Reply to “Old Habits Die Hard: Screening for and Treating Asymptomatic Bacteriuria After Kidney Transplantation”

To the Editor We appreciate the comments of Coussement et al (1Coussement J Nagler EV Abramowicz D Old habits die hard: Screening for and treating asymptomatic bacteriuria after kidney transplantation.Am J Transplant. 2006; (DOI: 10.1111/ajt.13888[Epub ahead of print])Google Scholar) about our prospective randomized study to determine the potential benefits of screening for and antimicrobial treatment of asymptomatic bacteriuria (AB) in kidney transplant (KTx) recipients. Indeed, the observed incidence of acute pyelonephritis (APN) in the control group turned out to be lower than expected; therefore, we acknowledge that our study could eventually be underpowered, as already discussed in the paper. Notwithstanding this potential limitation, we would like to make some observations. Most previous studies in this field did not offer separate rates for symptomatic and asymptomatic episodes of posttransplant urinary tract infection (UTI), and the follow-up periods varied widely across studies. The figure used as incidence of APN in the control group to estimate our sample size (23%) was based on a cohort of 161 KTx recipients from a Spanish center who were followed up prospectively for 180 days (2Valera B Gentil MA Cabello V Fijo J Cordero E Cisneros JM Epidemiology of urinary infections in renal transplant recipients.Transplant Proc. 2006; 38: 2414-2415Crossref PubMed Scopus (111) Google Scholar), as we assumed that the immunosuppression regimen and the species distribution would be similar to ours. Other authors have reported roughly comparable rates (16.5–18.7%). In addition, it is likely that the expected impact for the tested intervention was too optimistic. Such estimation was based on a previous observational study from our group, in which we found a 3-year cumulative incidence of APN of 10% among KTx recipients in whom AB was systematically searched for and treated (3Fiorante S Fernández-Ruiz M López-Medrano F et al.Acute graft pyelonephritis in renal transplant recipients: Incidence, risk factors and long-term outcome.Nephrol Dial Transplant. 2011; 26: 1065-1073Crossref PubMed Scopus (68) Google Scholar). Relying on the fact that our follow-up period would be shorter, that adherence to the treatment protocol for AB would be strict in the intervention group (antibiotic therapy was not given in ≈30% of episodes in the aforementioned observational study), and that APN episodes occurring within the first 2 mo after transplantation would be excluded, we estimated an absolute risk reduction of 20% between study groups, which was sensibly higher than that finally observed. Small randomized trials have prompted changes in the clinical management of AB in other populations. The trial performed by Harding et al (4Harding GK Zhanel GG Nicolle LE Cheang M Manitoba Diabetes Urinary Tract Infection Study G. Antimicrobial treatment in diabetic women with asymptomatic bacteriuria.N Engl J Med. 2002; 347: 1576-1583Crossref PubMed Scopus (194) Google Scholar) among diabetic women with AB enrolled an overall number of 105 patients (50 in the placebo group and 55 in the antimicrobial therapy group), whereas the recently published study by Kazemier et al (5Kazemier BM Koningstein FN Schneeberger C et al.Maternal and neonatal consequences of treated and untreated asymptomatic bacteriuria in pregnancy: A prospective cohort study with an embedded randomised controlled trial.Lancet Infect Dis. 2015; 15: 1324-1333Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar) included 248 pregnant women, with 40 of them randomly assigned to treatment with nitrofurantoin and 45 with placebo. Despite its limitations, our results suggest that the potential benefit derived from systematically treating posttransplant AB in the clinical arena would be modest at best for several reasons: The strict compliance with antimicrobial treatment in each of the numerous episodes of AB occurring in some patients was extremely difficult; half of the episodes of symptomatic UTI were not preceded by AB; urine sterilization was not achieved in as many as half of the treated episodes, whereas a third of them spontaneously cleared without therapy; and the proportion of multidrug-resistant uropathogens in the KTx setting is high and increasing (6Origüen J Fernández-Ruiz M López-Medrano F et al.Progressive increase of resistance in Enterobacteriaceae urinary isolates from kidney transplant recipients over the past decade: Narrowing of the therapeutic options.Transpl Infect Dis. 2016; (doi:10.1111/tid.12547)Crossref PubMed Scopus (39) Google Scholar). We concur with Coussement et al that it will be of most interest to corroborate these findings by means of larger multicenter trials. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

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