Ana del Río

Health care-associated native valve endocarditis: importance of non-nosocomial acquisition.

BACKGROUND The clinical profile and outcome of nosocomial and non-nosocomial health care-associated native valve endocarditis are not well defined. OBJECTIVE To compare the characteristics and outcomes of community-associated and nosocomial and non-nosocomial health care-associated native valve endocarditis. DESIGN Prospective cohort study. SETTING 61 hospitals in 28 countries. PATIENTS Patients with definite native valve endocarditis and no history of injection drug use who were enrolled in the ICE-PCS (International Collaboration on Endocarditis Prospective Cohort Study) from June 2000 to August 2005. MEASUREMENTS Clinical and echocardiographic findings, microbiology, complications, and mortality. RESULTS Health care-associated native valve endocarditis was present in 557 (34%) of 1622 patients (303 with nosocomial infection [54%] and 254 with non-nosocomial infection [46%]). Staphylococcus aureus was the most common cause of health care-associated infection (nosocomial, 47%; non-nosocomial, 42%; P = 0.30); a high proportion of patients had methicillin-resistant S. aureus (nosocomial, 57%; non-nosocomial, 41%; P = 0.014). Fewer patients with health care-associated native valve endocarditis had cardiac surgery (41% vs. 51% of community-associated cases; P < 0.001), but more of the former patients died (25% vs. 13%; P < 0.001). Multivariable analysis confirmed greater mortality associated with health care-associated native valve endocarditis (incidence risk ratio, 1.28 [95% CI, 1.02 to 1.59]). LIMITATIONS Patients were treated at hospitals with cardiac surgery programs. The results may not be generalizable to patients receiving care in other types of facilities or to those with prosthetic valves or past injection drug use. CONCLUSION More than one third of cases of native valve endocarditis in non-injection drug users involve contact with health care, and non-nosocomial infection is common, especially in the United States. Clinicians should recognize that outpatients with extensive out-of-hospital health care contacts who develop endocarditis have clinical characteristics and outcomes similar to those of patients with nosocomial infection. PRIMARY FUNDING SOURCE None.

Infective endocarditis in intravenous drug abusers and HIV-1 infected patients

Infective endocarditis (IE) is one of the most severe complications of parenteral drug abuse. The incidence of IE in intravenous drug abusers (IVDAs) is 2% to 5% per year, being responsible for 5% to 20% of hospital admissions and 5% to 10% of the overall death rate. IVDAs often develop recurrent IE. The prevalence of HIV infection among IVDAs with IE ranges between 30% and 70% in urban areas in developed countries. The incidence of IE in IVDAs is currently decreasing in some geographical areas, probably due to changes in drug administration habits undertaken by addicts in order to avoid HIV transmission. Overall, Staphylococcus aureus is the most common etiological agent, being in most geographical areas sensitive to methicillin (MSSA). The remainder of cases is caused by streptocococci, enterococci, GNR, Candida spp, and other less common organisms. Polymicrobial infection occurs in 2% to 5% of cases. The tricuspid valve is the most frequently affected (60% to 70%), followed by the mitral and aortic valves (20% to 30%); pulmonic valve infection is rare (< 1%). More than one valve is infected in 5% to 10% of cases. HIV-positive IVDAs have a higher ratio of right-sided IE and S. aureus IE than HIV-negative IVDAs. Response to antibiotic therapy is similar among HIV-infected or non-HIV-infected IVDAs. Drug addicts with non-complicated MSSA right-sided IE can be treated successfully with an i.v. short-course regimen of nafcillin or cloxacillin for 2 weeks, with or without addition of an aminoglycoside during the first 3 to 7 days. Surgery in HIV-infected IVDAs with IE does not worsen the prognosis. The prognosis of right-sided endocarditis is generally good; overall mortality is less than 5%, and with surgery less than 2%. In contrast, the prognosis of left-sided IE is less favorable; mortality is 20% to 30%, and even with surgery is 15% to 25%. IE caused by GNB or fungi has the worst prognosis. Mortality between HIV-infected or non-HIV-infected IVDAs with IE is similar. However, among HIV-infected IVDAs, mortality is significantly higher in those who are most severely immunosuppressed, with CD4+ cell count < 200/microL or with AIDS criteria. Finally, IE in HIV-infected patients who are not drug abusers is rare.

HIV and syphilis: when to perform a lumbar puncture?

Objectives: The objectives of this study were to determine predictive factors for neurosyphilis in HIV-infected patients with syphilis and optimize the use of lumbar puncture. Study Design: The authors reviewed 112 cases of HIV-infected patients with syphilis who underwent a lumbar puncture. Diagnosis of neurosyphilis was based on a cerebrospinal fluid white blood cells count ≥20/&mgr;L, and/or a reactive cerebrospinal fluid–Venereal Disease Research Laboratory, and/or a positive intrathecal T. pallidum antibody (ITPA) index. Results: Twenty-six of 112 had neurosyphilis. Neurologic manifestations and serum rapid plasma reagin (RPR) were associated with neurosyphilis (P = 0.036, P = 0.018, respectively). In multivariate analysis, log2RPR was still associated with neurosyphilis (P = 0.005). In patients without neurologic manifestations, the risk of neurosyphilis increases gradually with log2RPR. A serum RPR of 1/32 seems to be the best cutoff point to decide the performance or not of a lumbar puncture (sensitivity 100%, specificity 40%). Conclusion: In HIV-infected patients with syphilis, lumbar puncture could be restricted to those with neurologic manifestations or a serum RPR ≥1/32.

Non-HACEK Gram-Negative Bacillus Endocarditis

Context Infective endocarditis due to non-HACEK organisms has been considered to be associated with injection drug use. Contribution Analysis of 2761 cases of patients with infective endocarditis from an international collaborative of 61 hospitals found that non-HACEK organisms account for fewer than 2% of the cases, and that most patients with non-HACEK endocarditis had infections associated with health care. Of patients with non-HACEK infections, 59% had implanted endovascular devices or prosthetic valves, but only 4% had injection drug use. More than one half of patients with non-HACEK infections required cardiac surgery and 24% died. Implication Infective endocarditis due to non-HACEK organisms is a rare but frequently fatal condition. It is much more frequently associated with implanted endovascular devices than with injection drug use. The Editors Infective endocarditis caused by non-HACEK (species other than Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, or Kingella species) gram-negative bacilli is a rare and poorly characterized disease. The literature describing non-HACEK gram-negative bacillus endocarditis primarily consists of several small case series from the 1970s and 1980s of outbreaks in injection drug users in large urban areas, such as Detroit (1, 2), Cleveland (3), and San Francisco (4, 5). As a result, endocarditis due to non-HACEK gram-negative bacilli has been considered to be almost exclusively associated with injection drug use (6, 7). In contrast to this reporting bias, however, non-HACEK gram-negative bacillus endocarditis has been occasionally reported to be a nosocomial problem, particularly in patients with early endocarditis after cardiac surgery (811). The International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS) database was created in 1999. From 1 January 2000 to 31 August 2005, 2761 patients with definite endocarditis from 61 centers in 28 countries were prospectively enrolled. This resource offers a unique opportunity to evaluate the epidemiology, characteristics, and outcome of endocarditis due to non-HACEK gram-negative bacilli in a large, contemporary, and international cohort of well-characterized patients with endocarditis. Methods The International Collaboration on Endocarditis Prospective Cohort Study Hospitalized patients with endocarditis (12) were identified prospectively by using site-specific procedures to ensure consecutive enrollment. Informed consent (oral or written) was obtained from all patients according to local institutional review board or ethics committee instructions. A standard case report form containing 275 variables was completed for each patient on enrollment at the participating site. The ICE-PCS database is maintained at the Duke Clinical Research Institute, Durham, North Carolina, which serves as the coordinating center for the ICE studies, with approval from the institutional review board. We included all patients with endocarditis from sites that met performance criteria for participation. These site criteria included 1) minimum enrollment of 12 cases per year in a center with access to cardiac surgery, 2) the presence of patient identification procedures to ensure consecutive enrollment and to minimize ascertainment bias (as described elsewhere) (13, 14), 3) high-quality data with query resolution, and 4) institutional review board or ethics committee approval or waiver based on local standards. All patients from sites that did not meet these criteria (totaling 494 case-patients from 14 sites) were excluded. Sample We included patients who had both definite endocarditis according to the modified Duke criteria (12) and isolation of a pure culture of an aerobic gram-negative bacillus from the bloodstream or valve. To ensure that the diagnosis of gram-negative endocarditis was accurate, the following additional criteria were applied when interpreting the blood culture results: 1) the patients bacteremia had to meet the definition for persistently positive blood cultures when applying the modified Duke criteria; 2) a single blood culture positive for a gram-negative organism was not considered to constitute a minor microbiological criterion when applying the modified Duke criteria; and 3) patients with endocarditis due to anaerobes, Brucella species, HACEK organisms, or other fastidious gram-negative pathogens (for example, Pasteurella species) or polymicrobial infections were excluded. Definitions We used published definitions of health carerelated variables (15, 16). Nonnosocomial health careassociated infection was defined as a health careassociated infection that was not acquired as a hospital inpatient (for example, hemodialysis, outpatient cancer chemotherapy, or receipt of intravenous antibiotics at home) (16). A nosocomial infection was defined as a health careassociated infection that was acquired after at least 48 hours as a hospital inpatient. Prosthetic endocarditis was defined as endocarditis involving a prosthetic heart valve or implanted endovascular device, such as a permanent cardiac pacemaker, cardioverter defibrillator, or aortic stent. Statistical Analysis Patients with definite non-HACEK gram-negative bacillus endocarditis were compared with all other patients with definite endocarditis in the ICE-PCS database. Continuous variables are presented as medians and 25th and 75th percentiles. Categorical variables are presented as frequencies and percentages of the specified group. Univariable comparisons were made by using the Wilcoxon rank-sum test or the chi-square test as appropriate. For all tests, a P value of 0.05 or less was considered statistically significant. Missing data for each variable were excluded from the denominator as indicated in Table 1. All statistical analyses were performed by using SAS software (version 8.2, SAS Institute, Cary, North Carolina). Table 1. Frequency of Individual Duke Criteria among 49 Patients with Non-HACEK Gram-Negative Bacillus Endocarditis* Role of the Funding Source The study did not receive funding. Results Of the 2761 patients with definite endocarditis, 49 (1.8%) had endocarditis due to non-HACEK gram-negative bacilli. Twenty-six of these patients (53%) were enrolled from Europe; 11 (22%) from North America; and the remainder from South America, New Zealand, Australia, the Middle East, and Asia. Patient enrollment was constant throughout the study period. Characteristics of Non-HACEK Gram-Negative Bacillus Endocarditis Patients with non-HACEK gram-negative bacillus endocarditis were more likely to have had symptoms for more than 1 month than were patients infected with other pathogens (90% [95% CI, 82% to 98%] vs. 77% [CI, 75% to 79%], respectively; P= 0.035) (Table 2). Injection drug use was uncommon in patients with non-HACEK gram-negative bacillus endocarditis and in patients with endocarditis due to other organisms (4% [CI, 0% to 9%] vs. 10% [CI, 9% to 11%]; P= 0.20). In contrast, health care contact was a statistically significant risk factor for non-HACEK gram-negative bacillus endocarditis (57% [CI, 43% to 71%] vs. 30% [CI, 28% to 32%]; P< 0.001), largely because the proportion of nosocomial infections was higher in the non-HACEK gram-negative bacillus endocarditis group (39% [CI, 25% to 53%] vs. 14% [CI, 13% to 15%]; P< 0.001). The Figure shows the routes of acquisition of non-HACEK gram-negative bacillus endocarditis compared with Staphylococcus aureus endocarditis (15) and all other causes of endocarditis in the ICE-PCS database. Table 2. Characteristics of Patients with Non-HACEK Gram-Negative Bacillus Infective Endocarditis and Those with Other Causes of Endocarditis* Figure. Routes of acquisition among patients with definite endocarditis due to non-HACEK gram-negative bacilli, Staphylococcus aureus , and other pathogens. HACEK = Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, or Kingella species. Implanted endovascular devices were more common in patients with non-HACEK gram-negative bacillus endocarditis than in patients with other pathogens (29% [CI, 16% to 42%] vs. 11% [CI, 10% to 12%]; P< 0.001). Patients with non-HACEK gram-negative bacillus endocarditis were also statistically significantly more likely than patients with other causes of endocarditis to have a presumed source of infection involving the genitourinary or nonoral gastrointestinal tract (35% [CI, 22% to 48%] vs. 12% [CI, 11% to 13%]; P< 0.001). A nondental invasive procedure within 60 days before symptom onset was more likely in patients with non-HACEK gram-negative bacillus endocarditis than in patients with other causes of endocarditis (38% [CI, 24% to 52%] vs. 19% [CI, 18% to 20%]; P= 0.002). Intracardiac abscesses were statistically significantly more common in patients with non-HACEK gram-negative bacillus endocarditis than in patients with endocarditis due to other organisms (25% [CI, 13% to 37%] vs. 14% [CI, 13% to 15%]; P= 0.034). The in-hospital mortality rate was 24% (CI, 12% to 36%) for patients with non-HACEK gram-negative bacillus endocarditis and 17% (CI, 16% to 18%) for patients with other causes of endocarditis (P= 0.190). Of the 49 patients with non-HACEK gram-negative bacillus endocarditis, 20 (41%) had native-valve endocarditis and 29 (59%) had prosthetic endocarditis. All 49 cases were confirmed as definite endocarditis by the modified Duke criteria: 22 (45%) were histopathologically (16 patients [33%]) or macroscopically (at surgery in 6 patients [12%]) confirmed (Table 1). Of the 16 patients with pathologic confirmation, 8 had valve cultures, 2 had device cultures, and 1 had an aortic aneurysm culture. Microbiology of Non-HACEK Gram-Negative Bacillus Endocarditis The most common pathogens in patients with non-HACEK gram-negative bacillus endocarditis were Escherichia coli (14 patients [29%]) and Pseudomonas aeruginosa (11 patients [22%]). Othe

Infective endocarditis and cardiac surgery in intravenous drug abusers and HIV-1 infected patients

Infective endocarditis (IE) is one of the most severe complications of parenteral drug abuse. The incidence of IE in intravenous drug abusers (IVDAs) is 2% to 5% per year, being responsible for 5% to 10% of the overall death rate. The prevalence of HIV infection among IVDAs with IE ranges between 30% and 70% in developed countries and HIV-infection by itself increases the risk of IE in IVDAs. The incidence of IE in IVDAs is currently decreasing in some areas, probably due to changes in drug administration habits by addicts to avoid HIV transmission. Overall, Staphylococcus aureus is the most common etiological agent, being usually sensitive to methicillin (MSSA). The tricuspid valve is the most frequently affected (60% to 70%), followed by the mitral and aortic valves (20% to 30%). HIV-positive IVDAs have a higher ratio of right-sided IE and S aureus IE than HIV-negative IVDAs. Response to antibiotic therapy is similar. Drug addicts with non-complicated MSSA right-sided IE can be treated with an i.v. short-course regimen of nafcillin or cloxacillin for 2 weeks, with or without addition of an aminoglycoside during the first 3 to 7 days. The prognosis of right-sided endocarditis is generally good; overall mortality is less than 5%, and with surgery is less than 2%. In contrast, the prognosis of left-sided IE is less favorable; mortality is 20% to 30%, and even with surgery is 15% to 25%. IE caused by GNB or fungi has the worst prognosis. Mortality between HIV-infected or non-HIV-infected IVDAs with IE is similar. However, among HIV-infected IVDAs, mortality is significantly higher in those who are most severely immunosuppressed, with CD4+ cell count < 200/microL or with AIDS criteria. Conversely, IE in HIV-infected patients who are not drug abusers is rare. The epidemiology of cardiac surgery in IVDAs and/or HIV-infected patients has changed in recent years. There is a decrease in IE and an increase of patients undergoing surgery (CABS) for coronary artery disease secondary to the hyperlipidemia and lipodystrophy induced by highly active antiretroviral therapy (HAART). Cardiac surgery in HIV-infected patients with or without IE does not worsen the prognosis because extracorporeal circulation did not affect the immune status after surgery. Morbidity and mortality seems to stay within the same range as the non-infected patients. In our experience, in the IE in HIV-infected IVDA group, the 1-year survival is 65% and the 5 and 10-year actuarial survival is 35%. For patients operated on for coronary artery disease, the 5-year survival is 100%.

Patients at Risk of Complications of Staphylococcus aureus Bloodstream Infection

Staphylococcus aureus is one of the most common causative pathogens of bloodstream infections (BSIs). In approximately one-half of patients with S. aureus BSI, no portal of entry can be documented. This group of patients has a high risk of developing septic metastases. Similarly, patient populations at high risk of S. aureus BSI and BSI-associated complications include patients receiving hemodialysis, injection drug users, patients with diabetes, and patients with preexisting cardiac conditions or other comorbidities. One of the most severe complications of S. aureus BSI is infective endocarditis, and S. aureus is now the most common cause of infective endocarditis in the developed world. Patients with methicillin-resistant S. aureus BSI or infective endocarditis have higher rates of mortality, compared with patients with methicillin-susceptible S. aureus infection. Nasal carriage is the most important source of S. aureus BSI. Better eradication and control strategies, including nasal decolonization and more-active antibiotics, are needed to combat S. aureus BSIs.

High-dose daptomycin plus fosfomycin is safe and effective in treating methicillin-susceptible and methicillin-resistant Staphylococcus aureus endocarditis.

ABSTRACT We describe 3 patients with left-sided staphylococcal endocarditis (1 with methicillin-susceptible Staphylococcus aureus [MSSA] prosthetic aortic valve endocarditis and 2 with methicillin-resistant S. aureus [MRSA] native-valve endocarditis) who were successfully treated with high-dose intravenous daptomycin (10 mg/kg/day) plus fosfomycin (2 g every 6 h) for 6 weeks. This combination was tested in vitro against 7 MSSA, 5 MRSA, and 2 intermediately glycopeptide-resistant S. aureus isolates and proved to be synergistic against 11 (79%) strains and bactericidal against 8 (57%) strains. This combination deserves further clinical study.

Efficacy of Telavancin in the Treatment of Experimental Endocarditis Due to Glycopeptide-Intermediate Staphylococcus aureus

ABSTRACT The efficacy of telavancin, a novel lipoglycopeptide, was evaluated in experimental endocarditis in rabbits using two clinical isolates of glycopeptide-intermediate Staphylococcus aureus: ATCC 700788 and HIP 5836. Infected rabbits were treated for 2 days with telavancin (10 mg/kg of body weight once daily intravenously) or vancomycin (1 g twice daily intravenously), administered with a computer-controlled infusion pump system simulating human serum kinetics. Vegetations were harvested at 16 h postinoculation in the control group and at the end of treatment in the drug-treated group. For ATCC 700788, MICs and minimal bactericidal concentrations (MBCs), respectively, were 1 mg/liter and 4 mg/liter for telavancin and 8 mg/liter and 128 mg/liter for vancomycin. For HIP 5836, MICs and MBCs, respectively, were 4 mg/liter and 8 mg/liter for telavancin and 8 mg/liter and 128 mg/liter for vancomycin. Peak and trough levels were 90 μg/ml and 6 μg/ml, respectively, for telavancin and 46 μg/ml and 6 μg/ml, respectively, for vancomycin. In glycopeptide-intermediate S. aureus ATCC 700788, telavancin sterilized 6 of 16 vegetations (37%), whereas vancomycin sterilized 4 of 20 (20%) (P = 0.29) compared with 0 of 17 in the control group. In HIP 5836 experiments, telavancin and vancomycin sterilized 5 of 16 (31%) and 1 of 15 (7%) vegetations (P = 0.17), respectively, compared with none in the control group. Telavancin reduced vegetation titers by 2.0 and 2.3 logs greater than vancomycin for the ATCC 700788 (4.6 [2.0 to 5.8] versus 6.6 [2.0 to 6.9] log CFU/g vegetation; P = 0.05) and HIP 5836 (4.4 [2.0 to 7.4] versus 6.7 [4.5 to 8.7] log CFU/g vegetation; P = 0.09) strains, respectively; these differences did not reach statistical significance. All isolates from vegetations remained susceptible to telavancin after therapy. The results suggest that telavancin may be an effective treatment for endocarditis caused by glycopeptide-intermediate S. aureus.

Effect of Vancomycin Minimal Inhibitory Concentration on the Outcome of Methicillin-Susceptible Staphylococcus aureus Endocarditis

BACKGROUND Staphylococcus aureus endocarditis has a high mortality rate. Vancomycin minimum inhibitory concentration (MIC) has been shown to affect the outcome of methicillin-resistant S. aureus bacteremia, and recent data point to a similar effect on methicillin-susceptible S. aureus bacteremia. We aimed to evaluate the effect of vancomycin MIC on left-sided S. aureus infective endocarditis (IE) treated with cloxacillin. METHODS We analyzed a prospectively collected cohort of patients with IE in a single tertiary-care hospital. Vancomycin, daptomycin, and cloxacillin MIC was determined by E-test. S. aureus strains were categorized as low vancomycin MIC (<1.5 µg/mL) and high vancomycin MIC (≥1.5 µg/mL). The primary endpoint was in-hospital mortality. RESULTS We analyzed 93 patients with left-sided IE treated with cloxacillin, of whom 53 (57%) had a vancomycin MIC < 1.5 µg/mL and 40 (43%) a vancomycin MIC ≥ 1.5 µg/mL. In-hospital mortality was 30% (n = 16/53) in patients with a low vancomycin MIC and 53% (n = 21/40) in those with a high vancomycin MIC (P = .03). No correlation was found between oxacillin MIC and vancomycin or daptomycin MIC. Logistic regression analysis showed that higher vancomycin MIC increased in-hospital mortality 3-fold (odds ratio, 3.1; 95% confidence interval, 1.2-8.2) after adjustment for age, year of diagnosis, septic complications, and nonseptic complicated endocarditis. CONCLUSIONS Our results indicate that vancomycin MIC could be used to identify a subgroup of patients with methicillin-susceptible S. aureus IE at risk of higher mortality. The worse outcome of staphylococcal infections with a higher vancomycin MIC cannot be explained solely by suboptimal pharmacokinetics of antibiotics.

Efficacy and safety of outpatient parenteral antibiotic therapy for infective endocarditis: a ten-year prospective study

BACKGROUND The length of treatment of infective endocarditis (IE) with parenteral antibiotics varies from 2 to 6 weeks. Although several studies indicate that outpatient parenteral antibiotic treatment (OPAT) could be safe for uncomplicated viridans-group streptococci (VGS) IE, the experience in Spain is limited and data on other types of endocarditis and OPAT are scarce worldwide. METHODS Prospective single center study of a cohort including all patients with IE admitted to the Hospital Clinic of Barcelona OPAT program from January 1997 to December 2006. RESULTS During the study period, 392 consecutive episodes of IE in non-drug abusers were attended to. Of these, 73 episodes (42 native-valve, 23 prosthetic-valve, and 8 pacemaker-lead) were admitted to the OPAT program (19%). The percentage of inclusion was higher for viridans group streptococci (VGS) or Streptococcus bovis (S. bovis) IE (32% of all VGS or S. bovis IE episodes diagnosed vs. 14% of the remaining etiologies, P<.001). Twelve patients (16%) were readmitted due to complications, of which 3 died (4%). Glycopeptides use was the only predictor factor of hospital readmission (OR 4.5, 95% confidence interval 1.2; 16.8, P=.026). No differences in OPAT outcome were found between VGS plus S. bovis IE and Staphylococcus aureus (S. aureus) plus coagulase-negative staphylococci IE. Patients spent a median of 17 day on OPAT (interquartile range 11-26.5), which enabled 1,466 days of hospital stay to be saved. CONCLUSIONS These data suggest that OPAT for IE may be a safe and effective therapeutic approach in the treatment of selected patients with types of endocarditis other than uncomplicated VGS or S. bovis endocarditis, although patients taking glycopeptides need close clinical OPAT monitoring.