CLARIBID - Medical Aspects

1. Epithelial Lining Fluid (ELF) is major site of infection in pneumonia and other LRTI .
2. Epithelial Lining Fluid (ELF) – It is present in the Inner layer of epithelium layer of Alveoli, It is a
complex mixture having WBC’s & Anti-Inflammatory properties …which provide protective
mechanism to alveoli & improves defense for Lower respiratory tract.
In comparision to Amox + Clav, Cefuroxime, Ciprofloxacin, Levofloxacin, Clarithromycin is the only
antibiotic that achieves ELF concentration that far exceed its serum concentrations within 6 hours of
intake thereby leading to faster therapeutic effect in LRTI.

3. Pneumolysin is a pore-forming toxin produced by Streptococcus pneumoniae. Pneumolysin damages

the host cells, and interfere with the function of cells and interferes with the host immune response.

Clarithromycin - Exhibits Good Antipneumolysin effect –

1) Claribid has the highest concentration in ELF & Highest inhibition of Pneumolysin toxin.
2) Claribid inhibits RNA dependent protein synthesis, thereby preventing the formation of pneumolysin by the bacteria.
3) In a study by Anderson et al (published in Journal of Antimicrobial Chemotherapy 2007) the inhibitory potency of Clarithromycin against
pneumolysin production was compared with other antibiotics (Amoxicillin, Azithromycin, Erythromycin, Ciprofloxacin, Ceftriaxone) and
Clarithromycin was found to be the most potent, which inhibits pneumolysin by inhibiting protein synthesis.

4. Biofilm:
A biofilm is a self-developed matrix produced by the bacteria, which provides protection from Host defense mechanism, facilitate attachment &
also aid in trapping nutrients.
One potential reason for this increased resistance is the penetration barrier that biofilms may present to antimicrobials.
This ensures multiplication of bacteria within the safe environment provided by this film and slowly the colony increases in size.
These Biofilms provide safe shelter to other free flowing bacteria and protect them from commonly used antibiotics.
These Biofilm forming bacteria release inflammatory mediators such as cytokines, which bring about the inflammation of epithelial cells.

Clarithromycin exhibits Good Immunomodulatory effects –

a) Claribid penetrates the Biofilm.
b) Claribid inhibits the production of “Glycolax” a major component of Biofilm, thereby prevents the formation of Biofilm.
c) Claribid also impairs the motility of bacteria and subsequently destroys shielded pathogens.
d) Claribid facilitates the activity of concomitantly (existing/accompanied) used antibacterial agents – like aminoglycosides, cephalosporins &
betalactums, which were previously ineffective, can now enter the Biofilm & exhibits antibacterial action.
e) Clarithromycin inhibit the production of many pro-inflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-
alpha.…thereby reducing Inflammation.
f) Claribid stimulates the phagocytic activity of Leucocytes…potentiating Immune activity.
g) Claribid brings about direct inhibition of mucus secretion by inhibiting the production of muc5ac.

Biofilm is responsible for several chronic diseases that are difficult to treat like
 Chronic sinusitis
 Chronic bronchitis
 Pneumonias
Upper respiratory tract Infections
 Rhinitis (common cold)
 Sinusitis (sinus infections)
 Acute Otitis Media (ear Infections)
 Acute laryngitis
 Acute Pharyngitis
 Tonsillitis
Typical pathogens causes upto 70% cases of CAP
o Streptococcus pneumoniae
o Haemophilus influenza
o Moraxella catarrhalis

Atypical pathogens are implicated in up to 40% of cases of community-acquired pneumonia,

o Mycoplasma pneumoniae,
o Chlamydia pneumoniae
o Legionella pneumophila
 Clarithromycin is a semi-synthetic derivative of erythromycin.
1. Well absorbed, oral bioavailability 57% & Unaffected by food.
2. Tissue concentration is much higher than plasma concentration in Lungs, Tonsils and Middle ear fluid.
3. Clarithromycin is the only antibiotic that achieves ELF concentration that far exceeds its serum concentrations within 6 hours of intake thereby
leading to better therapeutic effect in LRTI.
4. Clarithromycin is absorbed rapidly from the gastro-intestinal tract after oral administration, but its bioavailability is reduced to 50%
to 55% because of rapid first-pass metabolism.
5. Peak plasma concentration occurs approximately 5 to 7 hours after administration. Clarithromycin may be given with or without
food. Clarithromycin is metabolised by the liver and 10-15 % converted in to the active metabolite, 14-hydroxyclarithromycin, which is 2
times more active than parent drug against H influenza.
6. Both clarithromycin and 14-hydroxyclarithromycin distribute widely throughout the body and achieve high intracellular
concentrations. Tissue concentrations generally exceed serum concentrations.
7. The elimination half-lives of clarithromycin and 14-hydroxyclarithromycin are approximately 3 to 7 and 5 to 9 hours respectively.
Longer half-lives are observed after larger doses as it is concentration-dependent. Clarithromycin is eliminated by renal and non-
renal routes. The amount of clarithromycin excreted unchanged in the urine ranges from 20 to 40%, depending on the dose
administered and the formulation. Between 10 and 15% of the dose is excreted in the urine as the 14-hydroxy metabolite.

Azithromycin Clarithromycin
Drug class Macrolide antibiotic Macrolide antibiotic
Exhibits Good Antipneumolysin effect - It is a potent
Antipneumolytic activity is low - Inhibited the
macrolide which inhibits Pneumolysin by inhibiting protein
production of Pneumolysin to 330 units / ml
synthesis …Inhibited the production of Pneumolysin to 150
ONLY
units / ml
Spectrum of
activity
Demonstrates high concentration in the ELF (Epithelial lining
Demonstrates LOW concentration in the ELF
fluid in the lungs) is an important parameter of efficacy in
(Epithelial lining fluid in the lungs) is an
LRTIs.
important parameter of efficacy in LRTIs.

MIC - .063
MIC MIC - .25

Guidelines that recommended first-line use of Macrolides in CAP

ERS ’05 – European Respiratory Society
ATS ‘01- American Thoracic Society
IDSA ’07 - Infectious Disease society of America
Guidelines that recommended use of Macrolides in CAP
NICE: National Institute of Health and Care Excellence
BTS: British Thoracic Society

IDSA: Infectious Disease society of America