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1.  Daptomycin for methicillin-resistant Staphylococcus epidermidis native-valve endocarditis: a case report 
Coagulase-negative staphylococci (CoNS) have been increasing in importance as a cause of native valve endocarditis (NVE). Most cases of NVE caused by CoNS are attributable to Staphylococcus epidermidis. NVE caused by CoNS acquired in a nosocomial setting may differ from cases acquired in the community in several ways. It may be associated with hemodialysis, the presence of a long-term indwelling central catheter or pacemaker, or a recent invasive procedure; nosocomial cases may have a higher rate of methicillin resistance among CoNS isolates, and so be more likely to be treated with vancomycin. Unfortunately, NVE caused by methicillin-resistant CoNS has been associated with significantly higher rates of persistent bacteremia and in-hospital mortality than methicillin-susceptible isolates. The poor outcomes in these cases point to the need for alternative therapies with potent activity against methicillin-resistant CoNS. In our medical center, a 76-year-old man presented with native-valve endocarditis and positive blood cultures for methicillin-resistant Staphylococcus epidermidis (MRSE). During each of three 6-week courses of treatment with vancomycin, blood cultures were negative, but they once again became positive for MRSE when vancomycin was discontinued. The minimum inhibitory concentration of the MRSE isolates for vancomycin remained stable at 2 μg/mL. Eventually, treatment with daptomycin was initiated (500 mg [7 mg/kg]) 3 times/week for 6 weeks. Over the following year, no positive cultures for MRSE were detected.
PMCID: PMC2836277  PMID: 20167084
2.  Analysis of the Impact of Early Surgery on In-hospital Mortality of Native Valve Endocarditis: Use of Propensity Score and Instrumental Variable Methods to Adjust for Treatment Selection Bias 
Circulation  2010;121(8):1005-1013.
The impact of early surgery on mortality in patients with native valve endocarditis (NVE) is unresolved. This study seeks to evaluate valve surgery compared to medical therapy for NVE, and to identify characteristics of patients who are most likely to benefit from early surgery.
Methods and Results
Using a prospective, multinational cohort of patients with definite NVE, the effect of early surgery on in-hospital mortality was assessed using propensity-based matching adjusting for survivor bias, and instrumental variable analysis. Patients were stratified by propensity quintile, paravalvular complications, valve perforation, systemic embolization, stroke, Staphylococcus aureus infection and congestive heart failure.
Of the 1552 patients with NVE, 720 (46%) underwent early surgery and 832 (54%) were treated with medical therapy. Compared to medical therapy, early surgery was associated with a significant reduction in mortality in the overall cohort (12.1% [87/720] vs. 20.7% [172/832]) and after propensity-based matching and adjustment for survivor bias (absolute risk reduction (ARR) = -5.9 %; p<0.001). Using a combined instrument, the instrumental variable adjusted ARR in mortality associated with early surgery was -11.2% (p<0.001). In sub-group analysis, surgery was found to confer a survival benefit compared to medical therapy among patients with a higher propensity for surgery (ARR= -10.9% for quintiles 4 and 5; p=0.002); those with paravalvular complications (ARR= -17.3 %; p<0.001), systemic embolization (ARR= -12.9%; p=0.002), S aureus NVE (ARR= -20.1%; p<0.001) and stroke (ARR= -13%; p=0.02) but not with valve perforation or congestive heart failure.
Early surgery for NVE is associated with an in-hospital mortality benefit compared to medical therapy alone.
PMCID: PMC3597944  PMID: 20159831
early surgery; infective endocarditis; medical therapy; in hospital mortality
3.  Combined computed tomography and fluorodeoxyglucose positron emission tomography in the diagnosis of prosthetic valve endocarditis: a case series 
BMC Research Notes  2014;7:32.
The diagnosis of prosthetic valve endocarditis is challenging. The gold standard for prosthetic valve endocarditis diagnosis is trans-esophageal echocardiography. However, trans-esophageal echocardiography may result in negative findings or yield images difficult to differentiate from thrombus in patients with prosthetic valve endocarditis. Combined computed tomography and fluorodeoxyglucose positron emission tomography is a potentially promising diagnostic tool for several infectious conditions and it has also been employed in patients with prosthetic valve endocarditis but data are still scant.
Case presentations
We reviewed the charts of 6 patients with prosthetic aortic valves evaluated for suspicion of prosthetic valve endocarditis, at two different hospital, over a 3-year period. We found 3 patients with early-onset PVE cases and blood cultures yielding Pseudomonas aeruginosa, Staphylococcus epidermidis and Staphylococcus lugdunensis, respectively; and 3 late-onset cases in the remaining 3 patients with isolation in the blood of Streptococcus bovis, Candida albicans and P. aeruginosa, respectively. Initial trans-esophageal echocardiography was negative in all the patients, while fluorodeoxyglucose positron emission tomography showed images suspicious for prosthetic valve endocarditis. In 4 out of 6 patients valve replacement was done with histology confirming the prosthetic valve endocarditis diagnosis. After an adequate course of antibiotic therapy fluorodeoxyglucose positron emission tomography showed resolution of prosthetic valve endocarditis in all the patients.
Our experience confirms the potential role of fluoroseoxyglucose positron emission tomography in the diagnosis and follow-up of prosthetic valve endocarditis.
PMCID: PMC3899623  PMID: 24418206
FDG-PET; Prosthetic valve endocarditis; Diagnosis; Duke’s criteria
4.  Related Clones Containing SCCmec Type IV Predominate among Clinically Significant Staphylococcus epidermidis Isolates 
Antimicrobial Agents and Chemotherapy  2003;47(11):3574-3579.
SCCmec is a mobile genetic element that carries the gene (mecA) mediating methicillin resistance in staphylococci. For Staphylococcus aureus, four SCCmec types have been described, one (type IV) of which has been associated with newly identified community-acquired methicillin-resistant S. aureus. However, the distribution of SCCmec types among S. epidermidis is not known. SCCmec typing of a collection of 44 methicillin-resistant Staphylococcus epidermidis (MRSE) isolates recovered between 1973 and 1983 from the blood of patients with prosthetic valve endocarditis (PVE) was performed by PCR amplification of key genetic elements (mecA, mecI, IS1272, and ccrAB). Of the 44 isolates, 1 (2%) harbored SCCmec type I, 15 (34%) harbored type II, 12 (28%) harbored type III, and 16 (36%) harbored type IV. The complete nucleotide sequence of SCCmec type IV was determined for 16 isolates and found to be identical in size (24 kb) and 98% homologous to DNA sequences published for S. aureus. Type IV SCCmec was also common (5 of 10 isolates) among a geographically dispersed collection of 10 recent (1998 to 2001) S. epidermidis bloodstream isolates. Multilocus sequence typing (MLST) (using the same seven genes presently employed for S. aureus MLST) of these MRSE isolates and of 10 additional recent geographically dispersed methicillin-susceptible isolates demonstrated that all 16 PVE isolates and 2 of 5 recent isolates harboring type IV SCCmec were in three related clonal groups. All three MSSE PVE isolates recovered from patients between 1976 and 1979 were in the same clonal groups as type IV SCCmec MRSE isolates. These data support the hypothesis of intra- and interspecies transfer of type IV SCCmec and suggest that there are clonal associations in S. epidermidis that correlate with SCCmec type.
PMCID: PMC253785  PMID: 14576120
5.  Plasmid pattern analysis of Staphylococcal epidermidis isolates from patients with prosthetic valve endocarditis. 
Infection and Immunity  1982;35(2):627-632.
The electrophoretic pattern formed by individual bacterial plasmid DNA molecules of differing molecular size was evaluated as an epidemiological marker among isolates of Staphylococcus epidermidis from patients with prosthetic valve endocarditis (PVE). Purified covalently closed circular plasmid DNA was obtained from selected isolates, and 79% of the plasmids were found to be less than 10 megadaltons in size; only these small plasmids were sought in subsequent screening gels. Crude cell lysates obtained by a rapid lysis technique and screened by agarose gel electrophoresis revealed the presence of one or more small plasmids in 54 of 58 (93%) PVE isolates; 79% contained two or more. Among 45 plasmid-containing isolates from cases of sporadic PVE at three institutions there were no identical plasmid patterns, although several isolates differed by a single plasmid. In contrast, among nine isolates from a cluster of cases of PVE in Canada, two groups of three isolates each had identical plasmid patterns. Additional clinical data suggested that these isolates were epidemiologically related. Phage typing distinguished one of the groups with plasmid pattern identity, but not the other, from the three isolates with dissimilar patterns. Plasmid pattern analysis shows promise as an epidemiological marker for clinically important isolates of S. epidermidis.
PMCID: PMC351087  PMID: 7056579
6.  New Approaches to the Diagnosis and Treatment of Infective Endocarditis 
Texas Heart Institute Journal  1989;16(4):250-257.
To assess the effect of our new, more aggressive approach to treating infective endocarditis, we retrospectively reviewed our recent experience with this disease. Between 1983 and 1989, we treated 100 patients with endocarditis, in 94 of whom the diagnosis was confirmed. Fifty-four (57%) of the 94 patients had native valve endocarditis, and the other 40 patients (43%) had prosthetic valve endocarditis. The patients' mean ages were 50 years for native valve disease and 58 years for prosthetic valve disease (p < 0.05). The male-to-female ratio was 4:1. Among the patients with confirmed endocarditis, 87 (93%) had significant underlying risk factors for endocarditis. Upon physical examination of the 94 patients, 16 (17%) were afebrile, 15 (16%) had negative blood cultures, and 26 (28%) had no cardiovascular symptoms or immunologic findings. Echocardiography was of limited value: its sensitivity was 56% for native valve endocarditis and 33% for prosthetic valve endocarditis. The ratio of affected valves was 5 aortic:4 mitral: 1 tricuspid in both forms of the disease. Viridans streptococcus was isolated in 23 (25%) of the confirmed cases, Enterococcus faecalis in 17 (18%), Staphylococcus aureus in 13 (14%), and coagulase-negative staphylococcus in 14 (15%). Gram-negative, anaerobic, and fungal organisms accounted for only 13 (14%) of the confirmed cases.
The mean duration of intravenous therapy was 29 days. Twenty (37%) of the native valve patients and 16 (40%) of the prosthetic valve patients received antibiotics on an outpatient basis. Vancomycin was used in 44 (47%) of the cases, nafcillin or ampicillin in 40 (44%), and other β-lactam agents in 9 (10%). The mean hospital stay was significantly longer for prosthetic valve endocarditis patients than for those with native valve disease (29 versus 23 days; p < 0.01). Cardiac catheterization was performed in 9 native valve patients (17%) and 6 prosthetic valve patients (15%). Valve surgery was performed in 33 native valve patients (61%) and 22 prosthetic valve patients (55%). Failure, defined as in-hospital death or recurrent endocarditis, accounted for 14 (28%) of the native valve cases (17% death and 11% relapse) and 8 (20%) of the prosthetic valve cases (10% death and 10% relapse), for an overall failure rate of 24%. The rate of failure was independent of the infecting pathogen or the type of antimicrobial therapy applied. Our experience verified that, in many patients with significant underlying risk factors, the diagnosis of endocarditis may be made on an empiric basis. (Texas Heart Institute Journal 1989;16:250-7)
PMCID: PMC326529  PMID: 15227377
Antibiotics; diagnosis; endocarditis, infective; heart valve diseases; heart valve prosthesis; infection
7.  Hemagglutination and adherence to plastic by Staphylococcus epidermidis. 
Infection and Immunity  1992;60(10):4322-4327.
Staphylococcus epidermidis is an important nosocomial pathogen responsible for intravenous catheter-related bacteremia and infections of other prosthetic medical devices. We found that the ability of S. epidermidis to hemagglutinate erythrocytes correlated with the adherence of bacteria to plastic and to intravenous catheters. S. epidermidis isolates responsible for prosthetic-valve endocarditis (n = 61) and isolates from intravenous catheters (n = 59) were significantly more likely to cause hemagglutination than isolates from the skin of preoperative cardiac surgery patients (n = 19) (P = 0.027). S. epidermidis isolates (n = 23) recovered from the skin of patients 7 to 10 days after cardiac surgery were significantly more likely to exhibit hemagglutination than the preoperative isolates (P = 0.015). By a quantitative adherence assay, we also observed that the hemagglutination titer and number of species of erythrocytes agglutinated correlated directly with adherence to polystyrene (P less than 0.001). In addition, hemagglutinating isolates were significantly more likely to be recovered in high number from intravenous catheters when semiquantitative catheter culture techniques were used (P less than 0.001). We speculate that hemagglutinin(s) either plays a direct role in adherence to polymers and thus prosthetic-device infection or serves as an easily demonstrable marker for adherence-prone isolates.
PMCID: PMC257468  PMID: 1398942
8.  Prosthetic valve endocarditis: who needs surgery? A multicentre study of 104 cases 
Heart  2005;91(7):954-959.
Objectives: To identify the prognostic markers of a bad outcome in a large population of 104 patients with prosthetic valve endocarditis (PVE), and to study the influence of medical versus surgical strategy on outcome in PVE and thus to identify patients for whom surgery may be beneficial.
Design: Multicentre study.
Methods and results: Among 104 patients, 22 (21%) died in hospital. Factors associated with in-hospital death were severe co-morbidity (6% of survivors v 41% of those who died, p  =  0.05), renal failure (28% v 45%, p  =  0.05), moderate to severe regurgitation (22% v 54%, p  =  0.006), staphylococcal infection (16% v 54%, p  =  0.001), severe heart failure (22% v 64%, p  =  0.001), and occurrence of any complication (60% v 90%, p  =  0.05). By multivariate analysis, severe heart failure (odds ratio 5.5) and Staphylococcus aureus infection (odds ratio 6.1) were the only independent predictors of in-hospital death. Among 82 in-hospital survivors, 21 (26%) died during a 32 month follow up. A Cox proportional hazards model identified early PVE, co-morbidity, severe heart failure, staphylococcus infection, and new prosthetic dehiscence as independent predictors of long term mortality. Mortality was not significantly different between surgical and non-surgical patients (17% v 25%, respectively, not significant). However, both in-hospital and long term mortality were reduced by a surgical approach in high risk subgroups of patients with staphylococcal PVE and complicated PVE.
Conclusions: Firstly, PVE not only carries a high in-hospital mortality risk but also is associated with high long term mortality and needs close follow up after the initial episode. Secondly, congestive heart failure, early PVE, staphylococcal infection, and complicated PVE are associated with a bad outcome. Thirdly, subgroups of patients could be identified for whom surgery is associated with a better outcome: patients with staphylococcal and complicated PVE. Early surgery is strongly recommended for these patients.
PMCID: PMC1769001  PMID: 15958370
echocardiography; endocarditis; prognosis; prosthetic valves; surgery
9.  Relevance of stroke subtype in vascular risk prediction 
Neurology  2013;81(6):575-580.
To ascertain the risk of a new vascular event (NVE) occurring after ischemic stroke and evaluate differences in risk based on stroke subtype.
This was a prospective observational study of consecutive patients with nonfatal stroke recruited at a single tertiary stroke center with follow-up ranging from 2 to 5 years (average, 31 ± 15.9 months). An NVE (vascular death, nonfatal stroke or myocardial infarction, and hospitalization for other atherothrombotic events) was defined according to criteria used in a previously developed large multicenter register of atherothrombotic patients (Reduction of Atherothrombosis for Continued Health Registry [REACH]). We analyzed age, sex, and atherosclerotic burden (AB) based on a number of vascular risk factors, affected vascular areas, and stroke subtype according to Stop Stroke Study Trial of Org 10172 in Acute Stroke Treatment (SSS-TOAST) criteria in cardioaortic, large artery atherosclerosis (LAA), unclassified (more than one causal mechanism), small-artery disease (SAD), and undetermined (without cause) stroke categories.
The final cohort consisted of 748 patients. An NVE occurred in 162 patients (21.7%), equivalent to a rate of 0.084 events per patient/year. Multivariate analysis revealed that higher NVE risk was associated with AB and 3 stroke subtypes, namely cardioaortic (hazard ratio [HR] = 2.58; 95% confidence interval [CI] 1.27–5.22), LAA (HR = 4.17; 95% CI 2.03–8.56), and unclassified (HR = 5.70; 95% CI 2.49–13.08). Patients with SAD or stroke of undetermined cause had lower NVE risk.
Patients who survive stroke are at increased risk for NVEs. The risk for NVE varies according to stroke subtype.
PMCID: PMC3775680  PMID: 23825174
10.  Detection of Virulence-Associated Genes Not Useful for Discriminating between Invasive and Commensal Staphylococcus epidermidis Strains from a Bone Marrow Transplant Unit 
Journal of Clinical Microbiology  2004;42(12):5614-5619.
Because of their biofilm-forming capacity, invasive Staphylococcus epidermidis isolates, which cause the majority of nosocomial catheter-related bloodstream infections (BSIs), are thought to be selected at the time of catheter insertion from a population of less virulent commensal strains. This fact allows the prediction that invasive and contaminating strains can be differentiated via detection of virulence-associated genes. However, the hospital environment may pave the way for catheter-related infections by promoting a shift in the commensal bacterial population toward strains with enhanced virulence. The distribution of virulence-associated genes (icaADBC, aap, atlE, bhp, fbe, embp, mecA, IS256, and IS257), polysaccharide intercellular adhesin synthesis, and biofilm formation were investigated in S. epidermidis strains from independent episodes of catheter-related BSIs in individuals who have received bone marrow transplantation (BMT). The results were compared with those obtained for commensal S. epidermidis isolates from hospitalized patients after BMT and from healthy individuals, respectively. The clonal relationships of the strains were investigated by pulsed-field gel electrophoresis. icaADBC, mecA, and IS256 were significantly more prevalent in BSI isolates than in commensal isolates from healthy individuals. However, the prevalence of any of the genes in clonally independent, endogenous commensal strains from BMT patients did not differ from that in invasive BSI strains. icaADBC and methicillin resistance, factors important for the establishment of catheter-related infections, already ensure survival of the organisms in their physiological habitat in the hospital environment, resulting in a higher probability of contamination of indwelling medical devices with virulent S. epidermidis strains. The dynamics of S. epidermidis populations reveal that detection of icaADBC and mecA is not suitable for discriminating invasive from contaminating S. epidermidis strains.
PMCID: PMC535265  PMID: 15583290
11.  Staphylococcal Biofilm Exopolysaccharide Protects against Caenorhabditis elegans Immune Defenses 
PLoS Pathogens  2007;3(4):e57.
Staphylococcus epidermidis and Staphylococcus aureus are leading causes of hospital-acquired infections that have become increasingly difficult to treat due to the prevalence of antibiotic resistance in these organisms. The ability of staphylococci to produce biofilm is an important virulence mechanism that allows bacteria both to adhere to living and artificial surfaces and to resist host immune factors and antibiotics. Here, we show that the icaADBC locus, which synthesizes the biofilm-associated polysaccharide intercellular adhesin (PIA) in staphylococci, is required for the formation of a lethal S. epidermidis infection in the intestine of the model nematode Caenorhabditis elegans. Susceptibility to S. epidermidis infection is influenced by mutation of the C. elegans PMK-1 p38 mitogen-activated protein (MAP) kinase or DAF-2 insulin-signaling pathways. Loss of PIA production abrogates nematocidal activity and leads to reduced bacterial accumulation in the C. elegans intestine, while overexpression of the icaADBC locus in S. aureus augments virulence towards nematodes. PIA-producing S. epidermidis has a significant survival advantage over ica-deficient S. epidermidis within the intestinal tract of wild-type C. elegans, but not in immunocompromised nematodes harboring a loss-of-function mutation in the p38 MAP kinase pathway gene sek-1. Moreover, sek-1 and pmk-1 mutants are equally sensitive to wild-type and icaADBC-deficient S. epidermidis. These results suggest that biofilm exopolysaccharide enhances virulence by playing an immunoprotective role during colonization of the C. elegans intestine. These studies demonstrate that C. elegans can serve as a simple animal model for studying host–pathogen interactions involving staphylococcal biofilm exopolysaccharide and suggest that the protective activity of biofilm matrix represents an ancient conserved function for resisting predation.
Author Summary
Biofilm is an agglomeration of microbes bound together by a slimy matrix composed of excreted proteins and polysaccharide polymers. Most bacteria in the environment reside in biofilms, as do 80% or more of those causing human infections, according to some estimates. During infection, biofilm matrix acts as a safe haven, protecting bacterial cells from antibiotics, immune cells, and antimicrobial factors. In this report, we demonstrate that the ability of Staphylococcus epidermidis to produce a lethal infection within the intestinal tract of the roundworm Caenorhabditis elegans depends on the S. epidermidis intercellular adhesion (ica) locus, which is responsible for the synthesis of the principal exopolysaccharide of staphylococcal biofilm, polysaccharide intercellular adhesin (PIA). Using a collection of bacterial and nematode mutants, we show that PIA promotes infection by working against protective immune factors controlled by the C. elegans SEK-1 PMK-1 p38 mitogen-activated protein kinase pathway. In addition to providing further evidence for the immunoprotective function of the biofilm polymer PIA, these results show that C. elegans can be used in a simple, live animal model for the study of host–pathogen interactions involving biofilm matrix.
PMCID: PMC1853117  PMID: 17447841
12.  Staphylococcus epidermidis in Orthopedic Device Infections: The Role of Bacterial Internalization in Human Osteoblasts and Biofilm Formation 
PLoS ONE  2013;8(6):e67240.
Staphylococcus epidermidis orthopedic device infections are caused by direct inoculation of commensal flora during surgery and remain rare, although S. epidermidis carriage is likely universal. We wondered whether S. epidermidis orthopedic device infection strains might constitute a sub-population of commensal isolates with specific virulence ability. Biofilm formation and invasion of osteoblasts by S. aureus contribute to bone and joint infection recurrence by protecting bacteria from the host-immune system and most antibiotics. We aimed to determine whether S. epidermidis orthopedic device infection isolates could be distinguished from commensal strains by their ability to invade osteoblasts and form biofilms.
Materials and Methods
Orthopedic device infection S. epidermidis strains (n = 15) were compared to nasal carriage isolates (n = 22). Osteoblast invasion was evaluated in an ex vivo infection model using MG63 osteoblastic cells co-cultured for 2 hours with bacteria. Adhesion of S. epidermidis to osteoblasts was explored by a flow cytometric approach, and internalized bacteria were quantified by plating cell lysates after selective killing of extra-cellular bacteria with gentamicin. Early and mature biofilm formations were evaluated by a crystal violet microtitration plate assay and the Biofilm Ring Test method.
No difference was observed between commensal and infective strains in their ability to invade osteoblasts (internalization rate 308+/−631 and 347+/−431 CFU/well, respectively). This low internalization rate correlated with a low ability to adhere to osteoblasts. No difference was observed for biofilm formation between the two groups.
Osteoblast invasion and biofilm formation levels failed to distinguish S. epidermidis orthopedic device infection strains from commensal isolates. This study provides the first assessment of the interaction between S. epidermidis strains isolated from orthopedic device infections and osteoblasts, and suggests that bone cell invasion is not a major pathophysiological mechanism in S. epidermidis orthopedic device infections, contrary to what is observed for S. aureus.
PMCID: PMC3696042  PMID: 23840636
13.  From Clinical Microbiology to Infection Pathogenesis: How Daring To Be Different Works for Staphylococcus lugdunensis 
Clinical Microbiology Reviews  2008;21(1):111-133.
Staphylococcus lugdunensis has gained recognition as an atypically virulent pathogen with a unique microbiological and clinical profile. S. lugdunensis is coagulase negative due to the lack of production of secreted coagulase, but a membrane-bound form of the enzyme present in some isolates can result in misidentification of the organism as Staphylococcus aureus in the clinical microbiology laboratory. S. lugdunensis is a skin commensal and an infrequent pathogen compared to S. aureus and S. epidermidis, but clinically, infections caused by this organism resemble those caused by S. aureus rather than those caused by other coagulase-negative staphylococci. S. lugdunensis can cause acute and highly destructive cases of native valve endocarditis that often require surgical treatment in addition to antimicrobial therapy. Other types of S. lugdunensis infections include abscess and wound infection, urinary tract infection, and infection of intravascular catheters and other implanted medical devices. S. lugdunensis is generally susceptible to antimicrobial agents and shares CLSI antimicrobial susceptibility breakpoints with S. aureus. Virulence factors contributing to this organism's heightened pathogenicity remain largely unknown. Those characterized to date suggest that the organism has the ability to bind to and interact with host cells and to form biofilms on host tissues or prosthetic surfaces.
PMCID: PMC2223846  PMID: 18202439
14.  In vitro assays of Staphylococcus epidermidis characteristics and outcome in an endocarditis model 
Staphylococcus epidermidis adherence to indwelling polymers is important in prosthetic valve endocarditis. Earlier studies have related streptococcal endocarditis to isolates with high levels of cell-associated hexoses. The objective of the present study was to determine if a relationship exists between an S epidermidis isolate assay score and production/severity of experimental endocarditis.
Groups of patient S epidermidis isolates were screened for surface hexoses and an animal model of endocarditis with isolates testing highest and lowest on the screen was produced. Disease severity produced by ‘high hexose’ versus ‘low hexose’ organisms was evaluated. Endocarditis responding variables were bacterial vegetation weight and log10 colony forming units (cfu) and in survival tests, comparative time to death with different isolates. Bacterial characteristics were not measured. Baseline data showed a vegetation weight difference so that with a β error of 0.20 and a two-tailed α error of 0.05, a significant difference would be noted using 30 animals. A total of 64 animals was used.
Population Studded:
Bacterial isolates from two patient groups (n=42 and n=68) on which in vitro assays were run. An animal model of endocarditis (n=64) was used to evaluate four selected isolates for vegetation size, log10 cfu/g, and survival time.
Main Results:
In a group of S epidermidis endocarditis animals evaluated for time of death, a significantly more rapid death time resulted in the group dosed with the high hexose-scoring organism (P<0.025). Vegetations and log10 cfu produced by test high hexose isolates averaged larger but were not significantly different.
A significantly more rapid death rate occurs in untreated endocarditis using a high hexose isolate than with S epidermidis with low surface hexoses. Using bacterial vegetation and cfu as endpoints, however, experimental endocarditis using patient isolates of S epidermidis does not show the same strong correlation to bacterial surface hexoses as does streptococcal endocarditis.
PMCID: PMC3250790  PMID: 22346449
Bacteremia; Bacterial assays; Endocarditis model; Staphylococcus epidermidis
15.  Characterization of clinically significant isolates of Staphylococcus epidermidis from patients with endocarditis. 
Journal of Clinical Microbiology  1988;26(4):613-617.
Biotyping, slime production, bacteriophage typing, serotyping, antibiograms, and plasmid profiles were used to characterize 19 Staphylococcus epidermidis strains isolated from 12 patients with prosthetic valve endocarditis and from 7 patients with native valve endocarditis. With the API Staph battery, 12 different biocodes with, at the most, three differences were obtained. Slime production was found for 10 strains (53%). Agglutinogens investigated by agglutination with two specific sera were found for 12 strains (63.1%). Three strains were phage typable (15.2%). Against a panel of nine antimicrobial agents, 15 different profiles were found. Multiply antibiotic-resistant strains were isolated from patients with prosthetic valve endocarditis when disease onset occurred less than 18 months after heart surgery and from patients with native valve endocarditis who received antibiotics immediately prior to their illness. All of the strains were available for plasmid analysis, and all the DNA profiles were distinct. On gels run in Tris-borate buffer, 73.7% of the strains had large plasmids of more than 30 megadaltons. A small plasmid of 2.8 megadaltons was found in multiply resistant strains and in strains resistant only to tetracyclines. None of the isolates appeared to be the same strain, and the bacteriological differences between the strains were confirmed mainly by the antibiotic susceptibility profile and the plasmid pattern analysis. These bacteriological results were in agreement with the clinical data.
PMCID: PMC266386  PMID: 3366858
16.  Imipenem therapy of experimental Staphylococcus epidermidis endocarditis. 
Imipenem was evaluated for its activity against Staphylococcus epidermidis in vitro and in a rabbit model of endocarditis. The MBC for imipenem of 55 methicillin-resistant S. epidermidis isolates from patients with prosthetic valve endocarditis increased by eightfold or greater with increasing inoculum size; there was no inoculum-associated increase in the imipenem MBC for 20 methicillin-susceptible S. epidermidis isolates. Endocarditis was produced in rabbits with either a methicillin-susceptible or a methicillin-resistant S. epidermidis isolate to investigate the correlation in vivo of the in vitro inoculum effect for imipenem. Six days of imipenem treatment eradicated methicillin-susceptible S. epidermidis from vegetations of infected rabbits significantly better than no therapy but was less effective against methicillin-resistant S. epidermidis in this regard. Among methicillin-resistant S. epidermidis-infected rabbits, 6 days of imipenem therapy (i) was not significantly better than that of the control and was significantly worse than that of vancomycin in eradicating bacteria from infected vegetations and (ii) increased the frequency of imipenem-resistant subpopulations in infected vegetations. Resistant subpopulations were not seen in vegetations from untreated or imipenem-treated, methicillin-susceptible S. epidermidis-infected rabbits. Imipenem may not be effective therapy for serious human methicillin-resistant S. epidermidis infections.
PMCID: PMC284147  PMID: 3460523
17.  Staphylococcus lugdunensis infective endocarditis: description of 10 cases and analysis of native valve, prosthetic valve, and pacemaker lead endocarditis clinical profiles 
Heart  2005;91(2):e10.
Objective: To evaluate the incidence and the clinical and echocardiographic features of infective endocarditis (IE) caused by Staphylococcus lugdunensis and to identify the prognostic factors of surgery and mortality in this disease.
Design: Prospective cohort study.
Setting: Study at two centres (a tertiary care centre and a community hospital).
Patients: 10 patients with IE caused by S lugdunensis in 912 consecutive patients with IE between 1990 and 2003.
Methods: Prospective study of consecutive patients carried out by the multidisciplinary team for diagnosis and treatment of IE from the study institutions. English, French, and Spanish literature was searched by computer under the terms “endocarditis” and “Staphylococcus lugdunensis” published between 1989 and December 2003.
Main outcome measures: Patient characteristics, echocardiographic findings, required surgery, and prognostic factors of mortality in left sided cases of IE.
Results: 10 cases of IE caused by S lugdunensis were identified at our institutions, representing 0.8% (four of 467), 1.5% (two of 135), and 7.8% (four of 51) of cases of native valve, prosthetic valve, and pacemaker lead endocarditis in the non-drug misusers. Native valve IE was present in four patients (two aortic, one mitral, and one pulmonary), prosthetic valve aortic IE in two patients, and pacemaker lead IE in the other four patients. All patients with left sided IE had serious complications (heart failure, periannular abscess formation, or shock) requiring surgery in 60% (three of five patients) of cases with an overall mortality rate of 80% (four of five patients). All patients with pacemaker IE underwent combined medical treatment and surgery, and mortality was 25% (one patient). In total 59 cases of IE caused by S lugdunensis were identified in a review of the literature. The combined analysis of these 69 cases showed that native valve IE (53 patients, 77%) is characterised by mitral valve involvement and frequent complications such as heart failure, abscess formation, and embolism. Surgery was needed in 51% of cases and mortality was 42%. Prosthetic valve endocarditis (nine of 60, 13%) predominated in the aortic position and was associated with abscess formation, required surgery, and high mortality (78%). Pacemaker lead IE (seven of 69, 10%) is associated with a better prognosis when antibiotic treatment is combined with surgery.
Conclusions: S lugdunensis IE is an uncommon cause of IE, involving mainly native left sided valves, and it is characterised by an aggressive clinical course. Mortality in left sided native valve IE is high but the prognosis has improved in recent years. Surgery has improved survival in left sided IE and, therefore, early surgery should always be considered. Prosthetic valve S lugdunensis IE carries an ominous prognosis.
PMCID: PMC1768720  PMID: 15657200
infective endocarditis; Staphylococcus lugdunensis; surgical treatment; mortality
18.  Native Valve Endocarditis Caused by Coagulase Negative Staphylococci; an Appeal to Start Outpatient Antimicrobial Therapy: An Unusual Case Report 
Oman Medical Journal  2011;26(4):269-270.
Coagulase negative staphylococci (CNS) were a rare cause of native valve endocarditis. However, they are emerging as an important cause of native valve endocarditis (NVE) in both community and healthcare settings. We describe a 64 yrs. old male who developed mitral valve endocarditis caused by coagulase negative staphylococci. There were no predisposing conditions or underlying cardiac disease that could have been the risk factor for the development of native valve infection. The patient had good recovery after six weeks of treatment with anti-staphylococcal antibiotics.
PMCID: PMC3191720  PMID: 22043433
Coagulase negative staphylococcus; CoNS; Native valve endocarditis; NVE; Outpatient antimicrobial therapy; OPAT
19.  Heart failure associated with infective endocarditis. A review of 40 cases. 
British Heart Journal  1986;55(2):191-197.
Thirty one (78%) of 40 consecutive patients (aged 13-79, mean 44 years) with infective endocarditis had congestive heart failure at presentation. Twenty six (65%) had had rheumatic heart disease and 17 (43%) patients had prosthetic valves. Eight (20%) patients had undergone dental procedures within three months of presentation. Blood cultures were positive in only 22 (55%) of the patients. In nine (41%) of them streptococci of the viridans group were isolated and in seven (32%) patients endocarditis was due to Staphylococcus aureus. Eight patients had Q fever endocarditis. Sixteen patients required operation because of haemodynamic deterioration while they were in hospital; 11 patients had native valves and five had prosthetic valves. Seven had emergency operations and were pyrexial at that time. Four of the seven died in hospital. Of the 12 who were alive and well after surgery only two required further surgery two and three years after the initial operation. Twelve (30%) of the 40 patients died in hospital; in 10 death was mainly due to left ventricular failure or congestive heart failure. All patients died who had renal failure (four cases), myocardial infarction (two cases), complete heart block (one case), or ventricular fibrillation (two cases) before operation. Six (33%) of the 18 patients with culture negative endocarditis died. Two of the four patients seen and treated more than 12 weeks after the onset of symptoms died, as did three of the five patients with prosthetic valves who required surgery while in hospital. Three patients with neurological complications survived and only two (29%) of the seven patients with blood cultures that were positive for Staphylococcus aureus died. Of these 40 high risk patients optimal antibiotic treatment and early surgery for haemodynamic difficulty ensured that 28 (70%) were discharged from hospital alive and well.
PMCID: PMC1232117  PMID: 3942652
20.  In Vitro Effects of Antimicrobial Agents on Planktonic and Biofilm Forms of Staphylococcus lugdunensis Clinical Isolates▿  
Staphylococcus lugdunensis is an atypically virulent coagulase-negative staphylococcal species associated with acute and destructive infections that often resemble Staphylococcus aureus infections. Several types of infection caused by S. lugdunensis (e.g., native valve endocarditis, prosthetic joint infection, and intravascular catheter infection) are associated with biofilm formation, which may lead to an inability to eradicate the infection due to the intrinsic nature of biofilms to resist high levels of antibiotics. In this study, planktonic MICs and MBCs and biofilm bactericidal concentrations of 10 antistaphylococcal antimicrobial agents were measured for 15 S. lugdunensis isolates collected from patients with endocarditis, medical device infections, or skin and soft tissue infections. Planktonic isolates were susceptible to all agents studied, but biofilms were resistant to high concentrations of most of the drugs. However, moxifloxacin was able to kill 73% of isolates growing in biofilms at ≤0.5 μg/ml. Relative to the effect on cell density, subinhibitory concentrations of nafcillin substantially stimulated biofilm formation of most isolates, whereas tetracycline and linezolid significantly decreased biofilm formation in 93 and 80% of isolates, respectively. An unexpected outcome of MBC testing was the observation that vancomycin was not bactericidal against 93% of S. lugdunensis isolates, suggesting widespread vancomycin tolerance in this species. These data provide insights into the response of S. lugdunensis isolates when challenged with various levels of antimicrobial agents in clinical use.
PMCID: PMC1803120  PMID: 17158933
21.  SdrF, a Staphylococcus epidermidis Surface Protein, Contributes to the Initiation of Ventricular Assist Device Driveline–Related Infections 
PLoS Pathogens  2009;5(5):e1000411.
Staphylococcus epidermidis remains the predominant pathogen in prosthetic-device infections. Ventricular assist devices, a recently developed form of therapy for end-stage congestive heart failure, have had considerable success. However, infections, most often caused by Staphylococcus epidermidis, have limited their long-term use. The transcutaneous driveline entry site acts as a potential portal of entry for bacteria, allowing development of either localized or systemic infections. A novel in vitro binding assay using explanted drivelines obtained from patients undergoing transplantation and a heterologous lactococcal system of surface protein expression were used to identify S. epidermidis surface components involved in the pathogenesis of driveline infections. Of the four components tested, SdrF, SdrG, PIA, and GehD, SdrF was identified as the primary ligand. SdrF adherence was mediated via its B domain attaching to host collagen deposited on the surface of the driveline. Antibodies directed against SdrF reduced adherence of S. epidermidis to the drivelines. SdrF was also found to adhere with high affinity to Dacron, the hydrophobic polymeric outer surface of drivelines. Solid phase binding assays showed that SdrF was also able to adhere to other hydrophobic artificial materials such as polystyrene. A murine model of infection was developed and used to test the role of SdrF during in vivo driveline infection. SdrF alone was able to mediate bacterial adherence to implanted drivelines. Anti-SdrF antibodies reduced S. epidermidis colonization of implanted drivelines. SdrF appears to play a key role in the initiation of ventricular assist device driveline infections caused by S. epidermidis. This pluripotential adherence capacity provides a potential pathway to infection with SdrF-positive commensal staphylococci first adhering to the external Dacron-coated driveline at the transcutaneous entry site, then spreading along the collagen-coated internal portion of the driveline to establish a localized infection. This capacity may also have relevance for other prosthetic device–related infections.
Author Summary
This study investigates the manner in which heart pumps become infected. Infections involving the driveline, the cord that connects the pump to its external power source, are a major complication of implantation of these devices. In this study, we examined why Staphylococcus epidermidis, a bacteria that is commonly found on the skin, is responsible for the majority of these infections. The ability of different surface molecules of S. epidermidis to attach to drivelines removed from patients undergoing transplantation was tested. SdrF, one of the S. epidermidis surface proteins studied, showed the highest adherence to the drivelines. This binding appeared to involve attachment of the B subunit of SdrF to collagen, a molecule that coats the driveline following implantation. SdrF also mediated attachment to the non-implanted Dacron material that is used to coat the drivelines. A mouse driveline infection model also demonstrated that SdrF was sufficient to initiate a driveline infection. Driveline infection can therefore be hypothesized to occur via: 1) skin colonization by S. epidermidis; 2) adherence of SdrF-positive S. epidermidis to the Dacron surface at the skin entry site; 3) migration of bacteria along the driveline; 4) adherence to the internal driveline via the collagen coating its surface; and 5) initiation of infection.
PMCID: PMC2670519  PMID: 19412528
22.  Prediction of Hemorrhagic Transformation Following Embolic Stroke in Patients with Prosthetic Valve Endocarditis 
Hemorrhagic transformation (HT) of stroke is a disastrous complication in patients with infective endocarditis (IE). In patients with mechanical heart valves complicated by IE, physicians struggle with the appropriateness of anticoagulation administration given the risk of thromboembolism and HT of stroke. In this study, we aimed to define predictive parameters of HT of stroke in patients with prosthetic valve endocarditis (PVE).
This study was a multicenter, retrospective design. We recruited from 7 institutions a total of 111 patients diagnosed with PVE during May, 2011 to April, 2012.
Complication of stroke was seen in 26/111 patients (23%), and HT of stroke was seen in 11/111 patients (10%). Most patients with HT (9/11, 82%) had supratherapeutic prothrombin times. However, there were no significant differences in clinical and laboratory values between PVE patients without stroke and those patients who had a stroke and with or without concurrent HT. Furthermore, echocardiographic parameters also did not show significant between-group differences.
Even though this was a multicenter study, a limited number of patients was identified and may explain the negative results seen here. However, a large number of PVE patients with stroke also developed HT. Therefore, further studies to define predictive parameters of HT should be implemented in a larger population.
PMCID: PMC3816162  PMID: 24198918
Infective endocarditis; Embolization; Hemorrhagic stroke
23.  Fungal Prosthetic Valve Endocarditis by Candida parapsilosis: A Case Report 
Fungal prosthetic valve endocarditis (PVE) is rare but serious complication of valve replacement surgery. Candida species, particularly Candida albicans is the most common isolated pathogen in fungal PVE (1–6%of cases).
Case Presentation:
We describe a 35-year-old woman who underwent mechanical mitral valve replacement about 3 years ago. She was admitted with neurological symptoms and later with dyspnea and hypotension. Transesophageal echocardiography showed large and mobile prosthetic valve vegetation. She underwent mitral valve surgery. The explanted valve and vegetation revealed lots of budding yeasts and the isolated yeast was identified as C. parapsilosis. Amphotericin B and broad spectrum antibiotic were started immediately. Unfortunately, the patient died two days after surgery, due to sepsis probably related to the candidemia.
Fungal endocarditis is uncommon infection, but it is a serious problem in patients with prosthetic valve. Fungal PVE can occur years after the surgery, thus long-term follow-up is essential.
PMCID: PMC4138648  PMID: 25147692
Candida; Fungi; Endocarditis; Prosthetic valve
24.  Prosthetic Valve Endocarditis and Bloodstream Infection Due to Mycobacterium chimaera 
Journal of Clinical Microbiology  2013;51(6):1769-1773.
Prosthetic valve endocarditis (PVE) due to fast-growing nontuberculous mycobacteria (NTM) has been reported anecdotally. Reports of PVE with slowly growing NTM, however, are lacking. We present here one case of PVE and one case of bloodstream infection caused by Mycobacterium chimaera. Randomly amplified polymorphic DNA (RAPD)-PCR indicated a relatedness of the two M. chimaera strains. Both patients had heart surgery 2 years apart from each other. A nosocomial link was not detected.
PMCID: PMC3716099  PMID: 23536407
25.  Epidemic of prosthetic valve endocarditis caused by Staphylococcus epidermidis. 
In an epidemic of prosthetic valve endocarditis caused by Staphylococcus epidermidis the surgeon was found to be the source of contamination. The probable route was accidental puncture of gloves during operation. During the epidemiological investigation a second cluster of patients contaminated with Staph epidermidis during open heart surgery was found also related to one surgeon. This strain caused no detectable signs or symptoms of infection. Carriage of virulent staph epidermidis has rarely been recognised as a hazard but may have serious consequences.
PMCID: PMC1417246  PMID: 3929975

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