Increasing Resistance in Community-Acquired Urinary Tract Infections in Latin America, Five Years After the Implementation of Na
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International Journal of Infectious Diseases 14 (2010) e770–e774 Contents lists available at ScienceDirect International Journal of Infectious Diseases journal homepage: www.elsevier.com/locate/ijid Increasing resistance in community-acquired urinary tract infections in Latin America, five years after the implementation of national therapeutic guidelines P.H.A. Bours a,1,*, R. Polak a,1, A.I.M. Hoepelman a, E. Delgado b, A. Jarquin b, A.J. Matute b a Department of Internal Medicine and Infectious Diseases, University Medical Center, PO Box 85500, Room F.02.126, 3508 GA Utrecht, the Netherlands b Department of Medicine, University Hospital, Universidad Nacional Auto´noma de Nicaragua (UNAN), Leo´n, Nicaragua ARTICLE INFO SUMMARY Article history: Background: The worldwide increasing resistance to antibiotics has complicated antimicrobial treatment Received 3 October 2009 of urinary tract infections (UTIs), especially in Latin America. This study aimed to report the present Accepted 25 February 2010 etiology and antimicrobial susceptibility of UTIs, and the effects of the national guidelines for UTIs introduced in 2003. Corresponding Editor: William Cameron, Methods: Urine samples were collected from 304 patients with a clinical suspicion of UTI at the Ottawa, Canada university hospital and primary health centers of Leo´ n, Nicaragua. When bacterial growth was reported, antimicrobial susceptibility tests for nine frequently used antibiotics were performed. Results: Ninety-one (29.9%) patients had a positive urine culture. The most frequently isolated Keywords: microorganisms were Escherichia coli (n = 44), Serratia spp (n = 11), and Escherichia fergusonii (n = 10). Urinary tract infections Resistance High resistance rates were observed in E. coli to ampicillin (61.4%), cefalothin (45.5%), trimethoprim– Antibiotics sulfamethoxazole (38.6%), ciprofloxacin (31.8%), and ceftriaxone (20.5%). Amikacin and nitrofurantoin Extended-spectrum beta-lactamase were the only drugs to which >90% of E. coli were susceptible. E. fergusonii and Serratia spp showed Epidemiology comparable high resistance patterns. Thirteen strains (29.5%) of E. coli were suspected to produce extended-spectrum beta-lactamase (ESBL). Conclusions: Resistance rates in community-acquired UTIs in Nicaragua are increasing. The introduction of therapeutic guidelines with ceftriaxone recommended for upper UTIs and nitrofurantoin for lower UTIs, has led to increasing resistance against both antibiotics. The emergence of ESBL-producing E. coli is worrisome, along with the appearance of Serratia spp in the population. ß 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. 1. Introduction regions and studies.1–7 In 2003 Matute et al., in the first large national prevalence study concerning patients with a symptomatic A high prevalence of symptomatic urinary tract infections UTI, showed that E. coli (56%), Klebsiella spp, (18%) and Enterobacter (UTIs) combined with high resistance rates to fluoroquinolones spp (11%) were the most commonly isolated uropathogens in and beta-lactam antibiotics is one of the greatest problems in the Nicaragua. health systems of Latin American countries.1–3 Globally, the clinical management of UTIs has been In the USA, epidemiological research estimates an incidence of 8 hampered by increasing resistance rates to frequently used million cases of UTI per year. Annually, this corresponds to a 10.8% antibiotics.5–7 In particular, in Latin American countries risk of a UTI for women aged 18 years and over. Consequently, where unregulated prescription of antibiotics is more likely, women have a lifetime risk of almost 50% of suffering a UTI, for the resistance patterns of frequently observed uropathogens which antimicrobial therapy is needed. In Latin American are alarming.1–3 Considering these patterns of high resistance, countries this problem appears to be even more severe.1–3 well chosen antibiotic prescription and usage will reduce the Escherichia coli is the most frequently isolated uropathogen in disease burden of UTIs and thereby lower its consequences and symptomatic UTIs worldwide. The prevalence of other isolated costs.8,9 uropathogens, such as Staphylococcus saprophyticus, Klebsiella spp, The main objective of this study was to gain an insight into the Proteus mirabilis, Serratia spp, and Enterobacter spp, varies between present situation regarding the etiology and antimicrobial susceptibility of uropathogens in Nicaragua. The secondary objective was to analyze the effects of the implementation of 1 * Corresponding author. Tel.: +31 338501281. national guidelines in 2003. These national guidelines were E-mail address: [email protected] (P.H.A. Bours). introduced to manage symptomatic UTIs in primary and secondary 1 P.H.A. Bours and R. Polak contributed equally to this work. care units in Leo´ n. 1201-9712/$36.00 – see front matter ß 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2010.02.2264 P.H.A. Bours et al. / International Journal of Infectious Diseases 14 (2010) e770–e774 e771 2. Patients and methods and area of residence). Additionally, a physical examination was performed. 2.1. Study design All included patients provided a midstream urine sample which was cultivated at 36 8C for 18–24 h on blood and MacConkey agars. The authors conducted a cross-sectional study between August When bacterial growth of a uropathogen occurred, disk diffusion 2007 and September 2008 in which 304 patients attending the tests were performed using the Kirby–Bauer method and the university hospital (Hospital Escuela Oscar Danilo Rosales Clinical and Laboratory Standards Institute (CLSI) criteria.12,13 Argu¨ ello; HEODRA) and the primary health centers (PHC) of Leo´ n, Significant bacterial infection was defined as the growth of 105 Nicaragua were included. colony forming units (CFU)/ml of a single species cultured from Symptomatic patients were included if they had at least two of urine 12. Resistance rates to the following antibiotics were the following inclusion criteria: dysuria, urgency, frequency, fever, examined: ampicillin, amoxicillin–clavulanate, cefalothin, cipro- chills, flank pain, nausea or vomiting, suprapubic sensitivity, use of floxacin, ceftriaxone, gentamicin, trimethoprim–sulfamethoxazole a Foley catheter, and fever without apparent focus. Patients who (TMP–SMX), nitrofurantoin, and amikacin. Resistance tests for had used antibiotics within the last 7 days were excluded. uropathogens other than Enterobacteriaceae were performed Recruitment of patients was carried out at four PHCs throughout according to CLSI guidelines 13. Non-susceptibility to the third- the urban region of Leo´ n and from the gynecology, pediatrics, and generation cephalosporin ceftriaxone was used as an indicator of internal medicine wards and the emergency rooms of HEODRA. extended-spectrum beta-lactamase (ESBL) production 13. UTIs were classified as complicated or uncomplicated according to a modification of the Infectious Diseases Society of America 2.3. Statistical analysis (IDSA) guidelines. An uncomplicated form of UTI occurs in women with a normal renal tract and function, who are not in the Differences between groups were tested using the Chi-square menopause, and who are over 12 years of age. Complicated UTIs test (or Fisher’s exact test when expected frequencies were too are those in pregnant women, male patients, and patients with an low), with the assumed level of statistical significance at a p-value abnormal renal tract, impaired renal function, impaired host of <0.05. Data analysis was performed with SPSS version 15.0 for defenses, or a catheter.4,10,11 Based upon the anatomy of the Windows (SPSS Inc., Chicago, IL, USA). urinary tract, infections were classified as lower (cystitis and urethritis) or upper (pyelonephritis) UTIs. 3. Results 2.2. Measurements 3.1. Study population All patients with a suspected UTI completed a questionnaire on In total we acquired valid data for 304 study subjects (Table 1). clinical symptoms and potential risk factors (e.g., diabetes mellitus, Ninety-one patients (29.9%) had a positive urine culture. The chronic obstructive pulmonary disease (COPD), chronic renal majority of the positive samples (75.8%) were collected from insufficiency, cancer, congenital abnormalities of the urinary tract, female patients. Sixteen percent of the patients with a demon- nephrolithiasis, pregnancy, use of a Foley catheter in the last 3 strated UTI had signs and symptoms of pyelonephritis. days, and previous UTI) and demographic data (e.g., age, gender, The most frequently isolated microorganisms for uncomplicat- ed and complicated UTI were successively E. coli (n = 44; 48.8%), Serratia spp (n = 11; 12.1%), and Escherichia fergusonii (n = 10; Table 1 Patient characteristics (N = 304) 11.0%) (Table 2). Seventy-five (80.2%) patients with a positive culture were No UTI (n = 213) UTI (n = 91) classified as having a complicated UTI.10 Of those with positive Age, mean (SD) years 20.81 (22.14) 31.81 (29.88) urine cultures, only eight (8.8%) patients were hospitalized more Age groups, years than 48 h before urine sampling. The following pathogens were <12 117 (54.9) 35 (38.5) 13–50 63 (29.6) 23 (25.3) cultured from these eight patients: four E. coli, two Cedecea davisae, >51 30 (14.1) 30 (33.0) one Acinetobacter spp, and one Enterobacter spp. Females 139 (65.3) 69 (75.8) Hospitalization >48 h 15 (7.0) 8 (8.8) 3.2. Antimicrobial resistance Location