2. Global Burden
•Enteric fever, a serious bloodstream infection caused
by the human-restricted bacterial
pathogens Salmonella enterica serovars Typhi
(S. Typhi) and Paratyphi A,B,C
•According to recent reports, around 21 million
people contract typhoid each year, causing 161,000
deaths by enteric fever worldwide each year, mostly
affecting children and young adults.
•It accounts for 30% of all community acquired blood
stream infections in Asia
3. Burden of disease
•The incidence of multidrug-resistant (MDR)
typhoid cases in a recently reported study in
India was 7%
•In recent studies in Pakistan, it has been
found that MDR has risen from 34.2% to
64.1%, while extensive drug resistance has
risen from 1.6% to 64.1% over the same
period.
4. What is MDR typhi
•Multidrug-resistant (MDR) typhoid, defined
as resistance to three first-line antibiotics
used to treat typhoid—chloramphenicol,
ampicillin, and cotrimoxazole
• The H58 strain is considered the globally
dominant strain of MDR typhoid.
5. MDR Typhi
•In response to this fluoroquinolones were
used as a preferred drug in the 1990s.
•Over a period of time emergence of
fluoroquinolone-resistant typhoid strains
occurred which are widespread in South Asia.
•This led to the choice of third-generation
cephalosporins and Azithromycin as a
preferred treatment option.
7. PAKISTAN STUDY
•In a 10-month period between 2016 and
2017, health authorities in Pakistan detected
more than 800 cases of extensively drug-
resistant (XDR) typhoid in the city of
Hyderabad alone.
•The risk of ceftriaxone-resistant S Typhi
infection was increased among children aged
15 years and younger, male individuals, and
those eating outside the house.
8.
9.
10. What is X D R Typhi
•These strains are resistant to five classes of
antibiotics: chloramphenicol, ampicillin,
cotrimoxazole, fluoroquinolones, and third-
generation cephalosporins.
•The existence of drug target modification and
three separate multidrug efflux pumps in the
bacterium is hypothesized as a mechanism for
resistance to these antibiotics.
11. Sensitivity pattern- Indian scenario
•In one of the study conducted in india recently,
out of 251 Salmonella isolates, 192 (76.5%)
were S. typhi and 59 (23.5%) were S. paratyphi A.
•All 251 (100%) Salmonella isolates were sensitive
to cefixime, ceftriaxone, and azithromycin;
•237/251 (94.4%) isolates to chloramphenicol and
•only 9/251 (3.6%) isolates were sensitive to
ofloxacin.
•This study confirms the re-emergence of
susceptibility of Salmonella isolates to
chloramphenicol.
12. Azithromycin
•MICs for Azithromycin are increasing
progressively
•Azithromycin has got 50-100 times
intracellular concentration as compared to
plasma
•So yet the drug remains effective
13. Current guidelines
•Oral cefixime and Iv ceftriaxone still first line
of therapy for managing patients on outdoor
and indoor basis respectively.
•Non responding enteric fever, Azithromycin is
a good second line drug
•Very rare incidence of XDR typhoid in India, if
found treatment should be based on
sensitivity pattern, with carbapenems or
aztreonam.
14. Adjunctive corticosteroids for
severe infection
•For patients with suspected or known enteric
fever and severe systemic illness (delirium,
obtundation, stupor, coma, or shock)
•adjunctive dexamethasone (3 mg/kg
followed by 1 mg/kg every 6 hours for a total
of 48 hours).
•These findings are based on old data (1984)
and have not been revalidated.
15. Patients with ileal perforation
•For patients with ileal perforation, prompt
surgical intervention is usually indicated, as is
broader antimicrobial coverage to cover
peritonitis and potential secondary
bacteremia with enteric organisms
16. References
• GBD Typhoid and Paratyphoid Collaborators. The global burden of typhoid and paratyphoid fevers: a
systematic analysis for the Global Burden of Disease Study 2017. Lancet Infect Dis. 2019;19(4):369–
81.
• Deen J, von Seidlein L, Andersen F, Elle N, White NJ, Lubell Y. Community-acquired bacterial
bloodstream infections in developing countries in South and Southeast Asia: a systematic review.
Lancet Infect Dis. 2012;12(6):480–7
• Maskey AP, Day JN, Phung QT, Thwaites GE, Campbell JI, Zimmerman M, et al. Salmonella enterica
serovar Paratyphi A and S. enterica serovar Typhi cause indistinguishable clinical syndromes in
Kathmandu, Nepal. Clin Infect Dis. 2006;42(9):1247–53.
• Ochiai RL, Wang X, von Seidlein L, Yang J, Bhutta ZA, Bhattacharya SK, et al. Salmonella paratyphi A
rates. Asia Emerg Infect Dis. 2005;11(11):1764–6.
• Sriparna Samajpati, Agila Kumari Pragasam, Subhranshu Mandal, Veeraraghavan Balaji, Shanta Dutta,
Emergence of ceftriaxone resistant Salmonella enterica serovar Typhi in Eastern India, Infection,
Genetics and Evolution, Volume 96, 2021, 105093,ISSN 1567-1348,
https://doi.org/10.1016/j.meegid.2021.105093.
• Silvia Argimón and others, Circulation of Third-Generation Cephalosporin Resistant Salmonella Typhi
in Mumbai, India, Clinical Infectious Diseases, Volume 74, Issue 12, 15 June 2022, Pages 2234–
2237, https://doi.org/10.1093/cid/ciab897
17. • Rasheed MK, Hasan SS, Babar ZU, Ahmed SI. Extensively drug-resistant typhoid fever in
Pakistan. Lancet Infect Dis. 2019;19:242–3.
• Sah R, Donovan S, Seth-Smith HM, Bloemberg G, Wüthrich D, Stephan R, et al. A novel lineage of
ceftriaxone-resistant Salmonella Typhi from India that is closely related to XDR S. typhi found in
Pakistan. Clin Infect Dis. 2020;71:1327–30.
• Patil N, Mule P. Sensitivity Pattern Of Salmonella typhi And Paratyphi A Isolates To
Chloramphenicol And Other Anti-Typhoid Drugs: An In Vitro Study. Infect Drug Resist. 2019 Oct
14;12:3217-3225. doi: 10.2147/IDR.S204618. PMID: 31686872; PMCID: PMC6800285.
• Enteric (typhoid and paratyphoid) fever: Treatment and prevention, UpTodate, Jason Andrews,
MDJacob John, MD, Richelle C Charles, MD
• Hoffman, S. L., Punjabi, N. H., Kumala, S., Moechtar, M. A., Pulungsih, S. P., Rivai, A. R., Rockhill, R.
C., Woodward, T. E., & Loedin, A. A. (1984). Reduction of mortality in chloramphenicol-treated
severe typhoid fever by high-dose dexamethasone. The New England journal of medicine, 310(2),
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