Infectious Diseases

Urinary Tract Infections (UTI): Pyelonephritis/Complicated

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OVERVIEW: What every practitioner needs to know

Are you sure your patient has pyelonephritis/complicated urinary tract infection? What should you expect to find?

  • Urinary tract infections (UTI) can be separated into distinct syndromes depending on host characteristics and the presence of symptoms. The syndromes of pyelonephritis, infection of the renal parenchyma, and complicated UTI, infections of the urinary tract in patients with functional or anatomical abnormalities, are covered here. The presence of bacteria in the urine without localizing urinary tract or systemic symptoms of infection is considered asymptomatic bacteriuria, a common condition that increases with advancing age and most often does not require treatment. In a patient with bacteriuria and systemic symptoms of infection without localizing genitourinary (GU) symptoms, UTI should be considered as a potential diagnosis; however, other causes of the systemic symptoms should also be evaluated, because the urine culture may simply be reflecting asymptomatic bacteriuria.

  • Pyelonephritis denotes infection of the renal parenchyma. Symptoms of pyelonephritis include:

    • local pain (costovertebral tenderness, back or flank pain)

    • systemic signs of infection (chills, fever, nausea, vomiting)

These symptoms may or may not be associated with symptoms of cystitis (dysuria, frequency, urgency, new incontinence).

  • Complicated UTI, implying that there is a reason for the UTI, presents with localizing GU symptoms or systemic symptoms and may not be distinguishable from uncomplicated UTI based on symptoms alone.

    • Focal GU symptoms include dysuria, frequency, urgency, and new incontinence.

    • Suprapubic discomfort or hematuria may also be reported.

    • Systemic symptoms of infection (i.e., fever, shaking chills, palpitations, lightheadedness, mental status change) and no other identifiable cause may be present.

  • The physical findings depend on the exact UTI syndrome. Localizing findings to the GU tract, including suprapubic tenderness, prostate tenderness, or costovertebral angle (CVA) tenderness may be elicited depending on the site of infection. In patients with complicated cystitis, the exam may be normal.

  • Systemic signs of infection, including tachycardia, fever, mental status change, and hypotension, may be present in any complicated UTI syndrome, but these findings are not specific to UTI.

How did the patient develop pyelonephritis/complicated urinary tract infection? What was the primary source from which the infection spread?

  • Pyelonephritis and complicated UTI most commonly occur by migration of enteric bacteria from the intestinal tract into the urethra and ascension into the urinary system.

Basic epidemiology

  • The term "complicated," as opposed to uncomplicated, suggests there is a predisposing reason for the infection, including the presence of abnormal voiding (e.g., neurogenic bladder, stricture, benign prostatic hypertrophy) or a foreign body (e.g., stone or stent or catheter). Known or suspected multi-drug resistance is also a complicating factor.

  • Complicated UTI can occur in any gender and at any age but is most common in men after the fifth decade when benign prostatic hypertrophy (BPH) is present and in both men and women who have voiding abnormalities related to other conditions.

  • Most UTIs in young premenopausal nonpregnant women and in young adult men are not complicated.

  • UTIs in patients with diabetes or in postmenopausal women should be considered complicated if there is abnormal voiding associated with those conditions.

  • Additional factors that suggest complicated UTI include conditions that make treatment more difficult, such as pregnancy, multidrug resistance, and immunosuppression.

Which individuals are at greater risk of developing pyelonephritis/complicated urinary tract infection?

  • Complicated UTI risk is greatest in patients with abnormal voiding and may be suggested by a history of urinary retention, recurrent UTI, or urinary procedures, including stent or catheter placement. Any condition or foreign body resulting in obstruction of normal urinary flow predisposes to complicated UTI. Diabetes increases the risk of perirenal abscess and emphysematous pyelonephritis.

  • Specific factors include:

    • current or recent use of a urinary catheter

    • BPH

    • pregnancy

    • pelvic or abdominal tumors or masses that impinge on the urinary tract

    • neurogenic bladder from diabetes mellitus, spinal cord injury, or multiple sclerosis

    • suprapubic catheters

    • ureteral stents

    • renal or bladder stones

Beware: there are other diseases that can mimic pyelonephritis/complicated urinary tract infection:

  • Urethritis due to sexually transmitted pathogens can mimic cystitis.

  • Nephrolithiasis (hematuria and flack pain) mimics pyelonephritis.

  • Chronic pelvic pain syndrome (CPPS) in males mimics prostatitis.

  • Systemic conditions and non-GU infections can result in fever, tachycardia, mental status change, and/or hypotension and may be misdiagnosed as UTI because of the presence of pyuria or asymptomatic bacteriuria. When making a diagnosis of complicated UTI on the basis of systemic symptoms alone, other diagnoses need to be excluded.

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

  • Urinalysis: pyuria with or without hematuria

  • Peripheral white blood cell (WBC) with differential: may be elevated in patients with systemic symptoms, but can be normal in patients with complicated UTIs localized to the bladder

  • Creatinine: may be elevated in patients with obstruction

Results that confirm the diagnosis

  • Urine culture: greater than 104CFU/mL of a uropathogen (if a catheter is in place >103CFU/mL meets the diagnostic criteria) confirms diagnosis. This criterion only stands in a patient with symptoms of UTI. A positive urine culture in the absence of symptoms is defined as asymptomatic bacteriuria and should not be treated except in very specific conditions (e.g., pregnancy).

  • In patients with complete obstruction of the urinary tract, a culture of initial urine from a newly placed nephrostomy tube can help identify the uropathogen.

  • Blood cultures: In patients with pyelonephritis or systemic signs of infection, blood cultures may be positive and should match the urinary pathogen. If the blood and urine isolates do not match, a search for the source of the blood isolate should be undertaken and a diagnosis other than complicated UTI should be considered (the urine isolate may represent asymptomatic bacteriuria).

What imaging studies will be helpful in making or excluding the diagnosis of pyelonephritis/complicated urinary tract infection?

Patients with pyelonephritis or complicated UTI should undergo imaging of the urinary tract in the following settings:

  • lack of response to antimicrobial therapy within 48 to 72 hours

  • sepsis that is worsening despite antimicrobial therapy

  • a rise in creatinine from baseline not attributable to other causes, such as hypovolemia

  • a history of urinary stones or other anatomical abnormalities (i.e., stents, strictures)

  • renal ultrasound for evaluation of obstruction and hydronephrosis

  • computed tomography (CT) scan without contrast to evaluate for stones, emphysematous pyelonephritis, abscess, and obstruction

  • limited CT scan ($$$)

  • renal ultrasound ($$$)

  • $$$ = $500-1,000

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

If you decide the patient has pyelonephritis/complicated UTI, what therapies should you initiate immediately?

Establish urine flow; this may require consultation with urology if a catheter is difficult to place or an obstructing stone needs to be removed. Consultation with interventional radiology may be helpful if an upper tract obstruction requires a percutaneous nephrostomy tube.

Antibiotics (preferably after cultures are obtained) should be given; consultation with Infectious Diseases may be required for optimal antimicrobial selection if there is known or suspected multidrug resistance.

Xanthogranulomatous pyelonephritis requires surgical consultation for possible nephrectomy; renal abscess and emphysematous pyelonephritis require urology consultation for percutaneous drainage.

Key principles of therapy

In patients who require hospitalization, broad spectrum intravenous (IV) therapy is indicated empirically while waiting for culture data. In patients who are clinically stable and who do not require IV fluids or other supportive care, outpatient oral antibiotics can be considered. In these patients, an initial one time IV dose of a broad spectrum antimicrobial may be helpful, especially if susceptibility of the infecting uropathogen is not known.

Antimicrobial resistance is more likely in complicated UTI since patients may have had previous hospital and antimicrobial exposures. If previous relevant microbiology is available (e.g., urine cultures from previous UTI), this can be used to guide antimicrobial choice. Otherwise, broad spectrum regimens are recommended initially, with tailoring of the regimen once susceptibility data are available.

Recent antimicrobial exposure should prompt broader spectrum agents initially since the infecting organism may be resistant not only to the class of drug previously used, but also to multiple other classes. Additional risk factors for multidrug resistant UTI include healthcare exposure and travel to areas with endemic resistance.

Antibiotics with excellent penetration into the prostate gland are preferred for treatment of prostatitis and include the fluoroquinolones and trimethoprim-sulfamethoxazole. The initial empiric choice may be broader (especially in patients requiring hospitalization) and then narrowed to one of these agents, if possible, based on susceptibility data and patient factors, such as allergy and drug interactions.

The optimal duration of therapy for complicated UTI is not well established and varies depending on clinical response and successful modification of the predisposing factor (e.g., can the urinary catheter be removed?). In most cases, 7 days of therapy is sufficient. Longer therapy is indicated if there is a nonremovable nidus of infection or delayed response to therapy.

1. Anti-infective agents

If I am not sure what pathogen is causing the infection, what anti-infective should I order?

The empiric choice of antimicrobial depends on known microbiology: Does a recent urine culture indicate susceptibility to a single class agent, such as trimethoprim-sulfamethoxazole (TMP-SMX) or a fluoroquinolone (FQ)? What is the estimated resistance prevalence for uropathogens (primarily Escherichia coli) in the region? Regional resistance thresholds are 20% for TMP-SMX and 10% for FQ, above which these agents should not be used alone to empirically treat UTI. Recent surveillance data found that multi-drug resistance and extended-spectrum beta-lactamases are increasingly identified among uropathogens isolated from patients with complicated UTI presenting to the emergency room.

Broad-spectrum regimens, such as an extended-spectrum cephalosporin with or without an aminoglycoside or combinations of a beta-lactam and a beta-lactamase inhibitor (e.g., ampicillin-sulbactam, ticarcillin-clavulanate, and piperacillin-tazobactam) should be considered for empiric therapy of hospitalized patients.

Patients with risk factors for pseudomonas or multi-drug resistance, or who are severely ill with an unknown susceptibility profile of the infecting pathogen, should receive therapy with a carbapenem (imipenem-cilastatin, ertapenem, meropenem, doripenem) or one of the newly approved agents, ceftazidime-avibactam or ceftolozane-tazobactam. These each have activity against multi-drug resistant gram-negatives, including pseudomonas and can be considered for treatment of complicated urinary-tract infections and pyelonephritis that are caused by pathogens that are fluoroquinolone-resistant, produce extended-spectrum β-lactamases, or both. Ceftolozane-tazobactam in particular should be considered for multidrug-resistant strains of Pseudomonas aeruginosa. Susceptibility testing has to be specifically requested for this agent as it is not part of standard panels yet.

The empiric therapy should include coverage for Pseudomonas sp. in patients who have had recent instrumentation, hospitalization, chronic indwelling catheters, prolonged antibiotics, or recurrent complicated UTIs, obstruction and in patients who are immunocompromised (e.g.. neutropenic).

The empiric therapy should include coverage for Proteus sp. and other urease-producing organisms (Citrobacter, Morganella, Providencia) in patients who have staghorn calculi.

If a patient has recently been treated with a specific class of antibiotics either for UTI, for procedural prophylaxis (e.g., transurethral resection of the prostate (TURP)), or for another infection, then consider the possibility of a multidrug resistant organism and use a different class of antimicrobial for empiric management of complicated UTI. For example, if the patient recently received therapy or prophylaxis with a fluoroquinolone or beta-lactam (cephalosporin or extended spectrum penicillin agent), the possibility of an extended spectrum beta lactamase (ESBL) organism needs to be considered and initial therapy should be with a carbapenem (imipenem, meropenem, ertapenem, doripenem) or with ceftazidime-avibactam or ceftolozane-tazobactam. In patients with known or anticipated carbapenem resistance that is not mediated by a Class B (metallo) beta-lactamase, ceftazidime-avibactam is a newly available agent that may have activity; specific susceptibility testing will need to be requested because it is not yet part of automated panels.

Additional factors associated with multi-drug resistant UTI include recent antibiotic use, travel to areas with high rates of gram-negative resistance, and health-care exposure. Multi-drug resistance may be present in absence of these factors, particularly in areas with higher rates of community based resistance.

The choice of oral versus IV antibiotics depends on whether the patient is able to tolerate oral intake and whether they require hospitalization. IV antibiotics may also be necessary in patients for whom there are no viable oral options due to known or anticipated multi-drug resistance. See Table I.

Table I.

Treatment Regimens for Complicated UTI (known organism and susceptibility)

Oral Agents

Oral agents can be considered in patients who are clinically stable (either as initial therapy or as step-down therapy after IV). Trimethoprim-sulfamethoxazole and the fluoroquinolones have excellent penetration into genito-urinary tissue and are preferred agents for complicated UTI and pyelonephritis when susceptibilities are known.

In patients who are clinically stable and have multi-drug resistant uropathogens, fosfomycin can be considered for cystitis as well as prostatitis. New data suggest that fosfomycin penetrates the prostate gland and can successfully be used to treat prostatitis. Nitrofurantoin retains activity against a majority of multi-drug resistant uropathogens and can be considered for therapy of complicated UTI if renal or prostate involvement is not suspected.

2. Next list other key therapeutic modalities.

  • If urinary obstruction, establish flow (e.g., place a Foley in a patient with urinary retention and UTI). This may require consultation with Urology (e.g., for ureteral stent placement or for stone removal) or with Interventional Radiology (percutaneous nephrostomy tube placement) for relief of upper urinary tract obstruction.

  • If chronic indwelling catheters are present, remove them or, if not possible to discontinue, replace with a fresh catheter.

  • If perinephric abscess or gangrenous/emphysematous pyelonephritis, consultation with urologic surgery for drainage (abscess) or possible nephrectomy (for xanthogranulomatous pyelonephritis).

  • If urinary stones are present, attempt to completely remove the stones, because they are a nidus for recurrent infection.

What complications could arise as a consequence of pyelonephritis/complicated urinary tract infection?

What should you tell the family about the patient’s prognosis?

  • Diabetes is associated with xanthogranulomatous, papillary necrosis, and emphysematous pyelonephritis, severe conditions requiring a combined surgical and medical approach.

  • Obstruction that cannot be relieved or presence of a stone or stricture increase the likelihood of infection and make treatment of infection more difficult.

  • The overall 28-day and 1-year all-cause mortality rates following a UTI associated with gram-negative bacteremia was found to be 4.9% (95% confidence interval [CI]: 3.0-6.8) and 15.6% (95% CI: 12.4-18.8), respectively, in a population-based retrospective study. Mortality rates were higher with advancing age and in patients with health-care acquired infections.

  • Catheter associated UTI was the third leading cause of hospital associated infection-related death in US hospitals in 2002.

Add what-if scenarios here:

If the urine culture reveals yeast, assess for symptoms of urinary tract infection because funguria most often represents asymptomatic colonization of the urinary tract (see “Are you sure your patient has pyelonephritis/complicated urinary tract infection?” and “Yeast”). If symptoms of urinary tract infection are present, assess for fungal balls within the urinary tract (by ultrasound or CT scan), control hyperglycemia (diabetes is a commonly associated condition), and institute anti-fungal therapy. Urology consultation may be needed for removal of fungal balls or irrigation of the urinary system with an antifungal agent (amphotericin B). (See below)

  • If the urine culture reveals mixed flora or more than two organisms, repeat the urine culture ensuring an uncontaminated specimen (consider sterile in and out catheterization) and search for an alternate source of infection. If a patient is systemically ill (fever, hypotension), provide empiric broad spectrum antimicrobial therapy while evaluating the urinary tract with repeat cultures and imaging.

  • If the urine culture reveals two gram-negative rods in similar quantities, consider both potentially pathogenic and provide antimicrobial therapy for both organisms.

  • If the urine culture reveals Staphylococcus aureus, yeast, or Salmonella in a patient who is systemically ill, consider the possibility of hematogenous seeding of the urinary tract. Perform blood cultures and consider evaluation of the upper tract with imaging for pyelonephritis or renal abscess. If the patient is not systemically ill and does not have focal GU symptoms, consider the possibility of asymptomatic colonization or possibly contamination from the intestinal tract (the latter is particularly relevant in the case of Salmonella).

How do you contract pyelonephritis/complicated urinary tract infection and how frequent is this disease?

Complicated UTI and pyelonephritis are infections of the urinary tract that occur in a wide spectrum of patients.

Complicated UTI should be suspected when there are anatomical or functional abnormalities predisposing to infection or infection caused by multidrug resistant bacteria making treatment more difficult. The risk factors associated with complicated UTI include:

  • urinary catheter use (either current or recent)

  • recent urinary instrumentation (e.g., TURP)

  • obstruction (e.g., related to stones, strictures, or external mass effect)

  • pregnancy

  • BPH

  • nephrolithiasis

  • ureteral stents

  • diabetes mellitus (increased risk of severe pyelonephritis syndromes, such as emphysematous and xanthogranulomatous pyelonephritis and papillary necrosis)

  • immunosuppression (including neutropenia and renal transplant)

  • neurogenic bladder (related to a variety of conditions including multiples sclerosis)

  • spinal cord injury

  • renal failure

Additional characteristics that warrant a "complicated" UTI diagnosis include:

  • cystitis symptoms for more than 7 days (may have upper tract involvement)

  • known multidrug resistance

  • recurrent UTI (except for cystitis in otherwise healthy premenopausal women)

There are few prospective data on the incidence of complicated UTI. Catheter-associated UTI occurs at a rate of three to five episodes per 1,000 Foley days in intensive care units (ICUs). In an observational study of women with type 1 diabetes mellitus, the prevalence of cystitis was 15%, similar to the prevalence in a separate cohort of women without diabetes. The prevalence of pyelonephritis was 3% in diabetics, higher than in the nondiabetic group.

UTI is an infection resulting from endogenous flora or nosocomial introduction of organisms. Although there are sporadic reports suggesting that uropathogens were transmitted between sexual partners and caused UTI, in general, person-to-person transmission is not a factor in UTI.

Complicated UTI encompasses a wide spectrum of infection syndromes involving the urinary tract in a diverse population of patients. Most UTIs occurring in patients other than premenopausal nonpregnant women are considered complicated for the purposes of diagnostic approach, meaning that a urine culture is indicated.

Although UTI is not a zoonotic infection, there are reports of isolation of pathogens with clonal relatedness from poultry and the urine of humans. The premise is that close contact or ingestion of poultry (or other animals) with multidrug resistant gram-negative flora might result in the acquisition of the bacteria by humans. For example, a strain of Enterococcus faecalis was isolated from the urine of a patient who had close contact with poultry carrying the same clone.

What pathogens are responsible for this disease?

UTI is primarily a gram-negative bacterial infection. In patients with an indwelling catheter, immunosuppression or diabetes mellitus or on broad spectrum antibacterials, yeast can cause UTI. The presence of an indwelling urinary catheter is often a risk factor for fungal UTI.

Enteric flora, including E. coli, Klebsiella, and Proteus, are the primary pathogens. E. coli is responsible for more than 50% of complicated UTI events and 80 to 90% of uncomplicated pyelonephritis cases. Klebsiella and Proteus may be more common among hospitalized or instrumented patients. Proteus is often a cause of UTI associated with stones.

Other gram-negative rods, including Serratia, Morganella, Citrobacter, Enterobacter, Acinetobacter, and Pseudomonas, are found in patients with previous health care and antimicrobial exposure. Gram-positive bacteria (Enterococcus, S. aureus, or streptococci) are less commonly pathogenic but can be considered causative if the clinical presentation is compatible with UTI and the bacteria are isolated as the sole organism from a properly collected urine sample.

Tuberculosis (TB) can affect the urinary tract and will present in patients who do not otherwise have criteria for complicated UTI (no anatomical or functional abnormalities). The presentation can be insidious and often localized to the GU tract (cystitis symptoms and finding of sterile pyuria) but can also present with systemic symptoms of fevers, sweats, and weight loss.

This diagnosis will only be made if there is a clinical suspicion of TB and a urine culture for mycobacteria is ordered. The sensitivity of urine cultures for mycobacteria can be low, thus, imaging of the GU tract, epidemiology, and other compatible findings should be considered when interpreting negative results of urine mycobacteria cultures. Treatment is the same as for disseminated TB, although surgery for management of focal disease is sometimes used adjunctively.

Symptoms of cystitis are common after bacille Calmette-Guerin (BCG) bladder instillation in patients with bladder cancer. These symptoms are usually self-limiting and do not require any therapy. However, the inflammatory reaction can be more severe and disseminated infection with this live attenuated strain of Mycobacterium bovis can occur. Systemic involvement with fever, sepsis, prostatitis, hepatitis, and pneumonitis has been reported. Management depends on the severity of illness and timing of onset after BCG instillation.

Yeast can cause symptomatic UTI but most often cause asymptomatic colonization of the urinary tract. Distinguishing between these entities can be difficult, because localizing symptoms may not be present in patients with true infection, and the colony count and presence of pyuria are not reliable indicators of infection. Candida species are the most common yeast identified in urine cultures. Risk factors for candiduria include:

  • presence of an indwelling urinary catheter

  • broad spectrum antimicrobials

  • diabetes mellitus

  • steroid exposure or other immunosuppression

  • anatomical abnormalities of the urinary tract

  • candidemia with secondary seeding of the urinary tract

Candidal UTI can be severe with papillary necrosis and emphysematous pyelonephritis (particularly in patients with diabetes).

Candidal UTI can also have a more chronic presentation with formation of fungal balls in the urinary tract and perinephric abscess.

Patients with candiduria and an indwelling catheter should have the catheter removed or replaced, with a repeat urine culture from a fresh catheter. If candiduria persists and there are local or systemic signs of infection without another identifiable cause, antifungal therapy should be initiated.

Imaging for fungus balls, abscesses, or other abnormalities should be performed in patients with recurrent candidal UTI, severe UTI, or acute changes in renal function. In each of these instances, antifungal therapy is warranted along with surgical management (i.e., drainage, relief of obstruction, removal of foreign body).

Other fungi, such as Aspergillus species, can also cause UTI but are much less common and usually occur in hosts with immunosuppression due to solid organ or bone marrow transplant or malignancy. Aspergillus has also been identified as a cause of UTI in patients with diabetes.

Viral UTI is uncommon but should be considered as a potential diagnosis in immunocompromised hosts, primarily transplant patients who present with hemorrhagic cystitis. The main pathogens are adenovirus, BK virus, and Cytomegalovirus. The presentation is usually fever with specific cystitis symptoms and gross hematuria. The diagnosis is made by real-time polymerase chain reaction (PCR) for the specific viruses. Initial treatment should include reduction in immunosuppression where possible. Antiviral therapy with cidofivir may be effective.

Schistosomiasis hematobium causes urinary tract disease and should be considered in patients who have travelled to endemic areas.

How do these pathogens cause pyelonephritis/complicated urinary tract infection?

UTI is primarily an ascending infection caused by organisms, primarily enteric bacteria, residing in the intestinal flora. Infection occurs when there is a disruption of the normal flow of urine through the urinary tract, for example, due to stones, strictures, catheters, or loss of bladder function.

Bacterial infection of the urinary tract is associated with elevation of acute phase reactants, including C-reactive protein. Interleukin 6 and 8 are also elevated. The presence of a P fimbrial adhesin on E. coli has been associated with pyelonephritis in women.

Less commonly, UTI can occur via hematogenous seeding of the kidneys in the setting of a primary bacteremia. This can occur with pathogens such as S. aureus, Candida sp., and Salmonella.

What other clinical manifestations may help me to diagnose and manage pyelonephritis/complicated urinary tract infection?

Additional diagnostics depend on the specific patient risk factors and may require urologic consultation for cystoscopy and voiding studies for assessment for anatomical or functional abnormalities.

UTI has an acute onset (days rather than months of symptoms).

Men with recurrent UTI should be evaluated for prostatitis.

Women with recurrent UTI may not have any complicating factors, because recurrence is part of the natural history of acute cystitis in women.

The physical exam may be normal in patients with complicated UTI.

In patients with primarily systemic findings or infection without focal GU symptoms, the exam should include evaluation for other infections.

Examination of the urethral meatus in men with cystitis symptoms should be performed to detect a discharge that would indicate urethritis. Likewise, in women with cystitis symptoms, a pelvic exam can be useful for ruling out vaginitis or cervicitis.

What other additional laboratory findings may be ordered?

Elevated procalcitonin has been associated with bacteremia in patients with febrile UTI and proposed as a diagnostic test in lieu of blood cultures. It is not commonly used in clinical practice for this purpose, because blood cultures also give added information about the identity of the infecting pathogen, which should match the urinary pathogen if UTI is the correct diagnosis.

How can pyelonephritis/complicated UTI be prevented?

Single dose antimicrobial prophylaxis is recommended for prevention of urosepsis in patients undergoing invasive GU procedures, such as transrectal prostate biopsy and bladder biopsy. The regimen of choice has been ciprofloxacin; however, increased resistance to ciprofloxacin has led to breakthrough episodes of sepsis and bacteremia. Optimal prophylaxis regimens other than the fluoroquinolones are currently being evaluated but can be guided by local resistance data or by rectal cultures.

Antimicrobial prophylaxis with TMP-SMX is used in patients undergoing renal transplantation.

Patients with recurrent episodes of complicated UTI due to a nidus of infection, such as stone, stent, or other foreign body, may be managed with antimicrobial prophylaxis while definitive management of the underlying disease process is planned. This strategy is not effective long-term because of issues of antibiotic resistance and adverse effects.

Reducing the use of urinary catheters is the primary method for preventing catheter-associated UTI.

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

Auer, S, Wojna, A, Hell, M. "Oral treatment options for ambulatory patients with urinary tract infections caused by extended-spectrum-β-lactamase-producing Escherichia coli". Antimicrobl Agents Chemother. vol. 54. 2010. pp. 4006-8.

(Expert consensus on approach to management of multidrug resistant uropathogens.)

Cek, M, Lenk, S, Naber, KG. "EAU guidelines for the management of genitourinary tuberculosis". Eur Urol. vol. 48. 2005. pp. 353-62.

(Additional information regarding diagnosis and management of TB infections of the urinary tract.)

Grabe, M, Bjerklund-Johansen, TE, Botto, H. "Guidelines on urological infections".

(Compendium of evidence for diagnosis and management of complicated UTI.)

Gupta, K, Hooton, TM, Naber, K. "International clinical practice guidelines for treatment of uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society of Clinical Infectious Diseases and Microbiology". Clin Infect Dis. vol. 52. 2011. pp. 103-20.

(An evidence based guideline synthesizing the current recommendations for treatment of uncomplicated cystitis and pyelonephritis.)

Hooton, TM, Bradley, SF, Cardena, DD. "Diagnosis prevention and treatment of catheter-associated UTI in adults: 2009 international clinical practice guidelines from the Infectious Diseases Society of America". Clin Infect Dis. vol. 5. 2010. pp. 625-63.

(A comprehensive outline of evidence-based recommendations for diagnosis and treatment of UTIs associated with urinary catheters.)

Nicolle, LE, Bradley, S, Colgan, R. "Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults". Clin Infect Dis. vol. 40. 2005. pp. 643-54.

(An excellent resource outlining the evidence for not treating asymptomatic bacteriuria in most circumstances and specific cases in which it should be diagnosed and treated.)

Peterson, J, Kaul, S, Khashab, M. "A double-blind, randomized comparison of levofloxacin 750 mg once-daily for five days with ciprofloxacin 400/500 mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis". Urology. vol. 71. 2008. pp. 17-22.

(A randomized clinical trial demonstrating efficacy of short-course fluoroquinolones for complicated UTI.)

Poulsen, LL, Bisgaard, M, Son, NT, Trung, NV, An, HM, Dalsgaard, A. "Enterococcus faecalis clones in poultry and in humans with urinary tract infections, Vietnam". Emerg Infect Dis. vol. 18. 2012. pp. 1096-1100.

(Observational study demonstrating sharing of a bacterial clone between a human and poultry.)

Taylor, AK, Zembower, TR, Nadler, RB. "Targeted antimicrobial prophylaxis using rectal swab cultures in men undergoing transrectal ultrasound guided prostate biopsy is associated with reduced incidence of postoperative infectious complications and cost of care". J Urol. vol. 187. 2012. pp. 1275-9.

(Randomized trial of standard prophylaxis compared to rectal culture directed prophylaxis for prostate biopsy.)

van der Starre, WE, van Dissel, JT, van Nieuwkoop, C. "Treatment duration of febrile urinary tract infections". Curr Infect Dis Rep. vol. 13. 2011. pp. 571-8.

(Review of data supporting short-course treatment of febrile UTI.)

van Nieuwkoop, C, Bonten, TN, van’t Wout, JW. "Procalcitonin reflects bacteremia and bacterial load in urosepsis syndrome: a prospective observational study". Critical Care. vol. 14. 2010. pp. R206.

(Observational study demonstrating elevated procalcitonin in patients with bacteremic UTI.)

van Nieuwkoop, C, van’t Wout, JW, Assendelft, WJ. "Treatment duration of febrile urinary tract infection (FUTIRST trial): a randomized placebo-controlled multicenter trial comparing short (7 days) antibiotic treatment with conventional treatment (14 days)". BMC Infect Dis. vol. 9. 2009. pp. 131-40.

(Randomized clinical study demonstrating efficacy of short-course treatment of febrile UTI.)

Talan, DA, Takhar, SS, Krishnadasan, A, Abrahamian, FM, Mower, WR, Moran, GJ. "Fluoroquinolone-resistant and extended-spectrum β-lactamase–producing Escherichia coli infections in patients with pyelonephritis, United States". Emerg Infect Dis. 2016 Sep.

Grayson, M.L., Macesic, N, Trevillyan, J, Ellis, A.G, Zeglinski, P.T, Hewitt, N.H, Gardiner, B.J, Frauman, A.G. "Fosfomycin for treatment of prostatitis: new tricks for old dogs". Clin Infect Dis. 2015.

Florian, M, Wagenlehner. "Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: a randomised, double-blind, phase 3 trial (ASPECT-cUTI)". Lancet. vol. 385. 2015. pp. 1949-56.

Carmeli, Y. "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. vol. 16. 2016. pp. 661-673.

DRG Codes and expected length of stay

Pyelonephritis, Cystitis, UTI: 590-599

Acute prostatitis: 601

Chronic prostatitis: 601.1

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