Unsuspected embolic fungal endocarditis of an aortic conduit diagnosed by transesophageal echocardiography.

A 66-year-old man with a history of hypertension and ascending aortic replacement because of a type A dissection had 3 successive embolic events (left lower limb, brain, and spleen). Two consecutive transesophageal echocardiography studies showed mobile masses in the ascending aorta. The patient was reoperated without a certain etiologic diagnosis, and an unsuspected fungal endocarditis caused by an unusual germ (Trichoderma species) was found. Transesophageal echocardiography proved very useful in the management of this uncommon case of endocarditis.     

Ampicillin therapy of experimental enterococcal endocarditis.

In rabbits with experimental enterococcal endocarditis, subcutaneously implanted perforated polyethylene chambers were used for ampicillin administration by intra-chamber injection. A total of 21 days of intra-chamber ampicillin therapy sterilized vegetations of 14 out of 14 rabbits with experimental enterococcal endocarditis. In rabbits treated for less than 21 days, the duration of therapy and quantitative vegetation cultures were inversely related. Peak serum minimal bactericidal titers were greater than or equal to 1:8 in 94% of the determinations. Trough serum minimal bactericidal titers were less than or equal to 1:2. The mean trough serum ampicillin concentration (2.6 micrograms/ml) was greater than the minimal bactericidal concentration of ampicillin for the infecting enterococcus and less than the mean trough chamber fluid ampicillin concentration (3.7 micrograms/ml). Relatively prolonged therapy with intrachamber injections seemed to be well tolerated. Combination drug therapy of enterococcal endocarditis may not always be required. The maintenance of serum minimal bactericidal titers greater than or equal to 1:8 throughout the therapy of endocarditis, as is often recommended, may be unnecessary.     

Use of transesophageal echocardiography for improving detection of valvular vegetations in subacute bacterial endocarditis

Subacute bacterial endocarditis is associated with significant morbidity and mortality. Valvular destruction, congestive heart failure, embolic phenomena, failure of medical therapy, and death are all more common in patients with echocardiographically discernible valvular lesions. Transthoracic echocardiography is often unsatisfactory for evaluation of vegetations in patients with chest wall deformities, lung disease, obesity, or prosthetic valves. The transesophageal approach affords uniformly high-quality images with excellent structural resolution. We present a case of suspected subacute bacterial endocarditis in a patient with equivocal diagnoses of vegetations on three separate transthoracic echocardiograms in whom transesophageal evaluation revealed obvious large vegetations that involved the aortic and mitral valves. Subsequent autopsy confirmed this diagnosis. The case illustrates the utility of a new imaging method for the detection of valvular vegetations. In view of the prognostic implications of detected vegetations, transesophageal echocardiography probably should be performed on all patients with suspected subacute bacterial endocarditis and equivocal results by transthoracic study.     

经胸二维和三维超声心动图诊断主动脉-左心室通道合并感染性心内膜炎一例

IntroductionAorto-left ventricular tunnel ( ALVT) is an extreme rare (0.001% ) congenital para-valvular communication between aorta and the left ventricle.It was first reported by Edwards and his colleagues in 1961[1].Only about 100 cases have been reported until now.We report our first case of ALVT with infective endocarditis demonstrated by two-dimensional and three-dimensional echocardiography and confirmed by surgery.     

Failure of trimethoprim-sulfamethoxazole therapy in experimental enterococcal endocarditis.

To assess the potential efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) against serious enterococcal infections, we used a rat enterococcal endocarditis model comparing TMP-SMX therapy (500 mg of TMP plus 2,500 mg of SMX per kg of body weight per day given every 8 h by intragastric gavage) with intravenous ampicillin therapy (1,000 mg/kg per day). Despite concentrations of active drug in serum well in excess of the MIC and MBC, the mean residual vegetation bacterial titer in TMP-SMX-treated rats was similar to that in untreated controls (8.4 +/- 1.1 versus 8.6 +/- 1.3 log10 CFU/g) and significantly higher than that in the ampicillin-treated group (3.6 +/- 1.5 log10 CFU/g; P less than or equal to 0.001). This demonstrates discordance between in vitro activity and in vivo efficacy of TMP-SMX in serious enterococcal infection.     

Antimicrobial activity of gentamicin in experimental enterococcal endocarditis.

The in vitro activity of gentamicin was compared with its therapeutic efficacy in rabbits with Streptococcus faecalis endocarditis. The test strain was resistant to gentamicin as measured by MICs and MBCs determined in Mueller-Hinton broth alone or in broth supplemented with 50% rabbit serum. Gentamicin also failed to manifest anti-enterococcal activity when evaluated by time-kill studies in broth. However, the addition of serum to the medium did enhance the activity of gentamicin. In the therapy of experimental endocarditis, gentamicin used alone demonstrated anti-enterococcal activity equivalent to that of ampicillin used alone. Vegetation titers in animals treated with gentamicin alone were lower than those of untreated controls (P less than 0.01) and comparable to those in animals treated with ampicillin alone. Thus, gentamicin demonstrated anti-enterococcal activity in vivo despite the resistance observed in vitro, as measured by conventional assays to determine MICs and MBCs.     

Therapeutic efficacy of teicoplanin in experimental enterococcal endocarditis.

The antimicrobial activities of teicoplanin and ampicillin, alone and in combination with gentamicin, were compared in experimental Streptococcus faecalis endocarditis. Bacterial titers in vegetations of rabbits treated with teicoplanin were significantly lower than those of untreated controls (P less than 0.01) and were equivalent to titers in ampicillin-treated animals. Gentamicin increased the activities of both drugs to a comparable degree.     

Continuous-infusion ampicillin therapy of enterococcal endocarditis in rats.

Intermittent administration of ampicillin alone has resulted in high failure rates in previously described animal models of enterococcal endocarditis. We developed a rat model of enterococcal endocarditis which permits comparison of continuous intravenous infusion of ampicillin with intramuscular therapy. Continuous low-dose ampicillin infusion (450 mg/kg [body weight] per day) was compared with the same dose given intramuscularly in three divided doses and with high-dose infusion (4.5 g/kg per day) of the drug. For the infecting strain of Streptococcus faecalis, the MIC and MBC were 1 microgram/ml. Mean ampicillin levels in serum were 53.9 +/- 4.8 (peak) and less than 1 (trough), 8.7 +/- 1.4, and 244 +/- 29 micrograms/ml for intramuscular, low-dose, and high-dose regimens, respectively. Ampicillin infusion therapy significantly increased the survival rate and sterilization of blood cultures. Continuous infusions were superior to intermittent therapy in eradicating bacteremia. After 5 days of treatment, low-dose ampicillin infusion was more effective than intermittent therapy in sterilizing cardiac vegetations (P less than 0.01). Continuous-infusion therapy at either dose was significantly more effective than intramuscular injection in reducing bacterial titers in cardiac vegetations (5.4 +/- 1.0 log10 CFU/g [low dose], 4.8 +/- 0.3 log10 CFU/g [high dose], and 7.7 +/- 0.3 log10 CFU/g [intramuscular]). However, no statistically significant advantage was found for high-dose compared with low-dose ampicillin infusion in lowering bacterial titers in vegetations (P greater than 0.3).     

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.     

Mortality in patients with paravalvular abscess diagnosed by transesophageal echocardiography.

BACKGROUND: Paravalvular abscess is a complication of endocarditis that may lead to persistent infection, conduction abnormalities, fistula formation, worsening congestive heart failure, and death. METHODS: Between 1991 and 2001, paravalvular abscess was identified on transesophageal echocardiography in 24 patients who subsequently underwent surgical treatment. Echocardiographic findings were reviewed for location of abscess, presence of a valvular prosthesis, valvular function, and presence of vegetations. Information gathered included the time interval between transesophageal echocardiography diagnosis and operation, inhospital mortality, and microbiologic data. RESULTS: Of 24 patients, 9 died, for a mortality of 38%. Of the patients who died, the average survival after operation was 43 days, with a range of 1 to 238 days. Of the 14 patients with significant valvular or paravalvular regurgitation, 8 died (57%). However, of the 10 patients with mild or no regurgitation, only 1 died (10%). This difference was statistically significant (P =.02). CONCLUSION: Patients without preserved valve function (those with moderate or severe regurgitation) have a significantly worse outcome (57% mortality) than do those with normal valvular function (10% mortality).     

Tissue factor is a major stimulus for vegetation formation in enterococcal endocarditis in rabbits.

We examined the possible mechanisms of local initiation of coagulation in vegetation formation in enterococcal endocarditis by using a rabbit model. Contact activation and tissue factor expression by freshly excised aortic valves were assessed using assays developed for use with cultured cells. Bacteria alone lacked procoagulant activity and contact activation of plasma by excised valves did not occur. 4-d infected but not control valves expressed significant tissue factor activity (231 +/- 17 mU vs. 51 +/- 7 SE), which did not correlate with numbers of bacteria in vegetations. Tissue factor activity was also present in valves from rabbits infected for 1 and 2 d, as well as those from granulocytopenic and monocytopenic animals. Our findings suggest that tissue factor, expressed by host cells in response to infection, is a major stimulus for fibrin deposition in vegetation development.     

Daptomycin (LY146032) treatment of experimental enterococcal endocarditis.

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 significantly 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.     

Significance of in-vitro penicillin tolerance in experimental enterococcal endocarditis

Although penicillin tolerance has been increasingly recognized among clinical isolates of many Gram-positive organisms, the significance of this phenomenon in vivo is not clear. The present study was performed to characterize penicillin-tolerant enterococci by several in-vitro parameters and to examine the significance in vivo in a rabbit model of infective endocarditis. Tolerant enterococci exhibited several characteristics which distinguished them from non-tolerant bacteria: significantly greater ratios of MIC to MBC of penicillin, resistance to penicillin-induced lysis and killing, and growth in areas of superinhibitory concentrations of penicillin upon transfer from penicillin gradient to penicillin-free plates. In-vivo studies of aortic valve endocarditis in rabbits treated with procaine penicillin G (300 mg/kg/day) revealed strikingly different responses between infections due to one tolerant and one non-tolerant strain. Animals infected with a tolerant enterococcus showed consistently greater bacterial counts in vegetations during ten days of therapy and significantly lower rates of vegetation sterilization. Serum penicillin levels were not significantly different between the two groups, but serum bactericidal titres were significantly lower for the tolerant than for the non-tolerant strains. These findings indicate that penicillin tolerance identified by several in-vitro criteria is a significant determinant of the in-vivo response of enterococci to penicillin therapy.     

Minimal concentrations of aminoglycoside that can synergize with penicillin in enterococcal endocarditis

Minimal concentrations of aminoglycoside that could produce a synergistic effect with penicillin were investigated in broth cultures containing 10(8) enterococci per ml, in vitro in vegetations infected with ca. 10(8) enterococci per g, and in vivo in an experimental model of enterococcal endocarditis. Penicillin G plus gentamicin (1.5 or 0.75 microgram/ml) sterilized a broth culture of a streptomycin-resistant strain (E1) at 48 h. In contrast, penicillin G plus gentamicin (1.5 or 0.75 microgram/ml) sterilized only 2 of 15 in vitro vegetations at 5 days. Similarly, doses of gentamicin that resulted in peak serum levels of 1.5 microgram/ml failed after 10 days of therapy with penicillin G plus gentamicin to sterilize in vivo vegetations infected with E1, and doses of gentamicin that resulted in peak serum levels of about 8 micrograms/ml sterilized four of six vegetations. Similar results were obtained with a streptomycin-susceptible strain. These studies indicated that the rate of bactericidal activity in broth cultures is greater than the bacteriological response in infected vegetations and that aminoglycoside concentrations that appear efficacious on the basis of synergy studies in broth cultures may not be satisfactory clinically.