Selasa, 17 Mei 2011


SENSITIVITY TO Salmonella typhi chloramphenicol
AND IN ceftriaxone Dr. SOETOMO SURABAYA AND
DI Dr. Saiful Anwar Malang PERIOD 2008-2009

Abstract: The sensitivity of Salmonella typhi bacteria to several antibiotics for the treatment of typhoid fever particularly chloramphenicol and Ceftriaxone constantly changing. For patients with typhoid fever at Dr. Soetomo chloramphenicol could be an option for the treatment of typhoid fever in the Ceftriaxone. As for patients with typhoid fever in RSSA Malang use of chloramphenicol and Ceftriaxone need consideration because of the high resistance rate against Salmonella typhi.

Key words: salmonella typhi, chloramphenicol, ceftriaxone

     Typhoid fever is an acute infectious disease in the small intestine with symptoms of fever a week or more with disorders of the digestive tract (Widodo, 2007). Typhoid fever is an endemic disease in countries that are developing, including Indonesia (Widodo, 2007). In Indonesia the incidence of typhoid fever ranges from 350-810 cases per 100,000 population per year with a death rate of 2%. Typhoid fever is found almost throughout the year especially in the summer (Rampengan, 2008).
In East Java incidence of typhoid fever at the health center and several hospitals respectively 4000 and 1000 cases per month, with a mortality rate of 0.8%. Results of previous studies in Surabaya showed that typhoid fever is estimated from year to year tend to increase. At Dr. Soetomo during the period 1991-1995 has treated 586 patients with typhoid fever death rate 1.4%, and during the period 1996-2000 has treated 1563 patients with typhoid fever death rate 1.09% (Soewandojo, 2007), while the prevalence of typhoid fever in Malang Regency as much as 1.2% of 10,966 samples in 2007 (Dinkesjatim, 2008)
Typhoid fever caused by Salmonella typhi, which is a Gram-negative bacteria that is transmitted is almost always occur through contaminated food and beverages. Multiplication of bacteria entered the bloodstream, then the absorption into the digestive tract and excreted along with feces such patients (Rampengan, 2008).
The most widely used drug in the treatment of typhoid fever is chloramphenicol, a drug used since 1948 and is still used as a drug of choice in Indonesia, especially at Dr. Soetomo General Hospital and Dr. Saiful Anwar Malang because efektvitasnya against Salmonella typhi was still high in addition to the price of drugs is relatively cheap (Musnelina, 2004). From the molecular level studies suggested that the Salmonella typhi bacteria become resistant to chloramphenicol due to the plasmid that produces the enzyme Chloramphenicol Acetyltransferase (CAT), which activates chloramphenicol (Balbi, 2004). This makes the experts look for another alternative is the best medicine for typhoid fever, among others, Ceftriaxone (Musnelina, 2004).
Ceftriaxone is an antibiotic effective in the treatment of typhoid fever caused by Salmonella typhi. Lucrative nature of this drug is having a network with good penetrating power and can penetrate into the inflammation that makes Ceftriaxone be one second choice drug for the treatment of typhoid fever particularly in hospitals and Dr Dr.Soetomo Surabaya. Saiful Anwar Malang (Darmowandowo, 2002). Ivanoff, 2002 showed that since 1990 more and more resistant Salmonella typhi Ceftriaxone.
The nature of the bacteria that often change change can affect the success of first-line treatment of infectious diseases and the effect on the cost of treatment of patients at the hospital. The absence of regular monitoring of data, especially Salmonella typhi bacteria sensitivity to the drug's first choice for typhoid fever, namely chloramphenicol and one second choice drugs are widely used namely Ceftriaxone in East Java, especially at Dr. Soetomo General Hospital and Dr. Saiful Anwar Malang makes researchers want to know the description of the sensitivity of Salmonella typhi to chloramphenicol and Ceftriaxone at Dr. Soetomo and in Dr. Saiful Anwar Malang period 2008-2009. Describing the sensitivity of Salmonella typhi to chloramphenicol and Ceftriaxone at Dr. Soetomo and in Dr. Saiful Anwar Malang period 2008-2009?

RESEARCH METHOD
- The research design used in this study is an observational descriptive cross sectional approach.
- The research instrument used is the record of the medical records of typhoid fever patients who do inpatient at Dr. Soetomo General Hospital and Dr.Saiful Anwar Malang Period from 2008 to 2009.
- Data were obtained from secondary data that the medical records of patients who did typhoid fever hospitalized at Dr. Soetomo General Hospital and Dr. Saiful Anwar Malang Period from 2008 to 2009.
- Data obtained from the medical records were analyzed descriptively and are presented in tables and graphs (bar chart) in the form of percentages.


DISCUSSION
Preview sensitivity of Salmonella typhi to chloramphenicol and Ceftriaxone at Dr. Soetomo and in Dr. Saiful Anwar Malang.
Salmonella typhi is a Gram-negative bacteria is the cause of typhoid fever infections (Darmowandowo, 2006). Until now, the trilogy still embraced the management of typhoid fever that is rest and treatment, diet and therapy support, as well as giving antibiotics (Widodo, 2007). The drugs most commonly used antibiotics to treat typhoid fever, among others, chloramphenicol, Tiamfenikol, Cotrimoxazole, Ampisillin and Amoxicillin, a third generation cephalosporin, and Florokuinolon (Widodo, 2007). Some antibiotic sensitivity test results against Salmonella typhi at Dr. Soetomo as shown in table 1:
 
Table 1 Table Frequency and Percentage of Each Antibiotics in Response Sensitivity Dr. Soetomo in 2008-2009
Jenis Antibiotik
Frekuensi Sensitivitas Antibiotik untuk S.typhi
Jumlah
Prosentase Sensitivitas Antibiotik untuk S.typhi
Jumlah
Sensitif
Intermediet
Resisten
Sensitif
Intermediet
Resisten
Amikasin
13
2
4
19
68.4
10.5
21.1
100
Amoksisilin
6
0
13
19
31.6
0
68.4
100
Amoksisilin-Asam Klavulanat
9
7
3
19
47.4
36.8
15.8
100
Seftriakson
6
0
13
19
31.6
0
68.4
100
Sefotaksim
6
0
13
19
31.6
0
68.4
100
Siprofloksasin
19
0
0
19
100
0
0
100
Meropenem
19
0
0
19
100
0
0
100
Kloramfenikol
12
1
6
19
63.2
5.3
31.6
100
(Primary Data, 2010)
Figure 1 Percentage Response SensitivityDiagram Each antibiotics at Dr. Soetomo in 2008-2009

Table 1 shows the antibiotics that are still sensitiveto Salmonella typhi that is amikacin, Ciprofloxacin,Meropenem, and chloramphenicol. Whileconducted in Dr. Saiful Anwar Malang as in table2:

Table 2 Table and Percentage FrequencyResponse Sensitivity Each Antibiotics in Dr Saiful Anwar Malang in 2008-2009

Jenis Antibiotik
Frekuensi Sensitivitas Antibiotik untuk S.typhi
Jumlah
Prosentase Sensitivitas Antibiotik untuk S.typhi
Jumlah
Sensitif
Intermediet
Resisten
Sensitif
Intermediet
Resisten
Amikasin
3
3
7
13
23.1
23.1
53.8
100
Amoksisilin
2
0
11
13
15.4
0
84.6
100
Amoksisilin-Asam Klavulanat
5
2
6
13
38.5
15.4
46.2
100
Seftriakson
3
3
7
13
23.1
23.1
53.8
100
Sefotaksim
3
1
9
13
23.1
7.7
69.2
100
Siprofloksasin
9
1
3
13
69.2
7.7
23.1
100
Meropenem
12
0
1
13
92.3
0
7.7
100
Kloramfenikol
3
0
10
13
23.1
0
76.9
100
(Primary Data, 2010)
Figure 2 Percentage Response Sensitivity GraphEach Antibiotics in Hospital
Dr. Saiful Anwar Malang in 2008-2009

Table 2 shows that are still sensitive to antibioticsof Salmonella typhi that is tto Ciprofloxacin andMeropenem. Preview sensitivity of Salmonellatyphi to several antibiotics in East Java, which was represented by Dr. Soetomo General Hospital andDr. Saiful Anwar Malang as in table 3

Table 3. Table Frequency Response SensitivityAnd the percentage of each antibiotic in theSecond Hospital in 2008-2009
Jenis Antibiotik
Frekuensi Sensitivitas Antibiotik untuk S.typhi
Jumlah
Prosentase Sensitivitas Antibiotik untuk S.typhi
Jumlah
Sensitif
Intermediet
Resisten
Sensitif
Intermediet
Resisten
Amikasin
16
5
11
32
50
15.6
34.4
100
Amoksisilin
8
0
24
32
25
0
75
100
Amoksisilin-Asam Klavulanat
14
9
9
32
43.8
28.1
28.1
100
Seftriakson
9
3
20
32
28.1
9.4
62.5
100
Sefotaksim
9
1
22
32
28.1
3.1
68.8
100
Siprofloksasin
28
1
3
32
87.5
3.1
9.4
100
Meropenem
31
0
1
32
96.9
0
3.1
100
Kloramfenikol
15
1
16
32
46.9
3.1
50
100

Figure 3 Percentage Response Sensitivity Graph Each antibiotics In Second  Hospital in 2008-2009 

Table 3 shows Siproloksasin and Meropenem has the highest sensitivity. The shift of the sensitivity of Salmonella typhi in the two places, namely at Dr.Soetomo and in Dr. Saiful Anwar Malang as written in his book Widodo, 2007. The big difference in the sensitivity pattern of Salmonella typhi at Dr. Soetomo and in Dr. Saiful Anwar Malang, shows the sensitivity pattern of Salmonella typhi to antibiotics the same can be varied.Because each region has a different sensitivity pattern and vary at different times and places.Sensitivity of bacteria is basically a natural ability of bacteria to survive (Ryan & Ray, 2004).According Dzen, 2004 the factors that affect it such as overuse and missuse antibiotics by doctors, free use of antibiotics by the public, a long treatment with low doses, where the resistance mechanism is by way of accumulation through the impermeability barrier to antibiotics, change ofantibiotic target so that antibiotics have no effects, antibiotic inactivation by the production of enzymes from bacteria, the bacteria form an enzyme which has undergone a change, the bacteria pump out (export), antibiotics (Ryan & Ray, 2004). 
Since 1948 chloramphenicol is the drug of choice for typhoid fever in Indonesia because of its effectiveness against Salmonella typhi was still high in addition to drug prices are relatively cheap (Musnelina, 2004). Results of sensitivity tests against Salmonella typhi chloramphenicol at Dr.Soetomo as shown in Table 1 shows the chloramphenicol is still sensitive to Salmonella typhi that is equal to 63.2%, this indicates chloramphenicol is still effective for the treatment of typhoid fever at Dr. Soetomo. But from the results of sensitivity tests as in table 2 shows that the sensitivity of chloramphenicol against Salmonella typhi in Dr. Saiful Anwar Malang, there is quite low at 76.9% of 13 isolates were already resistant.Wandana, 2008 stating that the price is relatively inexpensive antibiotics such as Ampisillin, Amoxicillin, and chloramphenicol sensitivity values
​​are higher in Jakarta than in Malang. And conversely, the price is relatively expensive antibiotic sensitivity value in Malang better than in Jakarta, this shows the purchasing power of influence to the increasing resistance rates.Moreover, chloramphenicol is often prescribed by doctors so that was ranked the 6th most common used in Dr. Saiful Anwar Malang (Budi, 2000).From the molecular level studies suggested that bacteria can become resistant Salmonella typhi as a result of enzyme-producing plasmid Chloramphenicol acetyltransferase (CAT), which inactivates chloramphenicol (Balbi, 2004). 
Second choice drug most widely used at Dr Soetomo and in Dr. Saiful Anwar Malang is Ceftriaxone (Darmowandowo, 2006). Sensitivity pattern of Salmonella typhi in typhoid fever cases performed at the General Hospital, Dr. Cipto Mangunkusomo Jakarta during 2000-2004 showed the sensitivity of Salmonella typhi Ceftriaxone is as high as 91.9%, but in contrast with the results conducted at Dr. Soetomo and in Dr Saiful Anwar poor as in table 1 to table 2 shows the numbers of Salmonella typhi Seftriakon sensitivity is quite low, at Dr Soetomo sensitive isolates of Salmonella typhi which only 31.6% and 68.4% resistant , the same thing also occurs in isolates of Salmonella typhi in Dr. Saiful Anwar Malang, there were 23.1% sensitive and 53.8% of 13 isolates of Salmonella typhi conducted sensitivity tests already experiencing resistance.Ceftriaxone is a high level of resistance against Salmonella typhi probably because the old treatment for MRS that is too short ie 3-6 days (Hussein, 2007) while the duration of treatment according to WHO 2003 guidelines typhoid fever duration of treatment with Ceftriaxone is 10-14 days, duration of treatment too short to induce resistance. Ivanoff, 2002 also showed that since 1990 more and more of Salmonella typhi are resistant not only to the oral antibiotics used previously useful such as chloramphenicol, ampicillin and Kotrimoxazol but also against new antibiotil like Ceftriaxone. Seftriakon included in a class of third-generation cephalosporin that works by inhibiting peptidoglycan transpeptidase that inhibited cell wall synthesis. Mechanisms of resistance against Salmonella typhi Ceftriaxone is a way to produce β-lactamase enzymes that break down β-lactam of Ceftriaxone and eliminate power antimikrobanya (Petri, 2007). 
Factors affecting antibiotic sensitivity pattern of Salmonella typhi among others a history of previous typhoid fever, history of antibiotic usage is the use of antibiotics when sick, I know the rules of use of antibiotics obtained by prescription and without a prescription that is whether or not recommended by doctors, both in terms of dosage, method and duration of administration.The spread of bacterial resistance to antibiotics can last a result of the selection process as well as genetically. The spread of resistance is a result of the selection process is due to selective pressure (selective pressure) than the use of antibiotics. On the spread of resistance is genetically according to Baron, 2005 and Madigan, 2000 there are three mechanisms of genetic changes in prokaryotic transformation, transduction and conjugation.Salmonella typhi is a prokaryotic so that genetic change can occur through three mechanisms.Nurtjahyani prove that the Salmonella typhi resistant to chloramphenicol if taken plasmidnya, then inserted into the culture of Salmonella typhi were sensitive to chloramphenicol, the sensitive Salmonella typhi that is turned into a resistant to chloramphenicol due to receive a transfer plasmid DNA from chloramphenicol-resistant Salmonella typhi. Shanahan in Nurtjahyani, 2007 in molecular clinical isolates of Salmonella typhi were also found antibiotic resistant Salmonella typhi encoded by one of 4 types of plasmids. Plasmid as an intermediary gene resistant to chloramphenicol, trimethoprim and Ceftriaxone is a CAT type I, dihydrofolate reductase type VII, and TEM-I β lactamase. 
From there the data above, indicates that the sensitivity of Salmonella typhi bacteria to some antibiotics for the treatment of typhoid fever particularly chloramphenicol and Ceftriaxone constantly changing. For patients with typhoid fever at Dr. Soetomo chloramphenicol could be an option for the treatment of typhoid fever in the Ceftriaxone. As for patients with typhoid fever in RSSA Malang use of chloramphenicol and Ceftriaxone need consideration because of the high resistance rate against Salmonella typhi. 
The disadvantage is the number of samples that were cultured typhoid fever patients are too few of 19 samples (4.4%) of 427 patients with typhoid fever being treated at Dr. Soetomo and 13 samples (5.2%) of 250 patients with typhoid fever treated at Dr. Saiful Anwar Malang. Samples which caused a little too strict inclusion criteria: only patients who were given the first treatment with chloramphenicol or Ceftriaxone and have studied the sensitivity test, and not all the antibiotics that have been carried out sensitivity tests on typhoid fever patients used as samples. Difficulties experienced in addition to conclusions because the sample is less, of researchers studied 32 patients who could not know that typhoid fever patients studied had a history of previous typhoid fever or not, history of use of chloramphenicol and Ceftriaxone are not listed in medical records. In addition, based on examination of specimens, samples used for a variety of specimens, which shows the course of the disease spisemen typhoid fever that can affect the sensitivity of Salmonella typhi. 

CONCLUSION 
The conclusion is as follows: 
1. In the period 2008 to 2009, chloramphenicol is still sensitive to Salmonella typhi at Dr. Soetomo that is equal to 63.3% 
2. In the period 2008 to 2009, chloramphenicol resistant to Salmonella typhi in Dr. Saiful Anwar Malang that is equal to 76.9% 
3. In the period 2008 to 2009, resistance to Salmonella typhi Ceftriaxone at Dr. Soetomo and in Dr. Saiful Anwar Malang. 


REFERENCES 

Darmowandodo Widodo, Udjiani Pawitro Edi, Monique Noorvitry, 2005, Typhoid Fever, Child Pathology Diagnosis & Penatalaksaan. EGC.Jakarta, pp: 1-49. 

Ministry of Health of East Java, 2008, Health Report 2008. 
Surabaya. 

Dzen, Sjoekoer M, 2004, Medical Bacteriology, Bayumedia Publishing. Malang, pp: 187-274. 

Balbi HJ, 2004, Chloramphenicol American Academy of Pediatrics, Pediatrics in Review 25, pp :284-288. 

Baron, 2005, Medical Microbiology, Edition 4 The University of Texas Medical at Galveston. 

Husein, Besse'Nurlinda Mustary, 2007. Study Use of Antibiotics in Patients with Typhoid Fever Children - Inpatient In Rumkital Dr. Ramelan Surabaya, ADLN Digital Collections 

Musnelina lilies, 2004, Cost Effectiveness Analysis of Treatment of Typhoid Fever Children 
 Using chloramphenicol and Ceftriaxone in Jakarta Fatmawati Hospital Year 2001 - 2002, (online), 


Petri WA Jr, 2007, penicillin, cephalosporins and other lactam antibiotics.In: Goodman & Gillman's, Basic Pharmacology and Therapeutics, edition XI.pp: 1127-225. 

Ryan J.K. & Ray GC, 2004, Sherris Medical Microbiology An Introduction to Infections diseases, Issue 4. USA. Mc Graw Hill, pp.55-215. 

Rampengan TH, 2008, Tropical Infectious Diseases in Children, Second Edition. EGC, Jakarta.pp: 46-64 

Soewandojo Eddy, Suharto, Usman Hadi, Nasronudin, 2007, Typhoid Fever Early Detection and Management, Textbook of Medicine.Airlangga University Press, Singapore, pp :293-300. 

Djoko Widodo, 2007, Typhoid Fever, IMU Disease, Fourth Edition, F akultas Medicine, University of Indonesia. Jakarta.pp: 1752-175. 

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