Enhanced in vitro bactericidal activity of amikacin or gentamicin combined with three new extended-spectrum cephalosporins against cephalothin-resistant members of the family Enterobacteriaceae

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Abstract
The in vitro bactericidal interactions of three new extended-spectrum cephalosporins (ceftriaxone, ceftizoxime, or ceftazidime) in combination with gentamicin or amikacin were compared against 40 recent nosocomial bloodstream Enterobacteriaceae isolates by the timed-kill curve technique. All of the study strains were cephalothin resistant, and 56% were resistant to cefamandole. Combinations of aminoglycosides plus ceftriaxone or ceftizoxime exhibited an enhanced bactericidal effect with the highest frequency (approximately 85 to 90%), whereas gentamicin-ceftazidime combinations demonstrated the lowest frequency (for 60% of assays, P less than 0.0005 against the nonceftazidime regimens). The enhanced bactericidal effects occurred within readily achievable drug levels in serum for all of the single antibiotic constituents. No bactericidal antagonism was observed. There was no discernible relationship between the relative in vitro susceptibilities of the 40 study isolates to ceftazidime and the potential for gentamicin-ceftazidime combinations to demonstrate enhanced bactericidal activity. In 14 of the 40 study strains (35%) all six drug combinations tested demonstrated an enhanced bactericidal effect. In nearly 50% of bactericidal interactions which resulted in enhanced bactericidal effect at 24 h, such enhanced killing was clearly demonstrable by 4 h of incubation. These results delineate a frequent and rapid enhancement of in vitro bactericidal activity between three new extended-spectra cephalosporins and aminoglycosides against nosocomial members of the family Enterobacteriaeceae.