Idea Transcript
Microorganisms Causing Cardiac Infections Dr. Edhie Djohan j Utama,, SpMK p Dep. Mikrobiologi FKUSU Medan
CARDITIS Carditis,, or inflammation of the heart,, is most conveniently broken down into three categories: Pericarditis -
Inflammation of the pericardium
Endocarditis -
Inflammation of the heart muscle
Myocarditis
Inflammation of the endocardium
Classification • OLD – Subacute Bacterial Endocarditis • Death in 3 3-6 6 months
– Acute Bacterial Endocarditis • Death in < 6 weeks
• NEW – Native N ti V Valve l E Endocarditis d diti – Prosthetic Valve Endocarditis
INFEKSI
PENYEBAB TERBANYAK
DIAGNOSE LABORATORIUM
E d Endocarditis diti
Streptococcus spp (60-80%) (60 80%)
3 sampell untuk t k kultur k lt darah d h yang di-ambil di bil pada 3 daerah berbeda dilakukan pengambilan 1 – 2 jam sebelum pemberian antimikroba antimikroba.
Staphylococcus spp (2035%) Batang Gram Neg. (2-13%) Bakteri lain2 (5%) Jamur (2-4%) (Candida) Kultur negatip (5-25%)
Sampel darah diambil 1 sampel untuk anaerob dan satu untuk kultur aerobic masing2 i 2 10 – 20 mll
Myocarditis / Pericarditis Virus
Enterovirus Adenovirus Herpes virus
Pemeriksaan serologic, g , jjika perlu p dikombinasikan dengan kultur dan untuk PCR.
Influenzae virus Parainfluenza virus
Bakteri
Staphylococcus aureus Streptococcus pneumoniae
Pemeriksaan mikroskopis dan kultur. Tes DNA jika perlu
Enterobacteriaceae Mycobacterium tuberculosis Mycoplasma pneumoniae
Tes serologik
INFEKSI
PENYEBAB TERBANYAK
DIAGNOSE LABORATORIUM
Bakteri a e
Staphylococcus aureus
Pemeriksaan e e saa mikroskopis os op s dan da kultur. u u . Tes es DNA jika perlu
Streptococcus pneumoniae Enterobacteriaceae Mycobacterium y tuberculosis Mycoplasma pneumoniae
Tes serologik
Neicceriae spp
Kultur dan mikroskopis
Gram negative anaerob Actinomyces & Nocardia Rickettsia
Tes serologik
Chl Chlamydia di trachomatis t h ti
Fungi
Candida spp Aspergillus spp
Mikroskopik dan kultur jamur Jikas perlu PCR
C Cryptococcus neoformans f
Protozoa
Toxoplasma gondii Trypanosoma cruzi
Helminthes Tricinella spiralis
Mikroskopik dan kultur jamur Jikas perlu PCR Tes serologik
Kayser, Medical Microbiology, 2005
Infective Endocarditis • Adult Ad lt population l ti : – Rheumatic Heart Disease • • • •
20 – 25% of cases of IE in 1970’s & 80’s 7 – 18% of cases in recent reported series Mitral site more common in women Aortic site more common in men
– Congenital g Heart Disease • 10 – 20% of cases in young adults • 8% of cases in older adults • PDA, VSD, bicuspid aortic valve (esp. in men>60)
• Pediatric population – The vast majority (75-90%) of cases after the neonatal period are associated with an underlying congenital abnormality • Aortic valve • VSD • Tetralogy of Fallot
– Risk Ri k off post-op t i f ti iin children infection hild with ith IE iis 50%
Infective Endocarditis • Typically involves the valves : – May involve all structures of the heart • Chordae tendinae • Sites of shunting • Mural lesions
– Infection I f ti off vascular l shunts, h t by b strict ti t definition, is endarteritis, but lesion is the same
Infective Endocarditis • Pathogenesis Endothelial damage
Platelet-fibrin thrombi
Microorganism adherence
Characteristics of Causative Organisms g • Adherence factors critical for g growth in the vegetation – Can adhere to damaged valves (Staph, Strep and Enterococci have adhesins that mediate attachment) – Staph adhesin binds fibrinogen and fibronectin – Bacteria trigger gg tissue-factor p production from local monocytes and induce platelet aggregation so the organisms become enveloped in the vegetation – Protection from immune clearance leads to large numbers of bacteria (109-1010 per g of tissue)
• In the vast majority j y of patients, endocarditis can be effectivelyy treated with medication and/or surgery. g y • Nevertheless, endocarditis can cause serious damage or even death if left untreated.
S. Aureus mitral valve vegetation, anterior t i lleaflet fl t
Risk Factors • Structural heart disease – Rheumatic, Rh ti congenital, it l aging i – Prosthetic heart valves
• • • •
IInjected j t d drug d use Invasive procedures (?) Indwelling vascular devices Other infection with bacteremia (e.g. pneumonia, meningitis) • History of infective endocarditis
Infective Endocarditis • Intravenous Drug Abuse – Risk is 2 – 5% per pt./year – Tendency to involve right-sided right sided valves • Distribution in clinical series – 46 – 78% tricuspid – 24 – 32% mitral – 8 – 19% aortic
– Underlying valve normal in 75 – 93% – S. aureus predominant organism (>50%, 6070% of tricuspid cases)
Infective Endocarditis Microbiology – Neonates – Older children
•
: S. aureus, coag – staph, group B strep : 40% strep, p, S. aureus
Majority of cases caused by (Adult Cases) : – – – –
streptococcus, staphylococcus, p y enterococcus, or fastidious gram negative cocco-bacillary forms : Gram negative organisms : • P P. aeruginosa most common • HACEK - slow growing, fastidious organisms that may need 3 weeks to grow out of culture – – – – –
Haemophilus sp. Actinobacillus Cardiobacterium Eikenella Kingella
INFECTIVE ENDOCARDITIS • • • • • • • • • •
Staphylococcus aureus (30-40%) group streptococci ((18%)) Viridans g Enterococci (11%) Coagulase-negative staphylococci (11%) Streptococcus bovis (7%) Other streptococci (5%) Non-HACEK Gram negatives (2%) HACEK Organisms (2%) Fungi (2%) “Culture negative” (2-20%)
• Portals of entry : = Oral, skin, URI : S. viridans, Staphylococci, HACEK = GI = GU = Nosocomial
: S. S bovis (ass (ass. Polyps & colonic tumors) : G –ve (Enterobacteriacae) : Enterococci : intravascular catheters : S.aureus
Like other oral viridans streptococci, S. sanguis commonly enters the bloodstream following dental procedures
Infective Endocarditis • Gram negative organisms –P P. aeruginosa most common – HACEK - slow growing, fastidious organisms that may need 3 weeks to grow out of culture • • • • •
Haemophilus sp. Actinobacillus Cardiobacterium Eikenella Kingella
• Lik Like other th orall viridans i id streptococci, t t i S. S sanguis i commonly enters the bloodstream following dental procedures
Prosthetic valve : 2mo , NI : Intraoperative contamination : Bacteremic postoperative : S.coag.-ve, S. aureus, G-ve rod, diphtheroids, fungi : >12mo. = Community-acquired native valve ::>85% 85% S.coag-ve S.coag ve : MRSA Transvenous pacemaker and/or implanted defibrillator : NI , within weeks, S. aureus, S.coag –ve Injection drug users - TV - S.aureus S aureus strains : MRSA - Lt side : varied etiology & abnormal valve : P.aeruginosa, Candida spp., : Bacillus, Bacillus Lactobacillus Lactobacillus, : Corynebacterium -Polymicrobial
Causative organisms of infective endocarditis d diti • • • • •
Enterococci* p Viridans streptococci* Staphylococcus aureus* Coagulase-negative Coagulase negative staphylococci Enterobacteriace
*most common organisms associated with native valve endocarditis
Native Valve IE • Viridans Streptococci and S. S bovis – Aqueous Penicillin G 12-20 million units/day continuously or divided q4 or q6 for 4 weeks – If intermediate susceptibility to penicillin, aqueous penicillin G 24 million units or ceftriaxone 2 g q24 PLUS aminoglycoside for the first 2 weeks
•
Aminoglycosides for synergy – Low concentrations are adequate (1-3 mcg/ml) – Gentamicin 3 mg/kg divided q12 or q8 – Little data for q24 dosing
• Enterococci, ampicillin sensitive – High g rates of failure – β-lactams are bacteriostatic, must combine with aminoglycoside for optimal therapy – High-level gentamicin resistance occurs in 35% • High-dose ampicillin for 8-12 weeks
•
Enterococci,, ampicillin p resistant – Vancomycin plus gentamicin
•
Enterococci, vancomycin resistant – Linezolid or daptomycin – Penicillin + vancomycin + gentamicin ?
DIAGNOSIS IE: IE: Because the clinical features of the disease can be quite variable and often nonspecific, nonspecific diagnosis is mainly based on laboratory tests. g testing g are the most important. p Blood culture and serologic Always use venous blood to isolate the organism. A positive blood culture with some or all of the symptoms listed is needed to obtain the diagnosis diagnosis. • • • •
Blood is normally considered sterile Means of delivery for many microbial agents Primary viremia/bacteremia clinically inapparent Secondary viremia/bacteremia have clinical signs due to activation of inflammatory process
Detection of Bacteremia • • • • • •
Specimen collection Specimen volume N b off bl Number blood d culture lt Miscellaneous Universal precautions Aseptic techniques
Blood Cultures (Microbiology Diagnostic) 3 sampel untuk kultur darah yang di-ambil pada 3 daerah berbeda Dilakukan pengambilan 1 – 2 jam sebelum pemberian antimikroba Sampell darah S d h di diambil bil 1 sampell untuk t k anaerob bd dan satu t untuk t k kultur k lt aerobic masing2 10 – 20 ml (Kayser, Medical Microbiology, 2005) Literatur lain : MULTIPLE BLOOD CULTURES BEFORE EMPIRIC THERAPY : • If not critically y ill – 3 blood cultures over 12-24 hour period – ? Delay therapy until diagnosis confirmed • If critically ill – 3 blood cultures over one hour • No more than 2 from same venipuncture • Relatively constant bacteremia
Specimen volume & number of bl d cultures blood lt • Bacteremia in adults have a number of CFU < 30 CFU/ml • Adults 10-20 10 20 ml, ml minimal 10 ml • Children 1-5 ml • Number of blood cultures – 1 bottles 80-92% – 2 bottles 90-99% – 3 bottles 99.6% (be space p an hour apart p ) Lecturer: Kanya Preechasuth : Clinical microbiology, Faculty of Associated Medical Sciences, CMU, Jan 12, 2006
Timing of collection > 1 hr
influx of bacteria
fever, chill
normall host h defense d f mechanisms h i
bacteria was cleared Ideal
30 min. before peak temperature
Miscellaneous • Blood culture media – Trypticase soy broth or Brain heart infusion broth – Thio broth or thioglycolate broth – Blood : culture media = 1:10 (5:50) • neutralized bactericidal property of blood • high ratio : prolonged detection time • low ratio : inhibit byy serum factors
Miscellaneous • Anticoagulant – 0.025-0.05% Sodium polyanetol sulphonate (SPS) • Inactivate neutrophils • Inactivate antimicrobial (amonoglycosides, polymixin) • Inhibit phagocytosis • Inhibit growth of Neisseria gonorrhoea, N. meningitidis • Prevent by add 1-1.2% gelatin Heparin EDTA, Heparin, EDTA and citrate inhibit numerous organisms
Miscellaneous • Additives – 10-20% Hypertonic sucrose or sorbitol – Penicillinase – Antimicrobial-adsorbing (resin): nonspecific adsorbtion
• Incubation at 35-370C and 5% CO2 • Ventilation for strictly aerobe (Pseudomonsa, and fungi)
Conventional culture •
Culture media – – – –
•
TSB 50 ml, 10 ml 0.025% SPS 1-1.2% gelatin 5% CO2
= Conventional culture = Lysis centrifugation = Automated blood culture system
Blood sample – Adults 5 ml, 3 bottles – Children 1 ml, 2 bottles
•
Blind subculture – – – –
•
Blind aerobic subculture : after 24 hrs Blind anaerobic subculture : after 48 hrs Earl blind ssubculture Early bc lt re : after 6 6- 18 hrs Final subculture : after 5-7 days (bacteria) or 14 days (fungal)
Chocolate agar at 35-370C and 5% CO2
Conventional culture • Microscopic examination • Gram’s stain (105 CFU/ml)
Conventional culture • Macroscopic examination • Sign of growth (106-107CFU/ml) – Turbidity – Gas bubbles in the medium – Hemolysis H l i off RBC RBCs – The appearance of small aggregates of bacterial or fungal growth on the surface of sedimented RBC
Growth detection : • • •
Preliminary report : by phone or report Isolated on an appropriated medium Identification & susceptibility test
Probable contamination : • • • •
2-3 % contamination Bacillus spp., Corynebacterium spp., or coagulase-negative staphylococci in only one of several cultures Multiple organisms from only one of several cultures The organisms causing the infection at a primary site of infection is not the same as the isolated from the blood culture (physician-based)
Probable pathogen : • •
Growth of the same organism in repeated cultures Growth of certain organisms such as member of Enterobacteriaceae, St Strep pneumoniae, i gram-negative ti anaerobe, b and d Strep St pyogenes
Automated blood culture system • BecT/Alert® (Organon Teknika) • BACTEC® 9240 (Becton Dickinson) • Detection unit - 120, 240 cells - agitate continuously - monitored it d 144 times/days ti /d (10 min. i iinterval) t l)
• Computer system • Culture medium - 20, 30, 40 ml. Trypticase soy broth - up p to 4 ml. blood (p (pediatric)) - up to 10 ml. blood (adult) - anticoagulant = SPS - supplements with BHI solids and activated charcoal
“Culture Negative” IE • Less common with improved blood culture methods • Special media required : – Brucella, Mycoplasma, Chlamydia, Histoplasma, Legionella, Bartonella
• Longer incubation may be required – HACEK
• Coxiella burnetii (Q Fever), Trophyrema whipplei pp will not g grow in cell-free media
Other microbiologic methods • PCR – Coxiella burnetii – Tropheryma whipplei – Bartonella henselae
• Serology – – – – –
Coxiella burnetii Bartonella Brucella Legionella Chlamydophila psittaci
Treatment of IE • Native vs. Prosthetic Valve • Bactericidal therapy is necessary • Eradication of bacteria in the vegetation g – May be metabolically inactive (stationary p phase) ) – May need higher concentrations of antimicrobial agents
Antimicrobial Therapy • Most patients are afebrile in 3-5 days • Long duration of therapy (4-6 (4 6 weeks or more) • Combination therapy most important for – Shorter course regimens – Enterococcal endocarditis – Prosthetic valve infections
• Viridans Streptococci and S. bovis – Aqueous Penicillin G 12-20 million units/day continuously or divided q4 or q6 for 4 weeks – If intermediate susceptibility to penicillin, aqueous penicillin G 24 million units or ceftriaxone 2 g q24 PLUS aminoglycoside for the first 2 weeks
Antimicrobial Therapy • Antibiotics are usually administered intravenously for 2-6 weeks. Duration depends on the virulence of the pathogen pathogen. • The drug of choice for most cases of viridians streptococcal endocarditis is penicillin penicillin. – The cure rate for viridans streptococcal endocarditis is above 90%. – Without treatment, VSE is typically fatal within six months.
• Antifungals alone are not enough to cure fungal IE, although Amphotericin B is often administered in conjunction with surgery.
Infective Endocarditis: Treatment Prolonged, parenteral, bactericidal antibiotics = Highly g y sensitive streptococci p ((MIC0.1, < 0.5) · Penicillin G 4 weeks and Gentamicin 2 weeks · Vancomycin (for Pen-allergic) 4 weeks = Enterococci · Pen G or Ampicillin and Gentamicin 4-6 weeks · Vancomycin (for Pen-allergic) 4-6 weeks and Gentamicin (Department of Internal Medicine, Tokyo Metropolitan Geriatric Hospital)
Treatment of IE = Antibiotic therapy must persist for at least 14 days, even if symptoms disappear prior to that time. = A combination of antibiotics, rather than a single antibiotic, is always used. If no organism has been isolated after repeated attempts the recommended therapy is: Ampicillin, given IV every 4 hours + Gentamycin, given every 8 hours.
= If an organism has been isolated isolated, then the antibiotic regimen is based on the species of the etiologic agent, the age of the patient and the extent of the disease. = If antibiotic tibi ti therapy th is i nott successful f l surgical i l removall off iinfected f t d endocardium may be necessary. This is especially true with fungal infections and when the patient has an intracardiovascular prosthesis. Nonspecific therapy includes:
Chemoprophylaxis Adult Prophylaxis: Dental, Oral, Respiratory, Esophageal Standard Regimen Amoxicillin 2g PO 1h before procedure or A i illi 2g Ampicillin 2 IM/IV 30m 30 before b f procedure d Penicillin Allergic Clindamycin y 600 mg PO 1h before procedure or 600 mg IV 30m before Cephalexin OR Cefadroxil 2g PO 1 hour before Cefazolin 1.0g IM/IV 30 min before procedure Azithromycin or Clarithromycin 500mg PO 1h before
Native Valve IE • S. S aureus – Penicillinase-resistant semi-synthetic penicillin (oxacillin or nafcillin) 1.52 g IV q4 or cephalosporin (cefazolin 1-2 g IV q8) for 4-6 weeks – Aminoglycoside synergistic but does not affect survival survival, not recommended – Short course in right-sided IE • 2 weeks of semi-synthetic penicillin and aminoglycoside
• MRSA (Methicillin-resistant S. aureus) – – – –
Vancomycin is bacteriostatic Vancomycin plus aminoglycoside or rifampin Daptomycin Linezolid
• HACEK – Ceftriaxone 2 g IV q 24 x 4-6 weeks
Prosthetic Valve IE • Staphylococci most common – Coagulase negative staphylococci
• Enterococcus • Nutritonally variant streptococci • Fungi
Candidal Endocarditis •
Candidal endocarditis is a severe condition that has been traditionally associated with an exceptional high mortality and recurrence rates. Both nati e and prosthetic valves native al es ma may be affected affected. Combining medical with ith surgical interventions, the hospital survival rates have been commonly below 50%. The highest long term survival rate is 67%
•
Open heart surgery is one of the most frequent risk factors for fungal endocarditis, with a rate of 0.23% to 1% of all cardiac surgeries.
•
Fungal prosthetic valve endocarditis has been reported to be 9.6% and 4 3% respectively 4.3%, respectively.
•
Intravenous drug abusers have the highest rates of fungal endocarditis. Candida spp. account for between 50 and 60% of cases [1982].
•
Neonates may develop endocarditis as part of the picture of disseminated neonatal candidiasis. Candida spp. causes all of the infections.
Candidal Pericarditis • Candida p pericarditis is a rare but serious condition that can lead to severe sepsis, cardiac tamponade and death if not diagnosed and treated p promptly p y [[1863]. ] Candidal pericarditis p may occur in relation to obvious hematogenous seeding from invasive candidiasis • Candida albicans is the most frequent species, followed by C. tropicalis. Of the 26 cases reviewed byy Rabinovici et al. only y 18 had species identification. Of these 78% of them were caused by Candida albicans.
Candidal Endocarditis 1.
Blood cultures. The sensitivity of blood cultures to detect invasive candidiasis is generally low. However, the intravascular site of this infection changes that rule rule. Indeed Indeed, when compared with other fungal agents able to cause endocarditis, Candida is the most frequently cultured [1981].
1.
Rates of 83 to 95% of positive blood cultures for Candida spp. have been reported in reviews of fungal endocarditis [1499 1640]. [1499, 1640] In the review by Nguyen et al al. of 18 prospectively identified cases of candidal prosthetic valve endocarditis, all patients had several positive blood cultures The mean and median number of positive blood cultures. cultures for this group were 7 and 5 respectively [1640].
Antifungal therapy Very few authors have reported successful treatment with a non-surgical approach for this condition. Indeed, the chronic nature of Candida makes eradication of this infection difficult and long-term antifungal therapy is usually necessary.
•
• •
Amphotericin B. Despite being the agent recommended by experts,
amphotericin B has two disadvantages when treating this candidal endocarditis. – First, its penetration into the vegetation has been shown to be poor. – Second, Second its toxicity profile frequently limits therapy therapy. Nevertheless, amphotericin B, alone or in combination with flucytosine, is still considered the gold standard for the initial phase of therapy. Daily doses should be the maximum tolerated dose in the range of 0.5 to 1 mg/kg/day, until a total dose of ~ 2 grams has been given.
Flucytosine. Because of the previously mentioned difficulty on curing Candida
endocarditis, the synergism between amphotericin B and flucytosine is attractive.
Azoles The Azoles. Th availability il bilit off orall antifungal tif l agents t h has added dd d a very iimportant t t ttooll for the long term treatment of a condition with a very high relapsing rate. Likewise, there are no useful data on the potential role of itraconazole. The characteristics of fluconazole make it attractive for the treatment of Candida endocarditis.
Candida species and Candida Pericarditis Candida albicans is the most frequent species, followed by C. tropicalis. Of the 26 cases reviewed by Rabinovici et al. only 18 had species identification. Of these 78% of them were caused by Candida albicans.
Specific Diagnostic Strategies To make the diagnosis of Candida pericarditis, one should : • Recognize the patient populations at risk, • Perform an echocardiogram when suspecting the picture, • Perform a pericardiocentesis, • Isolate Candida from the pericardial fluid or tissue, and • Ideally, Id ll h have a hi histopathologic t th l i confirmation fi ti off yeastt fforms iin pericardial i di l tissue.
Therapies •
Treating T ti Candida C did pericarditis i diti requires i an aggressive i approach h th thatt combines surgical and medical treatment.
•
prolonged courses of amphotericin B but the precise length of therapy is not defined
Less prevalent causative agents include • Other bacteria – The HACEK Group • Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis,, Eikenella corrodens,, and Kingella g species
– Usual bacterial causes • Bacillus cereus, Clostridium perfringens, Mycobacterium tuberculosis, Nocardia asteroides,, Coxiella burnetii,, etc.
• Fungi – Candida and Aspergillis p g species p
Drugs (usually causing hypersensitivity myocarditis)) – Chemotherapeutic p drugs g - Doxorubicin and anthracyclines, streptomycin, cyclophosphamide, interleukin-2, anti-HER-2 receptor antibody/Herceptin – Antibiotics - Penicillin, chloramphenicol, sulfonamides – Antihypertensive drugs - Methyldopa, spironolactone – Antiseizure drugs - Phenytoin, carbamazepine – Amphetamines, cocaine, catecholamines
Pericarditis • Also called: Adhesive Pericarditis, Postmyocardial Pericarditis, Acute Pericarditis, Bacterial Pericarditis, Polyserositis, Chronic Pericarditis, Constrictive Pericarditis. • Pericarditis is an inflammation of the pericardium, the thin, fluid-filled sac surrounding the heart. It can cause severe chest pain (especially upon taking a deep breath) and shortness of breath.
• Most patients p with pericarditis also have some fluid in the pericardial sac.
Myocarditis • Also called: Fulminant Myocarditis, Acute Myocarditis • Myocarditis is an uncommon inflammation of the heart muscle ((myocardium). y ) This inflammation can be caused by infectious agents, toxins, drugs or for unknown reasons. It may be localized to one area of the heart heart, or it may affect the entire heart. pp y 50% of the time,, myocarditis y is • Approximately classified as idiopathic although a viral etiology is often suspected but unproved.
Myocarditis y • Despite three decades of study, the diagnosis and d managementt remain i controversial. t i l • The exact incidence and prevalence remain unknown. • Clinical p presentation varies • Most patients are asymptomatic and recover without treatment
Etiology Agents of Myocarditis • Viral - Enterovirus, coxsackie B, adenovirus, influenza, cytomegalovirus, poliomyelitis, Epstein-Barr virus, HIV-1, viral hepatitis, mumps, rubeola, varicella variola/vaccinia varicella, variola/vaccinia, arbovirus arbovirus, respiratory syncytial virus virus, herpes simplex virus, yellow fever virus, rabies • Rickettsial - Scrub typhus, Rocky Mountain spotted fever, Q fever • B Bacterial t i l - Diphtheria, Di hth i ttuberculosis, b l i streptococci, t t i meningococci, i i brucellosis, clostridia, staphylococci, melioidosis, Mycoplasma pneumoniae, psittacosis • Spirochetal - Syphilis, Syphilis leptospirosis / Weil disease disease, relapsing fever/Borrelia, Lyme disease • Fungal - Candidiasis, aspergillosis, cryptococcosis, histoplasmosis, actinomycosis blastomycosis, actinomycosis, blastomycosis coccidioidomycosis coccidioidomycosis, mucormycosis • Protozoal - Chagas disease, toxoplasmosis, trypanosomiasis, malaria, leishmaniasis, balantidiasis, sarcosporidiosis • Helminthic - Trichinosis, echinococcosis, schistosomiasis, heterophyiasis, cysticercosis, visceral larva migrans, filariasis
Etiology Agents of Myocarditis Viruses :
Enteroviruses Influenza A and B Adenovirus Herpes HIV
Bacteria :
Beta-hemolytic Streptococcus Corynebacterium diphtheria B Borrelia li b burgdorferi d f i Enterococcus spp Chlamydia y psittaci p Neisseria meningitidis Mycoplasma pneumonia Staphylococcus aureus •
pto
Protozoa
:
Trypanosoma cruzii Toxoplasma gondi
Helminths
:
Trichinella spiralis Echinococcus
Autoimmunity :
Infection associated Auto--immune disease associated Auto Primary autoimmunity
Hypersensitivity:: Penicillins Hypersensitivity Methyldopa Sulfamethoxazole T i i Toxicity:
C Catecholamines h l i Cocaine Ethanol
Viral Myocarditis • Coxsackievirus A9 is a self-limiting myocarditis, whereas coxsackievirus B3 causes severe myocarditis resulting in a high mortality rate rate. – The induction of the coxsackie-adenovirus receptor (CAR) and the complement deflecting protein decay accelerating factor (DAF, CD55) may allow efficient internationalization of the viral genome. Viral replication may lead to further di disruption ti off metabolism t b li and d perturbation t b ti off inflammation i fl ti and d itits response. Vasospasm induced by endothelial cell viral infection may also contribute to further damage. New evidence of dystrophin disruption by expression of enteroviral protease 2A points to yet another unique pathogenic mechanism.
• Approximately 50% of the time, myocarditis is classified as idiopathic, although a viral etiology is often suspected but unproved – Viral - Enterovirus, coxsackie B, adenovirus, influenza, cytomegalovirus, poliomyelitis, Epstein-Barr virus, HIV-1, viral hepatitis, mumps, rubeola, varicella, variola/vaccinia, arbovirus, respiratory syncytial virus, herpes simplex virus, yyellow fever virus,, rabies
Viral Infection of Heart (Myocarditis) Viral myocarditis results when the muscles in the walls of heart become infected with a virus. Entereoviruses and adenoviruses are the primary p y causative agents of viral myocarditis. Symptoms • Fever • Cough • Nausea • Vomiting • Myalgia • Arthralgia • Palpitation • Heart failure (in severe cases)
Candidal Myocarditis • Hematogenous seeding of Candida into the myocardium was frequently found in the early autopsy reviews of patients dying with systemic invasive candidiasis. • The lack of inflammatory response is most notable in immunosuppressed patients
Medical Care •
Treatment of myocarditis includes supportive therapy for symptoms of acute heart failure with use of diuretics, nitrates/sodium nitroprusside, and angiotensin-converting enzyme (ACE) inhibitors. – Inotropic drugs (eg, dobutamine, milrinone) may be necessary for severe decompensation, although they are highly arrhythmogenic. – Long-term treatment follows the same medical regimen, including ACE inhibitors, beta-blockers beta blockers, and aldosterone receptor antagonists antagonists. However However, in some instances, some of these drugs cannot be implemented initially because of hemodynamic instability. • No benefit has been established for the use of antiviral agents, although some ssmall a se series es have a e de demonstrated o st ated their t e efficacy e cacy (the (t e efficacy e cacy o of interferon-alpha te e o a p a will be evaluated in the ongoing ESETCID).
• Viral myocarditis is typically a mild disease and responds well to bed rest. Bacterial, fungal and protozoan myocarditis can be treated with the appropriate antibiotics. antibiotics Gl Glucosteroids costeroids and other immunosuppressive drugs are CONTRAINDICATED.
Chlamydia pneumoniae as an emerging risk factor in cardiovascular disease. •
Seroepidemiologic studies have associated C. pneumoniae antibody with coronary artery disease, myocardial infarction, carotid artery disease, and cerebrovascular disease. The association of C. pneumoniae with atherosclerosis th l i iis corroborated b t db by th the presence off th the organism i iin atherosclerotic lesions throughout the arterial tree and the near absence of the organism in healthy arterial tissue. C. pneumoniae has also been isolated from coronary and carotid atheromatous plaques.
•
Compelling evidence of the association between C. pneumoniae and atherosclerosis has been obtained by polymerase chain reaction (PCR), immunocytochemical (ICC) staining, and electron microscopy, which have detected C. pneumoniae in atherosclerotic lesions
•
A causative role of C. pneumoniae infection in cardiovascular disease has not yet been firmly established established. However However, the high frequency of infection found in human atherosclerotic tissue in comparison to normal tissue, the induction and progression of atherosclerotic-like inflammatory changes in infected animal models of atherosclerosis, and the early results from antichlamydial intervention studies in humans are consistent with a causative role of C. pneumoniae in the disease process.
Infection, inflammation and atherosclerosis • C. pneumoniae, H. pylori, Porphyromonas gingivalis, Cytomegalovirus, Herpes simplex virus, Hepatitis A, B, and C virus linked with an increased risk of cardiovascular diseases • Proinflammatory effects of infection – increased CRP, cytokines
MYOCARDIAL INFARCTION • Myocardial infarction can occur in the absence of the common risk factors such as h hypercholesterolemia, h l l i di diabetes b mellitus lli or cigarette smoking. The sequence of events that leads to acute myocardial y infarction includes atherosclerotic plaque formation, plaque rupture, coronary artery thrombosis and coronary occlusion. occ us o Anything yt g tthat at leads eads to p plaque aque rupture uptu e can result in myocardial infarction. ETIOLOGY ETIOLOGY: • Chylamydia pneumoniae, a Gram-, pleomorphic, obligate intracellular parasite.
DIAGNOSIS MYOCARDIAL INFARCTION : 1. Non-specific indices of tissue necrosis and inflammation a. Polymorphonuclear leukocytosis b. Erythrocyte sedimentation rate that rises more slowly than the WBC count 2. The electrocardiogram 3. Serum enzyme changes a Creatine phosphokinase (CK) a. b. Lactic dehydrogeinase (LDH) 4. Cardiac imaging 4 5. Presence of chlamidia in the plaque 6. Presence of antibiodies to C. pneumoniae
TREATMENT:
MYOCARDIAL INFARCTION
= Treatment for the infection is administration of one of these compounds (listed in order from most effective to least efficatious):
= Macrolide M lid antibiotics tibi ti ((erythromycin, th i azithromycin, ith i clarithromycin) Tetracyclines Fluoroquinolones (ciprofloxacin, norfloxacin and ofloxacin)
Infectious arthritis •
An infection of native joints leads generally to suppurative arthritis, which may be of one joint (monarticular) or several joints (oligoarticular).
•
Bacteria that produce symptoms in multiple joints during bacteraemia bacteraemia, such as Neisseria gonorrhoeae, may also induce inflammation in the neighbouring tendon sheaths. Viral infections frequently involve multiple joints and produce inflammation without suppuration.
•
Chronic granulomatous monarticular arthritis may occur because of infection with either mycobacteria or fungi, which must be differentiated from other causes of chronic monarticular arthritis.
•
A sterile arthritis may occur early in infection (as with hepatitis B), or later (as with a post-infectious arthritis). Any patient presenting with an inflamed joint should have infection as a diagnostic possibility and appropriate cultures must be performed performed.
Clinical Microbiology and Infection 12 (4), Volume 12 Issue 4, Page 309 – 314 April 2006 314,
Rheumatoid arthritis • An inflammatory joint disorder primarily characterised by symmetrical polyarticular synovitis. • * Affects ff 1-3% % off population. • * F 2-3x > M. • * Onset any age – more common 25 to 50 years (peak age of onset is 35-45 years). • * Associated with reduced life expectancy and increased disability. disability • * Generally considered as a systemic disease – but, in the early stages it is only an articular disease, with the systemic t i extra-articular t ti l manifestations if t ti nott developing d l i until late in the disease
Aetiology: • Unknown – probably multifactorial inappropriate inflammatory response response. • Genetic predisposition (HLA-DR4 antigen increases risk by 5x) – localised to a pentapeptide in HLA-DRB1. • Environmental, Environmental infectious (parvovirus) (parvovirus), diet, trauma or psychological factors may play a role in initiating immune response response. • Pathogenesis
Pathogenesis • Inciting agent activates immune system --> immunological reactions --> immune complexes in synovial fluid activate complement --> > inflammatory response --> > joint destruction destruction. • Earliest change is inflammation and oedema of synovium with increased vascularity and increased production of synovial fl id – shows fluid h evidence id off CD4 CD4+ T helper h l cells ll migrating i ti iinto t the joint. hypertrophy, synovial cells proliferation, proliferation • Next the synovial villi hypertrophy increased vascularisation (angiogenesis) and pannus form (granulation tissue that grows across surface of articular cartilage g from adjacent j synovium). y ) • This is followed by destruction of cartilage by pannus – mediated by pro-inflammatory cytokines (eg TNF-alpha, interleukin 1 beta interferon interleukin-1-beta, interferon-gamma) gamma) and metalloproteases (eg collagenases).
Lab tests are not diagnostic Blood – increased ESR in 90%; normochromic normocytic anaemia Synovial fluid – during active joint inflammation --> cloudy, sterile, reduced viscosity, and increased white blood cells. Rheumatoid factor – present in 75% of those with rheumatoid arthritis – higher prevalence in those with extrarticular manifestations – good prognostic test test, as those who are positive for rheumatoid factor have a poorer prognosis. Higher prevalence of other autoantibodies are also seen (antikeratin antibodies, antiperinuclear antibodies, anti-RA 33 antibodies)
Cardiovascular Syphilis • Although morphological involvement of the cardiovascular system occurs in 80% of cases of.tertiary syphilis only about 10% of these are manifested clinically. • The spirochetes evoke endarteritis in the vasa vasorum of the aorta and coronary ostia. Clinical manifestations occur in 15 - 30 years after infection. – 1 Aortic aneurysm y – 2 Aortic Valve Disease – 3 Coronary Artery Disease
Treatment of syphilis Early: • Benzathine Penicillin, 2.4 MU intramuscularly, (1.2 MU into each buttock ) Two doses, buttock.) doses one week apart. apart • Second line treatments (all oral) are: Doxycycline 100mgs b.d for 14 days. Or Erythromycin (oral) 500mgs qid for 14 days. Or Azithromycin 50 mg daily for 14 days. Late, latent: • 3 doses of Benzathine penicillin 2.4 MU IM given at weekly intervals (or doxycycline 100-200mg 100 200mg bd for 28 days). days) Late, neurosyphilis or eye involvement or any stage with coincident HIV infection: • Procaine penicillin IM (1.8-2.4g) plus oral probenecid 500mg qid for 17 days (or doxycycline 200mg bd for 28 days).
Diagnosis • Acute myocarditis is defined histologically as inflammation of the myocardium m ocardi m with ith associated myocellular m ocell lar necrosis necrosis. • Gold Standard is endomyocardial biopsy. • Previously Dallas criteria were used, now WHO/ I t International ti l Society S i t and d Federation F d ti off Cardiology C di l T Task k Force define: - Active myocarditis: > 14 leucocytes/mm with necrosis and dd degeneration ti - Chronic myocarditis >14 leucocytes/mm but no necrosis or degeneration • Further classified according to inflammatory infiltrate i.e. neutrophils, monocytes and macrophages in the acute stage, with lymphocytes and fibroblasts in the later stages.
Mucous membrane or other colonized tissue
Valvular endothelium trauma turbulence metabolic Platelet fibrin deposition Platelet-fibrin
Trauma
Nonbacterial thrombotic endocarditis (NBTE)
Bacteremia Complement Ab Adherence Colonization bacterial division fibrin depositon platelet aggregation extracellular proteases neutrophils protection mature vegetation
Candidal Endocarditis •
Candida endocarditis carries a high rate of mortality. Medical treatment alone usually fails. Surgical replacement of the infected valve as well as the administration of a prolonged antifungal regimen is strongly recommended d d [1915] [1915]. Non-surgical N i l candidates did t h have b been ttreated t d with ith long-term suppressive oral therapy, but this approach should be used only in extreme cases as is considered non-curative [153]. Attempts to treat Candida endocarditis with antifungal agents alone were invariably unsuccessful [1982]. The best ever reported survival rate of this fatal infection (more than 50% at 5 years) has been achieved by combining an aggressive perioperative antifungal regimen with radical surgical debridement of all infected tissue and valve replacement replacement, ideally using biologic tissue [1513, 1593
Pathways involved in inflammation and destruction in the rheumatoid joint The five key factors of intracellular signaling and proliferation, adhesion, inflammation, angiogenesis, and matrix degradation are linked by various inflammatory effector cells such as tumor necrosis cells, factor, interleukin-1 and interleukin-6, and matrixdegrading enzymes, including matrix metalloproteinases and cathepsins, finally resulting in a persisting vicious circle. IL, interleukin; MMPs MMPs, matrix metalloproteinases; TNF, tumor necrosis factor. From: Muller –Ladner et al., N t Nature Cli Clin. P Practice ti Rheumatol. 1:102, 2005