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Ceftriaxone versus Chloramphenicol for Treatment of Acute Typhoid Fever

Authors:

Abstract

Typhoid fever is a global health problem, with an estimated 20 million cases and 700.000 deaths annually. In Egypt, since the beginning of the 1980s, there had been an increase in the prevalence of multidrug resistance to the first line antimicrobials used in the treatment of the disease such as chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole (TMP-SMX) and thus other drugs, the fluoroquinolones and third generation cephalosporins, had to be evaluated for their efficacy in the treatment and their side effects. The aim of this study was to compare the efficacy of chloramphenicol, which was the classical drug for treatment of acute typhoid fever in Abbassia fever hospital (AFH), with ceftriaxone which became a first line drug for treatment of it after the appearance of multidrug resistant (MDR) isolates of Salmonella typhi (S. typhi)in the last fifteen years. As a part of the study we investigated whether or not the organisms were still sensitive to the quinolones and third generation cephalosporins. We also investigated if multidrug resistant (MDR) typhoid fever was still a problem in Egypt. A phase IV open label, prospective, randomized clinical trial study was implemented in the period between March 2007 and June 2009. Fifty two patients with positive blood culture for S. typhi were included in this study. They were 32 (62%) males and 20 (38%) females ranging in age from 3 to 47 years (mean±SD: 22±8.5years). Drug sensitivity tests showed that 4 (8%) of Salmonella typhi isolates were resistant to chloramphenicol and 18 (35%) and 21 (40%) isolates were resistant to ampicillin and TMP-SMX respectively. Two (4%) isolates were resistant to chloramphenicol, ampicillin and TMP-SMX. No isolates were resistant to ciprofloxacin or ceftriaxone. Twenty seven (52%) patients were treated with chloramphenicol and twenty five (48%) patients were treated with ceftriaxone. All patients were cured. The mean time (mean±SD) for patients to become afebrile was 3.3±1.2 days for ceftriaxone and 5.8±1.2 days for chloramphenicol. In patients treated with ceftriaxone the time taken to become afebrile was shorter with chronic infection as compared to those treated with chloramphenicol(P value= 0.0001 95% CI= 1.831-3.169). From this study, it can be concluded that: ceftriaxone was associated with a significantly shorter period of defervescence making it the drug of choice for treatment of typhoid fever.There is a marked reduction of the prevalence of MDR Salmonella typhi isolates and marked increase in the susceptibility of these isolates to chloramphenicol, returning it to be one of the drugs that could be used in the treatment of acute typhoid fever.No drug resistance to ceftriaxone and ciprofloxacin was reported after many years of using them for treatment of acute typhoid fever.Due to high degree of resistance to ampicillin and TMP-SMX, they should not be used as first line drugs for treatment of acute typhoid fever.
Life Science Journal, 2011;8(2) http://www.lifesciencesite.com
Ceftriaxone versus Chloramphenicol for Treatment of Acute Typhoid Fever
Osama Mohamed Hammad1, Tamer Hifnawy2*, Dalia Omran3, Magda Anwar El Tantawi4 and
Nabil Isaknder Girgis5
1Tropical Medicine Department, Faculty of Medicine, Beni Suef University-Egypt.
2Public Health & Community Medicine Department Faculty of Medicine, Beni Suef University-Egypt.
3Tropical Medicine Department, Faculty of Medicine, Cairo University, Egypt.
4Bacteriology Department, Abbassia Fever Hospital.
5Former NAMRU3, Cairo, Egypt.
*daliaomran2007@yahoo.com
Abstract: Typhoid fever is a global health problem, with an estimated 20 million cases and 700.000 deaths
annually. In Egypt, since the beginning of the 1980s, there had been an increase in the prevalence of multidrug
resistance to the first line antimicrobials used in the treatment of the disease such as chloramphenicol, ampicillin and
trimethoprim-sulfamethoxazole (TMP-SMX) and thus other drugs , the fluoroquinolones and third generation
cephalosporins, had to be evaluated for their efficacy in the treatment and their side effects. The aim of this study
was to compare the efficacy of chloramphenicol, which was the classical drug for treatment of acute typhoid fever in
Abbassia fever hospital (AFH), with ceftriaxone which became a first line drug for treatment of it after the
appearance of multidrug resistant (MDR) isolates of Salmonella typhi (S. typhi )in the last fifteen years. As a part of
the study we investigated whether or not the organisms were still sensitive to the quinolones and third generation
cephalosporins. We also investigated if multidrug resistant (MDR) typhoid fever was still a problem in Egypt. A
phase IV open label, prospective, randomized clinical trial study was implemented in the period between March
2007 and June 2009. Fifty two patients with positive blood culture for S. typhi were included in this study. They
were 32 (62%) males and 20 (38%) females ranging in age from 3 to 47 years (mean±SD: 22±8.5years). Drug
sensitivity tests showed that 4 (8%) of Salmonella typhi isolates were resistant to chloramphenicol and 18 (35%) and
21 (40%) isolates were resistant to ampicillin and TMP-SMX respectively. Two (4%) isolates were resistant to
chloramphenicol, ampicillin and TMP-SMX. No isolates were resistant to ciprofloxacin or ceftriaxone. Twenty
seven (52%) patients were treated with chloramphenicol and twenty five (48%) patients were treated with
ceftriaxone. All patients were cured. The mean time (mean±SD) for patients to become afebrile was 3.3±1.2 days for
ceftriaxone and 5.8±1.2 days for chloramphenicol. In patients treated with ceftriaxone the time taken to become
afebrile was shorter with chronic infection as compared to those treated with chloramphenicol(P value= 0.0001
95% CI= 1.831-3.169). From this study, it can be concluded that: ceftriaxone was associated with a significantly
shorter period of defervescence making it the drug of choice for treatment of typhoid fever.There is a marked
reduction of the prevalence of MDR Salmonella typhi isolates and marked increase in the susceptibility of these
isolates to chloramphenicol, returning it to be one of the drugs that could be used in the treatment of acute typhoid
fever.No drug resistance to ceftriaxone and ciprofloxacin was reported after many years of using them for
treatment of acute typhoid fever.Due to high degree of resistance to ampicillin and TMP-SMX, they should not be
used as first line drugs for treatment of acute typhoid fever.
[Osama Mohamed Hammad, Tamer Hifnawy, Dalia Omran, Magda Anwar El Tantawi and Nabil Isaknder Girgis.
Ceftriaxone versus Chloramphenicol for Treatment of Acute Typhoid Fever. Life Science Journal. 2011;8(2):100-
105] (ISSN:1097-8135). http://www.lifesciencesite.com.
Key words: Typhoid fever, Multidrug resistance, Chloramphenicol, Ceftriaxone.
1. Introduction
Typhoid fever occurs in over 20 million
cases annually, with at least 700.000 deaths. The main
burden of disease is in developing countries,
particularly the Indian subcontinent and South East
Asia (1). Historically, the infection was treated with
chloramphenicol, ampicillin or trimethoprim-
sulfamethoxazole (TMP-SMX). However, the
widespread emergence of antibiotic resistant
Salmonella typhi (S.typhi) has presented an important
public health problem during the past decades (2). In
Egypt, chloramphenicol resistant Salmonella typhi
was first reported in 1981 (3). Mourad et al. (4) found
that 43% of Salmonella typhi isolates at Alexandria
fever hospital were multidrug resistant (MDR)
isolates. In another study done in Egypt, Wasfy et al.
(5) found that 71% of patients with typhoid fever had
MDR Salmonella typhi isolates. Recently, Salmonella
typhi strains resistant to quinolones and third
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generation cephalosporins have been documented by
many authors (6-7).
Typhoid fever caused by MDR organisms is
a significant public health and therapeutic problem as
a large number of cases of MDR typhoid fever occur
in childhood and are accompanied with significantly
high morbidity and mortality rates (8).
The aim of this study was to evaluate the
efficacy of chloramphenicol,which remained for many
for many years as the drug of choice for treatment of
acute typhoid fever in Abbassia Fever Hospital (AFH)
and compare it to ceftriaxone which became the main
drug for treatment of typhoid fever after the
appearance of MDR isolates in the last fifteen years.
As a part of the study we investigated whether or not
the organisms were still sensitive to the quinolones
and third generation cephalosporins. We also
investigated if multidrug resistant (MDR) typhoid
fever was still a problem in Egypt.
2. Patients and Methods
A phase IV open label, prospective,
randomized clinical study was implemented in the
period between March 2007 and June 2009. After
having their informed consent to participate in our
study, fifty two patients with acute typhoid fever in
Abbassia Fever Hospital (AFH) “The main fever
hospital in Cairo Governorate, Egypt” were included
in this study.
Our Inclusion criteria were to have a
diagnosis for typhoid fever with a positive blood
culture for Salmonella typhi and a consent to
participate in this study. Criteria for exclusion were
patients with deteriorated general condition,
hyperpyrexia (40.5 C or above), hypotension,
meleana, bleeding per rectum and or disturbed level of
consciousness
All recruited patients were subjected to:
Careful history and thorough clinical examination,
complete blood picture. On the day of admission to
the hospital before initiation of antibiotic therapy, an
aliquot of each patient blood was collected and
inoculated onto bi-phasic blood culture bottles and
incubated at 37oC. Bottles were checked daily for 7
days and when growth was noted, an aliquot of blood
was streaked onto MacConkey and blood agar plates
to allow for final identification of the organism by
using standard serological and biochemical methods
(9).Widal agglutination test was done to all patients
(10). Susceptibility of Salmonella typhi to
ampicillin (10 ug), chloramphenicol (30 ug), TMP-
SMX (25 ug), ciprofloxacin (5 ug) and ceftriaxone (30
ug) was performed using the disc diffusion Kirby-
Bayer method (11).
Twenty seven (52%) patients were randomly
allocated to be treated with chloramphenicol (50
mg/kg/day orally or intravenously) given 6 hourly till
defervescence (primary outcome measure) and for a
further 5 days (secondary outcome measure). The
time of defervescence was defined as the time interval
from starting an appropriate antimicrobial
chemotherapy until the documentation of normal body
temperature (8).
Twenty five (48%) patients were randomly
allocated to be treated with ceftriaxone parenterally
(80 mg/kg/day for children and 2 gm/day for adults)
given once daily for 7 days.
Any patient infected with a strain resistant to
the drug with which he was being treated, was shifted
to another drug to which the isolates were sensitive
and was not included in final analysis of results.
Patients presenting with complications
(gastrointestinal hemorrhage or perforation, toxic
myocarditis, hepatitis) were excluded from the study.
Subjects were randomized with equal distribution to
the 2 treatment regimens using block of 6 and
randomization envelops were prepared by the
biostatician
This study was open label, therefore no
blinding procedures were required.
Patient was considered cured if there was no
fever,abdominal tenderness,,toxic look or tympanitic
abdomen at the end of treatment course.
Statistical analysis:
Regarding our sample size, a time frame was
applied to recruit all cases of typhoid fever diagnosed
clinically with confirmed laboratory diagnosis from
the period between the 1st of March 2007 till the end
of June 2009 after signing an informed consent to
participate.
Descriptive summaries were presented using
summary statistics for continuous (quantitative)
variables and frequency for discrete (qualitative)
variables.
Data were collected coded and analyzed
using SPSS software version 15 under windows XP.
Unpaired student t-test was used to compare time of
defervescence between those who were treated with
chloramphenicol versus ceftriaxone. The threshold of
significance was fixed at the 5% level.
No interment analysis was done and the final
analysis was conducted at the end of the study after all
patients had completed the study protocol.
Ethical Consideration: All patients
participating in this study were asked to sign an
informed consent form describing all study
procedures, risk and benefits. For children and minors
“less than 21 years” parent guardian informed consent
was taken
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3. Results:
Fifty two patients of acute typhoid fever with
positive blood culture for Salmonella typhi were
enrolled in this study. They were 32(62%) males and
20(38%) females ranging in age from 3 to 47 years
(mean±SD 22±8.5 years). The clinical picture of these
patients upon admission is shown in table (1).
Table (1) Clinical picture of (52) acute typhoid fever patients
Number (%)
Chloramphenicol treated
patients Ceftriaxone treated
patients Total
Symptoms
No. = 27 No. = 25 No. = 52
Fever 27 (100) 25 (100) 52 (100)
Abdominal discomfort 22 (81) 18 (72) 40 (77)
Headache 21 (72) 19 (76) 40 (77)
Epistaxsis 13 (48) 14 (56) 27 (52)
Cough 16 (59) 16 (64) 32 (62)
Vomiting 12 (44) 11 (44) 23 (44)
Diarrhea 9 (33) 8 (32) 17 (33)
Signs
Fever 27 (100) 25 (100) 52 (100)
Toxic look 21 (78) 22 (88) 43 (83)
Abdominal tenderness 23 (85) 21 (81) 44 (85)
Splenomegaly 22 (81) 18 (72) 40 (77)
Abdominal distension 20 (74) 19 (76) 39 (75)
Hepatomegaly 10 (37) 10 (40) 20 (38)
Jaundice 0 1 (4) 1 (2)
The hematological profile and Widal
agglutination test results are shown in table (2).
Normal hematological profile was seen in most of the
patients. Thirty eight (73%) and forty patients (77%)
had anti-O antibody and anti-H titers of > 1/160
respectively
Table (2) Haematological profile and Widal agglutination titer of (52) acute typhoid fever patients
Complete blood picture Range Mean
Haemoglobin 5.5-14.8 gm% 11 ± 1.8
Total white blood cell count 2.3 - 11.4X 10³ / cmm 5 ± 2.3
Platelet count 46-458 x 10³/ cmm 185 ± 87.4
Widal agglutination titer
Chloramphenicol treated
patients (27)
No. (%)
Ceftriaxone treated
patients (25)
No. (%)
Total patients (52)
No. (%)
Anti-O = 1/80 - Anti-H = 1/80 1 (4) - 2 (7) 1 (4) - 2 (8) 2 (4%) - 4 (8%)
Anti-O = 1/160 - Anti-H = 1/160 7 (26) - 5 (19) 5 (20) - 5 (20) 12 (23%) - 10 (19%)
Anti-O = 1/320 - Anti-H = 1/320 6 (22) - 9 (33) 5 (20) - 6 (24) 11 (21%) - 15 (29%)
Anti-O = 1/640 - Anti-H = 1/640 8 (30) - 8 (30) 7 (28) - 7 (28) 15 (29%) - 15 (29%)
Anti-O 1/160 - Anti-H 1/160 21 (78) - 22 (81) 17 ( 68) - 18 (72) 38 (73%) - 40 (77%)
Drug sensitivity tests revealed that 4 (8%) of
isolates were resistant to chloramphenicol and 18
(35%) and 21 (40%) isolates were resistant to
ampicillin and TMP-SMX respectively. Two (4%)
isolates were MDR resistant to chloramphenicol,
ampicillin and TMP-SMX. No isolates were resistant
to ciprofloxacin or ceftriaxone (table 3).Seven isolates
had no resistance to any of the tested five drugs.
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Table (3): Antimicrobial susceptibility patterns of
52 Salmonella typhi isolates
There were no reported complications
throughout the study.
All patients were cured. The mean time
(mean±SD) of defervescence for ceftriaxone and
chloramphenicol was 3.3±1.2 and 5.8±1.2 days
respectively. P value= 0.0001 95% CI= 1.8-3.2.
Ceftriaxone was significantly associated with a short
time of defervescence compared with
chloramphenicol
4. Discussion
Enteric fever continues to be a major public
health problem, especially in the developing countries
of the tropics. The sensitivity pattern of S. typhi is
changing and there is re-emergence of sensitivity to
chloramphenicol but rising resistance to ciprofloxacin
(12). In this study, 4%, of the isolated strains of
Salmonella typhi were resistant to chloramphenicol,
ampicillin and TMP-SMX. In a study done by
Mourad et al.(4) MDR Salmonella typhi isolates were
detected in 15 (43%) of 35 patients with culture
positive S. typhi. Wasfy et al.(5) studied 537 S.typhi
isolates collected between 1990-1994 in Egypt; 71%
of isolates were MDR. This period represented the
peak of MDR reisolates in Egypt. In another study
done in Abbassia Fever Hospital, Wasfy et al. (2)
reported that MDR Salmonella typhi increased from
19% in 1987 to 100% in 1993, but it subsequently
decreased again to only 5% by the year 2000. In
Fayoum Governorate “One of Upper Egypt
governorates”,MDR Salmonella typhi isolates were
detected in 26 (29%) of 90 patients with culture
positive S.typhi (13). Decline of MDR Salmonella
typhi isolates were reported in many studies world
wide and was reported to be 5.6% by Chitnis et al.
(14), 5% by Pokharel et al. (15), 18.6% by Ray et al.
(16) and 22% by Cooke et al. (17). In Imbaba fever
hospital, Giza province, Egypt El-Din et al. (18)
reported that 25% of Salmonella typhi isolates were
resistant to chloramphenicol.
In our study, 8% of the isolates were
chloramphenicol resistant. Due to the development of
MDR isolates, there was a decrease in the use of
chloramphenicol for treatment of typhoid fever in
Egypt and this, in addition to the use of more-
effective antibiotics could have caused a decrease in
the prevalence of persons with chronic infection in the
community and hence the circulation of resistant
strains. The improvement in susceptibility of
Salmonella typhi to chloramphenicol (although its
lower performance compared to ceftriaxone), will
cause it to be re-considered as one of the drugs of
choice for treatment of typhoid fever in Egypt. Similar
studies should be considered in some parts of the
world where medical resources are limited.
Chloramphenicol has a cheaper price and well
established efficiency. (2,14,19). In this study, 35%
and 40% of isolates were resistant to ampicillin and
TMP-SMX respectively and this is in agreement with
that reported by Srikantiah et al. (13). Until
improvement in the susceptibility of Salmonella typhi
to these two drugs, they should not be used as a first
line drugs for treatment of typhoid fever. None of our
Salmonella typhi isolates were resistant to
ciprofloxacin or ceftriaxone. This was in agreement
with Wasfy et al. (2) and Ray et al.(16). Resistance to
ciprofloxacin (3%) and ceftriaxone (2%) were
documented by Srikantiah et al. (13) in the Fayoum
governorate,Egypt. Resistance to ciprofloxacin was
reported by Butt et al. (20); Capoor et al. (6) and
Dimitrov et al. (7).
Susceptibility pattern Number
of isolates
%
Any resistance
Chloramphenicol
TMP-SMX
Ampicillin
Ciprofloxacin
Ceftriaxone
4
21
18
0
0
8
40
35
0
0
Multidrug resistance (MDR) to
chloramphenicol,TMP- SMX and
ampicillin
2 4
Isolates with no resistance to any
of the five tested drugs
7 13
The main symptoms in our 52 patient with
acute typhoid fever were fever (100%), headache
(77%), vomiting (44%) abdominal discomfort (77%)
cough (62%) and epistaxsis (52%). The main signs
were fever (100%), toxic look (83%), abdominal
tenderness (85%), abdominal distention (75%),
splenomegaly (77%), and hepatomegaly (38%). These
symptoms and signs agreed with Abdel Wahab et al.
(21) As regards the blood picture, our patients
showed anemia (mean hemoglobin ±SD 11±1.8 gms
%), within normal white blood cell count (mean
5±2.3) and within normal blood platelets (mean
185±87.4). Anemia may be due Salmonella
endotoxaemia. Within normal white blood cell count
is similar to that reported by Abdool Gaffar et al.(22).
In accordance with our results, The peripheral blood
changes did not influence the outcome of the disease,
since all patients recovered completely after treatment
(23). In our patients anti-O > 1/160 and anti-H >
1/160 titers were detected in 73% and 77% of the
patients respectively. This was considered as a
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significant titer suggestive of acute typhoid fever in
Egypt and this is in agreement with Hassanein et al.
(24) and Frimpiong et al. (25).The results of Widal
test should be interpreted in concerns with a patients
clinical presentation in making a diagnosis of typhoid
fever. Both the somatic and flagellar agglutinins are
important for this purpose (26).
Both chloramphenicol and ceftriaxone were
effective for treatment of our 52 patients with acute
typhoid. Ceftriaxone was significantly associated with
a shorter time of defervescence compared to
chloramphenicol. This agrees with other studies (8,
21). From this study, we concluded that
ceftriaxone was significantly associated with short
time of defervescence making it the drug of choice for
treatment of acute typhoid fever .There is marked
reduction in the prevalence of MDR Salmonella typhi
isolates and marked increase in susceptibility of these
isolates to chloramphenicol, returning it to be one of
the drugs of choice for treatment of acute typhoid
fever. No drug resistance to ceftriaxone and
ciprofloxacin were reported after many years of using
them in the treatment of acute typhoid fever. Due to
the high degree of resistance to ampicillin and TMP-
SMX, they should not be used as first line drugs for
treatment of acute typhoid fever.
Correspondence author
Dalia Omran, Department of Tropical Medicine,
Faculty of Medicine, Cairo University, Cairo, Egypt
Tel: + 010 0087802
daliaomran2007@yahoo.com
5. References:
1-Cooke F, Wain J. The emergence of antibiotic
resistance in typhoid fever. Travel Med Infec Dis.
2004; 2 (2): 67-74.
2-Wasfy M, Frenck R, Ismail T, Mansour H,
Malone J. and Mahoney F. Trends of multiple drug
resistance among Salmonella serotype typhi
isolates during a 14 year period in Egypt. Clin
Infect Dis. 2002; 35 (10): 1265-8.
3- Sippel JE, Diab AS, Mikhail AI. Chloramphenicol
resistant Salmonella typhi in Egypt. Trans R Soc
Trop Med Hyg. 1981; 75: 613.
4- Mourad AS, Metwally M, el Deen AN, Threlfall
EJ, Rowe B, Mapes T,et al. Multiple drug resistant
Salmonella typhi. Clin Infect Dis.1993; 17: 135-6.
5- Wasfy MO, Moustafa DA, El-Gendy AM, Mohran
ZS, Ismail TF, El-Etr SH, et al. Prevalence of
antibiotic resistance among Egyptian Salmonella
typhi strains. J Egypt Public Health Assoc. 1996;
LXXI: 149-60.
6-Capoor MR, Nair D, Hasan AS, Aggarwal P, Gupta
B.Typhoid fever: narrowing therapeutic options in
India. Southeast Asian. J Trop Med Public
Health.2006;37 (6): 1170-4.
7-Dimitrov T, Udo EE, Albaksami O, Kilani AA,
Shehab el-DM. Ciprofloxacin treatment failure in
a case of typhoid fever caused by Salmonella
enterica serotype paratyphi A with reduced
susceptibility to ciprofloxacin. J Med
Microbiol.2007; 56 (pt. 2): 277-9.
8-Kumar R, Gupta N, Shalini N. Multidrug-resistant
typhoid fever. Indian J Pediatr. 2007; 74(1):39-42
9-Ohashi M. In: Balows, A.; Hausler, W.; Lennette, E.
(eds). Laboratory diagnosis of infectious disease:
principles and practice. 1988 ;Vol. I. Springer
Verlag; 525-32.
10-House D, Wain J, Ho VA, Diep TS, Chinh NT,
Bay PV, et al.Serology of typhoid fever in an area
of endemicity and its relevance to diagnosis
.Journal of ClinicalMicrobiology.2007;39(3):1002-
1007
11-Esser VM, Elefson DE. Experiences with the
Kirby-Bauer method of antibiotic susceptibility
testing. 1970; Am J Clin Pathol, 54: 193-8.
12- Gogia A, Agarwal PK, Khosla P, Jain S, Jain KP.
Quinolone resistant typhoid fever. Indian J Med
Sci.2006; 60 (9): 389-90.
13- Srikantiah P, Girgis FY, Luby SP, Jennings G,
Wasfy MO, Crump JA, et al. Population based
surveillance of typhoid fever in Egypt. Am J Trop
Med Hyg.2006; 74 (1): 114-9.
14- Chitnis S, Chitnis V, Hemvani N, Chitnis DS.
Ciprofloxacin therapy for typhoid fever needs
reconsideration, J Infect Chemother.2006; 12 (6):
402-4.
15- Pokharel BM, Koirala J, Dahal RK, Mishra SK,
Khadga PK, Tuladhar NR. Multidrug resistant and
extended spectrum beta lactamase (ESBL)
producing Salmonella enterica (serotypes typhi and
paratyphi A) from blood isolates in Nepal:
Surveillance of resistance and a search for newer
alternatives. Int J Infect Dis.2006; 10 (6): 434-8.
16- Ray P, Sharma J, Marak RS, Garg RK. Predictive
efficacy of nalidixic acid resistance and as marker
of fluoroquinolone resistance in Salmonella
enterica var typhi.2006; Indian J Med Res,124 (1):
105-8.
17- Cooke FJ, Day M, Wain J, Ward LR, Threlfall
EJ.Cases of typhoid fever imported into England,
Scotland and Wales (2002-2003). Trans R Soc
Med Hyg.2007; 101 (4): 398-404.
18- El-Din SS, Haseeb NM, Hussein MM, Abdel
Wahab MF, Helmy AZ, El-Sagheer M.
Chloramphenicol drug failure in typhoid fever. J
Egypt Public Health Assoc.1996;71 (1-2): 63-78.
19- Manchanda V, Bhalla P, Sethi M, Sharma VK.
Treatment of enteric fever in children on the basic
current trends of antimicrobial susceptibility of
http://www.sciencepub.net/life lifesciencej@gmail.com
104
Life Science Journal, 2011;8(2) http://www.lifesciencesite.com
Salmonella enterica serovar typhi, and paratyphi.
Indian. J Med Microbiol.2006; 24 (21): 101-6.
20- Butt T, Ahmad RN, Salman M, Kazmi SY.
Changing trends in drug resistance among typhoid
salmonellae in Rawlpindi, Pakistan. East Mediter
Health J.2005;11 (5-6): 1038-44.
21- Abdel Wahab MF, el-Gindy IM, Sultan Y, el-
Naby HM. Comparative study on different recent
diagnostic and therapeutic regimens in acute
typhoid fever. J Egypt Public Health Assoc.1999;
74 (1-2): 193-205.
22- Abdool Gaffar MS, Seedat YK, Coovadia YM.
The white cell count in typhoid fever.Trop Geogr
Med.1992;44(1-2):23-7.
23- James J, Dutta TK, Jayanthi S. Correlation of
clinical and hematological profile with bone
marrow response in typhoid fever.Am J Trop Med
Hyg.1997;57(3):313-6
24- Hassanein F, Mostafa FM, Elbehairy F, Hammam
HM, Allam FA, El-Rehaiwy M, et al. Study of the
pattern of Widal test in infants and children; II.
Pattern of Widal test in children with enteric
fevers. An attempt to define the diagnostic titer for
Upper Egypt. Gaz Egypt Paediatr Assoc.1975;23
(2): 173-80.
25- Frimpong EH, Feglo P, Essel-Ahun M, Addy PA.
Determination of diagnostic Widal titers in
Kumasi, Ghana. West Afr J Med.2000;19 (1): 34-
8.
26-Dimitrov T, Udo EE, Albaksami O, Al-Shehab S,
Kilani A, Shehab M, et al. Clinical and
microbiological investigations of typhoid fever in
an infectious disease hospital in Kuwait. J Med
Microbiol.2007; 56,538-544.
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... (2) Widal agglutination test was conducted on all patients [9]. Susceptibility of S. typhi to chloramphenicol (30 µg), ciprofloxacin (5 µg), and ceftriaxone (30 µg) was performed using the disc diffusion Kirby-Bauer method [10]. (3) A total of 20 (33.3%) patients were randomly allocated to be treated with chloramphenicol (50 mg/kg/day or ally or intravenously) given 6 h till defervescence (primary outcome measure) and for further 5 days (secondary outcome measure). ...
... In our study, the blood culture of the all studied patients was positive. This in agreement with the results of Hammad et al. [10]. ...
... In our study, the drug sensitivity test on chloramphenicol was in disagreement with Hammad et al. [10] who found that four (8%) cases of isolates were resistant to chloramphenicol. ...
Article
Objective: This study was conducted to evaluate the status in antimicrobial susceptibility patterns of Salmonella typhi obtained from blood culture in Shebin El-Kom Fever Hospital. Background: Enteric fever is a global health problem, and rapidly developing resistance to various drugs makes the situation more alarming. Drug sensitivity in S. enterica typhi and paratyphi A isolated from 60 blood culture-positive cases of enteric fever was tested to determine in-vitro susceptibility pattern of prevalent strains. Materials and methods: Strains isolated from 60 blood culture-positive cases of typhoid and paratyphoid fever over a period of 5 months were studied about their sensitivity patterns to chloramphenicol and ciprofloxacin, and were analyzed. Results: Our study revealed that there was a high sensitivity of S. enterica typhi and paratyphi A to chloramphenicol and ceftriaxone (100%) and resistance to ciprofloxacin (20%). Conclusion: These findings suggest changing patterns of antibiotic resistance in enteric fever with re-emergence of chloramphenicol sensitivity and ciprofloxacin resistance in Shebin El-Kom Fever Hospital, Egypt.
... The articles found were as follows: (1 10 These articles were appraised using the criteria from Center of Evidence Based Medicine Oxford University (Table 2). Articles by Islam et al and Acharya et al were published more than 20 years ago and therefore are not included in this review. ...
... Hammad et al did a study on 2007 to re-asses the effectiveness of chloramphenicol as typhoid treatment in response to the increase of multidrug resistance to the first- line antimicrobials in Egypt for the last 30 years. 10 Fifty-two patients of acute typhoid fever with positive blood culture for Salmonella typhi were divided into 2 groups. Twenty-seven patients were randomly allocated to be treated with chloramphenicol (50 mg/kg bw/day orally or intravenously) which is given 6 times hourly until defervescence for further 5 days. ...
... Twenty-seven patients were randomly allocated to be treated with chloramphenicol (50 mg/kg bw/day orally or intravenously) which is given 6 times hourly until defervescence for further 5 days. 10 Twenty five patients were randomly allocated to be treated with ceftriaxone parenterally (80 mg/kg/day for children and 2 gm/day for adults) the treatment is given once a day for 7 days. 10 Clinical cure occurred on all patients. ...
Article
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Typhoid fever is a disease caused by the gram-negative bacterium Salmonella typhi. Since its introduction in 1949, chloramphenicol for decades become a first-line treatment of typhoid fever. Until now, chloramphenicol is still the first line treatment of typhoid fever in rural areas in Indonesia, especially due to its low cost. However, in addition to the problem of bacterial resistance, chloramphenicol is known to cause side effect such as bone marrow suppression. Right now many other antibiotics are used as regimens for treatment of typhoid fever, one of which is ceftriaxone. This report is created to answer the clinical question whether ceftriaxone is more effective compared to chloramphenicol as first-line treatment of typhoid fever. Structured search was performed on PubMed, EBSCO, and ScienceDirect and after a screening process and appraisal using criteria from Center of Evidence Based Medicine at Oxford University, three articles were selected. Two of the three articles demonstrate higher effectiveness of chloramphenicol in term of defervescence rate (P = 0.35 and P > 0.05). On the other hand, the third article shows higher effectiveness of ceftriaxone in term of defervescence rate (P = 0.0001). The conclusion drawn is that ceftriaxone showed better effectiveness in the treatment of typhoid fever compared to chloramphenicol.
... Similarly, a recent report described changes in Salmonella antibiograms, including 60-80% sensitivity to chloramphenicol [46]. Additionally, another study in Egypt on Salmonella reported 92% sensitivity to chloramphenicol [47]. ...
Article
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Citation: Tahoun, A.; Elnafarawy, H.K.; El-Sharkawy, H.; Rizk, A.M.; Alorabi, M.; El-Shehawi, A.M.; Youssef, M.A.; Ibrahim, H.M.M.; El-Khodery, S. The Prevalence and Molecular Biology of Staphylococcus aureus Isolated from Healthy and
... Similarly, a recent report described changes in Salmonella antibiograms, including 60-80% sensitivity to chloramphenicol [46]. Additionally, another study in Egypt on Salmonella reported 92% sensitivity to chloramphenicol [47]. ...
Article
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This work aimed to characterize S. aureus isolates from the eyes of healthy and clinically affected equines in the Kafrelsheikh Governorate, Egypt. A total of 110 animals were examined for the presence of S. aureus, which was isolated from 33 animals with ophthalmic lesions and 77 healthy animals. We also investigated the antimicrobial resistance profile, oxacillin resistance mechanism, and the major virulence factors implicated in many studies of the ocular pathology of pathogenic S. aureus. The association between S. aureus eye infections and potential risk factors was also investigated. The frequency of S. aureus isolates from clinically affected equine eyes was significantly higher than in clinically healthy equids. A significant association was found between the frequency of S. aureus isolation from clinically affected equine eyes and risk factors including age and season but not with sex or breed factors. Antimicrobial resistance to common antibiotics used to treat equine eyes was also tested. Overall, the isolates showed the highest sensitivity to sulfamethoxazole (100%) and the highest resistance to cephalosporin (90.67%) and oxacillin (90.48%). PCR was used to demonstrate that mecA was present in 100% of oxacillin- and β-lactam-resistant S. aureus strains. The virulence factor genes Spa (x region), nuc, and hlg were identified in 62.5%, 100%, and 56%, of isolates, respectively, from clinically affected equines eyes. The severity of the eye lesions increased in the presence of γ-toxin-positive S. aureus. The phylogenetic tree of the Spa (x region) gene indicated a relationship with human reference strains isolated from Egypt as well as isolates from equines in Iran and Japan. This study provides insight into the prevalence, potential risk factors, clinical pictures, zoonotic potential, antimicrobial resistance, and β-lactam resistance mechanism of S. aureus strains that cause eye infection in equines from Egypt.
... Jaundice was present in only (01%) patient in our study, whereas [16] reported 04% in their series. Contrary to adult, relative bradycardia is not common in children, which was observed in only 3 patient in present study, which is similar to the observation of [17]. Rose spot was observed in none of our series, which is in conformity with the findings of Yaramis A et.al [18]. ...
... is consistent with similar ndings from the studies in Nepal [23] Egypt [24,25] and India [26]. The mean defervescence time between blood culture positive and negative, it was observed that it took longer in culture positive than in the culture negative cases (4.6 versus 3.9 days) with statistically signi cance (p=0.04). ...
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Background: Enteric fever (EF) continuous to be a serious health threat in Nepal and children are mostly affected from this systemic illness with gruesome complications if left untreated. Accurate diagnosis and appropriate antimicrobial therapy still remain a challenge here. Though ceftriaxone is used as the drug of choice in hospitalized patients, there are concerns on emerging cephalosporin resistance in adults, though not reported in children yet. The objectives of this study were to assess the defervescence time and outcomes of children hospitalized with EF treated with ceftriaxone. Methods: This prospective observational study was conducted at Kathmandu tertiary hospital, Nepal for 12 consecutive months. Children (5-16 years) diagnosed with enteric fever using WHO or validated clinical diagnostic criteria were eligible for recruitment. After taking written informed consent, enrolled children were treated as per the institutional treatment protocol with a same brand of ceftriaxone of standard daily dose and duration of 7 days for uncomplicated and 10 days for complicated. Data on defervescence time, treatment outcomes and their clinical and laboratory profile were collected in the predesigned proforma and analyzed. Results: Of 106 enrolled children, the predominant manifestations were headache (95.3%), loss of appetite (94.3%) and abdominal pain (90.6%). The main laboratory findings were positive Widal test (74%) and thrombocytopenia (50%). Nine children (8.5%) showed blood culture positivity. Salmonella typhi with nalidixic acid resistant strains and Salmonella paratyphi A were isolated (2:1) and were sensitive to ceftriaxone (100%). The defervescence mean time was 3.94 days (± 0.96 SD). Children with positive blood culture had significantly longer defervescence time than those with negative culture (4.56 versus 3.89 days; p=0.04). One child developed complication (pneumonia). No children died or encountered treatment failure. Thrombophlebitis (38.7%) was the only adverse effect of ceftriaxone. Conclusion: Ceftriaxone of once daily dosing regimen exhibited safe and satisfactory treatment outcomes with approximate four days to defervescence. Ceftriaxone can still be drug of choice for the treatment of EF in hospitalized children. Further studies with a greater number of isolates for the classical clinical profile of EF and cephalosporin susceptibility in children may confirm or refute these findings.
... Surprisingly, the isolates resistance to the phenicol member, Florfenicol is only about 20%. The high susceptibility of C. pseudotuberculosis isolates to phenicol in this study is in accordance with the increased sensitivity pattern of bacteria to chloramphenicol that was recently reported from study in Egypt, where 92% of the salmonella isolates were sensitive to chloramphenicol (Hammad et al., 2011). This is in line with the assumption drown by (Tatavarthy et al., 2012) that antibiotic recycling by reusing traditional first-line drugs (e.g., tetracycline, chloramphenicol, and trimethoprim) should be carefully considered. ...
... Pilihan terapi utama pada tifoid adalah siprofloksasin, 16 meski penggunaan seftriakson fase akut juga menghasilkan outcome klinis yang baik. 17 Dengan kata lain, ketidaktepatan pemilihan antibiotik ini memengaruhi hasil penelitian jika dilihat dari outcome ekonomi berupa perbaikan konversi angka leukosit. ...
Article
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Antibiotic conversion from intravenous form to oral form (IV to oral switch) after 48 hours therapy in hemodynamically stable patients can save the cost of treatment without neglecting the effectiveness of therapy. This study aimed to determine the influence of early switch antibiotic from iv to oral on economic clinical humanistic outcome (length of stay in hospital and white blood cell conversion as clinical outcome; quality of life as humanistic outcome using WHOQOL-BREF, and antibiotic cost as economic outcome). This was a quasi-experimental research with control and intervention group, without blinding and randomization. Subjects were inpatients who received ceftriaxone at internal medicine wards of Prof. Dr. Margono Soekarjo hospital for 2 months period from September until October 2017. Intervention group received early antibiotic conversion after 2 days. Length of stay, white blood cell count, quality of life and antibiotic cost were compared between control and intervention groups using Mann-Whitney and Independent t-test. The result showed that from the total of 22 subjects who were divided into intervention group (6 subjects) and control group (16 subjects), there was a decrease in average length of stay of intervention group compared to control (3.167 days and 5 days, respectively). The average of antibiotic cost in intervention group was lower than control group (IDR 73,886.8 and IDR 173,091.125, respectively). The average of white blood cell count in intervention group was 218.33/mm3 while in control group was 2,076,875/mm3. Quality of life of control group was higher (+6,6875) compared to intervention group (–1,33) but was not statistically significant. Early antibiotic switch from ceftriaxone to cefixime could reduce the length of stay and antibiotic cost significantly (0.017 and 0.003).
... The acute illness is characterized by prolonged fever, headache, nausea, loss of appetite, and constipation or sometimes diarrhea. Symptoms are often non-specific and clinically nondistinguishable from other febrile illnesses [17][18][19]. Complete blood picture of our study participants has shown Hb of less than 10gm% in 41.6% and lymphocytosis. Fig. 1. ...
Article
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Introduction: Typhoid fever is a major public health issue in Pakistan. Variations in clinical manifestations make diagnosis a challenging task. Over use of antibiotics make the organism resistant. Antibiotic resistance is currently the most threatening issue as regards to infection control and our study would be helpful in the understanding of this feature of the microbes. The main purpose of this study was to determine the antimicrobial drug resistance and sensitivity pattern in Salmonella typhi and S. paratyphi. Methods: This is a descriptive study carried out in a private hospital in Karachi, Pakistan. One hundred consecutive patients, children from age one day till 12 years admitted in the hospital with Short Communication Siddiqui et al.; AJRID, 2(1): 1-9, 2019; Article no.AJRID.47097 2 the history of fever and had positive blood culture for Salmonella typhi and S.paratyphi were included, 9 antimicrobial drugs were taken into account to check their sensitivity. Statistical analysis was performed using SPSS (IBM SPSS Statistics 20.0). Data was expressed in frequencies and percentages. Results: Most of the children belong to middle class 58% with 62% male and common age group (40%) was 1 day to 4 years. Nearly half of them drinking un-boiled water and had ladder pattern of high grade fever. Most pronounced symptoms were abdominal pain, nausea and anorexia. Resistance pattern was ciprofloxacin 100%, chloramphenicol 89.1%, Ampicillin 87.1% Ceftriaxone 76.2%, Cefixime 75.2%, Amoxicillin 65.3%. Conclusion: Typhoid fever is most commonly observed with unhygienic practices, eating of unhealthy outside food and contaminated water. Pattern of anti microbial resistance gives us a little choice to select antibiotic for typhoid fever. Typhoid fever still remains the commonest bacteraemic illness in Pakistan with children being especially susceptible. Antimicrobial non-susceptibility continues to complicate management.
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Inappropriate use of antibiotics may lead to antimicrobial resistance. In 2012, Dr. Soetomo Hospital conducted training for pediatric residents on the proper use of antibiotics to limit antimicrobial resistance. Objective To evaluate the impact of a rational, antibiotic-use training program for pediatric residents on their antibiotic prescriptions for patients with typhoid fever. Methods A cross-sectional, analytic study was conducted. We collected data from children with typhoid fever who were hospitalized in Dr. Soetomo Hospital, pre- and post-training on antibiotic prescriptions. Children with other known bacterial infections or who were discharged on request were excluded. Antibiotic prescriptions were evaluated using Gyssens algorithm based on the local protocol. Chi-square test was used to compare the quality of antibiotic prescriptions, before (year 2012) and after (year 2013) the training. Results Forty-nine patients with 67 prescriptions in 2012 and 34 patients with 48 prescriptions in 2013 fulfilled the inclusion criteria. Patients’ ages ranged from 1-18 years. Diagnoses of uncomplicated and complicated typhoid were found in 74% and 26% of subjects, respectively. First line (chloramphenicol, thiamphenicol, ampicillin, trimetroprim and sulfametoxazol) and second line (ceftriaxone and cefixime) use were 72% and 28%, respectively. All patients were discharged in good condition. Appropriate use of antibiotics was noted in 61% of subjects in 2012 and in 81% of subjects in 2013 (P=0.036). The most common type of error in 2012 and 2013 was dosage imprecision (25% and 17%, respectively). Conclusion Training on appropriate use of antibiotics significantly improved the quality of antibiotics prescribed in children with typhoid fever in Dr. Soetomo Hospital.
Article
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Leucopenia with neutropenia and a relative lymphocytosis are believed to be common findings in patients with typhoid fever. This paper reviews 191 adult patients with typhoid. The total and differential leucocyte counts done on admission were analysed. In this study leucopenia was found in only 24.6% of patients. Whilst complications occurred at any white cell count, the prevalence of complications increased significantly to 70% in patients with a white cell count above 8 x 10(9)/l. Neutropenia was found in 25% of patients, and none of the patients had an absolute lymphocytosis, whereas 75.8% of patients had true lymphopenia.
Article
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Currently, the laboratory diagnosis of typhoid fever is dependent upon either the isolation of Salmonella enterica subsp. enterica serotype Typhi from a clinical sample or the detection of raised titers of agglutinating serum antibodies against the lipopolysaccharide (LPS) (O) or flagellum (H) antigens of serotype Typhi (the Widal test). In this study, the serum antibody responses to the LPS and flagellum antigens of serotype Typhi were investigated with individuals from a region of Vietnam in which typhoid is endemic, and their usefulness for the diagnosis of typhoid fever was evaluated. The antibody responses to both antigens were highly variable among individuals infected with serotype Typhi, and elevated antibody titers were also detected in a high proportion of serum samples from healthy subjects from the community. In-house enzyme-linked immunosorbent assays (ELISAs) for the detection of specific classes of anti-LPS and antiflagellum antibodies were compared with other serologically based tests for the diagnosis of typhoid fever (Widal TO and TH, anti-serotype Typhi immunoglobulin M [IgM] dipstick, and IDeaL TUBEX). At a specificity of ≥0.93, the sensitivities of the different tests were 0.75, 0.55, and 0.52 for the anti-LPS IgM, IgG, and IgA ELISAs, respectively; 0.28 for the antiflagellum IgG ELISA; 0.47 and 0.32 for the Widal TO and TH tests, respectively; and 0.77 for the anti-serotype Typhi IgM dipstick assay. The specificity of the IDeaL TUBEX was below 0.90 (sensitivity, 0.87; specificity, 0.76). The serological assays based on the detection of IgM antibodies against either serotype Typhi LPS (ELISA) or whole bacteria (dipstick) had a significantly higher sensitivity than the Widal TO test when used with a single acute-phase serum sample (P ≤0.007). These tests could be of use for the diagnosis of typhoid fever in patients who have clinical typhoid fever but are culture negative or in regions where bacterial culturing facilities are not available.
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those who deal with infectious diseases on a daily This two volume work stems from the belief of the Editors that infectious diseases are not only very basis. much with us today but, more importantly, that they There are several excellent textbooks dealing will continue to playa significant global role in mor­ with medical microbiology, and there are equally well-recognized books devoted to infectious dis­ bidity and mortality in all people. A continuing need for an informed and knowledgeable community of eases. The Editors of this work, on the other hand, laboratory scientists is fundamental. Data describing were persuaded that there was a need for a publica­ the global impact of infectious diseases are difficult tion that would bring together the most pertinent and to come by. Fortunately, a recent thoughtful and relevant information on the principles and practice of provocative publication by Bennett et al. (1987) pro­ the laboratory diagnosis of infectious diseases and vides us with data derived from several consultants include clinical relationships. While this two volume that clearly delineate the impact of infectious dis­ text is directed toward the role of the laboratory in eases on the United States today.
Article
Cystic fibrosis (CF) is the most common autosomal recessive disease of the caucasian population and is caused by mutations in the CF transmembrane conductance regulator (CFTR), a cAMP-regulated chloride channel. The most common mutation—a deletion of phenylalanine at residue 508 (ΔF508)—is a trafficking defect where the CFTR becomes trapped in the endoplasmic reticulum. Pier et al.[1xSalmonella typhi uses CFTR to enter intestinal epithelial cells. Pier, G.B. et al. Nature. 1998; 393: 79–82Crossref | PubMed | Scopus (224)See all References[1]have now explored the question of why the incidence of CF is so high and have suggested that there is a selective advantage in being heterozygous for CFTR: resistance to gastrointestinal (GI) infection by Salmonella typhi. By testing epithelial cell lines expressing or not expressing wild-type CFTR, they have discovered that S. typhi, but not the related mouse pathogen Salmonella typhimurium, uses CFTR as the receptor for internalization. This difference in receptor utilization may explain, in part, the different hosts and symptoms of these bacteria. The levels of S. typhi translocated from the GI lumen to the submucosa in wild-type mice, mice heterozygous for the ΔF508 allele of murine CFTR, and mice homozygous for the ΔF508 allele were measured. Compared with the wild-type mice, 86% less bacteria were detected in heterozygous mice and virtually none were found in the homozygous CF mice. Moreover, quantitative electron microscopy using antibodies to CFTR revealed that, after infection with S. typhi, submucosal tissue from heterozygous mice showed lower levels of CFTR than did tissue from wild-type mice, correlating with the reduced translocation of S. typhi. These results suggest that decreased expression of CFTR in people heterozygous for ΔF508 CFTR may increase resistance to typhoid fever, favoring maintenance of this mutation in the population.
Article
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. 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. 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. 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.
Article
The wide variety of bacterial susceptibility test methods has become a major concern of clinical laboratories. In response to this situation, the World Health Organization and the National Communicable Disease Center have set up an expert committee on antibiotics to assess the possibility of establishing internationally acceptable standards for susceptibility testing. One of the technics under examination is the Kirby-Bauer method. It was the purpose of our study to evaluate this method as a standard technic. Seven organisms were selected and tested against 23 high-potency antimicrobial agents. Susceptibility studies of these organisms were made according to the Kirby-Bauer method, using two media-Mueller-Hinton and the Oxoid sensitivity test medium. Other variables also were examined to determine whether they would significantly alter the interpretation of the zone diameter readings. Our experiments showed that either medium provides consistently reproducible results. However, it appears best to preincubate the test organisms in trypticase soy broth. Refrigerated cultures did not yield altered zone diameters, but we do not recommend refrigerating the plates prior to overnight incubation. In general, we found the Kirby-Bauer method to be simple, accurate, and reproducible, and recommend it as a standard testing method for interpretation of susceptibility to chemotherapeutic agents.
Article
Thirty-six adult patients with typhoid fever were studied. Severe, moderate, and mild typhoid fevers were observed in 17 (47.2%), 17 (47.2%), and two (5.6%) patients, respectively. Twenty-eight (77.8%) had either isolated anemia (i.e., anemia unaccompanied by other blood component cytopenias) or mixed cytopenias. Three patients (8.3%) had pancytopenia. Sixteen patients (44.5%) had either total or partial bone marrow suppression. In five (31.3%) with partial suppression, the effect of bone marrow suppression was not reflected in peripheral blood. Sixteen (48.5%) of 33 had peripheral blood cytopenias that were not accompanied by concurrent bone marrow suppression, suggesting a peripheral mechanism responsible for the blood dyscrasia in those cases. No patient had evidence of disseminated intravascular coagulopathy. There was no correlation between clinical severity of disease and bone marrow changes. Bone marrow/peripheral blood changes did not influence the outcome of the disease, since all the patients recovered fully after treatment.
Article
Three hundred and seven healthy food handlers and 34 blood-culture positive enteric fever patients were screened for Salmonellae agglutinins using the Widal test. Of the 307 healthy food handlers, only 3 (1.0%) had an anti-O titre of > or = 1/160 and 8 (2.6%) an anti-H titre of > or = 1/320 for Salmonella typhi, but the majority, 214 (69.7%) and 149 (48.5%) had titres of < 1/20 for O and H agglutinins respectively. Similar agglutinin titres were also seen for S. Paratyphi A, B, and C. In the 34 enteric fever patients, for S typhi, based on anti-O titre of > or = 1/160, 25 persons showed a significant titre, a sensitivity of 73.5%, and a specificity of 99.0%. And 21 persons showed a significant titre of > or = 1/320 for anti-H, a sensitivity of 61.8% and a specificity of 97.4%. Based on these findings, titres of > or = 1/160 and > or = 1/320 for anti-0 and anti-H respectively, were considered diagnostic for enteric fever in Kumasi, Ghana.