Infective Endocarditis :Approach andManagementChaired by: Dr. Ardaman SinghPresented by: Dr. Amith Kumar S.
Case 32 year old male, a k/c/o RHD, who hasundergone mitral valve repair, presentedto emergency department with complaintsof fever (101 f), with chills andrigor, myalgia and shortness of breath. On examination patient wasnormotensive with tachycardia and wasfebrile. Systemic examination revealedPSM with thrill in mitral area, andsplenomegaly. Head to foot examinationshowed splinter hemorrhages in nails andred tender lesion over pulp of left middle
Pathogenesis◦ Endothelial injury High velocity jet striking endothelium Flow from a high pressure to a low pressurechamber Flow across a narrow orifice at a highvelocity◦ Hypercoagulable state◦ Virulent organisms may seed theinjured site directly◦ Bacteremia seeds the sterile NBTE
Vegetations - Hallmark of IE“…variably sizedamorphous mass ofplatelets and fibrinwith abundantenmeshedmicroorganisms andmoderateinflammatory cells…”
Native Valve EndocarditisAcute NVE Subacute NVESite Normal/damaged valvesDamaged valvesCourse ofdiseaseDays to weeks(aggressive)Weeks to months(Indolent)Microbiology Staph. aureus(MC)Group BstreptococciViridans streptococci,Enterococci,Coagulase-negativestaphylococci,Gram-negativecoccobacilliMetastaticinfectionOften Rarely
Intravenous Drug Abusers Tricuspid valve (46 to 78%) MC involved Risk factor for recurrent NVE. Staph. aureus (>50% of IE occurring in IVdrug abusers overall) Streptococci, Enterococci, Pseudomonas aeruginosa (Infection of right- and left-sidedheart valves) Fungi - left-sided heart valves Corynebacteriumspecies, Lactobacillus, Bacillus cereusnonpathogenic Neisseria species
Prosthetic Valve Endocarditis Constitutes 10% to 30% of all cases of IEin developed countries. Early◦ Symptoms begin within 60 days of valvesurgery.◦ Mostly due to complication of valve surgery.◦ MC organism involved CoNS Late◦ Onset thereafter◦ Usually from later infection, most likely to becommunity acquired◦ MC organism Streptococci
Health Care – AssociatedEndocarditis Includes..◦ Nosocomial IE (54%)◦ Arising in the community after a recenthospitalization (44%)◦ As a direct consequence of long-termindwelling devices (such as centralvenous lines and hemodialysis catheters).
Clinical Features Fever – almost universal Dyspnea, cough, and chest pain -common with intravenous drug users. Cardiac murmurs
Classic peripheralmanifestations of IE Petechiae (most common)found on the palpebralconjunctiva, the buccaland palatalmucosa, and theextremities. Splinter or subungualhemorrhages are darkred, linear, oroccasionally flame-shaped streaks in theproximal nailbed.
Classic peripheral manifestationsof IE – Contd… Osler nodes are small, tendersubcutaneous nodules in the pulp of thedigits, or occasionally more proximal, thatpersist for hours to several days. Janeway lesions are smallerythematous or hemorrhagic macularnontender lesions on the palms and solesand are the consequence of septic embolicevents.
Chest X ray PA view showing septic emboli inleft lung fields in a patient with infectiveendocarditis involving right heart valves
Work Up◦ Complete hemogram◦ CRP/ ESR◦ BLOOD CULTURE◦ Renal function tests◦ Culture form the sites of septic emboli◦ Electrocardiogram◦ Echocardiogram◦ Multislice CT with contrast◦ Chest xray
Obtaining Blood Culture Three separate sets ofblood cultures, eachfrom a separatevenipuncture, afterproper asepticprecautions, obtainedduring 24 hours, arerecommended toevaluate patients withsuspected endocarditis.
Each set should includea bottle containing anaerobic medium andone containingthioglycollate broth(anaerobic medium); atleast 10 mL of bloodshould be placed intoeach bottle.
EchocardiographyAims Determine the presence, location andsize of vegetations Assess the damage to the valveapparatus and determine thehaemodynamic effects. The dimensions and function of theventricles. Identify any abscess formation Need for surgical intervention.
Above: TEE shows a large mitralvegetation (broken arrow) and aperforation of anterior mitralleaflet (arrowhead). LA, leftatrium; LV, left ventricle; RV, rightventricle.Below: TTE shows a large mitravegetation
TTE vs TEETTE TEEResoulution Poor BetterMinimum size ofvegetation seen> 2mm <2mmSensitivity NVE 45% - 65% 85% - 95%PVE 42% - 60% 82% - 96%Indications for TEE•Prosthetic valve endocarditis•Poor trans thoracic views•Continuing sepsis in spite of adequate antibiotic therapy•New PR prolongation•No signs of endocarditis on trans thoracicechocardiography, but high clinical suspicion.
Making the Diagnosis Pelletier and Petersdorf criteria (1977) Von Reyn criteria (1981) Duke criteria (1994)
Major Criteria◦ Positive Blood Culture Typical organism for IE from two separatecultures (viridans strep, Strep bovis, HACEKgroup or Staph aureus or community acquiredenterococci in the absence of primary focus) OR Persistently positive blood culture –recovery of microorganism consistent with IE from- Blood culture (>2) drawn more than 12hrs apart OR- All of the three or a majority of four ormore separate blood culture , with the first and thelast drawn at least one hr apart Single positive blood culture for Coxiella burnettior anti phase IgG antibody titer > 1:800
Major Criteria Contd…◦ Evidence of EndocardialInvolvement Positive Echocardiogram Oscillating intracardiac mass, On valve or supporting structures In the path of regurgitant jets Implanted material , in the absence of analternative anatomic explanationOR AbscessOR New partial dehiscence of prosthetic valveOR New valvular regurgitation
Minor Criteria Predisposition – predisposing heartcondition or IV drug use Fever (>100.4 F) Vascular phenomena◦ Major arterial emboli◦ Septic pulmonary infarcts◦ Mycotic aneurysm◦ Intracranial hemorrhage◦ Conjunctival hemorrhage◦ Janeway lesions
Minor Criteria - Contd Immunologic Phenomena◦ Glomerulonephritis◦ Osler Nodes◦ Roth Spots◦ Rheumatoid factor Microbiological Evidence◦ Positive blood culture, but not meeting themajor criterion OR◦ Serological evidence of active infectionwith organism consistent with IE
Definitive InfectiveEndocarditis Pathologic Criteria◦ Micro-organisms demonstrated by culture or histology in avegetation OR in a vegetation that has embolized OR In an intracardiac abscessOR◦ Pathologic Lesions Vegetations or intracardiac abscess presentconfirmed by histology showing activeendocarditis
Definitive Infective Endocarditis –contd.. Clinical Criteria◦ Two Major CriteriaOR◦ One Major and Three Minor CriteriaOR◦ Five Minor Criteria
Possible InfectiveEndocarditis One major and one minor criteriaOR Three minor criteria
Rejected Firm alternative diagnosis formanifestations of endocarditisOR Sustained resolution of manifestationsof endocarditis, with antibiotic therapyfor 4 days or lessOR No pathologic evidence of IE atsurgery or autopsy after antibiotictherapy for 4 days or less
TreatmentIntiation In Acute IE and for those withhemodynamic decompensation – Startempirical therapy In hemodynamically stable patients -delay of antibiotic therapy brieflypending the results of the initial bloodcultures.
Antibiotic Dosage and Route[†] DurationAqueouspenicillin G12-18 million units/24 hr IV either continuously orevery 4 hr in six equally divided doses4 weeksOrCeftriaxone 2 g once daily IV or IM 4 weeksAqueouspenicillin G12-18 million units/24 hr IV either continuously orevery 4 hr in six equally divided doses2 weeksOrCeftriaxone 2 g once daily IV or IM 2 weeksPlusGentamicin 3 mg/kg/day IM or IV as a single daily dose or dividedin equal doses every 8 hr2 weeksVancomycin 30 mg/kg/24 hr IV in two equally divided doses, not toexceed 2 g/24 hr unless serum levels are monitored4 weeksTreatment of Native Valve Endocarditis Caused byPenicillin-Susceptible Viridans Streptococci andStreptococcus gallolyticus (bovis)
Antibiotic Dosage and route[†] DurationAqueouspenicillin G24 million units/24 hr IV eithercontinuously or every 4 hr in six equallydivided doses4 weeksorCeftriaxone 2 g once daily IV or IM 2 weeksplusGentamicin 3 mg/kg/day IM or IV as a single dailydose or divided in equal doses every 8 hr2 weeksVancomycin 30 mg/kg/24 hr IV in two equally divideddoses, not to exceed 2 g/24 hr unlessserum levels are monitored4 weeksTreatment of Native Valve Endocarditis Caused byStrains of Viridans Streptococci and Streptococcusgallolyticus (bovis) Relatively Resistant to Penicillin G
Streptococcus Pyogenes, StreptococcusPneumoniae, and Group B, C, and GStreptococci Refractory to antibiotic therapy or associatedwith extensive valvular damage.Dosage and Route DurationGroup AstreptococcalendocarditisPenicillin G in a dose of 3 millionunits intravenously every 4 hours4 weeksGentamycin i/m First 2 weeksEarly cardiac Surgery
Dosage and RoutePneumococci(with or withoutconcomittantmeningitis)Penicillin G 4 million unitsintravenously every 4 hoursCeftriaxone 2 g intravenously every12 hours ORCefotaxime 4 g intravenously every 6hoursIn the absence of meningitis, these regimens areeffective for IE caused by pneumococci that arerelatively penicillin resistant
Antibiotic Dosage and route[†] DurationAqueouspenicillin G18-30 million units/24 hr IV givencontinuously or every 4 hr in six equallydivided doses4-6 weeksplusGentamicin 1 mg/kg IM or IV every 8 hr 4-6 weeksAmpicillin 12 g/24 hr IV given continuously or every 4 hrin six equally divided doses4-6 weeksplusGentamicin 1 mg/kg IM or IV every 8 hr 4-6 weeksVancomycin 30 mg/kg/24 hr IV in two equally divideddoses not to exceed 2 g/24 hr unless serumlevels are monitored4-6 weeksplusGentamicin 1 mg/kg IM or IV every 8 hr 4-6 weeksStandard Therapy for EndocarditisCaused by Enterococci*
Antibiotic Dosage and route* DurationMethicillin-susceptible staphylococci†Nafcillin oroxacillin2 g IV every 4 hr 4-6 weeksorCefazolin 2 g IV every 8 hr 4-6 weeksorVancomycin 15 to 20 mg/kg actual bodyweight, IV every 8 to 12 hr4-6 weeksMethicillin-resistant staphylococci‡Vancomycin[?] 15 to 20 mg/kg actual bodyweight, IV every 8 to 12 hr4-6 weeksTreatment of Staphylococcal Endocarditisin the Absence of Prosthetic Material
Antibiotic Dosage and route* DurationRegimen for methicillin-resistant staphylococci†Vancomycin 15 to 20 mg/kg actual body weight, IV every 8to 12 hr≥6 weeksPlusRifampin 300 mg PO every 8 hr ≥6 weeksAndGentamicin 1.0 mg/kg IM or IV every 8 hr 2 weeksRegimen for methicillin-susceptible staphylococciNafcillin oroxacillin2 g IV every 4 hr ≥6 weeksPlusRifampin 300 mg PO every 8 hr ≥6 6weeksAndGentamicin 1.0 mg/kg IM or IV every 8 hr 2 weeksTreatment of Staphylococcal Endocarditis in the Presence of aProsthetic Valve or Other Prosthetic Material
Antibiotic Dosage and route[†] DurationCeftriaxone 2 g once daily IV or IM 4 weeksorAmpicillin-sulbactam12 g/24 hr IV given every4 hr in six equally divideddoses4 weeksTreatment of Endocarditis Caused byHACEK Microorganisms*
Organisms DrugsCandida IE Amphotericin desoxycholate or liposomal amphotericinformulation, at full doses, often combined with 5-fluorocytosine. Surgical intervention shortly afterbeginning of medical treatment is advised.SporadicCandida PVEand NVECaspofungin, with prolonged or indefinite oral azole therapyhas been advocated for patients treated either medically orsurgically.Corynebacteria(diphtheroids) IEPenicillin combined with aminoglycosides ORvancomycinCorynebacteriumjeikeium IEOften resistant to penicillin and aminoglycosides, is sensitive tovancomycin.Pseudomonasaeruginosa IETobramycin (8 mg/kg/day intravenously once daily pluspiperacillin, ceftazidime, or cefipime.Coxiella burnetiiIEDoxycycline (100 mg twice daily) combined with a quinolonefor at least 4 years. Treatment with doxycycline combinedwith hydroxychloroquine for 18 to 48 months may be more
Culture-Negative Endocarditis Recommended therapySuspected IE Received confounding antibiotictherapyNVE Ampicillin-sulbactam plusgentamicin (3 mg/kg/day) orvancomycin plus gentamicin andciprofloxacinPVE Vancomycin plus gentamicin,cefepime, and rifampin.
Anticoagulant therapy in IE Patients with PVE involving devices thatnecessitates maintenanceanticoagulation Anticoagulant therapy in patients withNVE is limited to patients for whomthere is a clear indication and noincreased risk for intracranialhemorrhage.
Monitoring Therapy ~70% of patients with NVE or PVE areafebrile, by one week of therapy Blood cultures should be repeateddaily until sterile, and rechecked ifthere is recrudescent fever andperformed again 4 – 6 weeks aftertherapy.
Relapse and Recurrence Relapse of IE usually occurs within 2months of discontinuation ofantibiotic treatment. IV drug abuse is now the mostcommon predisposing factor forrecurrent IE
Surgery in IE - Indications Congestive Heart Failure Unstable Prosthesis Uncontrolled infection or unavailableeffective therapy Staph aureus PVE Perivalvular invasive infection Left sided Staph aureus IE Unresponsive culture negative IE Large vegetations (>10mm)
Cardiac Conditions Associated with the Highest Risk ofAdverse Outcome from Endocarditis for WhichProphylaxis with Dental Procedures Is Recommended
Regimens for Prophylaxis AgainstEndocarditis: Use with Dental, Oral, andUpper Respiratory Tract Procedures
Future Perspectives Staphylococcal vaccines Against Staph aureus surface carbohydrates poly-N-acetylglucosamine or poly-N-succinylglucosamine(PNSG) Newer Antibiotics◦ Linezolid,◦ Quinupristin-dalfopristin,◦ Daptomycin
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