09/21/2015 ABSTRACT FROM ICAAC 2015 MEETING, SEPTEMBER 17 – 21, 2015 IN SAN DIEGO, CALIFORNIA.

ICAAC 2015

Study of Mul-1867 a drug candidate for inhalation therapy of pulmonary exacerbations caused by Burkholderia cepacia in patients with cystic fibrosis and COPD patients

Background. 

Most patients with cystic patients (CF) and chronic obstructive pulmonary disease (COPD) are infected with Burkholderia cepacia that, once established, is impossible to eradicate and is associated with major morbidity. The aim of the present study was to evaluate clinical efficacy of nebulized solution of novel, first in class, antimicrobial drug candidate Mul-1867 in patients with СF and COPD during pulmonary exacerbation caused by B.cepacia.

 Methods.

This compassionate use trial was conducted between 08.2014 and 10.2014. Subjects provided written informed consent before enrollment.

Ten patients with CF and COPD during pulmonary exacerbation participated. The patients were evaluated at day 0 and day 14. Presence of B.cepacia as a primary cause of pulmonary exacerbation was proved by microbiological analysis. The MICs were determined by using the broth macrodilution method. Mul-1867 0.25% solution was nebulized 3 times daily for 14 days (10 mg Mul-1867 dissolved in 4 ml of sterile NaCl 0,9%) with an Omron Compressor Nebulizer System NE-C25. The microbiological response was assessed at day 14 based as the log10 value of CFU per gram of sputum after plating on selective B.cepacia agar medium (Oxoid, UK).

Results.

The sensitivity of isolated B.cepacia strains to piperacllin and minocycline varied from 2 to 256 and from 0.5 to 64 respectively. Mul-1867 was the most active antimicrobial and inhibited the growth of all strains, with MIC values ranging from 0.03 to 0.5 mg/L.

Of the 10 subjects, 100% were evaluable for microbiologic response. Changes from baseline of mean sputum B.cepacia density were significantly different between day 0 and 14 (p < 0.001),   as determined by statistical analysis. Subjects with B.cepacia lung infection treated with nebulized Mul-1867 had mean reductions in bacterial counts of 4.25 log10 CFU/ml, respectively between baseline and day 14 (Fig.1).

One subject had piperacillin-resistant (MIC, ≥ 128 μg/mL) and one myinocycline resistant B.cepacia infection by the first study visit (MIC, ≥ 32 μg/mL). Both patients (100%) exhibited either clinical cure and eradication of B.cepacia on day 14.