Ceftolozane–tazobactam (C/T) was designed to have enhanced activity against P. aeruginosa and has been shown to retain activity against many isolates that are resistant to other antipseudomonal β-lactams. However, there are no data comparing outcomes in patients with and without cystic fibrosis (CF).
Retrospective, multicenter cohort study conducted at 5 hospitals that included all patients with P. aeruginosa infections who received C/T as definitive therapy between November 2016 and December 2018. The primary outcome at 90 days was a composite of mortality, recurrence, readmission, and inappropriate response at end of therapy (EOT). The secondary outcome was to describe baseline C/T susceptibility and emergence of resistance. All outcomes were adjudicated by 2 infectious diseases specialists.
Thirty-five, 27 non-CF and 8 CF, patients were included. CF patients were younger, had greater baseline C/T resistance (50.0% vs. 8.3%, P = 0.02) and were more likely to receive combination therapy. The most common site of infection was pulmonary (71.4%) followed by intra-abdominal (14.3%) and osteomyelitis (5.7%). Overall, 54.3% of patients had an unsuccessful outcome with no difference between CF and non-CF patients (62.5% vs. 51.9%, P = 0.70). There was also no difference between each component of the primary outcome. All 4 CF patients with a baseline-resistant isolate had an appropriate response at EOT, while neither of the 2 non-CF patients did. The C/T MIC distribution in CF and non-CF patients was ≤ 2 μg/mL (0.0%, 64.2%), 4 μg/mL (50.0%, 25%) ≥ 8 μg/mL (50.0%, 8.4%). The median duration of C/T in CF and non-CF patients was 18.5 days (interquartile range [IQR], 14–37.5 days) and 15 days (IQR, 10–25 days). Ten, 7 non-CF and 3 CF, patients had a P. aeruginosa isolate cultured and tested for C/T susceptibility within 90 days of index culture with 80% having an MIC increase. Non-CF patients treated for > 14 days were more likely to have an MIC increase ( P = 0.047). All CF patients had an MIC increase.