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Induction of a putative laminin-binding protein of Streptococcus gordonii in human infective endocarditis.

There is evidence to suggest that the virulence of Streptococcus strains in infective endocarditis might be due to the expression of binding sites for the extracellular matrix proteins of damaged valves. In this communication, we draw attention to one laminin-binding protein from a strain of Streptococcus gordonii isolated from a patient with human endocarditis. This 145-kDa protein was found on the cell wall of the bacterium. The level of expression of this binding protein might be regulated by the presence of extracellular matrix proteins: the protein was lacking after in vitro selection of laminin, collagen I, and fibronectin nonbinding variants, and it was recovered after growth of the variants when laminin or collagen I was added to the growth medium. It was also missing after 10 subcultures in minimal medium, indicating some positive control. Furthermore, the 145-kDa protein was recognized as a major antigen by sera from patients treated for streptococcal infective endocarditis, while sera from patients with valvulopathies gave only slight recognition, suggesting an increase of the expression of this protein during infective endocarditis. It was also shown that the 145-kDa protein carried a collagen I-like determinant detected with anti-human collagen I antibodies.

Collagen↗

Upregulation of tumor necrosis factor alpha and interleukin-1 beta in Q fever endocarditis.

The occurrence of Q fever endocarditis likely involves some alterations in the responses of monocytes, the in vivo targets of Coxiella burnetii. To test this hypothesis, the production of the inflammatory cytokines tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 was assessed in monocytes from patients with Q fever endocarditis. Spontaneous transcription and secretion of tumor necrosis factor and interleukin-1 were significantly higher in patient monocytes than in healthy controls. The interleukin-6 transcripts were also upregulated in patient cells. Moreover, in patients with recent endocarditis exhibiting high titers of immunoglobulin G directed to C. burnetii in phase I, monocytes released significantly higher levels of tumor necrosis factor and interleukin-1 than in patients with stabilized endocarditis. Immunoglobulin G titers and the overproduction of tumor necrosis factor and interleukin-1 were significantly correlated. Hence, the overproduction of inflammatory cytokines might be a marker of disease activity.

Adult↗

Phenotypic resistance to thrombin-induced platelet microbicidal protein in vitro is correlated with enhanced virulence in experimental endocarditis due to Staphylococcus aureus.

Thrombin-induced platelet microbicidal protein (tPMP) is secreted by rabbit platelets following thrombin stimulation, and it kills common endovascular pathogens in vitro, including Staphylococcus aureus. Therefore, pathogens which exhibit tPMP resistance in vitro possess a potential survival advantage in vivo at sites of endovascular damage. We generated an isogenic S. aureus strain pair, differing in tPMP susceptibility, by transposon (Tn551) mutagenesis of a tPMP-susceptible (tPMPs) parental strain (ISP479) to derive a stably tPMP-resistant (tPMPr) strain, ISP479R. ISP479 and ISP479R were equivalent in vitro in the following phenotypes: biotyping, antiobiograms, platelet adherence and aggregation, growth kinetics, cell wall-associated protein A expression, and fibrinogen binding. Genotypic comparisons of chromosomal DNA of strains ISP479 and ISP479R following restriction endonuclease digestion revealed indistinguishable pulsed-field gel electrophoretic patterns. The genotype exhibited by strain ISP479R was linked to the tPMP-resistant phenotype, as it was transducible into the initially tPMP-susceptible parental strain, ISP479. Southern hybridization verified the presence of a single copy of Tn551 in the same chromosomal restriction site of both ISP479R and tPMPr transductants of ISP479. The correlation of in vitro tPMP susceptibility phenotypes with the ability to induce experimental endocarditis (a prototypical endovascular infection) was evaluated. Despite equivalent rates of endocarditis induction, animals infected with strain ISP479R achieved significantly higher vegetation bacterial densities over a 7-day post-challenge period than did animals infected with strain ISP479. These data suggest that tPMPr microbial strains have a selective advantage in experimental staphylococcal endocarditis. Furthermore, the major impact of tPMP resistance upon endocarditis pathogenesis appears to involve a postvalvular adherence event(s), most probably by facilitating bacterial proliferation within vegetations.

Animals↗

Endocarditis caused by Actinobacillus actinomycetemcomitans.

Actinobacillus actinomycetemcomitans is a gram-negative coccobacillus which is a very rare cause of bacterial endocarditis. Preexisting cardiac lesions are a main contributing factor, and antibiotic prophylaxis has long been felt necessary before dental or other manipulation to prevent endocarditis. Penicillin in combination with an aminoglycoside has been the most often used treatment regimen. We present a case of endocarditis caused by this organism which developed after antibiotic prophylaxis for dental cleaning. Streptomycin and rifampin therapy resulted in the cure of the infection. The treatment and epidemiology of Actinobacillus endocarditis are reviewed.

Actinobacillus Infections↗

Serodiagnosis of Streptococcus faecalis endocarditis by immunoblotting of surface protein antigens.

We describe a method for the serodiagnosis of Streptococcus faecalis in infective endocarditis which could be of value in culture-negative cases. Serum-grown cells of S. faecalis produced three major characteristic protein antigens (73,000, 40,000, and 37,000 molecular weight) which were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of solubilized whole cells. After electrophoretic transfer to a nitrocellulose membrane, these antigens were visualized by probing with serum from patients with endocarditis caused by S. faecalis. Serum from patients with endocarditis caused by other organisms did not react with the S. faecalis-specific antigens. This procedure should facilitate positive early diagnosis of S. faecalis endocarditis or establish its absence in culture-negative cases.

Antibodies, Bacterial↗

Characterization of clinically significant isolates of Staphylococcus epidermidis from patients with endocarditis.

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.

Bacteriophage Typing↗

Molecular identification of Gemella species from three patients with endocarditis.

Gemella morbillorum and Gemella haemolysans are opportunistic pathogens which cause endocarditis and other severe infections. We report on three patients with endocarditis, one with endocarditis caused by G. haemolysans and two with endocarditis caused by G. morbillorum. The paucity of reports concerning these bacteria is probably related to the difficulties associated with their identification. For example, one of the strains reported in this study was originally sent to our laboratory with a preliminary characterization as a short "gram-negative" coccobacillus, highlighting the specific problem associated with Gram staining of these bacteria. The usefulness of 16S rRNA gene amplification, partial sequencing, and comparison of the nucleotide sequence to those in databases when standard phenotypic identification schemes are not helpful is emphasized. We also suggest that the use of simple tests, such as testing susceptibility to vancomycin for gram-negative bacteria and colistin for gram-positive bacteria, could prevent misinterpretation of Gram staining in gram-variable bacteria such as Gemella spp.

Aged↗

Bartonella vinsonii subsp. berkhoffii and related members of the alpha subdivision of the Proteobacteria in dogs with cardiac arrhythmias, endocarditis, or myocarditis.

Cardiac arrhythmias, endocarditis, or myocarditis was identified in 12 dogs, of which 11 were seroreactive to Bartonella vinsonii subspecies berkhoffii antigens. Historical abnormalities were highly variable but frequently included substantial weight loss, syncope, collapse, or sudden death. Fever was an infrequently detected abnormality. Cardiac disease was diagnosed following an illness of short duration in most dogs, but a protracted illness of at least 6 months' duration was reported for four dogs. Valvular endocarditis was diagnosed echocardiographically or histologically in eight dogs, two of which also had moderate to severe multifocal myocarditis. Four dogs lacking definitive evidence of endocarditis were included because of seroreactivity to B. vinsonii antigens and uncharacterized heart murmurs and/or arrhythmias. Alpha proteobacteria were not isolated from the blood by either conventional or lysis centrifugation blood culture techniques. Using PCR amplification and DNA sequencing of a portion of the 16S rRNA gene, B. vinsonii was identified in the blood or heart valves of three dogs. DNA sequence alignment of PCR amplicons derived from blood or tissue samples from seven dogs clustered among members of the alpha subdivision of the Proteobacteria and suggested the possibility of involvement of one or more alpha proteobacteria; however, because of the limited quantity of sequence, the genus could not be identified. Serologic or molecular evidence of coinfection with tick-transmitted pathogens, including Ehrlichia canis, Babesia canis, Babesia gibsonii, or spotted fever group rickettsiae, was obtained for seven dogs. We conclude that B. vinsonii subsp. berkhoffii and closely related species of alpha proteobacteria are an important, previously unrecognized cause of arrhythmias, endocarditis, myocarditis, syncope, and sudden death in dogs.

Alphaproteobacteria↗

Aortic valve endocarditis in a dog due to Bartonella clarridgeiae.

We report the first documented case of endocarditis associated with Bartonella clarridgeiae in any species. B. clarridgeiae was identified as a possible etiological agent of human cat scratch disease. Infective vegetative valvular aortic endocarditis was diagnosed in a 2.5-year-old male neutered boxer. Historically, the dog had been diagnosed with a systolic murmur at 16 months of age and underwent balloon valvuloplasty for severe valvular aortic stenosis. Six months later, the dog was brought to a veterinary hospital with an acute third-degree atrioventricular block and was diagnosed with infective endocarditis. The dog died of cardiopulmonary arrest prior to pacemaker implantation. Necropsy confirmed severe aortic vegetative endocarditis. Blood culture grew a fastidious, gram-negative organism 8 days after being plated. Phenotypic and genotypic characterization of the isolate, including partial sequencing of the citrate synthase (gltA) and 16S rRNA genes indicated that this organism was B. clarridgeiae. DNA extraction from the deformed aortic valve and the healthy pulmonic valve revealed the presence of B. clarridgeiae DNA only from the diseased valve. No Borrelia burgdorferi or Ehrlichia sp. DNA could be identified. Using indirect immunofluorescence tests, the dog was seropositive for B. clarridgeiae and had antibodies against Ehrlichia phagocytophila but not against Ehrlichia canis, Ehrlichia ewingii, B. burgdorferi, or Coxiella burnetii.

Animals↗

Culture-negative endocarditis due to Chlamydia pneumoniae.

We report on the case of a 54-year-old woman diagnosed as having culture-negative endocarditis (clinical and histopathologic evidence compatible with a recent episode of endocarditis). The responsibility of Chlamydia pneumoniae in this episode of endocarditis was suggested by a serological study and was then confirmed by the positive results of PCR and in situ hybridization tests with aortic and mitral valves tissues. To our knowledge, this is the first case of endocarditis due to C. pneumoniae confirmed by molecular biology-based techniques.

Blood↗

Musculoskeletal manifestations of bacterial endocarditis.

The records of 180 patients out of 247 with bacterial endocarditis were examined. 50 patients had rheumatic manifestations. In 10 there was arthritis of 2-12 weeks' duration before diagnosis; 19 had myalgia/arthralgia; 17 had back or neck pain; 14 had demonstrable arthritis; and 2 tenosynovitis of the foot. Of the 14 patients with arthritis, 8 had monarticular arthritis and 6 polyarticular. All but one patient had a raised erythrocyte sedimentation rate, and in one patient rheumatoid factor was positive. The rheumatic features responded when the endocarditis was treated. Some of the symptoms undoubtedly resulted from the infection and fever of the endocarditis, and emboli may have caused the transient aches but there was no evidence that they caused the synovitis in the patients with arthritis. The rheumatic manifestations of bacterial endocarditis can mimic other rheumatic diseases and disguise the underlying disease.

Adolescent↗

Mortality from infective endocarditis: clinical predictors of outcome.

OBJECTIVE: To identify clinical markers available within the first 48 hours of admission that are associated with poor outcome in infective endocarditis. DESIGNS: Retrospective cohort study. SETTING: Teaching hospital. PATIENTS: 208 of 220 patients with infective endocarditis. METHODS: Consecutive patients with infective endocarditis presenting between 1981 and 1999 to a tertiary centre were studied. Clinical, echocardiographic, and haematological data recorded within 48 hours of admission were obtained. Data were analysed using logistic regression models. MAIN OUTCOMES MEASURES: Mortality at discharge and at six months. RESULTS: Data were obtained for 93% of patients who were eligible for inclusion. 194 (93%) were positive for Duke criteria. Mean age was 52 (1.2) years, and 138 (66%) were men. 82 (39%) were transferred from other hospitals. 181 (87%) were blood culture positive, and 47 (23%) infections were Staphylococcus aureus. The infection was located on aortic (n = 85, 41%), mitral (n = 77, 37%), tricuspid (n = 18, 9%), and multiple valves (n = 20, 10%). 67 (32%) had prosthetic valve endocarditis. 48% of the cohort were managed with antibiotics alone. Mortality at discharge was 18% and at six months 27%. Duration of illness before admission, age, sex, valve infected, infecting organism, and left ventricular function were not predictors of adverse mortality. However, abnormal white cell count, serum albumin concentration, serum creatinine concentration, or cardiac rhythm, the presence of two major Duke criteria, or visible vegetation conferred a poor prognosis. CONCLUSIONS: Conventional prognostic factors in this study did not appear to predict outcome early during hospital admission. However, simple clinical indices, which are readily available, are reliable, cheap, and potentially powerful predictors of poor outcome.

Biomarkers↗

Mitral valve repair for active culture positive infective endocarditis.

OBJECTIVE: To describe the clinical and echocardiographic outcome after mitral valve (MV) repair for active culture positive infective MV endocarditis. PATIENTS AND METHODS: Between 1996 and 2004, 36 patients (mean (SD) age 53 (18) years) with positive blood culture up to three weeks before surgery (or positive culture of material removed at operation) and intraoperative evidence of endocarditis underwent MV repair. Staphylococci and streptococci were the most common pathogens. All patients had moderate or severe mitral regurgitation (MR). Mean New York Heart Association (NYHA) class was 2.3 (1.0). Follow up was complete (mean 38 (19) months). RESULTS: Operative mortality was 2.8% (one patient). At follow up, endocarditis has not recurred. One patient developed severe recurrent MR and underwent valve replacement and one patient had moderate MR. There were two late deaths, both non-cardiac. Kaplan-Meier five year freedom from recurrent moderate to severe MR, freedom from repeat operation, and survival were 94 (4)%, 97 (3)%, and 93 (5)%, respectively. At the most recent review the mean NYHA class was 1.17 (0.3) (p < 0.0001). At the latest echocardiographic evaluation, left atrial diameters, left ventricular end diastolic diameter, and MV diameter were significantly reduced (p < 0.05) compared with preoperative values. CONCLUSIONS: MV repair for active culture positive endocarditis is associated with low operative mortality and provides satisfactory freedom from recurrent infection, freedom from repeat operation, and survival. Hence, every effort should be made to repair infected MVs and valves should be replaced only when repair is not possible.

Adolescent↗

Heart failure associated with infective endocarditis. A review of 40 cases.

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.

Adolescent↗

Prosthetic valve endocarditis. A survey.

Fifty eight patients (aged 8-59 years, mean 27) treated for prosthetic valve endocarditis from January 1966 to January 1985 were studied retrospectively by review of case notes. There were 12 cases of early and 46 cases of late prosthetic valve endocarditis. These developed in 28 patients with an isolated aortic valve, in 26 with an isolated mitral valve, and in four with both aortic and mitral prosthetic valves. Streptococci were the most commonly isolated microorganisms, followed by staphylococci, Gram negative bacteria, and fungi. A surgical (34 cases) or a necropsy specimen (10 cases) from 44 cases was examined. Eighty two per cent of the patients had congestive heart failure. Twenty four of the 58 patients were medically treated and 17 died (70% mortality). Combined medical and surgical treatment was used in 34 patients; the main indication for surgery was congestive heart failure. Fourteen patients on combined treatment died (40% mortality). Persistent sepsis and prosthetic valve dehiscence were the most common early and late operative complications. The most important influences on outcome were congestive heart failure, the type of micro-organism, the severity and extent of anatomical lesions, the time of onset of prosthetic valve endocarditis, and the type of treatment. This survey indicates that only patients without congestive heart failure or embolic complications and with sensitive micro-organism should be treated medically. In view of the poor prognosis patients with prosthetic valve endocarditis associated with congestive heart failure, persistent sepsis, and repeat arterial emboli should be treated by early surgical intervention.

Adolescent↗

Enhanced morphological diagnosis in infective endocarditis by transoesophageal echocardiography.

Thirty three consecutive patients with clinically suspected endocarditis were studied by both precordial cross sectional echocardiography and transoesophageal echocardiography. The diagnostic value of both techniques was assessed. The data were compared with findings at operation in 25 patients. In 21 patients with native valve endocarditis precordial echocardiography showed evidence of vegetations in six patients and suggested their presence in nine. Transoesophageal echocardiography identified vegetations in 18 patients. Complications were seen in four patients at precordial echocardiography and in nine patients at transoesophageal echocardiography. Precordial echocardiography did not show vegetations in any of the 12 patients with prosthetic valve endocarditis whereas transoesophageal echocardiography showed vegetations in four. Complications were seen in four patients at precordial echocardiography and in 10 at transoesophageal echocardiography. Echocardiographic findings were confirmed at operation in all 25 operated patients. In two patients both echocardiographic techniques had missed the perforation of the cusps of the aortic valve that was seen at operation, but this had no effect on patient management. Transoesophageal echocardiography is the best diagnostic approach when infective endocarditis is suspected in patients with either native or prosthetic valves.

Adolescent↗

Serological differentiation between acute (late control) and endocarditis Q fever.

AIMS: To differentiate the serological profiles of chronic (endocarditis) Q fever from the late follow up of acute cases. METHODS: Twenty patients (10 diagnosed with acute and 10 with endocarditis Q fever) were studied. Those diagnosed with acute infection were followed up from 2.5 to 88 months (mean 35.8 months). Serological variables included indirect immunofluorescence against phase I and II of Coxiella burnetii (IgM, IgG, and IgA), complement fixation and rheumatoid factor (RF). RESULTS: All patients with titres of IgA against phase I, after IgG removal, equal to or above 320 and a complement fixation value equal to or above 128 had endocarditis. No patient with acute Q fever had such a serological profile. CONCLUSIONS: The combination of IgA against phase I and complement fixation values may be sufficient to differentiate the serological profile of chronic (endocarditis) Q fever from the late follow up of acute cases.

Acute Disease↗

The use of a new glycopeptide antibiotic, teicoplanin, in the treatment of bacterial endocarditis.

Teicoplanin, a new glycopeptide antibiotic, has been used to treat twelve patients with bacterial endocarditis due to Gram-positive organisms. Teicoplanin has activity against Gram-positive bacteria similar to vancomycin but therapeutic levels are maintained by a single daily dose, given as an intravenous bolus. Of six patients with native valve infections, two cases, due to viridans streptococci, were successfully treated with teicoplanin alone and two others, caused by Streptococcus faecalis, were cured by combinations including teicoplanin. One of these patients sustained high tone hearing loss during treatment. The remaining two patients were drug addicts with endocarditis due to Staphylococcus aureus which recurred despite repeated multiple therapy. Of six prosthetic valve infections, antibiotic combinations including teicoplanin cured three cases, caused by streptococci. Infection persisted or treatment was curtailed in three cases of Staphylococcus epidermidis endocarditis. In this small open study, teicoplanin appeared as effective as vancomycin in the treatment of endocarditis but had the considerable advantage of ease of administration.

Anti-Bacterial Agents↗