A comparison of the effect of tiamulin hydrogen fumarate and tylosin tartrate on mycoplasmas of ruminants and some animal ureaplasmas.

The in vitro efficacy of tiamulin was compared to that of tylosin against 7 bovine, 7 ovine and 3 caprine mycoplasma strains isolated from various organs and belonging to different species, as well as 7 ureaplasma strains cultured from cattle, sheep, swine, chickens and turkeys. The minimal mycoplasmacidal concentrations of tiamulin varied between 0.01 and 10.0 micrograms ml-1, while tylosin proved to be active in concentrations of 0.5 and 100.0 micrograms ml-1. Five of 17 mycoplasma strains showed identical sensitivities to both antibiotics while all other strains, including the ureaplasmas, were sensitive to tiamulin at concentrations 5-5000-times lower than tylosin.

Blood level studies in chickens, turkey poults and swine with tiamulin, a new antibiotic.

Tiamulin concentrations have been determined in the serum of chickens, turkeys and swine after a single oral administration of various doses. The compound peaked between 2 and 4 hours after drug supply. In the highest dose used (50 mg/kg body weight), mean concentrations of 3.5, 2.9, 4.5 microgram/ml for chickens, turkeys and swine, respectively, could be obtained. In poultry, the levels declined between 12 and 24 hours to values not useful for calculation. In swine at 24 hours after administration measurable values could still be detected.

In vitro activity of tiamulin (81.723 HFU), a new pleuromulin derivative, against clinically significant anaerobes.

The susceptibility of more than 40 strains of Gram-negative and Gram-positive anaerobes to tiamulin (Sandoz 81.723 hfu), a new pleuromulin (pleuromutilin) derivative, was determined by broth dilution and agar dilution tests. The influences of density of the inoculum upon MICs was studied by a specially designed pour plate-technique. Bacteroides fragilis, B. vulgatus, B. splanchnicus, B. oralis, B. asaccharolyticus, B. melaninogenicus, Fusobacterium fusiforme (F. nucleatum), Sphaerophorus necrophorus, Clostridium perfringens, C. fallax, Propionibacterium acnes and several species of Peptococcaceae showed broth dilution MICs of 0.03 similar to 1 microgram/ml. Members of B. thetaiotaomicron, B. distasonis and S. freundii (F. mortiferum) were inhibited by 8 similar to 32 microgram/ml and 2 strains of S. varius had a broth dilution MIC of 256 microgram/ml. With most strains, the agar dilution MICs were 2 similar to 4 similar to 8 times the broth dilution MICs. In pour plate-tests, the MICs were not considerably influenced influenced by varying initial concentrations of viable cells. With most anaerobes, the MBCs of tiamulin were more than 100-fold higher than the MICs. The results obtained indicated that, apart from S. varius, B. thetaiotaomicron, B. distasonis and S. freundii (F. mortiferum), members of 16 other anaerobic species including B. fragilis were without exception sensitive to tiamulin.

Simultaneous treatment of chickens with salinomycin and tiamulin in feed.

Laboratory and field experiments involving more than 100,000 birds were performed to assess the effect of simultaneous in-feed medication of chickens with salinomycin and tiamulin at various concentrations. In an artificial infection study with Mycoplasma gallisepticum, low levels of tiamulin (10-40 ppm) did not induce signs of ionophore intoxication with salinomycin at 60 ppm in the feed, whereas levels of 50 ppm caused early signs with a mild growth depression. A level of 20 ppm gave a maximum average improvement in growth rate of 12.5%. There was a dose-related response in mycoplasma lesion inhibition, with 50 ppm reducing lesions by 75%. In the two field trials, chickens suffering from mycoplasmosis complicated with infectious bronchitis and receiving 60 ppm salinomycin in the feed showed marked improvements in mortality rates, lesion scores, and feed-conversion efficiency when tiamulin was added at 20 ppm and 30 ppm in the feed. There were no signs of incompatibility between the two antibiotics at these levels.

Tiamulin, a new antibiotic for eliminating mycoplasmas from bovine serum 1. Investigations on Spermatozoal Toxicity.

Tiamulin, a new diterpene antibiotic, was investigated for toxicity to spermatozoa. The compound was added to ejaculates via semen extender at a concentration of 50 to 90 mg per 100 ml of total liquid. Motility and the proportion of non-viable spermatozoa were used as criteria of the drug's effect. Tiamulin proved to be safe up to doses of 70 mg per 100 ml of semen extender.

Prophylactical and therapeutical efficacy of Tiamuline in mycoplasmosis of chickens and turkeys.

To evaluate efficacy of Tiamuline in mycoplasmosis of chickens and turkeys under controlled field conditions 2 prophylactical and 3 therapeutical trials were conducted. The compound was administered via drinking water for 3 days in comparison to Tylosin tartrate. In both prophylactical and therapeutical tests, Tiamuline showed a superior efficiacy, as measured by clinical symptoms, pathological lesions and microbiological findings. Therefore, Tiamuline can be recommended for treatment of mycoplasmosis in chickens and turkeys in a dosage of 0.025% and in a dosage of 0.0125% for prophylaxis in flocks at risk.

Activity of various compounds against a pathogenic strain of Treponema hyodysenteriae.

A test method for in vitro investigations of chemotherapeutics against a pathogenic strain of Treponema hyodysenteriae is described. The sensitivity of this organism against various compounds especially against the pleuromutilin derivative 81723 hfu, a new antibiotic, was evaluated.

Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs.

Kinetic variables for tiamulin in the normal dog have been determined. Serum concentrations of tiamulin were compared after intramuscular (i.m.) and subcutaneous (s.c.) administration of a single dose of tiamulin. Following a single i.m. dose of 10 mg/kg body weight, the compound was calculated to have a Cmax = 0.61 +/- 0.15 micrograms/ml, a Tmax = 6 h and a t1/2 = 4.7 +/- 1.4 h. Tiamulin showed dose-dependent pharmacokinetics when given as a single s.c. dose of either 10 mg or 25 mg/kg body weight. For the lower dose, the values Cmax = 1.55 +/- 0.11 micrograms/ml, Tmax = 8 h and t1/2 = 4.28 +/- 0.18 h were obtained. For the higher dose Cmax = 3.14 +/- 0.04 micrograms/ml, Tmax = 8 h and t1/2 = 12.4 +/- 3.4 h were calculated. When tiamulin was administered subcutaneously at a dose rate of 10 mg/kg body weight, higher and better maintained serum levels were achieved than those following i.m. administration. After repeated s.c. doses no significant accumulation of tiamulin occurred. Assuming that a continuous effective serum concentration is necessary throughout the course of therapy, these data would indicate that tiamulin should be given every 24 h.

[Hematological investigations in rats experimentally infected with m. arthritidis (author's transl)]. / Hämatologische Untersuchungen bei Ratten mit experimenteller Mykoplasma-Polyarthritis

Hematological investigations were carried out regularly during the course of an experimental M. arthritidis-infection in rats. The alterations observed in the peripheral blood were essentially those usually found in infections. In addition, a moderate thrombocytosis and a depression of the parameters of the red blood count could be seen. In lymphnodes and spleen phagocyting RES-cells were increased 4 days post inoculationem (p.i.) and vacuolized makrophages could be observed 7 days p.i. On the 10. day p.i. very immature cells could be seen in these organs, morphologically resembling hemohistioblasts. Mature cells as well as precursors of this type of cell were found to be increased 2-3 weeks p.i. Bone marrow and thymus have been found normal during the whole period of investigation.

In vivo efficacy of 81.723 hfu, a new pleuromutilin derivative against experimentally induced airsacculitis in chicks and turkey poults.

The efficacy of the pleuromutilin derivative 81.723 hfu was tested in chicks and turkey poults by experimentally infecting them with Mycoplasma gallisepticum. The data were treated to obtain the mean effective doses, and these were compared to those obtained with tylosin tartrate. The compounds were administered either by ingluvial catheter or via the drinking water. Therapy was started on the day of inoculation or 7 days thereafter, respectively. The experiments showed that the compound 81.723 hfu was significantly more active in chickens than tylosin tartrate by both methods of administration of drinking water. In turkey poults the pleuromutilin derivative and tylosin tartrate had comparable activity.

[In vitro and in vivo activity of tiamulin against leptospires (author's transl)]. / Wirksamkeit von Tiamulin gegen Leptospiren in vitro und in vivo.

The minimal growth inhibiting concentration of tiamulin, a derivative of the diterpen antibiotic pleuromutilin, was evaluated in vitro against 11 different serogroups of leptospira interrogans by twofold serial dilution technique, in comparison to tetracyclin, dihydrostreptomycin and tylosin. The range of the MIC values of tiamulin is between 0.07 and 2.5 microgram/ml and thus comparable to the activities of the standard antibiotics tested (see table 1). The chemotherapeutic efficacy (ED50) of the compound was examined in two experimental leptospiral infections of the Syrian hamster, in comparison to tetracyclin. Both compounds were administered orally for 3 days. In the L. canicola infection, the ED50 values were 103.8 mg/kg and 306.3 mg/kg body-weight for tiamulin and tetracyclin, respectively. In the L. grippotyphosa infection, the ED50 values amounted to 35.16 and 277.5 mg/kg bodyweight for tiamulin and tetracyclin, respectively. Based on these values, tiamulin in comparison to tetracyclin showed 3-8 fold higher efficacy in vivo after oral administration.

[Clinical and histopathological findings in mycoplasmal polyarthritis of rats. II. Course of disease between the 2. and 6. week (authors transl)]. / Klinische und histopathologische Befunde bei der Mykoplasma-Polyarthritis der Ratte. II. Der Krankheitsablauf in der 2. bis 6. Woche

Between the 9th and 42nd day p.i. the clinical features and microbiological findings of rats infected intraperitoneally with mycoplasma arthritidis were recorded and a histological investigation was carried out. From the 12th day p.i. arthritic lesions clinically showed a gradual regression. Until the 42nd day p.i. mycoplasmas and purulent exudate were present within the joint cavity. During the course of infection a gradual increase of mesenchymal cell activity was found, leading to the formation of considerable amounts of secondary synovialis. Between the epiphysis the pannus formed tissue laces, which after the 3rd week p. i. showed sequestration. During the further course of disease an increased number of focal plasma cell accumulations was observed within the joint capsule. Partial erosions of hyaline cartilage, especially near its edge, could frequently be seen. Within the cellular exudate of the joint cavity the number of macrophages steadily increased whereas remmants of exudate were mainly located in the recesses of the joint capsule. In the periarticular tissue, cellular infiltration, mesenchymal cell proliferation and purulent necrotic foci were present. In the supporting osseous tissues osteomyelitis, abscesses, periosteal new bone formation and the occurrence of mosaic bone could be observed. The lesions found in spleen and lymph-nodes indicated the persistence of a systemic reaction within the RES.

Measurements of antimicrobial drug concentrations in renal interstitial fluid using the diffusion chamber technique.

A technique is described to obtain renal interstitial fluid (RIF) from rabbits after implantation of diffusion chambers with permeable membranes of 0.45 mu porosity in both kidneys. Pharmacokinetic studies were conducted two to three weeks after implantation. No difference in gentamicin concentrations, as measured microbiologically, was seen between RIF withdrawn from the left and right kidney chambers at the same points in time. Simultaneous drug concentrations were determined in RIF and serum of rabbits after oral administration of ampicillin or nalidixic acid and after intramuscular injection of gentamicin. Ampicillin concentrations in RIF peaked at two hours with about one fourth of the peak concentration measured in serum at one hour. These curves crossed at 3.45 hours. In RIF, the maximum concentration of gentamicin found at two hours was again approximately one fourth of the serum peak level determined at half an hour. The gentamicin curves crossed at 3.15 hours. No levels of nalidixic acid could be detected microbiologically in serum and RIF. In collected urine, however, concentrations of this drug could be measured for several sampling periods. Our results show that this diffusion chamber technique can be useful in the pharmacokinetic examination of drugs, also with respect to their distribution in the kidneys.

Sensitivity of various spiroplasma strains against ethanol, formalin, glutaraldehyde, and phenol.

The efficacy of four different disinfectants on spiroplasmas pathogenic for plants, insects and vertebrates was determined using a microtiter technique. The results of the sensitivity testing indicate that spiroplasmas display a considerable resistance in comparison to cell wall bearing organisms. Particularly honey bee spiroplasmas proved to be less sensitive to the disinfectants tested, whereas Spiroplasma citri and the tick spiroplasmas showed a susceptibility comparable to E. coli and Staph. aureus. The findings are discussed in relation to the technique used and in respect of the implications for laboratory work.

[Clinical and histopathological findings in mycoplasmal polyarthritis of rats. I. Course of infection during the first 8 days (author's transl)]. / Klinische und histopathologische Befunde bei der Mykoplasma-Polyarthritis der Ratte. I. Der Ablauf der Infektion in den ersten 8 Tagen

Polyarthritis in rats could be induced by intraperitoneal infection with M. arthritidis. The mycoplasma culture alone or in combination with infusorial earth was used as inoculum. The histopathological changes consisted of initial lesions in the transitional zone of the articular capsule which could be attributed to disturbances of vascular permeability. After two days suppurative arthritis occurred, which was accompanied by massive inflammatory lesions of the articular capsule and of the periarticular tissues. Towards the end of the observation period erosions of cartilage, pannus formation and periarticular foci of purulent necrobiosis were found. Especially the synovial membrane was subjected to profound changes and dense cellular infiltration. The cell infiltration, mesenchymal proliferation and changes of vascular permeability showed variations in timing and degree depending on the modi of infection. The histological examinations of organs indicated generalization of the infection.

[Nitroblue tetrazolium (NBT) test as a potential diagnostic aid in the preoperative detection of patients at risk for infection]. / Der Nitroblau-Tetrazolium (NBT)-Test als potentiell diagnostisches Hilfsmittel zur präoperativen Erfassung infektionsgefährdeter Patienten.

The clinical application of a simple quantitative NBT-test to investigate the "killing function" of granulocytes in surgical patients with various underlying diseases is described. In this test preoperative patients showing a decreased NBT-reduction in their leucocytes always developed infectious complications after surgery. Taken together, these results indicate that the NBT-test could be used as a "simple indicator" of the granulocyte function in respect to the predictability for patients with high risk of infection.

[Clinical and histopathological findings in mycoplasmal polyarthritis of rats. III. Course of infection during the weeks 7-30 and 54-61 (author's transl)]. / Klinische und histopathologische Befunde bei der Mykoplasma-Polyarthritis der Ratte. III. Der Krankheitsablauf in der 7.-30. und 54.-61. Woche

Clinical, microbiological and histological findings of the late phase of experimentally induced Mycoplasma-polyarthritis in rats are described. Investigations were carried out between the 7.-30. week and between the 54-61. week p.i. M. arthritidis could be reisolated from affected joints regularly up to the 7th week p.i. Thereafter until 12th week only occasional recovery was possible. The healing process of affected joints dominated signs of arthritis which could be confirmed histologically as a purulent process. The alterations of carpal and tarsal joints were divided into purulent, chronic deforming and chronic minor lesions. The findings derived from investigation of joints and parenchymatous organs during the course of the disease are discussed.