Synergistic activities of the selected antibiotics of fluoroquinolones, β-lactams, aminoglycosides, glycopeptides and streptogramins against gentamicin-resistant Enterococcus faecalis and Enterococcus faecium

Abstract

There is a need for new agents or combination of agents for treatment of serious infections caused by gentamicin and vancomycin-resistant enterococci, which may be resistant to all available antimicrobial agents. The enterococci resistance against antimicrobial agents may be due to both intrinsic and acquisition of the resistance genes to counter antibiotics which were once effective. However, there have been only a few antimicrobial agents which have any activity against these resistant organisms and it is likely that the pathogens will soon become resistant to these as welL One strategy to preserve the efficacy of these new compounds may be to use them in combination. Similarly, combination therapy might be the only strategy that might be effective against some strains, particularly those responsible for endocarditis, intra-abdominal sepsis and urinary tract infections. It is therefore, impottant to study further the combination of agents against enterococci especially those with high-level resistant to gentamicin to establish the synergistic activities of the antibiotics. Also to identify by PCR technique the existence of some resistance genes involved, for example, in gentamicin and ciprofloxacin antibiotics. The aim of this study was to investigate synergistic activities of the combined antibiotics against the gentamicin resistant Enterococcus faecalis and Enterococcus faecium and to establish the existence of some genes involved in the resistance of enterococci against gentamicin and ciprofloxacin. The total of 81 clinical isolates were collected for the study and all were found to be resistant to gentamicin ( MICs range 32->256mg/1 ). 50 isolates were found to be resistant to ciprofloxacin with MICs range 64->256mg/1. The synergistic activities of the antibiotics combinations were established against E.faecalis and E.faecium clinical isolates. The combination between amoxicillin and gentamicin against Efaecalis resulted into synergy with MIC at 90% of 0.5mg/l and for E.faecium MIC at 90% was 2mg/l. Vancomycin and gentamicin combination had MIC at 90% of 2mg/l for E.faecalis and 1 mg/1 for E.faecium. T e icoplanin and synercid combination showed synergistic activity of MlC at 90% of 0.5mg/1 for E.faecalis while E.faeciurn had also 0.5mg/1. The combination between teicoplanin and ciprof1oxacin had synergy with MIC at 90% of <0.25mg/1 for E.faecalis and E.faecium had the same activity MIC at 90% of <0.25mg/1. The combination between amoxicillin and synercid resulted into synergistic activity at MIC at 90% of 4mg/l for E.faecalis and also 4mg/l for E.faecium. The antagonistic activity was observed between th e combination of vancomycin and synercid with MIC at 90% of 32mg/l for E.faecalis and MIC at 90% of 16mg/l for E.faecium. The combination between synercid and ci profloxacin resulted into synergistic activi ty at 90% M IC of 4mg/1 for E.faecium. The checkerboard test of the combination between synercid and ciprofloxacin against four clinical isolates of E.faecium resulted into FIC indices of 0.4 for isola te D002 and 0.4 for isolate 0051. While isolate 788/ 5/95 had 0.3 and NCTC 12202 had also 0.3. These indices confirm the synergistic activity of the combined antibiotic of the two drugs. Of 27 clinical isoaltes tested for the presence of aminoglycoside modifying enzymes using PCR technique, only 8 ( 2 E.faecium and 6 E.faecalis ) showed the positive results of th e presence of AME. However, the presence of the AME did not prevent the synergistic activities of the combin ed drugs against E.faecafis and E.faeciurn. The PFGE s tudy showed the hete rogeneous existence of these gentamicin resistance isolates from RJE. Also, of the isolates ( all E.faecalis ) tested for the presence of gyrA and parC among th e isolates with MICs >256mg/1 and one with MIC of 0.5mg/ l against ciprofloxacin, 6 ( 5 with MICs 256m gil and one with MTC of 0.5mg/l ) were found to have parC mutation and 7 were found to have gyrA mutation.