Efficacy of Moxifloxacin against Mycobacterium abscessus in Zebrafish Model in vivo.

OBJECTIVE: Moxifloxacin (MFX) shows good in vitro activity against Mycobacterium abscessus and can be a possible antibiotic therapy to treat M. abscessus infection; however, other studies have shown a lower or no activity. We aimed to evaluate MFX activity against M. abscessus using zebrafish (ZF) model in vivo. METHODS: A formulation of M. abscessus labeled with CM-Dil was micro-injected into ZF. Survival curves were determined by recording dead ZF every day. ZF were lysed, and colony-forming units (CFUs) were enumerated. Bacteria dissemination and fluorescence intensity in ZF were analyzed. Inhibition rates of MFX and azithromycin (AZM, positive control) were determined and compared. RESULTS: Significantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference. CONCLUSION: MFX showed limited efficacy against M . abscessus in vivo using ZF model. Its activity in vivo needs to be confirmed.

Prevalence and Risk Factors Associated with Adverse Drug Reactions among Previously Treated Tuberculosis Patients in China.

We assessed the incidence of adverse drug reactions (ADRs) with anti-TB medications and evaluated the risk factors for developing ADRs in previously treated tuberculosis patients in China. All patients received the first-line anti-TB regimen (2HREZS/6HRE) as recommended by the national guidelines. Clinical and laboratory evaluations were performed once a month. Out of the 354 participants, 262 (74.0%) experienced ADRs such as hyperuricemia (65.0%, 230/354), hepatotoxicity (6.2%, 22/354) and hearing disturbances (4.8%, 17/354). ADRs were significantly associated with diabetes mellitus [OR (95% CI): 15.5 (2.07-115.87)]; however, weight more than 50 kg [OR (95% CI): 0.41 (0.22-0.85)] was a protective factor for occurrence of ADRs. Hyperuricemia is the most common adverse event but, most patients with hyperuricemia showed increased tolerance for high uric acid levels. Low body weight and diabetes mellitus increased the risk of the occurrence of ADRs during anti-TB treatment.

[Comparison of clinical manifestations between Mycobacterium avium-intracellulare complex and Mycobacterium abscessus pulmonary diseases].

OBJECTIVE: To compare the clinical manifestations of nontuberculous mycobacterial (NTM) pulmonary diseases caused by Mycobacterium avium-intracellulare complex (MAC) and Mycobacterium abscessus. METHODS: The clinical manifestations of 18 patients with MAC and 9 patients with Mycobacterium abscessus pulmonary diseases diagnosed from 2010 to 2011 were reviewed. RESULTS: There were no significant differences in the gender, age, body mass index, predisposed diseases, symptoms and positive sputum acid-fast bacillus between MAC and Mycobacterium abscessus groups. Upper lobe cavities were more frequently observed in the MAC group (13/18), whereas nodular bronchiectatic changes were more frequent in the Mycobacterium abscessus group (3/9). Compared with MAC pulmonary diseases, several imaging characteristics were more common in the Mycobacterium abscessus group, including bilateral micro nodules (Mycobacterium abscessus group 8/9 vs MAC group 7/18), tree-in-bud sign (Mycobacterium abscessus group 7/9 vs MAC group 6/18) and multiple bronchiectasis (Mycobacterium abscessus group 8/9 vs MAC group 5/18). CONCLUSIONS: There was considerable overlap in clinical characteristics of MAC and Mycobacterium abscessus pulmonary diseases. However, bilateral micro nodules, tree-in-bud sign and multiple bronchiectasis were more frequently seen in Mycobacterium abscessus than in MAC pulmonary diseases, while upper lobe cavities were more frequently seen in MAC than in Mycobacterium abscessus pulmonary diseases.

[A preliminary study on the definition of resistant breakpoints of ofloxacin and levofloxacin for Mycobacterium tuberculosis].

OBJECTIVE: To test the MIC of ofloxacin and levofloxacin (MIC(F) and MIC(V)) in 101 strains of Mycobacterium tuberculosis (M. tb) isolated from patients with active tuberculosis and to analyze the relation between MIC and past history of fluoroquinolones (FQs) administration. And according to the analysis of the therapeutic effect of the regimen including FQs, we want to define the resistant breakpoints of OFLX and LVFX clinically. METHOD: All isolates from sputa or pus obtained from in-patients in our hospital from Jan 1999 to Sept 2000 were tested for MIC and susceptibility. 47 patients with pulmonary tuberculosis received regimens including FQs were observed consecutively. Chi-square test was applied for the statistical analysis. RESULT: (1) The MIC(V) of 96% clinical isolates tested were 2 times lower than MIC(F). (2) The MIC(F) < 8 microg/ml and MIC(V) < 4 microg/ml were found among 91% and 92% patients without previous FQs administration, while only the MIC(F) > or = 8 microg/ml and MIC(V) > or = 4 microg/ml were found among 54% and 57% for the patients with FQs administration history. (3) If MIC(F) > or = 8 microg/ml and MIC(V) > or = 4 microg/ml were defined as the clinical resistant breakpoints, in susceptible group, the sputum negative conversion rates were 54%, 75% and 82% respectively after receiving the regimens including FQs in 3, 6, and 12 months, while 16%, 32%, and 42% respectively in resistant group, (P < 0.01). Also, there were significant differences between these two groups for chest X-ray improvements after 12 months' treatment, (P < 0.01). There were significant differences for sputum conversion rates and chest X-ray improvement between MIC(V) < 4 microg/ml and MIC(V) > or = 4 microg/ml groups (P < 0.01). CONCLUSIONS: According to the evaluation for the therapeutic effects of regimens including FQs, it is suggested that MIC(F) > or = 8 microg/ml and MIC(V) > or = 4 microg/ml be defined as resistant breakpoints clinically. The emergence of resistance to FQs in patients with tuberculosis can influence the therapeutic effects.