Synergism of Vancomycin-Gentamicin and Vancomycin-Streptomycin Against Enterococci

Watanakunakorn, Chatrchai; Bakie, Cheryl

doi:10.1128/aac.4.2.120

Cited by 88 publications

(33 citation statements)

References 20 publications

(24 reference statements)

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“…Other investigators have demonstrated this in vitro bactericidal action of daptomycin against various strains of enterococci (4-6, 19, 20). However, in 100% rabbit serum the MBC increased at least sevenfold for daptomycin, and no bactericidal activity was present in time-kill studies by 24 h. Adding gentamicin to daptomycin, penicillin G procaine, or vancomycin led to (2,22). In serum, similar bactericidal activity occurred, but daptomycin-gentamicin was less rapidly bactericidal than penicillin G procaine-gentamicin, vancomycin-gentamicin, or daptomycin-gentamicin in broth.…”

Section: Discussionmentioning

confidence: 70%

Daptomycin (LY146032) treatment of experimental enterococcal endocarditis

Bush

Boscia

Kaye

1988

Antimicrob Agents Chemother

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This study compared daptomycin (LY146032) with penicillin G procaine and vancomycin without and with gentamicin for treatment of experimental enterococcal endocarditis. The strain of Streptococcus (Enterococcus) faecalis used in this study was killed by daptomycin in vitro in broth but not in serum. In rabbits treated for 3 days, daptomycin signfficantly reduced bacterial counts of vegetations compared with no therapy but was significantly less effective than penicillin G procaine or vancomycin. Daptomycin-gentamicin significantly reduced bacterial counts of vegetations compared with daptomycin alone but was significantly less effective than vancomycin plus gentamicin. The efficacy of daptomycin-gentamicin did not differ significantly from that of penicillin G procaine-gentamicin. The lack of enterococcal killing by daptomycin alone in serum and in experimental endocarditis is probably related to the high protein binding of the agent.Enterococci are the third most common cause of infective endocarditis and are responsible for about 10% of infective endocarditis cases (8). Unlike most other streptococcal species, enterococci demonstrate resistance to a wide range of antimicrobial agents, and rarely is a single agent bactericidal against the organisms in vitro (15). To achieve in vitro bactericidal activity against enterococci, an aminoglycoside must be added to penicillin G, ampicillin, or vancomycin (16, 21). Although controlled trials are lacking, the recommended treatment of serious enterococcal infections, e.g., endocarditis, involves a combination of penicillin G or vancomycin plus an aminoglycoside (9, 11).The emergence of clinical enterococcal isolates which demonstrate high-level streptomycin resistance (16) and, more recently, strains with high-level gentamicin resistance (12, 23) threatens our ability to provide bactericidal antimicrobial therapy in cases of enterococcal endocarditis. In vitro experiments (12) and animal studies (2) have shown a loss of bactericidal activity with penicillin G plus an aminoglycoside against enterococcal isolates which demonstrate high-level aminoglycoside resistance. These developments, together with the recent demonstration of ,B-lactamase production by isolates of Streptococcus (Enterococcus)faecalis (17), illustrate the need for alternative antimicrobial therapy for serious enterococcal infections.Daptomycin (LY146032) is a cyclic lipopeptide compound that belongs to a class of antibiotics produced by Streptomyces roseosporus (4). It has a spectrum of activity against aerobic, facultative, and anaerobic gram-positive bacteria. Although its spectrum of activity is similar to those of the glycopeptide antibiotics vancomycin and teicoplanin, daptomycin differs from these antibiotics in structure and mechanism of action. Another characteristic of daptomycin which distinguishes it from the glycopeptide antibiotics is the in vitro demonstration of bactericidal activity against enterococci at concentrations near the MIC (4, 19). These features suggest that daptomycin may be...

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Section: Discussionmentioning

confidence: 70%

Daptomycin (LY146032) treatment of experimental enterococcal endocarditis

Bush

Boscia

Kaye

1988

Antimicrob Agents Chemother

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“…As with penicillin and vancomycin, N-formimidoyl thienamycin is not bactericidal against enterococci. Also similar to penicillin and vancomycin (6,7), synergism of Nformimidoyl thienamycin with gentamicin and N-formimidoyl thienamycin with tobramycin was demonstrated against almost all strains tested. Both combinations failed to show synergism against one strain of Streptococcusfaecalis.…”

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confidence: 87%

Synergism Between N -Formimidoyl Thienamycin and Gentamicin or Tobramycin Against Enterococci

Watanakunakorn

Tisone

1982

Antimicrob Agents Chemother

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By the time-kill curve method, the combination of N-formimidoyl thienamycin and gentamicin showed synergism against 47 of 48 strains of enterococci, whereas the combination of N-formimidoyl thienamycin and tobramycin was synergistic against 46 strains. N-Formimidoyl' thienamycin (MK0787) is a stable derivative of thienamycin, a novel Plactam not containing a sulfur atom in the secondary ring, derived from Streptomyces cattleya. N-Formimidoyl thienamycin has been shown to have a wide antimicrobial spectrum, including gram-positive cocci and gram-negative bacilli (2,3,5). In contrast to the third-generation cephalosporins and other new 1-lactams, Nformimidoyl thienamycin has been reported to be active against enterococci (2, 3). In this investigation, we studied the in vitro activity of N-formimidoyl thienamycin against enterococci and the effects of combining N-formimidoyl thienamycin with gentamicin or with tobramycin against enterococci by the time-kill curve method.Forty-eight strains of enterococci were used in this study. All strains grew in 6.5% NaCl brain heart infusion broth and grew as colonies surrounded by black zones on bile-esculin agar. Identification of the enterococci to species level was performed by the API 20S Streptococcus System (Analytab Products, Plainview, N.Y. 16 ,ug/ml (median, 16 ,ubg/ml, and the MBC ranged from 8 to 64 ,ug/ ml (median, 32 ,ug/ml). The MIC of tobramycin ranged from 4 to >64 ,ug/ml (median, 16 ,ug/ml),

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“…To cast further doubt on the bacteriologic identification, all of the enterococci were said to be susceptible to cephalothin and one to clindamycin, unusual properties for enterococci (79). In vitro, vancomycin is usually not bactericidal, and it does no better in animal models than penicillin alone (27,99,104,135,205,217). Among other agents that have been evaluated, ciprofloxacin was less effective than procaine penicillin in controlling enterococcal endocarditis (75,104,195).…”

Section: Management Of Enterococcal Infections Therapymentioning

confidence: 99%

The life and times of the Enterococcus

Murray¹

1990

Clin Microbiol Rev

1,697

1,221

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Enterococci are important human pathogens that are increasingly resistant to antimicrobial agents. These organisms were previously considered part of the genus Streptococcus but have recently been reclassified into their own genus, called Enterococcus. To date, 12 species pathogenic for humans have been described, including the most common human isolates, Enterococcus faecalis and E. faecium. Enterococci cause between 5 and 15% of cases of endocarditis, which is best treated by the combination of a cell wall-active agent (such as penicillin or vancomycin, neither of which alone is usually bactericidal) and an aminoglycoside to which the organism is not highly resistant; this characteristically results in a synergistic bactericidal effect. High-level resistance (MIC, greater than or equal to 2,000 micrograms/ml) to the aminoglycoside eliminates the expected bactericidal effect, and such resistance has now been described for all aminoglycosides. Enterococci can also cause urinary tract infections; intraabdominal, pelvic, and wound infections; superinfections (particularly in patients receiving expanded-spectrum cephalosporins); and bacteremias (often together with other organisms). They are now the third most common organism seen in nosocomial infections. For most of these infections, single-drug therapy, most often with penicillin, ampicillin, or vancomycin, is adequate. Enterococci have a large number of both inherent and acquired resistance traits, including resistance to cephalosporins, clindamycin, tetracycline, and penicillinase-resistant penicillins such as oxacillin, among others. The most recent resistance traits reported are penicillinase resistance (apparently acquired from staphylococci) and vancomycin resistance, both of which can be transferred to other enterococci. It appears likely that we will soon be faced with increasing numbers of enterococci for which there is no adequate therapy.

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Synergism of Vancomycin-Gentamicin and Vancomycin-Streptomycin Against Enterococci

Cited by 88 publications

References 20 publications

Daptomycin (LY146032) treatment of experimental enterococcal endocarditis

Daptomycin (LY146032) treatment of experimental enterococcal endocarditis

Synergism Between N -Formimidoyl Thienamycin and Gentamicin or Tobramycin Against Enterococci

The life and times of the Enterococcus

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