|Year : 2016 | Volume
| Issue : 2 | Page : 234-239
Comparison between different lines of treatment of typhoid fever
Reda S Badra1, Sabry A Shoeiba1, Amira A El-Hendy2, Asmaa M Mousa Nasr1
1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
|Date of Submission||09-Mar-2015|
|Date of Acceptance||22-Mar-2015|
|Date of Web Publication||18-Oct-2016|
Asmaa M Mousa Nasr
Shebin El-Kom, Menoufia, 32511
Source of Support: None, Conflict of Interest: None
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.
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.
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%).
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.
Keywords: ceftriaxone, chloramphenicol, ciprofloxacin, typhoid fever
|How to cite this article:|
Badra RS, Shoeiba SA, El-Hendy AA, Mousa Nasr AM. Comparison between different lines of treatment of typhoid fever. Menoufia Med J 2016;29:234-9
|How to cite this URL:|
Badra RS, Shoeiba SA, El-Hendy AA, Mousa Nasr AM. Comparison between different lines of treatment of typhoid fever. Menoufia Med J [serial online] 2016 [cited 2020 Feb 17];29:234-9. Available from: http://www.mmj.eg.net/text.asp?2016/29/2/234/192405
| Introduction|| |
Typhoid feverand paratyphoid fever (also known as enteric fever, but collectively referred to here as typhoid fever) are severe systemic illnesses characterized by sustained fever and abdominal symptoms.
The organism classically responsible for the enteric fever syndrome is S. enterica serotype typhi (formerly S. typhi). Other Salmonella More Details serotypes, particularly S. enterica serotype paratyphi A, B, or C, can cause a similar syndrome; however, it is usually not clinically useful or possible to reliably predict the causative organism based on clinical findings .
Typhoid fever continues to be a global health problem with an estimated 16–22 million cases of typhoid and 200 000–600 000 deaths occur annually, based on extrapolation from endemic region. Regions with a high incidence of typhoid fever (>100/100 000 cases/year) include South Central and South East Asia . Regions of medium incidence (10–100/100 000 cases/year) include the rest of Asia, Africa, Latin America, the Caribbean, and Oceania, except for Australia and New Zealand .
In Egypt, a laboratory-based surveillance project was conducted in Upper Egypt, involving governorate health officers, clinicians, and several healthcare centers (from the regional hospital to the rural health units and primary care physicians). The results from this study showed that the incidence of typhoid fever was 59/100 000 persons/year which remains Egypt as a country with medium incidence of typhoid fever .
The sensitivity pattern of S. typhi changing and there is re-emergence of sensitivity to chloramphenicol but rising resistance to ciprofloxacin .
Antimicrobial drugs used for treatment of typhoid fever are increasingly being used in the treatment of other diseases, leading to problems with antibiotic resistance owing to acquisition by S. typhi of resistance – encoding plasmids from other infections bacteria .
| Materials and Methods|| |
Randomized clinical study was implemented in the period between April 2013 and August 2013. After having their informed consent to participate in our study, a total of 60 patients with acute typhoid fever in Shebin El-Kom Hospital were included in this study.
Our inclusion criteria were to have a diagnosis for typhoid fever with positive blood culture for S. typhi and a consent to participate in this study. Criteria for exclusion were patients with deteriorated general condition, hypotension hyperpyrexia (40.5c or above) melena, bleeding per rectum, or disturbed level of consciousness.
All recruited patients were subjected to
- Careful history and through 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 into biphasic blood culture bottles and incubated at 37°C. Bottles were checked daily for 7 days, and when growth was noted an aliquot of blood was streaked into MacConkey and blood agar plates to allow for final identification of the organism by using standard serological and biochemical methods.
- Widal agglutination test was conducted on all patients . Susceptibility of S. typhi to chloramphenicol (30 µg), ciprofloxacin (5 µg), and ceftriaxone (30 µg) was performed using the disc diffusion Kirby-Bauer method .
- 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). The time of defervescence was defined as the time interval from starting an appropriate antimicrobial chemotherapy until the documentation of normal body temperature .
- A total of 20 (33.3%) patients were randomly allocated to be treated with ceftriaxone parenterally (2 g/kg/day) given once daily for 7 days.
- A total of 20 (33.3%) patients were randomly allocated to be treated with ciprofloxacin orally (500 mg) twice daily for 10 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 the final analysis of results.
- Patients presenting with complications (gastrointestinal hemorrhage or perforation, toxic myocarditis, hepatitis) were excluded from the study.
- Patients were considered cured if there was no fever, abdominal tenderness, toxic look, or tympanitic abdomen at the end of the treatment course.
The data collected were tabulated and analyzed by SPSS version 17 (SPSS; SPSS Inc., Chicago, Illinois, USA) on IBM-compatible computer.
Two types of statistics were done
Descriptive statistics: for example, percentage (%), mean (X), (SD).
Analytic statistics: for example, χ2-Test: It was used to study association between two qualitative variables.
Fischer exact test for 2 × 2 tables when expected cell count of more than 25% of cases was less than 5 and P-value less than 0.05 was considered significant.
Quantitative data were presented in mean and SD. Qualitative data were presented in frequency and its related percentage.
One-way analysis of variance test was used for the comparison of quantitative variables among more than two independent groups. The least significant difference from post-hoc test was used to analyze the significance between each two groups.
Significance level (P-value):
- P > 0.05 is insignificant (NS).
- P ≤ 0.05 is significant (S).
| Results|| |
A total of 60 patients with acute typhoid fever with positive blood culture for S. typhi were enrolled in this study. They were 42 (70%) male and 18 (30%) female patients ranging in the age range from 16 to 74 years (± 36.53 years). The clinical picture of these patients upon admission is shown in [Table 1].
The hematological profile results were showed in [Table 2].
Anemia and leukopenia were seen in most of the patients.
Drug sensitivity tests revealed that four (20%) isolates were resistant to ciprofloxacin, and no isolates (0%) were resistant to chloramphenicol and ceftriaxone ([Table 3]).
There were no reported complications throughout study. All patients were cured.
In this study, no significant difference was found between both methods with regard to age, sex, and clinical presentation.
Significant difference was found between both groups with regard to resistance hematological profile, and drug sensitivity.
| Discussion|| |
The present study aimed to assess the different lines of treatment of typhoid fever and focusing on the usage of chloramphenicol, ciprofloxacin, and ceftriaxone.
In our study, 60 patients with acute typhoid fever were admitted in Shebin El-Kom Fever Hospital from April 2013 to August 2013. The included patients were subjected to full medical history, clinical examination, and laboratory investigations including complete blood picture, blood culture for S. typhi, and Widal test.
The age of these patients ranged from 16 to 74 years (±36.53 years). There were 42 (70%) male and 18 (30%) female patients ranging in age from 34 to 47 years. Hammad et al.  studied 30 (62%) male and 20 (38%) female patients in their study in the age range from 34 to 47 years; this difference may be attributed to small number of patients.
Khoharo and Memon  studied a total number of 67 cases, of which 41 (61.1%) were male and 26 (38.8%) were female.
In our study, there were 34 (56.7%) patients from the rural areas and 26 (43.3%) patients from the urban areas. This may be owing to bad hygiene, negligence, and reluctance to seek medical care.
In our study, the clinical presentations of these patients were: fever in 60 (100%) cases, anorexia in 42 (70%) cases, vomiting in 24 (40%) cases, diarrhea in 18 (30%) cases, abdominal pain in 18 (30%) cases, headache in 12 (20%) cases, myalgia in four (10%) cases, hepatomegaly in 24 (40%) cases, and splenomegaly in 12 (20%) cases. According to Hammad et al.  the clinical presentations of patients were: fever in 52 (100%) cases, vomiting in 23 (44%) cases, diarrhea in 17 (33%) cases, abdominal pain in 44 (85%) cases, headache in 40 (70%) cases, hepatomegaly in 20 (38%) cases, and splenomegaly in 40 (70%) cases. According to Khoharo and Memon  the clinical presentations of 67 patients were: fever in 67 (100%) cases, hepatomegaly in 53 (79.1%) cases, anorexia in 65 (97%) cases, vomiting in 21 (31.3%) cases, diarrhea in 11 (16.4%) cases, hepatomegaly in five (7.4%) cases, and splenomegaly in 19 (28.3%) cases.
In our study, the hematological profiles showed that red blood cells ranged from 3.4 to 4.4 million/mm (mean ± 2.8 thousands/cm 2), hemoglobin ranged from 8.5 to 12.8 g/dl (mean ± 10.14 g/dl), hematocrit ranged from 28 to 40% (mean ± 32.7%), white blood cell counts ranged from 1.8 to 3.8 thousands/cm 2, and platelet counts ranged from 80 to 180 km 2 (mean ± 116.2 thousands/cm 2).
In our study, the blood culture of the all studied patients was positive. This in agreement with the results of Hammadet al. .
In our study, drug sensitivity tests revealed that four (20%) isolates were resistant to ciprofloxacin, and no isolates were resistant to chloramphenicol or ceftriaxone. Wasfy et al.  found the improvement in susceptibility of S. typhi to chloramphenicol, although its lower performance was compared 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.
In our study, the drug sensitivity test on chloramphenicol was in agreement with Choudhary et al. , who found that of 322 isolates, none was resistant to chloramphenicol. Since its introduction in 1948, chloramphenicol has been the treatment of choice for typhoid fever and remains the standard against which newer antimicrobials are compared. Treatment with chloramphenicol reduces mortality because of typhoid fever from about 20 to 1%, and the duration of fever from 14–28 days to 3–5 days .
Our study was in agreement with Bhatia et al.  who found that of the 45 culture-positive patients, S. enterica serovar typhi was isolated from 25 patients, and S. enterica serovar paratyphi A from 20 patients. All isolates of S. enterica serotypes paratyphi A were sensitive to chloramphenicol [20 (100%)], and 24 isolates of S. enterica serotype typhi were sensitive to chloramphenicol (96%).
In our study, the drug sensitivity test on chloramphenicol was in disagreement with Hammad et al.  who found that four (8%) cases of isolates were resistant to chloramphenicol.
However Hammad et al.  found that four (8%) cases of isolates were resistant to chloramphenicol. Owing 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. As for ciprofloxacin and ceftriaxone, they should not be used as first-line drugs for treatment of acute lymphoid fever.
Our study on chloramphenicol was in disagreement with Gupta et al.  who found that of 87 isolates, there are 81 (93.2) sensitive to chloramphenicol. Chloramphenicol is cheaper than the third-generation cephalosporins, is administered orally and its clinical efficacy is well established. Where drug sensitivity tests are not available, chloramphenicol can be given in uncomplicated typhoid fever and the response be monitored carefully. If fever subsides within 5 days, the drug must be continued. Otherwise, if the temperature does not become normal within 7 days, one should resort to ciprofloxacin therapy. In complicated cases, or patients in whom diagnosis and therapy had been delayed beyond 2 weeks, there may be justification for the institution of ciprofloxacin therapy. In complicated cases or patients in whom diagnosis and therapy had been delayed beyond 2 weeks, there may be justification for the institution of ciprofloxacin therapy .
Our study on chloramphenicol was in disagreement with Butler  who found that the cure rate of chloramphenicol was 83–96%.
In the USA, chloramphenicol is virtually obsolete because of its bone marrow toxicity. Most patients receive ceftriaxone, often in combination with and fluoroquinolones . The synergistic effects of these two classes of drugs have not been evaluated, thus combined therapy is not recommended routinely .
Our study on chloramphenicol was in disagreement with Kumar et al.  who found that of the 128 isolates, there are 122 (95%) resistant to chloramphenicol. The re-emergence of susceptibility to these drugs may be a result of the emergence of de-novo susceptible strains  or the loss of high molecular weight self-transmissible plasmids .
In our study, the drug sensitivity test on ceftriaxone found that no isolates were resistant to ceftriaxone and this was in agreement with Hammad et al.  who found that of the 52 (100%) isolates, none were resistant to ceftriaxone.
In addition, it is in agreement with Choudhary et al.  who found that of the 322 (100%) isolates, none were resistant to ceftriaxone.
This was in agreement with Bhatia et al.  who found that 25 (100%) cases of isolates, none were resistant to ceftriaxone.
This was in agreement with Gupta et al.  who found that of the 87 (100%) isolates, none were resistant to ceftriaxone.
In our study, the drug sensitivity test revealed that four (20%) isolates were resistant to ciprofloxacin. This is in agreement with Bhatia et al.  who found that of the 45 culture-positive patients, salmonella enterica typhi was isolated from 25 patients and sensitivity to ciprofloxacin was 22 (88%).
Our study was in agreement with Choudhary et al.  who found that of the 322 cases, there were 175 (54.3%) resistant to ciprofloxacin. It is believed that nalidixic acid resistance is a marker for ciprofloxacin resistance as clinical failures have been documented in cases where ciprofloxacin has been used (based on susceptibility) for nalidixic acid-resistant strains .
Our study was in disagreement with Gupta et al.  who found that of the 87 isolates of S. enterica serotype typhither, 84 (96.6%) were sensitive to ciprofloxacin. The selective pressure on the bacterial population from uncontrolled use of quinolones has led to the emergence of resistance to this group of antimicrobials. One imitation in the 9 yr A gene mediated full resistance to narrow spectrum quinolones. A second mutation in either the 9 yr A or the 9yr B genes mediate full resistance to fluoroquinolones.
Owing to the unpredictable resistance to treatment with ciprofloxacin, nalidixic acid susceptibility testing must be included with ciprofloxacin susceptibility testing. Treatment with ciprofloxacin should be avoided in nalidixic acid resistants enterica typhi, although higher doses may be helpful in few cases .
Our study was in disagreement with Hammad et al.  who found that of all the cases, there were no isolates that were resistant to ciprofloxacin [Figure 1] and [Figure 2].
|Figure 2: Comparison between response to treatment in the studied groups|
Click here to view
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ghenghesh KS, Franka E, Tawil K, Wasfy MO, Ahmed SF, Rubino S, Klena JD. Enteric fever in Mediterranean north Africa. J Infect Dev Ctries 2009; 3:753–761.
Lynch MF, Blanton EM, Bulens S, Polyak C, Vojdani J, Stevenson J, et al
. Typhoid fever in the United States, 1999–2006. JAMA 2009; 302:859–865.
Baker S, Favorov M, Dougan G. Searching for the elusive typhoid diagnostic. BMC Infect Dis 2010; 10:45.
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; 74:114–119.
Gogia A, Agarwal PK, Khosla P, Jain S, Jain KP. Quinolone-resistant typhoid fever. Indian J Med Sci 2006; 60:389–390.
Kumar Y, Sharma A, Mani KR. Re-emergence of susceptibility to conventionally used drugs among strains of Salmonella Typhi in central west India. J Infect Dev Ctries 2011; 5:227230.
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. J Clin Microbiol 2001; 39:1002–1007.
Kumar R, Gupta N, Shalini N. Multidrug-resistant typhoid fever. Indian J Pediatr 2007; 74:39–42.
Khoharo HK, Memon IA, Kazi SA, Qureshi F. Serum cobalamin and dyslipidemia in type 2 diabetics. J Liaquat Uni Med Health Sci 2015; 14:21-5.
Wasfy MO, Frenck R, Ismail TF, Mansour H, Malone JL, Mahoney FJ. Trends of multiple-drug resistance among Salmonella serotype Typhi isolates during a 14-year period in Egypt. Clin Infect Dis 2002; 35:1265–1268.
Choudhary A, Gopalakrishnan R, Senthur Nambi P, Ramasubramanian V, Abdul Ghafur K, Thirunarayan MA. Antimicrobial susceptibility of Salmonella enterica serovars in a tertiary care hospital in southern India.. Indian J Med Res 2013; 137:800–802.
Mirza SH, Beeching NJ, Hart CA. Multi-drug resistant typhoid: a global problem. J Med Microbiol1996; 44:317–319.
Bhatia JK, Mathur AD, Arora MM. Reemergence of chloramphenicol sensitivity in enteric fever. MJAFI 2007; 63:212–214.
Gupta V, Kaur JKaisthaN. Re-emerging chloramphenicol sensitivity and emerging low level ciprofloxacin resistance among Salmonella enterica
serotype Typhi isolates in North India. Trop Doct 2009; 39:28–30.
Jesudason MV, John R, John TJ. The concurrent prevalence of chloramphenicol-sensitive and multi-drug resistant Salmonella typhi
in Vellore, S. India. Epidemiol Infect 1996; 116:225–227.
Butler T. Department of Microbiology and Immunology, Ross University School of Medicine, North Brunswick, NJ, USA. Clin Microbiol Infect 2011; 17:959–963.
Crump JA, Kretsinger K, Gay K, Hoekstra RM, Vugia DJ, Hurd S, et al
., Emerging Infections Program FoodNet and NARMS Working Groups. Clinical response and outcome of infection with Salmonella enterica serotype Typhi with decreased susceptibility to fluoroquinolones: a United States foodnet multicenter retrospective cohort study. Antimicrob Agents Chemother 2008; 52:1278–1284.
Dutta S, Sur D, Manna B, Bhattacharya SK, Deen JL, Clemens JD. Rollback of Salmonella enterica serotype Typhi resistance to chloramphenicol and other antimicrobials in Kolkata, India. Antimicrob Agents Chemother 2005; 49:1662–1663.
Misra RN, Bawa KS, Magu SK, Bhandari S, Nagendra A, Menon PK. Outbreak of multidrug resistant Salmonella typhi
enteric fever in Mumbai garrison. MJAFI 2005; 61:148–150.
Mandal S, Mandal MD, Pal VK. Nalidaxic acid resistance 11. predicting reduced ciprofloxacin susceptibility of Salmonella enterica
seroval typhi. Asian Pacific J Trop Dis2012; 2:S585–S587.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]