MANAGEMENT OF

COMMUNITY ACQUIRED
INFECTIONS
The Importance of
Quinolones
 History and Development
 Nalidixic Acid was the first Quinolone
antibiotic synthesized in 1962
 It has activity against most Gram -ve
bacteria (except Pseudomonas spp.)
 And no activity against Gram +ve bacteria
 Use was limited to urinary tract infections as
therapeutic concentrations are high,
especially for Proteus spp.

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 History and Devlpmt.
 In the 1980’s the structure of Nalidixic acid was
modified by addition of fluorine atom and a
piperazine ring to form 6-fluoroquinolone
structure
 This conferred improved activity against Gram
+ve organisms and an extended Gram -ve
spectrum
 These are second generation fluoroquinolones
 Further basic quinolone structure modification
has produced third generation quinolones.

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 Mechanism of Action
 Act by inhibition of bacteria DNA synthesis
 During bacteria cell multiplication, the
chromosomal DNA must uncoil to allow
replication
 During uncoiling, there are points of localized
strain along individual strands
 These torsional stresses are relieved by 2
enzymes- DNA gyrase and Topoisomerase 4
 Topoisomerase 4 maintains the structural
integrity of the DNA strands
 Quinolones inhibit this enzyme and the
bacteria DNA degrades.
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 Mech of Action
 When bacterial duplication is complete, the long double
strand of DNA must be recoiled accurately in order to
assume the normal resting state
 Positive supercoiling is balanced by negative
supercoiling so that there is no strain on the DNA
molecule
 +ve & -ve supercoiling are controlled by different sets
of enzymes
 Quinolones inhibit the enzyme DNA gyrase responsible
for negative supercoiling
 The DNA thereby undergoes only positive supercoiling
and irreparable damages occur along the strands
 The bacteria are unable to function with damaged DNA
and the bacteria cells die.

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 Spectrum of Activity
First Generation
 Nalidixic acid, inhibits gram negative
bacteria including proteus spp.
 Inactive against G+ve bacteria and
Gram-ve Psudomonas spp.
Second Generation
 Ciprofloxacin
 Ofloxacin
 Pefloxacin
 Norfloxacin
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 Spectrum of Activity
Third Generation
 Sparfloxacin
 Levofloxacin

These inhibit both Gram +ve and Gram -ve

bacteria especially;
– Salmonella
- Shigella
- Helicobacter
- Neisseria
- Psudomonas

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 Spectrum of Activty
 Third generation quinolones retain the
activity of First and Second generations
against G-ve and have extended activity
against G+ve, anaerobes and atypical
pathogens e.g. Chlamydia, Mycoplasma,
and Legionella spp.
 They are active against S. pneumonia and
other respiratory pathogens.

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 Quinolones Use in Clinical
Practice
First Generation
 Used for uncomplicated UTI’s only
Second Generation
 Widely used in UTIs, RTIs, SSTIs, etc
 Only Norfloxacin is used in UTI only
Third Generation
 Used in treating different types of infections
 Particularly useful in both upper and lower
RTIs, UTIs and some Skin and Soft Tissue
Infections

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 Prescribers’ Perspective on the
Quinolones
Doctors who use quinolones regularly find
them
 Reliable
 Highly effective (if prescribed for the right
indication and patient)
 Fast acting
 Convenient to dose (once or twice daily)
 Safe in elderly except in hepatic and renal
impairment
 Useful in urinary tract infections
 Restricted use especially in young adults.
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 Development of Resistance
 Development of resistance to the quinolones is
extremely rare and has not been reported

 Plasmidmediated resistance can be found with β-

lactam antibiotics and tetracycline

 Fluoroquinolones are neither chemically nor

structurally related to other bactericidal agents,
thus cross resistance cannot occur.

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 KRISTAB
 KRISTAB is the brand of CIPROFLOXACIN marketed
by Crystal Foods and Drugs Ltd.

 Actsby inhibiting the enzyme DNA gyrase which is

responsible for negative supercoiling of the DNA
strands

 KRISTAB exhibits a high selectivity/specificity for

the bacteria gyrase, leaving the mammalian
enzyme un-inhibited.

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 Pharmacokinetics of KRISTAB
 KRISTAB is adm orally and parenterally
 Has good tissue penetration and excellent G-
ve cover.
 Peak plasma concentration is achieved within
2hrs
 Bioavailability is 70-85% and is not altered in
patients with renal insufficiency
 Elimination half life is 4-5hrs
 Protein binding is 20-30%
 Absorption is not affected by food
 Mainly eliminated unchanged via the kidneys
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 Indications
KRISTAB is mainly used in;
 Upper and Lower Respiratory tract
infection (URTI/LRTI)
 Kidney & Urinary tract infections
 Gonorrhoea
 Skin and Soft tissue infections
 Bacteria infection of the GIT (including
Typhoid fever)
 Septicemia
 Bones and Joint infections
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 Dosage and Administration
Most infections:
 Adults – 500mg to be taken twice
daily for 5days.

PRESENTATION
 KRISTAB is available in blister packs
as 500mg x 10 tablet and
200mg/100ml infusion.
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 Contraindications and
Restrictions
 Hypersensitivity to the Quinolones
 Children and adolescents in the
growth phase.
 Pregnant women and breast feeding
mothers
 Ciprofloxacin interacts with antacids,
hence defered administration may be
necessary
 Concomitant administration with
theophyline.
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 OFLOMORE
 OFLOMORE is a brand of OFLOXACIN
marketed by CF&D.
 It is a fluoroquinolone containing a
fluorine atom at the 4-quinolone ring
and a piperazinyl group at position 7
of the ring
 This piperazinyl grp is methylated
and contributes to greater
bioavailability of OFLOMORE
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 Pharmacokinetics of
 OFLOMORE
OFLOMORE
is rapidly and almost
completely absorbed from the GIT
 Widely distributed into the following body
tissues/fluids after oral administration
- bones & cartilages, skin, sputum,
aqueous humor, tears, tonsils
- gynecological tissues, prostatic tissue
and fluid
 Elimination half life is 4-8 hrs
 Ofloxacin and its metabolites are excreted
in the urine.
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 Indications
 Complicated and Uncomplicated Urinary tract
infection such as cystitis, pyelonephritis, etc
 Prostatitis caused by susceptible E. coli & other G –
ve bacteria
 Lower respiratory tract infections – bronchitis, lung
abscesses, pneumonia & acute cases of bronchitis
caused by susceptible organisms
 Skin & soft tissue infections
 Acute PID (combination with metrnidazole)
 Salmonella infections (200-400mg bd x 7-14 days)

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 Drug Interactions & Side Effects
 Interacts with Antacids, iron and
multivitamin preparations
 Anti diabetic drugs (monitor blood glucose
level)
OFLOMORE is generally well tolerated, but
the following side effects have been
reported;
 Diarrhoea, nausea, vomiting
 Insomnia, dizziness
 Rashes, pruritis, urticaria, vasculitis,
photosensitivity rxns.
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 Dosage & Administration

Depending on the severity of infection and

for most infections:
 200-400mg every 12hrs for 5-14 days.

PRESENTATION
 Blister packs containing 200mg Ofloxacin
caplets x 10’s

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 CRIFLACIN
 Second generation fluoroquinolone
 A brand of PEFLOXACIN marketed by CF&D
 Administered orally (and parenterally) acts by
inhibition of DNA via interaction with DNA-gyrase
subunit
 Has an oral bioavailability of almost 100%
 Major elimination pathway is non-renal
 One of its metabolise is a drug (Norfloxacin)

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 Pharmacokinetics of CRIFLACIN
 Absorption is rapid (cin 30mins) and total on a
400mg dose
 Peak plasma level is reached in 1-3 hrs
 Elimination half life is 11-12hrs
 Low plasma protein binding of 20-30%
 60% of metabolites are active and include;
- N-Demethylpefloxacin (Norfloxacin)
- Pefloxacin-N-oxide
- Oxo- Pefloxacin
- Oxo-desmethylpefloxacin
 Low MIC for sensitive strains
 High level and prolonged plasma and tissue
concns Quinolones- Crystal Foods and Drugs 23
 Excellent Bioavailability
J A Chemotherapy 1992

CRIFLACIN CIPROFLOXACIN

CSF 50-60% 15-20%

BONE TISSUE 40% 25-40%
AQUEOUS 60% 20-30%
HUMOUR
GYNEACOLOGICA 95% 62%
L TISSUES

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 Indications
 Sepsis and Endocarditis,
 Cerebrospinal meningitis (CSM)
 Infections of the respiratory, renal or
urinary tract, gynecological and
obstetrical infections
 Hepato-billiary infection
 Bone and Joint infections
 Skin infections
Quinolones- Crystal Foods and Drugs 25
 Dosage and Administration
 Usually 400mg twice daily for 5-10 days
 An initial dose of 800mg may be given to
achieve an effective blood concentration
quickly
 Dosage adjustment is needed in patients
with severe hepatic dysfunction
 To be taken with meals to avoid GIT
disturbances.

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 Side Effects
 GIT include stomach ache, nausea and
vomiting
 CNS includes sleep disturbances,
headache, seizure
 SKIN: Allergic syndrome,
photosensitivity rxns
 BLOOD: Thrombocytopenia might occur
 Others include muscle & joint pain,
tendinitis.
Quinolones- Crystal Foods and Drugs 27
 Contraindications
 Pregnancy and breast feeding mothers
 Children under 15 years
 Glucose -6- phosphate dehydrogenase
deficiency patients
 Hypersensitivity to quinolones
 Epileptic patients
 Patients with history of tendonitis, tendon
damage related to quinolones.

Quinolones- Crystal Foods and Drugs 28

 THANK YOU

FOR COMING AND FOR YOUR

ATTENTION