zithromax and Tuberculosis--Avian

Mycobacteriosis caused by Mycobacterium avium subsp. avium was observed in a parental loft of 70 meat-breed pigeons. It was decided to undertake treatment as the birds represented a substantial value to the owner. A multiagent therapy using azithromycin, marbofloxacin, and ethambutol was administered. After 4 mo of therapy, the desired results were not obtained. At the end of treatment, the birds were in poor general condition, with white blood cells above 20 g/L, and after clutching, 2-yr-old and older birds were euthanatized. Overall, postmortem lesions were found in 17 out of 49 necropsied individuals. Slide agglutination tests with a M. avium subsp. avium lysate were conducted in all examined pigeons. In 28 pigeons, blood count was conducted once a month during therapy, while in 24 pigeons, a tuberculin sensitivity test was conducted before the planned euthanatization. The tuberculin sensitivity test did not prove useful in the diagnosis of ill individuals. Slide agglutination yielded positive results in only four birds, all of which also had postmortem lesions. Blood count in a large number of cases allowed distinguishing between ill and healthy individuals, which was used for subsequent selection. The comparison of cultured strains with the (CCG)4-based PCR method showed the variation of M. avium isolates up to a maximum of 30%. The described case proves that the treatment of mycobacteriosis in pigeon flocks is not effective, mainly due to the high resistance to M. avium subsp. avium. In addition, therapy may contribute to an even greater increase in mycobacterial resistance to antibiotics, which may pose a potential risk to public health.

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Breeding; Columbidae; Drug Therapy, Combination; Ethambutol; Female; Fluoroquinolones; Male; Meat; Mycobacterium; Poultry Diseases; Treatment Outcome; Tuberculosis, Avian

Mycobacterium avium is an intracellular pathogen that can invade and multiply within macrophages of the reticuloendothelial system. Current therapy is not highly effective. Particulate drug carriers that are targeted to the reticuloendothelial system may provide a means to deliver antibiotics more efficiently to M. avium-infected cells. We investigated the formulation of the antibiotics ciprofloxacin and azithromycin in liposomes and tested their antibacterial activities in vitro against M. avium residing within J774, a murine macrophage-like cell line. A conventional passive-entrapment method yielded an encapsulation efficiency of 9% for ciprofloxacin and because of aggregation mediated by the cationic drug, was useful only with liposomes containing < or = 50 mol% negatively charged phospholipid. In contrast, ciprofloxacin was encapsulated with > 90% efficiency, regardless of the content of negatively charged lipids, by a remote-loading technique that utilized both pH and potential gradients to drive drug into preformed liposomes. Both the cellular accumulation and the antimycobacterial activity of ciprofloxacin increased in proportion to the liposome negative charge; the maximal enhancement of potency was 43-fold in liposomes of distearoylphosphatidylglycerol-cholesterol (DSPG-Chol) (10:5). Azithromycin liposomes were prepared as a freeze-dried preparation to avoid chemical instability during storage, and drug could be incorporated at 33 mol% (with respect to phospholipid). Azithromycin also showed enhanced antimycobacterial effect in liposomes, and the potency increased in parallel to the moles percent of negatively charged lipids; azithromycin in DSPG-Chol (10:5) liposomes inhibited intracellular M. avium growth 41-fold more effectively than did free azithromycin. Thus, ciprofloxacin or azithromycin encapsulated in stable liposomes having substantial negative surface charge is superior to nonencapsulated drug in inhibition of M.avium growth within cultured macrophages and may provide more effective therapy of M.avium infections.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Cell Line; Ciprofloxacin; Drug Carriers; Liposomes; Macrophages; Mice; Microscopy, Electron; Microscopy, Video; Mycobacterium avium; Tuberculosis, Avian