Complicated UTI Diagnosis: An In-Depth Guide for Clinicians

Urinary tract infections (UTIs) stand as a significant cause of sepsis, especially in hospitalized settings. The spectrum of UTIs is broad, ranging from simple infections easily managed with outpatient antibiotics to complicated UTIs that can progress to life-threatening urosepsis. This article offers a comprehensive guide focusing on the evaluation, diagnosis, and management of both simple and, crucially, complicated UTIs. It aims to provide clinicians with updated insights based on current guidelines, covering appropriate first-line antibiotic use, risk factor assessment, essential imaging techniques, and the management of specific UTI complications such as pyonephrosis, emphysematous cystitis, and recurrent infections.

A particular focus is placed on addressing the existing practice gap in antibiotic selection, specifically the overuse of broad-spectrum antibiotics, and the complexities of managing UTIs in high-risk patient groups. These vulnerable populations include patients with indwelling catheters, pre-existing renal failure, or those post-transplantation. Furthermore, this educational activity underscores the critical role of interprofessional collaboration, comprehensive patient education, and the integration of innovative diagnostic tools and emerging treatments, such as bacteriophage therapy and advanced imaging modalities, in enhancing UTI management. Ultimately, this resource is designed to empower clinicians to achieve improved patient outcomes, minimize the inappropriate use of antibiotics, and effectively navigate the complexities inherent in diverse clinical presentations of UTIs.

Objectives:

Differentiate between uncomplicated and complicated urinary tract infections based on a thorough assessment of risk factors, varied clinical presentations, and potential for complications.
Conduct comprehensive evaluations of patients suspected of having complicated urinary tract infections to accurately identify underlying anatomical abnormalities, assess immune status, and pinpoint potential sources of infection.
Implement evidence-based management protocols to ensure the judicious use of antibiotics and tailor treatment strategies to each patient’s specific risk profile.
Foster effective collaboration within interprofessional healthcare teams to enhance and maintain continuity of care for patients suffering from complicated urinary tract infections.

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Introduction to Complicated UTI Diagnosis

Urinary tract infections (UTIs) are frequently identified as a primary source of sepsis in hospitalized patients. The clinical presentation of UTIs is incredibly diverse. While simple UTIs often respond favorably to outpatient antibiotic treatments and typically result in positive patient outcomes, at the opposite end of the spectrum, severe urosepsis in patients with comorbidities can be life-threatening. Furthermore, a range of risk factors can complicate UTIs, leading to treatment failures, recurrent infections, and significantly increased morbidity and mortality with poorer overall outcomes. Therefore, it’s crucial to determine if a UTI presentation is linked to underlying risk factors and to accurately assess the likelihood of its resolution with standard first-line antibiotics.[1, 2, 3, 4]

Differentiating between simple and complicated UTIs is paramount for effective patient management. A complicated urinary tract infection (UTI) is defined as an infection that carries a heightened risk of treatment failure. Accurate identification is vital because these infections frequently necessitate extended treatment courses, alternative antibiotic choices, and, in some instances, further diagnostic investigations to ensure successful management. Therefore, a precise and timely Complicated Uti Diagnosis is the cornerstone of effective treatment.

In contrast, a simple UTI (or cystitis) is characterized as a urinary tract infection caused by susceptible bacteria in a clinical context where treatment failure or adverse outcomes are unlikely. Typically, this is an infection occurring in a nonpregnant, immunocompetent female patient who is afebrile. It’s important to note that pyuria and/or bacteriuria alone, without accompanying symptoms, do not constitute a UTI and may not require treatment. For example, an incidental positive urine culture in an asymptomatic, afebrile, nonpregnant, and immunocompetent female would not be classified as a UTI requiring immediate intervention.

Conversely, a complicated UTI encompasses any UTI that does not meet the criteria of a simple UTI as described. This definition broadly includes all UTIs in immunocompromised patients, males, pregnant individuals, and infections associated with fever, kidney stones, sepsis, urinary obstruction, catheters, or kidney involvement. Thus, accurate complicated UTI diagnosis relies on recognizing these broader risk factors and clinical contexts.

The female urinary tract, due to its relatively short urethra, is inherently more susceptible to bacterial colonization and subsequent ascending infections. This anatomical predisposition contributes to a higher incidence of infections in females. While simple cystitis, isolated episodes of ascending pyelonephritis, and even recurrent cystitis in certain contexts can be categorized as simple UTIs, this classification is contingent upon a prompt response to first-line antibiotics and the absence of long-term complications. However, any UTI that deviates from this clinical presentation or trajectory should be considered a complicated UTI.

In cases of complicated UTI diagnosis, underlying protective factors that typically prevent infection are often compromised, or risk factors are present that hinder resolution, increase morbidity, lead to treatment failures, and elevate the risk of reinfection.[5, 6, 7] The significance of differentiating between simple and complicated UTIs lies in the fact that complicated infections are often caused by a wider range of bacterial pathogens and pose a considerably higher risk of clinical complications.[8] The presence of urinary tract stones or indwelling catheters further increases the likelihood of recurrent infections compared to patients without these predisposing factors.[9] Therefore, a thorough approach to complicated UTI diagnosis is essential for identifying and mitigating these risks.

Examples of conditions that qualify as a complicated UTI include:

Infections occurring despite normal anatomical defenses (UTIs in males are inherently classified as complicated UTIs).
Infections resulting from anatomical abnormalities, such as obstructions, hydronephrosis, renal tract calculi, or colovesical fistulas.
Infections arising from immunocompromised states, including steroid use, post-chemotherapy, diabetes mellitus, HIV infection, and advanced age.
UTIs caused by atypical or drug-resistant organisms.
Recurrent infections despite previous adequate treatment, often involving multidrug-resistant organisms.
Infections occurring during pregnancy, including asymptomatic bacteriuria in pregnant women.
Infections developing post-instrumentation, such as following the placement or replacement of nephrostomy tubes, ureteric stents, suprapubic tubes, or Foley catheters.
Infections in renal transplant recipients and patients with spinal cord injuries.
Infections in patients with impaired renal function, those undergoing dialysis, or experiencing anuria.
Infections occurring after surgical prostatectomies or radiotherapy treatment.

Image alt text: Urine sample collection for UTI diagnosis, emphasizing the importance of sterile containers and dipstick testing for preliminary analysis.

Etiology of Complicated UTIs

The majority of UTIs originate from the colonization of the urogenital tract by bacteria from the rectal and perineal flora. The most commonly implicated organisms include Escherichia coli, Enterococcus species, Klebsiella species, Pseudomonas aeruginosa, and various Enterococcus or Staphylococcus species. Among these, E. coli is the most prevalent, followed by Klebsiella. In patients residing in care facilities, those with diabetes, and individuals with indwelling catheters or immunocompromised conditions, colonization with Candida species is also frequently observed.[10] While E. coli and possibly Klebsiella are the predominant causes of simple UTIs, complicated UTIs are typically associated with a significantly broader spectrum of organisms. This is a critical distinction, especially given the rising rates of multidrug resistance, which necessitates tailored antibiotic regimens based on the specific causative agents identified during complicated UTI diagnosis.

Epidemiology of Complicated UTIs

In the United States, complicated UTIs represent a substantial healthcare burden, accounting for over 626,000 hospital admissions each year, which is approximately 1.8% of all hospitalizations. Notably, a significant majority, around 80% of these cases, are not associated with catheter use.[11] Cohorts with multiple risk factors exhibit a higher incidence of UTIs. Key risk factors include female gender, advancing age, diabetes mellitus, obesity, long-term indwelling catheters, and frequent sexual intercourse (although UTI is not classified as a sexually transmitted infection).

Simple UTIs in nonpregnant, immunocompetent females are estimated to occur at a rate as high as 0.7 infections per person per year. It is estimated that 50% of all females will experience at least one UTI during their lifetime.
The incidence of complicated UTIs is strongly correlated with specific risk factors. For instance, patients with indwelling bladder catheters have a daily risk of approximately 10% for developing bacteriuria, and up to 25% of these cases progress to symptomatic UTIs.
Around 20% of all bacteremia cases associated with healthcare settings originate from the urinary tract. Mortality rates associated with these urinary tract-based bacteremias can be as high as 10%.[12]
Bacteriuria is prevalent in up to 14% of diabetic females, although it does not appear to occur with a higher frequency in diabetic males.
Asymptomatic bacteriuria incidence increases with age in females, affecting up to 80% of the older female population. It is less common among younger healthy males but can be present in up to 15% of older males.
Approximately 9.4% of all urological inpatients develop a complicated UTI during their hospital stay.[13, 14]
An increased incidence of UTIs has been observed in patients using dapagliflozin (SGLT2 inhibitors), a medication used to treat diabetes by inducing glycosuria.[15]
UTIs are the most common infections in renal transplant recipients. Up to 25% of these patients will develop a UTI within the first year following transplantation.
UTIs are the seventh most common reason for emergency department visits in the US, accounting for over 1 million visits annually. Approximately 22% (220,000) of these visits are classified as complicated UTIs, with about 100,000 patients being admitted to hospitals each year.[16, 17]

These epidemiological data underscore the importance of accurate complicated UTI diagnosis and effective management strategies to reduce morbidity, mortality, and healthcare costs associated with these infections.

Image alt text: Prevalence of common bacterial organisms in complicated urinary tract infections, highlighting Escherichia coli, Klebsiella, Pseudomonas, and Enterococcus as leading pathogens.

Pathophysiology of Complicated UTIs

Biofilms play a significant role in the pathogenesis of complicated UTIs. A biofilm is a structured community of microorganisms encased within a self-produced polymeric matrix, enabling them to adhere to biological tissues, urinary stones, or foreign bodies like catheters.[18] Biofilms can harbor various pathogens, often of relatively low virulence individually, yet collectively capable of causing severe, potentially life-threatening infections.[9, 10] Urinary stasis, whether due to dysfunctional voiding or physical obstruction, promotes bacterial invasion into tissues and triggers a host immune response.[19]

Foreign materials such as urinary stones and indwelling catheters are frequently associated with biofilm formation. Catheters, in particular, provide a direct pathway for bacteria to enter the urinary tract, and the biofilm subsequently shields these organisms from the host’s immune system and antibiotic treatments. Biofilms are often polymicrobial, involving multiple bacterial species.[20] A critical challenge in treating biofilm-associated UTIs is that most antibiotics cannot effectively penetrate the biofilm matrix to eradicate the embedded bacteria.[21, 22] Bacteria within biofilms typically exhibit slower growth rates, which further reduces the effectiveness of antibiotics that primarily target rapidly dividing cells.[23, 24] While techniques such as bladder irrigation and maintaining free urinary flow can help minimize biofilm development, they cannot entirely prevent it. The most effective approach to managing biofilm-related infections is often the removal and replacement of the affected foreign body, such as exchanging an indwelling catheter. This highlights why complicated UTI diagnosis must consider the presence of foreign bodies and potential biofilm involvement.

For Foley catheters that have been in place for one to two weeks or longer, replacement prior to obtaining a urinalysis or urine culture is recommended to avoid contamination from the biofilm that has accumulated on the catheter surface. A mature biofilm can fully form on a urinary catheter in approximately two weeks. For patients who experience frequent catheter-associated UTIs, more frequent catheter changes may be beneficial in reducing infection risk.

History and Physical Examination in Complicated UTI Diagnosis

UTIs, especially complicated UTIs, are frequently encountered in hospital environments and often contribute to diagnostic ambiguity and clinical uncertainty. This diagnostic challenge can lead to a significant number of inappropriate antibiotic prescriptions. Therefore, a thorough history and physical exam are crucial in guiding complicated UTI diagnosis.

The primary clinical indicators for diagnosing a simple UTI include characteristic symptoms such as increased urinary frequency, urgency, hematuria, dysuria, and suprapubic pain. The diagnosis should be made within a clinical context where a urogenital tract infection is the most probable cause of these symptoms. In such cases, empiric treatment with first-line antibiotics is typically appropriate. Ideally, a urine sample should be collected for microscopy and culture before initiating antibiotic therapy, although this is not always practically feasible. The urine analysis in simple UTIs almost invariably reveals abnormal red or white blood cell counts, positive nitrites, and the presence of bacteria.

Any UTI that fails to resolve following first-line antibiotic therapy or occurs in a patient belonging to a high-risk population should be considered a complicated UTI. Symptoms of complicated UTIs can include those seen in simple UTIs, such as urinary frequency, urgency, hematuria, dysuria, and suprapubic pain, but are often accompanied by additional, more systemic signs. These include fever, chills, flank pain, sepsis of urological origin, cystitis symptoms persisting for more than seven days, and acute changes in mental status (particularly in older adults). Risk factors that should raise suspicion for complicated UTIs include a history of multidrug-resistant organisms, the presence of indwelling Foley or suprapubic catheters, and belonging to high-risk patient populations such as pregnant women, immunocompromised individuals, post-renal transplant patients, those with neurogenic or dysfunctional bladders, patients in the immediate post-urological surgery period, individuals with renal failure, and pediatric patients.[8] Recognizing these factors is essential for accurate complicated UTI diagnosis.

Complicated UTIs can sometimes present with nonspecific or atypical symptoms, which can further complicate complicated UTI diagnosis. Examples include delirium in older individuals, symptoms mimicking an acute abdomen, or triggers for diabetic emergencies such as diabetic ketoacidosis. In some instances, complicated UTIs may even manifest without noticeable symptoms, as is often the case with asymptomatic bacteriuria during pregnancy. In severe cases, complicated UTIs can escalate rapidly to undifferentiated sepsis or septic shock, requiring prompt recognition and immediate, aggressive management.

Evaluation and Diagnostic Approaches for Complicated UTI Diagnosis

Obtaining a high-quality urine specimen is essential for accurate complicated UTI diagnosis. However, it’s equally important to emphasize that treatment should not be unduly delayed if the clinical presentation strongly suggests a UTI.[25, 26, 27]

Most patients are capable of providing a suitable midstream urine sample if given proper instructions on collection technique. When obtaining a clean-catch urine sample is not feasible, a catheterized urine sample, collected via an indwelling catheter or a sterile straight in-and-out catheter, can be used. It is important to acknowledge that catheter insertion carries inherent risks, and these risks must be carefully weighed against the diagnostic benefits of obtaining a urine specimen for analysis and culture. Obtaining a urine specimen for culture prior to initiating antibiotic administration is recommended whenever practically possible. Pyuria is commonly observed in patients with complicated UTIs. The presence of white blood cell casts in the urine strongly suggests kidney involvement, indicating pyelonephritis. It is important to note that normal white blood cell ranges in urine can vary depending on the method of collection and analysis, and results should be interpreted accordingly.

Urine samples from patients with prostatitis may not always be diagnostically conclusive, particularly if the patient has already received partial antibiotic treatment. In these situations, a pre- and post-prostate massage urine sample, known as the 4-glass test or the abbreviated 2-glass test, can enhance diagnostic accuracy in identifying prostatitis. Clinical indicators that suggest prostatitis include pelvic or perineal pain, difficulties with urination, failure of initial UTI therapy, and rapid symptom recurrence. These considerations are crucial in refining complicated UTI diagnosis in male patients.

It is also important to note that some patients with clinical signs of a UTI may not exhibit bacterial growth in urine cultures. Conversely, patients with asymptomatic bacteriuria will have significant bacterial growth on urine culture but lack typical urinary symptoms.[8] Cloudy urine appearance or a foul odor may raise suspicion of infection, but these findings alone have not been consistently shown to correlate with either bacteriuria or the presence of a UTI.[28]

Older patients, especially those with dementia, are at increased risk for complicated UTIs.[29] Dementia can lead to a decline in personal hygiene practices and an increased prevalence of voiding dysfunctions. Furthermore, the risk of urinary catheterization is also elevated in this population. Complicated UTI diagnosis in older adults with dementia can be more challenging because these patients may present with altered mental status, increased confusion, or agitation rather than the typical lower urinary tract symptoms.[30]

Blood cultures can be valuable in more severe, septic presentations of complicated UTIs. A positive blood culture can corroborate urine culture results and reduce concerns about urine sample contamination, strengthening the complicated UTI diagnosis.

Radiological investigations are generally not necessary for the initial diagnosis of uncomplicated infections limited to the genitourinary tract. Sufficient diagnostic information can usually be gathered from the patient’s medical history, physical examination, and basic laboratory findings. However, imaging modalities such as ultrasound and CT scans become highly valuable, and sometimes critical, for diagnosing complications such as perinephric abscesses, urinary retention, hydronephrosis, and obstructive pyelonephritis secondary to stones in septic patients.

Imaging is strongly recommended for all febrile and septic patients who do not show clinical improvement within 48 to 72 hours of starting appropriate broad-spectrum antibiotics. Imaging is essential to rule out potential complications such as abscess formation, urinary retention, urinary calculi, gas formation, obstructive uropathy, pyonephrosis, and hydronephrosis. Renal ultrasonography is a quicker and less expensive option that avoids radiation exposure, but CT imaging is considered the definitive standard for detailed evaluation. CT imaging should be strongly considered in complex or refractory cases, even if initial ultrasound findings are negative, as CT results can be life-saving in guiding further management.[31] This makes imaging a vital component of complicated UTI diagnosis.

In all patients diagnosed with a complicated UTI, including those with a first-time presentation of ascending pyelonephritis in nonpregnant immunocompetent females, a renal tract ultrasound is recommended as a minimum to assess for underlying anatomical abnormalities, hydronephrosis, kidney stones, or other lesions. Because there is no reliable clinical method to definitively exclude urinary obstructions, such as kidney stones, in complicated UTIs, clinicians must utilize imaging, such as ultrasound or CT scans, to either confirm or rule out obstruction.[32] This proactive use of imaging is crucial for accurate complicated UTI diagnosis and subsequent effective treatment planning.

Image alt text: CT scan revealing hydronephrosis of the kidney, illustrating the diagnostic utility of imaging in identifying complications associated with urinary tract infections.

Treatment and Management Strategies for Complicated UTIs

A UTI, particularly when complicated, can manifest with severe, life-threatening sepsis and multi-organ system involvement. In such critical presentations, immediate resuscitation often takes precedence over definitive treatment. Patients presenting with septic shock may require aggressive fluid resuscitation and prompt administration of broad-spectrum antibiotics in the emergency department setting. Antibiotic selection must always be guided by local bacterial resistance patterns and established treatment guidelines.[33, 34, 35, 36]

Patients in septic shock may not respond adequately to fluid resuscitation alone, and clinicians should have a low threshold for considering vasopressor support if the initial response to fluid therapy is poor.[8, 37, 38] Conversely, patients who are hemodynamically stable and not septic may be suitable for outpatient management.

Empiric broad-spectrum antibiotics should be promptly de-escalated to targeted, narrow-spectrum antibiotics once urine culture and sensitivity results become available. Initial broad-spectrum antibiotic options often include penicillins or beta-lactam/beta-lactamase inhibitor combinations, cephalosporins, fluoroquinolones, and carbapenems, particularly for infections suspected to involve extended-spectrum beta-lactamase (ESBL)-producing organisms. The specific choice of antibiotics should be informed by the hospital’s local microbiology data, including antibiograms that detail local resistance patterns.[39]

Patients presenting with recurrent UTIs may be initially treated based on their previous urine culture results pending new culture data. In cases of relapsing infections involving the same organisms, imaging studies to identify a persistent source of infection, such as an abscess or kidney stone, should be performed.[40] For patients who initially presented with hematuria, a repeat urinalysis to check for urinary blood is recommended after successful treatment of the infection.

Clinical response to treatment should typically be evident within 24 to 48 hours. A lack of improvement may indicate several factors, including inappropriate antibiotic selection, polymicrobial or atypical infections, hydronephrosis, an obstructing stone causing pyonephrosis, or other complications like perinephric abscess, emphysematous UTI, fluid collections (e.g., urinary retention), or anatomical abnormalities (e.g., nephrocalcinosis, obstructive lesions, urinary calculi, or fistulas). Ensuring adequate bladder drainage is crucial, especially in septic patients or those with elevated post-void residual volumes, and temporary Foley catheterization is often recommended in these situations.

Antibiotic therapy for complicated UTIs typically extends for 10 to 14 days. While technically any UTI in a male is classified as complicated, many experts manage uncomplicated lower urinary tract infections in otherwise healthy men without bladder dysfunction, stones, or other high-risk factors similarly to simple UTIs. First-line antibiotic agents in such cases may include fosfomycin, trimethoprim-sulfamethoxazole, or nitrofurantoin. In recurrent infections in men, prostatitis should be considered and managed accordingly, especially if the same organism is repeatedly identified.

The majority of patients (approximately 97%) with mild to moderate pyelonephritis who do not have significant comorbidities can be effectively treated as outpatients following initial parenteral antimicrobial therapy and a brief period of observation.[41]

Men presenting with recurrent UTIs or bacterial prostatitis may require a longer course of antibiotics, typically 4 to 6 weeks or more, to completely eradicate the infecting bacteria. In men with benign prostatic hyperplasia (BPH) and recurrent or intractable UTIs, surgical intervention should be considered as a potential therapeutic strategy.[42] Nitrofurantoin is generally not recommended for complicated UTIs in men due to its limited tissue penetration, particularly into the kidneys, testicles, and prostate.

Failure to respond to appropriate antibiotics should raise suspicion for a possible urinary blockage, such as obstructive pyelonephritis. In such cases, renal ultrasound or noncontrast CT scan should be performed to confirm the diagnosis. If an obstructed, infected kidney is identified, immediate surgical drainage is necessary, typically achieved through double-J stenting or percutaneous nephrostomy.

Successful treatment of complicated UTIs depends on proper antibiotic selection, appropriate dosage adjustments, and the correct duration of therapy. Addressing and eliminating underlying high-risk factors, such as removing infected stones or indwelling catheters, is also a critical component of management.

Prophylactic antibiotics are generally not recommended for routine use due to the potential for rapid development of bacterial resistance. When prophylaxis is clinically indicated, nitrofurantoin is often the preferred initial agent, typically given at a dose of 50 mg/day, usually taken at bedtime.[43, 44]

Patients with permanent Foley catheters or suprapubic tubes should generally avoid prophylactic antibiotics and should only be treated when they become symptomatic. More frequent changes of urinary catheters are advisable in chronically catheterized patients who experience recurrent or frequent infections. Patients with long-term Foley catheters may have fewer infections if converted to suprapubic catheterization.[45] Catheter replacement is recommended to eliminate the contaminated biofilm and reduce recurrent infections if a catheterized patient develops a UTI.[8]

Methenamine mandelate is an oral medication administered twice daily that, in acidic urine, is converted to formaldehyde, a potent urinary antiseptic. This agent can be useful in patients with multidrug-resistant infections or persistently elevated postvoid residuals as an alternative to prophylactic antibiotics.[46] Methenamine mandelate is often administered in conjunction with ascorbic acid (1000 mg twice daily) to help maintain urinary acidity, which is necessary for formaldehyde production.[47] This medication should not be used concurrently with sulfonamides due to the risk of precipitate formation. Methenamine mandelate is not recommended for patients with a glomerular filtration rate below 10 mL/min.

Cranberry supplements have been studied for their efficacy in treating complicated or recurrent UTIs, but the evidence is conflicting and inconclusive.[48, 49, 50] Similarly, probiotics have not demonstrated significant benefit compared to placebo in the treatment of complicated UTIs.[51]

Fosfomycin has shown promising activity against bacteria within urinary tract stones.[52, 53] Fosfomycin exhibits significant penetration into urinary calculi and has been shown to be more effective than cefuroxime in this context.[53] Parenteral fosfomycin is also utilized as empiric therapy for complicated UTIs in some regions of the world; however, its use remains limited in the US.[54, 55] It is generally recommended to reserve its use for cases where carbapenems cannot be used to preserve its efficacy against highly resistant organisms.

Pivmecillinam received FDA approval in 2024 as a first-line oral therapy for uncomplicated UTIs in females. Pivmecillinam is a prodrug of mecillinam, a unique extended-spectrum β-lactam penicillin-based antibiotic with good activity against multidrug-resistant and ESBL-producing E. coli, Staphylococcus saprophyticus, and Proteus mirabilis, as well as many other gram-negative bacteria.[56, 57, 58] Fosfomycin, in contrast, is less effective against most gram-positive bacteria, Pseudomonas, Acinetobacter, and Enterococcus, and is not recommended for pyelonephritis or systemic infections due to its poor tissue penetration. However, fosfomycin is highly effective for lower urinary tract infections caused by susceptible organisms, particularly those resistant to many other antibiotics.[59]

Pivmecillinam has been widely used in Europe and Canada for over 30 years, demonstrating a strong safety profile and low bacterial resistance rates (1% to 6%), making it a reliable option for treating UTIs.[60] The recommended dosage of pivmecillinam in the United States is 185 mg orally three times a day for 3 to 7 days. However, in Europe, a higher dosage of 400 mg three times a day is often suggested, based on evidence indicating potentially greater efficacy.[61, 62] The dose should be reduced in patients with an estimated glomerular filtration rate (GFR) less than 30 mL/min, and it should be avoided altogether if the GFR falls below 10 mL/min, as it is primarily excreted renally.

Long-term use of pivmecillinam may lead to carnitine deficiency, which can manifest as mental confusion, cardiomyopathy, generalized weakness, hyperammonemia, unexplained muscle aches, and fatigue.[63]

Intermittent bladder instillations of antibiotic or antiseptic solutions have been successfully used in patients with recurrent or relapsing UTIs, particularly those with renal failure, oliguria, pyocystis, or frequent recurrences, especially in patients already performing intermittent self-catheterization. Gentamicin solution is the most commonly used antimicrobial for this purpose.[64] The recommended dosage is to instill 30 cc to 60 cc of a solution containing 480 mg of gentamicin per 1 liter of normal saline after draining the bladder.[65] When administered intravesically in this manner, gentamicin exhibits minimal systemic absorption, allowing it to be used regardless of renal function. While gentamicin is the preferred initial agent, tobramycin, hyaluronic acid, Lactobacillus rhamnosus, povidone-iodine solution, or Neosporin can be used as alternatives if gentamicin is unavailable.[64, 66]

Neomycin alone has not shown efficacy in controlling bacteriuria, but chlorhexidine and povidone-iodine have demonstrated effectiveness in reducing UTIs and bacteriuria.[64] Neosporin can also be used as short-term (10 days) continuous bladder irrigation using a 3-way Foley catheter.[67] Bladder antibiotic instillations are particularly useful in dialysis patients and those with anuria or pyocystis because their efficacy is not dependent on renal excretion of antibiotics. Interestingly, heparin bladder instillations have also shown some activity in reducing recurrent UTIs, likely by providing a protective mucopolysaccharide coating to the urothelial bladder surface.[68]

Empiric Initial Antibiotic Therapy for Patients With Urosepsis:

Initial antibiotic selection in septic or systemically ill patients, before culture results are available, should be tailored to individual patient characteristics and local bacterial resistance antibiograms. For example, fluoroquinolones are generally not recommended for empiric use if local resistance rates are 10% or higher. Consultation with a local infectious disease specialist can help determine the most appropriate empiric approach for a specific community. Parenteral antibiotics are generally recommended for patients with systemic or severe illness until urine culture results can guide antibiotic selection. If no clear antibiotic choice is evident, infectious disease consultation is advisable.

Ceftriaxone or piperacillin-tazobactam can be used in patients who are less severely ill. Piperacillin-tazobactam is preferred if Enterococcus, Staphylococcus, or Pseudomonas is suspected due to its broader spectrum of activity.
Vancomycin, linezolid, or daptomycin should be added if methicillin-resistant Staphylococcus aureus (MRSA) is suspected.
If Pseudomonas is suspected, options include piperacillin-tazobactam, fluoroquinolones, cefepime, or ceftazidime.
Parenteral fosfomycin has also been used for complicated UTIs and is effective against many highly resistant organisms, including ESBL-producing bacteria, although parenteral fosfomycin is not currently available in the US.
Pivmecillinam is not indicated for systemic infections or urosepsis.
Quinolones should be considered when local resistance patterns indicate they are a viable option.
Aminoglycosides are typically reserved for situations where other less nephrotoxic drugs cannot be used due to resistance or allergy concerns.
For critically ill patients requiring maximal coverage, a combination of a carbapenem with anti-pseudomonal activity, such as imipenem (effective against ESBL-producing organisms), and vancomycin (targeting MRSA), should be considered. Ertapenem generally has limited activity against Pseudomonas and is not a suitable choice in these cases.

Newer Antibiotic Agents For Multidrug-Resistant Infections:

The increasing prevalence of multidrug-resistant organisms has prompted renewed interest in older antimicrobials (primarily aminoglycosides and tetracyclines) and the development of new antibiotics and combination therapies, including:

Aztreonam/avibactam
Cefepime-enmetazobactam
Cefepime-zidebactam
Cefiderocol
Ceftazidime/avibactam
Ceftolozane/tazobactam
Eravacycline
Fosfomycin
Glycylcyclines
Imipenem/relebactam
Meropenem/vaborbactam
Omadacycline
Pivmecillinam
Plazomicin
Tebipenem[69, 70]

Ceftazidime/avibactam combines a potent third-generation cephalosporin with a beta-lactamase inhibitor and is used to treat complicated UTIs. FDA-approved in 2015, it is intended for use when other medications are likely to be ineffective due to resistance.[71, 72]

Cefiderocol is a novel, FDA-approved synthetic siderophore-conjugated cephalosporin antibiotic that can be used for complicated UTIs involving highly resistant organisms. Cefiderocol utilizes bacterial iron transport mechanisms to facilitate drug uptake into bacterial cells, resulting in very high intracellular concentrations.[73] This medication is well-tolerated and active against many multidrug-resistant organisms, including those resistant to carbapenem antibiotics.[74] It is intended for limited use as a last-resort option for multidrug-resistant infections. While promising, some bacterial isolates have already demonstrated resistance, limiting its widespread use.[73]

Meropenem-vaborbactam enhances the activity of meropenem against organisms that produce Klebsiella pneumoniae carbapenemase (KPC). This combination is FDA-approved for complicated UTIs, including pyelonephritis caused by susceptible organisms.[75, 76]

Plazomicin is a unique, FDA-approved injectable aminoglycoside specifically developed for multidrug-resistant organisms, including those producing aminoglycoside-modifying enzymes (AMEs), extended-spectrum beta-lactamases (ESBLs), and carbapenemases. Standard aminoglycosides often have limited activity against bacteria that produce AMEs, and carbapenem-resistant organisms are increasingly prevalent. Plazomicin was chemically designed to overcome the activity of most AMEs. Plazomicin is effective against approximately 90% of coliform bacteria, except for Proteus mirabilis and Morganella morgagnii. It is also effective against 90% of E. coli and Klebsiella pneumoniae isolates, regardless of ESBL production. Similar to other aminoglycosides, it carries a risk of nephrotoxicity.[77, 78, 79]

Tebipenem is an oral carbapenem that has demonstrated non-inferiority to parenteral ertapenem in treating susceptible organisms causing pyelonephritis and other complicated UTIs.[80] Upon FDA approval, it will likely be the first orally available carbapenem.

Special Patient Risk Groups in Complicated UTI Diagnosis and Management:

Catheter-Associated UTIs (CAUTIs):

The Infectious Disease Society of America (IDSA) defines a catheter-associated UTI (CAUTI) based on the following criteria:

Presence of an indwelling catheter for at least 2 days post-insertion.
At least one symptom of a UTI (e.g., dysuria, urgency, frequency) or one sign (e.g., fever, chills, suprapubic pain, costovertebral angle tenderness, flank pain).
In older patients, altered mental status or hypotension may be indicative of CAUTI.
Urine culture showing at least 1,000 CFU/mL of a single bacterial species/pathogen.[81, 82, 83]

The US Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) defines CAUTI somewhat differently:

Presence of an indwelling urinary catheter: The catheter must have been in place for more than 2 calendar days on the event date or removed the day before the event.
At least one of the following signs or symptoms: fever, suprapubic tenderness, or costovertebral angle pain or tenderness, along with a positive urine culture with ≥100,000 CFU/mL of no more than two microorganisms.[84] This definition does not account for other potential sources of fever, leading many experts to consider it less clinically useful and prone to overestimating actual CAUTI rates.[85] Therefore, the IDSA definition is generally preferred in clinical practice for complicated UTI diagnosis in catheterized patients.

Between 15% and 25% of all hospitalized patients will have a urinary catheter at some point during their hospital stay. Approximately 21% to 50% of these catheters are deemed unnecessary and do not meet established guidelines for initial placement.[86] The CDC estimates that 17% to 69% of all CAUTIs are preventable with optimal infection control measures, potentially avoiding up to 9,000 deaths and 380,000 infections annually.

Twenty percent of hospital-acquired bacteremias in acute care facilities and 50% in long-term care centers are attributed to urinary catheterization.[87, 88] According to the NHSN, this translates to about 450,000 CAUTI events annually, with 13,000 deaths and a total annual cost ranging from $340 to $450 million.[89]

Bacteriuria is expected in catheterized patients due to colonization and biofilm development. The rate of bacterial colonization is approximately 3% to 10% per catheterization day, reaching 100% colonization after 30 days. Besides catheterization duration, other identified risk factors include female gender, older age, diabetes, bacterial colonization of the drainage bag, urethral catheterization (compared to suprapubic), and breaches in sterile catheter insertion or maintenance procedures.

Proper urine specimen collection is crucial in catheterized patients suspected of CAUTI to avoid culturing biofilm bacteria. Ideally, the catheter should be removed, and the patient should void for specimen collection. If catheter removal is not feasible, the catheter should be replaced before specimen collection. If neither of these is possible, a designated drainage system side port should be used. As a last resort, the catheter can be separated from the drainage system. Urine cultures should never be obtained from the drainage bag.[90] For patients with a condom catheter, a clean-catch midstream specimen is preferred.[91] If not obtainable, a sample can be collected from a new condom catheter after cleaning the glans.

In catheterized patients, bladder inoculation can occur via two primary routes: extraluminal (along the external catheter biofilm, ~66% of cases) or intraluminal (due to catheter blockage or drainage bag contamination, ~34% of cases).[92] Understanding these pathways is crucial for developing effective prevention strategies.

The most common organisms causing CAUTIs include E. coli (24%), Candida or yeast (24%), Enterococcus (14%), Pseudomonas (10%), and Klebsiella (10%). Increasingly, these organisms exhibit resistance to antibiotics, including fluoroquinolones, third- and fourth-generation cephalosporins, aminoglycosides, and carbapenems.[93]

Routine instillation of antiseptics into urinary drainage bags can help reduce calcium phosphate precipitates and bacterial counts. However, hydrogen peroxide 3% and chlorhexidine have minimal to no effect on urinary bag bacteriuria.[94] More effective agents include 1/4% acetic acid, diluted household white vinegar (1:3 dilution), and household bleach (1:10 dilution).[95, 96] Diluted vinegar is most effective at dissolving calcium phosphate precipitates, while diluted bleach is most effective for bacterial growth control. Despite these measures, none have been proven to reduce CAUTIs, and IDSA guidelines advise against routine antiseptic addition to drainage bags due to lack of proven efficacy.[82] Surprisingly, many seemingly logical catheter-related interventions have failed to demonstrate clear CAUTI reductions, including:

Sterile technique for catheter insertion
Antiseptic or antibiotic ointments for meatal care
Antiseptic filters and antireflux mechanisms in drainage bags
Dual-chambered drainage bags
Routine bladder or catheter irrigation
Frequent drainage bag changes (every 7-14 days)
Antiseptic solutions in drainage bags [96, 97, 98]

The most effective strategy for reducing CAUTIs is avoiding indwelling catheters whenever possible, discontinuing them as soon as clinically indicated, and using optimal sterile placement and maintenance techniques.[88]

Additional helpful measures to minimize CAUTIs include:

Mandatory educational programs for healthcare workers involved in catheter insertion or care.
Strict adherence to guidelines for indwelling catheter placement.
Utilizing alternative urinary control measures (pads, condom catheters, mechanical suction devices, suprapubic tubes, Cunningham clamps, intermittent catheterization, Pickwick, etc.) whenever possible.
Daily checklists to justify continued indwelling catheter use.
Automatic catheter removal orders at initial insertion unless otherwise specified and justified.
Strict adherence to CAUTI diagnosis and treatment guidelines to avoid overtreating asymptomatic bacteriuria.
Minimizing unnecessary urine cultures, which can lead to inappropriate antibiotic use.
Obtaining urine cultures when treating UTI to have results if initial treatment fails.
Following guidelines for correct specimen collection for urinalysis and cultures.
Investigating alternative infection sources before diagnosing CAUTI.
Never using indwelling Foley catheters solely for incontinence management.

Purple urine bag syndrome is a rare condition in long-term catheter patients, typically older women with constipation. Dietary tryptophan is converted to indole in the intestines, then to indoxyl sulfate by the liver, and excreted in urine. In alkaline urine, bacterial enzymes convert indoxyl sulfate to indigo (blue) and indirubin (red), causing the purple color.[99, 100, 101] Treatment includes catheter and bag change, constipation management, hydration, and reassuring nursing staff.

Spinal cord injury patients with catheters present unique diagnostic and management challenges for CAUTIs. Many require permanent or intermittent catheterization, leading to high asymptomatic bacteriuria rates that do not require treatment.[102] Impaired sensation may delay symptom onset. Nonspecific symptoms like fever, bacteriuria, and positive cultures may lead to CAUTI diagnosis even when infection is elsewhere, resulting in overdiagnosis and overtreatment.[103]

At least 35% of spinal cord injured patients diagnosed and treated for CAUTI may only have asymptomatic bacteriuria.[104] Increased spasticity and autonomic dysreflexia have been suggested as potential CAUTI symptoms in this population, but clinical utility is unclear.[82]

Early catheter removal may not apply to spinal cord injured patients without safe bladder drainage alternatives. Inappropriate removal risks urinary retention, vesicoureteral reflux, renal failure, autonomic dysreflexia, and sepsis. Clean intermittent self-catheterization is safer and associated with lower bacteriuria and CAUTI rates, but infection risks, false passages, urethral strictures, bladder issues, and caregiver dependence remain.[105, 106]

Long-term nitrofurantoin and D-mannose prophylaxis may reduce CAUTIs in spinal cord-injured patients.[107, 108] Silver and hydrophilic-coated catheters may also help, but studies are limited.[109, 110] Cranberry supplements and other nutraceuticals have shown no or conflicting results.[111, 112]

Guidelines-based urine culture and antibiotic ordering have significantly reduced overdiagnosis and overtreatment of asymptomatic bacteriuria in long-term catheterized patients by over 70%.[113, 114]

UTIs in Pregnancy:

Asymptomatic bacteriuria develops in 2% to 7% of pregnant women, usually early in pregnancy.[102] Higher risk groups include women with prior UTIs, diabetes, multiple deliveries, and lower socioeconomic status.[115] Untreated, up to 35% progress to symptomatic UTI and/or pyelonephritis during pregnancy.[116] Untreated bacteriuria is associated with increased risk of low birth weight, prematurity, preeclampsia, and perinatal mortality.[115, 117, 118] Pyelonephritis is also linked to poor pregnancy outcomes, particularly prematurity.[119] Treatment for asymptomatic bacteriuria and cystitis typically involves 3 to 7 days of amoxicillin-clavulanate, cephalexin, cefpodoxime, or single-dose fosfomycin.[120] Nitrofurantoin and sulfamethoxazole/trimethoprim can also be used, but are avoided in the first trimester and near term.[116, 121, 122]

Pyelonephritis during pregnancy often requires hospitalization. Standard therapy includes ceftriaxone, cefepime, and ampicillin/gentamicin. Aztreonam is suggested for beta-lactam allergy. Treatment is adjusted based on culture results. More severe infections may require piperacillin/tazobactam, meropenem, ertapenem, or doripenem.[123] Aminoglycosides should be used cautiously due to potential fetal ototoxicity.

UTIs in Renal Failure and Dialysis:

Chronic renal disease reduces urinary antibiotic excretion, but other factors also contribute.[124] These include reduced urinary antibacterial function, uremic immunosuppression, lower antibiotic levels in bladder and renal tissues, inhibited urothelial antimicrobial functions, and possibly reduced urinary volume.[8, 125, 126, 127] Diabetics with glucosuria have increased bacterial adherence to detrusor urothelium and decreased neutrophil efficacy.[128]

Complicated UTI diagnosis in dialysis patients is challenging; 30% to 40% may have pyuria without infection.[129] Diagnosis requires symptoms and positive urine culture. Infections are often catheter-related, with Candida being the most common organism.[130]

Antibiotics must be used cautiously in severe or end-stage renal failure. Nitrofurantoin and tetracyclines (except doxycycline) should be avoided. Aminoglycosides can be used cautiously due to nephrotoxicity. Other antibiotics like trimethoprim-sulfamethoxazole, trimethoprim, cephalexin, second- and third-generation cephalosporins, pivmecillinam, and fluoroquinolones can generally be used at reduced (usually 50%) doses.[131, 132, 133] Ertapenem has renal failure dosing, but neurotoxicity has been reported even at recommended doses.[134] Moxifloxacin is usable in renal failure but does not achieve adequate urinary concentrations for UTI treatment.

Antibiotics generally not requiring adjustment even in severe renal failure include azithromycin, ceftriaxone, clindamycin, doxycycline, fosfomycin, linezolid, nafcillin, rifampin, and trimethoprim.

For patients with severe renal failure (GFR < 30 mL/min), preferred agents include ceftaroline, ceftazidime, ceftolozane/tazobactam, and meropenem-vaborbactam. For end-stage renal failure, quinolones (ciprofloxacin, levofloxacin) are first-line; cefdinir and cefpodoxime are second-line.[135, 136]

Intermittent bladder instillations of gentamicin, tobramycin, amikacin, neomycin/polymyxin B/bacitracin, or antiseptic solutions like povidone-iodine can benefit patients with severe or end-stage renal failure, minimal urinary volume, or those performing intermittent self-catheterization.[64, 65] Standard intravesical gentamicin dose is 80 mg in 50-60 mL normal saline. Bladder instillations are also useful for pyocystis in anuric patients.[137, 138, 139]

UTIs in Renal Transplants:

Complicated UTI diagnosis can be difficult in renal transplant patients. Symptoms can be subtle and nonspecific, like nausea or fatigue. Fever and graft tenderness are more likely UTI than acute rejection. Renal transplant patients with UTI symptoms and systemic signs should have blood and urine cultures. About 9% of blood cultures are bacteremic.[140] Renal biopsy should be considered in questionable pyelonephritis cases or UTI with graft dysfunction, especially within 6 months post-transplant.[141] Acute rejection is more likely with azotemia, worsening proteinuria, and hypertension.

All symptomatic UTIs in renal transplant patients are considered complicated. Morbidity and mortality from UTIs are increased in kidney transplant patients due to immunosuppression.[142, 143] The 1-year mortality rate from infectious complications is now less than 5%, down from nearly 50% historically, due to surgical and postoperative care advances.[144]

UTIs are most common in the first year post-transplant, occurring in about 25% of recipients.[140, 145] About 7% develop recurrent UTIs, with increased risk of antibiotic resistance, transplant failure, and death.[146] Ascending UTIs with pyelonephritis are more common due to short ureters and lack of antireflux mechanism. Pyelonephritis is linked to rejection episodes and recurrent UTIs, often causing persistent increases in serum creatinine and decreased creatinine clearance.[147]

Screening for asymptomatic bacteriuria post-transplant in the first 90 days is controversial.[148, 149] No strong evidence supports its benefit in the first 3 months.[150] If screening is performed, urinalysis and urine cultures are recommended at 2, 4, 8, and 12 weeks post-transplant.[150]

Screening for asymptomatic bacteriuria after 3 months is not recommended as treatment beyond this point has not shown benefit and may increase antibiotic resistance.[151, 152] Historically, graft and patient survival were thought unaffected by treated complicated UTIs, but recent data suggests acute and recurrent pyelonephritis are significant risk factors for decreased long-term graft and patient survival.[153, 154]

Post-transplant UTI risk factors include female gender, older age, longer dialysis before transplant, pre-transplant recurrent UTIs, polycystic kidney disease, Foley catheterization, ureteral stent placement, deceased donor transplant, and urinary tract obstruction or dysfunction.[155, 156, 157]

Antibiotic prophylaxis is common for the first 6 to 12 months post-transplant, and some experts continue it indefinitely.[158, 159] Trimethoprim-sulfamethoxazole is common prophylaxis, but resistance is a concern. Cephalexin and norfloxacin prophylaxis are alternatives.[160] Methenamine hippurate (1000 mg twice daily) with or without vitamin C (1000 mg twice daily) has also been used successfully.[161, 162] Fosfomycin is used adjunctively with trimethoprim-sulfamethoxazole before urologic procedures and for UTI/asymptomatic bacteriuria treatment in this population.[152, 163]

Renal transplant patients have increased Klebsiella pneumoniae UTI incidence.[143] Other common pathogens include Enterobacter cloaca, Pseudomonas aeruginosa, and Enterococcus. Due to reduced host resistance, treatment is typically 14 to 21 days. Patients with suspected UTI but negative cultures should be tested for Corynebacterium urealyticum, requiring special culture media.[164]

Simple cystitis is typically treated for 10 to 14 days. Nitrofurantoin may be used if GFR ≥30 mL/min.[165, 166, 167] Optimal complicated UTI duration is unclear, but standard is 14 to 21 days, potentially longer. Infected cysts may need 4 to 6 weeks. Trimethoprim-sulfamethoxazole is less ideal if local resistance ≥20%.[168, 169, 170]

Selective imaging can be helpful in renal transplant UTIs. Ultrasound is initial test. Polycystic kidney disease patients may have infected cysts, challenging to identify, presenting with flank pain rather than graft discomfort. CT-PET scan can be useful.[171, 172, 173] Noncontrast CT scan is reasonable if ultrasound is negative, especially with nephrolithiasis history. Voiding cystourethrograms identify reflux, and urodynamics diagnose bladder dysfunction and outflow obstruction.

Specific Infections:

Emphysematous cystitis is a lower bladder UTI with gas in the bladder wall from gas-forming bacteria, usually E. coli or K. pneumoniae. Other gas-producing organisms include Proteus, Enterococcus, Pseudomonas, Clostridium, and rarely Aspergillus and Candida. Rarely, infectious colitis causes emphysematous cystitis without UTI signs.[174] It typically occurs in diabetics, older individuals, and those with urinary obstruction, more common in females.[175] High bladder wall glucose levels likely contribute, but etiology is poorly understood.[175] Mean presentation age is ~68 years, with ~50% having ≥2 comorbidities. Symptoms vary: 1/3 develop sepsis, 25% abdominal pain, 17% UTI symptoms, 6% hematuria, 8% asymptomatic (incidental imaging finding).[176] Diagnosis can be by ultrasound or KUB X-ray, but mostly CT scans. Treatment is culture-specific antibiotics, bladder drainage, supportive care, and risk factor elimination. 90% are managed conservatively, 5% to 10% require surgery.[176]

Emphysematous pyelonephritis is a severe necrotizing kidney infection with gas in renal parenchyma or perinephric space, diagnosed by CT scan. Most patients have diabetes (95%); 6 times more common in women. Associated with renal failure, obstruction, polycystic kidneys, and immunocompromise.[177, 178] Poor prognostic factors include azotemia, thrombocytopenia, shock, hyponatremia, confusion, and hypoalbuminemia.[179] Treatment includes renal drainage, blood sugar control, and parenteral antibiotics for 3-4 weeks. Nephrectomy is less frequently recommended; surgery is generally for multiple risk factors in nonfunctioning kidney or lack of response to conservative measures.[179, 180]

Pyonephrosis (obstructive pyelonephritis) describes an acutely infected, hydronephrotic kidney, usually with an obstructing calculus. Sepsis ensues rapidly without drainage via double-J stent or percutaneous nephrostomy. Patients are typically very ill with high fever, chills, tachycardia, diaphoresis, and flank pain. Pyonephrosis is a surgical emergency leading to urosepsis, shock, and death. Urine may not show infection signs if the renal unit is obstructed. Ultrasound quickly identifies the problem, but noncontrast CT scan better shows obstruction level and nature, and other pathologies like cancers or retroperitoneal fibrosis. Management includes fluids and antibiotics, but urgent drainage is critical.[180, 181] Risk factors include nephrolithiasis history, diabetes (poorly controlled), elevated CRP, positive urinary nitrites, larger stone size (>5 mm), and perirenal fat stranding.[182]

Definitive obstruction treatment is usually delayed until infection is controlled. Percutaneous nephrostomy is preferred for severe cases due to minimal stone manipulation and no risk of retrograde bypass failure.[183] Large stone collections should also be initially drained percutaneously.[181, 184] Definitive stone surgery should be within 3 weeks of ureteral stent placement. Complications, especially postoperative UTIs, are minimized if operative time is <75 minutes.[185]

Xanthogranulomatous pyelonephritis is a chronic renal infection with obstruction, hydronephrosis, necrosis, and severe renal parenchyma inflammation. Often in immunocompromised and/or diabetic patients. Diagnosed reliably by CT scan. Xanthogranulomatous pyelonephritis (XGP) can be mistaken for renal cell carcinoma because foamy, lipid-laden histiocytes (xanthoma cells) may resemble cancer cells on biopsy.[186, 187] XGP cells stain positive for periodic acid-Schiff (PAS), aiding differentiation.[188] Initial treatment is antibiotics and drainage, but surgical excision (focal or total) is usually needed for cure.[188] Laparoscopic and robotic surgery are possible but difficult, so open approach is usually recommended.[187]

Other specific urinary tract infections are discussed in companion articles, including tuberculosis, candidiasis, schistosomiasis, filariasis, prostatitis, orchitis, epididymitis, necrotizing fasciitis, and renal and scrotal abscesses.

New diagnostic methods and guideline implementation guides are being developed to accelerate complicated UTI diagnosis, minimize inappropriate antibiotic use, and improve antimicrobial selection. These include AI algorithms, biomarkers, and cell-free DNA analysis. New catheter materials, coatings, bacterial growth interference agents, and anti-infective vaccinations are being studied. New antibiotic classes are being developed.[189] Bacteriophages (viruses attacking specific bacteria) have been used anecdotally and successfully for highly resistant infections.[103, 190, 191] Bacteriophages can prevent biofilm formation and produce polysaccharide depolymerase, penetrating existing biofilms and unaffected by bacterial antibiotic resistance mechanisms.[103, 192]

Differential Diagnosis of Complicated UTIs

The differential diagnosis for complicated UTI diagnosis includes:

Abscess
Acute pyelonephritis
Bladder cancer
Chlamydial genitourinary infection
Cystitis
Focal nephronia
Herpes simplex
Interstitial cystitis
Obstructive pyelonephritis
Pelvic inflammatory disease
Prostatitis
Sexually transmitted infections
Urethritis
Urolithiasis
Vaginitis

Prognosis of Complicated UTIs

The FDA recommends dual primary endpoints for assessing complicated UTI eradication: clinical response (symptom resolution, no new UTI symptoms) and microbiological response (urine culture demonstrating eradication of the original pathogen).[8]

Complications of Complicated UTIs

Inadequate treatment of complicated UTIs increases risks of early recurrence or treatment failure. Infection can spread, cause abscesses, progress to sepsis, and potentially lead to death.

Deterrence and Patient Education for Complicated UTIs

Patients should be educated on proper antibiotic use, emphasizing adherence to prescribed dosing and completing the full course, even if symptoms resolve early. They should also be encouraged to adopt prophylactic lifestyle measures and avoid inappropriate antimicrobial use to reduce resistance and recurrence risks.

Pearls and Other Issues in Complicated UTI Diagnosis and Management

Diagnostic Pitfalls in Complicated UTI Diagnosis:

UTIs are primarily a clinical diagnosis; expert opinion is needed before treating isolated positive results in asymptomatic patients.
Clinicians often treat positive culture reports, not patients with genuine UTIs. Positive cultures in asymptomatic patients may result from poor sampling technique.
Septic, delirious older individuals unable to provide history or examination signs are often presumed to have UTI without clear septic source.
UTI-associated radiological changes can take months to resolve and should be interpreted cautiously in recurrent/persistent infections.
UTI should be considered in differential diagnosis of pelvic inflammatory disease or acute abdomen.
Male UTI patients should be screened for STIs.
Interstitial cystitis is often misdiagnosed as UTI and should be considered in patients with cystitis symptoms and negative cultures.
“Sterile pyuria” (persistent urinary WBCs, negative cultures) may indicate tuberculosis, requiring special cultures.
Bacterial infections account for ~80% of UTIs; antibiotics may be ineffective for others.
Spinal cord injury patients with UTI may present with increased spasticity or autonomic dysreflexia.
Obstructive pyonephrosis (surgical emergency) cannot be clinically distinguished from acute pyelonephritis (medical treatment); consider imaging (ultrasound, CT scan) in presumed pyelonephritis, especially if no improvement with antibiotics.

Management Pitfalls in Complicated UTIs:

Frail, older, debilitated patients with nonspecific signs like falls or mental status changes are often suspected of UTI. While possible, these nonspecific changes are unreliable UTI predictors, and antibiotics may not help without urine study confirmation.[193, 194]

Multidrug-resistant infections are a major source of in-hospital morbidity and mortality. Suppressive antibiotic regimens are sometimes used for poor responders or resistant cases. Infectious disease specialists should guide these plans, as long-term suppressive antibiotics have unique complications.

Long-term antibiotic prophylaxis should be used cautiously due to resistance risk and susceptibility changes. Residual urinary symptoms may persist for months (especially with catheters, post-prostatectomy, post-bladder surgery, or radiotherapy) and do not always indicate UTI. Long-term nitrofurantoin prophylaxis is linked to hypersensitivity pneumonitis; patients should be counseled.

Identifying and correcting predisposing infection factors is helpful (e.g., glycemic control in diabetics, anatomical abnormalities, immunocompromising factors, nephrotoxic medications). Consult infectious disease specialists for assistance with complex cases.

Consider oral fosfomycin, pivmecillinam, or intravesical gentamicin for intractable cystitis, even in multidrug-resistant or ESBL-producing infections.

Enhancing Healthcare Team Outcomes in Complicated UTI Management

Complicated UTI management is best done by an interprofessional team (urologist, nephrologist, infectious disease expert, internist, primary care clinicians, pharmacist, nurses). Healthcare professionals need diverse skills. Physicians must diagnose and manage infections, interpret tests, and select antibiotics. Nurses need expertise in medication administration, wound care, and sepsis monitoring. Pharmacists optimize drug therapy and ensure antibiotic stewardship. All team members share patient education, infection prevention, and monitoring responsibilities.

A well-defined management strategy is essential, including evidence-based guidelines and protocols prioritizing patient safety, infection control, and antimicrobial resistance. Strategies like catheter care and hygiene education are also vital for prevention.

Complicated UTIs require careful treatment to serve patients and avoid antibiotic overuse, leading to more resistance. Right antibiotic and duration are critical. Consult infectious disease specialists for complex cases. Failure of standard UTI/pyelonephritis treatment should suggest other issues like diabetes, sepsis, abscess, urinary retention, or obstructing stone with pyonephrosis. Bladder drainage and imaging can identify these problems. Close monitoring is needed due to potential complications. Prognosis for severe complicated UTIs is guarded, with prolonged recovery even in survivors.[75, 195, 196]

Effective team communication and collaboration are crucial for patient-centered care. Physicians, advanced practitioners, nurses, pharmacists, and other team members must share patient condition, treatment plan, and complication information. Clear, timely communication improves coordination, reduces errors, and enhances safety. Collaborative care plans addressing infection, underlying conditions, and potential complications are essential, including clear roles, regular team meetings, and seamless transitions between care settings.

Team performance can be improved through ongoing education in infection management, multidisciplinary collaboration, and communication skills. Regular debriefings, case discussions, and quality improvement initiatives can refine team approaches to complicated UTIs, leading to better outcomes and patient safety.

Review Questions

(Original review questions are kept in the online article)

References

(Original references are kept in the online article)

Disclosure: Ayan Sabih declares no relevant financial relationships with ineligible companies.

Disclosure: Stephen Leslie declares no relevant financial relationships with ineligible companies.