Abstract
Purpose of review
Our goal was to summarize recent evidence regarding recurrent urinary tract infections and asymptomatic bacteriuria in different adult populations.
Recent findings
Several research groups are focused on the description of resident bacterial flora in the bladder and urinary dysbiosis in the microbiome era. Even the definitions might change in light of these discoveries. However, the role of urinary microbiome and bacterial interference has still to be determined.
Summary
Systematic treatment of asymptomatic bacteriuria is not recommended and even classic indications such as asymptomatic bacteriuria in pregnant women are controversial. In fact, its treatment is associated with a higher probability of symptomatic UTI and a higher prevalence of antibiotic-resistant bacteria. Improving the diagnosis of asymptomatic bacteriuria and optimizing the management of recurrent urinary tract infections, especially through non-antibiotics measures, are needed in order to minimise antimicrobial resistance.
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Introduction
Urinary tract infection (UTI) is a colonization of the urinary system by uropathogenic bacteria, leading to different degrees of inflammatory response. The clinical spectrum is highly variable, ranging from uncomplicated UTIs (cystitis or pyelonephritis in healthy, young women without urinary tract abnormalities) to complicated UTIs affecting frail individuals (including transplant patients, elderly population, neurogenic bladder patients, urinary diversion, catheter related UTIs) and being a frequent cause of morbimortality in these populations, with a high risk of developing urosepsis, acute and/or chronic renal failure, and even death [1].
Recurrent UTIs (rUTIs) are recurrences of complicated or uncomplicated UTIs occurring three or more times per year, or two in the last six months [1]. Non-complicated rUTIs are relatively frequent in healthy, premenopausal, sexually active women, and especially in postmenopausal women. Recurrent cystitis can be considered uncomplicated, but recurrent pyelonephritis must be considered complicated [2] and prompt extended diagnostic evaluation sought to identify specific aetiology such as stones, neurogenic bladder disorders or vesicoureteral reflux.
Classically considered as “sterile” in healthy individuals, the development of expanded quantitative urine cultures (EQUC) and sequencing-based techniques have shifted this paradigm identifying a wide range of bacterial species in the urine of healthy individuals [3•]. This resident microbial community in the urinary tract or urinary microbiome probably has a role in both sporadic and rUTIs, and recent investigations have suggested a relationship between the urinary flora and the response to oral anticholinergics and intradetrusor botulinum toxin injections in urge incontinence [4, 5], although its contribution is still not well understood [6].
Given these findings, experts have suggested the use of the term “urinary tract dysbiosis” instead of “UTI” [7••], given that most pathogenic bacteria are part of the resident urinary tract bacteria, and their pathogenicity may occur following an imbalance of this microbiota [8]. Similarly, it has been demonstrated that urinary microbiome changes preceded the development of a catheter-associated UTI (studying the biofilm flora), and that the former returned to normality after treatment [9].
Asymptomatic bacteriuria (AB) is the term used when a microbiologically-significant bacterial growth in the urine is reached in individuals without signs or symptoms of UTI [10] (which will be discussed in the Diagnosis section of this review). In view of the previously stated concepts, we can assume that AB does not require antibiotic treatment except in very specific situations. Furthermore, AB has demonstrated a protective role in women with rUTIs, and treating it is associated with a higher probability of symptomatic UTI and a higher prevalence of antibiotic-resistant bacteria [11].
However, AB is frequently unnecessarily treated with antibiotics. This, together with the widespread use of antibiotics to treat UTI, have been identified among the factors involved in the emergence of dangerous multiresistant bacteria with very large morbimortality, and human, social, and health costs [12, 13].
The aim of this review is to summarise the most recent findings and future perspectives in urinary tract infections and asymptomatic bacteriuria in the adult population.
Epidemiology of rUTI and AB
UTIs are extremely frequent, especially in women, with an estimated 50 to 60% of women affected at some point during their lifetime. Except for a spike between 15 and 24 years, the prevalence of UTIs increases with age, with almost 10% of postmenopausal women being referred with a UTI in the past year [14].
They represent significant burden for all health care systems, with more than 10 million outpatient visits per year in the USA [15], and around 100,000 hospital admissions yearly with estimated annual costs of between 1.6 and 3.5 billion dollars [16]. Moreover, UTIs are the most frequent infection within a hospitalized population, especially in Urology units. The Global Prevalence Study on Infections in Urology (GPIU) estimates that 9.4% of urological patients hospitalized between 2005 and 2017 developed a complicated UTI during their hospital stay [17]. In general, the prevalence of healthcare-associated UTIs (HAUTIs) ranges between 13 and 19% in the USA and Europe, to up to 24% in developing countries [18, 19].
The prevalence of AB ranges widely from 1 to 5% for healthy premenopausal women, to 100% in patients with indwelling catheters [20]. In healthy individuals, AB increases with age from 2% in children to 50% in elderly residents of long-term care facilities. Different factors also are associated with a higher incidence of AB such as diabetes, neurogenic lower urinary tract dysfunction (NLUTD) and pregnancy [21••], as we discuss below.
Risk Factors of rUTI and AB
Female gender is one of the main risk factors in the development of UTIs and AB, probably due to anatomical factors such as the proximity of the external urethral meatus to anus, and the shorter urethral length compared to men. Other risk factors associated to rUTI in women are: the use of spermicides, increased frequency of sexual intercourse, family history, reduced oestrogen levels, increased postvoid residual urine, urinary incontinence and pelvic organ prolapse [1].
Pregnancy is also a risk factor for symptomatic UTI. Prevalence of AB is just slightly superior to non-pregnant women (2–9% vs. 1–5%), but the associated anatomical and physiological changes predispose pregnant women affected by AB to develop upper UTIs, that have been associated to adverse perinatal outcomes [22].
Asymptomatic bacteriuria is also more frequent in diabetic patients than in healthy controls (17% vs. 10%), and it can progress to symptomatic UTI in up to 20% of them within 6 months, especially if glycemic control is suboptimal [23, 24].
Catheterization, both indwelling or intermittent, or even the use of a condom catheter, is another well-known risk factor for rUTI and bacteriuria. The daily risk of UTI per catheterization day is approximately 3–7%, and we must assume AB in every patient on permanent catheterization. Patients on clean intermittent self-catheterization also have an increased risk, with 15–85% of them affected by one or more UTIs per year and a prevalence of asymptomatic bacteriuria between 23 and 89% [25].
NLUTD, even in patients voiding spontaneously, is also associated with a higher likelihood of rUTI, with an overall rate of one to 10 UTIs per patient per year. Also, AB rates in this population vary between 42 and 91% depending on the type of bladder emptying method [26]. Specific risk factors that have been proposed in this population are incomplete voiding (postvoid residual urine > 100 cc), bladder or kidney stones, low bladder compliance, vesicoureteral reflux, younger age, and higher levels of disability [27, 28].
Microbiology of rUTI and AB
In the last decade, several groups of investigators have been focusing on the definition of resident bacterial flora of the urinary bladder [8, 29]. The development of 16S rRNA gene amplification and sequencing (and other techniques generally referred to as next-generation sequencing [NGS]) helped in the assessment of microbial diversity in the human microbiota [30•]. This microbial community (also including fungi, protozoa, viruses, and archaebacteria) is supposed to participate in bladder homeostasis, urothelial integrity, protection against infection, regulation of neurotransmission, and promotion of normal immune functions [31], but the initial steps are focused on investigating the components of commensal and pathogenic flora.
The sensitivity of urine NGS is significantly higher than that of conventional urine culture (69.0% vs. 16.7% in a study by Yoo et al. [32]). Initial approaches to decipher the normal urinary microbiome showed that most frequent taxa are Proteobacteria (E. coli), Firmicutes (Enterococcus faecalis), Actinobacteria (Gardnerella), and Bacteroidetes [8, 33]. In the urine of female patients with acute uncomplicated cystitis, Phylum Proteobacteria and Class Gammaproteobacteria (Pseudomonas aeruginosa) have been more frequently detected, whereas in those with recurrent cystitis, a higher proportion of Phylum Bacteroidetes, Class Bacteroidia, Order Bacteroidales, Family Prevotellaceae, and Phylum Firmicutes (Streptococcus agalactiae, Aerococcus urinae, Staphylococcus aureus, Streptococcus anginosus) have been found [32, 34, 35]. In fact, the proportion of species comprising the urinary microbiome is dynamic and might change in different states of diseases, as happens with cutaneous, gastric, colon, and gut microbiomes [36].
However, we should consider that not all bacterial strains have the same ability to develop UTI (or virulence potential); furthermore, some strains could be protective. The most studied genus is Enterobacteriaciae, particularly the species Escherichia coli. Type 1 pili, with the adhesin FimH in their tip, are essential in bladder colonization and UTI progression. The adhesin binds specifically to mannosylated uroplakins and proteins in both the superficial bladder ephitelium and underlying layers, allowing the creation of biofilm-like intracellular bacterial communities (IBC) [37,38,39,40]. In a comparative genomic study of E. coli isolates from women with recurrent UTI, it was shown that putative urovirulence factors (PUFs) are mostly associated to the phylogenetic clade B2, and that they are not necessarily linked to pathogenicity [37]. Moreover, certain E. coli strains were able to outcompete other strains even when presenting with fewer PUFs [37]. The authors also revealed that bacterial gene expression may vary under certain culture conditions, and that particular mouse models were more reluctant to become infected, hypothesizing that barriers to infection are different among them based on their genetic background [37]. In other words, they suggest that both bacterial virulence phenotypes and host susceptibility are key factors in the development of UTIs.
Diagnosis of rUTI and AB
Diagnosis of AB is based on positive cultures in the absence of urinary symptoms. Two consecutive cultures are necessary in women [1, 21••, 41,42,43], while only one positive sample is necessary to diagnose men with AB [1, 44•].
rUTI are usually defined, as previously mentioned, as two or more episodes of urinary infection in 6 months or three or more in one year [1, 45, 46]. Every episode of UTI should be assessed through symptoms’ consideration and a urine culture (using midstream urine) [41, 46, 47]. This definition entails a period without infection in between recurrences. However, it is not clear whether it is necessary to perform a urine culture to confirm bacteria eradication between episodes given that if a urine culture is positive in an asymptomatic patient in this scenario, it can be considered as AB and there is no indication to treat it [45].
A detailed clinical history should be taken for each UTI episode enquiring about common acute-onset symptoms: i.e., dysuria, frequency, urgency, suprapubic pain, haematuria, malaise, malodorous urine, and, in frail patients, cognitive impairment [45, 48, 49].
A physical exam should be performed in all patients with rUTI. Men with rUTI or AB should undergo a digital examination in order to assess bacterial prostatitis or prostatic enlargement [1]; in peri- and post-menopausal women, pelvic organ prolapse and signs of genital atrophy have to be ruled out [45, 46, 48]. Post-void residual urine may be measured in order to exclude incomplete emptying [45, 48, 50].
Urine culture is essential; up to a 33% of patients complaining of UTI symptoms and 41% of those who have pyuria in the urinalysis will have a negative urine culture that may rule out common microorganisms UTI [51]. Moreover, cultures help in the differential diagnosis of the urinary or pelvic symptoms, which might be caused by other conditions such as sexually transmitted diseases [52], overactive bladder [53, 54], vulvovaginitis [50, 55], genitourinary syndrome of menopause [56], or even COVID-19 [57]. Similarly, if we disregard urinary symptoms and base our diagnosis only in urine culture results, we will diagnose (and might treat) many cases of AB [58]. The most common bacterial genus isolated is Escherichia, followed by Klebsiella species, Enterococcus species and Pseudomonas species, but the isolated pathogen may depend upon patients’ urological background [59].
In general, a urine culture is considered positive (i) if originating from a mid-stream sample, it shows ≥ 105 colony-forming units (CFU) per ml, or (ii) when collected from a catheterised sample, shows ≥ 102 CFU per ml [1, 43, 60]. However, this threshold has not been updated since 1956, and it is based on a study performed in asymptomatic women; therefore, it may not be useful for symptomatic patients [61].
Some societies recommend lowering this cut-off value in symptomatic uncomplicated infections with only one identified uropathogen to 102 CFU/ml [41, 42, 46, 55, 62], as this low count of CFU suggests significant bacteria in these patients. It has even been proposed that for a more accurate diagnosis, each uropathogen should have its own unique threshold [35, 50] due to the fact that even when a low CFU count is found, it might have a role in maintaining persistent inflammation in the bladder, especially for those bacteria having specific virulence factors [63].
New modalities of urine culture, such as the expanded quantitative urinary culture (EQUC), have arisen and have allowed a more precise identification of uropathogens as they use a higher volume of urine, different media for culturing (including anaerobic conditions), and a lower cut-off value for considering the test positive [29, 35, 64•]. Others, such as DNA identification with polymerase chain reaction (PCR), might even detect genes conferring resistance to different antibiotics [59, 65].
For rUTI, imaging and invasive tests are not mandatory except for cases where a complicated UTI is suspected, such as in the presence of cancer, fistulae, bladder outlet obstruction, NLUTD, renal calculi, or other relevant diagnoses [1, 46, 48, 55], as the diagnostic yield of these tests is low [66, 67]. Likewise, for AB, only urinary stones must be ruled out when urine cultures are positive for urease-producing bacteria.
Prophylaxis of Recurrent UTI
It is well-known that antibiotic resistance in common uropathogens is increasing, which jeopardises the efficacy of the treatment of severe infections with multiresistant strains [68, 69], and the World Health Organization (WHO) has stated that “the world is heading towards a post-antibiotic era in which common infections could once again kill” [70]. For this reason, Antimicrobial Stewardship programs have been developed, which aim to optimise clinical outcomes and ensure cost-effective therapy whilst minimising unintended side effects of antimicrobial use [1, 71]. Objective 3 of the WHO’s Global Action Plan on Antimicrobial Resistance includes the reduction of the incidence of infection through effective sanitation, hygiene and infection prevention measures [70]. In this regard, prophylaxis of recurrent UTIs is of utmost importance, and should focus on the reduction of risk factors, aetiological treatment, and non-antibiotic prophylactic measures, where possible.
Hormonal Replacement
Vaginal oestrogen is indicated in post-menopausal women with recurrent UTIs [1]. Two types of oestrogenic receptors (ER) can be identified in the urogenital tract: ERβ, which is the major ER type in the urinary bladder and is involved in epithelial differentiation and maintenance, whereas ERα dominates in the vagina [72]. Also, the G protein-coupled receptor for oestrogen (GPR30 or GPER-1) has been described, which is a membrane receptor present in the cellular surface that has been widely studied in gynaecological tumours, but also in bladder [73] and prostate cancer [74]. In vitro studies have shown that oestrogen promotes proliferation of epithelial cells of the lower urinary tract and induces the expression of intercellular junction proteins including E-cadherin via the ERβ [72]. More pronounced focal adhesions and more stress fibres, predominantly at the cell periphery, can be found in urothelial cells exposed to oestradiol [75].
Dr-adhesins bearing Escherichia coli are considered a virulence factor through which the bacteria can evade the host immune system by internalizing into the uroepithelial cells by binding to CD55 expressed on host-cell membranes [76]. A lack of intercellular junction proteins as explained before can favour this mechanism and the development of quiescent intracellular reservoirs in deeper layers of the urothelium, facilitating recurrent UTIs [72].
The human antimicrobial peptide cathelicidin LL-37/hCAP-18 is expressed by various epithelia but also by neutrophils and other immune cells. In a study by Lüthje et al., serum cathelicidin was significantly lower in postmenopausal women, and they showed that peptide levels correlated directly to oestradiol levels, implying that oestrogen has an influence on the expression of this and possibly other antimicrobial peptides like hBD1, hBD2, hBD3, psoriasin, or RNase 7 [75].
Immunoactive Prophylaxis
To understand the mechanism of action of oral immunomodulation or trained immunity for the prevention of UTIs, we must cast our mind back to innate immunity, which is likely to be mediated via toll-like receptors and recognition of lipopolysaccharide in the outer membrane of E. coli and most other gram-negative bacteria. Since various classes of uropathogens share similar antigenic structures, they can be recognized by the same pattern recognition receptor [77]. This trained immunity is based on epigenetic reprogramming of myeloid cells (dendritic cells, macrophages, NK-cells) that result in changes in their phenotypic and metabolic behaviour [78]. It has been described that dendritic cells have the capacity to generate Th1/Th17 and IL-10-producing T cells [79]. Also, modulation of myeloid progenitors in the bone marrow of mice has been shown [80].
The oral immunostimulant OM-89 (Uro-Vaxom®), an oral tablet with an extract of 18 different serotypes of heat-killed uropathogenic E. coli, is taken once a day for three months, and afterwards a booster tablet is indicated for the first 10 days of months six–nine [81]. The risk ratio for the development of at least one UTI in the female population was significantly lower in the OM-89 group (RR 0.61, 95% CI 0.48–0.78), and the mean of UTIs was about half compared to placebo [77]. Recently, the utility in neuro-urological patients has also been suggested in a small RCT [82] and in a retrospective study [83], and the results of the clinical trial NCT02591901 are expected [84].
MV140 (also known as Uromune®) is a polyvalent bacterial preparation of whole heat-inactivated bacteria including equal amounts of Escherichia coli; Klebsiella pneumoniae; Proteus vulgaris; and Enterococcus faecalis. Giving 2 puffs (each containing 108 bacteria) daily sublingually for three months, patients treated with MV140 had significantly higher UTI-free rates (35–90%) than subjects treated with six months of antibiotic prophylaxis (0%) over 15 months [81, 85]. However, these outcomes come from retrospective studies and the results of randomised, placebo-controlled clinical trials are pending.
Urovac® is a vaginal vaccine which contains heat-killed bacteria including six different serotypes of uropathogenic E. coli, and one strain each of Proteus vulgaris, Klebsiella pneumoniae, Morganella morganii and Enterococcus faecalis. The original dosage was three vaginal suppositories at weekly intervals (of one or two ampules of 2 × 109 organisms per suppository), and afterwards a booster immunization was added which consisted of three additional vaccine suppositories at monthly intervals. Thus, results are heterogeneous and, although a reduction in the occurrence of UTI has been noted [81, 86], no recommendation has been made in the latest EAU Guidelines [1].
Other Preventive Non-antibiotic Measures
No new reports supporting a change in the evidence about the usefulness of other prophylactic measures like probiotics, cranberry preparations (rich in proanthocyanidines), D-mannose, or endovesical instillations of hyaluronic acid and chondroitin sulphate (for glycosaminoglycan [GAG] layer replenishment) have been published [1].
Antibiotic Prophylaxis
In the EAU Guidelines, fosfomycin trometamol 3 g every 10 days and trimethoprim 100 mg once daily are proposed as continuous low-dose prophylaxis for 3 to 6 months; during pregnancy, cephalexin 125 mg or 250 mg or cefaclor 250 mg once daily may also be counselled if the patient has suffered from previous recurrent UTIs [1]. However, we must take into consideration the suggestion that a subinhibitory concentration of antibiotics might cause significant changes in the repertoire of bacterial virulence and biofilm formation in uropathogenic E. coli, corresponding to acquired cross-resistance due to genomic changes [87].
Although nitrofurantoin 50 mg or 100 mg once daily can also be recommended, serious pulmonary and hepatic complications have been described in long-term users (usually over six months), specially diffuse interstitial pneumonitis or pulmonary fibrosis [88]. For example, the Spanish Drug Agency (Agencia Española de Medicamentos y Productos Sanitarios, AEMPS) prevents the use of this antibiotic agent as a prophylactic treatment and advises limiting its indication to acute UTI episodes for seven days or less [89].
Asymptomatic Bacteriuria
The new evidence summarised above supports the current recommendation in clinical guidelines against treating most cases of AB to decrease or decelerate antibiotic resistance and reduce side effects in patients. Future studies may find even more harmful effects of this inappropriate treatment. In the following paragraphs we shall summarize the most recent advice in specific populations.
Pregnancy
Asymptomatic bacteriuria in pregnancy still indicates screening and treatment according to most international guidelines (for example, EAU, AUA, US Preventive Services Task Force, Infectious Diseases Society of America), but the level of evidence for this recommendation is low due to different reasons. First, there is a lack of complete understanding of the mechanisms linking AB, pyelonephritis, and perinatal complications. Furthermore, most available studies have a high risk of bias and were published between the 1960s and 1980s, making it difficult to compare them with current health protocols and services [90].
The first randomized controlled trial since 1987 with high methodological quality was conducted in 13 centres in The Netherlands between 2011 and 2014, and it did not show any differences between treatment and observation of asymptomatic bacteriuria. They compared the effect of screening and subsequent treatment with nitrofurantoin, placebo, or observation in more than 5,000 pregnant women. The study showed a slightly higher incidence of UTIs and pyelonephritis (2.4 vs. 0.6%) in those women with asymptomatic bacteriuria without treatment, but no differences in perinatal complications were observed, thus not supporting the policy of screen-and-treat frequently followed in most countries [91]. A systematic review with stricter inclusion criteria (only studies with asymptomatic women were included) failed to show consistent evidence to support routine screening of AB in pregnant women [92].
Postmenopausal Women
AB incidence in postmenopausal women ranges from 2.8 to 8.6% [21••]. This can be explained by the reduction in Lactobacillus in the vaginal flora due to low oestrogen levels, the elevation of normal pH, thus facilitating the vaginal colonisation by gut bacteria [72]. However, no advantage has been shown in the development of UTI or AB clearance by antibiotic treatment [44•].
Elderly and Frail Patients
We outlined earlier that approximately half of elderly residents in long-term care facilities may have AB [21••]. Institutionalized adults frequently have a variable association of more comorbidities, functional impairment, and cognitive deficits, which predispose them to higher rates of AB and UTIs [93]. Bowel and/or bladder incontinence, functional disability, and dementia have been classically associated with persistent AB in women [93, 94]. However, no benefit has been proven if AB is systematically treated [44•].
A recent systematic review showed that the studies exploring the relationship between confusion and UTI have poor case definitions for both concepts, and even an inadequate control of confounding factors, thus impeding to determine the association between them [95]. Therefore, the Infectious Diseases Society of America recommends investigating other causes of delirium in older patients with functional or cognitive impairment and AB who do not present with systemic signs of infection or genitourinary symptoms [21••, 96].
Neurogenic LUTD
As emphasized before, the prevalence of AB in neurogenic LUTD is high, but only a low proportion of these bacteriuric patients develop symptomatic UTI even after invasive investigations such as urodynamics [26]. Thus, antibiotic treatment in this population must be limited to those with symptomatic UTI. Reducing antibiotics exposure is crucial in a group of patients that have shown up to 50% of multiresistant bacteria in urine due to frequent hospitalizations and antimicrobial treatments. “Pathological” urine findings such as a positive urine culture, pyuria and/or nitrite positivity do not justify the prescription of antibiotics, and clinical criteria should always prevail [97].
Transplant and Immunosuppressed Patients
Incidence of AB in kidney transplant recipients is between 5 and 27% [98, 99], and current guidelines do not recommend treating it [1, 100•]. In fact, many societies even advise not screening for AB, at least in the first month after surgery [1, 21••, 41]. No recommendations for the first/second months after kidney transplantation can be made [21••, 60, 100•].
Up to 37% of kidney transplant recipients may suffer from a clinically relevant UTI after surgery [101, 102], and these infections are known to cause graft dysfunction and high morbidity and mortality [101, 103, 104]. However, modern studies have not shown these effects in transplant recipient’s patients with AB [105, 106].
A recent systematic review comprising over 200 patients compared treatment of AB versus no treatment and found that antibiotics did not significantly change the risk of suffering a symptomatic UTI (RR 0.86, 95% CI 0.51 to 1.45), alter all-cause mortality (RR 2.23, 95% CI 0.21 to 23.86), graft loss (RR 1.11, 95% CI 0.07 to 17.36), acute rejection (RR 0.93, 95% CI 0.44 to 1.97) or graft function (mean difference in serum creatinine concentration -0.06 mg/dL, 95% CI -0.19 to 0.08) [107]. And one randomized clinical trial found higher rates of resistant bacteria in patients who had received antibiotics for AB compared with those who had not [108]. Therefore, treating AB in organ recipient patients does not seem to be worthwhile.
Nevertheless, outcomes may depend upon the microbe causing the colonization, as some reviews have found Ureaplasma spp. and Mycoplasma spp. causing severe damage to kidney grafts [109]. It has also been shown that the presence of specific virulence factors may directly influence the pathogenesis of UTI [110].
For other solid organ transplants, screening and treatment of AB is not recommended [21••] as effects of bacteriuria or even UTI do not seem to significantly affect organ function or increase patients’ morbidity [111].
There is a knowledge gap regarding screening and treatment of AB in patients with high-risk neutropenia [21••, 41, 60].
Catheter Associated
Patients with transurethral, suprapubic or nephrostomy catheters must be considered bacteriuric, as a rule. It is crucial to distinguish between catheter-associated UTI, which requires antibiotic treatment, and catheter-associated bacteriuria, which does not. Transurethral and suprapubic catheter exchanges or placements in patients with AB do not require antibiotic treatment or prophylaxis; however, in case of AB and nephrostomy tube or ureteral stent manipulation, treatment of asymptomatic bacteriuria prior to procedure is recommended [1].
Periprocedural and Perioperative Investigation of Bacteriuria
Urological Procedures (UDS, Endourological Procedures, Prosthesis, etc.)
Strong recommendations have been made by many societies advocating urine culture prior to urological procedures breaking the mucosa. If AB is confirmed in the culture, a short course [112] of directed antibiotic treatment must be administered at least 30 min before the intervention [1, 21••, 41, 43, 46, 113] and it might be continued until catheter removal (if this is intended to be done in the short-term) [41].
However, a recent observational study performed in a cohort of patients undergoing urological surgery showed no association between AB and postoperative infectious complications (HR, 1.02; 95% CI, 0.26–3.96) [114]. Furthermore, another study analysing pre-TURP urine samples and intra-procedure serialised blood cultures found that microbes causing bacteraemia were not the same as those cultured in the urine [115•].
A recent report also assessed the need to treat AB prior to prostate biopsies and found that none of the men with preoperatively diagnosed AB developed any infectious complication after the biopsy [116].
Evidence supports not treating bacteriuria if the urological procedure does not damage the mucosa:
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An observational study made in patients undergoing a cystoscopy showed that less than 5% of patients with AB developed a febrile UTI after the test and none of them progressed to sepsis [117].
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A study assessed the need of AB screening before vesical instillations with BCG and showed the same number of patients having a UTI in both cohorts (screened and unscreened); moreover, they reported delays in 2.5% of BCG treatment in AB patients due to the need to perform urine culture [118].
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Controversy exists regarding AB treatment prior to urodynamic studies or intravesical treatments. Most societies recommend against treating it, as many studies have not found any benefit from antibiotics [119]. Nevertheless, a recent meta-analysis found a higher rate of symptomatic UTI in patients with previous AB who did not receive antibiotic prophylaxis (RR = 0.65, 95% CI: 0.48–0.88) [120]. However, they did not analyse more severe complications (sepsis, hospitalization, and death). In this regard, a study examining the association between AB and adverse events in patients receiving intra-detrusor onabotulinumtoxinA injections found that untreated AB did increase the risk of symptomatic UTI, but it did not increase the risk of urosepsis, hospitalization, or therapy failure [121].
To our knowledge, there are no studies addressing screening and treatment of AB in patients undergoing urological prosthetic surgeries. However, the Infectious Diseases Society of America does not recommend screening for it.
Orthopaedics and Other Surgery (Vascular, and so on.)
Although peri-operative ITU is known to increase the risk of prosthetic infection [122, 123], this is not the case with non-urological prosthetic infection in patients with AB [124, 125•, 126, 127]. Furthermore, some studies have found that bacteria causing prosthetic joint infection are not the same as those producing AB [128, 129]. Therefore, most societies advocate not screening for or treating AB in these patients [1, 21••, 41, 130].
The Spanish Society of Clinical Microbiology and Infectious Diseases only recommends screening and treating AB in neurogenic or incontinent patients, as well as those with indwelling urine catheters, prior to prosthetic spinal surgery to avoid Gram-negative surgical site infections [41]. However, a recent study did not find differences in terms of surgical site infection, readmission or symptomatic UTI [131]; therefore, no consensus exists in these particular cases.
Conclusions
Systematic treatment of asymptomatic bacteriuria is not recommended, and it is associated with a higher probability of symptomatic UTI and a higher prevalence of antibiotic-resistant bacteria. Improving the diagnosis of asymptomatic bacteriuria and optimizing the management of recurrent urinary tract infections, especially through non-antibiotic measures, are needed in order to minimise antimicrobial resistance. Advances in microbiome description and assessment are expected.
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Bonkat (Chair) G, Bartoletti R, Bruyère F, Cai T, Geerlings SE, Köves B, et al. European Association of Urology (EAU) Guidelines on Urological Infections. presented at the EAU Annual Congress Milan Italy 2021 ed. Arnhem, the Netherlands: EAU Guidelines Office; 2021.
Dason S, Dason JT, Kapoor A. Guidelines for the diagnosis and management of recurrent urinary tract infection in women. Can Urol Assoc J. 2011;5(5):316–22. https://doi.org/10.5489/cuaj.11214.
• Groah SL, Pérez-Losada M, Caldovic L, Ljungberg IH, Sprague BM, Castro-Nallar E, et al. Redefining Healthy Urine: A Cross-Sectional Exploratory Metagenomic Study of People With and Without Bladder Dysfunction. J Urol. 2016;196(2):579–87. https://doi.org/10.1016/j.juro.2016.01.088. Thereareimportantdifferencesintheurinemicrobiomeofhealthyindividualswithrespecttootherswithneurogenicbladder.
Brubaker L, Nager CW, Richter HE, Visco A, Nygaard I, Barber MD, et al. Urinary bacteria in adult women with urgency urinary incontinence. Int Urogynecol J. 2014;25(9):1179–84. https://doi.org/10.1007/s00192-013-2325-2.
Pearce MM, Zilliox MJ, Rosenfeld AB, Thomas-White KJ, Richter HE, Nager CW, et al. The female urinary microbiome in urgency urinary incontinence. Am J Obstet Gynecol. 2015;213(3):347.e1-11. https://doi.org/10.1016/j.ajog.2015.07.009.
Neugent ML, Hulyalkar NV, Nguyen VH, Zimmern PE, De Nisco NJ. Advances in Understanding the Human Urinary Microbiome and Its Potential Role in Urinary Tract Infection. mBio. 2020;11(2). https://doi.org/10.1128/mBio.00218-20.
•• Finucane TE. “Urinary Tract Infection”-Requiem for a Heavyweight. J Am Geriatrics Soc. 2017;65(8):1650–5. https://doi.org/10.1111/jgs.14907. Significant bacteriuria and urinary symptoms often occur simultaneously, and that should not trigger antibiotic treatment . The term UTI maybe shoul be revised.
Morand A, Cornu F, Dufour JC, Tsimaratos M, Lagier JC, Raoult D. Human Bacterial Repertoire of the Urinary Tract: a Potential Paradigm Shift. J Clin Microbiol. 2019;57(3). https://doi.org/10.1128/jcm.00675-18.
Bossa L, Kline K, McDougald D, Lee BB, Rice SA. Urinary catheter-associated microbiota change in accordance with treatment and infection status. PLoS One. 2017;12(6): e0177633. https://doi.org/10.1371/journal.pone.0177633.
Cai T, Koves B, Johansen TE. Asymptomatic bacteriuria, to screen or not to screen - and when to treat? Curr Opin Urol. 2017;27(2):107–11. https://doi.org/10.1097/mou.0000000000000368.
Cai T, Bartoletti R. Asymptomatic bacteriuria in recurrent UTI - to treat or not to treat. GMS Infect Dis. 2017;5:Doc09. https://doi.org/10.3205/id000035.
Lee MJ, Kim M, Kim NH, Kim CJ, Song KH, Choe PG, et al. Why is asymptomatic bacteriuria overtreated?: A tertiary care institutional survey of resident physicians. BMC Infect Dis. 2015;15:289. https://doi.org/10.1186/s12879-015-1044-3.
Cai T, Mazzoli S, Lanzafame P, Caciagli P, Malossini G, Nesi G, et al. Asymptomatic Bacteriuria in Clinical Urological Practice: Preoperative Control of Bacteriuria and Management of Recurrent UTI. Pathogens (Basel, Switzerland). 2016;5(1). https://doi.org/10.3390/pathogens5010004.
Medina M, Castillo-Pino E. An introduction to the epidemiology and burden of urinary tract infections. Ther Adv Urol. 2019;11:1756287219832172. https://doi.org/10.1177/1756287219832172.
Schappert SM, Rechtsteiner EA. Ambulatory medical care utilization estimates for 2007. Vital and health statistics Series 13, Data from the National Health Survey. 2011(169):1-38.
MacVane SH, Tuttle LO, Nicolau DP. Demography and burden of care associated with patients readmitted for urinary tract infection. J Microbiol Immunol Infect. 2015;48(5):517–24. https://doi.org/10.1016/j.jmii.2014.04.002.
Tandogdu Z, Cek M, Wagenlehner F, Naber K, Tenke P, van Ostrum E, et al. Resistance patterns of nosocomial urinary tract infections in urology departments: 8-year results of the global prevalence of infections in urology study. World J Urol. 2014;32(3):791–801. https://doi.org/10.1007/s00345-013-1154-8.
Allegranzi B, Bagheri Nejad S, Combescure C, Graafmans W, Attar H, Donaldson L, et al. Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis. Lancet (London, England). 2011;377(9761):228–41. https://doi.org/10.1016/s0140-6736(10)61458-4.
Tandogdu Z, Wagenlehner FM. Global epidemiology of urinary tract infections. Curr Opin Infect Dis. 2016;29(1):73–9. https://doi.org/10.1097/qco.0000000000000228.
Colgan R, Nicolle LE, McGlone A, Hooton TM. Asymptomatic bacteriuria in adults. Am Fam Physician. 2006;74(6):985–90.
•• Nicolle LE, Gupta K, Bradley SF, Colgan R, DeMuri GP, Drekonja D, et al. Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2019;68(10):1611–5. https://doi.org/10.1093/cid/ciz021. ClinicalpracticeguidelineoftheInfectiousDiseasesSocietyofAmericasummarisingtheevidence-basedrecommendationsregardingthemanagementofasymptomaticbacteriuria.
Glaser AP, Schaeffer AJ. Urinary Tract Infection and Bacteriuria in Pregnancy. Urol Clinics N Am. 2015;42(4):547–60. https://doi.org/10.1016/j.ucl.2015.05.004.
Laway BA, Nabi T, Bhat MH, Fomda BA. Prevalence, clinical profile and follow up of asymptomatic bacteriuria in patients with type 2 diabetes-prospective case control study in Srinagar, India. Diabetes Metab Syndrome. 2021;15(1):455–9. https://doi.org/10.1016/j.dsx.2020.12.043.
Czajkowski K, Broś-Konopielko M, Teliga-Czajkowska J. Urinary tract infection in women. Przeglad Menopauzalny Menopause Rev. 2021;20(1):40–7. https://doi.org/10.5114/pm.2021.105382.
Mitchell BG, Prael G, Curryer C, Russo PL, Fasugba O, Lowthian J, et al. The frequency of urinary tract infections and the value of antiseptics in community-dwelling people who undertake intermittent urinary catheterization: A systematic review. Am J Infect Control. 2021. https://doi.org/10.1016/j.ajic.2021.01.009.
Tornic J, Wöllner J, Leitner L, Mehnert U, Bachmann LM, Kessler TM. The Challenge of Asymptomatic Bacteriuria and Symptomatic Urinary Tract Infections in Patients with Neurogenic Lower Urinary Tract Dysfunction. J Urol. 2020;203(3):579–84. https://doi.org/10.1097/ju.0000000000000555.
Kim BR, Lim JH, Lee SA, Kim JH, Koh SE, Lee IS, et al. The Relation between Postvoid Residual and Occurrence of Urinary Tract Infection after Stroke in Rehabilitation Unit. Ann Rehabil Med. 2012;36(2):248–53. https://doi.org/10.5535/arm.2012.36.2.248.
Castle AC, Park A, Mitchell AJ, Bliss DZ, Gelfand JA, De EJB. Neurogenic Bladder: Recurrent Urinary Tract Infections—Beyond Antibiotics. Curr Bladder Dysfunct Rep. 2018;13(4):191–200. https://doi.org/10.1007/s11884-018-0481-4.
Hilt EE, McKinley K, Pearce MM, Rosenfeld AB, Zilliox MJ, Mueller ER, et al. Urine is not sterile: Use of enhanced urine culture techniques to detect resident bacterial flora in the adult female bladder. J Clin Microbiol. 2014;52(3):871–6. https://doi.org/10.1128/JCM.02876-13.
• Milestones in human microbiota research. Nature portfolio. 2019. https://www.nature.com/collections/microbiota-milestone. Review of the most important milestones in the discovery and research in human microbiota.
Ackerman AL, Chai TC. The Bladder is Not Sterile: an Update on the Urinary Microbiome. Curr Bladder Dysfunct Rep. 2019;14(4):331–41. https://doi.org/10.1007/s11884-019-00543-6.
Yoo JJ, Shin HB, Song JS, Kim M, Yun J, Kim Z, et al. Urinary Microbiome Characteristics in Female Patients with Acute Uncomplicated Cystitis and Recurrent Cystitis. J Clin Med. 2021;10(5). https://doi.org/10.3390/jcm10051097.
Meštrović T, Matijašić M, Perić M, Čipčić Paljetak H, Barešić A, Verbanac D. The Role of Gut, Vaginal, and Urinary Microbiome in Urinary Tract Infections: From Bench to Bedside. Diagnostics (Basel, Switzerland). 2020;11(1). https://doi.org/10.3390/diagnostics11010007.
Brubaker L, Wolfe AJ. The female urinary microbiota, urinary health and common urinary disorders. Ann Transl Med. 2017;5(2):34. https://doi.org/10.21037/atm.2016.11.62.
Price TK, Dune T, Hilt EE, Thomas-White KJ, Kliethermes S, Brincat C, et al. The Clinical Urine Culture: Enhanced Techniques Improve Detection of Clinically Relevant Microorganisms. J Clin Microbiol. 2016;54(5):1216–22. https://doi.org/10.1128/jcm.00044-16.
Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet. 2012;13(4):260–70. https://doi.org/10.1038/nrg3182.
Schreiber HLt, Conover MS, Chou WC, Hibbing ME, Manson AL, Dodson KW, et al. Bacterial virulence phenotypes of Escherichia coli and host susceptibility determine risk for urinary tract infections. Sci Transl Med. 2017;9(382). https://doi.org/10.1126/scitranslmed.aaf1283.
Justice SS, Hung C, Theriot JA, Fletcher DA, Anderson GG, Footer MJ, et al. Differentiation and developmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis. Proc Natl Acad Sci USA. 2004;101(5):1333–8. https://doi.org/10.1073/pnas.0308125100.
Schwartz DJ, Kalas V, Pinkner JS, Chen SL, Spaulding CN, Dodson KW, et al. Positively selected FimH residues enhance virulence during urinary tract infection by altering FimH conformation. Proc Natl Acad Sci USA. 2013;110(39):15530–7. https://doi.org/10.1073/pnas.1315203110.
Robino L, Scavone P, Araujo L, Algorta G, Zunino P, Vignoli R. Detection of intracellular bacterial communities in a child with Escherichia coli recurrent urinary tract infections. Pathogens Dis. 2013;68(3):78–81. https://doi.org/10.1111/2049-632x.12047.
de Cueto M, Aliaga L, Alós JI, Canut A, Los-Arcos I, Martínez JA, et al. Executive summary of the diagnosis and treatment of urinary tract infection: Guidelines of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC). Enferm Infecc Microbiol Clin. 2017;35(5):314–20. https://doi.org/10.1016/j.eimc.2016.11.005.
Management of suspected bacterial urinary tract infection in adults. A national clinical guideline (SIGN publication no. 88). Edinburgh: Scottish Intercollegiate Guidelines Network (SIGN); 2012.
Choe HS, Lee SJ, Yang SS, Hamasuna R, Yamamoto S, Cho YH, et al. Summary of the UAA-AAUS guidelines for urinary tract infections. Int J Urol. 2018;25(3):175–85. https://doi.org/10.1111/iju.13493.
• Köves B, Cai T, Veeratterapillay R, Pickard R, Seisen T, Lam TB, et al. Benefits and Harms of Treatment of Asymptomatic Bacteriuria: A Systematic Review and Meta-analysis by the European Association of Urology Urological Infection Guidelines Panel. Eur Urol. 2017;72(6):865–8. https://doi.org/10.1016/j.eururo.2017.07.014. Recent systematic review and meta-analysis of the evidence about treating AB. Currently the only strong evidence to treat AB is prior to endourological procedures.
Brubaker L, Carberry C, Nardos R, Carter-Brooks C, Lowder JL. American Urogynecologic Society Best-Practice Statement: Recurrent Urinary Tract Infection in Adult Women. Female Pelvic Med Reconstr Surg. 2018;24(5):321–35. https://doi.org/10.1097/spv.0000000000000550.
Anger J, Lee U, Ackerman AL, Chou R, Chughtai B, Clemens JQ, et al. Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline. J Urol. 2019;202(2):282–9. https://doi.org/10.1097/ju.0000000000000296.
Epp A, Larochelle A. No. 250-Recurrent Urinary Tract Infection. J Obstet Gynaecol Canada. 2017;39(10):e422–31. https://doi.org/10.1016/j.jogc.2017.08.017.
Jung C, Brubaker L. The etiology and management of recurrent urinary tract infections in postmenopausal women. Climacteric. 2019;22(3):242–9. https://doi.org/10.1080/13697137.2018.1551871.
Dune TJ, Price TK, Hilt EE, Thomas-White KJ, Kliethermes S, Brincat C, et al. Urinary Symptoms and Their Associations With Urinary Tract Infections in Urogynecologic Patients. Obstet Gynecol. 2017;130(4):718–25. https://doi.org/10.1097/aog.0000000000002239.
Caron F, Galperine T, Flateau C, Azria R, Bonacorsi S, Bruyère F, et al. Practice guidelines for the management of adult community-acquired urinary tract infections. Med Maladies Infect. 2018;48(5):327–58. https://doi.org/10.1016/j.medmal.2018.03.005.
Watson JR, Sánchez PJ, Spencer JD, Cohen DM, Hains DS. Urinary Tract Infection and Antimicrobial Stewardship in the Emergency Department. Pediatr Emerg Care. 2018;34(2):93–5. https://doi.org/10.1097/pec.0000000000000688.
Shapiro T, Dalton M, Hammock J, Lavery R, Matjucha J, Salo DF. The prevalence of urinary tract infections and sexually transmitted disease in women with symptoms of a simple urinary tract infection stratified by low colony count criteria. Acad Emerg Med Off J Soc Acad Emerg Med. 2005;12(1):38–44. https://doi.org/10.1197/j.aem.2004.08.051.
Robinson D, Åkervall S, Wagg A, Chapple C, Milsom I, Gyhagen M. Prevalence and predictors of overactive bladder in nonpregnant nulliparous women below 65 years of age. Int Urogynecol J. 2018;29(4):531–7. https://doi.org/10.1007/s00192-017-3435-z.
Nik-Ahd F, Lenore Ackerman A, Anger J. Recurrent Urinary Tract Infections in Females and the Overlap with Overactive Bladder. Curr Urol Rep. 2018;19(11):94. https://doi.org/10.1007/s11934-018-0839-3.
Kranz J, Schmidt S, Lebert C, Schneidewind L, Mandraka F, Kunze M, et al. The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics, Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in Adult Patients: Part 1. Urol Int. 2018;100(3):263–70. https://doi.org/10.1159/000486138.
Portman DJ, Gass ML. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women’s Sexual Health and the North American Menopause Society. Menopause (New York, NY). 2014;21(10):1063–8. https://doi.org/10.1097/gme.0000000000000329.
Mumm JN, Osterman A, Ruzicka M, Stihl C, Vilsmaier T, Munker D, et al. Urinary Frequency as a Possibly Overlooked Symptom in COVID-19 Patients: Does SARS-CoV-2 Cause Viral Cystitis? Eur Urol. 2020;78(4):624–8. https://doi.org/10.1016/j.eururo.2020.05.013.
Hartley S, Valley S, Kuhn L, Washer LL, Gandhi T, Meddings J, et al. Overtreatment of asymptomatic bacteriuria: identifying targets for improvement. Infect Control Hosp Epidemiol. 2015;36(4):470–3. https://doi.org/10.1017/ice.2014.73.
Viswanath NA, Shanmugam P, Rompicherla V, Education K, Shanmugam P. A clinico bacteriological profile of urinary tract infections occurring in patients with pre-existing urinary tract diseases in a tertiary care hospital. Ann Trop Med Public Health. 2020;23(S20):SP232222. https://doi.org/10.36295/ASRO.2020.232222.
Wiley Z, Jacob JT, Burd EM. Targeting Asymptomatic Bacteriuria in Antimicrobial Stewardship: the Role of the Microbiology Laboratory. J Clin Microbiol. 2020;58(5). https://doi.org/10.1128/jcm.00518-18.
Kass EH. Asymptomatic infections of the urinary tract. Trans Assoc Am Phys. 1956;69:56–64.
Hooton TM, Roberts PL, Cox ME, Stapleton AE. Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med. 2013;369(20):1883–91. https://doi.org/10.1056/NEJMoa1302186.
Naboka YL, Mavzyiutov AR, Kogan MI, Gudima IA, Ivanov SN, Naber KG. Does Escherichia coli have pathogenic potential at a low level of bacteriuria in recurrent, uncomplicated urinary tract infection? Int J Antimicrob Agents. 2020;56(1): 105983. https://doi.org/10.1016/j.ijantimicag.2020.105983.
• Hochstedler BR, Burnett L, Price TK, Jung C, Wolfe AJ, Brubaker L. Urinary microbiota of women with recurrent urinary tract infection: collection and culture methods. Int Urogynecol J. 2021. https://doi.org/10.1007/s00192-021-04780-4. In this study, clinically-significant differences can be found between culturing the urine with standard urine culture or Expanded quantitative urine culture, and also between culturing urine from midstream voided and catheterized specimens.
Mouraviev V, McDonald M. An implementation of next generation sequencing for prevention and diagnosis of urinary tract infection in urology. Can J Urol. 2018;25(3):9349–56.
Wu YR, Rego LL, Christie AL, Lavelle RS, Alhalabi F, Zimmern PE. Recurrent Urinary Tract Infections Due to Bacterial Persistence or Reinfection in Women-Does This Factor Impact Upper Tract Imaging Findings? J Urol. 2016;196(2):422–8. https://doi.org/10.1016/j.juro.2016.01.111.
Pagano MJ, Barbalat Y, Theofanides MC, Edokpolo L, James MB, Cooper KL. Diagnostic yield of cystoscopy in the evaluation of recurrent urinary tract infection in women. Neurourol Urodyn. 2017;36(3):692–6. https://doi.org/10.1002/nau.22998.
Antimicrobial resistance: global report on surveillance. Geneva, Switzerland: World Health Organization; April 2014.
Prioritization of pathogens to guide discovery. research and development of new antibiotics for drug resistant bacterial infections, including tuberculosis. Geneva: World Health Organization; 2017.
Antimicrobial Resistance Division, National Action Plans and Monitoring and Evaluation. Global action plan on antimicrobial resistance. Geneva, Switzerland: 2015.
Dellit TH, Owens RC, McGowan JE Jr, Gerding DN, Weinstein RA, Burke JP, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis. 2007;44(2):159–77. https://doi.org/10.1086/510393.
Lüthje P, Hirschberg AL, Brauner A. Estrogenic action on innate defense mechanisms in the urinary tract. Maturitas. 2014;77(1):32–6. https://doi.org/10.1016/j.maturitas.2013.10.018.
Huang W, Chen Y, Liu Y, Zhang Q, Yu Z, Mou L, et al. Roles of ERβ and GPR30 in Proliferative Response of Human Bladder Cancer Cell to Estrogen. Biomed Res Int. 2015;2015: 251780. https://doi.org/10.1155/2015/251780.
Xu S, Yu S, Dong D, Lee LTO. G Protein-Coupled Estrogen Receptor: A Potential Therapeutic Target in Cancer. Frontiers in Endocrinology. 2019;10(725). https://doi.org/10.3389/fendo.2019.00725.
Lüthje P, Brauner H, Ramos NL, Övregaard A, Gläser R, Hirschberg AL, et al. Estrogen Supports Urothelial Defense Mechanisms. Sci Transl Med. 2013;5(190):190ra80-ra80. https://doi.org/10.1126/scitranslmed.3005574.
Pham T, Kaul A, Hart A, Goluszko P, Moulds J, Nowicki S, et al. dra-related X adhesins of gestational pyelonephritis-associated Escherichia coli recognize SCR-3 and SCR-4 domains of recombinant decay-accelerating factor. Infect Immun. 1995;63(5):1663–8. https://doi.org/10.1128/iai.63.5.1663-1668.1995.
Beerepoot MAJ, Geerlings SE, van Haarst EP, van Charante NM, ter Riet G. Nonantibiotic Prophylaxis for Recurrent Urinary Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Urol. 2013;190(6):1981–9. https://doi.org/10.1016/j.juro.2013.04.142.
Larenas-Linnemann D, Rodríguez-Pérez N, Arias-Cruz A, Blandón-Vijil MV, Del Río-Navarro BE, Estrada-Cardona A, et al. Enhancing innate immunity against virus in times of COVID-19: Trying to untangle facts from fictions. World Allergy Org J. 2020;13(11): 100476. https://doi.org/10.1016/j.waojou.2020.100476.
Benito-Villalvilla C, Cirauqui C, Diez-Rivero CM, Casanovas M, Subiza JL, Palomares O. MV140, a sublingual polyvalent bacterial preparation to treat recurrent urinary tract infections, licenses human dendritic cells for generating Th1, Th17, and IL-10 responses via Syk and MyD88. Mucosal Immunol. 2017;10(4):924–35. https://doi.org/10.1038/mi.2016.112.
Mitroulis I, Ruppova K, Wang B, Chen L-S, Grzybek M, Grinenko T, et al. Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity. Cell. 2018;172(1):147-61.e12. https://doi.org/10.1016/j.cell.2017.11.034.
Prattley S, Geraghty R, Moore M, Somani BK. Role of Vaccines for Recurrent Urinary Tract Infections: A Systematic Review. Eur Urol Focus. 2020;6(3):593–604. https://doi.org/10.1016/j.euf.2019.11.002.
Wade DT, Cooper J, Peckham N, Belci M. Immunotherapy to reduce frequency of urinary tract infections in people with neurogenic bladder dysfunction; a pilot randomised, placebo-controlled trial. Clin Rehabil. 2020;34(12):1458–64. https://doi.org/10.1177/0269215520946065.
Krebs J, Fleischli S, Stoyanov J, Pannek J. Effects of oral immunomodulation therapy on urinary tract infections in individuals with chronic spinal cord injury-A retrospective cohort study. Neurourol Urodyn. 2019;38(1):346–52. https://doi.org/10.1002/nau.23859.
Wade D, Cooper J, Derry F, Taylor J. Uro-Vaxom® versus placebo for the prevention of recurrent symptomatic urinary tract infections in participants with chronic neurogenic bladder dysfunction: a randomised controlled feasibility study. Trials. 2019;20(1):223. https://doi.org/10.1186/s13063-019-3275-x.
Nickel JC, Saz-Leal P, Doiron RC. Could sublingual vaccination be a viable option for the prevention of recurrent urinary tract infection in Canada? A systematic review of the current literature and plans for the future. Can Urol Assoc J. 2020;14(8):281–7. https://doi.org/10.5489/cuaj.6690.
Aziminia N, Hadjipavlou M, Philippou Y, Pandian SS, Malde S, Hammadeh MY. Vaccines for the prevention of recurrent urinary tract infections: a systematic review. BJU Int. 2019;123(5):753–68. https://doi.org/10.1111/bju.14606.
Adamus-Białek W, Wawszczak M, Arabski M, Majchrzak M, Gulba M, Jarych D, et al. Ciprofloxacin, amoxicillin, and aminoglycosides stimulate genetic and phenotypic changes in uropathogenic Escherichia coli strains. Virulence. 2019;10(1):260–76. https://doi.org/10.1080/21505594.2019.1596507.
Lewis D. Furadantin® (nitrofurantoin) Oral Suspension. Food and Drug Administration (FDA). 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/009175Orig1s048lbl.pdf.
NITROFURANTOÍNA (FURANTOÍNA®): NUEVAS RESTRICCIONES DE USO. Ministerio de Sanidad, Servicios Sociales e Igualdad: Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)2016 7/22/2016 Contract No.: MUH (FV), 16/2016.
Wingert A, Pillay J, Sebastianski M, Gates M, Featherstone R, Shave K, et al. Asymptomatic bacteriuria in pregnancy: systematic reviews of screening and treatment effectiveness and patient preferences. BMJ Open. 2019;9(3): e021347. https://doi.org/10.1136/bmjopen-2017-021347.
Kazemier BM, Koningstein FN, Schneeberger C, Ott A, Bossuyt PM, de Miranda E, 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(11):1324–33. https://doi.org/10.1016/s1473-3099(15)00070-5.
Angelescu K, Nussbaumer-Streit B, Sieben W, Scheibler F, Gartlehner G. Benefits and harms of screening for and treatment of asymptomatic bacteriuria in pregnancy: a systematic review. BMC Pregnancy Childbirth. 2016;16(1):336. https://doi.org/10.1186/s12884-016-1128-0.
Rodriguez-Mañas L. Urinary tract infections in the elderly: a review of disease characteristics and current treatment options. Drugs in context. 2020;9. https://doi.org/10.7573/dic.2020-4-13.
Eberle CM, Winsemius D, Garibaldi RA. Risk Factors and Consequences of Bacteriuria in Non-Catheterized Nursing Home Residents. J Gerontol. 1993;48(6):M266–71. https://doi.org/10.1093/geronj/48.6.M266.
Mayne S, Bowden A, Sundvall PD, Gunnarsson R. The scientific evidence for a potential link between confusion and urinary tract infection in the elderly is still confusing - a systematic literature review. BMC Geriatr. 2019;19(1):32. https://doi.org/10.1186/s12877-019-1049-7.
Colgan R, Jaffe GA, Nicolle LE. Asymptomatic Bacteriuria. Am Fam Phys. 2020;102(2):99–104.
Dinh A, Davido B, Duran C, Bouchand F, Gaillard JL, Even A, et al. Urinary tract infections in patients with neurogenic bladder. Med Maladies Infect. 2019;49(7):495–504. https://doi.org/10.1016/j.medmal.2019.02.006.
Coussement J, Scemla A, Hougardy JM, Sberro-Soussan R, Amrouche L, Catalano C, et al. Prevalence of asymptomatic bacteriuria among kidney transplant recipients beyond two months post-transplant: A multicenter, prospective, cross-sectional study. PLoS One. 2019;14(9): e0221820. https://doi.org/10.1371/journal.pone.0221820.
Kotagiri P, Chembolli D, Ryan J, Hughes PD, Toussaint ND. Urinary Tract Infections in the First Year Post-Kidney Transplantation: Potential Benefits of Treating Asymptomatic Bacteriuria. Transpl Proc. 2017;49(9):2070–5. https://doi.org/10.1016/j.transproceed.2017.07.008.
• Goldman JD, Julian K. Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019;33(9): e13507. https://doi.org/10.1111/ctr.13507. Societyguidelinesaboutinfectiuoustreatmentintransplantrecipients.ItdoesnotrecommendtreatingABinthesepatients,atleastafterthe2firstmonths.
Mukherjee D, Sharma S, Nair RK, Datt B, Arora D, Rao A. Urinary tract infection in renal transplant recipients at a tertiary care center in India. Saudi J Kidney Dis Transplant. 2018;29(2):361–8. https://doi.org/10.4103/1319-2442.229294.
van Delden C, Stampf S, Hirsch HH, Manuel O, Meylan P, Cusini A, et al. Burden and Timeline of Infectious Diseases in the First Year After Solid Organ Transplantation in the Swiss Transplant Cohort Study. Clin Infect Dis. 2020;71(7):e159–69. https://doi.org/10.1093/cid/ciz1113.
Rodríguez Sánchez MP, Afanador Rubio DC, Luna IM, García Padilla PK, Contreras Villamizar KM, González González CA, et al. Impact of Complicated Urinary Tract Infection on Renal Graft Function. Transpl Proc. 2020;52(4):1173–7. https://doi.org/10.1016/j.transproceed.2020.01.066.
Al Midani A, Elands S, Collier S, Harber M, Shendi AM. Impact of Urinary Tract Infections in Kidney Transplant Recipients: A 4-Year Single-Center Experience. Transpl Proc. 2018;50(10):3351–5. https://doi.org/10.1016/j.transproceed.2018.08.022.
Origüen J, López-Medrano F, Fernández-Ruiz M, Polanco N, Gutiérrez E, González E, et al. Should Asymptomatic Bacteriuria Be Systematically Treated in Kidney Transplant Recipients? Results From a Randomized Controlled Trial. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2016;16(10):2943–53. https://doi.org/10.1111/ajt.13829.
Sabé N, Oriol I, Melilli E, Manonelles A, Bestard O, Polo C, et al. Antibiotic Treatment Versus No Treatment for Asymptomatic Bacteriuria in Kidney Transplant Recipients: A Multicenter Randomized Trial. Open Forum Infect Dis. 2019;6(6):ofz243. https://doi.org/10.1093/ofid/ofz243.
Coussement J, Scemla A, Abramowicz D, Nagler EV, Webster AC. Antibiotics for asymptomatic bacteriuria in kidney transplant recipients. Cochrane Database Syst Rev. 2018;2(2):Cd011357. https://doi.org/10.1002/14651858.CD011357.pub2.
Coussement J, Kamar N, Matignon M, Weekers L, Scemla A, Giral M, et al. Antibiotics versus no therapy in kidney transplant recipients with asymptomatic bacteriuria (BiRT): a pragmatic, multicentre, randomized, controlled trial. Clin Microbiol Infect. 2021;27(3):398–405. https://doi.org/10.1016/j.cmi.2020.09.005.
Gerber L, Gaspert A, Braghetti A, Zwahlen H, Wüthrich R, Zbinden R, et al. Ureaplasma and Mycoplasma in kidney allograft recipients-A case series and review of the literature. Transplant Infect Dis. 2018;20(5): e12937. https://doi.org/10.1111/tid.12937.
Coussement J, Argudín MA, Heinrichs A, Racapé J, de Mendonça R, Nienhaus L, et al. Host and microbial factors in kidney transplant recipients with Escherichia coli acute pyelonephritis or asymptomatic bacteriuria: a prospective study using whole-genome sequencing. Nephrol Dial Transplant. 2019;34(5):878–85. https://doi.org/10.1093/ndt/gfy292.
Abdo-Cuza AA, Gómez-Bravo MA, Pérez-Bernal JB, Suárez-López J, Gómez-Peire F, Leiva-Torres JL, et al. Health Care-Associated Infection in Solid Organ Transplant Recipients. Transpl Proc. 2020;52(2):509–11. https://doi.org/10.1016/j.transproceed.2019.12.010.
Sayin Kutlu S, Aybek Z, Tekin K, Okke D, Akalin S, Altintas S, et al. Is short course of antimicrobial therapy for asymptomatic bacteriuria before urologic surgical procedures sufficient? J Infect Dev Ctries. 2012;6(2):143–7. https://doi.org/10.3855/jidc.1781.
Yamamoto S, Ishikawa K, Hayami H, Nakamura T, Miyairi I, Hoshino T, et al. JAID/JSC Guidelines for Clinical Management of Infectious Disease 2015 - Urinary tract infection/male genital infection. J Infect Chemother. 2017;23(11):733–51. https://doi.org/10.1016/j.jiac.2017.02.002.
Ramos-Castaneda JA, Ruano-Ravina A, Munoz-Price LS, Toro-Bermúdez R, Ruiz-Londoño D, Segura-Cardona AM, et al. Risk of infection in patients undergoing urologic surgery based on the presence of asymptomatic bacteriuria: A prospective study. Am J Infect Control. 2019;47(12):1474–8. https://doi.org/10.1016/j.ajic.2019.06.024.
• Mohee AR, Gascoyne-Binzi D, West R, Bhattarai S, Eardley I, Sandoe JA. Bacteraemia during Transurethral Resection of the Prostate: What Are the Risk Factors and Is It More Common than We Think? PLoS One. 2016;11(7):e0157864. https://doi.org/10.1371/journal.pone.0157864. Outstanding study showing that there is no relationship between AB and bacteriemia in TUR-P: different microorganisms cause these two entities.
Qi DZ, Lehman K, Dewan K, Kirimanjeswara G, Raman JD. Preoperative urine culture is unnecessary in asymptomatic men prior to prostate needle biopsy. Int Urol Nephrol. 2018;50(1):21–4. https://doi.org/10.1007/s11255-017-1752-2.
Herr HW. Should antibiotics be given prior to outpatient cystoscopy? A plea to urologists to practice antibiotic stewardship. Eur Urol. 2014;65(4):839–42. https://doi.org/10.1016/j.eururo.2013.08.054.
Zhao LC, Meeks JJ, Helfand BT, Ross FR, Herr HW, Kundu SD. Screening urine analysis before bacille Calmette-Guérin instillation does not reduce the rate of infectious complications. BJU Int. 2012;109(12):1819–21. https://doi.org/10.1111/j.1464-410X.2011.10735.x.
Hirakauva EY, Bianchi-Ferraro A, Zucchi EVM, Kajikawa MM, Girão M, Sartori MGF, et al. Incidence of Bacteriuria after Urodynamic Study with or without Antibiotic Prophylaxis in Women with Urinary Incontinence. Rev Bras Ginecol Obstet. 2017;39(10):534–40. https://doi.org/10.1055/s-0037-1604066.
Wu XY, Cheng Y, Xu SF, Ling Q, Yuan XY, Du GH. Prophylactic Antibiotics for Urinary Tract Infections after Urodynamic Studies: A Meta-Analysis. Biomed Res Int. 2021;2021:6661588. https://doi.org/10.1155/2021/6661588.
Aharony S, Przydacz M, Van Ba OL, Corcos J. Does asymptomatic bacteriuria increase the risk of adverse events or modify the efficacy of intradetrusor onabotulinumtoxinA injections? Neurourol Urodyn. 2020;39(1):203–10. https://doi.org/10.1002/nau.24169.
Yassa RR, Khalfaoui MY, Veravalli K, Evans DA. Pre-operative urinary tract infection: is it a risk factor for early surgical site infection with hip fracture surgery? A retrospective analysis. JRSM Open. 2017;8(3):2054270416675083. https://doi.org/10.1177/2054270416675083.
Schmitt DR, Schneider AM, Brown NM. Impact of Perioperative Urinary Tract Infection on Surgical Site Infection in Patients Undergoing Primary Hip and Knee Arthroplasty. J Arthroplasty. 2020;35(10):2977–82. https://doi.org/10.1016/j.arth.2020.05.025.
Gallegos Salazar J, O’Brien W, Strymish JM, Itani K, Branch-Elliman W, Gupta K. Association of Screening and Treatment for Preoperative Asymptomatic Bacteriuria With Postoperative Outcomes Among US Veterans. JAMA Surg. 2019;154(3):241–8. https://doi.org/10.1001/jamasurg.2018.4759.
• Lamb MJ, Baillie L, Pajak D, Flynn J, Bansal V, Simor A, et al. Elimination of Screening Urine Cultures Prior to Elective Joint Arthroplasty. Clin Infect Dis. 2017;64(6):806–9. https://doi.org/10.1093/cid/ciw848. RecommendationofanInfectiousSocietyagainstABscreeningpriortoelectivearthroplasties.
Hellinger WC, Haehn DA, Heckman MG, Irizarry Alvarado JM, Bosch W, Pai SL. Improving Value of Care: Cessation of Screening Urine Culture Prior to Orthopedic and Spinal Surgery. Mayo Clin Proc Innov Qual Outcomes. 2020;4(2):126–31. https://doi.org/10.1016/j.mayocpiqo.2019.12.007.
Rodríguez-Pardo D, Del Toro MD, Guío-Carrión L, Escudero-Sánchez R, Fernández-Sampedro M, García-Viejo M, et al. Role of asymptomatic bacteriuria on early periprosthetic joint infection after hip hemiarthroplasty. BARIFER randomized clinical trial. Eur J Clin Microbiol Infect Dis. 2021. https://doi.org/10.1007/s10096-021-04241-2.
Partridge JSL, Daly M, Hemsley C, Shah Z, Sathanandan K, Mainwaring C, et al. Using implementation science to develop and implement a guideline to reduce unnecessary preoperative testing for asymptomatic bacteriuria prior to elective arthroplasty. J Bone Joint Infect. 2020;6(3):57–62. https://doi.org/10.5194/jbji-6-57-2020.
Sousa RJG, Abreu MA, Wouthuyzen-Bakker M, Soriano AV. Is Routine Urinary Screening Indicated Prior To Elective Total Joint Arthroplasty? A Systematic Review and Meta-Analysis. J Arthroplasty. 2019;34(7):1523–30. https://doi.org/10.1016/j.arth.2019.03.034.
Sendi P, Borens O, Wahl P, Clauss M, Uçkay I. Management of Asymptomatic Bacteriuria, Urinary Catheters and Symptomatic Urinary Tract Infections in Patients Undergoing Surgery for Joint Replacement: A Position Paper of the Expert Group “Infection” of swissorthopaedics. J Bone Joint Infect. 2017;2(3):154–9. https://doi.org/10.7150/jbji.20425.
Fitzpatrick MA, Suda KJ, Burns SP, Poggensee L, Ramanathan S, Evans CT. Pre-operative screening for asymptomatic bacteriuria and associations with post-operative outcomes in patients with spinal cord injury. J Spinal Cord Med. 2019;42(2):255–9. https://doi.org/10.1080/10790268.2018.1451237.
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David Hernandez-Hernandez reports speaker honorarium from Pierre Fabre, Astellas, Asofarma, Lacer, Almirall and Alter; and travel grants from Pierre Fabre and Lacer, all outside of the submitted work.
Barbara Padilla-Fernandez reports personal fees and other from QPharma, outside the submitted work.
David Castro Diaz reports other from Pierre Fabre, other from Astellas, other from Medtronic, other from Lacer, other from Boston Scientific, all outside the submitted work.
Yanira Ortega-Gonzalez declares no conflict of interest.
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Hernández-Hernández, D., Padilla-Fernández, B., Ortega-González, M.Y. et al. Recurrent Urinary Tract Infections and Asymptomatic Bacteriuria in Adults. Curr Bladder Dysfunct Rep 17, 1–12 (2022). https://doi.org/10.1007/s11884-021-00638-z
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DOI: https://doi.org/10.1007/s11884-021-00638-z