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Frequency Of blaCTX-M, blaTEM and blaSHV Genes in

Citrobacters Isolated from Imam Reza Hospital in Kermanshah


1
Alisha Akya ,
2
Somayeh Jafari ,
3
Kamal Ahmadi ,
3
Azam Elahi
1
Associate Professor, Department of Medical Microbiology, Nosocomial Infection Research Center, Kermanshah University of
Medical Sciences, Kermanshah, Iran
2
MSc in Medical Microbiology, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
3
MSc in Medical Microbiology, Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

(Received June 16, 2015 ; Accepted July 12, 2015)

Abstract

Background and purpose: Citrobacter species can cause opportunistic hospital-acquired


infections and their treatment has become problematic following the acquisition of extended spectrum
beta- lactamases (ESBLs). The purpose of this study was to determine the frequency of ESBL genes in
clinical isolates in Kermanshah Imam Reza Hospital.
Materials and methods: In this study, 70 Citrobacter isolates were collected from various
clinical specimens and confirmed by standard bacteriological tests and API20E Kit. After antibiotic
susceptibility testing using disk diffusion method, the presence of ESBL phenotype was determined by
combined disk test. Specific primers were used to detect blaCTX-M, blaTEM and blaSHV genes among
isolates using PCR. Data was analyzed in SPSS V.18 applying Chi-Square test and Fisher's exact test.
Results: From 70 isolates of Citrobacter, 5 (7.1%) were phenotypically positive for ESBL. The
PCR test determined 19 isolates (31.6%) genetically positive for ESBL, and the frequency of blaCTX-M,
blaTEM and blaSHV genes were 21.3%, 11.4% and 1.4%, respectively. The highest antibiotic resistance
of isolates was to cefazolin (84.8%), ampicillin (71.2%) and co-trimoxazole (36.4%), and the lowest was
to gentamicin (9.1%), piperacillin/tazobactam (4.5%), and imipenem (1.5%).
Conclusion: The results showed that Citrobacter freundiii was the dominant species for
hospital-acquired infections in Kermanshah. A high percentage of isolates contained ESBL genes and
blaCTX-M was the most common. There was a high gap between the frequencies of genotypic and
phenotypic for ESBL, which may indicate ESB genes are not highly expressed in Citrobacter isolates.

Keywords: blaCTX-M, blaSHV, blaTEM, Citrobacter Spp

J Mazandaran Univ Med Sci 2015; 25(127): 65-73 (Persian).

65
‫ﭘﮋوﻫﺸﻲ‬

‫ﻣﺠـــﻠـــــﻪ داﻧـﺸــــﮕﺎه ﻋـــﻠــــﻮم ﭘــﺰﺷــﻜــــﻲ ﻣــﺎزﻧـــــﺪران‬


‫دوره ﺑﻴﺴﺖ و ﭘﻨﺠﻢ ﺷﻤﺎره ‪ 127‬ﻣﺮداد ﺳﺎل ‪(65-73) 1394‬‬

‫ﻓﺮاواﻧﻲ ژن ﻫﺎي ‪ blaTEM ،blaCTX-M‬و ‪ blaSHV‬در اﻳﺰوﻟﻪ ﻫﺎي‬


‫ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ ﺟﺪاﺷﺪه از ﺑﻴﻤﺎرﺳﺘﺎن اﻣﺎم رﺿﺎ )ع( در ﻛﺮﻣﺎﻧﺸﺎه‬
‫‪1‬‬
‫ﻋﻠﻴﺸﺎ اﻛﻴﺎ‬
‫‪2‬‬
‫ﺳﻤﻴﻪ ﺟﻌﻔﺮي‬
‫‪3‬‬
‫ﻛﻤﺎل اﺣﻤﺪي‬
‫‪3‬‬
‫اﻋﻈﻢ اﻟﻬﻲ‬

‫ﭼﻜﻴﺪه‬
‫ﺳﺎﺑﻘﻪ و ﻫـﺪف‪ :‬ﮔﻮﻧـﻪﻫـﺎي ﺳـﻴﺘﺮوﺑﺎﻛﺘﺮ ﻋﻔﻮﻧـﺖﻫـﺎي ﻓﺮﺻـﺖ ﻃﻠـﺐ ﺑﻴﻤﺎرﺳـﺘﺎﻧﻲ اﻳﺠـﺎد ﻣـﻲﻛﻨﻨـﺪ و ﺑـﻪ دﻧﺒـﺎل ﻛﺴـﺐ‬
‫ﺑﺘﺎﻻﻛﺘﺎﻣﺎزﻫﺎي داﻣﻨﻪ ﮔﺴﺘﺮده )‪ (ESBL‬درﻣﺎن آن ﻫﺎ ﻣﺸﻜﻞ ﺳﺎز ﺷﺪه اﺳﺖ‪ .‬ﻫﺪف از اﻳـﻦ ﻣﻄﺎﻟﻌـﻪ ﺑﺮرﺳـﻲ ﻓﺮاواﻧـﻲ ژن ﻫـﺎي‬
‫‪ ESBL‬در اﻳﺰوﻟﻪﻫﺎي ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ در ﺑﺰرگ ﺗﺮﻳﻦ ﺑﻴﻤﺎرﺳﺘﺎن ﺷﻬﺮ ﻛﺮﻣﺎﻧﺸﺎه )اﻣﺎم رﺿﺎ( در ﺳﺎل ‪ 1393-1392‬ﺑﻮد‪.‬‬
‫ﻣﻮاد و روشﻫﺎ‪ :‬ﻣﻄﺎﻟﻌﻪ ﺣﺎﺿﺮ از ﻧﻮع ﺗﻮﺻﻴﻔﻲ‪ -‬ﺗﺤﻠﻴﻠﻲ ﺑﻮد‪ .‬در اﻳﻦ ﻣﻄﺎﻟﻌﻪ ‪ 70‬ﺟﺪاﻳﻪ ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ از ﻧﻤﻮﻧﻪﻫﺎي ﺑﺎﻟﻴﻨﻲ‬
‫ﺟﻤﻊآوري ﺷﺪ و ﺑﻪ وﺳﻴﻠﻪ ﺗﺴﺖﻫﺎي اﺳﺘﺎﻧﺪارد ﺑﺎﻛﺘﺮيﺷﻨﺎﺳﻲ و ﻛﻴﺖ ‪ API 20E‬ﺗﺎﻳﻴﺪ ﺷﺪﻧﺪ‪ .‬ﭘﺲ از ﺳﻨﺠﺶ ﺣﺴﺎﺳﻴﺖ‬
‫آﻧﺘﻲﺑﻴﻮﺗﻴﻜﻲ ﺑﻪ روش اﻧﺘﺸﺎر دﻳﺴﻚ‪ ،‬وﺟﻮد آﻧﺰﻳﻢﻫﺎي ‪ ESBL‬از ﻧﻈﺮ ﻓﻨﻮﺗﻴﭙﻲ ﺑﻪ روش آزﻣﺎﻳﺶ دﻳﺴﻚ ﺗﺮﻛﻴﺒﻲ ﻣﺸﺨﺺ ﺷﺪ‪.‬‬
‫از ﭘﺮاﻳﻤﺮﻫﺎي اﺧﺘﺼﺎﺻﻲ ﺟﻬﺖ ﺗﻌﻴﻴﻦ ژنﻫﺎي ‪ blaTEM ،blaCTX-M‬و ‪ blaSHV‬در ﻣﻴﺎن ﺟﺪاﻳﻪﻫﺎ در آزﻣﺎﻳﺶ ‪ PCR‬اﺳﺘﻔﺎده‬
‫ﺷﺪ‪ .‬دادهﻫﺎ ﺗﻮﺳﻂ ﻧﺮماﻓﺰار ‪ SPSS‬ﻧﺴﺨﻪ ‪ 18‬و آزﻣﻮن ﻓﻴﺸﺮ و ﻛﺎي اﺳﻜﻮﻳﺮ )‪ (Chi-Square‬ﻣﻮرد ﺗﺠﺰﻳﻪ و ﺗﺤﻠﻴﻞ ﻗﺮار ﮔﺮﻓﺖ‪.‬‬
‫ﻳﺎﻓﺘﻪﻫﺎ‪ :‬از ‪ 70‬ﺟﺪاﻳﻪ ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ‪ 7/1) 5 ،‬درﺻﺪ( ﺟﺪاﻳﻪ از ﻧﻈﺮ ﻓﻨﻮﺗﻴﭙﻲ ﺑﺮاي ﺗﻮﻟﻴﺪ آﻧﺰﻳﻢﻫﺎي ﺑﺘﺎﻻﻛﺘﺎﻣﺎز داﻣﻨﻪ ﮔﺴـﺘﺮده‬
‫ﻣﺜﺒﺖ ﺷـﺪﻧﺪ‪ .‬آزﻣـﺎﻳﺶ ‪ PCR‬ﻧﺸـﺎن داد از ﻧﻈـﺮ ژﻧـﻮﺗﻴﭙﻲ ‪ 19‬اﻳﺰوﻟـﻪ )‪ 31/6‬درﺻـﺪ( ‪ ESBL‬ﻣﺜﺒـﺖ ﺷـﺪﻧﺪ و ﻓﺮاواﻧـﻲ ژنﻫـﺎي‬
‫‪ blaTEM ،blaCTX-M‬و ‪ blaSHV‬ﺑﻪ ﺗﺮﺗﻴﺐ ‪ 21/3‬درﺻﺪ‪ 11/4 ،‬درﺻﺪ و ‪ 1/4‬درﺻﺪ ﺑﻮد‪ .‬ﺑﻴﺶﺗﺮﻳﻦ ﻣﻘﺎوﻣﺖ آﻧﺘﻲﺑﻴﻮﺗﻴﻜﻲ ﺑﻪ‬
‫ﺳﻔﺎزوﻟﻴﻦ )‪ 84/8‬درﺻﺪ(‪ ،‬آﻣﭙﻲﺳـﻴﻠﻴﻦ )‪ 71/2‬درﺻـﺪ( و ﻛﻮﺗﺮﻳﻤﻮﻛﺴـﺎزول )‪ 36/4‬درﺻـﺪ( و ﻛـﻢﺗـﺮﻳﻦ ﻣﻘﺎوﻣـﺖ ﻧﺴـﺒﺖ ﺑـﻪ‬
‫ﺟﻨﺘﺎﻣﺎﻳﺴﻴﻦ )‪ 9/1‬درﺻﺪ(‪ ،‬ﭘﻴﭙﺮاﺳﻴﻠﻴﻦ‪/‬ﺗﺎزوﺑﺎﻛﺘﺎم )‪ 4/5‬درﺻﺪ( و اﻳﻤﻲﭘﻨﻢ )‪ 1/5‬درﺻﺪ( ﺑﻮد‪.‬‬
‫اﺳﺘﻨﺘﺎج‪ :‬ﻧﺘﺎﻳﺞ ﻧﺸﺎن داد ﻛﻪ ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ ﻓﺮوﻧﺪي ﮔﻮﻧﻪ ﻏﺎﻟﺐ در اﻳﺠﺎد ﻋﻔﻮﻧﺖﻫـﺎي ﺑﻴﻤﺎرﺳـﺘﺎﻧﻲ در ﻛﺮﻣﺎﻧﺸـﺎه ﻣـﻲﺑﺎﺷـﺪ‪.‬‬
‫ﻓﺮاواﻧﻲ ﻛﻠﻲ ﺟﺪاﻳﻪﻫﺎي ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ داراي ژنﻫﺎي ‪ ESBL‬ﺑﺎﻻ اﺳﺖ و در اﻳﻦ ﻣﻴﺎن ژن ‪ blaCTX-M‬داراي ﺑﻴﺶﺗـﺮﻳﻦ ﺷـﻴﻮع‬
‫ﻧﺴﺒﻲ ﻣﻲﺑﺎﺷﺪ‪ .‬ﺑﻴﻦ ﻓﺮاواﻧﻲ ﻓﻨﻮﺗﻴﭙﻲ و ژﻧﻮﺗﻴﭙﻲ ‪ ESBL‬در اﻳﺰوﻟﻪﻫﺎي ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ اﺧﺘﻼف زﻳﺎدي وﺟﻮد داﺷﺖ ﻛﻪ ﻣﻤﻜﻦ اﺳﺖ‬
‫ﻧﺸﺎﻧﮕﺮ ﻋﺪم ﺑﻴﺎن ﺑﺎﻻي ژنﻫﺎي ‪ ESBL‬در اﻳﺰوﻟﻪ ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ ﺑﺎﺷﺪ‪.‬‬

‫واژه ﻫﺎي ﻛﻠﻴﺪي‪ ،blaSHV ،blaTEM ،blaCTX-M :‬ﮔﻮﻧﻪ ﻫﺎي ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ‬

‫ﻣﻘﺪﻣﻪ‬
‫ﮔﻮﻧﻪ ﻫﺎي ﻣﻬﻢ اﻳﻦ ﺑـﺎﻛﺘﺮي ﺷـﺎﻣﻞ ﺳـﻴﺘﺮوﺑﺎﻛﺘﺮ ﻓﺮوﻧـﺪي‬ ‫ﺳــﻴﺘﺮوﺑﺎﻛﺘﺮ )‪ (Citrobacter‬ﺑﺎﺳــﻴﻞ ﮔــﺮم ﻣﻨﻔــﻲ و‬
‫)‪ ،(Citrobacter freundiii‬ﺳﻴﺘﺮوﺑﺎﻛﺘﺮﻛﻮﺳﺮي)‪،(C.koseri‬‬ ‫ﺑﻲﻫﻮازي اﺧﺘﻴﺎري از ﺧﺎﻧﻮاده اﻧﺘﺮوﺑﺎﻛﺘﺮﻳﺎﺳﻪ ﻫـﺎ اﺳـﺖ و‬

‫‪E-mail: bartar2004@yahoo.com‬‬ ‫ﻣﻮﻟﻒ ﻣﺴﺌﻮل‪ :‬ﺳﻤﻴﻪ ﺟﻌﻔﺮي‪ -‬ﻛﺮﻣﺎﻧﺸﺎه‪ :‬ﺑﺎغ اﺑﺮﻳﺸﻢ‪ ،‬ﺑﻠﻮار ﭘﺮﺳﺘﺎر‪ ،‬ﺑﻴﻤﺎرﺳﺘﺎن اﻣﺎم رﺿﺎ )ع(‪ ،‬آزﻣﺎﻳﺸﮕﺎه‬
‫‪ .1‬داﻧﺸﻴﺎر‪ ،‬ﮔﺮوه ﻣﻴﻜﺮوب ﺷﻨﺎﺳﻲ ﭘﺰﺷﻜﻲ‪ ،‬ﻣﺮﻛﺰ ﺗﺤﻘﻴﻘﺎت ﻋﻔﻮﻧﺖ ﻫﺎي ﺑﻴﻤﺎرﺳﺘﺎﻧﻲ‪ ،‬داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﻛﺮﻣﺎﻧﺸﺎه‪ ،‬ﻛﺮﻣﺎﻧﺸﺎه‪ ،‬اﻳﺮان‬
‫‪ .2‬ﻛﺎرﺷﻨﺎس ارﺷﺪ ﻣﻴﻜﺮوب ﺷﻨﺎﺳﻲ‪ ،‬ﺑﻴﻤﺎرﺳﺘﺎن اﻣﺎم رﺿﺎ‪ ،‬داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﻛﺮﻣﺎﻧﺸﺎه‪،‬ﻛﺮﻣﺎﻧﺸﺎه‪ ،‬اﻳﺮان‬
‫‪ .3‬ﻛﺎرﺷﻨﺎس ارﺷﺪ ﻣﻴﻜﺮوب ﺷﻨﺎﺳﻲ‪ ،‬ﻛﻤﻴﺘﻪ ﺗﺤﻘﻴﻘﺎت داﻧﺸﺠﻮﻳﻲ‪ ،‬داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﻛﺮﻣﺎﻧﺸﺎه‪ ،‬ﻛﺮﻣﺎﻧﺸﺎه‪ ،‬اﻳﺮان‬
‫ﺗﺎرﻳﺦ ﺗﺼﻮﻳﺐ ‪1394/4/21 :‬‬ ‫ﺗﺎرﻳﺦ ارﺟﺎع ﺟﻬﺖ اﺻﻼﺣﺎت ‪1394/3/18:‬‬ ‫‪ ‬ﺗﺎرﻳﺦ درﻳﺎﻓﺖ ‪1394/3/16:‬‬

‫دوره ﺑﻴﺴﺖ و ﭘﻨﺠﻢ‪ ،‬ﺷﻤﺎره ‪ ، 127‬ﻣﺮداد ‪1394‬‬ ‫ﻣﺠﻠﻪ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﻣﺎزﻧﺪران‬ ‫‪66‬‬
‫ﻋﻠﻴﺸﺎ اﻛﻴﺎ و ﻫﻤﻜﺎران‬ ‫ﭘﮋوﻫﺸﻲ‬

‫اﻳﻦ ﻣﻄﺎﻟﻌـﻪ ﺑﺮرﺳـﻲ ﻓﺮاواﻧـﻲ ‪ 3‬ﻧـﻮع ﺷـﺎﻳﻊ ‪ ESBL‬ﻳﻌﻨـﻲ‬ ‫ﺳــــــــﻴﺘﺮوﺑﺎﻛﺘﺮ اﻣــــــــﺎﻻﻧﺘﻴﮕﻮس )‪،(C.amalantigus‬‬
‫‪ blaTEM ،blaCTX-M‬و ‪ blaSHV‬و ﻣﻘﺎوﻣــــــــــــﺖ‬ ‫ﺳــﻴﺘﺮوﺑﺎﻛﺘﺮ ﺑﺮاﻛﻴـﻲ )‪ (C.braakii‬و ﺳــﻴﺘﺮوﺑﺎﻛﺘﺮ ﻳــﺎﻧﮕﺌﻲ‬
‫آﻧﺘـــﻲﺑﻴـــﻮﺗﻴﻜﻲ اﻳﺰوﻟـــﻪﻫـــﺎي ﺳـــﻴﺘﺮوﺑﺎﻛﺘﺮ ﺟﺪاﺷـــﺪه از‬ ‫)‪ (C.youngae‬ﻫﺴﺘﻨﺪ‪ .‬اﻳﻦ ﺑـﺎﻛﺘﺮيﻫـﺎ ﺑـﻴﺶﺗـﺮ در ﻣﻨـﺎﺑﻊ‬
‫ﻧﻤﻮﻧﻪﻫﺎي ﺑﺎﻟﻴﻨﻲ ﺑﻮد‪.‬‬ ‫آب‪ ،‬ﺧﺎك‪ ،‬ﻏﺬا و ﻣﺠﺎري ﮔﻮارﺷﻲ ﺣﻴﻮاﻧﺎت و اﻧﺴﺎنﻫـﺎ‬
‫وﺟﻮد دارﻧﺪ)‪ .(1‬ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ از ﺟﻤﻠﻪ ﭘﺎﺗﻮژنﻫﺎي ﻓﺮﺻـﺖ‬
‫ﻣﻮاد و روش ﻫﺎ‬ ‫ﻃﻠﺒﻲ اﺳﺖ ﻛﻪ ﻣﻲﺗﻮاﻧﺪ ﺑﺎﻋﺚ ﺑﻴﻤﺎريﻫﺎي ﻣﺨﺘﻠﻔﻲ از ﺟﻤﻠـﻪ‬
‫ﻣﻄﺎﻟﻌﻪ ﺣﺎﺿﺮ از ﻧﻮع ﺗﻮﺻﻴﻔﻲ ﺗﺤﻠﻴﻠـﻲ ﺑـﻮد‪ .‬در اﻳـﻦ‬ ‫اﺳﻬﺎل‪ ،‬ﺳﭙﺘﻲ ﺳﻤﻲ‪ ،‬ﻣﻨﻨﮋﻳﺖ و ﻋﻔﻮﻧﺖ ﻣﺠـﺎري ادراري و‬
‫ﺗﺤﻘﻴﻖ ﺗﻌﺪاد ‪ 70‬ﺟﺪاﻳﻪ ﺳـﻴﺘﺮوﺑﺎﻛﺘﺮ از ‪ 180‬ﻧﻤﻮﻧـﻪ ﺑـﺎﻟﻴﻨﻲ‬ ‫ﺗﻨﻔﺴﻲ ﺑﻪ ﺧﺼﻮص در ﮔﺮوهﻫﺎي ﭘﺮﺧﻄﺮ ﻣﺜـﻞ ﻧـﻮزادان و‬
‫ﻣﺨﺘﻠﻒ )ادرار‪ ،‬ﻣﺪﻓﻮع‪ ،‬ﺧﻠﻂ‪ ،‬زﺧﻢ و ﺧـﻮن( از ﺑﻴﻤـﺎران‬ ‫اﻓﺮاد داراي ﻧﻘﺺ ﺳﻴﺴﺘﻢ اﻳﻤﻨﻲ ﺷﻮد)‪ .(2‬ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ ﺑﻪ ﻋﻨﻮان‬
‫ﺑﺰرگﺗﺮﻳﻦ ﺑﻴﻤﺎرﺳﺘﺎن در ﺷﻬﺮ ﻛﺮﻣﺎﻧﺸـﺎه )اﻣـﺎم رﺿـﺎ( در‬ ‫ﻳﻚ ﭘﺎﺗﻮژن ﺑﻴﻤﺎرﺳﺘﺎﻧﻲ ﺑﺎ ﻣﻘﺎوﻣﺖ ﭼﻨﺪ داروﻳﻲ و ﺑـﺎ ﺷـﻴﻮع‬
‫ﺳﺎل ‪ 1392-1393‬ﺟﺪا ﺷﺪ و ﻣﻮرد ﺑﺮرﺳﻲ ﻗـﺮار ﮔﺮﻓـﺖ‪.‬‬ ‫در ﺣﺎل اﻓـﺰاﻳﺶ در ﺟﻬـﺎن ﺷـﻨﺎﺧﺘﻪ ﺷـﺪه اﺳـﺖ)‪ .(3‬اﻳـﻦ‬
‫ﻧﻤﻮﻧــﻪﻫــﺎي ﻣــﺬﻛﻮر ﭘــﺲ از ﺟﻤــﻊآوري اوﻟﻴــﻪ در ﻛﻨــﺎر‬ ‫ﺑﺎﻛﺘﺮي ﺑﻪ دﻟﻴﻞ ﺑﺎﻻ ﺑﻮدن ﻧﺮخ ﻣﺮگ و ﻣﻴﺮ ﻋﻔﻮﻧﺖﻫـﺎي آن‬
‫ﺑﺎﻛﺲ ﻳﺦ و رﻋﺎﻳﺖ ﺷﺮاﻳﻂ اﺳﺘﺮﻳﻞ ﺑﻪ آزﻣﺎﻳﺸـﮕﺎه اﻧﺘﻘـﺎل‬ ‫)‪ 30-60‬درﺻﺪ( و ﻫﻢﭼﻨﻴﻦ ﺗﻮاﻧﺎﻳﻲ اﻳﺠـﺎد ﻋﻔﻮﻧـﺖﻫـﺎي‬
‫داده ﺷﺪ‪ .‬ﭘﺲ از ﺟﺪاﺳﺎزي اوﻟﻴﻪ ﺑﺎ اﺳـﺘﻔﺎده از روشﻫـﺎي‬ ‫ﺗﻬﺪﻳﺪﻛﻨﻨﺪه ﺣﻴﺎت در اﻓـﺮاد ﺑﺴـﺘﺮي در ﺑﻴﻤﺎرﺳـﺘﺎن ﻫـﺎ و‬
‫ﻣﻴﻜﺮوبﺷﻨﺎﺳﻲ و ﺑﻴﻮﺷﻴﻤﻴﺎﻳﻲ‪ ،‬ﺑﺎﻛﺘﺮيﻫﺎ ﺟﺪا ﺷﺪﻧﺪ و ﺟﻬﺖ‬ ‫ﻣﻘﺎوﻣﺖ ﺑﺎﻻي داروﻳﻲ داراي اﻫﻤﻴﺖ اﺳﺖ)‪.(3-5‬‬
‫ﺗﺄﻳﻴﺪ ﻧﻬﺎﻳﻲﮔﻮﻧﻪﻫﺎ ازﻛﻴﺖ ‪) API-20E‬ﻓﺮاﻧﺴﻪ ‪(BioMérieux‬‬ ‫ﺑﺘﺎﻻﻛﺘﺎﻣﺎزﻫﺎي داﻣﻨﻪ ﮔﺴﺘﺮده )‪ (ESBL‬از ﺟﻤﻠﻪ ﻋﻮاﻣﻞ‬
‫اﺳﺘﻔﺎده ﺷﺪ‪ .‬ﺳﭙﺲ ﺑﻪﻣﻨﻈﻮر ﺷﻨﺎﺳﺎﻳﻲ ﻣﻘﺎوﻣﺖ آﻧﺘﻲﺑﻴـﻮﺗﻴﻜﻲ‬ ‫اﻧﺘﺸﺎر وﺳﻴﻊ ﻣﻘﺎوﻣﺖﻫﺎي آﻧﺘﻲﺑﻴﻮﺗﻴﻜﻲ در ﺑﺎﻛﺘﺮيﻫﺎ ﺑﻮده‬
‫ﺑﺎﻛﺘﺮيﻫﺎ از روش اﻧﺘﺸﺎر دﻳﺴﻚ ﺑﺎ ﺳﻮش ﻛﻨﺘﺮل اﺳـﺘﺎﻧﺪارد‬ ‫و اﻧﺘﻘﺎل آنﻫﺎ ﺑﻪ ﻃﻮر ﭘﻴﻮﺳﺘﻪ در ﻣﻴﺎن اﻧﺘﺮوﺑﺎﻛﺘﺮﻳﺎﺳﻪﻫـﺎ از‬
‫)‪ (E.coli ATCC 25922‬اﺳﺘﻔﺎده ﺷﺪ‪ .‬از اﻳﺰوﻟﻪﻫﺎي ﻣـﻮرد‬ ‫ﺟﻤﻠﻪ ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ ﺻﻮرت ﻣـﻲﮔﻴـﺮد)‪ .(6-8‬اﻳـﻦ آﻧـﺰﻳﻢﻫـﺎ‬
‫ﺑﺮرﺳﻲ ﺳﻮﺳﭙﺎﻧﺴﻴﻮﻧﻲ ﺑﺮاﺑﺮ ﻏﻠﻈﺖ ﻧﻴﻢ ﻣﻚ ﻓﺎرﻟﻨﺪ ﺗﻬﻴﻪ ﺷـﺪ‪.‬‬ ‫داراي ﭼﻬﺎر ﮔﺮوه از ‪ A‬ﺗﺎ ‪ D‬ﺑـﻮده و داراي ﺗﻨـﻮع ﺑـﺎﻻﻳﻲ‬
‫ﭘﺲ از ﻛﺸﺖ ﺑـﺮ روي ﻣﺤـﻴﻂ ﻣـﻮﻟﺮ ﻫﻴﻨﺘـﻮن آﮔـﺎر )ﻣـﺮك‬ ‫ﻫﺴﺘﻨﺪ‪ ،‬و در ﻃﻲ زﻣﺎن و ﻧﻴﺰ از ﻣﻜﺎﻧﻲ ﺑﻪ ﻣﻜـﺎن دﻳﮕـﺮ ﺗﻨـﻮع‬
‫آﻟﻤﺎن(‪ ،‬دﻳﺴﻚﻫﺎي آﻧﺘﻲﺑﻴﻮﺗﻴﻚ ﺑﺎ ﻓﺎﺻﻠﻪ ‪ 2/5‬ﺳﺎﻧﺘﻲﻣﺘـﺮي‬ ‫ﭘﻴﺪا ﻣﻲﻛﻨﻨﺪ)‪ .(7-10‬وﺟﻮد اﻳﻦ آﻧﺰﻳﻢﻫﺎ ﺑـﻪﻃـﻮر ﮔﺴـﺘﺮده‬
‫از ﻫﻢ روي ﭘﻠﻴﺖ ﻗﺮار داده ﺷﺪﻧﺪ و ﺳﭙﺲ ﺑـﻪ ﻣـﺪت ‪18-24‬‬ ‫در اﻧﺘﺮوﺑﺎﻛﺘﺮﻳﺎﺳــﻪﻫــﺎي ﺟــﺪا ﺷــﺪه از ﺑﻴﻤــﺎران ﺑﺴــﺘﺮي و‬
‫ﺳﺎﻋﺖ در دﻣﺎي ‪ 35-37‬درﺟﻪ ﺳﺎﻧﺘﻴﮕﺮاد اﻧﻜﻮﺑـﻪ ﮔﺮدﻳﺪﻧـﺪ‪.‬‬ ‫ﻫﻢﭼﻨﻴﻦ ﺑﺮرﺳـﻲ آﻟـﻮدﮔﻲ در ﺑﺨـﺶﻫـﺎي ﺑﻴﻤﺎرﺳـﺘﺎنﻫـﺎ‬
‫ﻧﺘﺎﻳﺞ ﺣﺎﺻﻞ ﺑﺎ ﻣﻌﻴﺎرﻫﺎي ‪ CLSI‬ﺳﺎل ‪ 2013‬ﻣﻘﺎﻳﺴﻪ ﺷﺪ)‪.(14‬‬ ‫ﮔــﺰارش ﺷــﺪه اﺳــﺖ)‪ .(11،10‬ﺑﻨــﺎﺑﺮاﻳﻦ اﻧﺠــﺎم آزﻣﺎﻳﺸــﺎت‬
‫ﺟﺪاﻳﻪﻫﺎﻳﻲ ﻛﻪ ﻗﻄﺮ ﻫﺎﻟﻪ ﻋﺪم رﺷﺪ آنﻫﺎ ﺣﺪاﻗﻞ ﺑﺮاي ﻳﻜـﻲ‬ ‫ﻓﻨﻮﺗﻴﭙﻲ ‪ ESBL‬و اﺳﺘﻔﺎده از روشﻫﺎي ﻣﻠﻜﻮﻟﻲ اﻃﻼﻋﺎت‬
‫از آﻧﺘﻲﺑﻴﻮﺗﻴﻚﻫﺎي ﺳﻔﺘﺎزﻳﺪﻳﻢ‪ ،‬ﺳﻔﻮﺗﺎﻛﺴﻴﻢ‪ ،‬ﺳﻔﺘﺮﻳﺎﻛﺴـﻮن‬ ‫ﺑﻬﺘﺮي از اﻧﺘﺸﺎر ﻣﻘﺎوﻣﺖ آﻧﺘﻲ ﺑﻴﻮﺗﻴﻜﻲ در اﻳﻦ ﺑﺎﻛﺘﺮيﻫـﺎ‬
‫و آزﺗﺮوﻧﺎم ﺑﻪﺗﺮﺗﻴﺐ ‪ 25 ،27 ،22‬و‪ 27‬ﻣﻴﻠﻲﻣﺘﺮ و ﻳﺎ ﻛﻢﺗـﺮ‬ ‫ﺑﻪ دﺳﺖ ﻣﻲدﻫﺪ)‪ .(13،12‬اﻧﺘﻈﺎر ﻣـﻲرود ﺷـﻴﻮع ‪ESBL‬ﻫـﺎ‬
‫ﺑﻮد‪ ،‬ﻃﺒﻖ ﭘﻴﺸـﻨﻬﺎد ‪ CLSI‬از ﻧﻈـﺮ داﺷـﺘﻦ ‪ ESBL‬ﺑﺮرﺳـﻲ‬ ‫در ﻣﻴــﺎن ﮔﻮﻧــﻪﻫــﺎي ﺳــﻴﺘﺮوﺑﺎﻛﺘﺮ ﺑــﻪ دﻟﻴــﻞ اﺳــﺘﻔﺎده از‬
‫ﺷﺪﻧﺪ)‪ .(14‬ﺳﭙﺲ ﺑﺮاي ﻏﺮﺑﺎﻟﮕﺮي ﻓﻨﻮﺗﻴﭙﻲ اﻳﺰوﻟﻪﻫـﺎ ﻣﻮﻟـﺪ‬ ‫آﻧﺘﻲﺑﻴﻮﺗﻴﻚﻫـﺎي ﻃﻴـﻒ ﮔﺴـﺘﺮده در ﻣﺮاﻛـﺰ درﻣـﺎﻧﻲ در‬
‫‪ ،ESBL‬از روش دﻳﺴﻚ ﺗﺮﻛﻴﺒﻲ اﺳﺘﻔﺎده ﺷﺪ‪ .‬در اﻳﻦ روش‬ ‫ﺣــﺎل اﻓــﺰاﻳﺶ ﺑﺎﺷــﺪ‪ .‬از ﻃﺮﻓــﻲ ﻣﻄﺎﻟﻌــﻪ روي ﮔﻮﻧــﻪﻫــﺎي‬
‫از دﻳﺴﻚﻫﺎي ‪ 30‬ﻣﻴﻜﺮوﮔﺮﻣﻲ ﺳﻔﻮﺗﺎﻛﺴﻴﻢ و ﺳﻔﺘﺎزﻳﺪﻳﻢ‬ ‫ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ در ﻣﻘﺎﻳﺴﻪ ﺑﺎ دﻳﮕﺮ ﺑـﺎﻛﺘﺮيﻫـﺎي ﺑﻴﻤـﺎريزاي‬
‫در ﻣﺠﺎورت دﻳﺴﻚ ﻣﺮﻛﺐ آنﻫﺎ‪ ،‬ﺣﺎوي ‪ 10‬ﻣﻴﻜﺮوﮔﺮم‬ ‫ﺧﺎﻧﻮاده اﻧﺘﺮوﺑﺎﻛﺘﺮﻳﺎﺳﻪ ﻛﻢﺗـﺮ ﺻـﻮرت ﮔﺮﻓﺘـﻪ اﺳـﺖ‪ .‬در‬
‫ﻛﻼوﻻﻧﻴﻚ اﺳﻴﺪ )اﻧﮕﻠﺴـﺘﺎن ‪ ،(MAST,‬در ﻣﺤـﻴﻂ ﻣـﻮﻟﺮ‬ ‫ﻧﺘﻴﺠﻪ اﻃﻼﻋﺎت ﻛﻤﻲ در اﻳـﻦ ﻣـﻮرد وﺟـﻮد دارد‪ .‬ﻫـﺪف‬

‫‪67‬‬ ‫دوره ﺑﻴﺴﺖ و ﭘﻨﺠﻢ‪ ،‬ﺷﻤﺎره ‪ ، 127‬ﻣﺮداد ‪1394‬‬ ‫ﻣﺠﻠﻪ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﻣﺎزﻧﺪران‬
‫ﻣﺸﺨﺼﺎت ﻧﻤﻮﻧﻪﻫﺎي ﻣﻮرد ﺑﺮرﺳﻲ در ﻳـﻚ ﻓﺎﻳـﻞ اﻛﺴـﻞ‬ ‫ﻫﻴﻨﺘﻮن آﮔﺎر اﺳﺘﻔﺎده ﺷﺪ و آزﻣـﺎﻳﺶ ﻣﺎﻧﻨـﺪ روش اﻧﺘﺸـﺎر‬
‫)‪ (Excel‬ﺟﻤﻊ آوري ﮔﺮدﻳﺪ و ﺑﺎ ﻧﺮم اﻓـﺰار ‪ SPSS‬ﻧﺴـﺨﻪي‬ ‫دﻳﺴﻚ اﻧﺠﺎم ﮔﺮﻓﺖ‪ .‬در ﺻﻮرﺗﻲﻛﻪ ﻗﻄﺮ ﻫﺎﻟﻪ ﻋﺪم رﺷـﺪ‬
‫‪ 18‬ارﺗﺒﺎط ﻣﺘﻐﻴﺮﻫﺎ ﺑﺎ اﺳﺘﻔﺎده از آزﻣﻮن ﻓﻴﺸﺮ و ﻛﺎي اﺳـﻜﻮﻳﺮ‬ ‫ﺑﺎﻛﺘﺮي اﻃﺮاف دﻳﺴﻚ ﺗﺮﻛﻴﺒﻲ ﺣـﺪاﻗﻞ ‪ 5‬ﻣﻴﻠـﻲﻣﺘـﺮ و ﻳـﺎ‬
‫)‪ (Chi-Square‬ﻣﻮرد ﺗﺠﺰﻳﻪ و ﺗﺤﻠﻴﻞ ﻗﺮار ﮔﺮﻓﺖ‪.‬‬ ‫ﺑﻴﺶﺗﺮ از ﻗﻄﺮ ﻫﺎﻟﻪ ﻋﺪم رﺷﺪ اﻃﺮاف دﻳﺴﻚ ﻣﻨﻔﺮد ﻫﻤﺎن‬
‫آﻧﺘﻲﺑﻴﻮﺗﻴﻚ ﺑﻮد‪ ،‬ﺑﻪ ﻋﻨـﻮان ﺳـﻮﻳﻪ ﻣﻮﻟـﺪ ﺑﺘﺎﻻﻛﺘﺎﻣﺎزﻫـﺎي‬

‫ﻳﺎﻓﺘﻪ ﻫﺎ‬ ‫داﻣﻨﻪ ﮔﺴﺘﺮده ﻗﻠﻤﺪاد ﮔﺮدﻳـﺪ)‪ .(14‬در ﻣﺮﺣﻠـﻪ ﺑﻌـﺪ ﺟﻬـﺖ‬
‫ﺑﺮرﺳﻲ ﻓﺮاواﻧﻲ ژنﻫﺎي ‪ blaTEM ،blaCTX-M‬و ‪blaSHV‬‬
‫از‪ 70‬ﻧﻤﻮﻧﻪ ﻣﻮرد ﺑﺮرﺳﻲ‪ 42 ،‬ﻧﻤﻮﻧﻪ از ﺑﻴﻤﺎران ﺧـﺎﻧﻢ‬
‫ﺑﻪ ﻛﻤﻚ ﭘﺮاﻳﻤﺮﻫـﺎي اﺧﺘﺼﺎﺻـﻲ ﻃﺒـﻖ ﺟـﺪول ﺷـﻤﺎره ‪،1‬‬
‫و ‪ 28‬ﻧﻤﻮﻧــﻪ ﻣﺮﺑــﻮط ﺑــﻪ آﻗﺎﻳــﺎن ﺑــﻮد‪ .‬ﻣﻴــﺎﻧﮕﻴﻦ ﺳــﻨﻲ ﻛــﻞ‬
‫واﻛﻨﺶ ‪ PCR‬اﻧﺠﺎم ﺷﺪ)‪ .(15-17‬اﺑﺘﺪا ﻛﻞ ﻣﺤﺘﻮاي ژﻧﻮﻣﻲ‬
‫ﺑﻴﻤــﺎران ‪ 39/8 ± 29/7‬ﺳــﺎل ﺑــﻮد‪ .‬ﺑــﻴﺶﺗــﺮﻳﻦ ﻓﺮاواﻧــﻲ‬
‫ﺑﺎﻛﺘﺮي ﺑﺎ روش ‪ Boiling‬اﺳـﺘﺨﺮاج ﺷـﺪ‪ .‬ﺑـﻪ اﻳـﻦ ﻣﻨﻈـﻮر‬
‫ﺟﺪاﻳﻪﻫـﺎ ﻣﺮﺑـﻮط ﺑـﻪ ﺳـﻴﺘﺮوﺑﺎﻛﺘﺮ ﻓﺮوﻧـﺪي ﺑـﺎ ‪ 60‬اﻳﺰوﻟـﻪ‬
‫ﭼﻨــﺪﻳﻦ ﻛﻠﻨــﻲ ﺧــﺎﻟﺺ ﺑــﺎﻛﺘﺮي در ‪ 0/5 ml‬آب ﻣﻘﻄــﺮ‬
‫)‪ 85/7‬درﺻﺪ( ﺑﻮد‪ .‬ﺑﻴﺶ ﺗﺮﻳﻦ ﻓﺮاواﻧﻲ ﻧﻤﻮﻧـﻪ ﻫـﺎ در اﻳـﻦ‬
‫اﺳﺘﺮﻳﻞ ﺣﻞ ﺷـﺪ و ﭘـﺲ از ‪ 5‬دﻗﻴﻘـﻪ ﺟﻮﺷـﺎﻧﺪن و ﺧﻨـﻚ‬
‫ﭘﮋوﻫﺶ ﻣﺮﺑﻮط ﺑﻪ ﻧﻤﻮﻧﻪ ادرار ﺑﺎ ‪ 55/7) 39‬درﺻﺪ( ﻧﻤﻮﻧﻪ‬
‫ﺷﺪن در ﻣﺮﺣﻠﻪ ﺑﻌﺪ‪ ،‬در دور ‪ 7000×g‬ﺑـﻪ ﻣـﺪت ‪ 1‬دﻗﻴﻘـﻪ‬
‫ﺑﻮد و ﺳﭙﺲ ﺑﻪ ﺗﺮﺗﻴﺐ ﻣﺪﻓﻮع ﺑﺎ ‪ 22/9) 16‬درﺻﺪ(‪ ،‬ﺧﻠـﻂ‬
‫ﺳﺎﻧﺘﺮﻳﻔﻴﻮژ ﺷﺪ‪ .‬ﻣﺤﻠﻮل روﻳﻲ ﺟﻬﺖ اﻧﺠﺎم واﻛـﻨﺶ ‪PCR‬‬
‫‪ 11/4) 8‬درﺻﺪ(‪ ،‬زﺧﻢ ‪ 7/1) 5‬درﺻﺪ( و ﺧﻮن ‪ 2/9) 2‬درﺻﺪ(‬
‫ﺑﻪ ﻟﻮﻟﻪﻫﺎي اﭘﻨﺪورف ﺟﺪﻳﺪ ﻣﻨﺘﻘﻞ ﺷﺪ و ﺑﻪ ﻋﻨـﻮان ‪DNA‬‬
‫ﻧﻤﻮﻧﻪ ﻗﺮار داﺷﺘﻨﺪ‪ .‬ﻣﻘﺎوﻣـﺖ آﻧﺘـﻲ ﺑﻴـﻮﺗﻴﻜﻲ ﺟﺪاﻳـﻪﻫـﺎي‬
‫ﺑﺎﻛﺘﺮي ﺑﻪ ﻛﺎر رﻓﺖ‪ .‬ﺑﺮاي واﻛﻨﺶ ‪ PCR‬ﺑﺎ ﺣﺠـﻢ ﻧﻬـﺎﻳﻲ‬
‫ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ ﻧﺴﺒﺖ ﺑﻪ ‪ 15‬آﻧﺘﻲ ﺑﻴﻮﺗﻴﻚ در ﺟﺪول ﺷﻤﺎره ‪ 2‬و‬
‫‪ 25‬ﻣﻴﻜﺮوﻟﻴﺘﺮ‪ ،‬از ‪ 12/5‬ﻣﻴﻜﺮوﻟﻴﺘﺮ ‪) Master Mix‬ﺳـﻴﻨﺎﻛﻠﻮن‬
‫ﻧﺘﺎﻳﺞ ‪ PCR‬ژنﻫﺎي ‪ blaTEM ،blaCTX-M‬و ‪blaSHV‬‬
‫اﻳﺮان(‪ 2 ،‬ﻣﻴﻜﺮوﻟﻴﺘﺮ ‪ DNA‬ﺑـﺎﻛﺘﺮي‪ 1 ،‬ﻣﻴﻜﺮوﻟﻴﺘـﺮ از ﻫـﺮ‬
‫در ﺟﺪول ﺷﻤﺎره ‪ 3‬و ﺗﺼﻮﻳﺮ ﺷﻤﺎره ‪ 1‬آﻣﺪه اﺳﺖ‪ .‬در ﻛـﻞ‬
‫ﭘﺮاﻳﻤﺮ و آب ﻣﻘﻄـﺮ دو ﺑـﺎر ﺗﻘﻄﻴـﺮ اﺳـﺘﺮﻳﻞ ﺗـﺎ ﺣﺠـﻢ ‪25‬‬
‫از ﻧﻈﺮ ژﻧﻮﺗﻴﭙﻲ ‪ 19‬اﻳﺰوﻟﻪ )‪ 31/6‬درﺻﺪ( ﻣﻮﻟﺪ ‪ ESBL‬ﺑﻮدﻧﺪ‪.‬‬
‫ﻣﻴﻜﺮوﻟﻴﺘﺮ اﺳﺘﻔﺎده ﺷﺪ‪ .‬ﻣﺮاﺣﻞ دﻣﺎﻳﻲ ‪ PCR‬ﺷﺎﻣﻞ ‪ 5‬دﻗﻴﻘﻪ‬
‫راﺑﻄﻪ ﻣﻌﻨﻲداري ﺑﻴﻦ ژنﻫﺎي ‪ ESBL‬ﺑﺎ ﺟﻨﺴـﻴﺖ )‪(p=0/61‬‬
‫دﻧﺎﭼﻮرﻳﺸﻦ اوﻟﻴـﻪ در ‪ 94‬درﺟـﻪ ﺳـﺎﻧﺘﻲﮔـﺮاد‪ ،‬ﺳـﭙﺲ ‪35‬‬
‫و ﺳﻦ ﺑﻴﻤﺎران )‪ (p=0/59‬وﺟﻮد ﻧﺪاﺷﺖ‪ .‬ﻫﻢﭼﻨﻴﻦ ﺑﻴﻦ ﺷﻴﻮع‬
‫ﺳﻴﻜﻞ ﻃﺒﻖ ﺟﺪول ﺷﻤﺎره ‪ 1‬و در آﺧﺮ ‪ 5‬دﻗﻴﻘﻪ اﮔﺴﺘﻨﺸـﻦ‬
‫ژنﻫﺎي ‪ ESBL‬و ﺑﺨـﺶﻫـﺎي ﺑﻴﻤﺎرﺳـﺘﺎﻧﻲ و ﻧﻴـﺰ ﺑﺴـﺘﺮي و‬
‫در ‪ 72‬درﺟﻪ ﺳﺎﻧﺘﻲ ﮔﺮاد ﺑﻮد‪ .‬ﻣﺤﺼﻮﻻت ‪ PCR‬ﺑﺎ اﺳـﺘﻔﺎده‬
‫ﺳﺮﭘﺎﻳﻲ ﺑﻮدن ﺑﻴﻤﺎران راﺑﻄﻪ ﻣﻌﻨﻲداري ﻧﺒﻮد )‪ .(p=0/8‬اﻣﺎ‬
‫از اﻟﻜﺘﺮوﻓﻮرز ﺑﺎ ژل آﮔﺎرز ﻳﻚ درﺻـﺪ و رﻧـﮓآﻣﻴـﺰي‬
‫ﺑﻴﻦ ژن ‪ CTX-M‬ﺑﺎ ﻣﻘﺎوﻣﺖ ﺑﻪ ﺳﻔﺘﺎزﻳﺪﻳﻢ )‪ (p=0/019‬و‬
‫ﺑﺎ اﺗﻴﺪﻳﻮم ﺑﺮوﻣﺎﻳﺪ ﺑﺎ دﺳﺘﮕﺎه ژل داك ﺑﺮرﺳﻲ ﺷﺪ‪.‬‬
‫ژن ‪ TEM‬ﺑــﺎ ﻣﻘﺎوﻣــﺖ ﺑــﻪ اﻳﻤــﻲﭘــﻨﻢ)‪ (p=0/014‬راﺑﻄــﻪ‬
‫ﻣﻌﻨﻲداري ﺑﺎ آزﻣﻮن ‪ Chi-Square‬ﺑﻪ دﺳﺖ آﻣﺪ )ﺟـﺪول‬ ‫آﻧﺎﻟﻴﺰ آﻣﺎري‬
‫ﺷﻤﺎره ‪.(4‬‬ ‫ﻧﺘﺎﻳﺞ آزﻣﺎﻳﺶﻫـﺎي ﻣﺨﺘﻠـﻒ اﻧﺠـﺎم ﺷـﺪه ﺑـﻪ ﻫﻤـﺮاه‬

‫ﺟﺪول ﺷﻤﺎره ‪ :1‬ﭘﺮاﻳﻤﺮﻫﺎ و ﺳﻴﻜﻞ ﻫﺎي دﻣﺎﻳﻲ ﻣﻮرد اﺳﺘﻔﺎده در ‪PCR‬‬


‫‪35 Cycles‬‬
‫)‪Product size (bp‬‬ ‫‪Extension 72˚C‬‬ ‫‪Annealing 30 Sec‬‬ ‫‪Denaturation94˚C‬‬ ‫)́‪Sequence (5́-3‬‬ ‫‪Primer‬‬

‫‪F:TTTGCGATGTGCAGTACCAGTAA‬‬
‫‪544‬‬ ‫‪40 Sec‬‬ ‫‪51˚C‬‬ ‫‪30Sec‬‬ ‫‪R:CGATATCGTTGGTGGTGCCATA‬‬ ‫‪blaCTX-M‬‬

‫‪F:AGTGCTGCCATAACCATGAGTG‬‬
‫‪431‬‬ ‫‪30 Sec‬‬ ‫‪61˚C‬‬ ‫‪30Sec‬‬ ‫‪R:CTGACTCCCCGTCGTGTAGATA‬‬ ‫‪blaTEM‬‬

‫‪928‬‬ ‫‪60 Sec‬‬ ‫‪64˚C‬‬ ‫‪30 Sec‬‬ ‫‪F:ATTTGTCGCTTCTTTACTCGC‬‬


‫‪blaSHV‬‬
‫‪R:TTTATGGCGTTACCTTTGACC‬‬

‫دوره ﺑﻴﺴﺖ و ﭘﻨﺠﻢ‪ ،‬ﺷﻤﺎره ‪ ، 127‬ﻣﺮداد ‪1394‬‬ ‫ﻣﺠﻠﻪ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﻣﺎزﻧﺪران‬ ‫‪68‬‬
‫ﻋﻠﻴﺸﺎ اﻛﻴﺎ و ﻫﻤﻜﺎران‬ ‫ﭘﮋوﻫﺸﻲ‬

‫ﺟﺪول ﺷﻤﺎره ‪ :3‬ﻓﺮاواﻧﻲ ﮔﻮﻧﻪ ﻫﺎي ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ و ﻓﺮاواﻧﻲ ژن ﻫﺎي‬ ‫ﺟﺪول ﺷﻤﺎره ‪ :2‬ﻓﺮاواﻧﻲ ﻣﻘﺎوﻣﺖ آﻧﺘﻲ ﺑﻴﻮﺗﻴﻜﻲ ﺟﺪاﻳﻪ ﻫﺎي ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ‬
‫‪ ESBL‬در آن ﻫﺎ‬ ‫ﺑﻪ آﻧﺘﻲ ﺑﻴﻮﺗﻴﻚ ﻫﺎ‬
‫ﻓﺮاواﻧﻲ ژن ﻫﺎي ‪ESBL‬‬ ‫ﺟﻤﻊ ﻣﻘﺎوﻣﺖ‬ ‫‪ 6‬ﺳﻴﺘﺮوﺑﺎﻛﺘﺮﻛﻮﺳﺮي‬ ‫‪ 60‬ﺳﻴﺘﺮوﺑﺎﻛﺘﺮﻓﺮوﻧﺪي‬
‫ﻓﻨﻮﺗﻴﭙﻲ ‪ESBL‬‬ ‫ﮔﻮﻧﻪ ﻫﺎ‬ ‫ﮔﻮﻧﻪ ﻫﺎي‬ ‫آﻧﺘﻲ ﺑﻴﻮﺗﻴﻚ ﻫﺎ‬
‫‪blaCTX-M‬‬ ‫‪blaTEM‬‬ ‫‪blaSHV‬‬
‫ﺗﻌﺪاد)درﺻﺪ(‬ ‫ﺗﻌﺪاد)درﺻﺪ(‬ ‫ﺗﻌﺪاد )درﺻﺪ(‬
‫ﺗﻌﺪاد )درﺻﺪ(‬ ‫ﺗﻌﺪاد )درﺻﺪ(‬ ‫ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ‬ ‫)‪56(84/8‬‬ ‫)‪4(66/7‬‬ ‫)‪52(86/7‬‬ ‫ﺳﻔﺎزوﻟﻴﻦ‬
‫ﺗﻌﺪاد )درﺻﺪ( ﺗﻌﺪاد )درﺻﺪ ﺗﻌﺪاد )درﺻﺪ‬
‫‪(%1/6) 1‬‬ ‫‪(%13/3) 8‬‬ ‫‪(%21/7) 13‬‬ ‫‪(%8/3) 5‬‬ ‫‪(%85/7) 60‬‬ ‫ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ ﻓﺮوﻧﺪي‬ ‫)‪18(27/3‬‬ ‫)‪2(33/3‬‬ ‫)‪16(26/7‬‬ ‫ﺳﻔﭙﻮدوﻛﺴﻴﻢ‬
‫‪0‬‬ ‫‪0‬‬ ‫‪(%33/3) 2‬‬ ‫‪0‬‬ ‫‪(%8/6) 6‬‬ ‫ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ ﻛﻮﺳﺮي‬ ‫)‪16(24/2‬‬ ‫)‪3(50‬‬ ‫)‪13(21/7‬‬ ‫ﺳﻔﻮﺗﺎﻛﺴﻴﻢ‬
‫‪0‬‬ ‫‪0‬‬ ‫‪0‬‬ ‫‪0‬‬ ‫‪(%5/7)4‬‬ ‫ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ ﺑﺮاﻛﺌﻲ‬ ‫)‪15(22/7‬‬ ‫)‪3(50‬‬ ‫)‪12(20‬‬ ‫ﺳﻔﺘﺎزﻳﺪﻳﻢ‬
‫‪(%1/4) 1‬‬ ‫‪(%11/4) 8‬‬ ‫‪(%21/4) 15‬‬ ‫‪(%7/1) 5‬‬ ‫‪(%100) 70‬‬ ‫ﺟﻤﻊ ﻛﻞ‬ ‫)‪13(19/6‬‬ ‫)‪3(50‬‬ ‫)‪10(16/7‬‬ ‫ﺳﻔﺘﺮﻳﺎﻛﺴﻮن‬
‫)‪47(71/2‬‬ ‫)‪4(66/7‬‬ ‫)‪43(71/7‬‬ ‫آﻣﭙﻲ ﺳﻴﻠﻴﻦ‬
‫)‪3(4/5‬‬ ‫)‪1(16/7‬‬ ‫)‪2(3/3‬‬ ‫ﭘﻴﭙﺮاﺳﻴﻠﻴﻦ‪/‬ﺗﺎزوﺑﺎﻛﺘﺎم‬
‫ﺟﺪول ﺷﻤﺎره ‪ : 4‬ﻣﻘﺎﻳﺴﻪ ﺣﺴﺎﺳﻴﺖ اﻳﺰوﻟﻪ ﻫﺎ ﺑﻪ ﺳﻔﺘﺎزﻳﺪﻳﻢ و اﻳﻤﻲ‬
‫)‪1(1/5‬‬ ‫)‪1(16/7‬‬ ‫)‪0(0‬‬ ‫اﻳﻤﻲ ﭘﻨﻢ‬
‫ﭘﻨﻢ ﺑﺎ ﺗﻮﺟﻪ ﺑﻪ داﺷﺘﻦ ژن ﻫﺎي ‪ CTXM‬و ‪TEM‬‬ ‫)‪1( 1/5‬‬ ‫)‪1(16/7‬‬ ‫)‪0( 0‬‬ ‫ارﺗﺎﭘﻨﻢ‬

‫ﺳﻄﺢ‬ ‫‪CTXM gene‬‬ ‫‪TEM gene‬‬ ‫ﺣﺴﺎﺳﻴﺖ‬ ‫ﻧﻮع‬ ‫)‪1(1/5‬‬ ‫)‪1(16/7‬‬ ‫)‪0(0‬‬ ‫ﻣﺮوﭘﻨﻢ‬

‫ﻣﻌﻨﻲ داري‬ ‫ﻣﺜﺒﺖ‬ ‫ﻣﻨﻔﻲ‬ ‫ﻣﺜﺒﺖ‬ ‫ﻣﻨﻔﻲ‬ ‫آﻧﺘﻲ ﺑﻴﻮﺗﻴﻜﻲ‬ ‫آﻧﺘﻲ ﺑﻴﻮﺗﻴﻚ‬ ‫)‪14( 21/2‬‬ ‫)‪2(33/3‬‬ ‫)‪12( 20‬‬ ‫آزﺗﺮوﻧﺎم‬

‫‪3‬‬ ‫‪5‬‬ ‫ﻣﻘﺎوم‬ ‫)‪13(19/7‬‬ ‫)‪1(16/7‬‬ ‫)‪12(20‬‬ ‫ﺗﻮﺑﺮاﻣﺎﻳﺴﻴﻦ‬


‫‪0/014‬‬ ‫اﻳﻤﻴﭙﻨﻢ‬ ‫)‪6(9/1‬‬ ‫)‪2(33/3‬‬ ‫)‪4(6/7‬‬ ‫ﺟﻨﺘﺎﻣﺎﻳﺴﻴﻦ‬
‫‪5‬‬ ‫‪57‬‬ ‫ﺣﺴﺎس‬
‫)‪24(36/4‬‬ ‫)‪3(50‬‬ ‫)‪21(35‬‬ ‫ﻛﻮﺗﺮﻳﻤﻮﻛﺴﺎزول‬
‫‪8‬‬ ‫‪12‬‬ ‫ﻣﻘﺎوم‬
‫‪0/019‬‬ ‫ﺳﻔﺘﺎزﻳﺪﻳﻢ‬ ‫)‪14(21/2‬‬ ‫)‪4(66/7‬‬ ‫)‪10(16/7‬‬ ‫ﺳﻴﭙﺮوﻓﻠﻮﻛﺴﺎﺳﻴﻦ‬
‫‪7‬‬ ‫‪42‬‬ ‫ﺣﺴﺎس‬

‫ﺑﺤﺚ‬
‫ﮔﻮﻧﻪﻫﺎي ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ ﺗﻤﺎﻳﻞ ﺑـﻪ اﻳﺠـﺎد ﻋﻔﻮﻧـﺖﻫـﺎي‬
‫ﻓﺮﺻﺖ ﻃﻠﺐ ﺑﻴﻤﺎرﺳﺘﺎﻧﻲ ﺑﺎ ﻣﻘﺎوﻣﺖ ﺑﺎﻻي آﻧﺘـﻲﺑﻴـﻮﺗﻴﻜﻲ‬
‫دارﻧﺪ‪ .‬ژنﻫﺎي ﻣﺨﺘﻠﻒ ‪ ESBL‬در ﺳﺎلﻫﺎي اﺧﻴﺮ در ﻧﻘﺎط‬
‫ﻣﺨﺘﻠﻒ ﺟﻬﺎن در ﻣﻴﺎن اﻧﺘﺮوﺑﺎﻛﺘﺮﻳﺎﺳﻪﻫﺎ از ﺟﻤﻠﻪ ﮔﻮﻧﻪﻫـﺎي‬
‫ﺳــﻴﺘﺮوﺑﺎﻛﺘﺮ ﮔﺴــﺘﺮش ﻳﺎﻓﺘــﻪاﻧـﺪ)‪ .(17-19‬در اﻳــﻦ ﻣﻄﺎﻟﻌــﻪ‬
‫ﺑﻴﺶﺗﺮﻳﻦ ﻣﻮارد ﻋﻔﻮﻧﺖ ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ در ﺑﻴﻤﺎران زن ﻣﻴﺎﻧﺴﺎل‬
‫و ﺑﻴﺶﺗﺮﻳﻦ ﻧﻤﻮﻧﻪﻫﺎ ﻣﺮﺑـﻮط ﺑـﻪ ادرار و ﺳـﭙﺲ ﺗﺮﺷـﺤﺎت‬
‫ﻣﺠﺎري ﺗﻨﻔﺴـﻲ ﺑـﻮد‪ .‬ﺑـﺎ ﺗﻮﺟـﻪ ﺑـﻪ ﺷـﻴﻮع ﺑـﺎﻻﺗﺮ ﻋﻔﻮﻧـﺖ‬
‫ادراري در ﺧﺎﻧﻢﻫﺎ‪ ،‬ﺷﻴﻮع ﺑﻴﺶﺗﺮ ﻋﻔﻮﻧﺖ ﺳـﻴﺘﺮوﺑﺎﻛﺘﺮ در‬
‫آنﻫﺎ ﻗﺎﺑﻞ ﺗﻮﺟﻴﻪ اﺳﺖ‪ .‬ﺑﻴﺶﺗﺮﻳﻦ اﻳﺰوﻟﻪﻫﺎي ﺟﺪا ﺷﺪه از‬
‫ﻧﻤﻮﻧﻪﻫﺎي ﺑﺎﻟﻴﻨﻲ در ﺑﻴﻦ ﮔﻮﻧﻪﻫـﺎي ﺳـﻴﺘﺮوﺑﺎﻛﺘﺮ ﻣﺘﻌﻠـﻖ ﺑـﻪ‬
‫ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ ﻓﺮوﻧﺪي ﺑﻮد ﻛﻪ اﻳﻦ ﻣﻴـﺰان ﻓﺮاواﻧـﻲ ﺑـﺎ ﻧﺘـﺎﻳﺞ‬
‫ﻣﻄﺎﻟﻌﺎت دﻳﮕﺮ ﻫﻤﺨﻮاﻧﻲ دارد و ﺑـﻪ ﻧﻈـﺮ ﻣـﻲرﺳـﺪ ﮔﻮﻧـﻪ‬
‫ﻏﺎﻟــﺐ در اﻳﺠــﺎد ﻋﻔﻮﻧــﺖﻫـﺎي ﺑﻴﻤﺎرﺳــﺘﺎﻧﻲ در ﻛﺮﻣﺎﻧﺸــﺎه‬
‫ﺑﺎﺷﺪ)‪ .(21،20‬در ﻣﻄﺎﻟﻌﻪ ﻣﺎ ﻣﻘﺎوﻣﺖ آﻧﺘﻲﺑﻴﻮﺗﻴﻜﻲ اﻳﺰوﻟﻪﻫﺎ‬
‫ﺑــﻪ آﻧﺘــﻲﺑﻴﻮﺗﻴــﻚﻫــﺎي ﻧﺴــﻞ ﺳــﻮم ﺳﻔﺎﻟﻮﺳــﭙﻮرﻳﻦﻫــﺎ و‬ ‫ﺗﺼﻮﻳﺮ ﺷﻤﺎره ‪ :1‬ﻧﺘﺎﻳﺞ ‪ PCR‬ژن ﻫﺎي ‪ blaTEM ،blaCTX-M‬و‬
‫ﻓﻠﻮروﻛﻴﻨﻮﻟﻮنﻫﺎ از ﻣﻄﺎﻟﻌﺎت دﻳﮕﺮ ﭘﺎﻳﻴﻦ ﺗﺮ ﺑـﻮد‪ .‬ﻣـﺜﻼً در‬ ‫‪ -1:( blaCTX-M): blaSHV‬ﻣﺎرﻛﺮ )‪ -2 ،(100 bp‬ﻛﻨﺘﺮل ﻣﺜﺒﺖ‬
‫)‪ -3 ،(544bp‬ﻛﻨﺘﺮل ﻣﻨﻔﻲ‪ -4 ،‬ﻧﻤﻮﻧﻪ ﻣﺜﺒﺖ )‪:(blaTEM) :،(544bp‬‬
‫ﻣﻄﺎﻟﻌﺎﺗﻲ ﻛﻪ در ﻫﻨﺪوﺳﺘﺎن و ژاﭘﻦ اﻧﺠﺎم ﺷﺪ‪ ،‬ﺑـﻴﺶﺗـﺮﻳﻦ‬
‫‪ -1‬ﻣﺎرﻛﺮ )‪ -2 ،(100 bp‬ﻛﻨﺘﺮل ﻣﺜﺒﺖ )‪ -3 ،(431bp‬ﻧﻤﻮﻧﻪ ﻣﺜﺒﺖ‬
‫ﻣﻘﺎوﻣﺖ ﺑﻪ ﺳﻔﻮﺗﺎﻛﺴﻴﻢ )‪ 89‬درﺻـﺪ(‪ ،‬ﺳـﻔﺘﺎزﻳﺪﻳﻢ )‪81/5‬‬ ‫)‪ -1 :(blaSHV) :،(431bp‬ﻣﺎرﻛﺮ )‪ -2 ،(100 bp‬ﻛﻨﺘﺮل ﻣﺜﺒﺖ‬
‫درﺻﺪ(‪ ،‬ﺳﻴﭙﺮوﻓﻠﻮﻛﺴﺎﺳـﻴﻦ )‪ 75/3‬درﺻـﺪ( و آزﺗﺮﺋﻮﻧـﺎم‬ ‫)‪ -3 ،(928bp‬ﻛﻨﺘﺮل ﻣﻨﻔﻲ‪ -4 ،‬ﻧﻤﻮﻧﻪ ﻣﺜﺒﺖ )‪.(928bp‬‬

‫‪69‬‬ ‫دوره ﺑﻴﺴﺖ و ﭘﻨﺠﻢ‪ ،‬ﺷﻤﺎره ‪ ، 127‬ﻣﺮداد ‪1394‬‬ ‫ﻣﺠﻠﻪ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﻣﺎزﻧﺪران‬
‫ﺑﺮرﺳﻲ دﻳﮕﺮي درﻛﺮه ﺟﻨﻮﺑﻲ ﺑـﻴﻦ ‪ 20/6‬ﺗـﺎ ‪ 4/9‬درﺻـﺪ‬ ‫)‪ 74/7‬درﺻﺪ( و ﻛﻢﺗﺮﻳﻦ ﻣﻘﺎوﻣﺖ ﺑـﻪ آﻣﻴﻜﺎﺳـﻴﻦ )‪17/9‬‬
‫ﮔﺰارش ﮔﺮدﻳﺪ‪ .‬ﻣﻄﺎﻟﻌﺎت دﻳﮕﺮي در آﻣﺮﻳﻜـﺎ ﻧﻴـﺰ ﺷـﻴﻮع‬ ‫درﺻﺪ(‪ ،‬ﺟﻨﺘﺎﻣﺎﻳﺴﻴﻦ )‪ 22/4‬درﺻـﺪ(ﮔـﺰارش ﺷـﺪ‪ .‬ﻧﺘـﺎﻳﺞ‬
‫‪ ESBL‬ﻫــﺎ در ﺳــﻴﺘﺮوﺑﺎﻛﺘﺮ ﻓﺮوﻧــﺪي ‪ 0/9‬درﺻــﺪ و در‬ ‫اﻳﻦ ﻣﻄﺎﻟﻌﺎت در ﻣـﻮرد آﻣﻴﻨﻮﮔﻠﻴﻜﻮزﻳـﺪﻫﺎ ﺑـﻪ ﻣﻄﺎﻟﻌـﻪ ﻣـﺎ‬
‫ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ ﻛﻮﺳﺮي ‪ 3/5‬درﺻﺪ ﺑﻪ دﺳﺖ آﻣﺪه اﺳﺖ)‪.(25‬‬ ‫ﻧﺰدﻳﻚ اﺳﺖ)‪ .(22 ،19‬ﻃـﻲ ﻣﻄﺎﻟﻌـﻪاي در ﺳـﺎل ‪ 2014‬در‬
‫ﺗﻔــﺎوت در ﻧﺘــﺎﻳﺞ اﻳــﻦ ﻣﻄﺎﻟﻌــﺎت ﻣــﻲﺗﻮاﻧــﺪ ﻧﺸــﺎن دﻫﻨــﺪه‬ ‫اﻳﺮان ﺑﺮ روي ‪ 12‬اﻳﺰوﻟﻪ ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ‪ ،‬ﺑﻴﺶﺗـﺮﻳﻦ ﻣﻘﺎوﻣـﺖ‬
‫ﺗﻔﺎوت در ﮔﺴـﺘﺮش ژنﻫـﺎي ‪ ESBL‬در ﻣﻨـﺎﻃﻖ ﻣﺨﺘﻠـﻒ‬ ‫آﻧﺘﻲﺑﻴﻮﺗﻴﻜﻲ ﺑﻪ ﺗﺘﺮاﺳﺎﻳﻜﻠﻴﻦ )‪ 92‬درﺻﺪ(‪ ،‬ﻧﺎﻟﻴﺪﻳﻜﺴـﻴﻚ‬
‫ﺟﻬﺎن ﺑﺎﺷﺪ و ﺑﻪ ﻧﻈﺮ ﻣﻲرﺳﺪ در ﻛﺸﻮرﻫﺎي در ﺣﺎل ﺗﻮﺳـﻌﻪ‬ ‫اﺳﻴﺪ )‪ 83‬درﺻﺪ(‪ ،‬ﺟﻨﺘﺎﻣﺎﻳﺴﻴﻦ )‪ 67‬درﺻﺪ( و ﺗﻮﺑﺮاﻣﺎﻳﺴـﻴﻦ‬
‫ﺷﻴﻮع ﺑﺎﻻﺗﺮ ﺑﺎﺷـﺪ‪ .‬از ﻧﻈـﺮ ﻣﻴـﺰان ﻓﺮاواﻧـﻲ اﻧـﻮاع ژنﻫـﺎي‬ ‫)‪ 50‬درﺻﺪ( دﻳﺪه ﺷﺪ ﻛﻪ از ﻧﺘﺎﻳﺞ ﻣﻄﺎﻟﻌﻪ ﻣﺎ ﺑﺎﻻﺗﺮ ﺑﻮد‪ .‬از‬
‫‪ ESBL‬در ﺳــﻴﺘﺮوﺑﺎﻛﺘﺮ در ﻣﻄﺎﻟﻌــﻪ ﻣــﺎ ﺑــﻴﺶﺗــﺮﻳﻦ ﺷــﻴﻮع‬ ‫ﻃﺮﻓــﻲ از ‪ 12‬اﻳﺰوﻟــﻪ ﺳــﻴﺘﺮوﺑﺎﻛﺘﺮ‪ 3 ،‬اﻳﺰوﻟــﻪ )‪ 25‬درﺻــﺪ(‬
‫ژنﻫﺎي ‪ ESBL‬ﻣﺮﺑـﻮط ﺑـﻪ ژن ‪ blaCTX-M‬ﺑـﻮد ﻛـﻪ ﺑـﺎ‬ ‫‪ ESBL‬ﻣﺜﺒــﺖ ﺑﻮدﻧــﺪ ﻛــﻪ اﻳــﻦ ﻧﺘﻴﺠــﻪ ﺑــﺎ ﻳﺎﻓﺘــﻪﻫــﺎي ﻣــﺎ‬
‫ﻧﺘــﺎﻳﺞ اﻛﺜــﺮ ﻣﻄﺎﻟﻌــﺎت ﻫﻤﺨــﻮاﻧﻲ دارد‪ .‬در ﻣﻄﺎﻟﻌــﻪ اي در‬ ‫ﻫﻤﺨــﻮاﻧﻲ دارد)‪ .(23‬از ﺳــﻮي دﻳﮕــﺮ در ﻣﻄﺎﻟﻌــﻪ ﻣــﺎ ﺑــﻴﻦ‬
‫ﻟﻬﺴﺘﺎن‪ ،‬ﺑﻴﺶﺗﺮﻳﻦ ﻓﺮاواﻧﻲ ﺑﺎ ‪ 25‬درﺻﺪ ﺑﺮاي ‪ CTX-M‬و‬ ‫ﻓﺮاواﻧﻲ ﻓﻨﻮﺗﻴﭙﻲ و ژﻧﻮﺗﻴﭙﻲ ‪ ESBL‬در اﻳﺰوﻟﻪﻫﺎي ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ‬
‫ﺳﭙﺲ ‪ SHV‬ﺑﺎ ‪ 4/5‬درﺻﺪ ﺑﻮد)‪ .(25،24‬در ﻣﻄﺎﻟﻌﻪي دﻳﮕﺮي‬ ‫اﺧﺘﻼف ﺑﺎﻻﻳﻲ وﺟﻮد داﺷـﺖ ﻛـﻪ ﻣﻤﻜـﻦ اﺳـﺖ ﻧﺸـﺎﻧﮕﺮ‬
‫در ﺗﺎﻳﻠﻨﺪ‪ ،‬ﺑﻴﺶﺗﺮﻳﻦ ﺷﻴﻮع در ژنﻫﺎي ‪ CTX-M‬و ‪TEM‬‬ ‫ﻋﺪم ﺑﻴﺎن ژنﻫﺎي ‪ ESBL‬در اﻳﺰوﻟﻪﻫﺎي ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ ﺑﺎﺷـﺪ‬
‫ﮔــﺰارش ﺷــﺪ ﻛــﻪ از اﻳــﻦ ﻟﺤــﺎظ ﺑــﺎ ﻧﺘــﺎﻳﺞ ﻣــﺎ ﺳــﺎزﮔﺎر‬ ‫و اﻳﻦ ﭘﺪﻳﺪه ﺗﺎ ﺣﺪي ﻣﻘﺎوﻣﺖ ﭘﺎﻳﻴﻦﺗﺮ اﻳﺰوﻟﻪﻫـﺎ را ﻧﺴـﺒﺖ‬
‫اﺳﺖ)‪ .(26‬از ﻃﺮف دﻳﮕﺮ در ﻣﻄﺎﻟﻌﺎت دﻳﮕﺮي ﺷـﻴﻮع ژن‬ ‫ﺑﻪ ﺳﻔﺎﻟﻮﺳﭙﻮرﻳﻦﻫﺎي ﻧﺴﻞ ﺳﻮم ﺗﻮﺟﻴﻪ ﻣﻲﻛﻨﺪ‪ .‬در ﻣﻄﺎﻟﻌـﻪ‬
‫‪ SHV‬از ژنﻫﺎي دﻳﮕﺮ ﺑﺎﻻﺗﺮ ﺑﻮده اﺳﺖ‪ .‬ﻣـﺜﻼً در ﻣﻄﺎﻟﻌـﻪاي‬ ‫ﻣﺎ ﺷﻴﻮع ﻧﺴـﺒﺘﺎً ﺑـﺎﻻﻳﻲ از ژنﻫـﺎي ‪ ESBL‬در ﺳـﻴﺘﺮوﺑﺎﻛﺘﺮ‬
‫در ﻛﺎﻧﺎدا ﺑـﺮ روي ﺳـﻴﺘﺮوﺑﺎﻛﺘﺮ‪ ،‬ﺑـﻴﺶﺗـﺮﻳﻦ ﻣﻴـﺰان ﺷـﻴﻮع‬ ‫ﻓﺮوﻧﺪي وﺟﻮد داﺷﺖ ﻛـﻪ ﺗﺎﻳﻴـﺪي ﺑـﺮ ﮔﺴـﺘﺮش ژنﻫـﺎي‬
‫ژنﻫــﺎي ‪ ESBL‬ﻣﺮﺑــﻮط ﺑــﻪ ‪ 22/2) SHV‬درﺻــﺪ( ﺑــﻮد‪.‬‬ ‫ﻣﻘﺎوﻣﺖ در اﻳﻦ ﭘﺎﺗﻮژن ﻓﺮﺻﺖ ﻃﻠﺐ اﺳﺖ‪ .‬در ﻣﻄﺎﻟﻌـﻪاي‬
‫ﻫﻢﭼﻨﻴﻦ در ژاﭘﻦ ﻣﻴﺰان ﺷﻴﻮع اﻳﻦ ژن ‪ 19/3‬درﺻـﺪ و در‬ ‫در ﻟﻬﺴــﺘﺎن از ﻣﺠﻤــﻮع ‪ 2388‬اﻳﺰوﻟــﻪ اﻧﺘﺮوﺑﺎﻛﺘﺮﻳﺎﺳــﻪ ﺑــﺎ‬
‫ﻛـﺮه ﺟﻨـﻮﺑﻲ ‪ 4/9‬درﺻـﺪ ﮔــﺰارش ﺷـﺪه اﺳـﺖ)‪ .(27‬اﻳــﻦ‬ ‫ﺑﻴﺶﺗﺮﻳﻦ ﻓﺮاواﻧﻲ ﻧﻤﻮﻧﻪﻫﺎي ادراري‪ 44،‬ﻧﻤﻮﻧـﻪ ﺑـﻪ ﻋﻨـﻮان‬
‫ﺗﻔﺎوت در ﻧﺘﺎﻳﺞ ﺑﻴﺎﻧﮕﺮ ﺗﻔـﺎوت در اﻧﺘﺸـﺎر ژنﻫـﺎي ﻣـﻮرد‬ ‫ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ ﻓﺮوﻧﺪي ﮔـﺰارش ﺷـﺪ ﻛـﻪ از اﻳـﻦ ﺗﻌـﺪاد ‪13‬‬
‫ﺑﺮرﺳﻲ در ﻣﻨﺎﻃﻖ ﻣﺨﺘﻠﻒ دﻧﻴﺎ ﻣﻲﺑﺎﺷﺪ‪.‬‬ ‫)‪ 29/5‬درﺻﺪ( ﻣﻮرد آنﻫﺎ داراي ژنﻫﺎي ‪ ESBL‬ﺑﻮدﻧـﺪ‪.‬‬
‫در ﭘﺎﻳﺎن ﻣﻲﺗﻮان ﻧﺘﻴﺠـﻪﮔﻴـﺮي ﻛـﺮد ﻛـﻪ ﻧﺘـﺎﻳﺞ اﻳـﻦ‬ ‫در ﻣﻄﺎﻟﻌﻪاي دﻳﮕﺮ در ﺗﺎﻳﻠﻨـﺪ از ‪ 105‬اﻳﺰوﻟـﻪ ﺳـﻴﺘﺮوﺑﺎﻛﺘﺮ‬
‫ﻣﻄﺎﻟﻌﻪ ﻧﺸﺎن داد ﻛﻪ درﺻﺪ ﺑﺎﻻﻳﻲ از ﺳﻴﺘﺮوﺑﺎﻛﺘﺮﻫﺎي ﺟﺪا‬ ‫‪ 18/7‬درﺻﺪ ﺣﺎوي ژنﻫﺎي ‪ ESBL‬ﺑﻮدﻧﺪ‪ .‬در ﻣﻄﺎﻟﻌـﻪاي‬
‫ﺷــﺪه داراي ژنﻫــﺎي ‪ ESBL‬ﻫﺴــﺘﻨﺪ و از ﻣﻴــﺎن آنﻫــﺎ ژن‬ ‫در ﻫﻨﺪوﺳﺘﺎن ‪ 37‬درﺻﺪ اﻳﺰوﻟـﻪﻫـﺎي ﺳـﻴﺘﺮوﺑﺎﻛﺘﺮ ‪ESBL‬‬
‫‪ blaCTX-M‬ﺑــﻴﺶﺗــﺮﻳﻦ ﻓﺮاواﻧــﻲ را در اﻳــﻦ ﻣﻨﻄﻘــﻪ دارا‬ ‫ﻣﺜﺒﺖ ﺑﻮدﻧﺪ)‪ .(22،25،24‬ﻧﺘﺎﻳﺞ اﻳﻦ ﻣﻄﺎﻟﻌﺎت ﺑﺎ ﻧﺘﺎﻳﺞ ﻣﻄﺎﻟﻌﻪ‬
‫ﻣــﻲﺑﺎﺷــﺪ‪ .‬از ﻟﺤــﺎظ ﻣﻘﺎوﻣــﺖ آﻧﺘــﻲﺑﻴــﻮﺗﻴﻜﻲ‪ ،‬ﻛــﻢﺗــﺮﻳﻦ‬ ‫ﻣﺎ ﻣﺸﺎﺑﻬﺖ دارد‪ .‬اﻣﺎ در ﻣﻄﺎﻟﻌﺎت دﻳﮕﺮ ﻣﻴـﺰان ﭘـﺎﻳﻴﻦﺗـﺮي‬
‫ﻣﻘﺎوﻣﺖ ﺑﻪ ﻛﺎرﺑﺎﭘﻨﻢﻫﺎ ﻣﺸﺎﻫﺪه ﺷﺪ‪ .‬وﻟـﻲ در اﻳـﻦ ﺗﺤﻘﻴـﻖ‬ ‫ﺑﺮاي ﺷﻴﻮع ‪ ESBL‬در اﻳﺰوﻟـﻪﻫـﺎي ﺳـﻴﺘﺮوﺑﺎﻛﺘﺮ ﮔـﺰارش‬
‫ﻣﻘﺎوﻣﺖ ﺑـﺎﻻﻳﻲ ﺑـﻪ آﻧﺘـﻲﺑﻴﻮﺗﻴـﻚﻫـﺎﻳﻲ ﻣﺜـﻞ ﺳـﻔﺎزوﻟﻴﻦ‪،‬‬ ‫ﺷﺪه اﺳﺖ‪ .‬ﻣﺜﻼً در ﻣﻄﺎﻟﻌﻪاي ﻛﻪ در ﺳﺎل ‪ 1996-1997‬ﺑﺮ‬
‫آﻣﭙﻲﺳﻴﻠﻴﻦ و ﻛﻮﺗﺮﻳﻤﻮﻛﺴﺎزول دﻳﺪه ﺷـﺪ‪ ،‬اﻣـﺎ در ﻣـﻮرد‬ ‫روي اﻳﺰوﻟﻪﻫﺎي اﻧﺘﺮوﺑﺎﻛﺘﺮﻳﺎﺳﻪ ﺣﺎﺻﻞ از ﺑﻴﻤﺎران ﺑﺴـﺘﺮي‬
‫ﺳﻔﺎﻟﻮﺳﭙﻮرﻳﻦﻫﺎي ﻧﺴﻞ ﺳﻮم ﻣﻘﺎوﻣﺖ ﭘـﺎﻳﻴﻦﺗـﺮ ﺑـﻮد‪ .‬ﺑـﻴﻦ‬ ‫ﺻﻮرت ﮔﺮﻓﺖ‪ 11/4 ،‬درﺻﺪ از اﻳﺰوﻟـﻪﻫـﺎي ﺳـﻴﺘﺮوﺑﺎﻛﺘﺮ‬
‫ﻓﺮاواﻧﻲ ﻓﻨﻮﺗﻴﭙﻲ و ژﻧﻮﺗﻴﭙﻲ ‪ ESBL‬در اﻳﺰوﻟﻪﻫﺎي ﺳﻴﺘﺮوﺑﺎﻛﺘﺮ‬ ‫ﻓﺮوﻧﺪي‪ ESBL ،‬ﻣﺜﺒﺖ ﺑﻮدﻧﺪ)‪ .(19‬ﻫﻢﭼﻨﻴﻦ در ﻣﻄﺎﻟﻌـﻪاي‬
‫اﺧﺘﻼف زﻳﺎدي وﺟﻮد داﺷـﺖ ﻛـﻪ ﻣﻤﻜـﻦ اﺳـﺖ ﻧﺸـﺎﻧﮕﺮ‬ ‫در ژاﭘﻦ ﺷﻴﻮع ‪ ESBL‬ﻫـﺎ ‪0/2‬درﺻـﺪ ﮔـﺰارش ﺷـﺪ و در‬

‫دوره ﺑﻴﺴﺖ و ﭘﻨﺠﻢ‪ ،‬ﺷﻤﺎره ‪ ، 127‬ﻣﺮداد ‪1394‬‬ ‫ﻣﺠﻠﻪ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﻣﺎزﻧﺪران‬ ‫‪70‬‬
‫ﻋﻠﻴﺸﺎ اﻛﻴﺎ و ﻫﻤﻜﺎران‬ ‫ﭘﮋوﻫﺸﻲ‬

‫ﺳﭙﺎﺳﮕﺰاري‬ ‫ در اﻳﺰوﻟـﻪ ﺳـﻴﺘﺮوﺑﺎﻛﺘﺮ‬ESBL ‫ﻋﺪم ﺑﻴـﺎن ﺑـﺎﻻي ژنﻫـﺎي‬


‫ﺑﺪﻳﻦوﺳﻴﻠﻪ از ﻫﻤﻜﺎري ﭘﺮﺳﻨﻞ آزﻣﺎﻳﺸﮕﺎه ﻣﻴﻜﺮوب‬ ‫ ﻧﺘﺎﻳﺞ اﻳﻦ ﻣﻄﺎﻟﻌﻪ ﻟﺰوم دﻗﺖ ﺑﻴﺶ ﺗـﺮ در اﺳـﺘﻔﺎده از‬.‫ﺑﺎﺷﺪ‬
‫ﺷﻨﺎﺳــﻲ داﻧﺸــﻜﺪه ﭘﺰﺷــﻜﻲ ﻛﺮﻣﺎﻧﺸــﺎه ﺗﻘــﺪﻳﺮ و ﺗﺸــﻜﺮ‬ ‫آﻧﺘﻲﺑﻴﻮﺗﻴﻚﻫﺎي ﻣﺨﺘﻠﻒ در درﻣﺎن ﻋﻔﻮﻧـﺖﻫـﺎي ﺳـﻴﺘﺮو‬
.‫ﻣﻲﮔﺮدد‬ .‫ﺑﺎﻛﺘﺮ را ﺧﺎﻃﺮ ﻧﺸﺎن ﻣﻲ ﻛﻨﺪ‬

References
1. Jones ME, Avison MB, Damdinsuren E, prevalence and susceptibility patterns. Rev
MacGowan AP, Bennett PM. Heterogeneity Infect Dis 1988; 10(4): 867-878.
at the beta-lactamase structural gene ampC 7. Sabate M, Tarrago R, Navarro F, Miro E,
amongst citrobacter spp. assessed by verges C, Barbe J, et al. Cloning and
polymerase chain reaction analysis: potential sequence of the gene encoding a novel
for typing at a molecular level. J Med cefotaxime-hydrolyzing B-lactamases (CTX-M)
Microbiol1994; 41(3): 209-214. from Escherichia coli in Spain. Antimicrob
2. Lavigne JP, Defez C, Bouziges N, Mahamat A, Agents Chemother 2000; 44(7): 1970-1973.
Sotto A. Clinical and molecular epidemiology 8. Jacoby GA, Han P. Detection of extended –
of multidrug-resistant Citrobacter spp. spectrum B-lactamases in clinical isolates of
Infections in a French university hospital. Klebsiella pneumoniae and Escherichia coli.
Eur J Clin Microbiol Infect Dis 2007; 26(6): J clin Microbiol 1996; 34(4): 908-911.
439-441. 9. Mulvey JR, Bryce E, Boyd D, Ofner-
3. Banjara MR, Sharma AP, Joshi AB, Tuladhar Agostini M, Christianson S, Simor AE, et al.
NR, Ghimire P, Bhatta DR. Surgical wound Ambler class A extended-spectrum β-lactamase-
infections in patients of Tribhuvan university producing Escherichia coli and Klebsiella
Teaching Hospital. Nepal Med Coll J 2003; spp in Canadian hospital. Antimicrob Agents
3: 41-45. Chemother 2004; 48(4): 1204-1214.
4. Jha AK, Singh JB, Dutta D. Microorganisms 10. Bush K, Jacoby GA, Medeires A. A functional
present in discharging otitis media in a group classification scheme for B-lactamases and
of patients in kathmandu. Nepal Med Coll J its correlation with molecular structure.
2007; 9(3): 196-198. Antimicrob Agents chemother. 1995; 39(6):
5. Misra B, Gandham N, Sardar M, Ujagare M, 1211-1233.
Angadi K, Vyawahare CH, et al. High 11. Bradford PA. Extended-spectrum B-lactamases
prevalence of Multi-Drug resistant Citrobacter in the 21st century: characterization,
spp. From tertiary car hospital, Pimpri, Pune, epidemiology, and detection of this important
India. J Pharm Biomed Sci 2012; 25(25): resistance threat. Clin Microbiol Rev 2001;
158-63. 14(4): 933-951.
6. Jarlier V, Nicolas MH, Fornier G. Extended 12. Mirelis B, Navarro F, Miro E, Mesa RJ, Coll
broad-spectrum B lactamases conferring P, Parta G. Community transmission of
transferable resistance to newer B lactan extended-spectrum B-lactamase. Emerg
agents in Enterobacteriaceae Hospital Infect Dis 2003; 9(8): 1024-1025.

71 1394 ‫ ﻣﺮداد‬، 127 ‫ ﺷﻤﺎره‬،‫دوره ﺑﻴﺴﺖ و ﭘﻨﺠﻢ‬ ‫ﻣﺠﻠﻪ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﻣﺎزﻧﺪران‬
13. Blondeau JM. Extended–spectrum beta- 20. Choi SH, Lee JE, Park SJ, Kim MN, Choo
lactamases. Semin Respir Infect 2001; 16(3): EJ, Kwak YG, et al. Prevalence, microbiology,
169-176. and clinical characteristics of extended-
14. Clinical And Laboratory Standard Institue. spectrum b-lactamase-producing Enterobacter
Performance standards for antimicrobial spp., Serratia marcescens, Citrobacter freundii,
th
susceptibility testing: twenty-second. 22 ed. and Morganella morganii in Korea. Eur J
USA: Wayne PA. M100-S22. 2012; 32(3): Clin Microbiol Infect Dis 2007; 26(8): 557-
50-51. 561.
15. Edelstein M, Pimkin M, Palagin I, Edelstein 21. DiPersio JR, Deshpande LM, Biedenbach
I, Stratchounski L. Prevalence and molecular DJ, Toleman MA, Walsh TR, Jones RN.
epidemiology of CTX-M extended-spectrum Evolution and dissemination of extended-
beta-lactamase-producing Escherichia coli spectrum B-lactamase-producing Klebsiella
and Klebsiella pneumoniae in Russian pneumoniae: epidemiology and molecular
hospitals. Antimicrob Agents Chemother report from the SENTRY Antimicrobial
2003; 47(12): 3724-3732. Surveillance Program (1997-2003). Diagn
16. Kim J, Jeon S, Rhie H, Lee B, Park M, Lee H, Microbiol Infect Dis 2005; 51(1): 1-7.
et al. Rapid Detection of Extended Spectrum 22. Mohan S, Agarwal J, Srivastava R, Singh
β-Lactamase (ESBL) for Enterobacteriaceae M.Observations on citrobacter species from a
by use of a Multiplex PCR-based Method. tertiary care health center with special
Infect Chemother 2009; 41(3): 181-184. reference to multi-drug resistance and
17. Keyvani H, Hakemivala M, Talebnia- presence of CTX-M gene. Indian J Pathol
chalanbari Z, Mirbagheri F, Baghri-bejestani Microbiol 2014; 57(3): 439-441.
F. Phenotypic and molecular study of ESBL 23. Ghorbani-Dalini S. Molecular detection of
production among Escherichia coli strains ESBL s production and antibiotic resistance
isolated from patients admitted to hospital patterns in Gram negative bacilli isolated
orthopedic wounds Akhtar and Firoozgar from urinary tract infections. Indian J Pathol
Tehran, 2000-2001. Iran J Infect Dis Trop Microbiol (IJPM) 2014; 57(2): 244-248.
Med 2012; 17(59): 29-31 (Persian). 24. Empel J, Baraniak A, Literacka E, Mrówka
18. Shahid M. Citrobacter spp. Simultaneously A, Fiett J, Sadowy E, et al. Molecular survey
Harboring blaCTX-M, blaTEM, blaSHV, of beta-lactamases conferring resistance to
blaampC, and Insertion Sequences IS26 and newer beta-lactams in Enterobacteriaceae
orf513: an Evolutionary Phenomenon of isolates from Polish hospitals. Antimicrob
Recent Concern for Antibiotic Resistance. J Agents Chemother 2008; 52(7): 2449-2454.
Clin Microbiol 2010; 45(5): 1833-1838. 25. Kanamori H, Yano H, Hirakata Y, Endo S,
19. Pałucha A, Mikiewicz B, Hryniewicz W, Arai K, Ogawa M, et al. High prevalence of
Gniadkowski M. Concurrent outbreaks of extended-spectrum b-lactamases and qnr
extended-spectrum beta-lactamase-producing determinants in Citrobacter species from
organisms of the family Enterobacteriaceae Japan: dissemination of CTX-M-2. J
in a Warsaw hospital. J Antimicrob Chemother Antimicrob Chemother 2011; 66(10): 2255-
1999; 44(4): 489-99. 2262.

1394 ‫ ﻣﺮداد‬، 127 ‫ ﺷﻤﺎره‬،‫دوره ﺑﻴﺴﺖ و ﭘﻨﺠﻢ‬ ‫ﻣﺠﻠﻪ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﻣﺎزﻧﺪران‬ 72
‫ﻋﻠﻴﺸﺎ اﻛﻴﺎ و ﻫﻤﻜﺎران‬ ‫ﭘﮋوﻫﺸﻲ‬

26. Kiratisin P, Henprasert A. Resistance AmpC β-lactamase genes in Thailand. Trans


phenotype-genotype correlation and molecular R Soc Trop Med Hyg 2011; 105(1): 46-51.
epidemiology of Citrobacter, Enterobacter, 27. Pepperell C, Kus JV, Gardam MA, Humar A,
Proteus, Providencia, Salmonella and Burrows LL. Low-Virulence Citrobacter
Serratia that carry extended-spectrum β- Species Encode Resistance to Multiple
lactamases with or without plasmid-mediated Antimicrobials. Antimicrob Agents Chemoter
2002; 46(11): 3555-3560.

73 1394 ‫ ﻣﺮداد‬، 127 ‫ ﺷﻤﺎره‬،‫دوره ﺑﻴﺴﺖ و ﭘﻨﺠﻢ‬ ‫ﻣﺠﻠﻪ داﻧﺸﮕﺎه ﻋﻠﻮم ﭘﺰﺷﻜﻲ ﻣﺎزﻧﺪران‬

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