Kefpod o Final Pres

8/13/2019 Kefpod o Final Pres

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Gastrointestinal tract


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Digestive System

Functions:

It is involved in

Ingestion

Digestion

Absorption

Excretion of the food


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Common worldwide bacterial

disease

An acute illness associated with

fever that is most often caused

by the Salmonella typhibacteria

Transmitted by the ingestion of

contaminated food or water


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Typhoid

Typhoid (Enteric fever) remains endemic in many areas of the

developing world

Causes over 26 million infections and over 2,00,000 deaths annually

Incidence is highest in south-central Asia and South East Asia (over

100/100 000 cases/year), with the highest burden of disease in

children aged 2-15 years

Thaver D. BMJ 2009;338:b1865
http://localhost/var/www/apps/conversion/tmp/scratch_7//upload.wikimedia.org/wikipedia/commons/5/58/Fievre_typhoide.png


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Typhoid

Causes:

Caused by several species of Salmonella: S. typhi, S.

paratyphi

The proximate cause in most cases is water or food

contamination by a human carrier


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Typhoid

Symptoms Incubation period - 1 to 2 wks

Duration of the illness - 4 to 6 wks

The patient experiences poor appetite

abdominal pain

headaches

generalized aches and pains;

fever, often up to 104 F;

lethargy (usually only if untreated);


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Some people with typhoid fever develop a rash called "rose

spots," which are small red spots on the abdomen and

chest.

Typhoid

Symptoms
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Diagnosis

A complete blood count (CBC) will show a high number of white blood cells.

A blood culture during the first week of the fever can show S. typhibacteria.

Widal test : "O" agglutinin antibody titer 1:80 and "H" 1:160 or "O" 4

times higher supports a diagnosis of typhoid fever

Other tests that can help diagnose this condition include:

ELISA urine test to look for the bacteria that cause Typhoid fever

Fluorescent antibody study to look for substances that are specific to Typhoid

bacteria

Platelet count (platelet count will be low)

Stool culture


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Complication

Intestinal hemorrhage

Intestinal perforation

Encephalitis

Metastatic abscesses

Cholecystitis

Endocarditis


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Antibiotics and supportive care (IV fluids)

Prior to the use of antibiotics, the fatality rate was 20%

With antibiotics and supportive care, mortality has

been reduced to 1%-2%

With appropriate antibiotic therapy, there is usually

improvement within 1-2 days and recovery within 7-10

days


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Antibiotics are the mainstay of the

therapy in the management of Typhoid


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Chloramphenicol

Ampicillin

Trimethoprim-sulfamethoxazole

Fluroquinolones like ciprofloxacin, ofloxacin

Third generation cephalosporins like ceftriaxone

(injectable)


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Treatment

Chloramphenicol was the original drug of choice for manyyears.

Advantages:

Low cost, wide availability

Disadvantage:

Not reduces the relapse rate

No effect on carrier state

Not useful for treating MDR s typhi.

Rare serious side effects


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Fluoroquinolones (ciprofloxacin, ofloxacin, enoxacin,

and pefloxacin) are a large family of anti-infective drugs

synthesized around the quinolone core and that

possess a broad antibacterial spectrum (Congeni 2002).

Fluoroquinolones effectively penetrate macrophages

and achieve high concentrations in bile (Miller 2000).

Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever) (Review) 10 Copyright 2008 TheCochrane Collaboration. Published by JohnWiley & Sons, Ltd.


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Antibiotics like fluroquinolones and thirdgeneration cephalosporins the mainstay

of the therapy in the management of

Typhoid


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MDR strains of S. Typhi, carrying resistance to all

conventional first-line antibiotics (chloramphenicol, co-

trimoxazole, and ampicillin or amoxicillin), have become

highly prevalent in several areas of the world since 1989

In the Indian subcontinent and China, the frequency of

these MDR strains ranged from 50% to 80% of all S. Typhiisolates and reached 100% during outbreaks (Lee 2000)

Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever) (Review) 10 Copyright 2008 TheCochrane Collaboration. Published by JohnWiley & Sons, Ltd.


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There is decreased susceptibility to drugs

(Chloramphenicol, Ampicillin, Chloramphenicol,

Cotrimoxazole & Ciprofloxacin) with consequent

therapeutic failure

To complicate further, it is often necessary to commence

treatment before the results of diagnosis or laboratory

sensitivity tests for resistance are available

Threlfall EJ. EID 2008;14[5]:860-


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Incidence of multi-drug resistant [MDR]

salmonella typhi is as high as 92%

Krishnan P. IJPM 2009;52[4]:505-8

Similarly ciprofloxacin resistant enteric fever

has evolved due to their rampant use Capoor MR. JMM 2007;56:1490-4


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Ciprofloxacin resistant Typhoid isolates

..rising incidence in Developed countries

Incidence of resistance to ciprofloxacin in isolates of S. typhi [UK, 2006]

%

Threlfall EJ. EID 2008;14[5]:860-1

Major concern..Antibacterial Resistance


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Ciprofloxacin resistant Typhoid isolates

rising incidence confirmed in India

Characterized by rising MIC levels [>0.25 mcg/ml]

MIC

[mcg/ml]>

S t hi i t t Fl i l


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S. typhi resistance to Fluoroquinolones

in vitro Study, New Delhi

Indiscriminate use of the existing therapeutic options forenteric fever has resulted in growing incidence of resistance

31 ciprofloxacin resistant isolates were evaluated for

sensitivity to advanced Fluoroquinolones & Azithromycin

Most of these drugs showed raised MIC levels

Advanced fluoroquinolones including Gatifloxacin showedresistance

Capoor MR. JMM 2007;56:1490-4


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Rationale for combination in

Typhoid fever


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Why Combination ?

Due to the increasing incidence of resistance of the

pathogens causing typhoid to the currently used

therapies , there is a need of Using combination of

drugs

The advantage of combination of drugs

Added synergy of the two drugs

Faster cure

Increases success rate

Increased pt compliance


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Ofloxacin + Cefpodoxime Rationale

Typhoid or Enteric fever is an endemic infection inIndia

Fluoroquinolones with their intracellular action and

longer half life offer quicker defervescence in suchcasesDrug of Choice

Inadequate or Rampant use of these drugs has

resulted in increased incidence of plasmid resistanceto DNA gyrase

Newer advanced fluoroquinolones too are resistant in

such cases


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Ofloxacin + Cefpodoxime Rationale

Second-line therapy including Ceftriaxone &

Cefotaxime require parenteral administration

Combination with Oral Cephalosporin offers

complementary site of action taking care of

resistant organisms when used in INITIALLINEsettings

Ofl i i T h id


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Ofloxacin in TyphoidClinical efficacy

Studies by Yousuf (1992), Parry(2007) have demonstrated efficacy of

Ofloxacin (200 mg or 10 mg/kg twice daily for 7 to 14 days)

in uncomplicated Typhoid


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9 pts with typhoid fever were given ofloxacin in a

daily dosage of 400 mg for 10 days

All patients recovered with no relapses

No case of Salmonella typhi carriage was recorded.

According to our results, ofloxacin could beconsidered as one of the alternatives for treating

typhoid fever

J P Stahl etal. Pathologiebiologie (1986) Volume: 34, Issue: 5, Pages: 505-507


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3rdgeneration cephalosporin

Reaches therapeutic concentrations in

respiratory tract and genitourinary tracts and

bile (PI)

C f d i P til


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Cefpodoxime Proxetil

TyphoidClinical efficacy

A study from Asian population has reported about

86% efficacy for cefpodoxime in the treatment of

typhoid fever.

In Bangladesh, where typhoid fever is also

endemic, a clinical trial showed cefpodoxime to be

highly efficacious in the treatment of typhoid fever

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Feb. 2008, p. 802803


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Kefpod O

Composition

Each tablet of Kefpod O contains

Cefpodoxime 200 mg + Ofloxacin 200 mg

Ofl i


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Ofloxacin

2nd generation fluroquinolone

BactericidalActs on DNA Gyrase and

topoisomerase IV

Broad Spectrum

S/E profile of ofloxacin is better than other

fluroquinolones

Ofl i


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Ofloxacin

Ofloxacin is widely distributed to body tissues

Between 65 % & 80% of an administered oral dose

of ofloxacin is excreted unchanged via the kidneys

within 48 hrs of dosing

Usual dose of ofloxacin : 200-400 mg BD for 5-7

days



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3rdGeneration cephalosporin

Bactericidalacts on the organisms by inhibiting

bacterial cell wall synthesis

Very active against gram positive and gram

negative organisms

Has excellent tissue penetration including bile and

good half life

The usual dosing is- 200 mg BD for 7-10 days

C f d i P il


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Expanded spectrum cephalosporins such asCefpodoxime Proxetil shows the promising

results in the management of typhoid

Cefpodoxime delivers the desired

characteristics of an antibiotic and may be the

treatment of choice for MDR typhoid fever

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Feb. 2008, p. 802803

K f d O


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Kefpod O

Cefpodoxime Proxetil Ofloxacin Benefits

3rdgeneration

cephalosporin

2ndgeneration

Fluroquinolone

Complementary different

site of actions & thereforemore useful in tackling

resistanceInhibits cell wall synthesis Inhibits nuclear DNA

gyrase for replication

Broad spectrum including

gm-ve organisms

Broad spectrum involving

gmve

Ideal for Typhoid

Achieve therapeutic

concentration in bile

Achieve therapeutic

concentration in bile

Target cell concentration

achieved for immediate &

sustained efficacy to

prevent further resistance

200 mg BD 200 mg BD for Typhoid Complementary BD dosage

Compatible Pharmacokinetic


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Side Effects

Nausea, Vomiting, GI disturbances

Drug Interactions

Antacid, Theophylline, Warfarin


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Indication :

Typhoid fever

Dosage:

1 tablet to be taken twice daily after meals for 7-

14 days depending upon the severity of

infections

USP OF Combination of Cefpodoxime and


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Ofloxacin

Synergistic effects of the drugs

Faster cure

Better success rate

Less chances of relapse

Less chances of Carrier stage

Better patient compliancethe patient has to take only

one tablet as against 2 separately



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Ofloxacin

The combination would have good potential and

would be useful addition for the physician in the

treatment of typhoid including MDR Typhoid

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