NRMJ_9_4_252-272

Introduction

Nosocomial urinary tract infections (UTIs) are among the most prevalent healthcare-associated infections (HAIs), accounting for approximately 30–50 % of all HAIs (Fekadu et al., 2025). These infections are often linked to prolonged catheterization, invasive urological procedures, and inadequate infection control practices in healthcare settings. The consequences include increased patient morbidity, prolonged hospitalization, and higher healthcare costs.

Gram (-) bacteria are the most common pathogens responsible for nosocomial UTIs. Among them, Escherichia coli (E. coli) is the most frequently isolated, particularly in catheter-associated urinary tract infections (CAUTIs). Many hospital-acquired E. coli strains exhibit multidrug resistance, including the production of extended-spectrum β-lactamases (ESBLs) (Padmini et al., 2017). Klebsiella pneumoniae (K. pneumonia) is also commonly associated with CAUTIs and bloodstream infections; with certain strains producing carbapenemase enzymes that complicate treatment (Mohd-Asri et al., 2021). Pseudomonas aeruginosa, known for its intrinsic resistance to multiple antibiotics, can cause severe infections, especially in immunocompromised patients (Paprocka et al., 2022).

In addition to Gram (-) bacteria, Gram (+) species such as Enterococcus faecalis and Enterococcus faecium are frequently implicated in UTIs. These microorganisms pose treatment challenges due to their high-level resistance to vancomycin (Gajdács et al., 2020). In patients with long-term indwelling catheters, certain pathogens; particularly urease-producing bacteria, can contribute to the formation of bladder and kidney stones, further complicating management (Armbruster et al., 2018).

Catheterization is the most significant risk factor for developing nosocomial UTIs. It disrupts the natural defense mechanisms of the urinary tract and facilitates microbial entry. Other contributing factors include prolonged hospitalization, prior use of antibiotics, immunosuppression, and poor adherence to infection control protocols (Hooton et al., 2020). Transmission can occur via contaminated medical devices, the hands of healthcare workers, or environmental surfaces (Magill et al., 2014).

Despite their prevalence, nosocomial UTIs are largely preventable. Key preventive strategies include minimizing unnecessary catheter use, ensuring aseptic techniques during insertion and maintenance, and adhering to strict hand hygiene. The increasing emergence of multidrug-resistant (MDR) pathogens underscores the urgent need for robust antimicrobial stewardship and infection surveillance programs (Patel et al., 2023).

Nosocomial UTIs, especially those caused by MDR organisms, pose a serious challenge to healthcare systems. However, through effective prevention strategies and improved antimicrobial management, their burden can be significantly reduced. The objective of this review is to provide an overview on the epidemiology, pathophysiology, antimicrobial resistance mechanisms, and preventive measures associated with nosocomial UTIs, aiming to support ongoing efforts in infection control and patients safety.

Definition of nosocomial urinary tract infections

Nosocomial UTIs (also known as healthcare-associated UTIs) are infections of the urinary system that develop during or post-hospitalization in patients who did not have an incubation period of the infection on admission. These infections are generally acquired at least 48 h after hospital admission and are frequently linked to the use of indwelling urinary catheters. UTIs are the most prevalent healthcare-associated infections and comprise more than 30 % of infections identified by acute care hospitals (Iacovelli et al., 2014). UTI is the second most common type of bacterial infection after respiratory tract infection and they mainly affect women. Herein, we note that up to 50 % of women experience at least one episode of UTI in their lifetimes and one in four of these women will develop a recurrence (Bennett and Blaser, 2015; Raphael and Huang, 2024). Signs and symptoms vary by site of infection; however, upper UTI (pyelonephritis) is typically characterized by fever and flank pain, while lower UTI (cystitis) is typically characterized by some or all of the following symptoms: Dysuria, frequency, hematuria, and suprapubic tenderness. The determinants of complicated UTIs can be divided into two categories, each of which can predispose an individual once the typical uropathogens have overcome the natural barrier of host resistance: (i) obstruction of normal urinary flow, attributed to congenital malformations, renal calculi, or prostate enlargement, and (ii) foreign body in the urinary tract (i.e., nonspecific catheters such as urethral or supra-pubic) (Bennett and Blaser, 2015). Understanding the magnitude of nosocomial UTIs is essential for improving patients care and clinical outcomes in healthcare settings. These infections, mainly caused by pathogens such as E. coli and K. pneumoniae, are associated with higher incidence of illness and longer duration of hospital stays, as well as increased healthcare costs that exceed billions $ each in the U.S. Multidrug resistance; especially among microorganisms associated with nosocomial UTIs, poses a serious barrier and complicates treatment, while highlighting the need for strong antibiotic stewardship programs. Learning about the epidemiology, risk factors, and resistance mechanisms for nosocomial UTIs will help healthcare practitioners implement targeted interventions, enhance infection control measures, and develop evidence-based recommendations for prevention and treatment (Dias, 2020). So, in summary, an in-depth understanding of nosocomial UTIs is crucial to improve patient outcomes and reduce the significant healthcare burden associated with these infections.

Classification of urinary tract infections

At present, UTIs are typically described in terms of two primary types: Uncomplicated UTIs and complicated UTIs (Wagenlehner et al., 2020). Simple UTIs usually mean bladder and surrounding structures infections with no structural abnormality or comorbid condition. Although these infections are common in otherwise healthy patients, they can certainly be more common in persons living with diabetes, those who have weakened immune systems, or during the pregnancy (Bono et al., 2021). Complicated UTIs has been associated with conditions affecting the urinary tract including urinary stones, obstruction, congenital malformations (or congenital deformities of the urinary tract), polycystic kidneys, neurogenic bladder, renal function impairment, and presence of foreign materials (Reyner et al., 2016; Dinh et al., 2019). UTIs can also be classified based on their location, usually known as upper or lower UTIs. UTIs can be characterized as lower UTIs, including urethritis, cystitis and prostatitis, and upper UTIs, mainly pyelonephritis (Johansen et al., 2011). Clinical symptoms differentiate among these types; however, fever that is often a sign of tissue damage and inflammation, usually occurs with upper UTIs (such as pyelonephritis or prostatitis), but in some cases it may also be seen in lower UTIs (Downey, 2019). Routine urine cultures are not routinely recommended for uncomplicated cystitis as the cultures do not improve symptom resolution (Al-Lawati et al., 2024). For complicated or recurrent UTIs, acute pyelonephritis, or patients at risk of infection with antibiotic-resistant bacteria, urine cultures are critical for diagnosis and treatment (Baron et al., 2013). Correct urine collection is imperative in diagnosing acute pyelonephritis since blood cultures may not provide clear evidence that the infection has been successfully treated. Anatomically, UTIs are divided into lower UTIs and upper UTIs (Sun et al., 2024), with pyelonephritis the more complex form of upper UTIs, while Cystitis is the most common type in the lower UTI (Fig. 1, Millner and Becknell, 2019).

Global burden of nosocomial urinary tract infections

Nosocomial urinary tract infections (UTIs) are among the most frequently reported HAIs worldwide, accounting for significant morbidity, mortality, and economic burden across both high-income and low- and middle-income countries (LMICs). According to the World Health Organization (WHO), UTIs represent a leading cause of HAIs globally; particularly in resource-limited settings, where infection control practices may be inadequate (Iacovelli et al., 2014; Mathur et al., 2022).

The incidence of hospital-acquired UTIs varies significantly by region. In high-income countries, UTIs comprise approximately 20–30 % of all HAIs, while in LMICs, prevalence rates can be substantially higher, often exceeding 40 % of reported infections (Haque et al., 2018; Odoom et al., 2024). Catheter-associated UTIs (CA-UTIs) are the most prevalent form, accounting for up to 75–80 % of nosocomial UTIs, especially in intensive care units and surgical wards (Bizuayehu et al., 2022; Duque et al., 2024).

Globally, the use of indwelling urinary catheters is widespread; with an estimated 15–25 % of hospitalized patients undergoing catheterization during their stay, creating a substantial risk factor for CA-UTIs (Nalbandian et al., 2022). The burden is compounded by the increasing prevalence of multidrug-resistant uropathogens such as E. coli, K. pneumoniae, and P. aeruginosa, particularly in hospitals with limited access to antimicrobial stewardship programs (Kang et al., 2003).

The economic consequences of nosocomial UTIs are also profound. In the United States alone, the additional healthcare costs related to CA-UTIs are estimated to exceed $400 million annually (Zimlichman et al., 2013). In LMICs, nosocomial UTIs not only increase treatment costs but also consume limited healthcare resources and contribute to higher in-hospital mortality rates (Haque et al., 2018).

Efforts to address the global burden of nosocomial UTIs must include standardized surveillance systems, improved infection prevention practices, and international collaboration to strengthen antimicrobial stewardship and healthcare infrastructure in resource-limited settings.

Risk factors for nosocomial urinary tract infections

Several risk factors contribute to the development of these infections, including patient-related and healthcare-related factors as shown in Table 1.

A pathophysiology of nosocomial urinary tract infections

The urinary system is made up of a complex of hollow organs that connect to each other, including the kidneys, ureters, bladder, and urethra. The kidneys, among others, perform an important function, eliminating wastes while reabsorbing the most vital things like water, glucose, and amino acids. After filtration, urine goes from the kidneys via the ureters to the bladder, a stretchy muscular organ that stores urine until it’s ejected through the urethra. Under normal conditions, the urinary tract is a closed system that prevents infections by creating a habitat unsuitable for pathogens. However, UTIs can occur when bacteria persue these defenses and cause infections that ascend from the bladder to the kidneys, causing kidney damage in some cases (Measley and Levison, 1991; Hickling et al., 2015). There are three main routes for bacteria to invade the urinary tract: ascending infection, hematogenous (blood-borne) spread, and lymphatics. The upward journey is the more common route; especially among women, thanks to anatomical elements including a shorter urethra, hormonal effects and proximity of the anus to the urethral opening. Infection starts when bacteria, most commonly from the Gastrointestinal (GI) tract or fecal flora, bind to the urethra, colonize the bladder, and ascend the ureters to the kidneys, causing cystitis (bladder infection) and pyelonephritis (kidney infection) (Walsh and Collyns, 2020; Mancuso et al., 2023; Baimakhanova et al., 2025).

Some things such as urinary catheters, spermicidal agents, pregnancy, and/or ureteral blockages can promote this process, but the precise mechanisms are still unclear. Less common routes include descending channel and hematogenous pathways, usually attributed to bacteria such as Streptococcus or Staphylococcus spp. These spp. contribute to less than 5 % of UTIs and have a higher incidence in patients

Table 1: Risk factors disposing for nosocomial urinary tract infections.

Risk factor	Description/ Examples	References
Indwelling urinary catheterization	Most common risk; especially when catheter is in place >48 h	(Letica-Kriegel et al., 2019)
Prolonged hospital stay	Longer duration increases exposure to resistant pathogens and invasive procedures	(AlHazmi, 2015).
Advanced age	Increased susceptibility due to comorbidities and immune senescence	(Yun et al., 2020).
Female sex	Shorter urethra and proximity to the anus increase risk	(Nicolle, 2014)
Diabetes mellitus	Hyperglycemia and impaired immune responses predispose to infection	(Geerlings, 2008)
Immunosuppression	Includes patients receiving corticosteroids, chemotherapy, or transplant recipients	(Kass, 2002)
Instrumentation of the urinary tract	Includes cystoscopy, catheter irrigation, and urological surgeries	(Herr, 2015; Wawrysiuk et al., 2022)
Recent antibiotic use	Disrupts normal flora and selects for MDR microorganisms	(Weinstein et al., 2005)
ICU admission	Higher use of catheters, critical illness, and exposure to MDR microorganisms	(Vincent et al., 2009)
Poor catheter care practices	Breaks in aseptic technique during insertion or maintenance	(Hooton et al., 2010)

suffering from ureteral blockages and in immunocompromised patients (Baimakhanova et al., 2025). In severe cases, bacteria can enter the bloodstream to cause bacteremia, which can result in infections in other organs such as the lymph nodes. Notably, in rare instances, the bacteria from adjacent organs can gain access to the urinary tract via the lymphatic system, such as might be seen with retroperitoneal abscesses or severe bowel infections (Baimakhanova et al., 2025).

Nosocomial urinary tract infections pathogens

The most common causes of UTIs in hospital settings are uropathogenic E. coli (UPEC), accounting for ~40 % of the incidence of such infections. Importantly, other MDR-microorganisms, such as K. pneumoniae, P. aeruginosa, and Enterococcus faecalis are vital pathogens with unique qualities that complicate the treatment (Flores-Mireles et al., 2019; Kuwa et al., 2021). The emergence of alternative pathogenic microorganisms’; particularly non-albicans species of Candida, have added an extra level of complexity to nosocomial UTIs induced by both bacterial and fungal pathogens, where this occurrence has currently been reported predominantly in immunocompromised individuals (Jahagirdar et al., 2018). Due to the wide variety and continuously evolving resistance mechanisms of uropathogens, effective management and treatment of UTIs remains a challenge in the hospital environment. Table 2 shows Common nosocomial urinary tract infections pathogens and their resistance mechanisms. UPEC is responsible for most UTIs and can be classified into four predominant phylogroups; mainly Phylogroup A, Phylogroup B1, Phylogroup B2, and Phylogroup D, according to the distribution of chromosomally encoded pathogenicity islands (PAI) (Terlizzi et al., 2017; Katongole et al., 2020). Studies of UPEC virulence profiles rely upon surface and secreted virulence factors, including fimbriae, flagella and capsular lipopolysaccharides, hemolysin, and siderophores (Shah et al., 2019).

Another relevant pathogen is Proteus mirabilis that accounts for 1–10 % of UTIs and is classified as a motile, rod-shaped bacterium that exhibits swarming behavior on solid media. This bacterium has also been previously linked to community-acquired and hospital-acquired UTIs (including CAUTIs). Virulence factors such as biofilm, adhesion molecules, urease, proteases, and toxins are responsible for pathogenicity (Hayder et al., 2020; Tabatabaei et al., 2021). A wide range of virulence factors employed by K. pneumoniae enables the pathogen to evade the immune response and instigate disease (Davoudabadi et al., 2023). Among the boldly opportunistic isolates, a special mention goes to P. aeruginosa, the most important cause of hospital-acquired UTIs not only does it possess a virulent arsenal that facilitates severe infections, particularly in immunocompromised hosts, but it also demonstrates other factors contributing to its pathogenicity (Heidary et al., 2016). While Staphylococcus aureus is a rare cause of UTIs in the average patient population, which is also capable of inducing severe systemic infections, such as bacteremia, septic shock, and even death (Xu et al., 2023). Methicillin-resistant Staphylococcus aureus (MRSA) UTIs, which are frequently linked to prior antibiotic therapy and use of catheters, remain a significant obstacle in the health care field due to extended hospital stays and increased complication rates (Al-Shomrani et al., 2023). These are bacteria with virulence factors that are essential for establishment of a UTI. For example, lipopolysaccharides from Gram (-) bacteria’s outer membrane can provoke a strong inflammatory response. But in order to take a ride, those uropathogens have to stick; itself a key early step in an infection, which is made possible by adhesion proteins on the surface of uropathogens. Biofilms, or clusters of bacteria ensconced in a protective matrix, provide bacteria with a safe home where they can escape from the immune system and avoid the effects of antibiotics. Katongole et al. (2020) argued that when the urine flow is obstructed or inhibited, it is easier for bacteria to attach, multiply, and cause infection.

Biofilms and catheters

A biofilm is a collection of micro-organisms that stick together in a protective matrix of polysaccharide, DNA, and other materials. These biofilms act as a barrier, protecting the microorganisms from both host immune response and external pressures such as antibiotics. For example, dormant intracellular reservoirs formed by UPEC biofilms in the urinary tract can account for relapsing infection (core urine). Similarly, P. aeruginosa will also adhere to the injured bladder wall and forms biofilms using the quorum sensing mechanisms. This causes the bacteria to produce rhamnolipids, subsequently changing the hydrophobicity of their cell-surface and promote microcolonies formation. A recent study reported that polymer-coated urinary catheters dramatically reduced biofilm biomass and mineralization compared to uncoated catheters. The coated catheters revealed decreased levels of fibrinogen deposition, which is known to improve bacterial colonization and hence reduce the incidence of CAUTIs (Kalenderski et al., 2024). They also utilize lectin adhesins and elastases along with extracellular DNA to stabilize their biofilms (Flores-Mireles et al., 2015). Urinary catheters, a type of medical device, may naturally be prone to biofilm formation. P. mirabilis, for instance, generates crystalline biofilms affixed to the surface of the catheter via its urease-generated crystals that are sequestered within a bacterial matrix. This biofilm can interfere with the flow of urine, leading to infection. For example, E. coli and Enterococcus faecalis use fibrinogen, which is released in large amounts during inflammation of the bladder, as both a nutrient source and a structure-giving component for biofilms formed on catheters (Flores-Mireles et al., 2015).

Urinary tract infection (UTI) is a common type of hospital-acquired infection, mainly occurs in patients with drainage devices (i.e., urinary catheters), and causes morbidity and prolonged hospital stay. Indeed, more than 80 % of hospital-acquired UTIs are associated with these devices (Johnson et al., 2006). Catheter related UTIs are the most common hospital-acquired infection, and while many patients with stable catheters no longer meet criteria for catheter use, studies have suggested that unnecessary catheterization contributes to infection rates (Kilonzo et al., 2014). In intensive care units (ICUs), UTIs account for up to 40 % of hospital-acquired infections and impose a particular burden on hospital resources because of comorbidity and mortality associated with these infections. Pathogens related with these infections are E. coli, Klebsiella spp., Proteus spp., Enterococcus spp., Enterobacter spp., and Pseudomonas spp. (Kilonzo et al., 2014). Most of the UTIs in hospital settings stem from catheter use, and although many are curable with the removal of the catheter, however; UTIs also lead to more severe complications such as bacteremia which is responsible for 18-20 % of hospital infections (Lam et al., 2014). In order to minimize these infections, guidelines advise limiting the use of catheters and using them for shorter periods of time. Alcohol-based hand rubs improve compliance, reduce nosocomial infections up to 40 %, and provide optimal hand hygiene (Lam et al., 2014).

Table 2: Common nosocomial urinary tract infections pathogens and their resistance mechanisms.

Pathogen	Resistance mechanisms	References
Escherichia coli	- Extended-spectrum β-lactamases (ESBLs), i.e., Cefotaximase-M (CTX-M), Temoniera (TEM), and Sulfhydryl Variable (SHV). - Fluoroquinolone resistance (gyrA and parC mutations). - Aminoglycoside-modifying enzymes.	(Bush and Bradford, 2020; Tamma et al., 2021).
Klebsiella pneumoniae	- ESBLs production - Carbapenemase production OXA-48 β-lactamase (OXA-48), Klebsiella pneumoniae Carbapenemase (KPC), and New Delhi Metallo-β-Lactamase(NDM). - Efflux pumps.	(Logan and Weinstein, 2017)
Pseudomonas aeruginosa	- Metallo-β-lactamases Verona Integron-Encoded, Metallo-β-Lactamase (VIT), and Imipenemase (IMP). - Loss of Outer Membrane Protein D. - Multidrug efflux pumps (MexAB-OprM).	(Pang et al., 2019)
Proteus mirabilis	- ESBLs. - AmpC β-lactamase. - Intrinsic resistance to nitrofurantoin.	(Datta et al., 2014)
Enterococcus faecalis/ faecium	- Vancomycin resistance (VanA and VanB). - Intrinsic cephalosporin resistance. - Linezolid resistance (23S rRNA mutations).	(Miller et al., 2014)
Enterobacter spp.	- AmpC β-lactamase (inducible or plasmid-mediated). - Carbapenem resistance via porin loss + β-lactamases.	(Patel and Bonomo, 2013)
Staphylococcus saprophyticus	- Resistance to novobiocin. - Occasionally methicillin resistance (mecA gene)	(Becker et al., 2014)
Candida spp.	- Azole resistance (ERG11 mutations and efflux pumps) - Echinocandin resistance (FKS mutations)	(Perlin et al., 2017)

Antimicrobial resistance in nosocomial urinary tract infections pathogens

Nosocomial UTIs, or hospital-acquired UTIs, are associated with several antibiotic-resistant mechanisms that complicate the use of antibiotics to treat these infections. One important mechanism of resistance is overproduction of β-lactamases that cleave the β-lactam structure of penicillins and cephalosporins, making these antibiotics ineffective. Extended spectrum β-lactamases (ESBLs) and more recent carbapenemases are mechanisms which provide resistance to an extensive range of β-lactam antibiotics, including the commonly last-line treatment option carbapenems (Bush and Bradford, 2020). Another major resistance mechanism is efflux pumps. These are membrane proteins that function as active transporters, expelling antibiotics from the bacterial cells and decreasing the concentration of the drug inside the cell. This allows bacteria to withstand antibiotic exposure that would otherwise be fatal. The AcrAB-TolC efflux pump in E. coli, for instance, affords the bacterium resistance to multiple classes of antibiotics, including fluoroquinolones and tetracyclines (Nikaido, 1996).

Biofilm formation is also central to antibiotic resistance. Biofilms are protective matrices of bacteria that are formed by the bacteria, shielding the bacteria from antibiotics and immune system, leading to harder-to-treat infections; particularly around indwelling devices such as urinary catheters. In these situations, infections frequently necessitate combination treatments or catheter removal (Wu et al., 2015). Multidrug-resistance (MDR) and extensively drug resistant (XDR) microorganisms in hospital-acquired UTIs have emerged as a major health problem. MDR means resistant to at least one antibacterial agent in three or more classes and the most typical pathogens are those of the family Enterobacteriaceae, P. aeruginosa, and species of the genus Enterococcus. Strains resistant to all but one or two classes of antibiotics (XDR) are even more challenging to treat (Magiorakos et al., 2012). The increasing prevalence of ermB-positive Enterococcus isolates has also been documented in hospitals, with resistance rates reported as high as 50 % in some areas (Tacconelli et al., 2018). Carbapenem-resistant Enterobacteriaceae (CRE) is one of the most important threats, which are also associated with high morbidity and mortality rates. Two other extremely important pathogens contributing to the growing issue of resistance, P. aeruginosa and Acinetobacter baumannii are inherently resistant to many antibiotics and are also developing MDR and XDR phenotypes (Tamma et al., 2021). Consequently, standard empiric therapies may become ineffective owing to the persistent rise of antibiotic resistance, leading to delayed treatment, prolonged hospital stays, and increased healthcare costs. And once again, with true antibiotics being few and far between, physicians increasingly have to resort to older and more antimicrobial agents as colistin, or to experimental antibiotics with unknown safety and efficacy profiles (Sorlí et al., 2019; Ahmed et al., 2019; Marantidis et al., 2023). The interactions among these biofilms and medical devices additionally complicate treatment, where biofilm-associated bacteria are notoriously difficult to eliminate, sometimes requiring multiple courses of antibiotics, leading to recurring infections. Globally, this issue transects or even promulgates by horizontal gene transfer of resistance genes, Therefore, strong infection control policies and proactive antimicrobial stewardship programs are needed to counteract the increasing infection risk (Karanika et al., 2016).

Diagnosis of nosocomial urinary tract infections

Urinary tract infection (UTI) is an important global health problem, and it is important to find it quickly to prevent serious health complications. The standard method for diagnosing UTI involves using a patient’s urine to identify the presence of bacteria, usually with a diagnosis of UTI when the counting of bacteria exceeds 105 CFU/ ml to clean urine. However, traditional cultural methods can be time -consuming, often the results require 24 to 48 h, delaying the treatment and giving rise to severe complications. Faster alternative such as polymerase chain reaction (PCR) provides quick findings with excellent sensitivity for detecting bacterial infections (Kapoor et al., 2024). Disadvantages involve the presence of exogenous DNA, resulting in false positives and often produce qualitative rather than quantitative data. Meanwhile, Immunoassays can deliver speedy results and are suitable for point-of-care testing. However, its efficiency depends on the availability of specific antigens and may not be sensitive enough to detect all diseases, which represent its main disadvantages.

The clinical gold standard for UTI diagnosis is quantitative urine culture; however, results take approximately 24 h, and an additional 24 h is required to assess antibiotic susceptibility. This delay allows the cause of infection to be established, and broad-spectrum antibiotics are empirically prescribed as a result. Another recent advance in UTI detection is via the use of surface-enhanced Raman spectroscopy, where the bacterial protein can accurately determine whether a particular bacterium is present and what strain it is by measuring the spectral signature of the different bacteria within the urine. Such a technique is faster and more efficient to detect UTI (Halpern et al., 2017).

Conventional methods

These diagnostic methods have been available for years and encompass culture-based and non-culture-based techniques. Widespread methodologies include enzyme-linked immunosorbent assay (ELISA), isothermal microcalorimetry, and PCR (Kaur and Kaur, 2021).

Non-culture methods

One of the most widespread tests for UTIs diagnosis is the urine dipstick test. This method employs Siemens Multistix, which can identify nitrites (metabolic byproducts of certain urinary pathogens), leukocyte esterase, protein, and blood, all of which can be indicative of an inflammation or infection. If positive, nitrites or leukocyte esterases increase the chance of a UTI. Nonetheless, dipstick testing for blood and protein has low sensitivity and specificity, which may lead to false positive results (Papava et al., 2022). Gram staining of un-centrifuged urine samples is another strategy that enables microscopic detection of bacterial growth, providing timely information regarding a microoorganism’s morphology and ability to form leaping chains. This method has a major drawback as it can only detect bacteremia with an upper limit of 105cfu/ mL, making it impossible to detect infections with lower bacterial counts (Kumar et al., 2016).

Culture methods

The oldest techniques for detecting microorganisms are culture-based methods. However, this methodology needs individual types of culture media and supplements based on each microorganism. Standard urine cultures are processed using a semi-quantitative plating method with calibrated loops to calculate bacterial cfu/ml of urine. Not only does this method quantitate bacterial growth, but it also enables colony isolation and antibiotic susceptibility testings. Some of the most commonly used culture media are MacConkey and blood agar, which promote growth of various bacterial spp. (Kumar et al., 2016).

Polymerase chain reaction (PCR)

Molecular methods detect bacteriuria in urine, blood, and other clinical samples via amplification of DNA with universal or selective primers. For instance, van Der Zee et al. (2016) developed and evaluated 2 semi-quantitative Real-time PCRs based on single-gene targets for both bacterial quantification and identification in urine. Furthermore, Wojno et al. (2020) demonstrated that multiplex PCR provides significantly improved detection of bacterial UTIs in symptomatic patients compared to standard urine culture.

Isothermal microcalorimetry

Isothermal microcalorimetry derives microbial growth curves from measuring on-line the heat generated by the microbial growth, representing the division of cells and metabolic processes. Braissant et al. (2014) demonstrated it possible deliver an antibiogram faster and more accurately (95 % sensitivity and 91 % specificity) from UTIs, which benefits quicker diagnosis of UTIs, which can generate antibiograms in about 7 h.

Enzyme-linked immunosorbent assay (ELISA)

Enzyme Linked Immunosorbent Assay (ELISA) is an effective laboratory technique that can be used to identify uropathogens and monitor their growth by detecting specific bacterial antigens in clinical samples. It can also be used for identification of antigens or antibodies; for differentiation among microbial strains and mapping of epitopes on bacterial surfaces. For example, Shih et al. (2015) invented a rapid, low-cost, paper-based format ELISA to diagnose E. coli UTIs or asymptomatic bacteriuria (ABU) in 5 h, providing an opportunity for cheaper and faster diagnostics.

Emerging diagnostic technologies for urinary tract infections

Urinary tract infections (UTIs) are among the most common healthcare-associated infections (HAIs), significantly contributing to patient morbidity, prolonged hospital stays, and increased healthcare expenditures. Traditional diagnostic approaches, such as urine culture, remain the gold standard but typically require 24–72 h to yield results. This delay often leads to empirical antibiotic use, which can contribute to inappropriate treatment and antimicrobial resistance. In response, several emerging diagnostic technologies have been developed to provide faster and more accurate detection of uropathogens and their resistance profiles (Davenport et al., 2017). Among the most promising tools are:

Flow cytometry

Flow cytometry enables rapid quantification of leukocytes, bacteria, and epithelial cells directly from urine samples. It offers high sensitivity and specificity and can serve as a pre-screening tool to reduce unnecessary cultures. Although it does not identify specific pathogens, it is valuable for triaging of urine samples (Gerace et al., 2022).

Mass spectrometry (MALDI-TOF MS)

Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) allows for rapid identification of bacterial species based on protein spectral fingerprints. When combined with short incubation periods or direct urine processing protocols, MALDI-TOF MS significantly reduces time for diagnosis. However, it requires specialized equipment and trained personnel, which can limit its use in smaller clinical settings (Bedenić and Meštrović, 2021).

Multiplex polymerase chain reaction

Multiplex PCR assays enable simultaneous detection of multiple uropathogens and resistance genes within few hours (Hatfield et al., 2024). This technology improves diagnostic accuracy and can guide targeted antibiotic therapy early in the course of infection. Its limitations include high cost, need for standardized panels, and potential detection of colonization rather than infection.

Microfluidics and biosensors

Microfluidic platforms and biosensors are at the forefront of point of care (POC) diagnostics. These devices miniaturize laboratory processes onto a single chip (i.e., a single chip is an electronic chip that integrates all system components, like the processor and memory) enabling rapid detection of pathogens and antibiotic susceptibility testing’s directly from urine. Biosensors can detect specific bacterial metabolites or nucleic acids with high precision. However, many remain in the developmental or validation stages and have yet to achieve widespread clinical implementations (Çelik et al., 2024).

Real-time microscopy and artificial intelligence integration in urinary tract infection diagnostics

Real-time microscopy enhanced by artificial intelligence (AI) algorithms can rapidly analyze urinary sediments, and identifying bacterial morphology and host response markers. Such platforms have the potential to automate diagnosis and reduce operator variability; however, their clinical validation is still ongoing.

A previous study conducted by Liou et al. (2024) presented an open dataset containing 300 images and 3,562 manually annotated urinary cells labeled into seven classes of clinically significant cell types. This dataset was used to train a Patch U-Net; a novel deep learning architecture, demonstrating the potential of AI in automating urinary sediment analysis. Similarly, Dedeene et al. (2024) discussed the development of AI-driven models for rapid prediction of urine culture test results. These models aim to enhance diagnostic accuracy and reduce the time required for UTI diagnosis. Naik et al. (2024) highlighted the current state of AI-based systems in supporting UTI diagnosis.

This review emphasizes the need for further studies utilizing large, heterogeneous datasets, and external validations to define the actual clinical workflow value of AI. Meanwhile, these previous studies underscore the potential of integrating AI with real-time microscopy to enhance the accuracy and efficiency of UTI diagnostics. However, they also highlight the necessity for further clinical validation and standardization before widespread clinical implementation.

Potential impact and limitations

Emerging technologies offer significant benefits, including reduced turnaround time, improved diagnostic precision, and enhanced antimicrobial stewardship. However, several barriers to implementation remain, such as:

High costs of equipment and reagents;
Lack of standardized interpretation criteria;
Limited integration into existing laboratory workflows; and
Variability in regulatory approval and reimbursement policies.

These innovations represent a paradigm shift in UTI diagnosisfrom culture-dependent to rapid, point-of-care, and molecular-driven platforms. Their widespread adoption depends on further clinical validation, cost-effectiveness analysis, and integration into national diagnostic guidelines. Table 3 presents a comparison of traditional and emerging diagnostic technologies for urinary tract infections

Biomarkers for detecting nosocomial urinary tract infections

Urinary tract infections (UTIs) are among the most common hospital-acquired infections associated with considerable morbidity and healthcare expenditure (Sihra et al., 2018). But antimicrobial resistance (AMR), a leading global threat to patient safety, is of even greater concern. AMR is associated with more serious infections, longer stays in hospital, and higher mortality. It is essential to have accurate and prompt diagnosis of UTIs in order to minimize the use of antibiotics and combat the emergence of AMR. Urine culture is still the gold standard for UTI diagnosis, but has notable shortcomings, such as a low positive detection rate and time-consuming processing, which renders it unable to meet urgent clinical needs. Consequently, increased attention is being given by researchers to discover new biomarkers for UTI diagnosis (Sun et al., 2024).

Multiple promising biomarkers have been explored:

Neutrophil gelatinase-associated lipocalin (NGAL) has proved to be a highly effective UTI biomarker and is now established;
The metabolites IL-1β, IL-8, and Heparin-binding protein (HBP) can be used to differentiate pyelonephritis from lower UTIs;
Matrix metalloproteinases-9 (MMP-9) and Lactoferrin (LF) may help in diagnosis of asymptomatic bacteriuria (ASB); however, further monitoring is needed;
Nucleic acid based-pathway biomarkers (e.g., 16S rRNA) show potential for pathogen identification; especially with increased interest in urinary microbiome and metagenomic sequencing studies; and
Diagnostic potential of metabolic and lipidomic markers and others. There have been advancements but challenges still remain.

Some well-described sensitivity and specificity of biomarkers have been reported according to age, gender, or other conditions that affect the clinical use of these biomarkers. Thus, they are required to be confirmed by clinical studies and replicate their performance in advanced diagnostic tests. Microbiological diagnosis remains a cornerstone for monitoring and detection of UTI while the search for reliable biomarkers is ongoing. This dual-component approach using microbiological-testing in tandem with other biomarker-based diagnostic methodologies may hold the key to transforming UTI diagnosis and treatment to extend far beyond clinical measures and improve patient outcomes in the future (Sun et al., 2024).

Novel intervention strategies for urinary tract infections in the face of growing antimicrobial resistance

Urinary tract infections (UTIs) caused by antibiotic-resistant Gram-(-) bacilli constitute a major healthcare challenge because of the reduced treatment options. Enterobacteriaceae is one of the predominant causes of both community-acquired and hospital-acquired UTIs. Their significance can’t be underestimated, as these microorganisms enjoy acquiring resistant traits such as extended-spectrum beta-lactamases (ESBLs), AmpC beta-lactamase, and carbapenemases, making them MDR and a cause of difficult to treat infections (Mazzariol et al., 2017). Diagnosis is based on typical symptoms, urinalysis with dipstick or microscopic analysis, and urine culture as needed. UTIs may be classified into upper or lower urinary tract infections, as well as complicated or uncomplicated ones. As antibiotic resistance becomes an increasing concern, prudent

Table 3: Comparison of traditional and emerging diagnostic technologies for urinary tract infections.

Technology	Time to result	Pathogen ID	Resistance detection	Cost
Urine culture	24-72 h	Yes	Yes (via antimicrobial susceptibility testing)	Low
Flow cytometry	< 1 h	No	No	Moderate
MALDI-TOF MS	1-4 h	Yes	Limited	High
Multiplex PCR	2-6 h	Yes	Yes	High
Microfluidics	< 2 h	Yes	Yes	Moderate–High
Real-time microscopy	< 1 h	Limited	No	Moderate

use of antibiotics with adherence to antimicrobial stewardship guidelines is vital (Khoshnood et al., 2017).Knowledge of typical UTI-causing bacteria and local antibiotic susceptibility patterns is fundamental to appropriate therapy. Acute uncomplicated bacterial cystitis in healthy non-pregnant women can be treated with a first-line regimen of 5 d of nitrofurantoin or a single 3-gram dose of fosfomycin tromethamine. If those are not appropriate, alternatives may include the fluoroquinolones and β-lactams (e.g., amoxicillin-clavulanate) (Colgan and Williams, 2011).

If a UTI is caused by an AmpC beta-lactamase producing bacteria, then appropriate medications to treat it include: fosfomycin, nitrofurantoin, fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems. In contrast, nitrofurantoin, fosfomycin, fluoroquinolones, cefoxitin, piperacillin-tazobactam, carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, and aminoglycosides are available to treat ESBL-producing Enterobacteriaceae. In case of mild to moderate infection, the use of non-carbapenem drugs can be considered. For UTIs due to carbapenem resistant Enterobacteriaceae (CRE), the available options are ceftazidime-avibactam, colistin, polymyxin B, fosfomycin, aztreonam, aminoglycosides, and tigecycline. Fluoroquinolones, ceftazidime, cefepime, piperacillin-tazobactam, carbapenems, aminoglycosides, colistin, ceftazidime-avibactam, and ceftolozane-tazobactam are used for treating infections due to MDR Pseudomonas spp. Because of increasing resistance rates, fluoroquinolones shouldn’t be automatically used as empirical first-line therapy for UTIs. Aminoglycosides, colistin, and tigecycline should be regarded as alternative therapies in the context of treatment options that are particularly scarce for MDR Gram (-) infections (Bader et al., 2017).

Role of antimicrobial stewardship

Antimicrobial stewardship is vital in addressing the growing issue of healthcare-associated urinary tract infections (HA-UTI), especially those caused by MDR microorganisms. Good stewardship programs focus on rational antibiotic prescription to limit unnecessary exposure to therapy, by using targeted antibiotics with narrow-spectrum activity for the shortest duration possible to maintain efficacy. This is important since resistance in some of the common uropathogens, such as E. coli and Klebsiella spp. (causative agents of CAUTIs) (Haque et al., 2018), is becoming an increasing worry. One of the aims is to decrease resistant infections and enhances patient’s outcomes, recognizing that the implementation of the targeted treatment pathways advocating for the responsible use of antibiotics should lead to this goal. The high incidence of healthcare-associated infections is a major cause of illness and death in hospitals (Vicentini et al., 2024), emphasizing the need for antimicrobial stewardship. The current guidelines suggest responsiveness-based registering of selected antibiotics such as local antibiotic resistance patterns (Kranz et al., 2024). This strategy not only maintains current antibiotics in the armamentarium but also seeks to elevate the standard of care for patients at highest risk for nosocomial UTIs.

Catheter-associated urinary tract infections management

A Comprehensive Approach to Preventing Catheter-Associated Urinary Tract Infections (CAUTIs): balancing evidence-based practices and antimicrobial stewardship in CAUTIs, a state of multidrug-resistant microorganisms (MDR) is alarming, where a previous study reported that such pathogens isolated from CAUTIs showed a disheartening rate of 88.1 % resistance (Oumer et al., 2021). This highlights the necessity for appropriate catheter management and early removal. There is an increased risk of catheter-associated urinary tract infection (CAUTI) with the duration of catheterization, most notably over periods longer than 7 d (Oumer et al., 2021), making it of utmost importance to make a frequent assessment regarding the necessity of catheterization. Aside from these, usage of antimicrobial-coated catheters and rigorous infection control measures can help lower the infection rates drastically. Educating hospital staff on the risks associated with catheter use and proper sanitization procedures may also help improve patient’s outcomes. All in all, integrated management plans targeting prevention, timely action, and regular surveillance can totally mitigate the burden of CAUTIs in healthcare facilities.

Non-antibiotic treatment options

The growing prevalence of antibiotic-resistance in UTIs, most notably those caused by MDR uropathogens, is stimulating the advancement of non-antibiotic solutions. These include probiotics used to modulate urinary microbiota and boost natural defenses, and phage therapy for selective clearance of uropathogens and preservation of commensal bacteria (Mishra et al., 2024). In addition, bacterial antigen- and monoclonal antibody-based immunotherapies have demonstrated successful enhancement of immune responses (Mancuso et al., 2023). Furthermore, the use of antimicrobial-coated catheters decreases bacterial adherence and biofilm formation, reducing the incidence of catheter-associated UTIs (Kuwa et al., 2021). These therapies are potential substitutes for antibiotics; however, more studies are needed to evaluate their effectiveness and use in clinical settings.

Strategies used for preventing urinary tract infections in hospitals

Nosocomial UTIs contribute significantly to patient morbidity and mortality and serve as critical indicators of healthcare quality. Effective prevention strategies are essential for improving outcomes and reducing hospital costs. One of the most effective interventions is limiting the use and duration of urinary catheters. Catheters should only be inserted when absolutely necessary and removed as soon as clinically appropriate to minimize infection risk (Kuwa et al., 2021). Healthcare staff must receive ongoing training on proper catheter insertion and maintenance techniques. Emphasizing aseptic technique; ensuring unobstructed urine flow and securing the catheter correctly are vital steps in daily care. The implementation of antimicrobial stewardship programs is also crucial. These programs help control the inappropriate use of antibiotics; particularly in high-risk patients, reducing the development of MDR microorganisms (Haque et al., 2018). Antibiotics should only be prescribed based on clear clinical indications and guided by local susceptibility patterns. Establishing active surveillance systems enables hospitals to monitor infection rates, identify resistance patterns, and assess compliance with preventive protocols. This data can support evidence-based decision-making and foster accountability among healthcare providers. As summarized in Table 4, several practical recommendations can help reduce the incidence of nosocomial urinary tract infections.

For practical implementation, healthcare facilities should be considered, including:

Using catheter reminder systems or nurse-driven protocols for early removal;
Providing patient and family education about catheter risks;
Conducting regular audits and feedback sessions on infection control practices; and
Promoting the use of alternatives to indwelling catheters, such as external devices or intermittent catheterization when appropriate.

Table 4: Practical recommendations for preventing nosocomial urinary tract infections.

Focus area	Actionable recommendation	Rationale	Reference
Catheter use	Use urinary catheters only when absolutely necessary and document the indication.	Minimizes unnecessary exposure and infection risk.	(Lo et al., 2014)
Duration of catheterization	Implement daily assessment protocols to evaluate catheter necessity.	Promotes timely removal and reduces infection duration.	(Saint et al., 2020; Meddings et al., 2017)
Insertion technique	Ensure sterile technique using gloves, drapes, antiseptic, and trained staff during insertion.	Reduces introduction of pathogens during the procedure.	(Hooton et al., 2010; Gould et al., 2021)
Catheter maintenance	Maintain closed drainage system, avoid disconnections, and keep bag below the bladder level.	Prevents retrograde infection and contamination.	Gould et al., 2021
Alternative options	Consider intermittent catheterization or external devices when appropriate.	Reduces continuous exposure to indwelling catheter risks.	(Lo et al., 2014; Meddings et al., 2017)
Staff education and competency	Conduct regular in-service training and competency checks on catheter care.	Enhances adherence to best practices among staff.	(Haque et al., 2018; Saint et al., 2020)
Antimicrobial stewardship	Prescribe antibiotics only when clinically indicated, and follow local antibiograms.	Prevents resistance and inappropriate treatment.	(Umscheid et al., 2011; Haque et al., 2018)
Surveillance and feedback	Track CAUTI rates and share feedback with staff to improve compliance and accountability.	Encourages continuous quality improvement.	(Umscheid et al., 2011; Saint et al., 2020)
Reminders and stop orders	Use EMR-based alerts or nursing protocols for catheter reassessment and removal.	Increases timely catheter removal.	(Meddings et al., 2017; Saint et al., 2020)
Patient and family education	Inform patients/ families about catheter risks and their role in prevention.	Promotes shared decision-making and enhances cooperation.	(Hooton et al., 2010)

Monitoring and follow-up care

Consistent follow-up and management are crucial for preventing UTI recurrence; especially in nosocomial infections. Vigilant monitoring of infection-related factors is necessary; particularly in high-risk groups such as catheterized or immunocompromised individuals. Observing antibiotic resistance patterns and isolating pathogens allows for evidence-based treatment decisions tailored to individual patients (Odabasi and Mert, 2019). Clear follow-up protocols, such as post-treatment urine cultures help distinguish between true reinfection and asymptomatic bacteriuria, facilitating treatment adjustments (Erdem et al., 2022). For example, asymptomatic candiduria is often self-limited and only needs treatment when symptomatic (Jahagirdar et al., 2018). Implementing a well-structured monitoring system based on studies on healthcare-associated infections improves patient’s safety and reduces costs associated with prolonged hospital stays and re-infections. This leads to more effective disease management, including UTIs (van der Werff et al., 2021; Capstick et al., 2024).

Impact of nosocomial urinary tract infections on healthcare systems

Hospital-associated UTIs have profound consequences not only for the immediate environment of the hospital, but also for the healthcare sector economically and logistically; through the undesired interactions across the entire in- and out-of-hospital care continuum. The cost to the healthcare system is enormous; estimates peg the bill at several billion dollars annually in increased hospital days, more extensive medical care, and greater morbidity and mortality due to these infections (Zhu et al., 2024). The problem is compounded by the emergence of antimicrobial resistance, which makes antibiotic treatment more difficult, and frequently results in more serious infections and requires the use of pricey second-line therapies. Previous studies showed that MDR microorganisms, including E. coli and Klebsiella spp. are common in the hospitals, and healthcare facilities struggle to control them (Trześniewska-Ofiara et al., 2022). Thus, we must re-emphasize the importance of sound infection control practices in outpatient settings and antibiotic stewardship programs directed at health care practitioners. These efforts are crucial, not only because they tackle the increasing threat of nosocomial UTIs but also because they protect patient’s health and conserve valuable resources within healthcare institutions.

Infection control measures in hospitals

Proper infection control measures play a crucial role in enhancing the prevention of hospital-acquired infections, especially UTIs. The practice of hygiene; specifically, hand hygiene guidelines provided by groups such as the World Health Organization (WHO), is among the foundational pillars of any infection prevention strategy in a healthcare setting. Isolation protocols and optimized catheter use significantly reduce CAUTIs, often complicated by device-related biofilms and MDR microorganisms (Oumer et al., 2021). Continuous surveillance of infection rates and resistance patterns allows hospitals to tailor infection control strategies into local pathogen trends. Crucially, comprehensive healthcare personnel training on infection control promotes a culture of safety and minimizes the spread of MDR strains (Jahagirdar et al., 2018). These integrated strategies improve patient outcomes and mitigate the broader public health impact of healthcare-associated infections.

Conclusions and Recommendations

Nosocomial UTIs remain the most frequently reported healthcare-associated infections, with significant clinical and economic consequences. This review highlights the multifactorial nature of nosocomial UTIs, driven by risk factors such as catheterization, prolonged hospitalization, immunosuppression, and lapses in infection control. The most common pathogens E. coli, K. pneumoniae, P. aeruginosa, and Enterococcus spp. exhibit increasing resistance to standard antimicrobials through multiple mechanisms, such as biofilm formation, β-lactamase production, and efflux pumps. These resistance patterns complicate treatment and contribute to recurrence and severe complications. Traditional diagnostic approaches, though being valuable, are often time-consuming and delay appropriate treatment. Emerging technologies including molecular diagnostics, biosensors, and artificial intelligence hold promise for rapid and accurate pathogen identification. In parallel, novel intervention strategies such as antimicrobial-coated devices, immunotherapies, probiotics, and phage therapy offer alternative treatment pathways. Despite these advancements, prevention remains the cornerstone of management. Evidence-based catheter protocols, staff education, antimicrobial stewardship, and continuous infection surveillance are critical to reducing infection rates and improving patient outcomes. Given the rising tide of antimicrobial resistance and the global burden of hospital-acquired infections, urgent and coordinated actions are essential. Nosocomial UTIs are largely preventable, and failure to address them effectively compromises patient safety, healthcare efficiency, and public health. Now more than ever, integrated and multidisciplinary strategies must be prioritized to mitigate this escalating threat. We recommend to developing strong infection control policies and improving cleanliness practices in hospital environments. Urinary catheters should be used sparingly and removed as soon as they are no longer required. Staff training seminars on catheter-related dangers are critical for maintaining awareness and adherence to optimal practices. Antibiotic stewardship initiatives based on local resistance patterns can help guide prudent antibiotic use. Furthermore, using rapid diagnostic tools, such as PCR, can help identify pathogens more quickly, allowing for better treatment.

Novelty Statement

This review provides an updated and comprehensive synthesis of current knowledge on nosocomial urinary tract infections, with a focus on recent advances in understanding pathogen biofilms, antimicrobial resistance patterns, and innovative preventive strategies, providing new insights to improve clinical management and infection rates.

Author’s Contribution

SKS: Conceptualization, software, formal, analysis, writing review and editing.

NTA: Formal analysis, software, writing review and editing.

MIA: Roles writing original drafts, formal analysis, software.

RWY: Conceptualization, formal analysis, software, writing review and editing.

Funding source

No fund was provided for this study.

Conflict of interests

The authors have declared no conflicts of interest.

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