Antimicrobial Susceptibility of Uropathogens in India

Urinary tract infections are among the most common bacterial infections caused by pathogens with an increasing resistance to several classes of antimicrobials including co-trimoxazole, beta-lactams, aminoglycosides, and fluoroquinolones. Our study was conducted to determine the antimicrobial susceptibility patterns of urinary isolates in Delhi and Post Graduate Institute of Medical Sciences, Rohtak, India, from 2000 to 2004. Multidrug resistance of three or more classes of antimicrobials in common uropathogens including Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa has approached 100 percent in our institute, and resistance of these pathogens to co-trimoxazole, ampicillin, and ciprofloxacin were 90 to 96 percent, 92 to 98 percent, and 55 to 65 percent, respectively. Hence, no particular group of antibiotics can be presumed to be 100 percent effective without antimicrobial susceptibility and minimal inhibitory concentration testing. Infection control policies and restriction of over-the-counter sale of antibiotics without physician prescription should be strictly followed in our country. At the same time, continuous monitoring of resistant phenotypes and surveillance studies should be carried out, and empirical treatment guidelines of urinary tract infection should be changed according to regional or institutional in vitro susceptibility data. (J Infect Dis Antimicrob Agents 2007;24:13-8.) INTRODUCTION Urinary tract infections (UTIs) are one of the most common bacterial infections in humans both in the community and hospital settings.1,2 In almost all cases, there is a need to initiate empirical antimicrobial treatment before obtaining the microbiological results. Surveillance studies provide information of the causative agents of UTIs and their antimicrobial resistance patterns which may aid clinicians in choosing the appropriate antimicrobial empirical treatment. Our study was conducted to determine the institutional antimicrobial susceptibility patterns of ampicillin, co-trimoxazole, nitrofurantoin, ciprofloxacin, norfloxacin, gentamicin, amikacin, and third-generation 14 J INFECT DIS ANTIMICROB AGENTS Jan.-Apr. 2007 cephalosporines among common uropathogens including Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa during a 5-year period from 2000 to 2004. MATERIAL AND METHODS During a 5-year period from January 2000 to December 2004, a total number of urine samples obtained from both outpatient and inpatient departments were 57,590. Patients who had significant pyuria and bacteriuria obtained from a clean-catch midstream urine were included in the microbiological analysis. Other urine specimens were excluded from the analysis. Only the first isolate of the same patient was included in the analysis. Antimicrobial susceptibility test of coliforms was determined by Kirby Bauer diffusion method with the discs (Hi-Media, Laboratories Pvt Ltd, Mumbai) containing 300g nitrofurantoin, 10g ampicillin, 25g co-trimoxazole, 10g gentamicin, 10g amikacin, 30g nalidixic acid, 10g norfloxacin, 5g ciprofloxacin, 30g cefotaxime, and 30g ceftizoxime. The discs used for susceptibility of P. aeruginosa included ciprofloxacin, gentamicin, and amikacin. Multidrug resistance (MDR) in uropathogens was defined as being resistant to three or more classes of antimicrobials. The minimal inhibitory concentration (MIC) was determined by agar dilution method on Mueller Hinton agar NCTC 10418 E. coli and NCTC 10662 were used as control strains. Forty-one isolates of E. coli and 25 K. pneumoniae were randomly selected to determine the MIC for five antibiotics including gentamicin, amikacin, nitrofurantoin, norfloxacin, and ceftriaxone with nine-dilution range (1.0 to 256 g/ml). RESULTS Of 57,590 urine specimens, 4,674 grew significant bacteria. The commonest isolate was E. coli (69.9%), followed by K. pneumoniae (25%), P. aeruginosa (0.89%), Enterococcus (0.8%), Citrobacter (0.68%), coagulase-negative Staphylococcus (0.59%), Proteus (0.4%), Staphylococcus aureus (0.19%), and Morganella (0.08%). E. coli, K. pneumoniae, and P. aeruginosa comprised 95.8 percent of all isolated uropathogens. E. coli isolates were mostly susceptible to amikacin (62-84%), followed by cefotaxime (60-72%), gentamicin (32-58%), ciprofloxacin (28-46%), norfloxacin (22-30%), ampicillin and co-trimoxazole (9.8-26%) (Table 1). Also, K. pneumoniae isolates were mostly susceptible to amikacin (36-68.2%), followed by cefotaxime, ciprofloxacin, gentamicin, norfloxacin, ampicillin, and co-trimoxazole. Most P. aeruginosa isolates were resistant to ciprofloxacin, amikacin, and gentamicin. There was generally no change of antimicrobial susceptibility patterns of these all three uropathogens from 2000 to 2004. All these three species were MDR strains. The MIC results of E. coli and K. pneumoniae are shown in Table 2. Both uropathogens were mostly susceptible to amikacin and ceftriaxone. K. pneumoniae were relatively more resistant to all antimicrobials tested, compared to E. coli. E. coli isolates were mostly susceptible to amikacin (80.4%), followed by ceftriaxone (60.9%), gentamicin (36.5%), nitrofurantoin (34.1%), and norfloxacin (19.5%). K. pneumoniae isolates were mostly susceptible to amikacin (68%), followed by ceftriaxone (60%), gentamicin (40%), nitrofurantoin (32%), and norfloxacin (16%). DISCUSSION More than 95 percent of UTIs are caused by a single bacterial species.1 Pathogens causing UTIs are almost always predictable, with E. coli the primary etiologic agent among both outpatients and inpatients.2 Infectious Diseases Society of America (IDSA) recently recommended that each hospital should establish routine mechanisms to determine the local resistance rates among uropathogens and that the Vol. 24 No. 1 15 Antimicrobial susceptibility of uropathogens:Gupta N, et al. 15 Ta bl e 1 . A nt im ic ro bi al su sc ep tib ili ty p at te rn s o f c om m on u ro pa th og en s i so la te d fr om 2 00 020 04 . A nt ib io ti cs Es ch er ic hi a co li K le bs ie lla p ne um on ia e P se ud om on as a er ug in os a 2 00 0 20 01 20 02 20 03 20 04 20 00 20 01 20 02 20 03 20 04 20 00 20 01 20 02 20 03 20 04 A m pi ci lli n (1 0 m g) 12 .6 20 24 16 12 2 3 2 9 8. 2 Co -tr im ox az ol e ( 25 m g) 9. 8 18 26 20 12 4 8 10 9 7. 3 N itr of ur an to in (3 00 m g) 41 .2 32 36 30 38 24 30 10 29 27 Ci pr of lo xa ci n (5 m g) 45 .7 28 36 46 34 48 48 44 36 .4 42 .4 33 .3 9. 1 0 66 .7 80 N al id ix ic ac id (3 0 m g) 7. 8 15 30 20 16 4 12 16 17 .3 10 .3 N or flo xa ci n (1 0 m g) 15 .7 22 30 30 24 16 22 14 16 .4 13 .3 11 .1 G en ta m ic in (1 0 m g) 49 .6 32 42 58 34 38 42 46 31 .8 33 .3 0 6. 1 8. 3 0 0 A m ik ac in (1 0 m g) 74 .5 62 74 82 84 58 57 .6 36 68 .2 63 .9 44 .4 39 .4 41 .7 40 Ce fo ta xi m e ( 30 m g) 69 .4 70 68 72 60 48 41 28 36 .4 42 .4 T ab le 2 . T he m in im al in hi bi to ry c on ce nt ra ti on ( M IC ) of E sc he ri ch ai a co li ( N = 4 1) a nd K le bs ie ll a pn eu m on ia e (N = 2 5) . A nt ib io ti c M IC b re ak po in t E sc he ri ch ia c ol i K le bs ie ll a pn eu m on ia e S us ce pt ib il it y G en ta m ic in ≤ 4 8 3 2 ≤ 1. 0 to 3 2 36 .5 1 6 6 4 ≤ 1 to 3 2 40 A m ik ac in ≤ 16 8 6 4 4. 0 to 1 28 80 .4 1 6 12 8 8 to 1 28 68 N itr of ur an to in ≤ 64 12 8 ≥ 25 6 8 to ≥ 2 56 34 .1 12 8 ≥ 25 6 16 to ≥ 2 56 32 N or fl ox ac in ≤ 8 32 12 8 4 to 1 28 19 .5 64 ≥ 25 6 4 to 1 28 16 C ef tr ia xo ne ≤ 32 32 ≥ 25 6 8 to ≥ 2 56 60 .9 32 12 8 4 to 1 28 60 M IC 50 M IC 90 M IC r an ge Su sc ep tib ili ty (% ) M IC 50 M IC 90 M IC r an ge Su sc ep tib ili ty (% ) 16 J INFECT DIS ANTIMICROB AGENTS Jan.-Apr. 2007 standard antimicrobial regimens for empiricaltreatment of UTIs should be reassessed periodicallyin light of changing susceptibility patterns. Physicianshould be aware of current antimicrobial susceptibilitypatterns for E. coli and other uropathogens in theirlocal communities as antimicrobial susceptibilitychanges over time.3 Although, IDSA does addressthe areas of MDR isolates, however our study showedthat MDR in most uropathogens isolates has alreadyreached 100 percent. Recent regional and nationalstudies in the United States have reported resistanceto co-trimoxazole among urinary isolates of E. coli tobe 20 percent to 30 percent.4-13 However, in our study,co-trimoxazole resistance ranged from 80 percent to90 percent. All these three uropathogens (E. coli, K.pneumoniae, and P. aeruginosa) in our study wereMDR isolates, thus susceptibility-based target therapyis of prime importance. In E. coli urinary isolates, acorrelation between ampicillin, co-trimoxazole, andciprofloxacin resistances has previously reported.14In addition, 80 percent of co-trimoxazole-resistant E.coli isolates were also resistant to ampicillin, but werestill susceptible to nitrofurantoin. E. coli highlyresistant to ampicillin (47.8% to 64.6%) and to co-trimoxazole (37.1% to 44.6%) has been reported fromTurkey.16 Even higher resistance rates to ampicillinand co-trimoxazole have been found in other countries,including Senegal17 (77% and 55%), Spain18 (65% and33%), Taiwan19 (80% and 50%), and Israel20 (66%and 26%). In our study, range of ampicillin resistanceis from 76 percent to 88 percent and co-trimoxazoleresistance ranges from 74 percent to 90 percentamong E. coli. In addition, among K. pneumoniae,ampicillin and co-trimoxazole resistance rates rangefrom 92 percent to 98 percent and 90 percent to 96percent, respectively. Thus, these two drugs shouldno longer be prescribed as initial empirical treatmentin our institute. Fluoroquinolones are a logical choicefor the empirical treatment of uncomplicated UTIs,however their widespread use has raised concern forincreasing fluoroquinoloneresistance15, along with co-trimoxazole and ampicillin resistances.13 The highprevalence of MDR urinary isolates may greatlyincrease the difficulty of treating UTIs in our institute.In addition, this high prevalence of MDR in ourinstitute will lead to the need for continuing surviellenceto determine the susceptibility patterns among urinaryisolates, which may aid clinicians in choosing theappropriate antimicrobial treatment of UTIs.In our study, most of the UTIs caused by P.aeruginosa were resistant to beta-lactams, amino-glycosides, and fluoroquinolones. Higher resistancerates to all antibiotics tested in our study may beexplained by high and uncontrolled consumption ofthese antibiotics during the past decade in our institute.All antimicrobials are available as over-the-counterdrugs without requiring the doctor prescriptions in ourcountry. A good infection control and antibiotic policywill certainly help in delaying the era of unabatedmicroorganisms for which no antibiotic is going to beeffective.Our study has some limitations includingincomplete susceptibility testing for all antimicrobialsused to treat UTIs caused by E. coli, K. pneumoniae,and P. aeruginosa; no testing for the presence ofextended-spectrum beta-lactamases among E. coliand K. pneumoniae; and incomplete data for someantimicrobial susceptibility among P. aeruginosa. References1. Winstanley TG, Limb DI, Eggington R, Hancock F. A10-year survey of the antimicrobial susceptibility ofurinary tract isolates in the UK: the Microbe Baseproject. 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