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Acute Pyelonephritis Treatment & Management

  • Author: Tibor Fulop, MD, FASN, FACP; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
 
Updated: Aug 06, 2016
 

Approach Considerations

Ambulatory younger women who present with signs and symptoms of uncomplicated acute pyelonephritis may be candidates for outpatient therapy. They must be otherwise healthy and must not be pregnant. In addition, they must be treated initially in the emergency department (ED) with vigorous oral or IV fluids, antipyretic pain medication, and a dose of parenteral antibiotics. Studies have shown that outpatient therapy for selected patients is as safe as inpatient therapy for a comparable group of patients and is much less expensive.

Use analgesics as needed. Early in the course of the illness, parenteral analgesics are often necessary to reduce morbidity from symptoms. Nonsteroidal anti-inflammatory drugs and narcotics are complementary; do not assume that one class is better than the other.

Admission is usually appropriate for patients who are severely ill, pregnant, or elderly or who have comorbid disorders that increase the complexity of management or the complication rate (eg, diabetes mellitus, chronic lung disease, congenital or acquired immunodeficiency). Admission may also be advisable for patients whose social situation is unstable, because of the possibility of poor compliance or poor follow-up.

Emergency surgery may be indicated in a patient with fever or positive blood culture results persisting longer than 48 hours; in a patient whose condition deteriorates; or in a patient who appears toxic for longer than 72 hours. These patients may have an abscess, emphysematous pyelonephritis, or an obstructing calculus. The etiology may not be immediately evident, but an unexpected change in the clinical picture warrants immediate evaluation for potential surgical intervention.

After recovery from the acute infection, patients may be candidates for elective surgery to reverse conditions that predispose the kidney to recurrent infections and renal damage. These conditions include congenital anomalies, fistulae involving the urogenital tract, prostatic hypertrophy, renal calculi, and vesicoureteral reflux.

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Antibiotic Selection

Antibiotic selection is typically empirical, because the results of blood or urine cultures are rarely available by the time a decision must be made. Initial selection should be guided by local antibiotic resistance patterns. Culture results from specimens collected before the initiation of therapy should be checked in 48 hours to determine antibiotic efficacy.

The pathogen in community-acquired infections is usually E coli or other Enterobacteriaceae. Acceptable regimens may include fluoroquinolones, cephalosporins, penicillins, extended-spectrum penicillins, carbapenems, and aminoglycosides.[12, 1] If enterococci are suggested on the basis of Gram stain results, ampicillin or vancomycin can replace the fluoroquinolone. If any doubt exists as to the diagnosis, coverage of both Enterobacteriaceae and enterococci is acceptable.

There is a higher incidence of enterococcal infections in hospitalized and other institutionalized patients. Ampicillin or amoxicillin should be included in the regimen. If the patient is allergic to penicillin, vancomycin should be substituted.

In choosing an empirical antibiotic regimen, consideration should include the local anti-biogram and drug-resistance rates. For example, in a community with growing fluoroquinolone resistance, agents in that class may not be an ideal first-line choice. In light of increasing resistance, short courses of treatment are preferred. In one clinical trial, a 7-day course of oral ciprofloxacin was shown to be a safe and successful treatment for acute pyelonephritis in women, including older women and those with more severe infection.[13]

Patient characteristics should also be considered. For example, patients who have been frequently exposed to antibiotics (eg, solid-organ transplant and hematopoietic transplant patients) or are from institutional facilities are at a greater risk for infection with drug-resistant pathogens, such as extended-spectrum beta-lactamase–producing or carbapenemase-producing organisms.

Oral versus parenteral administration

Growing data suggest that oral antibiotic therapy, parenteral antibiotic therapy, and initial parenteral antibiotic therapy followed by oral antibiotic therapy are equally effective regimens, although most of the studies have been small.[14, 15] Some clinicians believe that initiating therapy with an intravenous or intramuscular dose of medication reduces the risk of therapeutic failure; other clinicians believe that a completely oral course is sufficient. Data exist to support both assertions.

To be considered for oral therapy, patients must meet several prerequisites. They must, of course, be able to tolerate oral medication. In addition, they must have no indication for admission, and close monitoring to ensure good compliance must be possible.

One prospective study supports using oral therapy alone in patients who can tolerate oral intake, lack signs of sepsis, and do not show signs of obstruction or renal suppuration on urinary tract ultrasonography. Another study (prospective, randomized, unblinded) in a controlled hospital setting found no difference in efficacy between oral and intravenous ciprofloxacin for the initial management of severe pyelonephritis.

The 2010 IDSA guidelines recommend that women with pyelonephritis who require hospitalization be treated initially with an intravenous antimicrobial regimen. The choice of antimicrobial agents should be based on local resistance data, with the regimen tailored on the basis of susceptibility results.[1]

Because of the high rate of resistance of E coli, the empirical use of trimethoprim-sulfamethoxazole (TMP-SMZ) should be avoided in patients who require hospitalization. If beta-lactam drugs and fluoroquinolones are contraindicated, administer aztreonam parenterally. As such, the patient will need to be admitted.

Regimens for complicated cases

With complicated acute pyelonephritis, treat patients parenterally until defervescence and improvement in the clinical condition warrants changing to oral antibiotics. Complete the course of therapy with an oral agent selected on the basis of culture results.[15] Acceptable regimens include the following:

  • Ampicillin and an aminoglycoside
  • Cefepime
  • Imipenem
  • Meropenem
  • Piperacillin-tazobactam
  • Ticarcillin-clavulanate
  • Ceftazidime-avibactam [16, 17]

If the patient is allergic to penicillin, vancomycin should be substituted. Vancomycin or linezolid are options if enterococci are a consideration.

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Outpatient Treatment

Antibiotic therapy

Patients presenting with acute pyelonephritis can be treated with a single dose of a parenteral antibiotic followed by oral therapy, provided they are monitored within the first 48 hours. In a study of febrile, nonpregnant women presenting with symptoms of acute pyelonephritis, 25% were hospitalized; of nonhospitalized patients, 80% were treated with a single parenteral dose of ceftriaxone or gentamicin, followed by oral therapy (usually trimethoprim-sulfamethoxazole [TMP-SMZ]). Twelve percent returned with persistent symptoms, most in the first day; most of these were admitted.[2]

Acute pyelonephritis has customarily been treated with 14 days of antibiotics, and 2010 IDSA guidelines maintain this recommendation for TMP-SMZ and beta-lactam agents. However, evidence suggests that in young, healthy women who are receiving a fluoroquinolone, including ciprofloxacin, the course of treatment can be shortened to 7 days. Levofloxacin, 750 mg/day, can be given for 5 days.[18, 19] Young, healthy males should complete a 14-day course.[1]

Outpatient treatment is appropriate for patients who have an uncomplicated infection that does not warrant hospitalization. Oral antibiotics are used to treat patients with mild to moderate illness. (See Table 2, below, for a description of outpatient treatments for pyelonephritis.)

Table 2. Outpatient Treatment for Pyelonephritis (Open Table in a new window)

First-line therapy
  • Ciprofloxacin (Cipro) 500 mg PO BID for 7d or
  • Ciprofloxacin extended-release (Cipro XR) 1000 mg PO daily for 7d or
  • Levofloxacin (Levaquin) 750 mg PO daily for 5d
  • If fluoroquinolone resistance is thought to be >10%, administer a single dose of ceftriaxone (Rocephin) 1g IV or  a consolidated 24-hour dose of an aminoglycoside (gentamicin 7 mg/kg IV or  tobramycin 7 mg/kg IV or amikacin 20 mg/kg IV)
Second-line therapy
  • Trimethoprim/sulfamethoxazole* 160 mg/800 mg (Bactrim DS, Septra DS) 1 tablet PO BID for 14d
  • If trimethoprim/sulfamethoxazole is used when the susceptibility is not known, an initial single IV dose of the following may also be given: ceftriaxone (Rocephin) 1 g IV or  a consolidated 24-h dose of an aminoglycoside (gentamicin 7 mg/kg IV or  tobramycin 7 mg/kg IV or amikacin 20 mg/kg IV)
Alternative therapy
  • Oral beta-lactams are not as effective for treating pyelonephritis; however, if they are used, administer with a single dose of ceftriaxone (Rocephin) 1 g IV or  a consolidated 24-h dose of an aminoglycoside (gentamicin 7 mg/kg IV or  tobramycin 7 mg/kg IV or amikacin 20 mg/kg IV)
  • Amoxicillin-clavulanate (Augmentin) 500 mg/125 mg PO BID for 14d or
  • Amoxicillin-clavulanate (Augmentin) 250 mg/125 mg PO TID for 3-7d or
  • Cefaclor 500 mg PO TID for 7d
*Should generally be avoided in elderly patients because of the risk of affecting renal function.

For female patients suspected of having acute pyelonephritis, 2010 guidelines from the Infectious Disease Society of America (IDSA) recommend sending urine for culture and susceptibility testing and then starting empirical antibiotic therapy.[1]

The fluoroquinolones are well tolerated and quite effective. They are probably the outpatient antibiotic treatment of choice for pyelonephritis. They (along with TMP-SMZ) do not eradicate the protective lactobacilli from the vagina. An important caveat for the use of fluoroquinolones in the elderly is their potential to cause a variety of neuropsychiatric symptoms, ranging from seizures to worsening of dementia.

In communities where the prevalence of resistance in uropathogens to fluoroquinolones is not known to be greater than 10%, the IDSA guidelines advise that patients who do not require hospitalization be treated with oral ciprofloxacin, 500 mg twice daily for 7 days, with or without an initial 400-mg dose of intravenous ciprofloxacin. If the uropathogen’s fluoroquinolone resistance is greater than 10%, an initial intravenous dose of a long-acting parenteral antimicrobial (eg, ceftriaxone, 1 g) is recommended.[1]

On an individual basis, for persons with community-onset UTI and fever, a case-control study found that the risk of fluoroquinolone-resistant E coli infection increased if the patient had undergone recent hospitalization or urinary catheterization or if the patient had used a fluoroquinolone within the past 6 months.[14]

IV fluids

If oral intake is not tolerated, intravenous hydration is warranted. Intravenous fluids should include 1 L of 5% dextrose in saline to reverse any existing ketosis, regardless of whether ketones are detected in the urine. Additional intravenous hydration is accomplished with normal saline. Exercise caution regarding conditions that might be adversely affected by improper amounts of fluid, saline, or glucose.

Follow-up

If the patient is not admitted at the time of diagnosis, follow-up reevaluation is important in 1-2 days to be sure the patient is progressing properly. A good rule based on common sense is that if the managing clinician is concerned that the patient may not respond well to outpatient management but still thinks the patient deserves a trial at home, the initial follow-up visit should take place in 24 hours. If the clinician thinks that the patient will do quite well with outpatient management, the initial follow-up visit can take place in 48 hours.

If the patient thinks that he or she is not progressing well or is getting worse, the patient should be evaluated emergently for consideration for admission and intravenous antibiotics.

Continue supportive care by prescribing antiemetics, antipyretics, analgesics, and urinary tract analgesics as needed. Have the patient complete a 14-day course of oral antibiotics. Evidence suggests that when treating a young, healthy female, the course of treatment can be shortened to 7 days from 14 days, if the antibiotic being used is a fluoroquinolone. Healthy young males should complete a 14-day course.

Obtain follow-up urine culture results in any patient with a complicated UTI, a complicated course, or increased risk of infection. Urine cultures are generally not indicated in healthy, nonpregnant women with resolved symptoms.[6] All patients with a complicated UTI should be considered for outpatient follow-up imaging of the urinary tract to identify abnormalities that predispose to further infections.

Rest is essential for recovery. Activity should be minimal. The patient should not return to work for 2 weeks, so as to allow time for the infection to be eliminated and for the patient to recover physical strength. Temper this recommendation depending on the physical condition of the patient and the presence of comorbid conditions.

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Inpatient Treatment

The decision regarding admission of a patient with acute pyelonephritis depends on age; host factors, such as immunocompromising chemotherapy or chronic diseases, known urinary tract structural abnormalities, renal calculi, recent hospitalization, or urinary tract instrumentation; and the patient's response to ED therapy.

Admit all patients with complicated UTI. Complicating factors include the following:

  • Structural abnormalities (eg, calculi, tract anomalies, indwelling catheter, obstruction)
  • Metabolic disease (eg, diabetes, renal insufficiency)
  • Impaired host defenses (eg, HIV, current chemotherapy, underlying active cancer)
  • Pregnancy

The following patients with clinically apparent uncomplicated pyelonephritis also should be admitted:

  • Patients who are unable to maintain adequate oral hydration or have evidence of vasomotor instability or unrelenting fever despite antipyretic therapy
  • Patients with debilitating pain or dehydration that cannot be corrected promptly in the ED
  • Patients with inadequate home care or resources to fill prescriptions or comply with the medical regimen (eg, homeless patients, adolescents, elderly patients in an acute illness setting who are at risk for clouded judgment, patients with substance abuse issues or other issues that will prevent adequate compliance)

Inpatient care includes the following:

  • Continue supportive care
  • Monitor urine and blood culture results
  • Monitor comorbid conditions for deterioration
  • Maintain hydration status with IV fluids until hydration can be maintained with oral intake
  • Continue IV antibiotics until defervescence and significant symptomatic improvement occur; convert to an oral regimen tailored to urine or blood culture results

In patients with acute pyelonephritis who require hospitalization, treatment begins with intravenous (IV) antibiotics. IV therapy should be given for 24-48 hours or until severe symptoms improve. A systematic review of 8 randomized, controlled trials in hospitalized patients with acute pyelonephritis found that early switching to oral antibiotic treatment appears to be as effective and safe as exclusively IV regimens.[20]

Duration of therapy should be at least 10-14 days, inclusive of initial IV therapy.  Patient circumstances may warrant more prolonged therapy.

Selection of a regimen should be based on local resistance data, and the regimen should be tailored on the basis of susceptibility results. Recommended regimens are listed in Table 3, below. However, a multinational study in 184 patients found that cefazolin is non-inferior to ceftriaxone for the empirical treatment of acute pyelonephritis in hospitalized patients. At 72 hours, defervescence or normalization of white blood cell count had occurred in 87.0% of the cefazolin group versus 85.9% of the ceftriaxone group; in addition, no difference was observed between the two groups for length of stay or 30-day readmission for cystitis or pyelonephritis.[21]

Table 3. Inpatient Treatment for Acute Pyelonephritis (Open Table in a new window)

First-line therapy
  • Ciprofloxacin (Cipro) 400 mg IV q12h for 10-14d or
  • Levofloxacin (Levaquin) 250 mg IV q24h for 10d or
  • Levofloxacin (Levaquin) 750 mg IV q24h for 5d
Second-line therapy
Extended-spectrum cephalosporins or penicillins:



  • Ampicillin-sulbactam (Unasyn) 1.5 g IV q6h or
  • Piperacillin-tazobactam (Zosyn) 3.375 g IV q6h or
  • Ticarcillin-clavulanate (Timentin) 3.1 g IV 4-6h or
  • Cefotaxime (Claforan) 1-2 g IV q8h or
  • Ceftriaxone (Rocephin) 1 g IV q24h or
  • Ceftazidime (Fortaz, Tazicef) 2 g IV q8h
  • All of the above can be administered with or without an aminoglycoside (except in pregnant patients); see Aminoglycosides, below
Carbapenems:



  • Meropenem (Merrem) 500 mg IV q8h or
  • Ertapenem (Invanz) 1 g IV q24h or
  • Doripenem (Doribax) 500 mg IV q8h
Monobactam (penicillin allergy):



  • Aztreonam (Azactam) 1 g IV q8-12h
Alternative therapy
Aminoglycosides (because of their potential nephrotoxicity, aminoglycoside antibiotics should be reserved for patients with serious and potentially life-threatening infections, and their dosage and blood levels should be carefully monitored to minimize the risk of nephrotoxicity):
  • Gentamicin 3 mg/kg/day IV/IM in 3 divided doses or 7 mg/kg/day pulsed dosing or
  • Tobramycin 3 mg/kg/day IV/IM in 3 divided doses or 7 mg/kg/day pulsed dosing or
  • Amikacin 10 mg/kg/day IV/IM in 3 divided doses or 20 mg/kg/day pulsed dosing
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Abscesses

For renal cortical abscesses (renal carbuncles), surgical drainage was once the only treatment. However, modern antibiotics alone often are curative. A semisynthetic penicillin, cephalosporin, fluoroquinolone, or vancomycin is recommended. Generally, parenteral antibiotics should be administered for 10-14 days, followed by oral therapy for 2-4 weeks. Fever should resolve within 5-6 days, and pain should resolve within 24 hours. If parenteral antibiotic therapy is successful, oral therapy is instituted for an additional 2-4 weeks.

If patients do not respond within 48 hours, percutaneous (or open) drainage should be performed. Other surgical options are enucleation of the carbuncle or nephrectomy.

Treatment of renal corticomedullary abscess includes parenteral antibiotics for 48 hours (usually successful), incision and drainage, and nephrectomy. If antibiotic therapy is successful, oral therapy is instituted for an additional 2 weeks.

Mortality associated with perinephric abscesses is 20-50%, but this rate can be decreased with early recognition, surgical drainage, and antimicrobial therapy (not adequate alone). Antibiotics should include an aminoglycoside and an antistaphylococcal agent. If Pseudomonas species are considered or demonstrated, an antipseudomonal beta-lactam antibiotic should be added. For enterococci, an aminoglycoside and ampicillin are recommended. Other organisms that have been reported include tuberculosis and fungi. Nephrectomy may be necessary.

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Calculi-Related Infections

A major challenge with calculi-related UTI is that the organisms can survive within the calculus. In the presence of acute infection, calculi must be removed immediately using cystoscopy or open surgical procedure.

The preferred method of treatment is surgical. Options include extracorporeal shockwave lithotripsy (ESWL), endoscopic methods, percutaneous methods, and open surgery. Mere observation is not recommended, as mortality is 28% with observation versus 7.2% in the surgically treated group. For staghorn calculus, the treatment of choice is to remove the whole stone. Fragments left behind remain infected and will grow again. Antibiotic therapy should be used in conjunction.

Although food and vitamin supplements that are rich in phosphorus and magnesium are advisable, remember that magnesium (and other divalent cations) can chelate fluoroquinolones, preventing their absorption from the gut.

Acidifying agents have been used. Ascorbic acid does not significantly decrease urinary pH, and ammonium chloride provides only temporary acidification. This approach is of little clinical usefulness. Urease inhibitors are effective in reducing stone formation, but long-term use is fraught with neurosensory, hematologic, and dermatologic adverse effects.

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Other Complicated Infections

Treatment for renal papillary necrosis is admission for intravenous antibiotics. The agents chosen should cover E coli and Enterobacter, Proteus, and Klebsiella species. Treatment for more serious infections also should cover Pseudomonas and Enterococcus species.

Parenteral agents that may be used empirically pending the result of a urine culture include the following:

  • Gentamicin
  • Cefotaxime
  • Ceftriaxone
  • Ceftazidime
  • Cefepime
  • Piperacillin-tazobactam
  • Imipenem-cilastatin
  • Meropenem
  • Ciprofloxacin

Parenteral therapy should be continued until the fever and other symptoms resolve. Duration of therapy generally is 14 days. If the response is not good, CT-guided drainage or surgical drainage with debridement is indicated.

The treatment of choice for xanthogranulomatous pyelonephritis is nephrectomy after the patient is stabilized. See the Medscape Reference article Xanthogranulomatous Pyelonephritis for more information.

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Pregnant Patients

Physiologic changes in the urinary tract predispose pregnant women to an increased risk of cystitis and pyelonephritis, which may lead to preterm labor and kidney damage. Hydroureter of pregnancy develops around the seventh week and progresses throughout the remainder of pregnancy; it resolves by 8 weeks post partum. The ureters may dilate sufficiently to contain 200 mL or more of urine. In addition, the kidneys enlarge and bladder capacity may double. The left kidney is more affected than the right.

The prevalence of bacteriuria in pregnancy is 2-25%, depending on the study criteria. Symptomatic UTI occurs in 1-3% of all pregnancies and leads to premature labor in 20-50% of cases.

The recommendation is that all pregnant women have a screening urine culture at 16 weeks' gestation. If the results are negative for a UTI, no additional cultures are indicated. If the patient has a history of recurrent UTIs, further cultures and other screening techniques (eg, nitrite dipstick or urine Gram stain) may be needed to detect the development of asymptomatic bacteriuria.

Accepted regimens for treating asymptomatic bacteriuria include amoxicillin (250 mg orally 3 times a day for 3 or 7 days; or 3 g in a single dose), cephalexin (2 or 3 g in a single dose), and nitrofurantoin (200 mg in a single dose; or 100 mg 4 times a day for 3 or 7 days). Successful treatment of bacteriuria prevents pyelonephritis. Fluoroquinolones and aminoglycosides should be avoided in pregnancy. (See Table 4, below, for regimens for pyelonephritis in pregnant patients.)

Inpatient admission is warranted for any pregnant patient with pyelonephritis. The treatment of choice during pregnancy includes the use of beta-lactam antibiotics. Intravenous antibiotics should be administered until the patient is afebrile for 24 hours and symptomatically improved. Therapy should be given for 24-48 hours or until severe symptoms improve. Once patients are afebrile for at least 48 hours, they can be switched to oral antibiotics and discharged to complete 10-14 days of treatment. It is recommended to avoid fluoroquinolones in pregnant patients. Aminoglycosides should also be avoided due to potential risk of ototoxicity following prolonged fetal exposure.

Presentation of pyelonephritis is similar in pregnant and nonpregnant females. The antibiotic regimen of choice is intravenous ampicillin and gentamicin. This is followed by an oral regimen to complete a 14-day course guided by results from susceptibility studies. Obtain an additional urine culture 1-2 weeks after the completion of therapy to verify eradication of the infection, and obtain monthly urine cultures until delivery to monitor the urine for recurrent infection.

Postcoital therapy with cephalexin or nitrofurantoin is recommended for prophylaxis against recurrent infection. If the initial infection requires a second agent for clearing the infection or a recurrent infection occurs, suppressive therapy until delivery is indicated with nitrofurantoin (50 mg or 100 mg at bedtime). Recurrent infection or persistent bacteriuria is an indication for urological evaluation 3-6 months after delivery.

Table 4. Treatment of Pyelonephritis During Pregnancy (Open Table in a new window)

Mild to moderate pyelonephritis
  • ceftriaxone (Rocephin) 1 g IV q24h or
  • cefepime (Maxipime) 1 g IV q12h or
  • cefotaxime (Claforan) 1-2 g IV q8h or
  • ceftazidime (Fortaz, Tazicef) 2 g IV q8h or
  • ampicillin 1-2 g IV q6h plus  gentamicin IV 1.5 mg/kg q8h
Severe pyelonephritis
If patient is immunocompromised and/or has incomplete urinary drainage:
  • ticarcillin-clavulanate (Timentin) 3.1 g IV q6h or
  • ampicillin-sulbactam (Unasyn) 1.5 g IV q6h or
  • piperacillin-tazobactam (Zosyn) 3.375 g IV q6h
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Pediatric Patients

In the pediatric population, indications for immediate urologic referral during acute pyelonephritis include the following:

  • Abnormal electrolyte values associated with acidosis
  • Elevated blood urea nitrogen level
  • Hypertension
  • A palpable bladder
  • Voiding difficulty (dribbling, poor stream, straining)

Aside from the effects of acute infection, the overriding concern is progressive renal deterioration of an already compromised kidney (hypoplastic or dysplastic) secondary to scarring from recurrent pyelonephritis with or without associated obstruction. The groups at greatest risk are infants and preschool-aged children. Initial management varies with patient age and presentation.

Close follow-up examination, regardless of whether the patient is initially admitted, is essential to ensure recovery. Immediate reevaluation is encouraged for any recurrence of symptoms, because neither treatment of asymptomatic bacteriuria nor long-term suppressive therapy has been found to be effective.

Urologic evaluation is necessary to establish the presence of any urologic abnormality. The preferred imaging study for the diagnosis of acute pyelonephritis is technetium-99m dimercaptosuccinic acid (99m Tc-DMSA) scintigraphy. Ultrasonography is the imaging study of choice for the diagnosis of urinary tract structural abnormalities.

Age-related data adapted from Harwood-Nuss and colleagues and Hansson and colleagues are presented below in Table 5.[22, 23]

Table 5. Pediatric Urinary Tract Infections (Open Table in a new window)

  Neonates Infants 6 weeks to 3 years of age Children 3-6 years of age Children 6-11 years of age
UTI frequency (%) 1 1.5-3 1.5-3 1.2
Female-to-male ratio 1:1.5 10:1 10:1 30:1
Route of infection Blood Ascending Ascending Ascending
Signs and symptoms Failure to thrive, fever, hypothermia, irritability, jaundice, poor feeding, sepsis, vomiting Diarrhea, failure to thrive, fever, irritability, poor feeding, strong-smelling urine, vomiting Abdominal pain, dysuria, enuresis, fever, gross hematuria, meningismus, strong-smelling urine, urinary urgency, urinary frequency, vomiting Dysuria, enuresis, fever, flank pain or tenderness, urinary urgency, urinary frequency
Predominant organism Klebsiella species E coli E coli, Proteus species in older boys E coli
Management Admit for intravenous ampicillin and gentamicin and further evaluation Admit for intravenous ampicillin and gentamicin and further evaluation Follow adult guidelines, but avoid fluoroquinolones, which are theoretically contraindicated due to potential effects on the musculoskeletal system Follow adult guidelines, but avoid fluoroquinolones, which are theoretically contraindicated due to potential effects on the musculoskeletal system

Diet and Activity

A regular diet is permitted as tolerated. Special diets, such as those for patients with diabetes mellitus, should be honored. Maintaining hydration is very important. If admission is not indicated and the patient will be monitored in an outpatient setting, hydration status should be normalized with intravenous fluids; the physician should not assume that the patient can or will accomplish this with oral hydration alone.

Rest is essential for recovery. Activity should be minimized. Patients who are treated in an outpatient setting should not return to work for 2 weeks in order to allow time for the infection to be eliminated. This time also allows the patient to recover physical strength. This recommendation can be tempered in special circumstances as warranted by the clinician.

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Deterrence and Prevention

Prevention of pyelonephritis involves identifying clinical situations that could lead to pyelonephritis and developing a strategy to decrease that likelihood. These strategies may include a change in contraceptive behavior, administration of prophylactic antibiotics, or early identification and treatment of cystitis.

If these strategies do not eliminate infection, recurrence of infection, or relapse (reinfection less than 14 days after completing an appropriate regimen), the patient needs to undergo systematic evaluation for predispositional anatomic, functional, or structural abnormalities.

For more information, see the Medscape Reference topic Prevention of Urinary Tract Infections.

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Consultations

Consultation is indicated if the infection is complicated. Most cases of acute pyelonephritis occur in adult women and are readily managed without consultation. The following are reasons for consulting various subspecialists:

  • A urologist may be consulted regarding patients with ureteral or urethral obstruction, urinary stones, urogenital abnormality, or recurrent pyelonephritis, or for the first episode of pyelonephritis in an infant or child
  • A renal specialist may be consulted regarding patients with acute renal failure or advanced chronic renal failure or for neonates or infants
  • An infectious disease specialist may be consulted regarding patients with an unusual or resistant pathogen, those who are immunocompromised, patients with persisting fever (>48 hours) or toxicity (>72 hours), or patients whose blood culture results are positive for more than 48 hours
  • An obstetrician may be consulted for patients who are pregnant
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Contributor Information and Disclosures
Author

Tibor Fulop, MD, FASN, FACP Professor of Medicine, Department of Medicine, Division of Nephrology, University of Mississippi Medical Center

Tibor Fulop, MD, FASN, FACP is a member of the following medical societies: American College of Physicians, American Society of Diagnostic and Interventional Nephrology, American Society of Hypertension, American Society of Nephrology

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Fresenius Medical Care, Hungary.

Specialty Editor Board

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, International Society of Nephrology, American Society for Biochemistry and Molecular Biology, American Federation for Medical Research, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, Kentucky Medical Association, National Kidney Foundation, Phi Beta Kappa

Disclosure: Received grant/research funds from Dept of Veterans Affairs for research; Received salary from American Society of Nephrology for asn council position; Received salary from University of Louisville for employment; Received salary from University of Louisville Physicians for employment; Received contract payment from American Physician Institute for Advanced Professional Studies, LLC for independent contractor; Received contract payment from Healthcare Quality Strategies, Inc for independent cont.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

Acknowledgements

Amy J Behrman, MD Associate Professor, Department of Emergency Medicine, Director, Division of Occupational Medicine, University of Pennsylvania School of Medicine

Amy J Behrman, MD is a member of the following medical societies: American College of Occupational and Environmental Medicine

Disclosure: Nothing to disclose.

Christopher Edwards, MD Resident Physician, Department of Emergency Medicine, University of Pennsylvania School of Medicine

Christopher Edwards, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Judith Green-McKenzie, MD, MPH Associate Professor, Director of Clinical Practice, Occupational Medicine Residency Director, University of Pennsylvania School of Medicine

Judith Green-McKenzie, MD, MPH is a member of the following medical societies: American College of Occupational and Environmental Medicine, American College of Physicians, American College of Preventive Medicine, National Medical Association, and Society of General Internal Medicine

Disclosure: Nothing to disclose.

Eleanor Lederer, MD Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa

Disclosure: Dept of Veterans Affairs Grant/research funds Research

Chike Magnus Nzerue, MD Associate Dean for Clinical Affairs, Vice-Chairman of Internal Medicine, Meharry Medical College

Chike Magnus Nzerue, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Society of Nephrology, and National Kidney Foundation

Disclosure: Nothing to disclose.

Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM Associate Professor, Education Officer, Department of Emergency Medicine, Hospital of the University of Pennsylvania; Director of Education and Research, PENN Travel Medicine

Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American Society of Tropical Medicine and Hygiene, International Society of Travel Medicine, Society for Academic Emergency Medicine, and Wilderness Medical Society

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William H Shoff, MD, DTM&H Director, PENN Travel Medicine; Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine

William H Shoff, MD, DTM&H is a member of the following medical societies: American College of Physicians, American Society of Tropical Medicine and Hygiene, International Society of Travel Medicine, Society for Academic Emergency Medicine, and Wilderness Medical Society

Disclosure: Glaxo Smith Kline None None; Glaxo Smith Kline Honoraria Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

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References
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  16. Wagenlehner FM, Sobel JD, Newell P, Armstrong J, Huang X, Stone GG, et al. Ceftazidime-avibactam Versus Doripenem for the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis: RECAPTURE, a Phase 3 Randomized Trial Program. Clin Infect Dis. 2016 Jun 16. [Medline].

  17. FDA approves new antibacterial drug Avycaz. U.S. Food and Drug Administration. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm435629.htm. February 26, 2015; Accessed: August 1, 2016.

  18. Nicolle L, Duckworth H, Sitar D, Bryski L, Harding G, Zhanel G. Pharmacokinetics/pharmacodynamics of levofloxacin 750 mg once daily in young women with acute uncomplicated pyelonephritis. Int J Antimicrob Agents. 2008 Mar. 31(3):287-9. [Medline].

  19. Peterson J, Kaul S, Khashab M, Fisher AC, Kahn JB. 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. 2008 Jan. 71(1):17-22. [Medline].

  20. Vouloumanou EK, Rafailidis PI, Kazantzi MS, Athanasiou S, Falagas ME. Early switch to oral versus intravenous antimicrobial treatment for hospitalized patients with acute pyelonephritis: a systematic review of randomized controlled trials. Curr Med Res Opin. 2008 Dec. 24(12):3423-34. [Medline].

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  22. Harwood-Nuss AL, Etheredge W, McKenna I. Urological Emergencies. Harwood-Nuss A, Wolfson AB, eds. The Clinical Practice of Emergency Medicine. 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001. 2227-61.

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  24. Juliano TM, Stephany HA, Clayton DB, Thomas JC, Pope JC 4th, Adams MC, et al. Incidence of Abnormal Imaging and Recurrent Pyelonephritis After First Febrile Urinary Tract Infection in Children 2-24 Months. J Urol. 2013 Jan 22. [Medline].

 
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Nonobstructing distal left ureteral calculus 2 X 1 X 2 cm.
Multiple abscesses, upper pole of left kidney.
Bilateral hydronephrosis.
Table 1. Bacterial Etiology of Urinary Tract Infections
Bacteria % Uncomplicated % Complicated
Gram negative    
Escherichia coli 70-95 21-54
Proteus mirabilis 1-2 1-10
Klebsiella spp 1-2 2-17
Citrobacter spp < 1 5
Enterobacter spp < 1 2-10
Pseudomonas aeruginosa < 1 2-19
Other < 1 6-20
Gram positive    
Coagulase-negative staphylococci 5-10* 1-4
Enterococci 1-2 1-23
Group B streptococci < 1 1-4
Staphylococcus aureus < 1 1-23
Other < 1 2
Adapted from Hooton TM. The current management strategies for community-acquired urinary tract infection. Infect Dis Clin North Am. Jun 2003;17(2):303-32. [Medline].



* S saprophyticus



Table 2. Outpatient Treatment for Pyelonephritis
First-line therapy
  • Ciprofloxacin (Cipro) 500 mg PO BID for 7d or
  • Ciprofloxacin extended-release (Cipro XR) 1000 mg PO daily for 7d or
  • Levofloxacin (Levaquin) 750 mg PO daily for 5d
  • If fluoroquinolone resistance is thought to be >10%, administer a single dose of ceftriaxone (Rocephin) 1g IV or  a consolidated 24-hour dose of an aminoglycoside (gentamicin 7 mg/kg IV or  tobramycin 7 mg/kg IV or amikacin 20 mg/kg IV)
Second-line therapy
  • Trimethoprim/sulfamethoxazole* 160 mg/800 mg (Bactrim DS, Septra DS) 1 tablet PO BID for 14d
  • If trimethoprim/sulfamethoxazole is used when the susceptibility is not known, an initial single IV dose of the following may also be given: ceftriaxone (Rocephin) 1 g IV or  a consolidated 24-h dose of an aminoglycoside (gentamicin 7 mg/kg IV or  tobramycin 7 mg/kg IV or amikacin 20 mg/kg IV)
Alternative therapy
  • Oral beta-lactams are not as effective for treating pyelonephritis; however, if they are used, administer with a single dose of ceftriaxone (Rocephin) 1 g IV or  a consolidated 24-h dose of an aminoglycoside (gentamicin 7 mg/kg IV or  tobramycin 7 mg/kg IV or amikacin 20 mg/kg IV)
  • Amoxicillin-clavulanate (Augmentin) 500 mg/125 mg PO BID for 14d or
  • Amoxicillin-clavulanate (Augmentin) 250 mg/125 mg PO TID for 3-7d or
  • Cefaclor 500 mg PO TID for 7d
*Should generally be avoided in elderly patients because of the risk of affecting renal function.
Table 3. Inpatient Treatment for Acute Pyelonephritis
First-line therapy
  • Ciprofloxacin (Cipro) 400 mg IV q12h for 10-14d or
  • Levofloxacin (Levaquin) 250 mg IV q24h for 10d or
  • Levofloxacin (Levaquin) 750 mg IV q24h for 5d
Second-line therapy
Extended-spectrum cephalosporins or penicillins:



  • Ampicillin-sulbactam (Unasyn) 1.5 g IV q6h or
  • Piperacillin-tazobactam (Zosyn) 3.375 g IV q6h or
  • Ticarcillin-clavulanate (Timentin) 3.1 g IV 4-6h or
  • Cefotaxime (Claforan) 1-2 g IV q8h or
  • Ceftriaxone (Rocephin) 1 g IV q24h or
  • Ceftazidime (Fortaz, Tazicef) 2 g IV q8h
  • All of the above can be administered with or without an aminoglycoside (except in pregnant patients); see Aminoglycosides, below
Carbapenems:



  • Meropenem (Merrem) 500 mg IV q8h or
  • Ertapenem (Invanz) 1 g IV q24h or
  • Doripenem (Doribax) 500 mg IV q8h
Monobactam (penicillin allergy):



  • Aztreonam (Azactam) 1 g IV q8-12h
Alternative therapy
Aminoglycosides (because of their potential nephrotoxicity, aminoglycoside antibiotics should be reserved for patients with serious and potentially life-threatening infections, and their dosage and blood levels should be carefully monitored to minimize the risk of nephrotoxicity):
  • Gentamicin 3 mg/kg/day IV/IM in 3 divided doses or 7 mg/kg/day pulsed dosing or
  • Tobramycin 3 mg/kg/day IV/IM in 3 divided doses or 7 mg/kg/day pulsed dosing or
  • Amikacin 10 mg/kg/day IV/IM in 3 divided doses or 20 mg/kg/day pulsed dosing
Table 4. Treatment of Pyelonephritis During Pregnancy
Mild to moderate pyelonephritis
  • ceftriaxone (Rocephin) 1 g IV q24h or
  • cefepime (Maxipime) 1 g IV q12h or
  • cefotaxime (Claforan) 1-2 g IV q8h or
  • ceftazidime (Fortaz, Tazicef) 2 g IV q8h or
  • ampicillin 1-2 g IV q6h plus  gentamicin IV 1.5 mg/kg q8h
Severe pyelonephritis
If patient is immunocompromised and/or has incomplete urinary drainage:
  • ticarcillin-clavulanate (Timentin) 3.1 g IV q6h or
  • ampicillin-sulbactam (Unasyn) 1.5 g IV q6h or
  • piperacillin-tazobactam (Zosyn) 3.375 g IV q6h
Table 5. Pediatric Urinary Tract Infections
  Neonates Infants 6 weeks to 3 years of age Children 3-6 years of age Children 6-11 years of age
UTI frequency (%) 1 1.5-3 1.5-3 1.2
Female-to-male ratio 1:1.5 10:1 10:1 30:1
Route of infection Blood Ascending Ascending Ascending
Signs and symptoms Failure to thrive, fever, hypothermia, irritability, jaundice, poor feeding, sepsis, vomiting Diarrhea, failure to thrive, fever, irritability, poor feeding, strong-smelling urine, vomiting Abdominal pain, dysuria, enuresis, fever, gross hematuria, meningismus, strong-smelling urine, urinary urgency, urinary frequency, vomiting Dysuria, enuresis, fever, flank pain or tenderness, urinary urgency, urinary frequency
Predominant organism Klebsiella species E coli E coli, Proteus species in older boys E coli
Management Admit for intravenous ampicillin and gentamicin and further evaluation Admit for intravenous ampicillin and gentamicin and further evaluation Follow adult guidelines, but avoid fluoroquinolones, which are theoretically contraindicated due to potential effects on the musculoskeletal system Follow adult guidelines, but avoid fluoroquinolones, which are theoretically contraindicated due to potential effects on the musculoskeletal system
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