Characteristics and clinical assessment of antibiotic delivery by chitosan sponge in the high-risk diabetic foot: a case series.

OBJECTIVE: The local delivery of antimicrobials is attractive for a number of reasons. Chitosan, a biodegradable polysaccharide sponge material, has been proposed as medium to deliver antibiotics directly to wounds. In this report we evaluate the safety and practicality of antimicrobial delivery via chitosan sponge. METHOD: We present the clinical course and systemic absorption characteristics of three cases of people with diabetic foot wounds treated with antibiotic soaked chitosan sponge (Sentrex BioSponge, Bionova Medical, Germantown, TN). The antibiotic sponge was made by reconstituting 1.2g tobramycin or 100mg doxycycline in 10-15ml saline and saturating the sponge with the solution. The sponge was then applied to the wounds. Serum levels of each respective antibiotic were evaluated after application. Additional in vitro studies were conducted evaluating elution of antibiotics from the chitosan sponge at established minimum inhibitory concentrations (MIC) for Staphylococcus aureus over 28 days. RESULTS: No patient experienced adverse local or systemic effects due to the sponge treatment. The measured serum levels applied antibiotics remained far less than established minimums after intravenous therapy. Each patient required further treatment, however local infection or contamination resolved during the course of their hospital stay after the chitosan/antibiotic application. CONCLUSION: The use of antibiotic-impregnated chitosan sponges appears a safe and effective mechanism of local delivery of antimicrobials in wounds. Future studies and clinical trials are ongoing to confirm these results and to guide clinical applications.

Efficacy assessment of local doxycycline treatment in periodontal patients using multivariate chemometric approach.

The aim of our study was application of chemometric algorithms for multivariate data analysis in efficacy assessment of the local periodontal treatment with doxycycline (DOX). Treatment efficacy was evaluated by monitoring inflammatory biomarkers in gingival crevicular fluid (GCF) samples and clinical indices before and after the local treatment as well as by determination of DOX concentration in GCF after the local treatment. The experimental values from these determinations were submitted to several chemometric algorithms: principal component analysis (PCA), partial least square discriminant analysis (PLS-DA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA). The data structure and the mutual relations of the selected variables were thoroughly investigated by PCA. The PLS-DA model identified variables responsible for discrimination of classes of data, before and after DOX treatment. The OPLS-DA model compared the efficacy of the two commonly used medications in periodontal treatment, chlorhexidine (CHX) and DOX, at the same time providing insight in their mechanism of action. The obtained results indicate that application of multivariate chemometric algorithms can be used as a valuable approach for assessment of treatment efficacy.

Use of a Monte Carlo analysis within a physiologically based pharmacokinetic model to predict doxycycline residue withdrawal time in edible tissues in swine.

The pharmacokinetics of doxycycline were studied following a single intravenous (I.V.) and intramuscular (I.M.) injection of 10 mg/kg into eight healthy pigs. The steady-state tissue/plasma partition coefficients were obtained via a 3-h constant rate infusion (CRI) in four pigs. Based on the results of in vivo studies and the parameters derived from published work, a physiologically based pharmacokinetic (PBPK) model was developed to predict the drug concentration in edible tissues. The predicted values were then compared with those derived from a previous study. To account for individual differences in the processes of drug metabolism and/or diffusion, a Monte Carlo (MC) run of 1000 simulations was incorporated into the PBPK model to predict the doxycycline residue withdrawal times in edible tissues in swine. The withdrawal periods were compared with those derived from linear regression analysis. The PBPK model presented here provided accurate predictions of the observed concentrations in all tissues except for the injection site. The withdrawal times in all edible tissues derived from the MC analysis were longer than those from linear regression analysis. Based on the residues in the injection site and muscle tissue, the MC analysis predicted a withdrawal time of 33 days. Here, we illustrate that MC analysis can be incorporated into the PBPK model to accurately predict doxycycline residue withdrawal time in edible tissues in swine.

Pharmacokinetics of doxycycline after administration as a single intravenous bolus and intramuscular doses to non-lactating Egyptian goats.

The pharmacokinetics of doxycycline hydrochloride (DoxHcl) at a dose of 5 mg kg-1 BW was studied after an intravenous (i.v.) bolus and intramuscular (i.m.) injections in non lactating goats. A microbiological assay employing Bacillus subtilis as the test organism was used to measure its concentrations in serum and urine. Following a single i.v. injection, the serum concentration-time curves of doxycycline hydrochloride were best represented by a two-compartment open model. The drug was rapidly distributed and slowly eliminated with half-lives of distribution (t1/2 alpha) and elimination (t1/2 beta) of 0.52 and 4.62 h, respectively. After i.m. injection of the same dose, the peak serum concentration C(max) was 1.60 microg ml-1 attained at 0.86 h (Tmax). Following i.v. and i.m. injections, the concentrations of doxycycline in urine were much higher than that in serum. Urinary drug concentrations decreased gradually till reaching its lowest detectable level 12 and 24h post-injections, respectively. The extent of serum protein binding percent was 32.8% and the systemic bioavailability was 99.40% after i.m. injection of 5 mg kg-1 BW

Assessment of plasma concentrations of doxycycline in budgerigars fed medicated seed or water.

OBJECTIVE: To determine whether plasma doxycycline concentrations considered effective for treatment of avian chlamydiosis could be safely established and maintained in budgerigars via administration of doxycycline in water or seed. DESIGN: Prospective study. ANIMALS: 68 healthy mature budgerigars. PROCEDURE: In 14-day trials, plasma doxycycline concentrations were measured in budgerigars provided with water containing 0, 50, 100, 200, or 400 mg of doxycycline hyclate/L or a hulled seed diet containing 0, 100, 200, or 400 mg of doxycycline hyclate/kg. On the basis of these results, birds were fed seed containing 300 mg of doxycycline/kg for 42 days, and a control group received unmedicated seed. Blood samples for plasma doxycycline analysis were collected either in the morning on treatment days 4, 7 14, 21, 28, 35, and 42 or in the afternoon on days 12, 26, and 40. Birds were observed daily. On days 14, 28, and 42, physical and plasma biochemical variables, PCV, and total solids concentration were measured; cloacal specimens were obtained for bacteriologic and fungal culture. RESULTS: During a 14-day period, treatment with water containing < or = 400 mg of doxycycline/L did not maintain plasma doxycycline concentrations of > or = 1 microg/mL, but seed containing 300 mg of doxycycline hyclate/kg maintained mean plasma doxycycline concentrations > 0.98 microg/mL for 42 days without notable adverse effects. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that hulled seed containing 300 mg of doxycycline hyclate/kg can safely establish and maintain plasma doxycycline concentrations that are considered adequate for treatment of chlamydiosis in adult nonbreeding budgerigars.

Assessment of a fluoroquinolone, three beta-lactams, two aminoglycosides, and a cycline in treatment of murine Yersinia pestis infection.

Amoxicillin, cefotaxime, ceftriaxone, gentamicin, doxycycline, and ofloxacin were active in vitro, like the reference drug streptomycin, against the virulent strain Yersinia pestis 6/69M. The comparative efficacies of these drugs in vivo were evaluated in a standardized and reproducible mouse model of systemic infection. Each antibiotic was injected intravenously once, at 24 h postinfection, and then repeatedly during 48 h. In vivo results were measured by counting the viable bacteria recovered from the whole spleens of mice sacrificed at selected times. All the drugs were manifestly successful; ceftriaxone, ofloxacine, and the reference drug were the most effective. Therefore, gentamicin and doxycycline could be used, depending on the clinical forms of the Y. pestis infection. Further investigations on beta-lactams, especially those used in the present study, could be carried out to confirm or not confirm their activities against Y. pestis. Ofloxacin appeared to be as active and to perform as rapidly as streptomycin in the treatment of murine Y. pestis infection, which is in agreement with the previous successes obtained with the use of fluoroquinolones in the treatment of murine infections caused by other pathogenic yersiniae.