The Rationality of Antibiotic Use on Patients of Typhoid Fever

TYPE OF ARTICLE: Research Abstract: Typhoid fever is an infectious disease caused by Salmonella typhi bacteria. The administration of antibiotics in typhoid fever is needed as a causative therapy to eradicate the bacteria based on the principles of rational therapy to avoid antibiotic resistance. However, there are still a considerable amount of cases of unnecessary antibiotic administration. This study aims to examine the rationality of antibiotic use on patients of typhoid fever. This research is a non-intervention study with descriptive analytic methods. Data were retrieved retrospectively by identifying the medical records of patients treated in the X Hospital Salatiga from January to August 2016 with a purposive sampling method based on the inclusion and exclusion criteria of 67 cases. The data was analyzed by using Gyssen criteria based on the standard of typhoid fever service of WHO 2011. The result showed that the percentage of female typhoid fever patients was higher than the male with the most prolonged 3-day hospitality. The most commonly used antibiotics are ceftriaxone, ciprofloxacin, and cefixime with the result of the rationality analysis of category 0 (55.22 %), category IIIA (1.49%), category IIIB ( 8.96% ), category IVA (17.91%), and category IVC (4.48%). It can be concluded that the rationality of antibiotics used in patients with typhoid fever at X Hospital Salatiga based on Gyssen criteria showed a good result.


INTRODUCTION
Antibiotics are chemicals that can inhibit growth or kill microorganisms. 1 Excessive and inappropriate use of antibiotics reaches 20-50% of all antibiotics used in the world. The Center for Disease Control and Prevention (CDC) in the United States estimates that around 50 million out of 150 million antibiotics are unnecessary. 2 A total of 13% to 37% of all patients hospitalized in developed countries obtain either single or combination antibiotics, while the use in developing countries reaches 30-80%. 3 One of the health problems that need to be treated with antibiotics is typhoid fever. Typhoid fever is an infectious disease caused by Salmonella typhi bacteria. The incidence of typhoid fever is still estimated to be high at around 17 million per year and also is considered to be the cause of 222,000 deaths per year. 4 Clinical symptoms of typhoid fever start from the mildest, such as fever and gastrointestinal disorders to severe complications such as seizures, encephalopathy, or intestinal bleeding. Therefore, a good treatment of typhoid fever is highly important. 5 The administration of antibiotics in typhoid fever is required as a causative therapy to eradicate the bacteria based on the principles of rational therapy.
It requires rules and clear instructions in the use of antibiotics on an ongoing basis, as well as a control system to increase the level of rationality of antibiotic use. The rationality of antibiotic use, according to Gyssen's criteria, includes precise indications, efficacious, safe, and affordable costs. The rationality in the use of antibiotics can prevent bacterial resistance whose main purpose is to reduce morbidity and mortality due to the use of antibiotics in patients, save treatment costs, shorten hospitality, save hospital operating costs and improve hospital service quality. 6 Based on the explanation above, it is necessary to examine the level of rationality of antibiotic use in patients of typhoid fever as a process of evaluation and control system of antibiotic use in hospitals.

MATERIALS AND METHOD
This research is a non-intervention study with descriptive analytic methods. Data were collected retrospectively by identifying the medical records of patients treated in the Internal Medicine Ward of X Hospital Salatiga with a purposive sampling method.
The inclusion criteria for sampling were the medical records of patients diagnosed with typhoid fever from January 2016 to August 2019 with the complete data of antibiotic use, including the type of drug, duration of administration, dose, frequency of administration, and the route of administration. The exclusion criteria of this study were medical records of typhoid fever patients who returned home under self-demand, referenced, or passed away that the administration of antibiotics stopped, or patients with typhoid fever and other infectious diseases.
The diagnosis of typhoid fever in this study referred to the diagnosis written by the doctor in the medical record without identifying how the doctor diagnosed. The rationality of antibiotic use was later analyzed descriptively by using Gyssen's assessment criteria with the procedure showed in Figure 1 The characteristics of the research subject in this study indicated that the prevalence of patients diagnosed with typhoid fever commonly happened more in women than men with the main fever as the main symptom and the gastrointestinal disorders as the additional symptom such as nausea, vomit, and abdominal pain. The fastest duration of treatment for typhoid fever patients in this study was two days and a maximum of seven days with three-day hospitality.
The result of the research is shown in the following table. The characteristics of the research subject are shown in Table 1. The characteristics of the use of antibiotics in patients of typhoid fever are shown in Table 2, and qualitative analysis of the rationality of the use of antibiotics in patients of typhoid fever in the Internal Medicine Ward X Hospital Salatiga is shown in Table 3.
Based on Table 1, the subject was dominated by female as were 39 (58.21%), by age, more than half of the sample (68.66%) were 26-35 years old. The clinical symptoms that most experienced was fever (89.55%) while the most rarely experienced  was dysphagia and epistaxis (1.49%). The duration of hospitalization varid between 2-7 days but most were between 2-4 days. Based on Table 2, it showed that Ceftriaxone is the most widely used antibiotics by 47 (70.15%) samples. The longest duration of the administration was similar in all the types of antibiotics, namely 7 days. Based on the dose, Ceftriaxone was the highest dose (2 gr) and most widely used. All the types of antibiotics administered two times a day, but Ceftriaxone is also given one times a day and intravenous route is the most common used administration route.
Based on the analysis, which is shown in Table 3, it can be identified that the use of antibiotics in patients of typhoid fever in Internal Medicine Ward in the X Hospital Salatiga has a high number in category 0 by 55.22 %. The effectiveness of antibiotic selection in patients of typhoid fever showed that 17.91 % of cases were in the IVA criteria

DISCUSSION
The greater number of female patients with a diagnosis of typhoid fever in this study is in line with several preliminary studies. The tendency is caused by the fact that women have a three-time greater risk of becoming a carrier or people who can remove the Salmonella typhi bacteria after a three-month infection even without showing apparent clinical symptoms. 8,9 However, several other studies are stating that typhoid fever has a 3.8-time higher risk for men due to the habit of drink and food stall consumption and less attention to cleanliness. 10,11 In this study, the main complaint found in the medical record data is fever. Two to seven days of fever onset characterized by the step-ladder fever in which the temperature continues to rise day to day and get worse at night is one of the typical symptoms of typhoid fever. Additional complaints such as nausea, vomiting, malaise also happened frequently to patients of typhoid fever. 12,13 The use of antibiotics in typhoid fever in the Internal Medicine Ward of X Hospital Salatiga has good rationality of 55.22% (category 0) compared to the result of the rationality study of antibiotic use in typhoid fever patients in other hospitals which showed the rationality above and below 50%. [14][15][16][17] Based on the result of this study, it can be seen that there is 17.91 % (12 patients) who previously received antibiotics Ciproflaxin and should be halted in the IVA category due to other more effective antibiotics (Table 3). 4,7 It is in line with the result of Butler's research (2011) 18 stating that antibiotic Ceftriaxone is considered more effective with a cure rate of 72% compared to Ciprofloxacin, which is only 62%. Furthermore, Sidabutar (2010) 19 also states that the use of Ceftriaxone in typhoid fever is faster in reducing the incidence of fever and changing in culture results, and has a low risk of resistance. Ceftriaxone is a cephalosporin antibiotic, including Cefixime, which in this study was given in 11.94 % of cases of typhoid fever ( Table 2).
The rationality analysis of antibiotic use in terms of cost-effectiveness in this study showed that there were 4.48% of cases (Table 3), including in the IVC category, namely cheaper antibiotic options. Antibiotics are considered to be expensive if the price is above Rp100,000.00 each injection ampoule or each oral antibiotic strip, such as patent antibiotics prescribed to 3 patients in this study. 20 The rationality analysis of the duration of antibiotic therapy in this study showed that 1.49% of cases were categorized as IIIA with an overlong duration of administration, and 8.96% of cases were categorized as IIIB with over concise duration of the administration. The duration of antibiotic administration in the case of infection is recommended to be within 5 to 7 days. It aims to eradicate the bacteria and avoid resistance altogether. 5  | 5

CONCLUSION
The rationality of the use of antibiotics in patients of typhoid fever in the Internal Medicine Ward of the X Hospital Salatiga from January 2016 to August 2019 based on Gyssen criteria is in a good category that is 55.22%.