Management of drug - resistant

Salmonella Typhi Infection

dr. Rizky Perdana, SpPD,KPTI,FINASIM

Division of Tropical Infectious Diseases
Department of Internal Medicine
University of Sriwijaya
2014

Global distribution of MDRST

USA (1996-2003)
Nalidixic Acid Resistance
S. Typhi
USA (2005) CeftiofurResistant Salmonella

Cuba (2006),
Mexico (2007)
Multidrugresistant
salmonella
Ethiopia(2011) ;
86.5% multiply resistant
to trim-sulpha, ceftr,
chloram and genta, ciprofl.

Canada (2009)
Cefoxitinresistant
Salmonella

Viet Nam (1997)

QuinoloneResistant S.
typhi

Makassar
(2007) :
resistant of
S.typhi
infection 6,8%.
Jakarta FKUI/RSCM
(1990-1994 ) :
resistant of S.typhi
infection 9,5%.
Australia (2006)
Antibiotic resistant
Salmonella infections

Clin.Infect.Diseases 1997; J of Antimicrobial Chemoth 2009

Commun Dis Intell 2006; Antimicrobial agents and chemoth. 200
Antimicrobial agents and chemoth. 20
J Infect Dev Ctries 20

DEFINITION

Relapse of typhoid fever:

1-3 weeks after the temperature is normalized.
milder pattern to the primary attack.
Blood culture is positive.
Recurrence of typhoid fever:
3-4months after the illness.
Blood culture is positive.
Antibiotic resistance of typhoid fever:
the ability of salmonella typhi to survive
and reproduce in the presence of antibiotic
doses that were previously thought to be effective.

Some example of commonly

Occurring 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

Mechanisms of MDRST
Drug resistance in most cases is the
result of :
genetic change (chromosomal
mutation in the organism)
Plasmid mediated resistance
Types pHCM2(cryptic plasmid)
The large plasmids

Masatomo : Antimicrobial agents and chemotherapy

2010
Getenet : J Infect Dev Ctries 2011J
Dhaka Med Coll. 2008

A Multi-Drug Resistant Salmonella typhi (MDRST)

was appeared by the present of gyrA and TEM-1 gene.

GENERAL MECHANISM of MDRST

Gyr A
Gene

Fluoroquinolone
Resistance

TEM-1
Gene

Betalactamase
but not ESBL

MDRST

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

Clinical Presentation of Typhoid Fever

Clinical sign and symptom
(n=119)
%
Headache
59 94.9
Epigastric pain
Nausea
90.7
Anorexia
90.2
Fever (>37.2)
Muscular pain
Rigor
Coated tongue
Vomiting
Cough
Relative bradicardia
Diarrhea
Constipation
Hepatomegaly
Splenomegaly

57
108

94.7

41
118
14
37
84
104
91
117
109
109
117
117

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)

Clinical Presentation of MDRST

Relapse rate 10-15%; chronic carrier 5%;
Intestinal
(haemorrhage 1-10%, perforation 0.5-3%),
pneumonia in 10% MDRST 20%
Fatality rate 4.2%; severe clinical illness like
(Similar results were observed in studies in
Thailand, Nigeria, and Zimbabwe);
Hepatomegaly, Abdominal pain, Hypotensive
shock, Diarrhea, Seizure, DIC,
Neuropsychiatric symptoms (catatonic
schizophrenia)
Masatomo : Antimicrobial agents and chemotherapy
2010
Getenet : J Infect Dev Ctries 2011J

Clinical Relevance MDRST

Clinical MDRST several facets
Decrease effect on the treatment
Patients require effective antimicrobial
therapy
Difficulty in treating patients increased
morbidity and mortality
Failure after optimal treatment of oral or
injection antibiotics suspect MDRST.

Masatomo : Antimicrobial agents and chemotherapy

2010
Getenet : J Infect Dev Ctries 2011J

Laboratory Examination
Peripheral blood count

Inflammatory
Serum transaminase
Albumin
Serology
Blood culture
Shigella)
PCR

leucopenia, leucocytosis
normal WBC count
mild anemia
thrombocytopenia
increased ESR
increased CRP
increased ALT and AST
Hypoalbuminemia
Widal,Typhidot
Tubex (Salmonella IgM)
Gall (Salmonela
Salmonella typhi

Amit , J Infect Developing Countries 2008;

General Treatment
Non Pharmacologic :
Bed rest
Nutrition

Pharmacologic
Symptomatic
Antibiotic :
Ampicillin/Amoxicillin
Chloramphenicol
Cotrimoxazole
Cephalosporin : Ceftriaxone
Fluoroquinolones : Ciprofloxaxin
Levofloxacin
John Wine, J Infect Developing Countries 2008

TREATMENT OF MDRST
The possibility of MDR-ST showed by
clinical impression in which there is no good
response after empirical therapy by :
Penicillin :
Amoxycillin, Ampicillin
Chloramphenicol
Cotrimoxazole
Fluoroquinolones :
Ciprofloxacin, Levofloxacin
Cephalosporines :
Ceftriaxone
Yonsei Med J 50(1):147 - 151, 2009

TREATMENT OF MDRST
MDRST 1 :

(resistant to chloramphenicol, ampicillin,

cotrimoxazole)

Ciprofloxacin / Levofloxacin
Third generation cephalosporin

MDRST 2 :

(resistant to ciprofloxacin, levofloxacin,

ceftriaxone)

Monobactam (Aztreonam) India,

Korsel
Carbapenem
John Wine, J Infect Developing Countries 2008
Yonsei Med J 50(1):147 - 151, 2009

Aztreonam in Salmonellosis (MDRST)

Report from Korea (2009) showed the successful
treatment of eradicating MDRST using aztreonam.
It exhibited superiority in antimicrobial activity
compared with other antibiotics such as
ciprofloxacin and ceftriaxone with MIC 90%
0.8mcg/ml (MIC 0.05 1.56 mcg/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

Aztreonam: What Is It?

The first group of new
family of -lactams,
i.e. the monocyclic lactams
Inactive against gram
positive aerobic bacteria
andnegative
anaerobes
Active against gram
aerobic
bacteria
MIC90 of Enterobacteriaceae isolates <4 g/ml
Pseudomonas aeruginosa:
MIC50 <4 g/ml; MIC90 <8 g/ml
Noc PL. Monocyclic -lactams. 2005. p. 336-346
Brogden RN, Heel RC. Drugs;31(2):96-130

Penetration into Various Tissue

Good

Poor

Bile
Bronchial
mucus
Effusion fluids
Cerebrospinal
Pulmonary
fluid
parenchyma
Prostate
Renal parenchyma
Aqueous humor
Skin
Female genital
Noc PL. Monocyclic -lactams. 2005. p. 336-346
organs
Childs SJ, Bodey GP. Aztreonam. Pharmacotherapy.6(4):138-52
Neu HC. Aztreonam: the first monobactam. Med Clin North Am. 72(3):555-66

SUMMARY
Incidence MDRST
MDRST genetic mutation and
lactamase production
Clinical important MDRST decrease
respons treatment
Aztreonam alternative treatment for
MDRST & typhoid carrier

THANK
YOU
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