Treatment outcomes of Mycobacterium avium complex pulmonary disease according to disease severity.

Mycobacterium avium complex pulmonary disease (MAC-PD) requires long-term treatment. We analyzed the outcomes of 992 MAC-PD patients according to disease severity and compared the outcomes of intermittent and daily therapy for mild disease. Patients were divided into groups according to severity using the body mass index, age, cavity, erythrocyte sedimentation rate, and sex (BACES) system, and culture conversion rates were evaluated. We also evaluated the effects of intermittent treatment on the culture conversion rates in mild disease group. Using the BACES, 992 patients were divided into mild (n = 331), moderate (n = 503), and severe (n = 158) disease groups, and culture conversion at the end of treatment was achieved in 85% (282/331), 80% (403/503), and 61% (97/158), respectively. Differences in culture conversion among the severity groups were significant (p < 0.001). In patients with mild disease, culture conversion rates were similar between intermittent (84%, 166/198) and daily (87%, 116/133) treatment (p = 0.396), and intermittent antibiotic therapy did not negatively impact culture conversion (adjusted hazard ratio 1.08; confidence interval 0.83-1.41; p = 0.578). MAC-PD patients with mild disease had higher culture conversion rates. Daily and intermittent therapy yielded similar culture conversion rates for mild disease. Treatment strategies with lower pill burden may be applicable in mild MAC-PD.

Case Study and Attempt of Treatment of Mycobacteriosis Caused by Mycobacterium avium in a Parental Flock of Meat-Breed Pigeons.

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.

Small-Cell Lung Cancer Comorbid with Pulmonary Mycobacterium avium Infection: A Case Report.

BACKGROUND: Small-cell lung cancer (SCLC) rarely coexists with pulmonary Mycobacterium avium intracellular complex (MAC) infection. The key drug for SCLC treatment is etoposide, which is metabolized by cytochrome P-450 (CYP) 3A4. Meanwhile, the key drugs for pulmonary MAC infection are clarithromycin (CAM) and rifampicin (RFP), and their metabolism influences CYP3A4. Therefore, treatment of concurrent SCLC and pulmonary MAC infection is difficult, and to the best of our knowledge, no report of treatments for concurrent SCLC and pulmonary MAC infection has been published. Patient Concerns and Diagnoses: A 65-year-old man presented to our hospital with abnormal findings of chest computed tomography: (1) a hilar region nodule in the left lung and mediastinal lymphadenopathy and (2) a thick-walled cavity lesion in the right upper lobe of the lung. After further examinations, the former lesions were diagnosed as SCLC, cT4N3M0, stage IIIC and the latter as pulmonary MAC infection, fibrocavitary disease. INTERVENTIONS AND OUTCOMES: Concurrent treatment was conducted with discontinuation of CAM and RFP before and after etoposide administration. Specifically, intravenous cisplatin and etoposide were administered on day 1 and days 1-3, respectively, and CAM, RFP, and ethambutol (EB) were administered orally on days 6-22 every 4 weeks. Concurrent radiotherapy was added to the drug administration on days 1-27 of the first cycle. The chemotherapy was continued for 4 cycles, followed by continuation of CAM and RFP administration. EB was discontinued because of optic nerve disorder. The treatments were conducted completely and safely, and both of the SCLC lesions and the MAC lesion were improved. CONCLUSIONS: Treatments for concurrent SCLC and pulmonary MAC infection may be successfully conducted with discontinuation of CAM and RFP before and after etoposide administration.

Multidrug therapy of Mycobacterium avium subsp. avium infection in experimentally inoculated budgerigars (Melopsittacus undulatus).

The aim of the study was to determine whether the four-month experimental therapy of mycobacteriosis in budgerigars may cause a complete recovery. A group of nine budgerigars was infected with a Mycobacterium avium subsp. avium isolate with proven pathogenicity for budgerigars. Five weeks post-inoculation, multidrug therapy was started. Another group comprising six birds received the same treatment but no infection, and the third group also comprising six birds was kept without infection or treatment as a control. The adopted antibiotic regimen included clarithromycin 61 mg/kg b.w., moxifloxacin 25 mg/kg b.w. and ethambutol 60 mg/kg b.w. administered by crop gavage every 12 h for 18 weeks. Despite a significant improvement in the condition of the infected, treated birds, the four-month therapy was not sufficient for the complete recovery of all.

Taking a rational approach in the treatment of avian mycobacteriosis.

Treatment for avian mycobacteriosis is still in its infancy and based on extrapolations from human medicine. The optimum drug choice, dose, or length of treatment has yet to be determined for most exotic animal species. Treatment should include multiple drugs for extended periods of time with appropriate monitoring of both drug levels and overall animal health. Risk to owners and handlers needs to be minimized through appropriate identification of the species of mycobacteri causing disease. More research is necessary on the pharmacokinetics of these drugs in other animal species and antibiotic resistance. Currently, euthanasia remains the most common action in the face of active mycobacteriosis.

Formulation and efficacy of liposome-encapsulated antibiotics for therapy of intracellular Mycobacterium avium infection.

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.

Therapeutic efficacy of the benzoxazinorifamycin KRM-1648 against experimental Mycobacterium avium infection induced in rabbits.

The therapeutic efficacy of the benzoxazinorifamycin KRM-1648 was studied in an experimental rabbit infection system with avian Mycobacterium avium. The infected rabbits died from Yersin type infections, a peculiar type of experimental bovine tuberculosis characterized by a very rapid course, enlargement of the spleen and liver, and septic infection, 14 to 20 days after bacterial challenge, as evidenced by bacteremia and severe bacterial loads in the visceral organs. Histopathologic studies of the visceral organs of the infected rabbits revealed the development of numerous typical granulomatous lesions. This experimental rabbit infection system, features of which resemble certain features of disseminated M. avium complex infections in AIDS patients, was used to evaluate the therapeutic efficacy of KRM-1648, a newly synthesized benzoxazinorifamycin. KRM-1648 given orally at 25 and 50 mg/kg of body weight reduced the incidence and degree of bacteremia in infected rabbits and protected against subsequent death. Moreover, the drug allowed almost complete recovery of infected rabbits by week 7. KRM-1648 cleared infections in the lungs, liver, spleen, and kidneys and restored histopathologic features of healthy tissue in the visceral organs. KRM-1648 exhibited a more potent therapeutic effect against M. avium infection than rifampin and clarithromycin.