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PubMed1964

Some differences in the action of penicillin, bacitracin, and vancomycin on Bacillus megaterium.

Hancock, R. (Harvard Medical School, Boston, Mass.), and P. C. Fitz-James. Some differences in the action of penicillin, bacitracin, and vancomycin on Bacillus megaterium. J. Bacteriol. 87:1044-1050. 1964.-Penicillin and cycloserine do not inhibit the growth of protoplasts of Bacillus megaterium, indicating that inhibition of cell-wall synthesis is the only significant process by which they inhibit growth of bacteria. In contrast, bacitracin and vancomycin inhibit growth of protoplasts and bacteria at similar concentrations, indicating that they have important sites of action other than their known inhibition of cell-wall synthesis. At concentrations which inhibit mucopeptide synthesis, penicillin, bacitracin, and vancomycin each cause an increased rate of efflux of K ions from growing bacteria. This effect of penicillin is prevented by chloramphenicol or hypertonic sucrose, whereas the effects of bacitracin and vancomycin are unchanged under these conditions. It is concluded that bacitracin and vancomycin have direct effects on the cytoplasmic membrane, and it is proposed that their inhibition of cell-wall synthesis could be a consequence of these effects. Bacitracin and vancomycin do not compete with penicillin for binding to cells of B. megaterium, a further indication that they have a different primary site of action.

Bacillus megaterium↗

PubMed1993

Application of DNA probes for rRNA and vanA genes to investigation of a nosocomial cluster of vancomycin-resistant enterococci.

DNA probes specific for genes encoding rRNA and the glycopeptide resistance gene vanA were used to investigate a cluster of vancomycin-resistant (MICs, > 512 mg/liter) Enterococcus faecalis and Enterococcus faecium isolated from separate patients in a renal unit in a London hospital. When digested with BamHI, 12 of 13 vancomycin-resistant E. faecalis isolates exhibited a common restriction fragment length polymorphism pattern of rRNA genes (ribotype). A vanA probe hybridized with chromosomal DNA in these 12 isolates. The other isolate of vancomycin-resistant E. faecalis had a different ribotype and the vanA gene was located on plasmid DNA. These data suggest that cross-infection with a single strain of vancomycin-resistant E. faecalis occurred in most instances. In contrast, 23 vancomycin-resistant E. faecium isolates showed greater heterogeneity, comprising 8 ribotypes, suggesting that multiple strains were present in the unit. Twenty-one of these 23 isolates harbored a 24-MDa plasmid which hybridized with the vanA probe, implying that interstrain dissemination of a vancomycin resistance plasmid may have occurred among E. faecium isolates in the renal unit.

Bacterial Proteins↗

PubMed1996

Revised approach for identification and detection of ampicillin and vancomycin resistance in Enterococcus species by using MicroScan panels.

The frequency of antimicrobial agent-resistant enterococci is increasing, making accurate identification and screening for susceptibility essential. We evaluated the ability of MicroScan Positive Breakpoint Combo Type 6 panels (Dade MicroScan Inc., West Sacramento, Calif.) to identify Enterococcus species and to detect ampicillin and vancomycin resistance. A total of 398 well-characterized Enterococcus isolates from two institutions were inoculated into MicroScan panels, into conventional biochemical assays, and into ampicillin and vancomycin agar dilution media. Resistance was verified by the broth macrodilution method. MicroScan panels accurately detected resistance to ampicillin in 132 of 132 enterococcal isolates, while three isolates for which the MICs were < 16 micrograms/ml were classified incorrectly by MicroScan panels as resistant. No beta-lactamase-producing enterococci were detected. All 64 isolates showing resistance to vancomycin (MICs > or = 32 micrograms/ml) were correctly classified by MicroScan panels. Seven isolates for which the vancomycin MICs were 8 and 16 micrograms/ml were incorrectly classified as susceptible by MicroScan panels, while eight isolates for which the MICs were 4 micrograms/ml were incorrectly labeled as intermediate. Fourteen of these 15 isolates were subsequently identified as motile enterococci. Overall, there were three major errors in susceptibility testing for ampicillin and 15 minor errors for vancomycin. Conventional testing confirmed the identity of 181 Enterococcus faecalis isolates, 157 E. faecium isolates, and 60 isolates of other species; however, 56 of these 60 isolates were misidentified by the MicroScan panels. After recognition of this problem, a revised approach which included tests for pigment, motility, and sucrose fermentation was devised. In combination with these additional assays, the conventional MicroScan panels accurately identified the 56 originally misidentified isolates. In summary, the ability of MicroScan panels to detect vancomycin and ampicillin resistance in enterococci was confirmed. Our study found that the inability of MicroScan panels to identify enterococci other than E. faecalis and E. faecium can be compensated for by the addition of standard assays.

Ampicillin Resistance↗

PubMed1997

Comparison of agar dilution, broth microdilution, E-test, disk diffusion, and automated Vitek methods for testing susceptibilities of Enterococcus spp. to vancomycin.

An evaluation was undertaken to determine the optimal method for testing the susceptibilities of 100 clinical isolates and two reference strains of Enterococcus spp. to vancomycin in vitro. Six testing methods were studied by using the following media and incubation times: agar screen with the Synergy Quad Plate (Remel, Lenexa, Kans.), an in-house-prepared brain heart infusion (BHI) agar plate, and an in-house-prepared Mueller-Hinton (MH) agar plate, all incubated for 24 or 48 h; broth microdilution (Sensititre Just One Strip; AccuMed International, Inc., West Lake, Ohio) with BHI or cation-adjusted MH broth incubated for 24 or 48 h; agar dilution with BHI or MH agar incubated for 24 or 48 h; epsilometer test (E test; AB BioDisk, Solna, Sweden) with BHI or MH agar incubated for 24 or 48 h; disk diffusion with BHI or MH agar incubated for 24 or 48 h; and the automated Vitek method with the gram-positive susceptibility Staphylococcus aureus card and R02.03 software (bioMerieux, Inc., Hazelwood, Mo.). Growth failures occurred with MH media (n = 6) but not with BHI media. One growth failure occurred with the Vitek method. Results for each testing method for each Enterococcus strain were interpreted as susceptible, intermediate, or resistant according to current National Committee for Clinical Laboratory Standards (NCCLS) criteria and compared to the vancomycin resistance genotype (i.e., vanA, vanB, vanC-1, or vanC-2/3). For all methods, extension of the incubation time from 24 h to 48 h either produced no difference in the results or gave poorer results. The following methods produced no very major or major interpretive errors: broth microdilution with BHI media incubated for 24 h, agar dilution with BHI media incubated for 24 or 48 h, and E test with BHI media incubated for 24 or 48 h. Unacceptable frequencies of very major errors (> 1%) occurred with all methods for which MH media were used. Minor interpretive errors were frequent with all methods. These minor interpretive errors also occurred most frequently with Enterococcus strains with vanC genes, which encoded low-level vancomycin resistance (MIC < or = 8 microg/ml), as opposed to Enterococcus strains which possessed vanA or vanB genes, which encoded higher-level vancomycin resistance (MIC > or = 64 microg/ml). Modification of NCCLS breakpoints, especially for motile Enterococcus spp. (E. casseliflavus, E. flavescens, and E. gallinarum), may resolve this problem; however, in the current study, one E. faecalis strain and one E. faecium strain carried only the vanC gene. The agar screen method may also require reformulation. The current agar screen plate contains 6 microg of vancomycin per ml, which may not detect all low-level resistance associated with vanC genotypes. Nevertheless, the clinical significance of this low-level vancomycin resistance remains unknown.

Agar↗

PubMed2000

Intraocular penetration of vancomycin eye drops after application to the medial canthus with closed lids.

AIMS: To investigate the intraocular penetration of vancomycin eye drops and to compare the conventional method of drop instillation to the lower cul de sac with applying drops to the medial canthus with closed lids. METHODS: This prospective randomised trial evaluated 53 eyes of 53 patients who had undergone extracapsular cataract extraction (ECCE) with intraocular lens implantation. Vancomycin (50 mg/ml) eye drops were applied to either the lower cul de sac with open lids (conventional method), or to the medial canthus with the patient in a supine position and with closed lids. After paracentesis performed during ECCE, an aqueous humour sample was taken and vancomycin concentration was measured using the TDX vancomycin assay (fluorescence polarisation immunoassay). RESULTS: Vancomycin concentration in the anterior chamber were above the minimal inhibitory concentration for Gram positive bacteria in the two methods of drop instillation examined (2.04 (SD 1.9) microg/ml and 1.49 (1.1) microg/ml in the open and closed methods, respectively (p =0.202)). CONCLUSIONS: Vancomycin (50 mg/ml) reaches therapeutic concentration in the anterior chamber after topical drop application. Comparable concentrations were reached when drops were applied in either the lower cul de sac or to the medial canthus with closed lids. The latter method is proposed as likely to improve patient compliance.

Administration, Topical↗

PubMed2001

Intravitreal vancomycin and gentamicin concentrations in patients with postoperative endophthalmitis.

BACKGROUND/AIMS: To study the intravitreal antibiotic concentrations and the efficacy of an intravitreal dosing regimen to treat patients with postoperative bacterial endophthalmitis. This regimen, based on pharmacokinetic/pharmacodynamic considerations, relies on a repeat antibiotic injection of a lower dose than is generally used. METHODS: In consecutive patients with suspected postoperative endophthalmitis a vitreous biopsy for bacterial culture was taken before 0.2 mg vancomycin and 0.05 mg gentamicin were injected intravitreally. After 3 or 4 days a second biopsy was taken for bacteriological culture and to measure intravitreal vancomycin and gentamicin concentrations, followed by a repeat injection of 0.2 mg vancomycin. RESULTS: 17 patients entered the study. In 11 patients the initial bacterial culture was positive, predominantly coagulase negative staphylococci. All second vitreous biopsies were sterile. Intravitreal vancomycin levels varied between 2.6 and 18.0 microg/ml (mean 10.3 (SD 4.1) microg/ml) after 3 days and between 3.1 and 16.6 microg/ml (mean 7.5 (6.2) microg/ml) after 4 days which is well above the minimal inhibitory concentration for most micro-organisms. Concentrations of intravitreal gentamicin varied between 0.90 and 3.3 microg/ml (mean 1.6 (0.72) microg/ml) after 3 days and between 1.2 and 2.6 microg/ml (mean 1.9 (0.99) microg/ml) after 4 days. CONCLUSION: This dosing regimen resulted both in adequate intravitreal vancomycin and gentamicin levels for over a week as well as in negative second cultures. This study also provides new information on intravitreal vancomycin and gentamicin concentration over time in patients with postoperative endophthalmitis.

Aged↗

PubMedDate not supplied

Stability and delivery of vancomycin hydrochloride when admixed in a total parenteral nutrition solution.

Vancomycin hydrochloride, 400 mg/liter was mixed in six standard pediatric parenteral nutrition solutions with and without heparin added. The solutions were stored over a period of 8 days (192 hr) under refrigeration and at room temperature. Aliquots from all six solutions were assayed in duplicate for vancomycin at time 0, 24, 96, and 192 hr. All samples were run through an Ivex 0.22-micron filter, observed for physical incompatibilities, and frozen at -70 degrees C until assay. Our results indicate that vancomycin was stable and was delivered with loss in concentration of less than 5% with and without storage under refrigeration. This study suggests an alternative method for delivering vancomycin when treating a catheter-related infection. If vancomycin is delivered in this fashion, less manipulations of the line would be required. In addition, there may be a theoretical advantage of constantly bathing the catheter with vancomycin when the catheter is suspected of harboring the infecting organism.

Drug Stability↗

PubMed1986

Vancomycin-induced neutropenia.

A case of vancomycin-induced neutropenia is presented with a review of other reported cases in the literature. A 59-year-old white female was started on vancomycin therapy for a chronic infection of a total left hip replacement. After 38 days of treatment, the patient developed a severe leukopenia with a white blood cell count of 1700/mm3 and the presence of only occasional neutrophils. Upon discontinuation of vancomycin, the leukocyte and neutrophil counts promptly increased with full recovery in one week. Subsequently, the patient was restarted on a five-day course of vancomycin at a lower dose that proved uneventful with no recurrence of neutropenia. It is unclear whether the neutropenia would have recurred with a longer course of vancomycin. A review of the literature suggests that an immunologic mechanism may be responsible for the reaction. Physicians and other health professionals should be aware that neutropenia is a potential reaction of patients receiving prolonged vancomycin treatment.

Agranulocytosis↗

PubMed1989

Evaluation of a Bayesian method for predicting vancomycin dosing.

The purpose of this study is to evaluate the performance of a vancomycin dosing program in predicting dosages necessary to achieve desired serum vancomycin concentrations in a relatively large patient population. With the completion of initial performance evaluation, revised pharmacokinetic parameter estimates derived in the initial evaluation are used to reevaluate program performance. The program uses population estimates of vancomycin's volume of distribution (Vd) and clearance (Cl) to initially predict dosing, then individualizes those estimates by a Bayesian algorithm (iterations) which uses dosing and the resulting serum vancomycin concentration data. Use of the Bayesian forecaster with one iteration significantly increases the calculated Cl value as compared with population estimates; two and three iterations significantly increase both Vd and Cl when compared with population estimates. Absolute values of the predicted minus observed peak serum vancomycin concentrations (accuracy) are 17.7 +/- 14.0, 6.1 +/- 3.6, and 3.4 +/- 2.1 mg/L for dosing using population estimates, Bayesian with one iteration, and Bayesian with two iterations, respectively. Similarly, accuracy of predictions for trough concentrations is 13.8 +/- 12.4, 3.5 +/- 3.2, and 3.2 +/- 2.6 mg/L for each method, respectively. Bias of dosing predictions in achieving desired peak and trough serum vancomycin concentrations is also significantly reduced by using the Bayesian algorithm. Use of the mean Vd and Cl values from three iterations as the starting parameters in a new group of 12 patients significantly improves program performance when compared with use of initial population parameters. Time of sampling for peak serum concentrations has no effect on program performance. In patients with impaired renal function, use of population estimates resulted in less accurate dosing prediction, but this less accurate performance was not observed with use of the Bayesian forecaster. These data demonstrate the accuracy and lack of bias in individualized dosing predictions using the Bayesian dosing method and the ability of revised pharmacokinetic parameter estimates to improve performance.

Bacterial Infections↗

PubMed1993

Vancomycin and tobramycin clearance in an infant during continuous hemofiltration.

OBJECTIVE: To report a case of vancomycin and tobramycin clearance by continuous veno-venous hemofiltration in an infant. Hemofiltration clearance (ClHF) was calculated by two methods and compared for ease and reliability. METHODOLOGY: Case report of a hospitalized four-month-old infant. With method A, ClHF calculation for vancomycin and tobramycin was determined by accurate collection of ultrafiltrate in five 24-hour periods and a midpoint serum sample. With method B, ClHF calculation was determined by obtaining prefilter sample, postfilter sample, and blood flow through filter (Fick principle) over three study periods, correlating to three of five study periods in method A. RESULTS: The infant received continuous veno-venous hemofiltration. With method A, vancomycin ClHF ranged from 0.27 to 0.80 mL/min; tobramycin ClHF ranged from 0.32 to 0.91 mL/min. With method B, ClHF for vancomycin ranged from 0 to 2.08 mL/min. Tobramycin ClHF ranged from 0 to 1.6 mL/min when calculated with method B. CONCLUSIONS: Continuous veno-venous hemofiltration increased the clearance of vancomycin and tobramycin requiring dosage modifications. It appears that method A, which uses the ultrafiltration concentration compared with the serum concentration is more accurate than method B, as it averages fluctuations in ultrafiltrate flow rates. Method B compares a single pre- to postfilter drug concentration and relies on an accurate measurement of ultrafiltration flow rate. Determining ClHF based upon one point in time may overestimate ClHF when the ultrafiltration flow rate varies, as it does in the critically ill. Daily serum concentrations for vancomycin and tobramycin are recommended during continuous veno-venous hemofiltration.

Female↗

PubMed1997

Agranulocytosis induced by vancomycin or ticarcillin/clavulanate.

OBJECTIVE: To reacquaint clinicians with a reportedly rare adverse event of agranulocytosis occurring after long-term administration of vancomycin and ticarcillin/clavulanate, with a subsequent review of other reported cases in the literature. CASE SUMMARY: A 45-year-old white woman with spina bifida developed agranulocytosis (2.7 x 10(3)/mm3 white blood cells with only 3% polymorphonuclear leukocytes and no reported eosinophils or basophils) after long-term administration of vancomycin and ticarcillin/clavulanate for decubitus ulcers and chronic osteomyelitis. Consequently, the cell counts rebounded rapidly on discontinuation of both medications and returned to normal within 1 week. DISCUSSION: The incidence of vancomycin-associated neutropenia is presumably rare, but the increased use of vancomycin may disclose a more frequent occurrence. It is suggested that the mechanism for the reaction is immunologically mediated, yet this remains unclear. Although it is difficult to determine the causative agent in this case, vancomycin was most suspect clinically. Ticarcillin/clavulanate is less likely because our patient has since been readmitted and treated with oxacillin, imipenem/cilastatin, and amoxicillin/clavulanate without affecting the white blood cell count. In that regard, it could be reasoned that an immunologic reaction to ticarcillin would have resulted in a similar outcome with other penicillins. CONCLUSIONS: This case serves as a reminder to clinicians that patients receiving long-term treatment with vancomycin should have their white blood cell count monitored at least weekly.

Agranulocytosis↗

PubMed2002

Pruritus: a useful sign for predicting the haemodynamic changes that occur following administration of vancomycin.

INTRODUCTION: The aim of this study was to investigate the haemodynamic changes that follow the appearance of pruritus during vancomycin administration. METHODS: We studied 50 patients scheduled for coronary artery bypass surgery, and we compared data from patients who exhibited pruritus with those from patients who did not. After the monitoring devices had been positioned, vancomycin (15 mg/kg) was continuously infused at a constant rate over 30 min, before induction of anaesthesia. Haemodynamic profiles were recorded before vancomycin infusion (time point 1); at 15 (time point 2) and 30 min (time point 3) after the beginning of vancomycin infusion; and 15 min after vancomycin infusion had been stopped (time point 4). At each time arterial and mixed venous blood samples were drawn to calculate the shunt fraction (Qsp/Qt). RESULTS: In patients who exhibited pruritus (group A, n = 17) at time point 3 versus time point 1, systemic vascular resistance index (SVRI) and arterial oxygen tension (PaO2) decreased significantly; cardiac index (CI), stroke volume index (SVI) and Qsp/Qt increased significantly; and mean systemic pressure and heart rate were stable. Those changes were observed only in patients not treated with a beta-blocker before surgery, whereas no change occurred in patients treated with the drug. In the patients who were free from pruritus (group B, n = 28), we did not observe any significant change. CONCLUSION: The appearance of pruritus during vancomycin administration indicates that SVRI is declining, thus exposing the patient to risk for hypotension. Therapy with a beta-blocker appears to confer protection against this hemodynamic reaction.

Anti-Bacterial Agents↗

PubMed1993

Vancomycin does not enhance hypotension under anesthesia.

The rapid administration of vancomycin is associated with flushing and hypotension, a consequence of histamine release. The manufacturer discourages administering vancomycin to anesthetized patients, stating that vancomycin aggravates the hypotensive effects of anesthetics. To test this, we randomly assigned 36 adults (ASA classes I through III) to one of two groups: preinduction (Preind, n = 19) and postinduction (Postind, n = 17). Both groups received two different infusions: vancomycin (1 g/250 mL normal saline) and saline (250 mL normal saline) over 30-60 min. The Preind group received vancomycin before anesthesia was induced and saline was administered immediately after anesthesia was induced; for the Postind group, this order was reversed. This was done in a double-blind fashion. The anesthetic induction was standardized by the intravenous administration of thiopental and vecuronium and anesthetic maintenance by inhalation of nitrous oxide and enflurane. End-tidal enflurane, heart rate (HR), and blood pressure (BP) were measured every 3 min. Independent (unpaired) t-test was used in data analysis. The groups did not differ significantly. We conclude that vancomycin infusion may be given under anesthesia without significant adverse hemodynamic consequences if administered over a 30-60 min period of time.

Adult↗

PubMed2006

Stability of vancomycin in icodextrin peritoneal dialysis solution.

BACKGROUND: Icodextrin is a glucose polymer used as an alternative osmotic agent in peritoneal dialysis (PD) solutions. There are few data regarding the long-term stability of vancomycin in icodextrin PD solution. OBJECTIVE: To determine the chemical stability of vancomycin in icodextrin PD solution in polyvinyl chloride containers over a 7 day period at 4, 24, and 37 degrees C. METHODS: Study samples were prepared by adding 2000 mg vancomycin HCl to commercially available 2.0 L bags of icodextrin 7.5% PD solution. Nine bags were prepared and stored in the following conditions: 3 under refrigeration (5 degrees C), 3 at room temperature (24 degrees C), and 3 at body temperature (37 degrees C). Samples were withdrawn from each bag immediately after preparation and at predetermined intervals over the subsequent 7 days. Solutions were visually inspected for precipitation, cloudiness, or discoloration at each sampling interval. Total concentration of vancomycin in dialysate fluid was determined by high performance liquid chromatography. RESULTS: Under refrigeration, a mean +/- SD of 99.7% +/- 0.5% of the initial vancomycin concentration remained at 168 hours (7 days). At room temperature, 97.5% +/- 3.4% remained at 168 hours. At body temperature, 94.3% +/- 3.9% remained at 24 hours. Stability was not assessed beyond these time points. CONCLUSIONS: Premixed vancomycin-icodextrin PD solutions, whether stored refrigerated or at room temperature, were found to be stable for up to 7 days. However, we recommend that these solutions be kept refrigerated whenever possible. Solutions stored at body temperature were stable for up to 24 hours, permitting the practice of prewarming solutions prior to administration.

Dialysis Solutions↗

PubMed2000

Efficacy of percutaneous abscess drainage in patients with vancomycin-resistant enterococci.

OBJECTIVE: We reviewed a 4-year experience draining fluid collections infected with vancomycin-resistant enterococci to determine the outcome of percutaneous intervention in patients with this highly resistant and increasingly common organism. MATERIALS AND METHODS: Charts of patients from whom vancomycin-resistant enterococci had been isolated during percutaneous drainage were reviewed to determine patient response to drainage, catheter management, and outcome of treatment. RESULTS: Twenty-one patients underwent percutaneous drainage of 28 fluid collections from which vancomycin-resistant enterococci were isolated, including 16 intraabdominal abscesses, seven biliary or urinary obstructions, and five empyemas. The drainage of 27 (96%) of 28 collections were technically successful. In seven patients, drainage provided the first isolation of vancomycin-resistant enterococci from the patient. Five patients also had blood cultures with positive findings for vancomycin-resistant enterococci, and 14 collections were coinfected with other bacteria or with fungi. Twenty collections (71%) or obstructions were successfully treated with percutaneous drainage. Drainage was unsuccessful in treating eight collections in seven patients. CONCLUSION: Despite high-level antibiotic resistance, fluid collections infected with vancomycin-resistant enterococci can be successfully drained percutaneously, resulting in a favorable likelihood of recovery for patients.

Abscess↗

PubMed2005

Evaluation of safety and pharmacokinetics of vancomycin after intravenous regional limb perfusion in horses.

OBJECTIVE: To evaluate clinical variables, regional concentrations, and pharmacokinetics of vancomycin in the synovial fluid of distal forelimb joints of horses after IV regional limb perfusion. ANIMALS: 6 horses. PROCEDURE: Vancomycin was administered via IV regional limb perfusion to the distal portion of the forelimbs of anesthetized horses. Drug (300 mg of vancomycin hydrochloride in 60 mL of saline [0.9% NaCl] solution) was infused into 1 forelimb, whereas the contralateral limb served as a control and was perfused with 60 mL of saline solution. Solutions were injected into the lateral digital vein after digital exsanguination. Synovial fluid from the metacarpophalangeal (MTCP) and distal interphalangeal (DIP) joints and systemic blood were collected prior to perfusion and 15, 30, 45, 65, and 90 minutes after initiation of the infusion. Synovial fluid from the MTCP joint and blood were also obtained at 4, 8, 12, and 24 hours after infusion. Plasma urea and creatinine concentrations, degree of lameness, and certain clinical variables involving the MTCP joint and infusion site were assessed for 7 days. Results were compared between the vancomycin treatment and control groups. RESULTS: No complications or significant differences in renal function, lameness, or clinical variables were observed between groups. Vancomycin concentrations exceeded 4 microg/mL in MTCP joints for approximately 20 hours. Higher concentrations were reached in DIP joints than in MTCP joints. CONCLUSIONS AND CLINICAL RELEVANCE: IV regional limb perfusion with 300 mg of vancomycin as a 0.5% solution was safe and may be useful in horses as treatment for distal limb infections.

Analysis of Variance↗

PubMed2006

Evaluation of safety and pharmacokinetics of vancomycin after intraosseous regional limb perfusion and comparison of results with those obtained after intravenous regional limb perfusion in horses.

OBJECTIVE: To evaluate the clinical effects and pharmacokinetics of vancomycin in plasma and synovial fluid after intraosseous regional limb perfusion (IORLP) in horses and to compare results with those obtained after IV regional limb perfusion (IVRLP). ANIMALS: 6 horses. PROCEDURES: 1 forelimb of each horse received vancomycin hydrochloride (300 mg in 60 mL of saline [0.9% NaCl] solution) via IORLP; the contralateral limb received 60 mL of saline solution (control). Solutions were injected into the medullary cavity of the distal portion of the third metacarpal bone. Synovial fluid from the metacarpophalangeal (MTCP) and distal interphalangeal (DIP) joints and blood were collected prior to perfusion and 15, 30, 45, 65, and 90 minutes after beginning IORLP, and synovial fluid from the MTCP joint only and blood were collected 4, 8, 12, and 24 hours after beginning IORLP. Plasma urea and creatinine concentrations and clinical appearance of the MTCP joint region and infusion sites were determined daily for 7 days. Results were compared with those of a separate IVRLP study. RESULTS: Clinical complications were not observed after IORLP. Mean vancomycin concentration in the MTCP joint was 4 microg/mL for 24 hours after IORLP. Compared with IORLP, higher vancomycin concentrations were detected in the DIP joint after IVRLP. Compared with IVRLP, higher vancomycin concentrations were detected in the MTCP joint for a longer duration after IORLP. CONCLUSIONS AND CLINICAL RELEVANCE: IORLP with 300 mg of vancomycin in a 0.5% solution was safe and may be clinically useful in horses. Intravenous and intraosseous routes may be better indicated for infectious processes in the DIP and MTCP joints, respectively.

Animals↗

PubMed1997

Nephrotoxicity of gentamicin and vancomycin given alone and in combination as determined by enzymuria and cortical antibiotic levels in rats.

The purpose of this study was to compare the nephrotoxicity of gentamicin and vancomycin alone and in combination. Thirty-two male Sprague-Dawley rats were randomized into 4 groups of 8 animals. Each group received 200mg/kg gentamicin (G) i.m., or 300 mg/kg vancomycin (V) i.v., or an association of 200 mg/kg gentamicin + 300 mg/kg vancomycin (i.m. and i.v., respectively), or 0.9% NaCl solution i.m. and i.v. (controls). To determine AAP, GGT, and NAG enzyme excretions, urine samples were taken over 24-h periods before and after the start of the experiment. A single renal cortical sample was obtained at necropsy for quantitation of antibiotic levels. No significant modifications of urinary excretions of creatinine and enzymuria were noted during the 24-h period before each drug administration or in controls. AAP, GGT, and NAG excretions were significantly increased after G and G + V injections (p < 0.001), whereas only AAP and GGT were statistically higher in rats receiving V (p < 0.05). NAG elimination (mean +/- SD) was higher in G + V (16.0 +/- 0.2 IU/mmol creatinine/24 h; p < 0.001) than g (8.8 +/- 0.6) or V (1.7 +/- 0.2). Surprisingly, mean vancomycin cortical levels decreased in the combination (827 +/- 131 vs. 1964 +/- 23 micrograms/g for V alone; p < 0.001), whereas gentamicin concentration was unchanged (826 +/- 66 vs. 839 +/- 28 micrograms/g for G alone). Determination of enzymuria allowed the nephrotoxicity of the antibiotics to be graded in the following order: vancomycin + gentamicin > gentamicin > vancomycin.

Acetylglucosaminidase↗