In vitro elution of gentamicin, amikacin, and ceftiofur from polymethylmethacrylate and hydroxyapatite cement

OBJECTIVE: To compare the elution characteristics of ceftiofur and liquid and powdered gentamicin and amikacin from polymethylmethacrylate (PMMA) and from hydroxyapatite cement (HAC). METHODS: PMMA and HAC beads in triplicate were impregnated with various amounts and formulations of antibiotics. Beads were immersed in 5 mL of phosphate buffered saline that was replaced at 1, 3, 6, and 12 hours, and 1, 2, 3, 5, 7, 10, 14, 18, 22, 26, and 30 days. The eluent was stored at -70 degrees C until assayed within 2 weeks by microbiological assay (gentamicin and amikacin) or capillary electrophoresis (ceftiofur). RESULTS: Rate of elution for all beads was greatest within the first 24 hours. Cumulative release of total antibiotic dose from beads over 30 days was significantly greater from HAC than PMMA. Antibiotic elution was directly related to the amount of antibiotic incorporated into the cement. Powdered and liquid forms of gentamicin had similar elution rates from PMMA. Elution of amikacin from PMMA beads was greater when the powdered form was used compared with liquid amikacin. Eluent concentrations of ceftiofur were similar to those of the aminoglycosides during the first 3 to 7 days but then decreased precipitously by comparison. CONCLUSIONS: Elution of antibiotics from HAC was greater than from PMMA. Gentamicin- and amikacin-impregnated PMMA and HAC released bactericidal concentrations of antibiotic for at least 30 days. Ceftiofur-impregnated PMMA or HAC is unlikely to provide long-term bactericidal concentrations. CLINICAL RELEVANCE: Gentamicin and amikacin elute effectively from PMMA and HAC.     

Disposition of gentamicin administered intravenously to horses with sepsis.

Plasma concentration of gentamicin was measured 1, 4, and 6 hours after IV administration in 35 hospitalized adult horses on days 1, 3, 5, and 10 of treatment. The mean apparent elimination rate constant beta was 0.53 +/- 0.10 h-1 on day 1 for horses with normal plasma creatinine concentration and 0.41 +/- 0.13 h-1 for horses with abnormally high plasma creatinine concentration. There was no significant difference between beta of the hospitalized horses and of 6 healthy horses treated with gentamicin, but total clearance for the hospitalized horses with normal plasma creatinine concentration was significantly greater than that of the healthy horses and the hospitalized horses with abnormally high plasma creatinine concentration. Gentamicin clearance was significantly correlated with plasma creatinine concentration for healthy horses and hospitalized horses, and beta was significantly correlated with plasma creatinine concentration for hospitalized horses. Twelve of the 35 hospitalized horses required an adjustment in gentamicin dosage. Ten required a reduction, 1 an increase, and 1 a change in dosage and interval with no net change in total daily dose. One horse of 35 (2.9%) developed signs compatible with nephrotoxicosis on day 14 of treatment, despite appropriate gentamicin concentrations on day 10.     

Concentrations of gentamicin in serum and bronchial lavage fluid after intravenous and aerosol administration of gentamicin to horses

OBJECTIVE: To compare concentrations of gentamicin in serum and bronchial lavage fluid after IV and aerosol administration of gentamicin to horses. ANIMALS: 9 healthy adult horses. PROCEDURE: Gentamicin was administered by aerosolization (20 ml of gentamicin solution [50 mg/ml]) and IV injection (6.6 mg of gentamicin/kg of body weight) to each horse, with a minimum of 2 weeks between treatments. Samples of pulmonary epithelial lining fluid were collected by small volume (30 ml) bronchial lavage 0.5, 4, 8, and 24 hours after gentamicin administration. Serum samples were obtained at the same times. All samples were analyzed for gentamicin concentration, and cytologic examinations were performed on aliquots of bronchial lavage fluid collected at 0.5, 8, and 24 hours. RESULTS: Gentamicin concentrations in bronchial lavage fluid were significantly greater 0.5, 4, and 8 hours after aerosol administration, whereas serum concentrations were significantly less at all times after aerosol administration, compared with IV administration. Neutrophil counts in bronchial lavage fluid increased from 0.5 to 24 hours, regardless of route of gentamicin administration. CONCLUSIONS AND CLINICAL RELEVANCE: Aerosol administration of gentamicin to healthy horses resulted in gentamicin concentrations in bronchial fluid that were significantly greater than those obtained after IV administration. A mild inflammatory cell response was associated with aerosol delivery of gentamicin and repeated bronchial lavage. Aerosol administration of gentamicin may have clinical use in the treatment of bacterial bronchopneumonia in horses.     

An aerogenic Pasteurella-like organism isolated from horses

Thirteen strains of a gram-negative, fermentative bacterium that produced gas from glucose were isolated from horses with a variety of clinical conditions. The morphological and biochemical characteristics of this bacterium are similar to those described for the family Pasteurellaceae. These strains appear to constitute a new taxon within the genus Pasteurella; however, the final taxonomic position of this group depends upon more detailed genetic studies. Case histories indicate that this bacterium may be a primary respiratory pathogen and may play a secondary role in various other disease conditions.     

Campylobacter-like organisms isolated from gastric mucosa of ferrets

Campylobacter-like organisms (CLO) were isolated from gastric lesions in 1 ferret and gastric mucosa of 2 healthy ferrets. The organism was not isolated from biopsies of gastric mucosa of 14 other healthy ferrets, 1 of which had small gastric lesions located at the pylorus. Lesions from which CLO were isolated were located in the antrum of 1 ferret and were classified as inflammation with repair. Affected gastric tissue was highly vascularized with fibrous connective tissue surrounding irregularly shaped glands. Necrosis and ulceration of adjacent mucosa also were observed. Using Warthin-Starry stain, Campylobacter-like organisms were seen on and in the glandular epithelium of the ferret with gastric lesions from which CLO were isolated.     

Plasma and synovial fluid concentrations of gentamicin in horses after intra-articular administration of buffered and unbuffered gentamicin

The concentration of gentamicin in plasma and synovial fluid of normal adult horses was measured periodically for 24 hours after IV (2.2 mg/kg of body weight), intra-articular (IA; 150 mg), and simultaneous IV and IA administrations. Gentamicin also was buffered with sodium bicarbonate (3 mEq) and then was administered IA and simultaneously IV and IA. Synovial fluid specimens were obtained via an indwelling catheter placed into the antebrachiocarpal joint. The peak mean plasma gentamicin concentration (8.30 micrograms/ml) after IV administration was significantly (P less than 0.05) greater than that (0.69 microgram/ml) after IA administration of gentamicin and that (0.55 microgram/ml) after administration of gentamicin buffered with sodium bicarbonate. Gentamicin concentration greater than a therapeutic concentration was not attained in the plasma after IA administration of buffered or unbuffered gentamicin. The peak mean synovial fluid concentration (1,828 micrograms/ml) after IA administration of unbuffered gentamicin was significantly (P less than 0.05) greater than that (2.53 micrograms/ml) after IV administration and significantly (P less than 0.05) less than that (5,720 micrograms/ml) after simultaneous IV and IA administration. The peak mean synovial fluid concentration after IA administration of buffered gentamicin, with and without simultaneous IV administration (2,128 and 2,680 micrograms/ml, respectively), was not significantly different than that after IA treatment with unbuffered gentamicin. Mean synovial fluid concentration did not differ significantly between groups after IA administration of gentamicin in any combination at postinjection hours 8, 12, and 24, but remained significantly (P less than 0.05) greater than that at the same times after IV administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Identification and characterization of Streptococcus agalactiae isolated from horses.

Seven group B streptococcal cultures isolated from three horses reacted with group B-specific antiserum, were CAMP positive, pigmented and showed the typical biochemical properties of Streptococcus agalactiae. The identification could be confirmed by PCR amplification of the 16S rRNA gene and a subsequent RsaI restriction pattern typical for S. agalactiae. In addition, the isolates were identified by amplification of species specific parts of the 16S rRNA gene, the 16S-23S rRNA intergenic spacer region and by amplification of the CAMP-factor (cfb) gene. Six isolates could be classified as serotype III/Rib, one isolate as serotype Ia/cbeta. The occurrence of the protein antigens Rib and cbeta could be confirmed by PCR amplification of the respective genes. The six isolates of serotype III/Rib were hyaluronidase negative, had a hylB gene with a size of 4.6 kb and an insertion element IS1548 of 0.98 kb. The isolate of serotype Ia/cbeta was hyaluronidase positive, had a hylB gene with a size of 3.3 kb and no insertion element IS1548. In addition, all seven isolates had the insertion element ISSag2 and the gene lmb encoding the laminin binding surface protein Lmb and the gene scpB encoding C5a peptidase. According to the present results the group B streptococci isolated from horses showed characteristics of human isolates of this species.     

Pharmacokinetic adjustment of gentamicin dosing in horses with sepsis

Serum gentamicin concentrations were measured and pharmacokinetic values were calculated for 12 equine patients receiving parenteral gentamicin therapy. Horses were selected for monitoring of gentamicin pharmacokinetics if they met several criteria of high risk for gentamicin-induced toxicosis. Two blood samples were obtained, one immediately before gentamicin dosing and one at 1 hour after dosing. Gentamicin serum concentrations were analyzed and dosage adjustments were made on the basis of calculated one-compartment pharmacokinetic values. Nine of the 12 horses required dosage adjustment to optimize therapeutic concentrations. Even for horses for which there was no evidence of decreased renal function, variation in the disposition of gentamicin was substantial. Because of the larger volume of distribution in foals, an initial dosage of 3 mg/kg every 12 hours was found to best approximate target concentrations. Therefore, published standard dosages were a poor means of achieving desired peak and trough concentrations in many animals. Seemingly, for optimal treatment of horses with sepsis, gentamicin dosage adjustments based on the patient's pharmacokinetic values is required.     

Molecular epidemiologic features of Corynebacterium pseudotuberculosis isolated from horses

OBJECTIVE: To characterize isolates of Corynebacterium pseudotuberculosis from horses, cattle, and sheep in Colorado, Kentucky, Utah, and California in samples collected during perceived epidemics of infection (increased numbers of cases identified) in 2002 and 2003, and determine how closely isolates were related and their possible source. SAMPLE POPULATION: 54 isolates of C pseudotuberculosis from 49 horses, 4 cattle, and 1 sheep. PROCEDURES: Random amplified polymorphic DNA (RAPD) polymerase chain reaction (PCR) assay, PCR assay for the gene encoding the phospholipase D (PLD) toxin, biochemical analyses, and tests for susceptibility to 17 antimicrobial drugs were performed. RESULTS: All isolates reduced nitrate to nitrite, most yielded positive results for the PLD toxin gene, and all were susceptible to antimicrobial drugs. Ten genetic types were detected by use of RAPD PCR assay; types III to X were isolated from horses, cattle, or both in 1 or more states. Types III and IX were isolated from both horses and cattle. Types VII and VIII were isolated in only 1 state, but the number of isolates in these groups was small. In contrast, all other types were isolated in 2 or more states. All isolates from Utah were type III, but the other 3 states had isolates from more than 1 type. CONCLUSIONS AND CLINICAL RELEVANCE: These data are consistent with a clonally expanding epidemic of infection in Utah and an increase in number of infections caused by multiple strains of C pseudotuberculosis not derived from a single source in the other states. The increase in number of infections could be the result of reporting bias, environmental factors facilitating infection, or host factors such as greater herd susceptibility.