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Guidelines for the antibiotic treatment of endocarditis in adults: report of the Working Party of the British Society for Antimicrobial Chemotherapy.

The BSAC Guidelines on Endocarditis were last published in 1998. The Guidelines presented here have been updated and extended to reflect changes in both the antibiotic resistance characteristics of causative organisms and the availability of new antibiotics. Randomized, controlled trials suitable for the development of evidenced-based guidelines in this area are still lacking, and therefore a consensus approach has again been adopted. The Guidelines cover diagnosis and laboratory testing, suitable antibiotic regimens and causative organisms. Special emphasis is placed on common causes of endocarditis, such as streptococci and staphylococci, however, other bacterial causes (such as enterococci, HACEK organisms, Coxiella and Bartonella) and fungi are considered. The special circumstances of prosthetic endocarditis are discussed.

Anti-Bacterial Agents↗

Haemophilus parainfluenzae infective endocarditis.

Seven young to middle-aged patients with Haemophilus parainfluenzae endocarditis are reported. Three patients had underlying heart disease and three patients had recent events predisposing for endocarditis. The clinical presentation was subacute or acute and new pathologic murmurs were uncommon. Diagnosis was prolonged because of difficulties in isolating the organism. Routine subculturing of blood cultures to chocolate agar with incubation in CO2 is recommended. A prominent complication, occurring in six patients, was major arterial occlusion secondary to emboli. Antibiotic control of infection was difficult and best achieved by the concomitant administration of ampicillin and gentamicin. Killing curves proved useful in assessing antibiotic efficacy. There were two medical failures and one death in the series. It appears H. parainfluenzae endocarditis is characterized by distinctive clinical features, difficult in vitro isolation of the organism, and the necessity for combination antibiotic therapy.

Adult↗

Infective endocarditis in a Sydney teaching hospital--1962-1971.

This report represents a comprehensive review of infective endocarditis in a major Australian centre between the years 1962 and 1971. During the later years of this study prosthetic valves were inserted in significant numbers and cardiac surgery became available in the treatment of endocarditis. The following major points emerged. There has been no reduction in the incidence of this disease within the period of study. A higher percentage of cases have followed surgery, particularly cardiac. There has been a decreased number of cases following dental extraction or urological surgery. A change in the pattern of the infective organisms was observed, particularly an increase in Staphylococcal infections, although Strep. viridans was the most frequent infecting agent. Infected prosthetic valves accounted for 11% of cases in the latter five year period, Staphylococcal infections being responsible for the majority of these cases. The mortality for prosthetic infections was 80%, and a loss of anticoagulant control contributed to death in 42% of patients. There was a reduction in mortality due to endocarditis from 39% between 1962 and 1966 to 24% between 1967 and 1971 (P less than 0-05).

Adult↗

Etiology and risk factors of 339 cases of infective endocarditis: report from a 10-year national prospective survey in the Slovak Republic.

The authors studied the etiology, outcome and risk factors of 339 cases of infective endocarditis (IE) in Slovakia over the last 10 years. Aortic valve was infected in 59.9%, mitral in 38.1% and tricuspidal/pulmonary in 5.0% of cases. The majority of IE were caused by staphylococci (29.2%), 15.0% were due to viridans streptococci, 7.4% due to Enterococcus faecalis, 3.9% due to the HACEK group (Haemophilus spp., Actinobacillus spp., Corynebacterium spp., Eikenella spp., Kingella spp.) and 39.2% were culture negative. The following risk factors were the most frequently identified: rheumatic fever in 24.2%, dental surgery in 13.3%, previous cardiosurgery in 7.1% and neoplasia in 7.1%. All patients were treated with antimicrobials and 42.5% of patients also with surgery (valvular prosthesis replacement): 61 (18.0%) died, and 278 (82.0%) survived at day 60 after the diagnosis of endocarditis was made. Univariate analysis did not show significant differences in most of the recorded risk factors between patients who died and those who survived: apart from staphylococcal etiology (44.3% vs. 26.6%, P < 0.01), persistent bacteremia (with three or more positive blood cultures 24.6% vs. 9.7% P < 0.002) which were significantly associated with higher attributable mortality, as was absence of surgery (55.7% vs. 6.1% P < 0.001), whereas antibiotic therapy in combination with surgery significantly predicted better outcome (P < 0.001). We compared risk factors, etiology, therapeutic strategies and outcome of IE in two periods: from 1991-1997 (180 cases) and from 1998-2001 (159 cases). Rheumatic fever was less commonly observed in second period (1998-2001) P < 0.01 since its prevalence in Slovakia is rapidly decreasing. Dental surgery was less frequent as well (20.5% vs. 5.0% P < 0.001). There was a significant shift in etiology within the second study period: negative-culture endocarditis (despite better bacteriological techniques) (P < 0.001) was more frequently observed in the 1st period and represented 53.3% of all cases in 1998-2001 in comparison to 26.7% in 1991-1997. Enterococci (P < 0.0002) were also more frequent in the 2nd period. Persistent bacteremia (3 or more positive blood cultures 20.5% vs. 3.1%, P < 0.001 was less commonly observed within the 2nd period (1998-2001) in comparison to 1991-1997. More patients in the second period (1998-2001) had complications of IE (P < 0.001) than in the 1st period. However mortality was lower (22.2% vs. 13.2%, P < 0.044) because of more surgical intervention in the 2nd period (52.8% vs. 33.3%, P < 0.001).

Adult↗

A genome-wide in vivo screen reveals fitness pathways required for streptococcal infective endocarditis.

Infective endocarditis (IE) is a life-threatening disease most often caused by blood-borne bacteria that infect previously damaged cardiac tissue. Despite the importance of this disease, the genetic basis for IE-associated fitness remains poorly defined. Here, we present the first genome-wide in vivo analysis of bacterial fitness in a vertebrate model of IE. We identified 146 genes in Streptococcus sanguinis required for IE fitness, the majority of which had not previously been linked to endocarditis. These determinants cluster into conserved metabolic, cell envelope, transport, and regulatory pathways, representing a vast reservoir of potential targets for novel antimicrobial intervention. A subset of these genes was examined in Streptococcus mutans; all were found to be essential for IE fitness in this distantly related oral species as well, suggesting broad conservation. Using experimental evolution, we further show that disruption of key fitness pathways triggers reproducible compensatory "bypass" mechanisms. Together, these findings provide a comprehensive, genome-wide map of the bacterial niche-requirements for streptococcal infective endocarditis.

Animals↗

Nonbacterial Thrombotic Endocarditis Unmasking Concomitant Monoclonal Gammopathy of Undetermined Significance (MGUS) by Manifesting as Stroke.

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition characterized by sterile platelet-fibrin vegetations on cardiac valves in the absence of systemic infection. The pathogenesis of marantic endocarditis is driven by endothelial dysfunction and a systemic hypercoagulable state. In contrast to infective endocarditis, vegetations in NBTE lack significant inflammatory infiltrates and do not yield positive blood cultures. NBTE typically comes to clinical attention via systemic embolic events, with cerebrovascular accidents serving as a clinical hallmark and constituting over 50% of cases. While NBTE is commonly associated with mucin-producing adenocarcinomas of the lung, pancreas, and gastrointestinal tract, its occurrence secondary to hematological malignancies or precursor plasma cell dyscrasias like monoclonal gammopathy of undetermined significance (MGUS) is exceedingly rare, particularly in young individuals. We report the case of a previously healthy 35-year-old woman who presented with acute-onset blurred vision. Neuroimaging via magnetic resonance imaging (MRI) revealed an acute left occipital infarct along with multiple chronic infarcts, raising a strong suspicion of a recurrent embolic process. A transesophageal echocardiogram (TEE) demonstrated two vegetations on the aortic valve with moderate transvalvular regurgitation; in the context of persistent negative blood cultures, these findings supported the diagnosis of NBTE. The patient was managed with systemic anticoagulation. A comprehensive hypercoagulable and autoimmune workup revealed an elevated lambda free light chain level with a decreased kappa/lambda ratio. Subsequent bone marrow biopsy and cytogenetic analysis established a diagnosis of MGUS featuring high-risk genomic aberrations, specifically an immunoglobulin heavy chain/musculoaponeurotic fibrosarcoma (IGH/MAF) rearrangement and the loss of chromosome 13 in a polyploid (3n, 4n) background, findings consistent with plasma cell neoplasia. The prevalence of MGUS in individuals under the age of 40 is exceptionally low, estimated at less than 0.3%. This case underscores NBTE as a critical finding that can unmask underlying, atypical plasma cell neoplasms. It highlights the necessity of an exhaustive diagnostic evaluation for occult hematological disorders and high-risk cytogenetic features in young patients presenting with multi-territory embolic strokes.

igh/maf rearrangement↗

Pulmonary valve endocarditis: mid-term follow up of pulmonary valvectomies.

Four males aged 20-37 years (three drug addicts and one with a congenital mixed pulmonary valve lesion) were diagnosed in 1989, 1991 and 1993 with pulmonary valve endocarditis without tricuspid infection. Three patients were positive for hepatitis B, C or both, and one patient was HIV-positive. The predominant organism in blood cultures was Staphylococcus aureus. Antibiotic treatment of pulmonary valve endocarditis had failed; thus partial or total valvectomies were performed. Postoperatively, all patients were cured of infection and initial recovery was good. At mid-term follow up (5-10 years) there were no recurrences, and tolerance of the resultant pulmonary insufficiency was good. Slight to severe tricuspid valve insufficiency developed, together with right ventricular dilatation, in all cases. Hepatomegaly was apparent in two cases and peripheral edema in one. Despite treatment, the latter patient remained in moderate right ventricular failure, and may require homograft valve replacement. The other three patients remained in good clinical condition. Eradication of the infection was achieved in all patients. It is concluded that pulmonary valve resection is the treatment of choice for pulmonary valve endocarditis when antibiotic treatment has failed. Complete resection of all affected tissue should be performed in these cases. Analysis of preoperative data did not permit differentiation of those patients likely to develop right heart failure.

Adult↗

The choice of antibiotic for treating infective endocarditis.

The bacteriological spectrum of infective endocarditis is very different when the disease occurs spontaneously from when it follows shortly after cardiac surgery or is associated with narcotic abuse or haemodialysis. It is therefore suggested that two categories of the illness, naturally occurring and extraneous, are recognized. The great majority of cases of naturally occurring infective endocarditis are caused by organisms highly sensitive to penicillin. Oral therapy is nearly always effective in such cases and amoxycillin given with probenecid is recommended as the regime of choice. Extraneous infective endocarditis is most often caused by staphylococci, with Gram-negative bacilli and fungi also quite frequent infecting agents. Intravenous and oral therapy with a variety of antibiotics is discussed in the management of this group.

Adolescent↗

Antibiotics in management of staphylococcal endocarditis; with special reference to increasing bacterial resistance.

Eighteen patients with staphylococcal endocarditis were observed at the Los Angeles County Hospital over a 3-year period (1947-49, inclusive). Twelve died. Bacterial sensitivity studies were carried out in 15 of the cases, and there was resistance to penicillin in ten. Aureomycin was effective in two cases of Staphylococcus aureus endocarditis in which there was no response to penicillin therapy. In one case of Staphylococcus aureus endocarditis the organism was resistant to penicillin and developed increasing resistance to aureomycin.

Anti-Bacterial Agents↗

[Surgical treatment of heart valve defects in infectious endocarditis].

The study makes an assessment of the results of surgical treatment of infectious endocarditis in 25 patients operated in 1982-1988 at the Institute of Experimental and Clinical Medicine. At the active stage of the disease, surgery was performed on 15 patients (60%), while prior to the operation, 16 persons' condition (64%) corresponded to the IIIrd and IVth degree of the NYHA functional classification. In infectious endocarditis, early mortality after valve replacement was 8%, late mortality--9% with an average of two-year post operative follow-up. Re-infection occurred in 12% patients, paravalvular regurgitation was found in 20 percento, out of whom 8% were haemodynamically significant and associated with the infection. Clinical post-operative improvement was observed in 76% patients, out of whom one half was totally asymptomatic and one third resumed their jobs. The results show that early surgical treatment of infectious endocarditis helps to reduce mortality. The post-operative risk of re-infection or of other complications was not high and the long-term post-operative functional effect was favourable in most patients.

Adolescent↗

Reparative approach for right-sided endocarditis. Operative considerations and results of valvuloplasty.

From 1981 to 1986, 12 patients were operated on for right-sided endocarditis after the failure of initial medical treatment (five staphylococcal, three streptococcal, two fungal, one gram-negative, and one mixed organism). The sources of infection were intravenous drugs in six patients, central catheters in two, and malformations in four. Preoperatively, 10 of 12 (83%) of these patients were in class III or IV. Reparative or reconstructive approaches, including valvuloplasty, were attempted for all these right-sided endocarditis lesions and were hemodynamically effective in 10 of 12 (83%) patients. The low right-sided intracardiac pressures and the three-leaflet configuration (one pulmonary and nine tricuspid valves) have lent themselves to this approach. Extensive annular invasion and multileaflet infections were technical limitations in the remaining patients. The overall outcome was favorable during the mean follow-up period of 25 months (hospital mortality 1/12, 8.3%; late death 1/11, 9%). Reparative or reconstructive approaches for right-sided infective endocarditis should be considered and can be successfully achieved. Their advantages include (1) improved hemodynamics, (2) low recurrence, and (3) favorable long-term results without staged or simultaneous prosthetic valve replacement.

Adult↗

Appearance of low molecular weight IgM during course of infective endocarditis.

Low molecular weight (LMW) IgM is the monomeric subunit of pentameric IgM. It is not found in healthy adults but occurs in a number of autoimmune, lymphoproliferative and infectious conditions. It has not been described before in infective endocarditis (IE). Eighteen patients with IE were studied; 16 with subacute bacterial endocarditis (SBE) and two with acute endocarditis. LMW IgM was detected in the sera of six patients, all having SBE in association with circulating rheumatoid factor (RF). Of the remaining 12 patients without LMW IgM only three had RF in low quantities. Sequential studies revealed that LMW IgM appeared during the later stages of the illness at or following the peak RF and IgM response. LMW IgM was not detected in any of 20 control sera. Immunoblot analysis of sera containing LMW IgM revealed the presence of small quantities of dimeric and oligomeric IgM in addition to monomeric IgM. We conclude that LMW IgM occurs predominantly in those patients with IE who have associated RF. Immunoblot analysis suggests that the presence of monomeric and oligomeric LMW IgM reflects a disorder of IgM polymerization occurring in those patients.

Adult↗

[Infectious endocarditis: its resistance to therapy, causative factors and means of combating it].

Based on the data obtained during observation over 270 patients with infectious endocarditis the authors discuss factors that cause antibacterial therapy resistance encountered particularly often over the recent decade. Among the factors, the authors mark polyetiology of the disease over the recent years, "new" patterns of endocarditis in terms of the pathogenesis, predominance of primary endocarditis with highly virulent microorganisms, late disease diagnosis, inadequate antibacterial treatment, and so forth. Approaches to overcoming treatment resistance are also considered.

Adolescent↗

[Physiopathology of infectious endocarditis].

Infectious endocarditis (IE) develops following bacteremic episodes during which bacteria may attach to sterile thrombotic vegetations. Such thrombotic vegetations result from the deposition of platelets and fibrin on lesioned endothelium. These sterile vegetations are the most susceptible to infection in the left side of the heart, since this localization is found in as much as 80% of the patients with IE. Any circulating bacterial or mycotic organism may induce endocarditis, but streptococci are most often responsible, possibly because of their high capacity to adhere to thrombotic vegetations. The host cell defenses apparently cannot penetrate the dense network of platelet and fibrin in the vegetation, and humoral immunity (antibodies and complement) are of no help against gram-positive cocci. Thus, the infected vegetation has been compared to a localized agranulocytic focus, permitting the survival of infection and allowing bacteria to be released freely and continuously into the circulation (hence the constant bacteremia, a hallmark of IE). In the subacute and chronic evolution of IE, the clinical findings are mainly due to immunization of the host against the infecting microbe, resulting in antigen-antibody-complex-mediated vasculitis, and in nonspecific symptoms. Only positive blood cultures at this stage will confirm the clinical suspicion of endocarditis. Embolism may occur in any organ and falsify the diagnosis because of focal signs. Local complications of IE are the major cause of mortality in this disease, and are due to valve perforation, paravalvular abscesses, cardiac metastatic abscesses etc. If these complications occur early in the course of IE, the course may be acute.(ABSTRACT TRUNCATED AT 250 WORDS)

Agranulocytosis↗

Pathological study of infective endocarditis on Hancock porcine bioprostheses.

A pathological study has been performed on 10 infected Hancock bioprostheses removed from nine patients who died of prosthetic endocarditis. The devices had been in place from 2 to 87 months (average 37.5), the interval between operation and onset of infection averaging 30 months. The offending organisms were Gram negative bacteria in three patients (Klebsiella pneumoniae, Enterobacter cloacae, and Serratia marcescens), Gram positive bacteria in two (Staphylococcus aureus and Streptococcus viridans), and fungi in four (Candida species in three and Aspergillus species in one). Gross examination of the explants revealed in most cases a vegetative endocarditis of one porcine valve leaflets. Septic embolization occurred in five cases owing to the high friability of the vegetations. Prosthetic valve incompetence was the commonest type to dysfunction observed because of tears, perforations, and even complete destruction of the cusps. Prosthetic valve stenosis following obstruction of the valve orifice by infected polypous masses was noted in two cases. Clumps of infective organisms were detected deep in the cusp tissue in most cases on histologic examination. Infection located on the paraprosthetic tissues, associated with ring abscess, valve detachment, and insufficiency, was observed only once. According to the results of investigation, endocarditis on porcine bioprostheses is associated with a better preserved native valvular ring as viewed at reoperation. Therefore surgical intervention appears appropriate in the presence of severe hemodynamic complications after adequate antibiotic treatment. However, infection of these particular prostheses still carries an extremely high mortality. In the present series, this poor outcome might be explained by the frequently associated septic and thromboembolic events.

Adult↗

[Bacterial endocardiitis complicating fibroplastic endocarditis: a case report (author's transl)].

A young Protugese man, who had never travelled outside of Europe, was found to have a bacterial complication of a fibroplastic endocarditis. The onset was by a spontaneous chest pain, associated with a posterolatero-apical subepicardial ischemia and giant T waves in V3, V4, and calcification in the apex of the heart on radiography. Diagnosis was confirmed by intracardiac explorations: ventricular telediastolic pressures were increased; the lower border of the right ventricle was smooth, the left ventricle had a globular appearance with a smooth anterior border, the apex appearing to be completely excluded; coronarography was normal. Histological examination confirmed the presence of fibrosis. Anticoagulant treatment was started. Four months after the onset of the disease, a high fever, an apical systolic murmur, and nine positive blood cultures for a streptococcus mitis, suggested the development of a bacterial endocarditis, though no direct evidence was discovered. Improvement occurred after appropriate antibiotic therapy, and the anticoagulants were continued. Cardiac ultrasonography recordings were normal following this episode. This case-report is of two-fold interest: on the one hand it represents an early form of fibroplastic endocarditis, diagnosed by intracardiac exploration, and on the other hand it emphasizes the rare nature of bacterial complications of this affection. Authors differ in their evaluation of the frequency of chest pain, but their inaugural and isolated nature are rarely described. In most cases the presence of the disease is revealed by a progressive cardiac insufficiency. A very positive factor is the presence of calcifications, and the absence of an eosinophilia does not exclude the diagnosis. Electrical anomalies of the ischemic type are possible, but are rarely isolated findings, and the giant appearance of the T waves in this case is rather atypical. Bacterial complications are rare, and are only reported in 12 of the 218 cases described in the published literature. They are rarely diagnosed during the life of the patient (1 case only). The infection affects the cords, the valves, the thrombus, or the fibrosis itself.

Adult↗

Evaluation of unstented aortic homografts for the treatment of prosthetic aortic valve endocarditis.

BACKGROUND: Prosthetic aortic valve endocarditis is a serious complication that carries a high morbidity and mortality. Aortic homografts have been used in this setting, but long-term results are not available. METHODS AND RESULTS: Over a 23-year period, 48 patients presented with infected aortic valve substitutes: 28 homografts, 15 mechanical, and 5 xenografts. Nineteen patients had emergency surgery, and the mean interval between the first and second operation was 5.9 years (range, 1 month to 22 years). In 28 patients, the preoperative New York Heart Association (NYHA) class was III or IV. Active endocarditis was present in 39 patients, and the microorganisms grown were Staphylococcus epidermidis (n = 13), Staphylococcus aureus (n = 6), Streptococcus viridans (n = 6), Streptococcus faecalis (n = 4), Candida albicans (n = 5), and Gram-negative spp (n = 2). Aortic root abscesses were found in 28 (58%) patients, and transesophageal echocardiography was 95% accurate in their localization. All patients received homograft aortic valves, 19 as root replacement and 29 using the freehand technique. There were four (8.3%) early deaths; poor left ventricular function and concomitant procedure were identified as risk factors. At a mean follow-up of 4 years (range, 2 months to 19 years) 95% of the patients were in NYHA class I or II without significant aortic regurgitation. The actuarial survival at 5 years was 97% (confidence limit, 84% to 100%), and freedom from endocarditis at 10 years was 97% (confidence limit, 84% to 100%). Multivariate analysis did not identify risk factors for these late events. CONCLUSIONS: Homograft aortic valves offer good early and long-term results in patients with infected aortic valve substitutes.

Actuarial Analysis↗

[Drug treatment of native valve infective endocarditis in patients not addicted to parenteral drugs].

Infectious endocarditis is an infection that is characterized by the presence of microorganisms in dense populations in vegetating lesions in the endocardium. Because phagocyte penetration to the interior of the vegetation is practically impossible, to cure infectious endocarditis, high doses of bactericidal antibiotics are administered, usually intravenously and for a long duration. In this article, antibiotic treatment is reviewed, depending on the isolated microorganism and in cases where necessary, treatment is initiated in an empirical manner. Once the microorganism was isolated, the recommended guidelines for antibiotic treatment have gone through some variations in recent years, due to the changing pattern of antibiotic sensitivity of some microorganisms, to the point of finding ourselves on occasion without an effective treatment (e.g. multiresistant enterococci). In addition, these variations are due to the introduction of new antibiotics that allow, in special cases, for the treatment to be administered on an outpatient basis. Using anticoagulation in infectious endocarditis is still considered controversial. In general, only patients having cardiac valvular prostheses seem to benefit from its use.

Algorithms↗