Acute Pyelonephritis Treatment & Management

Supportive care is as follows:

• Rest
• Antipyretics as needed
• Oral or parenteral pain medications as needed
• Oral or parenteral antiemetics as needed
• Urinary tract analgesics to relieve dysuria (up to 3 days)
• IV or oral fluids to maintain hydration status

Reasons for hospital admission may include the following:

• Cannot tolerate oral intake
• Unstable social situation - Eg, possibility of poor compliance or poor follow-up
• Unstable vital signs
• Severe signs and symptoms
• Pregnancy
• Comorbid disorders that increase the complexity of management or the complication rate - Eg, diabetes mellitus, chronic lung disease, congenital or acquired immunodeficiency syndrome (monitor comorbid conditions for deterioration)

Parenteral antibiotics are often initially administered at the time of diagnosis, regardless of whether the patient is admitted or discharged home. Continuing IV antibiotics for the admitted patient is essential until defervescence and improvement in the clinical condition warrants changing to oral antibiotics to complete the course. Once the patient has improved, due consideration can be given to discharge and close follow-up care in an outpatient setting.^[15]

Activity

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 recuperate physical strength. This recommendation can be tempered in special circumstances as warranted by the clinician.

Transfer

When patients are treated in an inpatient setting, the facility to which they are admitted should be able to provide an appropriate level of care for pyelonephritis and any comorbid conditions. If the admitting facility is unable to provide an appropriate level of care, the patient should be transferred to a facility that is able to meet that patient's needs.

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. Urine culture collected at the initiation of therapy should be checked in 48 hours to determine antibiotic efficacy.

When using an oral-only regimen, the initial dose should be administered at the time of the evaluation.

The etiology of community-acquired infections is usually Escherichia coli or another member of Enterobacteriaceae. Infections usually involve women aged 18-50 years and, infrequently, men of the same age. Accepted outpatient regimens include the following:

• Administer ceftriaxone (1 g intravenous/intramuscular [IV/IM]) or gentamicin (single 24-h dose or divided every 8 h) or tobramycin (single 24-h dose or divided every 8 h) on day 1, followed by an oral fluoroquinolone from day 2 to days 10-14 (for pediatric dosing, see the Medication section, below)^[16]
• Prescribe oral fluoroquinolone for 10-14 days^{[16, 17]}
• Prescribe amoxicillin-clavulanate potassium for 14 days
• Prescribe trimethoprim-sulfamethoxazole or trimethoprim or oral cephalosporin for 14 days; use only if the organism is known to be sensitive
• If beta-lactam drugs and fluoroquinolones are contraindicated, administer aztreonam parenterally; in such a case, the patient will need to be admitted

The fluoroquinolone course can be shortened to a 7-day course, instead of 10-14 days, in healthy, young women with uncomplicated pyelonephritis. A similar course probably could be used in healthy, young men without any complicating comorbidity, particularly if there is a prompt response to therapy.^{[18, 19]}

Studies have demonstrated the efficacy of levofloxacin (750 mg/day for 5 days) in the treatment of uncomplicated pyelonephritis and complicated urinary tract infection (UTI).^{[16, 17]} This same regimen has also been demonstrated to be safe and efficacious in comparison with ciprofloxacin (400-500 mg twice daily for 10-14 days).^[17]

Growing data suggest that oral antibiotic therapy alone, parenteral antibiotic therapy alone, and initial parenteral antibiotic therapy followed by oral antibiotic therapy are all equally efficacious, although most of the studies have been small.^{[20, 15]}

Some clinicians believe that initiating therapy with an IV or IM dose of medication reduces the risk of therapeutic failure; other clinicians believe that an oral course is sufficient. Data exist to support both assertions.

One prospective study supported 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 ultrasonographic findings.

Another study (prospective, randomized, unblinded), in a controlled hospital setting, compared oral versus IV ciprofloxacin for the initial management of severe pyelonephritis. Both regimens were equally efficacious.

If the patient can tolerate oral medication, there is no indication for admission, and the patient can be monitored closely to ensure good compliance. An oral antibiotic therapy ̶ only regimen appears to have increasing efficacy.

If enterococci are suggested based on Gram stain results, then ampicillin or vancomycin can replace fluoroquinolone. If any doubt exists as to the diagnosis, then coverage of Enterobacteriaceae and enterococci is acceptable.

Enterococci have a higher incidence in patients in hospitals and other institutions. Ampicillin or amoxicillin should be included in the regimen. If the patient is allergic to penicillin, then vancomycin should be substituted.

Admit patients who appear toxic, if they are not already hospitalized. If complicated acute pyelonephritis is suggested, use one of the following regimens:

• Treat patients parenterally until they improve clinically; complete the course of therapy with an oral agent selected based on culture results
• Acceptable regimens include the following: (1) ampicillin and an aminoglycoside, (2) cefepime, (3) imipenem, (4) meropenem, (5) piperacillin-tazobactam, or (6) ticarcillin-clavulanate; if the patient is allergic to penicillin, substitute vancomycin
• Vancomycin or linezolid are options if enterococci are a consideration

Additional medications used in pharmacologic therapy include the following:

• Antipyretics - May be beneficial
• Antiemetics - Use oral and parenteral antiemetics as needed; early in the course of the illness, parenteral medication is often necessary to reduce morbidity from symptoms
• Analgesics - Use oral and parenteral analgesics as needed
• Nonsteroidal medications and narcotics - These are complementary; do not assume that one is better than the other
• Urinary tract analgesics – May be beneficial if the patient has dysuria to such an extent that it disrupts the activities of daily living

Surgical intervention may be emergent if it occurs during active infection, or it may be elective if it occurs after recovery from infection. Emergent surgery is performed to preserve kidney function or to save the life of the patient. Elective surgical intervention reduces or prevents future morbidity.

Elective surgery is performed 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.

An emergent surgical condition may be indicated by a patient with fever or positive blood culture results persisting longer than 48 hours, a patient with a deteriorating condition, or a patient who appears toxic for longer than 72 hours. The etiology may not be immediately evident, but an unexpected change in the clinical picture warrants immediate evaluation for potential surgical intervention.

A regular diet is permitted as tolerated. Special dietary considerations, such as those associated with diabetes mellitus, should be honored. Hydration status is very important.

If oral intake is not tolerated, IV hydration is warranted. IV 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 IV hydration is accomplished with saline.

If admission is not indicated and the patient will be monitored in an outpatient setting, hydration status should be normalized with IV fluids; the physician should not assume that the patient can or will accomplish this with oral hydration alone.

When hydrating intravenously, exercise caution regarding conditions that might be adversely affected by improper amounts of fluid, saline, or glucose.

Continue supportive care by prescribing antiemetics, antipyretics, analgesics, and urinary tract analgesics as needed.

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.^[12]

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

If the patient is not admitted at the time of diagnosis, follow-up reevaluation is important in 1-2 days to be sure that 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 that the patient deserves a trial at home, then the initial follow-up visit should take place in 24 hours. If the clinician thinks that 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, then the patient should be evaluated emergently for consideration for admission and IV antibiotics.

All patients with a complicated UTI should be considered for outpatient follow-up imaging of their urinary tract to evaluate for abnormalities that predispose them to further infections.

The 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 UTIs. Several such strategies are elaborated below. Failure of these strategies to eliminate infection, recurrence of infection, or relapse (reinfection < 14 days after completing an appropriate regimen) indicates the need to refer the patient for systematic evaluation for predispositional anatomic, functional, or structural abnormalities.^[21]

Children with recurrent UTIs or urinary tract structural abnormalities require prompt evaluation of urinary tract symptoms and appropriate treatment.

Premenopausal or postmenopausal women with recurrent, uncomplicated UTIs

In this population, recurrent UTIs may be defined as 2-2.6 UTIs per year; they occur in approximately 25% of women who develop acute uncomplicated UTIs.

Various behavioral and nutritional techniques have been recommended to decrease the recurrence of UTIs in young women. Daily cranberry juice intake has been suggested to be beneficial, but no conclusive evidence has been found. Behavioral techniques such as postcoital voiding and front-to-back wiping after defecation have been considered efficacious measures for lessening the risk of UTI; however, in a study of college-aged women, they accorded no benefit. Additionally, oral contraceptive use and tampon use were not associated with UTIs.

If the patient is using a diaphragm with spermicide for contraception, another method of contraception should be substituted so that spermicide-associated colonization of the vagina by uropathogens is avoided.

If the patient has 3 or more UTIs per year, postcoital or continuous antibiotic therapy is recommended for 6 months, followed by a reevaluation. Postcoital regimens include trimethoprim-sulfamethoxazole at 40 mg/200 mg, cephalexin at 125-250 mg, and nitrofurantoin at 50 mg (effective in pregnancy). Regimens for continuous dosing (daily or 3 times weekly) include trimethoprim-sulfamethoxazole at 40 mg/200 mg, trimethoprim at 100 mg, norfloxacin at 200 mg, nitrofurantoin at 200 mg, and cephalexin at 125-250 mg.

If the patient has fewer than 3 UTIs per year, patient-initiated therapy is recommended using standard regimens, such as single-dose therapy or 3-day therapy. Referral for urologic evaluation is indicated if the patient is not responding, if the patient has any complicating condition, or if the patient has a relapse.

Catheter-related infections or neurogenic bladder

Indwelling catheters have a cumulative incidence rate of associated bacteriuria of 3-10% per day. Two strategies for reducing bacteriuria and its sequelae are removal of the catheters as soon as possible and keeping the closed system closed.

After the indwelling catheter has been removed, alternative strategies that can be applied for emptying the bladder that reduce, but do not eliminate, the risk of infection are the use of condom catheters, intraurethral catheters, and suprapubic catheters and the employment of intermittent catheterization (1-3% risk of bacteriuria per catheterization).

Situations in which treatment of asymptomatic bacteriuria (ABU) are indicated include culture of Serratia marcescens, clearance of an organism responsible for an infection cluster in an institution, and clearance of an organism in a high-risk patient (eg, neutropenic, posttransplantation, pregnant).

Chronic bacterial prostatitis

This condition produces recurrent bacteriuria interspersed with prolonged periods without bacteriuria. Treatment involves 2-3 months of a fluoroquinolone that has good prostate penetration. The goal of therapy is to eradicate infection from the prostate.

Renal transplant recipients

The frequency of UTIs (35-79%) and the potential morbidity of transplant pyelonephritis are relatively high in this population. Transplant recipients typically receive prophylaxis with trimethoprim-sulfamethoxazole for at least the first 6-12 months following transplantation. The antibiotic chosen may be modified depending on local organism sensitivities.

Owing to physiologic changes in the urinary tract, pregnant women are at an increased risk for UTI 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 postpartum. The ureters may dilate sufficiently to contain 200 mL of urine or more. In addition, the kidneys enlarge and bladder capacity may double. The left kidney is more affected than the right. The prevalence rate of bacteriuria in pregnancy is 2-25%, depending on the study criteria.

Symptomatic UTI (1-3% of all pregnancies) 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 ABU.

Accepted regimens for treating ABU include amoxicillin (250 mg 3 times daily for 3 days or 7 days; 3-g single dose), cephalexin (2 g or 3 g single dose), and nitrofurantoin (200 mg single dose; 100 mg 4 times daily for 3 days or 7 days). Successfully treated bacteriuria prevents pyelonephritis.

The presentation of pyelonephritis is similar in pregnant and nonpregnant females. The antibiotic regimen of choice is IV 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 urologic evaluation 3-6 months after delivery.

The manifestation of symptomatic UTI and pyelonephritis varies in the pediatric population based on the age of the patient. The classic signs and symptoms observed in adults are often absent in children, particularly neonates and infants. When fever is present, pyelonephritis should be in the differential diagnosis.

Indications for immediate urologic referral during acute pyelonephritis are abnormal electrolyte values associated with acidosis, elevated blood urea nitrogen (BUN) level, hypertension, a palpable bladder, and 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 treatment of ABU and long-term suppressive therapy have not been found to be efficacious.

Urologic evaluation is necessary to establish the presence of any urologic abnormality. The preferred imaging study for the diagnosis of acute pyelonephritis is dimercaptosuccinic acid (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 in Table 4.^{[22, 23]}

Table 4. Pediatric Urinary Tract Infections (Open Table in a new window)

Consultation is indicated if the infection is complicated. Most cases of acute pyelonephritis occur in adult women and are readily managed without consultation. An obstetrician may be consulted for patients who are pregnant.

A urologist may be consulted regarding patients with ureteral or urethral obstruction, urinary stones, urogenital abnormality, 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 diseases specialist may be consulted regarding patients with an unusual or resistant pathogen, those who are immunocompromised, patients with persisting fever (>48 h) or toxicity (>72 h), or patients whose blood culture results are positive beyond 48 hours.