22 a-sensitivity pattern of salmonella.p65

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SENSITIVITY PATTERN OF SALMONELLA
TYPHI IN PATIENTS WITH TYPHOID SMALL
BOWEL PERFORATIONS

ALTAF AHMED TALPUR
ABSTRACT
NAND LAL KELLA
ABDUL RASHID SURAHIO
Background: Enteric fever caused by Salmonella Typhi, gram negative bacilli, is counted
MUHAMMAD JAVED
as a major public health problem, especially in underdeveloped countries of tropic region.
PROFESSOR AKMAL JAMAL
One of the notorious and potentially lethal complications of typhoid fever is small bowelperforation. Chloramphenicol, in 1948 converted this lethal disease to curable one.
Efficacy of this drug reduced within 2 years. These strains of salmonella typhi were alsofound resistant to sulphonamide, tetracycline and streptomycin and are called as multidrug-resistant strains salmonella typhi (MDRST). Due to this resistance amoxycilin, andtrimethprim with sulphamethoxazole replaced these drugs. Emergence of MDRST led to Assistant Professor,
the use of quinolones as the first line drug. With the developing resistance to flouroquinolones, 3rd generation cephalosporins such as ceftriaxone and cefotaxime are now increasingly being used in the treatment of typhoid fever.
Materials and Methods: This prospective, descriptive study was conducted at surgical
Assistant Professor,
ward- III of Liaquat university hospital, Hyderabad from Jan 2007 to Dec 2010. All patients of either sex above the age of 02 years having high-grade fever for more than 1 week associated with features of peritonitis secondary to hollow viscus perforation and later on confirmed through various investigations as cases of perforation of hollow Assistant Professor,
viscus due to typhoid were included in the study.
Subject’s data was collected for age, sex, mode of presentation, treatment history, & blood culture and sensitivity pattern. Variable studied in this study were age, sex & Sensitivity pattern of Salmonella Typhi in Typhoid small bowel perforation Antibiotics Microbiology Technologist Raheela
assessed for sensitivity after culture of the organism were: ampicillin, amoxycilin, augmentin, ceftriaxone, cefotaxime, ceftazidime, cefixime, cefipime, cefuroxime, chloramphenicol, amikacin, gentamicin, Ciprofloxacin, ofloxacin, levofloxacin, moxifloxacin, imipenem, Professor and Chairman
meropenem, Piperacillin with Cefbactum and sulphonamide derivative.
Results: During the study period of 4 years; a total of 41/187(21.92%) blood culture
isolates were identified for salmonella typhi. Mean age of this group of patients was 27.35 years. Amongst them 113(60.42%) were male and 74(39.57%) were female. Theantibiotics sensitivity showed that all organisms were sensitive to imipenem and meropenemwhile sensitivity of the organism to Piperacillin with Sulbactum was 97.56%. 90.24%isolates were sensitive to cefotaxime and ceftazidime while 95.12% & 92.68% to Cefipime& Ceftriaxone respectively. Sensitivity pattern of salmonella typhi to ciprofloxacin,ofloxacin, levofloxacin and moxifloxacin was 80.48%, 73.17%, 82.92% and 85.36% CORRESPONDENCE
respectively. 41.46% Isolates were resistant to amoxycilin; and 63.41% to Chloramphenicol.
DR. ALTAF AHMED TALPUR
Conclusion: This study concludes that there is an increasing resistant trend of salmonella
typhi to 2nd line drugs like ciprofloxacin, and 3rd generation cephalosporins. At the same time there is re-emergence of chloramphenicol sensitivity.
Keywords: Typhoid fever, Perforation of small bowel, Blood culture & sensitivity
INTRODUCTION
Salmonella typhi are gram-negative bacilli, which are transmitted through faeco-oral Quarterly Medical Channel
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MC Vol. 19 - No.2 - 2012 ( 93 - 96 ) Talpur A. A. et al
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route, and is responsible for typhoid fever1. One of the notorious from these patients especially in data related to age, symptomatology and potentially lethal complications of typhoid fever is small especially symptoms of high grade fever with step-ladder pattern, bowel perforation2. Enteric fever is counted as a major public duration of symptoms of peritonitis, and duration, dose and type health problem, especially in underdeveloped countries of tropic of antibiotic used during this illness; and any prior investigation region3. In one study it has been reported that highest incidence performed to diagnose disease. Thorough examination was performed of typhoid fever is found in South East Asia, Africa, and in Latin with special focus on variables like fever, anemia, and abdominal America4.In India, Nigeria and in Indonesia mortality rate due to examination. Investigations were performed to establish diagnosis typhoid fever is noted at 12-32% in different studies5, 6. The and to assess general fitness. These include complete blood count, factors responsible for increase in the incidence of typhoid fever blood sugar, blood urea, serum electrolytes; blood culture and in these countries is due to poor sanitary conditions, supply of sensitivity, typhidot test, x-ray abdomen in erect position, ultrasound contaminated water, rapid population growth, and increased abdomen and where required ECG and chest x-ray. Preoperative urbanization and overburden health care system1, 4.
diagnosis was made. General management of the patients was In 1948 with the introduction of chloramphenicol this lethal started which includes I/V fluids, I/V antibiotics like injection disease was converted to curable disease7. Efficacy of this drug ceftriaxone 1 gram and metronidazole 500mg(after getting blood reduced within 2 years. However until in 1970 when resistance samples for blood culture), nasogastric suction, measurement of to it lead to major public health problem through out the world, urinary volume after passing two ways foley’s catheter. Preoperative especially in Latin America8 and in Asia9, 10.Although chloramphenicol resuscitation performed and patient’s condition was optimized.
is still the drug of choice in many countries in the management Patients were briefed about the diagnosis and procedure to be of typhoid fever but is used to limited extent due to its severe undertaken or performed. Patients were informed and permission toxicity11. These strains of salmonella typhi were also found was obtained. They were assured that their participation is voluntary resistant to sulphonamide, tetracycline and streptomycin7. Due to with no harms to them in terms of getting due treatment. They this resistance amoxycilin, and trimethprim with sulphamethoxazole were also given right to withdraw from study without putting any reasons. Postoperatively same antibiotics continued until blood It was until late 1990’s when resistance to these all-first line drugs erupted & in one series it was found to be near 68.9% in one area Subject’s data was collected on preformed proforma for age, sex, of India7, 12. These strains are called as multidrug-resistant strains mode of presentation, treatment history and blood culture & salmonella typhi (MDRST). In Karachi typhoid fever caused by sensitivity pattern. Variable studied in this study were age, sex, MDRST has been isolated in 1986. However its frequency has & Antibiotic sensitivity pattern of Salmonella Typhi in these increased to a very large extent for the last 7 years14.
Emergence of MDRST led to the use of quinolones as the first All the blood samples submitted for culture & sensitivity. Initial line drug in the treatment of adult patients with typhoid fever13.
identification of salmonella typhi was made with routine culture However sensitivity to ciprofloxacin of salmonella typhi has technique that was later confirmed by slide agglutination method.
decreased in endemic areas of Asia, especially in Indian subcontinent Antibiotic sensitivities were assessed by stokes or Kirby Bauer as shown by Threlfall and Ward in their study15. In 1997 such disc diffusion method. Antibiotics assessed for sensitivity after strains caused typhoid fever in 8000 people and killed 150 of culture of the organism were: ampicillin, amoxycilin, augmentin, ceftriaxone, cefotaxime, ceftazidime, cefixime, cefipime, cefuroxime, With the developing resistance to flouroquinolones, 3rd generation chloramphenicol, amikacin, gentamicin, Ciprofloxacin, ofloxacin, cephalosporins such as ceftriaxone and cefotaxime are now levofloxacin, moxifloxacin, imipenem, meropenem, Piperacillin with increasingly being used in the treatment of typhoid fever. In study Sulbactum and sulphonamide derivative. Results were compiled by Threlfall and Ward they have mentioned that all strains of and compared to national and international literature. Data was salmonella typhi were sensitive to these drugs15. However in another study by Saha SK et al17 there has been reports ofsporadic resistance to these drugs as well.
Because of this increasing resistance of salmonella typhi to 2nd During the study period of 4 years a total of 187 patients of small line drugs and at the same time presentation of many cases of bowel perforations, most probably due to typhoid, were admitted.
small bowel perforation secondary to typhoid fever compelled us Blood of all these patients was sent for culture & sensitivity. Out to conduct study to assess sensitivity pattern of this organism in of these 41 patients (21.92%) yielded positive blood culture for salmonella typhi. All these cultured organisms were submitted todifferent antibiotics for sensitivity.
MATERIALS AND METHODS
Mean age of this group of patients was 27.35 years. Amongst This was a prospective, descriptive study conducted at surgical them 113(60.42%) were male and 74(39.57%) were female making ward- III of Liaquat university hospital, Hyderabad, Pakistan the male to female ratio of 1.52: 1.00.
from Jan 2007 to Dec 2010. All patients of either sex above the The antibiotics sensitivity using disc diffusion method (Table.1) age of 02 years having high-grade fever for more than 1 week showed that all organisms were sensitive to imipenem and meropenem associated with features of peritonitis secondary to hollow viscus while sensitivity of the organism to Piperacillin with Sulbactum perforation and later on confirmed through various investigations was found in 40 (97.56%) patients. 39 (95.12%) organisms were as cases of perforation of hollow viscus due to typhoid were sensitive to Cefepime and 37 (90.24%) organisms to cefotaxime included in the study. All patients below the age of 02 years and and ceftazidime. Sensitivity of Ceftriaxone was present in 38 with non-typhoid hollow viscus perforation were excluded.
(92.68%) organisms. Cefixime and Cefuroxime showed sensitivity These patients were admitted in ward. Detailed history was taken in 31 (75.60%) and in 32 (78.04%) patients respectively.
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to these 2nd line drugs18. These patients have also been found incountries like USA and UK after their visits to south east asia17, NUMBER OF SALMONELLA TYPHI ISOLATES
FOUND SENSITIVE TO ANTIBIOTICS BY DISC
The sensitivity of salmonella typhi has continuously changed.
DIFFUSION METHOD (N=41)
Initially chloramphenicol was used to treat this infection. However Antibiotics screened
No & % of isolates
emergence of resistant strains to this and other first line drugs likesulphonamide derivatives, ampicillin, amoxicillin, and tetracycline decreased their usage to treat typhoid fever. The can be depicted from the study by Sadarsana et al at Calicut in which they havementioned that resistance of salmonella typhi to first line drugs was < 15% in 1982 and it increased to 68.9% in 1988-89. However recent studies have clearly mentioned the decreasing trend of resistance of this organism to Chloramphenicol and other first linedrugs. One such study varied out by Raveendran R et al20 mentioned 27% resistance in 2003 which reduced to 14.9% in 2008.
Same trend has also been reported by Ranju C et al and Gautum V et al in their studies. In this study 36.59% organisms wereresistant to Chloramphenicol and other first line drugs.
Since the emergence of multidrug-resistant salmonella typhi (MDRST) in early 90’s Quinolones are the drug of choice to treat these MDRST infections. In one study by Shaikh RB et al21 sensitivityof salmonella typhi to quinolones was reported as > 98%. Studies by Munir T et al22 and Nadeem et al23 reported 100% sensitivity of salmonella typhi to ciprofloxacin and ceftriaxone. In our study sensitivity of both drugs was 80.48% and 92.68% respectively.
However studies by Akhtar R et al 24 at Karachi, and Raveendran R et al at India mentioned increasing resistance of salmonella typhi to ciprofloxacin. In their studies they have mentioned 29/ 82 organisms and 24/431 isolates were resistant to ciprofloxacinrespectively.
Due to this increasing resistance of salmonella typhi to ciprofloxacin case of typhoid perforation has increased to the significant extent.
In their studies by Raveendran R et al, Gautum V et al, andAkhtar R et al 100% sensitivity of the organism to 3rd generationcephalosporins especially ceftriaxone has been mentioned. In study Amongst the Quinolones, Moxifloxacin has got the highest by Shaikh RB et al 90 –91% sensitivity of salmonella typhi to sensitivity i-e in 35 (85.36%) patients while sensitivity pattern ceftriaxone has been reported. Mushtaque MA in his study has of salmonella typhi to ciprofloxacin, ofloxacin & levofloxacin was reported 17.5% organisms resistant to Ceftriaxone.
33(80.48%), 30(73.17%) and 34(82.92%) respectively.
Sensitivity of salmonella typhi to meropenem & imipenem was From the penicillin derivatives 17(41.46%), 7 (17.07%) and 100% while of Piperacillin with Sulbactum; it was 97.56% in this 18(43.90%) isolates were sensitive to amoxicillin, ampicillin, and study. Study by Mushtaque MA has also reported 100% sensitivity of organism to these antibiotics. These drugs are now considered Among the aminoglycoside group gentamicin, and amikacin showed safe choice in patients with typhoid bowel perforation.
positive sensitivity ratio of salmonella typhi in 27(65.85%) and32(78.04%) patients respectively.
CONCLUSION
Twenty six (63.14%) & 06(14.63%) isolates were found sensitive This study concludes that there is an increasing resistant trend of to Chloramphenicol and sulphamethoxazole-Trimethoprim.
salmonella typhi to 2nd line drugs like ciprofloxacin, and 3rd generationcephalosporins. At the same time there is re-emergence of DISCUSSION
chloramphenicol sensitivity. Therefore sensitivity pattern of Salmonella typhi, the organism responsible for enteric fever is salmonella typhi must be sought if patient is not responding to counted as leading cause of morbidity and mortality through out conventional antibiotics so that life- threatening complicationsassociated with typhoid fever like typhoid perforation of small the world. It is one of the common causes of small bowel perforation bowel may be decreased. In surgical wards patient presenting in many developing countries especially in south East Asia. However with typhoid perforation may be started to meropenem or imipenem after the introduction of chloramphenicol in 1948 this lethal disease group until sensitivity pattern is defined through blood or tissue was counted as the completely curable disease. With the passage of time organism got resistance to this and other first line drugslike sulphonamide derivatives, ampicillin and tetracycline. These ACKNOWLEDGEMENT
organisms were called as MDRST organisms. These organisms We highly appreciate the support made by Raheela Research & were now treated with quinolones and 3rd generation cephalosporins.
reference lab, Hyderabad and High- Q pharmaceuticals in this There have been reports that organism is getting increasing resistance Quarterly Medical Channel
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FRP SERVICES & COMPANY Website: http://www.frpservices.com/ [email protected] Intermediates (Z)-2-(2-Aminothiazole-4-yl)-2-Methoxyimino Acetic Acid CAS# 65872-41-5 The side chain of Cefotaxime, Ceftriaxone, Cefepime, Ceftiofur, Cefteram Ethyl (Z)-2-(2-Aminothiazole-4-yl)-2-Methoxyimino Acetate CAS# 64485-88-7 The side chain of Ceftriaxone and Cefotaxim

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