Update not Nostalgia

Dr Diya Saleh

(Medical Registrar)

General Medicine A

MICROORGANISMS’ WONDERLAND

CASE 132 years old male

• PC:

• Fever and generalized body stiffness for 12 days

• Bed ridden for this period

• Passing Cola-colored urine on day 5 of fever

• PHx:

• Hepatitis C

• Psoriasis

• Ex-IVDU: last used 6 years ago, now on Methadone

• 2004: L arm abscess

• 2005: R arm cellulitis (Group A, B hemolytic Strep on BC)

• FHx:

• SLE

• Epilepsy

• Social Hx:

• Lives with girlfriend and son

• Smoker

• Denied heavy alcohol drinking

• O/E:

• GCS: 15/15

• T 38.7, HR 108, BP 122/65, PO2sat 94% RA, RR 16

• Generalized Lymphadenopathy

• No rash

• Chest: clear (CXR: hilars LN enlargements)

• Heart: no murmur

• Abdo: generalized tenderness, hepatosplenomegaly (confirmed by US), ?ascites

• CNS: neck stiffness, ?papilodema

• Inestigations:

• VBG: PH 7.48, PO2 41, PCO2 40, HCO3 29, Lactate 1.4

• Hb 11.3, WCC 13.8, Neutro 11.9, Platlets 125

• CRP 156

• Na 125, K 4.3, Cr 54, Urea 5.6

• Bil 16, ALT 15, AST 25, GGT 133, ALP 221

• Urine:Leuc 2+, Blood 5+, Prot 3+, Urobilinogen 1+

DIAGNOSIS?

•CTB: NAD

•LP: NAD

WHAT DO YOU WANT TO DO NEXT?

CASE 2

• 45 years old male presented with

• fever, productive cough and SOB,

• Hx of IVDU.

• O/E: Temp 39 C, HR 100, BP 105/65

• Chest: R basal crepitation

• First Differentia?

EASILY MISSED! INFECTIVE ENDOCARDITIS

ROADMAP

1. Epidemiology2. Pathology3. Diagnosis

1. Duke criteria2. Blood cultures3. Echocardiography

4. Treatment basics5. Complications6. Prophylaxis7. Summary

EPIDEMIOLOGY

• Incidence: 2.6 - 7.0 cases / 100,000 population / year.

• New Trends:

• Mean age was 30 in 1926, now > 50% of patients are over 60

• Decline in incidence of rheumatic fever

• More prosthetic valves

• More nosocomial cases, injected drug use

• More staphylococcal infection

• Mitral valve alone 28-45% (MV > AV > TV)

PATHOLOGY

• Staphylococcus (40%) , NOT Streptococcus (34%) is now the leading pathogen*, in the developed world.

• IVDU: may get unusual pathogen. Polymicrobial infection is common

• Risk of prosthetic (Mechanical = tissue) valve endocarditis is 4% first year then decline to 1% per year.

• Regurgitation valve lesions are more susceptible than stenotic ones.

• Transvenous pacemaker lead and/or implanted defibrillator associated endocarditis is usually nosocomial. Onset within weeks of implantation.

• 100% fatal if undiagnosed and untreated vs 20% fatal if diagnosed and treated.

*Karchmer, Scientific American Medicine, 1999

CLASSIFICATIONS• Acute vs Subacute: causative microorganism is primarily responsible for the

temporal course.

• S.aureus Acute

• Viridans Strep, Enterococcus Faecalis Subacute IE: classic PUO

• Bartonella species and the agent of Q fever, C. burnetii, is exceptionally indolent

• Right vs Left sided heart: IVDU. May present as pneumonia

• Native vs Prostatic valve: IVDU

• Negative (5 - 15%) vs Positive blood culture

• Bad isolation/identification technique

• Fastidious isolate:

• HACEK organisms: Haemophilusaphrophilus, H. paraphrophilus, parainfluenzaeActinobacillusactinomycetemcomitansCardiobacteriumhominisEikenellacorrodens, Kingellakingae

• Bartonella species have now been established as an important cause

• Non-bacterial

• Antibiotics administration pre-culture: 1/3 - 1/2 of cases

DIAGNOSIS

• In 1994 investigators from Duke University modified the von Reyn criteria (1981) to include:

• Role of echocardiography

• IVDU as risk factor

• In 2000, further modification to include:

• Role of TOE

• Q fever (Coxiella brunetti)

MODIFIED DUKE CRITERIA

Major Criteria•Isolation of causative organism by two separate blood cultures at least 12hrs apart, or Three or more positive cultures taken at least one hour apart•Endocardial involvement evidence by echo. Oscillating mass, prosthetic valve dehiscence, abscess, new regurgitation.

Minor criteria•Predisposing lesion or IVDU•Fever >38C•Signs of embolization: Janeway lesion, Intracranial infarct/ bleeding.•Immunologic phenomena: Glomerulonephritis, Oslers nodes, Rheumatoid factor, Roths spots.•Positive blood culture not meeting major criteria.•Echo finding, but not meeting major criteria.

MODIFIED DUKE CRITERIA

Definite Infective Endocarditis

Pathologic criteria:Microorganisms demonstrated by culture or histology in a vegetation or

embolus.

Clinical criteria:2 major or1 major + 3 minor or5 minor

Possible endocarditisFindings that are suggestive of IE but fall short of definite, but not rejected.

Rejected Infective EndocarditisFirm, alternative diagnosis explaining the evidence suggesting infective endocarditis.Resolution of syndrome with antibiotic therapy in 4 days or less.No pathologic evidence at surgery with Abx therapy of four days or less.

painful, nodules found in the pulp of fingers and toes and are seen more often in subacute IE

Macular, blanching, nonpainful, erythematous lesions on the palms and soles

Septic Retinal EmbolusRoth’s spots 5%retinal haemorrhages with pale centres

THE CAUSATIVE ORGANISMS CAN BE AS MANY AS THIS

BLOOD CULTURE ENDOCARDITIS VS NON-ENDOCARDITIS

TRANSTHORACIC (TTE) VSTRANSOESOPHAGEAL (TOE) ECHOCARDIOGRAPHY

• TTE does not detect vegetations <2 mm in diameter

• TOE is 90% sensitive (vs 60% in TTE) in detecting vegetations and is particularly useful for identifying valve ring abscesses as well as prosthetic valve endocarditis

• However, TTE may be used in pts with a low pretest likelihood of endocarditis (<5%).

TTE VS TEE (TOE)

• Vegetation

• Abscess

• Pseudoaneurysm

• Perforation

• Fistula

• Valve aneurysm

• Dishence of prosthetic valve

ECHOCARDIOGRAPHIC FINDINGS

“ECHO SHOULD BE DONE IN ALL CASES OF SUSPECTED

ENDOCARDITIS.”

(This is not all patients with fever or positive blood cultures).

Circulation 1997; 95: 1686-1784

COMPLICATIONS

• CARDIAC COMPLICATIONS:

• Heart failure- acute or insidious

• Paravalvular abscesses- esp aortic, increased in IVDU

• Heart block

• Other extravalvular complications- pericarditis, fistulas

• EMBOLIZATION: Vegetations >10 mm in diameter and those located on the mitral valve are more likely to embolize:

• Stroke

• Blindness

• Painful ischemic or frankly gangrenous extremities

• Unusual pain syndromes (eg, due to splenic or renal infarction)

• Hypoxia (due to pulmonary emboli in right-sided endocarditis)

• Paralysis (due to embolic infarction of either the brain or spinal cord)

• Effect of antibiotic therapy on embolic risk- decreases, but can occur wks after initiation

• Predictors of embolization- strep bovis, saureus, L sided, seen on TTE, not just TOE

• NEUROLOGIC COMPLICATIONS

• Acute encephalopathy

• Meningoencephalitis

• Purulent or aseptic meningitis

• Embolic stroke

• Cerebral hemorrhage (due to stroke or a ruptured mycotic aneurysm)

• Brain abscess or cerebritis

• Seizures (secondary to abscess or embolic infarction)

• MYCOTIC ANEURYSMS (most feared)

• cerebral and systemic

• RENAL DISEASE

• renal infarction due to emboli

• drug induced acute interstitial nephritis

• glomerulonephritis due to deposition of immunoglobulins and complement in the glomerular membrane- pre commencement of antibiotics

• METASTATIC ABSCESSES

• rare- kidneys, spleen, brains, soft tissues

• MUSCULOSKELETAL COMPLICATIONS

• osteomyelitis- esp vertebral (staph aureus)

• COMPLICATIONS OF MEDICAL OR SURGICAL THERAPY

• Aminoglycoside-induced ototoxicity or nephrotoxicity

POOR PROGNOSTIC MARKERS:

• Low serum albumin

• Infection with S. aureus

• Heart failure

• Diabetes mellitus

• Apache II score

• Embolic events

• Paravalvular abscess

• Vegetation size

• Female sex

TREATMENT

EMPIRICAL TREATMENT IN FULMINANT INFECTION

At least three blood cultures (no more than one from each venipuncture) must be obtained before therapy is commenced:

• benzylpenicillin 1.8 g IV, 4-hourly

PLUS  

•  di/flucloxacillin 2 g IV, 4-hourly

PLUS  

•  gentamicin 4 to 6 mg/kg IV, for 1 dose, then determine dosing interval for a maximum of either 1 or 2 further doses based on renal function

ALTERNATIVE EMPIRICAL TREATMENT

• vancomycin 1.5 IV, 12-hourly (adjust initial dosage for renal function and monitor blood concentrations

PLUS  

•  gentamicin 4 to 6 mg/kg IV, for 1 dose, then determine dosing interval for a maximum of either 1 or 2 further doses based on renal function

• Indications:

• prosthetic cardiac valve, pacemaker or intra-cardiac device

• health care–associated infection

• penicillin hypersensitivity

• MRSA is suspected

NON FULMINANT INFECTIONWAIT FOR BLOOD CULTURE RESULT

• methicillin-susceptible staphylococci

• di/flucloxacillin 2 g IV, 4-hourly for 4 to 6 weeks

• methicillin-resistant staphylococci

• vancomycin 1.5 g IV, 12-hourly for 6 weeks

+/- Rifampicin & Fusidic Acid

• Viridans streptococci susceptible to benzylpenicillin

• benzylpenicillin 1.8 g IV, 4-hourly for

• 2 weeks (uncomplicated endocarditis)

• 4 weeks (complicated endocarditis)

PLUS  

• gentamicin 1 mg/kg IV, 8-hourly for 2 weeks

• Viridans streptococci resistant to benzylpenicillin

• vancomycin 1.5 g IV, 12-hourly for 4 - 6 weeks

PLUS  

• gentamicin 1 mg/kg IV, 8-hourly for for 4 - 6 weeks

HITH CRITERIA (MUST FULFILL ALL)

• afebrile for at least 72 hours with negative blood cultures

• no evidence of cardiac failure (or if cardiac failure present, stable and well controlled with medical therapy)

• vegetations less than 10 mm and no intracardiac abscess on transoesophageal echocardiogram

• no new cardiac conduction abnormalities

• no neurological findings that may result from cerebral embolism or mycotic aneurysm

• continuing supervision by a cardiologist, and an infectious diseases physician or clinical microbiologist

ANTICOAGULANT??

• Anticoagulation is contraindicated in native valve endocarditis because increases the risk of intracerebral bleed.

• “If anticoagulation is indicated for another reason, it should be continued, with INR at low therapeutic range.

• Anticoagulation does not prevent embolization due to IE.”

ACC guidelines on Diagnosis and Management of Infective Endocarditis.

RELAPSES

• Mostly occur within 1-2 months after completion of therapy.

• Obtaining one or two blood cultures during this period is prudent.

TIME TO OPERATE?

severe valve regurgitation that

impairs cardiac function

PROPHYLAXIS

• No randomised controlled trial has been performed to decide the role of antibiotic prophylaxis and there are no human studies showing that it can prevent endocarditis.

• Guidelines produced in different parts of the world rely on expert consensus and consequently can differ in their recommendations.

• Australian guidelines follow the lead of the American Heart Association

Antibiotic prophylaxis is recommended in patients with the following cardiac conditions if undergoing a specified dental or other procedure

• prosthetic cardiac valve or prosthetic material used for cardiac valve repair

• previous infective endocarditis

• congenital heart disease but only if it involves:

• unrepaired cyanotic defects, including palliative shunts and conduits

• completely repaired defects with prosthetic material or devices, whether placed by surgery or catheter intervention, during the first 6 months after the procedure (after which the prosthetic material is likely to have been endothelialised)

• repaired defects with residual defects at or adjacent to the site of a prosthetic patch or device (which inhibit endothelialisation)

• cardiac transplantation with the subsequent development of cardiac valvulopathy

• rheumatic heart disease in Indigenous Australians only

Prevention of Infective Endocarditis. Guidelines (2007)

ARE DENTISTS INNOCENT?

• “Toothbrushing for 1 year has a greater risk of producing bacteraemia than a single extraction”

Roberts GJ 1999 Pediatr Cardiol 20:317-325

Dentists are innocent!

• First and most important – proper oral hygiene & Regular dental review

STANDARD PROPHYLAXIS

• amoxycillin 2 g orally, 1 hour before the procedureoramoxy/ampicillin 2 g IV, just before the procedureoramoxy/ampicillin 2 g IM, 30 minutes before the procedure.

• hypersensitive to penicillin

• clindamycin 600 mg orally, 1 hour before the procedureorclindamycin 600 mg IV over at least 20 minutes, just before the procedure

OR  

• lincomycin 600 mg IV over at least 1 hour, just before the procedure

OR  

• vancomycin 25 mg/kg up to 1.5 g IV, ending the infusion just before the procedure

MCQ1

• A 60 year old male has a previous rash whist talking flucoxacillin. He presents with aortic valve endocarditis with Staphylococcus Aureus sensitive to flucoxacillin. He is treated with IV Cephazolin 2g every 8 hours for the past week. He develops pulmonary oedema and a new early diastolic murmur in the aortic area.

What is the best management ?

A. Add Gentamycin to Cephazolin

B. B. Start flucoxacillin after rapid desensitisation

C. Change to Vancomycin and Rifampin

D. Transfer to ICU for Intra-aortic balloon pump insertion

E. Urgent aortic valve repair.

MCQ2

• 60 years old man presents with a Streptococcus Bovis endocarditis which is adequately diagnosed and treated.

which of the following is the next most appropriate investigation?

A. Iron Studies

B. Small bowel series

C. Gallium scan

D. Colonoscopy

E. HIV antibody test

ANSWER MCQ2

D – colonoscopy

Strep bovis typically comes from the gut

and is associated with bowel polyps and

carcinoma

WHAT DO WE NEED TO KNOW?

• IE is rare but serious disease, with high mortality rate

• IVDU and the elderly are at greatest risk of developing IE.

• Every case of PUO should be suspected for IE

• The signs and symptoms of IE are nonspecific and varied.

• A thorough but timely evaluation (including serial blood cultures, adjunct labs, and an echo) is crucial to accurately diagnose and treat IE.

• Beware of life-threatening complications.

• Antibiotics prophylaxis is reserved for high risk patients

MANY THANKS

• For your attendance and attention

• To Department of Medicine for the support:

• Dr Bassi

• Dr Vidyarantna

• Debbie Hobbs & Kim Adams

• And all others

• Frankston Hospital Library staff

• Finally not to forget our hard working interns, Linda and Victor

QUESTIONS?