Curriculum Vitae

Nama : Dr. Ronald Irwanto, SpPD, KPTI

Pendidikan :
SMA Canisius, Jakarta, 1994
Dokter Umum, FK TRISAKTI, 2001
Spesialis Penyakit Dalam (Internist), FKUI, 2009
Konsultan / Sub Spesialis Penyakit Tropik dan Infeksi, Divisi Penyakit
Tropik & Infeksi, Departemen Ilmu Penyakit Dalam, FKUI - RSCM,
2013

Managing Typhoid Fever in Special Cases :

Pregnancy and
MDR-Salmonella typhi (MDR-ST) Infection

Ronald Irwanto
Division of Tropical Medicine and Infectious Disease
Department of Internal Medicine
Faculty of Medicine University of Indonesia

AGENDA
Typhoid fever : The Epidemiology and
Microorganism Characteristic
Clinical Appearance and Diagnostic of
Typhoid Fever
Treatment of Typhoid Fever : General and
in Pregnancy
Treatment of MDR-ST
Conclusion

Typhoid fever : The Epidemiology

and Microorganism Characteristic

Typhoid Fever
Typhoid fever is an acute systemic
infection caused by Salmonella
enterica serotype typhi or paratyphi
which is also known as Salmonella
typhi

Risk factors for Typhoid & Paratyphoid Fever

in Jakarta
Among 1019 subjects with fever, Salmonella typhi was
identified in 88 (9%) and Salmonella paratyphi A in 26 (3%)
patients
Paratyphoid fever was independently associated with:
consumption of food from street vendors
and and flooding.
Typhoid fever using the community control group were mostly
related to the household, ie, to recent typhoid fever in the
household:
no use of soap for handwashing;
sharing food from the same plate,
and no toilet in the household.
also, typhoid fever was associated with young age in years.

Vollaard, AM., JAMA. 2004;291(21):2607-2615

Factors that Influence Infectivity

Ingestion of
105 organism cause clinical disease in 25%
107 organisms caused disease in 50%
109 organisms caused disease in 95%
Strains that do not have Vi antigen are less
infective and less virulent

Epidemiology of Typhoid Fever

Global health problem and highly endemic in
Indonesia
Global annual incidence 33 million cases and
15 million deaths.
Incidence in Indonesia estimated 350-810
cases/100.000 population per year
Case fatality rate 2.8-16%
3 % of all mortality (50.000 death/year)

Seowandojo E, 1998

Salmonella:
Structure, Classification, & Antigenic Types
1. Gram-negative, flagellated and
facultative anaerobic bacteria
2. The cell envelope contains a complex
lipopolysaccharide (LPS) structure. (an
outer O-polysaccharide coat, a middle
portion, the R core, and an inner lipid A
coat)
3. This LPS structure is thought as an
endotoxin, and important in
determining virulence of the
organisms.

Some example of commonly

Occuring Salmonella serotypes and groups
Group
A
B

Serotype
S. paratyphi A
S. paratyphi B
S. stanley
S. saintpaul
S. agona
S. typhimurium
S. paratyphi C
S. choleraesuis
S. virchow
S. thompson
S. typhi
S. enteritidis
S. dublin
S. gallinarium

Clinical Appearance and Diagnostic of

Typhoid Fever

Clinical Presentation of Typhoid Fever

Clinical sign and symptom
Headache
Epigastric pain
Nausea
Anorexia
Fever (>37.2)
Muscular pain
Rigor
Coated tongue
Vomiting
Cough
Relative bradicardia
Diarrhea
Constipation
Hepatomegaly
Splenomegaly

sum (n=119)
59
57
108
41
118
14
37
84
104
91
117
109
109
117
117

%
94.9
94.7
90.7
90.2
89.8
78.6
78.4
41.8
57.7
46.2
34.2
32.1
33.9
12.3
0.8

Pohan HT, Indones J Int Med 2004;36(2)

Diagnostic criteria
Definite :
Positive gall culture or PCR Salmonella typhi
Widal serology agglutinin O titer > 1/640
or H titer >1/1280
Increased of O titer twice or more
Probable :
Widal serology agglutinin O titer 1/320
or H titer 1/640.

Blood culture and PCR results in

diagnosis of Typhoid Fever

Treatment of Typhoid Fever : General

and in Pregnancy

General Treatment in Typhoid Fever

Non Pharmacologic : Bed rest, Nutrition
Pharmacologic
Symptomatic
Antibiotic :
Ampicillin/Amoxicillin
Chloramphenicol 4x500mg
Cephalosporin : Ceftriaxone 3-4 g/days
Fluoroquinolones : Ciprofloxaxin 2x500 mg
Ofloxacin 2x400 mg
Pefloxacin 1x400 mg
Fleroxacin 1x500 mg
Levofloxacin 1x500mg

Antibiotics during pregnancy and lactation (1)

Embryionic
period*

Post
Embryonic
period**

Peripartal
period***

Lactation

Penicillin

None known

Cephalosporins

None known

Aminoglycosides

Inner ear damage

Erythromycin

(+)

None known, dont use

erythromycin estolate

Clincamycin

(+)

(+)

(+)

(+)

None known,
pseudomembranous
enterocolitis im mother

Tetracyclines

Disturbance of bone and

tooth growth

Chloramphenicol

Gray syndrome,
myelosuppresion

Co-trimoxazole

(+)

(+)

Teratogenic in animal
experiments, kernicterus

Agent

- Contraindicated or
not recommended

+ safe for use

when indicated

Possible foetal
impairment

(+) only if clearly

indicated

* Embryonic period (1st to 12th wk. of pregnancy)

** Postembryonic period (13th to 39th wk. of
pregnancy) *** Peripartal period (40th wk. of pregnancy till delivery )

to be prescribed
only in exceptional cases

Antibiotics during pregnancy and

lactation(2)
Embryionic
period *

Post
Embryonic
period **

Peripartal
period ***

(+)

None known

Coagulation disorder, liver

damage in mother and fetus

Vancomycin

(+)

(+)

(+)

(+)

Quinolones

Disturbance of chodral
growth

Nitrofurantoin

(+)

(+)

Teratogenic in animal
experiments

Metronidazole

Teratogenic in animal
experiments

Amphotericin
B

A(+)

A(+)

Abortion and foetal

retardation reported

Agent
Fusicid Acid
Rifampicin

* Embryonic period
wk. of pregnancy)

(1st to 12th

** Postembryonic period
wk. of pregnancy)

(13th to 39th

*** Peripartal period

pregnancy till delivery )

(40th wk. of

- Contraindicated
or
not
recommended

(+) only if clearly

indicated

Possible foetal
impairment

Lactation

None known

+ safe for use

when indicated

to be prescribed

only in exceptional
cases

Typhoid Treatment Choice in

Pregnancy

Communicable Disease Control and provincial Laboratory Services, Kwazulu Natal

Dept. of Health

Treatment of MDR-ST

What is MDR-ST?
MDR-ST is Salmonella typhi which has a
mutagen (Gyr-A or TEM-1) that can
resistant to fluorquinolens or partially to
beta-lactam (not all)

MDR Salmonella Typhi(MDR-ST)

Case Possibility
The possibility of MDR-ST showed by
clinical impression in which theres no good
response after empirical adequate therapy
By :
- Penicillin
:
Amoxycillin, Ampicillin
- Fluorquinolones
:
Ciprofloxacin
Levofloxacin
- Cephalosporines :
Ceftriaxone
Yoon HJ, Cho SH, Kim SH, A case of MDR Salmonella enterica serovar typhi treated with a bench to bedside
Approach, Yonsei J Med, 2009 : 50(1) : 147-51

A Multi-Drug Resistant Salmonella typhi

(MDRST) was appeared by the present of
gyrA and TEM-1 gene.
GENERAL MECHANISM of RESISTANCE

Gyr A
Gene

Fluorquinolone
Resistance

TEM-1
Gene

Betalactamase
But not ESBL

MDRT

Penicillins resistance
Ceftriaxone resistance
Yoon HJ, Cho SH, Kim SH, A case of MDR Salmonella enterica serovar typhi treated with a bench to bedside
Approach, Yonsei J Med, 2009 : 50(1) : 147-51

Eradicating MDR-ST
Case report from Korea (2009) showed the
successful treatment with aztreonam and
Carbapenem (meropenem) for eradicating MDRT
In this case, Aztreonam exhibited superiors
antimicrobial activity compared to other antibiotics,
including ceftazidime with MIC90% 0,8ug / ml (MIC
0,05 to 1,56 ug / ml)
Yoon HJ, Cho SH, Kim SH, A case of MDR Salmonella enterica serovar typhi treated with a bench to bedside
Approach, Yonsei J Med, 2009 : 50(1) : 147-51

Conclusion
1. Typhoid fever : acute systemic illness due to Salmonella
typhi and paratyphi
2. Treatment : Supportive and symptomatic
Antimicrobial : Ampicillin, Chloramphenicol
Fluorquinolones
3rd Gen Cephalosporine
3. Treatment choices in pregnancy : Penicillin and
Cephalosporines
4. Treatment option for MDR-ST : Azteronam+Carbapenem