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Gastrointestinal tract
Digestive System
Functions:
It is involved in
Ingestion Digestion Absorption Excretion of the food
Typhoid
Typhoid (Enteric fever) remains endemic in many areas of the developing world
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
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;
Typhoid Symptoms
Typhoid Symptoms
Some people with typhoid fever develop a rash called "rose spots," which are small red spots on the abdomen and chest.
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. typhi bacteria.
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
Complication
Intestinal hemorrhage
Intestinal perforation
Encephalitis
Metastatic abscesses
Cholecystitis Endocarditis
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
Chloramphenicol Ampicillin Trimethoprim-sulfamethoxazole Fluroquinolones like ciprofloxacin, ofloxacin Third generation cephalosporins like ceftriaxone (injectable)
Treatment
Chloramphenicol was the original drug of choice for many years. Advantages:
Low cost, wide availability
Disadvantage:
Not reduces the relapse rate
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 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd.
Third generation cephalosporins ( both oral and injectable) achieve good concentration in bile and are effective in the management of typhoid
conventional first-line antibiotics (chloramphenicol, cotrimoxazole, 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. Typhi
Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever) (Review) 10 Copyright 2008 The Cochrane Collaboration. Published by JohnWiley & Sons, Ltd.
There is decreased susceptibility to drugs (Chloramphenicol, Ampicillin, Chloramphenicol, Cotrimoxazole & Ciprofloxacin) with consequent therapeutic failure
Similarly ciprofloxacin resistant enteric fever has evolved due to their rampant use
Capoor MR. JMM 2007;56:1490-4
MIC [mcg/ml]
>
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
Faster cure
Increases success rate Increased pt compliance
Ofloxacin in Typhoid
Clinical 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
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 be
3rd generation cephalosporin Reaches therapeutic concentrations in respiratory tract and genitourinary tracts and bile (PI)
typhoid fever.
In Bangladesh, where typhoid fever is also
Kefpod O
Composition
Each tablet of Kefpod O contains
Cefpodoxime 200 mg + Ofloxacin 200 mg
Ofloxacin
2nd generation fluroquinolone Bactericidal Acts on DNA Gyrase and topoisomerase IV Broad Spectrum S/E profile of ofloxacin is better than other
fluroquinolones
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
Cefpodoxime Proxetil
3rd Generation cephalosporin Bactericidal acts 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
Cefpodoxime Proxetil
Expanded spectrum cephalosporins such as
Kefpod O
Cefpodoxime Proxetil 3rd generation cephalosporin Inhibits cell wall synthesis Ofloxacin 2nd generation Fluroquinolone Inhibits nuclear DNA gyrase for replication Benefits Complementary different site of actions & therefore more useful in tackling resistance
Target cell concentration achieved for immediate & sustained efficacy to prevent further resistance
200 mg BD
Complementary BD dosage
Compatible Pharmacokinetic
Side Effects
Nausea, Vomiting, GI disturbances
Drug Interactions
Antacid, Theophylline, Warfarin
Indication :
Typhoid fever
Dosage:
1 tablet to be taken twice daily after meals for 714 days depending upon the severity of infections