Letter to the Editor: Urinary infection in European guidelines 2025 vs microbiology culture results in the management of urinary infection

Abstract

We read with great interest the study by Yadav et al published in the World Journal of Experimental Medicine, which postulated a nomogram including patient’s critical factors, other than urine sample. European Association of Urology (EAU) published the guidelines on urological infection 2025. The EAU guidelines 2025 of urinary infections (UIs) has classified in two distanced categories: Localized UTs and systemic UTs according to specific patient’s symptoms and clinical signs, this new practical classification replaced previous concept of non-complicated urinary tract infection (UTI) against complicated UTI. The new EAU classification categorizes UIs as either localized or systemic, according to the presence of specific clinical signs and symptoms, this new practical classification replaced previous concept of non-complicated UTI against complicated UTI, irrespective of the results of bacteriological findings. In the new classification of UIs, the classification is based on clinical set-up on which the practitioner or urologist will manage the patient. Management of UIs is crucial to consider the urinary and gut microbiota. It was established recently that antibiotic use affects microbiota homeostasis in the gut and urinary tract that will initiate dysbiosis.

Key Words: Microbial communities; Urinary infection; Urine culture; Microbiome; Probiotics; Metagenomics; Antibiotic

Core Tip: The European Association of Urology guidelines 2025 for urinary infections (UIs) published new classification describing localized and systemic UIs. Patient’s Symptoms, clinical examinations, laboratory, and imaging investigation are required to set up the diagnosis. Localized UIs could be treated on an ambulatory basis, while systemic infection indicates hospitalization and monitoring. Urine culture would not reveal all bacterial community in urine. Second generation sequencing reveals bacterial community including dysbiosis and helper microbiota. Implementing the new guidelines would lead to personalized medicine, minimizing antibiotics use, avoid antibiotic resistance, and considering probiotics in treatment of localized infections.

TO THE EDITOR

Recently, Yadav et al[1] published a study in the World Journal of Experimental Medicine, which defined the pathogenic bacteria that necessitate anti-microbial therapy and differentiate it from non-pathogenic bacteria. Urinary infections (UIs) comprise a broad spectrum of pathological and clinical condition that affects various urinary tract components. Every clinical condition necessitates specific diagnostic and treatment approaches, the new European Association of Urology (EAU) guidelines 2025 emphasizing the necessity of a uniform classification. There are now a number of classification schemes in use, while they have many limitations[2].

Most guidelines for clinical practice[3-6], and research[7-10] are based on classification of UIs as uncomplicated or complicated infections, this concept is misjudged in most cases, and is often a determined source of confusion among urologists, general practitioners, and particularly among medical doctors who are not specialized in infectious disease[8,9].

THE NEW EAU CLASSIFICATION 2015 OF UIS

As either localized or systemic, depending on the patient symptoms, and the presence of specific clinical signs. Localized UIs include cystitis that does not exhibit signs or symptoms of a systemic infection in either gender. Symptoms may include dysuria, supra-pubic pain, burning micturition, stinging, urgency, frequency of micturition, incomplete incontinence, urethral discharge, and discomfort or cramping in the lower abdomen.

Systemic UIs manifest with symptoms and signs of systemic infection, accompanied with or without localized symptoms. Systemic UIs would originate from any site in the urinary tract in either male or female, and in children. Manifestations of system UIs are fever, rigors, hypothermia, shaking chills, delirium, hypotension, and tachycardia.

Co-existence of risk factors with either localized or systemic UIs would increase the challenging clinical course and alter the success of treatment. In clinical practice the clinicians should consider the risk factors to personalize the treatment. Risk factors are infants and geriatric age groups, the presence of anatomic or functional abnormalities as congenital anomalies of the urinary tract, or kidney insufficiency. Presence of urinary stones, urethral indwelling urinary catheters, double J urinary stent, considerable post void residual urine volume, immunocompromised state, neurourological patients, recent use of antibiotic, antimicrobial resistant organisms, urinary obstruction at any site of the urinary tract, recent instrumentation, prostatic hypertrophy and prostatitis, and pregnancy.

The EAU guidelines 2025 on UIs presented an example of localized infection in cases of cystitis, the systemic infection are the cases of pyelonephritis or prostatitis. Based upon the 2025 EAU classification of UIs, it would manifest as either localized infection as in cases of cystitis, or systemic infection which is typical in cases of pyelonephritis, orchitis, and prostatitis. The nomenclature uncomplicated and complicated urinary tract infection are no longer used.

The differentiation between localized UIs and systemic UIs is crucial, because it influence the treatment plan and therapeutic decisions. In cases of cystitis which presents with local symptoms without associated systemic manifestations of illness. Systemic UIs as in cases of pyelonephritis or acute prostatitis are characterized by fever, high body temperature, shivering, and, in severe cases, bacteremia, or septicemia.

The 2025 EAU classification of UIs guides the medical clinicians to differentiate between localized UIs, which can be managed on an outpatient or ambulatory basis, the systemic UIs requires definitive diagnostic and treatment measurements, these measurements include imaging, blood cultures, intravenous antimicrobial therapy, and hospitalization for monitoring. This new EAU approach direct clinicians to focus on management of the systemic infection irrespective of categorizing the UI as complicated or uncomplicated. The new EAU classification could reduce the risk of improper classification bias. The proper therapeutic plan will minimize the abuse of antibiotics which is important in an era of increasing antimicrobial resistance[10].

URINE MICROBIAL CULTURING AND THE PRESENCE OF UROPATHOGENS

Culture-dependent methods test for the presence of uropathogens in urine samples from urinary tract has been the standard for decades. Diagnosis of UI involves using standard urine culture methods. This process includes spreading urine samples onto agar plates that contain 5% sheep blood agar and MacConkey agar, then incubating them aerobically at 35 °C for 24 hours to obtain quantitative colony counts[11]. This standard method has critical impediments for the detection of bacteria in urine, with diagnostic thresholds being ≥ 10⁵ culturable CFU/mL[12].

MOLECULAR METHODS SUPPORT THE NEW CLASSIFICATION OF UI AND REVEAL THE PATHOGENS OF RECURRENT INFECTION AND ROLE OF DYSBIOSIS MICROBIOTA

Next generation sequencing (NGS) utilizing 16S rRNA amplicon sequencing indicates the presence of viable bacteria in approximately 90% of samples with no growth by standard urine culture[10]. NGS, and the enhanced quantitative urine culture (EQUC) are two advanced molecular techniques that are implemented in selected cases to unveil the presence of pathogenic, commensal species, and microbiota within the urinary tract. Both molecular methods are not replacing standard urine culture, rather than they are supplement in selected cases and reveal in-depth information on bacterial community in urine which is not detected via standard urine culture. The EQUC technique encompasses diverse combinations of urine volume, incubation duration, and culture medium types, along with aerobic, anaerobic, microaerobic, and CO₂-supplemented environments[11-13].

In contrast to EQUC, the standard urine culture was designed to distinguish the major uropathogen Escherichia coli (E. coli) and different bacterial species that colonize in a similar growth requirements. Comparison between the two techniques revealed that standard urine culture missed 67% of all uropathogens and 88% of non- E. coli uropathogens that were detected by EQUC.

EQUC protocol detected 84% of potential uropathogens, whereas standard urine culture detected 33% of potential uropathogens[13]. NGS is used for detection of microbial community in urine and detect dysbiosis and helper microbiota. Application of NGS showed that the urinary microbiomes of women are Lactobacillus, Corynebacterium, Streptococcus, Actinomyces, and Staphylococcus, which were the most prevalent genera isolated from urine by EQUC, followed genera detected by NGS metagenomics. NGS detect phyla Actinobacteria (Propionimicrobium, Varibaculum, Atopobium), Firmicutes (Peptoniphilus, Megasphaera, Finegoldia), and Bacteroidetes (Prevotella) by Aerococcus, Gardnerella, Bifidobacterium, and Actinobaculum[14]. The EQUC captured approximately 72% of the uropathogenes[15]. NGS is the accurate method to detect urinary pathogenies and microbiomes[16]. The cumulative data on the results of NGS in urine of women with recurrent localized UIs showed that Lactobacillus supplement in the form of probiotic would cure UIs, consequently, limit the antibiotic use and avoid development of antimicrobial resistance.

The development of UIs classifications drives towards a personalized approach to providing an improved treatment outcome. Previous classification systems, which depended on the results of urine culture, and classification of non-complicated and complicated subtypes were often short of providing the clinical clarity needed to make appropriate decisions. The new EAU classification, published in the year 2025 version of the EAU guidelines on urological infections, provides more precise items focused on clinically applicable framework that emphasized the clinical signs and symptoms of UIs. The new guidelines expedite clinician decision-making to ensure that patients receive the most appropriate treatment based on the severity of their infection, minimizing the risk of over-or under-treatment and improving patient safety.

Recently, available evidence of new treatments facilities for recurrent UIs ranging from oral antibiotic therapy to intravesical antimicrobials, and probiotics. Prophylactic strategies for recurrent UIs including long-term antibiotic prophylaxis, estrogen hormone therapy for women, and dietary supplements.

CONCLUSIONS

In conclusion we recommend the use of EAU guidelines 2025 in daily practice for diagnosis of UIs. The two categories of localized and systemic are well defined in the guidelines, implementing this classification will secure personalized medicine, avoid unnecessary antibiotic administration, possibility of the use of probiotics, and will diminish the development of antimicrobial resistance.