Bactericidal Activity Of Amikacin Research Articles

EPS7.3 Oxygen is necessary for the bactericidal activity of amikacin on Mycobacterium abscessus

EPS7.3 Oxygen is necessary for the bactericidal activity of amikacin on Mycobacterium abscessus

Phagolysosomal Alkalinization and Intracellular Killing of Staphylococcus aureus by Amikacin

The aminoglycosides are ineffective against intracellular Staphylococcus aureus, which resides within lysosomes, despite a strong extracellular bactericidal activity. Since they are slowly concentrated within lysosomes it was hypothesized that acidity within these cell compartments might impair antibiotic activity. The bactericidal activity of amikacin alone and combined with lysosomotropic alkalinizing agents (LAA), which can alkalinize acidic cell compartments, was evaluated. Before antibiotic challenge, some cells were preincubated with amikacin for 3 days to allow intracellular accumulation of drug. No intracellular killing activity was shown when non-preincubated cells were used. Conversely, with preincubated cells, S. aureus was killed within 4 h when LAA were incorporated into the incubation media but not with amikacin alone. Enhanced antimicrobial activity correlated with increase in lysosomal pH. Intracellular accumulation of amikacin was not changed by LAA. These results provide evidence that acidic pH within lysosomes impairs amikacin in killing S. aureus.

Emergence of 4',4"-aminoglycoside nucleotidyltransferase in enterococci

Enterococcus faecium BM4102 was resistant to macrolide-lincosamide-streptogramin B-type (MLS) antibiotics; tetracycline-minocycline; and high levels of kanamycin, neomycin, tobramycin, and dibekacin but not gentamicin. This aminoglycoside resistance phenotype is new in enterococci. The genes conferring resistance to aminoglycosides and MLS antibiotics in this strain were carried on a plasmid, pIP810, that was self-transferable to to other Enterococcus strains. Resistance to tobramycin and structurally related aminoglycosides, kanamycin, neomycin, and dibekacin, was due to synthesis of a 4',4"-aminoglycoside nucleotidyltransferase. Homology was detected by hybridization between pIP810 DNA and a probe specific for a gene encoding an enzyme with identical site specificity in staphylococci. The bacteriostatic activity of amikacin apparently was not affected by the presence of the enzyme, although it was modified in vitro. However, the bactericidal activity of amikacin and the synergism of this aminoglycoside with penicillin were abolished.

Synergistic Activity of Trimethoprim and Amikacin Against Gram-Negative Bacilli

The in vitro effect of trimethoprim on the inhibitory and bactericidal activity of amikacin against 20 strains each of Klebsiella pneumoniae and Serratia marcescens, 15 strains of Escherichia coli, and 10 strains of Pseudomonas aeruginosa was examined by the checkerboard technique in microtiter plates. Trimethoprim had a synergistic effect on the inhibitory and bactericidal activity of amikacin against the majority of non-pseudomonas strains tested. The mean +/- standard deviation fractional inhibitory concentration indexes were 0.59 +/- 0.19 for the Klebsiella strains, 0.48 +/- 0.18 for the Serratia strains, and 0.60 +/- 0.22 for the E. coli strains tested. Respective mean +/- standard deviation fractional bactericidal concentration indexes for these organisms were 0.55 +/- 0.17, 0.54 +/- 0.29, and 0.61 +/- 0.22. A total of 40% of the Klebsiella strains, 80% of the Serratia strains, and 46% of the E. coli strains had a fractional inhibitory concentration equal to or less than 0.25 for both of these antimicrobial agents and were considered to be synergistically inhibited by the combination. By applying this criterion to bactericidal activity, synergy was demonstrated against 50, 65, and 46% of these strains, respectively. All of the Enterobacteriaceae tested were inhibited by clinically achievable concentrations of trimethoprim and amikacin. Antagonism was not demonstrated with any of the organisms tested. Trimethoprim had no antibacterial effect on the Pseudomonas strains and did not alter amikacin's activity against these bacteria.

Bactericidal Activity of Amikacin and Gentamicin

Using the membrane filtration method bactericidal activity of amikacin and gentamicin as a function of time and concentrations was determined. Amikacin was bactericidal against all Pseudomonas aeruginosa (n = 7) and Klebsiella pneumoniae strains (n = 8) tested. In 5 of the 7 P. aeruginosa and 3 of the 8 K. pneumoniae strains we saw a secondary regrowth at 24h. There was no difference between amikacin and gentamicin. The experiments to determine the effect of concentration on bactericidal activity showed that higher concentrations lead to a faster kill rate.