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PubMed1990

Drug utilization review in a teaching hospital: experience with vancomycin.

A prospective, two-phase, drug utilization review (DUR) was performed at the Royal Adelaide Hospital (RAH) to determine the extent and pattern of vancomycin use. For all patients commencing oral or parenteral vancomycin, treatment indication, route of administration, duration of therapy, results of culture and sensitivity tests, adverse drug reactions and results of therapeutic drug level monitoring were recorded. Vancomycin courses were classified as being for therapy or prophylaxis and compared with predetermined audit criteria to assess appropriateness of use. During the 8 week initial phase, data on 62 treatment courses in 59 patients were recorded, 50% for therapy and 50% for prophylaxis. Sixty four percent were classified as inappropriate, occurring in 32% of therapeutic courses and 97% of those for prophylaxis. During the 10 week re-evaluation, conducted 10 months later, data for 43 treatment courses in 43 patients were reviewed, 42% for therapy and 58% for prophylaxis. Sixty five percent were inappropriate occurring in 17% of therapeutic courses and 100% of the prophylactic courses. When compared with the initial phase, the re-evaluation demonstrated a decrease in the empirical use of vancomycin in the combination treatment of neutropaenic fever and also in the duration of vancomycin use for surgical prophylaxis. During both study phases, criteria contraventions were mostly due to inappropriate indication or duration of therapy. The cost of inappropriate vancomycin use was reduced by over 50% between survey phases, from $Aus11,500 or 55% of total vancomycin cost during the initial phase to $Aus3,600 or 25.7% during the re-evaluation. The most effective of the remedial strategies implemented after the initial phase was direct consultation with prescriber groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Influence of fosfomycin and tobramycin on vancomycin-induced nephrotoxicity.

Since combinations of fosfomycin and vancomycin or tobramycin and vancomycin could be of advantage in the therapy of staphylococcal infections, we studied renal tolerance of both combinations. The experimental animal was the rat and the parameters of nephrotoxicity were cyturia and enzymuria. The experiments showed that fosfomycin at dosages of 50 and 250 mg/kg protected against nephrotoxicity caused by vancomycin (dose: 50 mg/kg), whereas the administration of both tobramycin (dose: 2.5 mg/kg) and vancomycin (dose: 50 mg/kg) resulted in an increase of cyturia and enzymuria. However, repeated dosing of vancomycin (single dose: 50 mg/kg) led to renal accumulation when combined with fosfomycin (single dose: 250 mg/kg); renal vancomycin concentrations were lower. This study suggests similarities in the renal handling of vancomycin and aminoglycosides and demonstrates the possibility of reducing drug-associated nephrotoxicity.

Animals↗

PubMed2006

Levels of vancomycin in the cerebral interstitial fluid after severe head injury.

OBJECTIVE: To evaluate the concentrations of vancomycin in the cerebral interstitial fluid after intravenous administration by multiple boli. DESIGN: Prospective non randomized study SETTING: University hospital general ICU. PATIENTS: Four patients undergone to craniotomy for evacuation of cerebral posttraumatic hemorrhage, who developed pneumonia 4-7 days from the injury METHODS: Two microdialysis catheters were placed in each patient: one in the edematous brain surrounding the focal lesion and one in the subcutaneous tissue of abdomen. Levels of vancomycin were measured in serum and in the microdialysates samples. RESULTS: Plasmatic concentration of 10-15 microg/ml in the trough level was obtained after four administrations of vancomycin. Levels of vancomycin in the subcutaneous tissue was above minimum inhibitory concentrations in all patients after the second administration. Mean serum/brain ratio was 8%. Cerebral interstitial concentration of vancomycin was never above minimum inhibitory concentrations; its maximum value was 1.2 microg/ml. CONCLUSIONS: In edematous brain close to a posttraumatic hemorrhage the levels of vancomycin do not differ from that in healthy subjects. At these plasmatic concentrations cerebral interstitial levels of vancomycin were insufficient while subcutaneous interstitial levels were effective for clinical use.

Adult↗

PubMed2006

Pharmacokinetic/pharmacodynamic analysis of vancomycin in ICU patients.

AIMS: To identify the variables affecting vancomycin pharmacokinetics in medical ICU patients and to evaluate the potential efficacy of dosage schedules by PK/PD analysis. DESIGN: A retrospective pharmacokinetic analysis of serum levels obtained in routine vancomycin monitoring was performed. SETTING: A 12-bed general ICU of a university teaching hospital. PATIENTS: Forty-six vancomycin-treated ICU patients fitting the following criteria: over 18 years old; more than three concentration data per patient; absence of renal replacement support, cardiac surgery and neoplastic disorders. INTERVENTIONS: Clinical information was collected from the patients' medical records. Details of vancomycin therapy, dosage and blood sampling times were obtained from pharmacokinetic reports. Population analysis were made by the standard two-stage approach. MEASUREMENTS AND MAIN RESULTS: Vancomycin clearance and distribution volume were estimated individually assuming a one-compartment pharmacokinetic model. PK/PD analysis was performed by Monte Carlo simulation. In the ICU patients, higher Vd (nearly twice the quoted value of 0.72 l/kg) and different vancomycin clearance-creatinine clearance relationship were found. Renal function, the APACHE score, age and serum albumin accounted for more than 65% of drug clearance variability. Vancomycin standard dosages led to a 33% risk of not achieving the recommended AUC(24h)/MIC breakpoint for Staphylococcus aureus. CONCLUSIONS: The population kinetics and PK/PD analyses based on Monte Carlo simulation procedures offer an excellent tool for selecting the therapeutic option with the highest probability of clinical success in ICU patients.

APACHE↗

PubMed2000

Rapid removal of vancomycin by continuous veno-venous hemofiltration.

We describe a 14-year-old girl with staphylococcal (coagulase-negative) ventriculo-peritoneal shunt infection, who developed oliguric acute renal failure and was found to have a serum vancomycin concentration of 250 microg/ml. Since only about 10%-50% of vancomycin is bound to protein in blood, we employed continuous veno-venous hemofiltration (CVVH) with a high ultrafiltration rate (1,800 ml/h) for increased convective clearance to remove vancomycin, which may have contributed to the acute renal failure. At the end of 38 h of CVVH, the vancomycin concentration had decreased in an exponential manner to 27 microg/ml. Over the subsequent 3-4 days, her renal function improved and the vancomycin concentration decreased further to <5 microg/ml. In conclusion, we believe that a high serum vancomycin concentration may be nephrotoxic and demonstrate that CVVH can be used effectively to remove vancomycin in children with acute renal failure.

Acute Kidney Injury↗

PubMed2000

Comparison of a commercial disk test with vancomycin and colimycin susceptibility testing for identification of bacteria with abnormal gram staining reactions.

In an effort to identify bacteria that fail to give the expected Gram reaction, thus leading to misidentification, two nonstaining tests for Gram reaction, vancomycin and colimycin susceptibility testing and the Gram-Sure test (Remel, USA), were employed on 145 strains from 42 gram-negative and gram-positive genera with contradictory Gram stain results. The Gram-Sure test is a commercially available disk that detects the presence of L-alanine-aminopeptidase, an enzyme usually found only in the cell wall of gram-negative bacteria. In this test, aminopeptidase activity is detected using a substrate that can be hydrolyzed to produce a fluorescent compound under long-wave UV light. The commercial disk test and vancomycin plus colimycin susceptibility testing appeared to perform equally well except in the identification of Erysipelothrix and Lactobacillus, for which the commercial disk test was better, and Moraxella, for which vancomycin and colimycin susceptibility testing was more helpful. An advantage of the commercial disk test is that it can be performed in 10 min, whereas vancomycin and colimycin susceptibility testing requires at least 18 h. The commercial disk test is also less expensive than vancomycin and colimycin susceptibility testing. However, since the same results can be obtained with the 5 microg and 30 microg vancomycin disks, it is possible to use only one vancomycin disk, with the cost then being equivalent to that of the commercial disk test. The major inconvenience of the commercial disk test is the requirement of a UV ray. However, this test could be a useful tool for the identification of unusual organisms.

Aminopeptidases↗

PubMed1998

Effect of the addition of vancomycin on the performance of an automated nonradioactive system for detection of mycobacteria.

A recently developed automated, nonradioactive system for the detection of mycobacteria (MB/BacT; Organon Teknika, Belgium) has provided good results, but the contamination rate was found to be higher than that obtained with the radiometric Bactec 460 system (Becton Dickinson, USA). In the present study, the effects of adding vancomycin (1 microg/ml) to the antibiotic mixture of the nonradioactive system were evaluated, and the performance of the system with versus without vancomycin was compared. Three hundred sputum samples were tested, using the radiometric system as the reference method. Mycobacteria were isolated from 47 (15.7%) samples. The nonradioactive system with and without vancomycin detected 42 and 43 strains, respectively; the time to detection was 1 day shorter with the medium without vancomycin (15.7 days vs. 14.3 days). The radiometric system detected 42 strains of mycobacteria in a mean detection time of 13.6 days. Contamination rates with the nonradioactive system were 6.7% in the medium without vancomycin and 2.7% in the medium with vancomycin. The latter figure was approximately the same as the contamination rate found with the radiometric system (2.3%). Our data suggest that the addition of vancomycin considerably reduces the number of contaminants in the MB/BacT medium without affecting the performance of the system.

Bacteriological Techniques↗

PubMed2006

Release of vancomycin and teicoplanin from a plasticized and resorbable gelatin sponge: in vitro investigation of a new antibiotic delivery system with glycopeptides.

BACKGROUND: The aim of this study was to evaluate the efficacy of sustained release of vancomycin and teicoplanin from a resorbable gelatin glycerol sponge, in order to establish a new delivery system for local anti-infective therapy. MATERIALS AND METHODS: 60 plasticized glycerol gelatin sponges containing either 10 or 20% gelatin (w/v) were incubated in vancomycin or teicoplanin solution at 20 degrees C for either 1 or 24 h. In vitro release properties of the sponges were investigated over a period of 1 week by determining the levels of vancomycin and teicoplanin eluted in plasma using fluorescent polarization immunoassay. The rate constant and the half-life for the antibiotic release of each group were calculated by linear regression assuming first order kinetics. RESULTS: Presoaking for 24 h was associated with a significant increase in the total antibiotic release in all groups opposed to 1 h of incubation, except for the 10% sponges presoaked in teicoplanin. Doubling the gelatin content of the sponges from 10 to 20% significantly increased the total release of antibiotic load only in teicoplanin-containing sponges after 24 h incubation. In all corresponding groups investigated, release of vancomycin was more prolonged compared to teicoplanin, which allowed a gradual release beyond 5 days. The half-life (h +/- SEM) of both types of vancomycin-containing sponges was significantly prolonged by 24 h incubation in comparison to 1 h incubation (29.1 +/- 5.9 vs 5.9 +/- 1.0; p < 0.001, 30.0 +/- 2.1 vs 11.1 +/- 1.9; p < 0.001). However, neither doubling the gelatin content of the sponges nor a prolonged incubation was associated with a significantly prolonged delivery of teicoplanin. CONCLUSION: This study demonstrated a better diffusion-controlled release of vancomycin-impregnated glycerol gelatin sponges compared to those pretreated with teicoplanin. The plasticized glycerol gelatin sponge may be a promising carrier for the application of vancomycin to infected wounds for local anti-infective therapy.

Anti-Bacterial Agents↗

PubMed1978

Vancomycin therapy of bacterial endocarditis.

Fifteen patients with bacterial endocarditis were treated with vancomycin between 1967 and 1976. The indications for vancomycin therapy were penicillin-cephalosporin allergy in six patients, antibiotic resistant bacteria in six, initial therapy in one and culture-negative endocarditis in two. The causative microorganisms were Staph. epidermidis (four patients), Staph. aureus (two patients), diphtheroids (four patients), viridans streptococci (two patients) and enterococci (one patient). Minimum inhibitory concentrations of vancomycin for these organisms ranged from 0.8 to 3.1 micrograms/ml. The patients received vancomycin for two to 10 weeks (mean five weeks). Cure was achieved in 13 patients, including six with prosthetic valve endocarditis (PVE). Two patients had a relapse of PVE and cultures of blood or heart valve were positive within two months of vancomycin therapy. Vancomycin serum levels did not exceed 50 micrograms/ml, and no serious drug toxicity was encountered in any patient. Three patients had minimal audiogram changes beyond the social hearing range. One patient had mild phlebitis and a rash, and one patient had a transient leukopenia. Vancomycin is an effective nontoxic antibiotic in patients with endocarditis when penicillin or cephalosporin therapy is not appropriate.

Adult↗

PubMed1986

Empiric use of vancomycin during prolonged treatment-induced granulocytopenia. Randomized, double-blind, placebo-controlled clinical trial in patients with acute leukemia.

Because gram-positive infections cause morbidity following intensive antileukemic chemotherapy, the effects of vancomycin versus placebo were evaluated in a randomized, double-blind, placebo-controlled trial in 60 adult patients with acute leukemia and first infectious fever during prolonged (mean of 32 days) granulocytopenia. Gram-positive sepsis was associated with first fever in 17 (28 percent) of the 60 patients. None of 31 patients randomly assigned to receive vancomycin demonstrated gram-positive infection, whereas 16 of 22 patients randomly assigned to receive placebo subsequently had gram-positive infection (seven had sepsis, and nine had local infections; p less than 0.005). All patients with gram-positive infection were then given vancomycin, and all showed prompt clinical responses. The predominant gram-positive organism causing infection was beta-lactam-resistant Staphylococcus epidermis (19 of 44 isolates). Patients randomly assigned to receive vancomycin had more rapid resolution of first infectious fever and fewer total febrile days during the granulocytopenic course than did patients randomly assigned to receive placebo. Although vancomycin had no effect on the presence or absence of documented fungal infection, patients treated with vancomycin received empiric amphotericin B for recurrent or persistent fever later (mean of 14 days after initial antibiotic coverage was begun) than did patients receiving placebo (mean of 9.9 days; p less than 0.005), and thus received fewer total days of empiric amphotericin B therapy (mean of 16.3 days) than did patients given placebo (mean of 24.6 days; p less than 0.01). These data demonstrate that empiric use of vancomycin reduces the morbidity of gram-positive infections following intensive antileukemic therapy and decreases the need for empiric use of toxic amphotericin B.

Adult↗

PubMed1987

Relationship of serum antibiotic concentrations to nephrotoxicity in cancer patients receiving concurrent aminoglycoside and vancomycin therapy.

Methicillin-resistant coagulase-negative staphylococci have become increasingly responsible for febrile episodes in cancer patients, often necessitating the addition of vancomycin to an aminoglycoside-containing broad-spectrum antibiotic regimen. A total of 229 courses of antibiotic therapy in 229 patients were evaluated for nephrotoxicity associated with the administration of an aminoglycoside and/or vancomycin. The incidence of nephrotoxicity observed in patients administered an aminoglycoside (Group A) was 18 percent; vancomycin (Group B) 15 percent; and an aminoglycoside concurrently with vancomycin (Group C) 15 percent. The following pharmacokinetic/dosing factors were significantly associated with increased nephrotoxicity in the groups: baseline serum creatinine level, mean daily dose during the first three days of therapy (Group B), and elevated serum trough aminoglycoside or vancomycin concentrations (2 micrograms/ml or more or 10 micrograms/ml or more, respectively). No cumulative nephrotoxicity was demonstrated with the concurrent administration of vancomycin and an aminoglycoside. A higher incidence of nephrotoxicity was seen in Group C (42 percent) and Group B (27 percent) patients, in whom trough serum vancomycin concentrations were 10 micrograms/ml or more.

Aminoglycosides↗

PubMed1989

Gentamicin-induced renal metabolic alterations in newborn rat kidney: lack of potentiation by vancomycin.

Daily subcutaneous administration of 20 or 100 mg/kg gentamicin for 4 days significantly decreased pyridoxal-5'-phosphate and lysosomal specific phosphatidylinositol-phospholipase C (PI-PLC) in newborn rat kidney. The fall in PI-PLC was associated with an elevation in renal phosphatidylinositol, phosphatidylserine, and phosphatidylcholine. The 100 mg/kg gentamicin dose also produced a rise in renal sphingomyelin, phosphatidylethanolamine, phosphatidylglycerol, and total phospholipid (TPL) accompanied by inhibition in the activities of Na+,K+-ATPase and alkaline phosphatase. In contrast, daily intraperitoneal injection of 100 mg/kg vancomycin for 4 days failed to markedly alter renal metabolic parameters. However, the 500 mg/kg vancomycin dose increased kidney weight, TPL, and all individual phospholipid class concentrations accompanied by inhibition of lysosomal specific PI-PLC activity and reduced pyridoxal-5'-phosphate levels. Simultaneous administration of 20 mg/kg gentamicin with either vancomycin dose resulted in renal alterations similar to those produced by gentamicin alone. Concurrent treatment with 100 mg/kg aminoglycoside and either vancomycin dose produced changes in kidney which were similar to those produced by gentamicin alone, except for a synergistic rise in PI as well as a greater fall in alkaline phosphatase and pyridoxal-5'-phosphate. Surprisingly, the concentration of gentamicin and vancomycin was less in newborn kidneys of rats receiving a simultaneous high dose of vancomycin and aminoglycoside treatment compared to levels found in animals given either antibiotic separately. The lack of potentiation of nephrotoxicity in newborns administered a combination of vancomycin and gentamicin may be due to decreased accumulation of either antibiotic in kidney.

Adenosine Triphosphatases↗

PubMed2006

Methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in Canada.

This study defines the characteristics of decreasing vancomycin susceptibility in multiple isolates of methicillin-resistant Staphylococcus aureus (MRSA) recovered from a hospitalized patient in Canada over a period of 6 months. The MICs of the isolates increased during therapy with vancomycin. The patient fractured her right hip while in the United States. She was started on treatment with vancomycin. The MICs of successive isolates increased from < or =1 to 4 mg/L over 6 months. Then, an isolate tested at 8 mg/L initially and 4 mg/L with confirmatory E-test (AB BIODISK, Solna, Sweden). One month later, MRSA was still present in her wound, and therapy was changed to linezolid with rifampin. Subsequent cultures were negative for MRSA. Susceptibility testing was performed on the BD Phoenix (Becton Dickinson Diagnostic Systems, Sparks, MD), Dade Microscan (Dade Behring Microscan, Sacramento, CA), Pasco MIC (Becton Dickinson, Sparks, MD), Vitek 2 (bioMerieux, St. Louis, MO), and Sensititre (Trek Diagnostic Systems, Cleveland, OH) systems, and by E-test. Molecular typing (pulsed-field gel electrophoresis [PFGE]) was used to verify the relatedness of the isolates. Transmission electron microscopy (TEM) was used to assess the cell wall thickness of isolates with differing MICs. Population analysis was performed to assess for vancomycin hetero-resistance. MICs of 4 mg/L were only obtained with BD Phoenix, E-test, and broth microdilution. All isolates were identical by PFGE. The most resistant isolate had a thicker cell wall on TEM. Vancomycin hetero-resistance was observed in the resistant isolates. This is the first strain of MRSA with reduced susceptibility to vancomycin reported in Canada. The breakpoints for vancomycin susceptibility have been revised in light of such observations.

Anti-Bacterial Agents↗

PubMed2005

Efficacy of vancomycin, teicoplanin and fusidic acid as prophylactic agents in prevention of vascular graft infection: an experimental study in rat.

OBJECTIVES: To compare the efficacy of a single prophylactic dose of intra-peritoneal vancomycin and teicoplanin with anti-biotic treated Dacron grafts (vancomycin, teicoplanin, 10 or 40% fusidic acid-soaked grafts) in preventing vascular graft infections in a rat model. DESIGN: Prospective, randomized, controlled animal study. MATERIALS AND METHODS: The graft infections were established in the subcutaneous tissues of 80 female Sprague-Dawley rats by the implantation of Dacron prostheses followed by the topical inoculation with methicillin-resistant Staphylococcus aureus. The study groups were as follows: (1) uncontaminated control group, (2) untreated contaminated group, (3) contaminated group with intra-peritoneal vancomycin, (4) contaminated group with intra-peritoneal teicoplanin, (5) contaminated group received vancomycin-soaked Dacron graft, (6) contaminated group received teicoplanin-soaked Dacron graft, (7) contaminated group received 40% fusidic acid-soaked Dacron graft, and (8) contaminated group received 10% fusidic acid-soaked Dacron graft prophylaxis. The grafts were removed after 7 days and evaluated by a quantitative culture analysis. RESULTS: No infection was detected in controls. The untreated contaminated group had a high bacteria count (6.0 x 10(4) CFU/cm2 Dacron graft). Groups that received intra-peritoneal vancomycin or teicoplanin had less bacterial growth (4.8 x 10(3) and 3.9 x 10(3)CFU/cm2 Dacron graft, respectively). Similarly, the group that received 10% fusidic acid-soaked graft showed less bacterial growth (3.6 x 10(3) CFU/cm2 Dacron graft). The groups with vancomycin-, teicoplanin- and 40% fusidic acid-soaked grafts showed no evidence of infection. Statistical analyses demonstrated that intra-peritoneal prophylactic antibiotic treatment was less effective in inhibiting bacterial growth than high concentration antimicrobial-soaking of grafts. CONCLUSION: The use of vancomycin-, teicoplanin- and 40% fusidic acid-soaked grafts was effective in preventing primary prosthetic vascular graft infection.

Animals↗

PubMed2005

Nosocomial infections due to methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci at a university hospital in Taiwan from 1991 to 2003: resistance trends, antibiotic usage and in vitro activities of newer antimicrobial agents.

A rapid increase of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection (from 39% in 1991 to 75% in 2003) and vancomycin-resistant enterococci (VRE) (from 1.2% in 1996 to 6.1% in 2003) at a university hospital in Taiwan was found. The noticeable rise of MRSA and VRE was significantly correlated with the increased consumption of glycopeptides, beta-lactam-beta-lactamase inhibitor combinations, extended-spectrum cephalosporins, carbapenems and fluoroquinolones (Pearson's correlation coefficient, P < 0.05). Minimum inhibitory concentrations (MICs) of 100 non-duplicate blood isolates of MRSA (in 2003) and of 25 non-duplicate isolates of vancomycin-resistant Enterococcus faecalis and 172 vancomycin-resistant Enterococcus faecium (in 1996-2003) causing nosocomial infection recovered from various clinical specimens of patients treated at the hospital to nine antimicrobial agents were determined by the agar dilution method. All of these isolates were susceptible to linezolid and were inhibited by 0.5mg/L of tigecycline, and all MRSA isolates were inhibited by daptomycin 1mg/L, including two isolates of MRSA with heteroresistance to vancomycin. Daptomycin had two-fold better activity against vancomycin-resistant E. faecalis (MIC90, 2 mg/L) than against vancomycin-resistant E. faecium (MIC90, 4 mg/L). Decreased susceptibilities of vancomycin-resistant E. faecium and MRSA to quinupristin/dalfopristin (non-susceptibility 25% and 8%, respectively) were found. Telithromycin had poor activity against the isolates tested (MIC90, 8 mg/L). Linezolid, daptomycin and tigecycline may represent therapeutic options for infections caused by these resistant Gram-positive organisms.

Anti-Bacterial Agents↗

PubMed2005

In vitro influence of vancomycin on adhesion of a Staphylococcus epidermidis strain encoding intercellular adhesion locus ica to intraocular lenses.

PURPOSE: To assess anti-adhesion and/or bactericidal properties of vancomycin in vitro and to determine when these effects are detectable to estimate its relevance to perioperative antibiotic prophylaxis and analyze the efficacy of a newly designed vancomycin insert prototype for endophthalmitis prevention. SETTING: University research laboratory, Lyon, France. METHODS: Staphylococcus epidermidis clinical strain N890074 containing the intercellular adhesion locus ica was used as the infectious agent. Vancomycin was used at 20 microg/mL. A sterile biocompatible, biodegradable vancomycin insert, releasing 230 microg of antibiotics over 100 minutes, was designed especially for this study. To obtain bacterial killing curves, experiments were first performed in a 103 colony-forming units (CFU/mL) bacterial suspension containing no intraocular lenses (IOL). Then IOLs were incubated in the suspension, and bacterial adherence was determined using bacterial counting with and without antibiotic. RESULTS: Vancomycin (solution and insert) had an anti-adhesion effect after 1 hour and a relevant bactericidal effect after 6 hours of incubation. CONCLUSIONS: Vancomycin used with irrigating solutions does not remain in the anterior chamber long enough to develop bactericidal effect. Even if it initially reduces bacterial adhesion, used at a drug level dropping below the bacterial minimal inhibitory concentration, it could result in a secondary increase of the adhesion of slime-producing bacteria. A sufficiently high concentration was obtained in vitro by the new sustained-release system, thereby overcoming the theoretical drawback of a short half-life within the anterior chamber. Anti-adhesion and bactericidal action of vancomycin inserts remains to be confirmed in clinical studies.

Anti-Bacterial Agents↗

PubMed2003

Continuation of a randomized, double-blind, multicenter study of linezolid versus vancomycin in the treatment of patients with nosocomial pneumonia.

BACKGROUND: The clinical efficacy and tolerability of linezolid were demonstrated in a previously published, randomized, double-blind, registration study comparing linezolid with vancomycin for the empiric treatment of 396 patients with nosocomial pneumonia. OBJECTIVES: The aims of this study were to obtain additional experience with linezolid and vancomycin in patients with nosocomial pneumonia and to satisfy international regulatory requirements. METHODS: Patients with pneumonia acquired after 48 hours in an inpatient facility were randomly assigned to receive either IV linezolid 600 mg or IV vancomycin 1 g every 12 hours for 7 to 21 consecutive days. Patients also received IV aztreonam 1 to 2 g every 8 hours, which could be discontinued if gram-negative pathogens were not identified. The primary efficacy variables were clinical and microbiologic outcomes in evaluable patients at the follow-up visit 15 to 21 days after the end of therapy. Results from the continuation study were analyzed separately and did not include patients from the previously reported study. RESULTS: A total of 623 patients were enrolled: 321 in the linezolid group and 302 in the vancomycin group. Mean (SD) ages were 63.1 (19.1) years and 61.9 (19.3) years, respectively. Mean (SD) Acute Physiology and Chronic Health Evaluation II scores were 14.1 (5.8) and 14.1 (6.2), respectively. There were no significant differences between the linezolid and vancomycin groups at the follow-up visit in clinical cure rates (114/168 [67.9%] and 111/171 [64.9%]) or microbiologic success rates (47/76 [61.8%] and 42/79 [53.2%]) in evaluable patients (excluding those who had indeterminate or missing outcomes). There were also no significant differences in the rates of all drug-related adverse events (14.0% and 14.0%) or those that occurred in > 1% of patients, including diarrhea (3.7% and 3.0%), nausea (0.3% and 1.3%), and rash (0.6% and 1.7%) in the linezolid and vancomycin groups, respectively. CONCLUSION: In the population studied, linezolid appeared to be as well tolerated and as effective as vancomycin, each in combination with aztreonam.

Acetamides↗

PubMed1988

Intraperitoneal (IP) vancomycin therapy for CAPD peritonitis--a prospective, randomized comparison of intermittent v continuous therapy.

The use of intraperitoneal (IP) vancomycin as initial, single agent therapy for gram positive and "no organism" continuous ambulatory peritoneal dialysis (CAPD) peritonitis is described, comparing continuous and intermittent administration schedules. "Continuous" therapy consisted of an IP 1-g loading dose of vancomycin followed by 30 mg/L dialysate effluent. "Intermittent" therapy consisted of 2 IP doses of 30 mg vancomycin/kg body weight--the initial dose delivered at diagnosis and the second dose 1 week later. All patients presenting with peritonitis (n = 90) were randomized to receive either continuous or intermittent vancomycin therapy. Patients in whom gram negative organisms and fungi were identified by microscopy and culture were transferred to therapy with a more appropriate antibiotic (n = 39). In the remainder (n = 51), CAPD peritonitis was treated solely with vancomycin (continuous, n = 21; intermittent, n = 30). Clinical resolution was seen in all patients, requiring a mean of 3.2 days for macroscopic clearing of dialysate effluent. Recurrence of peritonitis within 1 month of cessation of therapy was unusual and did not vary between treatment protocols (4/21 v 3/30; P = NS). There were no differences in observed side effects. Thus, IP vancomycin proved to be a useful single agent therapy for gram positive and no organism CAPD peritonitis. Therapy with two IP doses was effective and as safe as continuous IP vancomycin therapy, and therefore should replace other vancomycin administration schedules in the treatment of CAPD peritonitis.

Drug Administration Schedule↗