Pranita Tamma, MD

Pseudomonas aeruginosa is a bacterium that causes serious infections, often with very poor outcomes in patients with chronic lung conditions such as cystic fibrosis and patients with ventilator dependence. Over time, P. aeruginosa becomes increasingly resistant to commonly used antibiotics. One of three drugs the FDA has recently approved that may have activity against very drug resistant P. aeruginosa is ceftolozane-tazobactam. We have found that for about 20% of patients receiving this antibiotic, their P. aeruginosa became resistant so the antibiotic was no longer effective. We will test patients taking the ceftolozane-tazobactam to understand why these bacteria become resistant to this drug; how often resistance to one drug translates to resistance to one of the other new drugs; and the approaches clinicians can take to limit the emergence of resistance to ceftolozane-tazobactam. Ultimately, we believe that this work will help with future drug development to prevent antibiotic resistance in the treatment of P. aeruginosa.

Update:

We found that approximately 50% of patients treated with ceftolozane-tazobactam (TOL-TAZ) with initial CR-P. aeruginosa bacterial isolates susceptible to TOL-TAZ, develop bacteria that become resistant to TOL-TAZ during therapy. Furthermore, we found that antibiotic resistance to TOL-TAZ leads to cross-resistance to another novel antibiotic, ceftazidime-avibactam, in about 86% of patients, because due to a common mechanism of antibiotic resistance. Fortunately, we found that when TOL-TAZ was administered over 3 hours instead of over 1 hour, no emergence of resistance to TOL-TAZ occurred. Although our findings need to be validated in a larger population, they suggest that a relatively simple change of prolonging the antibiotic infusion time may be protective against the development of resistance. This could be practice changing if these findings extend to other antibiotics as well.