Complicated Urinary Tract Infections

Ayan Sabih; Stephen Leslie

Complicated Urinary Tract Infections

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Continuing Education Activity

Urinary tract infections (UTIs) are a leading cause of sepsis in hospitalized patients and present a wide spectrum of severity, from simple UTIs that respond well to outpatient antibiotics to complicated UTIs that can escalate to life-threatening urosepsis. This activity provides an in-depth guide to the evaluation, diagnosis, and management of both simple and complicated UTIs. Participants gain insights into current guidelines, including the appropriate use of first-line antibiotics, risk factor assessment, imaging techniques, and the management of specific complications like pyonephrosis, emphysematous cystitis, and recurrent infections.

Special emphasis is placed on addressing the practice gap in antibiotic selection, the overuse of broad-spectrum agents, and the challenges of managing UTIs in high-risk populations, including patients with catheters, renal failure, or posttransplantation. This course also highlights the importance of interprofessional collaboration, patient education, and the integration of emerging diagnostic tools and treatments, such as bacteriophages and advanced imaging. This activity equips clinicians to improve patient outcomes, minimize inappropriate antibiotic use, and effectively manage the complexities of UTIs in diverse clinical scenarios.

Objectives:

Differentiate between simple and complicated urinary tract infections based on risk factors, clinical presentation, and potential complications.
Assess patients with complicated urinary tract infections to identify underlying anatomical abnormalities, immune status, and potential sources of infection.
Implement evidence-based management protocols for the appropriate use of antibiotics and treatment strategies tailored to specific risk profiles.
Collaborate amongst the interprofessional team to enhance and ensure continuity of care for patients affected by complicated urinary tract infections.

Introduction

Urinary tract infections (UTIs) are among the most common causes of sepsis in hospitalized patients. UTIs have a wide variety of presentations. Some simple UTIs can be managed with outpatient antibiotics and carry a reassuring clinical course with an almost universally good outcome. On the other end of the spectrum, florid urosepsis in a comorbid patient can be fatal. UTIs can also be complicated by several risk factors leading to treatment failure, repeat infections, or significant morbidity and mortality with a poor outcome. It is essential to determine whether the presenting episode is associated with underlying risk factors and assess its likelihood of resolving with first-line antibiotics.[1][2][3][4]

A complicated urinary tract infection (UTI) is an infection with a higher risk of treatment failure. Proper identification is crucial, as these infections often require longer treatment durations, alternative antibiotics, and sometimes additional diagnostic evaluations to ensure effective management.

A simple UTI (or cystitis) is a urinary tract infection due to appropriate susceptible bacteria in a clinical context not associated with treatment failure or poor outcomes. Typically, this is an infection in an afebrile, nonpregnant, immune-competent female patient. Pyuria and/or bacteriuria without any symptoms is not a UTI and may not require treatment. An example would be an incidental positive urine culture in an asymptomatic, afebrile, nonpregnant immune-competent female. A complicated UTI is any UTI other than a simple UTI, as defined above. Therefore, all UTIs in immunocompromised patients, males, pregnant patients, and those associated with fevers, stones, sepsis, urinary obstruction, catheters, or involving the kidneys are considered complicated infections.

The female urinary tract, with its relatively short urethra, is inherently predisposed to bacterial seeding and proximal spread. This anatomy increases the frequency of infections. Simple cystitis, a single episode of ascending pyelonephritis, and even recurrent cystitis in certain contexts may be classified as simple UTIs, provided they respond promptly to first-line antibiotics and result in no long-term complications.

Any UTI that does not conform to the above description or clinical trajectory is considered a complicated UTI. In these scenarios, one can almost always find protective factors that failed to prevent infection or risk factors that lead to poor resolution of sepsis, higher morbidity, treatment failures, and reinfection.[5][6][7] The reason for the distinction is that complicated UTIs have a broader spectrum of bacteria as an etiology and have a significantly higher risk of clinical complications.[8] The presence of urinary tract stones and catheters is likely to increase the incidence of recurrences compared to patients without these foci of bacterial colonization.[9]

Examples of a complicated UTI include:

Infections despite the presence of anatomical protective measures (UTIs in males are, by definition, considered complicated UTIs)
Infections due to anatomical abnormalities, for example, an obstruction, hydronephrosis, renal tract calculi, or colovesical fistula
Infections due to an immunocompromised state, for example, steroid use, postchemotherapy, diabetes, HIV, older individuals
Atypical organisms causing UTI
Recurrent infections despite adequate treatment (multidrug-resistant organisms)
Infections occurring in pregnancy (including asymptomatic bacteriuria)
Infections occurring after instrumentation, such as placing or replacement of nephrostomy tubes, ureteric stents, suprapubic tubes, or Foley catheters
Infections in renal transplant and spinal cord injury patients
Infections in patients with impaired renal function, dialysis, or anuria
Infections following surgical prostatectomies or radiotherapy

Etiology

Most UTIs are due to the colonization of the urogenital tract with rectal and perineal flora. The most common organisms include Escherichia coli, Enterococcus, Klebsiella, Pseudomonas, and other Enterococcus or Staphylococcus species. Of these, E coli is the most common, followed by Klebsiella. Residential care patients, diabetics, and those with indwelling catheters or immunocompromise can also colonize with Candida.[10] E coli and possibly Klebsiella overwhelmingly cause simple UTIs. Complicated UTIs tend to be caused by a much wider range of organisms, which is significant because multidrug resistance is increasing, and therefore, specific antibiotic regimens vary.

Epidemiology

In the United States, complicated UTIs account for over 626,000 hospital admissions annually, representing approximately 1.8% of all hospitalizations. Notably, 80% of these cases are non-catheter-related.[11] Cohorts with more risk factors show an increased incidence of UTIs. Risk factors include female gender, increasing age, diabetes, obesity, long-term catheters, and frequent intercourse (although UTI is not defined as a sexually transmitted infection).

Simple UTIs in nonpregnant immune-competent females have been estimated to occur with as high as 0.7 infections per person per year. Fifty percent of females will have at least 1 UTI during their lives.
Complicated UTI incidence is associated with specific risk factors. For example, there is a 10% daily risk of developing bacteriuria with indwelling bladder catheters and up to a 25% risk of bacteriuria progressing to a UTI.
About 20% of all bacteremias associated with health care originate from the urinary tract. The mortality associated with these urinary tract-based bacteremias can be up to 10%.[12]
Bacteriuria occurs in up to 14% of diabetic females but does not tend to occur with a higher frequency in diabetic males.
Asymptomatic bacteriuria tends to increase with age in females and is present in up to 80% of the older female population. It is rare among younger healthy males but can be present in up to 15% of older males.
About 9.4% of all urological inpatients developed a complicated UTI during their hospital stay.[13][14]
An increased incidence of UTI has been described in patients using dapagliflozin (SGLT2i), which treats diabetes by producing glycosuria.[15]
UTIs are the most common infections in renal transplant patients. Up to 25% of these patients will develop a UTI within the first year after a transplant.
UTIs are the seventh most common reason for a patient to be seen in an emergency department in the US, constituting over 1 million visits annually. About 22% (220,000) of these are considered complicated UTIs, and about 100,000 are admitted to hospitals yearly.[16][17]

Pathophysiology

A biofilm is an encapsulated, structured microorganism colony that has created its polymeric matrix to protect and adhere to bodily structures, stones, or foreign bodies.[18] Biofilms also involve various pathogens of relatively low virulence and can cause severe, potentially life-threatening infections.[9][10] Urinary stasis due to dysfunctional voiding or obstruction facilitates bacterial invasion of tissues and provokes a host response.[19]

Foreign bodies such as stones and catheters are commonly associated with biofilms. Catheters, in particular, offer access to the urinary tract by bacteria, and the biofilm then protects the organisms from elimination. Multiple organisms are often involved in biofilms.[20] Most antibiotics cannot effectively penetrate biofilms and cannot treat bacteria located there.[21][22] Biofilm bacteria typically grow at a slower rate, which diminishes the effectiveness of antibiotics that target rapidly dividing organisms.[23][24] While irrigation and free urinary flow can help minimize biofilm development, they cannot prevent it. The only effective therapy is to remove and replace the affected foreign body.

Foley catheters that have been in place for 1 to 2 weeks or longer should be replaced before obtaining a urinalysis or urine culture to avoid contamination from the biofilm that has developed on the catheter. A complete biofilm will form on a urinary catheter in about 2 weeks. Patients with frequent catheter-associated UTIs may benefit from more frequent catheter changes.

History and Physical

UTIs, particularly complicated ones, are common in hospital settings and often contribute to clinical uncertainty and diagnostic challenges, leading to a significant number of inappropriate antibiotic prescriptions.

The primary clinical criteria for diagnosing a simple UTI include symptoms such as increased urinary frequency, urgency, hematuria, dysuria, or suprapubic pain. Diagnosis should occur within a clinical context where a urogenital tract infection is the most likely cause. In such cases, empiric treatment with first-line antibiotics is appropriate. A urine sample should also be sent for microscopy and culture before beginning treatment, although that is not always possible. The urine sample almost always shows an abnormal red or white cell count, positive nitrites, and bacteria.

Any UTI that fails to resolve with first-line therapy or occurs in a high-risk patient population should be considered a complicated UTI. Symptoms of complicated UTIs include those seen in simple UTIs, such as urinary frequency, urgency, hematuria, dysuria, and suprapubic pain, along with additional signs like fever, chills, flank pain, sepsis of urological origin, cystitis symptoms persisting for more than 7 days, and acute mental status changes (particularly in older adults). Risk factors include known multiple antibiotic resistance, the presence of permanent Foley or suprapubic catheters, and high-risk patient populations, such as those who are pregnant, immunocompromised, post-renal transplantation, have neurogenic or dysfunctional bladders, are in the immediate post-urological surgery period, have renal failure, or are pediatric patients.[8]

Complicated UTIs can present with nonspecific or atypical symptoms, such as delirium in older individuals, signs resembling an acute abdomen, or triggers for diabetic emergencies like diabetic ketoacidosis. In some cases, they may manifest without symptoms, as seen in asymptomatic bacteriuria during pregnancy. Severe cases of complicated UTIs can escalate to undifferentiated sepsis or septic shock, requiring prompt recognition and management.

Evaluation

A good quality urine specimen is vital in making the diagnosis. However, treatment must not be delayed if the clinical scenario strongly suggests a UTI.[25][26][27]

Most patients can provide a high-quality midstream urine sample with appropriate instructions. If obtaining a clean-catch urine sample is not feasible, a catheterized urine sample, either through an indwelling catheter or a straight in-out catheter, may be used. Catheter insertion is not without some risk, and this risk must be weighed against the diagnostic advantage of having a urine specimen for analysis and culture. Obtaining a urine specimen for culture before initial antibiotic administration is recommended whenever possible and feasible. Most patients with complicated UTIs demonstrate pyuria. The presence of white blood cell casts strongly suggests renal involvement. Different normal white cell ranges depend on the urine sample, and the results should be interpreted accordingly.

Urine samples in prostatitis patients may not always be diagnostic, especially if the patients have already been partially treated. A pre- and post-prostate massage urine sample, known as the 4-glass test or the shortened 2-glass test, can enhance diagnostic accuracy in patients with prostatitis. In general, pelvic or perineal pain, difficulty in urination, failure of initial therapy, and rapid recurrence of symptoms suggest prostatitis.

Some patients with clinical signs of a UTI may not demonstrate any urinary bacteria on culture. Patients with asymptomatic bacteriuria exhibit no urinary symptoms but have significant bacterial growth on urine culture.[8] Urine with a cloudy appearance or foul odor may suggest infection, but these findings have not been clearly demonstrated to correlate with either bacteriuria or a UTI.[28]

Older patients, especially those with dementia, are at increased risk for complicated UTIs.[29] Dementia can cause a decline in personal hygiene and an increase in various voiding issues. There is also an increased risk for urinary catheterization. Diagnosis can be more difficult as patients with dementia may present with altered mental status, increased confusion, or agitation instead of the usual lower urinary tract symptoms.[30]

Blood cultures are useful in more severe septic presentations. A positive blood culture can sometimes help corroborate a urine sample result and reduce any suspicion of contamination.

Radiological investigations are not helpful in initially diagnosing most infections limited to the genitourinary tract. Sufficient clues for diagnosis should be gathered from the patient’s history, physical examination, and laboratory results. Ultrasound and CT scans may be helpful or even critical for diagnosing a perinephric abscess, urinary retention, hydronephrosis, and obstructive pyelonephritis from stones in septic patients.

All febrile and septic patients who fail to respond to appropriate broad-spectrum antibiotics within 48 to 72 hours should undergo imaging to exclude complications such as abscesses, urinary retention, calculi, gas, and obstructive uropathy, pyonephrosis, and hydronephrosis. Renal ultrasonography is quicker, less expensive, and avoids radiation exposure to the patient, but CT imaging is the definitive standard. CT imaging should be strongly considered in complex or intractable cases, even if the ultrasound is negative, as the results can sometimes be life-saving.[31]

All patients with a complicated UTI, including a first presentation of ascending pyelonephritis in nonpregnant immunocompetent females, should undergo at least a renal tract ultrasound to assess for anatomical abnormalities, hydronephrosis, stones, or other lesions. Because no reliable clinical method exists to rule out urinary obstructions, such as stones, in complicated UTIs, the treating clinician must use imaging, such as an ultrasound or CT scan, to confirm or exclude obstruction.[32]

Treatment / Management

A UTI can present with severe, life-threatening sepsis and multiorgan involvement. Resuscitation often precedes definitive treatment. The severely septic patient might need aggressive fluid resuscitation and broad-spectrum antibiotics administered in the emergency department. Antibiotic choices should always be made according to local bacterial resistance patterns and guidelines.[33][34][35][36]

Patients presenting with septic shock may not respond to fluid resuscitation alone, and there should be a low threshold to consider vasopressor support in light of a poor initial response to fluids.[8][37][38] Alternatively, nonseptic-stable patients may be treated as outpatients.

Broad-spectrum empiric antibiotics should be promptly de-escalated to targeted narrow-spectrum antibiotics once culture results are available. Initial broad-spectrum options often include penicillins or beta-lactams, cephalosporins, fluoroquinolones, and carbapenems, particularly for infections involving extended-spectrum beta-lactamase (ESBL) organisms. The selection of antibiotics should be guided by the hospital's specific microbiological spectrum and antibiogram.[39]

Patients who present with repeat infections may be initially treated as per their previous urine culture results until new cultures are available. Imaging to identify a source of infection, such as an abscess or stone, should be performed with relapsing infections that involve the same organisms.[40] Patients who presented initially with hematuria should be rechecked for urinary blood after the infection has been successfully treated.

Treatment response should be evident in 24 to 48 hours in most cases. A poor response may indicate an inappropriate antibiotic selection, polymicrobial or atypical infections, hydronephrosis, an obstructing stone causing pyonephrosis, or complications like a perinephric abscess, emphysematous UTI, fluid collections (eg, urinary retention), or anatomical abnormalities (eg, nephrocalcinosis, obstructive lesions, urinary calculi, or fistulas). Ensuring adequate bladder drainage is critical for patients who are septic or have increased post-void residual volumes, and a temporary Foley catheter is often recommended.

Antibiotic therapy for complicated UTIs typically lasts 10 to 14 days. Although any UTI in a male is technically considered a complicated UTI, many experts treat clear-cut cases of lower urinary tract infections in otherwise healthy men without bladder dysfunction, stones, or other high-risk factors, similar to simple UTIs. First-line agents in such cases include fosfomycin, trimethoprim-sulfamethoxazole, or nitrofurantoin. In recurrent infections, prostatitis should be suspected and treated accordingly, especially if the same organism is encountered. See StatPearls' references Acute Bacterial Prostatitis at Chronic Prostatitis and Chronic Pelvic Pain Syndrome in Men for more information.

Most patients (97%) with mild to moderate pyelonephritis and no major comorbidities can be effectively managed as outpatients following initial parenteral antimicrobial therapy and a brief observation period.[41]

Men presenting with recurrent UTIs or bacterial prostatitis may require 4 to 6 weeks or longer to eradicate the infecting bacteria completely. Men with benign prostatic hyperplasia (BPH) and recurrent or intractable UTIs should be considered for surgical therapy.[42] Nitrofurantoin is not generally recommended in complicated UTIs in men due to poor tissue penetration, particularly in the kidneys, testicles, and prostate.

Failure to respond to appropriate antibiotics should suggest a possible urinary blockage, such as obstructive pyelonephritis. In such cases, a 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 a percutaneous nephrostomy.

Treatment success involves proper antibiotic selection, appropriate dosage adjustment, and correct duration of therapy. Eradicating high-risk factors, such as removing infected stones or indwelling catheters, is also warranted.

Prophylactic antibiotics are seldom recommended routinely due to the rapid development of bacterial resistance. When the clinical situation requires prophylaxis, nitrofurantoin is usually the preferred initial agent at 50 mg/d, generally taken before bed.[43][44]

Patients with permanent Foley catheters or suprapubic tubes should avoid prophylactic antibiotics and only be treated when symptomatic. More frequent changes of urinary catheters are recommended in chronically catheterized patients with recurrent or frequent infections. Patients with long-term Foley catheters tend to have fewer infections if converted to a suprapubic tube.[45] Changing the Foley is recommended to eliminate the contaminated biofilm and reduce recurrences if a catheterized patient develops an infection.[8]

Mandelamine is a twice-daily medication that, in acidic urine, is converted to formaldehyde, a potent urinary antiseptic. This can be useful in patients with multidrug-resistant infections or persistently elevated postvoid residuals instead of prophylactic antibiotics.[46] Mandelamine is often given together with ascorbic acid (1000 mg twice daily) to help maintain urinary acidity, which is necessary to produce formaldehyde.[47] This drug should not be given with sulfonamides as it can cause a precipitate. Mandelamine is not recommended for patients with a glomerular filtration rate of less than 10 mL/min.

Cranberry supplements have been studied with conflicting evidence of efficacy in treating complicated or recurrent UTIs.[48][49][50] Probiotics have not shown any significant benefit compared with placebo in treating complicated UTIs.[51]

Fosfomycin has shown effective activity in patients with urinary tract stones.[52][53] Fosomycin has significant penetration inside urinary calculi and is more effective than cefuroxime.[53] Fosfomycin is also being used parenterally as empiric therapy for complicated UTIs in some parts of the world; however, its use remains limited in the US.[54][55] It is recommended that its use be reserved for cases where carbapenems cannot be used to preserve its efficacy.

Pivmecillinam was approved by the FDA in 2024 as a first-line oral therapy for uncomplicated female urinary tract infections. Pivmecillinam is the metabolic precursor of mecillinam, a unique extended-spectrum β-lactam penicillin-based antibiotic, which has good activity against multidrug-resistant and ESBL-producing E coli, Staphylococcus saprophyticus, and Proteus mirabilis as well as many gram-negative organisms.[56][57][58] Fosfomycin is ineffective 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, it is highly effective for lower urinary tract infections caused by susceptible organisms, especially 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 urinary tract infections.[60] The recommended dosage of pivmecillinam in the United States is 185 mg orally 3 times a day for 3 to 7 days. However, in Europe, a higher dosage of 400 mg 3 times a day is suggested, based on evidence indicating that this may be more effective.[61][62] The dose should be reduced in patients with an estimated glomerular filtration rate (GFR) of less than 30 mL/min, and it should not be used if the GFR falls to less than 10 mL/min as it is primarily excreted by the kidneys.

Long-term use may cause a carnitine deficiency, which can result in mental confusion, cardiomyopathy, generalized weakness, hyperammonemia, unexplained muscle aches, and fatigue.[63] For more information, see StatPearls' companion reference, Carnitine Deficiency.

Intermittent bladder instillations of an antibiotic or antiseptic solution have been used successfully in recurrent or relapsing UTI patients with renal failure, oliguria, pyocystis, or frequent recurrences, especially in patients already performing intermittent self-catheterization. The most commonly used antimicrobial for this purpose is a gentamicin solution.[64] The recommended dosage is to instill 30 cc to 60 cc of a solution of 480 mg gentamicin/1 liter of normal saline after draining the bladder.[65] When introduced in this fashion, gentamicin has no significant systemic absorption, so it can be used regardless of renal function. While gentamicin is the recommended agent initially, if it is not available, tobramycin, hyaluronic acid, Lactobacillus rhamnosus, povidone-iodine solution, or Neosporin can be used as alternatives.[64][66]

Neomycin alone showed no efficacy in controlling bacteriuria, but chlorhexidine and povidone-iodine have been shown to reduce UTIs and bacteriuria.[64] Neosporin can also be used as a short-term (10 day) continuous bladder irrigation with a 3-way Foley catheter.[67] Bladder antibiotic installations are particularly useful in dialysis and patients with anuria or pyocystis because they are not dependent on the renal excretion of antibiotics. Interestingly, heparin bladder instillations have also shown some activity in reducing recurrent UTIs, most likely by providing a 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 receiving specific culture results depends on individual patient characteristics and local bacterial resistance antibiograms. For example, fluoroquinolones are generally not recommended for empiric use if the local resistance is greater than or equal to 10%. A discussion with a local infectious disease specialist can help determine the best initial empiric approach for the specific local community. Generally, parenteral antibiotics are recommended for patients with systemic or severe illness until urine culture results can guide the antibiotic selection. If no such antibiotic is apparent, consider an infectious disease consultation.

Ceftriaxone or piperacillin-tazobactam can be used in patients who are less severely ill. Due to its greater activity, piperacillin-tazobactam is preferred if Enterococcus, Staphylococcus, or Pseudomonas is suspected.
Vancomycin, linezolid, or daptomycin should be added if methicillin-resistant Staphylococcus aureus (MRSA) is suspected.
If Pseudomonas is suspected, piperacillin-tazobactam, fluoroquinolones, cefepime, or ceftazidime should be used.
Parenteral fosfomycin has also been used for complicated UTIs and has good activity against many highly resistive organisms, such as ESBL-producing bacteria. Parenteral fosomycin is not 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 usually reserved for patients when other less nephrotoxic drugs cannot be used due to resistance or allergy.
For critically ill patients requiring maximum 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 little activity against Pseudomonas and would not be an appropriate choice.

Newer Antibiotic Agents For Multidrug-Resistant Infections

The development of multidrug-resistant organisms has prompted the investigation of older antimicrobials (primarily aminoglycosides and tetracyclines) as well as the development of new antibiotics and combinations, such as:

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 to treat complicated UTIs. This medication was FDA-approved in 2015 and is intended for use where other medications are not likely to be effective due to resistance.[71][72]

Cefiderocol is a new, unique, FDA-approved synthetic siderophore-conjugated cephalosporin antibiotic that can be used for complicated UTIs involving highly resistant organisms. Cefiderocol uses the bacterial cell iron transport mechanism to facilitate the cellular introduction of drugs, providing very high intracellular concentrations of medications.[73] This medication is well tolerated and active against many multidrug-resistant organisms, including those resistant to carbapenem antibiotics.[74] It is intended only for limited use as a last resort option for multidrug-resistant infections. While promising, some bacterial isolates have already demonstrated resistance, so usage is limited.[73]

Meropenem-vaborbactam enhances the activity of meropenem against organisms that manufacture Klebsiella pneumonia-producing carbapenemase (KPC). This medication is FDA-approved for complicated UTIs, including pyelonephritis in susceptible organisms.[75][76]

Plazomicin is a unique, FDA-approved injectable aminoglycoside specifically developed for multidrug-resistant organisms, including those that produce aminoglycoside-modifying enzymes (AMEs), extended-spectrum beta-lactamases (ESBLs), and carbapenemases. Standard aminoglycosides have limited activity against bacteria that produce AMEs, and carbapenem-resistant organisms are emerging. Plazomicin was chemically designed to block the activity of most AMEs. Plazomicin is effective against 90% of coliform bacteria except for Proteus mirabilis and Morganella morgagnii. It is also effective against 90% of E coli and Klebsiella pneumoniae isolates, whether ESBL-producing or not. Like other aminoglycosides, it has some nephrotoxicity.[77][78][79]

Tebipenem is an oral carbapenem that has shown equivalence (noninferiority) to parenteral ertapenem in treating susceptible organisms causing pyelonephritis and other complicated UTIs.[80] When it receives FDA approval, it will probably be the first available oral carbapenem.

Special Patient Risk Groups

Catheter-Associated UTIs

The Infectious Disease Society of America (IFDSA) defines a catheter-associated UTI (CAUTI) as meeting the following criteria:

Presence of an indwelling catheter for at least 2 days after initial insertion.
At least 1 symptom of a UTI (eg, dysuria, urgency, or frequency) or 1 sign (eg, fever, chills, suprapubic pain, costovertebral angle tenderness, or flank pain).
In older patients, altered mental status or hypotension may be indicative.
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 catheter-associated urinary tract infection (CAUTI) differently from the IDSA.

Presence of an indwelling urinary catheter: The patient must have had the catheter 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 2 microorganisms.[84] This definition does not consider other potential sources of fever, so many experts feel this definition is less useful and tends to overestimate the actual CAUTI rate.[85] Therefore, the IFDSA definition is usually preferred in clinical practice.

Between 15% to 25% of all hospitalized patients will have a urinary catheter at some time during their hospital stay. Approximately 21% to 50% of such catheters are unnecessary and do not meet guidelines for initial placement.[86] The CDC has estimated that from 17% to 69% of all CAUTIs are preventable with optimally applied infection control measures. This means up to 9,000 deaths and 380,000 infections a year are potentially avoidable.

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

Catheterized patients are expected to have bacteriuria due to colonization and the development of biofilms. The rate of bacterial colonization is approximately 3% to 10% per catheterization day. This translates into 100% bacterial colonization after the first 30 days. Besides the duration of Foley catheterization, other identified risk factors include female gender, older patient age, diabetes, bacterial colonization of the drainage bag, urethral catheterization (compared to suprapubic), and errors in sterile catheter insertion procedures or maintenance care.

Proper urine specimen collection is important in catheterized patients suspected of a CAUTI to avoid culturing the biofilm. If possible, the optimal method is to remove the catheter and have the patient urinate for the specimen. If this is impossible, the catheter should be replaced before specimen collection. If it is necessary to collect a sample without removing the catheter, a designated drainage system side port access is suggested. If none of these techniques are possible, the last resort is to separate the catheter from the drainage system. Urine cultures should not be obtained from the drainage bag.[90] For patients with a condom catheter, a clean-catch midstream specimen is preferred.[91] If this is not obtainable, the sample can be collected from a new condom catheter after carefully cleaning the glans.

In catheterized patients, bacterial inoculation of the bladder can occur through 2 primary routes: extraluminal or intraluminal. The extraluminal route, which accounts for approximately 66% of cases, involves bacterial migration along the external biofilm on the catheter surface. In contrast, the intraluminal route, responsible for about 34% of cases, occurs due to catheter blockage or contamination of the drainage bag. Understanding these pathways is crucial for developing and implementing effective strategies to prevent CAUTIs.[92]

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

Routine instillation of various antiseptics into the urinary drainage bags can help reduce calcium phosphate precipitates and decrease bacterial counts. Hydrogen peroxide 3% and chlorhexidine have minimal to no effect in reducing urinary bag bacteriuria.[94] The most effective agents are 1/4% acetic acid, diluted household white vinegar (1:3 dilution), and household bleach (1:10 dilution).[95][96] Diluted vinegar is the most effective in dissolving calcium phosphate grit, precipitate, and debris, which clogs catheters and bags and lowers the bacteria count. The diluted bleach solution is the most effective in controlling bacterial growth, but none of these measures has been proven to reduce CAUTIs. Therefore, the IFDSA guidelines advise against the routine addition of antiseptics to the drainage bag of catheterized patients because of a lack of proven efficacy.[82] Surprisingly, many of the recommended, obvious, or suggested catheter-related interventions have failed to demonstrate clear evidence of reductions in CAUTIs, including:

Sterile technique for catheter insertion
Use of antiseptic or antibiotic ointments for routine meatal care
Antiseptic filters and antireflux mechanisms built into the urinary drainage bags
Use of dual-chambered drainage bags
Routine bladder or catheter irrigation
More frequent changes of the urinary drainage bags (every 7 to 14 days)
Placing antiseptic solutions in the drainage bags [96][97][98]

The most effective strategy in reducing CAUTIs is to avoid indwelling catheters whenever possible, discontinue them as soon as clinically feasible, and use optimal sterile placement techniques and maintenance procedures.[88]

Additional helpful measures to minimize CAUTIs include the following:

Require mandatory educational programs for all healthcare workers involved in urinary catheter insertion or care.
Strictly adhering to guidelines for indwelling catheter placement.
Use alternative urinary control measures (pads, condom catheters, mechanical suction devices, suprapubic tubes, Cunningham clamps, intermittent catheterization, Pickwick, etc) whenever possible.
Use a daily checklist to justify continuing all indwelling catheters.
Implement automatic catheter removal orders at the time of initial Foley insertion unless specifically instructed otherwise and justification is provided.
Strictly adhere to guidelines for diagnosing and treating CAUTIs to avoid overtreating asymptomatic bacteriuria.
Minimize unnecessary urine cultures, which often produce positive cultures even in uninfected patients, is a strong temptation for inappropriate antibiotic use.
Obtain urine cultures when treating patients for a UTI so culture results are available if the initial treatment fails.
Follow guidelines for correct specimen collection procedures for urinalyses and cultures.
Carefully investigate all alternative sources of infections and fevers before diagnosing a CAUTI.
Never use indwelling Foley catheters solely for incontinence.

Purple bag urine syndrome is a rare disorder in patients with long-term catheters, usually older women with constipation. Dietary tryptophan is broken down in the intestinal tract into indole, which the liver absorbs and converts into indoxyl sulfate. This is eventually excreted into the urine, where the indoxyl sulfate is converted by bacterial enzymes (in alkaline urine) to indigo (blue) and indirubin (red), which causes the intense purple color.[99][100][101] Treatment generally includes changing the catheter and bag, treating constipation, avoiding dehydration, and reassuring the nursing staff.

Spinal cord injury patients with catheters present unique challenges in diagnosing, preventing, and treating CAUTIs. Many of these patients require permanent or intermittent catheterization, which leads to a high incidence of asymptomatic bacteriuria that does not require treatment.[102] Impaired patient sensation may delay the appearance of pertinent, relevant symptoms. The development of nonspecific symptoms such as fever, bacteriuria, and positive urine cultures will often lead to a diagnosis of CAUTI, even when the actual infection may be elsewhere. This leads to the frequent overdiagnosis and overtreatment of CAUTI in this patient population.[103]

At least 35% of spinal cord injured patients diagnosed and treated for CAUTI are estimated to have only asymptomatic bacteriuria.[104] To facilitate diagnosis, it has been suggested that increased spasticity and autonomic dysreflexia be included as potential symptoms of a CAUTI in this population, but it is unclear how clinically useful this is.[82]

The general principle of early catheter removal does not necessarily apply to spinal cord injured patients who may not have a suitable alternative for safe bladder drainage. Inappropriate Foley catheter removal puts them at risk for urinary retention, vesicoureteral reflux, renal failure, autonomic dysreflexia, and sepsis. Clean intermittent self-catheterization is safe, effective, and associated with a lower incidence of bacteriuria and CAUTIs, but there are still increased risks of infection, false passages, urethral strictures, bladder overdistention or retention, and a heavy reliance on caregivers for logistical support and supplies.[105][106]

Evidence suggests that long-term use of nitrofurantoin and D-mannose prophylaxis can effectively reduce CAUTI in spinal cord-injured patients.[107][108] Silver and hydrophilic-coated catheters also appeared to help reduce CAUTIs, but the studies were small and not considered definitive.[109][110] Cranberry supplements and other nutraceuticals have demonstrated either no activity or conflicting results in reducing CAUTIs in this population.[111][112]

A guidelines-based model for ordering urine cultures and antibiotics has significantly reduced overdiagnosis and overtreatment of asymptomatic bacteriuria in long-term catheterized patients by over 70%.[113][114]

UTIs in Pregnancy

Between 2% and 7% of pregnant women develop asymptomatic bacteriuria, usually early in their pregnancy.[102] Patients with a history of prior UTIs, diabetes, a larger number of prior deliveries, and lower socioeconomic status are at higher risk.[115] Without treatment, up to 35% progress to a symptomatic UTI and/or pyelonephritis during the pregnancy.[116] Most studies suggest untreated bacteriuria during pregnancy is associated with an increased risk of low birth weight babies, prematurity, preeclampsia, and perinatal mortality.[115][117][118] Pyelonephritis has also been associated with poor pregnancy outcomes, particularly prematurity.[119] Treatment of asymptomatic bacteriuria and cystitis generally includes 3 to 7 days of amoxicillin-clavulanate, cephalexin, cefpodoxime, or a single dose of fosfomycin.[120] Nitrofurantoin and sulfamethoxazole/trimethoprim may also be used, but not during the first trimester or close to term.[116][121][122]

Pyelonephritis during pregnancy can be challenging and generally requires hospitalization. Standard therapy would include ceftriaxone, cefepime, and ampicillin/gentamicin. Aztreonam is suggested if there is a beta-lactam allergy. Treatment can be adjusted after culture reports are available. 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 decreases urinary excretion of antibiotics, but other factors also play a role.[124] There is reduced urinary antibacterial function, uremic immunosuppression, lower antibacterial levels within the bladder and renal tissues, inhibition of urothelial antimicrobial functions, and possibly reduced urinary volume.[8][125][126][127] People with diabetes who have glucosuria will demonstrate increased bacterial adherence to the detrusor urothelium and decreased neutrophil efficacy.[128]

Diagnosing a UTI in dialysis patients can be challenging, as 30% to 40% of patients will typically demonstrate pyuria without infection.[129] The diagnosis, therefore, also requires symptoms and a positive urine culture. Infections are often related to catheterization, and Candida is the most common organism in this population.[130]

Antibiotics must be used cautiously in patients with severe or end-stage renal failure. Nitrofurantoin and tetracyclines (other than doxycycline) should be avoided. Aminoglycosides can be used cautiously, as they are potentially nephrotoxic. Other antibiotics, such as trimethoprim-sulfamethoxazole, trimethoprim alone, cephalexin, second- and third-generation cephalosporins, pivmecillinam, and fluoroquinolones, can generally be used at a reduced (usually 50%) dose.[131][132][133] Ertapenem has a renal failure- and dialysis-suggested dosing schedule, but neurotoxicity has been reported even when using the recommended dosages.[134] Moxifloxacin can be used in patients with renal failure but will not achieve adequate urinary concentrations and, therefore, cannot be recommended for UTIs.

A number of antibiotics generally do not require any adjustment, even in severe renal failure, including:

Azithromycin
Ceftriaxone
Clindamycin
Doxycycline
Fosfomycin
Linezolid
Nafcillin
Rifampin
Trimethoprim

For patients with severe renal failure (<30 mL/min.), nitrofurantoin, aminoglycosides, and methenamine should not be used. Preferred agents for a UTI in such patients would be trimethoprim or fosfomycin. Other agents that can be used include carbapenems, cephalosporins, doxycycline, penicillins, pivmecillinam, and quinolones.

For patients with end-stage renal failure, quinolones (ciprofloxacin, levofloxacin) are considered first-line agents for UTIs. Cefdinir and cefpodoxime are considered second-line backup therapy.[135][136]

Intermittent bladder instillations of antibiotics, such as gentamicin, tobramycin, amikacin, or neomycin/polymyxin B/bacitracin, or antiseptic solutions like povidone-iodine, can be beneficial for patients with severe or end-stage renal failure, minimal urinary volume, or those already performing intermittent self-catheterization. These approaches are particularly useful when alternative methods have proven unsuccessful.[64][65] The standard dose for intravesical antibiotic instillation therapy is 80 mg of gentamicin in 50 mL to 60 mL of normal saline. Antibiotic bladder instillations (intermittent or continuous) can also be used for pyocystis, which is defined as a collection of pus in the bladder of an anuric patient.[137][138][139]

UTIs in Renal Transplants

Diagnosing a complicated UTI can be difficult in renal transplant patients. Symptoms may be subtle and nonspecific, such as nausea or unusual fatigue. Fever and palpable tenderness over the graft site are more likely to be associated with a UTI than acute rejection. Renal transplant patients with UTIs who exhibit systemic signs of infection, such as fever or graft tenderness on palpation, should undergo blood cultures and standard urine cultures to guide appropriate management. About 9% of blood cultures ultimately return positive for bacteremia.[140] A diagnostic renal biopsy should be considered in questionable cases of pyelonephritis in renal transplant recipients or when a UTI is associated with graft dysfunction, especially during the first 6 months after the transplant.[141] Patients with acute rejection are more likely to have azotemia, worsening proteinuria, and hypertension.

All symptomatic UTIs in renal transplant patients are considered complicated UTIs. Morbidity and mortality from UTIs increase in kidney transplant patients as the required immunosuppression increases infection risk and interferes with therapy.[142][143] The current 1-year mortality rate from infectious complications in renal transplant recipients is less than 5%, having dropped from almost 50% historically, mostly due to advances in surgical techniques and postoperative care.[144]

UTIs are most common during the first year after transplantation and occur in approximately 25% of transplant recipients during that time.[140][145] About 7% of renal transplant recipients develop recurrent UTIs associated with an increased risk of multiple antibiotic resistance, transplant failure, and death.[146] Ascending UTIs with the early progression to frank pyelonephritis are more common in renal transplant recipients as they have very short ureters and will often lack an effective antireflux mechanism. The incidence of acute pyelonephritis also appears to be related to the frequency of rejection episodes and recurrent UTIs. Renal transplant patients who develop pyelonephritis are more likely to develop increases in serum creatinine along with a decrease in creatinine clearance, which is often persistent.[147]

Screening for asymptomatic bacteriuria immediately posttransplantation for the first 90 days is controversial, as many experts recommend it while others do not.[148][149] No strong evidence supports that screening or treating asymptomatic bacteriuria during the first 3 months after transplantation is helpful, so this remains a judgment call by the transplant team. If screening is performed, microscopic urinalyses with urine cultures are recommended at 2, 4, 8, and 12 weeks after surgical transplantation.[150]

Screening for asymptomatic bacteriuria after the first 3 months is not recommended as treatment beyond this point has not been effective in UTI prevention or graft preservation and may lead to unnecessary antibiotic use and increased bacterial resistance.[151][152] Historically it was thought that graft and patient survival were not affected by adequately treated complicated UTIs, but more recent data suggests that acute and recurrent graft pyelonephritis are significant risk factors for decreased long-term graft and patient survival.[153][154]

Posttransplantation risk factors for UTIs include female gender, advanced patient age, longer time on dialysis before transplantation, recurrent UTIs in the recipient before transplantation, polycystic kidney disease, Foley catheterization, ureteral stent placement, use of a deceased donor transplant, and urinary tract obstruction or dysfunction.[155][156][157]

Antibiotic UTI prophylaxis is commonly used for the first 6 to 12 months posttransplantation.[158] Some experts continue the prophylaxis indefinitely.[159] Trimethoprim-sulfamethoxazole is the most commonly used prophylactic agent, but there are concerns about increasing bacterial resistance. Cephalexin and norfloxacin prophylaxis has been used successfully in patients unable to take trimethoprim-sulfamethoxazole.[160] Methenamine hippurate (1000 mg twice daily) with or without vitamin C (1000 mg twice daily) has also been used successfully for UTI prophylaxis in renal transplant patients.[161][162] Further, it can be safely used in patients with a creatinine clearance of greater than 10 mL/min but should not be used with sulfa drugs due to the potential formation of bladder precipitates. Fosfomycin has been used effectively in addition to standard trimethoprim-sulfamethoxazole therapy before urologic procedures and for this population's UTI/asymptomatic bacteriuria treatment.[152][163]

Renal transplant patients have an increased incidence of Klebsiella pneumoniae being the infecting organism in UTI.[143] Other common pathogenic bacteria besides E coli and K pneumoniae include Enterobacter cloaca. Pseudomonas aeruginosa, and Enterococcus. Due to reduced host resistance factors, treatment is typically 14 to 21 days. Patients suspected of having a UTI but demonstrating a negative urine culture should be tested for Corynebacterium urealyticum, which requires special culture media for identification.[164]

Simple cystitis is typically treated for 10 to 14 days. Nitrofurantoin may be used if the GFR is ≥30 mL/min.[165][166][167] The optimal duration of antibiotic therapy for complicated UTIs is unclear, but the standard treatment period is 14 to 21 days, although this can be extended. Infected cysts, for example, may need 4 to 6 weeks of treatment. Trimethoprim-sulfamethoxazole would be less ideal if the local resistance prevalence is reported as ≥20%.[168][169][170]

Selective imaging can be helpful in some renal transplant patients with UTIs. The initial test is usually ultrasonography. Patients with polycystic kidney disease may have an infected cyst which can be challenging to identify. Such patients often have flank pain related to the infected renal cyst rather than graft discomfort. In such cases, a CT-PET scan can be beneficial.[171][172][173] A noncontrast CT scan is a reasonable next step if the ultrasound is negative, especially in patients with a history of nephrolithiasis. (While contrast is useful, it also is potentially nephrotoxic and cannot be used safely in patients with elevated serum creatinine levels.) Voiding cystourethrograms can identify reflux, and urodynamics will diagnose bladder dysfunction and outflow obstruction.

Specific Infections

Emphysematous cystitis is a lower bladder UTI characterized by gas within the bladder wall produced by gas-forming bacteria. Such gas-forming bacteria are usually E coli or K pneumonia. Other organisms that can produce gas include Proteus, Enterococcus, Pseudomonas, Clostridium, and rarely Aspergillus and Candida. Infrequently, infectious colitis has caused emphysematous cystitis without clinical signs or evidence of a UTI.[174] It typically develops in people with diabetes, older individuals, and those with some urinary obstruction; it's more prevalent in females than males. High glucose levels in the bladder wall tissue certainly play a part, but the precise etiology of emphysematous cystitis is poorly understood.[175] The mean age of presentation is about 68 years, and approximately 50% of patients have 2 or more significant comorbidities. Emphysematous cystitis presents with varied symptoms: one-third of patients develop sepsis, 25% experience abdominal pain, 17% exhibit UTI symptoms, 6% have hematuria, and 8% are asymptomatic, with the condition identified incidentally during imaging.[176] While the diagnosis can sometimes be made by ultrasound or plain KUB X-ray, most are identified by CT scans. Treatment primarily involves culture-specific antibiotics, bladder drainage, supportive care, and elimination of risk factors. Ninety percent of cases can be managed conservatively, and only 5% to 10% require surgery.[176]

Emphysematous pyelonephritis is a particularly debilitating necrotizing kidney infection characterized by gas within the renal parenchyma or perinephric space, typically diagnosed on a CT scan. Most patients with the condition have diabetes (95%); it is 6 times more common in women than men. It is associated with renal failure, obstruction, polycystic kidneys, and an immunocompromised state.[177][178] Poor prognostic factors include azotemia, thrombocytopenia, shock, hyponatremia, confusion, and hypoalbuminemia.[179] Treatment includes renal drainage, blood sugar control, and parenteral antibiotics, typically for 3 to 4 weeks. Emergency nephrectomy is being recommended less often than previously, as early surgery generally negatively affects outcomes. Surgery is generally recommended if there are multiple risk factors in a nonfunctioning kidney or if the patient is not responding to conservative measures.[179][180]

Pyonephrosis (obstructive pyelonephritis) describes an acutely infected, hydronephrotic kidney, usually with an obstructing calculus. Sepsis rapidly ensues unless the obstruction is quickly relieved by drainage from a double-J stent or percutaneous nephrostomy. These patients are generally quite ill with high fevers, chills, tachycardia, diaphoresis, and flank pain. Pyonephrosis is considered an urgent surgical emergency as patients rapidly progress to urosepsis, shock, and death. The urine may sometimes not show any obvious signs of infection if the affected renal unit is obstructed. Ultrasonography can identify the problem quickly, but a noncontrast CT scan will more clearly show the level and nature of the obstruction. A CT scan can also show other pathologies, such as various cancers, retroperitoneal fibrosis, and other disorders. Management includes fluids and antibiotics, but the critical component is urgent drainage of the hydronephrotic, infected kidney.[180][181] Known risk factors include a history of nephrolithiasis, diabetes (especially poorly controlled), elevated C-reactive protein, positive urinary nitrites, larger stone size (>5 mm), and perirenal fat stranding.[182]

Definitive treatment of the obstruction is usually delayed until the immediate infectious process has been controlled. Percutaneous nephrostomy is usually preferred for the most severe cases as there is minimal manipulation of the infected stone and no risk of possible failure to bypass the obstruction cystoscopically from a retrograde approach.[183] A particularly large collection of stones should also be initially drained and managed percutaneously.[181][184] It has been suggested that definitive stone surgery be conducted within 3 weeks of ureteral stent placement. Complications, specifically reduced postoperative UTIs, are minimized if the stone removal operative time is less than 75 minutes.[185]

Xanthogranulomatous pyelonephritis is a chronic renal infection where the kidney is almost always obstructed and hydronephrotic with necrosis and severe inflammation of the renal parenchyma. This infection is often seen in patients who are immunocompromised and/or diabetic. Xanthogranulomatous pyelonephritis is diagnosed most reliably by a CT scan. Xanthogranulomatous pyelonephritis (XGP) can sometimes be mistaken for renal cell carcinoma because foamy, lipid-laden histiocytes (xanthoma cells) may resemble cancer cells on biopsy.[186][187] A distinguishing feature is that XGP cells stain positive for periodic acid-Schiff (PAS), aiding in differentiation.[188] Initial treatment involves antibiotics and drainage, but surgical excision (focal or, more often, total) is usually necessary for a cure.[188] Laparoscopic and robotic surgery is possible but can be difficult even for experienced surgeons, so an open approach is usually recommended.[187]

Other specific infections involving the urinary tract are best found in our companion articles on those specific topics. These include 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 hasten proper diagnosis, minimize inappropriate antibiotic use, and improve antimicrobial selection accuracy. These new aides include computer programs with artificial intelligence algorithms, new classes of biomarkers, and cell-free DNA analysis, among others. New catheter materials, coatings, innovative bacterial growth interference agents, and anti-infective vaccinations for high-risk populations are being studied. Entirely new classes of antibiotics are being designed and created.[189] Bacteriophages (viruses that attack only specific bacteria) have been used anecdotally but successfully on a very limited basis for highly resistant infections.[103][190][191] Bacteriophages can not only prevent the formation of biofilms but can produce polysaccharide depolymerase, which allows for phage penetration deep into existing biofilms where antibiotics cannot reach them. They are also unaffected by bacterial antibiotic resistance mechanisms.[103][192]

Differential Diagnosis

The differential diagnosis of a complicated UTI 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

The FDA recommends using dual primary endpoints to assess the eradication of complicated UTIs: a clinical response (symptom resolution with no new UTI symptoms) and a microbiological response (urine culture demonstrating <1000 CFU/mL).[8]

Complications

Inadequate treatment of complicated UTIs increases the likelihood of an early recurrence or even an outright failure of therapy. The infection can spread to other organs, result in an abscess, or progress to sepsis and sometimes death.

Deterrence and Patient Education

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

Pearls and Other Issues

Diagnostic Pitfalls

UTIs are primarily a clinical diagnosis, and expert opinion should be sought before initiating treatment of an isolated positive result in an otherwise asymptomatic patient.

Often, clinicians treat a positive culture report rather than a patient with a genuine UTI. A positive culture in an asymptomatic patient can usually be traced to a poor sampling technique.

Another confusing scenario is that of a septic, delirious older individual who cannot provide a history or demonstrate adequate examination signs to help localize a septic source. These patients are often treated as having a presumed UTI without a clear alternative septic source.

UTI-associated radiological changes can sometimes take several months to resolve and must be interpreted with care in recurrent or persistent infections.

UTI must be considered in the differential diagnosis of a patient with pelvic inflammatory disease or an acute abdomen.

Male patients with UTIs should also be screened for sexually transmitted infections.

Interstitial cystitis is frequently misdiagnosed and treated as a UTI and must be considered an alternative diagnosis in patients who repeatedly present with cystitis symptoms and negative cultures.

"Sterile pyuria," with persistent urinary WBCs but negative standard urine cultures, could indicate tuberculosis, which requires special cultures.

Bacterial infections only tend to account for 80% of all UTIs, and antibiotics may sometimes prove ineffective.

Spinal cord injury patients with a UTI may present with increased spasticity or autonomic dysreflexia.

Since there is no way to clinically distinguish obstructive pyonephrosis (a surgical emergency) from acute pyelonephritis (treated medically), consider reasonable urinary tract imaging (ultrasound, CT scan) in all cases of presumed pyelonephritis, especially in those patients who fail to improve on appropriate antibiotics.

Management Pitfalls

Frail, older, or debilitated patients with nonspecific signs such as unexplained falls or changes in mental status are often suspected of having a UTI. While this is correct, such nonspecific changes are unreliable predictors of a UTI, and antibiotics may not help unless urine studies confirm the UTI.[193][194]

Multidrug-resistant infections are becoming a significant source of in-hospital morbidity and mortality. Suppressive antibiotic regimens are sometimes used in cases where patients respond poorly or are resistant. A dedicated infectious disease team should optimally guide these care plans, as long-term suppressive antibiotics have unique complications.

Long-term antibiotic prophylaxis must also be used with caution, as it increases the risk of resistance and changes the susceptibilities of colonized organisms. Occasionally, residual urinary symptoms may take several months to resolve or might never resolve (especially in patients with indwelling catheters, post-prostatectomy cases, post-bladder surgery, or radiotherapy) and do not always indicate a genuine UTI. Long-term prophylaxis with nitrofurantoin is associated with hypersensitivity pneumonitis. Patients should be counseled accordingly.

Identifying predisposing factors for the infection and correcting them, if possible, is helpful. For example, a diabetic patient would benefit from improving glycemic control. Renal tract anatomic abnormalities should be assessed to see if an intervention is appropriate (renal calculi, BPH, ureteric strictures). Immunocompromising factors should be addressed if possible (steroids, HIV). Finally, nephrotoxic medications should be avoided whenever possible in patients with any degree of renal compromise. If unavoidable, care should be taken to use the optimal dose and duration of therapy with regular, routine monitoring of renal function. Finally, do not hesitate to consult your local infectious disease specialists for assistance. Their primary mission is optimally managing complicated, challenging, and complex infections.

Consider using oral fosfomycin, pivmecillinam, or intravesical gentamicin in otherwise intractable cystitis cases. These agents can be effective even in multidrug-resistant or ESBL-producing infections.

Enhancing Healthcare Team Outcomes

The management of complex UTIs is best performed by an interprofessional team that may include a urologist, nephrologist, infectious disease expert, internist, primary care clinicians, pharmacist, and nurses. Healthcare professionals need a range of clinical skills. Physicians must be adept at diagnosing and managing these infections, including interpreting diagnostic tests and selecting appropriate antibiotics. Nurses require expertise in administering medications, providing wound care, and monitoring patients for signs of sepsis. Pharmacists play a vital role in optimizing drug therapy and ensuring appropriate antibiotic stewardship. All team members share the responsibility of patient education, infection prevention, and monitoring for treatment response.

A well-defined management strategy is essential. This includes establishing evidence-based clinical guidelines and treatment protocols prioritizing patient safety, infection control, and antimicrobial resistance considerations. Strategies such as catheter care and hygiene education should also encompass prevention efforts.

Complicated UTIs need to be treated more carefully to serve patients with these infections and avoid overuse and misuse of antibiotics that will ultimately result in more resistant infections. Using the right antibiotic for the appropriate duration is critical. Practitioners should not hesitate to use infectious disease specialty services in these situations to help optimize antibiotic use. Failure of a standard UTI or pyelonephritis to respond to initial treatment should suggest other medical problems such as diabetes, sepsis, an abscess, urinary retention, or an obstructing stone with a possible pyonephrosis. Bladder drainage with a Foley catheter and appropriate imaging tests can identify these problems. These patients need close monitoring because of potential complications. The outlook for patients with severe, complicated UTIs is guarded, and even those who recover tend to have a prolonged recovery period.[75][195][196]

Effective communication and collaboration among healthcare professionals are crucial for patient-centered care. Physicians, advanced care practitioners, nurses, pharmacists, and other team members must share information about the patient's condition, treatment plan, and complications. Clear and timely communication enhances coordination, reduces errors, and promotes safer care. The team should work collaboratively to develop comprehensive care plans that address the infection, underlying conditions, and any potential complications. This includes clear roles and responsibilities, regular team meetings, and seamless care transitions between settings.

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

Details

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