Treatment Of Enterococcal Endocarditis Research Articles

A rationale for combination ampicillin and daptomycin in renal transplant patients with enterococcal infective endocarditis.

Treatment of enterococcal endocarditis in patients with history of renal transplantation is complicated. Treatment failure and/or drug toxicities are not uncommon. Treatment with ampicillin and daptomycin in a renal transplant patient has been rarely reported. Here we report a patient who was successfully treated with this novel combination.

What's New in the Treatment of Enterococcal Endocarditis?

Enterococcus spp. are among the common pathogens causing infective endocarditis (IE). Despite major medical advances and new potent antimicrobial agents, the mortality has not significantly improved for several decades. The usual lack of bactericidal activity of penicillin or ampicillin, the toxicity from the combination of penicillin plus aminoglycosides, and the increased reports of high-level resistance to aminoglycosides have led to the exploration of other regimens for treatment of Enterococcus faecalis IE. As an example, ampicillin plus ceftriaxone is now a well-recognized regimen for this organism. However, the emerging of new drug resistances in Enterococcus faecium dramatically reduces the therapeutic alternatives for this organism in IE whichcontinues to be an immense challenge for clinicians even with the availability of newer antimicrobial agents. This article summarizes the current treatment options for enterococcal endocarditis and reviews of recent publications on the topic.

Efficacy of daptomycin in the treatment of enterococcal endocarditis: a 5 year comparison with conventional therapy

Enterococcus spp. account for 10% of infective endocarditis (IE). Although daptomycin is a bactericidal drug with in vitro activity against Enterococcus, there is little experience of its use in IE. We analysed the effectiveness of daptomycin in the treatment of enterococcal IE (EIE). This was a retrospective descriptive study comparing the efficacy of daptomycin versus ampicillin/ceftriaxone versus conventional antibiotic regimens (ampicillin or vancomycin ± gentamicin) in EIE. From January 2007 to December 2011, 6 patients with EIE treated with daptomycin monotherapy were compared with 21 patients treated with ampicillin/ceftriaxone and 5 patients treated with ampicillin or vancomycin ± gentamicin. The three groups had similar epidemiological and clinical characteristics. Daptomycin indications were allergy to β-lactams (n = 3), therapy simplification (n = 2), renal failure (n = 2) and Enterococcus faecium resistant to ampicillin/gentamicin (n = 1). Daptomycin MICs ranged from 1 to 2 mg/L and the doses were 6-10 mg/kg/day intravenously. Daptomycin patients had longer duration of bacteraemia (6 versus 1 day, P < 0.01) and greater need of therapy switch due to complications (66.7% versus 0%, P < 0.01). There were no differences regarding duration of hospital stay or mortality. Daptomycin-treated patients more frequently required a therapeutic change due to worse microbiological and clinical response, although mortality was not increased. Our findings do not support the use of daptomycin as single therapy in the treatment of EIE. Its role in combined strategies should be further investigated.

Aminoglycosides

Aminoglycoside antibiotics (AGAs) have proved an invaluable part of our antimicrobial armamentarium since their introduction into practice over 60 years ago. This review summarizes recent developments, defining their role in the context of the current global epidemic of antibiotic resistance, raising awareness of their toxicity profile, and highlighting current data on their utility as synergistic agents. Clinicians are facing an unprecedented threat from antibiotic resistance, resulting in an increased reliance on the addition of an AGA to provide adequate empirical cover in cases of severe sepsis. Concurrently, an increased awareness of the potential for severe disability, particularly from vestibular toxicity, has restrained directed therapy of AGAs to situations in which there are no appropriate alternatives. Their role as synergistic agents in the treatment of enterococcal endocarditis is currently under reevaluation, and new data have emerged on combination therapy for Pseudomonas aeruginosa bacteremia. AGAs are themselves coming under increasing threat from resistance, predominately from aminoglycoside modifying enzymes (mediating selective resistance) and 16S rRNA methyltransferases (conferring class-wide resistance). New agents and the development of alternate ways to circumvent resistance are likely to have important roles in future clinical care. Aminoglycosides retain an invaluable but well defined role, and will remain important agents into the foreseeable future.

Is an Aminoglycoside Still Required for the Treatment of Enterococcal Endocarditis?

Is an Aminoglycoside Still Required for the Treatment of Enterococcal Endocarditis?

Efficacy of Teicoplanin, Administered in Two Different Regimens, in the Treatment of Experimental Endocarditis Due to Enterococcus faecalis

Using a rabbit model of endocarditis, we studied the efficacy of teicoplanin against a strain of Enterococcus faecalis resistant to ampicillin. Rabbits were randomly assigned to receive no antibiotics, teicoplanin 12 or 18 mg/kg of body weight every 12h, for 9 days. The effect of treatment on bacterial counts of vegetations and survival of the animals was evaluated at the end of treatment and 10 days thereafter. The two treatment regimens of teicoplanin produced peak serum levels 18.51±1.84 and 34.66±4.19 μg/ml, and trough levels above 10×MIC of teicoplanin for the infecting organism. Both regimens resulted in significant bacterial reduction in the vegetations as compared to the control group (p<0.001). The drug prevented relapse of the infection 10 days after discontinuation of treatment. By increasing the teicoplanin dosage no additional therapeutic benefit was observed in terms of bacterial killing, sterilization of the vegetations, and survival of the animals, although the higher doses gave numerically superior results. These findings may have meaning for the optimum use of teicoplanin in the treatment of enterococcal endocarditis.

Successful Use of Linezolid in the Treatment of Enterococcal Endocarditis: an Effective and Safe Option?

Successful Use of Linezolid in the Treatment of Enterococcal Endocarditis: an Effective and Safe Option?

Aminoglycosides in Enterococcal Endocarditis: Longer May Not Be Better

Combining an aminoglycoside with an antibiotic that is active at the bacterial cell wall (for example, a β-lactam or vancomycin) is generally believed to provide optimal treatment for enterococcal endocarditis. Based on results of limited clinical studies, major U.S. and British treatment guidelines recommend 4 to 6 weeks of combined therapy. However, prolonged aminoglycoside …

Teicoplanin in the treatment of enterococcal endocarditis: clinical and microbiological study.

Seven cases of enterococcal endocarditis treated with teicoplanin (7-10 mg/kg/day for 28-105 days) alone (one case) or in combination with aminoglycosides (six cases) were reviewed. All patients were cured. Serum bactericidal activity titres after intravenous gentamicin (5 mg/kg every 24 h) and teicoplanin (10 mg/kg every 24 h) were measured on day 7 of treatment in four patients against five enterococcal isolates: mean titres were 1:54 (range 1:16-64) and 1:22 (1:8-32) at 0.5 and 24 h post-infusion, respectively. Time-kill studies showed synergy between teicoplanin and gentamicin against three isolates. We conclude that single daily-dose teicoplanin/gentamicin combined therapy may represent a rational alternative to standard penicillin/gentamicin therapy and a useful regimen for home treatment of selected cases of enterococcal endocarditis.

Can the third-generation cephalosporins eliminate the need for antimicrobial combinations?

Antimicrobial combinations have been widely utilized since the beginning of the chemotherapeutic era. This is true despite the fact that the use of such combinations has a number of potential disadvantages, including (1) antibiotic antagonism; (2) an increased incidence of toxicity; (3) the emergence of multi-resistant organisms; (4) promotion of a false sense of security; and (5) increased expense. The reasons generally given for the use of such combinations include (1) antimicrobial synergism, (2) suppression of antimicrobial resistance, (3) decreased toxicity, and (4) broader coverage. Although there are clearly some situations in which synergistic combinations have been shown to be useful (such as in the treatment of enterococcal endocarditis and severe Pseudomonas infections), the use of combination therapy to reduce the emergence of resistance (excluding the treatment of mycobacterial infections and of infections in which rifampin is used) or to reduce toxicity has not met with widespread success. Indeed, most combinations are used simply to broaden the spectrum of antimicrobial coverage. The development of new penicillins and cephalosporins with broader spectra of activity has raised the distinct possibility that these drugs could be used as single agents for the treatment of most serious infections. Although comparative studies performed to date suggest that the new broad-spectrum penicillins and cephalosporins may be useful as single agents in the treatment of infections in a variety of clinical situations in which combinations are now commonly employed, additional studies enrolling greater numbers of patients are necessary to determine whether these agents can replace combination therapy. The use of single-drug therapy in the management of febrile episodes and documented infections in neutropenic patients remains problematic because of the greater likelihood of infections with organisms such as Pseudomonas aeruginosa, in which case combination therapy is often required. Earlier studies have clearly documented that combinations of antibiotics that are synergistic are more effective in treating bacteremias and other serious infections in neutropenic patients than are combinations that have failed to demonstrate synergism. Because of the increased activity of some of the newer drugs, such as ceftazidime, against P. aeruginosa it is possible that such agents could be used as monotherapy for patients with severe neutropenia. This possibility is an attractive one, but it should be studied carefully to make certain that it will not be associated with significant failure due to the emergence of resistant organisms.

Lack of in vivo and in vitro bactericidal activity of N-formimidoyl thienamycin against enterococci.

The minimal bactericidal concentrations of N-formimidoyl thienamycin (N-f-thienamycin) against 21 strains of enterococci isolated from patients with infective endocarditis were determined by macro- and microdilution methods. By a macrodilution technique with the minimal bactericidal concentration defined as greater than or equal to 99.9% killing of an initial inoculum, all 21 strains of enterococci were found to have minimal bactericidal concentration/minimal inhibitory concentration ratios of greater than or equal to 32. The mean minimal inhibitory concentration was 1.5 micrograms/ml (range, 0.5 to 4 micrograms/ml), and the minimal bactericidal concentration was greater than or equal to 128 micrograms/ml. The disparity between the results of our study and those published elsewhere, which reported that N-f-thienamycin is bactericidal in vitro against enterococci, may represent the relative insensitivity of the microdilution method in determining greater than or equal to 99.9% killing. The lack of in vitro bactericidal activity of N-f-thienamycin against enterococci was confirmed in vivo in the rabbit model of experimental endocarditis. N-f-Thienamycin was no more effective than penicillin alone in the treatment of experimental enterococcal endocarditis and was less effective than the combination of penicillin and gentamicin. The results indicate that N-f-thienamycin should not be used alone in the treatment of enterococcal endocarditis.

Penicillin and netilmicin in treatment of experimental enterococcal endocarditis.

Successful therapy of enterococcal endocarditis requires the use of a combination of penicillin plus an aminoglycoside. The effectiveness of penicillin (Pen), streptomycin (Str), and netilmicin (Net), a new aminoglycoside, alone and in combination, were studied in vitro and in the treatment of left-sided enterococcal endocarditis in rabbits. In vitro Pen+Str or Net resulted in a more rapid and more complete bactericidal effect than Pen, Str, or Net alone against a Str-susceptible strain of enterococcus (strain 1). Against a highly Str-resistant strain (strain 2), Pen+Net showed an advantage over Pen, Str, or Net alone, or Pen+Str. Endocarditis was produced in rabbits with strain 1 or 2, and treatment was initiated 24 h later. Rabbits were treated for 48 h or 5 days with procaine Pen, Pen+Str, or Pen+Net. With strain 1, numbers of enterococci in the vegetations decreased more rapidly with Pen+Str or Pen+Net treatment than with Pen, Str, or Net alone. With strain 2, Pen+Net showed a clear advantage over Pen, Str, Net, or Pen+Str. Net in combination with Pen showed synergistic in vitro activity and was more effective than Pen alone in the treatment of enterococcal endocarditis in rabbits caused by both Str-susceptible and Str-resistant strains.

Treatment of enterococcal endocarditis with oral amoxicillin and intramuscular gentamicin.

A patient with enterococcal endocarditis relapsed after four weeks of treatment with penicillin administered iv and streptomycin administered im; the patient relapsed again after two weeks of treatment with vancomycin administered iv. Treatment in both instances was stopped because of complications of iv therapy. The patient was successfully treated with a six-week course of oral amoxicillin, 1 g every 4 hr, and im gentamicin, 80 mg every 8 hr (decreased to 80 mg daily after 25 days).

Treatment of Enterococcal Endocarditis

Treatment of Enterococcal Endocarditis

BACTERIAL versatility.

BACTERIAL versatility.

Treatment of enterococcal endocarditis and bacteremia: Results of combined therapy with penicillin and streptomycin

Results are reported of the concurrent administration of penicillin and streptomycin to seven patients with enterococcal endocarditis. An eighth patient infected with a similar organism is included. Two of the seven patients received combined therapy for only brief periods prior to death and are not considered as having had adequate trials of therapy. In the remaining five patients results of the combined treatment were striking, permanent arrest of the infection being readily achieved in four. The fifth patient sustained a questionable relapse and subsequently died. However, there was no evidence of uncontrolled infection. These results are superior to those which have been achieved by the use of penicillin alone. It is believed that this form of therapy represents the treatment of choice for enterococcal endocarditis and bacteremia at the present time. The results appear to represent a summative (synergistic) effect of the two antimicrobial drugs upon the enterococcus in vivo. Evidence for a combined effect in vitro is presented and an hypothesis as to the possible mechanism of such an effect is discussed. The use of combinations of antimicrobial agents appears to offer an effective method of achieving permanent arrest of some infections which can be suppressed only temporarily by the administration of a single drug.