Amikacin, an Aminoglycoside with Marked Activity against Antibiotic-Resistant Clinical Isolates

Abstract

A total of 319 clinical isolates known to be resistant to one or more aminoglycoside antibiotics were tested for their susceptibility to 10 aminoglycosides. The percentages of isolates found by an agar dilution method to be susceptible were: amikacin, 83.7%; tobramycin, 41.4%; butirosin A, 33.2%; dideoxykanamycin B, 32.6%; gentamicin C, 27.3%; lividomycin A, 17.6%; neomycin B, 10.7%; paromomycin, 10.3%; kanamycin A, 10.0%; and ribostamycin, 7.2%. The effectiveness of the antibiotics was related to their degree of resistance to bacterial enzymes; e.g., of the nine enzymes known to inactivate antibiotics containing 2-deoxystreptamine, amikacin was affected by one enzyme, tobramycin by five, and gentamicin and kanamycin by six. Examination of cell-free extracts from the 52 strains resistant to amikacin revealed that only four contained the amikacin-inactivating enzyme aminoglycoside-6'-acetyltransferase, a finding indicating that this mechanism of resistance is rare. Other experiments suggest that most amikacin-resistant strains, which are almost invariably resistant to all aminoglycosides, lack the ability to accumulate effectively either amikacin or presumably the other antibiotics intracellularly.

The increasing isolation ofSerratiaspecies from clinical specimens

“…The majority of our strains were sensitive to trimethoprim, chloramphenicol and nalidixic acid, yet a high incidence of resistance to both chloramphenicol and nalidixic acid was reported by Dodson (1968) and Schaefler et al (1971). Amikacin is active against strains resistant to other aminoglycosides, but amikacin-resistant Serratia do occasionally occur (Price, DeFuria & Pursiano, 1976). Antibiotic resistance transfer has been demonstrated in only a small proportion of Serratia strains but some of the R factors detected are unusually widespread (Hedges et al 1975 (Traub, 1972;Maki et al 1973).…”

Antimicrobial activity of amikacin combinations against Enterobacteriaceae moderately susceptible to third-generation cephalosporins

“…Indifference was rare (8.1% for moxalactam), and true antagonistic interactions were not observed. Strains resistant or susceptible to these new cephalosporins were also synergistically inhibited by the addition of amikacin, reducing resistant cephalosporin minimal inhibitory concentrations to clinically achievable levels.Amikacin has been recognized as the currently available aminoglycoside most refractory to bacterial enzyme inactivation (18). This stability has generally limited the use of amikacin to those clinical bacterial strains resistant to kanamycin, gentamicin, and tobramycin by enzyme plasmid-mediated mechanisms.…”

“…Amikacin has been recognized as the currently available aminoglycoside most refractory to bacterial enzyme inactivation (18). This stability has generally limited the use of amikacin to those clinical bacterial strains resistant to kanamycin, gentamicin, and tobramycin by enzyme plasmid-mediated mechanisms.…”

Amikacin pharmacokinetics in pediatric patients with malignancy

“…It is effective in the treatment of patients with serious infections due to gram-negative bacilli and is particularly useful in therapy of infections involving organisms that are resistant to other aminoglycoside antibiotics (1,21). Pharmacokinetic data related to its use in adults (3,4,6,11,16,18) and neonates (5,12,22) are available; however, infornation supporting the recommended dose and frequency ofadministration for older infants and children is scant (15,25).…”

“…Renal function before and after completion of (1,21). The occurrence of gram-negative bacilli as the major cause of infection in children with cancer necessitates the use of an antibiotic with activity against these microorganisms (J. L. Hoecker, L. K. Pickering, S. Kohl, D. Groschel, and J. van Eys, Cancer, in press).…”