Assessment of the antimicrobial activity of Ceftolozane-Tazobactam and Ceftazidime-Avibactam alone and in combination against Pseudomonas aeruginosa isolated from four different Lebanese hospitals

Abstract

Antibiotics overuse and misuse have pushed the resistance to dangerously high levels all over the world. Our ability to treat common infectious diseases is becoming harder and sometimes impossible due to the emergence and spreading of new resistance mechanisms. In recent years, Multi-Drug resistant Pseudomonas aeruginosa clones has become a major public health threat. And the lack of therapeutic options poses a considerable menace regarding the high morbidity and mortality infections caused by these bacteria. Efforts are being made to find antibiotic alternatives that can stop or slow the crisis. Developing new antibiotic adjuvant combinations have shown therapeutic benefits in protecting some antibiotics' activity against common resistance mechanisms. Also, the proper use of combination antimicrobial therapy has improved in some cases prognosis and lowered resistance dissemination. Thus, in this study, the antimicrobial activity of two novels Antibioticadjuvant: Ceftolozane-Tazobactam and Ceftazidime-Avibactam, was assessed and compared to the activity of Polymixin E, on 134 clinical Pseudomonas aeruginosa strains collected from four different hospitals in Lebanon, using the broth micro-dilution method. Then the combined effect of these two antibiotics was investigated using the Checkerboard Technique. Out of 134 strains, Ceftolozane-Tazobactam had the highest level of resistance 6% (8/134) compared to Polymixin E and Ceftazidime-Avibactam, and the lowest MIC50 = 0.061 μg/mL. Ceftazidime-Avibactam had activity similar to Polymixin E with only 3 % (4/134) resistance and a MIC 90 similar to the MIC 90 of Ceftolozane-Tazobactam = 1 μg/mL. Moreover, Ceftazidime-Avibactam had a MIC 50 lower than the MIC50 of Polymixin E with 0.125 μg/mL and 1 μg/mL respectively. Polymixin E had the highest MIC90= 2 μg/mL. These data showed an encourging activity of Ceftolozane-Tazobactam and Ceftazidime- Avibactam where it covered above 90% of collected isolates with an MIC 90= 1 μg/mL 8 folds lower than the CLSI resistance breakpoint. All the 134 average ΣFICs calculated were between 0.922 and 1.469 indicating that the combined effect of these two antibiotics is indifferent or with a small additive effect on some strains. Whereas no evidence suggested Synergistic or Antagonistic effects.