Investigation of the synergic effects of aminoglycoside-fluoroquinolone and third-generation cephalosporin combinations against clinical isolates of Pseudomonas spp.

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Abstract
Antimicrobial synergy resulting from antibiotic combination therapy is often important in the treatment of serious bacterial infections. Previous studies have demonstrated synergy between an aminoglycoside and β-lactam antibiotics in the treatment of Pseudomonas aeruginosa infections. The present paper investigates the synergic effects of aminoglycosides (amikacin and netilmicin) and fluoroquinolones (ciprofloxacin, ofloxacin and pefloxacin) in combination with third-generation cephalosporins (cefoperazone, ceftriaxone and ceftazidime) against 18 clinical isolates of Pseudomonas spp. The effects of these drugs were examined by three methods (disc diffusion, ‘chequerboard’ titration and the time- killing method), to evaluate the activities of the antibiotics alone and in combination against selected isolates. Fractional inhibitory concentration indices were calculated for all isolates with all combinations. Use of the disc diffusion method revealed that amikacin and netilmicin in combination with the three cephalosporins exhibited synergy against 7- 12 isolates, whereas the combinations of quinolones and ceftazidime displayed synergic effects only in the case of 3- 5 isolates. On ‘chequerboard’ titration, amikacin and ceftriaxone exerted synergy against seven of the isolates. The other combinations showed synergy against fewer isolates, but every combination demonstrated synergic effect against some of the isolates. The tested combinations had different effects against various Pseudomonas spp. With the time- killing method, the ½ ×MIC of amikacin or ciprofloxacin in combination with the ½ ×MIC of third-generation cephalosporins proved to be most effective. No antagonism was found with these combinations. Discrepancies in the detection of synergy were observed for the different methods.

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