbreak were investigated further. The surgical intensive care unit was the first and most involved service. The hospital outbreak of vanA vancomycin-resistant enterococcal bacteremia occurred between 1994 and 1995 and was caused by Enterococcus faecalis. This is believed to be the first and only such outbreak described in a Spanish hospital thus far.

Adolescent↗

Vancomycin-induced neutropenia complicating bone marrow recovery in a patient with leukemia. Case report and review of the literature.

Neutropenia associated with intravenous vancomycin therapy is reported in a patient with chronic myelogenous leukemia. The patient received 12 days of vancomycin therapy without incidence; however, a second course of vancomycin initiated on hospital day 14 produced severe neutropenia. This delayed onset is typical of vancomycin-induced neutropenia. The neutropenia reversed, without complications, as soon as the vancomycin was discontinued.

Adult↗

Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens.

PURPOSE: High-dose (500 mg orally four times daily) vancomycin is considered by many investigators to be the most effective treatment for antibiotic-associated Clostridium difficile colitis. However, a lower dosage of 125 or 150 mg given three or four times a day has become popular, has been shown to be effective, and is less expensive than the high-dose regimen. We therefore decided to compare two vancomycin dosage regimens in a randomized trial. PATIENTS AND METHODS: The study involved 46 hospitalized patients with serious underlying diseases complicated by C. difficile diarrhea or colitis. Patients were assigned (according to a table of random numbers) to treatment with either 125 or 500 mg of vancomycin orally four times daily for an average of 10 days. RESULTS: No significant differences in measurable responses to the two regimens were noted. There were no treatment failures. The mean duration of diarrhea after initiation of therapy was about four days, and almost all patients had no diarrhea after one week. The organism continued to be demonstrated in the stools of about 50 percent of patients for the first few weeks after completion of therapy, and nine (20 percent) patients developed a recurrence of their diarrheal illness. Vancomycin was well tolerated by all patients. CONCLUSION: Since the dose of 125 mg appeared to be as effective as the 500-mg dose, which is more expensive, the 125-mg dose is preferred when vancomycin is used in treatment of this disease, unless the patient is critically ill.

Administration, Oral↗

Vancomycin during pregnancy: does it cause hearing loss or nephrotoxicity in the infant?

Vancomycin was administered intravenously to 10 pregnant women for the treatment of methicillin-resistant Staphylococcus aureus infections. Auditory brainstem response testing and renal function studies were performed on the 10 babies in the experimental group and 10 babies in each of two control groups to determine the safety of vancomycin use during pregnancy. Auditory brainstem responses were not normal at birth in six infants from the three different groups studied (N = 30) but were normal at 3 months in five. The sixth infant had conductive hearing loss unrelated to vancomycin use that spontaneously disappeared at 12 months of age. Renal function was normal in all infants. Vancomycin was detected in cord blood in two patients and in breast milk in one. Adequate serum levels were achieved with routine doses in eight mothers tested; no adverse reactions occurred. It appears that vancomycin use during the second and third trimesters of pregnancy does not produce sensorineural hearing loss or nephrotoxicity in the infant.

Blood Urea Nitrogen↗

Simplified dosing and monitoring of vancomycin for the burn care clinician.

Vancomycin has excellent activity against Gram-positive bacteria and is often selected for use in the infected burn patient. Because of multiple-compartment pharmacokinetics, vancomycin serum concentrations can decrease dramatically in a short time period following the end of an intravenous infusion. This accounts for the widely divergent recommendations for serum vancomycin peak concentrations, e.g. from 15 mg/l up to 80 mg/l, when the time for blood sampling following the end of intravenous infusion is different. It is in general not necessary to monitor vancomycin peak concentrations, not only because its toxic potential is overrated but also because potential toxicity and therapeutic efficacy are correlated with trough concentrations. Post-distribution 'peak' concentrations are generally only useful for determining the optimal dosing interval for patients with impaired renal function. A dosing and monitoring paradigm for vancomycin therapy in burned adults has been devised for burn care clinicians. It provides suggested dose and dosing intervals based on body weight and creatinine clearance, with specific recommendations for regimen modification based upon the results of trough serum concentration determinations.

Adult↗

Early identification of neutropenic patients at risk of grampositive bacteraemia and the impact of empirical administration of vancomycin.

The aim of this multicentre randomised trial was to determine whether it was possible to predict grampositive bacteraemia, and whether the empirical use of vancomycin would lead to reduced morbidity and mortality. 35 of 113 patients (31%; confidence interval, CI 8.5), who presented with a skin or soft tissue infection and had received empirical vancomycin in addition to either ceftazidime or piperacillin-tobramycin, had initial bacteraemia with a single gram-positive bacterium compared with 135 of the 784 (17%; CI 2.6), who presented with another infection and who had been given ceftazidime or piperacillin-tobramycin without vancomycin (P < 0.001). Empirical vancomycin resulted in a higher rate of eradication (P = 0.033, relative risk 1.2), but not a better clinical outcome and was associated with more toxicity (P = 0.042, relative risk 1.6). Irrespective of the initial treatment regimen, fever lasted an average of 8 days, the empirical regimen was modified in more than 50% of cases and mortality attributed to gram-positive infection was less than 2%. Incorporating vancomycin in the initial empirical antibiotic regimen for febrile neutropenic patients does not appear necessary, even for skin and soft tissue infections associated with gram-positive bacteraemia.

Adult↗

Linezolid eradicates MRSA better than vancomycin from surgical-site infections.

BACKGROUND: The purpose of this analysis was to compare the efficacy of linezolid versus vancomycin in patients with suspected or proven gram-positive methicillin-resistant Staphylococcus aureus (MRSA) surgical-site infections. METHODS: An open-label, randomized, comparator-controlled, multicenter, multinational study was conducted in hospitalized patients. Patients were randomized 1:1 to receive linezolid 600 mg (intravenous [IV] or oral) every 12 hours (n = 66) or vancomycin 1 g every 12 hours IV (n = 69) for 7 to 21 days. Patients were assessed at the test-of-cure (TOC) visit, 7 days after completing therapy. RESULTS: Clinical success at TOC was documented in similar proportions of patients treated with linezolid or vancomycin. Of those with MRSA isolated, significantly more patients who received linezolid compared with those who received vancomycin were microbiologically cured (87% vs 48%, respectively; 95% confidence interval 16.51 to 60.27; P = 0.0022). CONCLUSION: Intravenous or oral linezolid was well tolerated and superior to vancomycin in treating patients with MRSA-infected surgical-site infections.

Acetamides↗

Effectiveness of hydroxyapatite-vancomycin bone cement in the treatment of Staphylococcus aureus induced chronic osteomyelitis.

In the field of local application of antimicrobials, a number of novel drugs and/or new drug delivery systems have been developed in recent years. The present study aimed to investigate hydroxyapatite cement (HAC) as a carrier for vancomycin in the treatment of chronic osteomyelitis due to Staphylococcus aureus strains with various mechanisms of resistance. The release of vancomycin from standard test cylinders was determined in vitro and the efficacy of the delivery system was measured in vivo using a rabbit model of chronic osteomyelitis. First, powdered HAC was mixed with vancomycin at 80, 160 and 240 mg/g. After hardening, formed cylinders were eluted in phosphate buffer and antibiotic release was measured by agar diffusion. High levels of release (1512+/-318 to 1937+/-336 microg/ml) were obtained for 12 to 20 days depending on the dosage of vancomycin. Additionally, bone infection was induced in the tibia of 30 New Zealand white rabbits by injecting either a methicillin-resistant S. aureus strain (MRSA) or a S. aureus strain with a small colony variant (SCV) phenotype. After 3 weeks (chronic infection), all animals were treated by debridement. Moreover, group 1 (challenged with SCVs) and group 2 (challenged with MRSA) were treated by filling the marrow with HAC alone, whereas in groups 3 (SCVs) and 4 (MRSA) the marrow was filled with HAC/vancomycin (160 mg/g). After 6 weeks all animals were sacrificed. At 3 weeks, pathogens were detected in 24 of 30 animals. All swabs of the control groups, positive for S. aureus on day 21, were also positive on day 42 and S. aureus strains recovered were shown to be clonal to the strains used for induction of osteomyelitis. By contrast, no growth was found in the treatment group following 7 days of incubation in BHI bouillon. HAC/vancomycin-treated animals showed no histological evidence of infection on day 42. In the other groups, different stages of chronic osteomyelitis were found histologically. No local or systemic side effects due to HAC or vancomycin were seen. HAC is an effective carrier material for antibiotic compounds even in refractory infections due to MRSA or S. aureus SCVs.

Animals↗

Controlled release of vancomycin from thin sol-gel films on titanium alloy fracture plate material.

Risk of infection is considerable in open fractures and its management is challenging, especially when fracture fixation material is used. Thus, it may be desirable to use a device from which antibiotics can be released in a controlled way. Room temperature processed silica sol-gels are novel, resorbable and biocompatible, controlled release materials. Vancomycin, a potent antibiotic used in treating osteomyelitis, can be released from silica sol-gels. Herein, we describe the synthesis of thin, resorbable, controlled release bactericidal sol-gel films on a Ti-alloy substrate and determine the effect of processing parameters on its degradation and vancomycin release. A close correlation between release and degradation rates suggests that film degradation is the main mechanism underlying the control of release. Using a multi-layer process and various concentrations of vancomycin, released concentrations exceed the minimal inhibitory concentration (MIC) of vancomycin against Staphylococcus aureus. The findings enable the tailoring of release and degradation properties of the films to therapeutic needs by controlling sol-gel processing parameters. Given the bactericidal properties of released vancomycin, and the biocompatibility of the sol-gel films, the present data suggest great promise to prevent and treat bone infections in a clinical setting.

Alloys↗

Vancomycin-resistant enterococci from animal sources in Korea.

Enterococci for which the minimum inhibitory concentration (MIC) of vancomycin was >/=8 mg/l were isolated from meat, feces, and raw milk samples collected in Korea from March to November 2003. Among the 243 vancomycin-resistant enterococci (VRE) that were identified the vanA vancomycin resistance gene was carried by 51 Enterococcus faecium and one Enterococcus sp., vanC1 was carried by 151 Enterococcus gallinarum, vanC2 was carried by 39 Enterococcus casseliflavus, and one Enterococcus sp. carried no van genes. Of the isolated enterococci carrying vanA, 4% were found to be highly resistant to gentamicin and 11% were resistant to ampicillin. Further genotyping of the E. faecium isolates carrying vanA using pulsed-field gel electrophoresis (PFGE) revealed extensive heterogeneity. The vancomycin resistance transferability test revealed that only two of the 52 enterococci carrying the vanA gene were able to transfer vancomycin resistance to other enterococci. The VRE were recovered from various animal sources with a particularly high prevalence of E. faecium carrying the vanA gene being found in poultry meat.

Animals↗

Effectiveness and safety of enteral vancomycin to control endemicity of methicillin-resistant Staphylococcus aureus in a medical/surgical intensive care unit.

A prospective trial was undertaken to assess the effectiveness and safety of enteral vancomycin in controlling methicillin-resistant Staphylococcus aureus (MRSA) in an endemic setting. Over the 49 month period patients aged >14 years were enrolled, following admission to a medical/surgical intensive care unit (ICU) and expected to require ventilation for three days or more. A total of 799 patients were included in the trial. Period one, 1 July 1996-30 April 1997, (N=140), was observational. During period two, 1 May 1997-30 September 1998, (N=258), surveillance samples were obtained. MRSA carriers were isolated and received enteral vancomycin. During period three, 1 October 1998-31 July 2000, (N=400), all ventilated patients were given selective digestive decontamination (SDD) with polymyxin E, tobramycin, amphotericin B and vancomycin and four days of intravenous cefotaxime. The primary endpoints were: (1) incidence of patients with diagnostic samples positive for MRSA acquired on the ICU; (2) incidence of patients with vancomycin-resistant enterococci (VRE) in surveillance or diagnostic samples; (3) incidence of patients with samples positive for S. aureus with intermediate sensitivity to glycopeptides (GISA). The incidence of patients with MRSA in diagnostic samples were 31%, 14%, and 2% in periods one, two and three, respectively (P<0.001). There was a VRE outbreak involving 13 patients during period three. VRE disappeared with no change in policy. GISA was not detected. These findings support the effectiveness and safety of enteral vancomycin in the control of MRSA.

Aged↗

Dalbavancin compared with vancomycin for prevention of Staphylococcus aureus colonization of devices in vivo.

OBJECTIVES: Although active against free-floating bacteria, vancomycin displays a poor activity against organisms embedded within the biofilm surrounding implanted devices. Dalbavancin is a novel glycopeptide antibiotic with strong activity against staphylococci and a long half-life that allows for once-a-week dosing. The objective of this animal study was to examine the ability of dalbavancin and vancomycin to prevent Staphylococcus aureus colonization of devices. METHODS: Twelve rabbits were randomized, in three groups of four each, to receive intravenous injections of dalbavancin, vancomycin or normal saline (control). Eight polyurethane catheter segments were subcutaneously implanted in the back of each rabbit, then inoculated with S. aureus. Rabbits were sacrificed a week later and explanted devices were cultured. RESULTS: The rates of device colonization were comparable in the vancomycin (53%) and control (47%) groups, whereas only 28% of devices in the dalbavancin group became colonized. There was a trend (although not statistically significant) toward a lower rate of device colonization following receipt of dalbavancin vs. vancomycin (P = 0.07) or saline (P = 0.02). CONCLUSIONS: The demonstrated efficacy of dalbavancin in this animal study suggest that this novel antibiotic may have an important role in the prevention and treatment of device-related infection.

Animals↗

The effect of topical povidone-iodine, intraocular vancomycin, or both on aqueous humor cultures at the time of cataract surgery.

PURPOSE: To investigate whether the use of topical povidone-iodine before surgery, the addition of vancomycin to the irrigating solutions during phacoemulsification, or both reduces the frequency of positive intraocular cultures at the end of surgery. METHODS: A two-part, clinical study was performed. In the preliminary study, intracameral antibiotic concentrations were measured immediately after surgery (in 11 eyes) and 2 hours after surgery (in 11 eyes) in patients treated with vancomycin. In the primary study, 400(1) patients were divided into four groups composed of 100 eyes each. The first and the second groups received vancomycin (20 microg/ml) in the irrigating fluid. The third and the fourth groups received irrigating fluid only without antibiotics. The first and third groups received a topical 5% povidone-iodine solution 10 and 5 minutes before surgery; a topical placebo solution was used in the second and the fourth groups. All patients in the primary study underwent anterior chamber aspiration after surgery, and culturing was performed 2 hours later. Identification and quantification of positive cultures in thioglycolate broth and chocolate agar were performed. RESULTS: In the preliminary study, the half-life of intraocular vancomycin was less than 2 hours. In the primary study, intraocular aspirates yielded positive cultures in two (2%), five (5%), 11 (11%), and 13 (13%) specimens from the first, second, third, and fourth groups, respectively. CONCLUSIONS: We found a lower rate of positive cultures in the group that received vancomycin in the irrigating fluid; 2 hours of contact between the antibiotic solution and bacteria produced results that reached statistical significance (P = 0.032).

Administration, Topical↗

Vancomycin prophylaxis and emerging resistance: are ophthalmologists the villains? The heroes?

PURPOSE: To determine whether the routine use of vancomycin prophylaxis in elective cataract surgery promotes emerging resistance and provides effective protection against post-operative endophthalmitis. METHODS: Critical review of the current scientific and clinical literature was undertaken including appropriate statistical analyses of published data. RESULTS: Public health concerns for emergent vancomycin-resistant life-threatening "super bugs" are legitimate. Evaluation of the risk factors that are known to promote emerging vancomycin resistance (sick patients, hospital intensive care unit setting, methicillin-resistant Staphylococcus aureus (MRSA) clonal infections, prolonged systemic therapy, sub-therapeutic dosing, indwelling intravascular and drainage catheters, total kilogram usage and agricultural use) suggest that ophthalmic usage in routine cataract surgery is unlikely to be a significant factor in promoting emerging worldwide resistance. Clinical and scientific studies purporting to prove the value of vancomycin prophylaxis in cataract surgery contain substantial biases and design flaws that seriously undermine their validity. Issues of potential intraocular toxicity, increased costs, absence of medical-legal protection, and compliance with current Centers for Disease Control and Prevention (CDC) and American Academy of Ophthalmology guidelines (in hospital) mitigate against this practice. CONCLUSIONS: Ophthalmologists who use vancomycin prophylaxis in routine cataract surgery are neither the villains nor heroes according to my interpretation of the currently available scientific data. Personal conscience and an ongoing critical review of the literature should guide each ophthalmologist's choice in this controversy.

Anti-Bacterial Agents↗

Adverse effects of vancomycin administered in the perioperative period.

Indications for the administration of vancomycin in the perioperative period have expanded in recent years. Used in this situation, vancomycin has caused adverse reactions, the most serious of which is hypotension. We describe five patients who had adverse reactions to vancomycin perioperatively. Vancomycin-induced hypotension usually results from a negative inotropic and vasodilator effect produced in part by a histamine-release phenomenon, which occurs most commonly with rapid intravenous infusion of the drug. Such a release of histamine may also produce an acute urticarial flushing of the upper torso (the "red neck syndrome") and symptoms of pain and muscle spasm in the chest or paraspinal muscles, which may mimic myocardial infarction. These effects usually abate promptly when the infusion of vancomycin is discontinued, and their resolution may be expedited by administration of an antihistamine.

Adult↗

Vancomycin.

Vancomycin is a nontoxic glycopeptide antibiotic most often used to treat serious gram-positive infections, C. difficile diarrhea/colitis, and endocarditis and hemodialysis shunt prophylaxis. Vancomycin should not be added to drug regimens for gram-positive coverage, and the empiric use of vancomycin should be discouraged to avoid the emergence of VRE. Vancomycin serum levels are no longer necessary or cost effective in most patients because vancomycin is not nephrotoxic.

Bacterial Infections↗

Vancomycin: a review.

This article reviewed the past experience and updated the present data on vancomycin. In recent years, with the release of more purified preparations of vancomycin and new clinical problems facing the clinician (that is, increasing prevalence of serious methicillin-resistant staphylococcal infections; use of hemodialysis and CAPD; widespread use of prosthetic devices; aggressive chemotherapy), the indication for vancomycin use has increased dramatically. More information is needed on the distribution of vancomycin in body tissues and the incidence and mechanisms of toxicity. Close surveillance of in vitro susceptibility patterns will be necessary as widespread use of vancomycin continues to increase.

Bacterial Infections↗

Oral vancomycin for antibiotic-associated pseudomembranous colitis.

Nine patients with antibiotic-associated pseudomembranous colitis were treated with oral vancomycin. All had severe diarrhoea, tissue-culture evidence of a clostridial toxin in stool, and typical lesions on sigmoidoscopic examination, despite discontinuation of all antimicrobials for periods of 10 days to 8 weeks. Oral vancomycin was given in doses of 2 g daily. All patients showed a good clinical response with gradual resolution of diarrhoea over 7 days and a rapid decrease in concentrations of the toxin in stools. Follow-up sigmoidoscopies in seven patients showed major improvement or complete clearing of lesions after 7-10 days of vancomycin treatment. The mean concentration of vancomycin in twenty-five stools obtained during treatment was 3100 microgram/g, levels in serum being very low. These results suggest a role for oral vancomycin treatment of antibiotic-associated pseudomembranous colitis which persists for extended periods despite discontinuation of the incriminated antimicrobial.

Administration, Oral↗