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.
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.
early surgery; infective endocarditis; medical therapy; in hospital mortality
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.
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.
Staphylococcus lugdunensis is a pathogen of heightened virulence that causes infections resembling those caused by Staphylococcus aureus rather than those caused by its coagulase-negative staphylococcal counterparts. Many types of S. lugdunensis infection, including native valve endocarditis, prosthetic joint infection, and intravascular catheter-related infection, are associated with biofilm etiology. Poly-N-acetylglucosamine (PNAG), a polysaccharide synthesized by products of the icaADBC locus, is a common mechanism of intercellular adhesion in staphylococcal biofilms. Here we report the characterization of ica homologues and the in vitro biofilm formation properties of a collection of S. lugdunensis clinical isolates. Isolates formed biofilms in microtiter wells to various degrees. Biofilm formation by most isolates was enhanced with glucose but diminished by sodium chloride or ethanol. icaADBC homologues were found in all S. lugdunensis isolates tested, although the locus organization differed substantially from that of other staphylococcal ica loci. icaR was not detected in S. lugdunensis, but a novel open reading frame with putative glycosyl hydrolase function is located upstream of the ica locus. icaADBC sequence heterogeneity did not explain the variability in biofilm formation among isolates. PNAG was not detected in S. lugdunensis extracts by immunoblotting with an anti-deacetylated PNAG antibody or wheat germ agglutinin. Confocal microscopy with fluorescently labeled wheat germ agglutinin showed a paucity of PNAG in S. lugdunensis biofilms, but abundant extracellular protein was visualized with SYPRO Ruby staining. Biofilms were resistant to detachment by dispersin B and sodium metaperiodate but were susceptible to detachment by proteases. Despite the genetic presence of icaADBC homologues in S. lugdunensis isolates, PNAG is not a major component of the extracellular matrix of in vitro biofilms formed by this species. Our data suggest that the S. lugdunensis biofilm matrix contains proteinaceous factors.
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.
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.
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.
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.
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.
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.
Coagulase negative staphylococci are the principal cause of prosthetic valve endocarditis but are a rare cause of native valve infections. However, the incidence of native valve endocarditis is increasing. Staphylococcus capitis is a coagulase negative staphylococcus with the capacity to cause endocarditis on native heart valves. Two cases of native valve endocarditis caused by S capitis are presented; both in patients with aortic valve disease. The patients were cured with prolonged intravenous vancomycin and rifampicin and did not need surgery during the acute phase of the illness. Five of the six previously described cases of endocarditis caused by this organism occurred on native valves and responded to medical treatment alone.
Keywords: Staphylococcus capitis; endocarditis; valvar disease; coagulase negative staphylococci
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.
Coagulase negative staphylococcus; CoNS; Native valve endocarditis; NVE; Outpatient antimicrobial therapy; OPAT
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.
In non-addicted patients, several states, such as permanent pacemakers, can provide the predisposing factors for tricuspid-valve endocarditis. In this report, we present a case of a 66-year-old man with pacemaker lead infection and tricuspid-native-valve endocarditis, related to Staphylococcus hominis, very rare cause of infective endocarditis that carries a high-mortality risk. Surgery was indicated for the patient due to persistent enlarging vegetation on the tricuspid valve, severe tricuspid regurgitation, septic pulmonary emboli and finally uncompensated respiratory and heart failure. Many ingenious methods have been devised to repair the tricuspid valve in patients with infective endocarditis. Valve replacement, however, is hazardous due to the possibility of prosthetic infection, and we choose to repair the native valve. The patient has now been weel for 3 years.
This study examines a series of phenotypic variants of Staphylococcus epidermidis that were generated from a pair of parent variants, isolated from valvular tissue of a patient with prosthetic valve endocarditis. The variants were initially classified by examining their colonial morphology on Congo red agar. In addition to differences in Congo red binding and colonial morphology, they differed in the expression of several surface components and enzymes. Despite these phenotypic differences, all variants had the same restriction endonuclease profile of plasmid DNA. Examination of a collection of clinical isolates demonstrated that phenotypic variation is a common property of S. epidermidis. The ability to express different combinations of surface components and enzymes could contribute to the virulence of S. epidermidis strains by enabling these organisms to colonize a range of diverse environments.
Methicillin-resistant Staphylococcus epidermidis is an important cause of cerebrospinal fluid shunt infections and prosthetic valve endocarditis. Agar dilution minimum inhibitory concentrations were determined for 100 strains of methicillin-resistant S. epidermidis which were isolated from clinical specimens. Vancomycin inhibited all 100 strains at ≤3.12 μg/ml, whereas clindamycin inhibited only 46 strains at ≤12.5 μg/ml. Methicillin-resistant S. epidermidis strains were resistant to achievable levels of erythromycin, with 90 strains having a minimum inhibitory concentration of ≥3.12 μg/ml. Of the five cephalosporins and one cephamycin tested, cefamandole was the most active in vitro, inhibiting 97 strains at ≤25 μg/ml. Antibiotic synergism was examined by a quantitative bacterial time-kill method. Synergism (≥102 kill by the combination over the most effective single antibiotic at 24 h) was demonstrated with vancomycin (1.56 μg/ml) plus cefamandole (6.25 μg/ml) in 14 of 14 strains, vancomycin plus cephalothin (6.25 μg/ml) in 14 of 14 strains, vancomycin plus rifampin (0.008 to 0.012 μg/ml) in 6 of 12 strains, rifampin plus cefamandole in 9 of 12 strains, and rifampin plus cephalothin in 10 of 12 strains. The emergence of populations of bacteria resistant to 0.2 μg of rifampin per ml developed in three of five methicillin-resistant S. epidermidis strains tested. The addition of either vancomycin, cephalothin, or cefamandole to the rifampin prevented the emergence of resistance in these three strains. Clinical trials of synergistic antibiotic combination therapy for serious methicillin-resistant S. epidermidis infections are indicated.
Staphylococcus epidermidis is a major pathogen in early prosthetic valve endocarditis and cerebrospinal fluid shunt infections. Approximately 10 to 15% of hospital isolates are methicillin resistant. Ten clinically significant isolates of the latter were collected for antibiotic studies in vitro and in an experimental infection in animals. Time-kill studies of five strains showed gentamicin to be the single most effective antibiotic; however, dwarf colony variants emerged as survivors with two of these strains when challenged with gentamicin alone. The addition of a second antibiotic to gentamicin did not significantly improve the bactericidal rate but prevented the emergence of variant strains. A blood culture isolate of methicillin-resistant S. epidermidis combined with 5% hog gastric mucin was used to establish an experimental intraperitoneal infection in mice. Neither methicillin nor nafcillin treatment reduced mortality below that of untreated animals. Cephalothin treatment delayed early mortality but did not diminish overall mortality. Gentamicin was the most effective single antibiotic, and gentamicin in combination with vancomycin was the most effective regimen overall. The combination of rifampin plus vancomycin was as effective as gentamicin alone. The combinations of cephalothin or nafcillin with gentamicin and cephalothin with vancomycin demonstrated antagonism. The antagonism was not due to multiple injections or drug-drug inactivation.
Staphylococcus lugdunensis is a virulent coagulase-negative staphylococcus. It behaves like and can be mistaken in culture for Staphylococcus aureus. While originally thought to be a skin commensal rarely responsible for opportunistic infection, it was rapidly established as a significant human pathogen. It has been mainly associated with native and prosthetic valve endocarditis, osteomyelitis, and skin and soft tissue cellulitis, but has also been reported as a cause of fasciitis as well as peritonitis. Staphylococcus lugdunensis has been reported as a cause of endometritis but has not been previously isolated from amniotic fluid. Here, amniotic fluid samples were collected in the course of a larger study on amniotic fluid bacteriology, with prior ethical approval and informed patient consent. Amniotic fluid was obtained at Caesarean Section by direct needle aspiration from the intact amnion. Analysis with Staphylococcal API test kits led to identification of Staphylococcus lugdunensis in two cases. The clinical significance of the finding in these reported cases is undetermined. Staphylococcus lugdunensis has been shown to be a cause of serious and potentially fatal morbidities, but this is the first report of its culture from amniotic fluid. As caesarean delivery is accepted as the single most important factor associated with post-partum infectious complications in both mother and neonate, the identification of this pathogen is a new concern.
Prosthetic valve endocarditis (PVE) is a rare and serious complication after heart valve replacement; its optimal management strategy, though, still needs to be defined.
To study the clinical, microbiological and echocardiographic characteristics of PVE and to analyse the influence of the adopted therapeutic strategy (medical or surgical) on short- and midterm outcome in a tertiary care centre in a developing country (Tunisia).
All cases of PVE treated in our institution between 1997 and 2006 were retrospectively analysed according to the modified DUKE criteria.
A total of 48 PVE episodes were diagnosed (30 men and 18 women), mean age was 37.93 years. Twenty-eight patients (58.33%) were exclusively medically treated, whereas 20 (41.66%) were treated by a combined surgical and medical strategy. Indications for surgery were haemodynamic deterioration in eight patients (40%), annular abscess in six (30%) and persisting sepsis in six (30%). In comparison with those from the medical group, operated patients had a longer delay to diagnosis (p=0.025), were more frequently in heart failure (p=0.04) and experienced more early complications (p=0.011); they also more frequently had prosthetic dehiscence (p=0.015), annular abscesses (p=0.039) and vegetations >10 mm (p=0.008). Conversely, no differences were found between the groups in terms of age, sex, or nature of involved organisms. In-hospital mortality for the medical group was 14.28% and for the surgical group 35% (p=0.09).
PVE is a very serious condition carrying high mortality rates regardless of the adopted strategy. Our study demonstrates that, in selected patients, medical treatment could be a successful and acceptable approach. (Neth Heart J 2009;17: 56-60.)
prosthetic valve endocarditis; surgery; medical treatment; mortality
O'Meara, J. B., Eykyn, Susannah, Jenkins, B. S., Braimbridge, M. V., and Phillips, I. (1974).Thorax, 29, 377-381. Brucella melitensis endocarditis: successful treatment of an infected prosthetic mitral valve. A 38-year-old man had a mitral valve replacement for rheumatic calcific mitral stenosis and regurgitation; following this operation he remained well for 10 months. He then presented with cough, abdominal pain, and rigors, and Brucella melitensis type 3 was repeatedly isolated from blood cultures. His clinical condition deteriorated rapidly and an emergency valve replacement was performed. He was then treated with co-trimoxazole for 12 months and made an excellent recovery. This is the first reported case of brucella endocarditis arising de novo on a prosthetic heart valve.
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.
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.
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.
Bacteremia; Bacterial assays; Endocarditis model; Staphylococcus epidermidis
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.
Historically regarded as a skin commensal, Staphylococcus epidermidis has been increasingly implicated in invasive foreign body infections such as catheter-related bloodstream infections, indwelling device infections, and prosthetic joint infections. We report a case of an aggressive, difficult-to-eradicate, invasive prosthetic hip infection occurring early after hardware implant and associated with a high-grade bacteremia and assess its salient molecular characteristics. The clinical and molecular characteristics of this isolate mirror the pathogenesis and persistence commonly seen with invasive methicillin-resistant S. aureus and may be attributed to the combination of resistance genes (SCCmec type IV), putative virulence factors (arcA and opp3a), cytolytic peptide production (α-type phenol-soluble modulins), and biofilm adhesion, interaction, and maturation (bhp, aap, and β-type phenol-soluble modulins).
Prosthetic heart valve sewing cuffs coated with minocycline and rifampin exhibited in vitro zones of inhibition against all 52 tested clinical isolates responsible for prosthetic valve endocarditis. An in vitro elution study of these coated sewing cuffs demonstrated residual zones of inhibition against Staphylococcus epidermidis for at least 4 weeks.