Complicated Urinary Tract Infections

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Continuing Education Activity

Urinary tract infections (UTIs) are among hospitals' most common presenting causes of sepsis. Some simple UTIs can be managed with outpatient antibiotics, leading to almost universally good outcomes. However, complicated UTIs may lead to florid urosepsis, which can be fatal. Several risk factors can complicate UTIs, leading to treatment failure, repeat infections, or significant morbidity and mortality. It is essential to determine if the patient's infection may have resulted from one of these risk factors and whether the episode will likely resolve with first-line antibiotics. Complicated UTIs present with more significant morbidity, carry a higher risk of treatment failure, and typically require longer antibiotic courses, frequently requiring additional workup. This activity reviews the evaluation and management of complicated UTIs and highlights the role of interprofessional team members in collaborating to provide well-coordinated care and enhance outcomes for affected patients.

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 presenting in hospitals. UTIs have a wide variety of presentations. Some are simple UTIs that 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 vitally important to determine if the presenting episode results from these risk factors and whether the episode is likely to resolve with first-line antibiotics.[1][2][3][4]

It is important to properly define a complicated UTI as an infection that carries a higher risk of treatment failure. These infections typically require longer courses of treatment, different antibiotics, and sometimes additional workups.

In a clinical context not associated with treatment failure or poor outcomes, a simple UTI (or simple cystitis) is an infection of the urinary tract due to appropriate susceptible bacteria. Typically this is an infection in an afebrile non-pregnant 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 non-pregnant 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 normal female urinary tract has a comparatively short urethra and, therefore, carries an inherent predisposition to proximal seeding of bacteria. This anatomy increases the frequency of infections. Simple cystitis, a one-off episode of ascending pyelonephritis, and occasionally even recurrent cystitis in the proper context can be considered a simple UTI, provided there is a prompt response to first-line antibiotics without any long-term sequela.

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 occurring despite the presence of anatomical protective measures (UTIs in males are, by definition, considered complicated UTIs)
  • Infections occurring due to anatomical abnormalities, for example, an obstruction, hydronephrosis, renal tract calculi, or colovesical fistula
  • Infections occurring due to an immunocompromised state, for example, steroid use, postchemotherapy, diabetes, HIV, older individuals
  • Atypical organisms causing UTI
  • Recurrent infections despite adequate treatment (multi-drug 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, Escherichia 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 will vary.

Epidemiology

In the United States, there are over 626,000 hospital admissions a year for complicated UTIs, comprising about 1.8% of all annual hospitalizations, with 80% of these being 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 at some stage in life.                   
  • 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. Of these, about 22% (220 000) are considered complicated UTIs, and about 100 000 are admitted to the hospital 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 also tend to grow slowly, reducing the effectiveness of antibiotics that are more effective in 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. 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 therefore benefit from more frequent catheter changes.

History and Physical

Given their frequency in hospitals, UTIs (especially complicated UTIs) remain a clinical entity, causing considerable confusion and diagnostic uncertainty and a source of significant inappropriate antibiotic prescriptions.

The most important clinical criteria for initially diagnosing a simple UTI are symptoms (increased urinary frequency, urgency, hematuria, dysuria, or suprapubic pain). There must also be an appropriate clinical scenario in which infection of the urogenital tract is the most likely explanation for these symptoms. It is appropriate to start empiric treatment with first-line antibiotics in this situation. 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. Complicated UTI symptoms include all of those listed above, as well as fever, chills, flank pain, sepsis from a urological source, cystitis symptoms lasting >7 days, known multiple antibiotic resistance, permanent Foley or suprapubic catheters, acute mental status changes (especially in older individuals) and high-risk patient populations (pregnancy, immunocompromised state, renal transplantation, abnormal urinary function as in patients with neurogenic or dysfunctional bladders, immediate post-urological surgery, renal failure, pediatrics, etc).[8] 

Complicated UTIs may also present with nonspecific symptoms, atypical presenting features (delirium in older individuals), signs mimicking an acute abdomen, triggers for precipitating diabetic emergencies (diabetic ketoacidosis), and even an absence of symptoms (asymptomatic bacteriuria in pregnancy). Severe complicated UTIs can present as undifferentiated sepsis or even septic shock.

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 that is not possible, a catheterized urine sample (indwelling catheter or a straight in-out catheter) may be used. Catheter insertion is not without some risk, and this 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 will 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.

Often, urine samples in prostatitis may not be diagnostic, especially if the patients have already been partially treated. A pre-and post-prostate massage urine sample (also known as the 4-glass test or even the shortened 2-glass test) can improve the diagnostic yield 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 have no urinary symptoms but grow large numbers of bacteria on 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. There should be sufficient clues from the 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 septic patients and febrile 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 the CT scan is the definitive standard. It 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 who present with a complicated UTI, even the first presentation of ascending pyelonephritis in non-pregnant immune-competent females, should undergo a renal tract ultrasound at a minimum to evaluate for anatomical abnormalities hydronephrosis, stones, or other lesions. Since there is no reliable clinical method to rule out urinary obstructions in complicated UTIs (such as a stone), the treating physician must do so with an ultrasound or CT scan.[32] 

Treatment / Management

As 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 always be switched to a targeted narrow-spectrum antibiotic once culture results are available. Initial broad-spectrum choices tend to be penicillins or beta-lactams, cephalosporins, fluoroquinolones, and carbapenems (especially if dealing with an extended-spectrum beta-lactamases (ESBL) organism). The specific choice will depend on the individual hospital's microbiological spectrum and antibiogram.[39]

Patients who present with repeat infections may also 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 done 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 infections, atypical infections, hydronephrosis, obstructing stone causing pyonephrosis, complications such as a perinephric abscess or emphysematous UTI, fluid collections such as urinary retention or anatomical lesions leading to poor response (nephrocalcinosis acting like an infective nidus, obstructive urinary tract lesions, urinary calculi, or fistulas). To guarantee good bladder drainage, a temporary Foley catheter is often recommended for these patients if they are septic, particularly if they have increased post-void residual volumes.

Antibiotic therapy in complicated UTIs is typically 10 to 14 days. While technically, any UTI in a male is considered a "complicated UTI," many experts will treat what appears to be an unambiguous lower urinary tract infection in an otherwise healthy man with no known bladder dysfunction, stones, or other high-risk factors the same as a simple UTI with first-line antibiotic agents such as fosfomycin, trimethoprim-sulfamethoxazole, or nitrofurantoin. In recurrent infections, prostatitis should be suspected and treated accordingly, especially if the same organism is encountered.

Most (97%) of patients with mild or moderate pyelonephritis without major comorbidities can be managed as outpatients after initial parenteral antimicrobial therapy and a short observation period.[41] 

Men presenting with recurrent UTIs or bacterial prostatitis may require 4 to 6 weeks or longer to eradicate their 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 non-contrast CT scan should be performed for diagnosis, and immediate surgical drainage performed if an obstructed, infected kidney is found (either by 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 whenever possible, 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 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] It is often given together with ascorbic acid (1000 mg twice daily) to help maintain urinary acidity, which is necessary to produce formaldehyde.[47] It should not be given with sulfonamides as it can cause a precipitate. It is not recommended for patients with a glomerular filtration rate <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 good activity in patients with urinary tract stones.[52][53] It has significant penetration inside urinary calculi and was more effective than cefuroxime.[53] Fosfomycin is also being used parenterally as empiric therapy for complicated UTIs in some parts of the world but not widely yet in the US.[54][55] It is suggested that its use be limited to cases where carbapenems cannot be used to maintain efficacy.

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.[56] 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.[57] 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.[56][58] 

Neomycin alone showed no efficacy in controlling bacteriuria, but chlorhexidine and povidone-iodine have been shown to reduce UTIs and bacteriuria.[56] Neosporin can also be used as a short-term (10-day) continuous bladder irrigation with a 3-way Foley catheter.[59] Bladder antibiotic installations are particularly useful in dialysis and anuric patients 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.[60]

Empiric Initial Antibiotic Therapy for Patients With Urosepsis

Initial antibiotic selection in septic or systemically ill patients prior to receiving specific culture results will depend on individual patient characteristics and local bacterial resistance antibiograms. For example, fluoroquinolones are generally not recommended for empiric use if the local resistance is ≥ 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 (not available in the US).
  • Quinolones should be considered whenever the local resistance patterns allow.
  • Aminoglycosides are usually reserved for patients where other less nephrotoxic drugs cannot be used due to resistance or allergy. 
  • For maximum coverage in the sickest patients, consider using a carbapenem with anti-pseudomonal activity, such as imipenem (which will cover ESBL-producing organisms) and vancomycin (for MRSA). Ertapenem generally has little activity against Pseudomonas and would not be an appropriate choice.

Newer Antibiotic Agents For Multidrug-Resistant Infections

The development of multiple drug-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
  • Glycylcyclines
  • Imipenem/relebactam
  • Meropenem/vaborbactam
  • Omadacycline
  • Plazomicin
  • Tebipenem[61][62]

Ceftazidime/avibactam combines a potent third-generation cephalosporin with a beta-lactamase inhibitor to treat complicated UTIs. It was FDA-approved in 2015 and is intended for use where other medications are not likely to be effective due to resistance.[63][64]

Cefiderocol is a new, unique, FDA-approved synthetic siderophore-conjugated cephalosporin antibiotic that can be used for complicated UTIs involving highly resistant organisms. It uses the bacterial cell iron transport mechanism to facilitate the cellular introduction of drugs, providing very high intracellular concentrations of medications.[65] It is well tolerated and active against many multidrug-resistant organisms, including those resistant to carbapenem antibiotics.[66] 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.[65]

Meropenem-vaborbactam enhances the activity of meropenem against organisms that manufacture Klebsiella pneumonia-producing carbapenemase (KPC). It is FDA-approved for complicated UTIs, including pyelonephritis in susceptible organisms.[67][68]

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. It is effective against 90% of coliform bacteria except for Proteus mirabilis and Morganella morganii. It is also effective against 90% of Escherichia coli and Klebsiella pneumoniae isolates, whether ESBL-producing or not. Like other aminoglycosides, it has some nephrotoxicity.[69][70][71]

Tebipenem is an oral carbapenem that has shown equivalence (non-inferiority) to parenteral ertapenem in treating susceptible organisms causing pyelonephritis and other complicated UTIs.[72] It will probably be the first available oral carbapenem when it receives FDA approval.

Special Patient Risk Groups

Catheter-Associated UTIs (CAUTIs)

The Infectious Disease Society of America (IFDSA) defines a CAUTI as:

  • Having an indwelling catheter for at least 2 days after initial insertion
  • One UTI symptom (dysuria, urgency, or frequency) or sign (fever, chills, suprapubic pain, costovertebral angle tenderness, or flank pain)
  • Older patients may present with altered mental status or hypotension
  • Urine culture with at least 1000 CFU/mL of a single bacterial species/pathogen[73][74][75]

The US Centers for Disease Control and Prevention (CDC): National Health Safety Network (NHSN) defines CAUTI differently. They include the presence of a fever, suprapubic tenderness, or costovertebral angle pain, along with a colony count >100 000 with no more than 2 different organisms.[76] 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.[77] 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. It is estimated that 21% to 50% of such catheters are unnecessary and do not meet guidelines for initial placement.[78] The CDC has estimated that from 17% to 69% of all CAUTIs are preventable with optimally applied infection control measures. This means up to 9000 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.[79][80] 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.[81] 

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 not possible, 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.[82] For patients with a condom catheter, a clean-catch midstream specimen is preferred.[83] If this is not obtainable, the sample can be collected from a new condom catheter after carefully cleaning the glans.

Bacterial inoculation of the bladder in catheterized patients may be extraluminal (through the external biofilm) or intraluminal (from catheter blockage or contamination of the drainage bag). Extraluminal is the more common method (66% vs 34%).[84]

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.[85]

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.[86] The most effective agents are 1/4% acetic acid, diluted household white vinegar (1:3 dilution), and household bleach (1:10 dilution).[87][88] 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.[74] 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[88][89][90]

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.[80] 

Additional helpful measures to minimize CAUTIs include:

  • Requiring mandatory educational programs for all health care workers involved in urinary catheter insertion or care
  • Strictly adhering to guidelines for indwelling catheter placement
  • Using alternative urinary control measures (pads, condom catheters, mechanical suction devices, suprapubic tubes, Cunningham clamps, intermittent catheterization, etc) whenever possible
  • Using a daily checklist to justify continuing all indwelling catheters
  • Implementing automatic catheter removal orders at the time of initial Foley insertion unless specifically instructed otherwise and justification is provided
  • Strictly adhering to guidelines for diagnosing and treating CAUTIs to avoid overtreating asymptomatic bacteriuria
  • Minimizing unnecessary urine cultures, which often produce positive cultures even in uninfected patients, is a strong temptation for inappropriate antibiotic use
  • Obtaining urine cultures when treating patients for a UTI so culture results are available if the initial treatment fails
  • Following guidelines for correct specimen collection procedures for urinalyses and cultures
  • Carefully investigating all alternative sources of infections and fevers before diagnosing a CAUTI
  • Never using indwelling 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.[91][92][93] Treatment generally includes changing the catheter and bag, treating constipation, avoiding dehydration, and reassuring the nursing staff.  

Spinal cord injury patients with catheters offer 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.[94] Impaired patient sensation may delay the appearance of pertinent, relevant symptoms. The development of non-specific 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.[95] 

At least 35% of spinal cord injured patients diagnosed and treated for CAUTI are estimated to have only asymptomatic bacteriuria.[96] 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 will be.[74] 

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.[97][98] 

There is some evidence that long-term use of nitrofurantoin and D-mannose prophylaxis can effectively reduce CAUTI in spinal cord-injured patients.[99][100] Silver and hydrophilic-coated catheters also appeared to help reduce CAUTIs, but the studies were small and not considered definitive.[101][102] Cranberry supplements and other nutraceuticals have demonstrated either no activity or conflicting results in reducing CAUTIs in this population.[103][104]

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%.[105][106] 

UTIs in Pregnancy 

Between 2% and 7% of pregnant women will develop asymptomatic bacteriuria, usually early in their pregnancy.[94] Patients with a history of prior UTIs, diabetes, a larger number of prior deliveries, and lower socioeconomic status are at higher risk.[107] Without treatment, up to 35% will progress to a symptomatic UTI and/or pyelonephritis during the pregnancy.[108] Most studies suggest untreated bacteriuria during pregnancy is associated with an increased risk of low birth weight babies, prematurity, preeclampsia, and perinatal mortality.[107][109][110] Pyelonephritis has also been associated with poor pregnancy outcomes, particularly prematurity.[111] Treatment of asymptomatic bacteriuria and cystitis generally includes 3 to 7 days of amoxicillin-clavulanate, cephalexin, cefpodoxime, or a single dose of fosfomycin.[112] Nitrofurantoin and sulfamethoxazole/trimethoprim may also be used but not during the first trimester or close to term.[108][113][114]

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.[115] Aminoglycosides should be used cautiously due to potential fetal ototoxicity.

UTIs in Renal Failure and Dialysis

It is well known that chronic renal disease will decrease urinary excretion of antibiotics, but other factors also play a role.[116] 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][117][118][119] People with diabetes who have glucosuria will demonstrate increased bacterial adherence to the detrusor urothelium as well as decreased neutrophil efficacy.[120]

Diagnosing a UTI in dialysis patients can be challenging, as 30% to 40% of patients will typically demonstrate pyuria without infection.[121] 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.[122]

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, and fluoroquinolones can generally be used at a reduced (usually 50%) dose.[123][124][125] Ertapenem has a renal failure- and dialysis-suggested dosing schedule, but neurotoxicity has been reported even when using the recommended dosages.[126] 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. These include:

  • 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, and quinolones.

For patients with end-stage renal failure, quinolones (ciprofloxacin, levofloxacin) are considered first-line agents for UTIs. Cefdinir and cefpodoxime as considered second-line backup therapy.[127][128]

Intermittent bladder instillations of antibiotics (gentamicin, tobramycin, amikacin, neomycin/polymyxin B/bacitracin) or antiseptic (povidone-iodine) solutions can be helpful in patients with severe or end-stage renal failure, those who have minimal urinary volume, are already performing intermittent self-catheterization, or where alternative means have not been successful.[56][57] Antibiotic bladder instillations (intermittent or continuous) can also be used for pyocystis, defined as a collection of pus in the bladder of an anuric patient.[129][130][131]

UTIs in Renal Transplants

Diagnosing a complicated UTI can be difficult in renal transplant patients. Symptoms may be subtle and non-specific 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. Therefore, renal transplant UTI patients with systemic signs of infection, such as fever or graft tenderness on palpation, should have blood cultures and standard urine cultures taken. About 9% of blood cultures will ultimately return positive for bacteremia.[132] 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.[133] (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.[134][135] The current 1-year mortality from infectious complications in renal transplant recipients is <5%, having dropped from almost 50% historically, mostly due to advances in surgical techniques and postoperative care.[136] 

UTIs are most common during the first year after transplantation and will occur in approximately 25% of transplant recipients during that time.[132][137] About 7% of renal transplant recipients will develop recurrent UTIs associated with an increased risk of multiple antibiotic resistance, transplant failure, and death.[138] 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.[139] 

Screening for asymptomatic bacteriuria immediately posttransplantation for the first 90 days is controversial, as many experts recommend it while others do not.[140][141] There is no good data suggesting 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 done, microscopic urinalyses with urine cultures are recommended at 2, 4, 8, and 12 weeks after surgical transplantation.[142] 

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.[143][144] 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.[145][146] 

Posttransplantation risk factors for UTIs include female gender, advanced patient age, longer time on dialysis prior to transplantation, recurrent UTIs in the recipient prior to transplantation, polycystic kidney disease, Foley catheterization, ureteral stent placement, use of a deceased-donor transplant, and urinary tract obstruction or dysfunction.[147][148][149] 

Antibiotic UTI prophylaxis is commonly used for the first 6 to 12 months posttransplantation.[150] Some experts continue the prophylaxis indefinitely.[151] 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.[152] 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.[153][154] Further, it can be safely used in patients with a creatinine clearance of >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.[144][155]

There is an increased incidence of Klebsiella pneumoniae being the infecting organism in renal transplant patients.[135] Besides Escherichia coli and Klebsiella pneumoniae, other common pathogenic bacteria 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.[156]

Simple cystitis is typically treated for 10 to 14 days. (Nitrofurantoin may be used if the GFR is ≥30 mL/min.)[157][158][159] 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%.[160][161][162]

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.[163][164][165] A non-contrast 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 UTI of the bladder where there is gas within the bladder wall caused by gas-producing bacteria. Such gas-forming bacteria are usually Escherichia coli or Klebsiella 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.[166] It typically develops in people with diabetes, females more than males, older individuals, and those with some urinary obstruction. High glucose levels in the bladder wall tissue certainly play a part, but the precise etiology of emphysematous cystitis is not well understood.[167] The mean age of presentation is about 68 years, and approximately 50% of patients will have 2 or more significant comorbidities. One-third of patients will present with sepsis, 25% with abdominal pain, 17% with UTI symptoms, 6% with hematuria, and 8% asymptomatic with incidental findings on an imaging examination.[168] 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% will require some type of surgery.[168] 

Emphysematous pyelonephritis is a particularly debilitating necrotizing infection of the kidney characterized by gas within the renal parenchyma or perinephric space. It is typically diagnosed on a CT scan. Most patients with the condition have diabetes (95%), which is 6 times more common in women than men. It is also associated with renal failure, obstruction, polycystic kidneys, and an immunocompromised state.[169][170] Poor prognostic factors include azotemia, thrombocytopenia, shock, hyponatremia, confusion, and hypoalbuminemia.[171] 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 has a negative effect on outcomes. Surgery is generally recommended if there are multiple risk factors in a non-functioning kidney or if the patient is not responding to conservative measures.[171][172] 

Pyonephrosis (obstructive pyelonephritis) describes an acutely infected, hydronephrotic kidney with usually obstructing calculus. Sepsis rapidly ensues unless the obstruction is quickly relieved by drainage from a double-J stent or percutaneously. These patients are generally quite ill with high fevers, chills, 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 non-contrast 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.[172][173] 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 peri-renal fat stranding.[174] 

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.[175] A particularly large collection of stones should also be initially drained and managed percutaneously.[173][176] 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 <75 minutes.[177]

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. It is often seen in patients who are immunocompromised and/or diabetic. It is diagnosed most reliably by a CT scan. It can sometimes be mistaken for renal cell carcinoma as foamy lipid-infused histiocytes (xanthoma cells) can appear to be cancer cells on biopsy.[178][179] One way to differentiate them is that xanthogranulomatous pyelonephritis (xanthoma) cells will stain positive for periodic acid-Schiff (PAS).[180] Initial treatment involves antibiotics and drainage, but surgical excision (focal or, more often, total) is usually necessary for a cure.[180] Laparoscopic and robotic surgery is possible but can be difficult even for experienced surgeons, so an open approach is usually recommended.[179]

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, renal and scrotal abscesses, etc.

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.[181] Bacteriophages (viruses that attack only specific bacteria) have been used anecdotally but successfully on a very limited basis for highly resistant infections.[95][182][183] 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.[95][184]

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 the use of dual primary endpoints to determine the eradication of complicated UTIs: both 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 will increase 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 informed of the correct use of antibiotics regarding dosing and completing the full treatment schedule even if they feel better, incorporating reasonable prophylactic lifestyle measures, and avoiding inappropriate antimicrobial drug use.

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. Usually, a positive culture in an asymptomatic patient can 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.[185][186]

Multidrug-resistant infections are becoming a major source of in-hospital morbidity and mortality. Suppressive antibiotic regimens are sometimes used in poorly responding or resistant cases. 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 will increase the risk of resistance and change 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 with 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. 

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. Health care 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 should also encompass prevention efforts, such as catheter care and hygiene education.

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.[67][187][188] 

Effective communication and collaboration among health care 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 transitions of care between different 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 continually refine their approach to complicated UTIs, leading to better outcomes and patient safety.

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Ayan Sabih

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References

[1]

Girgenti V, Pelizzo G, Amoroso S, Rosone G, Di Mitri M, Milazzo M, Giordano S, Genuardi R, Calcaterra V. Emphysematous Pyelonephritis Following Ureterovesical Reimplantation for Congenital Obstructive Megaureter. Pediatric Case Report and Review of the Literature. Frontiers in pediatrics. 2019:7():2. doi: 10.3389/fped.2019.00002. Epub 2019 Jan 24     [PubMed PMID: 30733936]

Level 3 (low-level) evidence

[2]

Habak PJ, Griggs, Jr RP. Urinary Tract Infection in Pregnancy. StatPearls. 2023 Jan:():     [PubMed PMID: 30725732]

[3]

Shortridge D, Duncan LR, Pfaller MA, Flamm RK. Activity of ceftolozane-tazobactam and comparators when tested against Gram-negative isolates collected from paediatric patients in the USA and Europe between 2012 and 2016 as part of a global surveillance programme. International journal of antimicrobial agents. 2019 May:53(5):637-643. doi: 10.1016/j.ijantimicag.2019.01.015. Epub 2019 Feb 1     [PubMed PMID: 30716448]

[4]

Shi H, Kang CI, Cho SY, Huh K, Chung DR, Peck KR. Follow-up blood cultures add little value in the management of bacteremic urinary tract infections. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 2019 Apr:38(4):695-702. doi: 10.1007/s10096-019-03484-4. Epub 2019 Jan 28     [PubMed PMID: 30689071]

[5]

Gomila A, Carratalà J, Eliakim-Raz N, Shaw E, Wiegand I, Vallejo-Torres L, Gorostiza A, Vigo JM, Morris S, Stoddart M, Grier S, Vank C, Cuperus N, Van den Heuvel L, Vuong C, MacGowan A, Leibovici L, Addy I, Pujol M, COMBACTE MAGNET WP5 RESCUING Study Group and Study Sites. Risk factors and prognosis of complicated urinary tract infections caused by Pseudomonas aeruginosa in hospitalized patients: a retrospective multicenter cohort study. Infection and drug resistance. 2018:11():2571-2581. doi: 10.2147/IDR.S185753. Epub 2018 Dec 18     [PubMed PMID: 30588040]

Level 2 (mid-level) evidence

[6]

Esposito S, Rinaldi VE, Argentiero A, Farinelli E, Cofini M, D'Alonzo R, Mencacci A, Principi N. Approach to Neonates and Young Infants with Fever without a Source Who Are at Risk for Severe Bacterial Infection. Mediators of inflammation. 2018:2018():4869329. doi: 10.1155/2018/4869329. Epub 2018 Nov 26     [PubMed PMID: 30581369]

[7]

Cruz J, Figueiredo F, Matos AP, Duarte S, Guerra A, Ramalho M. Infectious and Inflammatory Diseases of the Urinary Tract: Role of MR Imaging. Magnetic resonance imaging clinics of North America. 2019 Feb:27(1):59-75. doi: 10.1016/j.mric.2018.09.001. Epub 2018 Oct 29     [PubMed PMID: 30466913]

[8]

Wagenlehner FME, Bjerklund Johansen TE, Cai T, Koves B, Kranz J, Pilatz A, Tandogdu Z. Epidemiology, definition and treatment of complicated urinary tract infections. Nature reviews. Urology. 2020 Oct:17(10):586-600. doi: 10.1038/s41585-020-0362-4. Epub 2020 Aug 25     [PubMed PMID: 32843751]

[9]

Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nature reviews. Microbiology. 2015 May:13(5):269-84. doi: 10.1038/nrmicro3432. Epub 2015 Apr 8     [PubMed PMID: 25853778]

[10]

Tandoğdu Z, Bartoletti R, Cai T, Çek M, Grabe M, Kulchavenya E, Köves B, Menon V, Naber K, Perepanova T, Tenke P, Wullt B, Johansen TE, Wagenlehner F. Antimicrobial resistance in urosepsis: outcomes from the multinational, multicenter global prevalence of infections in urology (GPIU) study 2003-2013. World journal of urology. 2016 Aug:34(8):1193-200. doi: 10.1007/s00345-015-1722-1. Epub 2015 Dec 11     [PubMed PMID: 26658886]

[11]

Zilberberg MD, Nathanson BH, Sulham K, Shorr AF. Descriptive Epidemiology and Outcomes of Hospitalizations With Complicated Urinary Tract Infections in the United States, 2018. Open forum infectious diseases. 2022 Jan:9(1):ofab591. doi: 10.1093/ofid/ofab591. Epub 2022 Jan 10     [PubMed PMID: 35036460]

[12]

Gould CV, Umscheid CA, Agarwal RK, Kuntz G, Pegues DA, Healthcare Infection Control Practices Advisory Committee. Guideline for prevention of catheter-associated urinary tract infections 2009. Infection control and hospital epidemiology. 2010 Apr:31(4):319-26. doi: 10.1086/651091. Epub     [PubMed PMID: 20156062]

[13]

Tandogdu Z, Cek M, Wagenlehner F, Naber K, Tenke P, van Ostrum E, Johansen TB. Resistance patterns of nosocomial urinary tract infections in urology departments: 8-year results of the global prevalence of infections in urology study. World journal of urology. 2014 Jun:32(3):791-801. doi: 10.1007/s00345-013-1154-8. Epub 2013 Aug 24     [PubMed PMID: 23979151]

[14]

Cek M, Tandoğdu Z, Wagenlehner F, Tenke P, Naber K, Bjerklund-Johansen TE. Healthcare-associated urinary tract infections in hospitalized urological patients--a global perspective: results from the GPIU studies 2003-2010. World journal of urology. 2014 Dec:32(6):1587-94. doi: 10.1007/s00345-013-1218-9. Epub 2014 Jan 23     [PubMed PMID: 24452449]

Level 3 (low-level) evidence

[15]

Donnan JR, Grandy CA, Chibrikov E, Marra CA, Aubrey-Bassler K, Johnston K, Swab M, Hache J, Curnew D, Nguyen H, Gamble JM. Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis. BMJ open. 2019 Feb 1:9(1):e022577. doi: 10.1136/bmjopen-2018-022577. Epub 2019 Feb 1     [PubMed PMID: 30813108]

Level 2 (mid-level) evidence

[16]

. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs. 2006 Feb:():     [PubMed PMID: 21413206]

[17]

Zilberberg MD, Nathanson BH, Sulham K, Shorr AF. Descriptive epidemiology and outcomes of emergency department visits with complicated urinary tract infections in the United States, 2016-2018. Journal of the American College of Emergency Physicians open. 2022 Apr:3(2):e12694. doi: 10.1002/emp2.12694. Epub 2022 Mar 17     [PubMed PMID: 35342898]

[18]

Tenke P, Köves B, Johansen TE. An update on prevention and treatment of catheter-associated urinary tract infections. Current opinion in infectious diseases. 2014 Feb:27(1):102-7. doi: 10.1097/QCO.0000000000000031. Epub     [PubMed PMID: 24345923]

Level 3 (low-level) evidence

[19]

Heyns CF. Urinary tract infection associated with conditions causing urinary tract obstruction and stasis, excluding urolithiasis and neuropathic bladder. World journal of urology. 2012 Feb:30(1):77-83. doi: 10.1007/s00345-011-0725-9. Epub 2011 Jul 1     [PubMed PMID: 21720861]

[20]

Steward DK, Wood GL, Cohen RL, Smith JW, Mackowiak PA. Failure of the urinalysis and quantitative urine culture in diagnosing symptomatic urinary tract infections in patients with long-term urinary catheters. American journal of infection control. 1985 Aug:13(4):154-60     [PubMed PMID: 3850728]

[21]

Tenke P, Kovacs B, Jäckel M, Nagy E. The role of biofilm infection in urology. World journal of urology. 2006 Feb:24(1):13-20     [PubMed PMID: 16402262]

[22]

Raz R, Schiller D, Nicolle LE. Chronic indwelling catheter replacement before antimicrobial therapy for symptomatic urinary tract infection. The Journal of urology. 2000 Oct:164(4):1254-8     [PubMed PMID: 10992375]

[23]

Tenke P, Köves B, Nagy K, Hultgren SJ, Mendling W, Wullt B, Grabe M, Wagenlehner FM, Cek M, Pickard R, Botto H, Naber KG, Bjerklund Johansen TE. Update on biofilm infections in the urinary tract. World journal of urology. 2012 Feb:30(1):51-7. doi: 10.1007/s00345-011-0689-9. Epub 2011 May 18     [PubMed PMID: 21590469]

[24]

Brown MR, Allison DG, Gilbert P. Resistance of bacterial biofilms to antibiotics: a growth-rate related effect? The Journal of antimicrobial chemotherapy. 1988 Dec:22(6):777-80     [PubMed PMID: 3072331]

[25]

Al Midani A, Elands S, Collier S, Harber M, Shendi AM. Impact of Urinary Tract Infections in Kidney Transplant Recipients: A 4-Year Single-Center Experience. Transplantation proceedings. 2018 Dec:50(10):3351-3355. doi: 10.1016/j.transproceed.2018.08.022. Epub 2018 Sep 7     [PubMed PMID: 30577206]

[26]

Belyayeva M, Jeong JM. Acute Pyelonephritis. StatPearls. 2023 Jan:():     [PubMed PMID: 30137822]

[27]

Bono MJ, Leslie SW, Reygaert WC. Uncomplicated Urinary Tract Infections. StatPearls. 2024 Jan:():     [PubMed PMID: 29261874]

[28]

Nicolle LE. Urinary catheter-associated infections. Infectious disease clinics of North America. 2012 Mar:26(1):13-27. doi: 10.1016/j.idc.2011.09.009. Epub     [PubMed PMID: 22284373]

[29]

Limpawattana P, Phungoen P, Mitsungnern T, Laosuangkoon W, Tansangworn N. Atypical presentations of older adults at the emergency department and associated factors. Archives of gerontology and geriatrics. 2016 Jan-Feb:62():97-102. doi: 10.1016/j.archger.2015.08.016. Epub 2015 Aug 21     [PubMed PMID: 26323650]

[30]

MacRae V, Holland S, MacLeod R. Diagnosing, managing and preventing urinary tract infections in older people with dementia in hospital. Nursing older people. 2022 May 31:34(3):28-33. doi: 10.7748/nop.2022.e1392. Epub 2022 Apr 20     [PubMed PMID: 35441502]

[31]

El-Ghar MA, Farg H, Sharaf DE, El-Diasty T. CT and MRI in Urinary Tract Infections: A Spectrum of Different Imaging Findings. Medicina (Kaunas, Lithuania). 2021 Jan 1:57(1):. doi: 10.3390/medicina57010032. Epub 2021 Jan 1     [PubMed PMID: 33401464]

[32]

Tamburrini S, Lugarà M, Iannuzzi M, Cesaro E, De Simone F, Del Biondo D, Toto R, Iulia D, Marrone V, Faella P, Liguori C, Marano I. Pyonephrosis Ultrasound and Computed Tomography Features: A Pictorial Review. Diagnostics (Basel, Switzerland). 2021 Feb 17:11(2):. doi: 10.3390/diagnostics11020331. Epub 2021 Feb 17     [PubMed PMID: 33671431]

[33]

. NICE Guidance - Complicated urinary tract infections: ceftolozane/tazobactam: © NICE (2016) Complicated urinary tract infections: ceftolozane/tazobactam. BJU international. 2018 Jun:121(6):825-834. doi: 10.1111/bju.14364. Epub     [PubMed PMID: 29878700]

[34]

Lemoine L, Dupont C, Capron A, Cerf E, Yilmaz M, Verloop D, Blanckaert K, Senneville E, Alfandari S. Prospective evaluation of the management of urinary tract infections in 134 French nursing homes. Medecine et maladies infectieuses. 2018 Aug:48(5):359-364. doi: 10.1016/j.medmal.2018.04.387. Epub 2018 May 7     [PubMed PMID: 29747905]

[35]

Expert Panel on Pediatric Imaging:, Karmazyn BK, Alazraki AL, Anupindi SA, Dempsey ME, Dillman JR, Dorfman SR, Garber MD, Moore SG, Peters CA, Rice HE, Rigsby CK, Safdar NM, Simoneaux SF, Trout AT, Westra SJ, Wootton-Gorges SL, Coley BD. ACR Appropriateness Criteria(®) Urinary Tract Infection-Child. Journal of the American College of Radiology : JACR. 2017 May:14(5S):S362-S371. doi: 10.1016/j.jacr.2017.02.028. Epub     [PubMed PMID: 28473093]

[36]

Yasuda M. [Urogenital infections]. Nihon rinsho. Japanese journal of clinical medicine. 2017 Apr:75(4):558-566     [PubMed PMID: 30549857]

[37]

Bima P, Orlotti C, Smart OG, Morello F, Trunfio M, Brazzi L, Montrucchio G. Norepinephrine may improve survival of septic shock patients in a low-resource setting: a proof-of-concept study on feasibility and efficacy outside the Intensive Care Unit. Pathogens and global health. 2022 Sep:116(6):389-394. doi: 10.1080/20477724.2022.2038051. Epub 2022 Feb 9     [PubMed PMID: 35138990]

Level 2 (mid-level) evidence

[38]

Xu F, Zhong R, Shi S, Zeng Y, Tang Z. Early initiation of norepinephrine in patients with septic shock: A propensity score-based analysis. The American journal of emergency medicine. 2022 Apr:54():287-296. doi: 10.1016/j.ajem.2022.01.063. Epub 2022 Feb 3     [PubMed PMID: 35227959]

[39]

Shahrami B, Sharif M, Sefidani Forough A, Najmeddin F, Arabzadeh AA, Mojtahedzadeh M. Antibiotic therapy in sepsis: No next time for a second chance! Journal of clinical pharmacy and therapeutics. 2021 Aug:46(4):872-876. doi: 10.1111/jcpt.13403. Epub 2021 Mar 12     [PubMed PMID: 33710622]

[40]

Golan R, Cooper KL, Shah O. Management of Small, Non-obstructing Renal Stones in Adults With Recurrent Urinary Tract Infections. Reviews in urology. 2020:22(2):52-56     [PubMed PMID: 32760228]

[41]

Ward G, Jorden RC, Severance HW. Treatment of pyelonephritis in an observation unit. Annals of emergency medicine. 1991 Mar:20(3):258-61     [PubMed PMID: 1996820]

[42]

Choi JB, Min SK. Complicated urinary tract infection in patients with benign prostatic hyperplasia. Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy. 2021 Sep:27(9):1284-1287. doi: 10.1016/j.jiac.2021.06.006. Epub 2021 Jun 16     [PubMed PMID: 34144904]

[43]

Ten Doesschate T, Hendriks K, van Werkhoven CH, van der Hout EC, Platteel TN, Groenewegen IAM, Muller AE, Hoepelman AIM, Bonten MJM, Geerlings SE. Nitrofurantoin 100 mg versus 50 mg prophylaxis for urinary tract infections, a cohort study. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2022 Feb:28(2):248-254. doi: 10.1016/j.cmi.2021.05.048. Epub 2021 Jun 8     [PubMed PMID: 34111584]

[44]

Muller AE, Verhaegh EM, Harbarth S, Mouton JW, Huttner A. Nitrofurantoin's efficacy and safety as prophylaxis for urinary tract infections: a systematic review of the literature and meta-analysis of controlled trials. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2017 Jun:23(6):355-362. doi: 10.1016/j.cmi.2016.08.003. Epub 2016 Aug 17     [PubMed PMID: 27542332]

Level 1 (high-level) evidence

[45]

Yates A. The risks and benefits of suprapubic catheters. Nursing times. 2016 Feb 10-23:112(6-7):19-22     [PubMed PMID: 27017651]

[46]

Lo TS, Hammer KD, Zegarra M, Cho WC. Methenamine: a forgotten drug for preventing recurrent urinary tract infection in a multidrug resistance era. Expert review of anti-infective therapy. 2014 May:12(5):549-54. doi: 10.1586/14787210.2014.904202. Epub 2014 Apr 1     [PubMed PMID: 24689705]

[47]

Kevorkian CG, Merritt JL, Ilstrup DM. Methenamine mandelate with acidification: an effective urinary antiseptic in patients with neurogenic bladder. Mayo Clinic proceedings. 1984 Aug:59(8):523-9     [PubMed PMID: 6379319]

[48]

Kranz J, Lackner J, Künzel U, Wagenlehner F, Schmidt S. Original Article Phytotherapy in Adults With Recurrent Uncomplicated Cystitis. Deutsches Arzteblatt international. 2022 May 20:119(20):353-360. doi: 10.3238/arztebl.m2022.0104. Epub     [PubMed PMID: 35101170]

Level 1 (high-level) evidence

[49]

Jeitler M, Michalsen A, Schwiertz A, Kessler CS, Koppold-Liebscher D, Grasme J, Kandil FI, Steckhan N. Effects of a Supplement Containing a Cranberry Extract on Recurrent Urinary Tract Infections and Intestinal Microbiota: A Prospective, Uncontrolled Exploratory Study. Journal of integrative and complementary medicine. 2022 May:28(5):399-406. doi: 10.1089/jicm.2021.0300. Epub 2022 Mar 14     [PubMed PMID: 35285701]

[50]

Freire Gde C. Cranberries for preventing urinary tract infections. Sao Paulo medical journal = Revista paulista de medicina. 2013:131(5):363. doi: 10.1590/1516-3180.20131315T1. Epub     [PubMed PMID: 24310806]

[51]

Schwenger EM, Tejani AM, Loewen PS. Probiotics for preventing urinary tract infections in adults and children. The Cochrane database of systematic reviews. 2015 Dec 23:2015(12):CD008772. doi: 10.1002/14651858.CD008772.pub2. Epub 2015 Dec 23     [PubMed PMID: 26695595]

Level 1 (high-level) evidence

[52]

Song F, Liu C, Zhang J, Lei Y, Hu Z. Antibacterial effect of fosfomycin tromethamine on the bacteria inside urinary infection stones. International urology and nephrology. 2020 Apr:52(4):645-654. doi: 10.1007/s11255-019-02358-0. Epub 2019 Dec 12     [PubMed PMID: 31832876]

[53]

De Lorenzis E, Alba AB, Cepeda M, Galan JA, Geavlete P, Giannakopoulos S, Saltirov I, Sarica K, Skolarikos A, Stavridis S, Yuruk E, Geavlete B, García-Carbajosa, Hristoforov S, Karagoz MA, Nassos N, Jurado GO, Paslanmaz F, Poza M, Saidi S, Tzelves L, Trinchieri A. Bacterial spectrum and antibiotic resistance of urinary tract infections in patients treated for upper urinary tract calculi: a multicenter analysis. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 2020 Oct:39(10):1971-1981. doi: 10.1007/s10096-020-03947-z. Epub 2020 Jun 16     [PubMed PMID: 32557326]

[54]

Kaye KS, Rice LB, Dane AL, Stus V, Sagan O, Fedosiuk E, Das AF, Skarinsky D, Eckburg PB, Ellis-Grosse EJ. Fosfomycin for Injection (ZTI-01) Versus Piperacillin-tazobactam for the Treatment of Complicated Urinary Tract Infection Including Acute Pyelonephritis: ZEUS, A Phase 2/3 Randomized Trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2019 Nov 27:69(12):2045-2056. doi: 10.1093/cid/ciz181. Epub     [PubMed PMID: 30861061]

Level 1 (high-level) evidence

[55]

Derington CG, Benavides N, Delate T, Fish DN. Multiple-Dose Oral Fosfomycin for Treatment of Complicated Urinary Tract Infections in the Outpatient Setting. Open forum infectious diseases. 2020 Feb:7(2):ofaa034. doi: 10.1093/ofid/ofaa034. Epub 2020 Jan 29     [PubMed PMID: 32123690]

[56]

Ziadeh T, Chebel R, Labaki C, Saliba G, Helou EE. Bladder instillation for urinary tract infection prevention in neurogenic bladder patients practicing clean intermittent catheterization: A systematic review. Urologia. 2022 May:89(2):261-267. doi: 10.1177/03915603211049883. Epub 2021 Oct 6     [PubMed PMID: 34612750]

Level 1 (high-level) evidence

[57]

Abrams P, Hashim H, Tomson C, Macgowan A, Skews R, Warren K. The use of intravesical gentamicin to treat recurrent urinary tract infections in lower urinary tract dysfunction. Neurourology and urodynamics. 2017 Nov:36(8):2109-2116. doi: 10.1002/nau.23250. Epub 2017 May 15     [PubMed PMID: 28503891]

[58]

Moussa M, Chakra MA, Papatsoris AG, Dellis A, Dabboucy B, Fares Y. Bladder irrigation with povidone-iodine prevent recurrent urinary tract infections in neurogenic bladder patients on clean intermittent catheterization. Neurourology and urodynamics. 2021 Feb:40(2):672-679. doi: 10.1002/nau.24607. Epub 2021 Jan 21     [PubMed PMID: 33476092]

[59]

Miles BJ, Skoog S. Treatment of malakoplakia of bladder with intravesical neosporin irrigation. Urology. 1986 Jan:27(1):32-3     [PubMed PMID: 3001994]

[60]

Chernyak S, Salamon C. Intravesical Antibiotic Administration in the Treatment of Recurrent Urinary Tract Infections: Promising Results From a Case Series. Female pelvic medicine & reconstructive surgery. 2020 Feb:26(2):152-154. doi: 10.1097/SPV.0000000000000810. Epub     [PubMed PMID: 31990805]

Level 2 (mid-level) evidence

[61]

Chou A, Welch E, Hunter A, Trautner BW. Antimicrobial Treatment Options for Difficult-to-Treat Resistant Gram-Negative Bacteria Causing Cystitis, Pyelonephritis, and Prostatitis: A Narrative Review. Drugs. 2022 Mar:82(4):407-438. doi: 10.1007/s40265-022-01676-5. Epub 2022 Mar 14     [PubMed PMID: 35286622]

Level 3 (low-level) evidence

[62]

Tilahun M, Kassa Y, Gedefie A, Ashagire M. Emerging Carbapenem-Resistant Enterobacteriaceae Infection, Its Epidemiology and Novel Treatment Options: A Review. Infection and drug resistance. 2021:14():4363-4374. doi: 10.2147/IDR.S337611. Epub 2021 Oct 21     [PubMed PMID: 34707380]

[63]

Di Pietrantonio M, Brescini L, Candi J, Gianluca M, Pallotta F, Mazzanti S, Mantini P, Candelaresi B, Olivieri S, Ginevri F, Cesaretti G, Castelletti S, Cocci E, Polo RG, Cerutti E, Simonetti O, Cirioni O, Tavio M, Giacometti A, Barchiesi F. Ceftazidime-Avibactam for the Treatment of Multidrug-Resistant Pathogens: A Retrospective, Single Center Study. Antibiotics (Basel, Switzerland). 2022 Feb 28:11(3):. doi: 10.3390/antibiotics11030321. Epub 2022 Feb 28     [PubMed PMID: 35326784]

Level 2 (mid-level) evidence

[64]

Carmeli Y, Armstrong J, Laud PJ, Newell P, Stone G, Wardman A, Gasink LB. Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): a randomised, pathogen-directed, phase 3 study. The Lancet. Infectious diseases. 2016 Jun:16(6):661-673. doi: 10.1016/S1473-3099(16)30004-4. Epub 2016 Apr 20     [PubMed PMID: 27107460]

Level 1 (high-level) evidence

[65]

Wang C, Yang D, Wang Y, Ni W. Cefiderocol for the Treatment of Multidrug-Resistant Gram-Negative Bacteria: A Systematic Review of Currently Available Evidence. Frontiers in pharmacology. 2022:13():896971. doi: 10.3389/fphar.2022.896971. Epub 2022 Apr 12     [PubMed PMID: 35496290]

Level 1 (high-level) evidence

[66]

Wang H, Palasik BN. Combating antimicrobial resistance with cefiderocol for complicated infections involving the urinary tract. Therapeutic advances in urology. 2022 Jan-Dec:14():17562872211065570. doi: 10.1177/17562872211065570. Epub 2022 Jan 31     [PubMed PMID: 35126672]

Level 3 (low-level) evidence

[67]

Kaye KS, Bhowmick T, Metallidis S, Bleasdale SC, Sagan OS, Stus V, Vazquez J, Zaitsev V, Bidair M, Chorvat E, Dragoescu PO, Fedosiuk E, Horcajada JP, Murta C, Sarychev Y, Stoev V, Morgan E, Fusaro K, Griffith D, Lomovskaya O, Alexander EL, Loutit J, Dudley MN, Giamarellos-Bourboulis EJ. Effect of Meropenem-Vaborbactam vs Piperacillin-Tazobactam on Clinical Cure or Improvement and Microbial Eradication in Complicated Urinary Tract Infection: The TANGO I Randomized Clinical Trial. JAMA. 2018 Feb 27:319(8):788-799. doi: 10.1001/jama.2018.0438. Epub     [PubMed PMID: 29486041]

Level 1 (high-level) evidence

[68]

Mouktaroudi M, Kotsaki A, Giamarellos-Bourboulis EJ. Meropenem-vaborbactam: a critical positioning for the management of infections by Carbapenem-resistant Enterobacteriaceae. Expert review of anti-infective therapy. 2022 Jun:20(6):809-818. doi: 10.1080/14787210.2022.2030219. Epub 2022 Jan 26     [PubMed PMID: 35034551]

[69]

Clark JA, Burgess DS. Plazomicin: a new aminoglycoside in the fight against antimicrobial resistance. Therapeutic advances in infectious disease. 2020 Jan-Dec:7():2049936120952604. doi: 10.1177/2049936120952604. Epub 2020 Sep 4     [PubMed PMID: 32953108]

Level 3 (low-level) evidence

[70]

Bassetti M, Giacobbe DR, Castaldo N, Russo A, Vena A. Role of new antibiotics in extended-spectrum β-lactamase-, AmpC- infections. Current opinion in infectious diseases. 2021 Dec 1:34(6):748-755. doi: 10.1097/QCO.0000000000000789. Epub     [PubMed PMID: 34581282]

Level 3 (low-level) evidence

[71]

Wagenlehner FME, Cloutier DJ, Komirenko AS, Cebrik DS, Krause KM, Keepers TR, Connolly LE, Miller LG, Friedland I, Dwyer JP, EPIC Study Group. Once-Daily Plazomicin for Complicated Urinary Tract Infections. The New England journal of medicine. 2019 Feb 21:380(8):729-740. doi: 10.1056/NEJMoa1801467. Epub     [PubMed PMID: 30786187]

[72]

Eckburg PB, Muir L, Critchley IA, Walpole S, Kwak H, Phelan AM, Moore G, Jain A, Keutzer T, Dane A, Melnick D, Talley AK. Oral Tebipenem Pivoxil Hydrobromide in Complicated Urinary Tract Infection. The New England journal of medicine. 2022 Apr 7:386(14):1327-1338. doi: 10.1056/NEJMoa2105462. Epub     [PubMed PMID: 35388666]

[73]

Parida S, Mishra SK. Urinary tract infections in the critical care unit: A brief review. Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine. 2013 Nov:17(6):370-4. doi: 10.4103/0972-5229.123451. Epub     [PubMed PMID: 24501490]

[74]

Hooton TM, Bradley SF, Cardenas DD, Colgan R, Geerlings SE, Rice JC, Saint S, Schaeffer AJ, Tambayh PA, Tenke P, Nicolle LE, Infectious Diseases Society of America. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2010 Mar 1:50(5):625-63     [PubMed PMID: 20175247]

Level 1 (high-level) evidence

[75]

Podkovik S, Toor H, Gattupalli M, Kashyap S, Brazdzionis J, Patchana T, Bonda S, Wong S, Kang C, Mo K, Wacker MR, Miulli DE, Wang S. Prevalence of Catheter-Associated Urinary Tract Infections in Neurosurgical Intensive Care Patients - The Overdiagnosis of Urinary Tract Infections. Cureus. 2019 Aug 26:11(8):e5494. doi: 10.7759/cureus.5494. Epub 2019 Aug 26     [PubMed PMID: 31667030]

[76]

Neelakanta A, Sharma S, Kesani VP, Salim M, Pervaiz A, Aftab N, Mann T, Tashtoush N, Karino S, Dhar S, Kaye KS. Impact of changes in the NHSN catheter-associated urinary tract infection (CAUTI) surveillance criteria on the frequency and epidemiology of CAUTI in intensive care units (ICUs). Infection control and hospital epidemiology. 2015 Mar:36(3):346-9. doi: 10.1017/ice.2014.67. Epub     [PubMed PMID: 25695177]

[77]

Bardossy AC, Jayaprakash R, Alangaden AC, Starr P, Abreu-Lanfranco O, Reyes K, Zervos MJ, Alangaden GJ. Impact and Limitations of the 2015 National Health and Safety Network Case Definition on Catheter-Associated Urinary Tract Infection Rates. Infection control and hospital epidemiology. 2017 Feb:38(2):239-241. doi: 10.1017/ice.2016.278. Epub 2016 Nov 24     [PubMed PMID: 27881213]

Level 3 (low-level) evidence

[78]

Lachance CC, Grobelna A. Management of Patients with Long-Term Indwelling Urinary Catheters: A Review of Guidelines. 2019 May 14:():     [PubMed PMID: 31449368]

[79]

Warren JW. Catheter-associated urinary tract infections. International journal of antimicrobial agents. 2001 Apr:17(4):299-303     [PubMed PMID: 11295412]

[80]

Van Decker SG, Bosch N, Murphy J. Catheter-associated urinary tract infection reduction in critical care units: a bundled care model. BMJ open quality. 2021 Dec:10(4):. doi: 10.1136/bmjoq-2021-001534. Epub     [PubMed PMID: 34949580]

Level 2 (mid-level) evidence

[81]

Klevens RM, Edwards JR, Richards CL Jr, Horan TC, Gaynes RP, Pollock DA, Cardo DM. Estimating health care-associated infections and deaths in U.S. hospitals, 2002. Public health reports (Washington, D.C. : 1974). 2007 Mar-Apr:122(2):160-6     [PubMed PMID: 17357358]

[82]

Shah PS, Cannon JP, Sullivan CL, Nemchausky B, Pachucki CT. Controlling antimicrobial use and decreasing microbiological laboratory tests for urinary tract infections in spinal-cord-injury patients with chronic indwelling catheters. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2005 Jan 1:62(1):74-7     [PubMed PMID: 15658076]

[83]

Warren JW. Catheter-associated urinary tract infections. Infectious disease clinics of North America. 1997 Sep:11(3):609-22     [PubMed PMID: 9378926]

[84]

Tambyah PA, Halvorson KT, Maki DG. A prospective study of pathogenesis of catheter-associated urinary tract infections. Mayo Clinic proceedings. 1999 Feb:74(2):131-6     [PubMed PMID: 10069349]

[85]

Weiner LM, Webb AK, Limbago B, Dudeck MA, Patel J, Kallen AJ, Edwards JR, Sievert DM. Antimicrobial-Resistant Pathogens Associated With Healthcare-Associated Infections: Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011-2014. Infection control and hospital epidemiology. 2016 Nov:37(11):1288-1301     [PubMed PMID: 27573805]

[86]

Washington EA. Instillation of 3% hydrogen peroxide or distilled vinegar in urethral catheter drainage bag to decrease catheter-associated bacteriuria. Biological research for nursing. 2001 Oct:3(2):78-87     [PubMed PMID: 11931525]

[87]

Nash MA. Best practice for patient self-cleaning of urinary drainage bags. Urologic nursing. 2003 Oct:23(5):334, 339     [PubMed PMID: 14621355]

[88]

Dailly S. Prevention of indwelling catheter-associated urinary tract infections. Nursing older people. 2011 Mar:23(2):14-9     [PubMed PMID: 21413662]

[89]

Chen YY, Chen CS, Chen IH, Lin CC. Comparison of the Incidence of Urinary Tract Infection by Replacement Time of the Urinary Drainage System. The journal of nursing research : JNR. 2021 May 28:29(4):e157. doi: 10.1097/JNR.0000000000000437. Epub 2021 May 28     [PubMed PMID: 34049325]

[90]

Moola S, Konno R. A systematic review of the management of short-term indwelling urethral catheters to prevent urinary tract infections. JBI library of systematic reviews. 2010:8(17):695-729     [PubMed PMID: 27820507]

Level 1 (high-level) evidence

[91]

Vallejo-Manzur F, Mireles-Cabodevila E, Varon J. Purple urine bag syndrome. The American journal of emergency medicine. 2005 Jul:23(4):521-4     [PubMed PMID: 16032624]

[92]

Benavides HA, Vargas Rodríguez LJ, Rozo Ortiz EJ. Purple urine bag syndrome. Medicina intensiva. 2022 Feb:46(2):119. doi: 10.1016/j.medine.2021.11.012. Epub 2021 Dec 2     [PubMed PMID: 34863669]

[93]

Shaeriya F, Al Remawy R, Makhdoom A, Alghamdi A, M Shaheen FA. Purple urine bag syndrome. Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia. 2021 Mar-Apr:32(2):530-531. doi: 10.4103/1319-2442.335466. Epub     [PubMed PMID: 35017348]

[94]

Nicolle LE, Gupta K, Bradley SF, Colgan R, DeMuri GP, Drekonja D, Eckert LO, Geerlings SE, Köves B, Hooton TM, Juthani-Mehta M, Knight SL, Saint S, Schaeffer AJ, Trautner B, Wullt B, Siemieniuk R. Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2019 May 2:68(10):e83-e110. doi: 10.1093/cid/ciy1121. Epub     [PubMed PMID: 30895288]

Level 1 (high-level) evidence

[95]

Skelton-Dudley F, Doan J, Suda K, Holmes SA, Evans C, Trautner B. Spinal Cord Injury Creates Unique Challenges in Diagnosis and Management of Catheter-Associated Urinary Tract Infection. Topics in spinal cord injury rehabilitation. 2019 Fall:25(4):331-339. doi: 10.1310/sci2504-331. Epub     [PubMed PMID: 31844385]

[96]

Skelton F, Grigoryan L, Holmes SA, Poon IO, Trautner B. Routine Urine Testing at the Spinal Cord Injury Annual Evaluation Leads to Unnecessary Antibiotic Use: A Pilot Study and Future Directions. Archives of physical medicine and rehabilitation. 2018 Feb:99(2):219-225. doi: 10.1016/j.apmr.2017.10.005. Epub 2017 Oct 26     [PubMed PMID: 29107038]

Level 3 (low-level) evidence

[97]

Consortium for Spinal Cord Medicine. Bladder management for adults with spinal cord injury: a clinical practice guideline for health-care providers. The journal of spinal cord medicine. 2006:29(5):527-73     [PubMed PMID: 17274492]

Level 1 (high-level) evidence

[98]

Duffy LM, Cleary J, Ahern S, Kuskowski MA, West M, Wheeler L, Mortimer JA. Clean intermittent catheterization: safe, cost-effective bladder management for male residents of VA nursing homes. Journal of the American Geriatrics Society. 1995 Aug:43(8):865-70     [PubMed PMID: 7636093]

[99]

Chew AB, Suda KJ, Patel UC, Fitzpatrick MA, Ramanathan S, Burns SP, Evans CT. Long-term prescribing of nitrofurantoin for urinary tract infections (UTI) in veterans with spinal cord injury (SCI). The journal of spinal cord medicine. 2019 Jul:42(4):485-493. doi: 10.1080/10790268.2018.1488096. Epub 2018 Jul 9     [PubMed PMID: 29985783]

[100]

Phé V, Pakzad M, Haslam C, Gonzales G, Curtis C, Porter B, Chataway J, Panicker JN. Open label feasibility study evaluating D-mannose combined with home-based monitoring of suspected urinary tract infections in patients with multiple sclerosis. Neurourology and urodynamics. 2017 Sep:36(7):1770-1775. doi: 10.1002/nau.23173. Epub 2016 Nov 4     [PubMed PMID: 27813195]

Level 2 (mid-level) evidence

[101]

Bonfill X, Rigau D, Esteban-Fuertes M, Barrera-Chacón JM, Jáuregui-Abrisqueta ML, Salvador S, Alemán-Sánchez CM, Borau A, Bea-Muñoz M, Hidalgo B, Andrade MJ, Espinosa JR, Martínez-Zapata MJ, ESCALE Study Group. Efficacy and safety of urinary catheters with silver alloy coating in patients with spinal cord injury: a multicentric pragmatic randomized controlled trial. The ESCALE trial. The spine journal : official journal of the North American Spine Society. 2017 Nov:17(11):1650-1657. doi: 10.1016/j.spinee.2017.05.025. Epub 2017 May 31     [PubMed PMID: 28578163]

Level 1 (high-level) evidence

[102]

Cardenas DD, Moore KN, Dannels-McClure A, Scelza WM, Graves DE, Brooks M, Busch AK. Intermittent catheterization with a hydrophilic-coated catheter delays urinary tract infections in acute spinal cord injury: a prospective, randomized, multicenter trial. PM & R : the journal of injury, function, and rehabilitation. 2011 May:3(5):408-17. doi: 10.1016/j.pmrj.2011.01.001. Epub     [PubMed PMID: 21570027]

Level 1 (high-level) evidence

[103]

Hess MJ, Hess PE, Sullivan MR, Nee M, Yalla SV. Evaluation of cranberry tablets for the prevention of urinary tract infections in spinal cord injured patients with neurogenic bladder. Spinal cord. 2008 Sep:46(9):622-6. doi: 10.1038/sc.2008.25. Epub 2008 Apr 8     [PubMed PMID: 18392039]

[104]

Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. The Cochrane database of systematic reviews. 2012 Oct 17:10(10):CD001321. doi: 10.1002/14651858.CD001321.pub5. Epub 2012 Oct 17     [PubMed PMID: 23076891]

Level 1 (high-level) evidence

[105]

Trautner BW, Bhimani RD, Amspoker AB, Hysong SJ, Garza A, Kelly PA, Payne VL, Naik AD. Development and validation of an algorithm to recalibrate mental models and reduce diagnostic errors associated with catheter-associated bacteriuria. BMC medical informatics and decision making. 2013 Apr 15:13():48. doi: 10.1186/1472-6947-13-48. Epub 2013 Apr 15     [PubMed PMID: 23587259]

Level 1 (high-level) evidence

[106]

Trautner BW, Grigoryan L, Petersen NJ, Hysong S, Cadena J, Patterson JE, Naik AD. Effectiveness of an Antimicrobial Stewardship Approach for Urinary Catheter-Associated Asymptomatic Bacteriuria. JAMA internal medicine. 2015 Jul:175(7):1120-7. doi: 10.1001/jamainternmed.2015.1878. Epub     [PubMed PMID: 26010222]

[107]

Schnarr J, Smaill F. Asymptomatic bacteriuria and symptomatic urinary tract infections in pregnancy. European journal of clinical investigation. 2008 Oct:38 Suppl 2():50-7. doi: 10.1111/j.1365-2362.2008.02009.x. Epub     [PubMed PMID: 18826482]

[108]

Moore A, Doull M, Grad R, Groulx S, Pottie K, Tonelli M, Courage S, Garcia AJ, Thombs BD, Canadian Task Force on Preventive Health Care. Recommendations on screening for asymptomatic bacteriuria in pregnancy. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2018 Jul 9:190(27):E823-E830. doi: 10.1503/cmaj.171325. Epub     [PubMed PMID: 29986858]

[109]

Romero R, Oyarzun E, Mazor M, Sirtori M, Hobbins JC, Bracken M. Meta-analysis of the relationship between asymptomatic bacteriuria and preterm delivery/low birth weight. Obstetrics and gynecology. 1989 Apr:73(4):576-82     [PubMed PMID: 2927852]

Level 1 (high-level) evidence

[110]

Minassian C, Thomas SL, Williams DJ, Campbell O, Smeeth L. Acute maternal infection and risk of pre-eclampsia: a population-based case-control study. PloS one. 2013:8(9):e73047. doi: 10.1371/journal.pone.0073047. Epub 2013 Sep 3     [PubMed PMID: 24019891]

Level 2 (mid-level) evidence

[111]

Wing DA, Fassett MJ, Getahun D. Acute pyelonephritis in pregnancy: an 18-year retrospective analysis. American journal of obstetrics and gynecology. 2014 Mar:210(3):219.e1-6. doi: 10.1016/j.ajog.2013.10.006. Epub 2013 Oct 5     [PubMed PMID: 24100227]

Level 2 (mid-level) evidence

[112]

Reeves DS. Treatment of bacteriuria in pregnancy with single dose fosfomycin trometamol: a review. Infection. 1992:20 Suppl 4():S313-6     [PubMed PMID: 1294525]

[113]

Vercaigne LM, Zhanel GG. Recommended treatment for urinary tract infection in pregnancy. The Annals of pharmacotherapy. 1994 Feb:28(2):248-51     [PubMed PMID: 8173146]

[114]

Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM, Infectious Diseases Society of America, American Society of Nephrology, American Geriatric Society. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2005 Mar 1:40(5):643-54     [PubMed PMID: 15714408]

[115]

Jolley JA, Wing DA. Pyelonephritis in pregnancy: an update on treatment options for optimal outcomes. Drugs. 2010 Sep 10:70(13):1643-55. doi: 10.2165/11538050-000000000-00000. Epub     [PubMed PMID: 20731473]

[116]

Bidell MR, Lodise TP. Suboptimal Clinical Response Rates with Newer Antibiotics Among Patients with Moderate Renal Impairment: Review of the Literature and Potential Pharmacokinetic and Pharmacodynamic Considerations for Observed Findings. Pharmacotherapy. 2018 Dec:38(12):1205-1215. doi: 10.1002/phar.2184. Epub 2018 Nov 9     [PubMed PMID: 30289995]

[117]

Neal DE Jr. Host defense mechanisms in urinary tract infections. The Urologic clinics of North America. 1999 Nov:26(4):677-86, vii     [PubMed PMID: 10584610]

[118]

Khan IH, Catto GR. Long-term complications of dialysis: infection. Kidney international. Supplement. 1993 Jun:41():S143-8     [PubMed PMID: 8320909]

[119]

Saitoh H, Nakamura K, Hida M, Satoh T. Urinary tract infection in oliguric patients with chronic renal failure. The Journal of urology. 1985 Jun:133(6):990-3     [PubMed PMID: 3999225]

[120]

Geerlings SE, Meiland R, Hoepelman AI. Pathogenesis of bacteriuria in women with diabetes mellitus. International journal of antimicrobial agents. 2002 Jun:19(6):539-45     [PubMed PMID: 12135845]

[121]

Fasolo LR, Rocha LM, Campbell S, Peixoto AJ. Diagnostic relevance of pyuria in dialysis patients. Kidney international. 2006 Dec:70(11):2035-8     [PubMed PMID: 16883321]

[122]

D'Agata EM, Mount DB, Thayer V, Schaffner W. Hospital-acquired infections among chronic hemodialysis patients. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2000 Jun:35(6):1083-8     [PubMed PMID: 10845821]

[123]

Aloy B, Launay-Vacher V, Bleibtreu A, Bortolotti P, Faure E, Filali A, Gauzit R, Gilbert M, Lesprit P, Mahieu R, Meyssonnier V, Ogielska M, Romaru J, Salmon D, Alfandari S, Lemaignen A. Antibiotics and chronic kidney disease: Dose adjustment update for infectious disease clinical practice. Medecine et maladies infectieuses. 2020 Jun:50(4):323-331. doi: 10.1016/j.medmal.2019.06.010. Epub 2019 Jul 17     [PubMed PMID: 31326299]

[124]

Gilbert DN. Urinary tract infections in patients with chronic renal insufficiency. Clinical journal of the American Society of Nephrology : CJASN. 2006 Mar:1(2):327-31     [PubMed PMID: 17699224]

[125]

Scherberich JE, Fünfstück R, Naber KG. Urinary tract infections in patients with renal insufficiency and dialysis - epidemiology, pathogenesis, clinical symptoms, diagnosis and treatment. GMS infectious diseases. 2021:9():Doc07. doi: 10.3205/id000076. Epub 2021 Dec 21     [PubMed PMID: 35106269]

[126]

El Nekidy WS, Elrefaei H, St John TJL, Attallah NM, Kablaoui F, Nusair A, Piechowski-Jozwiak B, Phillips J, Ghazi IM. Ertapenem Neurotoxicity in Hemodialysis Patients-Safe and Effective Dosing Is Still Needed: A Retrospective Study and Literature Review. The Annals of pharmacotherapy. 2021 Jan:55(1):52-58. doi: 10.1177/1060028020938059. Epub 2020 Jul 3     [PubMed PMID: 32618479]

Level 2 (mid-level) evidence

[127]

Yamashita K, Ishiyama Y, Yoshino M, Tachibana H, Toki D, Konda R, Kondo T. Urinary Tract Infection in Hemodialysis-Dependent End-Stage Renal Disease Patients. Research and reports in urology. 2022:14():7-15. doi: 10.2147/RRU.S346020. Epub 2022 Jan 16     [PubMed PMID: 35079597]

[128]

Behzadi P, Urbán E, Matuz M, Benkő R, Gajdács M. The Role of Gram-Negative Bacteria in Urinary Tract Infections: Current Concepts and Therapeutic Options. Advances in experimental medicine and biology. 2021:1323():35-69. doi: 10.1007/5584_2020_566. Epub     [PubMed PMID: 32596751]

Level 3 (low-level) evidence

[129]

Sherwin E, King C, Hasen H, May S. Single-dose intravesical amikacin instillation for pyocystis in a patient with autonomic dysreflexia: A case report. The journal of spinal cord medicine. 2022 Nov:45(6):965-968. doi: 10.1080/10790268.2021.1922832. Epub 2021 May 13     [PubMed PMID: 33983103]

Level 3 (low-level) evidence

[130]

Ito K, Yamamoto T, Mori N. Pyocystis in an anuric patient undergoing chronic haemodialysis. Nephrology (Carlton, Vic.). 2017 May:22(5):420. doi: 10.1111/nep.12805. Epub     [PubMed PMID: 28378536]

[131]

Suzuki S, Sanda M, Kashiwagi Y. Pyocystis. The American journal of medicine. 2022 Feb:135(2):e49-e50. doi: 10.1016/j.amjmed.2021.08.032. Epub 2021 Sep 22     [PubMed PMID: 34560037]

[132]

Ariza-Heredia EJ, Beam EN, Lesnick TG, Kremers WK, Cosio FG, Razonable RR. Urinary tract infections in kidney transplant recipients: role of gender, urologic abnormalities, and antimicrobial prophylaxis. Annals of transplantation. 2013 May 6:18():195-204. doi: 10.12659/AOT.883901. Epub 2013 May 6     [PubMed PMID: 23792521]

[133]

Simsek C, Karatas M, Tatar E, Tercan IC, Tasli Alkan F, Uslu A. Acute Allograft Pyelonephritis: Vague Symptoms, Indeterminate Laboratory Results, and the Necessity of Indication Biopsy. Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 2022 Mar:20(Suppl 1):117-124. doi: 10.6002/ect.MESOT2021.P51. Epub     [PubMed PMID: 35384820]

[134]

Tandogdu Z, Cai T, Koves B, Wagenlehner F, Bjerklund-Johansen TE. Urinary Tract Infections in Immunocompromised Patients with Diabetes, Chronic Kidney Disease, and Kidney Transplant. European urology focus. 2016 Oct:2(4):394-399. doi: 10.1016/j.euf.2016.08.006. Epub 2016 Oct 5     [PubMed PMID: 28723471]

[135]

Krawczyk B, Wysocka M, Michalik M, Gołębiewska J. Urinary Tract Infections Caused by K. pneumoniae in Kidney Transplant Recipients - Epidemiology, Virulence and Antibiotic Resistance. Frontiers in cellular and infection microbiology. 2022:12():861374. doi: 10.3389/fcimb.2022.861374. Epub 2022 Apr 21     [PubMed PMID: 35531341]

[136]

Simon DM, Levin S. Infectious complications of solid organ transplantations. Infectious disease clinics of North America. 2001 Jun:15(2):521-49     [PubMed PMID: 11447708]

[137]

Lee JR, Bang H, Dadhania D, Hartono C, Aull MJ, Satlin M, August P, Suthanthiran M, Muthukumar T. Independent risk factors for urinary tract infection and for subsequent bacteremia or acute cellular rejection: a single-center report of 1166 kidney allograft recipients. Transplantation. 2013 Oct 27:96(8):732-8. doi: 10.1097/TP.0b013e3182a04997. Epub     [PubMed PMID: 23917724]

[138]

Britt NS, Hagopian JC, Brennan DC, Pottebaum AA, Santos CAQ, Gharabagi A, Horwedel TA. Effects of recurrent urinary tract infections on graft and patient outcomes after kidney transplantation. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2017 Oct 1:32(10):1758-1766. doi: 10.1093/ndt/gfx237. Epub     [PubMed PMID: 28967964]

[139]

Pellé G, Vimont S, Levy PP, Hertig A, Ouali N, Chassin C, Arlet G, Rondeau E, Vandewalle A. Acute pyelonephritis represents a risk factor impairing long-term kidney graft function. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2007 Apr:7(4):899-907     [PubMed PMID: 17286620]

[140]

Goh YSB, Deng Z, Cheong PSC, Raman L, Goh THA, Vathsala A, Tiong HY. Screening for asymptomatic bacteruria at one month after adult kidney transplantation: Clinical factors and implications. Clinical transplantation. 2017 May:31(5):. doi: 10.1111/ctr.12954. Epub 2017 Apr 9     [PubMed PMID: 28295630]

[141]

Nicolle LE, Gupta K, Bradley SF, Colgan R, DeMuri GP, Drekonja D, Eckert LO, Geerlings SE, Köves B, Hooton TM, Juthani-Mehta M, Knight SL, Saint S, Schaeffer AJ, Trautner B, Wullt B, Siemieniuk R. Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria: 2019 Update by the Infectious Diseases Society of America. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2019 May 2:68(10):1611-1615. doi: 10.1093/cid/ciz021. Epub     [PubMed PMID: 31506700]

Level 1 (high-level) evidence

[142]

Parasuraman R, Julian K, AST Infectious Diseases Community of Practice. Urinary tract infections in solid organ transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2013 Mar:13 Suppl 4():327-36. doi: 10.1111/ajt.12124. Epub     [PubMed PMID: 23465025]

[143]

Moradi M, Abbasi M, Moradi A, Boskabadi A, Jalali A. Effect of antibiotic therapy on asymptomatic bacteriuria in kidney transplant recipients. Urology journal. 2005 Winter:2(1):32-5     [PubMed PMID: 17629893]

[144]

Origüen J, López-Medrano F, Fernández-Ruiz M, Polanco N, Gutiérrez E, González E, Mérida E, Ruiz-Merlo T, Morales-Cartagena A, Pérez-Jacoiste Asín MA, García-Reyne A, San Juan R, Orellana MÁ, Andrés A, Aguado JM. Should Asymptomatic Bacteriuria Be Systematically Treated in Kidney Transplant Recipients? Results From a Randomized Controlled Trial. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2016 Oct:16(10):2943-2953. doi: 10.1111/ajt.13829. Epub 2016 May 23     [PubMed PMID: 27088545]

Level 1 (high-level) evidence

[145]

Pacaud M, Colas L, Kerleau C, Le Borgne F, Giral M, Brouard S, Dantal J. Impact of Late and Recurrent Acute Graft Pyelonephritis on Long-Term Kidney Graft Outcomes. Frontiers in immunology. 2022:13():824425. doi: 10.3389/fimmu.2022.824425. Epub 2022 Mar 2     [PubMed PMID: 35418982]

[146]

Powers HR, Hellinger WC, Cortese C, Elrefaei M, Khouzam S, Spiegel M, Li Z, Wadei HM. Histologic acute graft pyelonephritis after kidney transplantation: Incidence, clinical characteristics, risk factors, and association with graft loss. Transplant infectious disease : an official journal of the Transplantation Society. 2022 Apr:24(2):e13801. doi: 10.1111/tid.13801. Epub 2022 Feb 7     [PubMed PMID: 35080081]

[147]

Abbott KC, Swanson SJ, Richter ER, Bohen EM, Agodoa LY, Peters TG, Barbour G, Lipnick R, Cruess DF. Late urinary tract infection after renal transplantation in the United States. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2004 Aug:44(2):353-62     [PubMed PMID: 15264195]

[148]

Chuang P, Parikh CR, Langone A. Urinary tract infections after renal transplantation: a retrospective review at two US transplant centers. Clinical transplantation. 2005 Apr:19(2):230-5     [PubMed PMID: 15740560]

Level 2 (mid-level) evidence

[149]

Papasotiriou M, Savvidaki E, Kalliakmani P, Papachristou E, Marangos M, Fokaefs E, Maroulis I, Karavias D, Goumenos DS. Predisposing factors to the development of urinary tract infections in renal transplant recipients and the impact on the long-term graft function. Renal failure. 2011:33(4):405-10. doi: 10.3109/0886022X.2011.568137. Epub     [PubMed PMID: 21529269]

[150]

Muñoz P. Management of urinary tract infections and lymphocele in renal transplant recipients. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2001 Jul 1:33 Suppl 1():S53-7     [PubMed PMID: 11389523]

[151]

Horwedel TA, Bowman LJ, Saab G, Brennan DC. Benefits of sulfamethoxazole-trimethoprim prophylaxis on rates of sepsis after kidney transplant. Transplant infectious disease : an official journal of the Transplantation Society. 2014 Apr:16(2):261-9. doi: 10.1111/tid.12196. Epub 2014 Mar 13     [PubMed PMID: 24621104]

[152]

Arabi Z, Al Thiab K, Altheaby A, Aboalsamh G, Kashkoush S, Almarastani M, Shaheen MF, Altamimi A, O'hali W, Bin Saad K, Alnajjar L, Alhussein R, Almuhiteb R, Alqahtani B, Alotaibi R, Alqahtani M, Tawhari M. Urinary Tract Infections in the First 6 Months after Renal Transplantation. International journal of nephrology. 2021:2021():3033276. doi: 10.1155/2021/3033276. Epub 2021 Nov 15     [PubMed PMID: 34820141]

[153]

Hollyer I, Varias F, Ho B, Ison MG. Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study. Transplant infectious disease : an official journal of the Transplantation Society. 2019 Jun:21(3):e13063. doi: 10.1111/tid.13063. Epub 2019 Mar 8     [PubMed PMID: 30776166]

Level 2 (mid-level) evidence

[154]

Quintero Cardona O, Hemmige VS, Puius YA. Methenamine hippurate may have particular benefit in preventing recurrent urinary tract infections in diabetic renal transplant recipients. Transplant infectious disease : an official journal of the Transplantation Society. 2020 Apr:22(2):e13247. doi: 10.1111/tid.13247. Epub 2020 Jan 29     [PubMed PMID: 31957150]

[155]

Rosado-Canto R, Parra-Avila I, Tejeda-Maldonado J, Kauffman-Ortega C, Rodriguez-Covarrubias FT, Trujeque-Matos M, Cruz-Martínez R, Maravilla-Franco E, Criollo-Mora E, Arreola-Guerra JM, Morales-Buenrostro LE, Sifuentes-Osornio J. Perioperative fosfomycin disodium prophylaxis against urinary tract infection in renal transplant recipients: a randomized clinical trial. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2020 Nov 1:35(11):1996-2003. doi: 10.1093/ndt/gfz261. Epub     [PubMed PMID: 31883327]

Level 1 (high-level) evidence

[156]

Soriano F, Tauch A. Microbiological and clinical features of Corynebacterium urealyticum: urinary tract stones and genomics as the Rosetta Stone. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2008 Jul:14(7):632-43. doi: 10.1111/j.1469-0691.2008.02023.x. Epub     [PubMed PMID: 18558935]

[157]

Santos JM, Batech M, Pelter MA, Deamer RL. Evaluation of the Risk of Nitrofurantoin Lung Injury and Its Efficacy in Diminished Kidney Function in Older Adults in a Large Integrated Healthcare System: A Matched Cohort Study. Journal of the American Geriatrics Society. 2016 Apr:64(4):798-805. doi: 10.1111/jgs.14072. Epub     [PubMed PMID: 27100576]

[158]

Singh N, Gandhi S, McArthur E, Moist L, Jain AK, Liu AR, Sood MM, Garg AX. Kidney function and the use of nitrofurantoin to treat urinary tract infections in older women. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2015 Jun 16:187(9):648-656. doi: 10.1503/cmaj.150067. Epub 2015 Apr 27     [PubMed PMID: 25918178]

[159]

Oplinger M, Andrews CO. Nitrofurantoin contraindication in patients with a creatinine clearance below 60 mL/min: looking for the evidence. The Annals of pharmacotherapy. 2013 Jan:47(1):106-11. doi: 10.1345/aph.1R352. Epub 2013 Jan 22     [PubMed PMID: 23341159]

[160]

Gupta K. Emerging antibiotic resistance in urinary tract pathogens. Infectious disease clinics of North America. 2003 Jun:17(2):243-59     [PubMed PMID: 12848469]

[161]

Raz R, Chazan B, Kennes Y, Colodner R, Rottensterich E, Dan M, Lavi I, Stamm W, Israeli Urinary Tract Infection Group. Empiric use of trimethoprim-sulfamethoxazole (TMP-SMX) in the treatment of women with uncomplicated urinary tract infections, in a geographical area with a high prevalence of TMP-SMX-resistant uropathogens. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2002 May 1:34(9):1165-9     [PubMed PMID: 11941541]

[162]

Wesolek JL, Wu JY, Smalley CM, Wang L, Campbell MJ. Risk Factors for Trimethoprim and Sulfamethoxazole-Resistant Escherichia Coli in ED Patients with Urinary Tract Infections. The American journal of emergency medicine. 2022 Jun:56():178-182. doi: 10.1016/j.ajem.2022.03.052. Epub 2022 Mar 31     [PubMed PMID: 35405469]

[163]

Jouret F, Lhommel R, Devuyst O, Annet L, Pirson Y, Hassoun Z, Kanaan N. Diagnosis of cyst infection in patients with autosomal dominant polycystic kidney disease: attributes and limitations of the current modalities. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2012 Oct:27(10):3746-51. doi: 10.1093/ndt/gfs352. Epub     [PubMed PMID: 23114901]

[164]

Pijl JP, Glaudemans AWJM, Slart RHJA, Kwee TC. (18)F-FDG PET/CT in Autosomal Dominant Polycystic Kidney Disease Patients with Suspected Cyst Infection. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018 Nov:59(11):1734-1741. doi: 10.2967/jnumed.117.199448. Epub 2018 Apr 13     [PubMed PMID: 29653972]

[165]

Ronsin C, Bailly C, Le Turnier P, Ville S. Value of FDG-PET/CT in monitoring cyst infections in patients with autosomal dominant polycystic renal disease. Clinical kidney journal. 2021 Oct:14(10):2273-2275. doi: 10.1093/ckj/sfab077. Epub 2021 Apr 19     [PubMed PMID: 34603707]

[166]

Hasan SMM, Salh BS. Emphysematous cystitis as a potential marker of severe Crohn's disease. BMC gastroenterology. 2022 Apr 11:22(1):181. doi: 10.1186/s12876-022-02253-6. Epub 2022 Apr 11     [PubMed PMID: 35410166]

[167]

Grupper M, Kravtsov A, Potasman I. Emphysematous cystitis: illustrative case report and review of the literature. Medicine. 2007 Jan:86(1):47-53. doi: 10.1097/MD.0b013e3180307c3a. Epub     [PubMed PMID: 17220755]

Level 3 (low-level) evidence

[168]

Ranjan SK, Navriya SC, Kumar S, Mittal A, Bhirud DP. Emphysematous cystitis: A case report and literature review of 113 cases. Urology annals. 2021 Jul-Sep:13(3):312-315. doi: 10.4103/UA.UA_61_20. Epub 2021 Jun 23     [PubMed PMID: 34421272]

Level 3 (low-level) evidence

[169]

Olvera-Posada D, García-Mora A, Culebro-García C, Castillejos-Molina R, Sotomayor M, Feria-Bernal G, Rodríguez-Covarrubias F. [Prognostic factors in emphysematous pyelonephritis]. Actas urologicas espanolas. 2013 Apr:37(4):228-32. doi: 10.1016/j.acuro.2012.03.021. Epub 2012 Dec 20     [PubMed PMID: 23260183]

[170]

Desai R, Batura D. A systematic review and meta-analysis of risk factors and treatment choices in emphysematous pyelonephritis. International urology and nephrology. 2022 Apr:54(4):717-736. doi: 10.1007/s11255-022-03131-6. Epub 2022 Feb 1     [PubMed PMID: 35103928]

Level 1 (high-level) evidence

[171]

Arrambide-Herrera JG, Robles-Torres JI, Ocaña-Munguía MA, Romero-Mata R, Gutiérrez-González A, Gómez-Guerra LS. Predictive factors for mortality and intensive care unit admission in patients with emphysematous pyelonephritis: 5-year experience in a tertiary care hospital. Actas urologicas espanolas. 2022 Mar:46(2):98-105. doi: 10.1016/j.acuroe.2021.01.010. Epub 2022 Feb 2     [PubMed PMID: 35120854]

[172]

Koch GE, Johnsen NV. The Diagnosis and Management of Life-threatening Urologic Infections. Urology. 2021 Oct:156():6-15. doi: 10.1016/j.urology.2021.05.011. Epub 2021 May 17     [PubMed PMID: 34015395]

[173]

Anıl H, Şener NC, Karamık K, Erol İ, Vuruşkan E, Erçil H, Gürbüz ZG. Comparison of Percutaneous Nephrostomy and Ureteral DJ Stent in Patients with Obstructive Pyelonephritis: A Retrospective Cohort Study. Journal of investigative surgery : the official journal of the Academy of Surgical Research. 2022 Jul:35(7):1445-1450. doi: 10.1080/08941939.2022.2062496. Epub 2022 Apr 12     [PubMed PMID: 35414347]

Level 2 (mid-level) evidence

[174]

Abi Tayeh G, Safa A, Sarkis J, Alkassis M, Khalil N, Nemr E, El Helou E. Determinants of pyelonephritis onset in patients with obstructive urolithiasis. Urologia. 2022 Feb:89(1):100-103. doi: 10.1177/03915603211035244. Epub 2021 Aug 2     [PubMed PMID: 34338097]

[175]

Young M, Leslie SW. Percutaneous Nephrostomy. StatPearls. 2024 Jan:():     [PubMed PMID: 29630257]

[176]

Chang CW, Huang CN. Pyonephrosis drained by double-J catheter. Clinical case reports. 2020 Dec:8(12):3586-3587. doi: 10.1002/ccr3.3204. Epub 2020 Sep 2     [PubMed PMID: 33363990]

Level 3 (low-level) evidence

[177]

Itami Y, Miyake M, Owari T, Iwamoto T, Gotoh D, Momose H, Fujimoto K, Hirao S. Optimal timing of ureteroscopic lithotripsy after the initial drainage treatment and risk factors for postoperative febrile urinary tract infection in patients with obstructive pyelonephritis: a retrospective study. BMC urology. 2021 Jan 15:21(1):10. doi: 10.1186/s12894-020-00754-8. Epub 2021 Jan 15     [PubMed PMID: 33451332]

Level 2 (mid-level) evidence

[178]

Cui C, Jiang J, Chen W, Cui LG, Wang JR. [Xanthogranulonatous pyelonephritis: report of 5 cases]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences. 2018 Aug 18:50(4):743-746     [PubMed PMID: 30122783]

Level 3 (low-level) evidence

[179]

Iskandar SS, Prahlow JA, White WL. Lipid-laden foamy macrophages in renal cell carcinoma. Potential frozen section diagnostic pitfall. Pathology, research and practice. 1993 Jun:189(5):549-52     [PubMed PMID: 8378177]

[180]

Jha SK, Aeddula NR. Xanthogranulomatous Pyelonephritis. StatPearls. 2024 Jan:():     [PubMed PMID: 32491331]

[181]

Werneburg GT. Catheter-Associated Urinary Tract Infections: Current Challenges and Future Prospects. Research and reports in urology. 2022:14():109-133. doi: 10.2147/RRU.S273663. Epub 2022 Apr 4     [PubMed PMID: 35402319]

[182]

Rigvava S, Kusradze I, Tchgkonia I, Karumidze N, Dvalidze T, Goderdzishvili M. Novel lytic bacteriophage vB_GEC_EfS_9 against Enterococcus faecium. Virus research. 2022 Jan 2:307():198599. doi: 10.1016/j.virusres.2021.198599. Epub 2021 Oct 12     [PubMed PMID: 34648886]

[183]

Slobodníková L, Markusková B, Kajsík M, Andrezál M, Straka M, Liptáková A, Drahovská H. Characterization of Anti-Bacterial Effect of the Two New Phages against Uropathogenic Escherichia coli. Viruses. 2021 Jul 12:13(7):. doi: 10.3390/v13071348. Epub 2021 Jul 12     [PubMed PMID: 34372554]

[184]

Chegini Z, Khoshbayan A, Vesal S, Moradabadi A, Hashemi A, Shariati A. Bacteriophage therapy for inhibition of multi drug-resistant uropathogenic bacteria: a narrative review. Annals of clinical microbiology and antimicrobials. 2021 Apr 26:20(1):30. doi: 10.1186/s12941-021-00433-y. Epub 2021 Apr 26     [PubMed PMID: 33902597]

Level 3 (low-level) evidence

[185]

Dasgupta M, Brymer C, Elsayed S. Treatment of asymptomatic UTI in older delirious medical in-patients: A prospective cohort study. Archives of gerontology and geriatrics. 2017 Sep:72():127-134. doi: 10.1016/j.archger.2017.05.010. Epub 2017 May 31     [PubMed PMID: 28624753]

[186]

Sundvall PD, Ulleryd P, Gunnarsson RK. Urine culture doubtful in determining etiology of diffuse symptoms among elderly individuals: a cross-sectional study of 32 nursing homes. BMC family practice. 2011 May 19:12():36. doi: 10.1186/1471-2296-12-36. Epub 2011 May 19     [PubMed PMID: 21592413]

Level 2 (mid-level) evidence

[187]

Bonine NG, Berger A, Altincatal A, Wang R, Bhagnani T, Gillard P, Lodise T. Impact of Delayed Appropriate Antibiotic Therapy on Patient Outcomes by Antibiotic Resistance Status From Serious Gram-negative Bacterial Infections. The American journal of the medical sciences. 2019 Feb:357(2):103-110. doi: 10.1016/j.amjms.2018.11.009. Epub 2018 Nov 22     [PubMed PMID: 30665490]

[188]

Karve S, Ryan K, Peeters P, Baelen E, Rojas-Farreras S, Potter D, Rodríguez-Baño J. The impact of initial antibiotic treatment failure: Real-world insights in patients with complicated urinary tract infection. The Journal of infection. 2018 Feb:76(2):121-131. doi: 10.1016/j.jinf.2017.11.001. Epub 2017 Nov 8     [PubMed PMID: 29128389]