Development and validation of a reversed phase liquid chromatographic method for analysis of oxytetracycline and related impurities.

A simple, robust and fast high-performance liquid chromatographic method is described for the analysis of oxytetracycline and its related impurities. The principal peak and impurities are all baseline separated in 20 min using an Inertsil C8 (150 mm × 4.6 mm, 5 µm) column kept at 50 °C. The mobile phase consists of a gradient mixture of mobile phases A (0.05% trifluoroacetic acid in water) and B (acetonitrile-methanol-tetrahydrofuran, 80:15:5, v/v/v) pumped at a flow rate of 1.3 ml/min. UV detection was performed at 254 nm. The developed method was validated for its robustness, sensitivity, precision and linearity in the range from limit of quantification (LOQ) to 120%. The limits of detection (LOD) and LOQ were found to be 0.08 µg/ml and 0.32 µg/ml, respectively. This method allows the separation of oxytetracycline from all known and 5 unknown impurities, which is better than previously reported in the literature. Moreover, the simple mobile phase composition devoid of non-volatile buffers made the method suitable to interface with mass spectrometry for further characterization of unknown impurities. The developed method has been applied for determination of related substances in oxytetracycline bulk samples available from four manufacturers. The validation results demonstrate that the method is reliable for quantification of oxytetracycline and its impurities.

Partial budgeting assessment of the treatment of pyometra, follicular cysts and ovarian inactivity causing postpartum anoestrus in dairy cattle.

A total of 412 multiparous German Holstein cows were screened for postpartum pyometra, follicular cysts and ovarian inactivity to assess economic and productivity losses in relation to pharmaceutical expenditures. Our results show that cows treated for pyometra with prostaglandin f2 alpha (PGF2α) and oxytetracycline had significantly (P<0.05) greater total and net returns than untreated cows or those treated with PGF2α+cephapirin or PGF2α alone. Milk yields from untreated cows affected by follicular cysts were significantly (P<0.05) lower than the yields from cows treated with gonadotrophin-releasing hormone (GnRH)- and GnRH+PGF2α. In addition, the use of GnRH to treat cows with ovarian inactivity resulted in significantly (P<0.05) lower costs and greater total and net return values compared to untreated controls.

[Oxytetracycline--mechanism of action and application in skin diseases]. / Mechanizm dzialania i zastosowanie oksytetracykliny w chorobach skóry.

Oxytetracycline is a bacteriostatic antibiotic. Newly discovered, additional mechanisms of action include antioxidant, antiinflammatory and immynosupresive activity of oxytetracycline and other tetracyclines. These activities were the basis for developing therapy regimens with oxytetracycline in subantimicrobial doses. Due to its significant efficacy, limited adverse effects and low therapy costs, oxytetracycline at the dose of 500 mg per day is presently considered as therapy of choice in papulopustulous acne. Rosacea and perioral dermatitis are other indications. Topical oxytetracycline shows significant efficacy in primary and secondary skin infections with inflammatory reaction.

Strategies, effectiveness and rationale of vector-borne disease control in the pastoralist system of south-western Uganda.

In Uganda, control of vector-borne diseases is mainly in form of vector control, and chemotherapy. There have been reports that acaricides are being misused in the pastoralist systems in Uganda. This is because of the belief by scientists that intensive application of acaricide is uneconomical and unsustainable particularly in the indigenous cattle. The objective of this study was to investigate the strategies, rationale and effectiveness of vector-borne disease control by pastoralists. To systematically carry out these investigations, a combination of qualitative and quantitative research methods was used, in both the collection and the analysis of data. Cattle keepers were found to control tick-borne diseases (TBDs) mainly through spraying, in contrast with the control of trypanosomosis for which the main method of control was by chemotherapy. The majority of herders applied acaricides weekly and used an acaricide of lower strength than recommended by the manufacturers. They used very little acaricide wash, and spraying was preferred to dipping. Furthermore, pastoralists either treated sick animals themselves or did nothing at all, rather than using veterinary personnel. Oxytetracycline (OTC) was the drug commonly used in the treatment of TBDs. Nevertheless, although pastoralists may not have been following recommended practices in their control of ticks and tick-borne diseases, they were neither wasteful nor uneconomical and their methods appeared to be effective. Trypanosomosis was not a problem either in Sembabule or Mbarara district. Those who used trypanocides were found to use more drugs than were necessary.

Randomised controlled multiple treatment comparison to provide a cost-effectiveness rationale for the selection of antimicrobial therapy in acne.

OBJECTIVES: To determine the relative efficacy and cost-effectiveness of five of the most commonly used antimicrobial preparations for treating mild to moderate facial acne in the community; the propensity of each regimen to give rise to local and systemic adverse events; whether pre-existing bacterial resistance to the prescribed antibiotic resulted in reduced efficacy; and whether some antimicrobial regimens were less likely to give rise to resistant propionibacterial strains. DESIGN: This was a parallel group randomised assessor-blind controlled clinical trial. It was a pragmatic design with intention-to-treat analysis. All treatments were given for 18 weeks, after a 4-week treatment free period. Outcomes were measured at 0, 6, 12 and 18 weeks. SETTING: Primary care practices and colleges in and around Nottingham and Leeds, and one practice in Stockton-on-Tees, England. PARTICIPANTS: Participants were 649 people aged 12--39 years, all with mild to moderate inflammatory acne of the face. INTERVENTIONS: Study participants were randomised into one of five groups: 500 mg oral oxytetracycline (non-proprietary) twice daily (b.d.) + topical vehicle control b.d.; 100 mg oral Minocin MR (minocycline) once daily (o.d.) + topical vehicle control b.d.; topical Benzamycin (3% erythromycin + 5% benzoyl peroxide) b.d. + oral placebo o.d.; topical Stiemycin (2% erythromycin) o.d. + topical Panoxyl Aquagel (5% benzoyl peroxide) o.d. + oral placebo o.d., and topical Panoxyl Aquagel (5% benzoyl peroxide) b.d. + oral placebo o.d. (the active comparator group). MAIN OUTCOME MEASURES: The two primary outcome measures were: (1) the proportion of patients with at least moderate self-assessed improvement as recorded on a six-point Likert scale, and (2) change in inflamed lesion count (red spots). RESULTS: The best response rates were seen with two of the topical regimens (erythromycin plus benzoyl peroxide administered separately o.d. or in a combined proprietary formulation b.d.), compared with benzoyl peroxide alone, oxytetracycline (500 mg b.d.) and minocycline (100 mg o.d.), although differences were small. The percentage of participants with at least moderate improvement was 53.8% for minocycline (the least effective) and 66.1% for the combined erythromycin/benzoyl peroxide formulation (the most effective); the adjusted odds ratio for these two treatments was 1.74 [95% confidence interval (CI) 1.04 to 2.90]. Similar efficacy rankings were obtained using lesion counts, acne severity scores and global rating by assessor. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective regimen (ratio of means 12.3; difference in means -0.051 units/GBP, 95% CI -0.063 to -0.039). The efficacy of oxytetracycline was similar to that of minocycline, but at approximately one-seventh of the cost. For all regimens, the largest reductions in acne severity were recorded in the first 6 weeks. Reductions in disability scores using the Dermatology Quality of Life Scales were largest for both topical erythromycin-containing regimens and minocycline. The two topical erythromycin-containing regimens produced the largest reductions in the prevalence and population density of cutaneous propionibacteria, including antibiotic-resistant variants, and these were equally effective in participants with and without erythromycin-resistant propionibacteria. The clinical efficacy of both tetracyclines was compromised in participants colonised by tetracycline-resistant propionibacteria. None of the regimens promoted an overall increase in the prevalence of antibiotic-resistant strains. Systemic adverse events were more common with the two oral antibiotics. Local irritation was more common with the topical treatments, particularly benzoyl peroxide. Residual acne was present in most participants (95%) at the end of the study. CONCLUSIONS: The response of mild to moderate inflammatory acne to antimicrobial treatment in the community is not optimal. Only around half to two-thirds of trial participants reported at least a moderate improvement over an 18-week study period; extending treatment beyond 12 weeks increased overall benefit slightly. Around one-quarter dropped out when using such treatments, and 55% sought further treatment after 18 weeks. Topical antimicrobial therapies performed at least as well as oral antibiotics in terms of clinical efficacy. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective therapy for facial acne. The efficacy of all three topical regimens was not compromised by pre-existing propionibacterial resistance. Benzoyl peroxide was associated with a greater frequency and severity of local irritant reactions. It is suggested that the use of a combination of topical benzoyl peroxide and erythromycin gives less irritation and better quality of life. There was little difference between erythromycin plus benzoyl peroxide administered separately and the combined proprietary formulation in terms of efficacy or local irritation, except that the former was nearly three times more cost-effective. The data on cost-effectiveness, and outcomes in patients with resistant propionibacterial floras, did not support the first line use of minocycline for mild to moderate inflammatory acne of the face. Three priority areas for clinical research in acne are: defining end-points in acne trials (i.e. what is a satisfactory outcome?); developing and validating better patient-based measures for assessing treatment effects on facial and truncal acne; and exploring patient characteristics that may modify treatment effects (efficacy and tolerability).

Comparison of five antimicrobial regimens for treatment of mild to moderate inflammatory facial acne vulgaris in the community: randomised controlled trial.

BACKGROUND: We investigated the efficacy and cost-effectiveness of five antimicrobial regimens for mild to moderate facial acne and whether propionibacterial antibiotic resistance affects treatment response. METHODS: In this randomised, observer-masked trial, 649 community participants were allocated one of five antibacterial regimens. Primary outcomes were patients' self-assessed improvement and reduction in inflamed lesions at 18 weeks. Analyses were by intention to treat. FINDINGS: Moderate or greater improvement at 18 weeks was reported in 72 (55%) of 131 participants assigned oral oxytetracycline plus topical placebo, 70 (54%) of 130 assigned oral minocycline plus topical placebo, 78 (60%) of 130 assigned topical benzoyl peroxide plus oral placebo, 84 (66%) of 127 assigned topical erythromycin and benzoyl peroxide in a combined formulation plus oral placebo, and 82 (63%) of 131 assigned topical erythromycin and benzoyl peroxide separately plus oral placebo. Most improvement occurred in the first 6 weeks. Treatment differences for the proportion of people with at least moderate improvement were: minocycline versus oxytetracycline -1.2% (unadjusted 95% CI -13.3 to 10.9); combined erythromycin and benzoyl peroxide versus oxytetracycline 11.1% (-0.7 to 22.9) and versus minocycline 12.3% (0.4 to 24.2); erythromycin and benzoyl peroxide separately versus combined formulation -3.5% (-15.2 to 8.2); benzoyl peroxide versus oxytetracycline 5.0% (-7.0 to 17.0), versus minocycline 6.2% (-5.8 to 18.2), and versus combined formulation -6.1% (-17.9 to 5.7). Benzoyl peroxide was the most cost-effective treatment. Efficacy of both tetracyclines was reduced by pre-existing tetracycline resistance. INTERPRETATION: Topical benzoyl peroxide and benzoyl peroxide/erythromycin combinations are similar in efficacy to oral oxytetracycline and minocycline and are not affected by propionibacterial antibiotic resistance.

A comparison of prophylactic efficacy of tilmicosin and a new formulation of oxytetracycline in feedlot calves.

Two replicated-pen field studies were performed under commercial feedlot conditions in western Canada to compare the administration of long-acting oxytetracycline at 30 mg/kg body weight (BW) versus tilmicosin at 10 mg/kg BW to feedlot calves upon arrival at the feedlot. Ten thousand nine hundred and eighty-nine, recently weaned, auction market derived, crossbred beef steer and bull calves were randomly allocated upon arrival at the feedlot to one of 2 experimental groups as follows: oxytetracycline, which received intramuscular long-acting oxytetracycline (300 mg/mL formulation) at a rate of 30 mg/kg BW; or tilmicosin, which received subcutaneous tilmicosin (300 mg/mL formulation) at a rate of 10 mg/kg BW. There were 20 pens in each experimental group. In Study 1 and in the combined analysis, the initial undifferentiated fever (UF) treatment rate was significantly (P < 0.05) higher in the oxytetracycline group as compared with the tilmicosin group. There were no significant (P > or = 0.05) differences in first UF relapse, second UF relapse, third UF relapse, overall chronicity, overall rail, overall mortality, bovine respiratory disease (BRD) mortality, hemophilosis mortality, arthritis mortality, or miscellaneous mortality rates between the experimental groups in either study or in the combined analysis. In addition, there were no significant (P > or = 0.05) differences in initial weight, final weight, weight gain, days on feed, daily dry matter intake, average daily gain, or the dry matter intake to gain ratio between the experimental groups in either study or in the combined analyses. In the economic analysis, there was a net economic advantage of $5.22 CDN per animal in the oxytetracycline group, due to a lower prophylactic cost, even though the UF therapeutic cost was higher.

An evaluation of the relative efficacy of a new formulation of oxytetracycline for the treatment of undifferentiated fever in feedlot calves in western Canada.

A field trial was performed under commercial feedlot conditions in western Canada to compare the efficacy of a new formulation of long-acting oxytetracycline (LA 30) to a standard long-acting oxytetracycline formulation (LA 20) and florfenicol (FLOR) for the treatment of undifferentiated fever (UF) in calves that received metaphylactic tilmicosin upon arrival at the feed-lot. Seven hundred and ninety-seven recently weaned, auction market derived, crossbred, beef calves suffering from UF were allocated to 1 of 3 experimental groups as follows: LA 30, which received intramuscular long-acting oxytetracycline (300 mg/mL formulation) at the rate of 30 mg/kg body weight (BW) at the time of allocation; LA 20, which received intramuscular long-acting oxytetracycline (200 mg/mL formulation) at the rate of 20 mg/kg BW at the time of allocation; or FLOR, which received intramuscular florfenicol administered at the rate of 20 mg/kg BW at the time of allocation and again 48 hours later. Two hundred and sixty-six animals were allocated to the LA 30 group, 265 animals were allocated to the LA 20 group, and 266 animals were allocated to the FLOR group. The relative efficacy of the LA 30 group, as compared with the LA 20 and FLOR groups, was assessed by comparing relapse, chronicity, wastage, and mortality rates. The overall mortality (RR = 0.50) rate in the LA 30 group was significantly (P < 0.05) lower than in the LA 20 group. However, the overall chronicity (RR = 2.56) and overall wastage (RR = 6.97) rates of the LA 30 group were significantly (P < 0.05) higher than in the LA 20 group. There were no significant (P > or = 0.05) differences in UF relapse rates or cause specific mortality rates between the LA 30 and LA 20 groups. In the economic analysis, there was an advantage of $28.59 CDN per animal in the LA 30 group compared with the LA 20 group. The overall chronicity (RR = 2.25) and overall wastage (RR = 2.80) rates of the LA 30 group were significantly (P < 0.05) higher than the FLOR group. There were no significant (P > or = 0.05) differences in UF relapse rates, overall mortality rates, or cause specific mortality rates between the LA 30 and FLOR groups. In the economic analysis, there was an advantage of $12.90 CDN per animal in the LA 30 group compared with the FLOR group. In summary, the results of this study indicate that it is more cost-effective to use a new formulation of long-acting oxytetracycline (300 mg/mL formulation administered at a rate of 30 mg/kg BW) than a standard long-acting oxytetracycline formulation (200 mg/mL formulation administered at a rate of 20 mg/kg BW) or florfenicol for the treatment of UF in feedlot calves that have previously received metaphylactic tilmicosin upon arrival at the feedlot.

The use of trypanocides and antibiotics by Maasai pastoralists.

Information was collected on the use of veterinary drugs by Maasai pastoralists in an area of Kenya where tsetse flies and trypanosomosis occur. Three herds of cattle were followed for between 4 and 5 years and records were kept of every veterinary drug treatment given by the livestock owners. Almost all treatments were either with the trypanocides homidium or diminazene, or with oxytetracycline by intramuscular injection. The rate of trypanocide use varied between 0.66 and 1.56 treatments per animal per year, while oxytetracycline use was between 0.20 and 1.00 treatments per animal per year. Farmers were injecting these drugs in the absence of veterinary supervision, obtaining their supplies mainly from local village shops or informal traders. Underdosing with trypanocides appeared to be uncommon and the indications were that farmers generally gave the drugs at dosage rates above the recommended standard dose. Accurate information on the dose rates of oxytetracycline could not be obtained, but it was noted that in most cases farmers gave a single injection rather than a course of treatment. In a proportion of cases, trypanocides and antibiotics were mixed together before injection. The farmers administered the drugs when disease was recognized and were rarely using trypanocides as prophylactics. Although necessity forces the livestock owners to obtain and use these drugs without veterinary supervision, there are concerns with regard to the possibility of drug misuse and the development of drug resistance.

[Ophthalmic preparations Polyspectran (combination of neomycin, polymyxin B and bacitracin/gramicidin) and Terramycin (oxytetracycline with polymyxin B) mistakenly no longer reimbursed]. / Oogheelkundige preparaten Polyspectran (combinatie van neomycine, polymyxine B en bacitracine/gramicidine) en Terramycine (oxytetracycline met polymyxine B) ten onrechte niet meer vergoed.

The Netherlands' Ministry of Health and the health insurance companies have drawn up a list of preparations which will no longer be reimbursed. The ocular antibiotic preparations Polyspectran and Terramycin are on the list. However, there are no satisfactory alternative with respect to the broadness of the antibiotic spectrum required. In addition, some alternatives have serious side effects or may induce bacterial resistance.

Control of Brucella melitensis infection in a large camel herd in Saudi Arabia using antibiotherapy and vaccination with Rev. 1 vaccine.

The authors describe an attempt to control Brucella melitensis infection in a large camel herd in Saudi Arabia. Sera from the entire herd (2,536) were examined by the Rose Bengal and standard United States of America buffered plate agglutination tests. The overall Brucella seroprevalence was 8%. Milk samples from the 120 seropositive milking camels were cultured on Brucella-selective media. B. melitensis biovars 1, 2 and 3 were isolated from 41 camels (34%). Seropositive camels (202) were treated for the first time with a combination of long-acting oxytetracycline (OTC) at a dose of 25 mg/kg administered intramuscularly (i.m.) every 2 days for 30 days and streptomycin at 25 mg/kg i.m. every 2 days for 16 days. In addition, milking camels were given OTC-intramammary infusion at a rate of 10 ml/teat every 2 days for 8 days. This regimen was found to be effective in eliminating the shedding of Brucella organisms by camels, with no relapse. Moreover, all treated camels became seronegative within 16 months after treatment. Seronegative camels (2,331) were vaccinated for the first time with the B. melitensis Rev. 1 strain vaccine, as follows: a) 175 young camels (aged three months to one year) were each inoculated subcutaneously with a full dose (1-2 x 10(9) viable organisms in 1 ml). Brucella antibody titres between 1:50 and 1:200 were detected 2-4 weeks post-vaccination. Brucella antibodies decreased gradually until the animals became seronegative 8 months after vaccination. b) 2,156 camels aged more than one year were each inoculated subcutaneously with a reduced dose (1-2 x 10(6) viable organisms in 1 ml). Antibody titres measured 2-4 weeks post-vaccination varied from 1:25 to 1:200. The titres decreased gradually, until the animals became seronegative 3 months post-vaccination. No Brucella organisms were recovered from repeated udder secretion samples from all vaccinated milking camels, and no abortions were recorded among pregnant vaccinated camels.

Efficacy of intramuscular oxytetracycline as a dry cow treatment for Staphylococcus aureus mastitis.

To determine the efficacy of intramuscular oxytetracycline as a supplemental dry cow treatment for Staphylococcus aureus mastitis, 37 Holstein cows were randomly assigned to two treatment groups: intracisternal infusion with a commercial preparation of cephapirin benzathine at drying off (20 cows) and infusion with cephapirin benzathine at drying off and intramuscular oxytetracycline at 11 mg/kg once daily on d 7, 8, 9, and 10 after drying off (17 cows). Milk samples collected 7, 14, 30, and 60 d after calving were plated for bacterial isolation within 24 h after collection and after 24 to 72 h of storage at -20 degrees C. Quarters were defined as infected if S. aureus was isolated from the fresh and frozen cultures from any one sample collected before drying off. An infected quarter was defined as cured if S. aureus was not isolated from the fresh or frozen culture from milk samples obtained following calving. The rate of cure by 30 d after calving for systemic oxytetracycline (in combination with cephapirin treatment) was 29.4% for infected quarters and 29.4% for infected cows, compared with 27.5 and 25.0%, respectively, for the cephapirin treatment only. Results including the culture at 60 d after calving were 21.2 and 22.5%, respectively, for combination therapy and cephapirin therapy only. Systemic oxytetracycline, in combination with intramammary dry cow treatment, did not improve the rate of cure for S. aureus mastitis.