Routine susceptibility testing of four antibiotic combinations for improvement of laboratory guide to therapy of cystic fibrosis infections caused by Pseudomonas aeruginosa

Abstract

Previous studies have demonstrated synergy between an aminoglycoside and a beta-lactam for treating Pseudomonas aeruginosa infections. Cystic fibrosis patients are prone to infection by this bacterium, which becomes very resistant with recurrent antibiotic treatments. The purpose of this study was to evaluate the susceptibility patterns of 122 isolates of P. aeruginosa isolated from cystic fibrosis patients to five individual antibiotics (tobramycin, ceftazidime, piperacillin, ticarcillin, and imipenem) and to four antibiotic combinations (tobramycin associated with one of the other antibiotics). Strains were selected because of their resistance to individual antimicrobial agents, which ranged from 21.3% for imipenem to 56.5% for tobramycin. By using an automated broth microdilution method, we were able to demonstrate synergy against 39 strains (32%) with tobramycin-ticarcillin, against 38 strains (31%) with tobramycin-piperacillin, against 47 strains (39%) with tobramycin-ceftazidime, and against 23 strains (19%) with tobramycin-imipenem. Of the 122 isolates, 77 (63%) were rendered significantly susceptible to at least one of the four antibiotic combinations by synergy. These results suggest that when appropriate technology is available, susceptibility to antibiotic combinations greatly improves the guide to antibiotic therapy for infections due to P. aeruginosa in cystic fibrosis patients.

In-Vitro Efficacy of Synergistic Antibiotic Combinations in Multidrug Resistant Pseudomonas Aeruginosa Strains

“…Synergistic interactions of these combinations have been reported in many studies 11-26. In the present study, we detected synergy only in ceftazidime-tobramycin (67%) and piperacillin/tazobactam-tobramycin (50%) combinations in resistant strains, and in ceftazidime-tobramycin (31%), piperacillin/tazobactam-tobramycin (46%), imipenem-tobramycin (15%) and imipenem-isepamycin (8%) combinations in susceptible strains.…”

In vitro activity of antimicrobial combinations against multidrug-resistant Pseudomonas aeruginosa

“…As observed in other studies 26,27 , the rate of synergy of antibacterial combinations varies according to isolate and is not strictly associated with susceptibility or resistance to imipenem. Comparison of the two multidrug-resistant P. aeruginosa isolates revealed more frequent and signifi cant drug MIC reductions for the 46R isolate than for the 72R isolate.…”

Clinical application of direct sputum sensitivity testing in a severe infective exacerbation of cystic fibrosis

“…These techniques are time-consuming and labor-intensive, with concerns about reproducibility, and neither is routinely used. 5,6 More recently, multiple combination bactericidal testing of CF Burkholderia cepacia isolates was reported, but this technique is similarly labor-and time-intensive, and still relies on Fig. 1.…”