Comparison of ampicillin-sulbactam with vancomycin for treatment of experimental endocarditis due to a beta-lactamase-producing, highly gentamicin-resistant isolate of Enterococcus faecalis

Abstract

whether treatment was continued for 3 or 7 days. The addition of gentamicin was not associated with increased killing in rabbits infected with the aminoglycoside-resistant isolate. Both high-dose ampicillin-sulbactam and vancomycin regimens demonstrated significant, continued reduction in bacterial titers with the longer periods of treatment (P c 0.05); 7-day treatment with high-dose ampicillin-sulbactam produced a greater reduction in bacterial titers in vegetation than 7-day treatment with vancomycin (P c 0.05). We conclude that ampicillinsulbactam and vancomycin are equally effective in the treatment of experimental endocarditis due to 13-lactamase-producing, highly gentamicin-resistant E. faecalis. The optimum therapy for such infections in humans is not known.Increasing antibiotic resistance has complicated the treatment of serious infections due to enterococci, particularly those due to Enterococcus faecalis. Such infections require a bactericidal therapy, which is usually obtained only with a synergistic combination of a cell-wall-active agent, such as a P-lactam antibiotic or vancomycin, and an aminoglycoside for cure (9,13,(20)(21)(22)24). The emergence of high-level aminoglycoside resistance and the appearance of 1-lactamase-producing strains of E. faecalis (15) and Enterococcus faecium (1) are noteworthy for two reasons: (i) the number of treatment options is reduced because synergism is not observed when aminoglycosides to which the organism has demonstrated high-level resistance are used (12), and (ii) ,-lactamase production has been shown to influence the clinical outcome of infections due to these organisms (23). We have previously shown that ampicillin-sulbactam was bactericidal by the time-kill method for 13 of 20 ,-lactamaseproducing, highly gentamicin-resistant strains of E. faecalis, while bactericidal activity was absent with vancomycin against all 20 strains (10). Currently, the optimum treatment of serious infections caused by I-lactamase-producing, highly gentamicin-resistant E. faecalis has not been determined. In the studies reported herein, we evaluated the efficacy of ampicillin-sulbactam and vancomycin (each alone * Corresponding author. and in combination with gentamicin) in the treatment of experimental aortic valve endocarditis caused by a 3-lactamase-producing, highly gentamicin-resistant isolate of E. faecalis and compared these data with the results obtained in the treatment of experimental endocarditis caused by a non-p-lactamase-producing, gentamicin-susceptible E. faecalis isolate.(This study was presented in part at the 92nd General Meeting of the American Society for Microbiology, 1992 [8].) MATERIALS AND METHODS Bacterial strain. E. faecalis E-48, a ,-lactamase-producing, gentamicin-resistant isolate, was used to inoculate rabbits. The MICs for E. faecalis E-48 were as follows: ampicillin, 4 ,ug/ml; sulbactam, .8 ,ug/ml; ampicillin-sulbactam, 1 ,ug of ampicillin per ml; vancomycin, 4 ,ug/ml; and gentamicin, .2,000 ,ug/ml. In addition, several rabbits were inoculated wi...

Enterococcal Endocarditis Revisited

“…Daptomycin, vancomycin and ampicillin-gentamicin each lowered intravegetation enterococcal densities significantly better than did ampicillin monotherapy or no treatment (p < 0.01); moreover, these three treatment regimens rendered significantly more vegetation cultures negative than did ampicillin monotherapy or no treatment (p < 0.05) Ampicillin-sulbactam + gentamicin High-level resistance to Beta-lactam (due to penicillinase) Lavoie et al (1993) [111] In vivo (rabbit experimental model)…”

“…In vivo analysis of the efficacy of ampicillin compared with vancomycin and daptomycin showed a clear superiority of the latter two, no matter if the mechanism of resistance was PBP or β-lactamase production [78]. Based on case reports [40,111], the AHA recommends a combination of gentamicin plus either vancomycin or ampicillin-sulbactam for 6 weeks [13]. The ESC recommends vancomycin plus gentamicin, and the BSAC proposes a combination of gentamicin plus either vancomycin or teicoplanin if MIC ≤4 μg/ml based on the in vivo studies of Chen et al [79].…”

“…High-level resistance to penicillin and HLAR do usually coincide, so other agents should be tested beforehand. In the case of penicillin resistance due to β-lactamase production, ampicillin-sulbactam may be used as the cell-wall agent [111]. On the other hand, high-dose ampicillin may be considered if MIC is between 16 and 64 μg/ml and penicillin resistance is not due to the production of β-lactamase [13,133].…”

Glycopeptide Resistance in Gram-positive Bacteria

“…Resistance caused by β‐lactamase production has been described, especially in the USA, and the β‐lactamase is susceptible to clavulanate and to sul‐bactam (33), but most β‐lactam‐resistant strains are resistant by a different mechanism: modification of penicillin‐binding proteins.…”

Synergistic activity of vancomycin and teicoplanin alone and in combination with streptomycin against Enterococcus faecalis strains with various vancomycin susceptibilities

“…The significance of enterococcal infections is increasing and vancomycin-resistant enterococci (VRE) as well as resistance to a broad range of antimicrobial agents including recently developed therapeutic agents (such as teicoplanin, quinupristin-dalfopristin (Q-D) and linezolid) are becoming widespread in many parts of the world [4][5][6][7][8][9]. Such infections require a bactericidal therapy, which is usually obtained only with a synergistic combination of a cell wall active agent (such as a penicillin or vancomycin), plus an aminoglycoside [10,11]. However, the increasing resistance to high levels of aminoglycosides and other antimicrobials often leads to loss of synergy and bactericidal activity between cell wall active agents (especially penicillins) and aminoglycosides as well as other agents [4,[12][13][14][15][16][17].…”