Infective Endocarditis

Transcription

1 بسم رلا هللا Infective Endocarditis In the beginning,we need to identify a term often used in the clinical as a differential diagnosis( DDx) which is Fever of unknown origin FUO, where the pt complains of relatively mild fever of 37.5 and may extend to 38 in its most of unknown cause,it can be observed in the outpatient clinic or in hospital admitted pts,in order to diagnose the cause full pt examination must be done to detect any wound,the oral cavity for tonsillitis,or maybe the pt has UTI. to some extent,few % of these cases are associated with infective Endocarditis,( which indicate inflammation of the endocardium,where the inner of the heart muscle and the epithelial lining of the heart valves are involved ). Generally, if there is any damage to the heart muscle or valves, whether congenital or acquired through repetitive attacks by certain microorganism, now the valves surface epithelial lining may become the site of interactions with the organism to produce vegetations :(accumulation of large #s of certain bacterial cells on the surface), where the host immune system and defensive WBCs are overwhelmed and fail to prevent it. The term (vegetations in endocarditis )means the accumulation of certain types of bacterial cells on the epithelial surface of the valves, that are covered by a very hard cover termed as biofilm these are composed of :platelets +fibrin filaments +few #s of leukocytes +bacterial cells (specially Gram + cocci), meaning that it is a clot like structure. These vegetations to some extent affect the heart,to produce Infective Endocarditis, that might later results in further complications like : embolisms, ischemia. Generally, due to the lack of blood supply to this area this will result in further damage and inflammatory RXNs.However, this feature is not necessarily to be diagnosed & recognized easily, even in the presence of fever & requires especial investigation to tell. Regarding the general incidence of Infective Endocarditis in any community,esp the western community where data are available and studies are done,it ranges between 3-9% so it is not low.however, in a study done in Saudi Arabia higher #s were found( 20%) and this is the case in our countries,mainly due to the stander of life as well as the low standers of hygiene specially oral hygiene also the stander of medicine( are we qualified enough to prescribe the proper antibiotic & do surgeries under aseptic condition with no complication?).actually, low oral hygiene is one of the factors contributing to Infective Endocarditis. Unfortunately, our communities are known of their low standers of oral hygiene.

2 Basically, there are several known predisposing factors linked with Infective Endocarditis especially: congenital and valvular heart diseases. Most IV infused drugs and all types of invasive surgeries like invasive catheterization used at different sites may ulcerate and produces abscess that enhances infection used in surgical procedures and the oral dental manipulations might also be associated with development of Infective Endocarditis. Historically, Infective Endocarditis has been associated with Rheumatic heart fever which is caused by group A streptococci.its incidence was higher previously,before the era of penicillins,so in our country at least few % of these pts progresses to Infective Endocarditis because they did not receive the proper antibiotic.however in recent years we have less and less cases of Rheumatic heart fever, since the discovery of penicillin around s. In addition, Infective Endocarditis is associated with prosthetic heart valves used in heart surgery,since nowadays we have a lot of heart surgeries and a lot of valves are replaced, thus the rate of Infective Endocarditis increased because native natural valves are less prone to Infective Endocarditis than the prosthetic. Other predisposing factors are mentioned in the slide.(any periodontal procedure in relation to the gum,damage to the gingival due accumulation of plaque and low stander of hygiene, dental extraction,dental implant (common in our country) all of these if not done under aseptic conditions may result in a problem ).Thats why prophylactic drugs are recommended, however, Sadly, many of our dentists and to a lesser extent GPs, don t emphasize the topic of resistance in our commensal flora, esp in staph and viridians ( as an anaphylactic they give any course of b-lactams which is enough to prevent the development of Infective Endocarditis and that s it,but resistance may develop & consequently,it has been found that 20% of viridans esp mutans and mitis which are found in our oral cavity in large #s, became resistant to erythromycin and penicillin. Group A Strept. is still 100% susceptible to penicillin good for us. Classically, Infective Endocarditis has been classified into acute & subacute.however, its sometimes difficult to differentiate between the two and there is no clear point of cut between the two. Acute Infective Endocarditis often is more associated with Gram + cocci in particular Staph.aureus (commonest), followed by 2-strept with its 2 types (viridians that produce green color when cultured on blood agar due to partial hemolysis,and B hemolytic strept.) and the enterococci which are related to the strept. Thus the classical form of acute Infective Endocarditis is mainly associated first with staph, then followed by strept and rarely others.in contrast, subacute Infective Endocarditis often develops in abnormal valves esp in the presence of congenital

3 abnormalities of the heart valves and rheumatic lesions and these lesions most commonly formed by group A strept. Viridians & enterococci might lead to Infective Endocarditis but less important than the acute. Pathogenesis Generally, all types of Infective Endocarditis ( acute or subacute ) are recognized by fever. this fever is not necessarily to be continuously present, it increases and falls at different times or days, however, the presence of other symptoms may lead us to the diagnosis, that s why its difficult clinically to diagnose Infective Endocarditis. selecting the specific type of the causative microorganism through classifying the streptococci is of great importance, because it helps determining the suitable drug to be used. i.e enterococci and strept. pneumonia are less susceptible to amoxicillin or ampicillin than group A,B think of another drug, knowing the causative agent means reaching 90% of the treatment and helping the pt to use useful drug of reasonable cost. Why group A streptococci? Group A Streptococci contain a special endogenous thin antigenic structure in its cell wall,that is M protein 80 types of it are present and this is important in the immune response and the serology, M protein also inhibits and resists phagocytosis, which cross reacts & interacts with the heart valves i.e mimicry to produce inflammation & damage to the epithelial cells.in addition, viridans esp ( mitis & mutans ) might be associated with M protein like group A & since it is present in the oral cavity it may contribute,with other organisms, to plaque accumulation that result in gingivitis that later may spread from the oral cavity to the lymphatic's and finally, disseminate to the heart to produce Infective Endocarditis. In the past, Group A strept.( known as pyogenes )was more imp. As a causative agent of sore throat and release 2 antigenic structures :M protein,. Carbohydrate cell structures.those now,esp M protein, are responsible for post streptococcal diseases like rheumatic heart disease and glomerulonephritis initially starts as repetitive attacks of sore throat in children then progresses to be observed in young adults. Diagnostic techniques: Usually, We take 3-6blood samples within few days, why???? (in infective endocarditis only few #s of the causative organism will be released to the blood

4 stream from the affected site & the time of this isn t known may be during day or night so more than 1 sample are taken to increase the chance in +culture), then we culture it to increase the # of bacterial cells on a special culture media like blood agar,then use gram stain. In the fig. in the slides the left one shows viridans that causes partial RBCs hemolysis to produce the green color.in the right. Staph. Appears in distinctive yellow color on a special culture media. N.B we use catalase test to tell if a bacteria is staph or strept, in the absence of other tech., using H2O2 solution that shows staph. is Catalase + and strept is catalase -. In relation to the enterococci,its associated with less interactions. Recently,its importance as accusative agent of infective endocarditis has increased due to the fact that larger #s of E.Fecalis or E.faecium is present in our intestines due to the wide usage of cephalosporin's and since these organisms are naturally resistant (intrinsically ) to this drug, the normal state of biological equilibrium has been disturbed and their #s elevated on expense of other commensal bacteria.providing the presence of a certain pathology in the intestines i.e perforation or procedure or colonoscopy, this Fecalis might reach the blood stream and the heart to cause Infective Endocarditis. Recently,70-80% of staph aureues (most common causative agent of acute Infective Endocarditis ) isolated from any specimen are Methicilin resistant i.e MERSA, meaning that penicillin which is the best in treating Infective Endocarditis is useless, in this case other drugs like vancomycin and ticoplanin are used..(ticoplanin is more expensive than penicillin and associated more with resistance, both vancomycin and ticoplanin are wide spectrum drugs against Gram + bacteria). Generally, according many investigation studies, 40% of acute Infective Endocarditis are caused by staph. Viridians are seen to be more in subacute Infective Endocarditis. Actually, any manipulation in the URT,the sinuses, even presence of simple oral or skin lesions, invasive procedures, catheterization and others may produce Infective Endocarditis if the proper anaphylaxis is nt given. The table in the slides is from American literature regarding the causes and the %s of Infective Endocarditis. In short, if we consider this table we see that 80% of Infective Endocarditis are associated with Gram+ cocci ( staph and strept ) NOT bacilli other causes as Gram bacteria associated with epidemiology of the infection in certain country (typhoid fever"salmonella",brucella..).other minor causes like

5 Haemophilus,Cardiobacterium,actinobacillus all of which are part of our normal oral flora,thus,any manipulation in the oral cavity may in the long run progresses to infective endocarditis,if the proper antibiotic isn t given. N.B in our country coagulase staph has been implicated as a causative agent of Infective Endocarditis, in USA its coagulase + mainly. Why? the explanation may be related in part to the life and hygiene standers ( esp. oral hygiene ). Can Fungi cause Infective Endocarditis? Certain category of patients (the immune-compromised, critically ill, those having severe infections, extensive use of antimicrobial drugs, nutritional deficient, invasive catheters' usage in urinary tract or respiratory tract) may develop Infective Endocarditis due to fungal infection mostly candida albicans "accounts to 70-80% of all candidacies", to a lesser extent C. glabrata and C.krusei. First, fungal Candidal infection in the oral cavity or upper respiratory tract URT or in the urinary genital tract i.e vagina that may then disseminate and reach the heart. Its known that fungal Infective Endocarditis is fatal no IV drugs present.the duration of treatment for bacterial Infective Endocarditis ranges between 2-6 weeks. 2-3 specialists must cooperate to determine the duration & the proper antibiotic (set by the experience of a surgeon, a cardiologist, and infectious specialist ). C. albicans : 1-most common in our commensal oral organisms (among fungi) others may be associated. 2-less resistant than Glabrata or krusei, nowadays these two are becoming more important as causative agents of infections because of the development of resistance due to the wide use of azol drugs.previously,70-80%of them were susceptible to flucanazol, this % has dropped to " 20-50%".This means vaginal candidiasis isn t easy to be treated. 3-now in vaginal discharge, the isolated C. albicans has become more resistant, which means there is a change in its epidemiology, after years this resistance may extend to the oral cavity, so albicans may become resistant. 4-any type of URT catheterization or intubation is risky esp. those older than 6o years & the immune-depressed pts where the Dx of candida is difficult because they rely on blood culture that is usu. Negative i.e no yeast in the blood. now, molecular tech.are used in a blood sample. Other causative agents:

6 Histoplasma capsulatum: its rare in our communities, and seen in (North & south USA) Aspergillus :often seen in immune- suppressed pts. How tell that a fungi is the cause of certain case of Infective Endocarditis? Simply, by excluding other causes" specially bacterial ones " : 1-if the culture is -. (At least 50% of pts with Infective Endocarditis had already taken antibiotics either by community physicians or by themselves and because the symptoms of Infective Endocarditis, may be mistakenly thought to be simple bacterial infection the pt may take an antibiotic then the symptoms don t resolve he visits a doctor and due to the misuse of the antibiotic the culture becomes -, so first we need to stop the offending drug ). 2-no response to antibiotics ( given for 2-4 weeks,still no improvement..think of candida!). 3-immune status 4-presense of oral thrush& lesions or manipulation by the endoscope, i.e. search for skin lesions even if mild, oral infection,sites for IV needles, etc. Diagnosis: Up to 90% of infective endocarditis is based on the signs or symptoms & require also ECG& ultrasound. The history is very imp. Esp in diagnosis of fungal infections, or if the pt had had any dental manipulation like tooth extraction,etc, all of this might help. The real problem is in knowing the offending agent, since most cultures are the Dr has to guess!! that's why a combination of penicillin & gentamycin was given to the pts in the past, now they shifted to gentamycin &Rifampen or third generation cephalosporin's to cover many causative agents if Gram+ bacteria, after 2-3 weeks and there is no response we shift to an anti-fungal. Recently, due to the large #s of cultures, the classical diagnostic tech. i.e to have a blood sample and to send to the lab.has largely been replaced by the easier molecular tech. i.e PCR, where we search for the DNA of certain fungi or bacteria these organisms like C.trachomatis, in UTIs, and Haemophilus Influanza or cardiobacterium are fastidious meaning that difficult to be cultured easily, so use molecular technique.. Remember that the basis of a good doctor starts in taking a good history. THE END Special thx to Azhar Done by: Abeer Shamasneh