Warior - Enteric Fever - 13 June 2011

Dr.
Muhammad Ali Akbar

Product Manager
Enteric Fever
Global Burden
 16 million cases and 600,000 deaths
Ivanoff B, et. al. Vaccination against typhoid fever: present
status. Bull World Health Organ. 1994;72(6):957-71
 21.7 million cases and 217,000 deaths - TF

 5.4 million cases - PaTF
Crump JA, Mintz ED. Global trends in typhoid and paratyphoid
Fever. Clin Infect Dis. 2010 Jan 15;50(2):241-6
Geographical distribution of typhoid
fever
Southeast Asia
Ref: Bulletin of WHO - 2004

Bulletin of WHO -
Crude typhoid fever incidence rates by region, 2000

Typhoid Fever
in
Pakistan
A study of typhoid fever in five Asian
countries: disease burden and
implications for controls
Ochiai RL, Bhutta ZA, et. al.
Bulletin of World Health Organization - April 2008

Study sites
 Five Asian countries (endemic for typhoid):
 Pakistan Slum areas in Karachi
1. Hijrat Colony
 India
2. Sultanabad
 China 3. Bilal Colony
 Indonesia
 Vietnam
Ochiai RL, Bhutta ZA, et. al. A study of typhoid fever in five Asian countries: disease burden and implications for
controls. Bull World Health Organ. 2008 Apr;86(4):260-8
Field Sites
Incidence rates (2-15 yrs. old)
Incidence Rates (Diff. age groups)
97%
Conclusion
 Typhoid fever remains a serious public health
problem in Pakistan
 with estimated incidence among 2-15 years of
age of 800/100,000 in urban populations
 Antibiotic-resistant typhoid is growing rapidly in
Pakistan, resulting in:
 greater difficulty in treating cases,
 prolonged treatment, &
 rising treatment costs
 Typhoid fever exerts a heavy economic burden on
affected families
Warior
in
Enteric Fever
Open study on efficacy and safety of
levofloxacin in treatment of
uncomplicated typhoid fever
Nelwan RH, Chen K, et. al.
Southeast Asian J Trop Med Public Health - Jan 2006

Objective
To determine clinical efficacy &

safety of levofloxacin for
typhoid fever cases
Nelwan RH, et. al. Open study on efficacy and safety of levofloxacin in treatment of uncomplicated typhoid fever.
Southeast Asian J Trop Med Public Health. 2006 Jan;37(1):126-30
Inclusion Criteria
 male or female - 18-65 years
 with clinical typhoid fever without signs of
complications
Exclusion Criteria
 age below 18 years
 pregnant or lactating females
 severe cases
 immunocompromised pts.
 renal insufficiency (creatinine >1.4 g/dl)
 history of allergy to fluoroquinolones, etc.
Method
 Final diagnosis of enteric fever was made by:
 positive blood culture
 polymerase chain reaction
 Serology
 Patients were treated with levofloxacin 500
mg once daily for 7 days
Results
 100% clinical efficacy was obtained

in pts. on levofloxacin 500 mg/day
 minimal adverse reactions
Clinical results of treatment
Adverse events experienced
Comparison of defervescence in
typhoid fever
Levofloxacin in enteric fever - a study
Kadam GS, Naikwadi A, et. al.
J Indian Med Assoc. - Aug 2005

Background
 Therapy with conventional drugs is associated with:
 increasing resistance,
 non-compliance to therapy, &
 toxicity
 Oral fluoroquinolones have been shown to be effective
compared to parenteral broad-spectrum cephalosporins in
treatment of uncomplicated typhoid
 There is no data available regarding use of levofloxacin in
treatment of typhoid fever
Kadam GS, Naikwadi A, et. al. Levofloxacin in enteric fever--a study. J Indian Med Assoc. 2005 Aug;103(8):441-2, 446
Objective
To evaluate efficacy, safety & tolerability

of oral levofloxacin 750 mg once daily
in treatment of typhoid fever
Results
 Levofloxacin 750 mg once daily was an:
effective
safe
well-tolerated, and
cost-effective option
 in treatment of typhoid fever in adult

males and non-pregnant females
Levofloxacin: Today’s Choice for the
Treatment of Typhoid Fever?
An Illustrative Case Report from Indonesia
R. H. H. Nelwan, MD, DTMH

Using Cipro for EF??
 Ciprofloxacin is accepted as a drug of choice
for typhoid fever & has been used for almost
two decades
 In recent years, emergence of a decline in

sensitivity of S. typhi to ciprofloxacin has been
reported
R. H. H. Nelwan, MD, DTMH. Levofloxacin: Today’s Choice for the Treatment of Typhoid Fever? - 2007
Using Cipro for EF?? - (Contd.)
 Lab. reports of increased resistance to
ciprofloxacin are on rise, esp. in South Asian
subcontinent
 Serious thought is being given about wisdom

of treating future typhoid fever cases with
ciprofloxacin
A case
 In a patient, GI intolerance to oral
ciprofloxacin was observed with possible
hepatic adverse reactions & subsequent
clinical failure of typhoid fever treatment
 Levofloxacin was substituted, as it has
already been shown to be better tolerated
Levofloxacin successfully cured the

patient’s typhoid infection without causing
any adverse GI reactions
Discussion
 There is a bright future for the use of
levofloxacin in typhoid fever patients in
general and, esp. in patients with impaired
liver function
 Levofloxacin offers a very high level of clinical

efficacy with a minimal no. of adverse GI
reactions
Conclusion
 Typhoid fever can be better treated with
levofloxacin because of its dual features
of:
highefficacy, and
lower rate of adverse reactions
compared with ciprofloxacin esp. in

S. typhi. infections
Limitations of ciprofloxacin in EF
 Lower serum drug concentration
 Short half-life
 Lower potency
 Higher bacterial resistance
 High rate of GI adverse reactions
Product Monograph Warior

Warior
(Levofloxacin)
Levofloxacin - Intro
 Broad spectrum of activity against both gram-positive
and gram-negative bacteria responsible for UTIs
 Appropriate choice for treatment of complicated UTIs,

uncomplicated UTIs, recurrent UTIs
 Effective against β-lactam and macrolide resistant

pathogens
David RD, DeBlieux PM, Press R. Rational antibiotic treatment of outpatient genitourinary infections in a changing
environment. Am J Med. 2005 Jul;118 Suppl 7A:7S-13S
Schaeffer AJ. The expanding role of fluoroquinolones. Dis Mon. 2003 Feb;49(2):129-47
Unique Structure
 More potent against gram-
negative bacteria
 Exhibits better
antipseudomonal activity
 Greater oral bioavailability
Ernst ME, Ernst EJ, Klepser ME. Levofloxacin and trovafloxacin: the next generation of
fluoroquinolones? Am J Health Syst Pharm. 1997 Nov 15;54(22):2569-84
Pharmacokinetic Profile
 Bioavailability → 100%
 Peak plasma level → 5.7 µg/ml
(500 mg tablet)
 Tmax → 1 - 2 hours
 Protein binding → 24 - 38%
 Distribution → 1.25 L/kg
 Metabolism → Liver (minimal)
 Half-life → 7.6 hours
 Excretion → Kidneys - 84%
unchanged (71%) in 24 hours
McGregor JC, Allen GP, Bearden DT. Levofloxacin in the treatment of complicated urinary tract
infections and acute pyelonephritis. Ther Clin Risk Manag. 2008 Oct;4(5):843-53
MICROMEDEX Levofloxacin - 2010
Mode of Action
 Enter bacterium by passive diffusion through
porins in outer membrane
 Once inside, they inhibit replication of

bacterial DNA by interfering with action of:
 DNA gyrase (topoisomerase II)
 Topoisomerase IV
during bacterial growth & reproduction
Harvey RA, Champe PC, eds. Pharmacology. 4th ed. Lippincott Williams & Wilkins; 2009:387
Antibacterial Spectrum
Gram +ve Gram -ve Atypical Anaerobes
S. aureus N. gonorrhoeae L. pneumophila B. fragilis

S. epidermidis M. catarrhalis M. pneumoniae C. perfringens
S. pneumoniae S. typhi & paratyphi C. pneumoniae Peptococcus
S. pyogenes H. influenzae Chlamydia
Enterococcus E. coli psittaci
Proteus sp
K. pneumoniae
Shigella
P. aeruginosa

Indications
 Enteric fever
 Acute sinusitis
 CAP
 AECB
 Uncomplicated UTI
 Complicated UTI including pyelonephritis
 Chronic bacterial prostatitis
 Skin and soft tissue infections

Dosage
Indication Daily Dose Duration
Uncomplicated
500 mg OD 7 days
typhoid fever
Contraindications
 Hypersensitivity to levofloxacin or other
quinolones
 Epilepsy
 History of tendon disorders related to
treatment with fluoroquinolones
 Children or growing adolescents
 Pregnancy & lactation

Price
250 mg tab (10’s) = Rs. 100/-
Per tab = Rs. 10/-
500 mg tab (10’s) = Rs. 180/-
Per tab = Rs. 18/-
Disclaimer
The material presented here does not reflect the views of the speaker or Nabiqasim Industries. These materials may discuss uses
and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified
health care professional should be consulted before using any therapeutic product discussed. All readers and continuing education
participants should verify all information and data before treating patients or employing any therapies described in this continuing
medical education activity.

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Dr.

Muhammad Ali Akbar

 21.7 million cases and 217,000 deaths - TF

Ref: Bulletin of WHO - 2004

Crude typhoid fever incidence rates by region, 2000

Ochiai RL, Bhutta ZA, et. al.

Bulletin of World Health Organization - April 2008

Nelwan RH, Chen K, et. al.

Southeast Asian J Trop Med Public Health - Jan 2006

To determine clinical efficacy &

 100% clinical efficacy was obtained

 minimal adverse reactions

Kadam GS, Naikwadi A, et. al.

J Indian Med Assoc. - Aug 2005

To evaluate efficacy, safety & tolerability

 in treatment of typhoid fever in adult

R. H. H. Nelwan, MD, DTMH

 In recent years, emergence of a decline in

 Serious thought is being given about wisdom

Levofloxacin successfully cured the

 Levofloxacin offers a very high level of clinical

compared with ciprofloxacin esp. in

Product Monograph Warior

 Appropriate choice for treatment of complicated UTIs,

 Effective against β-lactam and macrolide resistant

 Once inside, they inhibit replication of

Gram +ve Gram -ve Atypical Anaerobes

S. aureus N. gonorrhoeae L. pneumophila B. fragilis

Product Monograph Warior

Product Monograph Warior

Indication Daily Dose Duration

Product Monograph Warior

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