Elsevier

European Urology

Volume 54, Issue 5, November 2008, Pages 1164-1178
European Urology

Infections
Surveillance Study in Europe and Brazil on Clinical Aspects and Antimicrobial Resistance Epidemiology in Females with Cystitis (ARESC): Implications for Empiric Therapy

https://doi.org/10.1016/j.eururo.2008.05.010Get rights and content

Abstract

Background

Uncomplicated cystitis in females is among the most frequent infections in community.

Objective

To determine clinical aspects, epidemiology, and antimicrobial susceptibility of uropathogens.

Intervention

Patients were investigated clinically and with urinalysis and urine culture.

Measurements

This survey started in 2003 and ended in 2006 including 68 centres in nine European countries and in Brazil. Female patients between 18 and 65 yr with symptoms of uncomplicated cystitis were consecutively enrolled and clinically evaluated. Uropathogens were identified and their susceptibility tested for nine antimicrobials.

Results and limitations

Clinical data of 4264 eligible patients were analysed. A positive urine culture was found in 74.6%. Within the 3018 pathogens, Escherichia coli (E. coli) was most frequent (76.7%), followed by Enterococcus faecalis (4.0%), Staphylococcus saprophyticus (3.6%), Klebsiella pneumoniae (3.5%), and Proteus mirabilis (3.5%). E. coli showed the highest rate of susceptibility to fosfomycin (98.1%) followed by mecillinam (95.8%), nitrofurantoin (95.2%), and ciprofloxacin (91.8%). The lowest rate was found for ampicillin (45.1%). For the total spectrum the order was fosfomycin (96.4%), mecillinam (95.9%), ciprofloxacin (90.3%), and nitrofurantoin (87.0%). In all countries a susceptibility rate to E. coli above 90% was found only for fosfomycin, mecillinam, and nitrofurantoin. The susceptibility rates varied significantly from country to country (p < 0.0001), except for fosfomycin, mecillinam, and nitrofurantoin.

Conclusions

Despite wide cross-country variability of bacterial susceptibility/resistance rates to the other antimicrobials tested, fosfomycin, mecillinam, and nitrofurantoin have preserved their in vitro activity in all countries investigated. They may represent good options for the empiric therapy of female patients with uncomplicated cystitis.

Introduction

Urinary tract infections (UTIs) are among the most frequent infections seen in women [1]. UTI is classified as uncomplicated if it occurs in patients with a structurally and functionally normal urinary tract. In otherwise healthy women, acute uncomplicated cystitis occurs frequently and is associated with high morbidity. Approximately 25–35% of women between 20 and 40 yr have experienced uncomplicated UTI [2]. Uncomplicated cystitis may occasionally occur in young adult males [3], [4]. Diabetic [5], pregnant [6], and postmenopausal women [7] are at higher risk to develop UTI as compared to otherwise healthy premenopausal women.

In acute uncomplicated UTI, Escherichia coli (E. coli) is the most frequent pathogen (75–95%), followed by Staphylococcus saprophyticus (5–10% of cases). Occasionally other Enterobacteriaceae, such as Proteus mirabilis and Klebsiella species, are isolated. Among other gram-positive bacteria, enterococci are rarely found [8].

Uncomplicated cystitis is generally treated empirically, when only clinical aspects are available. Moreover microbiologic investigations are not performed in routine practice. But for recommendation of first-line treatment epidemiology and local pathogens’ susceptibility to antibiotics have to be known, which depend on proper patient's selection (diagnosis) and on time and geographic areas. Systematic studies are necessary to reassess the epidemiology and susceptibility pattern in correlation to clinical aspects and immediately available laboratory tests, like urinalysis.

Section snippets

Patients, materials, and methods

The protocol of the ARESC study was first approved by a central ethical committee (Bayerische Landesärztekammer, Munich, Germany, No. 03172) and then by the respective local ethical committees. The study complies with the Declaration of Helsinki (Edinburgh, Scotland 2000), good clinical practice (GCP), and the applicable regulatory requirements. Written consent was obtained from all patients. The study was a prospective, multicentre, multinational observational epidemiologic survey.

Results

This survey started in September 2003 and ended in June 2006. Sixty-eight centres in nine European countries and in Brazil were involved.

A total of 4384/4400 female patients with uncomplicated lower UTI (cystitis) were screened/planned. One hundred and twenty patients (2.8%) were not eligible for protocol violations, mainly because of complicating factors, or no written consent, so that the clinical data of 4264 (urine samples only from 4244) eligible patients were analysed—from Austria 97/100,

Discussion

This survey has assessed the clinical aspects, epidemiology, and susceptibility pattern for standard antimicrobials used in the treatment of uncomplicated lower UTI (cystitis) in nine European countries and in Brazil. The enrolled female patients represent the general population with this infection concerning age, menopausal status, and presence of common risk factors such as diabetes mellitus, pregnancy, and recurrent UTI.

Of the patients presenting with typical symptoms of cystitis, about one

Conclusion

Despite wide cross-country variability of bacterial susceptibility/resistance rates to the other antimicrobials tested, fosfomycin, mecillinam, and nitrofurantoin have preserved their in vitro activity in all countries investigated. They may represent effective options for the empiric therapy of patients with uncomplicated lower UTI (cystitis).

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