due to its significant ability to up - regulate or acquire resistant determinants , there are serious challenges associated with choosing and monitoring appropriate antibiotic treatments ( 1 ) . although carbapenems are generally considered to be the most promising antibiotic to use against acinetobacter baumannii , the increasing resistance to treatment with carbapenems may lead to limitations od their use and effectiveness in some cases
. the use of unconventional antibiotics , such as the polymyxins , rifampicin , and tetracyclines has been described , but there are little data on in vitro antibiotic susceptibilities of these agents ( 2 ) .
colistin appears to be very effective against multidrug - resistant ( mdr ) a. baumannii isolates in vitro ; however , it is not used extensively in treatment because of side effects , such as neurotoxicity and nephrotoxicity ( 3 ) .
colistin is now considered as the last line of treatment against mdr acinetobacter infections , but there are still reports of these infections being resistant to colistin .
the mechanism of colistin resistance is the modification of the lipid a of the outer lipopolysaccharide ( lps ) membrane .
more recently , it has been identified that mutations in pmra and pmrb and complete loss of lps production may mediate colistin resistance by a. baumannii ( 4 ) .
a new glycycline , tigecycline also was found to have an excellent in - vitro activity against a. baumannii isolates .
tigecycline was licensed for use in the united states and latin america in 2005 , and it was licensed in canada , europe , the asia / pacific region , and the middle east in 2006 and 2007 ( 5 ) .
tigecycline is a substrate for the ade abc efflux pump system , and resistance to it can be mediated by efflux or ribosomal protection ( 6 ) .
tetracycline - resistant bacteria are often sensitive to tigecycline , and a broad spectrum of activity has been demonstrated against gram - negative bacteria , even extended - spectrum b - lactamase ( esbl)producing escherichia coli and klebsiella pneumonia ( 7 ) .
increasing carbapenem resistance among a. baumannii isolates has led clinicians to look for new treatment alternatives .
many carbapenemase - producing a.baumannii isolates are also resistant to all available antibiotics except polymyxins .
tigecycline , which is active against most carbapenemase - producing strains , may be a useful alternative to polymyxins ( 3 ) , but very little data have been published on the anti - microbial resistance among isolates of acinetobacter species to colistin and tigecycline .
the knowledge of changes in the resistance rates of bacteria in our local hospitals will improve empirical therapy .
since the mobility of the population is a risk factor for the distribution of antimicrobial , drug  resistant organisms , this study was conducted to evaluate the in vitro activity of tigecycline and colistin against clinical isolates of a. baumannii in hospitals of tehran and bandar - abbas , two cities in iran that have many immigrants .
the study was conducted from march 2009 to november 2010 at hospitals in tehran and bandar - abbas , iran .
the clinical acinetobacter isolates were identified by conventional methods ( 8) , stored in sterile trypticase soy broth with 30% glycerol , and preserved at 70 c .
acinetobacter isolates were collected from affected patients , ( i.e. , sputum , urine , cerebrospinal fluid , ascites , and pleural effusion ) .
all isolates were subjected to pcr to detect the blaoxa-51-like gene that is unique to the acinetobacter baumannii species ( 9 ) .
the pcr assay was conducted using the primer bla 
 oxa-51-like ( 353bp 5  f- taa tgc ttt gat cgg cct tg-3 and 5 r - tgg att gca ctt cat ctt gg-3 ) .
pcr reactions were conducted in 25-l reaction volumes with 3 l of extracted dna , 10 pmol of each primer , and 0.2 l of 500 u taq dna polymerase in 10x pcr buffer containing 1 mm mgcl2 and 0.5 l of a 25-mm solution of deoxynucleoside triphosphate .
conditions for the pcr were 95 c for 4 min and then 34 cycles at 95 c for 45 s , 34 cycles at 52 c for 45 s , and 34 cycles at 72 c for 30 s. this was followed by a final extension at 72 c for 10 min ( 10 ) .
the susceptibility tests for tigecycline and colistin were performed in the microbiology laboratory at tarbiat modares university using the disk agar diffusion ( dad ) method , as recommended by the clinical and laboratory standards institute ( 11 ) .
since no interpretive criteria have been approved for tigecycline against acinetobacter species , the results were interpreted by the criteria ( s  16 mm ; i = 1315 mm ; r  12 mm ) recommended by jones et al .
fda for enterobacteriaceae , i.e. , s  19 mm ; i = 1518 mm ; r  14 mm ) ( tygacil package insert [ june , 2005 ] , wyeth pharmaceuticals , inc . ,
we collected the data of the antibiogram pattern of the a. baumannii isolates to commonly - used antibiotics , e.g. , imipenem , ciprofloxacin , amikacin , cefepime , ceftazidime , and polymyxin - b .
the susceptibility testing of these antibiotics was performed by the disk diffusion method on mueller - hinton agar plates .
the study was conducted from march 2009 to november 2010 at hospitals in tehran and bandar - abbas , iran .
the clinical acinetobacter isolates were identified by conventional methods ( 8) , stored in sterile trypticase soy broth with 30% glycerol , and preserved at 70 c .
acinetobacter isolates were collected from affected patients , ( i.e. , sputum , urine , cerebrospinal fluid , ascites , and pleural effusion ) .
all isolates were subjected to pcr to detect the blaoxa-51-like gene that is unique to the acinetobacter baumannii species ( 9 ) .
the pcr assay was conducted using the primer bla 
 oxa-51-like ( 353bp 5  f- taa tgc ttt gat cgg cct tg-3 and 5 r - tgg att gca ctt cat ctt gg-3 ) .
pcr reactions were conducted in 25-l reaction volumes with 3 l of extracted dna , 10 pmol of each primer , and 0.2 l of 500 u taq dna polymerase in 10x pcr buffer containing 1 mm mgcl2 and 0.5 l of a 25-mm solution of deoxynucleoside triphosphate .
conditions for the pcr were 95 c for 4 min and then 34 cycles at 95 c for 45 s , 34 cycles at 52 c for 45 s , and 34 cycles at 72 c for 30 s. this was followed by a final extension at 72 c for 10 min ( 10 ) .
the susceptibility tests for tigecycline and colistin were performed in the microbiology laboratory at tarbiat modares university using the disk agar diffusion ( dad ) method , as recommended by the clinical and laboratory standards institute ( 11 ) .
since no interpretive criteria have been approved for tigecycline against acinetobacter species , the results were interpreted by the criteria ( s  16 mm ; i = 1315 mm ; r  12 mm ) recommended by jones et al .
fda for enterobacteriaceae , i.e. , s  19 mm ; i = 1518 mm ; r  14 mm ) ( tygacil package insert [ june , 2005 ] , wyeth pharmaceuticals , inc . ,
we collected the data of the antibiogram pattern of the a. baumannii isolates to commonly - used antibiotics , e.g. , imipenem , ciprofloxacin , amikacin , cefepime , ceftazidime , and polymyxin - b .
the susceptibility testing of these antibiotics was performed by the disk diffusion method on mueller - hinton agar plates .
this study included 165 acinetobacter isolates that were collected from hospitals in tehran and bandar - abbas .
one hundred and fifty - seven isolates ( 95.15% ) that gave a band for blaoxa-51-like identified as a.baumannii , figure ( 1 ) .
thirty - four isolates were from bandar - abbas , and 123 were from tehran .
nine of the isolates were from sputum ( 5.7% ) , 25 were from pus ( 15.1% ) , 12 were from urine ( 7.64% ) , four were from cerebrospinal fluid ( 2.54% ) , two were from ascites ( 1.27% ) , two were from ears ( 1.27% ) , three were from catheters ( 1.9% ) , 24 were from burn wounds ( 15.28% ) , and 84 were from pleural effusion ( 53.5% ) .
the quantities of isolates related to wards were as follows : among the isolates 114(72.6% ) were from intensive care unit , 26 ( 16.56% ) were from internal ward , 9 ( 5.73% ) were from surgical ward , 3 ( 1.9% ) from neaurosurgery ward , 2 ( 1.27% ) from pediatric ward , 7 ( 4.45% ) from emergency unit , 1 ( 1.9% ) from coronary care unit , and 2 ( 2.27% ) from ear , nose , and throat ward .
for the two cities , table 1 shows the results of susceptibility to tigecycline and compares the susceptibility rates of the isolates to eight antibiotics .
a high prevalence of multi - drug resistance by a. baumannii limits the therapeutic options for the treatment of infections caused by these bacteria .
it is clear that new drugs are needed for the treatment of mdr a. baumannii . in some studies
, tigecycline has been found to be active in about 87 to 93% in of acinetobacter species ( 3 ) . in our study , according to the jones criteria , the susceptibility rate to tigecycline in the hospital in tehran was 66.7% , and it was 76.5% in the hospital bandar - abbas . however , based on the fda criteria , the rates were 24.2% in tehran and 23.5% in bandar - abbas .
all isolates ( 100% ) were susceptible to colistin and polymyxin b. several studies have reported the susceptibility to colistin as 98 to 100% ( 3 ) .
first , the u.s . food and drug administration ( fda ) has not assigned tigecycline breakpoints for acinetobacter species , and no interpretive criteria are currently available ( 7 ) . the u.s .
fda - approved breakpoints of tigecycline were defined against enterobacteriaceae , and the diameter of the inhibition zone is  19 mm and mic  2 mg / l ( 14 ) .
fda - approved breakpoint of tigecycline against enterobacteriaceae was not applicable to tigecycline against a. baumannii .
the breakpoint for an inhibition zone diameter of 13 mm was more accurate in predicting the susceptibility of a. baumannii to tigecycline with a sensitivity of 99% and a specificity of 100% ( 15 ) . in bouchillon
s study , tigecycline was the most active drug against all species of acinetobacter ( 7 ) .
the tigecycline mic90 of 2 g / ml was 16-fold and 64-fold more potent than the b - lactams and carbapenems , respectively , against all tested strains .
tigecycline was 8-fold and 16-fold more potent against acinetobacter species than levofloxacin and doxycycline , respectively ( 7 ) .
a taiwanese study showed that the overall susceptibility rate of a. baumannii to tigecycline was 80.9% .
the rates of susceptible , intermediate , and resistant isolates by the disk diffusion method , using the criteria of jones et al .
, were 88.3 , 9.9 , and 1.8% , whereas they were 44.0 , 51.7 , and 4.3% by the u.s .
fda s criteria . by comparison with their previous report on tigecycline activity against a. baumannii
isolates in taiwan , they observed a seven - fold increase ( from 3% in 2003 to 20% in 2007 ) in the number of a. baumannii isolates that are not susceptible to tigecycline ( 13 ) .
since the most probable resistance mechanism for tigecycline in a. baumannii is the presence of an efflux pump mechanism , exposure to sub - therapeutic levels of tigecycline for even short periods of time may promote the rapid emergence of tigecycline resistance and cause therapeutic failure . in our study ,
a possible explanation for increased tigecycline resistance was the exposure to multiple antibiotics in our hospitals in which the efflux systems of these strains already are highly active .
the disk diffusion method is the most commonly used ( > 90% ) susceptibility method in our hospitals , since automated susceptibility test systems are not available in most microbiology laboratories .
it appeared to be a good option in the treatment of mdr a. baumannii , but adverse reactions limit its extensive use .
however , colistin resistance is rare worldwide at the current time , which likely reflects its very limited use .
colistin - resistant isolates have recently been identified in several gram - negative species , such as a. baumannii , klebsiella pneumoniae , and p. aeruginosa ( 4 )
. only sporadic cases of colistin resistance have been reported in the literature in clinical isolates of patients admitted to the icus of an argentinian university hospital .
the findings of this study showed that colistin and polymyxin - b still show the highest potency against a.baumannii in our hospitals .
however , the resistance of a.baumannii to tigecycline may limit their use in the future . the broad - spectrum in vitro activity of tigecycline and colistin
may make them a suitable candidate for use in the empirical treatment of serious infections .
however , it should be noted that in vitro data do not equate to clinical efficacy , and resistance rates should be monitored continuously .
finding cases of resistance to tigecycline suggests an efflux - based mechanism , and further work is ongoing to elucidate this mechanism .
 background : the acinetobacter species , particularly a. baumannii , has emerged as one of the main causes of nosocomial infections in recent years . the high prevalence of drug resistance in a. baumannii limits the therapeutic options for treating infections caused by these bacteria . 
 the objective of this study was to determine the in vitro activity of tigecycline and colistin against clinical isolates of a. baumannii in tehran and bandar abbas , iran.methods:this study was conducted from march 2009 to november 2010 at three hospitals in tehran and bandar abbas , iran , using 165 acinetobacter species isolated from clinical specimens . 
 all isolates were subjected to pcr to detect blaoxa-51-like genes that are unique to acinetobacter baumannii . 
 isolates that gave a band for the blaoxa-51-like genes were identified as a. baumannii . 
 anti - microbial susceptibility tests were performed for tigecycline , colistin , and other antibiotics.results:sensitivity rates to colistin and polymyxin - b were 100% . 
 resistance rates for tigecycline were 4.2% in tehran and 8.8% in bandar - abbas according to jones criteria , whereas , according to u.s . 
 fda criteria , the resistance rates were 20.8% and 17.6% , respectively.conclusions:new alternative drugs are needed for the treatment of drug resistant a. baumannii . 
 although colistin appears to be a good choice , adverse reactions have limited its usage . 
 tigecycline is effective against a. baumannii isolates , and it shows promise for solving the problem . 
Introduction
Materials and methods
Hospital setting and collection of bacteria
Detection of the 
Susceptibility to Tigecycline and Colistin
Susceptibility to antibiotics other than Tigecycline and Colistin
Results
Discussion
Conclusions