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PubMed1993

The vanB gene confers various levels of self-transferable resistance to vancomycin in enterococci.

Thirty-nine strains of Enterococcus faecium and Enterococcus faecalis resistant to vancomycin and susceptible to teicoplanin on disk susceptibility testing (phenotypic class B) were isolated in 15 hospitals in Europe and the United States. The MICs of vancomycin for these strains ranged from 4 to 1024 micrograms/mL. Part of the vancomycin resistance gene vanB from E. faecalis V583 hybridized with a single but variably sized HindIII-KpnI fragment of total DNA from all 39 strains. This indicates that a single class of resistance determinants accounts for the VanB phenotype. No hybridization was detected with DNA from intrinsically resistant Enterococcus gallinarum or Enterococcus casseliflavus. Hybridization with DNA from enterococcal strains susceptible to or with acquired resistance to vancomycin and teicoplanin was not observed. The genes conferring resistance to vancomycin were self-transferable to other Enterococcus strains in 14 of the 39 strains. It thus appears that vanB confers various levels of conjugative vancomycin resistance in enterococci.

Bacterial Proteins↗

PubMed1993

Comparative prophylactic efficacy of cefazolin and vancomycin in a guinea pig model of Staphylococcus aureus wound infection.

The increasing prevalence of methicillin-resistant Staphylococcus aureus as a wound pathogen in some institutions has prompted the use of vancomycin for surgical prophylaxis, although clinical data comparing vancomycin and cephalosporins are not available. A guinea pig model was used to compare the efficacy of vancomycin and cefazolin in preventing intermuscular abscess formation by 7 S. aureus strains. Both antibiotics were administered to achieve peak serum levels at the time of bacterial inoculation, and each remained > 1 micrograms/mL for a comparable duration. Vancomycin provided equivalent protection from infection by 1 methicillin-susceptible strain and significantly better protection against 4 methicillin-susceptible and both methicillin-resistant S. aureus strains. For most strains, the bacterial inoculum with a 50% probability of causing an abscess was 2 to 4 log10-fold higher with vancomycin than cefazolin prophylaxis. Prophylaxis with vancomycin is superior to cefazolin in preventing intermuscular infection by methicillin-susceptible and -resistant S. aureus.

Animals↗

PubMed1993

Triple combination penicillin-vancomycin-gentamicin for experimental endocarditis caused by a highly penicillin-and glycopeptide-resistant isolate of Enterococcus faecium.

A combination of low-dose penicillin (75,000 IU/kg twice daily [b.i.d.]) vancomycin (30 mg/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) has been shown to be as effective as a combination of high-dose penicillin (500,000 IU/kg b.i.d.) and gentamicin (6 mg/kg b.i.d.) in the treatment of rabbit endocarditis caused by an Enterococcus faecium strain moderately resistant to beta-lactams and highly resistant to glycopeptides. The same regimens were evaluated against an E. faecium strain highly resistant to both penicillin (MIC, 128 micrograms/mL) and vancomycin (MIC, 512 micrograms/mL). High doses of penicillin-gentamicin and vancomycin-gentamicin had no effect in in vitro killing-curve studies or in rabbits after treatment for 5 days. High doses of penicillin-vancomycin were only bacteriostatic in killing curves and provided a small reduction in the bacterial titers of the vegetations. In contrast, high-dose penicillin-vancomycin-gentamicin was bactericidal in vitro and highly effective in treating rabbits. However, the emergence of a bacterial subpopulation resistant to the synergistic effect of penicillin and vancomycin could reduce the clinical utility of this combination.

Animals↗

PubMed1985

Vancomycin toxicity: a prospective study.

A prospective study of 34 patients treated with 39 courses of intravenous vancomycin, was undertaken in order to assess toxicity. Six patients received vancomycin alone and 27 courses were associated with aminoglycoside administration either concurrently or within two weeks of the first dose of vancomycin. Hearing loss was slight and uncommon; patients were unaware of its occurrence. Tinnitus and dizziness was noted by two patients and resolved on withdrawal of vancomycin. Diminution of renal function was seen both during (7%) and after (9%) vancomycin therapy. A striking feature of these patients with renal deterioration was the severity of their underlying disease. No evidence of synergistic toxicity between vancomycin and aminoglycosides was seen.

Adolescent↗

PubMed1990

Pharmacokinetics of once daily intra-peritoneal aztreonam and vancomycin in the treatment of CAPD peritonitis.

The pharmacokinetics of aztreonam and vancomycin were studied in six adult patients who developed peritonitis during Continuous Ambulatory Peritoneal Dialysis. Aztreonam 3 g was added to the first exchange in each 24 h period with vancomycin 500 mg on the first day and 250 mg on each subsequent day (provided the pre-dose serum vancomycin concentration was less than 10 mg/l) for a total of ten days. Aztreonam and vancomycin concentrations were measured in the serum and dialysate at 1, 2, 6, 12, 18 and 24 h after the initial dose and pre-dose on days 5 and 10. By the end of the ten day study all patients had recovered clinically and had a normal dialysate. For aztreonam, the mean peak serum concentration was 84.3 mg/l (range 59.6-102.8), the mean 24 h pre-dose serum concentration was 23.0 mg/l (range 8.6-39.2) and the mean 24 h pre-dose dialysate concentration was 15.5 mg/l (range 5.0-32.0). For vancomycin, the mean peak serum concentration was 10.2 mg/l (range 8.1-12.6), the mean 24 h pre-dose concentration was 5.5 mg/l (range 3.6-6.4), and the mean 24 h pre-dose dialysate concentration was 3.4 mg/l (range 2.4-4.6). In the treatment of CAPD peritonitis, once daily intra-peritoneal administration of aztreonam 3 g with vancomycin 500 mg initially and 250 mg on subsequent days (serum concentrations permitting) provides concentrations of antibiotic in both the serum and dialysate throughout the 24 h period in excess of the inhibitory concentrations of those organisms most frequently encountered in this condition.

Aztreonam↗

PubMed1993

Nephrotoxicity of vancomycin and aminoglycoside therapy separately and in combination.

There is conflict by evidence as to whether therapy with vancomycin plus an aminoglycoside is more nephrotoxic than therapy with either agent alone. Here we report the results of a prospective, non-randomized, open-label study of the incidence of nephrotoxicity in elderly patients who received vancomycin alone (32 patients) or an aminoglycoside alone (67 patients) or in combination (37 patients). The mean (95% confidence limits) incidence of nephrotoxicity, defined as an increase of > or = 44.2 mumol/L in the serum creatinine, was 19% (5-32%) in patients receiving vancomycin alone, 24% (10-38%) in patients receiving vancomycin plus an aminoglycoside, and 12% (4-20%) in patients receiving an aminoglycoside alone (P > 0.05 for all comparisons). The corresponding absolute increases of the serum creatine were 20.3 +/- 23.0 mumol/L (-24.8 to +65.4 mumol/L), 37.1 +/- 53.0 mumol/L (-67.2 to +140.4 mumol/L), and 22.1 +/- 31.8 mumol/L (-40.7 to +94.6 mumol/L). The absolute increase was significantly greater (P < 0.05) in patients receiving vancomycin plus an aminoglycoside than in patients receiving an aminoglycoside alone. A meta-analysis of seven previously published studies combined with our data revealed that the incidence of nephrotoxicity associated with combination therapy is 13.3 +/- 3.1% (7.3-19.4%) greater than therapy with vancomycin alone (P < 0.01) and 4.3 +/- 1.4% (1.6-7.0%) greater than therapy with an aminoglycoside alone (P < 0.05). The clinical relevance of this finding may be limited in that the mean duration of antimicrobial therapy in three of the studies was greater than 21 days.

Aged↗

PubMed1994

A comparative assessment of vancomycin-associated nephrotoxicity in the young versus the elderly hospitalized patient.

The incidence of vancomycin-associated nephrotoxicity was determined in a younger (age < 60 y) versus elderly (age > or = 60 y) hospitalized adult population to identify associated drug- and nondrug-related risk factors. Nephrotoxicity was defined as an acute increase in serum creatinine of > or = 44.2 mumol/L if baseline serum creatinine was < or = 221 mumol/L or an increase in serum creatinine of > or = 88.4 mumol/L if baseline serum creatinine > 221 mumol/L. A total of 289 patients, 141 younger (mean age, +/- S.D. 37.9 +/- 12.4 y) and 148 elderly (73.6 +/- 8.5 years), was retrospectively reviewed. Nephrotoxicity occurred in 7.8% younger vs 18.9% elderly patients (P = 0.003). Using multivariate logistic regression models for the pooled patient population, concurrent loop diuretic use was significantly associated with vancomycin-associated nephrotoxicity (relative risk (R.R.) = 5.06); for the younger population, only concurrent amphotericin B use was significantly associated with vancomycin-associated nephrotoxicity (R.R. = 6.65); and for the elderly population, only concurrent loop diuretic use was significantly associated with vancomycin-associated nephrotoxicity (R.R. = 9.70). These data suggest that elderly patients are at significantly greater risk of vancomycin-associated nephrotoxicity than are younger patients. However, because age was not a significant risk factor for nephrotoxicity in comparing the pooled vancomycin-associated nephrotoxicity group compared to the non-nephrotoxicity group, the differences observed between age groups probably reflect differences in risk factor prevalence.

Adolescent↗

PubMed1995

Characterization of vancomycin resistance in Enterococcus durans.

During investigation of an outbreak of vancomycin resistant Enterococcus faecium in a paediatric hospital, an isolate of Enterococcus durans resistant to vancomycin, teicoplanin, ampicillin and highly resistant to gentamicin and streptomycin was found in the stools of a patient also colonized with a strain of E. faecium with the same resistance pattern. Minimal inhibitory concentrations of vancomycin and teicoplanin were 512 and 64 mg/mL, respectively. Resistance to vancomycin as well as high-level resistance to gentamicin was transferable to an E. faecium recipient strain. Both multiresistant E. faecium and E. durans isolates as well as the transconjugant presented only one plasmid. The vanA gene was detected and localized to the high molecular weight plasmid by DNA hybridization with a vanA gene probe. Growth in vancomycin resulted in induction of an approximately 40 kDa protein visible in membrane preparations from these cells. Genetic linkage between vancomycin and gentamicin resistance genes in the same plasmid is suggested.

Anti-Bacterial Agents↗

PubMed1998

Increase in glutamine-non-amidated muropeptides in the peptidoglycan of vancomycin-resistant Staphylococcus aureus strain Mu50.

The peptidoglycan compositions of vancomycin-resistant Staphylococcus aureus (VRSA) strain Mu50 (MIC 8 mg/L) and hetero-VRSA strain Mu3 (MIC 3 mg/L) were compared in order to understand the mechanism of vancomycin resistance. As compared with Mu3, the cell wall of Mu50 had increased amounts of glutamine-non-amidated muropeptides and decreased cross-linking of peptidoglycan with a greatly decreased dimer/monomer ratio of muropeptides. In agreement with this observation, the peptidoglycan of Mu50 bound 1.4 times more vancomycin than that of Mu3. The increase in non-amidated muropeptides and the reduced cross-linking of the cell-wall peptidoglycan may contribute to the vancomycin resistance by increasing the consumption of vancomycin by the pre-existing cell wall of Mu50 and reducing the amount of vancomycin reaching the cytoplasmic membrane where the vital targets of the antibiotic are situated.

Amino Acids↗

PubMed2003

Comparative efficacy of daptomycin and vancomycin in the therapy of experimental foreign body infection due to Staphylococcus aureus.

The therapeutic activity of daptomycin was compared with that of vancomycin in a rat model of subcutaneously implanted tissue cages chronically infected with strain Rev1, a spontaneous methicillin-susceptible revertant of the methicillin-resistant Staphylococcus aureus strain MRGR3, showing equivalent virulence to its parent. The MIC and MBC of daptomycin (in Mueller-Hinton broth supplemented with 50 mg/L Ca2+) or vancomycin for strain Rev1 were 1-2 and 2-4 or 1 and 2 mg/L, respectively. In vitro elimination of strain Rev1 in the presence of 50% tissue cage fluid was more rapid with daptomycin 4 mg/L compared with vancomycin. After 2 weeks of infection, viable counts of strain Rev1 averaged 6.49 log10 cfu/mL of tissue cage fluid (n = 87). Intraperitoneal administration of daptomycin 30 mg/kg once daily, or vancomycin 50 mg/kg twice daily, produced antibiotic levels continuously above MBC. After 7 days of therapy with daptomycin or vancomycin, mean +/- S.E.M. counts of Rev1 decreased (P < 0.05) by 1.11 +/- 0.25 (n = 28) or 0.80 +/- 0.31 (n = 35) log10 cfu/mL, respectively, compared with cages of untreated animals, but were not significantly different from each other. In daptomycin-treated rats, three cages yielded subpopulations with reduced susceptibility to daptomycin. In conclusion, a low dose regimen of daptomycin was at least equivalent to vancomycin against chronic foreign body infections due to S. aureus. Drug dosage should be adapted to obtain inflammatory fluid levels of daptomycin minimizing emergence of resistant subpopulations.

Animals↗

PubMed2003

Tolerance to vancomycin in a multiresistant, Colombian isolate of Streptococcus pneumoniae.

The present study was set up to determine vancomycin tolerance in Colombian, multiresistant, invasive, paediatric isolates of Streptococcus pneumoniae. A total of seven clinical isolates of penicillin-resistant S. pneumoniae, serotype 14, corresponding to the Spain(9v)-3 clone, were studied. Isolates were grown in Todd Hewitt broth at 37 degrees C. Growth (A(595)) and cell viability (cfu/ml) were monitored hourly for 4 h after addition of vancomycin at 10x MIC. S. pneumoniae R6 was used as a control for growth. For R6, the mean decrease in A(595) and cell viability (log(10) cfu/ml) after 4 h of vancomycin treatment (in 10 independent experiments) was 95.1% and 4.2 log(10), respectively. Six out of seven isolates exhibited similar behaviour. In contrast, for S. pneumoniae E239, the mean decrease in A(595) and cell viability was 48.5% and 2.2 log(10) after 4 h of vancomycin exposure, which suggested the presence of tolerance to vancomycin. The emergence of vancomycin-tolerant strains is of great concern in Colombia, owing to the alarming increase in resistance to penicillin.

Colombia↗

PubMed2005

Antibacterial activity of linezolid and vancomycin in an in vitro pharmacodynamic model of gram-positive catheter-related bacteraemia.

OBJECTIVES: The aim of this study was to compare the activity of linezolid and vancomycin in an in vitro pharmacodynamic model to assess potential differences in activity against biofilm-embedded organisms. METHODS: Single-lumen central venous catheters colonized with biofilm-embedded Staphylococcus aureus, Staphylococcus epidermidis or vancomycin-resistant Enterococcus faecium (VRE) were treated with simulated clinical dosing regimens of linezolid 600 mg every 12 h or vancomycin 1 g every 12 h in a one-compartment in vitro pharmacodynamic model. Quantitative cultures were sampled through the catheter and peripheral ports over 48 h to dynamically assess changes in the burden of catheter colonization and organism seeding, respectively. At 24 and 48 h catheters were removed, sonicated and cultured for adherent organisms. RESULTS: Both linezolid and vancomycin suppressed bacterial growth on the catheter and release of S. aureus and S. epidermidis into the model compared with controls (P < 0.05), while linezolid also suppressed counts compared with control and vancomycin versus VRE. Neither agent completely eradicated bacterial colonization of the catheters. MICs for the isolates recovered from the model did not increase over time with linezolid or vancomycin exposure. CONCLUSIONS: Lack of activity against biofilm-embedded organisms appeared to be the primary reason for microbiological failure of both drugs in the model.

Acetamides↗

PubMed2005

Varying linezolid susceptibility of vancomycin-resistant Enterococcus faecium isolates during therapy: a case report.

OBJECTIVES: Linezolid is an oxazolidinone antibiotic used in the treatment of infections caused by vancomycin-resistant enterococci. Resistance to linezolid has been associated with a G2576U mutation in domain V of the 23S rRNA. PATIENT AND METHODS: We present clinical details and susceptibility data from multiple Enterococcus faecium strains isolated from a liver transplant patient over 13 months. MICs of linezolid, vancomycin and quinupristin/dalfopristin were determined using Etest. Molecular typing was performed by pulsed-field gel electrophoresis. Domain V of the 23S rRNA gene in the vancomycin-resistant Enterococcus faecium was amplified. Linezolid concentrations were analysed by HPLC. RESULTS: We report the emergence of resistance to linezolid in a vancomycin-resistant Enterococcus faecium during linezolid treatment. After discontinuation of the linezolid therapy, the isolate reverted to susceptibility. However, after re-administration of linezolid the vancomycin-resistant Enterococcus faecium became resistant to linezolid again. The isolates that were resistant to linezolid had a G2576T mutation in their 23S rDNA. CONCLUSION: We describe a clinical case that shows the shift of a vancomycin-resistant Enterococcus faecium from linezolid resistance to susceptibility and then back to resistance again related to linezolid therapy.

Acetamides↗

PubMed2006

Evaluation of fosfomycin alone and in combination with ceftriaxone or vancomycin in an experimental model of meningitis caused by two strains of cephalosporin-resistant Streptococcus pneumoniae.

OBJECTIVES: To study the in vitro and in vivo efficacy of fosfomycin, alone and in combination with ceftriaxone or vancomycin, against two strains of Streptococcus pneumoniae: HUB 2349 (fosfomycin and ceftriaxone, MICs 16 and 2 mg/L) and ATCC 51916 (MICs 4 and 32 mg/L). METHODS: Pharmacokinetics/pharmacodynamics data were collected from the study of eight infected animals after a single intravenous dose of 300 mg/kg of fosfomycin. Time-kill curves were plotted using CSF antibiotic concentrations achievable clinically. In the rabbit model, we studied the efficacy and effects on inflammation of treatment with fosfomycin 1200 mg/kg/day, ceftriaxone 100 mg/kg/day and vancomycin 30 mg/kg/day, over 26 h. RESULTS: Fosfomycin peak level in serum was 324.48 +/- 102.1 mg/L at 0.5 h; CSF penetration was 49.2%. Time-kill curves showed that fosfomycin was bactericidal against the ATCC 51916 strain and that the addition of fosfomycin to ceftriaxone or vancomycin was synergic against the HUB 2349 strain. Resistance to fosfomycin was detected both when fosfomycin was studied alone and in combination. In the rabbit model, fosfomycin showed bactericidal activity only against the ATCC 51916 strain. Combinations of fosfomycin with ceftriaxone or vancomycin were bactericidal against both strains; they improved efficacy and decreased CSF inflammatory parameters over monotherapies, without showing statistical differences in comparison with the combination of ceftriaxone and vancomycin. CONCLUSIONS: Fosfomycin in combination with ceftriaxone or vancomycin appeared to be effective for the treatment of experimental cephalosporin-resistant pneumococcal meningitis. These combinations are possible alternatives in cases of allergy or intolerance to first-line drugs or in rare meningitis caused by highly cephalosporin-resistant pneumococci.

Animals↗

PubMedDate not supplied

The influence of serum albumin and alpha 1-acid glycoprotein on vancomycin protein binding in patients with burn injuries.

Ten patients with burn injuries (mean total body surface area burn = 29% +/- 16) were studied at various points in the course of their burn therapy. Alpha 1-Acid glycoprotein, albumin, and vancomycin concentrations were determined with either a trough or peak vancomycin quantitative determination. Alpha 1-Acid glycoprotein concentrations ranged from 125 to 333 mg/dl and albumin concentrations ranged from 1.7 to 4.2 gm/dl. Vancomycin protein binding, as determined by ultrafiltration, averaged 29% +/- 6%. There was a strong (r = 0.92) relationship between percent protein-bound vancomycin and albumin. There was a poor statistical relationship between percent protein-bound vancomycin and alpha 1-acid glycoprotein (r = 0.28). Alpha 1-Acid glycoprotein appeared to have virtually no effect on the protein-binding characteristics of vancomycin over the range of concentrations studied.

Adult↗

PubMed1999

Clinical, demographic, and immunohistologic features of vancomycin-induced linear IgA bullous disease of the skin. Report of 2 cases and review of the literature.

Administration of intravenous vancomycin has been associated with the development of linear IgA bullous disease (LABD). In contrast to the idiopathic variant, vancomycin-induced LABD (VILABD) appears to be more transient and to be associated with lower morbidity. The characteristics of this entity remain undefined. Our analysis of clinical, demographic, and immunopathologic features of 2 new and 14 previously reported patients with VILABD reveals that VILABD is clinically and immunopathologically indistinguishable from its idiopathic variant. A variety of premorbid conditions and concomitant medications were observed, none of which was consistently associated with the development of VILABD. VILABD occurs independently of vancomycin trough levels, resolves promptly upon discontinuation of vancomycin, and recurs more severely and with shorter onset latency with vancomycin rechallenge. This entity should be recognized as 1 of the adverse cutaneous effects of intravenous vancomycin, and warrants prompt diagnosis through direct immunofluorescence skin examination.

Adult↗

PubMed1995

Influence of malignancy on the pharmacokinetics of vancomycin in infants and children.

This prospective, controlled study evaluates the influence of malignancy on the pharmacokinetics and dosage requirements of vancomycin in 33 infants and children with cancer (age 5.72 +/- 4.11 years, mean +/- SD) compared with 31 patients without cancer (age 4.18 +/- 5.10 years) using a two-compartment Bayesian pharmacokinetic program. Patients in the malignancy group required a vancomycin dosage regimen of 71.5 +/- 13.9 mg/kg/day to attain a mean peak serum vancomycin concentration (SVC) of 22.38 +/- 4.54 mg/liter and a mean trough SVC of 6.84 +/- 2.78 mg/liter. Patients without cancer in the control group required a mean vancomycin dosage regimen of 50.2 +/- 13.0 mg/kg/day to attain a mean peak SVC of 21.70 +/- 6.70 mg/liter and a mean trough SVC of 8.05 +/- 3.01 mg/liter. Comparative analysis of pharmacokinetic data revealed an increase in vancomycin clearance (0.149 +/- 0.028 liter/hour/kg) in the malignancy group as compared with that (0.114 +/- 0.031 liter/hour/kg) in the control group. There were no significant differences with respect to the mean values of volume of distribution between two groups (0.638 +/- 0.079 liter/kg vs. 0.618 +/- 0.102 liter/kg). Analysis of the predictive performance of the Bayesian program indicated that final sets of peak and trough SVCs were predicted with minimal bias and accurate precision in both study groups. This study showed that the presence of malignancy in infants and children increased vancomycin clearance resulting in larger dosage requirements.

Anti-Bacterial Agents↗

PubMed1998

Selective use of vancomycin to prevent coagulase-negative staphylococcal nosocomial bacteremia in high risk very low birth weight infants.

OBJECTIVE: To determine whether vancomycin added to parental nutrition (PN) fluids could prevent nosocomial infections in very low birth weight newborns and which infants would benefit most from prophylaxis. DESIGN: Double blind, randomized controlled study. SETTING AND STUDY POPULATION: Very low birth weight infants receiving PN in a tertiary neonatal intensive care unit. METHODS: Thirty-eight infants with and without central vascular catheters were randomized to receive no medication or 25 microg/ml vancomycin added to PN for the duration of the infant's PN requirements. RESULTS: The addition of 25 microg/ml vancomycin to PN prevented bacteremia in very low birth weight infants receiving PN. There was a significant reduction in the number of coagulase-negative staphylococcal (CONS) bacteremias (defined as isolation of the same organism from two positive blood cultures) during PN (5 vs. 0; P = 0.037) as well as the total number of bacteremias and fungemias (9 vs. 1; P = 0.036). The total number of hospital days (108 +/- 13 vs. 76 +/- 6; P = 0.039) were reduced in infants receiving vancomycin. Infants with birth weights of < 1000 g who received corticosteroids for treatment of chronic lung disease benefitted most from treatment. No vancomycin-resistant strains of CONS or enterococci were detected during the study period. CONCLUSIONS: Prophylactic treatment with vancomycin effectively prevented CONS bacteremia under the conditions of the study. Its use was most effective in infants with birth weights of <1000 g.

Anti-Bacterial Agents↗