For patients with cystic fibrosis (CF) and non-CF bronchiectasis, chronic airway infection
with Gram-negative organisms such as Pseudomonas aeruginosa and Burkholderia cepacia complex
species (BCC) is highly challenging to treat and associated with significant morbidity and
mortality. These organisms are naturally resistant towards many antibiotic classes, limiting
the available arsenal of effective antibiotics for their treatment and eradication.
Therefore, there is a pressing need for new antimicrobial therapy options for infective
exacerbations associated with these organisms.
There are clear logistical and financial benefits for acute infective exacerbations of CF and
non-CF bronchiectasis to be managed on OPAT programs. Many acute infective exacerbations can
be safely managed in this way, and a substantial body of evidence supports non-inferiority of
OPAT compared with inpatient care. From a logistical perspective, feasibility of OPAT
programs is greatly improved by antibiotics being infused over a 24-hour period rather than
via bolus several times per day. Unfortunately, many mainstay anti-pseudomonal and
anti-Burkholderia antibiotics (including meropenem, imipenem and ceftazidime) are not stable
for 24 hours at room/body temperature therefore are unsuitable for use on OPAT.
This study aims to assess viability of ceftolozane/tazobactam (C/T) administered via OPAT in
adult patients with exacerbations of CF or non-CF bronchiectasis. Secondary aims are to
describe clinical outcomes of patients receiving C/T, tolerability of C/T, relative sputum
bacterial load throughout treatment and assess development of resistance to C/T and other
antibiotics. We aim to recruit 30 patients, colonized with either pseudomonas aeruginosa or
burkholderia cepacia complex, with a current infectious exacerbation requiring intravenous
antibiotic treatment. We propose to administer C/T via infusion for 10-14 days with review at
day 0-3, 5-7 and 10-14. Blood testing, sputum testing, lung function testing, administration
of CF- and bronchiectasis-specific questionnaires and adverse event reporting will be carried
out at these times. Serum levels of C/T will be monitored using a validated assay. Clinical
review at day 28-42 will be carried out to assess for recrudescence of symptoms and further
need for antibiotics and a follow-up phone call will be made at 3 months to assess whether
any further antibiotics were needed for new/recrudescent symptoms of infection.
We expect to find that C/T is safe, well-tolerated and effective in treating infective
exacerbations of bronchiectasis in OPAT settings. We expect to find that bacterial density in
sputum samples reduces over the course of treatment, and that development of antimicrobial
resistance is minimal.