Spiramyin-loaded PLGA implants for the treatment of ocular toxoplasmosis: development, characterization, biocompatibility, and anti-toxoplasma activity.

Ocular toxoplasmosis is the major cause of infectious posterior uveitis worldwide, inducing visual field defect and/or blindness. Despite the severity of this disease, an effective treatment is still lacking. In this study, spiramycin-loaded PLGA implants were developed aiming at the treatment of ocular toxoplasmosis. Implants were manufactured by a hot-molding technique, characterized by Fourier Transform Infrared Spectroscopy, X-Ray Diffraction, Differential Scanning Calorimetry, Scanning Electron Microscopy; evaluated in terms of ocular biocompatibility by immunofluorescence, flow cytometry, cell migration, Hen's egg test-chorioallantoic membrane (HET-CAM) irritation test; and investigated in terms of in vitro efficacy against Toxoplasma gondii . Characterization techniques indicated that spiramycin was dispersed into the polymeric chains and both substances preserved their physical structures in implants. The HET-CAM test indicated that implants did not induce hemorrhage or coagulation, being non-irritant to the CAM. ARPE-19 cells showed viability by MTT assay, and normality in cell cycle kinetics and morphology, without stimulating cell death by apoptosis. Finally, they were highly effective against intracellular parasites without inducing human retinal pigment epithelial cell death. In conclusion, spiramycin-loaded PLGA implants represent a promising therapeutic alternative for the local treatment of ocular toxoplasmosis.

Successful treatment of acute experimental toxoplasmosis by spiramycin-loaded chitosan nanoparticles.

Spiramycin-metronidazole and spiramycin-loaded chitosan (CS) nanoparticles (NPs) were tested in comparison with the current spiramycin treatment of T.gondii concerning tissue penetration and blood brain barrier (BBB) passage. Swiss Albino mice were inoculated intraperitoneally with 2500 T. gondii tachyzoites RH strain and were divided into experimental and control groups. The experimental groups orally received CS NPs, spiramycin, spiramycin-metronidazole, spiramycin-loaded CS NPs 400 mg/kg and spiramycin-loaded CS NPs 100 mg/kg. Drug efficacy was assessed by mice survival time, mortality rate, parasite load in different organs and morphological study of the tachyzoites movement by light microscope and the ultra-structure by SEM. The results revealed that the maximum survival time of more than 200 days with no mortality on the sacrifice day (8th) was observed in mice receiving spiramycin-loaded NPs. Spiramycin-loaded NPs showed the highest significant percent reduction of tachyzoites (about 90% reduction) in liver, spleen and brain as compared to the other used drugs denoting successful bypass of BBB. Light microscopy of the treated peritoneal tachyzoites showed sluggish tachyzoites movement while the NPs caused loss of their movement. SEM of the treated tachyzoites were more mutilated and some of them appeared rupturing in those receiving CS NPs and spiramycin-loaded NPs. In conclusion, spiramycin-loaded NPs showed the highest efficiency in the treatment of acute toxoplasmosis. The non-toxic nature and the anti-parasitic effect of both CS and spiramycin make the use of spiramycin-loaded CS NPs a potential material for treatment of human toxoplasmosis.

Assessment of laboratory methods used in the diagnosis of congenital toxoplasmosis after maternal treatment with spiramycin in pregnancy.

BACKGROUND: The different laboratory methods used in the diagnosis of congenital toxoplasmosis have variable sensitivity and specificity. There is no evidence to prove that maternal treatment reduces the risk of fetal infection. The purpose of this study was to assess methods for the confirmation of congenital toxoplasmosis after maternal treatment with spiramycin during pregnancy, and to evaluate the effect of this treatment on clinical manifestations of the disease in newborns (NB). METHODS: This was a community-based, cross-sectional study of acute toxoplasmosis in newborns at risk of acquiring congenital infection. Participating newborns were born in the Clinical Hospital Maternity Ward of the Federal University of Goiás. Eligible participants were divided into 2 groups: group 1 consisted of 44 newborns born to mothers treated with spiramycin during pregnancy and group 2 consisted of 24 newborns born to mothers not treated with spiramycin during pregnancy because the diagnosis of toxoplasmosis was not performed. The sensitivity and specifity of PCR for T. gondii DNA in peripheral blood and serological testing for specific anti-T. gondii IgM and IgA, and the effects of maternal spiramycin treatment on these parameters, were determined by associating test results with clinical manifestations of disease. RESULTS: The sensitivity of the markers (T. gondii DNA detected by PCR, and the presence of specific anti-T. gondii IgM and IgA) for congenital toxoplasmosis was higher in group 2 than in group 1 (31.6, 68.4, 36.8% and 3.7, 25.9, 11.1% respectively). Even with a low PCR sensitivity, the group 2 results indicate the importance of developing new techniques for the diagnosis of congenital toxoplasmosis in newborns. Within group 1, 70.4% of the infected newborns were asymptomatic and, in group 2, 68.4% showed clinical manifestations of congenital toxoplasmosis. CONCLUSIONS: The higher proportion of infants without clinical symptoms in group 1 (70.4%) suggests the maternal treatment with spiramycin delays fetal infection, reducing the clinical sequelae of the disease in newborns. Given the low sensitivity of the tests used, when there is suspicion of congenital transmission several serological and parasitological tests are required in order to confirm or exclude congenital toxoplasmosis in newborns.

[Management of cervical cellulitis with and without mediastinal extension: report of 17 cases]. / Prise en charge des cellulites cervicales avec on sans extension médiastinale: à propos de 17 cas.

OBJECTIVES: Cervical cellulitis is infrequent but serious. The aim of our study was to describe the way we care and to identify certain factors that promote the development of such a condition. PATIENTS AND METHODS: We conducted a retrospective study covering the period 2004 to 2009 and included patients with cervical cellulitis with or without mediastinal extension surgically supported by ENT department of the University Hospital of Dijon. Data were collected clinical, radiological, treatment, type of surgery and complications. RESULTS: Seventeen patients met our inclusion criteria, four of which had a form associated with mediastinitis. Eight patients had taken NSAIDs and/or corticosteroids and fifteen patients antibiotics before their hospitalization. All have benefited from surgery with an average of 1.35 interventions (range 1 to 3) and support postoperative resuscitation. In both cases the outcome was unfavourable. CONCLUSION: The use of NSAIDs and/or corticosteroids was a factor in promoting this type of infection. In the context of surgical treatment, it does not seem necessary to surgically reoperate systematically.

[Hemophagocytic syndrome and toxoplasmic primo-infection]. / Syndrome d'activation macrophagique et primo-infection toxoplasmique.

Hemophagocytic syndrome (HPS) is a clinical entity that combines the clinical, biological and histological symptoms. The physiopathological mechanism involves the interaction between T lymphocytes/NK cells and macrophages, at the origin of an uncontrolled activation of the macrophages. The consequence is a hemophagocytosis extending to numerous organs, preferentially bone marrow. Clinical symptoms include cytopenia, fever unresponsive to antibiotics and multiple organ dysfunctions. Infections, lymphoproliferative disorders, cancers, systemic diseases are the most prevalent triggers or etiologies of HPS. Because of its high risk of mortality, HPS constitutes a diagnostic and therapeutic urgency. The search for an aetiology, in particular by serological testing, is essential because it conditions the treatment and thus the evolution of the disease. We report here the case of a 12 years-old boy presenting a HPS secondary to a toxoplasmic primo-infection. The objective of this work is to present the step of the biological diagnosis of HPS. Moreover, this observation allows the study of a very rare clinical presentation of toxoplasmic primo-infection, in an immunocompetant patient.

[Oral spiramycin for prevention of restenosis in coronary arteries].

Restenosis is the main problem of percutaneous coronary intervention (PCI). We investigated influence of oral Spiramycin (oral 16- cyclic macrolide antibiotic) on restenosis rate after uncovered metal stents implantation. 73 patients with acute myocardial infarction (1month) and one vessel lesion were divided into two groups. The first group composed of 42 patients, were treated with 100 mg aspirin +75 mg clopidogrel per day. The second group composed of 31 patients (12 patients were diabetic and 14 had long stenosis) received aspirin+clopidogrel+ spiramycin (one tablet - 3.000.000 IU per day during 6 weeks). Mean vessel diameter in first group patients was 3,2+0,4 millimeters; in second group patients was 3,1+0,3 millimeters. Angiography was performed twice: after six months of stent implantation and after an year of stent implantation. At 12-month follow up there were no major adverse cardiac events in both groups. Restenosis rate was significantly higher in the first group of patients (14,3% vs 6,4%; p<0,001; 4,8% vs 3,2% p<0,01). Oral administration of spiramycin for prevention of restenosis is safe and cost-effective in case of uncovered metal stents.

The Impact of Short-Term, Intensive Antifolate Treatment (with Pyrimethamine and Sulfadoxine) and Antibiotics Followed by Long-Term, Secondary Antifolate Prophylaxis on the Rate of Toxoplasmic Retinochoroiditis Recurrence.

PURPOSE: To assess the impact of intensive antifolate treatment, followed by secondary antifolate prophylaxis (A-SP) on the recurrence rate of toxoplasmic retinochoroiditis (TRC). To investigate whether there are any other factors potentially predisposing for recurrence. MATERIAL AND METHODS: A total of 637 medical records of TRC patients, who had been treated in the years 1994-2013 were reviewed. All patients were treated with pyrimethamine /sulfadoxine one 25mg/500mg tablet daily (P/S 25/500mg) for 21 days with a double loading dose for the first two days. From Day 2 the patients also received prednisone at a starting dose of 40mg and spiramycine 3 million IU three times daily, given for 10 days followed by azithromycin 500mg once daily for another 6 days. The analysis of the recurrence rate involved 352 patients who had completed 6-month secondary prophylaxis (P/S one 25 mg/500mg tablet twice a week). RESULTS: When secondary antifolate prophylaxis (A-SP) was instituted immediately after the treatment for TRC, the probability of 3-year recurrence-free survival after the first course of A-SP was 90.9%. A recurrence was most likely approximately 3.5 years after the first treatment. A univariate Cox regression model demonstrated that a risk for recurrence was 2.82 times higher (p = 0.02) in patients with retinal scars. In the multivariate analysis, the risk for recurrence was 2.41 higher (p = 0.06). In patients with haemorrhagic lesions the risk for recurrence was lower, aRR = 0.17 (approaching borderline statistical significance p = 0.08). CONCLUSIONS: With the institution of A-SP of immediately after the intensive treatment for TRC, i.e. when a reactivation was most likely, there was no recurrence during A-SP. Following A-SP the recurrence rates were low and recurrence-free periods tended to be longer. The treatment regimen employed had a beneficial effect on the recurrence interval as it reduced and delayed the highest probability of recurrence.

Effectiveness of spiramycin in murine models of acute and chronic toxoplasmosis.

The antitoxoplasmic activity of spiramycin (SPI) was evaluated in murine models of infection using a type-1 (RH) or type-2 (Me49) strain of Toxoplasma gondii. In mice infected with 10(2) tachyzoites of the RH strain, treatment with 100 and 200 mg SPI/kg/day had only a limited effect; despite some dose-dependent prolongation of survival, it was unable to protect mice against death. In contrast, in acute infection induced by peroral inoculation of 10, but not 20, cysts of the Me49 strain, a 3-week course of 100 mg SPI/kg/day and a 4-week course of 200 mg/kg/day significantly enhanced protection and markedly reduced brain cyst burdens at 6 months post infection (p.i.). In chronic infection established by inoculation of 10 cysts 3 months previously, a 3-week course of 200 mg SPI/kg/day resulted in significantly decreased brain cyst burdens compared with controls, both 2 weeks after treatment cessation and by 6 months p.i. Although a favourable effect on chronic infection may be specific for mice, these data merit investigation, since they may have clinical ramifications.

[Parallel catalytic hydrogen wave of acetylspiramycin caused by dissolved oxygen and its application].

AIM: To propose a novel polarographic method for the determination of acetylspiramycin (ASPM) is proposed. METHODS: In 0.1 mol x L(-1) NH4Cl-NH3 x H2O (pH 8.9) buffer containing dissolved oxygen, ASPM yielded a sensitive parallel catalytic hydrogen wave with the peak potential of -1.63 V (vs SCE) by single sweep polarography. RESULTS: The 2nd order derivative peak currents (i(p)") of the parallel catalytic hydrogen waves of ASPM showed a linear relationship with its concentrations in the range from 1.74 x 10(-3) microg x mL(-1) to 3.84 microg x mL(-1) (r = 0.9979, n=13). Its detection limit was 5.80 x l0(-4) microg x mL(-1) (3sigma) and RSD (n=13) was 1.24% at the concentration level of 0.871 microg x mL(-1). CONCLUSION: The proposed method could be applied to the determination of ASPM in ASPM tablets.

Spiramycin/cotrimoxazole versus pyrimethamine/sulfonamide and spiramycin alone for the treatment of toxoplasmosis in pregnancy.

OBJECTIVE: To compare the effectiviness of spiramycin/cotrimoxazole (Sp/C) versus pyrimethamine/sulfonamide (Pyr/Sul) and spiramycin alone (Spy) on mother-to-child transmission of toxoplasmosis infection in pregnancy. STUDY DESIGN: Retrospective study of pregnant women evaluated for suspected toxoplasmosis between 1992 and 2011. RESULT: A total of 120 mothers and their 123 newborns were included. Prenatal treatment consisted of spiramycin in 43 mothers (35%), spiramycin/cotrimoxazole in 70 (56.9%) and pyrimethamine/sulfonamide in 10 (8.1%). A trend toward reduction in toxoplasmosis transmission was found when Sp/C was compared with Pyr/Sul and particularly with Spy alone (P=0.014). In particular, Spy increased the risk of congenital infection when compared with Sp/C (odds ratio (OR) 4.368; 95% CI: 1.253 to 15.219), but there was no significant reduction when Sp/C was compared with Pyr/Sul (OR 1.83; 95% CI: 0.184 to 18.274). CONCLUSION: The treatment based on Sp/C has significant efficacy in reducing maternal-fetal transmission of Toxoplasma gondii when compared with Pyr/Sul and particularly to Spy. Randomized controlled trials would be required.

Effects of therapy with two combinations of antibiotics on the imbalance of MMP-2÷TIMP-2 in chronic periodontitis.

UNLABELLED: Periodontitis represents a chronic bacterial infection that induces immuno-inflammatory conditions affecting gingiva and tooth-supporting tissues. The role of some biological mediators in periodontal disease was widely investigated, especially that of MMP-8 and MMP-9. Recently, MMP-2 was also considered to be an appropriate therapeutic target for prevention of periodontal disease progression. However, effects of the combination of metronidazole with amoxicillin or spiramycin on the release and activation of MMP-2 and the balance MMP-2÷TIMP-2 were rarely studied. This study was designed to assess the influence of two combinations of antibiotics used for treatment of periodontitis on the balance MMP-2÷TIMP-2. Gingival samples obtained from patients with no pharmacological treated chronic periodontitis and those receiving either the association between amoxicillin-metronidazole and spyramicin-metronidazole were processed for paraffin embedding and then used to perform immunohistochemical reactions in order to detect MMP-2 and TIMP-2. All subjects were evaluated clinically and radiographic at the first visit and after treatment completed, the Loe & Silnees gingival index at six sites per tooth for the whole mouth being recorded. Statistical analysis was performed using non-parametrical techniques. Gingiva samples from untreated chronic periodontitis patients revealed a diffuse positive reaction for MMP-2 in the epithelium and also in fibroblasts and macrophages from the lamina propria. For gingiva samples from patients treated with antibiotics, MMP-2 positive reaction was restricted to deep epithelial layers and few cells of the connective tissue. No significant difference was observed for TIMP-2 expression. The clinical indexes were in accordance with immunohistochemical results. After treatment, gingival index values were significantly lower then before (p<0.001) in both groups treated with antibiotics. CONCLUSIONS: The two combinations of antibiotics tested in our study seem to have a dual ability to reduce inflammation as well as to inhibit MMP-2 activity.

Pharmacodynamics and pharmacokinetics of spiramycin and their clinical significance.

The absolute bioavailability of oral spiramycin is generally within the range of 30 to 40%. After a 1 g oral dose, the maximum serum drug concentration was found to be within the range 0.4 to 1.4 mg/L. The tissue distribution of spiramycin is extensive. The volume of distribution is in excess of 300 L, and concentrations achieved in bone, muscle, respiratory tract and saliva exceed those found in serum. The intracellular penetration of spiramycin is also rapid and extensive, with the concentrations in alveolar macrophages 10 to 20 times greater than simultaneous serum concentrations. Spiramycin is less metabolised than some of the other macrolides. The renal excretion of spiramycin is low, with 4 to 20% of the dose being excreted by this route. High concentrations of spiramycin are achieved in bile, which is an important route of elimination. The serum elimination half-life of spiramycin is between 6.2 and 7.7 hours. Of significance to clinicians may be the finding that spiramycin is highly concentrated in the respiratory tract and other tissues and macrophages. The post-antibiotic effect of spiramycin is significant and this effect is more prolonged than that of erythromycin against Staphylococcus aureus. Spiramycin has also been shown to greatly reduce the capacity of strains of Gram-positive cocci to adhere to human buccal cells.

Spiramycin is comparable to oxytetracycline in eradicating H. pylori when given with ranitidine bismuth citrate and metronidazole.

BACKGROUND: We have consistently achieved about 90% eradication of H. pylori with liquid bismuth, metronidazole and oxytetracycline. AIM: To test eradication and adverse events of ranitidine bismuth citrate (RBC) when given with metronidazole and either oxytetracycline or spiramycin. METHODS: One hundred and eighty-three patients were randomized to one of four 10-day regimens: RBC400OM: RBC 400 mg b.d., oxytetracycline 500 mg q.d.s.; RBC400SM: RBC 400 mg b.d., spiramycin 1 g q.d.s.; RBC200OM: RBC 200 mg q.d.s., oxytetracycline 500 mg q.d.s.; RBC200SM: RBC 200 mg q.d.s., spiramycin 1 g q.d.s. Additionally, all patients received metronidazole 400 mg q.d.s. A 14C-urea breath test was performed at 8 weeks. RESULTS: Intention-to-treat eradication rates were 94%, 91%, 94% and 89% with RBC400OM, RBC400SM, RBC200OM and RBC200SM, respectively (P = 0.81). Eradication was significantly higher in ulcer patients (97%) than in those with diagnoses other than ulcer (86%) (P = 0.009). There was a strong tendency to better eradication among those who had never smoked (100%) compared with ex-smokers (93%) and smokers (89%) (P = 0.06). Fifty-three per cent experienced at least one moderate or severe adverse event, and women had more adverse events than men (P = 0.0002). CONCLUSIONS: All four regimens had comparable efficacy and adverse events. Eradication was significantly better in ulcer patients but there was a trend to better eradication in those who smoked less, used less alcohol and exercised more. Adverse events were frequent, perhaps because of the large dose of metronidazole used, but few patients stopped treatment.

Primary Toxoplasma gondii infection in a pregnant human immunodeficiency virus-infected woman.

We report a 36-year-old HIV-infected woman who developed primary Toxoplasma gondii infection during pregnancy that was treated with spiramycin and antiretroviral drugs. There was no vertical transmission of toxoplasmosis and HIV.

In vitro study of the effect of titanium on porphyromonas gingivalis in the presence of metronidazole and spiramycin.

Septic peri-implantitis is the main clinical complication encountered following the insertion of titanium implants. It may be resistant to conventional antibiotic treatments. Reports in the literature about antibiotic behavior in the presence of titanium remain controversial. They vary from a bacteriostat to a decreased effect of antibiotic. This study examined, in vitro, the viability of Porphyromonas gingivalis, frequently associated with periodontal diseases, in the presence of titanium and antibiotics (spiramycin and metronidazole alone or in combination). Viability of P. gingivalis was determined, versus a standard curve using the Live/dead Baclight Bacteria Viability Kit on 96 well microplates. The results of 48 experiments (60 measurements each) were compiled in a database and compared to each other using the chi2p < 0.05 test. When used alone, titanium enhanced bacterial growth as the nickel-chrome control. However, when titanium was used in the presence of antibiotics, antibiotics kept their own effects. Even more, titanium was shown to potentialize the effect of metronidazole. The strengthening of effectiveness of metronidazole by titanium may be due to the oxidation potential of the metal. This chemical property could explain the conflicting data reported in the literature.

Neonatal screening for congenital toxoplasmosis in a cohort of 165 women infected during pregnancy and influence of in utero treatment on the results of neonatal tests.

The aim of this study was to determine the performances of methods used for the neonatal diagnosis of congenital toxoplasmosis. We included 165 pregnant women infected during pregnancy over a 10-year period. Fifty-seven cases of congenital toxoplasmosis were demonstrated (34.5%). Neonatal diagnosis gave positive results in 50 cases (88%). Parasites were isolated from placenta or cord blood in 61% of the infected newborns, more frequently from placenta (60%) than from cord blood (43%). This method was the only criterion of infection in 18% of these infected infants. The detection of specific IgM and IgA antibodies performed on 42 sera of infected infants allowed the diagnosis of congenital infection in 34 cases (81%). IgA antibodies were more frequently detected (60%) than specific IgM (50%). Neonatal and prenatal screening were carried out for 143 pregnant women. This combination diagnosed 39 of 40 infected infants (98%). Prenatal diagnosis identified 30 of 40 cases (75%). Nine cases were diagnosed through neonatal screening and one case with the postnatal follow-up. When prenatal diagnosis was positive, pyrimethamine and sulfadoxine were administered to the mothers (25 cases) in addition to spiramycin. Toxoplasma gondii was less frequently isolated in the placenta and the cord blood of these women (32% and 19%, respectively) than in women treated by spiramycin alone (83% and 63%) proving the antiparasitic action of these drugs. In conclusion, neonatal screening combining parasite detection in placenta and immunological methods on cord blood is essential particularly when prenatal diagnosis is negative. Therefore, when this diagnosis is positive, a treatment with pyrimethamine and sulfamide can be started in the first month of life.

Distribution of penicillin-G and spiramycin to tissue cages and subcutaneous tissue fluid in calves.

Antibacterial drug concentrations in serum, tissue cage fluid (TCF) and subcutaneous tissue fluid (SF), sampled either by filter paper discs or by microcapillaries, were measured after single intramuscular injections of potassium penicillin-G (KPG), procaine penicillin-G (PPG) and spiramycin adipate in calves. Concentration-time curves had essentially similar profiles in serum and SF, but peak levels were lower and occurred later in SF. From approximately four hours after drug administration, penicillin-G levels in SF were similar to levels in serum after KPG as well as after PPG administration. Elimination half-life (t1/2) of penicillin-G in serum was similar to t1/2 in SF after PPG administration but was longer in SF than in serum after KPG administration. Spiramycin concentrations were higher in SF than in serum and the t1/2 of spiramycin in SF was longer than in serum. For all three drugs, the t1/2 was longer in TCF than in serum and concentration-time curves in TCF were characterised by a slow rise and decline. The two methods of sampling SF, by filter paper discs and by microcapillaries, gave similar but not identical results. Penetration into SF and TCF, measured as the total area under curve ratio, was better for spiramycin than for penicillin-G, but the latter drug had a higher penetration ratio to TCF in the first 12 hours.

Pharmacokinetics and tissue residues of spiramycin in cattle after intramuscular administration of multiple doses.

Pharmacokinetic variables of spiramycin and its distribution in muscle, liver, kidney, and injection sites were studied in 18 mixed-sex 1-year-old calves to assess drug withdrawal time after 2 IM administrations of 100,000 IU of spiramycin/kg of body weight at 48-hour intervals. Presence of a compound, other than spiramycin I (ie, neospiramycin), was observed in tissues used for withdrawal time determination. High concentrations observed at the injection sites decreased slowly to maximal residue limit with half-life of 109.5 hours for neospiramycin and 77.5 hours for spiramycin. At 14 days, neospiramycin concentrations were higher in kidney than in liver and half-life was different between these 2 tissues. Two methods of withdrawal time determination were used and the part of the samples without residue detected, in the calculation, was discussed. Withdrawal time of 35 days can be proposed on the basis of average daily intake determined for spiramycin, with concentration at injection sites representing 10% of the whole muscle concentration.

Pharmacokinetics and bioavailability of spiramycin in pigs.

The pharmacokinetics of spiramycin in pigs were investigated after intravenous and oral administration. The potential therapeutically effective blood level was established after a single administration and examined in a subsidiary five day study. The rapid intravenous injection of 25 mg spiramycin/kg bodyweight produced marked salivation in all the test animals. The elimination half-life (2.3 +/- 1.2 hours) was relatively short, in accordance with the total body clearance rate (27.3 +/- 10.1 ml/minute/kg). The high volume of distribution (5.2 +/- 2.2 litres/kg) was due to the accumulation of the drug in the body tissues. The maximum plasma concentration (4.1 +/- 1.7 micrograms/ml) after oral administration of 85 to 100 mg spiramycin/kg bodyweight was reached after 3.7 +/- 0.8 hours and the half-life of the elimination phase was 6.0 +/- 2.4 hours. The oral bioavailability was 45.4 +/- 23.4 per cent. Ad libitum feeding of a diet containing 2550 mg spiramycin/kg produced a steady state concentration of 0.96 +/- 0.27 micrograms/ml. This plasma concentration would provide a potentially therapeutically effective blood concentration against Mycoplasma species, Streptococcus species and Staphylococcus species.

Successful treatment of mycoplasmosis in layer chickens with single dose therapy.

The efficacy of treatment with single dose administration of 5 drugs at different dosages to layer hens naturally infected with Mycoplasma gallisepticum was studied. The drugs were tiamulin, which was administered orally, tylosin (parenterally and orally), spiramycin (orally), long-acting oxytetracycline (parenterally) and tylosindihydrostreptomycin (parenterally). Cure was assessed by the absence of nasal discharge. The cure rate was significantly higher (P less than 0.05) in treated hens than in untreated hens, as early as 1 day after treatment. Remission for 33 days was achieved in 60% of hens treated with 100 mg oxytetracycline, in 100% of hens treated with 100 mg or 200 mg spiramycin, in 92% and 85% of hens treated with 100 mg tylosin, parenterally and orally, and in 89% and 88% of birds given 100 mg tiamulin and tylosin-dihydrostreptomycin, respectively.