Transcript clindamycin

CLINDAMYCIN
USES AND CONCERNS
Dr.T.V.Rao MD
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CLINDAMYCIN
• Clindamycin rINN is a Lincosamides
antibiotic. It is usually used to treat
infections with anaerobic bacteria but can
also be used to treat some protozoal
diseases, such as malaria. It is a common
topical treatment for acne and can be
useful against some methicillin-resistant
Staphylococcus aureus (MRSA)
infections.
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ANTIBACTERIAL ACTIVITY
• Active against G+
cocci, including
penicillin- resistant
Staph. and many
anaerobes, esp.
Bacteroides sp.
• Not effective
against G-ve
aerobes.
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CLINDAMYCIN
• Inhibits protein synthesis ( 50 s subunit )
• Pharmacokinetics
• May be given orally or parenterally
• Widely concentrated in tissues ( including bones ) &
body fluids
• It diffuses across the placenta but not BBB
• 90% protein bound
• Metabolized in liver ( active )( enter hepatic circulation),
10 % excreted unchanged
• Excretion – urine and bile
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CLINICAL USES
Staphylcoccal joint & bone
infections such as
osteomyelitis
Staph. Conjunctivitis ( eye drops )
Diabetic foot infections
Acne ( 1% topical gel & lotion )
Use Limited because of
pseudomembrano
us colitis- can be
fatal
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TESTING FOR ANTIBIOTIC RESISTANCE IN CLINDAMYCIN'S
DIFFERS FROM OTHER BACTERIA
The detection of its three resistance phenotypes
(sensitive, resistant, inducible resistance) is crucial to
guide antimicrobial therapy. Standard disk diffusion
and broth micro dilution fail to detect inducible
clindamycin resistance . Clinical and Laboratory
Standards Institute (CLSI) recommends the double
disk diffusion test (D-test) to detect the presence
of inducible clindamycin resistance . Also, the
incidence of clindamycin resistance varies with
geographic area and therefore local statistics are
crucial to guide empiric therapy
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CLINDAMYCIN-ERYTHROMYCIN DISCORDANT
• Clindamycin-susceptible, erythromycin-resistant
Staphylococcus aureus (clindamycin-erythromycin
discordant) may develop clindamycin resistance. The
erm gene product is a ribosome methylase whose
expression is normally minimal. Erythromycin induces
the production of this methylase, which is why these
strains are erythromycin resistant, but mutations in the
promoter region of erm allow production of methylase
without an inducer
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TESTING FOR ERYTHROMYCIN AND
CLINDAMYCIN RESISTANCE IS A PRIORITY
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THE D-TEST FOR MACROLIDE-INDUCIBLE
RESISTANCE TO CLINDAMYCIN
• A positive D test indicates the presence of macrolide-inducible resistance to
clindamycin produced by an inducible methylase that alters the common
ribosomal binding site for macrolides, clindamycin and the group B
Streptogramins (Quinpristin) (Woods, 2009) .
• The cross-resistance, called the MLS-B phenotype, results from enzymatic
methylation of an adenine residue of the 23S component of the 50S
ribosomal subunit that these 3 drug groups bind to. The methylase is
encoded by a plasmid-borne gene erm.
• This genotype has been associated with clinical reports of clindamycin
failure. As a result the “Clinical and Laboratory Standards Institute” (a
nonprofit standards organization) recommends that laboratories report Dtest+ isolates as “resistant to clindamycin” (NCCLS 2004; Woods, 2009).
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D TEST WILL IDENTIFY THE INDUCIBLE
RESISTANCE
• These mutants are stably
erythromycin and
clindamycin resistant. Since
erythromycin resistance
can occur with other
mechanisms. (e.g., efflux
pumps and enzymatic
modification) the D-test
identifies inducible
resistance that might
presage mutational
clindamycin constitutive
resistance.
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A NEGATIVE D- TEST
•
A negative D-test observed for an
erythromycin-resistant culture of
S. aureus. The small discs labeled
E & C represent disks containing
either 15 μg erythromycin (E) or 2
μg clindamycin (C) placed 15 to
20 mm apart on an agar plate that
has been inoculated with the
clinical isolate (indicated by the
green background). The lack of a
zone of inhibition around the
erythromycin disc indicates
bacterial resistance to macrolides
The large clear zone of inhibition
around the clindamycin disc
indicates sensitivity to
clindamycin
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A POSITIVE D- TEST
•
A positive D-test. Diffusion of
erythromycin from the disc towards
the clindamycin disc does not kill
bacteria due to S. aureus resistance
to macrolides. However, in this case
the bacterial isolate contains a
strain of S. aureus with an
erythromycin-inducible methylase
(iMLS-B) resulting in inhibited
growth. The inhibition of bacterial
growth in zone 2 but not zone 1
produces a “ D” shape surrounding
the clindamycin disk, which is
considered a “positive” D-test.
(Adapted from Woods 2009).
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PERFORMING D- TEST
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• The D-test is performed by
placing clindamycin and
erythromycin disks at an
edge-to-edge distance of
15 to 20 mm and looking
for flattening of the
clindamycin zone nearest
the erythromycin disk . A
positive D-test suggests the
presence of an erm gene
that could result in
constitutive clindamycin
resistance and clinical
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failure.
WHEN TO AVOID USE OF CLINDAMYCIN
• Clindamycin may still be effective in some patients with
this phenotype, the working assumption is that the
isolate is “presumed” to be resistant based upon
detection of inducible clindamycin resistance. For
serious infections such as sepsis, pneumonia, or
other invasive S. aureus infections, even the small
risk of emergence of resistance to clindamycin as
indicated by a positive D-test should lead to
avoidance of use of clindamycin (Woods, 2009).
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CLINDAMYCIN IN MALARIA
• Given with chloroquine or quinine, clindamycin is
effective and well-tolerated in treating Plasmodium
falciparum malaria; the latter combination is particularly
useful for children, and is the treatment of choice for
pregnant women who become infected in areas where
resistance to chloroquine is common. Clindamycin
should not be used as an antimalarial by itself, although
it appears to be very effective as such, because of its
slow action. Patient-derived isolates of Plasmodium
falciparum from the Peruvian Amazon have been
reported to be resistant to clindamycin as evidenced by
in vitro drug susceptibility testing. [
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ADVERSE COMPLICATIONS WITH
CLINDAMYCIN
• Common adverse drug reactions (ADRs) associated with
clindamycin therapy — found in over 1% of patients — include:
diarrhea, pseudomembranous colitis, nausea, vomiting,
abdominal pain or cramps, rash, and/or itch. High doses (both
intravenous and oral) may cause a metallic taste, and topical
application may cause contact dermatitis. Diarrhea, vomiting,
and nausea are common if the individual lies down for an
extended period of time within 30 minutes of taking clindamycin.
In addition, severe heartburn can be expected for up to three
days if the individual does not stay in an elevated position for at
least 30 minutes.
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COLITIS IS A FEARED COMPLICATION
• Clindamycin has been associated with colitis
(inflammation of the bowel); this is caused by a toxin
produced from an overgrowth of a bacterium,
Clostridium difficile. Symptoms can range from mild
watery Diarrhoea to severe, persistent Diarrhoea with
fever, abdominal cramps and the passage of blood and
mucus. It may be potentially serious. If significant
Diarrhoea develops whilst taking clindamycin, the drug
should be stopped. A stool test may show the presence
of the toxin.
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PSEUDOMEMBRANOUS COLITIS IS A
POTENTIALLY LETHAL CONDITION
• Pseudomembranous colitis is a potentially lethal
condition commonly associated with clindamycin, but
which occurs with other antibiotics, as well. Overgrowth
of Clostridium difficile, which is inherently resistant to
clindamycin, results in the production of a toxin that
causes a range of adverse effects, from diarrhea to
colitis and toxic mega colon.
• Rarely — in less than 0.1% of patients — clindamycin
therapy has been associated with anaphylaxis, blood
dyscrasias, polyarthritis, jaundice, raised liver enzyme
levels, and/or hepatotoxicity.
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PRECAUTIONS IN USE OF CLINDAMYCIN
•
The safety of use in pregnancy has
not been established.
• Clindamycin has been reported
to appear in breast milk.
• If therapy is prolonged, liver and
renal function tests may be
monitored periodically.
• May enhance the action of
neuromuscular blocking agents.
• May counteract the effects of
erythromycin
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• Programme created by Dr.T.V.Rao MD for
Medical and Health Care workers in the
Developing world
• Email
• [email protected]
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