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PubMed1980

Single-dose kinetics of intravenous vancomycin.

The pharmacokinetic properties of intravenously administered vancomycin were studied in four healthy volunteers. Reversible adverse effects (flushing, tachycardia, pruritus) occurred in two subjects who received high-dose rapid intravenous infusions. Distribution of vancomycin proceeded as a biphasic process in all four subjects. The initial distribution half-life (t1/2 alpha) was less than 8 minutes in all cases, with intermediate half-lives (t1/2 pi) varying from 0.43 to 1.48 hour and elimination half-lives (t1/2 beta) varying from 4.7 to 11.2 hours. Vancomycin clearance was less than creatinine clearance, probably because of serum protein binding, which was determined to be 55 per cent.

Adult↗
PubMedDate not supplied

A simplified dosing method for initiating vancomycin therapy.

Vancomycin dosing regimens should be individualized for each patient. The routine use of standard doses 500 mg every 6 hours or 1.0 g every 12 hours regardless of patients' age, weight or kidney function is no longer appropriate. A simplified method for initiating vancomycin therapy was developed and evaluated prospectively in 30 patients. Average doses of 8.3 +/- 0.6 mg/kg lean body weight (rounded to the nearest 50 mg) were administered to patients with varying degrees of renal function (estimated creatinine clearances 19-113 ml/min). The dosing interval was predicted by the patient's estimated creatinine clearance. Our simplified schedule resulted in desired serum levels and required no modification in 25 of 30 patients. Only slight dosage changes were needed in the remaining five patients. Mean peak and trough serum concentrations of vancomycin were 26.9 +/- 5.8 micrograms/ml (range 18.8-39.7 micrograms/ml) and 7.7 +/- 2.0 micrograms/ml (range 4.5-11.8 micrograms/ml) respectively. Our regimen is practical and simple and requires limited patient information.

Adult↗
PubMed1987

Evaluation of a new vancomycin dosing method.

Thirty-one patients who were prescribed vancomycin therapy at our institution since January 1, 1986, were dosed using the guidelines as described by Lake and Peterson. Peak and trough vancomycin serum concentrations were measured at steady state: 24 (77%) peak serum concentrations were within the range of 20-30 mg/L, and 24 (77%) trough serum concentrations were within the range of 5-10 mg/L. We have found that the method of Lake and Peterson is satisfactory for initiating vancomycin therapy in most patients. Some, however, may not achieve optimal serum concentrations using these guidelines alone, and their regimens may have to be adjusted based upon actual serum concentration data.

Adolescent↗
PubMedDate not supplied

Effect of human serum on killing activity of vancomycin and teicoplanin against Staphylococcus aureus.

STUDY OBJECTIVE: To investigate the effects of pooled human serum (PHS) on the killing activity of vancomycin and teicoplanin against two isolates of Staphylococcus aureus from patients treated for endocarditis. DESIGN: An in vitro assessment of antibiotic susceptibility and killing rates. SETTING: An urban university teaching hospital. PATIENTS: Pooled human serum from patients treated for endocarditis. INTERVENTIONS: Two clinical isolates of Staphylococcus aureus were obtained from patients treated for endocarditis. Media consisted of cation-supplemented Mueller-Hinton broth alone and in 1:1 dilutions with PHS, 2-hour heat-inactivated PHS (HI-PHS), ultrafiltrate (UF), and 2-hour heat-inactivated ultrafiltrate (HI-UF). Heat inactivation of PHS and UF was accomplished by treatment at 56 degrees C for 2 hours. MEASUREMENTS AND MAIN RESULTS: Killing curves with vancomycin and teicoplanin were performed using drug concentrations of 45 micrograms/ml and a starting inoculum of approximately 1 x 10(6) colony-forming units (cfu)/ml. Bactericidal rates (-log cfu/ml/hr) were calculated from the slope of the killing curves over 0-12 hours (mean 3-8 replicates). CONCLUSIONS: The killing activity of vancomycin in PHS and HI-PHS against both isolates was significantly greater than all other media tested (p < 0.0001). Ultrafiltrate tended to reverse this enhancement effect. Addition of PHS or UF did not enhance teicoplanin's killing activity against either isolate. Further investigations in our laboratory will determine if the factor is antibiotic class or organism specific.

Blood Bactericidal Activity↗
PubMed2001

Vancomycin, teicoplanin, and ramoplanin: synthetic and mechanistic studies.

Vancomycin, teicoplanin, and ramoplanin are potent glycopeptide antibiotics that act by inhibiting bacterial cell wall biosynthesis. The former are used clinically as the antibiotics of last resort for the treatment of methicillin-resistant Staphylococcus aureus and the latter is a promising new antibiotic that is not susceptible to the emerging bacterial resistance to vancomycin and teicoplanin. A summary of our recent total synthesis of the vancomycin aglycon, our first and second generation total syntheses of the teicoplanin aglycon, and our progress on the total synthesis of the ramoplanins is presented. This work lays the foundation for ongoing structure-function studies on the antibiotics that may clarify or define their site and mechanism of action leading to the development of improved or reengineered antibiotics.

Anti-Bacterial Agents↗
PubMed2002

Salt resistance and synergistic effect with vancomycin of alpha-helical antimicrobial peptide P18.

P18 (KWKLFKKIPKFLHLAKKF-NH(2)) is an alpha-helical antimicrobial peptide designed from a cecropin A-magainin 2 hybrid. In this study, P18 was found to show strong antimicrobial activity against several antibiotic-resistant bacterial and fungal strains. Both the salt resistance on antimicrobial activity and the synergistic effect with clinically used antibiotic agents are critical factors in developing effective peptide antibiotic drugs. For this reason, we investigated the salt resistance of P18 to antagonism by NaCl, CaCl(2), and MgCl(2) on antimicrobial activity and the synergistic effect of P18 with vancomycin against vancomycin-resistant Enterococcus faecium (VREF). Compared to magainin 2, P18 showed strong resistance on antimicrobial activity against bacterial strains and C. albicans under high NaCl concentrations of 100-200 mM. In addition, P18 displayed much greater salt resistance on antibacterial activity against Gram-negative bacteria at the physiological or elevated concentrations of CaCl(2) and MgCl(2) than magainin 2. Furthermore, the combination study revealed that P18 has a relatively effective synergistic effect with vancomycin against VREF. Thus, these results support that P18 may prove to be a salt-resistant antibiotic peptide potentially useful in the treatment of cystic fibrosis patients as well as a valuable adjuvant for antimicrobial chemotherapy.

Adjuvants, Pharmaceutic↗
PubMed1993

Use of vancomycin in vitrectomy infusion solution and evaluation of retinal toxicity.

The retinal toxicity of vancomycin in infusion solution used in vitrectomy and lensectomy was investigated in rabbit eyes by means of electroretinography and histologic study (light microscopy). Concentrations of 8 micrograms/ml, 16 micrograms/ml, and 32 micrograms/ml of vancomycin in balanced salt solution caused no abnormal ERG or histologic changes. However, ERG amplitude depression and abnormal histologic changes occurred when the concentration of 100 micrograms/ml of vancomycin was used.

Animals↗
PubMed1989

Clostridium difficile colitis secondary to intravenous vancomycin.

Nearly every known antibiotic has been implicated as a cause of Clostridium difficile colitis. We report the first case resulting from monotherapy with intravenous vancomycin. The patient was on chronic hemodialysis and was treated with intravenous vancomycin for presumed cervical osteomyelitis. After 29 days of therapy he developed abdominal pain and diarrhea and his stool was found to contain both C. difficile and cytotoxin. The patient responded with symptomatic and microbiological recovery to withdrawal of the drug and treatment with oral metronidazole. The prolonged elevation of serum vancomycin levels in patients with renal failure may predispose them to the development of C. difficile colitis.

Aged↗
PubMed1996

Selective medium for screening for vancomycin-resistant enterococci in faeces.

Infections caused by vancomycin-resistant enterococci (VRE) are becoming increasingly prevalent throughout the world. Control measures include detection and isolation of carriers of VRE. A selective medium to detect faecal carriage of VRE is described. The medium has a high productivity ratio (90.4%) for VRE with VanA resistance phenotype, a moderate productivity ratio (79.2%) for VRE with VanB resistance phenotype, and a relatively low productivity ratio (65.5%) for VRE with VanC resistance phenotype. There was no breakthrough of vancomycin-susceptible enterococci. The medium selected the growth of all three types of VRE, which were used to spike faecal specimens. In a limited clinical trial, six faecal specimens of carriers and contacts were screened using the selective medium. Vancomycin-resistant enterococci (Enterococcus faecalis, VanA phenotype) were detected in four of the specimens. In all four specimens the growth of VRE was nearly pure and easily identifiable.

Anti-Bacterial Agents↗
PubMedDate not supplied

Three-step empiric treatment for severely neutropenic patients with fever: ceftazidime--vancomycin--amphotericin B.

In a prospective study 50 febrile episodes in severely neutropenic patients (neutrophils less than 500/mm3) were empirically treated with ceftazidime monotherapy. If no response was seen after 48 h, vancomycin was added. After another 72 h period, patients with persisting fever additionally received amphotericin B. In 29 episodes (58%) patients became afebrile with ceftazidime monotherapy. Another seven patients (14%) responded to the addition of vancomycin and five patients (10%) needed amphotericin B to become afebrile. A success of the study drugs without modification was seen in 40 episodes (80%), success with modification in three episodes (6%) and failure in six episodes (12%). One patient died of myocardial infarction. No other death occurred during the two-week observation period after entering the study. Though there were two gram-negative isolates resistant to ceftazidime, these patients were successfully treated with modification. It is concluded that the response-adapted additive sequence of ceftazidime, vancomycin and amphotericin B is an effective approach towards febrile episodes in severely neutropenic patients.

Adolescent↗
PubMed1991

In vitro activity of flomoxef and cefazolin in combination with vancomycin.

207 clinical isolates from strains of patients from the University Children's Hospital of Kiel were investigated for their in vitro activity with the agar dilution method against flomoxef and cefazolin (alone and partially in combination with vancomycin). Staphylococci were also tested with other cephalosporins (cefoxitin, cefamandole, cefotaxime, cefotetan and latamoxef). Flomoxef and cefazolin always acted more vigorously on staphylococci than the other cephalosporins. Resistance of Staphylococcus aureus strains against flomoxef and cefazolin did not occur but was found in 15 and 5 of 98 Staphylococcus epidermidis strains, respectively. Enterococcus faecalis strains were always resistant against both drugs; Streptococcus faecium strains were only moderately sensitive. Combined testing of flomoxef or cefazolin with vancomycin showed synergism in almost all staphylococcal strains. Synergism was stronger when S. epidermidis strains were only weakly sensitive to or resistant against flomoxef and cefazolin in comparison to highly sensitive strains. Flomoxef (or cefazolin) acted synergistically in combination with vancomycin on E. faecalis and S. faecium with the exception of two strains of E. faecalis which showed an additive effect of both drugs.

Cefazolin↗
PubMedDate not supplied

Enhanced killing of methicillin-resistant Staphylococcus aureus in human macrophages by liposome-entrapped vancomycin and teicoplanin.

The antibacterial effects of liposomal vancomycin and teicoplanin against intracellular methicillin-resistant Staphylococcus aureus (MRSA) were evaluated using a macrophage infection model. Human blood-derived monocytes were cultured for 7 days to obtain adherent macrophages. Uptake of each drug by macrophages was markedly enhanced by liposomal encapsulation. Following phagocytosis and removal of residual extracellular MRSA, the infected macrophages were exposed to clinically achievable concentrations of teicoplanin and vancomycin. The free (untrapped) and liposome-entrapped forms of each drug were used at the same concentration. The number of intracellular surviving bacteria was determined by colony counts after lysis of the macrophages at different time intervals following drug treatment. Intracellular antimicrobial effect of each drug was significantly (p < 0.001) increased by entrapment in liposomes. Also, the efficacies of the free and liposomal forms of both drugs were correspondingly comparable (p > 0.05). It is, therefore, concluded that liposomal encapsulation of vancomycin and teicoplanin results in an increased availability of the antibiotics for efficient elimination of intracellular MRSA infection.

Biological Availability↗
PubMed1990

Vancomycin-aminoglycoside combinations in therapy of endocarditis caused by Enterococcus species and Streptococcus bovis.

Between 1974 and 1986, five patients with enterococcal endocarditis (three of whom had a prosthetic valve) and three patients with Streptococcus bovis endocarditis were treated with a combination of vancomycin and an aminoglycoside for a mean duration of 40 days. This regimen was prescribed because of allergy to beta-lactam (n = 7) and/or failure of previous treatment (n = 4). Three of the eight patients underwent valve replacement. In the six evaluable patients cure was achieved with the vancomycin-aminoglycoside combination. An increase of the creatinine serum levels was observed in all cases but it was never necessary to discontinue treatment, adjustment of the vancomycin and aminoglycoside dosage according to the serum and/or serum creatinine levels allowing continuation of therapy.

Adult↗
PubMed1989

Comparative in vitro activity of daptomycin (LY146032) and vancomycin against gram-positive cocci determined using a pharmacokinetic model.

The activity of daptomycin (LY146032) and vancomycin was compared for methicillin-sensitive and methicillin-resistant (MRSA) strains of Staphylococcus aureus and for Enterococcus faecalis, using a semi-automated model that allows examination of time-kill curves with diminishing drug concentrations, thus reflecting in vivo pharmacokinetics. Exposure to daptomycin resulted in rapid killing of all strains of staphylococci and Enterococcus faecalis tested. Methicillin-sensitive staphylococcal strains appeared marginally more susceptible than MRSA. By contrast, the activity of vancomycin appeared much reduced. For all strains, greater than 90% kill was not observed within 24 h. Enterococcus faecalis was uniformly less susceptible to both agents than were staphylococci. The results suggest that despite similar values for MICs, the activity of daptomycin against strains of Staphylococcus aureus and Enterococcus faecalis is comparable to and may exceed that of vancomycin, although the significance of such differences is uncertain.

Daptomycin↗
PubMed1984

The activity of vancomycin and teicoplanin alone and in combination with gentamicin or ampicillin against Streptococcus faecalis.

The in vitro activities of vancomycin and teicoplanin against 56 strains of Streptococcus faecalis were compared. Killing curves showed that vancomycin and teicoplanin were bacteriostatic and that synergy was achieved when each was combined with gentamicin. The bactericidal activity displayed by 4 mg/l of ampicillin against Streptococcus faecalis was antagonized by 4 mg/l of vancomycin and 0.5 mg/l of teicoplanin respectively.

Ampicillin↗
PubMed2004

[MRSA-infections-treatment with intraoperatively produced gentamycin-vancomycin PMMA beads].

INTRODUCTION: We present gentamicin-vancomycin-impregnated beads that can be produced intraoperatively in moulds and demonstrated their successful use in ten cases of problematic Methicillin-resistant Staphylococcus aureus (MRSA) infection. METHODS: To produce the antibiotically loaded PMMA beads, a two-part mould of polyoxymethylene was used. The mixture of PMMA and antibiotic is poured into the mould halves, and during polymerisation the halves bond together. The in vivo antibiotic concentrations of wound secretion from the redon drainage were measured by fluorescence-polarisation immunoassay, and a concentration/time function was determined. The PMMA beads (2 g of vancomycin plus 0.5 g of gentamicin plus 40 g of PMMA) were implanted in ten patients aged 41-76 years. RESULTS: In all ten patients, the infection was cured (follow-up 15 months). CONCLUSION: The combination of gentamicin and vancomycin in the PMMA of standardised beads represents a good alternative in the treatment of MRSA infections. Understanding of the mechanism of antibiotic release from PMMA allows differentiated dosing during systemic application.

Adult↗
PubMed2001

Outbreak of acute renal failure due to cefodizime-vancomycin association in a heart surgery unit.

OBJECTIVE: To describe an outbreak of acute renal failure (ARF) occurring in a group of patients undergoing open-heart surgery, simultaneously to a change in perioperative antibiotic prophylaxis. DESIGN: Case series. SETTING: A nine-bed heart surgery intensive care unit, serving a 1,300-bed University teaching hospital. PATIENTS: Thirty-two patients undergoing open-heart surgery during an 11-day period, when the preoperative surgical prophylaxis protocol had been changed from the usual antibiotic association of ceftriaxone + vancomycin to cefodizime + vancomycin. RESULTS: ARF occurred in 16 of the 32 (50%) patients exposed to the new antibiotic prophylaxis regimen; seven patients had oliguric ARF, and nine patients had an increase in serum creatinine (SCr) levels >50% over 24-48 h. In the seven patients with oliguric ARF, SCr increased from a median preoperative level of 88 micromol/l (80-115 micromol/l) to a peak value of 725 micromol/l (521-857 micromol/l) in 5 days (4-6). Eight patients out of the sixteen with ARF (50%) were diabetics, as opposed to none of the 16 patients not experiencing ARF. Renal biopsy (three patients) showed tubular dilation and necrosis, interstitial edema, and lymphomononuclear infiltrate of moderate degree. Only one patient required hemodialysis, and all recovered renal function. No other cases of unexplained ARF occurred in the unit after the original prophylaxis protocol was resumed. CONCLUSION: The simultaneous infusion of cefodizime and vancomycin may involve a high risk of substantial renal function derangement, especially in diabetics.

Acute Kidney Injury↗
PubMed2001

Decompressive colonoscopy with intracolonic vancomycin administration for the treatment of severe pseudomembranous colitis.

BACKGROUND: We explored the potential of early decompressive colonoscopy with intracolonic vancomycin administration as an adjunctive therapy for severe pseudomembranous Clostridium difficile colitis with ileus and toxic megacolon. METHODS: We reviewed the symptoms, signs, laboratory tests, radiographic findings, and outcomes from the medical records of seven patients who experienced eight episodes of severe pseudomembranous colitis with ileus and toxic megacolon. All seven patients underwent decompressive colonoscopy with intracolonic perfusion of vancomycin. RESULTS: Fever, abdominal pain, diarrhea, abdominal distention, and tenderness were present in all patients. Five of seven patients were comatose, obtunded, or confused, and six of the seven required ventilatory support. The white blood cell count was greater than 16,000 in seven cases (six patients). Colonoscopy showed left-side pseudomembranous colitis in one patient, right-side colitis in one patient, and diffuse pseudomembranous pancolitis in five patients. Two patients were discharged with improvement. Five patients had numerous medical problems leading to their death. Complete resolution of pseudomembranous colitis occurred in four patients. One patient had a partial response, and two patients failed therapy. CONCLUSION: Colonoscopic decompression and intracolonic vancomycin administration in the management of severe, acute, pseudomembranous colitis associated with ileus and toxic megacolon is feasible, safe, and effective in approximately 57% to 71% of cases.

Aged↗