Early ceftolozane-tazobactam initiation may improve drug-resistant Pseudomonas aeruginosa infection outcomes
Early initiation of the antimicrobial combination of ceftolozane and tazobactam may improve outcomes in patients with multidrug-resistant Pseudomonas aeruginosa infections, according to results of a US-based study.
Researchers of this retrospective, observational study used data from 20 hospitals in the US to identify 205 adults (median age 60 years, 58.5 percent male) with multidrug-resistant Pseudomonas aeruginosa infections who had received treatment with ceftolozane-tazobactam for >24 hours between December 2014 and February 2018.
The most common infection was pneumonia (59 percent) and 51.2 percent of patients were in the intensive care unit. Patients had a median APACHE II* score of 19 and a median Charlson Comorbidity Index of 4, with a high rate of comorbidities which included, among others, pulmonary disease (40 percent), diabetes (33.7 percent), renal disease (26.3 percent), heart failure (22.9 percent), and previous organ transplant (17.1 percent). The median duration of hospitalization was 31.5 days.
The median time between culture collection and initiation of ceftolozane-tazobactam treatment was 9 days and patients received treatment for a median 10 days. Of the 139 patients tested for ceftolozane-tazobactam susceptibility, 125 (89.9 percent) were susceptible.
The Pseudomonas aeruginosa infections were most frequently nonsusceptible to antipseudomonal carbapenems (96.8 percent), followed by piperacillin-tazobactam (94.2 percent), aztreonam (92.8 percent), and cefepime/ceftazidime (85.6 percent).
Thirty-nine deaths (19 percent) occurred within 30 days. Clinical success, defined as an improvement in signs and symptoms between baseline and treatment end as well as fever abatement, occurred in 73.7 percent of patients, while 70.7 percent of patients experienced microbiological cure (negative culture at treatment end). [Open Forum Infect Dis 2018;doi:10.1093/ofid/ofy280]
Early initiation of ceftolozane-tazobactam (within 4 days of culture collection) was associated with an elevated likelihood of clinical success (adjusted odds ratio [adjOR], 2.93, 95 percent confidence interval [CI], 1.40–6.10) and microbiological cure (adjOR, 2.59, 95 percent CI, 1.24–5.38).
In contrast, patients who initiated ceftolozane-tazobactam more than 4 days after culture collection had an elevated mortality risk (adjOR, 5.55, 95 percent CI, 2.14–14.40).
High doses of ceftolozane-tazobactam (intravenous administration of 3 g Q8H), received by 47.3 percent of patients, did not confer additional benefit nor did the administration of concomitant antibiotics, with concomitant antibiotic use associated with an increased risk for microbiological failure (adjOR, 3.85, 95 percent CI, 1.86–7.93). Patients with pneumonia had an elevated risk of microbiological failure (adjOR, 8.06, 95 percent CI, 3.34–19.49), though the risk did not extend to clinical failure or mortality.
“The lack of a detected positive effect from concomitant therapy suggests that ceftolozane-tazobactam monotherapy may be sufficient for the treatment of Pseudomonas aeruginosa infections that are susceptible to this agent,” said the researchers.
According to the researchers, the benefits demonstrated specifically with early initiation of the drug combination is crucial.
“Although de-escalation approaches are commonly recommended by clinical guidelines in many syndromes, the elevated costs associated with new antimicrobial agents and a desire to reserve these agents for highly resistant organisms may lead to a reversion to an “escalation” approach in patients with these organisms,” they said.
“Antimicrobial stewardship programmes and individual practitioners alike need to strike a difficult balance between early use of agents such as ceftolozane-tazobactam in appropriate patients who may benefit from it and the economic and microbiological consequences of overuse,” they added, pointing out the potential of rapid diagnostic and scoring systems to help identify patients who would derive the most benefit from these agents.