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

Abstract

PurposeCombination antibiotic treatment is preferred in nosocomial infections caused by Pseudomonas aeruginosa (P. aeruginosa). In vitro synergism tests were used to choose the combinations which might be used in clinic. The aim of this study was to investigate the synergistic efficacy of synergistic antibiotic combinations in multidrug resistant P. aeruginosa strains.Materials and MethodsSynergistic efficacies of ceftazidime-tobramycin, piperacillin/tazobactam-tobramycin, imipenem-tobramycin, imipenem-isepamycin, imipenem-ciprofloxacin and ciprofloxacin-tobramycin combinations were investigated by checkerboard technique in 12 multiple-resistant and 13 susceptible P. aeruginosa strains.ResultsThe ratios of synergy were observed in ceftazidime-tobramycin and piperacillin/tazobactam-tobramycin combinations as 67%, and 50%, respectively, in resistant strains, whereas synergy was not detected in other combinations. The ratios of synergy were observed in ceftazidime-tobramycin, piperacillin/tazobactam-tobramycin, imipenem-tobramycin, imipenem-ciprofloxacin and imipenem-isepamycin combinations as 31%, 46%, 15%, 8%, 8%, and respectively, in susceptible strains, whereas synergy was not detected in ciprofloxacin-tobramycin combination. Antagonism was not observed in any of the combinations.ConclusionAlthough the synergistic ratios were high in combinations with ceftazidime or piperacillin/tazobactam and tobramycin, the concentrations in these combinations could not usually reach clinically available levels. Thus, the solution of the problems caused by multiple resistant P. aeruginosa should be based on the prevention of the development of resistance and spread of the causative agent between patients.

Molecular characterisation of multidrug-resistant Pseudomonas aeruginosa from a private hospital in Durban, South Africa

“…As a result, it is coresistant to several antibiotics such as the β-lactams, aminoglycosides and fluoroquinolones. 2 Treatment options for infections caused by multi-drug resistant (MDR) P. aeruginosa are limited, making it one of the most challenging pathogens for antimicrobial chemotherapy. Patients in the intensive care, burn and surgery units are particularly prone to infection by MDR P. aeruginosa, thus contributing to high mortality rates as well as high treatment cost.…”

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

“…Combinations of these antibiotics with tobramycin exhibited synergy in 83% of the tests performed with the four P. aeruginosa isolates. In another study assessing multidrug-resistant P. aeruginosa, ceftazidime plus tobramycin and piperacillintazobactam plus tobramycin combinations were evaluated, and synergy ratios of 67% and 50%, respectively, were observed 17 . With respect to fosfomycin, synergistic interactions with other antibacterial drugs were verifi ed in 57% of the tests, a rate similar to that reported previously for multidrug-resistant P. aeruginosa 18 .…”

Potentiation of Aminoglycoside Activity in Pseudomonas aeruginosa by Targeting the AmgRS Envelope Stress-Responsive Two-Component System

“…In the face of this intrinsic and acquired multidrug resistance, the use of agents historically used less commonly owing to issues of toxicity (e.g., the polymyxins) (10,11) and the use of drug combination therapy (12,13) are increasingly promoted. Still, despite much in vitro evidence for synergistic drug combinations being effective against MDR P. aeruginosa (14)(15)(16)(17)(18)(19)(20), the clinical benefits of drug combinations are less obvious (13,21,22).…”

“…Aminoglycosides (AGs) have a long history in the management of P. aeruginosa infections, particularly in the case of lung infections in patients with cystic fibrosis (23,24), and are often used in combination with ␤-lactams (25-27) owing to a well-established synergy between these two antimicrobial classes (18,20,(26)(27)(28)(29). ␤-Lactam synergy with AGs has been suggested to result from ␤-lactam-promoted AG uptake owing to cell wall damage or lessening of this barrier.…”

“…In the face of this intrinsic and acquired multidrug resistance, the use of agents historically used less commonly owing to issues of toxicity (e.g., the polymyxins) (10, 11) and the use of drug combination therapy (12, 13) are increasingly promoted. Still, despite much in vitro evidence for synergistic drug combinations being effective against MDR P. aeruginosa (14-20), the clinical benefits of drug combinations are less obvious (13,21,22).Aminoglycosides (AGs) have a long history in the management of P. aeruginosa infections, particularly in the case of lung infections in patients with cystic fibrosis (23,24), and are often used in combination with ␤-lactams (25-27) owing to a well-established synergy between these two antimicrobial classes (18,20,(26)(27)(28)(29). ␤-Lactam synergy with AGs has been suggested to result from ␤-lactam-promoted AG uptake owing to cell wall damage or lessening of this barrier.…”