Aminoglycoside-Inactivating Enzymes in Clinical Isolates of Streptococcus Faecalis

Abstract

A B S T R A C T Clinical isolates of enterococci (Streptococcus faecalis) with high-level resistance to both streptomycin and kanamycin (minimal inhibitory concentration >2,000 ,ug/ml), and resistant to synergism with penicillin and streptomycin or kanamycin were examined for aminoglycoside-inactivating enzymes. All of the 10 strains studied had streptomycin adenylyltransferase and neomycin phosphotransferase activities; the latter enzyme phosphorylated amikacin as well as its normal substrates, such as kanamycin. Substrate profiles of the neomycin phosphotransferase activity suggested that phosphorylation occurred at the 3'-hydroxyl position, i.e., aminoglycoside 3'-phosphotransferase. A transconjugant strain, which acquired high-level aminoglycoside resistance and resistance to antibiotic synergism after mating with a resistant clinical isolate, also acquired both enzyme activities. Quantitative phosphorylation of amikacin in vitro by a sonicate of the transconjugant strain inactivated the antibiotic, as measured by bioassay, and the phosphorylated drug failed to produce synergism when combined with penicillin against a strain sensitive to penicillin-amikacin synergism.No differences were found in the sensitivity of ribosomes from a sensitive and resistant strain when exam-

Susceptibility Patterns of Enterococci Causing Infections

“…Generally, enteroccocal infections are treated with combination therapies and HLAR is a great concern, since it eliminates synergy with cellwall active antibiotics (Krogstad et al 1978). Our present data indicate the significant frequency of strains with HLAR phenotypes.…”

The life and times of the Enterococcus

“…These various genes confer resistance by two different mechanisms; tetL mediates active efflux of tetracycline from cells, the same mechanism commonly found in gram-negative bacilli (133), while tetM and tetN mediate resistance by a mechanism that protects the ribosomes from inhibition by tetracycline (25 (30). The prevalence of strains highly resistant to various aminoglycosides varies from place to place but is generally highest for streptomycin (112,144,152). Two mechanisms have been described which account for HLR of clinical isolates to streptomycin: ribosomal resistance and enzymatic modification by an adenylyltransferase (57,112).…”

“…The prevalence of strains highly resistant to various aminoglycosides varies from place to place but is generally highest for streptomycin (112,144,152). Two mechanisms have been described which account for HLR of clinical isolates to streptomycin: ribosomal resistance and enzymatic modification by an adenylyltransferase (57,112). This enzyme appears to adenylylate the 6-hydroxyl position since it is not active against spectinomycin; unfortunately, even without HLR, spectinomycin is not a bactericidal agent and does not show synergism against enterococci (44, 112, 135).…”

“…Eliopoulos et al found streptomycin MICs of 4,000 to 16,000 pLg/ml (on dextrose phosphate agar) for strains with streptomycin adenylyltransferase, while MICs were up to 128,000 ,ug/ml for strains with ribosomal resistance (57). HLR to kanamycin in strains without HLR to gentamicin is due to production of an aminoglycoside 3'-phosphotransferase (44,112,135). This enzyme also has activity against amikacin.…”

Antimicrobial resistance among enterococci

“…Although several investigators confirmed the synergistic activity of penicillin and streptomycin against the enterococcus both in vitro (22,25,47) (29). Later investigations by Eliopoulos et al showed that while some clinical strains of enterococci with high-level streptomycin resistance produced inactivat-ing enzymes, others possessed a ribosomally mediated mechanism of streptomycin resistance (9).…”