Beruflich Dokumente
Kultur Dokumente
Original Article
ABSTRACT
Objective. To study the epidemiological pattern, clinical picture, the recent trends of multidrug-resistant typhoid fever (MDRTF),
and therapeutic response of ofloxacin and ceftriaxone in MDRTF.
Methods. The present prospective randomized controlled parallel study was conducted on 93 blood culture-proven Salmonella
typhi children. All MDRTF cases were randomized to treatment with ofloxacin or ceftriaxone.
Results. Of 93 children, 62(66.6%) were MDRTF. 24 cases were below 5 years, 26 between 5-10 years and 12 were above
10 years. Male to female ratio was 1.85: 1. Majority of cases came from lower middle socio-economic classes with poor
personal hygiene. Fever was the main presenting symptom. Hepatomegaly and splenomegaly was present in 88% and 46%
cases respectively. 19(30.6%) cases developed complications. Mean defervescence time with ceftriaxone and ofloxacin was
4.258 and 4.968 days respectively.
Conclusion. MDRTF is still emerging as serious public and therapeutic challenge. Ceftriaxone is well-tolerated and effective
drug but expensive whereas ofloxacin is safe, cost-effective and therapeutic alternative in treatment of MDRTF in children with
comparable efficacy to ceftriaxone. [Indian J Pediatr 2007; 74 (1) : 39-42] E-mail: drrajivkumar@hotmail.com
Key words : Multidrug-resistant; Typhoid fever; Salmonella typhi; Ceftriaxone and Ofloxacin
40
Rajiv Kumar et al
A detailed epidemiological and clinical history, a
thorough clinical examination and laboratory
investigations at the time of admission and during the
course of hospital stay were performed in all cases and
the findings were recorded in the pre-made proforma.
Epidemiological and clinical history: In addition to
patients name, age, sex, address, socio-economic status,
hygiene and sanitation, some epidemiological
information like education, occupation, family income,
number of family members, level of personal hygiene
(practice of hand washing with soap by family members
after defecation and before eating and preparing food),
source of drinking and portable water supply, and habit
of defecation (use of sanitary latrine, open pit latrine) by
family members were also obtained from parents. Socio
economic status of the parents was estimated by
Kuppuswamys classification. On admission, a detailed
clinical history was taken in each case.
Clinical examination: A detailed general and systemic
examination was done in all cases. In general
examination, authors took note of general condition, toxic
look, level of consciousness, temperature, pulse rate,
pulse character, respiratory rate, blood pressure, pallor,
jaundice, icterus, rash, petechiae and lymphadenopathy.
In systemic examination, children were thoroughly
examined for throat congestion, altered sensorium,
rhonchi, meningismus, abdominal distension, abdominal
tenderness, hepatomegaly and splenomegaly. All
associated findings and complications were noted in all
children.
Laboratory investigations: A blood sample for complete
hemogram, serum bilirubin, liver enzymes, serum urea,
serum creatinine, serum sodium, serum potassium, Widal
test and blood culture was obtained in all children on
admission and thereafter if the childrens condition
warranted it. Stool and urine samples were also sent for
culture examination. The chest and abdominal X-rays
were done in children where it was indicated.
Treatment : The patients with a presumptive clinical
diagnosis of typhoid fever were initially treated with
chloramphenicol (75 mg/Kg/day) by oral or intravenous
route. The mid-course modification of therapy was done
after the availability of blood culture and sensitivity
report. All MDRTF cases were randomized to treatment
with ofloxacin (20 mg/Kg/day) or ceftriaxone (100 mg/
Kg/day). The clinical course was closely monitored and
the period of defervescence was recorded. The time to
defervescence is defined as the time interval from starting
an appropriate antimicrobial chemotherapy until the
documentation of normal body temperature. The clinical
response to therapy was considered inadequate if there
was deterioration or no clinical improvement within 7-10
days of starting specific therapy. The drug efficacy was
judged primarily by the patients clinical response with
particular attention being given to the number of days of
40
RESULTS
Of 93 blood culture-proven S. typhi cases, 62(66.6%) were
MDRTF. The incidence was highest (30.6%) seen in the
age group of 2 5 years. The second peak (25.8%) was
observed among age group of 7 10 years. It was seen
only in a one infant. 22(35.5%) cases were females and
40(64.5%) cases were males. Therefore, male: female ratio
was 1.85: 1.
MDRTF cases were seen throughout the year but the
rate of both hospitalization of cases and isolation of S.
typhi were relatively low during the months of October
and December. The majority of children belonged to
lower middle socio-economic classes with poor personal
hygiene. A history of travel away from the community
was not observed in any of the children. Most of the
affected families consumed either municipal supplied
water or water from tube wells. Majority (88.7%) of the
families and their children used sanitary latrines.
Fever was the main presenting symptom in all the
cases. High-grade fever was observed in 75.8% cases. The
duration of fever was of more than seven days in the
majority (72.6%) of cases at the time of admission. The
pattern of fever was intermittent in majority (71%) of
cases. Only 6 (9.6%) cases had fever with chills and rigors.
Headache was associated with fever in 34(54.8%) cases.
Other features seen were diarrhea (74.2%), abdominal
pain (62.9), vomiting (61.2%), malaise (48.3%), anorexia
(33.8%), nausea (32.2%), cough (32.2%), constipation
(14.5%) and GIT bleeding (12.9%).
46(74.1%) cases were toxic at time of presentation.
Relative bradycardia and coated tongue were seen in
7(11.2%) and 22(35.4%) cases respectively. Hypotension
was noted in 4 (6.4%) cases, one patient was unconscious
and two patients had loose motions and vomiting at the
time of admission. Clinically pallor and icterus was
present in 26(41.9%) and 18(29%) cases respectively.
Hepatomegaly and splenomegaly was present in 88% and
46% cases respectively.
Laboratory examination of blood revealed that anemia
Indian Journal of Pediatrics, Volume 74January, 2007
41
Ampicillin
Co-trimoxazole
Chloramphenicol
Amoxicillin
Amikacin
Gentamicin
Norfloxacin
Ciprofloxacin
Ofloxacin
Ceftriaxone
Cefotaxime
*
Present
study
(n=93)
Kabra
et al4
(n=100)
Mishra
et al5
(n=50)
25.8
31.1
33.4
29.0
91.3
90.3
51.6
74.1
92.8
97.8
76.3
16
2
8
16
85
85
100
100
100
36
50
42
36
100
100
100
100
100
Agarwal
et al6
(n=68)
54.4
38.2
55.8
97.0
97.0
92.64
100
89.7
88.23
42
Rajiv Kumar et al
typhoid fever in children is a particularly important
finding because ofloxacin, which constitute the other
group of drugs being used as alternative treatment for
MDRTF. Ofloxacin is not recommended in children due
to arthropathic toxicity in growing animals. The
examination of available clinical data to date provides no
absolute evidence that ofloxacin induces significant
arthropathy in children, in contrast to data reported in
some animal species. However, literature does say that
ofloxacin should be used with caution in children below
12 years of age. Ofloxacin has been used with good
clinical response without significant side effects in
typhoid fever20 and cystic fibrosis21.
CONCLUSION
MDRTF is still emerging as serious public and therapeutic
challenge. Ceftriaxone is well-tolerated and effective drug
for MDRTF in children but expensive. Ofloxacin is safe,
cost-effective and therapeutic alternative in treatment of
MDRTF with comparable efficacy to ceftriaxone.
However, further studies in a larger group of patients are
needed to validate our findings. The rapid spread of
MDRTF over a large geographic area presents multiple
challenges, especially in developing countries where
access to newer and more expensive antimicrobial agents
may be limited. Therefore, research efforts must be
continued to focus on oral agents with chances of high
cure rate.
REFERENCES
1. Wasfy MO, Oyofo BA, David JC et al. Isolations and antibiotic
susceptibility of Salmonella, Shigella, and Campylobacter from
acute enteric infections in Egypt. J Health Popul Nutr 2000; 18:
33-38.
2. Ivanoff B, Levine MM, Lambert PH. Vaccination against
typhoid fever: present status. Bull World Health Organ 1994;
72 : 957-971.
42