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PubMed1994

A randomized double-blind trial of vancomycin versus teicoplanin for the treatment of gram-positive bacteremia in patients with cancer.

In a prospective, randomized, double-blind study comparing teicoplanin and vancomycin for the treatment of gram-positive bacteremias in neutropenic patients, teicoplanin was given at 6 mg/kg of body weight every 24 h intravenously (i.v.) after initial loading every 12 h for three doses, while vancomycin was administered at 15 mg/kg every 12 h i.v. At enrollment, both groups were comparable in age, sex, underlying hematologic or neoplastic disorder, baseline renal functions, and incidence of neutropenia. Treatment was successful in 19 (90%) of 21 patients who received teicoplanin and 24 (96%) of 25 who received vancomycin (P = .58). Adverse reactions occurred more often in the vancomycin group (31%) than in the teicoplanin group (9%; P = .06) and were primarily cutaneous or gastrointestinal. In conclusion, teicoplanin was better tolerated than vancomycin, and no statistically significant difference in efficacy was detected with the sample size in this study.

Adult↗

PubMed1984

Pharmacokinetics of vancomycin.

Vancomycin is poorly absorbed when administered by mouth and, for systemic infections, must be given intravenously. The pharmacokinetics of vancomycin have been well defined in a number of recent studies in man. Since the drug is excreted primarily via the kidneys, dosage modification is imperative in patients with impaired renal function. With the possible exception of aqueous humour and cerebrospinal fluid, vancomycin penetrates well into most body fluids. It appears that excessively high serum concentrations of vancomycin may be associated with ototoxicity. It has not been possible to relate the development of nephrotoxicity to determined previously serum concentrations of vancomycin.

Adult↗

PubMed1984

Vancomycin pharmacokinetics in critically ill patients.

Peak and trough vancomycin serum levels were measured in 37 severely ill patients following dosing using the Moellering nomogram. The peak and trough serum concentrations were 61.2 +/- 23 and 22.6 +/- 16.5 mg/l, respectively, and higher than expected. Vancomycin pharmacokinetics obtained from 10 other patients were also studied. In five patients with a creatinine clearance greater than 1 ml min-1 kg-1, a mean plasma elimination half-life of 7.8 +/- 2.8 h was calculated. In the five other patients with markedly reduced renal function (creatinine clearance less than or equal to 1 ml min-1 kg-1), the mean elimination half-life was 18.3 +/- 10.2 h. A correlation was observed between the vancomycin and creatinine clearance. Important inter-patient variations of vancomycin clearance for the same creatinine clearance was also noted. Tubular damage in critically ill patients with severe sepsis may explain our results of the decreased vancomycin elimination.

Creatinine↗

PubMed1985

A prospective study of adverse reactions associated with vancomycin therapy.

A prospective evaluation of the efficacy and safety of vancomycin was conducted in 54 consecutive patients over a 16-month period. Vancomycin was curative in 95% of 43 patients with proven infection. Drugs were ceased in six patients because of adverse reactions; in three of these vancomycin was considered the likely cause. Reactions included thrombophlebitis (20 of 54 patients), rash (4 of 54), nephrotoxicity (4 of 50), proteinuria (1 of 50) and ototoxicity (1 of 11 patients tested by audiometry). Thrombophlebitis occurred only with infusion through peripheral cannulae; nephrotoxicity and ototoxicity were confined to patients receiving an aminoglycoside plus vancomycin. We conclude that vancomycin, administered appropriately, constitutes safe, effective therapy for infections caused by susceptible bacteria.

Adolescent↗

PubMed1986

Comparison of pharmacokinetics and bactericidal activity of teicoplanin and vancomycin.

Teicoplanin (0.2 g) or vancomycin (1 g) were infused over 3 and 50 min respectively to six male volunteers in a cross-over study. Each drug was administered twice at a 14 h interval. The pharmacokinetics of both drugs were accurately described using a two-compartment model. Vancomycin had a shorter half-life (5.8 +/- 1.8 h) compared to teicoplainin (33.2 +/- 5.1 h; P less than 0.001). One hour serum was tested for serum bactericidal activity against ten strains each of Staphylococcus aureus (median serum bactericidal activity 1:16 for teicoplanin; 1:32 for vancomycin), Staph. epidermidis (1:32 for teicoplanin and for vancomycin) and Streptococcus faecalis (1:2 for both drugs). Serum killing rate studies showed a slower rate of killing of Staph. aureus with teicoplanin (less than 1 log10 cfu/ml over 6 h) than with vancomycin (4 log10 cfu/ml over 6 h).

Adult↗

PubMed1987

Pharmacokinetics of vancomycin in serum and tissue of patients undergoing open-heart surgery.

Penetration of vancomycin into serum, heart valves, subcutaneous tissue and muscle was determined in 33 adult patients undergoing open-heart surgery. Each patient received 15 mg/kg vancomycin as a 30-min intravenous infusion preoperatively. Within 6 h vancomycin plasma concentrations declined from 28.9 to 4.2 mg/l. Vancomycin concentrations decreased in subcutaneous tissue slowly and varied in muscle between 1.2 and 3.2 mg/kg, in subcutaneous tissue between 1.3 and 4.4 mg/kg and in heart valves between 2.3 and 4.2 mg/kg. Vancomycin concentrations in heart valves are high enough to inhibit most oxacillin-resistant Staphylococcus aureus, and coagulase-negative staphylococci causing postoperative wound infections and endocarditis.

Adipose Tissue↗

PubMed1987

Bactericidal activity and killing rate of serum in volunteers receiving vancomycin or teicoplanin with and without amikacin given intravenously.

We have studied the interaction between vancomycin or teicoplanin and amikacin in two groups of five volunteers randomized to receive either (a) vacomycin, amikacin, vancomycin+amikacin, or (b) teicoplanin, amikacin, teicoplanin+amikacin. Each administration was given on separate days, in random order with a 48 hours washout period between each infusion. The serum concentrations measured microbiologically at time 0, 1 and 6 h were: 42.6, 11.4 and 4.1 mg/l respectively for teicoplanin; 27.6, 13.9, and 4.2 mg/l for vancomycin, and 44.9, 17.8, and 1.9 mg/l for amikacin. Teicoplanin was also measured using a solid-phase enzyme-receptor assay (SPERA). The serum bactericidal titres and the rate of killing in serum were measured 1 and 6 h after infusion against Staphylococcus aureus susceptible or resistant to oxacillin (5 strains each), S. epidermidis susceptible and resistant to oxacillin (5 strains each), Corynebacterium JK (5 strains), Listeria monocytogenes (5 strains), and Mycobacterium fortuitum (3 strains). The addition of amikacin to either teicoplanin or vancomycin increased the serum bactericidal titres against staphylococci with the exception of oxacillin-resistant S. epidermidis. Teicoplanin+amikacin was the most active regimen against L. monocytogenes and was equivalent to vancomycin+amikacin against M. fortuitum. Teicoplanin alone and teicoplanin+amikacin had a significantly lower killing rate against staphylococci than amikacin alone.

Amikacin↗

PubMed1988

Comparison of the investigational drug, LY146032, with vancomycin in experimental pneumonia due to methicillin-resistant Staphylococcus aureus.

The efficacy of LY146032 was compared with that of vancomycin in experimental pneumonia due to methicillin-resistant Staphylococcus aureus (MRSA). Emphysematous hamsters were challenged intratracheally with MRSA and given LY146032 (20 mg/kg 24h), vancomycin (40 mg/kg/24h) or normal saline by subcutaneous injection. Following infection with 2 X 10(9) cfu, survival among antibiotic-treated animals was significantly greater than that of the control group (P less than 0.01 at 96 h); however, no significant difference in survival between the hamsters given LY146032 and vancomycin was seen. To evaluate the influence of the antibiotics on the rate of bacterial killing within the lungs (pulmonary clearance), animals were challenged with a high inoculum (1 X 10(9) cfu) or low inoculum (1 X 10(6) cfu). Animals treated with LY146032 demonstrated a significant advantage in pulmonary clearance versus controls at both inocula; however, animals treated with vancomycin showed a statistically significant increase in pulmonary clearance versus controls only at the lower inoculum. We conclude that in this experimental model, LY146032 was as effective as vancomycin in treating infection with MRSA.

Animals↗

PubMed1988

Teicoplanin compared with vancomycin in methicillin-resistant Staphylococcus aureus infections: preliminary results.

Twenty-one patients were included in an open randomized study comparing vancomycin 1 g bd with teicoplanin 400 mg daily in severe methicillin-resistant Staphylococcus aureus infections. The median duration of therapy was 15 days for vancomycin and 21 days for teicoplanin. Most patients presented with severe underlying conditions, such as major surgery (8), solid tumours (5), multiple trauma (3). The infections treated, included septicaemia, osteomyelitis, bronchopneumonia, cellulitis and acute pyelonephritis. Mean MICs of the strains were 0.39 mg/l for vancomycin and 0.195 mg/l for teicoplanin. Mean trough and peak serum concentrations of vancomycin were 14.3 +/- 5 mg/l and 34.3 +/- 13 mg/l, while the teicoplanin values were 7.5 +/- 4 mg/l and 17 +/- 7 mg/l. The cure rate was seven of 12 in the teicoplanin group and six of nine in the vancomycin group, with four and three cases, respectively, of improvement and one failure in the teicoplanin group. Transient renal impairment occurred in two cases with both regimens; superinfection and colonization in three patients and one patient, respectively, with both regimens.

Adult↗

PubMed1988

The in-vitro degradation at 37 degrees C of vancomycin in serum, CAPD fluid and phosphate-buffered saline.

Solutions of vancomycin in phosphate-buffered saline, peritoneal dialysis effluent fluid and human serum were incubated at 37 degrees C for ten days and sampled at daily intervals. The samples were assayed for vancomycin content by a microbiological assay, HPLC and polarisation fluoroimmunoassay (Abbott TDX). The results obtained by HPLC and microbiological assay agreed well and indicated approximately 50% loss over ten days in serum and buffered saline and over 70% loss in dialysate. TDX results indicated losses of only 20% and 40%, respectively. Degradation products were prepared from vancomycin by acid hydrolysis and purified by HPLC. These purified products were shown to cross-react in the TDX assay. It is suggested that the TDX assay becomes non-specific in the presence of vancomycin breakdown products and thus overestimates true vancomycin concentrations.

Bacteriological Techniques↗

PubMed1995

vanA genes in vancomycin-resistant clinical isolates of Oerskovia turbata and Arcanobacterium (Corynebacterium) haemolyticum.

We report the cloning and sequencing of vanA genes present in the high-level vancomycin- and teicoplanin-resistant clinical isolates Oerskovia turbata 892 and Arcanobacterium (Corynebacterium) haemolyticum 872. The presence of vanA was detected by Southern blotting and PCR and confirmed by DNA sequencing. vanA-like sequences were encoded on plasmids of 15 and 20 kb respectively. The A. haemolyticum 872 DNA sequence was identical to the published vanA sequence of vancomycin-resistant Enterococcus faecium BM4147, but the O. turbata 892 sequence showed three coding changes. Induction experiments indicated that vancomycin resistance in A. haemolyticum 872 and O. turbata 892 was constitutive. SDS-PAGE analysis of membrane proteins showed the presence of a c. 39 kD protein in both clinical isolates whose expression was unaltered in the presence of vancomycin, while a similar protein in E. faecium BM4147 was inducible. Since A. haemolyticum and O. turbata are naturally susceptible to vancomycin, the high-level constitutive resistance seen in these isolates appears to be mediated by vanA. This is the first report confirming the presence of vanA in genera other than Enterococcus.

Actinomycetaceae↗

PubMed1996

Comparative in-vitro activity of SCH 27899, a novel everninomicin, and vancomycin.

The antibacterial activity of SCH 27899, was compared with vancomycin in vitro against 210 recent clinical isolates representing eight major genera of Gram-positive organisms. MIC90 values for everninomicin were consistently better than those of vancomycin for all Gram-positive bacteria tested. Although everninomicin was less bactericidal than vancomycin against staphylococci, it was inhibitory against vancomycin-resistant enterococci. This novel antibiotic may, therefore, provide a clinical alternative to penicillin and vancomycin for therapy of Gram-positive infections.

Aminoglycosides↗

PubMed1996

Impact of glycopeptide therapy after hospital discharge on inpatient costs: a comparison of teicoplanin and vancomycin.

Data were collected prospectively from 59 patients receiving vancomycin and 20 patients receiving teicoplanin. The mean daily drug cost was 52.40 pounds for teicoplanin and 31.13 pounds for vancomycin; the 95% Confidence Intervals (CI) for the difference in mean drug costs varied between 14.40 pounds and 28.10 pounds in favour of vancomycin. Use of a loading dose of teicoplanin significantly increased mean daily drug costs if the duration of treatment was less than 10 days. Costs of preparation, administration and monitoring were consistently higher for vancomycin than for teicoplanin and inclusion of these costs reduced the difference in mean daily costs to 13.01 pounds (95% CI 6.10 to 19.90 pounds). In Dundee 11 of 20 patients who received teicoplanin had received some of their treatment after discharge from the hospital and a survey of UK hospitals confirmed that teicoplanin treatment after discharge is being used in a wide range of conditions. The median proportion of teicoplanin treatment in Dundee given after discharge was 28.4% for each patient who received the drug: the median proportion of non-inpatient therapy was 50% per patient of those who received any teicoplanin treatment after discharge. Assuming that teicoplanin costs 20 pounds per day more than vancomycin, use of teicoplanin implies an investment of 70.42 pounds to gain one hospital day through earlier discharge of patients receiving teicoplanin.

Adolescent↗

PubMed1996

Penetration of vancomycin into human lung tissue.

Vancomycin penetration into lung tissue was evaluated in thirty patients following the administration of 1 g of vancomycin as a 1 h i.v. infusion. Mean concentrations (range) of vancomycin in lung tissue were 9.6 (6.3-12.1) mg/kg at 1h, 5.7 (4.7-7.4) mg/kg at 2 h, 4.2 (0.8-6.5) mg/kg at 3-4 h, 2.4 (1.4-4.7) mg/kg at 6 h, and 2.8 (0.9-7.8) mg/kg at 12 h after the end of infusion. Ratios of lung tissue to serum concentration ranged 0.24 to 0.41 at 1 and 12 h, respectively. One of six patients observed at 6 h, and 3 of 7 patients at 12 h did not have detectable levels of vancomycin in lung tissue. A 1 h iv infusion of a 1 g dose of vancomycin does not achieve sustained lung concentrations above the MIC for susceptible staphylococci over a dosing interval of 12 h. Therefore, a more appropriate modality of administration, such as continuous infusion, should be considered.

Aged↗

PubMed1998

Evaluation of the in-vitro activity of the glycopeptide antibiotic LY333328 in comparison with vancomycin and teicoplanin.

The in-vitro activity of a new glycopeptide antibiotic, LY333328, was compared with vancomycin and teicoplanin against clinical isolates of Staphylococcus aureus, coagulase-negative staphylococci, vancomycin and teicoplanin resistant enterococci, and vancomycin sensitive and resistant enterococci. MIC, MBC, and time-kill kinetics were determined for each agent. LY333328 displayed similar or improved MIC/MBC values in comparison with vancomycin and teicoplanin. Time-kill kinetics for LY333328 demonstrated significantly improved bactericidal activity against the isolates. These findings suggest that LY333328 has improved in-vitro activity over vancomycin and teicoplanin against a range of gram-positive organisms.

Anti-Bacterial Agents↗

PubMed1999

In-vitro activity of fosfomycin against vancomycin-resistant enterococci.

The effect of fosfomycin against 69 vancomycin-resistant isolates of Enterococcus faecium (VanA), five of E. faecium (VanB), 11 of Enterococcus faecalis (VanA), three of E. faecalis (VanB), 10 of Enterococcus gallinarum (VanC1) and two of Enterococcus casseliflavus (VanC2) and glycopeptide-sensitive E. faecium (n = 8) and E. faecalis (n = 10) was tested in vitro. Fosfomycin inhibited 97%, 94% and 96% of the vancomycin-resistant strains, according to results of agar dilution, broth microdilution, and a disc diffusion method (DIN 58940). The disc diffusion test by the NCCLS method does not include fosfomycin; using breakpoints suggested by Andrews et al. (< or = 11 mm, resistant; > or = 18 mm, susceptible), 5% of the vancomycin-resistant strains tested would have been considered fosfomycin resistant. Minimal inhibitory concentrations of most vancomycin-resistant isolates were in the intermediate sensitivity range, yielding an MIC50 of 32 mg/L and an MIC90 of 64 mg/L. Moreover the majority of inhibitory zone sizes by the disc diffusion method (DIN 58940) corresponded to intermediate susceptibility. These results suggest that fosfomycin at a high dosage and possibly used in combination with other drugs could be a potentially useful drug for the treatment of infections caused by vancomycin-resistant enterococci.

Anti-Bacterial Agents↗

PubMed2000

Pharmacokinetics and tissue penetration of vancomycin in patients undergoing prosthetic mammary surgery.

Vancomycin concentrations in periprosthetic breast tissues were evaluated in 24 women undergoing reconstructive surgery after mastectomy for breast cancer. Patients were given a single prophylactic dose of vancomycin (1 g iv) 1-8 h before surgery, and mean capsular and pericapsular tissue concentrations were measured by HPLC. Vancomycin was not detectable in the majority of patients belonging to the 1-3 h post-dose groups, whereas in the 4-8 h post-dose groups, mean capsular and pericapsular concentrations were as follows: at 4 h, 4.0 mg/kg and 5.9 mg/kg; at 6 h, 4.1 mg/kg and 4. 8 mg/kg; at 8 h, 5.9 mg/kg and 11.1 mg/kg, respectively. Vancomycin tissue concentrations thus were equal to or exceeded the breakpoint of 4 mg/L in most samples collected 4-8 h after dosing. In conclusion, our data suggest that appropriate timing of vancomycin prophylaxis should be considered to allow the maintenance of adequate tissue concentrations throughout the surgical procedure.

Aged↗

PubMed2001

In vitro antimicrobial susceptibility of Aerococcus urinae to 14 antibiotics, and time-kill curves for penicillin, gentamicin and vancomycin.

Aerococcus urinae is a newcomer in clinical and microbiological practice, causing urinary tract infections, bacteraemia/septicaemia and/or endocarditis. This study presents for the first time an evaluation of the activity of a representative panel of antibiotics against a large number of A. urinae isolates. The in vitro susceptibilities (MICs) of 56 isolates of A. urinae to 14 antibiotics were determined by agar dilution. In general, A. urinae isolates showed little inter-isolate variability, and had low MICs of penicillin, amoxicillin, piperacillin, cefepime, vancomycin and rifampicin. High-level aminoglycoside resistance was not found for any of the isolates. Moderate to good activity was seen with quinolones, erythromycin and tetracycline. Isolates from two patients with endocarditis were studied with time-kill curves for penicillin, gentamicin and vancomycin. Penicillin and vancomycin alone exhibited slow or no bactericidal activity against the two strains. When combining either penicillin or vancomycin with gentamicin, rapid bactericidal activity was obtained for both strains with both combinations. The treatment options for A. urinae seem to include penicillins for less severe cases. In severe cases, i.e. endocarditis, the time-kill investigations suggest a beneficial effect of combination with gentamicin. In the penicillin-allergic patient vancomycin in combination with gentamicin represents the most obvious alternative.

Anti-Bacterial Agents↗