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Staphylococcus aureus is the leading cause of infectious endocarditis and its mortality has remained high despite better diagnostic and therapeutic procedures over time. We conducted a retrospective review of 133 cases of definite S. aureus endocarditis seen at a single tertiary care hospital over 22 years to assess changes in the epidemiology and incidence of the infection, manifestations, outcome, risk factors for mortality, and impact of cardiac surgery on prognosis.Patients were classified into 2 groups: 1) right-sided endocarditis (64 patients) and 2) left-sided endocarditis (69 patients). While the number of cases of left-sided endocarditis remained steady at 1-3 cases per 10,000 admissions, the incidence of right-sided endocarditis, after a peak in the early 1990s, declined to almost disappear in 2001. Among the cases of right-sided endocarditis, we found 2 subsets of patients with different clinical features and prognosis: the first subset comprised 53 intravenous drug abusers, and the second subset comprised 11 patients with catheter-associated S. aureus bacteremia and endocarditis. Fifty-one patients were human immunodeficiency virus (HIV)-positive drug abusers, most of whom (80.3%) had right-sided endocarditis. We did not find differences in mortality between HIV-positive and HIV-negative individuals; mortality seemed to depend more on the site of the heart involved than on HIV status.Among the cases of left-sided endocarditis, the mitral valve was more commonly involved than the aortic valve (61% vs. 30%). Overall, 74% of patients with left-sided endocarditis developed 1 or more cardiac or extracardiac complication. In comparison, only 23.4% of patients with right-sided endocarditis developed complications.Prosthetic valve endocarditis (PVE) was hospital-acquired more frequently than native valve endocarditis (NVE). Patients with PVE had a shorter duration of symptoms until diagnosis and presented with or developed cardiac murmurs less frequently than patients with NVE. Cardiac failure (49%), renal failure (43%) and central nervous system (CNS) events (35%) were frequently observed in patients with both PVE and NVE. Valve replacement was more frequently needed and more rapidly performed in patients with PVE than in their counterparts with NVE.The overall mortality of patients with right-sided endocarditis was 17%. While the mortality of right-sided endocarditis in injection drug users was 3.7%, the mortality of patients with right-sided endocarditis associated with infected intravenous catheters was 82% (odds ratio [OR], 0.01; 95% confidence interval [CI], 0.001-0.07). For left-sided endocarditis mortality was 38% and was not significantly different in patients with NVE or PVE (OR, 0.65; 95% CI, 0.23-1.87). CNS complications were associated with mortality in both NVE (OR, 6.55; 95% CI, 1.78-24.04) and PVE (OR, 32; 95% CI, 2.63-465.40). Development of 2 or 3 complications was associated with an increased risk of mortality (OR, 5.59; 95% CI, 1.08-28.80 and OR, 9.25; 95% CI, 1.36-62.72 for 2 vs. 1 complication and for 3 vs. 2 complications, respectively).Surgical treatment did not significantly influence mortality in cases of NVE, (OR, 3.19; 95% CI, 0.76-13.38) but significantly improved the prognosis of patients with PVE (OR, 69; 95% CI, 2.89-1647.18).S. aureus endocarditis is an aggressive, often fatal, infection. The results of the current study suggest that valve replacement will improve the outcome of infection, particularly in patients with PVE.

Enterococci are the third leading cause of infectious endocarditis, and despite advances in diagnosis and treatment, the mortality of enterococcal endocarditis has not changed in recent decades. Although variables such as advanced age, cardiac failure, and brain emboli have been recognized as risk factors for mortality, cooperative multi-institutional studies have not assessed the role of other variables, such as nosocomial acquisition of infection, the presence of comorbidities, or the changing antimicrobial susceptibility of enterococci, as factors determining prognosis.We conducted the current study to determine the risk factors for mortality in patients with enterococcal endocarditis in a single institution. We reviewed 47 consecutive episodes of enterococcal endocarditis in 44 patients diagnosed according to the modified Duke criteria from a retrospective cohort study of cases of infectious endocarditis. The main outcome measure was inhospital mortality. We applied stepwise logistic regression analysis to identify risk factors for mortality.Predisposing heart conditions were observed in 86.3% of patients, and 17 had prosthetic valve endocarditis. A portal of entry was suspected or determined in 38.2%; the genitourinary tract was the most common source of the infection (29.7%). Comorbidities were present in 52.2% of cases. Twelve episodes (25.5%) were acquired during hospitalization. Only 3 isolates of Enterococcus faecalis were highly resistant to gentamicin. Eighteen patients (40.9%) needed valve replacement due to cardiac failure or relapse. Comparing cases of native valve and prosthetic valve endocarditis, we found no differences regarding complications, the need for surgical treatment, or mortality. Eight of 44 (18%) episodes were fatal. Age over 70 years (p = 0.05), heart failure (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.15-2.25; p = 0.001), presence of 1 or more comorbidities (OR, 3.2; 95% CI, 1.11-9.39; p = 0.02), and nosocomial acquisition (OR, 8.05; 95% CI, 1.50-43.2; p = 0.01) were associated with mortality. In the multivariate analysis, only nosocomial acquisition increased the risk of mortality. In patients with enterococcal endocarditis, nosocomial acquisition of infection is an important factor determining outcome. As the incidence of bacteremia and the population of elderly people at risk continue to grow, the hazard of acquiring nosocomial enterococcal endocarditis may increase; hence, major emphasis must be put on prevention.

Objectives: To compare the activity of cloxacillin and vancomycin against methicillin-susceptible Staphylococcus aureus and to determine how rapidly their bactericidal activity occurs in cardiac vegetations., Methods: In vitro and in vivo studies using an experimental model of endocarditis in rabbits. Animals were treated for 1, 2 or 3 days with cloxacillin 200 mg/kg intramuscularly three times a day or vancomycin 25 mg/kg intravenously twice a day., Results: Cloxacillin and vancomycin at concentrations 4- and 16-fold the MIC produced a modest decrease in the number of microorganisms at 4 h. After 24 h, cloxacillin produced a decrease in the counts of staphylococci from 2.19 to 4.84 log10 cfu/mL of inoculum. Only concentrations of vancomycin from 16- to 32-fold the MIC resulted in equivalent decreases. After 24 h of treatment, both antibiotics were equally effective in preventing mortality of rabbits. Cloxacillin produced a greater decrease in the number of staphylococci than vancomycin (3.50+/-2.18 log10 cfu/g vegetation and 6.25+/-1.28 log10 cfu/g vegetation, respectively; P<0.05) and 41% of rabbits had sterile vegetations in comparison with none with vancomycin (P=0.035). After 48 and 72 h of treatment, both antimicrobials exhibited equivalent activity., Conclusions: Vancomycin was less rapidly bactericidal than cloxacillin in vivo.

Study Objectives: To study the changing etiology of prosthetic valve endocarditis (PVE) and the impact of nosocomial acquisition of the infection on prognosis in a single hospital., Methods: Retrospective review of 121 cases of PVE during a period of 34 years. Two different periods (the period from 1970 to 1986 [P1], and the period from 1987 to 2003 [P2]) were analyzed., Results: During P1, 58 patients with PVE were treated (30 early PVE and 28 late PVE); during P2, 63 patients with PVE were treated (13 early PVE and 50 late PVE). The frequency of early-onset PVE decreased from 0.94% in P1 to 0.34% in P2 (p < 0.001), but the incidence rate of late-onset PVE did not change (0.33% and 0.42% per year, respectively). The microbiology of early PVE changed over the years: Gram-negative bacilli decreased from 40% during P1 to 7.7% in P2 (p = 0.033). Staphylococci remained the main causes of early PVE in both periods. The microbial etiology of late PVE also changed over the years with enterococci and Staphylococcus aureus as the leading causes during P2. Streptococcus viridans decreased from a leading position to a fourth position. Methicillin-resistant S aureus endocarditis appeared first in 1992. Eleven cases of late-onset PVE in P2 were hospital acquired (22%). In comparison, only two cases (7.1%) of hospital-acquired, late-onset PVE were seen in P1 (p = 0.11). Mortality of early-onset PVE decreased from 80% in P1 to 46% in P2 (p = 0.026). The overall mortality of late-onset PVE did not change between periods: 39% vs 34%. Mortality associated with nosocomial PVE in P2 was 63.6% (7 of 11 patients). In comparison, the mortality of community-acquired cases was 25.6% (10 of 39 patients; p = 0.03). In the multivariate analysis, the presence of comorbidities and hospital acquisition were associated with an excess of mortality (odds ratio [OR], 13.9; 95% confidence interval [CI], 1.23 to 158 [p = 0.033]; and OR, 10.8; 95% CI, 2.16 to 54.7 [p = 0.0037], respectively)., Conclusion: Although the mortality associated with early-onset PVE has significantly decreased, in this series the mortality of patients with late-onset PVE remained high due mainly to an increasing number of patients with comorbidities who acquired the infection during admission for other diseases.

Introduction: Endocarditis due to Listeria monocytogenes is a rare but serious disease often leading to valve dysfunction and heart failure. Two cases of listerial prosthetic valve endocarditis are reviewed along with 66 cases previously reported., Results: The mean age of patients with listerial endocarditis increased from 47.1 years in the decades from 1955-1984 to 65.5 years from 1985-2000. Chronic debilitating diseases, solid tumours and immunosuppression associated with organ transplantation, hematologic neoplasia or AIDS were found in 41.1% of cases. Listerial endocarditis was a vegetative and destructive process, with dehiscense of the prosthesis and occasionally, abscess formation, fistulization and pericarditis. Treatment with penicillin or ampicillin alone or combined with gentamicin was adequate therapy in most cases. Vancomycin together with gentamicin may be a reasonable alternative therapy., Conclusions: Despite problems associated with microbial persistence and relapses in other forms of human listeriosis, antimicrobial therapy alone may be a successful treatment for listerial endocarditis, including cases occurring on prosthetic valves. Valve replacement may be reserved for complicated cases with valve dehiscense, cardiac failure or myocardial abscess. Overall mortality was 35.3%, although most patients who died did so before 1985 and since then mortality has been significantly reduced to 12%.

Objectives: Enterococci are a major leading cause of infectious endocarditis and also a common cause of hospital-acquired bacteraemia, which is not believed to represent a serious hazard for the endocarditis. The incidence and risk factors for infectious endocarditis in patients with hospital-acquired enterococcal bacteraemia is determined., Methods: Prospective analysis of 116 patients with enterococcal bacteraemia admitted to medical or surgical wards of a tertiary-care, university affiliated hospital during a period of 5 years. Echocardiography was performed when indicated by clinical criteria., Results: Seventy-five (61.4%) episodes were hospital-acquired and 47 (38.5%) were community-acquired. Most patients had one or more underlying chronic diseases and major abdominal (58.6%) or genitourinary (38.6%) surgery. Seventeen patients (14.6%) developed enterococcal endocarditis. By univariate analysis the risk factors associated with endocarditis were community-acquired infection (P 0.012); monomicrobial bacteraemia (P 0.006); three or more positive blood cultures (P < 0.001); underlying valvulopathy (P < 0.001); presence of a prosthetic valve (P < 0.001) and age (P 0.012). Six patients (8%) developed nosocomial endocarditis. In this group of patients, three or more positive blood cultures (P < 0.01), bacteraemia as a result of Enterococcus faecalis (P 0.007); underlying valvulopathy (P < 0.001) and presence of a prosthetic valve (P < 0.001) were associated with endocarditis. By logistic regression, the presence of underlying valvulopathy and three or more positive blood cultures were associated with endocarditis (OR 21.0; CI 95% 1.65-26.9; P 0.019)., Conclusions: The risk of developing infectious endocarditis in patients with hospital-acquired enterococcal bacteraemia is significant. Patients with underlying valvulopathy and three or more positive blood cultures with E. faecalis are prone to nosocomial enterococcal endocarditis.

Using two strains of Salmonella enteritidis, one susceptible and one resistant to ampicillin, we studied the efficacies of ampicillin, gentamicin, ampicillin plus gentamicin, ofloxacin, and cefotaxime for the treatment of experimental salmonella endocarditis. Rabbits were treated for 3 days with dosages of antibiotic selected to achieve concentrations in serum equivalent to those obtained in humans during therapy. Aortic salmonella endocarditis seemed to be very difficult to treat, and all antimicrobial regimens failed to achieve the complete sterilization of cardiac vegetations. In vitro studies did not accurately predict the in vivo response to therapy, and no correlations regarding the synergistic activity of the combination of ampicillin plus gentamicin were observed. For the ampicillin-susceptible S. enteritidis isolate, ampicillin and cefotaxime produced the greatest reduction in the number of organisms in vegetations, with no significant differences between them. For the ampicillin-resistant strain, the combination of ampicillin with gentamicin produced a synergistic effect that was not anticipated by the in vitro studies. Both cefotaxime and ofloxacin were effective in reducing the number of microorganisms in the vegetations, although the reduction produced by cefotaxime was less that that produced against the ampicillin-susceptible strain. Monotherapy with gentamicin exhibited only modest activity against the ampicillin-susceptible S. enteritidis strain.

Using two strains of Staphylococcus aureus, one susceptible and one heterogeneously resistant to methicillin, for which MICs and MBCs of trimethoprim-sulfamethoxazole (TMP-SMX) were 0.06 and 0.06 micrograms/ml and 0.06 and 0.25 microgram/ml, respectively (concentrations are those of TMP), we studied the efficacies of TMP-SMX and cloxacillin, teicoplanin, and vancomycin for treatment of experimental staphylococcal endocarditis. Rabbits were treated with dosages of TMP-SMX selected to achieve concentrations in serum equivalent to that obtained in humans treated for Pneumocystis carinii pneumonia. The overall mortality rate of rabbits treated with TMP-SMX was 84% at day 3, not different from that of the control groups (P > 0.1). No sterile vegetations were observed to be present in control groups or in animals treated with TMP-SMX. However, 26, 60, and 75% of rabbits treated with teicoplanin, cloxacillin, and vancomycin, respectively, showed sterile vegetations. For methicillin-susceptible S. aureus (MSSA), the mean vegetation counts were not significantly different between the control group and the group treated with TMP-SMX (P > 0.1). For methicillin-resistant S. aureus (MRSA), treatment with TMP-SMX was more effective than no therapy, decreasing the number of organisms in vegetations (P < 0.01). For both strains, therapy with cloxacillin and therapy with teicoplanin or vancomycin were significantly more effective than therapy with TMP-SMX. Despite high concentrations of teicoplanin in serum which exceeded MBCs for staphylococci more than 50 times at the peak and 10 times at the trough, therapy with cloxacillin or vancomycin was superior to therapy with teicoplanin against both MSSA and MRSA. These data do not support the use of TMP-SMX in treatment of endocarditis and other severe staphylococcal infections with high bacterial counts.