Urinary tract infections (UTI) represent a common problem in primary care consultations.1 Uncomplicated community-acquired cystitis is caused by Escherichia coli in approximately 90% of cases.2 The current management of acute uncomplicated cystitis is usually empirical, with neither urine cultures or susceptibility testing being used to guide therapy. Thus, empirical treatment in UTIs should cover E. coli. Resistance of this bacterium to amoxicillin and clavulanic acid and quinolones, albeit variable, is increasing in Spain and may lead to clinical failure.3 The aim of this study was to evaluate the non-susceptibility of Escherichia coli to five commonly prescribed antibiotics in 2006 and 2009.A retrospective analysis of susceptibility towards five antimicrobial agents (amoxicillin and clavulanic acid, cefuroxime, third generation cephalosporins – expressed as percentage of extended-spectrum β-lactamases – ciprofloxacin, trimethoprim and sulfamethoxazole, and fosfomycin) among E. coli strains was carried out in urine cultures requested in 2006 and 2009 by primary care physicians, microbiologists and doctors working in the hospital setting. The susceptibility to these antibiotics was determined using automatic microdilution systems – Microscan (Baxter), Wider (Soria-Melguizo), Vitek (Bio-Mérieux) and Phoenix (Bekton-Dickinson) and/or disc-plates. The participating centres were the Hospital of Basurto (Bilbao), Bon Pastor laboratory (Barcelona), Hospital of Donostia (San Sebastián), Instituto Navarro de Salud (Pamplona), Hospital Puerta de Hierro (Madrid), Hospital General de Segovia (Segovia), Hospital Virgen de la Macarena (Sevilla), Hospital Royo Villanova (Zaragoza). Urine cultures were heterogeneous, despite most being from the community setting (mainly young women with uncomplicated cystitis). Only in Hospital Royo Villanova, more than half of the cultures corresponded to complicated UTIs in elderly men. In the Bon Pastor laboratory, however, all the urine cultures were requested by primary care physicians and the data from 2010 are presented instead of those of 2009. A descriptive analysis was carried out with the global results of the susceptibility testing.
As shown in Table 1 the rates of non-susceptibility of E. coli to amoxicillin and clavulanic acid increased in nearly all the centres analysed from 2006 to 2009, with percentages ranging from 8.7% to 29% in the latter year. Resistance to ciprofloxacin has also increased, with rates ranging from 23.4% to 42.9% in 2009. Over the two years analysed the rates of resistance to fosfomycin also increased but currently account for less than 5% of all the E. coli strains. In the Bon Pastor laboratory fosfomycin, third-generation cephalosporins and nitrofurantoin showed the lowest resistance rates for the E. coli isolates with percentages lower than 10%.
Non-susceptibility rates of Escherichia coli towards five common antibiotics in 2006 and 2009 in eight different laboratories in Spain.
Antibiotic | Year | BB | BPa | DO | PH | PA | SG | VM | RV |
Amoxicillin and clavulanic acid | 2006 | 20.8 | 17.6 | 9.3 | 8.8 | 10.0 | 14.0 | 6.8 | 1.8 |
2009 | 20.2 | 29.0 | 8.7 | 21.7 | 12.0 | 22.0 | 21.4 | 12.2 | |
Ciprofloxacin | 2006 | 26.1 | 25.6 | 22.4 | 20.2 | 19.2 | 27.0 | 40.7 | 40.4 |
2009 | 28.2 | 27.0 | 23.4 | 27.8 | 24.4 | 30.0 | 41.7 | 42.9 | |
Cefuroxime | 2006 | 8.7 | 19.2 | 8.6 | 2.9 | NA | 9.0 | 12.0 | 10.2 |
2009 | 11.1 | 13.0 | 11.2 | 9.0 | NA | 12.0 | 11.3 | 12.5 | |
Trimethoprim and sulfamethoxazole | 2006 | NA | 29.6 | 26.8 | 30.1 | 26.6 | 36.0 | NA | NA |
2009 | NA | 34.0 | 27.8 | 34.1 | 25.3 | 33.0 | NA | NA | |
Fosfomycin | 2006 | 5.7 | NA | 1.7 | 2.8 | NA | 4.0 | 1.1 | 4.0 |
2009 | 9.5 | 3.0 | 2.8 | 3.3 | NA | 4.0 | 1.1 | 9.5 | |
Third generation cephalosporins | 2006 | 3.3 | 2.0 | 4.0 | 1.0 | 2.9 | 5.0 | 10.0 | 4.0 |
2009 | 6.2 | 4.0 | 6.8 | 7.6 | 3.9 | 5.0 | 7.0 | 6.0 |
B: Basurto, Bilbao; BP: Bon Pastor, Barcelona; DO: Donostia, San Sebastián; PH: Puerta de Hierro, Madrid; PA: Pamplona; SG: Segovia; VM: Virgen de la Macarena, Sevilla; RV: Royo Villanova, Zaragoza; NA: not available.
The most important limitation of this study is the heterogeneity of the urine cultures analysed. Even though most cultures were requested by family physicians, some were also ordered in the hospital setting. Another issue is the type of UTI. Despite requests for urine cultures only being recommended in cases of recurrent and complicated UTIs, cultures are also often requested in many cases corresponding to uncomplicated UTIs.4 Another limitation is that the urine cultures were not matched with the characteristics of the patients, such as age and comorbidity. We attempted to only report raw data in the present study. Even though the results of antimicrobial susceptibility testing are not always related to the clinical outcome, since bacterial resistance has been shown to overestimate the risk of therapeutic failure in UTI,5 these updated resistance rates against amoxicillin and clavulanic acid and quinolones should be taken into account by general practitioners. According to the recommendations of the Infectious Diseases Society of America and the study by Guay, the antibiotic should be substituted when the rates of resistance surpass 20%.6 Taking the microbiological data into account neither of these antibiotics should continue to be recommended as first choice for empirical treatment of uncomplicated UTIs in Spain.
Conflicts of interestNo conflicts declared. The results have partially been presented in the meetings of the Sociedad de Enfermedades Infecciosas del Norte (SEINORTE) held in Santander and the Grupo de Estudio de la Infección en Atención Primaria de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (GEIAP-SEIMC) held in Zaragoza, both carried out in 2011.
The authors wish to acknowledge the contribution of the following principal investigators to this study in each centre: M. Gomáriz (microbiology unit at Hospital of Donostia, San Sebastián, R. Martínez-Álvarez (internal medicine unit at Unidad de enfermedades Infecciosas, Hospital Royo Villanova, Zaragoza), P. Carrero (microbiology unit at Hospital General of Segovia), J. Oteo (Laboratorio de Antibióticos, Centro Nacional de Microbiología at Instituto Carlos III, Majadahonda, Madrid), M.J. Aldea (microbiology unit, Hospital Royo Villanova, Zaragoza), B. Orden (microbiology unit at Hospital Puerta de Hierro, Madrid), A. Gil-Setas (microbiology unit at Instituto Navarro de Salud in Pamplona), J.L. Díaz de Tuesta (microbiology unit at Hospital of Basurto, Bilbao), and L. López (microbiology unit at Hospital Virgen de la Macarena, Sevilla).