Should we treat asymptomatic bacteriuria after renal transplantation?

Abstract

Infections remain a major cause of morbidity and mortality in the modern kidney transplantation era [1]. Symptomatic urinary tract infections (UTIs), which are defined as the association of a positive urine culture with the presence of symptoms or signs referable to UTI, are usually divided into lower tract (cystitis) and upper tract (pyelonephritis) infections. It is the most common infection in this population, both short-term as well as long-term post-transplantation [2]. As a consequence, UTI is the leading cause of antibiotic administration in kidney transplant recipients [3]. The highest incidence of symptomatic UTIs occurs during the first months after transplantation [4, 5]. In a registry study conducted by the Spanish Network for Research on Infection in Transplantation (RESITRA) in 2052 kidney transplant recipients with at least 1 year of follow-up, symptomatic UTIs occurred in 150 patients (7.3%) with an incidence rate of 0.45 episodes per 1000 transplantation days [4]. Escherichia coli and Enterococcus are known to account for more than half of bacterial UTIs post-kidney transplantation [2–5]. In a time of increasing resistance to antimicrobial agents and rising health-related costs, factors that trigger UTIs need to be understood, and if possible prevented. As in the general population, female gender is the strongest risk factor for UTI in kidney transplant recipients [4, 6, 7]. In comparison with men, the shorter urethra contributes to this phenomenon. Other risk factors such as advanced age, diabetes mellitus, primary end-stage renal disease, urinary tract abnormalities, cadaveric donor kidney, graft dysfunction and rejection, CMV infection and prolonged time on dialysis prior to transplantation have been pinpointed in some series [2, 6–10]. Identification of treatable risk factors is of interest as it may lead to a reduction in the frequency of symptomatic UTIs. Whether asymptomatic bacteriuria is a modifiable risk factor for symptomatic episodes and could impact the global prognosis of the transplanted patient (and should therefore be screened for and treated) remains controversial [11]. The Infectious Diseases Society of America (IDSA) defines asymptomatic bacteriuria as isolation of a specified quantitative count of bacteria (≥10 CFU/mL) in an appropriately collected urine sample obtained from a person without symptoms or signs referable to a UTI [12]. While a single urine specimen is sufficient to define asymptomatic bacteriuria in men, it is usually defined in women as two consecutively voided urine specimens with isolation of the same bacterial strain in quantitative counts ≥10 CFU/mL. This definition stems from a study showing that, in non-transplanted women, when the first specimen contains at least 10 bacteria per millilitre of urine, there is an 80% probability that the patient has true bacteriuria [13]. That 20% of women have a negative second culture is thought to reflect transient bacteriuria rather than contamination [14]. Asymptomatic bacteriuria is a common event after renal transplantation. For instance, Fiorante et al. showed that 51% of the recipients develop asymptomatic bacteriuria—as defined by the IDSA guidelines—during the 3 years following transplantation [15]. Therefore, the question of its management remains a daily unsolved problem for transplant physicians. Antibiotic overuse could lead to the emergence of bacterial resistance and antimicrobial agents’ side effects. In addition, important costs are associated with the strategy of systematic screening and treatment of post-kidney transplantation asymptomatic bacteriuria, such as the costs of urinalyses, antibiotics and even hospitalization of asymptomatic patients. This is a matter of concern in a time of limited health-care resources. To date, no study has demonstrated a clear benefit in treating asymptomatic bacteriuria with antimicrobial agents in kidney transplant recipients [15–17]. Of the studies published addressing this question, only one was prospective. This small trial, conducted in 88 Iranian patients, did not show a statistically significant decreased rate of symptomatic UTIs when kidney transplant recipients with asymptomatic bacteriuria were treated with a 10-day course of antibiotics [17]. Nine of the 43 treated patients (21%) developed symptomatic UTI during the 9–12 months of follow-up, in comparison with 14 F U L L R E V IE W