urinary tract infection ( uti ) is one of the most common clinical entities encountered by the medical practitioners . the most common organisms causing uti are all known to harbor multiple drug resistance ( mdr ) mechanisms , both inherited or transmissible and chromosomal or extrachromosomal against the commonly used oral antimicrobial agents for uti caused by gram - negative organisms , i.e. , fluoroquinolones , trimethoprim - sulfamethoxazole , nitrofurantoin , and second and third - generation cephalosporins . with rampant overuse and abuse of these drugs , particularly in the developing countries like india with availability of over the counter drugs , gram - negative organisms have become overwhelmingly resistant to all or most of these agents , making outpatient oral therapy increasingly difficult . extended spectrum beta - lactamase ( esbl ) production is common among clinical isolates of enterobacteriaceae . since carbapenems are considered drug of choice for serious infections caused by these microorganisms , use of these drugs is increasing , which is contributing to the selection and spread of carbapenem - resistant gram - negative bacilli . the most commonly used definition is bacteria which is resistant to three or more antimicrobial classes . it achieves high concentration in urine of 2000 g / ml and maintains high levels for over 24 h. hence , single - time oral therapy with fosfomycin has been recommended in uncomplicated uti . this study was done with the objective to determine in vitro fosfomycin susceptibility of common uropathogens and determining the resistance pattern of these organisms against commonly prescribed antimicrobial agents . a prospective study was conducted from november , 2015 , to april , 2016 in the department of microbiology in a 380 bedded tertiary care hospital and medical college in eastern india . urine samples were collected from patients who had clinical features suggestive of uti from the inpatients and outpatients departments . freshly collected mid - stream clean catch urine samples were collected from the non - catheterized , alert , conscious , adult patients with indications for urine culture as assessed by the clinicians from the various departments . surgically collected urine samples and suprapubic aspirates were collected from some patients as indicated . if the patients were catheterized ; then , urine samples were collected from the catheter with proper surgical asepsis with needle and syringe as described in erstwhile standard technique guidelines . direct microscopy of the uncentrifuged urine sample was done , and pus cells and bacteria were noted . the urine samples were plated by semi - quantitative method on blood agar and macconkey agar and incubated at 37c overnight and if required , till 48 h. the growth of organisms and colony count were taken . the isolates obtained from the samples with significant bacteriuria in the background of relevant supportive clinical features of uti and/or the presence of significant pus cells on direct microscopy , as described in the standard guidelines , were only included in the study . the identification of the organism was done by conventional biochemical tests and vitek 2 compact system ( biomrieux inc . the antimicrobial susceptibility was performed for these isolates on mueller - hinton agar plates by kirby - bauer disc diffusion method and interpreted according to the clinical and laboratory standards institute guidelines m100-s25 version published in 2015 . the different antimicrobial agents that were tested for different organisms are given in table 1 . for enterobacteriaceae other than e. coli , minimum inhibitory concentration ( mic ) testing was done for fosfomycin by e - test for confirmation , and interpretation was done according to eucast guidelines 2015 as given by falagas et al . as per the previously published guidelines , cefazolin susceptibility can be used to predict the susceptibility toward all oral cephalosporins when used for treating uncomplicated utis caused by e. coli , klebsiella spp . , and proteus mirabilis . for detection of esbl producers , screening was done using disc diffusion method with ceftriaxone and cefotaxime , and confirmation was done by simultaneous testing with cefotaxime ( 30 g ) and combination of cefotaxime / clavulanate ( 30/10 g ) by disc diffusion method . modified hodge test the different antimicrobial agents tested for susceptibility mdr enterobacteriaceae ( mdre ) are the organisms resistant to any three different classes of antibiotics as defined by the previous guidelines . in our study , it includes resistance to any three of the following groups  cephalosporins , fluoroquinolones , aminoglycosides , folate pathway inhibitors ( trimethoprim - sulfamethoxazole ) , and nitrofurantoin . a total of 2229 urine samples were received fulfilling the inclusion criteria . among these , 345 samples showed growth of significant colony count of one or two organisms , yielding a sum of 356 isolates fulfilling the criteria for significance . of these 345 patients with significant growth of organisms , 92 ( 26.67% ) were male and 253 ( 73.33% ) were female . 16 ( 4.63% ) were children below 12 years of age . out of the positive isolates , 147 were from opd , 206 from inpatient wards , and 3 from the icu [ table 2 ] . there were 216 ( 60.67% ) isolates of e. coli , 67 ( 18.82% ) isolates of k. pneumoniae , 15 ( 4.21% ) isolates of pseudomonas spp . the distribution of organisms from outpatient , ward , intensive care unit among the 216 isolates of e. coli , high rate of resistance was seen to cephalosporins , fluoroquinolones , and trimethoprim - sulfamethoxazole . all 216 ( 100% ) were susceptible to colistin , and 212 ( 98.14% ) were susceptible to fosfomycin [ table 3 ] . among the 67 isolates of k. pneumoniae , the majority were resistant to cephalosporins and fluoroquinolones . all 67 ( 100% ) were susceptible to colistin , and 64 ( 95.52% ) isolates were susceptible to fosfomycin . the susceptibility of isolated organisms to different antibiotics among the 15 isolates of pseudomonas spp . high resistance rates were seen against ciprofloxacin and levofloxacin , and none were resistant to colistin [ table 3 ] . among the 44 enterococcus spp . , high resistance was seen against ampicillin , ciprofloxacin , levofloxacin , and high - level gentamicin . only 1 ( 2.27% ) was resistant to fosfomycin , and all ( 100% ) were susceptible to vancomycin , teicoplanin , and linezolid . there were total 284 isolates of e. coli , k. pneumoniae , and p. mirabilis . among these 184 ( 64.78% ) were esbl producers , of which 137 were e. coli and 47 were k. pneumoniae and 100 ( 35.21% ) were non - esbl producers , of which 79 were e. coli , 20 were k. pneumoniae , and one p. mirabilis [ table 4 ] . among 288 enterobacteriaceae isolates , 45 ( 15.62% ) were carbapenem - resistant enterobacteriaceae , and 123 ( 42.7% ) isolates were found to be mdre . fosfomycin sensitivity among extended spectrum beta - lactamase producers and non - extended - spectrum beta - lactamase producers among the total isolates tested for susceptibility , 337 ( 95.18% ) out of 354 were found to be fosfomycin susceptible , 95.93% of mdre [ table 5 ] and 89.13% of cre [ table 6 ] were found to be susceptible to fosfomycin ( mic range for fosfomycin was 0.25512 g / ml ) . the mic90 and mic50 of fosfomycin for enterobacteriaceae were found to be 8 and 2 g / ml , respectively . the mic90 and mic50 of fosfomycin for k. pneumoniae were found to be 8 and 2 g / ml , respectively . there was only one enterobacter with mic of 1 g / ml . fosfomycin resistance were found among 4 isolates of e. coli , 3 k. pneumoniae , 4 pseudomonas spp . , 3 a. baumannii complex , and one isolate each of m. morganii , b. cepacia , and enterococcus spp . fosfomycin is a novel antibiotic with good in vitro activity against the common pathogens causing uti , particularly toward the enterobacteriaceae . fosfomycin is active against both gram - negative and gram - positive pathogens , including entererococcus spp . fosfomycin was found to possess somewhat lower activity against staphylococcus aureus compared with other penicillins ; however , it showed powerful activity toward e. coli , klebsiella spp . , and p. mirabilis . in a study done by gupta et al . from chandigarh , among 150 uropathogenic strains of e. coli , 52.6% of isolates were esbl producers , and all strains were susceptible to fosfomycin . in another study by mittal et al . , it was found that fosfomycin was 100% sensitive to uropathogenic e. coli strains . in this present study , 95.18% isolates were susceptible to fosfomycin which is similar to the findings of a study done by sabharwal and sharma where it was found that 94.4% of the isolates causing uti were susceptible to fosfomycin . there is also a report of a person who returned to canada after hospitalization in india with a resistant metallo - beta - lactamase - producer strain who was successfully treated with ertapenem and fosfomycin . in a study done by rajenderan et al . , it was found that fosfomycin was the only antibiotic that effectively inhibited 90% of the strains of e. coli and klebsiella spp . stated that fosfomycin susceptibility was found in 83% e. coli and 90% enterococcus spp . and m. morganii is resistant to fosfomycin as shown in this study also . in our study , the susceptibility among carbapenem - resistant enterobacteriaceae was also found to be quite high , at 89.13% , which is really encouraging in the grim scenario of more commonly prescribed nephrotoxic polymyxins as the salvage therapy for these cases . following the standard definitions accepted , our study revealed about 42.7% mdre isolates . out of the total of 123 mdre isolates , which were resistant to at least three ( or more ) groups of antibiotics , 118 ( 95.93% ) were susceptible to fosfomycin . the most frequent gram - positive uropathogen encountered in our study was enterococcus spp . , which were found to be highly susceptible ( 97.72% ) to fosfomycin . these findings also corroborate to that of sultan et al . , who found that fosfomycin was effective in 100% of methicillin - resistant s. aureus , vancomycin - resistant enterococci , esbl , high - level aminoglycoside resistance , and overall , susceptibility to fosfomycin in ampc producers was also extremely high . marie et al . reported that fosfomycin and colistin were the two most effective antimicrobial agents . despite of these reports of high percentage of in vitro susceptibility of fosfomycin , it was by far an underprescribed antimicrobial agent in india as well as in many parts of the world . it is also an underrated agent for complicated uti cases though urinary concentration and safety profile is way above many other commonly prescribed antibiotics for the mdre and cre pathogens . this study was done for the evaluation of in vitro activity of fosfomycin and not a clinical evaluation of efficacy . there were very few enterobacteriaceae isolates other than e. coli and k. pneumoniae found in the study . this study was done for the evaluation of in vitro activity of fosfomycin and not a clinical evaluation of efficacy . there were very few enterobacteriaceae isolates other than e. coli and k. pneumoniae found in the study . this study was done for the evaluation of in vitro activity of fosfomycin and not a clinical evaluation of efficacy . there were very few enterobacteriaceae isolates other than e. coli and k. pneumoniae found in the study . fosfomycin is shown to have high in vitro activity against common uropathogens , including mdr isolates , esbl producers , and carbapenem - resistant enterobacteriaceae . it has a high potential to emerge as a promising and safe alternative oral agent for both outpatient and inpatient therapy of utis , particularly in countries , where its prescription habits among clinicians are scarce . however , further studies are needed to evaluate the various in vitro phenotypic and genotypic profiles of fosfomycin resistance among uropathogens .
introduction : urinary tract infection ( uti ) is one of the most common infectious diseases . with the emergence of multidrug resistance ( mdr ) , 
 therapeutic options for treatment of utis are becoming limited . 
 fosfomycin has emerged as a novel oral therapeutic option with bactericidal activity against the mdr uropathogens . 
 we evaluated the susceptibility pattern of uropathogens to this antibiotic.methods:a prospective study was conducted for 6 months in a tertiary care hospital in eastern india to evaluate whether the common uropathogens were susceptible to fosfomycin . 
 identification of organisms causing significant bacteriuria was done by conventional biochemical and vitek 2 compact system. antimicrobial susceptibility testing was performed against these pathogens by kirby - bauer disc diffusion method . 
 minimum inhibitory concentrations were measured for certain drugs by e - strips and vitek 2 compact system.results:a total of 2229 urine samples were referred for culture during the study period , which yielded 356 significant bacterial isolates . among these isolates , 64.78% were extended - spectrum beta - lactamases producers , 
 15.97% were carbapenem - resistant enterobacteriaceae , and 42.7% isolates were found to be mdr enterobacteriaceae ( mdre ) . however 
 , 95.18% of the total isolates and 95.93% of mdre were found to be susceptible to fosfomycin.conclusion:the common uropathogens , including mdr isolates , show high in vitro susceptibility to fosfomycin , which therefore has the potential to emerge as a promising alternative oral agent for outpatient therapy of utis .