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PubMed1988

Transscleral and transcorneal iontophoresis of vancomycin in rabbit eyes.

We examined the ability of transscleral and transcorneal iontophoresis to deliver vancomycin into the aqueous humor, the vitreous humor, and the cornea of rabbit eyes. Control eyes receiving subconjunctival injection (25 mg) attained peak aqueous, vitreous, and corneal concentrations (mean +/- S.E.M.) of 14.73 +/- 0.35 mcg/ml (at 4 hours after injection), 1.10 +/- 0.78 mcg/ml (2 hours), and 1167 +/- 63 mcg/g (1 hour), respectively. Eyes receiving transscleral iontophoresis (3.5 mA for 10 minutes) attained significantly higher vitreal levels than controls: 6.33 +/- 0.25 mcg/ml (p less than 0.001; 1 hour), 13.43 +/- 2.32 mcg/ml (p less than 0.01; 2 hours), 11.93 +/- 0.76 mcg/ml (p less than 0.001; 4 hours), 8.40 +/- 0.60 mcg/ml (p less than 0.001; 8 hours). Eyes receiving transcorneal iontophoresis (0.5 mA for 5 minutes) attained earlier and significantly higher aqueous and corneal levels than controls. Aqueous humor levels were 16.20 +/- 3.19 mcg/ml (p less than 0.05; 1 hour) and 20.20 +/- 0.43 mcg/ml (p less than 0.001; 2 hours). Corneal levels were 10799 +/- 755 mcg/g (p less than 0.001; 0.5 hour), 4856 +/- 606 mcg/g (p less than 0.005; 1.0 hour), 2185 +/- 71 mcg/g (p less than 0.001; 2 hours), and 710 +/- 112 mcg/g (p less than 0.025; 4 hours). Corneal endothelial cell counts were decreased by 8.8% (p = 0.08) after transcorneal iontophoresis of vancomycin and 5.4% (p less than 0.02) following Balanced Salt Solution (BSS). However, corneal thickness were not significantly increased by iontophoresis of either vancomycin or BSS. These experiments show that transscleral and transcorneal iontophoresis are efficacious in delivering high concentrations of vancomycin into the aqueous and vitreous humor and the cornea.

Animals↗

PubMed2006

A case of ventricular drainage infection with a rare pathogen in cerebrospinal fluid: vancomycin-resistant Enterococcus faecium.

The purpose of this study was to describe a patient, 7-month-old child with ventriculoperitoneal shunts for hydrocephalus with ventriculitis caused by vancomycin-resistant Enterococcus faecium. Two ventriculoperitoneal shunts were inserted just after birth and on the second month. On the sixth month, both shunts were removed because of dysfunction, and external drainage was inserted. The child developed fever, and lumbar puncture revealed a high leukocyte count and protein concentration after external drainage. Cerebrospinal fluid (CSF) cultures yielded E. faecium, which was resistant to ampicillin, erythromycin, gentamicin, penicillin G, vancomycin, and teicoplanin and was susceptible to chloramphenicol, ciprofloxacin, streptomycin, levofloxacin, and rifampin, as determined by the disk diffusion method. As a result of the antimicrobial susceptibility tests, multidrug antibiotic therapy was changed from vancomycin and ceftazidime to chloramphenicol, rifampin, and meropenem. In addition, a rifampin-clindamycin-impregnated shunt (The Codman Hakim Bactiseal, Raynham, MA) was inserted. The patient became afebrile, and CSF cultures were sterile after 15 days of yielding E. faecium. Implantation of the rifampin-clindamycin-impregnated shunt and timely use of appropriate antibiotics for 10 days according to antimicrobial susceptibility testing seem to be important in the resolution of vancomycin-resistant enterococci infections, especially in countries where linezolid and quinupristin-dalfopristin are not in use yet.

Cerebrospinal Fluid↗

PubMed2002

Significant impairment of high-dose methotrexate clearance following vancomycin administration in the absence of overt renal impairment.

BACKGROUND: Methotrexate is an antimetabolite cytotoxic drug which is predominantly renally excreted. Vancomycin, a glycopeptide antibiotic that is used in the febrile neutropaenic patient, can be nephrotoxic. There are no previous reports of any interactions between these two drugs. PATIENTS AND METHODS: We describe two patients with osteosarcoma treated with high-dose methotrexate-containing chemotherapy who had significantly delayed methotrexate clearance several weeks following exposure to vancomycin. RESULTS: These patients were treated with alternating chemotherapy consisting of 12 g/m2 methotrexate, 60 mg/m2 cisplatin, 75 mg/m2 adriamycin and 15 g/m2 ifosfamide. In both patients, serum methotrexate levels fell to below 0.2 micromol/l within 48-96 h during initial treatment cycles. However, following recent exposure to therapeutic vancomycin in the preceding 10 days and in the absence of overt renal impairment, both patients manifested markedly prolonged methotrexate clearance, requiring 170-231 h to reach serum levels of less than 0.2 microM. Subclinical renal impairment was documented by impaired glomerular filtration rates in both cases by technetium 99 m diethylene triamine penta-acetic acid scanning. Subsequent methotrexate cycles using an unmodified schedule were cleared within 72 h. Both cases had their glomerular filtration rate re-assessed, which showed marked improvement. CONCLUSIONS: Recent exposure to vancomycin, even in the absence of overt renal impairment, may adversely affect methotrexate excretion, which can subsequently lead to increased toxicity of the antimetabolite. The glomerular filtration rate should be measured in such cases so that appropriate dose modification of methotrexate can be made.

Adult↗

PubMed1999

High-dose aprotinin with gentamicin-vancomycin antibiotic prophylaxis increases blood concentrations of creatinine and cystatin C in patients undergoing coronary artery bypass grafting.

Both aprotinin and gentamicin-vancomycin antibiotic prophylaxis have been used widely in cardiac surgery to prevent bleeding and infections, respectively. As the drugs are excreted almost entirely by glomerular filtration, we investigated their action on renal function when administered either separately or together. To increase consistency, we measured serum concentrations of creatinine and cystatin C, a new marker of glomerular filtration rate, that many recent studies have shown to be more sensitive than serum creatinine. One hundred patients undergoing coronary artery bypass surgery were allocated randomly to one of four groups: group A received antibiotic prophylaxis with cefamandole and no aprotinin; group B received cefamandole and high-dose aprotinin; group C received antibiotic prophylaxis with gentamicin and vancomycin, but no aprotinin; and group D received both high-dose aprotinin and gentamicin-vancomycin antibiotic prophylaxis. Data from 84 patients, for whom data collection was complete, were analysed. In the first week after operation, mean serum concentrations of cystatin C and creatinine either remained constant or decreased slowly in all groups, except for group D. In group D, both markers increased gradually from postoperative day 2 onwards. The increase in cystatin C was significant on postoperative day 5 (from mean 1.02 (SD 0.11) mg litre-1 before operation to 1.35 (0.32) mg litre-1; P < 0.05), reaching a peak on postoperative day 7 (1.45 (0.35) mg litre-1; P < 0.05), while the increase in creatinine concentration was significant on postoperative day 6 (from 1.05 (0.16) mg dl-1 before operation to 1.29 (0.34) mg dl-1; P < 0.05). We conclude that simultaneous administration of high-dose aprotinin and prophylactic use of gentamicin with vancomycin increased serum concentrations of cystatin C and creatinine in the first postoperative week in patients undergoing cardiac surgery.

Aged↗

PubMedDate not supplied

Ceftazidime plus amikacin versus ceftazidime plus vancomycin as empiric therapy in febrile neutropenic children with cancer.

Two antibiotic regimens, ceftazidime plus amikacin and ceftazidime plus vancomycin, were compared in a prospective, randomized clinical trial as empiric therapy in febrile granulocytopenic children with cancer. The rate of response was similar in the two groups (66% vs. 77%). The prevalence of secondary gram-negative bacteremia was higher--but not significantly higher--in the group receiving vancomycin. Adverse reactions also occurred more often in the latter group (35% vs. 4%). Mortality did not differ significantly in the two groups. Adjustment for independent predictors of response to treatment by means of multivariate analysis confirmed the lack of any remarkable difference between the responses to the two regimens. We conclude that the use of vancomycin instead of amikacin in combination with ceftazidime does not significantly improve the outcome of treatment of fever and infection in granulocytopenic children with cancer and that the use of vancomycin is associated with an increased frequency of both secondary infections due to gram-negative bacteria and adverse reactions.

Amikacin↗

PubMed1996

Risk factors associated with vancomycin-resistant Enterococcus faecium infection or colonization in 145 matched case patients and control patients.

Risk factors and mortality associated with vancomycin-resistant Enterococcus faecium (VREF) infection or colonization were examined at a tertiary care hospital by comparing 145 patients who had VREF isolates (cases) to 145 patients with vancomycin-susceptible Enterococcus faecium (VSEF) isolates (controls). The number of deaths per 100 person-days of hospitalization after diagnosis did not differ significantly between VREF patients (1.2) and VSEF patients (0.8). Multivariate analyses found that the duration of hospitalization ( > or = 7 days), intrahospital transfer between floors, use of antimicrobials (i.e., vancomycin and third-generation cephalosporins), and duration of vancomycin use ( > or = 7 days) was independently associated with VREF infection or colonization. This study, which has a large sample size, confirms some earlier observations regarding risks for VREF infection or colonization and identifies factors that may be potentially exploited to develop interventional strategies for the control of this emerging nosocomial problem.

Adolescent↗

PubMed1991

Instillation of vancomycin into a cerebrospinal fluid reservoir to clear infection: pharmacokinetic considerations.

Vancomycin instilled in an Ommaya reservoir was used to treat a reservoir-associated infection. Vancomycin concentrations in cerebrospinal fluid (CSF) were measured, and derivation of pharmacokinetic parameters allowed tailoring of dosing. First-order kinetics were observed. The calculated half-life of 3.52 h was less than reported by others, and the apparent volume of distribution (60 ml) was less than anticipated. The elimination constant was 0.197 h-1. Empiric dosing based on schedules suggested in the literature would have led to high peak and low mean concentrations of intrareservoir vancomycin. Patients with reservoir-associated infections have a variety of pathophysiologic conditions that can result in alteration of normal CSF dynamics. Pharmacokinetic analysis is useful to individualize dosing and to optimize therapy with intrareservoir vancomycin.

Adult↗

PubMed1991

Synergistic bactericidal activity of rat serum with vancomycin against enterococci.

Animal models of infectious diseases may not predict clinical efficacy when species-related factors come into play. Recently, unexpected bactericidal activity of vancomycin alone against enterococci was observed in a rat model of endocarditis. A factor or factors in rat serum, but not rabbit or human serum, enhanced in vitro killing by vancomycin in four of five clinical isolates of enterococci. Bactericidal activity was maintained on dilution of rat serum to 5.0% and after exposure of serum to 56 degrees C for 30 min. Activity was lost by heating at 60 degrees C for 2 h, ultrafiltration, or absorption with bentonite or heat-killed bacteria. Rat serum appears to contain a factor or factors that contribute bactericidal activity to vancomycin, a drug normally bacteriostatic for these enterococci. The mechanism by which this factor enhances killing of enterococci by vancomycin is unknown.

Animals↗

PubMed1994

Vancomycin penetration into biofilm covering infected prostheses and effect on bacteria.

To evaluate the adequacy of penetration of antibiotics into biofilm, a novel in vitro model for prosthesis-related infection was developed. Sterile stainless steel orthopedic nuts were incubated with slime-producing Staphylococcus epidermidis. Biofilm-covered nuts were exposed to varying concentrations of vancomycin; then biofilms were harvested. Vancomycin levels in biofilm, as measured by fluorescent polarization immunoassay, far exceeded the MIC and MBC of vancomycin for the organism. Bacterial growth in biofilm was inversely related to vancomycin concentration in biofilm, but even extremely high drug concentrations did not eradicate bacteria embedded in biofilm. The MICs and MBCs for bacteria recovered from biofilm did not differ from those for incubating organisms. Thus, failure of glycopeptide antibiotics to cure prosthesis-related infection is not due to poor penetration of drugs into biofilm but likely due to diminished antimicrobial effect on bacteria in the biofilm environment.

Bioprosthesis↗

PubMed1995

Epidemiology and mortality risk of vancomycin-resistant enterococcal bloodstream infections.

Risk factors for vancomycin-resistant enterococcal (VRE) bloodstream infection (BSI) were studied at a tertiary-care hospital by comparing 46 patients with VRE-BSI with 46 randomly selected patients with vancomycin-susceptible enterococcal (VSE) BSI. Among patients with an enterococcal BSI, risk factors for mortality were determined. Independent risk factors for VRE-BSI were increasing APACHE II score (odds ratio [OR], 2.3/5-point increase; 95% confidence interval [CI], 1.4-3.9), receipt of vancomycin (OR, 11; 95% CI, 5.5-21), or diagnosis of hematologic malignancy (OR, 8.4; 95% CI, 3.9-18). After controlling for APACHE II score and gender, patients with VRE- versus VSE-BSI did not have a significantly elevated risk of mortality (OR, 3.3; 95% CI, 0.7-15). Five of 28 VRE blood isolates typed using pulsed-field gel electrophoresis had identical banding patterns. These data suggest that increasing severity of illness, underlying disease, and receipt of vancomycin are major risk factors for VRE-BSI.

APACHE↗

PubMed1997

Treatment of experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis with intravitreal vancomycin and intravitreal dexamethasone.

The use of intravitreal steroids to treat bacterial endophthalmitis remains controversial. The efficacy of intravitreal vancomycin alone (group 1), intravitreal dexamethasone alone (group 2), and a combination of intravitreal vancomycin and dexamethasone (group 3) in the treatment of experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis was evaluated in a rabbit model: 24 h after bacterial inoculation of all eyes, right eyes were treated and left eyes served as infected controls. Vitreal aspirations and grading of vitreal inflammatory reaction were done regularly until sacrifice. Group 2 eyes demonstrated more inflammation histologically than control eyes. Vitreal aspirations demonstrated no growth by 5 days from groups 1 and 3 eyes. Although the clinical appearance was not significantly different between groups 1 and 3, the histologic appearance of group 3 eyes showed less intense intraocular inflammation. Treatment with dexamethasone in the absence of appropriate antibiotics was more harmful than no treatment at all (P < .05). Therapy with both intravitreal vancomycin and dexamethasone results in less inflammation than intravitreal vancomycin alone in this model.

Animals↗

PubMed1984

Vancomycin use--an historical review.

In the early 1950s the increase of antibiotic-resistant strains of Staphylococcus aureus in hospitalized patients with infection stimulated a screening program to develop an effective new agent. A soil sample found in the jungles of Borneo contained a microorganism, Streptomyces orientalis, that produced a substance later called vancomycin. Vancomycin was shown to have antistaphylococcal activity and to be relatively safe when administered to patients. With the resurgence of staphylococcal infections resistant to the newer antistaphylococcal antibiotics, there has been a corresponding increase in the use of vancomycin. Vancomycin is also being used for prophylaxis in patients with reduced renal function undergoing dialysis, for the treatment of patients with antibiotic-induced enterocolitis, and in combination with other antibiotics for 'sterilization' of the intestinal tract in patients with cancer.

Animals↗

PubMed1984

In-vitro effects of vancomycin and rifampicin, alone and in combination, against methicillin-sensitive and methicillin-resistant staphylococci.

The in-vitro inhibitory and bactericidal activities of vancomycin and rifampicin were tested against several Staphylococcus strains recently isolated from clinical material. All strains were first tested for their susceptibility to methicillin, and typed by lyogroup. With vancomycin, minimum inhibitory concentrations (MICs) fell within a narrow range (0.62-2.5 mg/l), and significant differences were not observed both among different lyogroups and between methicillin-sensitive (M-S) and methicillin-resistant (M-R) strains. Minimum bactericidal concentrations (MBCs) of vancomycin either equalled or exceeded by twofold the MICs. With rifampicin, MICs were found to be distributed over a wide range (0.002 to greater than 5 mg/l), and susceptibility appeared to be less in M-R than in M-S isolates. Although MICs greater than or equal to mg/l were only observed in three of the six lyogroups, data appeared insufficient to substantiate definite interspecies differences in staphylococcal susceptibility to rifampicin. MBCs of rifampicin either equalled or exceeded by two- to eightfold the MICs. In-vitro interactions between vancomycin and rifampicin, were investigated both by checkerboard and time-kill tests. By both methods, indifference was observed with the great majority of isolates. Synergism was a rare event, and antagonism was never observed.

Drug Combinations↗

PubMed1984

The treatment of endocarditis by vancomycin.

The narrow spectrum of vancomycin includes the common causal bacteria of endocarditis. This agent has been used since the 1960s for therapy and prophylaxis of infections when first-line drugs are inappropriate because of antibiotic resistance or drug allergy. Some personal experiences of vancomycin usage and a literature survey are presented in this paper which is based on the subdivision of endocarditis into medical, surgical (early--less than 60 days after operation--or late), and addict-related. The commonest bacterial causes of medical or late surgical infections are streptococci, and of the early surgical and addict-related infections are staphylococci. Vancomycin is bactericidal for Gram-positive cocci, except enterococci, but for optimal action it is arguable that combinations with gentamicin, fusidic acid, rifampicin or erythromycin should be used for staphylococcal endocarditis. The attainment of bactericidal blood levels may still be accompanied by failure of monotherapy and the need for early surgery is stressed. The prophylaxis of endocarditis is primarily required for tooth extraction and for cardiac surgery. The streptococci and staphylococci involved are normally vancomycin-susceptible, and the rabbit model shows that it is a suitable alternative to a beta-lactam and aminoglycoside combination. The combination is therefore suitable for patients already in hospital, especially those with prosthetic valves or undergoing cardiac surgery.

Adult↗

PubMed1984

Treatment of antibiotic-associated colitis with vancomycin.

Sixty-five patients were treated with oral vancomycin for Clostridium difficile colitis associated with treatment of infection by antibiotics. Colitis was confirmed by endoscopy in patients with diarrhoea and positive tests on diarrhoeal stools for Cl. difficile and/or its cytotoxin or, if endoscopy could not be performed, by the presence of fever and peripheral or faecal leucocytosis. Vancomycin dosage ranged from 125 to 500 mg four times daily for an average of about ten days. The mean duration of diarrhoea after starting therapy was four days; abdominal pain and fever usually resolved in two or three days. Post-treatment carriage of Cl. difficile was common. Eighteen per cent of patients developed a recurrence of colitis after treatment was discontinued, but responded to treatment with oral vancomycin, metronidazole, or bacitracin. After comparison of our results with those reported by others we concluded that vancomycin remains the treatment of choice for patients who are acutely and severely ill with Cl. difficile.

Adult↗

PubMed1987

Intraventricular vancomycin for treatment of shunt-associated ventriculitis.

Twenty episodes of shunt-associated ventriculitis caused by staphylococci or streptococci were treated with intraventricular vancomycin together with removal of the shunt and insertion of an external drain. Systemic antibiotics given concurrently included intravenous vancomycin or flucloxacillin. All the patients responded to therapy although five had re-infections and one had a relapse. Four patients were treated solely with intrathecal vancomycin. We now use intraventricular vancomycin alone for 'blind' treatment of uncomplicated shunt-associated infections when Gram-positive cocci are seen in the ventricular CSF.

Adult↗

PubMed1987

Teicoplanin, vancomycin, rifampicin: in-vivo and in-vitro studies with Staphylococcus aureus.

Groups of mice infected with 3.3 X 10(8) Staphylococcus aureus via the tail vein were treated three days later with rifampicin (13 mg/kg), vancomycin (33 mg/kg), or teicoplanin (33 mg/kg). Rifampicin was the most effective agent (28 out of 29 survivors). Vancomycin and teicoplanin were of equivalent efficacy (21 of 29 and 24 of 29 survivors, respectively). When intraleucocytic staphylococci were incubated with rifampicin (1 or 20 mg/l), vancomycin (100 mg/l), or teicoplanin (100 mg/l), rifampicin was the most active drug. Vancomycin and teicoplanin were similar.

Animals↗

PubMed1987

Comparative in-vitro activity of LY146032 a new peptolide, with vancomycin and eight other agents against gram-positive organisms.

The in-vitro activity of LY146032, a new biosynthetic peptolide antibiotic, was compared with vancomycin and eight other antibiotics against 190 Gram-positive bacteria. Organisms tested included streptomycin-susceptible and resistant enterococci, nafcillin-susceptible and resistant Staphylococcus aureus, and nafcillin-susceptible and resistant Staph. epidermidis. LY146032 had excellent in-vitro inhibitory and bactericidal activity against nafcillin-susceptible and resistant staphylococci (MIC90 less than or equal to 0.5 mg/l) and against enterococci (MIC90 less than or equal to 2.0 mg/l). LY146032 was more active than vancomycin against the majority of isolated tested. With the exception of trimethoprim-sulphamethoxazole, LY146032 was the most active agent in vitro against enterococci, and was the most active against nafcillin-resistant staphylococci. LY146032 and vancomycin showed a marked increase in MIC when the inoculum was increased from 10(5) to 10(7) cfu/ml. LY146032 and vancomycin were bactericidal at concentrations within two dilutions of the MIC for staphylococci. LY146032 was bactericidal at less than or equal to 8 mg/l for all enterococcal isolates tested.

Anti-Bacterial Agents↗