Rheumatic Heart disease

Acute rheumatic fever

Highest incidence -children and young adults between the ages of 5 and 15 years

Pathogenesis

- immune reaction to infection with group A hemolytic streptococci

Cell wall antigen -M protein (Similar with human cardiac antigens (myosin) and human
heart tissue)

Antibodies against the streptococcal antigens

Damage to heart muscle and valve

Inflammation in the endocardium, myocardium and pericardium, Joints, skin

Clinical features

Jones criteria

two or more major manifestations,

or

one major and two or more minor

manifestations

1
Management

Aims

- to relieve symptoms
- to limit cardiac damage

Bed rest

- Lessens joint pain and reduces cardiac workload

- Duration should be guided by symptoms, along with temperature, leucocyte count and
ESR
- Return to normal physical activity but strenuous exercise should be avoided in those
who have had carditis

Antibiotics (for curative therapy)

Non Penicillin allergic patients Penicillin-allergic patients

- Penicillin G (benzathine Pen G) -1. 2
million U IM) or
- Phenoxymethylpenicillin (oral, 250 mg
4 times daily for 10 days)
- Erythromycin or a cephalosporin can
be used
- Sulphonamides prevent infection but
are not effective in the eradication of
group A streptococci

*Long-term prophylaxis with penicillin should be given with oral phenoxymethylpenicillin (250
mg twice daily) or as benzathine benzylpenicillin (1.2 million U IM monthly) → if Patients are
susceptible to further attacks of rheumatic fever/ if adherence is in doubt

Duration of treatment

- Further attacks of rheumatic fever are unusual after the age of 21, when antibiotic treatment
can usually be stopped.
- The duration of prophylaxis should be extended if an attack has occurred in the last 5 years, If
the patient lives in an area of high prevalence and high risk of exposure to streptococcal
infection.
- In those with residual heart disease, prophylaxis should continue until 10 years after the last
episode or 40 years of age, whichever is later.
- While long-term antibiotic prophylaxis prevents further attacks of acute rheumatic fever, it does
not protect against infective endocarditis.

2
For symptomatic control

Aspirin

- relieves the symptoms of arthritis rapidly

- should be continued until the ESR has fallen and then gradually tailed off

Starting dose is 60 mg/kg body weight/day, divided into six doses.

In adults, 100 mg/kg per day may be needed up to the limits of tolerance or a maximum of 8 g
per day.

Glucocorticoids

- more rapid symptomatic relief than aspirin and are indicated in cases with carditis or
severe arthritis
- Prednisolone (1.0–2.0 mg/kg per day in divided doses) should be continued until the ESR
is normal and then tailed off.

Bacterial endocarditis
Infective Endocarditis
- a serious illness; the case fatality is approximately
Causal organisms 20% even with treatment,
- higher in those with prosthetic valve endocarditis
Streptococci and those infected with antibiotic-resistant
Staphylococci organisms

Subacute endocarditis
Mainly- viridans Streptococci
Others- Enterococcus fecalis, strep. pneumoniae

Acute endocarditis
- Strep. pneumoniae and Strep. pyogenes
- Staph. aureus -from skin infections, abscesses or vascular access sites such as intravenous and
central lines, or from intravenous drug use (IVDA)
- Staph. epidermidis - prosthetic heart valves or other prosthetic materials

3
Management of infective endocarditis

Empirical treatment depends on

- Mode of presentation,
- Suspected organism
- Presence of a prosthetic valve
- Penicillin allergy

Subacute IE

- antibiotic treatment should ideally be withheld until the results of blood cultures are
available
- if empirical antibiotic treatment is considered necessary, amoxicillin (2 g 6 times daily
IV) should be considered (with or without gentamicin).

Acute IE

- empirical therapy should be started with vancomycin (1 g twice daily IV) and gentamicin
(1 mg/kg twice daily IV)
- same regimen is used in true penicillin allergy

Patients with suspected prosthetic valve endocarditis

- Should be treated with vancomycin and gentamicin at the above-mentioned doses, plus
rifampicin orally in a dose of 300–600 mg twice daily.

*Following identification of the causal organism, determination of the minimum inhibitory

concentration (MIC) for the organism helps guide antibiotic therapy. Recommended regimens
for some of the most common scenarios are shown in Box.

4
5
***AMINOGLYCOSIDE ANTIBIOTICS (HIGHLY IONIZED)
Gentamicin Tobramycin Streptomycin
Kanamycin Paromomycin Neomycin
Amikacin Netilmicin Spectinomycin

**Mechanism of action
- bactericidal action
- aminoglycoside binds irreversibly to the 30S - ribosomal subunit and interferes with
initiation of protein synthesis

***Antibacterial spectrum
- mainly active against Gram-negative bacteria (Pseudomonas, Shigella, E.coli, Proteus,
Haemophilus, Brucella, Klebsiella, Pasteurella)
- active against some Gram-positive bacteria
- Mycobacteria (Streptomycin, Amikacin, Netilmicin, Kanamycin)-2nd line Anti TB
- anaerobic bacteria are resistant to aminoglycosides

Uses of Aminoglycosides
- Gram-negative bacillary infections
Streptomycin
- bacterial endocarditis (together with penicillin), plague, tularaemia, tuberculosis
Gentamicin, Tobramycin
- urinary tract infections (including Pseudomonas) - gram-negative bacillary infections
Amikacin, Netilmicin
- broader spectrum among the aminoglycosides, less toxic
- resistant to aminoglycoside inactivating enzyme: active against gentamicin and tobramycin
resistant bacteria, suitable for hospital Gram-negative infections
- reserve drugs for Tuberculosis
Neomycin (poorly absorbed)
- topically for wounds, burns, dermatitis
- orally for bowel sterilization in hepatic coma and before intestinal surgery
Spectinomycin – drug resistance gonorrhea or gonorrhea in penicillin allergic patients
Kanamycin with Clindamycin - for penetrating abdominal wounds
Paromomycin - intestinal amoebiasis (orally) cysts

Pharmacokinetics
- highly polar cations, so poorly absorbed from GI tract (IM, IV). Some drugs act locally in GI
tract (oral, per-rectal).

6
- do not penetrate into most cells, CNS and the eyes and distributed throughout extracellular
space (Vd = ECF). High concentration is found in the renal cortex, endolymph & perilymph of
inner ear.
- excreted unchanged by glomerular filtration (useful in UTI) leading to toxic blood levels in
renal impairment.
- They are more active in alkaline media (alkalinisation of urine in UTI).

Untoward effects
1. Ototoxicity (irreversible)
a) Vestibular dysfunction (Gentamicin, Streptomycin, Netilmicin)
- intense headache, vertigo, dizziness, nystagmus, ataxia, loss of equilibrium
b) Auditory dysfunction (Kanamycin, Amikacin)
- tinnitus, fullness in the ear, deafness (potent diuretics potentiate ototoxicity)
- Tobramycin affects both equally and netilmicin is less ototoxic than others
2. Nephrotoxicity (Neomycin, Tobramycin, Gentamicin)-reversible
- due to accumulation of aminoglycosides in the proximal tubular cells
- reduction in glomerular filtration rate (GFR)
- mild increase in plasma creatinine level
- mild albuminuria, hypokalaemia, hypocalcaemia, hypophosphataemia
3. Neuromuscular blockade (reversible)
- due to inhibition of prejunctional release of acetylcholine
- respiratory paralysis can occur in patients with myasthenia gravis (CI)
- Aminoglycosides potentiate neuromuscular blocking agents (tubocurarine)-DI
- these effects can be reversed by calcium gluconate IV or neostigmine
4. Other Untoward Effects
- rare - hypersensitive reactions
- vague feelings of paraesthesia of the lips or circumoral region
- prolong use - superinfection, diarrhoea, malabsorption can occur with neomycin
Contraindications- pregnancy, allergy, myaesthenia gravis, renal failure, patient with perforated
ear drum, avoid concurrent use of other nephrotoxic drugs, e.g., cephalosporins, frusemide

7
MACROLIDE ANTIBIOTICS (ERYTHROMYCIN GROUP)- Erythromycin, Azithromycin, Roxithromycin,
Clarithromycin, Troleandomycin, Spiramycin

Mechanism of action
- bacteriostatic agents that inhibit protein synthesis by binding reversibly to 50s ribosomal subunit of
sensitive micro-organisms
Antibacterial activity -similar spectrum to pen Uses
G***
1. **Gram- positive bacteria accumulate about 1. Alternative to penicillins in streptococcal
100 times more erythromycin than do gram- pharyngitis, staphylococcal infections, tetanus,
negative micro-organisms. syphilis, prophylaxis of bacterial endocarditis and
Effective against pneumococci, Streptococci, rheumatic fever
Staphylococci, corynebacterial
2. **Mycoplasma, Chlamydia trachomatis, 2.drug of choice for Chlamydial infections,
Legionella, Listeria monocytogenes Mycoplasma pneumonia in children (Tetracycline
is a drug of choice in adult), Diphtheria, Pertussis,
Legionnaires’ disease
3. Clarithromycin is more potent than 3.Eradication of H. pylori in peptic ulcer
Erythromycin against Streptococci, (Clarithromycin)
Staphylococci, H.pyori**, M. catarrhalis,
Chlamydia and Mycoplasma
4. Azithromycin is slightly less active than 4. Community acquired pneumonia
erythromycin and clarithromycin against (Azithromycin given as a 500mg loading dose,
staphylococci and streptococci and slight followed by a 250mg single daily dose for the
more active against H. influenzae.*** next 4 days)
5. Azithromycin and Clarithromycin - effective 5. mycobacterial infection (Clarithromycin,
against Mycobacterium avium intracellurae Azithromycin)
6. Antiamoebic action – luminal amoebicidal
action (E. histolytica) by changing intestinal 6. intestinal amoebiasis (Erythromycin)
bacterial flora
PET -intestinal amoebiasis

8
Pharmacokinetics
- Erythromycin base - must be administered with enteric coating (destroyed by stomach acid)
- Food interferes with absorption. It is concentrated in the liver and excreted in the bile. Dosage
reduction is not routinely recommended in patients in renal failure.
- Clarithromycin is metabolized in the liver and is partially eliminated in the urine. The major
metabolite, 14-hydroxyclarithromycin, also has antibacterial activity and is eliminated in the urine.
Dosage reduction (e.g., a 500-mg loading dose, then 250 mg once or twice daily) is recommended for
patients with creatinine clearances less than 30 mL/min).
- Azithromycin- slowly released from tissues (tissue half-life of 2–4 days) to produce an elimination half-
life approaching 3 days. These unique properties permit once-daily dosing and shortening of the
duration of treatment in many cases.

Untoward Effects
- Anorexia, nausea, vomiting and diarrhea are common
- GI intolerance is the most common reason for discontinuing of erythromycin (lower incidence with
Clarithromycin).
- Cholestatic hepatitis is common with Erythromycin estolate (contraindicated in pregnancy).
- Allergy, arrhythmia, reversible hearing loss
- Prolong the electrocardiographic QT interval due to an effect on potassium ion channels.
Contraindication
- liver disease (Erythromycin estolate)

9
 Pencillin G (or) Benzyl Penicillins
Crystalline Penicillin G, IV
Procaine Penicillin G, IM
Benzathine Penicillin G, IM

Antibacterial spectrum (all cocci, G(+) bacilli, spiochetes)

- gram(+)ve cocci- streptococci, staphylococci, pneumococci (not against penicillanase producing
staphylococci)
- gram (-) cocci – meningococci, gonococci
- gram (+) bacilli – C. diphteriae, B. anthracis, Clostridium, Actinomyces
- spirochetes

Penicillin V (oral) ---Phenoxymethyl penicillin (PEN V)

- Only gram (+)ve cocci (except penicillanase producing staphylococci)- for Only in minor infections
(streptococcal pharyngitis)

Extended- spectrum penicillins (amoxicillin, ampicillin)

- Similar antibacterial spectrum to that of Penicillin G but are more effective against gram (-)ve
bacilli. (H. influenza, E.coli and Proteus )
(resistance is now a major problem because of inactivation by β-lactamase)
- -formulation with a β-lactamase inhibitor (clavulanate or sulbactam), sensitive against β-lactamase
producing strains of G (+)ve & G (–)ve bacteria

Pharmacokinetics
- Pen G is destroyed by acid and should be given parenterally.
- orally active penicillins are acid stable (Pen V, dicloxacillin, amoxicillin and ampicillin), absorption of
most oral Pen. (except amoxicillin ) is impaired by food
- rapidly excreted by the kidney, small amount is excreted by other route, 10% of renal excretion is by
glomerular filtrations and 90% by tubular secretion
- Probenecid inhibits active renal tubular secretion of penicillin via the organic acid transporter and
prolong its action
Untoward effects
- relatively free from direct toxic effects
1. Hypersensitivity reactions - acute anaphylactic shock – may be fatal
A delayed type of serum sickness (now rare, urticaria, fever, joint swelling, angioneurotic oedema,
intense pruritus), hypotension, skin rash, oral lesions, fever, interstitial nephritis and vasculitis may
occur.
2. Nausea, vomiting, diarrhoea due to superinfection (common with oral penicillins )
Larger dose – pseudomembranous colitis (with ampicillin)
3. Rash: not allergic in nature (ampicillin and amoxicillin)

10
Cephalosporins
First generation Second generation Third generation

-good activity against Gram-
positive
- modest activity against Gram-
negative
- Bacteroids fragilis is resistant
Antipseudomonal cephalosporins
- increased activity against - much more active against
Gram-negative microorganisms enterobacteriaceae
but less active than the third-
generation -less active than first-generation
agents against gram-positive
- Not as active against gram-
positive organisms as first- cocci, although ceftriaxone and
generation agents
cefotaxime have excellent
- Cefoxitin and Cefotetan are antistreptococcal activity
modest activity against
Bacteroids fragilis
Anti-MRSA cephalosporins

Ceftazidime, Ceftolozane, Cefepime Ceftaroline, Ceftobiprole

- Gram-negative activity similar to third Similar activity to 3rd generation but with activity
generation with addition of activity against against methicillin resistant Staphylococcus aureus
Pseudomonas

Untoward effects
1. Hypersensitivity is most common side effect. Immediate reactions such as anaphylaxis,
bronchospasm, urticaria and more commonly maculopapular rash are observed. Patients with a
history of a mild or a temporally distant reaction to penicillin appear to be at low risk of allergic
reaction following the administration of a cephalosporin.
(Because of the common β-lactam ring structure, there is potential for patients who are allergic to one
class of β-lactam antibiotics to manifest cross-reactivity to a member of the other class)
2. Diarrhoea
3. Positive Coombs’ test (large dose)
4. Renal tubular necrosis (Cephaloridine in doses greater than 4g/d)
5. Neonatal jaundice (high binding affinity of Ceftriaxone for serum albumin may displace bilirubin)
6. Biliary pseudolithiasis (Ceftriaxone’s high biliary concentrations combined with its affinity for calcium)
7. Prolong prothrombin time (Cefamandole, Cefotetan, Cefoperazone = cephalosporins-containing
methylthiotetrazole group)

11
Vancomycin

Gram-positive cocci and bacilli including β-lactamase producing staphylococci and nafcillin and
methicillin resistant strains

- synergistic in vitro with gentamicin and streptomycin against Enterococcus faecium and
Enterococcus faecalis strains
- active against many Gram-positive anaerobes including C difficile, corynebacterium species.

Pharmacokinetics

- poorly absorbed from gut and must be administered parenterally to treat systemic infections, though
it is given orally to treat gastrointestinal C.difficile infections.**

Untoward Effects
- Nephrotoxicity, ototoxicity and vestibular dysfunction (ataxia, vertigo, nystagmus and nausea)
- Hypotension & erythematous rash on the face and upper body (red neck and red man syndrome)

12