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PubMed1998

Vancomycin dosing in morbidly obese patients.

OBJECTIVES AND METHODS: Vancomycin hydrochloride dosing requirements in morbidly obese patients with normal renal function were computed to determine the dose of vancomycin necessary to achieve target steady-state peak and trough concentrations and compared with a normal weight population. RESULTS: Morbidly obese patients [total body weight (TBW) 165 kg, ideal body weight (IBW) 63 kg] required 31.2 mg x kg(-1) x d(-1) TBW or 81.9 mg x kg(-1) x d(-1) IBW to achieve the target concentrations. Normal weight patients (TBW 68.6 kg) required 27.8 mg x kg(-1) x d(-1) to achieve the same concentrations. Because of altered kinetic parameters in the morbidly obese patients (obese: t1/2 = 3.3 h, V = 52 L, CL = 197 ml x min(-1); normal: t1/2=7.2 h, V=46 L, CL=77 ml x min(-1), 20 of 24 patients required q8h dosing (1938 mg q8h) compared with q12h dosing (954 mg q12h) in all normal weight patients in order to avoid trough concentrations that were too low for prolonged periods. There was a good correlation between TBW and CL, but only fair correlation between TBW and V. CONCLUSION: Doses required to achieve desired vancomycin concentrations are similar in morbidly obese and normal weight patients when TBW is used as a dosing weight for the obese (approximately 30 mg x kg(-1) x d(-1)). Shorter dosage intervals may be needed when dosing morbidly obese patients so that steady-state trough concentrations remain above 5 microg x ml(-1) in this population. Because of the large amount of variation in required doses, vancomycin serum concentrations should be obtained in morbidly obese patients to ensure that adequate doses are being administered. Dosage requirements for morbidly obese patients with renal dysfunction require further study.

Adult↗

PubMed2005

Results of vancomycin-impregnated cancellous bone grafting for infected tibial nonunion.

INTRODUCTION: Bone grafting plays a critical role in promoting bone healing in infected nonunion, although recurrent infection is of concern. Cancellous bone grafting as an antibiotic delivery system has been reported as an effective method to combat infections. In this study, we report the clinical results of vancomycin-impregnated cancellous bone grafting for the treatment of infected tibial nonunion. MATERIALS AND METHODS: Between January 1996 and March 2001, 18 patients with infected tibial nonunion treated with vancomycin-impregnated cancellous bone grafting were available for follow-up. According to the Cierny-Mader classification, all patients belonged to type IVA and IVB osteomyelitis. Adequate debridement, stabilization with external fixation, and staged vancomycin-impregnated cancellous bone grafting were used in all patients. Regular clinical and radiographic follow-ups were conducted. RESULTS: Infection control was obtained in all 18 patients with a 100% infection arrest rate. Bone union was achieved in 13 of 18 patients at an average of 5.8 months. Bone union was obtained subsequently in the remaining five patients after closed nailing in four, and plating and bone grafting in one patient. Radiographs showed good consolidation and hypertrophy of grafted bone at an average follow-up of 48 months. CONCLUSION: We conclude that vancomycin-impregnated cancellous bone grafting is a safe method for the treatment of infected tibial nonunion.

Adult↗

PubMed2006

Biopsy-proven acute tubular necrosis in a child attributed to vancomycin intoxication.

Acute renal failure in children treated with vancomycin typically presents with interstitial nephritis. There is debate as to the extent of direct tubular toxicity attributable to vancomycin, especially in the absence of aminoglycoside treatment. We report a case of acute tubular necrosis (ATN) associated with vancomycin toxicity in an 8-year-old boy where there is no likely alternate explanation for toxic or ischemic injury. Treatment with hemodialysis resulted in the elimination of vancomycin from the circulation and subsequent improvement in renal function.

Anti-Bacterial Agents↗

PubMed2001

Hemodiafiltration for vancomycin overdose in a patient with end-stage renal failure.

A 17-year-old anuric female patient with end-stage renal failure received a massive overdose of vancomycin and was treated with high-flux hemodiafiltration, as described in this report. The hemodiafiltration procedure with a polysulfone membrane was performed 3 times. The vancomycin concentration was decreased from 101 mg/l to 16.59 mg/l at the end of the procedure. No adverse effects were noted from either vancomycin or hemodiafiltration. Hemodiafiltration with a high-flux polysulfone membrane is a novel and safe treatment modality for vancomycin overdose in pediatric patients.

Adolescent↗

PubMed1986

Agranulocytosis related to vancomycin therapy.

A patient with renal failure due to Goodpasture's syndrome was treated with vancomycin. After he had received 3 g of the drug, his white blood cell count fell to a level of 200/microliter. Bone marrow biopsy disclosed severe myeloid hypoplasia. The patient subsequently recovered fully from this episode of vancomycin-induced agranulocytosis, but he eventually died of other causes. Vancomycin-related leukopenia has been reported, but the severely depressed white blood cell count and myeloid hypoplasia observed in this patient have not previously been described. Vancomycin must be excluded as the cause of leukopenia in any patient who is receiving this drug.

Adult↗

PubMed1996

Investigation of enantioselective separation of quinolonecarboxylic acids by capillary zone electrophoresis using vancomycin as a chiral selector.

When a chiral selector that is a pharmaceutical compound is added to the separation buffer in capillary electrophoresis, the enantioselectivity and the mobility of analytes which interact with that chiral selector may be altered. The changes in enantioselectivity and mobility of the analyte are a function of the strength of the affinity interaction, which depends on the structure of each. The macrocyclic antibiotic vancomycin contains a variety of functionalities that are known to be useful for enantioselective interactions (e.g., hydrogen bonding groups, hydrophobic pockets, aromatic groups, amide linkages). Capillary electrophoresis with vancomycin as a buffer additive was used to separate the enantiomers of different compounds. In this study, the chiral separation of quinolonecarboxylic acids that exhibit marked antibacterial activity and of related compounds was achieved by capillary electrophoresis using vancomycin. The correlations between the separation parameters and analyte structures were investigated. The molecular interaction, which is based on the differences of structure, and the effect of experimental parameters on the enantioselective separation between the quinolonecarboxylic acids and vancomycin are discussed.

Anti-Infective Agents↗

PubMed1988

Effect of topical administration of vancomycin versus chlorhexidine on alpha-hemolytic streptococci in oral cavity.

In a crossover study the effect of local vancomycin (paste containing 0.5% vancomycin applied to the gums three times a day for 7 days) versus chlorhexidine mouth rinsing (0.2% chlorhexidine solution twice a day for 7 days) on alpha-hemolytic streptococci in the oral cavity was investigated in eight volunteers. Mixed saliva and dental plaque samples were collected for microbiologic analysis before administration, during treatment, and after withdrawal of the agents. The numbers of different alpha-hemolytic streptococci were determined in the samples. The total numbers of Streptococcus mitior, Streptococcus mutans, and Streptococcus sanguis were significantly reduced by the vancomycin treatment compared with the chlorhexidine treatment (p less than 0.05) after 2 days of administration. Two days after the treatment was stopped the numbers of alpha-hemolytic streptococci had returned to pretreatment levels. Local prophylaxis with vancomycin as a complement to systemic antimicrobial prophylaxis may therefore be useful in the prevention of infective endocarditis.

Administration, Topical↗

PubMed1986

Activity of teicoplanin compared with vancomycin alone, and combined with gentamicin, against penicillin tolerant viridans streptococci and enterococci causing endocarditis.

Teicoplanin had greater inhibitory activity than vancomycin against most of 22 penicillin tolerant strains of streptococci, but both drugs failed to kill 99.9% of the inoculum when tested alone at concentrations less than 16mg 1(-1). Bactericidal synergy between teicoplanin combined with gentamicin and vancomycin combined with gentamicin was always demonstrated in further tests with 16 penicillin tolerant strains. Teicoplanin had greater bactericidal activity than vancomycin against five of seven strains of viridans streptococci and five of nine strains of enterococci in MBC experiments, where each drug was combined with gentamicin. Killing curve experiments with five penicillin tolerant streptococci showed teicoplanin and vancomycin to have similar bactericidal activity within 24 h when tested at 5 mg 1(-1) with 2 mg 1(-1) gentamicin. However, at 0.5 mg 1(-1) only teicoplanin had a bactericidal synergic effect with gentamicin.

Anti-Bacterial Agents↗

PubMed1990

Double-blind placebo controlled study of vancomycin prophylaxis for central venous catheter insertion in cancer patients.

To assess whether vancomycin administration at the time of central venous catheter insertion would prevent catheter-related sepsis (CRS) in immunocompromised patients, 98 cancer patients were entered into a randomized placebo-controlled trial. Patients were stratified according to whether they were having therapy for acute leukaemia or undergoing bone-marrow transplantation (group A) or required chemotherapy for a solid tumour (group B). Eligible patients were randomized to receive either 500 mg vancomycin in 250 ml of 0.9% saline prior to catheter insertion followed by a further 500 mg infused via the established catheter, or the same regimen with 0.9% saline alone. In group A, there were 32 instances of CRS occurring in 20 of the 35 evaluable catheters (57%). Six catheters were removed because of CRS. No significant difference was found in the incidence of CRS between the two arms. Of the 37 evaluable catheters in group B, CRS occurred in 6 (16%), and none of the catheters required removal because of CRS. Again, no significant differences were found in the incidence of CRS between the patients given vancomycin or placebo. These findings indicate that the incidence of CRS is greater in patients who have more severe and prolonged immunosuppression and that vancomycin prophylaxis fails to reduce CRS in patients undergoing chemotherapy for malignant disease.

Adolescent↗

PubMedDate not supplied

In vitro activity of 43 antimicrobial agents tested against ampicillin-resistant enterococci and gram-positive species resistant to vancomycin.

A total of 57 strains of ampicillin-resistant and -susceptible enterococci representing 10 species and 23 strains of vancomycin-resistant Gram-positive bacteria (Leuconostoc and Pediococcus) were tested to determine their susceptibility to 43 antimicrobial agents by the reference broth microdilution method. The drug MICs for the ampicillin-resistant enterococci were generally similar to those of ampicillin-susceptible strains, that is, highly resistant to cephalosporins, moderately susceptible or resistant to quinolones, and susceptible to "glycopeptides." Some investigational quinolones (PD127391, sparfloxacin, WIN57273), minocycline, and rifampin were highly active. Vancomycin-resistant strains were usually resistant to other "glycopeptides," for which correlation coefficients of MICs ranged from 0.881 to 0.978, except ramoplanin (MICs, 0.008-0.5 micrograms/ml). Most isolates resistant to vancomycin were susceptible to the newer quinolones, penicillins, aminoglycosides, clindamycin, and erythromycin, but highly resistant to cephalosporins. Discrepancies between the MICs and MBCs for glycopeptides were noted (greater than or equal to 8-fold, MBC50/MIC50), but not for ramoplanin. The vancomycin disk test was in 96.1% absolute agreement by identifying resistant strains without contributing false-susceptible, very major error.

4-Quinolones↗

PubMedDate not supplied

Comparative in vitro activity of teicoplanin and vancomycin against United States teicoplanin clinical trial isolates of gram-positive cocci.

In this study, the in vitro activity of teicoplanin and vancomycin was directly compared against 503 Gram-positive cocci isolated during the U.S. teicoplanin clinical trials. Both antibiotics were equally active against oxacillin-sensitive Staphylococcus aureus, oxacillin-sensitive and oxacillin-resistant Staphylococcus epidermidis, and other coagulase-negative staphylococci, except Staphylococcus haemolyticus. Teicoplanin was fourfold more active than vancomycin against oxacillin-resistant S. aureus (MIC90, 0.5 vs. 2.0 micrograms/ml), whereas vancomycin was more active than teicoplanin (MIC90, 2.0 vs. 8.0 micrograms/ml) against oxacillin-resistant S. haemolyticus. Teicoplanin was two- to eightfold more active than vancomycin against the streptococci and enterococci tested.

Anti-Bacterial Agents↗

PubMedDate not supplied

Diffusion of teicoplanin and vancomycin in agar.

Teicoplanin, although more active than vancomycin [by minimum inhibitory concentration (MIC)], produces smaller inhibition zones in sensitivity testing with 30-microgram disks. Our data support the hypothesis that this is due to lower diffusion of teicoplanin in agar media. After 6 hr of incubation, approximately 70% of vancomycin, but only 20% of teicoplanin entered the agar from a paper disk charged with 30 micrograms of antibiotic. This is due to a difference between the diffusion coefficients: 0.47 mm2/hr for teicoplanin and 0.72 mm2/hr for vancomycin. With the methodology used in this work, it is possible to calculate the range of concentrations of the antibiotic occurring at times likely to include the critical time--the time when the inhibition zone is formed--of most strains at any given distance from the reservoir. One can thus estimate the breakpoint diameter for a given MIC breakpoint; for example, an MIC breakpoint of less than or equal to 4 micrograms/ml would correspond to a greater than or equal to 15-mm breakpoint diameter for vancomycin (30-microgram disk) and a greater than or equal to 13-mm breakpoint diameter for teicoplanin (30-microgram disk).

Agar↗

PubMed1996

Synthesis and in vitro antibacterial activity of spermidine-based mixed catechol- and hydroxamate-containing siderophore--vancomycin conjugates.

The first antibiotic conjugates of vancomycin (1) and siderophore analogues containing spermidine-based catechol ligands (conjugate 11) as well as mixed catechol and hydroxamate ligands (conjugate 13) are described. The design of the conjugates was based on the earlier observation that conjugation of siderophore components to beta-lactam antibiotics induced active iron transport-mediated drug delivery. The novel conjugates (11 and 13) were synthesized by selective acylation of the primary amino group of 1. Preliminary biological studies indicated that siderophore modified vancomycins lost some activity (4- to 16-fold) against Gram-positive bacteria relative to vancomycin itself, and were generally similar to vancomycin in activity against Gram-negative bacteria under iron-sufficient conditions. However, under iron-depleted conditions which mimic human serum, conjugate 11 displayed enhanced antibacterial activity against an antibiotic hypersensitive strain of Pseudomonas aeruginosa.

Anti-Bacterial Agents↗

PubMed2006

In vitro activity of fluoroquinolones, vancomycin, and gentamicin against methicillin-resistant Staphylococcus aureus ocular isolates.

PURPOSE: To determine the antibacterial activity of fluoroquinolones, vancomycin, and gentamicin against methicillin-resistant Staphylococcus aureus (MRSA) ocular surface isolates. DESIGN: Retrospective review. METHODS: MRSA isolates were obtained from 21 patients. The MIC(50) (mean inhibitory concentration)(microg/ml) values of 31 MRSA ocular surface isolates were determined for gatifloxacin, moxifloxacin, ciprofloxacin, ofloxacin, vancomycin, and gentamicin using the Etest (AB Biodisk, Solna, Sweden) or the VITEK system (bioMérieux, Inc, Durham, North Carolina, USA). Susceptibility data were interpreted based on criteria specified by the Clinical and Laboratory Standards Institute (CLSI). MAIN OUTCOME MEASURES: MIC(50) values in microg/ml and interpretation of susceptibility or resistance. RESULTS: In vitro resistance rates and median MIC(50) in microg/ml for the MRSA isolates were: gatifloxacin (71%, 8.0), moxifloxacin (68%, 8.0), ciprofloxacin (94%, 8.0), ofloxacin (94%, 8.0), vancomycin (0%, 1.0), and gentamicin (3%, 0.5). CONCLUSIONS: MRSA ocular isolates exhibited a relatively high rate of in vitro resistance to all fluoroquinolones tested, including the fourth generation. In contrast, MRSA isolates were found to be highly sensitive to vancomycin and gentamicin.

Anti-Bacterial Agents↗

PubMed2005

Clinical and economic outcomes of oral linezolid versus intravenous vancomycin in the treatment of MRSA-complicated, lower-extremity skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus.

BACKGROUND: Resistant bacteria often complicate the management of skin and soft tissue infections of the lower extremities. This open-label study compared oral linezolid and intravenous vancomycin for management of complicated skin and soft-tissue infections caused by methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Patients aged 18 years or older with proven MRSA-related complicated skin and soft-tissue infections requiring surgical intervention were randomized to receive oral linezolid (n=30) or intravenous vancomycin (n=30) for 7 to 21 days. Clinical and microbiological outcomes, duration of hospitalization and drug treatment, and outpatient charges were determined. RESULTS: Linezolid was associated with greater rates of clinical cure and improvement (P=.015), a 3-day shorter median length of stay (P=.003), and reduced outpatient charges (P<.001). Vancomycin therapy was associated with more treatment failures and subsequent lower-extremity amputations (P=.011). CONCLUSIONS: Clinical outcomes were significantly better with linezolid than with vancomycin. Additionally, linezolid was associated with reduced length of stay and outpatient charges.

Acetamides↗

PubMed2005

Vancomycin release behaviour from amorphous calcium polyphosphate matrices intended for osteomyelitis treatment.

Calcium polyphosphate (CPP) antibiotic delivery matrices were prepared using a unique processing technique involving the exposure of antibiotic-loaded CPP pastes to high humidity for 0, 5, or 24 h. After the designated gelling period, samples were dried for a minimum of 24 h. At several time points out to 130 h, the elution medium was monitored for vancomycin, Ca2+ ion and ortho and poly phosphate release levels. Vancomycin activity was also assessed after 1, 24 and 130 h, while solution 31P-NMR was used to monitor changes in chain length within a 24 hr gelled VCM disc throughout the elution process. The gelling and drying process significantly reduced the rate of vancomycin release during the initial 2-4 h of elution, while extending the effective antibiotic release period by an additional 80 h. The mild conditions associated with matrix fabrication readily allowed for vancomycin incorporation within an environment that did not disrupt antibiotic activity. Throughout the elution process, all sample groups experienced considerable swelling followed by some apparent bulk erosion. Phosphate chain lysis was clearly observed by the end of the elution period. Generally, no strong or consistent correlation existed between matrix degradation and antibiotic release for the treatment groups investigated. An ability to delay antibiotic release using CPPs in conjunction with this protocol supports further investigations into the potential of this matrix as a localized drug delivery system.

Anti-Bacterial Agents↗

PubMed2005

Rifampicin+ceftriaxone versus vancomycin+ceftriaxone in the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis in an experimental rabbit model.

This study was planned to compare the efficacy of ceftriaxone+vancomycin with ceftriaxone+rifampicin in a rabbit model of penicillin and cephalosporin-resistant Streptococcus pneumoniae meningitis. Meningitis was induced by intracisternal inoculation of S. pneumoniae. After 18 h of incubation, Group 1 was given saline solution (control group), whilst Groups 2 and 3 were given ceftriaxone+vancomycin and ceftriaxone+rifampicin, respectively. Cerebrospinal fluid bacterial concentrations were measured at 0, 2, 12, 14 and 24 h after therapy was initiated. In the control group, bacterial growth was present at all time points, whereas no growth was observed in either the ceftriaxone+vancomycin group or the ceftriaxone+rifampicin group after 2 h of therapy. Ceftriaxone+rifampicin was found to be as effective as ceftriaxone+vancomycin in the treatment of penicillin-resistant S. pneumoniae meningitis in experimental rabbit model.

Animals↗

PubMed2005

Vancomycin versus teicoplanin in the therapy of experimental methicillin-resistant Staphylococcus aureus (MRSA) meningitis.

The aim of this study was to compare the antibacterial activity of teicoplanin and vancomycin in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) meningitis using a rabbit meningitis model. The MRSA strain ATCC 43300 was used to infect the rabbits. The vancomycin group received 20 mg/kg vancomycin every 12h (q12h), the teicoplanin group received 6 mg/kg teicoplanin q12h and the control group did not receive any treatment. Drug levels were measured using a bioassay technique. Bacterial counts in the treatment groups were significantly lower (P<0.05) than those of the control group at 12 h and 24 h after treatment. When the treatment groups were compared, the bacterial counts after 12 h or 24 h of treatment were similar (P>0.05). These data suggest that the antibacterial activity of vancomycin and teicoplanin are similar in experimental MRSA meningitis of rabbits.

Animals↗