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Co-trimoxazole and quinolone resistance in Escherichia coli isolated from urinary tract infections over the last 10 years
International Journal of Antimicrobial Agents 26 (2005) 75–77
Co-trimoxazole and quinolone resistance in Escherichia coli isolated from urinary tract infections over the last 10 years Yılmaz Karaca, Nilay Coplu ∗ , Ayseg¨ul Gozalan, Ozgur Oncul, Burak E. Citil, Berrin Esen Refik Saydam National Hygiene Center, Communicable Diseases Research Department, Sihhiye, 06100 Ankara, Turkey Received 11 February 2005; accepted 31 March 2005
Abstract Over the last 10 years the treatment of choice for urinary tract infections (UTIs) in Turkey has changed from co-trimoxazole to quinolones owing to the rate of resistance to co-trimoxazole and its high level of therapeutic failure. The resistance ratio of 1939 UTI Escherichia coli from outpatients (1994–2003) was evaluated by Kirby–Bauer disc diffusion method for the aforementioned antibiotics to determine the change in resistance. The co-trimoxazole resistance ratio decreased during this period, with the highest ratio in 1996 (69.3%) and the lowest ratio in 2003 (38.5%) (P < 0.001). The lowest resistance ratios occurred in 1995 (4.1%) for ofloxacin and in 1996 (5.2%) for ciprofloxacin, and the highest resistance ratios occurred in 2002 (25.3% and 27.6%) for ofloxacin and ciprofloxacin, respectively (P < 0.001, P < 0.001). These findings emphasise that antibiotic usage policies, especially empirical therapies, should be based on antimicrobial resistance surveillance studies. © 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. Keywords: Co-trimoxazole; Quinolone; E. coli; Drug resistance microbial
1. Introduction Urinary tract infection (UTI) is one of the most common infectious diseases diagnosed in outpatients and also constitutes the most common nosocomial infection in many hospitals, accounting for up to 35% of all hospital-acquired infections [1]. Escherichia coli remains the principal causative pathogen of UTIs both in outpatients and inpatients [2,3]. The antimicrobial susceptibility of urinary pathogens has been changing over the years and is influenced by such factors as the changing patient population and the extensive use and misuse of antimicrobial agents, which contribute to alterations in the microbial profile of urinary tract isolates [1]. Co-trimoxazole was frequently the treatment of choice for UTIs as well as other outpatient infections from the early 1980s to the 1990s in Turkey. Increased co-trimoxazole resistance rates led to its therapeutic failure and subsequent ∗
Corresponding author. Tel.: +90 312 435 56 80; fax: +90 312 435 35 46. E-mail address: [email protected] (N. Coplu).
limited usage. Consequently, quinolones became the first choice in empirical treatment and their widespread use has also resulted in a rise in their resistance rate. The goal of this study was to assess the activity of relevant antibiotics against E. coli strains of urinary tract isolates from outpatients at Refik Saydam National Hygiene Center Laboratory during the period in which co-trimoxazole was replaced by quinolones as the most frequently used antibiotics.
2. Materials and methods The 1939 E. coli isolated between 1994 and 2003 were evaluated for their antibiotic resistance ratio. The number of strains studied were 1644, 1565 and 1277 for co-trimoxazole, ofloxacin and ciprofloxacin, respectively; there were no data for ciprofloxacin in 1995. Isolated bacteria were identified by standard laboratory techniques, and antibiotic susceptibility tests were performed by Kirby–Bauer disc diffusion method according to the National Committee for Clinical Laboratory
0924-8579/$ – see front matter © 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/j.ijantimicag.2005.03.012
76
Y. Karaca et al. / International Journal of Antimicrobial Agents 26 (2005) 75–77
Standards (NCCLS) criteria [4,5]. For this purpose, inoculum of McFarland 0.5 opacity was applied to a Mueller–Hinton agar plate. Co-trimoxazole, ofloxacin and ciprofloxacin discs (Becton Dickinson, MD) were added after the plates had completely dried and they were incubated at 35 ◦ C in ambient air overnight. Following interpretation, the strains were evaluated as susceptible or resistant, with the intermediate group being considered resistant. The data were studied by SPSS 10.0 statistical program, identified by percentage, and analysed by Chi-square (χ2 ) test.
3. Results The distribution of the resistance ratios of the studied antibiotics by year is shown in Fig. 1. The ratio for cotrimoxazole resistance showed high levels at the beginning of the period, with a peak in 1996 (69.3%), and then decreased to the minimum level in 2003 (38.5%). This reduction in resistance ratio is statistically significant (P < 0.001). Quinolones showed an opposite distribution, with the lowest resistance ratio occurring in 1995 (4.1%) and 1996 (5.2%) for ofloxacin and ciprofloxacin, respectively. The resistance ratio increased over the years, showing the highest ratio in 2002 of 25.3% and 27.6% for ofloxacin and ciprofloxacin, respectively, with a statistically significant difference (P < 0.001, P < 0.001).
4. Discussion In the field of UTIs there has been a steady increase in the level of resistance to commonly used antibiotics, including co-trimoxazole, as well as reports of emerging resistance to quinolones in some countries [6]. Both cotrimoxazole and quinolones began to be used in the early 1980s [7]. In Turkey, co-trimoxazole was used extensively and the increasing resistance ratio resulted in therapeutic failure. Therefore, clinicians decreased its use and quinolones became the treatment drug of choice. It is thought that the reduction in co-trimoxazole resistance ratio from 69.8% to 38.5% during the study period is a consequence of this reduced rate of use. Evaluation of other studies of cotrimoxazole resistance in Turkey during the same period are in accordance with our findings, with resistance ratios of more than 50–60% at the beginning of the 1990s reducing to 30–44% in the early 2000s [8–15]. After quinolones became the first choice for empirical therapy of UTIs, their subsequent overuse was reflected in an increase in the resistance ratio both of ofloxacin and ciprofloxacin. In addition, it was reported that short-term treatment with quinolones for UTI and/or the low-dose use of more potent compounds, such as ciprofloxacin, may result in selection of mutant isolates [1]. These factors are valid in Turkey and might have additionally influenced the rise of quinolone resistance found in this study. Alarmingly, other studies in Turkey show similar results for quinolones, with a resistance ratio of less than 10%
Fig. 1. The resistance ratio, including intermediate ratio, of ciprofloxacin, ofloxacin and co-trimoxazole by year from 1994 to 2003.
Y. Karaca et al. / International Journal of Antimicrobial Agents 26 (2005) 75–77
during the 1990s and increasing up to 37% in the 2000s [8–15]. The resistance rates for co-trimoxazole and quinolones vary from one country to another and depend upon local epidemiological factors, yet many other regions in addition to Turkey can no longer consider co-trimoxazole a firstline drug for empirical treatment of clinically evident UTI [1,16,17]. Co-trimoxazole resistance ratios ranged between 15% and 45% in reports from Israel, Europe, Canada, the USA and Latin America in 2000, and its extensive use has been demonstrated to be a major contributor to resistance among urinary pathogens [2,3,6,18,19]. In some reports from the USA and Europe, it is said that if co-trimoxazole resistance is >10–20% it may be replaced by alternative therapies such as fluoroquinolones or nitrofurantoin [19,20]. Quinolones are generally effective in the USA, Canada and France, with >95% susceptibility in some reports published in 2000 [1,18]. Meanwhile, a dramatic increase in the prevalence of quinolone resistance has been reported from some European countries [1,17,21]. In an international survey of the antimicrobial susceptibility of pathogens from uncomplicated UTIs, called the ECO.SENS Project, the resistance ratio for quinolones in some parts of Europe was found to be less than 3%, but in Spain, Portugal and Luxembourg it was 14.7%, 5.8% and 4.2%, respectively, and this increase is worthy of close attention [6,22]. In conclusion, the results presented in this study indicate that it is time to reconsider the empirical use of quinolones and to develop clear strategies to counteract the development of further resistance. Furthermore, it should be generally emphasised that the establishment of antimicrobial resistance surveillance systems appears to be an important step in detecting the emergence of resistance patterns, helping in the selection of the most efficacious empirical therapy at the local level, and supporting the implementation of preventive measures.
References [1] Gales AC, Jones RN, Gordon KA, et al. Activity and spectrum of 22 antimicrobial agents tested against urinary tract infection pathogens in hospitalized patients in Latin America: report from the second years of the SENTRY Antimicrobial Surveillance Program. J Antimicrob Chemother 2000;45:295–303. [2] Zhanel GG, Karlowsky JA, Harding GK, et al. A Canadian national surveillance study of urinary tract isolates from outpatients: comparison of the activities of trimethoprim–sulfamethoxazole, ampicillin, mecillinam, nitrofurantoin and ciprofloxacin. The Canadian urinary isolate study group. Antimicrob Agents Chemother 2000;44:1089–92. [3] Farrell DJ, Morrissey I, De Rubies D, Robbins M, Felmingham D. A UK multicenter study of the antimicrobial susceptibility of bacterial pathogens causing urinary tract infection. J Infect 2003;46:94–100.
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[4] Koneman EW, Allen SD, Janda WM, Schreckenberger PC, Winn WC. Color atlas and textbook of diagnostic microbiology. 5th ed. Lippincott-Raven Publishers; 1997. [5] National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial disk susceptibility tests, approved standard. 5th ed. (M2-A5). NCCLS; 1993. [6] Kahlmeter G. An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO.SENS Project. J Antimicrob Chemother 2003;51:69–76. [7] Kucers A, Crowe SM, Grayson ML, Hoy JF. The use of antibiotics: a clinical review of antibacterial, antifungal and antiviral drugs. 5th ed. Oxford, Boston, Johannesburg, Melbourne, New Delhi, Singapore: Butterworth Heinemann; 1997. p. 836–63, 965–1121. [8] Kılıc¸ H, Karahan M. The in vitro sensitivity of the Gram negative bacteria isolated from urinary tract infections for various antibiotics. Mikrobiyol Bul 1991;1:28–35. [9] Ozhan M, Aksoy AM, Karaarslan A. In vitro susceptibility of Escherichia coli strains isolated from urinary tract infections to various antibiotics. Turk Mikrobiyol Cem Derg 1993;23:142–4. [10] Yorgancıgil B, Aydemir M. Bacteria isolated from urinary tract infections and susceptibilities to various antibiotics. 10th Antibiotic and Chemotherapy Congress; Antalya. Ankem Derg 1995;2:120. [11] Altındis M, Tanır HM. Microbiological evaluation of urine samples taken from patients with urinary tract infection symptoms and susceptibilities to various antibiotics against of the Gram-negative microorganisms isolated from those women. Turk Mikrobiyol Cem Derg 2001;3–4:192–7. [12] Tolun V, Akbulut-Torumkuney D, Catal C, Turan N, Ang-Kucuker M, Ang O. The antibiotic susceptibilities of Gram negative rods isolated as causative agents of urinary tract infections from in- and outpatients. Turk Mikrobiyol Cem Derg 2002;32:69–74. [13] Akan OA, Yildiz E, Uysal S. The antibiotic resistance and the effect of hospitalisation in antibiotic resistance in urinary tract Escherichia coli isolates. In: Proceedings of the 6th Antimicrobic Chemotherapy Days Clinical-Laboratory Practice and Reforms, P10. Istanbul, Turkey; 8–10 April 2004. [14] Ay S, Iseri LA, Duman B. The antibiotic susceptibility of Gram negative microorganisms isolated from urine samples. Inonu Univ Tip Fak Derg 2003;10:59–62. [15] Kibar F, Yaman A, Dundar IH. The bacteria isolated from urinary samples and their antibiotic susceptibilities. Turk Mikrobiol Cem Derg 2004;34:162–70. [16] Colodner R, Keness Y, Chazan B, Raz R. Antimicrobial susceptibility of community-acquired uropathogens in northern Israel. Int J Antimicrob Agents 2001;18:189–92. [17] Farra A, Skoog G, Wallen L, et al. Antibiotic use and Escherichia coli resistance trends for quinolones and co-trimoxazole in Sweden. Scand J Infect Dis 2002;34:449–55. [18] Chomarat M. Resistance of bacteria in urinary tract infections. Int J Antimicrob Agents 2000;16:483–7. [19] Talan DA, Naber KG, Palou J, Elkharrat D. Extended-release ciprofloxacin (Cipro XR) for treatment of urinary tract infections. Int J Antimicrob Agents 2004;23(Suppl. 1):S54–66. [20] Karlowsky JA, Thornsberry C, Jones ME, Sahm DF. Susceptibility of antimicrobial-resistant urinary Escherichia coli isolates to fluoroquinolones and nitrofurantoin. Clin Infect Dis 2003;36:183–7. [21] Talon D, Lallemand-De-Conto S, Thouverez M, Bertrand X. E. coli: resistance to quinolones and beta-lactams of clinical strains isolated in the Franche-Comte region of France. Pathol Biol 2004;52:76–81. [22] Kahlmeter G. Prevalence and antimicrobial susceptibility of pathogens in uncomplicated cystitis in Europe. The ECO.SENS study. Int J Antimicrob Agents 2003;22:49–52.
Co-trimoxazole and quinolone resistance in Escherichia coli isolated from urinary tract infections over the last 10 years Yılmaz Karaca, Nilay Coplu ∗ , Ayseg¨ul Gozalan, Ozgur Oncul, Burak E. Citil, Berrin Esen Refik Saydam National Hygiene Center, Communicable Diseases Research Department, Sihhiye, 06100 Ankara, Turkey Received 11 February 2005; accepted 31 March 2005
Abstract Over the last 10 years the treatment of choice for urinary tract infections (UTIs) in Turkey has changed from co-trimoxazole to quinolones owing to the rate of resistance to co-trimoxazole and its high level of therapeutic failure. The resistance ratio of 1939 UTI Escherichia coli from outpatients (1994–2003) was evaluated by Kirby–Bauer disc diffusion method for the aforementioned antibiotics to determine the change in resistance. The co-trimoxazole resistance ratio decreased during this period, with the highest ratio in 1996 (69.3%) and the lowest ratio in 2003 (38.5%) (P < 0.001). The lowest resistance ratios occurred in 1995 (4.1%) for ofloxacin and in 1996 (5.2%) for ciprofloxacin, and the highest resistance ratios occurred in 2002 (25.3% and 27.6%) for ofloxacin and ciprofloxacin, respectively (P < 0.001, P < 0.001). These findings emphasise that antibiotic usage policies, especially empirical therapies, should be based on antimicrobial resistance surveillance studies. © 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. Keywords: Co-trimoxazole; Quinolone; E. coli; Drug resistance microbial
1. Introduction Urinary tract infection (UTI) is one of the most common infectious diseases diagnosed in outpatients and also constitutes the most common nosocomial infection in many hospitals, accounting for up to 35% of all hospital-acquired infections [1]. Escherichia coli remains the principal causative pathogen of UTIs both in outpatients and inpatients [2,3]. The antimicrobial susceptibility of urinary pathogens has been changing over the years and is influenced by such factors as the changing patient population and the extensive use and misuse of antimicrobial agents, which contribute to alterations in the microbial profile of urinary tract isolates [1]. Co-trimoxazole was frequently the treatment of choice for UTIs as well as other outpatient infections from the early 1980s to the 1990s in Turkey. Increased co-trimoxazole resistance rates led to its therapeutic failure and subsequent ∗
Corresponding author. Tel.: +90 312 435 56 80; fax: +90 312 435 35 46. E-mail address: [email protected] (N. Coplu).
limited usage. Consequently, quinolones became the first choice in empirical treatment and their widespread use has also resulted in a rise in their resistance rate. The goal of this study was to assess the activity of relevant antibiotics against E. coli strains of urinary tract isolates from outpatients at Refik Saydam National Hygiene Center Laboratory during the period in which co-trimoxazole was replaced by quinolones as the most frequently used antibiotics.
2. Materials and methods The 1939 E. coli isolated between 1994 and 2003 were evaluated for their antibiotic resistance ratio. The number of strains studied were 1644, 1565 and 1277 for co-trimoxazole, ofloxacin and ciprofloxacin, respectively; there were no data for ciprofloxacin in 1995. Isolated bacteria were identified by standard laboratory techniques, and antibiotic susceptibility tests were performed by Kirby–Bauer disc diffusion method according to the National Committee for Clinical Laboratory
0924-8579/$ – see front matter © 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/j.ijantimicag.2005.03.012
76
Y. Karaca et al. / International Journal of Antimicrobial Agents 26 (2005) 75–77
Standards (NCCLS) criteria [4,5]. For this purpose, inoculum of McFarland 0.5 opacity was applied to a Mueller–Hinton agar plate. Co-trimoxazole, ofloxacin and ciprofloxacin discs (Becton Dickinson, MD) were added after the plates had completely dried and they were incubated at 35 ◦ C in ambient air overnight. Following interpretation, the strains were evaluated as susceptible or resistant, with the intermediate group being considered resistant. The data were studied by SPSS 10.0 statistical program, identified by percentage, and analysed by Chi-square (χ2 ) test.
3. Results The distribution of the resistance ratios of the studied antibiotics by year is shown in Fig. 1. The ratio for cotrimoxazole resistance showed high levels at the beginning of the period, with a peak in 1996 (69.3%), and then decreased to the minimum level in 2003 (38.5%). This reduction in resistance ratio is statistically significant (P < 0.001). Quinolones showed an opposite distribution, with the lowest resistance ratio occurring in 1995 (4.1%) and 1996 (5.2%) for ofloxacin and ciprofloxacin, respectively. The resistance ratio increased over the years, showing the highest ratio in 2002 of 25.3% and 27.6% for ofloxacin and ciprofloxacin, respectively, with a statistically significant difference (P < 0.001, P < 0.001).
4. Discussion In the field of UTIs there has been a steady increase in the level of resistance to commonly used antibiotics, including co-trimoxazole, as well as reports of emerging resistance to quinolones in some countries [6]. Both cotrimoxazole and quinolones began to be used in the early 1980s [7]. In Turkey, co-trimoxazole was used extensively and the increasing resistance ratio resulted in therapeutic failure. Therefore, clinicians decreased its use and quinolones became the treatment drug of choice. It is thought that the reduction in co-trimoxazole resistance ratio from 69.8% to 38.5% during the study period is a consequence of this reduced rate of use. Evaluation of other studies of cotrimoxazole resistance in Turkey during the same period are in accordance with our findings, with resistance ratios of more than 50–60% at the beginning of the 1990s reducing to 30–44% in the early 2000s [8–15]. After quinolones became the first choice for empirical therapy of UTIs, their subsequent overuse was reflected in an increase in the resistance ratio both of ofloxacin and ciprofloxacin. In addition, it was reported that short-term treatment with quinolones for UTI and/or the low-dose use of more potent compounds, such as ciprofloxacin, may result in selection of mutant isolates [1]. These factors are valid in Turkey and might have additionally influenced the rise of quinolone resistance found in this study. Alarmingly, other studies in Turkey show similar results for quinolones, with a resistance ratio of less than 10%
Fig. 1. The resistance ratio, including intermediate ratio, of ciprofloxacin, ofloxacin and co-trimoxazole by year from 1994 to 2003.
Y. Karaca et al. / International Journal of Antimicrobial Agents 26 (2005) 75–77
during the 1990s and increasing up to 37% in the 2000s [8–15]. The resistance rates for co-trimoxazole and quinolones vary from one country to another and depend upon local epidemiological factors, yet many other regions in addition to Turkey can no longer consider co-trimoxazole a firstline drug for empirical treatment of clinically evident UTI [1,16,17]. Co-trimoxazole resistance ratios ranged between 15% and 45% in reports from Israel, Europe, Canada, the USA and Latin America in 2000, and its extensive use has been demonstrated to be a major contributor to resistance among urinary pathogens [2,3,6,18,19]. In some reports from the USA and Europe, it is said that if co-trimoxazole resistance is >10–20% it may be replaced by alternative therapies such as fluoroquinolones or nitrofurantoin [19,20]. Quinolones are generally effective in the USA, Canada and France, with >95% susceptibility in some reports published in 2000 [1,18]. Meanwhile, a dramatic increase in the prevalence of quinolone resistance has been reported from some European countries [1,17,21]. In an international survey of the antimicrobial susceptibility of pathogens from uncomplicated UTIs, called the ECO.SENS Project, the resistance ratio for quinolones in some parts of Europe was found to be less than 3%, but in Spain, Portugal and Luxembourg it was 14.7%, 5.8% and 4.2%, respectively, and this increase is worthy of close attention [6,22]. In conclusion, the results presented in this study indicate that it is time to reconsider the empirical use of quinolones and to develop clear strategies to counteract the development of further resistance. Furthermore, it should be generally emphasised that the establishment of antimicrobial resistance surveillance systems appears to be an important step in detecting the emergence of resistance patterns, helping in the selection of the most efficacious empirical therapy at the local level, and supporting the implementation of preventive measures.
References [1] Gales AC, Jones RN, Gordon KA, et al. Activity and spectrum of 22 antimicrobial agents tested against urinary tract infection pathogens in hospitalized patients in Latin America: report from the second years of the SENTRY Antimicrobial Surveillance Program. J Antimicrob Chemother 2000;45:295–303. [2] Zhanel GG, Karlowsky JA, Harding GK, et al. A Canadian national surveillance study of urinary tract isolates from outpatients: comparison of the activities of trimethoprim–sulfamethoxazole, ampicillin, mecillinam, nitrofurantoin and ciprofloxacin. The Canadian urinary isolate study group. Antimicrob Agents Chemother 2000;44:1089–92. [3] Farrell DJ, Morrissey I, De Rubies D, Robbins M, Felmingham D. A UK multicenter study of the antimicrobial susceptibility of bacterial pathogens causing urinary tract infection. J Infect 2003;46:94–100.
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[4] Koneman EW, Allen SD, Janda WM, Schreckenberger PC, Winn WC. Color atlas and textbook of diagnostic microbiology. 5th ed. Lippincott-Raven Publishers; 1997. [5] National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial disk susceptibility tests, approved standard. 5th ed. (M2-A5). NCCLS; 1993. [6] Kahlmeter G. An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO.SENS Project. J Antimicrob Chemother 2003;51:69–76. [7] Kucers A, Crowe SM, Grayson ML, Hoy JF. The use of antibiotics: a clinical review of antibacterial, antifungal and antiviral drugs. 5th ed. Oxford, Boston, Johannesburg, Melbourne, New Delhi, Singapore: Butterworth Heinemann; 1997. p. 836–63, 965–1121. [8] Kılıc¸ H, Karahan M. The in vitro sensitivity of the Gram negative bacteria isolated from urinary tract infections for various antibiotics. Mikrobiyol Bul 1991;1:28–35. [9] Ozhan M, Aksoy AM, Karaarslan A. In vitro susceptibility of Escherichia coli strains isolated from urinary tract infections to various antibiotics. Turk Mikrobiyol Cem Derg 1993;23:142–4. [10] Yorgancıgil B, Aydemir M. Bacteria isolated from urinary tract infections and susceptibilities to various antibiotics. 10th Antibiotic and Chemotherapy Congress; Antalya. Ankem Derg 1995;2:120. [11] Altındis M, Tanır HM. Microbiological evaluation of urine samples taken from patients with urinary tract infection symptoms and susceptibilities to various antibiotics against of the Gram-negative microorganisms isolated from those women. Turk Mikrobiyol Cem Derg 2001;3–4:192–7. [12] Tolun V, Akbulut-Torumkuney D, Catal C, Turan N, Ang-Kucuker M, Ang O. The antibiotic susceptibilities of Gram negative rods isolated as causative agents of urinary tract infections from in- and outpatients. Turk Mikrobiyol Cem Derg 2002;32:69–74. [13] Akan OA, Yildiz E, Uysal S. The antibiotic resistance and the effect of hospitalisation in antibiotic resistance in urinary tract Escherichia coli isolates. In: Proceedings of the 6th Antimicrobic Chemotherapy Days Clinical-Laboratory Practice and Reforms, P10. Istanbul, Turkey; 8–10 April 2004. [14] Ay S, Iseri LA, Duman B. The antibiotic susceptibility of Gram negative microorganisms isolated from urine samples. Inonu Univ Tip Fak Derg 2003;10:59–62. [15] Kibar F, Yaman A, Dundar IH. The bacteria isolated from urinary samples and their antibiotic susceptibilities. Turk Mikrobiol Cem Derg 2004;34:162–70. [16] Colodner R, Keness Y, Chazan B, Raz R. Antimicrobial susceptibility of community-acquired uropathogens in northern Israel. Int J Antimicrob Agents 2001;18:189–92. [17] Farra A, Skoog G, Wallen L, et al. Antibiotic use and Escherichia coli resistance trends for quinolones and co-trimoxazole in Sweden. Scand J Infect Dis 2002;34:449–55. [18] Chomarat M. Resistance of bacteria in urinary tract infections. Int J Antimicrob Agents 2000;16:483–7. [19] Talan DA, Naber KG, Palou J, Elkharrat D. Extended-release ciprofloxacin (Cipro XR) for treatment of urinary tract infections. Int J Antimicrob Agents 2004;23(Suppl. 1):S54–66. [20] Karlowsky JA, Thornsberry C, Jones ME, Sahm DF. Susceptibility of antimicrobial-resistant urinary Escherichia coli isolates to fluoroquinolones and nitrofurantoin. Clin Infect Dis 2003;36:183–7. [21] Talon D, Lallemand-De-Conto S, Thouverez M, Bertrand X. E. coli: resistance to quinolones and beta-lactams of clinical strains isolated in the Franche-Comte region of France. Pathol Biol 2004;52:76–81. [22] Kahlmeter G. Prevalence and antimicrobial susceptibility of pathogens in uncomplicated cystitis in Europe. The ECO.SENS study. Int J Antimicrob Agents 2003;22:49–52.